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Peptic ulcers (PU) are a breach in the mucosa of the digestive tract and are related to several factors including an altered immune system and an unbalanced diet. Current treatment carries to long-term complications; therefore, the use of medicinal plants is an alternative for several inflammatory diseases including ulcerative lesions. Kalanchoë gastonis-bonnieri, is a succulent plant and, has been used in traditional medicine against gastric ulcers, inflammation, and cancer among others. The main goal of this work was to analyze the anti-ulcerogenic potential of extracts from leaves of K. gastonis-bonnieri in an assay of ethanol-induced gastric ulcers. An ethanolic extract was obtained by maceration from fresh leaves of K. gastonis-bonnieri, and fractions were obtained through bipartition and chemical fractioning. The chemical characterization of the extract was made through HPLC, GC-MS, and NMR. Total extract and fractions showed an anti-ulcerogenic effect in specimens of male ICR mice with a gastric ulcer index (UI) of 3.27-5.47. The recorded effect is attributed to the presence of terpenoid compounds such as ß-Amyrin acetate, which showed antioxidant properties and lessened formations of ulcers induced by ethanol administration in mice stomach.
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The widely believed Helicobacter pylori infection has never explained the birth-cohort phenomenon of peptic ulcers. Although numerous studies have observed that environmental factors are associated with peptic ulcers, their role in the disease has yet to be identified. A new etiological theory proposed that environmental factors cause peptic ulcers via inducing psychological stress. Starting from this etiology, an integration of the mortality rates caused by social and natural environmental factors reproduced a representative fluctuation curve in the birth-cohort phenomenon, where a causal role of environmental factors in peptic ulcers was hidden. The reproduced fluctuation curve revealed that multiple environmental factors caused the birth-cohort phenomenon by Superposition Mechanism, and the causal role of each individual environmental factor surfaced if the fluctuation curves in the birth-cohort phenomenon were properly differentiated. A full understanding of the birth-cohort phenomenon highlights the importance of environmental management in improving clinical outcomes, and suggests that the Superposition Mechanism is an indispensable methodological concept for life science and medicine.
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Peptic ulcers are a common condition that arises from an imbalance between acid production and gastroduodenal protective factors. Various drugs, including non-steroidal anti-inflammatory drugs (NSAIDs), potassium supplements, bisphosphonates, and doxycycline, can increase the development of peptic ulcers. NSAIDs are one of the most common medications prescribed for pain relief, and they also inhibit the formation of cyclooxygenase-1 (COX-1). COX-1 helps in the production of mucus that lines the stomach, so by inhibiting COX-1, NSAIDs reduce the mucus produced by the stomach and increase the likelihood of gastric ulcer formation. Additionally, NSAIDs are acidic, and increasing the amount of any acid in the stomach can result in promoting ulcer development. Potassium supplements are used to reduce the effects of hypertension, decrease the development of kidney stones, and treat hypokalemia. The various types of transporters and channels used to move potassium across cell membranes increase hydrogen being pumped, increasing gastric acid production and ulcer formation. Bisphosphonates are used to treat a variety of skeletal disorders that require inhibition of osteoclast activity. Nitric oxide (NO) has been shown to have a therapeutic effect on gastric ulcers, and some bisphosphonates have been shown to decrease the production of nitric oxide, resulting in increased damage to the gastric mucosa. Finally, doxycycline is a broad-spectrum tetracycline antibiotic that is typically used to treat anthrax poisoning, skin lesions, and sexually transmitted diseases. A harmful adverse effect of doxycycline is the formation of peptic and gastric ulcers related to the drug being highly acidic once it has dissolved.
