Study of Antiulcer activity of a hydrogel based on chitosan

In this study, the antiulcer activity of a gel based on high-viscosity chitosan was studied in models of NSAID and ethanol-induced ulcerogenesis. To simulate damage to the gastric mucosa in the NSAID model, diclofenac sodium was administered to experimental animals at a dose of 50mg/kg. An antiseptic intestinal and astringent agent was chosen as reference drug: bismuth tripotassium dicitrate at a dose of 0.017g/kg. The studied gel was used in 3 doses (0.08, 0.16 and 0.24ml/100g of body weight). In ethanol model, ulcers were induced by a single administration of ethanol 96% at a dose of 5ml/kg. Omeprazole at a dose of 20mg/kg was used as reference drug in this model. Chitosan-based gel was administrated in this model at a dose of 0.16ml per 100g of animals, which corresponds to the minimum available dose with antiulcer activity in the NSAID model. All investigated substances were injected intragastrically using a gastric tube. As a result of this research, it was found that the chitosan-based gel is effective in the NSAID gastropathy model but not effective in the ethanol model. In the NSAID gastropathy model, after a single oral administration of chitosan-based gel at doses of 0.16 and 0.24ml/ 100g, sufficient antiulcer activity was revealed, which was 2.4 and 4.694, respectively, and exceeded the effect of the reference drug, bismuth tripotassium dicitrate. In the ethanol model, the results of experimental studies showed that the reference drug, omeprazole, provides antiulcer activity with a calculated value of the antiulcer activity index of 2.18. After the administration of a chitosan-based gel at a dose of 0.16 ml per 100g of body weight of animals, compared with the control, the calculated value of antiulcer activity was 1.18, which characterizes the absence of an antiulcer effect.

SHORT- AND LONG-TERM EFFECTS OF NSAIDS ON THE GASTROINTESTINAL MUCOSA: COMPLEX ANALYSIS OF BENEFITS AND COMPLICATIONS PREVENTION

The aim: To analyse data from recent studies, dedicated to the use of non-steroidal anti-inflammatory drugs (NSAIDs); to evaluate the best clinical practice in the use of NSAIDs in order to prevent side effects (SEs) in different clinical scenarios; to optimise treatment of patients at risk of NSAIDs-related SEs. Materials and methods: A comprehensive bibliographic search was performed using the keywords “NSAIDs”, “NSAID gastropathy”, “NSAID enteropathy”, “complications of NSAID therapy”, “cardiovascular disease”, “cardiovascular risk” in the PubMed, Web of Science, Cochrane Library, Google Academy databases. Conclusions: NSAID-induced gastrointestinal lesions are а relevant problem of internal medicine, this is due to the fact that the pathogenic mechanisms of this process are still unclear. All the gastrointestinal tract (GIT) related risk factors(RFs) for gastro- and enterocolonopathies associated with the use of NSAIDs should be taken into consideration by physicians of all specialties. The examination and diagnostic of the GIT should be performed regularly to prevent complications. Uncontrolled, long-lasting, unprescribed NSAID usage should draw the attention of doctors, especially in patients with comorbid states.

Peculiarities and new prospects of management of patients with NSAID-gastropathy on the background of chronic pancreatitis in general-therapy practice

