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Ultrasonics Sonochemistry Sep 2019This study mainly covered the cavitation erosion in probe sonication and its electrochemical behavior. The activated graphite was exfoliated by the probe sonication...
This study mainly covered the cavitation erosion in probe sonication and its electrochemical behavior. The activated graphite was exfoliated by the probe sonication wherein the titanium alloy (TA) is used as a probe (micro-tip). The sonication performed in the aqueous solution contains a mixture of sulfuric acid and nitric acid (1:1). The exfoliated graphite (EG) was examined by field emission scanning electron microscope, Raman and X-ray diffraction pattern analysis. The results showed that some TA particles dissolute from the TA micro-tip accompanied with graphite exfoliation. This dissolution experienced from the cavitation erosion, because the acoustic cavitation makes severe deformation on probe tips due to the bubble collapse. The dissolution rate increased when increasing sonication time; the resultant TA particles are randomly distributed over the EG. These EGTAs applied to the electrochemical oxidation of acebutolol which revealed an appreciable electrochemical performance and also exhibited better analytical performances to the electrochemical determinations. The obtained analytical parameters viz., sensitivity (0.234 µA µM cm), linear range (0.01-15.1 µM), and limit of detection (0.003 µM) are highly comparable with the previous reports. Moreover, it has an acceptable tolerance with the interfering substances.
PubMed: 31101266
DOI: 10.1016/j.ultsonch.2019.04.025 -
International Journal of Legal Medicine Jan 2020Acebutolol is a β1-selective adrenergic receptor antagonist with moderate membrane-stabilizing activity and intrinsic sympathomimetic activity; accordingly, the drug is...
Acebutolol is a β1-selective adrenergic receptor antagonist with moderate membrane-stabilizing activity and intrinsic sympathomimetic activity; accordingly, the drug is indicated in hypertension, angina pectoris, and arrhythmia. However, acebutolol's beta-blocking properties also extend the QRS and QTc intervals, and may predispose the patient to ventricular tachydysrhythmia. Here, we report autopsy and toxicological findings on a fatal case of acebutolol self-poisoning in a 70-year-old woman. Toxicological analyses of post-mortem samples (using a liquid chromatography high-resolution mass spectrometry (LC-HR-MS) method) highlighted high concentrations of acebutolol and its metabolite diacetolol in femoral blood (92.8 mg/L and 21.2 mg/L, respectively) and other matrices (cardiac blood, urine, bile, and gastric contents). A molecular networking approach provided useful information on acebutolol's metabolism and revealed the existence of an unknown phase II metabolite of acebutolol. Molecular networking also facilitated visualization of the complex LC-HR-MS/MS datasets and the sample-to-sample comparisons that confirmed massive acebutolol intoxication by ingestion.
Topics: Acebutolol; Aged; Autopsy; Chromatography, Liquid; Female; Humans; Molecular Imaging; Suicide; Tandem Mass Spectrometry
PubMed: 30997571
DOI: 10.1007/s00414-019-02062-9 -
Environmental Science and Pollution... May 2019In this study, we report an effective degradation method for trace level beta-blockers (propranolol and acebutolol) in hospital wastewater using a new droplet...
In this study, we report an effective degradation method for trace level beta-blockers (propranolol and acebutolol) in hospital wastewater using a new droplet flow-assisted heterogeneous electro-Fenton reactor (DFEF) system. Biogenic iron-carbon nanocomposites (RHS/C-x% Fe) as eco-friendly and low-cost heterogeneous Fenton catalysts were synthesized from rice husk via hydrolytic sol-gel routes. Here, we demonstrate the use of natural air as a nebulizing agent for fast and continuous catholyte air saturation and Fenton catalyst transfer to the cathode electrode. The effects of key operational parameters were evaluated and optimized using central composite design. Results clearly indicated that enhanced beta-blocker degradation was mainly dependent on the interactive effects of electrolysis time, current density, and catalyst dosage. Fast degradation efficiencies (≥ 99.9%) was recorded at neutral pH conditions. The decay followed pseudo-first-order kinetics with degradation rates of up to 2.72 × 10 and 2.54 × 10 min for acebutolol and propranolol, respectively. The synergistic contribution of OH attributable to DFEF process and OH for anodic oxidation (AO) at the anode electrode significantly enhanced the degradation process. Compared to AO, the conventional flow-assisted electro-Fenton (FEF), and the batch electro-Fenton (BEF), DFEF degradation efficiency followed a decreasing order: DFEF ˃ FEF ˃ BEF˃ AO. This trend in performance was mainly due to the fast and continuous cathodic electro-generation of HO and Fe regeneration. Additionally, in order to elucidate degradation mechanism, we used a combination of DFEF approach with liquid chromatography-tandem mass spectrometry analysis. This approach demonstrates a simple, cleaner, and highly efficient degradation approach for trace level recalcitrant pollutants in a complex aquatic matrix, without the need for external chemical addition and pH adjustment.
