-
Bulletin of Experimental Biology and... Mar 2024Leukocyte elastase is a marker of inflammation. Previously, a relationship was found between the severity of mental disorders in patients and elastase-like activity of...
Leukocyte elastase is a marker of inflammation. Previously, a relationship was found between the severity of mental disorders in patients and elastase-like activity of blood plasma. The effect of various neurotropic drugs on leukocyte elastase activity was analyzed in an in vitro experiment. We revealed an inhibitory effect of the benzodiazepine tranquilizers diazepam and bromodihydrochlorophenylbenzodiazepine and immunomodulators aminodihydrophthalazinedione and diclofenac on the plasma elastase-like activity of healthy donors and pure human neutrophil elastase. The antipsychotics chlorpromazine and alimemazine, as well as the nootropic vinpocetine increased elastase-like activity in a dose-dependent manner. The activating effect of chlorpromazine and vinpocetine, but not alimemazine, was reproduced in neutrophil elastase. We hypothesized that these drugs can affect the development of inflammatory reactions in the complex therapy of mental disorders.
Topics: Humans; Leukocyte Elastase; Chlorpromazine; Diazepam; Antipsychotic Agents; Diclofenac; Nootropic Agents; Tranquilizing Agents; Immunologic Factors; Vinca Alkaloids
PubMed: 38724813
DOI: 10.1007/s10517-024-06072-5 -
Neuroscience and Biobehavioral Reviews Jul 2024Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with executive function deficits that are improved with medications. However, meta-analyses of stimulant... (Meta-Analysis)
Meta-Analysis Review
Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with executive function deficits that are improved with medications. However, meta-analyses of stimulant effects on cognition have mostly tested single-dose effects, and there is no meta-analysis of non-stimulant effects. This systematic review and meta-analysis tested the clinically more relevant longer-term effects of Methylphenidate (20 studies; minimum 1 week) and Atomoxetine (8 studies; minimum 3 weeks) on reaction time, attention, inhibition, and working memory, searching papers on PubMed, Embase, Ovid MEDLINE, and PsycINFO. The meta-analysis of 18 studies in 1667 subjects showed that methylphenidate was superior to placebo in all cognitive domains with small to medium effect sizes (Hedges g of 0.34-0.59). The meta-analysis of atomoxetine included 7 studies in 829 subjects and showed no effects in working memory, but superior effects in the other domains with medium to large effect sizes (Hedge's g of 0.36-0.64). Meta-regression analysis showed no drug differences on cognitive effects. The meta-analyses show for the first time that chronic Methylphenidate and Atomoxetine have comparable effects of improving executive functions in people with ADHD.
Topics: Humans; Attention Deficit Disorder with Hyperactivity; Executive Function; Central Nervous System Stimulants; Methylphenidate; Atomoxetine Hydrochloride; Memory, Short-Term
PubMed: 38718988
DOI: 10.1016/j.neubiorev.2024.105703 -
Communications Biology May 2024Chemogenetic approaches employing ligand-gated ion channels are advantageous regarding manipulation of target neuronal population functions independently of endogenous...
Chemogenetic approaches employing ligand-gated ion channels are advantageous regarding manipulation of target neuronal population functions independently of endogenous second messenger pathways. Among them, Ionotropic Receptor (IR)-mediated neuronal activation (IRNA) allows stimulation of mammalian neurons that heterologously express members of the insect chemosensory IR repertoire in response to their cognate ligands. In the original protocol, phenylacetic acid, a ligand of the IR84a/IR8a complex, was locally injected into a brain region due to its low permeability of the blood-brain barrier. To circumvent this invasive injection, we sought to develop a strategy of peripheral administration with a precursor of phenylacetic acid, phenylacetic acid methyl ester, which is efficiently transferred into the brain and converted to the mature ligand by endogenous esterase activities. This strategy was validated by electrophysiological, biochemical, brain-imaging, and behavioral analyses, demonstrating high utility of systemic IRNA technology in the remote activation of target neurons in the brain.
Topics: Animals; Neurons; Brain; Ligands; Mice; Phenylacetates; Receptors, Ionotropic Glutamate; Male
PubMed: 38714803
DOI: 10.1038/s42003-024-06223-4 -
Chemosphere Jun 2024In this study, neural networks and support vector regression (SVR) were employed to predict the degradation over three pharmaceutically active compounds (PhACs):...
