The burden of cardiovascular disease (CVD) is rising in Kenya and non-adherence to cardiovascular pharmacotherapy is a growing global public health issue that leads to treatment failure, an increased risk of cardiac events and poor clinical outcomes. This study assessed adherence to selected cardiovascular therapy medications among CVD patients attending outpatient clinics at Kenyatta National Hospital, Kenya by determining drug concentration(s) in patient dried blood spot (DBS) samples. Patients who had been taking one or more of the five commonly prescribed CVD medications (amlodipine, atenolol, atorvastatin, losartan, and valsartan) for at least six months were enrolled. Each patient completed a short questionnaire about their medication history and then provided a finger-prick blood spot sample from which drug concentrations were determined by liquid chromatography-high resolution mass spectrometry analysis. Two hundred and thirty-nine patients (62.3% female) participated in the study. The median number of medications used by patients was 2 (IQR 75%-25% is 3-1). Less than half (117; 49.0%) of patients were adherent to their prescribed CVD pharmacotherapy. Binary regression analysis revealed a significant correlation between non-adherence and the number of medications in the treatment regimen (Odds Ratio (OR) 1.583; 95%CI: 0.949-2.639; P-value = 0.039) and that gender was not an independent predictor of medication adherence (OR 1.233; 95%CI: 0.730-2.083; P-value = 0.216). Valuable information about adherence to each medication in the patient's treatment regimen was obtained using quantitative DBS analysis showing that adherence to CVD medications was not uniform. DBS sampling, due its minimally invasive nature, convenience and ease of transport is a useful alternative matrix to monitor adherence to pharmacotherapies objectively, when combined with hyphenated mass spectrometry analytical techniques. This information can provide physicians with an evidence-based novel approach towards personalization and optimization of CVD pharmacotherapy and implementing interventions in the Kenyan population, thereby improving clinical outcomes.

With outstanding analytical performances, mass spectrometry (MS) has shown great potential for clinical applications. To facilitate the sampling process and quantitative analysis, a capillary-in-capillary electrospray ionization (CC-ESI) source was developed in this study. Utilizing two nested capillaries as a sampler and an ESI emitter, the source enabled spontaneous liquid sampling based on the capillary phenomenon and electrospray ionization mass spectrometry (ESI-MS) analysis. Apart from the cheap price, high portability, and disposability, the CC-ESI had merits of quantitation capability as well as adequate sensitivity. By coupling CC-ESI to a miniature mass spectrometer (mini-MS), a limit of detection (LOD) of 1 ng/mL was achieved for standard imatinib at collision-induced dissociation (CID) tandem MS mode, and a LOQ of 1 ng/mL was obtained for atenolol and imatinib (with isotopic internal standard) at multiple ion reaction monitoring (MRM) modes. As two demonstrations for analysis of practical samples, rapid analysis of abused drugs on surface and quantitative analysis of therapeutic drugs in whole blood were also performed with a CC-ESI mini-MS.

Physiologically, β-adrenoceptors are major regulators of lipid metabolism, which may be reflected in alterations in lipid droplet dynamics. β-adrenoceptors have also been shown to participate in breast cancer carcinogenesis. Since lipid droplets may be seen as a hallmark of cancer, the present study aimed to investigate the role of β-adrenoceptors in the regulation of lipid droplet dynamics in MCF-7 breast cancer cells. Cells were treated for up to 72 h with adrenaline (an endogenous adrenoceptor agonist), isoprenaline (a non-selective β-adrenoceptor agonist) and salbutamol (a selective β2-selective agonist), and their effects on lipid droplets were evaluated using Nile Red staining. Adrenaline or isoprenaline, but not salbutamol, caused a lipid-accumulating phenotype in the MCF-7 cells. These effects were significantly reduced by selective β1- and β3-antagonists (10 nM atenolol and 100 nM L-748,337, respectively), indicating a dependence on both β1- and β3-adrenoceptors. These effects were dependent on the cAMP signalling pathway, involving both protein kinase A (PKA) and cAMP-dependent guanine-nucleotide-exchange (EPAC) proteins: treatment with cAMP-elevating agents (forskolin or 8-Br-cAMP) induced lipid droplet accumulation, whereas either 1 µM H-89 or 1 µM ESI-09 (PKA or EPAC inhibitors, respectively) abrogated this effect. Taken together, the present results demonstrate the existence of a β-adrenoceptor-mediated regulation of lipid droplet dynamics in breast cancer cells, likely involving β1- and β3-adrenoceptors, revealing a new mechanism by which adrenergic stimulation may influence cancer cell metabolism.