Topics: Adrenergic beta-Antagonists; Catalysis; Electrodes; Electrolysis; Hydrogen Peroxide; Hydrogen-Ion Concentration; Iron; Kinetics; Nanocomposites; Oxidation-Reduction; Wastewater; Water Pollutants, Chemical; Water Purification
PubMed: 30864040
DOI: 10.1007/s11356-019-04551-1 -
Molecules (Basel, Switzerland) Feb 2019This paper presents an application of high performance liquid chromatography coupled with quadrupole orbitrap high-resolution mass spectrometry (HPLC-Q-Orbitrap HRMS)...
This paper presents an application of high performance liquid chromatography coupled with quadrupole orbitrap high-resolution mass spectrometry (HPLC-Q-Orbitrap HRMS) for the analysis of 27 β-blockers and metabolites in milk powder. Homogenized milk power samples were extracted by acetonitrile and purified by using Oasis PRiME HLB solid-phase extraction cartridges. The Ascentis C8 chromatographic column was used to separate the analytes. The quantification was achieved by using matrix-matched standard calibration curves with carazolol-d₇ and propranolol-d₇ as the internal standards. The results show an exceptional linear relationship with the concentrations of analytes over wide concentration ranges (0.5⁻500 μg kg) as all the fitting coefficients of determination r² are > 0.995. All the limits of detection (LODs) and quantitation (LOQs) values were within the respective range of 0.2⁻1.5 μg kg and 0.5⁻5.0 μg kg. Overall average recoveries were able to reach 66.1⁻100.4% with the intra- and inter-day variability under 10%. This method has been successfully applied to the screening of β-blockers and metabolites in commercial milk powders. At the same time, the corresponding characteristic fragmentation behavior of the 27 compounds was explored. The characteristic product ions were determined and applied to the actual samples screening.
Topics: Acebutolol; Adrenergic beta-Antagonists; Animals; Chromatography, High Pressure Liquid; Ethanolamines; Limit of Detection; Milk; Molecular Structure; Principal Component Analysis; Propanolamines; Propranolol; Solid Phase Extraction; Tandem Mass Spectrometry
PubMed: 30823583
DOI: 10.3390/molecules24040820 -
Scientific Reports Jan 2019In the present study, we measured the spontaneous post synaptic currents (sPSCs) at the post synaptic principle cells of the medial nucleus of the trapezoid body (MNTB)...
In the present study, we measured the spontaneous post synaptic currents (sPSCs) at the post synaptic principle cells of the medial nucleus of the trapezoid body (MNTB) in early postnatal mice after exposure to 1850 MHz radiofrequency electromagnetic fields (RF-EMF). sPSC frequencies and amplitudes were significantly increased in the RF-EMF exposed group. Moreover, the number of synaptic vesicles in the calyx of Held was significantly increased in presynaptic nerve terminals. Following RF-EMF exposure, the number of docking synaptic vesicles in the active zone increased, thereby expanding the total length of the presynaptic active zone in the calyx of Held. These data suggest that the increased sPSCs are a result of greater synaptic vesicle release from presynaptic nerves. However, we found no morphological changes in the inner hair cell ribbon synapses. Further, there were no significant changes in the hearing threshold of the auditory brainstem response at postnatal day 15. Our results indicate that exposure to RF-EMF at an early postnatal stage might directly affect brainstem auditory circuits, but it does not seem to alter general sound perception.
Topics: Acebutolol; Animals; Animals, Newborn; Evoked Potentials, Auditory, Brain Stem; Mice, Inbred ICR; Radio Waves; Synaptic Transmission; Synaptic Vesicles; Trapezoid Body
PubMed: 30674958
DOI: 10.1038/s41598-018-36868-1 -
Journal of Separation Science Mar 2019In order to have deep insights into the mechanisms of enantiomer affinity pattern in both aqueous and non-aqueous systems, an approach combining capillary...
Combination of capillary electrophoresis and molecular modeling to study the enantiomer affinity pattern between β-blockers and anionic cyclodextrin derivatives in a methanolic and water background electrolyte.
