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Environment International Sep 2022Analysis of untreated municipal wastewater is recognized as an innovative approach to assess population exposure to or consumption of various substances. Currently,...
Analysis of untreated municipal wastewater is recognized as an innovative approach to assess population exposure to or consumption of various substances. Currently, there are no published wastewater-based studies investigating the relationships between catchment social, demographic, and economic characteristics with chemicals using advanced non-targeted techniques. In this study, fifteen wastewater samples covering 27% of the Australian population were collected during a population Census. The samples were analysed with a workflow employing liquid chromatography high-resolution mass spectrometry and chemometric tools for non-target analysis. Socioeconomic characteristics of catchment areas were generated using Geospatial Information Systems software. Potential correlations were explored between pseudo-mass loads of the identified compounds and socioeconomic and demographic descriptors of the wastewater catchments derived from Census data. Markers of public health (e.g., cardiac arrhythmia, cardiovascular disease, anxiety disorder and type 2 diabetes) were identified in the wastewater samples by the proposed workflow. They were positively correlated with descriptors of disadvantage in education, occupation, marital status and income, and negatively correlated with descriptors of advantage in education and occupation. In addition, markers of polypropylene glycol (PPG) and polyethylene glycol (PEG) related compounds were positively correlated with housing and occupation disadvantage. High positive correlations were found between separated and divorced people and specific drugs used to treat cardiac arrhythmia, cardiovascular disease, and depression. Our robust non-targeted methodology in combination with Census data can identify relationships between biomarkers of public health, human behaviour and lifestyle and socio-demographics of whole populations. Furthermore, it can identify specific areas and socioeconomic groups that may need more assistance than others for public health issues. This approach complements important public health information and enables large-scale national coverage with a relatively small number of samples.
Topics: Australia; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Public Health; Social Class; Socioeconomic Factors; Wastewater
PubMed: 35914338
DOI: 10.1016/j.envint.2022.107436 -
Environmental Toxicology and Chemistry Nov 2022The (bio)availability of pharmaceuticals at solid/water interfaces is governed by their sorption, which determines their concentrations in groundwaters and surface...
The (bio)availability of pharmaceuticals at solid/water interfaces is governed by their sorption, which determines their concentrations in groundwaters and surface waters in contact with biota, and can be affected by the presence of other contaminants such as metallic trace elements likely to compete for adsorption sites and form complexes with pharmaceuticals. We studied the adsorption of the pharmaceuticals propranolol and sotalol-two β-blockers-on one soil and one sediment using batch experiments to assess their (bio)availability. The influence of contact time, pH, and concentration was studied. As in the real environment these contaminants are not alone but in mixtures, and they were studied alone, simultaneously added, and in the presence of Cu , which is known to form coordination complexes with propranolol and sotalol, but their presence in mixtures did not alter their adsorption properties. Sotalol was more mobile in water and thus more bioavailable for organisms than propranolol. The mobility in surface waters of both β-blockers and thus their bioavailabity for organisms is more important than their risk of transfer to groundwater during rainwater infiltration and to surface water due to runoff. Environ Toxicol Chem 2022;41:2700-2707. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Topics: Soil; Adsorption; Copper; Trace Elements; Propranolol; Sotalol; Coordination Complexes; Adrenergic beta-Antagonists; Water Pollutants, Chemical; Water; Pharmaceutical Preparations
PubMed: 35899978
DOI: 10.1002/etc.5448 -
Drug Testing and Analysis Oct 2022Adherence to therapy is the key to a successful therapeutic intervention, especially in cardiovascular diseases in which a lack of adherence may have serious...
Hair analysis for beta-blockers and calcium-channel blockers by using liquid chromatography-tandem mass spectrometry as a tool for monitoring adherence to antihypertensive therapy.
Adherence to therapy is the key to a successful therapeutic intervention, especially in cardiovascular diseases in which a lack of adherence may have serious consequences in terms morbidity and/or mortality. In this context, hair analysis can be an excellent tool to monitor adherence to therapy. Indeed, drugs present in blood are incorporated into the hair matrix, where drugs and metabolites can stay unaltered for a long time protected from metabolism and degradation. In the present study, a simple, specific, and sensitive ultra-high performance liquid-chromatography-tandem mass spectrometry (UHPLC-MS/MS) method set up to determine in human hair seven beta-blockers (viz., metoprolol, sotalol, labetalol, atenolol, nebivolol, bisoprolol, and nadolol) and two calcium-channel blockers (lercanidipine and amlodipine), which are widely prescribed to treat medium-to-severe hypertensive conditions. The optimized method was successfully validated in terms of accuracy, repeatability, reproducibility, matrix effect and extraction recovery. Moreover, the applicability of the method was evaluated by analyzing 34 real samples of hair obtained from patients under long-term therapy with calcium channel blockers and beta-blockers.
