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PloS One 2024The objectives of the present study were to evaluate the acute toxicity, gastroprotective, therapeutic, anti-inflammatory and anti H. pylori activities of T. vulgaris...
The objectives of the present study were to evaluate the acute toxicity, gastroprotective, therapeutic, anti-inflammatory and anti H. pylori activities of T. vulgaris total plant extract against ethanol-induced gastric ulcers in Sprague Dawley rats. Animals were divided into five groups i.e G-1 (Normal Control), Group 2 (ulcer control) were administered orally with 0.5% Carboxymethylcellulose (CMC), Group 3 (omeprazole treated) was administered orally with 20 mg/kg of omeprazole and Groups 4 and 5 (Low dose and High dose of the extract) were administered orally with 250, and 500 mg/ kg of Thymus vulgaris extract, respectively. After 1 hour, the normal group was orally administered with 0.5% CMC (5 ml/kg), whereas absolute alcohol (5ml/ kg) was orally administered to the ulcer control group, omeprazole group, and experimental groups. Stomachs were examined macroscopically and microscopically. Grossly, rats pre-treated with T. vulgaris demonstrated significantly decreased ulcer area and an increase in mucus secretion and pH of gastric content compared with the ulcer control group. Microscopy of gastric mucosa in the ulcer control group showed severe damage to gastric mucosa with edema and leukocytes infiltration of the submucosal layer. However, rats pretreated with omeprazole or Thyme vulgaris exhibited a mild to moderate disruption of the surface epithelium and lower level of edema and leukocyte infiltration of the submucosal layer. The T. vulgaris extract caused up-regulation of Hsp70 protein, down-regulation of Bax protein, and intense periodic acid Schiff uptake of the glandular portion of the stomach. Gastric mucosal homogenate of rats pre-treated with T. vulgaris exhibited significantly increased superoxide dismutase (SOD) and catalase (CAT) activities while malondialdehyde (MDA) level was significantly decreased. Based on the results showed in this study, Thymus vulgaris extract can be proposed as the safe medicinal plants for use and it has considerable gastroprotective potential via stomach epithelium protection against gastric ulcers and stomach lesions.
Topics: Rats; Animals; Rats, Sprague-Dawley; Stomach Ulcer; Thymus Plant; Ulcer; Ethanol; Plant Extracts; Gastric Mucosa; Omeprazole; Antioxidants; Anti-Ulcer Agents; Edema
PubMed: 38271407
DOI: 10.1371/journal.pone.0287569 -
The Korean Journal of Gastroenterology... Apr 2024() is the most prevalent infection in the world and is strongly associated with gastric adenocarcinoma, lymphoma and gastric or duodenal ulcers. Different regimens have... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND/AIMS
() is the most prevalent infection in the world and is strongly associated with gastric adenocarcinoma, lymphoma and gastric or duodenal ulcers. Different regimens have been used for eradication. We aimed to compare the efficacy of two different regimens as first-line eradication regimens, in an area with high antibiotic resistance.
METHODS
In this RCT, we assigned 223 patients with infection, who were naïve to treatment. They were randomly divided into two groups to receive either 12-day concomitant quadruple therapy (consisting of pantoprazole 40 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg every 12 hours) or 14-day high dose dual therapy (consisting of esomeprazole 40 mg and amoxicillin 1 g TDS). eradication was assessed eight weeks after the end of treatment.
RESULTS
eradication rate by PP analysis for 12-day concomitant quadruple therapy and 14-day high dose dual therapy were 90.4% and 79.1%, respectively (p=0.02). According to ITT analysis, the eradication rates were 86.2% and 76.3%, respectively (p=0.06). Adverse drug reactions were 12.3% in high dose dual therapy and 36.8% in concomitant quadruple therapy (p<0.001).
CONCLUSIONS
Twelve-day concomitant therapy seems to be an acceptable regimen for first-line eradication in Iran, a country with a high rate of antibiotic resistance. Although, high dose dual therapy did not result in an ideal eradication rate, but it had fewer drug side effects than the 12-day concomitant regimen.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Amoxicillin; Anti-Bacterial Agents; Clarithromycin; Drug Administration Schedule; Drug Therapy, Combination; Esomeprazole; Helicobacter Infections; Helicobacter pylori; Metronidazole; Pantoprazole; Proton Pump Inhibitors; Treatment Outcome
PubMed: 38659251
DOI: 10.4166/kjg.2024.012 -
BMC Health Services Research Jan 2024Uganda imports approximately 90% of its medicines, with about 60% being distributed by the private sector. To discourage importation and promote local production of 37...