In order to have deep insights into the mechanisms of enantiomer affinity pattern in both aqueous and non-aqueous systems, an approach combining capillary electrophoresis and molecular modeling was undertaken. A chiral β-blocker; acebutolol, was enantioseparated in aqueous capillary electrophoresis and non-aqueous capillary electrophoresis using two anionic β-cyclodextrin derivatives. The enantiomer affinity pattern of acebutolol was found to be opposite when an aqueous background electrolyte was replaced with non-aqueous background electrolyte in the presence of heptakis(2,3-di-O-acetyl-6-sulfo)-β-cyclodextrin but remained the same in the presence of heptakis(2,3-di-O-methyl-6-sulfo)-β-cyclodextrin. Molecular docking of acebutolol into two β-cyclodextrin derivatives indicated two distinct binding modes called 'up' and 'down' conformations. After structure optimization by molecular dynamics and energy minimization, both enantiomers of acebutolol were preferred to the 'up' conformation with heptakis(2,3-di-O-methyl-6-sulfo)-β-cyclodextrin while 'down' conformation with heptakis(2,3-di-O-acetyl-6-sulfo)-β-cyclodextrin. The further calculation of the complex energy with solvent effect indicated that heptakis(2,3-di-O-acetyl-6-sulfo)-β-cyclodextrin had higher affinity to S-acebutolol than R-acebutolol in non-aqueous capillary electrophoresis while it showed better binding to R-acebutolol in aqueous capillary electrophoresis. However, the heptakis(2,3-di-O-methyl-6-sulfo)-β-cyclodextrin bound better to R-acebutolol in both aqueous and non-aqueous capillary electrophoresis, implying that the binding mode played more important role in chiral separation of heptakis(2,3-di-O-methyl-6-sulfo)-β-cyclodextrin while the solvent effect had prevailing impact on heptakis(2,3-di-O-acetyl-6-sulfo)-β-cyclodextrin.
Topics: Acebutolol; Adrenergic beta-Antagonists; Anions; Cyclodextrins; Electrolytes; Electrophoresis, Capillary; Methanol; Models, Molecular; Molecular Conformation; Stereoisomerism; Water
PubMed: 30659744
DOI: 10.1002/jssc.201800884 -
Journal of Bone and Mineral Research :... May 2019Normal bone mass is maintained by balanced bone formation and resorption. Myosin X (Myo10), an unconventional "myosin tail homology 4-band 4.1, ezrin, radixin, moesin"...
Normal bone mass is maintained by balanced bone formation and resorption. Myosin X (Myo10), an unconventional "myosin tail homology 4-band 4.1, ezrin, radixin, moesin" (MyTH4-FERM) domain containing myosin, is implicated in regulating osteoclast (OC) adhesion, podosome positioning, and differentiation in vitro. However, evidence is lacking for Myo10 in vivo function. Here we show that mice with Myo10 loss of function, Myo10 , exhibit osteoporotic deficits, which are likely due to the increased OC genesis and bone resorption because bone formation is unchanged. Similar deficits are detected in OC-selective Myo10 conditional knockout (cko) mice, indicating a cell autonomous function of Myo10. Further mechanistic studies suggest that Unc-5 Netrin receptor B (Unc5b) protein levels, in particular its cell surface level, are higher in the mutant OCs, but lower in RAW264.7 cells or HEK293 cells expressing Myo10. Suppressing Unc5b expression in bone marrow macrophages (BMMs) from Myo10 mice by infection with lentivirus of Unc5b shRNA markedly impaired RANKL-induced OC genesis. Netrin-1, a ligand of Unc5b, increased RANKL-induced OC formation in BMMs from both wild-type and Myo10 mice. Taken together, these results suggest that Myo10 plays a negative role in OC formation, likely by inhibiting Unc5b cell-surface targeting, and suppressing Netrin-1 promoted OC genesis. © 2019 American Society for Bone and Mineral Research.
Topics: Acebutolol; Animals; HEK293 Cells; Humans; Mice; Mice, Knockout; Myosins; Netrin Receptors; Netrin-1; Osteoclasts; Osteoporosis; RANK Ligand; RAW 264.7 Cells
PubMed: 30645777
DOI: 10.1002/jbmr.3667 -
American Family Physician Jan 2019Migraines impose significant health and financial burdens. Approximately 38% of patients with episodic migraines would benefit from preventive therapy, but less than 13%...
