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Heliyon Oct 2023A straightforward approach for creating fast and novel potentiometric sensors that are modified with multi-walled nanotubes (MWCNTs) was described. The impact of the...
Fast and novel multiwalled carbon nanotubes decorated with metal oxide nanoparticles for potentiometric detection of a prohibited medication in sports acebutolol hydrochloride.
A straightforward approach for creating fast and novel potentiometric sensors that are modified with multi-walled nanotubes (MWCNTs) was described. The impact of the selective sensor's material was studied. The suggested sensors were successfully fabricated for instant and fast detection of the prohibited β-adrenoreceptor blocking agent acebutolol hydrochloride (AC) in commercial products. Acebutolol-phosphomolybdate (AC-PM) carbon paste sensor was formed by mixing AC and phosphomolybdic acid and graphite powder in the presence of -nitrophenyl octyl ether (-NPOE) as a plasticizing agent. The functionalized AC-PM-MWCNTs and AC-PM-MWCNTs-AlO nanocomposite sensors were prepared and all parameters affecting the sensors' potential responses have been investigated as well as the green synthesis of AlONPs has been characterized using various microscopic and spectroscopic techniques. AC-PM-MWCNTs and AC-PM-MWCNTs-AlO nanocomposite sensors demonstrated linearity of 1.0 × 10-1.0 × 10 and 1.0 × 10-1.0 × 10 mol L, respectively with regression equations -53.571x + 423.24 (r = 0.999) and -57.107x + 518.54 (r = 0.999). It also revealed excellent selectivity and sensitivity for the determination and quantification of AC. The developed potentiometric system was suitable for the determination of AC in bulk powder and commercial products.
PubMed: 37876475
DOI: 10.1016/j.heliyon.2023.e20997 -
Nephrology, Dialysis, Transplantation :... Nov 2020β-blocker (BB) dialyzability has been proposed to limit their efficacy among hemodialysis (HD) patients. We attempted to confirm this hypothesis by comparing health...
BACKGROUND
β-blocker (BB) dialyzability has been proposed to limit their efficacy among hemodialysis (HD) patients. We attempted to confirm this hypothesis by comparing health outcomes associated with the initiation of dialyzable or nondialyzable BBs in a nationwide cohort of HD patients.
METHODS
We created a prospective cohort study of 15 699 HD patients who initiated dialyzable BBs (atenolol, acebutolol, metoprolol and bisoprolol) and 20 904 hemodialysis patients who initiated nondialyzable BBs (betaxolol, carvedilol and propranolol) between 2004 and 2011 in Taiwan healthcare. We compared the risk of all-cause mortality and major adverse cardiovascular events (MACEs, a composite of the acute coronary syndrome, ischemic stroke and heart failure) between users of dialyzable versus nondialyzable BBs during a 2-year follow-up.
RESULTS
New users of dialyzable BBs were younger, more often men, with diabetes mellitus, hypertension and hyperlipidemia compared with users of nondialyzable BBs. Compared with nondialyzable BBs, initiation of dialyzable BBs was associated with lower all-cause mortality {hazard ratio [HR] 0.82 [95% confidence interval (CI) 0.75-0.88]} and lower risk of MACEs [HR 0.89 (95% CI 0.84-0.93)]. Results were confirmed in subgroup analyses, censoring at BB discontinuation or switch, after 1:1 propensity score matching, reclassifying bisoprolol or excluding bisoprolol/carvedilol users.
CONCLUSIONS
This study does not offer support for the hypothesis that the dialyzability of BBs reduces their efficacy in HD patients.
Topics: Adrenergic beta-Antagonists; Cardiovascular Diseases; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prognosis; Prospective Studies; Renal Dialysis; Survival Rate; Taiwan
PubMed: 32719861
DOI: 10.1093/ndt/gfaa058 -
Critical Care (London, England) Jun 2021β-adrenergic antagonists (BAAs) are used to treat cardiovascular disease such as ischemic heart disease, congestive heart failure, dysrhythmias, and hypertension....
BACKGROUND
β-adrenergic antagonists (BAAs) are used to treat cardiovascular disease such as ischemic heart disease, congestive heart failure, dysrhythmias, and hypertension. Poisoning from BAAs can lead to severe morbidity and mortality. We aimed to determine the utility of extracorporeal treatments (ECTRs) in BAAs poisoning.
METHODS
We conducted systematic reviews of the literature, screened studies, extracted data, and summarized findings following published EXTRIP methods.
