Objective: To explore anti-inflammatory activities of organic extract and its semi-purified fractions(ethanol, acetone, methanol/dichloromethane) from the Mediterranean gorgonian Eunicella singularis. Methods: The ant...Objective: To explore anti-inflammatory activities of organic extract and its semi-purified fractions(ethanol, acetone, methanol/dichloromethane) from the Mediterranean gorgonian Eunicella singularis. Methods: The anti-inflammatory and analgesic activities were evaluated, using the carrageenan-induced rat paw edema model and the acetic acid writhing test in mice. The gastroprotective activity was determined using HCl/Et OH induced gastric ulcers in rats. The purification and structure elucidation of compound(s) from the more effective fraction were determined by chromatographic and spectroscopic methods and in comparison with data reported in the literature. Results: The fraction F-Et OH showed an important antiinflammatory activity associated with significant analgesic and gastroprotective properties. The purification and structure elucidation of compound(s) from this fraction lead to the identification of one diterpenoid and four sterols. Conclusions: These results suggested that components from the active fraction can be used to treat various anti-inflammatory diseases.展开更多
The gut-brain axis is a bidirectional communication system that exists between the brain and gut. Several studies claimed that some types of headaches are associated with various gastrointestinal(GI) disorders.In Pers...The gut-brain axis is a bidirectional communication system that exists between the brain and gut. Several studies claimed that some types of headaches are associated with various gastrointestinal(GI) disorders.In Persian medicine(PM), physicians believed that gastric disturbances could stimulate headache and introduced some herbs for boosting gastric function as a therapeutic remedy for headache. Here we review the current evidence for the gastroprotective and antiheadache effects of herbs used in PM.Herbs used for their gastrotonic effects in PM were identified from selected Persian medical and pharmaceutical textbooks. Pub Med, Scopus and Google Scholar were used to search for contemporary scientific evidence relating to the gastric and neurologic effects of these plants. A total of 24 plants were recorded from the selected sources included in this review, most of which belonged to the Rosaceae family.Phyllanthus emblica, Zingiber officinale, Boswellias errata, Punica granatum and Hypericum perforatum had the most recent studies related to GI disorder and headache, while current research about quince, rose,apple, hawthorn and pear was limited. Reducing Helicobacter pylori growth, gastritis, erosion of the stomach lining, hemorrhage and perforation, improving gastric mucosal resistance, antisecretary, antiulcer,antipyretic, analgesic, sedative, anxiolytic, anti-inflammatory, anticonvulsant, neuroprotective and antioxidant effects as well as improvement in memory scores were some of the gastrotonic and neuroprotective mechanisms described in the current research. These results confirmed that medicinal plants prescribed in PM may improve headache in patients through the management of GI abnormalities.However, further studies are recommended to investigate the efficacy and safety of the mentioned medicinal plants.展开更多
Objective:The study was aimed al evaluating the antiulcer activity of ethanolic extract of Achyranthes aspera(EEAA) leaf.Methods:The anti-ulcer assays were performed on pylorus ligation and chronic ethanol induced ulc...Objective:The study was aimed al evaluating the antiulcer activity of ethanolic extract of Achyranthes aspera(EEAA) leaf.Methods:The anti-ulcer assays were performed on pylorus ligation and chronic ethanol induced ulcer model.The effects of the EEAA on gastric content volume,pH.free acidity,total acidity and ulcer index were evaluated.Results:The percentage of ulcer protection(59.55%and 35.58%) was significantly(P 【 0.001) higher in the groups treated with the high dose of EEAA(600 mg/kg),it also reduced the volume of gastric juice and total acidity whereas,gastric pH was increased signiGcandy.Conclusions:The results of this study show significant gastroprotective activity of EEAA may be due to presence of phyto-constituents like flavanoids,saponins and tannins.展开更多
Syzygium cumini Linn.,commonly known as Jamun,is a member of the Myrtaceae family and is also referred to by synonyms such as Eugenia djouant Perr.,Eugenia cumini,Eugenia jambolana Lam.,Syzygium jambolana Lam.,and Myr...Syzygium cumini Linn.,commonly known as Jamun,is a member of the Myrtaceae family and is also referred to by synonyms such as Eugenia djouant Perr.,Eugenia cumini,Eugenia jambolana Lam.,Syzygium jambolana Lam.,and Myrtus cumini Linn.This review provides an overview of its medicinal value,including taxonomical classification,geographic distribution,cultivation techniques,pharmacognostical aspects,phytochemical constituents,traditional uses,and pharmacological applications.In India,‘Ram Jamun’or‘Raja Jamun’is cultivated in the north,while the‘Paras’variety is grown in central regions.Various components of S.cumini fruits are utilized to enhance the nutritional quality of wines,jellies,jams,and fermented products.Rich in essential nutrients like vitamins,carbohydrates,minerals,antioxidants,and anthocyanins,S.cumini also contains bioactive phytoconstituents such as gallic acid,tannins,and polyphenols,which contribute to its pharmacological properties.Traditionally,black plums have been used as carminatives,diuretics,and remedies for stomach ailments,spleen enlargement,diarrhea,and urinary retention.Additionally,S.cumini has been historically administered to women post-abortion and is recognized for its role in managing diabetes and dysentery.Polyphenolic compounds in Jamun exhibit potential therapeutic benefits against diabetes,arthritis,cancer,asthma,and cardiovascular diseases.Given its promising ethnopharmacological profile,extensive research has been conducted on various plant parts,highlighting their antioxidant,antifungal,antibacterial,antidiabetic,and anticancer properties.This review aims to provide a comprehensive understanding of Syzygium cumini’s traditional and therapeutic significance,serving as a valuable resource for future research.展开更多
Objective To evaluate the gastroprotective activity of ascaridole. Methods The gastroprotective effect of ascaridole was evaluated on ulcer healing in rats with acetic acid-induced chronic gastric ulcer, pylorus ligat...Objective To evaluate the gastroprotective activity of ascaridole. Methods The gastroprotective effect of ascaridole was evaluated on ulcer healing in rats with acetic acid-induced chronic gastric ulcer, pylorus ligation- and Aspirin-induced gastric ulcer. Ascaridole was ig administered with the dosages of 10 and 20 mg/kg once daily for 7 d. Results Ascaridole showed the significant anti-ulcer effects. In acetic acid-induced gastric ulcer rats, the ulcer areas after 10 and 20 mg/kg of ascaridole treatment were (65.1 ± 20.0) and (50.6 ± 11.0) mm2, respectively, which were significant lower (P < 0.01) than that of the control group [(116.7 ± 35.8) mm2]. For pylorus ligation model, ascaridole showed a gastric ulcer healing effect in a dose-dependent manner. Ascaridole at the dose of 20 mg/kg showed 50% ulcer protection and had a significant (P < 0.05) gastroprotective activity since it decreased the total acidity and pepsin activity. Compared to the control group, the two dosages of ascaridole showed the significant reduction (P < 0.05) in the ulcer index on Aspirin-induced ulcer. Conclusion This study provides evidence that ascaridole shows potential efficacy on the healing of gastric ulcers induced by acetic acid, Aspirin, and pylorus ligation.展开更多
Objective:To assess the fruit of Feijoa sellowiana Berg var.coolidge and gorgiona,cultured in Sicily,for its gastroprotective effect,in association with performing phytochemical evaluation.Methods:The gastroprotective...Objective:To assess the fruit of Feijoa sellowiana Berg var.coolidge and gorgiona,cultured in Sicily,for its gastroprotective effect,in association with performing phytochemical evaluation.Methods:The gastroprotective effect was investigated on ethanol-induced ulcers in rats,with sucralfate as reference drug.Samples of gastric mucosae,stained by periodic acid-Shiff and haematoxylin/eosin,were observed by light microscopy.Results:By means of HPLC,vitamin E complex and polyphenol compounds were determined.identified,while δ was only in var.coolidge.In whole fruit of two varieties,catechin,eriodictyol,eriocitrin,pyrocatechol,quercetin,rutin,ellagic,gallic and syringic acid were determined.The fruit showed gastroprotective effect(ulcer index:var.coolidge=1.07,var.gorgiona=1.02).The efficacy was comparable to that of sucralfate(ulcer index 1.10).Histological examination confirmed the inhibition of ulcerogenic activity of the ethanol.Conclusions:In pulp and peel samples of both varieties of fruit α,β and γ tocopherols were and show beneficial effects on various diseases,particularly those caused by oxidative processes resulting in cell damage.The amount of polyphenols and vitamin E complex confirms the nutritional value of this fruit,grown in pedoclimatic condition very different from the origin area.Active principles of Feijoa sellowiana can play an important role in human diet and show beneficial effects on various diseases,particularly those caused by oxidative processes resulting in cell damage.The amount of polyphenols and vitamin E complex confirms the nutritional value of this fruit,grown in pedoclimatic condition very different from the origin area.展开更多
