Reduction Of Gastric Acid Secretion Research Articles

Gastroprotective Activity of Aerial Leaves of Allium cepa

The present study was performed to evaluate the Antiulcer activity of Methanolic extract of Allium cepa leaves (MEAC) in Albino rats. Antiulcer activity of MEAC was investigated by using Ethanol induced gastric mucosal damage and Pylorous ligated gastric ulcers. Evaluation was done on both models comparing with reference standard Omeprazole (20mg/kg). The parameters taken to assess anti-ulcer for pylorus ligation method were volume gastric secretion, pH, free acidity, total acidity and ulcer index. In vivo studies were carried on the plant extract and results were found that protection of the Methanolic extract of Allium cepa leaves against characteristic lesions may be due to both reduction in gastric acid secretion and gastric cycloprotein and this may be due to the presence of Flavanoids. In this study we observed that, Methanolic extract of leaves of Allium cepa (MEAC) provides significant antiulcer activity against gastric ulcers in rats. The result of MEAC showed significant reduction in the ulcer index, when compared to control. The antiulcer activity extract may be attributed to their flavanoids content and antioxidant property. These findings indicate that MEAC display potential antiulcerogenic activity.

Helicobacter pylori-Associated Iron Deficiency Anemia in Childhood and Adolescence-Pathogenesis and Clinical Management Strategy.

Many epidemiological studies and meta-analyses show that persistent Helicobacter pylori infection in the gastric mucosa can lead to iron deficiency or iron deficiency anemia (IDA), particularly in certain populations of children and adolescents. Moreover, it has been demonstrated that H. pylori infection can lead to and be closely associated with recurrent and/or refractory iron deficiency and IDA. However, the pathogenesis and specific risk factors leading to this clinical outcome in H. pylori-infected children remain poorly understood. In general, most of pediatric patients with H. pylori-associated IDA do not show evidence of overt blood loss due to gastrointestinal hemorrhagic lesions. In adult populations, H. pylori atrophic gastritis is reported to cause impaired iron absorption due to impaired gastric acid secretion, which, subsequently, results in IDA. However, significant gastric atrophy, and the resultant substantial reduction in gastric acid secretion, has not been shown in H. pylori-infected children. Recently, it has been hypothesized that competition between H. pylori and humans for iron availability in the upper gastrointestinal tract could lead to IDA. Many genes, including those encoding major outer membrane proteins (OMPs), are known to be involved in iron-uptake mechanisms in H. pylori. Recent studies have been published that describe H. pylori virulence factors, including specific OMP genes that may be associated with the pathogenesis of IDA. Daily iron demand substantively increases in children as they begin pubertal development starting with the associated growth spurt, and this important physiological mechanism may play a synergistic role for the microorganisms as a host pathogenetic factor of IDA. Like in the most recent pediatric guidelines, a test-and-treat strategy in H. pylori infection should be considered, especially for children and adolescents in whom IDA is recurrent or refractory to iron supplementation and other definitive causes have not been identified. This review will focus on providing the evidence that supports a clear biological plausibility for H. pylori infection and iron deficiency, as well as IDA.

Natural Medicines as Gastro-protective Therapy in the Treatment of Peptic Ulcer: A Multifaceted Approach

Abstract: Gastrointestinal (GI) disorders are the ailments of the digestive tract that affect its function, including digestion, absorption, and excretion. The dysfunction of the gastrointestinal tract may occur due to infections by bacteria, parasites, and viruses. Peptic ulcer disease is a gastrointestinal tract disorder of the stomach and duodenum associated with infection of Helicobacter pylori. Helicobacter pylori is regarded as the worldwide causative agent responsible for the etiology of peptic ulcer and gastric carcinoma. The existing drug therapies are good healers in this situation, but due to resistance problems and side effects of drugs, researchers have been working to find out some safe alternatives. Interestingly, the medicinal herbs have been used for treating several disorders, including peptic ulcers, and are considered an effective and safer alternative to existing drugs. They are also considered eco-friendly, easily available, safe, and less toxic than traditional treatment therapy. Combining herbal medicines with natural products has been shown effective in treating peptic ulcers. In this review, the medicinal plants used against H. pylori infection have been discussed. The mechanisms of herbal drugs in healing peptic ulcers involve inhibition of H+ K+ ATPase pump, reduction in gastric acid secretion, and protection of gastric mucosa that have also been elaborated in this review. The phytochemicals responsible for biological activity have been summarized in the present article. The combination of herbs and natural products in the form of the polyherbal formulation may also be helpful as an effective therapy for treating peptic ulcers. Medicinal plants may offer the researchers new chemical molecules to explore as future drugs or as biochemical agents to unravel the etiology of the disease.

