pH-independent effects of acid suppressants in dogs and cats: a One Health perspective and case for further investigation.

Our understanding of the use of acid-suppressant drugs (ASDs) in companion animals is largely centered around the treatment of acid-related disorders including gastroesophageal reflux and gastrointestinal ulceration. The companion article by Grady et al, JAVMA, October 2024, summarizes our current knowledge of the efficacy of and indications for ASDs for the treatment of acid-related disorders. Far less is understood about both the benefits of and potential for adverse effects of ASDs outside of the parietal cell including those directed toward inflammation and immunomodulation, tumorigenesis, fibrosis, and oxidative stress. In this Currents in One Health article, we summarize the pH-independent properties of ASDs as demonstrated in studies conducted largely in humans and rodents. The objective of this review is to highlight and increase awareness of the pH-independent effects of ASDs to elucidate the need for further veterinary research in this area.

Rational design on loop regions for precisely regulating flexibility of catalytic center to mitigate overoxidation of prazole sulfides by Baeyer-Villiger monooxygenase.

S-omeprazole and R-rabeprazole are important proton pump inhibitors (PPIs) used for treating peptic disorders. They can be biosynthesized from the corresponding sulfide catalyzed by Baeyer-Villiger monooxygenases (BVMOs). During the development of BVMOs for target sulfoxide preparation, stereoselectivity and overoxidation degree are important factors considered most. In the present study, LnPAMO-Mu15 designed previously and TtPAMO from Thermothelomyces thermophilus showed high (S)- and (R)-configuration stereoselectivity respectively towards thioethers. TtPAMO was found to be capable of oxidating omeprazole sulfide (OPS) and rabeprazole sulfide (RPS) into R-omeprazole and R-rabeprazole respectively. However, the overoxidation issue existed and limited the application of TtPAMO in the biosynthesis of sulfoxides. The structural mechanisms for adverse stereoselectivity between LnPAMO-Mu15 and TtPAMO towards OPS and the overoxidation of OPS by TtPAMO were revealed, based on which, TtPAMO was rationally designed focused on the flexibility of loops near catalytic sites. The variant TtPAMO-S482Y was screened out with lowest overoxidation degree towards OPS and RPS due to the decreased flexibility of catalytic center than TtPAMO. The success in this study not only proved the rationality of the overoxidation mechanism proposed in this study but also provided hints for the development of BVMOs towards thioether substrate for corresponding sulfoxide preparation.

Effect of proton pump inhibitors on susceptibility and melanogenesis of Sporothrix species.

Introduction. Sporotrichosis is a subcutaneous infection caused by dimorphic Sporothrix species embedded in the clinical clade. Fungi have virulence factors, such as biofilm and melanin production, which contribute to their survival and are related to the increase in the number of cases of therapeutic failure, making it necessary to search for new options.Gap statement. Proton pump inhibitors (PPIs) have already been shown to inhibit the growth and melanogenesis of other fungi.Aim. Therefore, this study aimed to evaluate the effect of the PPIs omeprazole (OMP), rabeprazole (RBP), esomeprazole, pantoprazole and lansoprazole on the susceptibility and melanogenesis of Sporothrix species, and their interactions with itraconazole, terbinafine and amphotericin B.Methodology. The antifungal activity of PPIs was evaluated using the microdilution method, and the combination of PPIs with itraconazole, terbinafine and amphotericin B was assessed using the checkerboard method. The assessment of melanogenesis inhibition was assessed using grey scale.Results. The OMP and RBP showed significant MIC results ranging from 32 to 256 µg ml-1 and 32 to 128 µg ml-1, respectively. Biofilms were sensitive, with a significant reduction (P<0.05) in metabolic activity of 52% for OMP and 50% for RBP at a concentration of 512 µg ml-1 and of biomass by 53% for OMP and 51% for RBP at concentrations of 512 µg ml-1. As for the inhibition of melanogenesis, only OMP showed inhibition, with a 54% reduction.Conclusion. It concludes that the PPIs OMP and RBP have antifungal activity in vitro against planktonic cells and biofilms of Sporothrix species and that, in addition, OMP can inhibit the melanization process in Sporothrix species.

Subcellular Fractionation and Metaproteogenomic Identification and Validation of Key Differentially Expressed Molecular Targets for Keloid Disease.