Neurosurgical patients,including those with severe traumatic brain injury,spinal cord injury,stroke,or raised intracranial pressure,are at heightened risk for stress ulcers and aspiration pneumonitis,leading to signif...Neurosurgical patients,including those with severe traumatic brain injury,spinal cord injury,stroke,or raised intracranial pressure,are at heightened risk for stress ulcers and aspiration pneumonitis,leading to significant morbidity and mortality.These patients are typically managed through both pharmacological interventions[e.g.,proton pump inhibitors(PPIs),histamine 2(H2)antagonists,sucralfate]and non-pharmacological measures(e.g.,nasogastric decompression,patient positioning)to mitigate adverse outcomes.The pathogenesis of stress ulcers in neurosurgical patients is multifactorial,but the routine use of stress ulcer prophylaxis remains controversial.While gastric acid suppression with H2 rece-ptor antagonists and PPIs is commonly employed,concerns have arisen regarding the association between elevated gastric pH,bacterial colonization,and ventilator-associated pneumonia.The lack of comprehensive data on gastroprotection in critically ill neurosurgical patients,who face a greater risk than non-neurosurgical counterparts,further complicates this issue.Recent studies,such as one by Gao et al on the efficacy of vonoprazan-amoxicillin dual therapy in elderly patients,highlight the potential of novel therapies,but the influence of pre-existing conditions like Helicobacter pylori infection remains unclear.Non-pharmacological interventions,including nasogastric decompression and early enteral nutrition,are critical in improving outcomes but require further research to refine strategies.This editorial underscores the need for tailored approaches and encourages further investigation into optimal gastroprotective strategies for neurosurgical patients.展开更多
Helicobacter pylori(H.pylori)infection has a protective effect on gastroesophageal reflux disease(GERD).Both of these diseases have a very high incidence and prevalence.As a result,GERD often recurs after anti-Helicob...Helicobacter pylori(H.pylori)infection has a protective effect on gastroesophageal reflux disease(GERD).Both of these diseases have a very high incidence and prevalence.As a result,GERD often recurs after anti-Helicobacter therapy.The problem of effective treatment of H.pylori infection and GERD is that the main groups of drugs[proton pump inhibitors(PPIs)and potassium-competitive acid blockers]have the possibility of side effects with use.Such supposed side effects have no evidence in randomized controlled trials that comply with the principles of evidence-based medicine.Morphological changes in the gastric mucosa after long-term use of antisecretory drugs should be considered as compensatory mechanisms of sanogenesis.The greatest concern for doctors who treat patients with antisecretory drugs is the risk of gastric carcinogenesis.This article presents an analysis of morphological and pathophysiological changes that occur after long-term use of antisecretory drugs(PPIs).Hypertrophy(hyperplasia)of G cells,enterochromaffin-like cells and possible fundic gland polyps(hyperplasia)are compensatory mechanisms of sanogenesis during long-term treatment with PPIs.These mechanisms are of primary importance for rehabilitation and prevention of complications in patients with GERD,non-steroidal anti-inflammatory drugsgastropathy and other diseases during long-term treatment with PPIs.Understanding the pathophysiological and morphological mechanisms of compensation and adaptation,the mechanisms of sanogenesis and carcinogenesis will increase the number of indications for long-term use of PPIs with a high level of efficiency and safety of treatment.In addition,understanding the pathophysiological and morphological mechanisms of compensation and adaptation,the mechanisms of sanogenesis will allow us to forecast the side effects of long-term use of potassium-competitive acid blockers.展开更多
OBJECTIVE: To evaluate the efficacy of Pistacia atlantica Desf. oleoresin essential oil on peptic ulcer(PU) and its antibacterial effect on metronidazole-resistant Helicobacter pylori, as well as chemi-cal composition...OBJECTIVE: To evaluate the efficacy of Pistacia atlantica Desf. oleoresin essential oil on peptic ulcer(PU) and its antibacterial effect on metronidazole-resistant Helicobacter pylori, as well as chemi-cal composition of the essential oil.METHODS: The essential oil was standardized using gas chromatography mass spectrometry(GC/MS) analysis. Acute toxicity of the essential oil was assessed in animal model. In vitro anti-Helicobacter pylori activity was performed through disc diffusion and minimum inhibitory concentration method. For gastroprotective assay, rats received Pistacia atlantica Desf. essential oil(25, 50 and 100 mg/kg orally) 1 h before induction of ulcer by ethanol.Macroscopic(ulcer index and protection rate) and microscopic examination were performed.RESULTS: The GC/MS analysis of the essential oil led to the identification of twenty constituents andα-pinene is predominant constituent. The essential oil was safe up to 2000 mg/kg. All Helicobacter pylori strains were susceptible to the essential oil and the MIC ranged from 275 to 1100 μg/m L. The ulcer index for treated groups was significantly reduced compared to control(P < 0.001) with EC50 value of 12.32 mg/kg. In microscopic examination, Pistacia atlantica attenuated destruction and necrosis of gastric tissue.CONCLUSION: Current study exhibited protective effect of standardized Pistacia atlantica essential oil against ethanol-induced gastric ulcer and its antibacterial activity on Helicobacter pylori. α-pinene might be the responsible agent.展开更多
The glyceride ester derivatives 6a and 6b were prepared by reacting 1,2,3-trihydroxy propane 1,3-dipalmitate/stearate with (S)-naproxen as potential prodrugs. The synthesis was achieved successfully with the aid of N,...The glyceride ester derivatives 6a and 6b were prepared by reacting 1,2,3-trihydroxy propane 1,3-dipalmitate/stearate with (S)-naproxen as potential prodrugs. The synthesis was achieved successfully with the aid of N,N’-dicyclohexyl- carbodiimide. These prodrugs were evaluated for anti inflammatory, analgesic and gastroprotective activity. It was found that prodrugs 6a and 6b showed less irritation to gastric mucosa as indicated by ulcer index. The synthesized glyceride esters were found to possess good pharmacological profile as shown by results of anti inflammatory and analgesic activity. The aqueous studies were performed in order to ensure the release of prodrugs. Both prodrugs were found to stable at acidic pH while undergoes hydrolysis at pH 7.4. These findings suggest that the glyceride prodrugs 6a and 6b might be used as potential biolabile derivatives.展开更多
AIM:To assess the relative bioavailability and pharmacokinetic properties of two formulations(test and reference) of Lafutidine 10 mg.METHODS:The study was performed as an open label,randomized,two-way,two-period,two-...AIM:To assess the relative bioavailability and pharmacokinetic properties of two formulations(test and reference) of Lafutidine 10 mg.METHODS:The study was performed as an open label,randomized,two-way,two-period,two-treatment,single dose cross-over bioequivalence study,under non-fed condition to compare the pharmacokinetic prof iles of the lafutidine formulation manufactured by Emcure Pharmaceuticals Ltd.,India using an indigenously developed active pharmaceutical ingredient(API) and the commercially available Stogra formulation,of UCB Japan Co.,Ltd.,Japan.The two treatments were separated by a washout period of 5 d.After an overnight fasting period of 10 h,the subjects were administered either the test or the reference medication as per the randomization schedule.Blood samples were collected at intervals up to 24 h,as per the approved protocol.Concentrations of lafutidine in plasma were analyzed by a validated liquid chromatography/tandem mass spectrometry(LC/MS/MS) method,and a non-compartmental model was used for pharmacokinetic analysis.The pharmacokinetic parameters were subjected to a 4-way ANOVA accounting for sequence,subjects,period and treatment.Statistical significance was evaluated at 95% conf idence level(P ≥ 0.05).RESULTS:The mean(±SD) values of the pharmacokinetic parameters(test vs reference) were Cmax(265.15±49.84 ng/mL vs 246.79±29.30 ng/mL,P<0.05),Area under the curve(AUC)(0-t)(1033.13±298.74 ng.h/mL vs 952.93±244.07 ng.h/mL,P < 0.05),AUC(0-∞)(1047.61±301.22 ng.h/mL vs 964.21±246.45 ng.h/mL,P<0.05),and tv2(1.92±0.94 h vs 2.05±1.01 h,P<0.05).The 90% conf idence intervals(CI) for the test/reference ratio of mean Cmax,AUC(0-t),and AUC(0-∞) were within the acceptable range of 80.00 to 125.00.The mean times(± SD) to attain maximal plasma concentration(tmax) of lafutidine were 0.95±0.24 h vs 1.01±0.29 h(P<0.05) for the test and the reference formulations respectively.Both the formulations were well tolerated.展开更多
AIM： To evaluate the gastro-protective effect of capsaicin against the ethanol- and indomethacin （IND）-induced gastric mucosal damage in healthy human subjects. METHODS： The effects of small doses （1-8 μg/mL, 10...AIM： To evaluate the gastro-protective effect of capsaicin against the ethanol- and indomethacin （IND）-induced gastric mucosal damage in healthy human subjects. METHODS： The effects of small doses （1-8 μg/mL, 100 mL） of capsaicin on the gastric acid secretion basal acid output （BAO） and its electrolyte concentration, gastric transmucosal potential difference （GTPD）, ethanol- （5 mL 300 mL/L i.g.） and IND- （3×25 mg/d） induced gastric mucosal damage were tested in a randomized, prospective study of 84 healthy human subjects. The possible role of desensitization of capsaicin-sensitive afferents was tested by repeated exposures and during a prolonged treatment. RESULTS： Intragastric application of capsaicin decreased the BAO and enhanced “non-parietal” component, GTPD in a dose-dependent manner. The decrease of GTPD evoked by ethanol was inhibited by the capsaicin application, which was reproducible. Gastric microbleeding induced by IND was inhibited by co-administration with capsaicin, but was not influenced by two weeks pretreatment with a daily capsaicin dose of 3×400μg i.g. CONCLUSION： Capsaicin in low concentration range protects against gastric injuries induced by ethanol or IND, which is attributed to stimulation of the sensory nerve endings.展开更多
AIM: To calculate the proportion of potentially preventable hospitalizations due to peptic ulcer disease (PUD), erosive gastritis (EG) or duodenitis (ED).