BACKGROUND
Uganda imports approximately 90% of its medicines, with about 60% being distributed by the private sector. To discourage importation and promote local production of 37 selected locally manufactured medicines, the Ugandan government through the Ministry of Health in 2017 increased the import verification fees from 2 to 12%. The increase in verification fees ultimately affects cost and availability of these medicines. This study aimed to assess the cost and availability of the selected essential medicines after the 12% increase in verification fees in Uganda.
METHODS
A cross sectional study among 328 wholesale and retail pharmacies and seven key informant interviews was conducted using a pretested data collection checklist and in-depth interview guide from February to September 2021 in Uganda. Data on the availability and prices of the medicines before (2017) and after (2020) the increase in verification fees was collected. Paired sample T-Test was used to test if there is a significant difference in prices before and after the 12% increase in verification fees.
RESULTS
Mean availability of imported medicines was higher (54.8%, CI: 49.3-60.4) than the locally produced medicines (37.1%, CI: 31.9-42.7) except for locally manufactured parenteral preparations (54.6.%, CI: 49.1-60.1). Availability of locally produced medicines was mainly low (45%) while the imported medicines were fairly high (74%). Most commonly available locally manufactured medicines were Surgical spirit (89.9%), ORS (86%), Dextrose 5% solution (74.4%), Paracetamol 500 mg Tablets (73.8%) and Sodium Chloride 0.9% solution (72.9%). Most commonly available imported medicines were; Omeprazole 20 mg (94.2%), Amoxicillin Trihydrate 125 mg/5 ml (92.4%), Ciprofloxacin 500 mg (91.4%), Paracetamol Suspension 120 mg/5 ml (91.5%) and Metronidazole 200 mg Tablets (88.1%). Increase in lowest-priced local and imported medicines was significant for 10 (23.8%) and 7 (15.9%) of the medicines respectively. The median prices of imported medicines were generally higher than locally produced medicines. The median unit prices of 12 (28.6%) locally produced medicines and 20 (47.6%) imported medicines were higher than the international median unit prices.
CONCLUSIONS
The overall availability of imported medicines was still higher than the local medicines. The median prices of local and imported medicines generally increased or remained the same after the introduction of import verification fees. There is a need for price controls and transparency in the private sector.
Topics: Humans; Cross-Sectional Studies; Acetaminophen; Public Sector; Health Services Accessibility; Drugs, Essential; Checklist
PubMed: 38178109
DOI: 10.1186/s12913-023-10433-7 -
Animals : An Open Access Journal From... Dec 2023A one-year-old, female intact Samoyed, 12.5 kg, was presented with coughing for 2 weeks, progressive appendicular and axial muscle weakness, megaesophagus and labored...
A one-year-old, female intact Samoyed, 12.5 kg, was presented with coughing for 2 weeks, progressive appendicular and axial muscle weakness, megaesophagus and labored breathing for 5 days. There was no improvement with standard treatment. Acquired myasthenia gravis was suspected and the dog was referred with increasing dyspnea. At presentation, the dog showed a severely reduced general condition, was non-ambulatory and showed abdominal and severely labored breathing. A marked hypercapnia (PvCO = 90.1 mmHg) was present in venous blood gas analysis. The serum anti-acetylcholine receptor antibody test was consistent with acquired myasthenia gravis (2.1 nmol/L). The dog was anesthetized with propofol and mechanically ventilated with a Hamilton C1 ventilator. Immunoadsorption was performed with the COM.TEC and ADAsorb platforms and a LIGASORB adsorber to eliminate anti-acetylcholine receptor antibodies. Local anticoagulation was performed with citrate. Treatment time for immunoadsorption was 1.5 h with a blood flow of 50 mL/min. A total plasma volume of 1.2 L was processed. Further medical treatment included intravenous fluid therapy, maropitant, esomeprazole, antibiotic therapy for aspiration pneumonia and neostigmine 0.04 mg/kg intramuscularly every 6 h for treatment of acquired myasthenia gravis. Mechanical ventilation was stopped after 12 h. A percutaneous gastric feeding tube was inserted under endoscopic control on day 2 for further medical treatment and nutrition. A second treatment with immunoadsorption was performed on day 3. Again, a total plasma volume of 1.2 L was processed. Immediately after this procedure, the dog regained muscle strength and was able to stand and to walk. After 6 days, the dog was discharged from the hospital. This is the first report of immunoadsorption for emergency management of a dog with acute-fulminant acquired myasthenia gravis. Immunoadsorption may be an additional option for emergency treatment in dogs with severe signs of acquired myasthenia gravis.