Topics: Adrenergic beta-Antagonists; Amlodipine; Antihypertensive Agents; Atenolol; Bisoprolol; Calcium; Calcium Channel Blockers; Chromatography, Liquid; Hair Analysis; Humans; Labetalol; Metoprolol; Nadolol; Nebivolol; Reproducibility of Results; Sotalol; Tandem Mass Spectrometry
PubMed: 35855505
DOI: 10.1002/dta.3346 -
Scientific Reports Jul 2022COVID-19 is a global pandemic impacting the daily living of millions. As variants of the virus evolve, a complete comprehension of the disease and drug targets becomes a...
COVID-19 is a global pandemic impacting the daily living of millions. As variants of the virus evolve, a complete comprehension of the disease and drug targets becomes a decisive duty. The Omicron variant, for example, has a notably high transmission rate verified in 155 countries. We performed integrative transcriptomic and network analyses to identify drug targets and diagnostic biomarkers and repurpose FDA-approved drugs for SARS-CoV-2. Upon the enrichment of 464 differentially expressed genes, pathways regulating the host cell cycle were significant. Regulatory and interaction networks featured hsa-mir-93-5p and hsa-mir-17-5p as blood biomarkers while hsa-mir-15b-5p as an antiviral agent. MYB, RRM2, ERG, CENPF, CIT, and TOP2A are potential drug targets for treatment. HMOX1 is suggested as a prognostic biomarker. Enhancing HMOX1 expression by neem plant extract might be a therapeutic alternative. We constructed a drug-gene network for FDA-approved drugs to be repurposed against the infection. The key drugs retrieved were members of anthracyclines, mitotic inhibitors, anti-tumor antibiotics, and CDK1 inhibitors. Additionally, hydroxyquinone and digitoxin are potent TOP2A inhibitors. Hydroxyurea, cytarabine, gemcitabine, sotalol, and amiodarone can also be redirected against COVID-19. The analysis enforced the repositioning of fluorouracil and doxorubicin, especially that they have multiple drug targets, hence less probability of resistance.
Topics: Biomarkers; Drug Repositioning; Host Microbial Interactions; Humans; MicroRNAs; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35831333
DOI: 10.1038/s41598-022-15898-w -
The American Journal of Case Reports Jul 2022BACKGROUND Pulmonary vein isolation is a method of cardiac ablation therapy used to treat irregular heart rhythm, including atrial fibrillation (AF). This report...
BACKGROUND Pulmonary vein isolation is a method of cardiac ablation therapy used to treat irregular heart rhythm, including atrial fibrillation (AF). This report presents a case of esophagopericardial fistula (EPF) and pneumopericardium as a complication of pulmonary vein isolation in a 62-year-old man with AF. CASE REPORT We report the rare case of a 62-year-old man with a medical history of persistent atrial fibrillation status after ablation 3 days prior to his initial Emergency Department visit for chest pain. Acute coronary syndrome was ruled out with normal electrocardiogram, echocardiography, and troponin tests. Fluid overload and sotalol adverse effects were presumed to be the cause of his symptoms. We discontinued sotalol with diuresis and he was discharged home when his chest pain subsided. Nine days later, he returned to the Emergency Department with worsening similar symptoms and was eventually diagnosed with EPF and pneumopericardium on a computed tomography scan of the chest with contrast. He was managed with esophagogastroduodenoscopy and stent placement along with subxiphoid pericardial window and pericardial drain placement. The patient was discharged in stable condition after removing the pericardial drain. At 10-day and 1-month follow-up, he had no recurrent symptoms. CONCLUSIONS This report shows that although EPF with pneumopericardium is a rare complication of pulmonary vein isolation, it should be rapidly diagnosed and treated as a life-threatening emergency.
Topics: Atrial Fibrillation; Chest Pain; Fistula; Humans; Male; Middle Aged; Pneumopericardium; Pulmonary Veins; Sotalol
PubMed: 35821628
DOI: 10.12659/AJCR.936315 -
Journal of Pharmacological and... 2022According to the ICH S7B guideline, drug candidates are screened for hERG block prior to first-in-human testing to predict the likelihood of delayed repolarization...