Keloid disease (KD) is a common connective tissue disorder of unknown aetiopathogenesis with ill-defined treatment. Keloid scars present as exophytic fibroproliferative reticular lesions post-cutaneous injury, remain benign yet behave locally aggressive and expansive. To date, there is limited understanding, and validation of biomarkers identified through combined proteomic and genomic evaluation of KD. Therefore, the aim here was to identify putative-causative candidates in KD, by performing a comprehensive proteomics analysis of subcellular fractions as well as the whole cell, coupled with transcriptomics data analysis of normal compared with KD fibroblasts. We then applied novel integrative bioinformatics analyses to demonstrate that NF-kappa-Beta-p65 (RELA) from the cytosolic fraction and Calpain-2 (CAPN2) from the whole cell lysate were significantly up-regulated in KD and associated with alterations in relevant key signalling pathways including apoptosis. Our findings were further confirmed by showing upregulation of both RELA and CAPN2 in KD using flow cytometry and immunohistochemistry. Moreover, functional evaluation using real-time cell analysis and flow cytometry, demonstrated that both omeprazole and dexamethasone inhibited the growth of KD fibroblasts by enhancing the rate of apoptosis. In conclusion, to our knowledge previously unreported, subcellular fractionation and metaproteogenomic analyses have identified two novel biomarkers of relevance to keloid diagnostics and therapeutics.

Should the use of omeprazole be allowed during equestrian competition?

BACKGROUND: Prioritising equine welfare, making evidenced-based policy, and consistent decision-making across sports are crucial to maintaining the social licence for equestrian sport. Regulations on the use of omeprazole during competition differ; all regulators argue that their rules prioritise welfare. This discrepancy is a matter of concern to the public and equestrian stakeholders. OBJECTIVES: To apply Campbell's Ethical Framework for the use of Horses in Sport to the question: 'Should the use of omeprazole be allowed during equestrian competition?' STUDY DESIGN: A desk-based ethico-legal study. METHODS: Campbell's Ethical Framework for the Use of Horses in Sport was applied in a stepwise fashion: definition of the ethical question; analysis of the evidence base; consideration of stakeholders' interests; harm:benefit analysis; application of the three central tenets of the framework, and formulation of conclusions and recommendations. RESULTS: Stakeholders in equine sports have a variety of (frequently conflicting) interests; all of them share an interest in optimising equine welfare. The incidence of EGUS in competition horses is high. Omeprazole is a cornerstone treatment. There are currently discrepancies in regulation about the use of omeprazole during competitions. Recent evidence suggests that withholding omeprazole treatment for two clear days before competition allows the recurrence of squamous EGUS, whereas withholding treatment on the day of competition only does not have that effect. MAIN LIMITATIONS: The current state of scientific knowledge about the use of omeprazole in horses. The analysis did not consider possible health and thus welfare effects of the out-of-competition treatment with omeprazole. CONCLUSIONS: Based on recent scientific evidence, if horses are being treated with omeprazole outside of competition then treatment on the day of competition should be permitted on welfare grounds. Revision of regulations around the use of omeprazole during competition by governing bodies is necessary to safeguard the ethical use of horses in sport.

CONTEXTO: Priorizar o bem­estar equino, elaborar políticas baseadas em evidências e tomar decisões consistentes em todos os esportes são cruciais para manter a licença social para o esporte equestre. As regulamentações sobre o uso de omeprazol durante a competição diferem; todos os reguladores argumentam que suas regras priorizam o bem­estar. Essa discrepância é motivo de preocupação para o público. OBJETIVOS: Aplicar o Modelo Ético de Campbell para o Uso de Cavalos em Esportes1 à pergunta: 'Deve o uso de omeprazol ser permitido durante a competição equestre?' DESENHO DO ESTUDO: Um estudo ético­legal baseado em pesquisa documental. METODOLOGIA: O Modelo Ético de Campbell para o Uso de Cavalos em Esportes1 foi aplicado de forma gradual: definição da questão ética; análise da base de evidências; consideração dos interesses do público alvo; uma análise de dano:benefício; aplicação dos três princípios centrais do modelo; e formulação de conclusões e recomendações. RESULTADOS: O público de esporte equino têm uma variedade de interesses (frequentemente conflitantes), enquanto todos compartilham o interesse em otimizar o bem­estar equino. A incidência de EGUS (Síndrome da Úlcera Gástrica Equina) em cavalos de competição é alta, a qual o omeprazol é um tratamento fundamental. Atualmente, há discrepâncias na regulamentação sobre o uso de omeprazol durante competições. Evidências recentes sugerem que a suspensão do tratamento com omeprazol por 2 dias antes da competição permite a recorrência da EGUS da porção escamosa, enquanto a suspensão do tratamento apenas no dia da competição não tem esse efeito. PRINCIPAIS LIMITAÇÕES: O estado atual do conhecimento científico sobre o uso de omeprazol em cavalos. A análise não considerou possíveis efeitos sobre a saúde e, portanto, sobre o bem­estar do tratamento com omeprazol fora da competição. CONCLUSÕES: Com base em evidências científicas recentes, se os cavalos estão sendo tratados com omeprazol fora da competição, o tratamento no dia da competição deve ser permitido por razões de bem­estar. A revisão das regulamentações sobre o uso de omeprazol durante a competição pelos órgãos reguladores é necessária para salvaguardar o uso ético dos cavalos no esporte.