Blood pressure medications are used to treat hypertension; however, low concentrations of beta-blockers in water systems can negatively impact aquatic wildlife. Here, we conducted a metabolic and behavioral study investigating atenolol, a beta-blocker frequently detected in global wastewater systems. The objectives were to determine the effects of low-level atenolol exposure on early stages of zebrafish. We measured survival, deformities, heartbeat, mitochondrial function, lipid and amino acid profiles, and locomotor activity to discern mechanisms of metabolic disruption. We hypothesized that atenolol disrupts lipid metabolism, which would negatively impact locomotor activity. Atenolol showed no overt toxicity to larval zebrafish up to 10 μg/L and deformities were infrequent (<5 %), and included cardiac edema and larvae with kinked tails. A hatch delay was observed at 2-day post-fertilization (dpf) for fish exposed to >5 μg/L atenolol. Heart rates were reduced in 2 and 3 dpf in fish treated with >500 ng/L atenolol. There was no change in oxygen consumption rates (basal and maximum respiration) of embryos when exposed to a range of atenolol concentrations, suggesting mitochondrial respiration was intact. Oil red staining for lipid content in larvae showed a global reduction in lipids with 10 μg/L exposure, prompting deeper investigation into the lipid profiles. Lipidomics quantified 86 lipids and revealed reduced abundance in Ceramide 18: 1 16:0 (Cer_NS d18:1_16:0), Ether linked Phosphatidylethanolamine 16:0 22:6 (EtherPE 16:0e_22:6), and Ether linked Phosphatidylcholine 16:0 22:6 (EtherPC 16:0e_22:6). We also quantified 12 amino acids and observed a subtle dose-dependent reduction in the levels of L-Histidine. Exposure to atenolol did not impact larval locomotor activity based on a Visual Motor Response test. Taken together, atenolol at environmentally relevant levels decreased heart rate of developing zebrafish and altered lipid content. As such, exposure to beta-blockers like atenolol may have negative consequences for developmental trajectories and growth of aquatic species.

In conventional reversed-phase liquid chromatography (RPLC) with hydro-organic solvents, basic cationic solutes yield retained, broad, asymmetric peaks, owing to their interaction with free anionic silanols in the stationary phase. RPLC mobile phases to which the anionic surfactant sodium dodecyl sulphate (SDS), or an ionic liquid (IL) are added, have been proposed as solutions, since these additives are able to block the silanol effect thus improving the chromatographic performance. With these additives, it is however necessary to increase the elution strength by adding an organic solvent, such as an alcohol or acetonitrile. A novel aqueous liquid chromatographic mode (in the absence of organic solvent) is here proposed, where the mobile phases contain only a mixture of aqueous solutions of SDS and an IL derived from 1-alkyl-3-methylimidazolium associated to chloride, both environmentally friendly. When these reagents are added, the anionic surfactant adsorbed on the stationary phase is able to attract the cationic solutes, whereas the adsorbed IL cation repels them. The combination of both effects (attraction and repulsion) allows the modulation of retention, by varying the IL/SDS ratio. Given the character of the additives, a type of green liquid chromatography is achieved. In this work, the chromatographic behavior of six basic compounds of pharmaceutical interest, the β-adrenoceptor antagonists acebutolol, atenolol, carteolol, metroprolol, oxprenolol and propranolol, is examined. In order to assess the chromatographic behavior of the mixed mobile phases containing SDS and IL, changes in retention, peak profile and resolution of mixtures of the analytes were explored at varying concentration of the additives.