AIM： To investigate the role of major non-protein and protein sulfhydryls and disulfides in chemically induced gastric hemorrhagic mucosal lesions （HML） and the mechanism of gastroprotective effect of sucralfate.ME...AIM： To investigate the role of major non-protein and protein sulfhydryls and disulfides in chemically induced gastric hemorrhagic mucosal lesions （HML） and the mechanism of gastroprotective effect of sucralfate.METHODS： Rats were given 1 mL of 75% ethanol, 25%NaCl, 0.6 mol/L HCI, 0.2 mol/L NaOH or 1% ammonia solutions intragastrically （i.g.） and sacrificed 1, 3, 6 or 12 min later. Total （reduced and oxidized） glutathione （GSH ＋ GSSG）, glutathione disulfide （GSSG）, protein free sulfhydryls （PSH）, protein-glutathione mixed disulfides （PSSG） and protein cystine disulfides （PSSP） were measured in gastric mucosa and liver.RESULTS： Reduced glutathione （GSH） was depleted in the gastric mucosa after ethanol, HCI or NaCl exposure,while oxidized glutathione （GSSG） concentrations increased, except by HCI and NaOH exposure. Decreased levels of PSH after exposure to ethanol were observed,NaCl or NaOH while the total protein disulfides were increased. Ratios of reduced to oxidized glutathione or sulfhydrils to disulfides were decreased by all chemicals.No changes in thiol homeostasis were detected in the liver after i.g. abbreviation should be spelled out the first time here administration of ethanol. Sucralfate increased the concentrations of GSH and PSH and prevented the ethanol-induced changes in gastric mucosal thiol concentrations.CONCLUSION： Our modified methods are now suitable for direct measurements of major protein and nonprotein thiols/disulfides in the gastric mucosa or liver.A common element in the pathogenesis of chemically induced HML and in the mechanism of gastroprotective drugs seems to be the decreased ratios of reduced and oxidized glutathione as well as protein sulfhydryls and disulfides.展开更多
Objective:To investigate the restorative effect of Pterocarpus erinaceus(P.erinaceus) and homopterocarpin.an isoflavonoid isolated from it.on indomethacin-indueed disruption in gastric homeostasis in rats.Methods:Adul...Objective:To investigate the restorative effect of Pterocarpus erinaceus(P.erinaceus) and homopterocarpin.an isoflavonoid isolated from it.on indomethacin-indueed disruption in gastric homeostasis in rats.Methods:Adult rats were dn ided into five groups and lasted for 48 h before treatment.Group I received olive oil(vehicle),group 2 received 25 ing/kg indomethaein while groups 3-5 received cimetidine(100 mg/kg).lioniopterocarpin(25 mg/kg) and P.erinaceus ethanolie stem hark extract(100 mg/kg) respectively.After 1 h.all the groups except group 2 were administered 25 mg/kg of indomethacin.One hour later,the rats were sacrificed and the ulcer index and other gaslroprotective indices were evaluated.Results:Indomethacin caused significant injury to the stomach of the rats as reflected in the ulcer indices(9.0±1.4) as compared with that of control(2.0±0.0).Equally,there were significant increases in gastric acid concentration and malondialdehvde level in the stomachs of the ulcerated animals compared with the control.However mucus content,reduced gluthatione level and gastric pH were significantly reduced in the ulcerated animals compared with the control.Pretreatment with either Pterocarpus bark extract or homopterocarpin reversed the effects of indomethaein on the evaluated parameters.Conclusions:These results indicate that both homopterocarpin and Plerocarpus extract offered gastroprotection against indomethacin-induced ulcer by antioxidative mechanism and the modulation of gastric homeostasis.The results also suggest that homopterocarpin might he responsible for.or contribute to the antiulcerogenic property of P.erinaceus.展开更多
AIM： Grapefruit-seed extract （GSE） containing flavonoids, possesses antibacterial and antioxidative properties but whether it influences the gastric defense mechanism and gastroprotection against ethanol- and stres...AIM： Grapefruit-seed extract （GSE） containing flavonoids, possesses antibacterial and antioxidative properties but whether it influences the gastric defense mechanism and gastroprotection against ethanol- and stress-induced gastric lesions remains unknown. METHODS： We compared the effects of GSE on gastric mucosal lesions induced in rats by topical application of 100% ethanol or 3.5 h of water immersion and restraint stress （WRS） with or without （A） inhibition of cyclooxygenase （COX）-1 activity by indomethacin and rofecoxib, the selective COX-2 inhibitor, （B） suppression of NO-synthase with L-NNA （20 mg/kg ip）, and （C） inactivation by capsaicin （125 mg/kg sc） of sensory nerves with or without intragastric （ig） pretreatment with GSE applied 30 min prior to ethanol or WRS. One hour after ethanol and 3.5 h after the end of WRS, the number and area of gastric lesions were measured by planimetry, the gastric blood flow （GBF） was assessed by H2-gas clearance technique and plasma gastrin levels and the gastric mucosal generation of PGE2, superoxide dismutase （SOD） activity and malonyldialdehyde （MDA） concentration, as an index of lipid peroxidation were determined. RESULTS： Ethanol and WRS caused gastric lesions accompanied by the significant fall in the GBF and SOD activity and the rise in the mucosal MDA content. Pretreatment with GSE （8-64 mg/kg i g） dose- dependently attenuated gastric lesions induced by 100% ethanol and WRS; the dose reducing these lesions by 50% （ID50） was 25 and 36 mg/kg, respectively, and this protective effect was similar to that obtained with methyl PGE2 analog （5 μg/kg i g）. GSE significantly raised the GBF, mucosal generation of PGE2, SOD activity and plasma gastrin levels while attenuating IVlDA content. Inhibition of PGE2 generation with indomethacin or rofecoxib and suppression of NO synthase by L-NNA or capsaicin denervation reversed the GSE-induced protection and the accompanying hyperemia. Cotreatment of exogenous calcitonine gene-related peptide （CGRP） with GSE restored the protection and accompanying hyperemic effects of GSE in rats with capsaicin denervation. CONCLUSION： GSE exerts a potent gastroprotective activity against ethanol and WRS-induced gastric lesions via an increase in endogenous PG generation, suppression of lipid peroxidation and hyperemia possibly mediated by NO and CGRP released from sensory nerves.展开更多
To evaluate the characteristics of the prescription of the proton pump inhibitor drugs (PPI) and the adherence to the indications of the guidelines regulating the reimbursement limitations set forth by the Italian Dru...To evaluate the characteristics of the prescription of the proton pump inhibitor drugs (PPI) and the adherence to the indications of the guidelines regulating the reimbursement limitations set forth by the Italian Drug Agency. METHODSThirty general practitioners (GP) participated in the study, providing data on more than 40000 patients in total. The population was divided into non occasional users of PPI drugs (PPI users) and non-users (PPI non-users) based on evidence of a prescription of at least 3 packs of PPIs in the last 90 d before analysis. The data provided allowed an assessment of compliance with the requirements of eligibility for PPI reimbursement according to the Italian Drug Agency rules, in order to obtain subpopulations which complied or not with the rules. RESULTSSix thousand three hundred and twenty-two patients were found to be PPI users, accounting for 14.9% of the patient population. PPI users were more frequently female, older and more frequently diagnosed with gastroesophageal reflux disease, gastric or duodenal ulcers, arthropathy, heart disease and cancer than the rest of the population. PPI users had more frequently received prescriptions for non-steroidal ant-inflammatory drugs (NSAIDS), acetylsalicylic acid (ASA), oral anticoagulant therapy (OAT) and systemic steroids. PPI reimbursement resulted applicable to 69.3% of the PPI users, but a potential for reimbursement of PPI prescriptions was identified in the non PPI users for the treatment of peptic or reflux disease (8.5%) and for the protection of gastric damage caused by NSAIDS (6.1%). Patients who are potentially eligible for reimbursement are older, diagnosed with arthropathy and heart disease more frequently and most commonly receive NSAID and ASA prescriptions compared with PPI users who do not satisfy eligibility requirements. Patients in whom it was not possible to identify conditions related to prescription suitability were more frequently associated with use of OAT. CONCLUSIONA substantial number of patients who apparently do not meet prescription suitability conditions can be identified, but among non PPI users on the contrary, it is possible to identify an equal number of patients for whom prescription would be suitable. Poor suitability can be identified in the population receiving OAT. Thus, there is scope for decreasing inappropriate use of PPI drugs by adhering to certain criteria and by involving all interested parties.展开更多