Establishing Virtual Bioequivalence and Clinically Relevant Specifications for Omeprazole Enteric-Coated Capsules by Incorporating Dissolution Data in PBPK Modeling.

Currently, Biopharmaceutics Classification System (BCS) classes I and III are the only biological exemptions of immediate-release solid oral dosage forms eligible for regulatory approval. However, through virtual bioequivalence (VBE) studies, BCS class II drugs may qualify for biological exemptions if reliable and validated modeling is used. Here, we sought to establish physiologically based pharmacokinetic (PBPK) models, in vitro-in vivo relationship (IVIVR), and VBE models for enteric-coated omeprazole capsules, to establish a clinically-relevant dissolution specification (CRDS) for screening BE and non-BE batches, and to ultimately develop evaluation criteria for generic omeprazole enteric-coated capsules. To establish omeprazole's IVIVR based on the PBPK model, we explored its in vitro dissolution conditions and then combined in vitro dissolution profile studies with in vivo clinical trials. The predicted omeprazole pharmacokinetics (PK) profiles and parameters closely matched the observed PK data. Based on the VBE results, the bioequivalence study of omeprazole enteric-coated capsules required at least 48 healthy Chinese subjects. Based on the CRDS, the capsules' in vitro dissolution should not be < 28%-54%, < 52%, or < 80% after two, three, and six hours, respectively. Failure to meet these dissolution criteria may result in non-bioequivalence. Here, PBPK modeling and IVIVR methods were used to bridge the in vitro dissolution of the drug with in vivo PK to establish the BE safety space of omeprazole enteric-coated capsules. The strategy used in this study can be applied in BE studies of other BCS II generics to obtain biological exemptions and accelerate drug development.

Association between Proton Pump Inhibitor Use and Risk of Incident Chronic Kidney Disease: Systematic Review and Meta-Analysis.

INTRODUCTION: Proton pump inhibitors (PPIs) are among the most commonly prescribed medications. Recently, PPI use has been linked to the development of chronic kidney disease (CKD) and cardiovascular events. Our study aimed to investigate the relationship between PPI use and the incidence of chronic kidney disease using a systematic review and meta-analysis. METHODS: We performed a comprehensive literature search in PubMed, Embase, and Cochrane databases from their inception until March 2024 for relevant studies. We compared outcomes between patients using PPIs, those not using PPIs, and those using histamine-2 receptor antagonists (H2RAs). Endpoints were pooled using the DerSimonian-and-Laird random-effects model as the hazard ratio (HR) with 95% confidence intervals (CIs). RESULTS: Our analysis included twelve studies with a total of 700,125 participants (286,488 on PPIs, 373,848 not on PPIs, and 39,789 on H2RAs), with follow-up periods ranging from three months to 14 years. The current meta-analysis revealed that PPI use is associated with a statistically significant increased risk of incident CKD (HR: 1.26, 95% CI: 1.16-1.38, p < 0.001) compared with non-users. Moreover, the risk of incident CKD is significantly higher in patients with PPI use compared to H2RA use (HR: 1.34, 95% CI: 1.13-1.59, p < 0.001). The results remained unchanged in terms of magnitude and direction after a leave-one-out analysis for both outcomes. CONCLUSIONS: Our multifaceted analysis showed that PPI use was associated with a higher incidence of CKD when compared to non-PPI use and H2RA use, respectively. These findings advocate for heightened vigilance and judicious use of long-term PPIs. Further large prospective longitudinal studies are warranted to validate these observations.