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Capsaicin (CAP) has been implicated as a gastroprotective agent in the treatment of peptic ulcers. However, its oral administration is hampered by its poor aqueous solubility and caustic effect at high administered doses. To address these limitations, we describe the development of gastric floating, sustained release electrospun films loaded with CAP. The nanofiber films were formulated using the polymers Eudragit RL/RS and sodium bicarbonate (SB) as the effervescent agent. The films were tested for their physicochemical properties, and film buoyancy and in vitro release of CAP were assessed in simulated gastric fluid. The cytocompatibility and anti-inflammatory properties of the films were evaluated in lipopolysaccharide (LPS)-stimulated Caco-2 cells. The amorphous films showed improved wettability, a short floating lag time (<1 s) and a total floating time of over 24 h accompanied by sustained CAP release for up to 24 h. CAP-loaded films demonstrated biocompatibility with Caco-2 cells and potential cytoprotective effects by attenuating inflammatory cytokine and reactive oxygen species (ROS) production in LPS-stimulated Caco-2 cells. The gastric floating electrospun films could serve as a platform for sustained and stomach-specific drug delivery applications.
Subject(s)
Capsaicin , Lipopolysaccharides , Humans , Delayed-Action Preparations/chemistry , Caco-2 Cells , Drug Delivery Systems , Solubility , TabletsABSTRACT
Gastric and small bowel emergencies are often seen in the emergency department and require rapid assessment and intervention as patients can deteriorate quickly. Some of the more frequently seen gastric emergencies include gastric volvulus and peptic ulcer disease, which can present with ischemia, strangulation, perforation, or severe bleeding. Swift diagnosis is crucial to ensuring the proper management whether that is endoscopic or with surgical exploration. Perforated peptic ulcers that are not contained will require surgical intervention, whereas bleeding ulcers can often be controlled with endoscopic interventions.
Subject(s)
Duodenal Ulcer , Peptic Ulcer Perforation , Humans , Duodenal Ulcer/surgery , Emergencies , Peptic Ulcer Perforation/surgery , Intestine, SmallABSTRACT
Penetrating peptic ulcers often lead to severe complications. The development of uretero-enteric fistulas is rare and can be challenging to diagnose and treat. Here, we present the case of a 41-year-old patient who previously underwent gastrojejunostomy for superior mesenteric artery syndrome and developed a peptic jejunal ulcer, leading to a uretero-jejunal fistula and finally causing acute pyelonephritis. The patient was managed with a multidisciplinary approach including medical therapy and endoscopic and radiologic interventions.
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BACKGROUND: Helicobacter pylori is an infection of concern for its chronic colonization leading to peptic ulcers and gastric cancer. In recent times, microRNAs have been extensively studied to understand their role in the pathogenesis of this bacteria in diverse contexts of gastric diseases. The current analysis reports the microRNA-mRNA interactions that are associated with effective survival and virulence of this pathogen. MATERIALS AND METHODS: We convened differentially regulated human microRNAs responsive to H. pylori infection (HP-hDEmiRs) at different multiplicity of infection and time points in human gastric cell lines through retrospective data mining of experimental studies. In view of the molecular disparity of clinical samples and animal models, data from tissue, serum/plasma, urine, and ascites were excluded. Further, we utilized diverse bioinformatics approaches to retrieve experimentally validated, high-confidence targets of the HP-hDEmiRs to analyze the microRNA-mRNA interactions that are relevant to H. pylori pathogenesis. RESULTS: A total of 39 HP-hDEmiRs that showed unidirectional expression of either overexpression or downregulation were identified to modulate 23 targets explicitly studied under this infection. We also identified 476 experimentally validated targets regulated by at least 4 of the HP-hDEmiRs. In addition to the pathways prior-associated with H. pylori infection, the microRNA-mRNA interactome analysis identified several cellular processes and pathways highly associated with cell cycle, cell division, migration, and carcinogenesis. CONCLUSION: This study generated a platform to study the mechanisms utilized by this pathogen using microRNAs as surrogate.
