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Environmental Research Jun 2024Over the last years, the strategy of employing inevitable organic waste and residue streams to produce valuable and greener materials for a wide range of applications...
Over the last years, the strategy of employing inevitable organic waste and residue streams to produce valuable and greener materials for a wide range of applications has been proven an efficient and suitable approach. In this research, sulfur-doped porous biochar was produced through a single-step pyrolysis of birch waste tree in the presence of zinc chloride as chemical activator. The sulfur doping process led to a remarkable impact on the biochar structure. Moreover, it was shown that sulfur doping also had an important impact on sodium diclofenac (S-DCF) removal from aqueous solutions due to the introduction of S-functionalities on biochar surface. The adsorption experiments suggested that General and Liu models offered the best fit for the kinetic and equilibrium studies, respectively. The results showed that the kinetic was faster for the S-doped biochar while the maximum adsorption capacity values at 318 K were 564 mg g (non-doped) and 693 mg g (S-doped); highlighting the better affinity of S-doped biochar for the S-DCF molecule compared to non-doped biochar. The thermodynamic parameters (ΔH, ΔS, ΔG) suggested that the S-DCF removal on both adsorbents was spontaneous, favourable, and endothermic.
Topics: Diclofenac; Kinetics; Thermodynamics; Adsorption; Water Pollutants, Chemical; Sulfur; Charcoal; Water Purification; Porosity
PubMed: 38462080
DOI: 10.1016/j.envres.2024.118595 -
Indian Journal of Pharmacology Jan 2024Stevens-Johnson syndrome is a severe adverse drug reaction affecting the skin and mucous membrane. The causes include Sulfonamides, Anticonvulsants, etc. A patient...
Stevens-Johnson syndrome is a severe adverse drug reaction affecting the skin and mucous membrane. The causes include Sulfonamides, Anticonvulsants, etc. A patient developed ulcerations in the lips and oral cavity with difficulty in swallowing and rashes over the back, abdomen, and genitalia following administration of injection ceftriaxone 1 g intravenous (IV) b.i.d, injection pantoprazole 40 mg IV b.i.d, tablet aceclofenac + paracetamol 325 mg b.i.d, tablet cetirizine 10 mg b.i.d, chlorhexidine mouth wash, and injection metronidazole 500 mg IV t.i.d for the treatment of traumatic facial injury after 4 days of treatment. Injection ceftriaxone and tablet aceclofenac + paracetamol were suspected as the cause of this reaction. The two drugs were stopped. The patient was treated with corticosteroids, other antimicrobials, and oral topical anesthetics. Health-care providers should be careful about the possible adverse drug reactions even to commonly used drugs.
Topics: Humans; Stevens-Johnson Syndrome; Acetaminophen; Ceftriaxone; Facial Injuries; Tablets; Diclofenac
PubMed: 38454591
DOI: 10.4103/ijp.ijp_485_23 -
Applied Microbiology and Biotechnology Mar 2024Homogentisate solanesyltransferase (HST) is a crucial enzyme in the plastoquinone biosynthetic pathway and has recently emerged as a promising target for herbicides. In...
Homogentisate solanesyltransferase (HST) is a crucial enzyme in the plastoquinone biosynthetic pathway and has recently emerged as a promising target for herbicides. In this study, we successfully expressed and purified a stable and highly pure form of seven times transmembrane protein Chlamydomonas reinhardtii HST (CrHST). The final yield of CrHST protein obtained was 12.2 mg per liter of M9 medium. We evaluated the inhibitory effect on CrHST using Des-Morpholinocarbony Cyclopyrimorate (DMC) and found its IC value to be 3.63 ± 0.53 μM, indicating significant inhibitory potential. Additionally, we investigated the substrate affinity of CrHST with two substrates, determining the K values as 22.76 ± 1.70 μM for FPP and 48.54 ± 3.89 μM for HGA. Through sequence alignment analyses and three-dimensional structure predictions, we identified conserved amino acid residues forming the active cavity in the enzyme. The results from molecular docking and binding energy calculations indicate that DMC has a greater binding affinity with HST compared to HGA. These findings represent substantial progress in understanding CrHST's properties and potential for herbicide development. KEY POINTS: • First high-yield transmembrane CrHST protein via E. coli system • Preliminarily identified active cavity composition via activity testing • Determined substrate and inhibitor modes via molecular docking.