Long-term proton pump inhibitors therapy and prevalence of hyperprolactinaemia: A cross-sectional study in outpatient gastroenterology clinics.

Objectives: To evaluate serum prolactin and macroprolactin levels in patients on long-term proton pump inhibitors therapy. METHODS: The cross-sectional study was conducted from January 2018 to November 2019 after approval from the ethics review committee of the Commission on Science and Technology for Sustainable Development in the South University, Abbottabad, Pakistan. The study included patients from two gastroenterology outpatient clinics in the Khyber Pakhtunkhwa province using proton pump inhibitors for ≥3 months either alone or in combination with either histamine receptor antagonists or prokinetics. Blood samples were collected from each patient for hormonal screening. Data was analysed using SPSS 25. RESULTS: Of the 166 patients, 101(60.8%) were females and 65(39.2%) were males. The overall mean age was 42.5±14.2 years, and the median serum prolactin level was 23.2ng/ml (interquartile range: 14.0-38.0ng/ml). There were 96(58%) patients with normoprolactinaemia and 70(42%) with hypreprolactinaemia. There were 19(11.4%) patients using combination therapy, while the rest were on proton pump inhibitors monotherapy. There was a significant increase in serum prolactin level with combination therapy compared to monotherapy (p=0.001). Patients having treatment duration 11-20 months (p=0.006) and >40 months (p=0.001) were at high risk of developing hyperprolactinaemia. CONCLUSIONS: Long-term use of proton pump inhibitors could increase serum prolactin levels, and appropriate evaluation is essential for clinical management.

Omeprazole-Loaded Copper Nanoparticles for Mitochondrial Damage Mediated Synergistic Anticancer Activity against Melanoma Cells.

Metallic nanoparticles are promising candidates for anticancer therapies. Among the different metallic systems studied, copper is an affordable and biologically available metal with a high redox potential. Copper-based nanoparticles are widely used in anticancer studies owing to their ability to react with intracellular glutathione (GSH) to induce a Fenton-like reaction. However, considering the high metastatic potential and versatility of the tumor microenvironment, modalities with a single therapeutic agent may not be effective. Hence, to enhance the efficiency of chemotherapeutic drugs, repurposing them or conjugating them with other modalities is essential. Omeprazole is an FDA-approved proton pump inhibitor used in clinics for the treatment of ulcers. Omeprazole has also been studied for its ability to sensitize cancer cells to chemotherapy and induce apoptosis. Herein, we report a nanosystem comprising of copper nanoparticles encapsulating omeprazole (CuOzL) against B16 melanoma cells. The developed nanoformulation exerted significant synergistic anticancer activity when compared with either copper nanoparticles or omeprazole alone by inducing cell death through excessive ROS generation and subsequent mitochondrial damage.

Uncommon triggers of insulin autoimmune syndrome: a case report.

BACKGROUND: Insulin autoantibody syndrome (IAS), or Hirata disease, is caused by high concentrations of insulin autoantibodies, which result in spontaneous, mainly post-prandial, hypoglycemic episodes. We report a case of a previously healthy 67-year-old man presenting with recurrent fasting hypoglycemia culminating in a diagnosis of insulin autoimmune syndrome linked to omeprazole and probably spices, namely, coriander, and ginger. CASE PRESENTATION: A previously healthy 67-year-old Sinhalese man presented with recurrent syncopal attacks for 3 months, which were found to be hypoglycemic episodes. He experienced mainly fasting hypoglycemic attacks, at a frequency gradually increasing to daily attacks. His cardiovascular, respiratory, abdominal, and neurologic examinations were normal. He was found to have insulin levels > 6000 mU/L and a post-polyethylene glycol insulin recovery of less than 9.5%. Contrast-enhanced computed tomography of the pancreas was normal. The diagnosis of insulin autoantibody syndrome was confirmed by testing for the insulin autoantibody level, yielding a level of > 300 U/mL. With regard to a possible trigger, he had a history of omeprazole intake for 2 weeks, 4 weeks prior to the onset of symptoms. He also consumed an herbal supplement containing coriander and ginger extracts daily for a period of 1 year, approximately 2 years prior to the onset of hypoglycemic attacks. He was commenced on prednisolone 30 mg daily, and hypoglycemic episodes responded dramatically, and thus he was tapered off corticosteroids. CONCLUSION: Omeprazole-induced insulin autoantibody syndrome is likely in this patient; however, the known hypoglycemic effects of coriander and ginger make it worthwhile to consider a possible association with insulin autoantibody syndrome. In addition, this case report highlights the need to consider insulin autoantibody syndrome even in patients presenting with fasting hypoglycemic attacks.