Introduction. The main pharmacological effects of NSAIDs are anti-inflammatory, the onset and conduction of a pain signal, the aggregation of blood elements, neoangiogenesis, cell apoptosis, etc. — make them indispensable in the treatment of inflammatory and degenerative diseases of the joints and spine, in particular osteoarthritis. NSAIDs account for 25% of all medical complications, including bleeding rates (25–40%), which is a serious medical and important socio-economic problem. The risk of developing NSAIDs-gastropathy is determined both by severity of COX-2 inhibitory effect and non-prostaglandin systemic and local effects. Use of proton pump inhibitors, histamine blockers (mainly children and adolescents), and synthetic analogues of prostaglandins, as well as drugs of cytoprotective action, is pathogenetically justified in the treatment of NSAIDs-gastropathy. One of the newest and most economically available, most metabolically high-technological is the vitamin drug Doctovit. Aim: to study the effectiveness of Doctovit in the complex therapy of patients with NSAIDs-gastropathy on the background of chronic pancreatitis by analyzing the morphological parameters, indices of antioxidant protection system and endotoxicosis system. Materials and methods. 42 patients with NSAID-gastropathy on the background of chronic pancreatitis were examined. Patients, comparable by clinical, gender criteria, severity of NSAID-gastropathy and treatment received — were divided into two groups: I control group (20 patients), 10-day treatment regimen: PPI pantoprazole (Controlok, Nolpase, Pantasan, etc.) 40 mg×2; cancellation of NSAIDs; II main group (22 patients), 10-day treatment regimen: PPI pantoprazole (Controlok, Nolpase, Pantasan, etc.) 40 mg×2; cancellation of NSAIDs; Doctovit 2 tablets per day after meals for 2 months. Compulsory components of medical complexes were outpatient regimen and normotrophic nutrition. All patients with NSAID-gastropathy underwent standardized clinical laboratory examination. At the beginning of the study and two months after the start of treatment EGDS + biopsy from 5 places with histological examination was performed. The level of endotoxicosis was defined by the level of sorption capacity of erythrocytes, which was determined according to A. A. Togaibayev technique. The state of lipid peroxidation was evaluated by the level of malonic aldehyde, the state of antioxidant protection system — by the levels of superoxide dismutase, catalase, SH-groups. Results and discussion. Morphological examination of gastric EGD biopsy specimens before and after treatment in the comparison groups showed statistically significant efficacy of the proposed treatment complex with the inclusion of Doctovit in influencing the established pathological features of NSAID-gastropathy. There was a statistically significant improvement in endotoxicosis in both study groups after treatment, but in the II group the positive effect was statistically more significant. The proposed correction programs had a positive effect on the lipid peroxidation, but the correction program used in II group had a statistically significantly better effect. Conclusion. In the complex treatment of NSAID-gastropathy on the background of chronic pancreatitis, it is advisable to use the vitamin complex Doctovit 2 tablets per day after meals for 2 months, which has a positive effect on the condition of the gastric mucosa, indices of lipid peroxidation and endotoxicosis.

CHARACTERISTICS OF GASTRIC MUCOSA INJURY IN PATIENTS WITH NSAID-INDUCED GASTROPATHY AND CONCOMITANT ISCHEMIC HEART DISEASE, AND WAYS TO CORRECT THIS CONDITION

The non-steroidal anti-inflammatory drugs (NSAIDs) in general clinical practice can provoke the development of NSAID-induced gastropathy, which can be complicated by bleeding. The aim of this article was to evaluate the effect of eupatilin on histological changes of the gastric mucosa in patients with NSAID-induced gastropathy and concomitant ischemic heart disease depending on the association with Helicobacter pylori. The study included 125 patients with NSAID-gastropathy and concomitant stable ischemic heart disease I-II functional class. Patients were divided into two groups: I (n=82) included individuals with NSAID-gastropathy, which was not associated with H. pylori, while II (n=43) included individuals with H. pylori-induced gastropathy. Depending on the prescribed treatment complexes, patients were subdivided as follows: I-A (n=44) included patients, who took proton pump inhibitors in standard doses and II-A group (n=23) included patients, who received antihelicobacter therapy according to Maastricht V (2016) guidelines. Patients of groups I-B (n=38) and II-B (n=20) were additionally prescribed 60 mg of eupatilin (1 tablet) 3 times a day for 28 days. The upper endoscopy with the gastric mucosa biopsy, followed by histological examination was done at the beginning of treatment and in 45±2 days. The severity of gastric mucosa erosive and ulcerative injury was assessed endoscopically using a modified Lanzascore scale; morphological changes were evaluated by a semi-quantitative method on a visual-analogue scale. H. pylori is an independent and significant factor determining the severity of endoscopic and morphological changes in NSAID-gastropathy patients with concomitant ischemic heart disease. Acid-suppressive and antihelicobacter therapy can reduce the intensity of the structural injury of the gastric mucosa, but the identified changes substantiate the feasibility of long-term proton pump inhibitors prescribed to the patients with NSAID-gastropathy. Prescribing eupatilin against the background of basic therapy can significantly reduce the severity of erosive-ulcerative gastric mucosa injury assessed by Lanzascore scale while histomorphological parameters by reducing the activity of neutrophilic inflammation, protective effect on mucosal barrier resistance and microcirculatory condition.

NSAID enteropathy

Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly used drugs in the world, and their side effects are very high. First of all, these are NSAID gastropathy, but in the long term, 5070% of NSAIDs cause damage to the small intestine (NSAID enteropathy), sometimes with serious consequences. To date, no drugs have been proposed with proven effectiveness to prevent this side effect. Apparently, this is not due to the fully clarified mechanism of pathogenesis. The most promising is the hypothesis of the participation of individual representatives of microflora in the development of enteropathy. Therefore, modulating the intestinal flora with the help of probiotics can be the basic therapeutic strategy for the prevention and treatment of such damage.