Safety Profile, In Vitro Anti-Inflammatory Activity, and In Vivo Antiulcerogenic Potential of Root Barks from Annona senegalensis Pers. (Annonaceae).

Annona senegalensis (Annonaceae) is a tropical shrub widely distributed in Burkina Faso. This plant is traditionally used as a medicine against many pathologies including typhoid fever, gastrointestinal disorders, ulcers, and inflammatory and infectious diseases. The present study was conducted to evaluate the anti-inflammatory and antiulcer properties of Annona senegalensis root bark extracts. Therefore, toxicity tests were first performed, followed by other biological tests. For this purpose, we first undertook to evaluate the toxicity tests before considering the other biological tests in a second step. The results showed that the extracted fractions had a significant effect for the different methods used (protein denaturation inhibition activity, hyaluronidase inhibition activity, and xanthine oxidase inhibition activity). However, of the extracted fractions used, the ethyl acetate fraction was the most anti-inflammatory fraction. The antiulcer activity was evaluated using the best bioactive fraction. The antiulcer effect of the ethyl acetate fraction may be due to both the reduction of gastric acid secretion and gastric cytoprotection. The results of this study also showed that the bioactive fraction reduced ethanol-induced ulceration and pyloric ligation in a dose-dependent manner, and at the highest dose (200 mg/kg), the effect was similar to that of the reference drug. In summary, the ethyl acetate fraction was found to have the best anti-inflammatory and antiulcerogenic activities. The ethyl acetate fraction at a dose of 200 mg/kg also showed a rather interesting level of cytoprotection. The anti-inflammatory and antiulcer activities could be due to the different secondary metabolites contained in the fractions extracted from Annona senegalensis, notably flavonoids, triterpenoids, steroids, saponins, and tannins. As the mechanisms of action are still little or not understood, we will consider in the future identifying the phytoconstituents and the mechanisms of action involved in the results.

Proton pump inhibitors and dysbiosis: Current knowledge and aspects to be clarified.

Proton pump inhibitors (PPIs) are common medications within the practice of gastroenterology. These drugs, which act through the irreversible inhibition of the hydrogen/potassium pump (H+/K+-ATPase pump) in the gastric parietal cells, are used in the treatment of several acid-related disorders. PPIs are generally well tolerated but, through the long-term reduction of gastric acid secretion, can increase the risk of an imbalance in gut microbiota composition (i.e., dysbiosis). The gut microbiota is a complex ecosystem in which microbes coexist and interact with the human host. Indeed, the resident gut bacteria are needed for multiple vital functions, such as nutrient and drug metabolism, the production of energy, defense against pathogens, the modulation of the immune system and support of the integrity of the gut mucosal barrier. The bacteria are collected in communities that vary in density and composition within each segment of the gastrointestinal (GI) tract. Therefore, every change in the gut ecosystem has been connected to an increased susceptibility or exacerbation of various GI disorders. The aim of this review is to summarize the recently available data on PPI-related microbiota alterations in each segment of the GI tract and to analyze the possible involvement of PPIs in the pathogenesis of several specific GI diseases.

