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European Journal of Case Reports in... 2021Drugs can cause fever of unknown origin. Drug fever is a diagnosis of exclusion and can lead to unnecessary investigations and prolonged hospitalization. Any drug can be...
UNLABELLED
Drugs can cause fever of unknown origin. Drug fever is a diagnosis of exclusion and can lead to unnecessary investigations and prolonged hospitalization. Any drug can be responsible. Here, we describe the case of a woman admitted because of acute hepatitis. Pantoprazole was started for stress ulcer prophylaxis when she was admitted to the ICU. Fever developed a few days later and an extensive diagnostic work-up was negative. Fever remitted after pantoprazole discontinuation and the diagnosis of drug fever was established.
LEARNING POINTS
Despite extensive diagnostic work-up, the aetiology of acute liver failure remains unclear in a large proportion of cases.Drug fever is a diagnosis of exclusion and must be considered in every patient with unexplained fever; any drug should be seen as a possible offending agent.Pantoprazole, a commonly prescribed drug, can be a rare cause of fever.
PubMed: 34123946
DOI: 10.12890/2021_002571 -
Cardiovascular Therapeutics Apr 2015The safety of all proton pump inhibitors (PPIs) in patients with intrinsic cardiac disease has not been well studied. In the present study, the effect of PPI... (Comparative Study)
Comparative Study
BACKGROUND
The safety of all proton pump inhibitors (PPIs) in patients with intrinsic cardiac disease has not been well studied. In the present study, the effect of PPI pantoprazole on ventricular arrhythmias induced by either ischemia or ischemia-reperfusion (I/R) was studied.
METHODS
The left main coronary artery (LAD) was ligated for 30 or 10 min followed by a 30-min reperfusion in anesthetized rats. Rats were pretreated with pantoprazole (1.3 mg/kg) or vehicle by gastric gavage (daily for 3 weeks) before ligation. Serum electrolytes levels were measured by the end of the third week before coronary ligation. Lactate dehydrogenase (LDH) activity and nitric oxide (NO) concentrations were measured at the end of the ischemia and IR injury.
RESULTS
Pantoprazole caused significant hyperkalemia by the end of third week compared with vehicle-treated rats. After LAD ligation (30 min), ventricular premature contractions (VPC), ventricular tachycardia (VT) and ventricular fibrillation (VF) were recorded in rats of the vehicle ischemia group. Pantoprazole pretreatment aggravate these arrhythmias and increased mortality. A 10-min period of ischemia followed by a 30-min reperfusion induced high incidence of VT (100%) and VF (80%) in the vehicle-treated group. The group of rats administered pantoprazole had significantly lower incidence and durations of VT and VF together with reduction of mortality rate. Pantoprazole significantly reduced serum LDH activity and NO release from myocardial tissue after both ischemia and I/R injury.
CONCLUSION
Pantoprazole aggravated ischemia-induced arrhythmias but had a significant antiarrhythmic effect on I/R-induced ventricular arrhythmias.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Disease Models, Animal; Heart Conduction System; Hyperkalemia; L-Lactate Dehydrogenase; Male; Myocardial Ischemia; Myocardial Reperfusion Injury; Nitric Oxide; Pantoprazole; Proton Pump Inhibitors; Rats, Wistar; Tachycardia, Ventricular; Time Factors; Ventricular Fibrillation; Ventricular Premature Complexes
PubMed: 25677801
DOI: 10.1111/1755-5922.12107 -
Frontiers in Oncology 2021The effective and economical therapeutic strategy for metastatic castration-resistant prostate cancer (mCRPC) is still requested from patients, who are not available for...
