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Materials (Basel, Switzerland) Mar 2024Adsorptive, catalytic, and antibacterial properties of clinoptilolite-rich tuffs (ZT) are presented here. ZT transformed into Fe-containing ZT (Fe-ZT) removes various... (Review)
Review
Adsorptive, catalytic, and antibacterial properties of clinoptilolite-rich tuffs (ZT) are presented here. ZT transformed into Fe-containing ZT (Fe-ZT) removes various organic and inorganic anions from water. Fe-ZT, which contains selenium, is beneficial for growing mushrooms. The fungi convert inorganic Se from Fe-ZT into a more useful organically bonded form. ZT and Fe-ZT as supplements retain nitrogen and potassium in sandy, silty loam and silty clay soils. ZT shows an affinity toward toxic metal cations, which are essential for cleaning contaminated water. The adsorption of atenolol, acetylsalicylic, and salicylic acid onto M-ZT (M-Cu, Mn, Ni, or Zn) from water solutions suggests that both the natures of M and pharmaceuticals have a significant impact on the adsorption mechanism and determine the adsorption capability of the ZT. ZT is an excellent carrier for ultrafine (2-5 nm) nano oxide particles, which have been shown to have catalytic activity in different chemical processes and photodegradation reactions of organic pollutants. ZT can also be transformed into SO-SnO-ZT, which is catalytically active as a solid acid. M-ZT is an effective carrier of valuable bacteria. Ag-ZT possesses beneficial bactericidal activity in disinfecting water and soil remediation.
PubMed: 38541460
DOI: 10.3390/ma17061306 -
Cardio-oncology (London, England) Mar 2024Cardiovascular (CV) disease is a leading cause of death in breast cancer (BC) patients due to the increased age and treatments. While individual β-blockers have been...
BACKGROUND
Cardiovascular (CV) disease is a leading cause of death in breast cancer (BC) patients due to the increased age and treatments. While individual β-blockers have been investigated to manage CV complications, various β-blockers have not been compared for their effects on CV death in this population. We aimed to compare CV mortality in older BC patients taking one of the commonly used β-blockers.
METHODS
This retrospective cohort study was conducted using the Surveillance, Epidemiology and End Results (SEER) - Medicare data (2010-2015). Patients of age 66 years or older at BC diagnosis receiving metoprolol, atenolol, or carvedilol monotherapy were included. The competing risk regression model was used to determine the risk of CV mortality in the three β-blocker groups. The multivariable model was adjusted for demographic and clinical covariates. The adjusted hazard ratio (HR) and 95% confidence intervals (CI) were reported for the risk of CV mortality.
RESULTS
The study cohort included 6,540 patients of which 55% were metoprolol users, 30% were atenolol users, and 15% were carvedilol users. Metoprolol was associated with a 37% reduced risk of CV mortality (P = 0.03) compared to carvedilol after adjusting for the covariates (HR = 0.63; 95% CI 0.41-0.96). No significant difference in the risk of CV mortality between atenolol and carvedilol users was observed (HR = 0.74; 95% CI 0.44-1.22).
CONCLUSIONS
Our findings suggest that metoprolol is associated with a reduced risk of CV mortality in BC patients. Future studies are needed to confirm these findings and understand the mechanism of action.
PubMed: 38532523
DOI: 10.1186/s40959-024-00217-1 -
Journal of Pharmacological Sciences Apr 2024Cardio-stimulatory actions of aciclovir have been considered to primarily depend on the sympathetically-mediated reflex resulting from its hypotensive effect. To further...