Intravenous iron in post-bariatric abdominoplasty anaemia: a pragmatic approach

There is a paucity of data addressing the use of different iron preparations for the treatment of patients with anaemia in the postoperative period after bariatric surgery and abdominoplasty. This cohort of patients is deemed at higher risk of developing iron deficiency anaemia and associated complications. Iron deficiency is common in these patients because of several factors, including lack of iron intake, reduction in gastric acid secretion, and impaired iron absorption of the duodenal and jejunal segments as a consequence of bariatric surgery. In The Lancet Haematology Juan Carlos Montano-Pedroso and colleagues 1 Montano-Pedroso JC Bueno Garcia E Alcântara Rodrigues de Moraes M Francescato Veiga D Masako Ferreira L. Intravenous iron sucrose versus oral iron administration for the postoperative treatment of post-bariatric abdominoplasty anaemia: an open-label, randomised, superiority trial in Brazil. Lancet Haematol. 2018; 5: e310-e320 Summary Full Text Full Text PDF PubMed Scopus (10) Google Scholar report the results of a randomised controlled trial that assessed the effect of oral iron polymaltose versus intravenous iron sucrose in patients with anaemia after bariatric and abdominoplasty surgery. Intravenous iron sucrose versus oral iron administration for the postoperative treatment of post-bariatric abdominoplasty anaemia: an open-label, randomised, superiority trial in BrazilPostoperative intravenous administration of iron increased haemoglobin concentrations at 56 days post-operatively and reduced iron deficiency, without adverse events. Although superiority of intravenous iron was not shown, intravenous administration might be useful in post-bariatric patients, especially in those who have body-contouring treatment involving a second surgery within a short period of time. Larger trials, and trials using higher intravenous doses of iron, are needed to further assess the potential efficacy and safety of intravenous iron administration after post-bariatric plastic surgery. Full-Text PDF

Intravenous iron sucrose versus oral iron administration for the postoperative treatment of post-bariatric abdominoplasty anaemia: an open-label, randomised, superiority trial in Brazil

Anaemia and iron deficiency are common after post-bariatric abdominoplasty, which can involve removal of large areas of skin with associated blood loss. Because the oral absorbability of iron is reduced after bariatric surgery (through reduced intake, reduction of gastric acid secretion for conjugation of iron, and separation of the iron-absorptive areas of the duodenum and jejunum), it has been hypothesised that postoperative intravenous iron supplementation might be used to treat anaemia and iron deficiency in patients submitted to post-bariatric plastic surgeries. We aimed to assess whether intravenous iron administered postoperatively in post-bariatric abdominoplasty could result in increased blood haemoglobin concentrations compared with oral iron supplementation. In this open-label, randomised, superiority trial, we recruited women aged 18-55 years undergoing post-bariatric abdominoplasty at two public tertiary referral hospitals in São Paulo, Brazil. Eligible women had been treated for previous obesity with bariatric surgery using the vertical banded gastroplasty technique with Roux-en-Y gastric bypass by laparotomy; had grade III contour deformity via the Pittsburgh rating scale; and had a post-bariatric body-mass index (BMI) lower than 32 kg/m2, with stabilised weight loss for at least 6 months. Women were randomly assigned (1:1) to receive postoperative iron supplementation with two intravenous infusions of 200 mg of iron sucrose (intravenous group) or 100 mg of iron polymaltose complex orally twice a day for 8 weeks (oral group). The primary outcome in both groups was blood haemoglobin concentration at postoperative day 56 after abdominoplasty, with a minimum clinically relevant difference of 1·5 g/dL. Analyses were performed on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01857011, and the Brazilian Clinical Trials Registry, number RBR-2JGRKQ. The trial is completed. From April 7, 2014, to June 27, 2016, 102 post-bariatric patients were assessed for eligibility. 56 patients were eligible and were randomly assigned, with 28 allocated to each group. Mean baseline haemoglobin concentration was slightly higher in the oral group than in the intravenous group (12·71 g/dL [SD 1·06] vs 12·24 g/L [1·09]), and by post-operative day 56 was 12·54 g/dL (SD 1·18) and 12·80 g/dL (0·81), respectively (mean difference of 0·26 g/dL, 95% CI -0·28 to 0·80; p=0·009 in favour of the intravenous group). The minimum clinically relevant difference in concentrations was not reached. No adverse events were recorded in the intravenous group, whereas in the oral group, constipation was recorded in five (18%) patients, diarrhoea in three (11%), and nausea in one (4%) patient. Postoperative intravenous administration of iron increased haemoglobin concentrations at 56 days post-operatively and reduced iron deficiency, without adverse events. Although superiority of intravenous iron was not shown, intravenous administration might be useful in post-bariatric patients, especially in those who have body-contouring treatment involving a second surgery within a short period of time. Larger trials, and trials using higher intravenous doses of iron, are needed to further assess the potential efficacy and safety of intravenous iron administration after post-bariatric plastic surgery. The São Paulo Research Foundation (FAPESP).