Migraines impose significant health and financial burdens. Approximately 38% of patients with episodic migraines would benefit from preventive therapy, but less than 13% take prophylactic medications. Preventive medication therapy reduces migraine frequency, severity, and headache-related distress. Preventive therapy may also improve quality of life and prevent the progression to chronic migraines. Some indications for preventive therapy include four or more headaches a month, eight or more headache days a month, debilitating headaches, and medication-overuse headaches. Identifying and managing environmental, dietary, and behavioral triggers are useful strategies for preventing migraines. First-line medications established as effective based on clinical evidence include divalproex, topiramate, metoprolol, propranolol, and timolol. Medications such as amitriptyline, venlafaxine, atenolol, and nadolol are probably effective but should be second-line therapy. There is limited evidence for nebivolol, bisoprolol, pindolol, carbamazepine, gabapentin, fluoxetine, nicardipine, verapamil, nimodipine, nifedipine, lisinopril, and candesartan. Acebutolol, oxcarbazepine, lamotrigine, and telmisartan are ineffective. Newer agents target calcitonin gene-related peptide pain transmission in the migraine pain pathway and have recently received approval from the U.S. Food and Drug Administration; however, more studies of long-term effectiveness and adverse effects are needed. The complementary treatments petasites, feverfew, magnesium, and riboflavin are probably effective. Nonpharmacologic therapies such as relaxation training, thermal biofeedback combined with relaxation training, electromyographic feedback, and cognitive behavior therapy also have good evidence to support their use in migraine prevention.
Topics: Combined Modality Therapy; Humans; Migraine Disorders; Secondary Prevention
PubMed: 30600979
DOI: No ID Found -
Journal of Pharmaceutical Analysis Dec 2018The aim of the present investigation was to demonstrate an approach involving use of liquid chromatography (LC) and liquid chromatography-mass spectrometry (LC-MS) to...
The aim of the present investigation was to demonstrate an approach involving use of liquid chromatography (LC) and liquid chromatography-mass spectrometry (LC-MS) to separate, identify and characterize very small quantities of degradation products (DPs) of acebutolol without their isolation from the reaction mixtures. The drug was subjected to oxidative, hydrolytic, thermal and photolytic stress conditions as per International Conference on Harmonization (ICH) guideline Q1A(R2). Among all the stress conditions the drug was found to be labile in hydrolytic (acidic & basic) and photolytic stress conditions, while it was stable in water-induced hydrolysis, oxidative and thermal stress conditions. A total of four degradation products were formed. A C column was employed for the separation of all the DPs on a gradient mode by using high-performance liquid chromatography (HPLC). All the DPs were characterized with the help of their fragmentation pattern and the masses obtained upon LC-MS/MS and MS analysis. All the hitherto unknown degradation products were identified as 1-(2-(2-hydroxy-3-(isopropylamino)propoxy)-5-(amino)phenyl)ethanone (DP-I), N-(4-(2-hydroxy-3-(isopropylamino)propoxy)-3-acetylphenyl)acrylamide (DP-II), 1-(2-(2-hydroxy-3-(isopropylamino)propoxy)-5-(hydroxymethylamino)phenyl)ethanone (DP-III) and 1-(6-(2-hydroxy-3-(isopropylamino)propoxy)-2,3-dihydro-2-propylbenzo[d]oxazol-5-yl)ethanone (DP-IV). Finally the in-silico carcinogenicity and hepatotoxicity predictions of the drug and all the DPs were performed by using toxicity prediction softwares viz., TOPKAT, LAZAR and Discovery Studio ADMET. The results of in-silico toxicity studies revealed that acebutolol (0.967) and DP-I (0.986) were found to be carcinogenic, while acebutolol (0.490) and DP-IV (0.437) were found to be hepatotoxic.
PubMed: 30595941
DOI: 10.1016/j.jpha.2018.03.001 -
The Science of the Total Environment Mar 2019The direct discharge of untreated wastewater has been identified as an important source of environmental contamination by active pharmaceutical ingredients and other...
The direct discharge of untreated wastewater has been identified as an important source of environmental contamination by active pharmaceutical ingredients and other 'down-the-drain' chemicals in developing countries. It necessitates the development of an environmental risk assessment approach for the resulting impact zone. This study was designed to investigate the impact of low level of dilution (<10) on the natural attenuation processes of distribution and degradation within the impact zone. Dilution of the untreated wastewater resulted in increased desorption and corresponding environmental concentrations. The presence/absence of the microbial population in the batches affected the degree of sorption depending on the compound charge (i.e. positive or negative), highlighting an experimental technical bias. The degradation half-lives of acebutolol and diclofenac increased with increasing dilution and resulted in higher environmental persistence. The modelling of the biochemical oxygen demand (BOD) allowed an estimate of the temporal end boundary of the impact zone to be predicted as 24h. Therefore, it was concluded that most of the investigated compounds would persist beyond the end of the impact zone as defined by the return to environmental BOD concentrations. It is proposed that, within environmental risk assessment protocols, the impact zone should be considered as a semi-natural wastewater treatment area in such a way to allow the estimate of environmental concentrations of pharmaceuticals beyond its end.
Topics: Environmental Monitoring; Pharmaceutical Preparations; Risk Assessment; Waste Management; Wastewater; Water Movements; Water Pollutants, Chemical
PubMed: 30577026
DOI: 10.1016/j.scitotenv.2018.12.191