Consumption of water polluted by crude oil is a major environmental problem typical in exploration areas. Numerous health complications such as high blood pressure, myocardial infarction, and other heart complications are prevalent and ravaging. These have gradually become age-defiling disease conditions that are usually maintained with lifestyle changes and diet control. The effect of dietary supplementation with 10% and 20% roasted cashew nuts (RCN) on systolic blood pressure and angiotensin converting enzyme I (ACE I) activities in mixed petroleum fraction (MPF) induced toxicity was studied in male Wistar rats through the modulation of the renin-angiotensin system. The phytochemicals in RCN were quantified using the high performance liquid chromatography (HPLC) technique. To predict likely binding affinity and stability, computational methods such as molecular docking, ADME, and molecular dynamic simulation were used. Out of the seven phytochemicals identified, rutin, gallic acid, and quercetin had the greatest quantities. Similarly, rutin had the highest binding affinities with ACE I, -10.7 kcal/mol, followed by quercetin, at -9.1 kcal/mol. During the molecular dynamics simulation, all of the identified phytochemicals demonstrated good pharmacokinetic capabilities and remained stable at their respective binding sites. Subsequent in vivo validation studies revealed that RCN was able to attenuate the effect of MPF by significantly (p < 0.05) lowering the systolic blood pressure and ACE I activity in comparison to the reference medication, atenolol. We recommend that cashew nuts be explored as dietary snacks as well as a low-cost, easily available component of supplements for the treatment of high blood pressure.

Human performance enhancing drugs (PEDs), frequently used in sport competitions, are strictly prohibited by the World Anti-Doping Agency (WADA). Biological samples collected from athletes and regular patients are continuously tested regarding the identification and/or quantification of the banned substances. Current work is focused on the application of a new analytical method, molecularly imprinted nanoparticles (nanoMIPs), to detect and determine concentrations of certain prohibited drugs, such as β-blockers, in water and human urine samples. These medications are used in the treatment of cardiovascular conditions, negative effects of adrenaline (helping to relief stress), and hypertension (slowing down the pulse and softening the arteries). They can also significantly increase muscle relaxation and improve heart efficiency. The new method of the detection and quantification of β-blockers is based on synthesis, characterization, and implementation of nanoMIPs (so-called plastic antibodies). It offers numerous advantages over the traditional methods, including high binding capacity, affinity, and selectivity for target molecules. Additionally, the whole process is less complicated, cheaper, and better controlled. The size and shape of the nanoMIPs is evaluated by dynamic light scattering (DLS) and transmission electron microscope (TEM). The affinity and selectivity of the nanoparticles are investigated by competitive pseudo enzyme-linked immunosorbent assay (pseudo-ELISA) similar to common immunoassays employing natural antibodies. To provide reliable results towards either doping detection or therapeutic monitoring using the minimal invasive method, the qualitative and quantitative analysis of these drugs is performed in water and human urine samples. It is demonstrated that the assay can detect β-blockers in water within the linear range 1 nmol·L-1-1 mmol·L-1 for atenolol with the detection limit 50.6 ng mL-1, and the linear range 1 mmol·L-1-10 mmol·L-1 for labetalol with the detection limit of 90.5 ng·mL-1. In human urine samples, the linear range is recorded in the concentration range 0.1 mmol·L-1-10 nmol·L-1 for atenolol and 1 mmol·L-1-10 nmol·L-1 for labetalol with a detection limit of 61.0 ng·mL-1 for atenolol and 99.4 ng·mL-1 for labetalol.