In this study, neural networks and support vector regression (SVR) were employed to predict the degradation over three pharmaceutically active compounds (PhACs): Ibuprofen (IBP), diclofenac (DCF), and caffeine (CAF) within a stirred reactor featuring a flotation cell with two non-concentric ultraviolet lamps. A total of 438 datapoints were collected from published works and distributed into 70% training and 30% test datasets while cross-validation was utilized to assess the training reliability. The models incorporated 15 input variables concerning reaction kinetics, molecular properties, hydrodynamic information, presence of radiation, and catalytic properties. It was observed that the Support Vector Regression (SVR) presented a poor performance as the ε hyperparameter ignored large error over low concentration levels. Meanwhile, the Artificial Neural Networks (ANN) model was able to provide rough estimations on the expected degradation of the pollutants without requiring information regarding reaction rate constants. The multi-objective optimization analysis suggested a leading role due to ozone kinetic for a rapid degradation of the contaminants and most of the results required intensification with hydrogen peroxide and Fenton process. Although both models were affected by accuracy limitations, this work provided a lightweight model to evaluate different Advanced Oxidation Processes (AOPs) by providing general information regarding the process operational conditions as well as know molecular and catalytic properties.
Topics: Machine Learning; Diclofenac; Neural Networks, Computer; Hydrogen Peroxide; Ibuprofen; Kinetics; Water Pollutants, Chemical; Caffeine; Oxidation-Reduction; Pharmaceutical Preparations; Ozone; Support Vector Machine; Cost-Benefit Analysis; Ultraviolet Rays; Catalysis; Photolysis
PubMed: 38714249
DOI: 10.1016/j.chemosphere.2024.142222 -
The Journal of Head Trauma...To understand how methylphenidate (MPH) is used in youth with traumatic brain injury (TBI) during inpatient pediatric rehabilitation.
OBJECTIVE
To understand how methylphenidate (MPH) is used in youth with traumatic brain injury (TBI) during inpatient pediatric rehabilitation.
SETTING
Inpatient pediatric rehabilitation.
PARTICIPANTS
In total, 234 children with TBI; 62 of whom received MPH and 172 who did not. Patients were on average 11.6 years of age (range, 2 months to 21 years); 88 of 234 were female; the most common mechanism of injury was motor vehicle collision (49%); median (IQR) acute hospital length of stay (LOS) and inpatient rehabilitation LOS were 16 (10-29) and 23 (14-39), respectively; 51 of 234 were in a disorder of consciousness cognitive state at time of inpatient rehabilitation admission.
DESIGN
Multicenter, retrospective medical record review.
MAIN MEASURES
Patient demographic data, time to inpatient pediatric rehabilitation admission (TTA), cognitive state, MPH dosing (mg/kg/day).
RESULTS
Patients who received MPH were older (P = .011); TTA was significantly longer in patients who received MPH than those who did not (P =.002). The lowest recorded dose range by weight was 0.05 to 0.89 mg/kg/d, representing an 18-fold difference; the weight-based range for the maximum dose was 0.11 to 0.97 mg/kg/d, a 9-fold difference. Patients in lower cognitive states at admission (P = .001) and at discharge (P = .030) were more likely to receive MPH. Five patients had side effects known to be associated with MPH; no serious adverse events were reported.
CONCLUSION
This multicenter study indicates that there is variable use of MPH during acute inpatient rehabilitation for children with TBI. Children who receive MPH tend to be older with lower cognitive states. Dosing practices are likely consistent with underdosing. Clinical indications for MPH use during inpatient pediatric rehabilitation should be better defined. The use of MPH, as well as its combination with other medications and treatments, during inpatient rehabilitation needs to be further explored.
Topics: Humans; Methylphenidate; Child; Female; Brain Injuries, Traumatic; Male; Adolescent; Child, Preschool; Retrospective Studies; Central Nervous System Stimulants; Infant; Practice Patterns, Physicians'; Young Adult; Inpatients; Length of Stay; Rehabilitation Centers
PubMed: 38709832
DOI: 10.1097/HTR.0000000000000889 -
Environmental Pollution (Barking, Essex... Jun 2024In this paper, the S-scheme/Schottky heterojunction photocatalyst (CuInS/Bi/BiMoO, CIS/Bi/BMO) was successfully constructed via a facile in-situ solvothermal method,...