PubMed: 38200764
DOI: 10.3390/ani14010033 -
Nutrients Nov 2023The objective of this research was to explore the protective impact of walnut peptides (WP) against ethanol-induced acute gastric mucosal injury in mice and to...
The objective of this research was to explore the protective impact of walnut peptides (WP) against ethanol-induced acute gastric mucosal injury in mice and to investigate the underlying defense mechanisms. Sixty male BALB-c mice were divided into five groups, and they were orally administered distilled water, walnut peptides (200 and 400 mg/kg bw), and omeprazole (20 mg/kg bw) for 24 days. Acute gastric mucosal injury was then induced with 75% ethanol in all groups of mice except the blank control group. Walnut peptides had significant protective and restorative effects on tissue indices of ethanol-induced gastric mucosal damage, with potential gastric anti-ulcer effects. Walnut peptides significantly inhibited the excessive accumulation of alanine aminotransferase (ALT), aspartate transferase (AST), and malondialdehyde (MDA), while promoting the expression of reduced glutathione (GSH), total antioxidant capacity (T-AOC), glutathione disulfide (GSSG), and mouse epidermal growth factor (EGF). Furthermore, the Western blot analysis results revealed that walnut peptides significantly upregulated the expression of HO-1 and NQO1 proteins in the Nrf2 signaling pathway. The defensive impact of walnut peptides on the gastric mucosa may be achieved by mitigating the excessive generation of lipid peroxides and by boosting cellular antioxidant activity.
Topics: Mice; Male; Animals; Ethanol; Juglans; Peptides; Stomach Ulcer; Gastric Mucosa; Glutathione; Antioxidants
PubMed: 38068724
DOI: 10.3390/nu15234866 -
Gastroenterology Apr 2024High-dose proton pump inhibitor (PPI) therapy has been recommended to prevent rebleeding of high-risk peptic ulcer (PU) after hemostasis. Vonoprazan has been proven to...
Comparison of Vonoprazan vs Intravenous Proton Pump Inhibitor for Prevention of High-Risk Peptic Ulcers Rebleeding After Successful Endoscopic Hemostasis: A Multicenter Randomized Noninferiority Trial.
BACKGROUND & AIMS
High-dose proton pump inhibitor (PPI) therapy has been recommended to prevent rebleeding of high-risk peptic ulcer (PU) after hemostasis. Vonoprazan has been proven to be noninferior to PPIs in various acid-related diseases. This study aimed to compare the efficacy of vonoprazan vs PPI for preventing high-risk PU rebleeding after hemostasis.
METHODS
A multicenter, randomized, noninferiority study was conducted in 6 centers. Pre-endoscopic and endoscopic therapy were performed according to standard protocol. After successful hemostasis, patients with high-risk PU bleeding (Forrest class Ia/Ib, IIa/IIb) were randomized into 1:1 to receive vonoprazan (20 mg twice a day for 3 days, then 20 mg once a day for 28 days) or high-dose PPI (pantoprazole intravenous infusion 8 mg/h for 3 days, then omeprazole 20 mg twice a day for 28 days). The primary outcome was a 30-day rebleeding rate. Secondary outcomes included 3- and 7-day rebleeding rate, all-cause and bleeding-related mortality, rate of rescue therapy, blood transfusion, length of hospital stay, and safety.
RESULTS
Of 194 patients, baseline characteristics, severity of bleeding, and stage of ulcers were comparable between the 2 groups. The 30-day rebleeding rates in vonoprazan and PPI groups were 7.1% (7 of 98) and 10.4% (10 of 96), respectively; noninferiority (within 10% margin) of vonoprazan to PPI was confirmed (%risk difference, -3.3; 95% confidence interval, -11.2 to 4.7; P < .001). The 3-day and 7-day rebleeding rates in the vonoprazan group remained noninferior to PPI (P < .001 by Farrington and Manning test). All secondary outcomes were also comparable between the 2 groups.