AIM: To investigate the gastroprotective effect of vardenafil against indomethacin-induced gastric damage. METHODS: Forty-eight female Wistar albino rats were randomly divided into 6 groups. Group 1 received saline on...AIM: To investigate the gastroprotective effect of vardenafil against indomethacin-induced gastric damage. METHODS: Forty-eight female Wistar albino rats were randomly divided into 6 groups. Group 1 received saline only. Group 2 (indomethacin) received indomethacin. Rats in group 3 and 4 were pretreated with different doses of famotidine. Group 5 and 6 were pretreated with different doses of vardenafil. Rats in groups 3 to 6 received 25 mg/kg indomethacin 30 min after pretreatment. The animals were sacrificed 6 h later and their stomachs were opened. Gastric lesions were counted and measured. The stomach of each animal was divided in two parts for histopathological examinations and nitric oxide (NO) and malondialdehyde (MDA) assays, respectively. RESULTS: There were no gastric mucosal lesion in the saline group but all rats in the indomethacin group had gastric mucosal ulcerations (ulcer count; 6.25 ± 3.49, and mean ulcer area; 21.00 ± 12.35). Ulcer counts werediminished with famotidine 5 mg/kg (4.12 ± 2.47, P > 0.05), 20 mg/kg (2.37 ± 4.43, P < 0.05), vardenaf il 2 mg/kg (4.37 ± 3.06), and vardenafil 10 mg/kg (1.25 ± 1.38, P < 0.05) compared to the indomethacin group. Gastric mucosal lesion areas were diminished with famotidine 5 mg/kg (8.62 ± 2.97, P < 0.001), famotidine 20 mg/kg (0.94 ± 2.06, P < 0.001), vardenafil 2 mg/kg (6.62 ± 5.87, P < 0.001), and vardenafil 10 mg/kg (0.75 ± 0.88, P < 0.001) compared to the indomethacin group. MDA levels were signif icantly higher in indometh-acin group (28.48 ± 14.51), compared to the famotidine 5 mg/kg (6,21 ± 1.88, P < 0.05), famotidine 20 mg/kg (5.88 ± 1.60. P < 0.05), vardenaf il 2 mg/kg (15.87 ± 3.93, P < 0.05), and vardenafil 10 mg/kg (10.97 ± 4.50, P < 0.05). NO concentration in gastric tissues of the fa-motidine groups were significantly increased (P < 0.05), but the NO increases in the vardenafil groups were not statistically significant. Histopathology revealed dimin-ished gastric damage for pretreatment groups compared to the indomethacin group (P < 0.05). CONCLUSION: Vardenafil affords a significant dose-dependent protection against indomethacin induced gastric mucosal lesions in rats.展开更多
AIM:To examine the antiulcerogenic effects of various extracts of Mentha arvensis Linn on acid,ethanol and pylorus ligated ulcer models in rats and mice.METHODS:Various crude extracts of petroleum ether,chloroform,or ...AIM:To examine the antiulcerogenic effects of various extracts of Mentha arvensis Linn on acid,ethanol and pylorus ligated ulcer models in rats and mice.METHODS:Various crude extracts of petroleum ether,chloroform,or aqueous at a dose of 2 g/kg po did not produce any signs or symptoms of toxicity in treated animals.In the pyloric ligation model oral administration of different extracts such as petroleum ether,chloroform and aqueous at 375 mg/kg po,standard drug ranitidine 60 mg/kg po and control group 1 Tween 80,5 mL/kg po to separate groups of Wister rats of either sex(n = 6) was performed.Total acidity,ulcer number,scoring,incidence,area,and ulcer index were assessed.RESULTS:There was a decrease in gastric secretion and ulcer index among the treated groups i.e.petroleum ether(53.4),chloroform(59.2),aqueous(67.0) and in standard drug(68.7) when compared to the negative control.In the 0.6 mol/L HCl induced ulcer model in rats(n = 6) there was a reduction in ulcerative score in animals receiving petroleum ether(50.5),chloroform(57.4),aqueous(67.5) and standard.drug(71.2) when compared to the negative control.In the case of the 90 ethanol-induced ulceration model(n = 6) in mice,there was a decrease in ulcer score in test groups of petroleum ether(53.11),chloroform(62.9),aqueous(65.4) and standard drug ranitidine(69.7) when compared to the negative control.It was found that pre-treatment with various extracts of Mentha arvensis Linn in three rat/mice ulcer models ie ibuprofen plus pyloric ligation,0.6 mol/L HCl and 90 ethanol produced significant action against acid secretion(49.3 ± 0.49 vs 12.0 ± 0.57,P < 0.001).Pre-treatment with various extracts of Mentha arvensis Linn showed highly-significant activity against gastric ulcers(37.1 ± 0.87 vs 12.0 ± 0.57,P < 0.001).CONCLUSION:Various extracts of Mentha arvensis Linn.375 mg/kg body weight clearly shows a protective effect against acid secretion and gastric ulcers in ibuprofen plus pyloric ligation,0.6 mol/L HCl induced and 90 ethanol-induced ulcer models.展开更多
OBJECTIVE Gastric ulcers affect people of all ages and half of the world's population,which is being considered as the new"plague of the 21st century".As is well known,gastric mucosa is known as the firs...OBJECTIVE Gastric ulcers affect people of all ages and half of the world's population,which is being considered as the new"plague of the 21st century".As is well known,gastric mucosa is known as the first guard to protect the stomach from ulcer injury,while the aetiology of gastric ulcer is relative to imbalances between gastric mucosal protective and aggressive factors.Therefore,reducing or eliminating the aggressive factors,returning to the balance of between mucosal protective and aggressive factors,and then restoring the normal functional of gastric mucosal barrier could be crucial for treating the gastric ulcer.The fruits of Chaenomeles speciosa(TCS),also known as"mugua",might be processed into edible and health care derived products,and used as a commonly used traditional medicine in China for thousands of years.In China folk,there is a saying that"apricot one benefit,pear two benefits,mgua hundred benefits",so it has a"hundred-benefit"fruit reputation.Tujia nationality inhabitants in Southwestern China should have rheumatic diseases and peptic ulcers for living in the damp environments and bingeing on spicy and pungent foods.For the exis⁃tence of the fruit derived products of Chaenomeles speciosa as their complementary foods or snacks,the habit makes them rarely suffer from the two kinds of diseases.Enlightened by these,we had investigated the structure-activity rela⁃tionships,screened out CSTT with gastroprotective activity.Our previous studies demonstrated that TCS owned effec⁃tively therapeutic effects on gastric ulcer patients and animals,and further confirmed that TFF1 and apoptotic pathway were closely interrelated with its exerting gastroprotection.However,its underlying molecular mechanisms involved have not been fully elucidated.The current study was to further investigate its protective effect on indomethacin(IND)-damaged RGM-1 cells and rats and its underlying mechanisms through modulating TFF1-mediated EGF/EGFR and apoptotic pathways.METHODS The gastroprotection of TCS was evaluated with IND-induced gastric lesions model in RGM-1 cells and rats.In vitro,the proliferation,migration,mitochondrial viability and apoptosis were assessed,In vivo,ulcer index,ulcer inhibition rate,gastric juice acidity,gastric wall mucus(GWM),histopathology of gastric mucosa were detected.The gastroprotective effects of TCS through the TFF1-mediated EGFR/EGFR and apoptotic pathways were presented and measured by qRT-PCR and Western blotting assays.RESULTS TCS had gastroprotective function,which was related to the amelioration in promoting IND-damaged RGM-1 cell proliferation and migration,hoisting gastric juice acidity and GWM,improving ulcer index and ulcer inhibition rate,attenuating the hemorrhage,edema,epithelial cell loss and inflammatory cell infiltration of gastric mucosa,upregulating proliferation cell nuclear antigen,Bcl-2,Bcl-xl mRNA and TFF1,EGF,p-EGFR,p-Src,pro-caspase-3,pro-caspase-9 protein expressions,mitochondrial viability,mitochondrial cytochrome C concentration and p-EGFR/EGFR,p-Src/Src,Bcl-2/Bax,Bcl-xl/Bad ratioes,downregulating Bax,Bad,Apaf-1 mRNA and cleaved-caspase-3,cleaved-caspase-9,cleaved-PARP-1 protein expressions,cytosol cytochrome C concentration.CONCLUSION TCS′s gastroprotective effect was closely connected with boosting TFF1 expression,acti⁃vating TFF1-mediated EGF/EGFR pathway,thus restraining mitochondrial-dependent apoptosis,which provided new insights into interpreting its underlying mechanism and promised to act as a candidate drug to treat gastric mucosal injury.展开更多