The use of reclaimed water for crop irrigation has been proposed as a suitable alternative for farmers in the coastal areas of Mediterranean countries, which suffer from greater water scarcity. In this work we study the impact on the water-soil-plant continuum of using reclaimed water for commercial crops irrigated over a long period, as well as the human risks associated with consuming the vegetables produced. Forty-four CECs were identified in the reclaimed water used for crop irrigation. Of these, twenty-four CECs were identified in the irrigated soil samples analysed. Tramadol, ofloxacin, tonalide, gemfibrozil, atenolol, caffeine, and cetirizine were the pharmaceuticals detected at the highest levels in the water samples (between 11 and 44 μg/L). The CECs with the highest average soil concentrations were tramadol (14.6 μg/kg), followed by cetirizine (13.2 μg/kg) and clarithromycin (12.7 μg/kg). In the irrigated vegetable samples analysed over the study period, carbamazepine, lidocaine, and caffeine were only detected at levels from 0.1 to 1.7 μg/kg. The CEC accumulation rate detected in the edible parts of the vegetables permanently irrigated with reclaimed water was very low (~1 %), whereas it was 33 % in the soils. The results revealed that consuming fruits harvested from plants irrigated for a long period with reclaimed water does not represent a risk to human health, opening the door to a circular economy of water. Nevertheless, for crop irrigation, future studies need to be conducted over longer periods and in other matrices to provide more scientific data on the safety of using reclaimed water.

Intrinsically, enteric capsule shells offer several advantages compared to coating of dosage forms with enteric polymers. We undertook a systematic investigation to elucidate capsule-fill parameters that may result in premature gastric drug release from Vcaps® Enteric capsules (Lonza CHI, Morristown, NJ, USA). Four model drugs with different ionization and solubility profiles were investigated: acetaminophen, ketoprofen, trimethoprim and atenolol. Different fill loads, diluents and drug-to-diluent ratios were explored. Enteric capsules were filled with drug or drug and diluent powder mix and underwent USP II dissolution testing using mini-vessels and paddles. Capsules were tested in pH 2 (0.01 M HCl) or pH 4.5 (3.2 × 10-5 M HCl) 200 mL acid media to simulate normal, fasted or hypochlorhydric gastric pH, respectively. Acetaminophen, trimethoprim and atenolol displayed premature gastric drug release from enteric capsules. The extent of premature release was dependent on drug solubility, ionization profile and capsule-fill level. At 100 mg drug-fill level, acetaminophen, trimethoprim and atenolol gave rise to 10.6, 12.2 and 83.1% drug release, respectively, in normal, fasted, gastric fluids. Diffusion layer pH of trimethoprim and atenolol in pH 2 media was determined to be pH 6.3 and 10.3, respectively. Upon increasing capsule-fill load using microcrystalline cellulose as a diluent, a significant reduction in premature gastric release was observed. However, including mannitol as a diluent was only effective at decreasing premature drug release at a low drug-to-diluent ratio. Systematic in vitro screening of enteric capsule fills needs to be conducted to ensure that drug product performance is not compromised.

The recalcitrant β-blockers have been widely detected in aquatic environments up to several hundred μg/L, which are major contributors to β1 antagonistic activities in wastewater. Their biodegradation mechanisms remain obscure, hindering the development of efficient removal techniques. This study constructed the biodegradation pathways for three typical β-blockers, namely atenolol, metoprolol, and propranolol, assessed the toxicity of their major biotransformation products, and identified the key enzyme catalyzing the O-dealkylation reaction leading to pollutant mineralization. Atenolol and metoprolol degradation was more efficient than that of propranolol by activated sludge, producing metoprolol acid (MTPA) as a major intermediate. Hydrogenophaga sp. YM1 isolated from activated sludge possess the α-ketoglutarate dependent dioxygenase (TfdA) responsible for O-dealkylation of MTPA and propranolol, producing 4-hydroxyphenylacetic acid (4-HPA) that can be further degraded and ultimately enters the TCA cycle. The role of TfdA was verified by proteomics, enzyme stimulation/inhibition tests, and gene knockout experiments. Molecular docking suggests its different interactions with MTPA and propranolol. Acetate facilitated the degradation of β-blockers efficiently. The results may shed light on enhanced biological removals of broader β-blockers and their transformation products in the environment.