According to the ICH S7B guideline, drug candidates are screened for hERG block prior to first-in-human testing to predict the likelihood of delayed repolarization associated with a rare, but life-threatening, ventricular tachyarrhythmia. The new ICH E14 Q&As guideline allows hERG results to be used in later clinical development for decision-making (Q&As 5.1 and 6.1). To pursue this path, the hERG assay should be conducted following the new ICH S7B Q&A 2.1 guideline, which calls for best practice considerations of the recording temperature, voltage protocol, stimulation frequency, recording/data quality, and concentration verification. This study investigated hERG block by cisapride, dofetilide, terfenadine, sotalol, and E-4031 - positive controls commonly used to demonstrate assay sensitivity - using the manual whole cell patch clamp method and an action potential-like voltage protocol presented at 0.2 Hz. Recordings were conducted at room and near physiological temperature. Drug concentrations were measured using samples collected during real patch clamp experiments and satellite experiments. Results showed temperature effects for E-4031, terfenadine, and sotalol, but not cisapride and dofetilide. Cisapride and terfenadine showed substantial concentration losses, largely due to nonspecific binding to the perfusion apparatus. Using concentrations measured from the real and satellite experiments to assess block potencies yielded comparable results, indicating that satellite sample collection may be viable for drugs with nonspecific binding concerns only. In summary, this study provides block potencies for 5 hERG positive controls, and serves as a case study for hERG assays conducted, and results illustrated in accordance with the new ICH E14/S7B Q&As.
Topics: Cisapride; Ether-A-Go-Go Potassium Channels; Humans; Phenethylamines; Sotalol; Sulfonamides; Temperature; Terfenadine
PubMed: 35792285
DOI: 10.1016/j.vascn.2022.107193 -
Frontiers in Pharmacology 2022Fetal arrhythmias are common cardiac abnormalities associated with high mortality due to ventricular dysfunction and heart failure, particularly when accompanied by...
Fetal arrhythmias are common cardiac abnormalities associated with high mortality due to ventricular dysfunction and heart failure, particularly when accompanied by hydrops. Although several types of common fetal tachycardias have been relatively identified medications, such as digoxin, flecainide, and sotalol, there is no first-line drug treatment protocol established for the treatment of various types of fetal tachycardias. We conducted a network meta-analysis using a Bayesian hierarchical framework to obtain a model for integrating both direct and indirect evidence. All tachycardia types (Total group), supraventricular tachycardia (SVT subgroup), atrial flutter (AF subgroup), hydrops subgroup, and non-hydrops subgroup fetuses were analyzed, and five first-line regimens were ranked according to treatment outcomes: digoxin monotherapy (D), flecainide monotherapy (F), sotalol monotherapy (S), digoxin plus flecainide combination therapy (DF), and digoxin plus sotalol combination therapy (DS). Effectiveness and safety were determined according to the cardioversion rate and intrauterine death rate. The pooled data indicated that DF combination therapy was always superior to D monotherapy, regardless of the tachycardia type or the presence of hydrops: Total, 2.44 (95% CrI: 1.59, 3.52); SVT, 2.77 (95% CrI: 1.59, 4.07); AF, 67.85 (95% CrI: 14.25, 168.68); hydrops, 6.03 (95% CrI: 2.54, 10.68); and non-hydrops, 5.06 (95% CrI: 1.87, 9.88). DF and F had a similar effect on control of fetal tachycardias. No significant differences were observed when comparing S, DS with D therapies across the subgroup analyses for the SVT, hydrops, and non-hydrops groups. No significant differences in mortality risks were among the various treatment regimens for the total group. And no significant differences were found in rates of intrauterine death rates at the same cardioversion amount. The flecainide monotherapy and combination of digoxin and flecainide should be considered the most superior therapeutic strategies for fetal tachycardia. (https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=288997), identifier (288997).
PubMed: 35770083
DOI: 10.3389/fphar.2022.935455 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... May 2022The risk of arrhythmia increases in diabetic patients. However, the effects of hyperglycemia and insulin therapy on the electrophysiological properties of human...
OBJECTIVES
The risk of arrhythmia increases in diabetic patients. However, the effects of hyperglycemia and insulin therapy on the electrophysiological properties of human cardiomyocytes remain unclear. This study is to explore the effects of high glucose and insulin on the electrophysiological properties and arrhythmias of cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs).
