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Pepsin Increases the Proliferation of Vocal Cord Leukoplakia Epithelial Cells by Inducing Autophagy.Otolaryngology--head and Neck Surgery :... Nov 2023To investigate the role of H /K ATPase in the proliferation of pepsin-induced vocal cord leukoplakia (VCL) cells.
OBJECTIVE
To investigate the role of H /K ATPase in the proliferation of pepsin-induced vocal cord leukoplakia (VCL) cells.
STUDY DESIGN
Translation research.
SETTING
Affiliated Hospital of University.
METHODS
Immunohistochemistry was used to detect pepsin, H /K ATPase (ATP4A and ATP4B subunits) in VCL cells with varying degrees of dysplasia. After primary cultures of VCL cells had been established, the effects of acidified pepsin on the proliferation, autophagy, and H /K -ATPase distribution of VCL cells were investigated.
RESULTS
The levels of pepsin, ATP4A, and ATP4B were significantly higher in VCL tissue with moderate-to-severe dysplasia than in normal tissue (p < .05); these levels gradually increased according to dysplasia severity. The expression levels of ATP4A and ATP4B were significantly correlated with the amount of pepsin in VCL cells (p < .01). Acidified pepsin enhanced the levels of proliferation and autophagy in human VCL epithelial cells. The cloning- and autophagy-promoting effects of acidified pepsin on VCL cells were partially reversed by pantoprazole; these effects were completely blocked by the autophagy inhibitor chloroquine. Finally, acidified pepsin promoted the colocalization of H /K -ATPase and lysosomes in VCL cells; it also mediated lysosome acidification.
CONCLUSION
Pepsin and H /K -ATPase may contribute to the progression of VCL. Specifically, acidified pepsin may regulate lysosome acidification by promoting lysosomal localization of H /K -ATPase.
Topics: Humans; Pepsin A; Vocal Cords; Laryngeal Diseases; Autophagy; Epithelial Cells; Adenosine Triphosphatases; Cell Proliferation; Leukoplakia
PubMed: 37264983
DOI: 10.1002/ohn.390 -
European Journal of Clinical... Aug 2023In a critical care setting, we aimed to identify and solve physico-chemical drug incompatibilities in central-venous catheters considering the staffs' knowledge and...
PURPOSE
In a critical care setting, we aimed to identify and solve physico-chemical drug incompatibilities in central-venous catheters considering the staffs' knowledge and assumptions about incompatibilities.
METHODS
(i) After positive ethical vote, an algorithm to identify incompatibilities was developed and applied. The algorithm was based on KIK database and Stabilis database, the drug label, and Trissel textbook. (ii) A questionnaire was created and used that asked staff for knowledge and assumptions about incompatibilities. (iii) A 4-step avoidance recommendation was developed and applied.
RESULTS
(i) At least one incompatibility was identified in 64 (61.4%) of 104 enrolled patients. Eighty one (62.3%) of 130 incompatible combinations affected piperacillin/tazobactam and in 18 (13.8%) each furosemide and pantoprazole. (ii) 37.8% (n = 14) of the staff members participated in the questionnaire survey (median age: 31, IQR: 4.75 years). The combination of piperacillin/tazobactam and pantoprazole was incorrectly judged to be compatible by 85.7%. Only rarely felt the majority of respondents unsafe in administering drugs (median score: 1; 0, never to 5, always). (iii) In those 64 patients with at least one incompatibility, 68 avoidance recommendations were given, and all were fully accepted. In 44 (64.7%) of 68 recommendations "Step 1: Administer sequentially" was suggested as a avoidance strategy. In 9/68 (13.2%) "Step 2: Use another lumen", in 7/68 (10.3%) "Step 3: Take a break", and in 8/68 (11.8%) "Step 4: Use catheters with more lumens" were recommended.
CONCLUSIONS
Although incompatibilities were common, the staff rarely felt unsafe when administering drugs. Knowledge deficits correlated well with the incompatibilities identified. All recommendations were fully accepted.