Cardio-stimulatory actions of aciclovir have been considered to primarily depend on the sympathetically-mediated reflex resulting from its hypotensive effect. To further clarify onset mechanisms of the cardio-stimulatory actions, we initially studied them using isoflurane-anesthetized dogs under thorough β-adrenoceptor blockade with atenolol (1 mg/kg, i.v.) (n = 4). Aciclovir (20 mg/kg/10 min, i.v.) decreased mean arterial blood pressure by 10 mmHg, whereas it increased heart rate by 10 bpm and maximum upstroke velocity of ventricular pressure by 928 mmHg/s, and shortened AH interval by 2 ms, indicating that cardio-stimulatory actions were not totally abolished by β-adrenoceptor blockade. Then, unknown mechanisms of cardio-stimulatory action were explored. Since aciclovir has a similar chemical structure to theophylline, in silico molecular docking simulation was performed, indicating aciclovir as well as theophylline possesses strong likelihood of interactions with phosphodiesterase 1A, 1C and 3A. Indeed, aciclovir inhibited phosphodiesterase 1A derived from the bovine heart (n = 4), moreover it exerted positive chronotropic action on the atrial tissue preparation of rats along with an increase of tissue cyclic AMP concentration (n = 4). These results indicate that cardio-stimulatory actions of aciclovir could result from not only hypotension-induced, reflex-mediated increase of sympathetic tone but also its inhibitory effects on phosphodiesterase in the heart.
Topics: Animals; Cattle; Rats; Dogs; Theophylline; Acyclovir; Molecular Docking Simulation; Blood Pressure; Hypotension; Heart Atria; Heart Rate; Phosphoric Diester Hydrolases; Receptors, Adrenergic
PubMed: 38485347
DOI: 10.1016/j.jphs.2024.02.005 -
Journal of Pharmacological and... 2024The strategic and targeted use of an anesthetized canine cardiovascular model early in drug discovery enables a comprehensive cardiovascular and electrophysiological...
The strategic and targeted use of an anesthetized canine cardiovascular model early in drug discovery enables a comprehensive cardiovascular and electrophysiological assessment of potential safety liabilities and guides compound selection prior to initiation of chronic toxicological studies. An ideal model would enable exposure-response relationships to guide safety margin calculations, have a low threshold to initiate, and have quick delivery of decision quality data. We have aimed to profile compounds with diverse mechanism of actions (MoAs) of "non-QT" cardiovascular drug effects and evaluate the ability of nonclinical in vivo cardiovascular models to detect clinically reported effects. The hemodynamic effects of 11 drugs (atropine, itraconazole, atenolol, ivabradine, milrinone, enalaprilat, fasudil, amlodipine, prazosin, amiloride, and hydrochlorothiazide) were profiled in an anesthetized dog cardiovascular model. Derived parameters included: heart rate, an index of left ventricular contractility, mean arterial pressure, systemic vascular resistance, and cardiac output. Species specific plasma protein data was generated (human, dog) and utilized to calculate free drug concentrations. Using the anesthetized dog cardiovascular model, 10 of the 11 drugs displayed the predicted changes in CV parameters based on their primary MoAs and corresponding clinically described effects. Interestingly but not unexpected, 1 of 11 failed to display their predicted CV pattern which is likely due to a delay in pharmacodynamic effect that is beyond the duration of the experimental model (hydrochlorothiazide). The analysis from the current study supports the strategic use of the anesthetized dog model early in the drug discovery process for a comprehensive cardiovascular evaluation with good translation to human.
Topics: Dogs; Animals; Humans; Drug Evaluation, Preclinical; Hemodynamics; Heart Rate; Pharmaceutical Preparations; Heart Ventricles; Hydrochlorothiazide; Blood Pressure
PubMed: 38479593
DOI: 10.1016/j.vascn.2024.107497 -
Journal of Hazardous Materials May 2024Enhancing Fe(VI) oxidation ability by generating high-valent iron-oxo species (Fe(IV)/Fe(V)) has attracted continuous interest. This work for the first time reports the...
Enhancing Fe(VI) oxidation ability by generating high-valent iron-oxo species (Fe(IV)/Fe(V)) has attracted continuous interest. This work for the first time reports the efficient activation of Fe(VI) by a well-known aza-aromatic chelating agent 2,2'-bipyridyl (BPY) for micropollutant degradation. The presence of BPY increased the degradation constants of six model compounds (i.e., sulfamethoxazole (SMX), diclofenac (DCF), atenolol (ATL), flumequine (FLU), 4-chlorophenol (4-CP), carbamazepine (CBZ)) with Fe(VI) by 2 - 6 folds compared to those by Fe(VI) alone at pH 8.0. Lines of evidence indicated the dominant role of Fe(IV)/Fe(V) intermediates. Density functional theory calculations suggested that the binding of Fe(III) to one or two BPY molecules initiated the oxidation of Fe(III) to Fe(IV) by Fe(VI), while Fe(VI) was reduced to Fe(V). The increased exposures of Fe(IV)/Fe(V) were experimentally verified by the pre-generated Fe(III) complex with BPY and using methyl phenyl sulfoxide as the probe compound. The presence of chloride and bicarbonate slightly affected model compound degradation by Fe(VI) in the presence of BPY, while a negative effect of humic acid was obtained under the same conditions. This work demonstrates the potential of N-donor heterocyclic ligand to activate Fe(VI) for micropollutant degradation, which is instructive for the Fe(VI)-based oxidation processes.