The effective and economical therapeutic strategy for metastatic castration-resistant prostate cancer (mCRPC) is still requested from patients, who are not available for Lu-177 or Ra-223 treatment. Drug repurposing as a cost-effective and time-saving alternative to traditional drug development has been increasingly discussed. Proton pump inhibitors (PPIs) such as pantroprazole, which are commonly used as antacids, have also been shown to be effective in cancer chemoprevention induction of apoptosis in multiple cancer cell lines. Vitamin C is an essential micronutrient for human body, has been proposed as a potential anti-cancer agent. In this context, have we investigated the combination of vitamin C and pantoprazole for the management of metastatic castration-resistant prostate cancer (mCRPC). Six chosen human adenocarcinoma cell lines were used to investigate the influence of pantoprazole on the microenvironment of cancer cells (extracellular pH and production of exosomes). Tumor growth and tumor 18F-FDG uptake in PC3 xenografts were analyzed following varied treatment. Our Results have suggested that pantoprazole enhanced the cytotoxic activity of vitamin C by regulating pH values and production of exosomes in cancer cells. Moreover, the synergistic effect of pantoprazole and vitamin C was pH-dependent since pantoprazole was more effective at a slightly acidic pH. In vivo, the combined treatment using pantoprazole and vitamin C produced better therapeutic outcomes than treatment with vitamin C or pantoprazole alone, as demonstrated tumor growth and uptake of 18F-FDG. Therefore, we suggest that pantoprazole combined with vitamin C could be as a possible strategy to manage mCRPC.
PubMed: 34307134
DOI: 10.3389/fonc.2021.660320 -
American Journal of Translational... 2021To investigate the protective effect of teprenone on gastric mucosal injury induced by dual antiplatelet therapy in rats.
OBJECTIVE
To investigate the protective effect of teprenone on gastric mucosal injury induced by dual antiplatelet therapy in rats.
METHODS
Healthy, specifically pathogen free SD, rats were selected and divided into 4 groups: Normal group (normal rats, without any treatment), Model group (rats received dual antiplatelet therapy: aspirin and clopidogrel), Teprenone group (rats received dual antiplatelet therapy and teprenone) and Pantoprazole group (rats received dual antiplatelet therapy and pantoprazole). The gastric mucosal blood flow, ulcer index, gastric gel mucus thickness, the levels of gastrin (Gas), prostaglandin (PG), prostaglandin E (PGE), endothelin-1 (ET-1) tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-10 in serum, the levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and myeloperoxidase (MPO) in the gastric mucosa, as well as the expression of vascular endothelial growth factor (VEGF) in the rat's stomach were measured.
RESULTS
Compared with the Normal group, the other groups showed more severe gastric injury, elevated levels of inflammatory factors (TNF-α, IL-1β, IL-6 and IL-10), elevated levels of MDA and MPO, as well as reduced levels of GSH, SOD and VEGF (all P<0.05). Compared with the Model group, the gastric mucosal lesions in the Teprenone group and the Pantoprazole group were improved significantly (both P<0.05). Compared with the Pantoprazole group, the Teprenone group had reduced levels of ET-1 and elevated levels of PG and PGE (all P<0.05).
CONCLUSION
Teprenone protects against gastric mucosal injury induced by dual antiplatelet therapy through inhibiting gastric mucosal inflammation inhibiting oxidative stress and improving gastric mucosa indices.
PubMed: 34017431
DOI: No ID Found -
World Journal of Gastroenterology Nov 2021The use of proton pump inhibitors (PPI) is common worldwide, with reports suggesting that they may be overused. Several studies have found that PPI may affect colorectal...
BACKGROUND
The use of proton pump inhibitors (PPI) is common worldwide, with reports suggesting that they may be overused. Several studies have found that PPI may affect colorectal cancer (CRC) risk.
AIM
To summarize current knowledge on the relationship between PPI and CRC from basic research, epidemiological and clinical studies.
METHODS
This systematic review was based on the patients, interventions, comparisons, outcome models and performed according to PRISMA guidelines. MEDLINE, EMBASE, Scopus, and Web of Science databases were searched from inception until May 17, 2021. The initial search returned 2591 articles, of which, 28 studies met the inclusion criteria for this review. The studies were categorized as basic research studies ( = 12), epidemiological studies ( = 11), and CRC treatment studies ( = 5). The quality of the included studies was assessed using the Newcastle-Ottawa Scale or Cochrane Risk of Bias 2.0 tool depending on the study design.