Lipid nanoparticles have gained much attention due to their potential as drug delivery systems. They are safe, effective, and be targeted to particular tissues to deliver their payload. Niosomes are one type of lipid nanoparticles that comprise non-ionic surfactants which have proven to be effective due to their stability and biocompatibility. Different manufacturing processes have been reported for niosome preparation, but many of them are not scalable or reproducible for pharmaceutical use. In this study, microfluidic mixing was used to prepare niosomes with different lipid compositions by changing the type of non-ionic surfactant. Niosomes were evaluated for their physicochemical characteristics, morphology, encapsulation efficacy, release profiles of atenolol as a model hydrophilic compound, and cytotoxic activities. Microfluidic mixing allows for particle self-assembly and drug loading in a single step, without the need for post-preparation size reduction. Depending on the lipid composition, the empty particles were <90 nm in size with a uniform distribution. A slight but not significant increase in these values was observed when loading atenolol in most of the prepared formulations. All formulations were spherical and achieved variable levels of atenolol encapsulation. Atenolol release was slow and followed the Korsmeyer-Peppas model regardless of the surfactant type or the percentage of cholesterol used.

In this article we applied drug consumption approach and chemical analysis in parallel to investigate the concentrations of a large number of pharmaceuticals in different streams of a General Hospital. Drugs consumption data was collected during two periods (Period 1, 2) and the predicted environmental concentrations (PECs) were estimated for the wastewater of a building housing specific medical services (Point A) and for the entire hospital (Point B). Hospital wastewater samples (HWW) samples were also collected from these points and periods and the measured environmental concentrations (MEC) were determined using UHPLC-ESI-QTOF-MS/MS. According to consumption data, the highest number of drugs was consumed in the departments of Hematology, Intensive Care Unit, Cardiology, Internal Medicine, and Oncology, while the number of active substances used in the hospital was 413 (Period 1) and 362 (Period 2). For most substances, much higher PEC and MEC values were found at the HWW of Point A indicating that on-site treatment of this stream could be examined in the future. The application of wide-scope target analysis allowed the quantification of 122 compounds, while 21 additional substances were identified using suspect screening. The highest mean concentrations in Period 1 were found for acetaminophen (1100 μg/L) and rifaximin (723 μg/L), while in Period 2 for iopromide (458 μg/L) and acyclovir (408 μg/L). Among the detected compounds, 19 metabolites were determined. Atenolol acid, 1-hydroxy-midazolam and clopidogrel carboxylic acid were quantified at concentrations much higher than parent compounds indicating the importance of metabolites' monitoring in HWW. Calculation of PEC/MEC ratio for 36 pharmaceuticals showed sufficient correlation of these values for 19 % to 33 % of the substances depending on the examined period and sampling point. The parallel collection of drugs consumption data and chemical analysis give a thorough picture of the substances present in HWW and their main sources, facilitating decision-making for their better management.

The absence of effective wastewater treatment technology to eliminate emerging pollutants from municipal sewage has become a pressing issue. In this study, the efficacy of a novel modified trickling filter (MTF), conventional activated sludge process (ASP) and two tertiary systems (UV and ozonation) were compared in eliminating antibiotic-resistant bacteria (ARB), antibiotic resistance genes (ARGs) and pharmaceuticals and personal care products (PPCPs) from urban sewage. MTF and ASP resulted in >1 log unit reduction in the abundance of ARB, while for ARGs, the removal was observed in the range of 0.1 to 1.7 log units. In MTF, ARGs were substantially removed in the aerobic zone compared to the anoxic zone. The relative abundance of most of the ARGs either decreased or remained unchanged during MTF and ASP operations. However, the relative abundance of most of the ARGs increased in the secondary sludge generated from ASP. The concentration of PPCPs such as atenolol, sulfamethazine, triclosan, and ranitidine was reduced by MTF by >80 %. Overall, the results indicated that MTF followed by ozonation is the most effective combination for removing emerging contaminants from municipal sewage.