METHODS
Immunofluorescent staining and flow cytometry were used to analyze the purity of hiPSC-CMs generated from human skin fibroblasts of a healthy donor. The hiPSC-CMs were divided into 3 group (treated with normal medium, high glucose and insulin for 4 days): a control group (NM group, containing 5 mmol/L glucose), a high glucose group (HG group, containing 15 mmol/L glucose), and a high glucose combined with insulin (HG+INS group, containing 15 mmol/L glucose+100 mg/L insulin). Electrophysiological changes of hiPSC-CMs were detected by microelectrode array (MEA) before or after treatment with glucose and insulin, including beating rate (BR), field potential duration (FPD) (similar to QT interval in ECG), FPDc (FPD corrected by BR), spike amplitude and conduction velocity (CV). Effects of sotalol on electrophysiological properties and arrhythmias of hiPSC-CMs were also evaluated.
RESULTS
The expression of cardiac-specific marker of cardiac troponin T was high in the hiPSC-CMs. The purity of hiPSC-CMs was 99.06%. Compared with the NM group, BR was increased by (9.14±0.8)% in the HG group (<0.01). After treatment with high glucose, FPD was prolonged from (460.4±9.0) ms to (587.6±23.7) ms in the HG group, while it was prolonged from (462.5±14.5) ms to (512.6±17.6) ms in the NM group. Compared with the NM group, FPD of hiPSC-CMs was prolonged by (16.8±1.4)% in the HG group (<0.01). The FPDc of hiPSC-CMs was prolonged from (389.1±13.7) ms to (478.3±31.5) ms in the HG group, and that was prolonged from (387.7±21.6) ms to (422.6±32.9) ms in the NM group. Compared with the NM group, the FPDc of hiPSC-CMs was prolonged by (13.9±1.3)% in HG group (<0.01). The spike amplitude and CV remained unchanged between the HG group and the NM group (>0.05). Ten µmol/L of sotalol can induce significant arrhythmias from all wells in the HG group. After treatment with insulin and high glucose, compared with the HG group, BR was increased by (8.3±0.5)% in the HG+INS group (<0.05). The FPD was prolonged from (463.4±9.7) ms to (532.6±12.8) ms in the HG+INS group, while it was prolonged from (460.4±9.0) ms to (587.6±23.7) ms in the HG group. Compared with the HG group, the FPD of hiPSC-CMs was shortened by (12.7±1.9)% in the HG+INS group (<0.01). The FPDc of hiPSC-CMs was prolonged from (387.4±4.1) ms to (422.4±10.0) ms in the HG+INS group, and that was prolonged from (384.8±4.0) ms to (476.3±11.5) ms in HG group. Compared with the HG group, the FPDc of hiPSC-CMs was shortened by (14.7±1.1)% in HG group (<0.01). After the insulin treatment, the spike amplitude of hiPSC-CMs was increased from (3.12±0.46) mV to (4.35±0.64) mV in the HG+INS group, while it was enhanced from (3.06±0.35) mV to (3.33±0.41) mV in the HG group. The spike amplitude of hiPSC-CMs was increased by (30.8±3.7)% in the HG+INS group compared with that in the HG group (<0.05). The CV in the HG+INS group was increased from (0.23±0.08) mm/ms to (0.32±0.08) mm/ms after insulin treatment, which was increased from (0.21±0.04) mm/ms to (0.30±0.07) mm/ms in the HG group, but there was no significant difference in CV between the HG+INS group and the HG group (>0.05). The induction experiment showed that 10 μmol/L of sotalol could prolong the FPDc of hiPSC-CMs by (78.9±11.6)% in the HG+INS group, but no arrhythmia was induced in each well.
CONCLUSIONS
High glucose can induce FPD/FPDc of hiPSC-CMs prolongation and increase the risk of arrhythmia induced by drugs. Insulin can reduce the FPD/FPDc prolongation and the risk of induced arrhythmia by high glucose.These results are important to understand the electrophysiological changes of the myocardium in diabetic patients and the impact of insulin therapy on its electrophysiology. Further study on the mechanism may provide new ideas and methods for the treatment of acquired and even inherited long QT syndrome.
Topics: Arrhythmias, Cardiac; Cells, Cultured; Glucose; Humans; Induced Pluripotent Stem Cells; Insulin; Myocytes, Cardiac; Sotalol
PubMed: 35753731
DOI: 10.11817/j.issn.1672-7347.2022.210408 -
British Journal of Pharmacology Sep 2022HERG blocking drugs known for their propensity to trigger Torsades de Pointes (TdP) were reported to induce a sympatho-vagal coactivation and to enhance High Frequency...
BACKGROUND AND PURPOSE
HERG blocking drugs known for their propensity to trigger Torsades de Pointes (TdP) were reported to induce a sympatho-vagal coactivation and to enhance High Frequency heart rate (HFHR) and QT oscillations (HFQT) in telemetric data. The present work aimed to characterize the underlying mechanism(s) leading to these autonomic changes.