CONCLUSION
In patients with high-risk PU bleeding, the efficacy of vonoprazan in preventing 30-day rebleeding was noninferior to intravenous PPI. (ClinicalTrials.gov, Number: NCT05005910).
PubMed: 38582271
DOI: 10.1053/j.gastro.2024.03.036 -
Molecules (Basel, Switzerland) Feb 2024is an important edible and medicinal plant, with the polysaccharide (DOP) being its primary active constituent, known for its diverse biological activities. In this...
is an important edible and medicinal plant, with the polysaccharide (DOP) being its primary active constituent, known for its diverse biological activities. In this study, DOP was extracted and characterized for its structural properties. The potential of DOP to ameliorate gastric ulcers (GUs) was investigated using an acetic-acid-induced GU model in rats. The results demonstrated that DOP exerted a multifaceted protective effect against GU, mitigating the deleterious impact on food intake and body weight in rats. DOP exhibited its protective action by attenuating cellular damage attributed to oxidative stress and inflammatory reactions mediated by enhanced activities of SOD, GSH, and GSH-PX, coupled with a downregulation in the expression of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α. Furthermore, DOP effectively inhibited apoptosis in gastric mucosa cells of acetic-acid-induced GU rat models and facilitated the self-repair of damaged tissues. Remarkably, the DOP-200 and DOP-400 groups outperformed omeprazole in reducing the expression of IL-6 and malondialdehyde (MDA) in tissues, as well as IL-1β, IL-6, and TNF-α in serum. These groups also exhibited an improved expression of SOD in tissues and SOD, GSH, and GSH-PX in serum. A Western blot analysis of gastric mucosa demonstrated that the DOP-200 and DOP-400 groups significantly reduced the expression of NF-κBp65, phosphorylated NF-κBp65, FoxO3a, and Bim. The observed antagonism to GU appeared to be associated with the NF-κB cell pathway. Additionally, qRT-PCR results indicate that DOP reduced the mRNA transcription levels of IL-6, and TNF-α, which shows that the healing of GU is related to the reduction in the inflammatory reaction by DOP. However, the expression of EGF and VEGF decreased, suggesting that the mechanism of DOP inhibiting GU may not be directly related to EGF and VEGF, or there is an uncertain competitive relationship between them, so further research is needed.
Topics: Rats; Animals; Dendrobium; Acetic Acid; Tumor Necrosis Factor-alpha; Stomach Ulcer; Epidermal Growth Factor; Interleukin-6; Vascular Endothelial Growth Factor A; Polysaccharides; Superoxide Dismutase
PubMed: 38398633
DOI: 10.3390/molecules29040880 -
Animals : An Open Access Journal From... Apr 2024The use of omeprazole as a preventive treatment for gastrointestinal ulcers in veterinary medicine has been questioned during previous years. The aim of the present...
The use of omeprazole as a preventive treatment for gastrointestinal ulcers in veterinary medicine has been questioned during previous years. The aim of the present study is to assess the long-term effect of omeprazole on cobalamin and serum gastrin levels in healthy dogs. Eighteen healthy dogs were included: 10 in the control group and 8 in the omeprazole group. Three samples were collected: before starting the treatment (T), 30 days after the start of treatment (T), and at 60 days (T). The mean cobalamin value (ng/L) in the control group was 481.4 (±293.70) at T, 481.4 (±170.21) at T, and 513.2 (±174.50) at T. In the omeprazole group, the values were 424.62 (±161.57) at T, 454.5 (±160.96) at T, and 414.87 (±127.90) at T. No statistically significant changes were detected in cobalamin levels between the three-time period in both study groups. These results agree with previous findings in felines but contrast with human medicine studies. The median gastrin values (pg/mL) in the control group were 62.45 [30.17-218.75] at T, 76.06 [30.67-199.87] at T, and 63.02 [35.81-176.06] at T. The median gastrin value in the omeprazole group was 67.59 [55.96-101.60] at T, 191.77 [75.31-1901.77] at T, and 128.16 [43.62-1066.46] at T. Statistically significant differences were detected ( = 0.008), indicating an increase in gastrin levels after initiating treatment with omeprazole. In conclusion, the increased levels of gastrin observed in this population underscore the importance of conducting a comprehensive clinical assessment to identify potential gastrointestinal disorders, particularly in consideration of the usage of omeprazole as a preventive treatment.