RESULTS
A total of 76 studies (4 in vitro and 2 animal experiments, 1 pharmacokinetic simulation study, 37 pharmacokinetic studies on patients with end-stage kidney disease, and 32 case reports or case series) met inclusion criteria. Toxicokinetic or pharmacokinetic data were available on 334 patients (including 73 for atenolol, 54 for propranolol, and 17 for sotalol). For intermittent hemodialysis, atenolol, nadolol, practolol, and sotalol were assessed as dialyzable; acebutolol, bisoprolol, and metipranolol were assessed as moderately dialyzable; metoprolol and talinolol were considered slightly dialyzable; and betaxolol, carvedilol, labetalol, mepindolol, propranolol, and timolol were considered not dialyzable. Data were available for clinical analysis on 37 BAA poisoned patients (including 9 patients for atenolol, 9 for propranolol, and 9 for sotalol), and no reliable comparison between the ECTR cohort and historical controls treated with standard care alone could be performed. The EXTRIP workgroup recommends against using ECTR for patients severely poisoned with propranolol (strong recommendation, very low quality evidence). The workgroup offered no recommendation for ECTR in patients severely poisoned with atenolol or sotalol because of apparent balance of risks and benefits, except for impaired kidney function in which ECTR is suggested (weak recommendation, very low quality of evidence). Indications for ECTR in patients with impaired kidney function include refractory bradycardia and hypotension for atenolol or sotalol poisoning, and recurrent torsade de pointes for sotalol. Although other BAAs were considered dialyzable, clinical data were too limited to develop recommendations.
CONCLUSIONS
BAAs have different properties affecting their removal by ECTR. The EXTRIP workgroup assessed propranolol as non-dialyzable. Atenolol and sotalol were assessed as dialyzable in patients with kidney impairment, and the workgroup suggests ECTR in patients severely poisoned with these drugs when aforementioned indications are present.
Topics: Adrenergic beta-Antagonists; Consensus; Drug Overdose; Extracorporeal Membrane Oxygenation; Humans
PubMed: 34112223
DOI: 10.1186/s13054-021-03585-7 -
La Tunisie Medicale Feb 2020Cardiac arrest (CA) is a public health problem, with various etiologies and a fatal issue in 90-95% of cases. Toxin-induced cardiac arrests (TICA) are poorly described....
BACKGROUND
Cardiac arrest (CA) is a public health problem, with various etiologies and a fatal issue in 90-95% of cases. Toxin-induced cardiac arrests (TICA) are poorly described. Scarcity of national data prompted us to carry-out this study.
AIM
To determine TICA frequency in a Tunisian reference center in toxicology and its hospital prognosis, and to describe its clinical and therapeutic aspects Methods : Data were collected retrospectively over an 8-years period. We included patients admitted for post-CA care with highly suspected or confirmed TICA. Clinical and toxicological data were recorded.
RESULTS
We recorded 21 cases of TICA, which represented 48.8% of CA. A single toxic agent was incriminated in 90% of cases. Main causative agents identified in our series were pesticides and betablockers: chloralosed (n = 6), carbamate inhibitor of cholinesterase (n = 5), acebutolol (n = 4) and organophosphate (n = 2). One case of opiates and cocaine poisoning was reported. Median duration of "no flow" was 0 minutes. Mean duration of "low flow" was 13.74±9.15 minutes. An initial shockable rhythm was noted only in three patients. Mortality rate was 76% (16/21). Four of the five survivors had a Cerebral Performance Category Scale (CPC) 1, only one patient survived with a CPC 3. Factors associated with mortality were : the duration of "low flow" (p=0.02) and APACHE II score (p=0.014). APACHE II≥29 was the only independent factor (OR=2.0, 95%CI [1.07;3.71]).
CONCLUSION
TICA were most frequently provoked by pesticides, mortality was high and was independently predicted by APACHE II score.
Topics: Adrenergic beta-Antagonists; Cardiotoxicity; Cocaine; Drug-Related Side Effects and Adverse Reactions; Heart Arrest; Hospital Mortality; Hospitalization; Humans; Incidence; Mortality; Organophosphates; Pesticides; Retrospective Studies; Risk Factors; Toxins, Biological; Treatment Outcome; Tunisia
PubMed: 32395801
DOI: No ID Found -
Journal of the American Society For... Feb 2022Combining solid phase microextraction (SPME) and mass spectrometry (MS) analysis has become increasingly important to many bioanalytical, environmental, and forensic...