RESULTS
Data from basic research indicates that PPI do not stimulate CRC development the trophic effect of gastrin but instead may paradoxically inhibit it. These studies also suggest that PPI may have properties beneficial for CRC treatment. PPI appear to have anti-tumor properties (omeprazole, pantoprazole), and are potential T lymphokine-activated killer cell-originated protein kinase inhibitors (pantoprazole, ilaprazole), and chemosensitizing agents (pantoprazole). However, these mechanisms have not been confirmed in human trials. Current epidemiological studies suggest that there is no causal association between PPI use and increased CRC risk. Treatment studies show that concomitant PPI and capecitabine use may reduce the efficacy of chemotherapy resulting in poorer oncological outcomes, while also suggesting that pantoprazole may have a chemosensitizing effect with the fluorouracil, leucovorin, oxaliplatin (FOLFOX) regimen.
CONCLUSION
An unexpected inhibitory effect of PPI on CRC carcinogenesis by way of several potential mechanisms is noted. This review identifies that different PPI agents may have differential effects on CRC treatment, with practical implications. Prospective studies are warranted to delineate this relationship and assess the role of individual PPI agents.
Topics: Capecitabine; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Proton Pump Inhibitors
PubMed: 34908809
DOI: 10.3748/wjg.v27.i44.7716 -
Wiadomosci Lekarskie (Warsaw, Poland :... 2021The aim: Was to characterize the morphological peculiarities of the gastric mucosa at early stage of prescription of acetylsalicylic acid (ASA) and clopidogrel as well...
OBJECTIVE
The aim: Was to characterize the morphological peculiarities of the gastric mucosa at early stage of prescription of acetylsalicylic acid (ASA) and clopidogrel as well as to study the impact of pantoprazole on the gastric mucosa to optimize the prophylaxis and treatment of gastropathies induced by ASA and clopidogrel.
PATIENTS AND METHODS
Materials and methods: The experiments were performed on 77 non-linear white male rats with the average weight of 150-180 g. Depending on the aim of research, the animals were divided into 7 groups.
RESULTS
Results: The administration of pantoprazole in combination with ASA and clopidogrel presented positive trends in neutral glycoproteins amount and contributes to preventing GM necrotic lesions by amplification of protective properties of mucus and stabilization of apoptotic activity of gastric epithelial cells.
CONCLUSION
Conclusions: 1. According to our study findings, administration of ASA in combination with clopidogrel results in 2,5 times higher risk of GM erosive lesions. 2. One of the most significant morphological manifestations of gastropathy in ASA and clopidogrel regimen is the development of microerosions, which are poorly diagnosed by macroscopic examination. 3. The use of PAS-reaction makes possible to identify damage to the basal membrane of superficial epitheliocytes, which may be a top-priority morphological criterion of gastropathy induced by ASA or clopidogrel in the absence of an inflammatory reaction. 4. Administration of pantoprazole in combination with ASA and clopidogrel contributes to preventing GM necrotic lesions by amplification of protective properties of mucus and stabilization of apoptotic activity of gastric epithelial cells.
Topics: Animals; Aspirin; Clopidogrel; Gastric Mucosa; Male; Pantoprazole; Rats; Ticlopidine
PubMed: 33813477
DOI: No ID Found -
Frontiers in Veterinary Science 2020Neonatal calves are at risk of developing abomasal ulceration, but there is a lack of pharmacokinetic data for potential anti-ulcerative therapies, such as...