Topics: Escherichia coli; Molecular Docking Simulation; Membrane Proteins; Amino Acids; Chlamydomonas reinhardtii; Herbicides; Phenylacetates
PubMed: 38451307
DOI: 10.1007/s00253-024-13094-6 -
JAMA Network Open Mar 2024There are concerns about the safety of medications for treatment of attention-deficit/hyperactivity disorder (ADHD), with mixed evidence on possible cardiovascular risk.
IMPORTANCE
There are concerns about the safety of medications for treatment of attention-deficit/hyperactivity disorder (ADHD), with mixed evidence on possible cardiovascular risk.
OBJECTIVE
To assess whether short-term methylphenidate use is associated with risk of cardiovascular events.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective, population-based cohort study was based on national Swedish registry data. Participants were individuals with ADHD aged 12 to 60 years with dispensed prescriptions of methylphenidate between January 1, 2007, and June 30, 2012. Each person receiving methylphenidate (n = 26 710) was matched on birth date, sex, and county to up to 10 nonusers without ADHD (n = 225 672). Statistical analyses were performed from September 13, 2022, to May 16, 2023.
MAIN OUTCOMES AND MEASURES
Rates of cardiovascular events, including ischemic heart disease, venous thromboembolism, heart failure, or tachyarrhythmias, 1 year before methylphenidate treatment and 6 months after treatment initiation were compared between individuals receiving methylphenidate and matched controls using a bayesian within-individual design. Analyses were stratified by history of cardiovascular events.
RESULTS
The cohort included 252 382 individuals (15 442 [57.8% men]; median age, 20 (IQR, 15-31) years). The overall incidence of cardiovascular events was 1.51 per 10 000 person-weeks (95% highest density interval [HDI], 1.35-1.69) for individuals receiving methylphenidate and 0.77 (95% HDI, 0.73-0.82) for the matched controls. Individuals treated with methylphenidate had an 87% posterior probability of having a higher rate of cardiovascular events after treatment initiation (incidence rate ratio [IRR], 1.41; 95% HDI, 1.09-1.88) compared with matched controls (IRR, 1.18; 95% HDI, 1.02-1.37). The posterior probabilities were 70% for at least a 10% increased risk of cardiovascular events in individuals receiving methylphenidate vs 49% in matched controls. No difference was found in this risk between individuals with and without a history of cardiovascular disease (IRR, 1.11; 95% HDI, 0.58-2.13).
CONCLUSIONS AND RELEVANCE
In this cohort study, individuals receiving methylphenidate had a small increased cardiovascular risk vs matched controls in the 6 months after treatment initiation. However, there was little evidence for an increased risk of 20% or higher and for differences in risk increase between people with and without a history of cardiovascular disease. Therefore, before treatment initiation, careful consideration of the risk-benefit trade-off of methylphenidate would be useful, regardless of cardiovascular history.
Topics: Male; Humans; Young Adult; Adult; Female; Methylphenidate; Cardiovascular Diseases; Bayes Theorem; Cohort Studies; Retrospective Studies; Risk Factors; Heart Disease Risk Factors
PubMed: 38446477
DOI: 10.1001/jamanetworkopen.2024.1349 -
European Review For Medical and... Feb 2024Aripiprazole, risperidone, atomoxetine, and methylphenidate are drugs commonly prescribed for many psychiatric conditions and can be used alone or in combination in...