Combining solid phase microextraction (SPME) and mass spectrometry (MS) analysis has become increasingly important to many bioanalytical, environmental, and forensic applications due to its simplicity, rapid analysis, and capability of reducing matrix effects for complex samples. To further promote the adoption of SPME-MS based analysis and expand its application scope calls for efficient and convenient interfaces that couple the SPME sample handling with the efficient analyte ionization for MS. Here, we report a novel interface that integrates both the desorption and the ionization steps in one device based on the capillary vibrating sharp-edge spray ionization (cVSSI) method. We demonstrated that the cVSSI is capable of nebulizing liquid samples in a pulled-tip glass capillary with a battery powered function generator. The cVSSI device allows the insertion of a SPME probe into the spray capillary for desorption and then direct nebulization of the desorption solvent in situ. With the integrated interface, we have demonstrated rapid MS analysis of drug compounds from serum samples. Quantitative determination of various drug compounds including metoprolol, pindolol, acebutolol, oxprenolol, capecitabine, and irinotecan was achieved with good linearity ( = 0.97-0.99) and limit of detection ranging from 0.25 to 0.59 ng/mL without using a high voltage source. Only 3.5 μL of desorption solvent and 3 min desorption time were needed for the present method. Overall, we demonstrated a portable SPME-MS interface featuring high sensitivity, short analysis time, small footprint, and low cost, which makes it an attractive method for many applications requiring sample cleanup including drug compound monitoring, environmental sample analysis, and forensic sample analysis.
Topics: Carbamazepine; Equipment Design; Limit of Detection; Metoprolol; Pindolol; Sensitivity and Specificity; Serum Albumin, Bovine; Solid Phase Microextraction; Spectrometry, Mass, Electrospray Ionization
PubMed: 35040644
DOI: 10.1021/jasms.1c00305 -
Annales Pharmaceutiques Francaises Sep 2021The aim of this study was to predict the plasma concentrations of acebutolol tablets with different dissolution profiles using computer modelling and evaluating whether...
PURPOSE
The aim of this study was to predict the plasma concentrations of acebutolol tablets with different dissolution profiles using computer modelling and evaluating whether they are bioequivalent using simulated population studies.
METHODS
The dissolution behaviour of acebutolol was studied in the USP Apparatus-II using different dissolution media for pH 1.2, 4.5, and 6.8 at 37±0.5°C. The obtained dissolution data, as well as plasma concentration-time data of the reference product from the literature were used as inputs to build pharmacokinetic model of acebutolol within GastroPlus™ software (version 9.7, Simulations Plus Inc., Lancaster, CA, USA) to simulate the in vivo profiles of the drug.
RESULTS
The dissolution profiles of the reference product Sectral® 400mg tablets and a locally produced generic product were>85% in 15min in three dissolution media. Simulation results demonstrated that the brand and generic products would show the same in vivo performance. Population simulation results of the ln-transformed 90% confidence interval for the ratio of C, AUC and AUC values for the two products were within the 80-125% interval, showing to be bioequivalent.
CONCLUSION
Based on the in vitro results combined with in silico simulations using GastroPlus™, a biowaiver for immediate release acebutolol tablets is justified. Furthermore, computer modelling has shown to be a very intersting tool to prove the bioequivalence for these products.
Topics: Acebutolol; Computer Simulation; Solubility; Tablets; Therapeutic Equivalency
PubMed: 33675740
DOI: 10.1016/j.pharma.2021.02.004 -
Frontiers in Cell and Developmental... 2022Female reproductive cycle, also known as menstrual cycle or estrous cycle in primate or non-primate mammals, respectively, dominates the reproductive processes in...
Female reproductive cycle, also known as menstrual cycle or estrous cycle in primate or non-primate mammals, respectively, dominates the reproductive processes in non-pregnant state. However, in addition to reproductive tissues, reproductive cycle could also perform global regulation because the receptors of two major female hormones fluctuating throughout the cycle, estrogen and progesterone, are widely distributed. Therefore, a multi-tissue gene expression landscape is in continuous demand for better understanding the systemic changes during the reproductive cycle but remains largely undefined. Here we delineated a transcriptomic landscape covering 15 tissues of C57BL/6J female mice in two phases of estrous cycle, estrus and diestrus, by RNA-sequencing. Then, a number of genes, pathways, and transcription factors involved in the estrous cycle were revealed. We found the estrous cycle could widely regulate the neuro-functions, immuno-functions, blood coagulation and so on. And behind the transcriptomic alteration between estrus and diestrus, 13 transcription factors may play important roles. Next, bioinformatics modeling with 1,263 manually curated gene signatures of various physiological and pathophysiological states systematically characterized the beneficial/deleterious effects brought by estrus/diestrus on individual tissues. We revealed that the estrous cycle has a significant effect on cardiovascular system (aorta, heart, vein), in which the anti-hypertensive pattern in aorta induced by estrus is one of the most striking findings. Inspired by this point, we validated that two hypotensive drugs, felodipine and acebutolol, could exhibit significantly enhanced efficacy in estrus than diestrus by mouse and rat experiments. Together, this study provides a valuable data resource for investigating reproductive cycle from a transcriptomic perspective, and presents models and clues for investigating precision medicine associated with reproductive cycle.