Analytical quality by design-based development of a capillary electrophoresis method for Omeprazole impurity profiling.

Omeprazole (OME) is a proton pump inhibitor used to treat gastroesophageal reflux disease associated conditions. The current study presents an Analytical Quality by Design-based approach for the development of a CE method for OME impurity profiling. The scouting experiments suggested the selection of solvent modified Micellar ElectroKinetic Chromatography operative mode using a pseudostationary phase composed of sodium dodecyl sulfate (SDS) micelles and n-butanol as organic modifier in borate buffer. A symmetric three-level screening matrix 37//16 was used to evaluate the effect of Critical Method Parameters, including Background Electrolyte composition and instrumental settings, on Critical Method Attributes (critical resolution values, OME peak width and analysis time). The analytical procedure was optimized using Response Surface Methodology through a Central Composite Orthogonal Design. Risk of failure maps made it possible to define the Method Operable Design Region, within which the following optimized conditions were selected: 72 mM borate buffer pH 10.0, 96 mM SDS, 1.45 %v/v n-butanol, capillary temperature 21 °C, applied voltage 25 kV. The method was validated according to ICH guidelines and robustness was evaluated using a Plackett-Burman design. The developed procedure enables the simultaneous determination of OME and seven related impurities, and has been successfully applied to the analysis of pharmaceutical formulations.

Protective effect of astaxanthin on indomethacin-induced gastric ulcerations in mice.

Gastric ulcer disease remains one of the common medical burdens affecting millions worldwide due to its prevalent risk factors with the chronic usage of non-steroidal anti-inflammatory drugs at the top, reportedly through the stimulation of oxidative stress and triggering of inflammatory and apoptotic cascades in the gastric mucosa. Astaxanthin, a dietary keto-carotenoid derived from marine organisms is gaining a wide interest as a nutraceutical for its pronounced antioxidant properties. Here, we aim to examine the potential modulatory role of astaxanthin on indomethacin-induced gastric ulceration in experimental mice. Twenty-four Swiss albino mice were randomly distributed into four groups: a control group, an indomethacin group, and two groups pre-treated with either omeprazole or astaxanthin. The gastric tissues were assessed using gross morphology, ulcer scoring, gastric juice acidity, as well as reduced glutathione (GSH) and malondialdehyde (MDA) levels. Histopathological examination and immunostaining for nuclear factor-kappa B (NF-κB) and caspase-3 levels were also employed. Indomethacin group tended to show a higher number of mucosal ulcerations relative to control and pre-treated groups. The indomethacin group also showed significantly lower GSH levels and higher MDA levels relative to control. Immunostaining of gastric tissue sections showed a higher reactivity to NF-κB and caspase-3 in indomethacin group. Astaxanthin pre-treatment significantly elevated gastric juice pH, normalized GSH levels, and lowered the indomethacin-induced elevations in MDA, NF-κB, and caspase-3 levels. These results indicate that astaxanthin exhibits a comparable protective effect to omeprazole, against indomethacin-induced gastric ulceration. This anti-ulcerogenic effect could be mediated through its antioxidant, anti-inflammatory, and anti-apoptotic modulatory activities.

Retrospective evaluation of the effect of acid suppressant drugs on leukocyte ratios in dogs with mast cell tumors.