文摘Objective: To explore anti-inflammatory activities of organic extract and its semi-purified fractions(ethanol, acetone, methanol/dichloromethane) from the Mediterranean gorgonian Eunicella singularis. Methods: The anti-inflammatory and analgesic activities were evaluated, using the carrageenan-induced rat paw edema model and the acetic acid writhing test in mice. The gastroprotective activity was determined using HCl/Et OH induced gastric ulcers in rats. The purification and structure elucidation of compound(s) from the more effective fraction were determined by chromatographic and spectroscopic methods and in comparison with data reported in the literature. Results: The fraction F-Et OH showed an important antiinflammatory activity associated with significant analgesic and gastroprotective properties. The purification and structure elucidation of compound(s) from this fraction lead to the identification of one diterpenoid and four sterols. Conclusions: These results suggested that components from the active fraction can be used to treat various anti-inflammatory diseases.
文摘The gut-brain axis is a bidirectional communication system that exists between the brain and gut. Several studies claimed that some types of headaches are associated with various gastrointestinal(GI) disorders.In Persian medicine(PM), physicians believed that gastric disturbances could stimulate headache and introduced some herbs for boosting gastric function as a therapeutic remedy for headache. Here we review the current evidence for the gastroprotective and antiheadache effects of herbs used in PM.Herbs used for their gastrotonic effects in PM were identified from selected Persian medical and pharmaceutical textbooks. Pub Med, Scopus and Google Scholar were used to search for contemporary scientific evidence relating to the gastric and neurologic effects of these plants. A total of 24 plants were recorded from the selected sources included in this review, most of which belonged to the Rosaceae family.Phyllanthus emblica, Zingiber officinale, Boswellias errata, Punica granatum and Hypericum perforatum had the most recent studies related to GI disorder and headache, while current research about quince, rose,apple, hawthorn and pear was limited. Reducing Helicobacter pylori growth, gastritis, erosion of the stomach lining, hemorrhage and perforation, improving gastric mucosal resistance, antisecretary, antiulcer,antipyretic, analgesic, sedative, anxiolytic, anti-inflammatory, anticonvulsant, neuroprotective and antioxidant effects as well as improvement in memory scores were some of the gastrotonic and neuroprotective mechanisms described in the current research. These results confirmed that medicinal plants prescribed in PM may improve headache in patients through the management of GI abnormalities.However, further studies are recommended to investigate the efficacy and safety of the mentioned medicinal plants.
文摘Objective:The study was aimed al evaluating the antiulcer activity of ethanolic extract of Achyranthes aspera(EEAA) leaf.Methods:The anti-ulcer assays were performed on pylorus ligation and chronic ethanol induced ulcer model.The effects of the EEAA on gastric content volume,pH.free acidity,total acidity and ulcer index were evaluated.Results:The percentage of ulcer protection(59.55%and 35.58%) was significantly(P 【 0.001) higher in the groups treated with the high dose of EEAA(600 mg/kg),it also reduced the volume of gastric juice and total acidity whereas,gastric pH was increased signiGcandy.Conclusions:The results of this study show significant gastroprotective activity of EEAA may be due to presence of phyto-constituents like flavanoids,saponins and tannins.
文摘Syzygium cumini Linn.,commonly known as Jamun,is a member of the Myrtaceae family and is also referred to by synonyms such as Eugenia djouant Perr.,Eugenia cumini,Eugenia jambolana Lam.,Syzygium jambolana Lam.,and Myrtus cumini Linn.This review provides an overview of its medicinal value,including taxonomical classification,geographic distribution,cultivation techniques,pharmacognostical aspects,phytochemical constituents,traditional uses,and pharmacological applications.In India,‘Ram Jamun’or‘Raja Jamun’is cultivated in the north,while the‘Paras’variety is grown in central regions.Various components of S.cumini fruits are utilized to enhance the nutritional quality of wines,jellies,jams,and fermented products.Rich in essential nutrients like vitamins,carbohydrates,minerals,antioxidants,and anthocyanins,S.cumini also contains bioactive phytoconstituents such as gallic acid,tannins,and polyphenols,which contribute to its pharmacological properties.Traditionally,black plums have been used as carminatives,diuretics,and remedies for stomach ailments,spleen enlargement,diarrhea,and urinary retention.Additionally,S.cumini has been historically administered to women post-abortion and is recognized for its role in managing diabetes and dysentery.Polyphenolic compounds in Jamun exhibit potential therapeutic benefits against diabetes,arthritis,cancer,asthma,and cardiovascular diseases.Given its promising ethnopharmacological profile,extensive research has been conducted on various plant parts,highlighting their antioxidant,antifungal,antibacterial,antidiabetic,and anticancer properties.This review aims to provide a comprehensive understanding of Syzygium cumini’s traditional and therapeutic significance,serving as a valuable resource for future research.
基金National Key Special Project of Science and Technology for Innovation Drugs of China (2008ZX09401-006)
文摘Objective To evaluate the gastroprotective activity of ascaridole. Methods The gastroprotective effect of ascaridole was evaluated on ulcer healing in rats with acetic acid-induced chronic gastric ulcer, pylorus ligation- and Aspirin-induced gastric ulcer. Ascaridole was ig administered with the dosages of 10 and 20 mg/kg once daily for 7 d. Results Ascaridole showed the significant anti-ulcer effects. In acetic acid-induced gastric ulcer rats, the ulcer areas after 10 and 20 mg/kg of ascaridole treatment were (65.1 ± 20.0) and (50.6 ± 11.0) mm2, respectively, which were significant lower (P < 0.01) than that of the control group [(116.7 ± 35.8) mm2]. For pylorus ligation model, ascaridole showed a gastric ulcer healing effect in a dose-dependent manner. Ascaridole at the dose of 20 mg/kg showed 50% ulcer protection and had a significant (P < 0.05) gastroprotective activity since it decreased the total acidity and pepsin activity. Compared to the control group, the two dosages of ascaridole showed the significant reduction (P < 0.05) in the ulcer index on Aspirin-induced ulcer. Conclusion This study provides evidence that ascaridole shows potential efficacy on the healing of gastric ulcers induced by acetic acid, Aspirin, and pylorus ligation.
基金Supported by Sicily Region-Department of Agriculture and Forestry-Department-structural measures.IX-Service-Development Services(D.D.S.n°2051).
