-
Przeglad Gastroenterologiczny 2024The eradication rate of () has decreased due to antibiotics resistance and inadequate acid suppression. Vonoprazan is a novel potassium-competitive acid blocker...
INTRODUCTION
The eradication rate of () has decreased due to antibiotics resistance and inadequate acid suppression. Vonoprazan is a novel potassium-competitive acid blocker (P-CAB), which has a rapid and sustained acid inhibitory effect and may be more effective than conventional proton pump inhibitors (PPIs) in eradication.
AIM
to study the efficacy and safety of vonoprazan as a component of first-line eradication treatment compared with conventional PPI-based therapy.
MATERIAL AND METHODS
This randomised (one to one) non-blinded study was conducted on 400 consecutive proven infected patients, of whom 200 received vonoprazan-based triple therapy, while 200 patients received PPI-based triple therapy for 14 days. The study outcomes were evaluated as eradication rate and adverse events in both patient groups.
RESULTS
The eradication rate was 86% in the vonoprazan group and 74.5% in the PPI group. The vonoprazan eradication rate was significantly higher than that of PPIs ( = 0.004). There was no significant difference regarding adverse events between both patient groups.
CONCLUSIONS
Vonoprazan-based therapy was more effective than PPI-based therapy as a first-line eradication treatment. Vonoprazan was generally safe and well tolerated.
PubMed: 38939071
DOI: 10.5114/pg.2024.139426 -
Przeglad Gastroenterologiczny 2024Proton pump inhibitors (PPIs) are effective drugs used for multiple gastrointestinal complications. They are commonly used in both hospitalised and outpatients. However,...
INTRODUCTION
Proton pump inhibitors (PPIs) are effective drugs used for multiple gastrointestinal complications. They are commonly used in both hospitalised and outpatients. However, little is known about its utilisation pattern in ambulatory patients.
AIM
To evaluate the inexpedient continuous use of PPIs in patients with respect to treatment duration.
MATERIAL AND METHODS
A cross-sectional observational study was conducted from January 2018 to November 2019 in Khyber Pakhtunkhwa, Pakistan. Regular proton pump inhibitor users were identified through patient histories.
RESULTS
During the study period, 171 patients were included using a non-probability consecutive sampling technique, who were using regular proton pump inhibitors for a longer duration, i.e. from 3 months to 15 years. The highest proportion (42.8%) were using PPI regularly from 3 months to 1 year followed by 22.9% for 1-2 years, 12.0% for 2-3 years, 7.8% for 3-4 years, 4.2% for 4-5 years, and 10.24% for > 5 years. Omeprazole and esomeprazole were the most commonly used drugs, with 71.1% and 23.5% prevalence, respectively. A total of 33.73% of patients had continued PPI use on their own after initially being prescribed by the physician.
CONCLUSIONS
It can be deduced that PPIs are used in outpatients beyond standard treatment guidelines. The inexpedient continuous use of proton pump inhibitors is of concern due to the risk of developing adverse effects. Therefore, patient counselling and periodic monitoring must be carried out to prevent the irrational use of PPIs.
PubMed: 38939068
DOI: 10.5114/pg.2024.139429 -
Molecular Therapy. Nucleic Acids Sep 2024Effective therapeutics are necessary for managing severe COVID-19 disease despite the availability of vaccines. Small interfering RNA (siRNA) can silence viral genes and...
Effective therapeutics are necessary for managing severe COVID-19 disease despite the availability of vaccines. Small interfering RNA (siRNA) can silence viral genes and restrict SARS-CoV-2 replication. Cell-penetrating peptides is a robust method for siRNA delivery, enhancing siRNA stability and targeting specific receptors. We developed a peptide HE25 that blocks SARS-CoV-2 replication by various mechanisms, including the binding of multiple receptors involved in the virus's internalization, such as ACE2, integrins and NRP1. HE25 not only acts as a vehicle to deliver the SARS-CoV-2 RNA-dependent RNA polymerase siRNA into cells but also facilitates their internalization through endocytosis. Once inside endosomes, the siRNA is released into the cytoplasm through the Histidine-proton sponge effect and the selective cleavage of HE25 by cathepsin B. These mechanisms effectively inhibited the replication of the ancestral SARS-CoV-2 and the Omicron variant BA.5 . When HE25 was administered , either by intravenous injection or inhalation, it accumulated in lungs, veins and arteries, endothelium, or bronchial structure depending on the route. Furthermore, the siRNA/HE25 complex caused gene silencing in lung cells . The SARS-CoV-2 siRNA/HE25 complex is a promising therapeutic for COVID-19, and a similar strategy can be employed to combat future emerging viral diseases.