BACKGROUND: Acid suppressant drugs (ASDs) are commonly used to decrease gastric acid production, but some evidence exists that ASDs exert immunomodulatory effects. Such an effect has not been investigated in dogs for which ASDs are routinely prescribed. HYPOTHESIS: Compared to naïve subjects, dogs treated with ASDs will exhibit differences in leukocyte ratios after treatment. ANIMALS: Fifty-one dogs with mast cell tumors (MCTs). MATERIALS AND METHODS: Dogs with MCT that were either AS naïve or treated with ASDs (i.e., histamine-2-receptor antagonists [H2RA] or proton pump inhibitors [PPI]) were included in this retrospective study. Subjects were categorized into 3 treatment groups (AS naïve, H2RA treated, and PPI treated), and leukocyte ratios (neutrophil:eosinophil, lymphocyte:monocyte, and neutrophil:lymphocyte [NLR]) were calculated before and after treatment. A mixed effects analysis of variance on ranks was used to assess differences in ratios between treatments, between pre- and post-treatment time points, and between pre- and post-time points for each treatment. Concurrent administration of antihistamines, corticosteroids, and chemotherapeutic drugs was assessed as a confounding factor. RESULTS: Famotidine (n = 14/14) and omeprazole (n = 12/12) were the only H2RA and PPI used, respectively. Dogs receiving famotidine had a significant increase in median NLR from pre- to post-treatment (3.429; range, 1.417-15 to 5.631; range, 2.654-92; P < 0.01) compared to PPI treated or AS naïve dogs. No differences existed in chemotherapeutic drug or corticosteroid use between groups. CONCLUSIONS: A significant difference in NLR was identified in famotidine treated dogs compared with omeprazole treated or AS naïve dogs.

Nuevas herramientas para la revisión de la medicación: PRM en pacientes en tratamiento con inhibidores de la bomba de protones / New tools for medication review: DRP in patients treatment with proton pump inhibitors

Objetivo Analizar mediante el programa de revisión de la medicación, Revisem®, la prevalencia de problemas relacionados con la medicación (PRM) en pacientes de la provincia de Valencia que estaban en tratamiento activo con inhibidores de la bomba de protones (IBP) en 2022. Diseño Estudio observacional descriptivo y retrospectivo. Material y métodos Se analizó el historial farmacoterapéutico (HFT) de 295 pacientes siguiendo los criterios propuestos por la Pharmaceutical Care Network Europe, utilizando la plataforma digital Revisem® del Muy Ilustre Colegio Oficial de Farmacéuticos de Valencia (MICOF). Resultados La edad media de los pacientes fue 81,8 ± 11,1 años y 66,4% fueron mujeres. Se detectó al menos un PRM en 97,3% de los pacientes. De los PRM analizados, 46,9% fueron interacciones, de las cuales 29,7% implicaban un IBP, siendo el omeprazol el de mayor frecuencia. Los PRM con IBP se relacionan de forma significativa con determinadas condiciones del paciente y grupos farmacológicos, como son el sexo femenino, la edad superior a 54 años y la polifarmacia. Conclusiones La plataforma digital Revisem®, permite la detección de una alta prevalencia de PRM a nivel provincial. La aplicación de nuevas herramientas tecnológicas para detectar la prevalencia de PRM es fundamental para optimizar los tratamientos de los pacientes. (AU)

Objective To analyze, using the medication review program, Revisem®, the prevalence of drug-related problems (DRP) in patients in the province of Valencia who were on active treatment with proton pump inhibitors (PPI) in 2022. Design Descriptive and retrospective observational study. Material and methods The pharmacotherapeutic history of 295 patients was analyzed following the criteria proposed by the Pharmaceutical Care Network Europe, using the Revisem® digital platform of the Muy Ilustre Colegio Oficial de Farmacéuticos (MICOF). Results The mean age of the patients was 81.8 ± 11.1 years and 66.4% were women. At least one DRP was detected in 97.3% of patients. 46.9% of the DRP analyzed were interactions, of which 29.7% involved a PPI, with omeprazole being the most frequent. DRPs with PPI are significantly related to certain patient conditions and pharmacological groups, such as female sex, age over 54 years and polypharmacy. Conclusions The application of the Revisem® digital platform allows the detection of a high prevalence of DRP at the provincial level. The application of new technological tools to detect the prevalence of DRP is essential to optimize patient treatments. (AU)

Omeprazole and risk of osteoarthritis: insights from a mendelian randomization study in the UK Biobank.