文摘Objective:To assess the fruit of Feijoa sellowiana Berg var.coolidge and gorgiona,cultured in Sicily,for its gastroprotective effect,in association with performing phytochemical evaluation.Methods:The gastroprotective effect was investigated on ethanol-induced ulcers in rats,with sucralfate as reference drug.Samples of gastric mucosae,stained by periodic acid-Shiff and haematoxylin/eosin,were observed by light microscopy.Results:By means of HPLC,vitamin E complex and polyphenol compounds were determined.identified,while δ was only in var.coolidge.In whole fruit of two varieties,catechin,eriodictyol,eriocitrin,pyrocatechol,quercetin,rutin,ellagic,gallic and syringic acid were determined.The fruit showed gastroprotective effect(ulcer index:var.coolidge=1.07,var.gorgiona=1.02).The efficacy was comparable to that of sucralfate(ulcer index 1.10).Histological examination confirmed the inhibition of ulcerogenic activity of the ethanol.Conclusions:In pulp and peel samples of both varieties of fruit α,β and γ tocopherols were and show beneficial effects on various diseases,particularly those caused by oxidative processes resulting in cell damage.The amount of polyphenols and vitamin E complex confirms the nutritional value of this fruit,grown in pedoclimatic condition very different from the origin area.Active principles of Feijoa sellowiana can play an important role in human diet and show beneficial effects on various diseases,particularly those caused by oxidative processes resulting in cell damage.The amount of polyphenols and vitamin E complex confirms the nutritional value of this fruit,grown in pedoclimatic condition very different from the origin area.
文摘Neurosurgical patients,including those with severe traumatic brain injury,spinal cord injury,stroke,or raised intracranial pressure,are at heightened risk for stress ulcers and aspiration pneumonitis,leading to significant morbidity and mortality.These patients are typically managed through both pharmacological interventions[e.g.,proton pump inhibitors(PPIs),histamine 2(H2)antagonists,sucralfate]and non-pharmacological measures(e.g.,nasogastric decompression,patient positioning)to mitigate adverse outcomes.The pathogenesis of stress ulcers in neurosurgical patients is multifactorial,but the routine use of stress ulcer prophylaxis remains controversial.While gastric acid suppression with H2 rece-ptor antagonists and PPIs is commonly employed,concerns have arisen regarding the association between elevated gastric pH,bacterial colonization,and ventilator-associated pneumonia.The lack of comprehensive data on gastroprotection in critically ill neurosurgical patients,who face a greater risk than non-neurosurgical counterparts,further complicates this issue.Recent studies,such as one by Gao et al on the efficacy of vonoprazan-amoxicillin dual therapy in elderly patients,highlight the potential of novel therapies,but the influence of pre-existing conditions like Helicobacter pylori infection remains unclear.Non-pharmacological interventions,including nasogastric decompression and early enteral nutrition,are critical in improving outcomes but require further research to refine strategies.This editorial underscores the need for tailored approaches and encourages further investigation into optimal gastroprotective strategies for neurosurgical patients.
文摘Helicobacter pylori(H.pylori)infection has a protective effect on gastroesophageal reflux disease(GERD).Both of these diseases have a very high incidence and prevalence.As a result,GERD often recurs after anti-Helicobacter therapy.The problem of effective treatment of H.pylori infection and GERD is that the main groups of drugs[proton pump inhibitors(PPIs)and potassium-competitive acid blockers]have the possibility of side effects with use.Such supposed side effects have no evidence in randomized controlled trials that comply with the principles of evidence-based medicine.Morphological changes in the gastric mucosa after long-term use of antisecretory drugs should be considered as compensatory mechanisms of sanogenesis.The greatest concern for doctors who treat patients with antisecretory drugs is the risk of gastric carcinogenesis.This article presents an analysis of morphological and pathophysiological changes that occur after long-term use of antisecretory drugs(PPIs).Hypertrophy(hyperplasia)of G cells,enterochromaffin-like cells and possible fundic gland polyps(hyperplasia)are compensatory mechanisms of sanogenesis during long-term treatment with PPIs.These mechanisms are of primary importance for rehabilitation and prevention of complications in patients with GERD,non-steroidal anti-inflammatory drugsgastropathy and other diseases during long-term treatment with PPIs.Understanding the pathophysiological and morphological mechanisms of compensation and adaptation,the mechanisms of sanogenesis and carcinogenesis will increase the number of indications for long-term use of PPIs with a high level of efficiency and safety of treatment.In addition,understanding the pathophysiological and morphological mechanisms of compensation and adaptation,the mechanisms of sanogenesis will allow us to forecast the side effects of long-term use of potassium-competitive acid blockers.
基金Tehran University of Medical Sciences(TUMS,Evaluation of the Effect of P.atlantica on Ethanol-Induced Gastric Ulcer in Rats,No.94018627690)
文摘OBJECTIVE: To evaluate the efficacy of Pistacia atlantica Desf. oleoresin essential oil on peptic ulcer(PU) and its antibacterial effect on metronidazole-resistant Helicobacter pylori, as well as chemi-cal composition of the essential oil.METHODS: The essential oil was standardized using gas chromatography mass spectrometry(GC/MS) analysis. Acute toxicity of the essential oil was assessed in animal model. In vitro anti-Helicobacter pylori activity was performed through disc diffusion and minimum inhibitory concentration method. For gastroprotective assay, rats received Pistacia atlantica Desf. essential oil(25, 50 and 100 mg/kg orally) 1 h before induction of ulcer by ethanol.Macroscopic(ulcer index and protection rate) and microscopic examination were performed.RESULTS: The GC/MS analysis of the essential oil led to the identification of twenty constituents andα-pinene is predominant constituent. The essential oil was safe up to 2000 mg/kg. All Helicobacter pylori strains were susceptible to the essential oil and the MIC ranged from 275 to 1100 μg/m L. The ulcer index for treated groups was significantly reduced compared to control(P < 0.001) with EC50 value of 12.32 mg/kg. In microscopic examination, Pistacia atlantica attenuated destruction and necrosis of gastric tissue.CONCLUSION: Current study exhibited protective effect of standardized Pistacia atlantica essential oil against ethanol-induced gastric ulcer and its antibacterial activity on Helicobacter pylori. α-pinene might be the responsible agent.
文摘The glyceride ester derivatives 6a and 6b were prepared by reacting 1,2,3-trihydroxy propane 1,3-dipalmitate/stearate with (S)-naproxen as potential prodrugs. The synthesis was achieved successfully with the aid of N,N’-dicyclohexyl- carbodiimide. These prodrugs were evaluated for anti inflammatory, analgesic and gastroprotective activity. It was found that prodrugs 6a and 6b showed less irritation to gastric mucosa as indicated by ulcer index. The synthesized glyceride esters were found to possess good pharmacological profile as shown by results of anti inflammatory and analgesic activity. The aqueous studies were performed in order to ensure the release of prodrugs. Both prodrugs were found to stable at acidic pH while undergoes hydrolysis at pH 7.4. These findings suggest that the glyceride prodrugs 6a and 6b might be used as potential biolabile derivatives.
文摘AIM:To assess the relative bioavailability and pharmacokinetic properties of two formulations(test and reference) of Lafutidine 10 mg.METHODS:The study was performed as an open label,randomized,two-way,two-period,two-treatment,single dose cross-over bioequivalence study,under non-fed condition to compare the pharmacokinetic prof iles of the lafutidine formulation manufactured by Emcure Pharmaceuticals Ltd.,India using an indigenously developed active pharmaceutical ingredient(API) and the commercially available Stogra formulation,of UCB Japan Co.,Ltd.,Japan.The two treatments were separated by a washout period of 5 d.After an overnight fasting period of 10 h,the subjects were administered either the test or the reference medication as per the randomization schedule.Blood samples were collected at intervals up to 24 h,as per the approved protocol.Concentrations of lafutidine in plasma were analyzed by a validated liquid chromatography/tandem mass spectrometry(LC/MS/MS) method,and a non-compartmental model was used for pharmacokinetic analysis.The pharmacokinetic parameters were subjected to a 4-way ANOVA accounting for sequence,subjects,period and treatment.Statistical significance was evaluated at 95% conf idence level(P ≥ 0.05).RESULTS:The mean(±SD) values of the pharmacokinetic parameters(test vs reference) were Cmax(265.15±49.84 ng/mL vs 246.79±29.30 ng/mL,P<0.05),Area under the curve(AUC)(0-t)(1033.13±298.74 ng.h/mL vs 952.93±244.07 ng.h/mL,P < 0.05),AUC(0-∞)(1047.61±301.22 ng.h/mL vs 964.21±246.45 ng.h/mL,P<0.05),and tv2(1.92±0.94 h vs 2.05±1.01 h,P<0.05).The 90% conf idence intervals(CI) for the test/reference ratio of mean Cmax,AUC(0-t),and AUC(0-∞) were within the acceptable range of 80.00 to 125.00.The mean times(± SD) to attain maximal plasma concentration(tmax) of lafutidine were 0.95±0.24 h vs 1.01±0.29 h(P<0.05) for the test and the reference formulations respectively.Both the formulations were well tolerated.