OBJECTIVE
Aripiprazole, risperidone, atomoxetine, and methylphenidate are drugs commonly prescribed for many psychiatric conditions and can be used alone or in combination in children and adolescents. This study aimed to investigate comparatively the possible genotoxic effects or genoprotective potentials of these drugs on human lymphocytes and HepG2 cells.
MATERIALS AND METHODS
Cytotoxicity analysis was performed with the cell viability test on human lymphocytes and HepG2 cells, and half-maximal inhibitory concentration (IC50) values of the drugs were determined, and three different doses (¼ IC50, ½ IC50, and IC50) were applied for genetic analysis. For the determined doses, cells with and without DNA damage were examined by comet analysis.
RESULTS
In lymphocytes, aripiprazole and risperidone increased DNA damage at moderate and maximum doses, whereas atomoxetine increased DNA damage only at the maximum dose. In HepG2 cells, risperidone reduced DNA damage at all doses, while atomoxetine increased DNA damage at all doses. On the other hand, in the DNA-damaged cells induced by hydrogen peroxide (H2O2), DNA damage decreased at all concentrations of all drugs in both lymphocytes and HepG2 cells.
CONCLUSIONS
As a result, the genotoxicity of the drugs was found to be dose-dependent, and all drugs showed a genoprotective effect on DNA-damaged cells.
Topics: Adolescent; Child; Humans; Antipsychotic Agents; Risperidone; Aripiprazole; Atomoxetine Hydrochloride; Methylphenidate; Hep G2 Cells; Hydrogen Peroxide; DNA Damage; Lymphocytes; DNA
PubMed: 38436168
DOI: 10.26355/eurrev_202402_35456 -
American Journal of Obstetrics and... Jul 2024Attention-deficit/hyperactivity disorder is a childhood-onset neurodevelopmental disorder that frequently persists into adulthood with 3% of adult women having a... (Review)
Review
Attention-deficit/hyperactivity disorder is a childhood-onset neurodevelopmental disorder that frequently persists into adulthood with 3% of adult women having a diagnosis of attention-deficit/hyperactivity disorder. Many women are diagnosed and treated during their reproductive years, which leads to management implications during pregnancy and the postpartum period. We know from clinical practice that attention-deficit/hyperactivity disorder symptoms frequently become challenging to manage during the perinatal period and require additional support and attention. There is often uncertainty among healthcare providers about the management of attention-deficit/hyperactivity disorder in the perinatal period, particularly the safety of pharmacotherapy for the developing fetus. This guideline is focused on best practices in managing attention-deficit/hyperactivity disorder in the perinatal period. We recommend (1) mitigating the risks associated with attention-deficit/hyperactivity disorder that worsen during the perinatal period via individualized treatment planning; (2) providing psychoeducation, self-management strategies or coaching, and psychotherapies; and, for those with moderate or severe attention-deficit/hyperactivity disorder, (3) considering pharmacotherapy for attention-deficit/hyperactivity disorder, which largely has reassuring safety data. Specifically, providers should work collaboratively with patients and their support networks to balance the risks of perinatal attention-deficit/hyperactivity disorder medication with the risks of inadequately treated attention-deficit/hyperactivity disorder during pregnancy. The risks and impacts of attention-deficit/hyperactivity disorder in pregnancy can be successfully managed through preconception counselling and appropriate perinatal planning, management, and support.
Topics: Humans; Female; Attention Deficit Disorder with Hyperactivity; Pregnancy; Pregnancy Complications; Postpartum Period; Central Nervous System Stimulants; Methylphenidate; Psychotherapy; Atomoxetine Hydrochloride
PubMed: 38432409
DOI: 10.1016/j.ajog.2024.02.297 -
ACS Applied Bio Materials Apr 2024Human liver microsomes containing various drug-metabolizing cytochrome P450 (P450) enzymes, along with their NADPH-reductase bound to phospholipid membranes, were...