PubMed: 38939051
DOI: 10.1016/j.omtn.2024.102227 -
Biomedical Reports Aug 2024Despite proton pump inhibitors (PPIs) being generally safe, there are questions about their potential long-term complications. The present study aimed to investigate the...
Despite proton pump inhibitors (PPIs) being generally safe, there are questions about their potential long-term complications. The present study aimed to investigate the association between PPI therapy and the incidence of hepatic steatosis and liver fibrosis in the outpatient population of the United States. The present study included 7,395 individuals aged ≥20 years who underwent hepatic vibration-controlled transient elastography (VCTE) examination. The data were obtained from the January 2017 to March 2020 pre-pandemic National Health and Nutrition Examination Survey. Among the 7,395 adults who were included (mean age, 50.59 years; 3,656 male), 9.8% were prescribed PPIs. Following multivariable adjustment, the use of PPIs was significantly associated with hepatic steatosis [odds ratio (OR), 1.25; 95% confidence interval (CI), 1.02-1.53]. Prolonged use of PPIs was found to increase the risk of developing hepatic steatosis over time (P=0.006). Sensitivity analyses using different definitions of hepatic steatosis, such as a controlled attenuation parameter ≥285 dB/m (OR, 1.19; CI, 1.01-1.40), non-alcoholic fatty liver disease (OR, 1.50; 95% CI, 1.16-1.93) and metabolic dysfunction-associated steatotic liver disease (OR, 1.26; 95% CI, 1.05-1.52), consistently demonstrated an association between PPI prescription and hepatic steatosis. The administration of PPI therapy was linked with hepatic steatosis in US adults, although no significant association was observed with liver stiffness, as determined by VCTE.
PubMed: 38938738
DOI: 10.3892/br.2024.1804 -
CHEST Critical Care Jun 2024Acute brain dysfunction during sepsis, which manifests as delirium or coma, is common and is associated with multiple adverse outcomes, including longer periods of...
BACKGROUND
Acute brain dysfunction during sepsis, which manifests as delirium or coma, is common and is associated with multiple adverse outcomes, including longer periods of mechanical ventilation, prolonged hospital stays, and increased mortality. Delirium and coma during sepsis may be manifestations of alteration in systemic metabolism. Because access to brain mitochondria is a limiting factor, measurement of peripheral platelet bioenergetics offers a potential opportunity to understand metabolic changes associated with acute brain dysfunction during sepsis.
RESEARCH QUESTION
Are altered platelet mitochondrial bioenergetics associated with acute brain dysfunction during sepsis?
STUDY DESIGN AND METHODS
We assessed participants with critical illness in the ICU for the presence of delirium or coma via validated assessment measures. Blood samples were collected and processed to isolate and measure platelet mitochondrial oxygen consumption. We used Seahorse extracellular flux to measure directly baseline, proton leak, maximal oxygen consumption rate, and extracellular acidification rate. We calculated adenosine triphosphate-linked, spare respiratory capacity, and nonmitochondrial oxygen consumption rate from the measured values.
RESULTS
Maximum oxygen consumption was highest in patients with coma, as was spare respiratory capacity and extracellular acidification rate in unadjusted analysis. After adjusting for age, sedation, modified Sequential Organ Failure Assessment score without the neurologic component, and preexisting cognitive function, increased spare respiratory capacity remained associated with coma. Delirium was not associated with any platelet mitochondrial bioenergetics.
INTERPRETATION
In this single-center exploratory prospective cohort study, we found that increased platelet mitochondrial spare respiratory capacity was associated with coma in patients with sepsis. Future studies powered to determine any relationship between delirium and mitochondrial respiration bioenergetics are needed.
PubMed: 38938510
DOI: 10.1016/j.chstcc.2024.100076 -
Scientific Reports Jun 2024In this study, polymer-coated anisotropic inorganic nanowires dispersed in PBI matrix were introduced to construct 1D proton conducting channels within PBI. Ionic-liquid...