PubMed: 36589755
DOI: 10.3389/fcell.2022.983712 -
Chemosphere Jan 2022Acebutolol (ACE) has been widely used for the treatment of cardiovascular disorders, and its photochemical fate in natural waters is a matter of concern due to its...
Acebutolol (ACE) has been widely used for the treatment of cardiovascular disorders, and its photochemical fate in natural waters is a matter of concern due to its ubiquitous occurrence and its toxicity to aquatic organisms. In this study, the photodegradation of ACE in river water and synthetic waters were investigated under simulated sunlight irradiation. The results demonstrated that ACE photodegradation rate in river water was 3.2 times higher than that in pure water. Then the influences of HCO, NO and DOM on ACE photolysis were investigated under their concentrations similar with the ones in river water. ACE photodegradation was significantly enhanced in the presence of HCO alone, and the scavenging experiments and the electron paramagnetic resonance experiments together proved that HCO could be oxidized by triplet-excited state of ACE to generate CO, which subsequently played a key role in ACE degradation. The presence of both NO and DOM also increased the ACE photodegradation rates, and •OH and DOM* were found to be involved in the degradation. In addition, when DOM was added to a solution with HCO, the enhancement effect of HCO on ACE photodegradation was weakened due to the scavenging of CO by DOM combined with the light screening effect of DOM.
Topics: Acebutolol; Carbonates; Hydroxyl Radical; Photolysis; Water Pollutants, Chemical
PubMed: 34826949
DOI: 10.1016/j.chemosphere.2021.132318 -
Journal of Separation Science Jul 2023In the present study, five simple, feasible, and sensitive Ultra-high-speed liquid chromatography combined with mass spectrometry detection methods, using electrospray...
Ultra-high-speed liquid chromatography combined with mass spectrometry detection analytical methods for the determination of nitrosamine drug substance-related impurities.
In the present study, five simple, feasible, and sensitive Ultra-high-speed liquid chromatography combined with mass spectrometry detection methods, using electrospray ionization are proposed. These methods were developed and validated for the determination of four different nitrosamine drug substance-related impurities-N-nitrosoacebutolol, N-nitrosobisoprolol, N-nitrosometoprolol, and N-nitrososotalol-in five beta blockers active pharmaceutical ingredients-acebutolol HCl, bisoprolol fumarate, metoprolol tartrate, metoprolol succinate, and sotalol HCl. The proposed methods were validated as per regulatory guidelines. Acquity HSS T3 (3.0 × 100 mm, 1.8 μm) column and formic acid 0.1% in water combined with methanol or acetonitrile were used for chromatographic separation in all methods. The limit of detection and the limit of quantification were found to be in the range of 0.02-1.2 and 2-20 parts per billion, respectively. The accuracy and precision of the five methods have been demonstrated in the working range of each one, giving values of recovery within the range of 64.1%-113.3%, and the regression coefficients (R) were found to be in the range of 0.9978-0.9999. These methods could be used for controlling nitrosamine drug substance-related impurities content for beta blockers drug substances batches manufactured at Moehs group.
Topics: Chromatography, High Pressure Liquid; Mass Spectrometry; Adrenergic beta-Antagonists; Drug Contamination; Bisoprolol; Metoprolol
PubMed: 37070833
DOI: 10.1002/jssc.202300125 -
Forensic Science, Medicine, and... Oct 2023The objective of this study was to investigate the degradation pattern of cardiac troponin I in rats in vivo, and to determine whether the pattern was dependent on the...
The objective of this study was to investigate the degradation pattern of cardiac troponin I in rats in vivo, and to determine whether the pattern was dependent on the cause of death, for the purpose of estimating the postmortem interval. The rats were categorized into three distinct groups depending on the factors leading to their demise: the control group, the group experiencing acebutolol-induced cardiotoxicity, and the group affected by asphyxia. The analysis encompassed the isolation and segregation of the protein, subsequently employing Western blotting as a means of visualizing the results. The results revealed a distinct degradation pattern of cTnI into smaller fragments over time, indicating that cardiac troponin I can serve as a reliable marker for estimating the postmortem interval. Furthermore, noteworthy variations were noted in the degradation pattern of cardiac troponin I among the different causes of death, which suggests that this method can also be used to determine whether cardiac failure was the cause of death or not.
PubMed: 37804400
DOI: 10.1007/s12024-023-00719-x