Neonatal calves are at risk of developing abomasal ulceration, but there is a lack of pharmacokinetic data for potential anti-ulcerative therapies, such as pantoprazole, in ruminant species. The study objectives were to estimate plasma pharmacokinetic parameters for pantoprazole in neonatal dairy calves after intravenous (IV) administration. A secondary objective was to quantify the concentrations of pantoprazole in edible tissues after IV dosing. Pantoprazole was administered to 9 neonatal Holstein calves at a dose of 1 mg/kg IV. Plasma samples were collected over 24 h and analyzed via HPLC-MS for determining pantoprazole concentrations. Pharmacokinetic parameters were derived via non-compartmental analysis. Tissue samples were collected at 1, 3, and 5 days after administration and analyzed via HPLC-MS. Following IV administration, plasma clearance, elimination half-life, and volume of distribution of pantoprazole were estimated at 4.46 mL/kg/min, 2.81 h, and 0.301 L/kg, respectively. The global extraction ratio was estimated at 0.053 ± 0.015. No pantoprazole was detected in the edible tissues 1, 3, or 5 days after administration. A metabolite, pantoprazole sulfone was detected in all the edible tissues 1 and 3 days after administration. The reported plasma clearance for pantoprazole is less than that reported for alpacas but higher than reported in foals. The elimination half-life in calves appears to be longer than observed in foals and alpacas. While pantoprazole sulfone was detected in the tissues after IV administration, further research is needed as to the metabolism and potential tissue accumulation of other pantoprazole metabolites in calves. Future pharmacodynamic studies are necessary to determine the efficacy of pantoprazole on abomasal acid suppression in calves.
PubMed: 33330703
DOI: 10.3389/fvets.2020.580735 -
Cell Death & Disease Oct 2019MET overactivation is one of the crucial reasons for tyrosine kinase inhibitor (TKI) resistance, but the mechanisms are not wholly clear. Here, COX2, TOPK, and MET...
MET overactivation is one of the crucial reasons for tyrosine kinase inhibitor (TKI) resistance, but the mechanisms are not wholly clear. Here, COX2, TOPK, and MET expression were examined in EGFR-activating mutated NSCLC by immunohistochemical (IHC) analysis. The relationship between COX2, TOPK, and MET was explored in vitro and ex vivo. In addition, the inhibition of HCC827GR cell growth by combining COX2 inhibitor (celecoxib), TOPK inhibitor (pantoprazole), and gefitinib was verified ex vivo and in vivo. We found that COX2 and TOPK were highly expressed in EGFR-activating mutated NSCLC and the progression-free survival (PFS) of triple-positive (COX2, MET, and TOPK) patients was shorter than that of triple-negative patients. Then, we observed that the COX2-TXA signaling pathway modulated MET through AP-1, resulting in an inhibition of apoptosis in gefitinib-resistant cells. Moreover, we demonstrated that MET could phosphorylate TOPK at Tyr74 and then prevent apoptosis in gefitinib-resistant cells. In line with these findings, the combination of celecoxib, pantoprazole, and gefitinib could induce apoptosis in gefitinib-resistant cells and inhibit tumor growth ex vivo and in vivo. Our work reveals a novel COX2/MET/TOPK signaling axis that can prevent apoptosis in gefitinib-resistant cells and suggests that a triple combination of FDA-approved drugs would provide a low-cost and practical strategy to overcome gefitinib resistance.
Topics: A549 Cells; Animals; Carcinoma, Non-Small-Cell Lung; Celecoxib; Cell Proliferation; Cyclooxygenase 2; Drug Resistance, Neoplasm; Female; Gefitinib; Gene Expression Regulation, Neoplastic; Humans; Male; Mice; Mitogen-Activated Protein Kinase Kinases; Pantoprazole; Progression-Free Survival; Proto-Oncogene Proteins c-met; Signal Transduction; Xenograft Model Antitumor Assays
PubMed: 31611604
DOI: 10.1038/s41419-019-2020-4 -
Wiadomosci Lekarskie (Warsaw, Poland :... 2021The aim: Of the work was to determine the content of pro- and anti-inflammatory cytokines in the blood serum of the control group rats and after 28 days of inhibiting...
OBJECTIVE
The aim: Of the work was to determine the content of pro- and anti-inflammatory cytokines in the blood serum of the control group rats and after 28 days of inhibiting HCl secretion in the stomach by proton pump blockers "Omeprazole" and "Pantoprazole".