In this study, polymer-coated anisotropic inorganic nanowires dispersed in PBI matrix were introduced to construct 1D proton conducting channels within PBI. Ionic-liquid and solvothermal methods were used for the synthesis of ZrO and WO NWs, which were coated with PVPA and PDDA polymers to increase their proton conductivity. Our results showed that, prepared membranes have amorphous nature due to the dominating presence of PBI. SEM analysis revealed the average thickness of membrane of about 36 µm. TG/DTA analysis detected lower weight loss of WO NWs (total 2.8%) compared to ZrO NWs (18%). Proton conductivity analysis showed that, PDDA/WO NWs possess relatively 4 times higher proton conductivity (4 10 Scm) compared to PDDA/ZrO NWs (1 10 Scm) at 80 ℃. In addition, PDDA-coated WO NWs dispersed PBI membranes showed the highest fuel cell current density (1.2 A/cm) and power density (215 mW/cm) at 150 ℃ after 24 h which is nearly 2.5 times higher than pure PBI membrane. In addition, they exhibited the lowest in-situ proton resistance of about (0.47 Ω) compared with that of pure PBI membrane (0.8 Ω). Our results are introducing new concepts towards the development of thin and efficient polymer electrolyte membranes for PEM fuel cells.
PubMed: 38937620
DOI: 10.1038/s41598-024-65955-9 -
Journal of Molecular Biology Jun 2024GPR68 is a proton-sensing G-protein Coupled Receptor (GPCR) involved in a variety of physiological processes and disorders including neoplastic pathologies. While GPR68...
GPR68 is a proton-sensing G-protein Coupled Receptor (GPCR) involved in a variety of physiological processes and disorders including neoplastic pathologies. While GPR68 and few other GPCRs have been shown to be activated by a decrease in the extracellular pH, the molecular mechanism of their activation remains largely unknown. In this work, we used a combined computational and in vitro approach to provide new insight into the activation mechanism of the receptor. Molecular Dynamics simulations of GPR68 were used to model the changes in residue interactions and motions triggered by pH. Global and local rearrangements consistent with partial activation were observed upon protonation of the inactive state. Selected extracellular histidine and transmembrane acidic residues were found to have significantly upshifted pK values during the simulations, consistently with their previously hypothesised role in activation through changes in protonation state. Moreover, a novel pairing between histidine and acidic residues in the extracellular region was highlighted by both sequence analyses and simulation data and tested through site-directed mutagenesis. At last, we identified a previously unknown hydrophobic lock in the extracellular region that might stabilise the inactive conformation and regulate the transition to the active state.
PubMed: 38936694
DOI: 10.1016/j.jmb.2024.168688 -
Gut Microbes 2024The microbiota significantly impacts digestive epithelium functionality, especially in nutrient processing. Given the importance of iron for both the host and the...
The microbiota significantly impacts digestive epithelium functionality, especially in nutrient processing. Given the importance of iron for both the host and the microbiota, we hypothesized that host-microbiota interactions fluctuate with dietary iron levels. We compared germ-free (GF) and conventional mice (SPF) fed iron-containing (65 mg/Kg) or iron-depleted (<6 mg/Kg) diets. The efficacy of iron privation was validated by iron blood parameters. Ferritin and Dmt1, which represent cellular iron storage and transport respectively, were studied in tissues where they are abundant: the duodenum, liver and lung. When the mice were fed an iron-rich diet, the microbiota increased blood hemoglobin and hepcidin and the intestinal ferritin levels, suggesting that the microbiota helps iron storage. When iron was limiting, the microbiota inhibited the expression of the intestinal Dmt1 transporter, likely via the pathway triggered by Hif-2α. The microbiota assists the host in storing intestinal iron when it is abundant and competes with the host by inhibiting Dmt1 in conditions of iron scarcity. Comparison between duodenum, liver and lung indicates organ-specific responses to microbiota and iron availability. Iron depletion induced temporal changes in microbiota composition and activity, reduced α-diversity of microbiota, and led to becoming particularly more abundant after 60 days of privation. By inoculating GF mice with a simplified bacterial mixture, we show that the iron-depleted host favors the gut fitness of .