Human liver microsomes containing various drug-metabolizing cytochrome P450 (P450) enzymes, along with their NADPH-reductase bound to phospholipid membranes, were absorbed onto 1-pyrene butylamine pi-pi stacked with amine-functionalized multiwalled carbon nanotube-modified graphite electrodes. The interfaced microsomal biofilm demonstrated direct electrochemical communication with the underlying electrode surface and enhanced oxygen reduction electrocatalytic activity typical of heme enzymes such as P450s over the unmodified electrodes and nonenzymatic currents. Similar enhancements in currents were observed when the bioelectrodes were constructed with recombinant P450 2C9 (single isoform) expressed bactosomes. The designed liver microsomal and 2C9 bactosomal bioelectrodes successfully facilitated the electrocatalytic conversion of diclofenac, a drug candidate, into 4'-hydroxydiclofenac. The enzymatic electrocatalytic metabolite yield was several-fold greater on the modified electrodes than on the unmodified bulk graphite electrodes adsorbed with a microsomal or bactosomal film. The nonenzymatic metabolite production was less than the enzymatically catalyzed metabolite yield in the designed microsomal and bactosomal biofilm electrodes. To test the throughput potential of the designed biofilms, eight-electrode array configurations were tested with the microsomal and bactosomal biofilms toward electrochemical 4'-hydroxydiclofenac metabolite production from diclofenac. The stability of the designed microsomal bioelectrode was assessed using nonfaradaic impedance spectroscopy over 40 h, which indicated good stability.
Topics: Humans; Diclofenac; Microsomes, Liver; Graphite; Cytochrome P-450 Enzyme System; Electrodes
PubMed: 38431903
DOI: 10.1021/acsabm.3c01170 -
Environmental Research Jun 2024This study endeavors to develop cost-effective environmentally friendly technology for removing harmful residual pharmaceuticals from water and wastewater by utilizing...
This study endeavors to develop cost-effective environmentally friendly technology for removing harmful residual pharmaceuticals from water and wastewater by utilizing the effective adsorption of pistachio shell (PS) biochar and the degradation potency of laccase immobilized on the biochar (L@PSAC). The carbonatization and activation of the shells were optimized regarding temperature, time, and NHNO/PS ratio. This step yielded an optimum PS biochar (PSAC) with the highest porosity and surface area treated at 700 °C for 3 h using an NHNO/PS ratio of 3% wt. The immobilization of laccase onto PSAC (L@PSAC) was at its best level at pH 5, 60 U/g, and 30 °C. The optimum L@PSAC maintained a high level of enzyme activity over two months. Almost a complete removal (>99%) of diclofenac, carbamazepine, and ciprofloxacin in Milli-Q (MQ) water and wastewater was achieved. Adsorption was responsible for >80% of the removal and the rest was facilitated by laccase degradation. L@PSAC maintained effective removal of pharmaceuticals of ≥60% for up to six treatment cycles underscoring the promising application of this material for wastewater treatment. These results indicate that activated carbon derived from the pistachio shell could potentially be utilized as a carrier and adsorbent to efficiently remove pharmaceutical compounds. This enzymatic physical elimination approach has the potential to be used on a large-scale.
Topics: Water Pollutants, Chemical; Charcoal; Laccase; Water Purification; Adsorption; Pistacia; Pharmaceutical Preparations; Enzymes, Immobilized; Wastewater; Waste Disposal, Fluid; Diclofenac; Carbamazepine
PubMed: 38431073
DOI: 10.1016/j.envres.2024.118565 -
BMJ Open Ophthalmology Mar 2024This study investigated the agreement between objective wavefront-based refraction and subjective refraction in myopic children. It also assessed the impact of...
OBJECTIVE
This study investigated the agreement between objective wavefront-based refraction and subjective refraction in myopic children. It also assessed the impact of cyclopentolate and refraction levels on the agreement.