PubMed: 38460256
DOI: 10.1016/j.jhazmat.2024.133982 -
Heliyon Mar 2024Atenolol (ATL) is a beta-blocker pharmaceutical product which is excreted mainly unchanged and may represent a long-term risk for organisms present in the sea and in...
Atenolol (ATL) is a beta-blocker pharmaceutical product which is excreted mainly unchanged and may represent a long-term risk for organisms present in the sea and in fresh water. Due to its low biodegradation rate, electrochemical advanced oxidation processes (EAOPs) can be used to remove this compound. In this work, ATL ecotoxicity was analyzed in the presence of sodium sulfate (NaSO), which is widely used as supporting electrolyte in EAOPs. Ecotoxicity values were expressed as the pollutant concentration that leads to a 50% inhibition of the root elongation of seeds in relation to the control (EC(5 days)). The obtained values for ATL showed an EC(5 days) of 1377 mg L towards . When NaSO was added, the toxicity of the sample increased but no synergy was detected between both compounds. With 2 g L NaSO, ATL showed an EC(5 days) of 972 mg L; and with 4 g L NaSO and higher concentrations, EC value for ATL was 0 mg L. Statistical tools were used to obtain the zones of the [ATL]-[NaSO] plane which are toxic towards . Solutions containing ATL and NaSO were treated by electrooxidation. Two anode materials (a boron-doped diamond electrode and a microporous Sb-doped SnO ceramic one); three operation currents (0.4, 0.6 and 1 A); and two reactor configurations (one-compartment reactor and two-compartment reactor separated by a cation exchange membrane) were used. seeds and bacterium tests were employed to evaluate the toxicity of the solutions before and after applying the electrooxidation process. In all the tests, the ecotoxicity of the treated sample increased. This fact is owing to the persulfate presence in the solution due to the sulfate electrochemical oxidation. Nevertheless, none of the final samples were toxic towards because ecotoxicity values were lower than 10 TU; and, in the case of the one-compartment reactor, practically all of them were also non-toxic towards . The toxicity of the treated samples increased when using the two-compartment reactor in the presence of the BDD anode, and when the operation current was increased. This is attributed to the highest formation of persulfates. Amongst all the tests performed in this work, the lowest toxicity value (i.e., 3 TU) together with the complete mineralization and degradation degrees was achieved with the two-compartment reactor using the BDD anode and operating at 0.6 A.
PubMed: 38449618
DOI: 10.1016/j.heliyon.2024.e27266 -
JCEM Case Reports Mar 2024Diffuse thyroid lipomatosis (DTL) is a rare entity of unknown etiology that can be associated with amyloidosis and rarely, thyrotoxicosis. Here, we present a case of DTL...
Diffuse thyroid lipomatosis (DTL) is a rare entity of unknown etiology that can be associated with amyloidosis and rarely, thyrotoxicosis. Here, we present a case of DTL with amyloid deposits and concurrent thyrotoxicosis. A 64-year-old South-Asian woman with a several-year history of an enlarging goiter, unintentional weight loss, and work-up 10 months prior suggestive of thyroiditis presented with a viral syndrome in setting of several weeks of progressive fatigue. Her examination was notable for resting sinus tachycardia and massive painless goiter. Initial work-up revealed nephrotic range proteinuria with hypoalbuminemia, which progressed to end-stage-renal disease, elevated inflammatory markers, and elevated free thyroxine (FT4) with a suppressed thyrotropin. Hemodialysis was initiated. Further testing revealed a negative antithyroid antibody panel, an enlarged fatty thyroid per thyroid ultrasound and neck computed tomography, and normal 24-hour uptake on radioactive iodine uptake scan. Both renal and thyroid core biopsies showed amyloid deposits, with the latter confirming benign adipose tissue with entrapped thyroid follicles. Given her rising FT4 levels and persistent tachycardia, methimazole and atenolol were initiated. FT4 levels nearly normalized after uptitration of methimazole and dosing after dialysis. Although the etiopathogenesis and natural history of DTL remain unclear, we discuss the possible mechanisms of thyrotoxicosis in our patient.