EXPERIMENTAL APPROACH
Effects of 15 torsadogenic hERG blocking drugs (astemizole, chlorpromazine, cisapride, droperidol, ibutilide, dofetilide, haloperidol, moxifloxacin, pimozide, quinidine, risperidone, sotalol, sertindole, terfenadine, and thioridazine) were assessed by telemetry in beagle dogs. Haemodynamic effects on diastolic and systolic arterial pressure were analysed from the first doses causing QTc prolongation and/or HFQT oscillations enhancement. Autonomic control changes were analysed using the high frequency autonomic modulation (HFAM) model.
KEY RESULTS
Except for moxifloxacin and quinidine, all torsadogenic hERG blockers induced parasympathetic activation or sympatho-vagal coactivation combined with enhancement of HFQT oscillations. These autonomic effects result from reflex compensatory mechanisms in response to mild haemodynamic side effects. These haemodynamic mechanisms were characterized by transient HR acceleration during HF oscillations. A phenomenon of concealed QT prolongation was unmasked for several torsadogenic hERG blockers under β-adrenoceptor blockade with atenolol. Resulting enhancement of HFQT oscillations was shown to contribute directly to triggering dofetilide-induced ventricular arrhythmias.
CONCLUSION AND IMPLICATIONS
This work supports for the first time a contribution of haemodynamic side properties to ventricular arrhythmias triggered by torsadogenic hERG blocking drugs. These haemodynamic side effects may constitute a second component of their arrhythmic profile, acting as a trigger alongside their intrinsic arrhythmogenic electrophysiological properties.
Topics: Animals; Arrhythmias, Cardiac; Dogs; Drug-Related Side Effects and Adverse Reactions; Electrocardiography; Ether-A-Go-Go Potassium Channels; Heart Rate; Long QT Syndrome; Moxifloxacin; Quinidine; Reflex; Torsades de Pointes
PubMed: 35751378
DOI: 10.1111/bph.15905 -
The Science of the Total Environment Oct 2022The removal of emerging pollutants from municipal wastewater was studied for the first time using a three-step pilot-scale system: 1) hybrid digester (HD) as first step,...
The removal of emerging pollutants from municipal wastewater was studied for the first time using a three-step pilot-scale system: 1) hybrid digester (HD) as first step, 2) subsurface vertical flow constructed wetland (VF) as second step, and 3) photodegradation (PD) unit as third step or post-treatment. The HD and VF units were built and operated in series with effluent recirculation at pilot scale. For the PD post-treatment, three alternatives were studied at lab-scale, i) UVC irradiation at 254 nm (0.5 h exposure time), ii) UVA irradiation at 365 nm using a TiO-based photocatalyst and iii) sunlight irradiation using a TiO-based photocatalyst, the last two for 1 and 2 h. Alternative iii) was also tested at pilot-scale. Degradation of nine compounds was evaluated: acetaminophen (ACE), caffeine (CAF), carbamazepine (CBZ), ketoprofen (KET), ibuprofen (IBU), diclofenac (DCL), clofibric acid (ACB), bisphenol A (BPA), and sotalol (SOT). Overall, the HD-VF-UVC system completely removed (>99.5 %) ACE, CAF, KET, IBU, DCL and ACB, and to a lesser extent SOT (98 %), BPA (83 %) and CBZ (51 %). On the other hand, the HD-VF-UVA/TiO system (at 2 h) achieved >99.5 % removal of ACE, CAF, KET, IBU and DCL while ACB, BPA, CBZ and SOT were degraded by 83 %, 81 %, 78 % and 68 %, respectively. Working also at 2 h of exposure time, in summer conditions, the HD-VF-Sol/TiO system achieved >99.5 % removal of ACE, CAF, KET, IBU, DCL and ACB, and to a minor extent BPA (80 %), SOT (74 %) and CBZ (69 %). Similar results, although slightly lower for SOT (60 %) and CBZ (59 %), were obtained in the pilot sunlight plus TiO catalyst unit. However, the use of sunlight irradiation with a TiO-based photocatalyst clearly showed lower removal efficiency in autumn conditions (i.e., 47 % SOT, 31 % CBZ).
Topics: Carbamazepine; Diclofenac; Environmental Pollutants; Photolysis; Waste Disposal, Fluid; Wastewater; Water Pollutants, Chemical; Wetlands
PubMed: 35750172
DOI: 10.1016/j.scitotenv.2022.156750