METHODS
A total of 84 eyes of myopic children aged 6-13 years were included in the analysis. Non-cycloplegic and cycloplegic objective wavefront-based refraction were determined and cycloplegic subjective refraction was performed for each participant. The data were converted into spherical equivalent, J and J, and Bland-Altman plots were used to analyse the agreement between methods.
RESULTS
Linear functions were used to determine the dependency between the central myopic refractive error and the difference between the method of refraction (=bias). The influence of central myopia was not clinically relevant when analysing the agreement between wavefront results with and without cyclopentolate (comparison 1). The bias for wavefront-based minus subjective spherical equivalent refraction (comparison 2) was ≤-0.50 D (95% limits of agreement -0.010 D to -1.00 D) for myopia of -4.55 D and higher when cycloplegia was used (p<0.05). When no cyclopentolate was used for the wavefront-based refraction (comparison 3), the bias of -0.50 D (95% limits of agreement -0.020 D to -0.97 D) was already reached at a myopic error of -2.97 D. Both astigmatic components showed no clinically relevant bias.
CONCLUSION
The spherical equivalent, measured without cycloplegic agents, led to more myopic measurements when wavefront-based refraction was used. The observed bias increased with the amount of myopic refractive error for comparisons 2 and 3, which needs to be considered when interpreting wavefront-refraction data.
TRIAL REGISTRATION NUMBER
NCT05288335.
Topics: Child; Humans; Mydriatics; Cyclopentolate; Refractive Errors; Myopia; Pupil
PubMed: 38429067
DOI: 10.1136/bmjophth-2023-001322 -
European Journal of Pharmaceutical... Jul 2024Time-dependent inhibition of cytochrome P450 (CYP) enzymes has been observed for a few glucuronide metabolites of clinically used drugs. Here, we investigated the...
Time-dependent inhibition of cytochrome P450 (CYP) enzymes has been observed for a few glucuronide metabolites of clinically used drugs. Here, we investigated the inhibitory potential of 16 glucuronide metabolites towards nine major CYP enzymes in vitro. Automated substrate cocktail methods were used to screen time-dependent inhibition of CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2J2 and 3A in human liver microsomes. Seven glucuronides (carvedilol β-D-glucuronide, diclofenac acyl-β-D-glucuronide, 4-hydroxyduloxetine β-D-glucuronide, ezetimibe phenoxy-β-D-glucuronide, raloxifene 4'-glucuronide, repaglinide acyl-β-D-glucuronide and valproic acid β-D-glucuronide) caused NADPH- and time-dependent inhibition of at least one of the CYPs investigated, including CYP2A6, CYP2C19 and CYP3A. In more detailed experiments, we focused on the glucuronides of carvedilol and diclofenac, which inhibited CYP3A. Carvedilol β-D-glucuronide showed weak time-dependent inhibition of CYP3A, but the parent drug carvedilol was found to be a more potent inhibitor of CYP3A, with the half-maximal inhibitor concentration (IC) decreasing from 7.0 to 1.1 µM after a 30-min preincubation with NADPH. The maximal inactivation constant (k) and the inhibitor concentration causing half of k (K) for CYP3A inactivation by carvedilol were 0.051 1/min and 1.8 µM, respectively. Diclofenac acyl-β-D-glucuronide caused time-dependent inactivation of CYP3A at high concentrations, with a 4-fold IC shift (from 400 to 98 µM after a 30-min preincubation with NADPH) and K and k values of >2,000 µM and >0.16 1/min. In static predictions, carvedilol caused significant (>1.25-fold) increase in the exposure of the CYP3A substrates midazolam and simvastatin. In conclusion, we identified several glucuronide metabolites with CYP inhibitory properties. Based on detailed experiments, the inactivation of CYP3A by carvedilol may cause clinically significant drug-drug interactions.
Topics: Humans; Microsomes, Liver; Glucuronides; Diclofenac; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme System; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP3A
PubMed: 38423227
DOI: 10.1016/j.ejps.2024.106735