The development of bacterial resistance to antibiotics is an increasing public health issue that worsens with the formation of biofilms. Quorum sensing (QS) orchestrates the bacterial virulence and controls the formation of biofilm. Targeting bacterial virulence is promising approach to overcome the resistance increment to antibiotics. In a previous detailed in silico study, the anti-QS activities of twenty-two β-adrenoreceptor blockers were screened supposing atenolol as a promising candidate. The current study aims to evaluate the anti-QS, anti-biofilm and anti-virulence activities of the β-adrenoreceptor blocker atenolol against Gram-negative bacteria Serratia marcescens, Pseudomonas aeruginosa, and Proteus mirabilis. An in silico study was conducted to evaluate the binding affinity of atenolol to S. marcescens SmaR QS receptor, P. aeruginosa QscR QS receptor, and P. mirabilis MrpH adhesin. The atenolol anti-virulence activity was evaluated against the tested strains in vitro and in vivo. The present finding shows considerable ability of atenolol to compete with QS proteins and significantly downregulated the expression of QS- and virulence-encoding genes. Atenolol showed significant reduction in the tested bacterial biofilm formation, virulence enzyme production, and motility. Furthermore, atenolol significantly diminished the bacterial capacity for killing and protected mice. In conclusion, atenolol has potential anti-QS and anti-virulence activities against S. marcescens, P. aeruginosa, and P. mirabilis and can be used as an adjuvant in treatment of aggressive bacterial infections.

The aim of the present study was to explore Cassia fistula L. seed mucilage as a natural polymer in controlled release floating drug delivery system. First, seed mucilage was extracted and evaluated for phytochemical screening, solubility studies, swelling index, viscosity and surface tension. Then, Atenolol floating systems were prepared with and without the C. fistula L. seed mucilage by direct compression method. Phytochemical screening resulted from the presence of secondary metabolite carbohydrates, glycosides, flavonoids and phenolic compounds in good amounts. Results of hardness, friability, drug content and swelling index were satisfactory. The floating behaviour can increase the gastric residence time and eventually improve the bioavailability of the drug as evidence from in vitro buoyancy and dissolution studies. Interestingly, developed floating system showed remarkable increase in dissolution. Conclusively, the results suggest that developed Atenolol floating system with C. fistula L. seed mucilage demonstrate interesting attributes to be explored for potential pharmaceutical application.

The targeting of bacterial virulence is proposed as a promising approach to overcoming the bacterial resistance development to antibiotics. Salmonella enterica is one of the most important gut pathogens that cause a wide diversity of local and systemic illnesses. The Salmonella virulence is controlled by interplayed systems namely Quorum sensing (QS) and type three secretion system (T3SS). Furthermore, the Salmonella spy on the host cell via sensing the adrenergic hormones enhancing its virulence. The current study explores the possible anti-virulence activities of β-adrenoreceptor blocker atenolol against S. enterica serovar Typhimurium in vitro, in silico, and in vivo. The present findings revealed a significant atenolol ability to diminish the S. typhimurium biofilm formation, invasion into HeLa cells, and intracellular replication inside macrophages. Atenolol significantly downregulated the encoding genes of the T3SS-type II, QS receptor Lux analogs sdiA, and norepinephrine membranal sensors qseC and qseE. Moreover, atenolol significantly protected mice against S. typhimurium. For testing the possible mechanisms for atenolol anti-virulence activities, an in silico molecular docking study was conducted to assess the atenolol binding ability to QS receptor SdiA and norepinephrine membranal sensors QseC. Atenolol showed the ability to compete on the S. typhimurium targets. In conclusion, atenolol is a promising anti-virulence candidate to alleviate the S. typhimurium pathogenesis by targeting its QS and T3SS systems besides diminishing the eavesdropping on the host cells.