Topics: Humans; Adult; Pantoprazole; Critical Care; Piperacillin, Tazobactam Drug Combination; Algorithms; Catheters
PubMed: 37284873
DOI: 10.1007/s00228-023-03509-0 -
World Journal of Gastrointestinal... Dec 2023Peptic ulcer (PU) is an abnormal phenomenon in which there is rupture of the mucosa of the digestive tract, which not only affects patients' normal life but also causes...
BACKGROUND
Peptic ulcer (PU) is an abnormal phenomenon in which there is rupture of the mucosa of the digestive tract, which not only affects patients' normal life but also causes an economic burden due to its high medical costs.
AIM
To investigate the efficacy of pantoprazole (PPZ) plus perforation repair in patients with PU and its effect on the stress response.
METHODS
The study subjects were 108 PU patients admitted between July 2018 and July 2022, including 58 patients receiving PPZ plus perforation repair [research group (RG)] and 50 patients given simple perforation repair [control group (CG)]. The efficacy, somatostatin (SS) concentration, stress reaction [malondialdehyde (MDA), lipid peroxide (LPO)], inflammatory indices [tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-1β], recurrence, and complications (perforation, hemorrhage, and pyloric obstruction) were compared.
RESULTS
The overall response rate was higher in the RG than in the CG. Patients in the RG had markedly elevated SS after treatment, which was higher than that of the CG, while MDA, LPO, TNF-, CRP, and IL-1β were significantly reduced to lower levels than those in the CG. Lower recurrence and complication rates were identified in the RG group.
CONCLUSION
Therefore, PPZ plus perforation repair is conducive to enhancing treatment outcomes in PU patients, reducing oxidative stress injury and excessive inflammatory reactions, and contributing to low recurrence and complication rates.
PubMed: 38222001
DOI: 10.4240/wjgs.v15.i12.2757 -
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 -
Journal of the American Society of... Apr 2024
PubMed: 38602780
DOI: 10.1681/ASN.0000000000000356 -
Medicine Nov 2023Acute generalized exanthematous pustulosis (AGEP) is a serious adverse skin reaction characterized by the rapid appearance of densely distributed, small, sterile...
RATIONALE
Acute generalized exanthematous pustulosis (AGEP) is a serious adverse skin reaction characterized by the rapid appearance of densely distributed, small, sterile pustules with erythema. However, its pathogenesis is not fully understood. Hydroxychloroquine is widely used for the treatment of autoimmune diseases. Some patients presenting with AGEP have IL36RN and CARD14 gene mutations. Our report describes a patient with rheumatoid arthritis and AGEP associated with hydroxychloroquine and a newly discovered CARD14 gene mutation.
PATIENT CONCERNS
A 28-year-old woman with rheumatoid arthritis, treated with leflunomide therapy without marked relief of joint pain, developed multiple rashes with pruritis covering the body 5 days after switching to hydroxychloroquine treatment.
DIAGNOSES
Based on the patient's history, symptoms, and histopathological findings, AGEP was diagnosed.
INTERVENTIONS
Whole-exome sequencing and Sanger validation revealed no mutations in the IL36RN gene; however, a CARD14 gene mutation was present. The patient was treated using ketotifen fumarate tablets, dexamethasone sodium phosphate, calcium gluconate injection, methylprednisolone injection, vitamins C and B12, hydrocortisone butyrate cream, Reed acne cream, potassium chloride tablets, and pantoprazole enteric-coated capsules.
OUTCOMES
The rash improved after 15 days.
LESSONS SUBSECTIONS
There has been little basic research on AGEP-related genetics, and the CARD14 mutation may underlie several pustular rashes, including AGEP and generalized pustular psoriasis. Follow-up studies and further accumulation of patient data are required.
Topics: Female; Humans; Adult; Hydroxychloroquine; Acute Generalized Exanthematous Pustulosis; Skin; Arthritis, Rheumatoid; Exanthema; Mutation; Guanylate Cyclase; Membrane Proteins; CARD Signaling Adaptor Proteins; Interleukins
PubMed: 38013380
DOI: 10.1097/MD.0000000000036168 -
Future Science OA 2024Ilaprazole due to its pharmacokinetic variability does not affect the clopidogrel efficacy during concomitant use. Prediction of DDI for Clopidogrel and PPIs performed...