Topics: Animals; Mice; Gastrointestinal Microbiome; Iron, Dietary; Cation Transport Proteins; Liver; Duodenum; Hepcidins; Ferritins; Germ-Free Life; Host Microbial Interactions; Lung; Iron; Basic Helix-Loop-Helix Transcription Factors; Bacteria; Mice, Inbred C57BL; Hemoglobins; Male
PubMed: 38935764
DOI: 10.1080/19490976.2024.2361660 -
Heliyon Jun 2024Modeling of proton exchange membrane (PEM) fuel cells is attracting more attention as fuel cell technology continues to develop. In this study, we considered a hybrid...
Using a three-dimensional computational fluid dynamics model and an agglomerate model to investigate the effect of varying agglomerate parameters and output voltages on proton exchange membrane fuel cell performance.
Modeling of proton exchange membrane (PEM) fuel cells is attracting more attention as fuel cell technology continues to develop. In this study, we considered a hybrid model that combines an agglomerate model based on the agglomeration of catalyst particles and the coverage-dependent kinetic equation of platinum oxide for ORR, and another 3D numerical model of a PEM fuel cell based on computational fluid dynamics (CFD). The obtained results from our developed models were validated with experimental results from literature. In fact, we investigated the effects of changing the agglomerate radius , the ionomer volume fraction within the agglomerate the effective agglomerate surface area , the distribution of the gases and the temperature on the cell performances. The results revealed that the cell performances are strongly influenced by changing and for medium and high current densities: The activation loss increases with increasing and decreasing . Also, increases with decreasing and increasing . In addition, the PEM fuel cell's power output is significantly enhanced when is decreased and is increased, the optimal power being obtained for values of and = 0.6. The numerical results also showed that decreasing the output voltage from 0.95V to 0.35V can accelerate the electrochemical reaction process.
PubMed: 38933966
DOI: 10.1016/j.heliyon.2024.e32277 -
Journal of Materials Chemistry. A Jun 2024The preparation of stable large pore aluminophosphate (AlPO) zeotypes offers materials for applications in adsorption and catalysis. Here we report the synthesis of the...
The preparation of stable large pore aluminophosphate (AlPO) zeotypes offers materials for applications in adsorption and catalysis. Here we report the synthesis of the pure AlPO with the SAO topology type (AlPO STA-1) using ,'-diethylbicyclo[2.2.2]oct-7-ene-2,3:5,6-dipyrrolidine (DEBOP) as the organic structure directing agent in the presence of fluoride. The AlPO STA-1 can be rendered microporous (pore volume 0.36 cm g) calcination and the calcined form remains stable in the presence of moisture. The structure of the dehydrated form has been established by Rietveld refinement (tetragonal 4̄2, = 13.74317(10) Å, = 21.8131(5) Å, = 4119.94(16) Å). Multinuclear Al and P MAS NMR, together with 2D COSY and CASTEP NMR calculations, enables resolution and assignment of the signals from all crystallographically distinct Al and P framework sites. Structural elucidation of the as-prepared aluminophosphate-fluoride is more challenging, because of the presence of partially protonated OSDA molecules in the 3D-connected channel system and in particular because the fluoride ions coordinate with positional disorder to some of the Al atoms to give 5-fold as well as tetrahedrally-coordinated framework Al species. These are postulated to occupy Al-F-Al bridging sites, where they are responsible for distortion of the framework [4̄2, = 13.3148(9) Å, = 22.0655(20) Å, = 3911.9(7) Å]. Calcination and removal of fluoride ions and OSDAs allows the framework to expand to its relaxed configuration. The SAO topology type aluminophosphate can also be synthesised with small amounts of Si and Ge in the framework, and these SAPO and GeAPO STA-1 materials are also stable to template removal. IR spectroscopy with CO as a probe at 123 K indicates all have weak-to-mild acidity, increasing in the order AlPO < GeAPO < SAPO. These STA-1 materials have been investigated for their activity in the Beckmann rearrangement of cyclohexanone oxime to ε-caprolactam at 598 K: while all are active, the AlPO form is favoured due to its high selectivity and slow deactivation, both of which are a consequence of its very weak acid strength, which is nevertheless sufficient to catalyse the reaction.
PubMed: 38933527
DOI: 10.1039/d4ta01132e