Gastric acid suppression promotes alcoholic liver disease by inducing overgrowth of intestinal Enterococcus

Chronic liver disease is rising in western countries and liver cirrhosis is the 12th leading cause of death worldwide. Simultaneously, use of gastric acid suppressive medications is increasing. Here, we show that proton pump inhibitors promote progression of alcoholic liver disease, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis in mice by increasing numbers of intestinal Enterococcus spp. Translocating enterococci lead to hepatic inflammation and hepatocyte death. Expansion of intestinal Enterococcus faecalis is sufficient to exacerbate ethanol-induced liver disease in mice. Proton pump inhibitor use increases the risk of developing alcoholic liver disease among alcohol-dependent patients. Reduction of gastric acid secretion therefore appears to promote overgrowth of intestinal Enterococcus, which promotes liver disease, based on data from mouse models and humans. Recent increases in the use of gastric acid-suppressive medications might contribute to the increasing incidence of chronic liver disease.

Submitted, Not Presented: Stomach.

Introduction: Osteoporosis is often regarded as the disease specific to female, whereas male patients with osteoporosis are increasing as well. Although the main factor of osteoporosis in female is the decrease of estrogen production, the etiology is not clear for men. In Western countries, infection of H. pylori, particularly CagA-positive strain, has been shown as a possible risk for osteoporosis in male. The absorption of calcium is affected by acidity of gastrointestinal tract. In Japan, most H. pylori strains are CagA-positive and severe gastric mucosal atrophy is often observed in infected patients causing the reduction of gastric acid secretion. Thus, there could be more clear relationship between H. pylori infection and loss of bone density in Japan comparing with Western populations. The aim of this study was to examine whether H. pylori infection associates with loss of bone density in Japanese healthy males. Methods: 295 healthy male adults who attended the mass survey in 2014 were enrolled into the study (mean age: 50.2 ± 15.4 years old). We measured H. pylori stool antigen and the titer of serum antibodies to H. pylori. H. pylori status was defined as positive or negative when both tests showed concordant results. The bone density was examined calcaneal osteo sono-assessment index (OSI) using quantitative ultrasound. Osteopenia was defined when measured OSI was less than 1.0 SD from the mean OSI of the young age (20-44 years old) according to WHO diagnostic criteria. We performed logistic regression models and calculated the adjusted odds ratio (OR) for having osteopenia as a dependent variable. The independent variables were age, BMI, serum level of estradiol, the intake of calcium per day, smoking, drinking, periodical exercise, last educational background and H. pylori infection. Results: Bivariate and multivariate analyses revealed that only age was significantly different between subjects with or without osteopenia. In multivariate analysis, the adjusted OR of age for osteopenia was 2.88 (95%CI: 1.46-5.68, p < 0.001). On the other hand, the adjusted OR of H. pylori infection for osteopenia was 0.92 (0.47-1.81; p=0.81). Conclusion: Age was a significant risk for developing osteopenia in Japanese males. Unlike Western populations, no significant association was found between H. pylori infection and osteopenia in this series of adult males.

Characteristics of the Human Upper Gastrointestinal Contents in the Fasted State Under Hypo- and A-chlorhydric Gastric Conditions Under Conditions of Typical Drug – Drug Interaction Studies

Evaluate the impact of reduced gastric acid secretion after administration of two acid-reducing agents on the physicochemical characteristics of contents of upper gastrointestinal lumen of fasted adults. Eight healthy male adults, fasted from food for 12h, participated in a three-phase crossover study. Phase 1: No drug treatment prior to aspirations. Phase 2: Oral administration of 40mg pantoprazole at ~9am the last 3days prior to aspirations and at ~7am on aspiration day. Phase 3: Oral administration of 20mg famotidine at ~7pm prior to aspirations and at ~7am on aspiration day. Samples from the contents of upper gastrointestinal lumen were aspirated for 50min, after administration of 240ml table waterat ~9 am. Reduction of gastric acid secretion was accompanied by reduced buffer capacity, chloride ion concentration, osmolality and surface tension in stomach and by increased pH (up to ~0.7 units) in upper small intestine during the first 50min post-water administration. The mechanism of reduction of acid secretion seems to be important for the buffer capacity in stomach and for the surface tension in upper gastrointestinal lumen. Apart from gastric pH, reduced acid secretion affects physicochemical characteristics of contents of upper gastrointestinal lumen which may be important for the performance of certain drugs/products in the fasted state.