Significant advancements in the field of preclinical in vitro blood-brain barrier (BBB) models have been achieved in recent years, by developing monolayer-based culture systems towards complex multi-cellular assays. The coupling of those models with other relevant organoid systems to integrate the investigation of blood-brain barrier permeation in the larger picture of drug distribution and metabolization is still missing. Here, we report for the first time the combination of a human induced pluripotent stem cell (hiPSC)-derived blood-brain barrier model with a cortical brain and a liver spheroid model from the same donor in a closed microfluidic system (MPS). The two model compounds atenolol and propranolol were used to measure permeation at the blood-brain barrier and to assess metabolization. Both substances showed an in vivo-like permeation behavior and were metabolized in vitro. Therefore, the novel multi-organ system enabled not only the measurement of parent compound concentrations but also of metabolite distribution at the blood-brain barrier.

Cardiac and hepatotoxicities are major concerns in the development of new drugs. Better alternatives to other treatments are being sought to protect these vital organs from the toxicities of these pharmaceuticals. In this regard, a preclinical study is designed to investigate the histopathological effects of a new succinimide derivative (Comp-1) on myocardial and liver tissues, and the biochemical effects on selected cardiac biomarkers, hepatic enzymes, and lipid profiles. For this, an initially lethal/toxic dose was determined, followed by a grouping of selected albino rats into five groups (each group had n = 6). The control group received daily oral saline for 8 days. The 5-FU (5-Fluorouracil) group received oral saline daily for 8 days, added with the administration of a single dose of 5-FU (150 mg/kg I.P.) on day 5 of the study. The atenolol group received oral atenolol (20 mg/kg) for 8 days and 5-FU (150 mg/kg I.P.) on day 5 of the protocol. Similarly, two groups of rats treated with test compound (Comp-1) were administered with 5 mg/kg I.P. and 10 mg/kg I.P. for 8 days, followed by 5-FU (150 mg/kg I.P.) on day 5. Toxicity induced by 5-FU was manifested by increases in the serum creatinine kinase myocardial band (CK-MB), troponin I (cTnI) and lactate dehydrogenase (LDH), lipid profile, and selected liver enzymes, including ALP (alkaline phosphatase), ALT (alanine transaminase), AST (aspartate aminotransferase), BT (bilirubin total), and BD (direct bilirubin). These biomarkers were highly significantly decreased after the administration of the mentioned doses of the test compound (5 mg/kg and 10 mg/kg). Similarly, histological examination revealed cardiac and hepatic tissue toxicity by 5-FU. However, those toxic effects were also significantly recovered/improved after the administration of Comp-1 at the said doses. This derivative showed dose-dependent effects and was most effective at a dose of 10 mg/kg body weight. Binding energy data computed via docking simulations revealed that our compound interacts toward the human beta2-adrenergic G protein-coupled receptor (S = -7.89 kcal/mol) with a slight stronger affinity than the calcium channel T-type (S = -7.07 kcal/mol). In conclusion, the histological and biochemical results showed that the test compound (Comp-1) had prominent cardioprotective, hepatoprotective, and lipolytic effects against 5-FU-induced toxicity in the subjected animal model.

Atenolol is a second-generation beta-1-selective adrenergic antagonist indicated in the treatment of hypertension, angina pectoris, and acute myocardial infarction. Non-FDA approved indications include treatment of arrhythmias, migraine prophylaxis, paroxysmal supraventricular tachycardia, alcohol withdrawal, thyrotoxicosis, and prophylaxis against secondary myocardial infarction. This activity outlines the indications, mechanism of action, safe administration, adverse effects, contraindications, monitoring, and toxicity of atenolol.

Photocatalysis is a promising technology for wastewater treatment. It is of great significance to find catalysts with high photoactivity. In this paper, a catalyst with high photocatalytic degradation efficiency to organic wastewater, carbon nitride modified by graphene quantum dots (SCN-GQDX), is prepared by supramolecular self-assembly thermal polycondensation method and doping graphene quantum dots (GQDs). The results show that SCN-GQD0.5 has the best catalytic performance, and its photocatalytic degradation efficiency to organic pollutants can reach 86% and still remains above 83% after five cycles, which shows the modified carbon nitride has high catalytic efficiency and stability. In a word, SCN-GQDX is a highly efficient, non-toxic and stable photocatalyst for organic pollutants in wastewater.