BACKGROUND: A former cohort study has raised concern regarding the unanticipated hazard of omeprazole in expediting osteoarthritis (OA) advancement. The precise nature of their causal evidence, however, remains undetermined. The present research endeavors to investigate the underlying causal link between omeprazole and OA through the application of mendelian randomization (MR) analysis. METHODS: The study incorporated the ukb-a-106 and ukb-b-14,486 datasets. The investigation of causal effects employed methodologies such as MR-Egger, Weighted median, Inverse variance weighted (IVW) with multiplicative random effects, and IVW (fixed effects). The IVW approach was predominantly considered for result interpretation. Sensitivity analysis was conducted, encompassing assessments for heterogeneity, horizontal pleiotropy, and the Leave-one-out techniques. RESULTS: The outcomes of the MR analysis indicated a causal relationship between omeprazole and OA, with omeprazole identified as a contributing risk factor for OA development (IVW model: OR = 1.2473, P < 0.01 in ukb-a-106; OR = 1.1288, P < 0.05 in ukb-b-14,486). The sensitivity analysis underscored the robustness and dependability of the above-mentioned analytical findings. CONCLUSION: This study, employing MR, reveals that omeprazole, as an exposure factor, elevates the risk of OA. Considering the drug's efficacy and associated adverse events, clinical practitioners should exercise caution regarding prolonged omeprazole use, particularly in populations with heightened OA risks. Further robust and high-quality research is warranted to validate our findings and guide clinical practice.

Omeprazole taken once every other day can effectively prevent aspirin-induced gastrointestinal mucosal damage in rats.

BACKGROUND: Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such as gastric polyps and enterochromaffin-like cell hyperplasia. Current research indicates that the abovementioned adverse reactions are mainly related to hypergastrinemia. We investigated whether low-frequency administration of omeprazole could effectively repair aspirin-induced mucosal damage and reduce the increase in gastrin levels associated with long-term use of PPIs. METHODS: Sprague‒Dawley rats were divided into four treatment groups: daily aspirin, daily aspirin and omeprazole once every day (qd), daily aspirin and omeprazole once every other day (qod), and daily aspirin and omeprazole once every three days (1/d3). After 15 days of feeding, blood samples were collected, and the stomachs of sacrificed rats were subjected to macroscopic, histological, and immunohistochemical studies. Moreover, in clinical practice, patients with peptic ulcers caused by aspirin took a standard dose of omeprazole (20 mg) every other day. Two months later, gastroscopy was performed to examine the healing of the ulcers. RESULTS: Both the omeprazole qd and omeprazole qod administrations effectively prevented aspirin-induced gastric peptic ulcers, with no significant difference between the two groups in the inhibition of parietal cell secretion of gastric acid and cell apoptosis. However, omeprazole 1/d3 failed to completely prevent aspirin-induced gastric mucosal injury. Notably, the gastrin levels, cell proliferation ability and cholecystokinin B receptor expression of the omeprazole qd group were significantly higher than those of the omeprazole qod group. In clinical work, patients with peptic ulcers caused by aspirin were given a standard dose of omeprazole every other day, and their ulcers healed after 2 months, as observed by gastroscopy. CONCLUSIONS: Omeprazole administration once every other day can effectively prevent aspirin-induced peptic ulcers and reduce hypergastrinemia, which may reduce the long-term adverse effects of PPI treatment.

The Role of Proton Pump Inhibitors in the Realm of Idiopathic Pulmonary Fibrosis and its Associated Comorbidities: A Systematic Review.

As the global incidence of idiopathic pulmonary fibrosis (IPF) is on the rise, there is a need for better diagnostic criteria, better treatment options, early and appropriate diagnosis, adequate care, and a multidisciplinary approach to the management of patients. This systematic review explores the role of proton pump inhibitors (PPIs) in IPF and answers the question, "Does proton pump inhibitor improve only the prognosis of gastroesophageal associated idiopathic pulmonary fibrosis or for other types of idiopathic pulmonary fibrosis too?" We used PubMed (PMC) and Google Scholar for data collection for this systematic review and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for conducting this review. After in-depth literature screening and quality appraisal, 12 articles were selected for this systematic review. On the one hand, the efficacy of PPI therapy is supported by research such as the CAPACITY and ASCEND trials, a pilot randomized control trial (RCT) investigating the role of omeprazole in IPF and a bidirectional two-sample Mendelian randomization (MR) study, respectively. On the other hand, a systematic review and meta-analysis on antacid and antireflux surgery in IPF negate these results and show no statistical significance. Questions regarding the efficacy of PPI therapy must be dealt with in an adequately powered multicenter and double-blinded randomized control trial. The anti-inflammatory properties of antacids can serve as the cornerstone for future trials. In the following systematic review, antacid, antireflux therapy, omeprazole, and proton pump therapy are synonymous with stomach acid suppression therapy.

Prospective Randomized Controlled Clinical Trial of the Long-Term Effects of Omeprazole on Healthy Dogs.