Subject(s)
Helicobacter Infections , Helicobacter pylori , MicroRNAs , Stomach Neoplasms , Animals , Humans , MicroRNAs/genetics , Helicobacter pylori/physiology , Retrospective Studies , Helicobacter Infections/microbiology , Stomach Neoplasms/pathology , RNA, Messenger , Gastric Mucosa/pathologyABSTRACT
Background: Acute upper gastrointestinal bleeding (AUGIB) remains a common medical emergency with considerable morbidity and mortality. The aim of this study was to describe the patient characteristics, diagnoses and clinical outcomes of patients presenting with AUGIB nowadays and compare these with those of patients 15 years ago. Methods: This was a single-center survey of adults (> 16 years) presenting with AUGIB to a tertiary hospital. Data from 401 patients presenting with AUGIB in a tertiary hospital between January 1, 2019 and December 31, 2020 were analyzed and compared with data from 434 patients presenting with AUGIB at the same hospital between January 1, 2004 and December 31, 2005. Results: Nowadays, patients were older, mean age was 69.5 (± 15.4) vs. 66.2 (± 16.0) years, they had more frequently coexisting diseases (83.5% vs. 72.8%), especially cardiovascular diseases (62.3% vs. 52.5%), and more individuals were inpatients at onset of bleeding (8.2% vs. 4.1%). In addition, more patients were under anticoagulants (18.5% vs. 6.2%), but less were under acetylsalicylic acid ± clopidogrel (36.9% vs. 33.9%). Carlson Comorbidity Index was higher nowadays (5.6 ± 6.4 vs. 3.4 ± 2.3). Moreover, a peptic ulcer was less frequently found as the cause of bleeding (38.4% vs. 56.9%), while more often nowadays endoscopy was negative (12.7% vs. 3.5%). In patients with peptic ulcer, active bleeding on endoscopy was less frequent (7.1% vs. 14.2%). Also, bleeding spots requiring hemostasis were less common on endoscopy (39.6% vs. 49.4%) and more patients were without spots of recent bleeding (49.4% vs. 38.9%). Finally, the rate of rebleeding statistically decreased (7.8% vs. 4.2%), while overall mortality remained relatively unchanged (5.0% vs. 6.2%). Conclusions: AUGIB episodes nowadays are less severe with less peptic ulcer bleeding, but the patients are older and with more comorbidities.
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Background Perforation of peptic ulcers is a common cause of emergency surgery and has significant morbidity and mortality. The use and range of laparoscopic surgery have greatly increased over the past three decades. Laparoscopic approach is an option for perforated peptic ulcers because of the simple nature of the intervention. The aim of this study was to evaluate the outcome of laparoscopic approach for peptic ulcer repair in emergency setting by means of operative time, post-operative pain, mean hospital stay, and post-operative complications. Methods In this study, we enrolled patients presenting with perforated peptic ulcers in the emergency department of a tertiary care hospital in Lahore, Pakistan. Approval from the hospital ethical committee and informed consent were taken from all patients. After resuscitation, the patient underwent laparoscopic repair of perforation. Post-operative course of patients was monitored. Duration of surgery, post-operative pain, length of hospital stay, and post-operative complications were noted for all patients. Results Between December 2018 and December 2021, 31 patients with perforated peptic ulcers underwent laparoscopic repair at our hospital. Mean age of patients was 37.25 ± 7.80 years. Most of the patients were male (70.76%). The mean operation time was 109.35 ± 17.02 minutes for laparoscopic repair. Mean duration of hospital stay was 5.10 ± 0.87 days. Mean post-operative pain was 3.55 ± 0.85 assessed using the Visual Analogue Scale. There were no mortalities during the 30-day post-operative window. Conclusion With proper patient selection, laparoscopic surgery offers better results as compared to open surgery in patients undergoing emergency surgery for perforated peptic ulcers.