Ulcer healing activity of Mumijo aqueous extract against acetic acid induced gastric ulcer in rats.

Objective:Gastric ulcer is an important clinical problem, chiefly due to extensive use of some drugs. The aim was to assess the activity of Mumijo extract (which is used in traditional medicine) against acetic acid induced gastric ulcer in rats.Materials and Methods:The aqueous extract of Mumijo was prepared. Animals were randomly (n = 10) divided into four groups: Control, sham-operated group (received 0.2 ml of acetic acid to induce gastric ulcer), Mumijo (100 mg/kg/daily) were given for 4 days postacetic acid administration, and ranitidine group (20 mg/kg). The assessed parameters were pH and pepsin levels (by Anson method) of gastric contents and gastric histopathology. Ranitidine was used as reference anti-ulcer drug.Results:The extract (100 mg/kg/daily, p.o.) inhibited acid acetic-induced gastric ulceration by elevating its pH versus sham group (P < 0.01) and decreasing the pepsin levels compared to standard drug, ranitidine (P < 0.05). The histopathology data showed that the treatment with Mumijo extract had a significant protection against all mucosal damages.Conclusion:Mumijo extract has potent antiulcer activity. Its anti-ulcer property probably acts via a reduction in gastric acid secretion and pepsin levels. The obtained results support the use of this herbal material in folk medicine.

Antiulcer and gastric antisecretory effects of dichloromethane fraction and piplartine obtained from fruits of Piper tuberculatum Jacq. in rats

Ethnopharmacological relevancePiper tuberculatum Jacq. (Piperaceae) is medicinally used as an analgesic and as a treatment for gastric complaints. Thus, the current study aimed to investigate the gastroprotective and antisecretory properties of the dichloromethane fraction of the fruit of Piper tuberculatum (DFPT) and piplartine, a compound isolated from the DFPT, in rats. Materials and methodsGastric ulcers were induced in fasted rats by oral administration of absolute ethanol and then mucus content and glutathione (GSH) levels were measured. Mechanisms underlying the antisecretory action were studied through gastric H+,K+-ATPase activity of highly purified rabbit gastric microsomes and pylorus ligature method in rats. ResultsIn the acute toxicity test the values of estimated LD50 for oral and intraperitoneal administration of DFPT were 1.6266 and 0.2684g/kg, respectively. The DFPT (ED50=29mg/kg, p.o.) and piplartine (4.5mg/kg, p.o.) promoted gastroprotection against acute lesions induced by ethanol, effect that could be related with the maintenance of GSH levels in the gastric mucosa. However, only DFPT stimulated gastric mucus secretion. In vitro, the DFPT and piplartine inhibited the H+,K+-ATPase activity and, in vivo DFPT and piplartine also reduced basal gastric acid secretion, as well as that stimulated by pentagastrin. ConclusionsThese results demonstrate that DFPT and piplatine cause marked gastroprotective effects accompanied by the increase and maintenance of gastric mucus and GSH levels, as well as a reduction in gastric acid secretion through the gastrinergic pathway.

Dietary agonists of TRPV1 inhibit gastric acid secretion in mice.