In shallow, open-water engineered wetlands, design parameters select for a photosynthetic microbial biomat capable of robust pharmaceutical biotransformation, yet the contributions of specific microbial processes remain unclear. Here, we combined genome-resolved metatranscriptomics and oxygen profiling of a field-scale biomat to inform laboratory inhibition microcosms amended with a suite of pharmaceuticals. Our analyses revealed a dynamic surficial layer harboring oxic-anoxic cycling and simultaneous photosynthetic, nitrifying, and denitrifying microbial transcription spanning nine bacterial phyla, with unbinned eukaryotic scaffolds suggesting a dominance of diatoms. In the laboratory, photosynthesis, nitrification, and denitrification were broadly decoupled by incubating oxic and anoxic microcosms in the presence and absence of light and nitrogen cycling enzyme inhibitors. Through combining microcosm inhibition data with field-scale metagenomics, we inferred microbial clades responsible for biotransformation associated with membrane-bound nitrate reductase activity (emtricitabine, trimethoprim, and atenolol), nitrous oxide reduction (trimethoprim), ammonium oxidation (trimethoprim and emtricitabine), and photosynthesis (metoprolol). Monitoring of transformation products of atenolol and emtricitabine confirmed that inhibition was specific to biotransformation and highlighted the value of oscillating redox environments for the further transformation of atenolol acid. Our findings shed light on microbial processes contributing to pharmaceutical biotransformation in open-water wetlands with implications for similar nature-based treatment systems.

In order to improve stability and antibacterial property, a novel super-hydrophilic partially reduced graphene oxide membrane was prepared by interfacial polymerization of piperazine and partially reduced graphene oxide as aqueous solution and trimesoyl chloride as organic solution. Fourier transform infrared spectroscopy, scanning electron microscope, and contact angle measurement were conducted to probe the morphology and properties of the membranes. The modified membrane possessed super-hydrophilicity, improved durability and swelling resistance. The optimized membrane had a molecular weight cut off of about 674 Da and possessed a pure water permeability of 49.86 L·m-2·h-1·MPa-1. The retention order of salts was Na2SO4 > MgSO4 > MgCl2 > Na2CO3 > CaCl2 > NaCl, while the rejection for four kinds of pharmaceuticals followed the order of ibuprofen (92%) > carbamazepine (87%) > amlodipine (80%) > atenolol (76%), indicating that the negatively charged membrane could improve the retention performance by the electrostatic repulsive effect. Moreover, the enhanced antibacterial performance of membrane attributed to the dual effects of the super-hydrophilicity and the tea polyphenols antibacterial material loading, which may alter the charge distribution on and within the membrane, leading to loss of cell viability.

This is a case study of a 25-year-old female, Ashkenazy Jewish, previously healthy, presented with a complaint of weakness. Her sugar level on the glucometer was 50 mg% and she felt better after ingestion of a small amount of sugar. Two weeks earlier, while traveling in Peru, she developed thyrotoxicosis and began taking Mercaptizol 30 mg a day and Atenolol 100 mg. She didn't drink iodine (iodinated preparations for water purification) while traveling and had no pain or fever. Her physical examination showed no goiter or exophthalmos. While I saw her she was already euthyroid and felt quite good except for fatigue. In the literature, we found a few case reports of Mercaptizol and PTU-induced insulin autoantibodies which cause symptomatic hypoglycemia. Most cases were described in the Asian population (especially Japanese people) and resolved a few weeks after stopping intake of the drug. In our patient, the hypoglycemia resolved after only one episode and discontinuation of Mercaptizol. Insulin antibodies were negative, and insulin levels (C-peptide) were relatively high. My conclusion is that physicians should be aware of Mercaptizol and PTU-induced hypoglycemia which can be life-threatening.