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Ischaemia and reperfusion (I/R)-induced gastrointestinal disorders are caused by free radicals, resulting in organ damage and functional disarrangement. This study aimed to investigate the healing effects of hydroalcoholic extracts from the leaves of Eugenia punicifolia (Kunth) DC. (HEEP) in male and female Wistar rats with I/R-induced peptic injuries, and the role of antioxidants in improving this response. After I/R-induced gastric and duodenal injuries, male and female [intact (INT) and ovariectomized (OVZ)] rats were orally treated with HEEP for 6 days. Biochemical analysis was used to determine the catalase (CAT), superoxide dismutase (SOD), and myeloperoxidase (MPO) activities, as well as malondialdehyde and reduced glutathione levels, to measure the gastric and duodenal healing process. Six days of HEEP treatment significantly decreased the I/R-induced gastric [male (73.68%), INT (52.83%), and OVZ (43.13%)] and duodenal damage [male (57.03%), INT (56.04%), and OVZ (54.83%)] in all groups. In OVZ rats, the healing effect of HEEP occurred because of the increased activity of SOD (2x) and CAT (1.16x) in the gastric mucosa. In the duodenal mucosa of INT rats, the extract reduced MPO (20.83%) activity. The 6-day HEEP treatment improved the healing of I/R-induced peptic ulcer injury, with the system acting differently in males and females. The antioxidant system is an important component of the HEEP activity during post-I/R mucosal recovery. This result revealed the importance of antioxidant compounds in minimizing the severity of I/R-related events.
Subject(s)
Eugenia , Peptic Ulcer , Reperfusion Injury , Stomach Ulcer , Animals , Antioxidants/metabolism , Antioxidants/pharmacology , Eugenia/chemistry , Eugenia/metabolism , Female , Gastric Mucosa , Ischemia/metabolism , Male , Peptic Ulcer/drug therapy , Peptic Ulcer/metabolism , Plant Extracts , Rats , Rats, Wistar , Reperfusion , Reperfusion Injury/drug therapy , Reperfusion Injury/metabolism , Stomach Ulcer/chemically induced , Superoxide Dismutase/metabolismABSTRACT
Background: It is unclear if the addition of antifungal therapy for perforated peptic ulcers (PPU) leads to improved outcomes. We hypothesized that empiric antifungal therapy is associated with better clinical outcomes in critically ill patients with PPU. Patients and Methods: The 2001-2012 Medical Information Mart for Intensive Care (MIMIC-III) database was searched for patients with PPU and the included subjects were divided into two groups depending on receipt of antifungal therapy. Propensity score matching by surgical intervention, mechanical ventilation (MV), and vasopressor administration was then performed and clinically important outcomes were compared. Multiple logistic regression was performed to calculate the odds of a composite end point (defined as "alive, hospital-free, and infection-free at 30 days"). Results: A total of 89 patients with PPU were included, of whom 52 (58%) received empiric antifungal therapy. Propensity score matching resulted in 37 pairs. On logistic regression controlling for surgery, vasopressors, and MV, receipt of antifungal therapy was not associated with higher odds (odds ratio [OR], 1.5; 95% confidence interval [CI], 0.5-4.7; p = 0.4798) of the composite end point. Conclusions: In critically ill patients with perforated peptic ulcer, receipt of antifungal therapy, regardless of surgical intervention, was not associated with improved clinical outcomes. Selection bias is possible and therefore randomized controlled trials are required to confirm/refute causality.
Subject(s)
Antifungal Agents , Peptic Ulcer Perforation , Antifungal Agents/therapeutic use , Humans , Logistic Models , Odds Ratio , Peptic Ulcer Perforation/complications , Peptic Ulcer Perforation/drug therapy , Peptic Ulcer Perforation/surgery , Propensity ScoreABSTRACT
BACKGROUND: Perforated peptic ulcer (PPU) is a surgical emergency needing swift operative resolution. While laparoscopic and open approaches are viable options, it remains unclear whether laparoscopic repair has significantly improved outcomes. We use a national surgical database to compare perioperative and 30-d postoperative (30POP) outcomes. MATERIALS AND METHODS: The 2016-2018 ACS-NSQIP database was used to create the patient cohort, using ICD-10 and CPT codes. An unmatched analysis identified factors that likely contributed to the laparoscopic versus open treatment allocation. Propensity score matching (PSM) was used to identify outcomes that were not explained by underlying differences in the patient cohorts. RESULTS: A total of 3475 patients were included: 3135 in open group (OG), 340 (~10%) in laparoscopic group (LG). After PSM to control for comorbidities and illness severity that differed between groups on univariate analysis, 288 patients remained in each group. Analysis of the matched cohorts revealed no statistically significant difference in mortality (5.9% OG versus 3.8% LG, P = 0.245). The LG had significantly longer operative times (92 versus 79 min, P = 0.003), shorter hospital stays (8.2 versus 9.4 d, P = 0.044) and higher probability of being discharged home (81% versus 73%, P = 0.017). 30POP outcomes were largely equivalent, except that OG had higher risk for bleeding (14.6% versus 8%, P = 0.012) and pneumonia (8.7% versus 4.5%, P = 0.044). CONCLUSIONS: While laparoscopic repairs take longer, they lead to shorter hospital stays and higher likelihood of discharge home. Further study to identify patients that are candidates for this technique is warranted.