Capsaicin and 6-gingerol, pungent components of chilli pepper and ginger, are known as dietary agonists of transient receptor potential vanilloid-1. Transient receptor potential vanilloid-1 nerve fibers are recognized to play a role in gastric mucosal integrity in rats. In the present studies, we examined the acute effects of peroral administration of capsaicin and 6-gingerol on gastric acid secretion in conscious mice. These agents were given p. o. 30 min before the pylorus was ligated. Oral administration of capsaicin (1.0-100 mg/kg) or 6-gingerol (1.5-50 mg/kg) significantly and dose-dependently inhibited basal acid secretion. Pretreatment with BCTC, a transient receptor potential vanilloid-1 antagonist, significantly reversed the reduced basal acid secretion by capsaicin or 6-gingerol. The combination of the lowest doses of capsaicin and 6-gingerol markedly inhibited basal acid secretion in conscious mice and this was also significantly reversed by BCTC. Moreover, the combination of the maximal dose of capsaicin and 6-gingerol inhibited basal acid secretion only to the level of a single administration of the maximal dose of capsaicin. These results suggest that the combination of capsaicin and 6-gingerol has an additive effect on the inhibition of gastric acid secretion through activation of transient receptor potential vanilloid-1. In separate experiments, intraduodenal administration of either capsaicin (30 mg/kg) or 6-gingerol (15 mg/kg), whose doses were observed to have a significant inhibitory effect by oral administration, tended to inhibit basal acid secretion compared with the vehicle. These results suggest that the combination of capsaicin and 6-gingerol has an additive effect on inhibition of gastric acid secretion through activation of transient receptor potential vanilloid-1, and oral administration of transient receptor potential vanilloid-1 agonists directly stimulates transient receptor potential vanilloid-1 in the gastric lumen, resulting in a potent reduction of gastric acid secretion.

Angiogenic and Anti-Angiogenic Therapy for Gastrointestinal Ulcers: New Challenges for Rational Therapeutic Predictions and Drug Design

Gastrointestinal (GI) ulcers are essentially internal wounds that resist normal healing processes. Since their pathogenesis is poorly understood, and the etiologic (e.g., gastric acid, aspirin-like drugs, stress) and aggravating factors (e.g., H. pylori) are not well characterized, the remaining therapeutic option is to accelerate healing. Superficial mucosal lesions, i.e., erosions usually heal by epithelial regeneration and restitution, but when ulcers involve the muscularis propria, smooth muscle cells do not divide/regenerate. These deep lesions are filled by granulation tissue, i.e., angiogenesis followed by proliferation of connective tissue fibroblasts that deposit collagen over which adjacent surviving and dividing epithelial cells migrate to complete the healing. Our laboratory was the first to postulate that stimulation of angiogenesis alone might be sufficient to accelerate ulcer healing in the GI tract. Indeed, daily treatment of rats with bFGF, PDGF or VEGF markedly improved the healing of cysteamine-induced chronic duodenal ulcers, without any reduction in gastric acid secretion. These results were reproduced by a single dose of gene therapy by adenoviral vectors encoding PDGF or VEGF genes. The molar potency of angiogenic growth factors was 2-7 million times better than the antiulcerogenic effect of antisecretory H2 antagonists. Since histologically & pathologically gastroduodenal ulcers look similar to ulcers in the lower GI tract, we also predicted that the healing of experimental ulcerative colitis might be also improved by these angiogenic growth factors. Rectal enemas containing bFGF or PDGF indeed accelerated the healing of chemically induced ulcerative colitis in rats. VEGF, also known as VPF (vascular permeability factor), however, had no effect or slightly aggravated the colonic lesions. Injection of anti-VEGF neutralizing antibodies, however, counteracted the increased vascular permeability in the early stages of experimental ulcerative colitis and subsequently decreased the number of inflammatory cells in colonic ulcers in rats, resulting in significantly improved healing in the lower GI tract lesions. Thus, the three angiogenic growth factors tested exerted beneficial effect on gastroduodenal ulcers, and rectal enemas with bFGF or PDGF also accelerated the healing of experimental ulcerative colitis. Surprisingly, we achieved the latter effect with anti-VEGF antibodies, most likely because of the pro-inflammatory actions of VEGF in the pathogenesis of ulcerative colitis.

Reduction of gastric acid secretion and ulcer formation by 3,3-dimethyl-1-(3-methylaminopropyl)-1-phenylphthalan (Lu 3-010); an inhibitor of noradrenaline uptake.