In this paper, the S-scheme/Schottky heterojunction photocatalyst (CuInS/Bi/BiMoO, CIS/Bi/BMO) was successfully constructed via a facile in-situ solvothermal method, aimed at enhancing its photocatalytic performance. The results of the study on the photocatalytic degradation of diclofenac sodium (DCF) under simulated solar light irradiation revealed that the as-prepared composite exhibited remarkable catalytic efficiency in comparison to the pristine BiMoO and CuInS. The plasmonic bismuth (Bi) was formed during the solvothermal process. Subsequently, CuInS and Bi were grown on the surface of BiMoO leading to forming CIS/BMO S-scheme heterojunction, along with a Schottky junction between Bi and BiMoO. The use of ethylene glycol as a support was the main reason for the significant improvement in photocatalytic efficiency in the degradation of DCF. Moreover, the probable photocatalytic mechanisms for the degradation of DCF had been proposed based on the active species quenching experiments. The eleven degradation products were detected by HPLC-MS, and the degradation reaction pathway of DCF was deduced. Additionally, the CIS/Bi/BMO photocatalyst exhibited a consistently high removal rate after four cycles. This study proposes a new strategy for designing efficient S-scheme/Schottky heterojunction photocatalysts for solar energy conversion.
Topics: Bismuth; Diclofenac; Catalysis; Photolysis; Copper; Water Pollutants, Chemical; Molybdenum; Indium; Photochemical Processes
PubMed: 38705447
DOI: 10.1016/j.envpol.2024.124077 -
Fitoterapia Jul 2024In Brazil, latex from Euphorbia umbellata (African milk tree) has been increasingly used in folk medicine to treat several types of cancer, including melanoma. The...
In Brazil, latex from Euphorbia umbellata (African milk tree) has been increasingly used in folk medicine to treat several types of cancer, including melanoma. The effect of lyophilized latex (LL), its hydroethanolic extract (E80), triterpene (F-TRI)- and diterpene (F-DIT)-enriched fractions, along with six isolated phorbol esters from LL and phorbol 12-myristate 13-acetate (PMA) on J774A.1, THP-1, SK-MEL-28, and B16-F10 cell line viability were evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. The compounds were identified by 2D-NMR and HRESIMS. The effect of the LL, extract and fractions on cell viability was also assessed through a resazurin reduction assay. At 100 μg/ml, LL, and its fractions moderately inhibited J774A.1 (37.5-59.5%) and THP-1 (12.6-43.6%) metabolism. LL (IC 70 μg/ml) and F-TRI (IC 68 μg/ml) were barely more effective against B16-F10 cells, and only F-TRI exerted an inhibitory effect on SK-MEL-28 cells (IC 66-75 μg/ml). The samples did not effectively inhibit THP-1 growth (IC 69-87 μg/ml, assessed by MTT). B16-F10 was susceptible to PMA (IC 53 μM) and two 12-phenylacetate esters (IC 56-60 μM), while SK-MEL-28 growth was inhibited (IC 58 μM) by one of these kinds of esters with an additional 4β-deoxy structure. Synagrantol A (IC 39 μM) was as effective as PMA (IC 47 μM) in inhibiting J774A.1 growth in a dose-dependent manner. Furthermore, an in silico study with target receptors indicated a high interaction of the compounds with the PKC proteins. These results provide useful knowledge on the effect of tigliane-type diterpenes on tumor cell from the perspective of medicinal chemistry.
Topics: Euphorbia; Latex; Phorbol Esters; Humans; Mice; Animals; Cell Line, Tumor; Molecular Structure; Plant Extracts; Brazil; Monocytes; Phytochemicals; Cell Survival; Diterpenes; Terpenes; Antineoplastic Agents, Phytogenic; Tetradecanoylphorbol Acetate; Melanoma
PubMed: 38703916
DOI: 10.1016/j.fitote.2024.105987 -
Journal of Hazardous Materials Jul 2024Diclofenac (DCF) is an environmentally persistent, nonsteroidal anti-inflammatory drug (NSAID) with thyroid disrupting properties. Electrochemical advanced oxidation...