Subject(s)
Duodenal Ulcer/surgery , Laparoscopy/statistics & numerical data , Peptic Ulcer Perforation/surgery , Stomach Ulcer/surgery , Adult , Aged , Duodenal Ulcer/complications , Female , Humans , Length of Stay , Male , Middle Aged , Operative Time , Quality Improvement , Retrospective Studies , Stomach Ulcer/complicationsABSTRACT
The development of sequencing technology has expanded our knowledge of the human gastric microbiome, which is now known to play a critical role in the maintenance of homeostasis, while alterations in microbial community composition can promote the development of gastric diseases. Recently, carcinogenic effects of gastric microbiome have received increased attention. Gastric cancer (GC) is one of the most common malignancies worldwide with a high mortality rate. Helicobacter pylori is a well-recognized risk factor for GC. More than half of the global population is infected with H. pylori, which can modulate the acidity of the stomach to alter the gastric microbiome profile, leading to H. pylori-associated diseases. Moreover, there is increasing evidence that bacteria other than H. pylori and their metabolites also contribute to gastric carcinogenesis. Therefore, clarifying the contribution of the gastric microbiome to the development and progression of GC can lead to improvements in prevention, diagnosis, and treatment. In this review, we discuss the current state of knowledge regarding changes in the microbial composition of the stomach caused by H. pylori infection, the carcinogenic effects of H. pylori and non-H. pylori bacteria in GC, as well as the potential therapeutic role of gastric microbiome in H. pylori infection and GC.
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BACKGROUND: Helicobacter pylori causes dangerous and deadly diseases such as gastric cancer and duodenal ulcers. Eradication and treatment of this bacterium are very important due to the deadly diseases caused by H. pylori and the high cost of treatment for countries. METHODS: Thus, we present a complete list of the most important causes of failure in the treatment and eradication of H. pylori, and address new therapeutic methods that may be effective in controlling this bacterium in the future. RESULTS: Many efforts have been made to control and eradicate this bacterium over the years, but no success has been achieved since its eradication is a complex process affected by the bacterial properties and host factors. Previous studies have shown that various factors are involved in the failure to eradicate H. pylori, such as new genotypes of the bacterium with higher pathogenicity, inappropriate patient cooperation, mutations, biofilm formation and dormant forms that cause antibiotic resistance, acidic stomach pH, high bacterial load, smoking, immunosuppressive features and intracellular occurrence of H. pylori. On the other hand, recent studies reported that the use of probiotics, nanoparticles, antimicrobial peptides, natural product and vaccines can be helpful in the treatment and eradication of H. pylori infections. CONCLUSION: Eradication of H. pylori is crucial for the treatment of important diseases such as gastric cancer. Therefore, it seems that identifying the failure causes of treating this bacterium can be helpful in controlling the infections. Besides, further studies on new therapeutic strategies may help eradicate H. pylori in the future.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Disease Eradication/trends , Drug Development/trends , Helicobacter Infections/drug therapy , Helicobacter pylori/drug effects , Probiotics/therapeutic use , Animals , Anti-Bacterial Agents/pharmacology , Drug Therapy, Combination , Helicobacter Infections/genetics , Helicobacter Infections/immunology , Helicobacter pylori/genetics , Helicobacter pylori/immunology , Humans , Probiotics/pharmacology , Stomach Neoplasms/genetics , Stomach Neoplasms/immunology , Stomach Neoplasms/prevention & control , Time FactorsABSTRACT
BACKGROUND/OBJECTIVES: Peptic ulcer disease (PUD) is one of the most common gastrointestinal disorders worldwide. Recent epidemiologic studies have suggested the protective effect of statins against the development of PUD although the results were inconsistent. This systematic review and meta-analysis was conducted with the aim to summarise all available data. METHODS: A literature review was performed using MEDLINE and EMBASE database from inception to December 2017. Cohort, case-control and cross-sectional studies that compared the risk of PUD among statins users versus non-users were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULTS: A total of 3 studies (1 case-control and 2 retrospective cohort studies) met the eligibility criteria and were included in this meta-analysis. The risk of PUD was numerically lower among statins-users compared with non-users with the pooled OR of 0.89. However, the result did not achieve statistical significance with 95% CI of 0.67-1.18. The between-study statistical heterogeneity was high (I2 = 80%). CONCLUSIONS: This systematic review and meta-analysis found that the risk of PUD was numerically lower among statin users. However, the results did not reach statistical significance. More studies are still required to further characterise this potential protective effect.
Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors , Peptic Ulcer , Cross-Sectional Studies , Humans , Odds Ratio , Peptic Ulcer/epidemiology , Retrospective StudiesABSTRACT
Background: Gastric stump ("remnant") cancer is the development of a malignancy related to previous gastric surgery. Prognosis in gastric stump cancer, compared with that in primary gastric cancer, is still controversial. Methods: From January 1988 to December 2012 at a single medical centre in Taiwan, 105 patients with gastric stump cancer, including 85 with previous peptic ulcer disease and 20 with previous gastric cancer, were analyzed for clinicopathologic characteristics and overall survival (os). Results: The 5-year os rates for patients with gastric stump cancer and with primary gastric cancer were 51.2% and 54.5% respectively (p = 0.035). Analysis of clinicopathologic characteristics indicated that, compared with patients having primary gastric cancer, those with gastric stump cancer had more lymph node metastasis (p < 0.001) and had been diagnosed at a more advanced stage (p = 0.047). Multivariate analysis with os as an endpoint showed that age [p = 0.015; hazard ratio (hr): 2.300; 95% confidence interval (ci): 1.173 to 4.509], tumour size (p = 0.037; hr: 1.700; 95% ci: 1.031 to 2.801), stromal reaction (p = 0.021; hr: 1.802; 95% ci: 1.094 to 2.969), and pathologic N category (p = 0.001; hr: 1.449; 95% ci: 1.161 to 1.807) were independent predictors in gastric stump cancer. The os rates for patients with gastric stump cancer who previously had gastric cancer or peptic ulcer disease were 72.9% and 50.0% respectively (p = 0.019). The Borrmann classification was more superficial (p = 0.005), lymph node metastases were fewer (p = 0.004), and staging was less advanced (p = 0.025) in patients with gastric stump cancer who previously had gastric cancer than in their counterparts who previously had peptic ulcer disease. Conclusions: Survival is poorer in patients with gastric stump cancer who previously had peptic ulcer disease than in those who previously had primary gastric cancer. Patients with gastric stump cancer who previously had gastric cancer and could receive curative gastrectomy tended to have a better prognosis because of a more superficial Borrmann classification. Regular follow-up in patients who have undergone gastric surgery is recommended for the early detection of gastric stump cancer.