文摘AIM： To evaluate the gastro-protective effect of capsaicin against the ethanol- and indomethacin （IND）-induced gastric mucosal damage in healthy human subjects. METHODS： The effects of small doses （1-8 μg/mL, 100 mL） of capsaicin on the gastric acid secretion basal acid output （BAO） and its electrolyte concentration, gastric transmucosal potential difference （GTPD）, ethanol- （5 mL 300 mL/L i.g.） and IND- （3×25 mg/d） induced gastric mucosal damage were tested in a randomized, prospective study of 84 healthy human subjects. The possible role of desensitization of capsaicin-sensitive afferents was tested by repeated exposures and during a prolonged treatment. RESULTS： Intragastric application of capsaicin decreased the BAO and enhanced “non-parietal” component, GTPD in a dose-dependent manner. The decrease of GTPD evoked by ethanol was inhibited by the capsaicin application, which was reproducible. Gastric microbleeding induced by IND was inhibited by co-administration with capsaicin, but was not influenced by two weeks pretreatment with a daily capsaicin dose of 3×400μg i.g. CONCLUSION： Capsaicin in low concentration range protects against gastric injuries induced by ethanol or IND, which is attributed to stimulation of the sensory nerve endings.
文摘AIM: To calculate the proportion of potentially preventable hospitalizations due to peptic ulcer disease (PUD), erosive gastritis (EG) or duodenitis (ED).
文摘AIM： To investigate the role of major non-protein and protein sulfhydryls and disulfides in chemically induced gastric hemorrhagic mucosal lesions （HML） and the mechanism of gastroprotective effect of sucralfate.METHODS： Rats were given 1 mL of 75% ethanol, 25%NaCl, 0.6 mol/L HCI, 0.2 mol/L NaOH or 1% ammonia solutions intragastrically （i.g.） and sacrificed 1, 3, 6 or 12 min later. Total （reduced and oxidized） glutathione （GSH ＋ GSSG）, glutathione disulfide （GSSG）, protein free sulfhydryls （PSH）, protein-glutathione mixed disulfides （PSSG） and protein cystine disulfides （PSSP） were measured in gastric mucosa and liver.RESULTS： Reduced glutathione （GSH） was depleted in the gastric mucosa after ethanol, HCI or NaCl exposure,while oxidized glutathione （GSSG） concentrations increased, except by HCI and NaOH exposure. Decreased levels of PSH after exposure to ethanol were observed,NaCl or NaOH while the total protein disulfides were increased. Ratios of reduced to oxidized glutathione or sulfhydrils to disulfides were decreased by all chemicals.No changes in thiol homeostasis were detected in the liver after i.g. abbreviation should be spelled out the first time here administration of ethanol. Sucralfate increased the concentrations of GSH and PSH and prevented the ethanol-induced changes in gastric mucosal thiol concentrations.CONCLUSION： Our modified methods are now suitable for direct measurements of major protein and nonprotein thiols/disulfides in the gastric mucosa or liver.A common element in the pathogenesis of chemically induced HML and in the mechanism of gastroprotective drugs seems to be the decreased ratios of reduced and oxidized glutathione as well as protein sulfhydryls and disulfides.
文摘Objective:To investigate the restorative effect of Pterocarpus erinaceus(P.erinaceus) and homopterocarpin.an isoflavonoid isolated from it.on indomethacin-indueed disruption in gastric homeostasis in rats.Methods:Adult rats were dn ided into five groups and lasted for 48 h before treatment.Group I received olive oil(vehicle),group 2 received 25 ing/kg indomethaein while groups 3-5 received cimetidine(100 mg/kg).lioniopterocarpin(25 mg/kg) and P.erinaceus ethanolie stem hark extract(100 mg/kg) respectively.After 1 h.all the groups except group 2 were administered 25 mg/kg of indomethacin.One hour later,the rats were sacrificed and the ulcer index and other gaslroprotective indices were evaluated.Results:Indomethacin caused significant injury to the stomach of the rats as reflected in the ulcer indices(9.0±1.4) as compared with that of control(2.0±0.0).Equally,there were significant increases in gastric acid concentration and malondialdehvde level in the stomachs of the ulcerated animals compared with the control.However mucus content,reduced gluthatione level and gastric pH were significantly reduced in the ulcerated animals compared with the control.Pretreatment with either Pterocarpus bark extract or homopterocarpin reversed the effects of indomethaein on the evaluated parameters.Conclusions:These results indicate that both homopterocarpin and Plerocarpus extract offered gastroprotection against indomethacin-induced ulcer by antioxidative mechanism and the modulation of gastric homeostasis.The results also suggest that homopterocarpin might he responsible for.or contribute to the antiulcerogenic property of P.erinaceus.
文摘AIM： Grapefruit-seed extract （GSE） containing flavonoids, possesses antibacterial and antioxidative properties but whether it influences the gastric defense mechanism and gastroprotection against ethanol- and stress-induced gastric lesions remains unknown. METHODS： We compared the effects of GSE on gastric mucosal lesions induced in rats by topical application of 100% ethanol or 3.5 h of water immersion and restraint stress （WRS） with or without （A） inhibition of cyclooxygenase （COX）-1 activity by indomethacin and rofecoxib, the selective COX-2 inhibitor, （B） suppression of NO-synthase with L-NNA （20 mg/kg ip）, and （C） inactivation by capsaicin （125 mg/kg sc） of sensory nerves with or without intragastric （ig） pretreatment with GSE applied 30 min prior to ethanol or WRS. One hour after ethanol and 3.5 h after the end of WRS, the number and area of gastric lesions were measured by planimetry, the gastric blood flow （GBF） was assessed by H2-gas clearance technique and plasma gastrin levels and the gastric mucosal generation of PGE2, superoxide dismutase （SOD） activity and malonyldialdehyde （MDA） concentration, as an index of lipid peroxidation were determined. RESULTS： Ethanol and WRS caused gastric lesions accompanied by the significant fall in the GBF and SOD activity and the rise in the mucosal MDA content. Pretreatment with GSE （8-64 mg/kg i g） dose- dependently attenuated gastric lesions induced by 100% ethanol and WRS; the dose reducing these lesions by 50% （ID50） was 25 and 36 mg/kg, respectively, and this protective effect was similar to that obtained with methyl PGE2 analog （5 μg/kg i g）. GSE significantly raised the GBF, mucosal generation of PGE2, SOD activity and plasma gastrin levels while attenuating IVlDA content. Inhibition of PGE2 generation with indomethacin or rofecoxib and suppression of NO synthase by L-NNA or capsaicin denervation reversed the GSE-induced protection and the accompanying hyperemia. Cotreatment of exogenous calcitonine gene-related peptide （CGRP） with GSE restored the protection and accompanying hyperemic effects of GSE in rats with capsaicin denervation. CONCLUSION： GSE exerts a potent gastroprotective activity against ethanol and WRS-induced gastric lesions via an increase in endogenous PG generation, suppression of lipid peroxidation and hyperemia possibly mediated by NO and CGRP released from sensory nerves.
文摘To evaluate the characteristics of the prescription of the proton pump inhibitor drugs (PPI) and the adherence to the indications of the guidelines regulating the reimbursement limitations set forth by the Italian Drug Agency. METHODSThirty general practitioners (GP) participated in the study, providing data on more than 40000 patients in total. The population was divided into non occasional users of PPI drugs (PPI users) and non-users (PPI non-users) based on evidence of a prescription of at least 3 packs of PPIs in the last 90 d before analysis. The data provided allowed an assessment of compliance with the requirements of eligibility for PPI reimbursement according to the Italian Drug Agency rules, in order to obtain subpopulations which complied or not with the rules. RESULTSSix thousand three hundred and twenty-two patients were found to be PPI users, accounting for 14.9% of the patient population. PPI users were more frequently female, older and more frequently diagnosed with gastroesophageal reflux disease, gastric or duodenal ulcers, arthropathy, heart disease and cancer than the rest of the population. PPI users had more frequently received prescriptions for non-steroidal ant-inflammatory drugs (NSAIDS), acetylsalicylic acid (ASA), oral anticoagulant therapy (OAT) and systemic steroids. PPI reimbursement resulted applicable to 69.3% of the PPI users, but a potential for reimbursement of PPI prescriptions was identified in the non PPI users for the treatment of peptic or reflux disease (8.5%) and for the protection of gastric damage caused by NSAIDS (6.1%). Patients who are potentially eligible for reimbursement are older, diagnosed with arthropathy and heart disease more frequently and most commonly receive NSAID and ASA prescriptions compared with PPI users who do not satisfy eligibility requirements. Patients in whom it was not possible to identify conditions related to prescription suitability were more frequently associated with use of OAT. CONCLUSIONA substantial number of patients who apparently do not meet prescription suitability conditions can be identified, but among non PPI users on the contrary, it is possible to identify an equal number of patients for whom prescription would be suitable. Poor suitability can be identified in the population receiving OAT. Thus, there is scope for decreasing inappropriate use of PPI drugs by adhering to certain criteria and by involving all interested parties.