Abstract Lu 3–010 [3,3-dimethyl-1-(3-methylaminopropyl)-1-phenylphthalan], administered intraperitoneally, blocks the uptake of [3H]noradrenaline into the mouse and rat heart and has an activity 5 times greater than imipramine and comparable to that of desipramine. Lu 3–010 inhibits basal gastric acid secretion in the rat and is 4 and 2 times more potent than imipramine and desipramine, respectively. The drug is about 9 times more potent than desipramine in preventing the pentagastrin-induced stimulation of gastric acid secretion in the rat. Lu 3–010 reduces the incidence of stress-induced gastric lesions in the rat, exhibiting an ED50 ± s.e. of 6.3 ± 1.4 mg/kg, and at 10 mg/kg, ulcer development in the 17-hour Shay test is reduced by 50%.

Effect of Feronia elephantum (Corr) Fruit Pulp Extract on Indomethacin-induced Gastric Ulcer in Albino Rats

Purpose: To investigate the activity of Feronia elephantum fruit pulp extract (which is used in folk medicine) against indomethacin-induced gastric ulcer in rats. Methods: The fruit pulp was extracted with ethanol and the anti-ulcer activity of the extract in indomethacin-induced gastric ulceration in Swiss albino rats was evaluated. The parameters assessed were pH and acid concentration of gastric contents, and gastric ulcer index. Ranitidine was used as the reference anti-ulcer drug. Acute toxicity studies were also carried out. Results: The extract (500 mg/kg, p.o.) inhibited indomethacin-induced gastric ulceration by decreasing acid concentration of gastric fluid while elevating its pH (p < 0.01), and compared well with the standard drug, ranitidine (p < 0.001). However, its anti-ulcer activity was not as potent as that of ranitidine. Acute toxicity studies showed thatthere was no mortality following the administration of the extract in a dose range of 250 - 5000 mg/kg, p.o. Conclusion: Feronia elephantum fruit pulp extract has potent antiulcer activity with low toxicity. Its anti-ulcer property probably acts via a reduction in gastric acid secretion. The results obtained support the use of this herbal material in folk medicine.Keywords: Anti-ulcer; Feronia elephantum (Corr.); Indomethacin; Ulcer; Gastric acidity

Safety of the long-term use of proton pump inhibitors

The proton pump inhibitors (PPIs) as a class are remarkably safe and effective for persons with peptic ulcer disorders. Serious adverse events are extremely rare for PPIs, with case reports of interstitial nephritis with omeprazole, hepatitis with omeprazole and lansoprazole, and disputed visual disturbances with pantoprazole and omeprazole. PPI use is associated with the development of fundic gland polyps (FGP); stopping PPIs is associated with regression of FGP. In the absence of Helicobacter pylori infection, the long-term use of PPIs has not been convincingly proven to cause or be associated with the progression of pre-existing chronic gastritis or gastric atrophy or intestinal metaplasia. Mild/modest hypergastrinemia is a physiological response to the reduction in gastric acid secretion due to any cause. The long-term use of PPIs has not been convincingly proven to cause enterochromaffin-like cell hyperplasia or carcinoid tumors. PPIs increase the risk of community acquired pneumonia, but not of hospital acquired (nosocomial) pneumonia. There is no data to support particular care in prescribing PPI therapy due to concerns about risk of hip fracture with the long-term use of PPIs. Long-term use of PPIs does not lead to vitamin B12 deficiencies, except possibly in the elderly, or in persons with Zollinger-Ellison Syndrome who are on high doses of PPI for prolonged periods of time. There is no convincingly proven data that PPIs increase the risk of Clostridium difficile-associated diarrhea in persons in the community. The discontinuation of PPIs may result in rebound symptoms requiring further and even continuous PPI use for suppression of symptoms. As with all medications, the key is to use PPIs only when clearly indicated, and to reassess continued use so that long-term therapy is used judiciously. Thus, in summary, the PPIs are a safe class of medications to use long-term in persons in whom there is a clear need for the maintenance of extensive acid inhibition.

Comparative study of proton pump inhibitors on dexamethasone plus pylorus ligation induced ulcer model in rats.