Subject(s)
Gastric Stump/physiopathology , Stomach Neoplasms/complications , Stomach Neoplasms/surgery , Aged , Female , Humans , Male , Prognosis , Retrospective Studies , Stomach Neoplasms/mortality , Survival AnalysisABSTRACT
BACKGROUND AND OBJECTIVES: Helicobacter pylori is a Gram-negative spiral-shaped bacterium that contaminates more than half of the world's inhabitants, and infection with this bacterium is associated with some gastric disorders. Also, 5% to 10% of H. pylori genes are specific to this bacterium and many bacterial virulence factors fall into this group. The cagA, vacA, sodB and hsp60 are among important virulence factors of H. pylori. MATERIALS AND METHODS: A gastric biopsy specimen was taken from 341 gastric patients and cultivated on a Colombia agar plate, containing various antibiotics, such as vancomycin, amphotericin B, and trimethoprim & polymyxin B, and incubated for 3 to 10 days under microaerophilic conditions at 37°C. PCR was used to detect the ureC, cagA, vacA, sodB and hsp60 genes. RESULTS: In this study, 131 isolates were identified as H. pylori. The prevalence of cagA, vacA, sodB and hsp60 were 74%, 100%, 92.4% and 96.2%, respectively. The correlation between the clinical forms of the disease and the virulence genes were analyzed by statistical tests and no significant correlation was found. CONCLUSION: The obtained results are similar to some studies conducted in different parts of the world and is different in other cases. This discrepancy is due to the difference in the type of gastric disorders, sample size and methodology.
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BACKGROUND: Trachyspermum ammi (L.) Sprague is used for treating gastrointestinal disorders. Several studies indicated gastric antiulcer activity of T. ammi extract, yet the effect of its essential oil has not been studied on. OBJECTIVES: The present study evaluates chemical composition of T. ammi essential oil and anti-peptic ulcer effect of the essential oil as well as its three major components in ethanol induced-gastric ulcers in rats. METHODS: Primarily chemical composition of the essential oil was analyzed by gas chromatography-mass spectrometry (GC/MS). Rats received the essential oil (500, 250, 125, 62.5, 31.25 mg/kg), thymol (30, 100 mg/kg), para-cymene (100, 150 mg/kg) and gamma-terpinene (100, 150 mg/kg) using gavage tube along with ethanol 80%. Finally, dissected stomachs were assessed both macroscopically and microscopically to evaluate anti-ulcerative effect of the essential oil and the pure compounds. Moreover, molecular docking was utilized to explore the interactive behavior of the main components with active site residues of H+/K+ ATPase. RESULTS: Analysis of the essential oil indicated that para-cymene (37.18%), gamma-terpinene (35.36%) and thymol (20.51%) are the main components. Administration of different doses of the essential oil noticeably diminished the number of peptic ulcers in a dose-dependent manner. Among the main components, thymol was more potent than para-cymene and gamma-terpinene. Administration of the essential oil (500 mg/kg) and thymol (100 mg/kg) observed maximum inhibition percentage (98.58% and 79.37%, respectively). Molecular docking study provides the evidence of thymol ability to inhibit H+/K+ ATPase. CONCLUSIONS: The findings revealed that T. ammi essential oil can be applied to treat gastric ulcer as a natural agent. Graphical abstract.
Subject(s)
Ammi/chemistry , Ethanol/adverse effects , Oils, Volatile/administration & dosage , Peptic Ulcer/drug therapy , Animals , Cyclohexane Monoterpenes/administration & dosage , Cyclohexane Monoterpenes/isolation & purification , Cyclohexane Monoterpenes/pharmacology , Cymenes/administration & dosage , Cymenes/isolation & purification , Cymenes/pharmacology , Disease Models, Animal , Dose-Response Relationship, Drug , Down-Regulation , Gas Chromatography-Mass Spectrometry , H(+)-K(+)-Exchanging ATPase/metabolism , Molecular Docking Simulation , Oils, Volatile/chemistry , Oils, Volatile/pharmacology , Peptic Ulcer/chemically induced , Peptic Ulcer/metabolism , Plant Oils/administration & dosage , Plant Oils/chemistry , Plant Oils/pharmacology , Rats , Thymol/administration & dosage , Thymol/isolation & purification , Thymol/pharmacologyABSTRACT