Diclofenac (DCF) is an environmentally persistent, nonsteroidal anti-inflammatory drug (NSAID) with thyroid disrupting properties. Electrochemical advanced oxidation processes (eAOPs) can efficiently remove NSAIDs from wastewater. However, eAOPs can generate transformation products (TPs) with unknown chemical and biological characteristics. In this study, DCF was electrochemically degraded using a boron-doped diamond anode. Ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry was used to analyze the TPs of DCF and elucidate its potential degradation pathways. The biological impact of DCF and its TPs was evaluated using the Xenopus Eleutheroembryo Thyroid Assay, employing a transgenic amphibian model to assess thyroid axis activity. As DCF degradation progressed, in vivo thyroid activity transitioned from anti-thyroid in non-treated samples to pro-thyroid in intermediately treated samples, implying the emergence of thyroid-active TPs with distinct modes of action compared to DCF. Molecular docking analysis revealed that certain TPs bind to the thyroid receptor, potentially triggering thyroid hormone-like responses. Moreover, acute toxicity occurred in intermediately degraded samples, indicating the generation of TPs exhibiting higher toxicity than DCF. Both acute toxicity and thyroid effects were mitigated with a prolonged degradation time. This study highlights the importance of integrating in vivo bioassays in the environmental risk assessment of novel degradation processes.
Topics: Animals; Diclofenac; Water Pollutants, Chemical; Thyroid Gland; Anti-Inflammatory Agents, Non-Steroidal; Risk Assessment; Electrochemical Techniques; Molecular Docking Simulation; Endocrine Disruptors; Xenopus laevis; Diamond; Oxidation-Reduction; Boron
PubMed: 38703679
DOI: 10.1016/j.jhazmat.2024.134458 -
Life Sciences Jun 2024Thyroid cancer is one of the most common primary endocrine malignancies worldwide, and papillary thyroid carcinoma (PTC) is the predominant histological type observed...
Thyroid cancer is one of the most common primary endocrine malignancies worldwide, and papillary thyroid carcinoma (PTC) is the predominant histological type observed therein. Although PTC has been studied extensively, our understanding of the altered metabolism and metabolic profile of PTC tumors is limited. We identified that the content of metabolite homogentisic acid (HGA) in PTC tissues was lower than that in adjacent non-cancerous tissues. We evaluated the potential of HGA as a novel molecular marker in the diagnosis of PTC tumors, as well as its ability to indicate the degree of malignancy. Studies have further shown that HGA contributes to reactive oxygen species (ROS) associated oxidative stress, leading to toxicity and inhibition of proliferation. In addition, HGA caused an increase in p21 expression levels in PTC cells and induced G1 arrest. Moreover, we found that the low HGA content in PTC tumors was due to the low expression levels of tyrosine aminotransferase (TAT) and p-hydroxyphenylpyruvate hydroxylase (HPD), which catalyze the conversion of tyrosine to HGA. The low expression levels of TAT and HPD are strongly associated with a higher probability of PTC tumor invasion and metastasis. Our study demonstrates that HGA could be used to diagnose PTC and provides mechanisms linking altered HGA levels to the biological behavior of PTC tumors.
Topics: Humans; Reactive Oxygen Species; Thyroid Neoplasms; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p21; Thyroid Cancer, Papillary; Cell Cycle Checkpoints; Homogentisic Acid; Female; Male; Middle Aged; Cell Line, Tumor; Oxidative Stress; Carcinoma, Papillary; Adult
PubMed: 38702025
DOI: 10.1016/j.lfs.2024.122682 -
Ecotoxicology and Environmental Safety Jun 2024Discharging pharmaceutically active drugs into water and wastewater has become a significant environmental threat. Traditional methods are unable to effectively remove...
Discharging pharmaceutically active drugs into water and wastewater has become a significant environmental threat. Traditional methods are unable to effectively remove these compounds from wastewater, so it is necessary to search for more effective methods. This study investigates the potential of MIL-101(Cr)-NH as a preferable and more effective adsorbent for the adsorption and removal of pharmaceutically active compounds from aqueous solutions. By utilizing its large porosity, high specific surface area, and high stability, the structural and transport properties of three pharmaceutically active compounds naproxen (NAP), diclofenac (DIC) and sulfamethoxazole (SMX)) studied using molecular dynamics simulation. The results indicate that the MIL-101(Cr)-NH adsorbent is suitable for removing drug molecules from aqueous solutions, with maximum adsorption capacities of 697.75 mg/g for naproxen, 704.99 mg/g for diclofenac, and 725.51 mg/g for sulfamethoxazole.
Topics: Water Pollutants, Chemical; Naproxen; Metal-Organic Frameworks; Sulfamethoxazole; Diclofenac; Molecular Dynamics Simulation; Adsorption; Water Purification; Wastewater; Pharmaceutical Preparations
PubMed: 38701652
DOI: 10.1016/j.ecoenv.2024.116333