文摘AIM: To investigate the gastroprotective effect of vardenafil against indomethacin-induced gastric damage. METHODS: Forty-eight female Wistar albino rats were randomly divided into 6 groups. Group 1 received saline only. Group 2 (indomethacin) received indomethacin. Rats in group 3 and 4 were pretreated with different doses of famotidine. Group 5 and 6 were pretreated with different doses of vardenafil. Rats in groups 3 to 6 received 25 mg/kg indomethacin 30 min after pretreatment. The animals were sacrificed 6 h later and their stomachs were opened. Gastric lesions were counted and measured. The stomach of each animal was divided in two parts for histopathological examinations and nitric oxide (NO) and malondialdehyde (MDA) assays, respectively. RESULTS: There were no gastric mucosal lesion in the saline group but all rats in the indomethacin group had gastric mucosal ulcerations (ulcer count; 6.25 ± 3.49, and mean ulcer area; 21.00 ± 12.35). Ulcer counts werediminished with famotidine 5 mg/kg (4.12 ± 2.47, P > 0.05), 20 mg/kg (2.37 ± 4.43, P < 0.05), vardenaf il 2 mg/kg (4.37 ± 3.06), and vardenafil 10 mg/kg (1.25 ± 1.38, P < 0.05) compared to the indomethacin group. Gastric mucosal lesion areas were diminished with famotidine 5 mg/kg (8.62 ± 2.97, P < 0.001), famotidine 20 mg/kg (0.94 ± 2.06, P < 0.001), vardenafil 2 mg/kg (6.62 ± 5.87, P < 0.001), and vardenafil 10 mg/kg (0.75 ± 0.88, P < 0.001) compared to the indomethacin group. MDA levels were signif icantly higher in indometh-acin group (28.48 ± 14.51), compared to the famotidine 5 mg/kg (6,21 ± 1.88, P < 0.05), famotidine 20 mg/kg (5.88 ± 1.60. P < 0.05), vardenaf il 2 mg/kg (15.87 ± 3.93, P < 0.05), and vardenafil 10 mg/kg (10.97 ± 4.50, P < 0.05). NO concentration in gastric tissues of the fa-motidine groups were significantly increased (P < 0.05), but the NO increases in the vardenafil groups were not statistically significant. Histopathology revealed dimin-ished gastric damage for pretreatment groups compared to the indomethacin group (P < 0.05). CONCLUSION: Vardenafil affords a significant dose-dependent protection against indomethacin induced gastric mucosal lesions in rats.
文摘AIM:To examine the antiulcerogenic effects of various extracts of Mentha arvensis Linn on acid,ethanol and pylorus ligated ulcer models in rats and mice.METHODS:Various crude extracts of petroleum ether,chloroform,or aqueous at a dose of 2 g/kg po did not produce any signs or symptoms of toxicity in treated animals.In the pyloric ligation model oral administration of different extracts such as petroleum ether,chloroform and aqueous at 375 mg/kg po,standard drug ranitidine 60 mg/kg po and control group 1 Tween 80,5 mL/kg po to separate groups of Wister rats of either sex(n = 6) was performed.Total acidity,ulcer number,scoring,incidence,area,and ulcer index were assessed.RESULTS:There was a decrease in gastric secretion and ulcer index among the treated groups i.e.petroleum ether(53.4),chloroform(59.2),aqueous(67.0) and in standard drug(68.7) when compared to the negative control.In the 0.6 mol/L HCl induced ulcer model in rats(n = 6) there was a reduction in ulcerative score in animals receiving petroleum ether(50.5),chloroform(57.4),aqueous(67.5) and standard.drug(71.2) when compared to the negative control.In the case of the 90 ethanol-induced ulceration model(n = 6) in mice,there was a decrease in ulcer score in test groups of petroleum ether(53.11),chloroform(62.9),aqueous(65.4) and standard drug ranitidine(69.7) when compared to the negative control.It was found that pre-treatment with various extracts of Mentha arvensis Linn in three rat/mice ulcer models ie ibuprofen plus pyloric ligation,0.6 mol/L HCl and 90 ethanol produced significant action against acid secretion(49.3 ± 0.49 vs 12.0 ± 0.57,P < 0.001).Pre-treatment with various extracts of Mentha arvensis Linn showed highly-significant activity against gastric ulcers(37.1 ± 0.87 vs 12.0 ± 0.57,P < 0.001).CONCLUSION:Various extracts of Mentha arvensis Linn.375 mg/kg body weight clearly shows a protective effect against acid secretion and gastric ulcers in ibuprofen plus pyloric ligation,0.6 mol/L HCl induced and 90 ethanol-induced ulcer models.
基金Research Foundation of Hubei Biological Enzyme Engineering Technology Research Center(JS2018-06)
文摘OBJECTIVE Gastric ulcers affect people of all ages and half of the world's population,which is being considered as the new"plague of the 21st century".As is well known,gastric mucosa is known as the first guard to protect the stomach from ulcer injury,while the aetiology of gastric ulcer is relative to imbalances between gastric mucosal protective and aggressive factors.Therefore,reducing or eliminating the aggressive factors,returning to the balance of between mucosal protective and aggressive factors,and then restoring the normal functional of gastric mucosal barrier could be crucial for treating the gastric ulcer.The fruits of Chaenomeles speciosa(TCS),also known as"mugua",might be processed into edible and health care derived products,and used as a commonly used traditional medicine in China for thousands of years.In China folk,there is a saying that"apricot one benefit,pear two benefits,mgua hundred benefits",so it has a"hundred-benefit"fruit reputation.Tujia nationality inhabitants in Southwestern China should have rheumatic diseases and peptic ulcers for living in the damp environments and bingeing on spicy and pungent foods.For the exis⁃tence of the fruit derived products of Chaenomeles speciosa as their complementary foods or snacks,the habit makes them rarely suffer from the two kinds of diseases.Enlightened by these,we had investigated the structure-activity rela⁃tionships,screened out CSTT with gastroprotective activity.Our previous studies demonstrated that TCS owned effec⁃tively therapeutic effects on gastric ulcer patients and animals,and further confirmed that TFF1 and apoptotic pathway were closely interrelated with its exerting gastroprotection.However,its underlying molecular mechanisms involved have not been fully elucidated.The current study was to further investigate its protective effect on indomethacin(IND)-damaged RGM-1 cells and rats and its underlying mechanisms through modulating TFF1-mediated EGF/EGFR and apoptotic pathways.METHODS The gastroprotection of TCS was evaluated with IND-induced gastric lesions model in RGM-1 cells and rats.In vitro,the proliferation,migration,mitochondrial viability and apoptosis were assessed,In vivo,ulcer index,ulcer inhibition rate,gastric juice acidity,gastric wall mucus(GWM),histopathology of gastric mucosa were detected.The gastroprotective effects of TCS through the TFF1-mediated EGFR/EGFR and apoptotic pathways were presented and measured by qRT-PCR and Western blotting assays.RESULTS TCS had gastroprotective function,which was related to the amelioration in promoting IND-damaged RGM-1 cell proliferation and migration,hoisting gastric juice acidity and GWM,improving ulcer index and ulcer inhibition rate,attenuating the hemorrhage,edema,epithelial cell loss and inflammatory cell infiltration of gastric mucosa,upregulating proliferation cell nuclear antigen,Bcl-2,Bcl-xl mRNA and TFF1,EGF,p-EGFR,p-Src,pro-caspase-3,pro-caspase-9 protein expressions,mitochondrial viability,mitochondrial cytochrome C concentration and p-EGFR/EGFR,p-Src/Src,Bcl-2/Bax,Bcl-xl/Bad ratioes,downregulating Bax,Bad,Apaf-1 mRNA and cleaved-caspase-3,cleaved-caspase-9,cleaved-PARP-1 protein expressions,cytosol cytochrome C concentration.CONCLUSION TCS′s gastroprotective effect was closely connected with boosting TFF1 expression,acti⁃vating TFF1-mediated EGF/EGFR pathway,thus restraining mitochondrial-dependent apoptosis,which provided new insights into interpreting its underlying mechanism and promised to act as a candidate drug to treat gastric mucosal injury.