The present study was designed to compare ulcer protective effect of proton pump inhibitors viz. omeprazole, rabeprazole and lansoprazole against dexamethasone plus pylorus ligation induced ulcer model. Dexamethasone (5 mg/kg) was used as an ulcerogen. Dexamethasone suspended in 1% CMC in water was given orally to all the rats 15 min after the pylorus ligation. Omeprazole (20 mg/kg), rabeprazole (20 mg/kg), and lansoprazole (20 mg/kg) were administered by oral route 30 min prior to ligation was used for ulcer protective studies, gastric secretion and mucosal studies. Effects of proton pump inhibitors were determined by the evaluation of various biochemical parameters such as ulcer index, free and total acidity, gastric pH, mucin, pepsin and total proteins. Oral administration of proton pump inhibitors showed significant reduction in gastric acid secretion and ulcer protective activity against dexamethasone plus pylorus ligation induced ulcer model. The % protection of omeprazole, rabeprazole and lansoprazole was 84.04, 89.36 and 79.78, respectively. Rabeprazole significantly inhibited the acid-pepsin secretion and increased the gastric mucin secretion. The observations made in the present study suggest that rabeprazole is the most effective gastric antisecretory and ulcer healing agent as compared to omeprazole and lansoprazole.

Gastroprotective effect of hydroalcoholic extract from barks of Persea major Kopp (Lauraceae) in rats

Persea major Kopp (Lauraceae) is used in folk medicine to treat skin wounds and gastric disorders. This study evaluates the potential of crude hydroalcoholic extract (EHA) as gastroprotective and its acute toxicity. Swiss mice were treated with EHA by oral (p.o.) and intraperitoneal (i.p.) routes with doses of 0.125 to 10 g/kg and were observed until 14 days after the administration of the extract. The calculated LD50 of EHA after i.p. administration was 480 mg/kg in mice and the LD50 values of EHA by the oral route were calculated to be up to 10 g/kg in mice. Wistar rats were orally pretreated with EHA (30, 100, 300 and 1000 mg/kg) before induction of gastric lesions by 70% ethanol (0.5 mL/animal, p.o.), indomethacin (20 mg/kg, s.c.) and hypothermic restraint stress (during 3 h at 4 ºC). The EHA protected the gastric mucosa against lesions induced by ethanol, but did not reduce the stress- and indomethacin-induced gastric lesions. When the EHA was injected into the duodenal lumen (i.d.), the volume, pH and total acidity of the gastric secretion of rats with pylorus ligature was not altered with different doses of the extract. Results therefore suggest that the cytoprotective effect of this extract against the direct necrosing action of ethanol and its effect were not related with reduction of gastric acid secretion.

Oral ranitidine and duration of gastric pH &gt;4.0 in infants with persisting reflux symptoms

Abstract Background: Ranitidine is a drug commonly used in pathological gastro‐oesophageal reflux (GOR) in infants. Non‐responsiveness has been reported. Data regarding the effect of ranitidine on oesophageal acid exposure and reduction of gastric acid secretion are limited in this age group. Objective: To evaluate oesophageal acid exposure, reduction of gastric acid secretion and histology of oesophageal biopsies in infants who clinically do not respond to oral ranitidine. Patients and design: 103 infants (mean age 3.3±1.8 mo) with persisting symptoms of reflux despite administration of ranitidine, prescribed previously by a referring physician, at a mean (SD) dose of 9.4 (±3.3) mg/kg/d for at least 2 wk (mean 30 d), were submitted to a 24‐h pH study and oesophageal biopsy (90/103 patients). Results: Histological oesophagitis was present in 21/90 (23%). The oesophageal reflux index (RI) was &gt;5% and &gt;10% in 21/103 (20%) and 6/103 (6%) infants, respectively. Gastric pH was &gt;4.0 during &lt;50%, &gt;50%, &gt;75% and &gt;90% of the duration of pH monitoring in 33/103 (32%), 70/103 (68%), 22/103 (21%) and 7/103 (7%), respectively. By simple regression analysis, the dosage of ranitidine correlated with the oesophageal RI (r=0.21; p=0.05), but not with the duration of time gastric pH was &gt;4.0 (r=0.09; p=0.39). Histological oesophagitis did not correlate with ranitidine dosage, duration of treatment, duration gastric pH was &gt;4.0 and oesophageal reflux index. Conclusion: Some infants presenting with symptoms assumed to be GOR and acid related fail to respond to acid suppression with ranitidine, either because they need better acid suppression or because the symptoms are not acid related.