Ilaprazole due to its pharmacokinetic variability does not affect the clopidogrel efficacy during concomitant use. Prediction of DDI for Clopidogrel and PPIs performed using (DDI-Pred) Way2Drug software. The probabilities ΔP, which estimate the potential DDIs resulting from interaction with CYP450 isoenzymes. Positive ΔP-values for CYP2C19 (0.955) indicate that it is involved in the drug interaction of Ilaprazole and Clopidogrel. Pantoprazole and Ilaprazole were found to have a low probability of CYP2C19 inhibition Compared with other PPIs, Pantoprazole and Ilaprazole were found to have a low probability of CYP2C19 inhibition; Since Ilaprazole has pharmacokinetic variability, further and studies are required on the ilaprazole and clopidogrel combination to assess the effect of drug-drug interaction.
PubMed: 38817377
DOI: 10.2144/fsoa-2023-0277 -
Food Technology and Biotechnology Dec 2023The role of dietary habits of patients with laryngopharyngeal reflux (LPR) is comparatively underexplored. The aim of the study is to examine dietary habits, onset and...
RESEARCH BACKGROUND
The role of dietary habits of patients with laryngopharyngeal reflux (LPR) is comparatively underexplored. The aim of the study is to examine dietary habits, onset and course of the disease as well as the quality of life of patients with LPR.
EXPERIMENTAL APPROACH
The results of the modified food frequency questionnaire (FFQ-m) and laryngopharyngeal reflux health-related quality of life (LPR-HRQL) questionnaires were compared between subjects with and without LPR. There were a total of 100 subjects with LPR and 65 subjects in the control group. The group of subjects with LPR was further randomly divided into two subgroups; the first subgroup was treated with esomeprazole at a dose of 20 mg twice daily combined with the instructions for dietary and general lifestyle changes, and the other with pantoprazole at a dose of 20 mg twice daily combined with the instructions for dietary and general lifestyle changes. Participants were instructed to fill out FFQ-m and LPR-HRQL questionnaires immediately after the initial examination and then after control examinations 30 and 60 days after the initial examination.
RESULTS AND CONCLUSIONS
Patients with LPR consume more food with high reflux potential, drink more carbonated drinks and juices and have a worse quality of life than the control group (p<0.001). Taking proton pump inhibitors at a dose of 20 mg twice daily in combination with a change in dietary habits such as substituting acidic, spicy, fermented, sweet, fried foods and other foods with a high reflux potential as well as carbonated drinks and juices with the food with a low reflux potential and water significantly reduced the symptoms of LPR and increased the quality of life of the patients (p<0.001).
NOVELTY AND SCIENTIFIC CONTRIBUTION
This is the first study showing the correlation between dietary habits and the quality of life of patients with LPR. The contribution of this research is an objective assessment of the follow-up of patients with LPR that could be used in their regular assessment.
PubMed: 38205049
DOI: 10.17113/ftb.61.04.23.8222 -
Caspian Journal of Internal Medicine 2023() has infected about 50% of the world's population and it is the main cause for peptic ulcer, gastric adenocarcinoma and even a major cause for gastric MALT lymphoma.
BACKGROUND
() has infected about 50% of the world's population and it is the main cause for peptic ulcer, gastric adenocarcinoma and even a major cause for gastric MALT lymphoma.
METHODS
This study was performed in Mazandaran, Sari, situated in North of Iran. Three-hundred and twenty-eight adult patients with endoscopically approved gastric or duodenal ulcers or erosions and infection were randomly divided into 2 groups to receive either 14 days PABT (Pantoprazole 40 mg, Amoxicillin 1 g, Bismuth 425 mg (all twice daily) and Tetracycline 500 mg four times a day) and PACM (Pantoprazole 40 mg, Amoxicillin 1g, Clarithromycin 500 mg, and Metronidazole 500 mg, all twice daily). To evaluate eradication, fecal antigen test was performed 8 weeks after treatment.
RESULTS
The eradication rates were 94.51% in the PABT and 91.46% in PACM group based on the intention to treat analysis. Moreover, the eradication rates were 95.58% and 92.72% according to per-protocol analysis, respectively. Also, both groups had very low rates of severe side effects.