Resumen: OBJETIVO: Evaluar la dosis acumulada ingerida de antiinflamatorios no esteroides (AINEs) en pacientes con úlcera péptica hemorrágica y sus complicaciones durante la hospitalización. MATERIAL Y MÉTODO: Estudio retrospectivo en el que de julio de 2015 a diciembre de 2017 se evaluaron dos grupos: uno con antecedente hospitalario de perforación, resangrado, reintervención endoscópica y muerte y otro sin complicaciones. Se ajustó la dosis ingerida de diferentes AINEs equivalente a 10 mg de ketorolaco; se registró el índice de Charlson, infección por H. pylori y la clasificación endoscópica de Forrest. RESULTADOS: Hubo 156 admisiones de úlcera péptica hemorrágica (edad promedio de 70 años, 53% hombres), las complicaciones ocurrieron en 53 (33.9%), la dosis promedio mensual de AINEs fue de 2121 mg (pacientes con complicaciones) vs 1970 mg (sin complicaciones; p = 0.2). La tasa de AINEs/semana de 7.1 se relacionó con perforación. A todos se les aplicó dosis de omeprazol de 40 mg cada 12 horas vía intravenosa durante la hospitalización. Las complicaciones se correlacionaron con mayor índice de Charlson. Hubo relación entre muerte, factores de riesgo de úlcera péptica por estrés (sepsis, traumatismo, etc.) y la administración de anticoagulantes. El tabaquismo y el género masculino se relacionaron con mayor resangrado. CONCLUSIONES: Existe mayor probabilidad de perforación con necesidad de cirugía, estancia hospitalaria más larga y mayor número de transfusiones con mayor dosis ingerida de AINEs.
Abstract: OBJECTIVE: To evaluate the cumulative dose of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with hemorrhagic peptic ulcer and their complications along hospitalization. MATERIAL AND METHOD: A retrospective study done from July 2015 to December 2017 including two groups: one with a hospitalization history of perforation, rebleeding, endoscopic reintervention and death, another group without complications. We registered doses of different NSAIDs according to 10 mg of ketorolac, Charlson index, H. pylori infection and endoscopic Forrest classification. RESULTS: There were 156 admissions of hemorrhagic peptic ulcer with the administration of NSAIDs (average age 70 years, 53% men), complications occurred in 53 (33.9%). The average monthly dose of NSAID in the cases was 2121 mg vs 1970 mg in controls. The NSAID/week rate of 7.1 was associated with perforation. Charlson index correlated with complications. Death and physiological stress related with the administration of anticoagulants. Smoking and the male gender related to higher rebleeding. CONCLUSIONS: The higher the NSAID/weekly rate, the higher the probability of perforation with the need for surgery, longer hospital stay and increased number of transfusions.
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BACKGROUND: The incidence of peptic ulcers unrelated to H. pylori infection and non-steroidal anti-inflammatory drugs (NSAIDs), termed idiopathic peptic ulcers (IPUs), has increased worldwide. We recently reported that IPUs were refractory to proton pump inhibitor (PPI) treatment. Vonoprazan, which was recently developed in Japan, has shown a more potent acid-inhibitory effect than ordinary PPIs. In the present study, we compared the healing rates among peptic ulcers of different etiologies following treatment with vonoprazan. METHOD: A multicenter observational study was performed at six participating hospitals in Akita Prefecture, Japan. Consecutive patients who had endoscopically confirmed gastro-duodenal ulcers were enrolled between August 2016 and March 2018. For each patient, the Helicobacter pylori infection status and NSAID use, including aspirin, were checked, and 20 mg vonoprazan was administered for 6 weeks for duodenal ulcers and 8 weeks for gastric ulcers. The healing status was checked by endoscopy at the end of vonoprazan treatment. Patients were divided into four subgroups according to the H. pylori status and NSAID usage. RESULTS: The proportion of IPUs was 18.2%. A total of 162 patients completed the study protocol. The healing rate of IPUs was marginally lower than that of simple H. pylori-associated ulcers (81.2% vs. 93.5%, P = 0.05). Similarly, the healing rate of NSAID-related ulcers, irrespective of concomitant H. pylori infection, was significantly lower than that of simple H. pylori-associated ulcers. CONCLUSIONS: Six- or 8-week vonoprazan treatment still seems to be insufficient for healing IPUs. Longer-term vonoprazan or another treatment option may be required to heal potentially refractory peptic ulcers.