PATIENTS AND METHODS
Materials and methods: The studies were performed on 30 white non-linear male rats weighing 160-180 g, divided into three groups with 10 animals in each. The control (group 1) were injected intraperitoneally with water for injections within 28 days once a day. Group 2 was administered omeprazole. Group 3 was administered pantoprazole. The concentration of cytokines in the blood serum of rats was determined by the enzyme immunoassay method. For statistic data processing, Student's t-criterion for independent samples was applied.
RESULTS
Results: After prolonged administration of omeprazole and pantoprazole, the blood serum concentrations of IFNγ, TNFα, IL-1 in rats increased by 58.5% and 3.41%, 73.3% and 48.4%, 80.2% and 40.8%, respectively, and IL-12B 40p decreased by 36.6% when using omeprazole and was almost indistinguishable from the control values when pantoprazole was administered. With administration of omeprazole, IL-4 concentration decreased by 39.8% and that of pantoprazole increased by 3.86% compared to the control. Administration of omeprazole and pantoprazole did not affect IL-6 concentration.
CONCLUSION
Conclusion: Inhibition of hydrochloric acid secretion in the stomach of rats for 28 days using omeprazole and pantoprazole led to an imbalance between pro- and anti-inflammatory cytokines. The adverse effect of pantoprazole was less pronounced than that of omeprazole.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Animals; Benzimidazoles; Cytokines; Male; Proton Pump Inhibitors; Serum; Sulfoxides
PubMed: 34459754
DOI: No ID Found -
Przeglad Gastroenterologiczny 2018Proton pump inhibitors therapy success in the treatment of gastroesophageal reflux disease (GERD) is a difficult task because the extent of mucosal damage has no...
INTRODUCTION
Proton pump inhibitors therapy success in the treatment of gastroesophageal reflux disease (GERD) is a difficult task because the extent of mucosal damage has no relation with the severity of the symptoms.
AIM
To establish the efficacy of pantoprazole treatment in patients with erosive reflux disease (ERD) and in those with non-erosive reflux disease (NERD), by assessing symptom relief and quality of life. Treatment duration and adverse events associated with pantoprazole treatment were analysed.
MATERIAL AND METHODS
This meta-analysis was based on three multicentre, prospective, open-label, phase IV trials conducted in Slovenia, Poland, and the Russian Federation. In total, 252 patients with GERD were included and treated with pantoprazole 40 mg once daily for 4 or 8 weeks, depending on the fulfilment of predefined healing criteria. Symptoms were assessed by patients on a scale from 0 to 3 and the quality of life on a rating scale from 1 to 10.
RESULTS
Forty-five percent of patients fulfilled the healing criteria after 4 weeks of treatment, and 70% of patients after 8 weeks of treatment. Patients who failed to reach the healing criteria reported significant reduction of symptoms severity. The response to 8-week treatment was significantly higher in patients with ERD (76%) when compared to patients with NERD (64%). Discontinuation of treatment after 4 weeks was not associated with worsening of symptoms and did not affect quality of life. Pantoprazole treatment was associated with improvement of symptoms and the quality of life of GERD patients over 8 weeks of treatment and showed that GERD patients with persisting symptoms benefit from prolonging treatment to 8 weeks. Treatment with pantoprazole 40 mg was very well tolerated - more than 90% of patients were without adverse events throughout the whole study and only 4 patients discontinued the treatment due to adverse events related to pantoprazole treatment.
CONCLUSIONS
Pantoprazole 40 mg was associated with complete relief of GERD-related symptoms in the majority of patients with ERD and NERD. Furthermore, the severity of symptoms was significantly reduced in patients without complete relief of symptoms. Pantoprazole also continuously improved the quality of life of GERD patients over 8 weeks of treatment and was very well tolerated throughout the whole study. Therefore, this meta-analysis suggests that pantoprazole 40 mg once daily is an effective and well-tolerated choice for providing symptom relief of patients with GERD.
PubMed: 29657605
DOI: 10.5114/pg.2018.74556