CONCLUSION
Regarding the ideal eradication rates achieved by both treatment groups and the low rates of severe side effects, both treatment protocols can be prescribed for H. pylori eradication in North of Iran.
PubMed: 38024162
DOI: 10.22088/cjim.14.4.676 -
JAMA Network Open Jun 2024Potentially inappropriate medication (PIM) exposes patients to an increased risk of adverse outcomes. Many lists of explicit criteria provide guidance on identifying PIM...
IMPORTANCE
Potentially inappropriate medication (PIM) exposes patients to an increased risk of adverse outcomes. Many lists of explicit criteria provide guidance on identifying PIM and recommend alternative prescribing, but the complexity of available lists limits their applicability and the amount of data available on PIM prescribing.
OBJECTIVE
To determine PIM prevalence and the most frequently prescribed PIMs according to 6 well-known PIM lists and to develop a best practice synthesis for clinicians.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study used anonymized electronic health record data of Swiss primary care patients aged 65 years or older with drug prescriptions from January 1, 2020, to December 31, 2021, extracted from a large primary care database in Switzerland, the FIRE project. Data analyses took place from October 2022 to September 2023.
EXPOSURE
PIM prescription according to PIM criteria operationalized for use with FIRE data.
MAIN OUTCOMES AND MEASURES
The primary outcomes were PIM prevalence (percentage of patients with 1 or more PIMs) and PIM frequency (percentage of prescriptions identified as PIMs) according to the individual PIM lists and a combination of all 6 lists. The PIM lists used were the American 2019 Updated Beers criteria, the French list by Laroche et al, the Norwegian General Practice Norwegian (NORGEP) criteria, the German PRISCUS list, the Austrian list by Mann et al, and the EU(7) consensus list of 7 European countries.
RESULTS
This study included 115 867 patients 65 years or older (mean [SD] age, 76.0 [7.9] years; 55.8% female) with 1 211 227 prescriptions. Among all patients, 86 715 (74.8%) were aged 70 years or older, and 60 670 (52.4%) were aged 75 years or older. PIM prevalence among patients 65 years or older was 31.5% (according to Beers 2019), 15.4% (Laroche), 16.1% (NORGEP), 12.7% (PRISCUS), 31.2% (Mann), 37.1% (EU[7]), and 52.3% (combined list). PIM prevalence increased with age according to every PIM list (eg, according to Beers 2019, from 31.5% at age 65 years or older to 37.4% for those 75 years or older, and when the lists were combined, PIM prevalence increased from 52.3% to 56.7% in those 2 age groups, respectively). PIM frequency was 10.3% (Beers 2019), 3.9% (Laroche), 4.3% (NORGEP), 2.4% (PRISCUS), 6.7% (Mann), 9.7% (EU[7]), and 19.3% (combined list). According to the combined list, the 5 most frequently prescribed PIMs were pantoprazole (9.3% of all PIMs prescribed), ibuprofen (6.9%), diclofenac (6.3%), zolpidem (4.5%), and lorazepam (3.7%). Almost two-thirds (63.5%) of all PIM prescriptions belonged to 5 drug classes: analgesics (26.9% of all PIMs prescribed), proton pump inhibitors (12.1%), benzodiazepines and benzodiazepine-like drugs (11.2%), antidepressants (7.0%), and neuroleptics (6.3%).
CONCLUSIONS AND RELEVANCE
In this cross-sectional study of adults aged 65 or older, PIM prevalence was high, varied considerably depending on the criteria applied, and increased consistently with age. However, only few drug classes accounted for the majority of all prescriptions that were PIM according to any of the 6 PIM lists, and by considering this manageable number of drug classes, clinicians could essentially comply with all 6 PIM lists. These results raise awareness of the most common PIMs and emphasize the need for careful consideration of their risks and benefits and targeted deprescribing.
Topics: Humans; Switzerland; Aged; Cross-Sectional Studies; Primary Health Care; Potentially Inappropriate Medication List; Female; Male; Inappropriate Prescribing; Aged, 80 and over; Prevalence; Practice Patterns, Physicians'
PubMed: 38904960
DOI: 10.1001/jamanetworkopen.2024.17988