PubMed: 38672316
DOI: 10.3390/ani14081168 -
Pharmacology Research & Perspectives Oct 2023Nivasorexant, a selective orexin-1-receptor antagonist, has recently been assessed in the treatment of humans with binge-eating disorder. Herein, the inhibitory...
Effect of nivasorexant (ACT-539313), a selective orexin-1-receptor antagonist, on multiple cytochrome P450 probe substrates in vitro and in vivo using a cocktail approach in healthy subjects.
Nivasorexant, a selective orexin-1-receptor antagonist, has recently been assessed in the treatment of humans with binge-eating disorder. Herein, the inhibitory potential of nivasorexant on cytochromes P450 (CYPs) 2C9, 2C19, and 3A4 was evaluated. Human liver microsomes/recombinant CYP enzymes were evaluated in vitro. In vivo, a single-center, open-label, fixed-sequence study was performed in healthy adults to explore the effect of 100 mg nivasorexant administered twice daily (b.i.d.) on the pharmacokinetics (PK) of flurbiprofen (50 mg, CYP2C9), omeprazole (20 mg, CYP2C19), midazolam (2 mg, CYP3A4) making use of a cocktail approach. Plasma PK sampling was performed over 24 h on Day 1 (Cocktail alone), 8 (Cocktail + nivasorexant), and 15 (Cocktail + nivasorexant at steady state). Genotyping of subjects' CYPs was performed while safety and tolerability were also assessed. In vitro, nivasorexant inhibited CYP2C9, 2C19, and 3A4 in competitive inhibition assays with IC values of 8.6, 1.6, and 19-44 μM, respectively, while showing a significant time-dependent CYP2C19 inhibition. In 22 subjects, exposure to flurbiprofen, omeprazole, and midazolam was generally higher during concomitant single- (i.e., area under the plasma concentration-time curve [AUC] ratio increased by 1.04-, 2.05-, and 1.56-fold, respectively) and repeated-dose (i.e., AUC ratio increased by 1.47-, 6.84-, and 3.71-fold, respectively) nivasorexant administration compared with the cocktail substrates administered alone. The most frequently reported adverse event was somnolence. According to regulatory guidance, nivasorexant is classified as a moderate CYP2C19 and weak CYP3A4 inhibitor after 1 day and as a weak CYP2C9, strong CYP2C19, and moderate CYP3A4 inhibitor after 8 days of 100 mg b.i.d. administration. Clinicaltrials.gov ID: NCT05254548.
Topics: Adult; Humans; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C9; Orexins; Midazolam; Cytochrome P-450 CYP3A Inhibitors; Healthy Volunteers; Flurbiprofen; Drug Interactions; Cytochrome P-450 Enzyme System; Omeprazole
PubMed: 37800597
DOI: 10.1002/prp2.1143 -
Scientific Reports Dec 2023Patients with enteral access usually receive oral drugs via feeding tubes and correct drug administration remains a challenge. The aim of this study was to identify...
Patients with enteral access usually receive oral drugs via feeding tubes and correct drug administration remains a challenge. The aim of this study was to identify common medication delivery errors (MDEs) in outpatients with percutaneous endoscopic gastrostomy (PEG) and evaluate their association with the need for tube replacement due to deterioration or clogging. A 2-year retrospective study that comprised adult outpatients with a placed/replaced PEG tube and whose electronic medical record included home medication was carried out. Treatment with medication that should not be crushed and administered through an enteral feeding tube was considered an MDE. We included 269 patients and 213 MDEs (20% of oral prescriptions) were detected in 159. Ninety-two percent of the medications associated with MDEs could be substituted by appropriate formulations. Tube replacement due to obstruction was needed in 85 patients. MDEs were associated with increased risk for tube replacement (OR 2.17; 95% CI 1.10-4.27). Omeprazole enteric-coated capsules were associated with the greatest risk (OR 2.24; 95% CI 1.01-4.93). PEG outpatients are highly exposed to MDEs, leading to a significant increase in the odds of tube replacement, mainly when treated with omeprazole. The use of appropriate alternative therapies would prevent unnecessary adverse events.
Topics: Adult; Humans; Enteral Nutrition; Gastrostomy; Outpatients; Retrospective Studies; Omeprazole
PubMed: 38066068
DOI: 10.1038/s41598-023-48629-w