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 (T0), 30 days after the start of treatment (T1), and at 60 days (T2). The mean cobalamin value (ng/L) in the control group was 481.4 (±293.70) at T0, 481.4 (±170.21) at T1, and 513.2 (±174.50) at T2. In the omeprazole group, the values were 424.62 (±161.57) at T0, 454.5 (±160.96) at T1, and 414.87 (±127.90) at T2. 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 T0, 76.06 [30.67-199.87] at T1, and 63.02 [35.81-176.06] at T2. The median gastrin value in the omeprazole group was 67.59 [55.96-101.60] at T0, 191.77 [75.31-1901.77] at T1, and 128.16 [43.62-1066.46] at T2. Statistically significant differences were detected (p = 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.

The Ptk2-Pma1 pathway enhances tolerance to terbinafine in Trichophyton rubrum.

The increasing prevalence of dermatophyte resistance to terbinafine, a key drug in the treatment of dermatophytosis, represents a significant obstacle to treatment. Trichophyton rubrum is the most commonly isolated fungus in dermatophytosis. In T. rubrum, we identified TERG_07844, a gene encoding a previously uncharacterized putative protein kinase, as an ortholog of budding yeast Saccharomyces cerevisiae polyamine transport kinase 2 (Ptk2), and found that T. rubrum Ptk2 (TrPtk2) is involved in terbinafine tolerance. In both T. rubrum and S. cerevisiae, Ptk2 knockout strains were more sensitive to terbinafine compared with the wild types, suggesting that promotion of terbinafine tolerance is a conserved function of fungal Ptk2. Pma1 is activated through phosphorylation by Ptk2 in S. cerevisiae. Overexpression of T. rubrum Pma1 (TrPma1) in T. rubrum Ptk2 knockout strain (ΔTrPtk2) suppressed terbinafine sensitivity, suggesting that the induction of terbinafine tolerance by TrPtk2 is mediated by TrPma1. Furthermore, omeprazole, an inhibitor of plasma membrane proton pump Pma1, increased the terbinafine sensitivity of clinically isolated terbinafine-resistant strains. These findings suggest that, in dermatophytes, the TrPtk2-TrPma1 pathway plays a key role in promoting intrinsic terbinafine tolerance and may serve as a potential target for combinational antifungal therapy against terbinafine-resistant dermatophytes.

Efficacy and safety of empiric treatment with omeprazole continuous infusion in critically ill children with gastrointestinal bleeding.

Introduction: Gastrointestinal bleeding (GI) is a prevalent condition among pediatric patients, with a reported incidence of 6.4%, often severe enough to require admission to the pediatric intensive care unit (PICU). There are multiple therapies utilized in the management of GI bleeding in pediatrics, among which continuous intravenous (IV) infusion of omeprazole is used off-label without standard pediatric dosing recommendations. Reviewing the current literature reveals a lack of studies assessing the efficacy, safety, and appropriate dosing regimen of continuous omeprazole infusion in children with GI bleeding. This study aimed to evaluate the efficacy and safety of continuous IV omeprazole infusion in comparison to other therapeutic modalities in children. Methods: This study is a single-center, retrospective chart review of children admitted to the PICU at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. The treatment group included pediatric patients with GI bleeding and receiving omeprazole IV continuous infusion over ≥24 h while the control group included pediatric patients with GI bleeding managed using other therapies. Primary outcomes were the efficacy of omeprazole continuous infusion in stopping GI bleeding, and PICU length of stay (LOS). Secondary outcomes included instances of rebleeding post- therapy discontinuation, transfusion requirements, and the safety of omeprazole continuous infusion. Results: The study included 81 critically ill pediatric patients, 22 of whom received continuous infusion omeprazole while 59 received other therapies. The results indicated that patients in the control group had a significantly shorter PICU LOS (8 vs. 18.5 days, p < 0.001) and bleeding episode (4 vs. 10.5 days, p < 0.001) than those in the treatment group. However, no significant differences were observed between the two groups regarding secondary outcomes. The treatment group had a significantly lower all-cause mortality rate during hospitalization compared to the control group (16 patients [72.7%] vs. 56 patients [94.9%], respectively, p = 0.005). Conclusion: Empirical use of omeprazole continuous intravenous infusion in children with GI bleeding was not favorable in terms of shortening PICU LOS and duration of GI bleeding. Our study results provide evidence supporting the safety and tolerability of omeprazole continuous infusion. Additional larger studies are necessary to determine the implication of such results.