PubMed: 38440128
DOI: 10.1210/jcemcr/luae030 -
Journal of Pharmaceutical Sciences May 2024This study aims to explore the impact of ADME on the Oral Bioavailability (OB) of drugs and to construct a machine learning model for OB prediction. The model is then...
OBJECTIVE
This study aims to explore the impact of ADME on the Oral Bioavailability (OB) of drugs and to construct a machine learning model for OB prediction. The model is then applied to predict the OB of modified berberine and atenolol molecules to obtain structures with higher OB.
METHODS
Initially, a drug OB database was established, and corresponding ADME characteristics were obtained. The relationship between ADME and OB was analyzed using machine learning, with Morgan fingerprints serving as molecular descriptors. Compounds from the database were input into Random Forest, XGBoost, CatBoost, and LightGBM machine learning models to train the OB 7prediction model and evaluate its performance. Subsequently, berberine and atenolol were modified using Chemdraw software with ten different substituents for mono-substitution, and chlorine atoms for a full range of double substitutions. The modified molecular structures were converted into the same format as the training set for OB prediction. The predicted OB values of the modified structures of berberine and atenolol were compared.
RESULTS
An OB database of 386 drugs was obtained. It was found that smaller molecular weight and a higher number of rotatable bonds (ten or less) could potentially lead to higher OB. The four machine learning models were evaluated using MSE, R2 score, MAE, and MFE as metrics, with Random Forest performing the best. The models' predictions for the test set were particularly accurate when OB ranged from 30% to 90%. After mono-substitution and double substitution of berberine and atenolol, the OB of both drugs was significantly improved.
CONCLUSIONS
This study found that some ADME properties of molecules do not have an absolute impact on OB. The database played a decisive role in the process of the machine learning OB prediction model, and the performance of the model was evaluated based on predictions within a range of strong generalization ability. In most cases, mono-substitution and double substitution were beneficial for enhancing the OB of berberine and atenolol. In summary, this study successfully constructed a machine learning regression prediction model that can accurately predict drug OB, which can guide drug design to achieve higher OB to some extent.
Topics: Biological Availability; Atenolol; Berberine; Machine Learning; Software
PubMed: 38430955
DOI: 10.1016/j.xphs.2024.02.026 -
The ISME Journal Jan 2024Organic pollutants are an increasing threat for wildlife and humans. Managing their removal is however complicated by the difficulties in predicting degradation rates....
Organic pollutants are an increasing threat for wildlife and humans. Managing their removal is however complicated by the difficulties in predicting degradation rates. In this work, we demonstrate that the complexity of the pollutant profile, the set of co-existing contaminants, is a major driver of biodegradation in wastewater. We built representative assemblages out of one to five common pharmaceuticals (caffeine, atenolol, paracetamol, ibuprofen, and enalapril) selected along a gradient of biodegradability. We followed their individual removal by wastewater microbial communities. The presence of multichemical background pollution was essential for the removal of recalcitrant molecules such as ibuprofen. High-order interactions between multiple pollutants drove removal efficiency. We explain these interactions by shifts in the microbiome, with degradable molecules such as paracetamol enriching species and pathways involved in the removal of several organic pollutants. We conclude that pollutants should be treated as part of a complex system, with emerging pollutants potentially showing cascading effects and offering leverage to promote bioremediation.
Topics: Humans; Wastewater; Environmental Pollutants; Ibuprofen; Acetaminophen; Water Pollutants, Chemical; Biodegradation, Environmental; Pharmaceutical Preparations
PubMed: 38423526
DOI: 10.1093/ismejo/wrae033