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Journal of the American Chemical Society Jun 2024Catalytic π-arene activation is based on catalysts that allow for arene exchange. To date, cyclopentadiene (Cp)-derived catalysts are the most commonly used in π-arene...
Catalytic π-arene activation is based on catalysts that allow for arene exchange. To date, cyclopentadiene (Cp)-derived catalysts are the most commonly used in π-arene activation despite their low arene exchange rates. Herein, we report the synthesis, analysis, and catalytic application of Ru(II) complexes supported by phenoxo ligands, which are isolobal alternatives to Cp. The phenoxo complexes exhibit arene exchange rates significantly faster than those of the corresponding Cp complexes. The rate can be further increased through the choice of appropriate counterions. The mechanism of the arene exchange process is elucidated by kinetic and computational analyses. We demonstrate the utility of the new catalysts through an SAr reaction between fluorobenzene and alcohols, including secondary alcohols that could not be used previously in related reactions. Moreover, the catalytic thermal decarboxylation of phenylacetic acids is presented.
PubMed: 38819390
DOI: 10.1021/jacs.4c02088 -
Brain Research Sep 2024Traumatic brain injury (TBI) is a complex pathophysiological process that results in a variety of neurotransmitter, behavioral, and cognitive deficits. The locus...
Traumatic brain injury (TBI) is a complex pathophysiological process that results in a variety of neurotransmitter, behavioral, and cognitive deficits. The locus coeruleus-norepinephrine (LC-NE) system is a critical regulator of arousal levels and higher executive processes affected by TBI including attention, working memory, and decision making. LC-NE axon injury and impaired signaling within the prefrontal cortex (PFC) is a potential contributor to the neuropsychiatric symptoms after single, moderate to severe TBI. The majority of TBIs are mild, yet long-term cognitive deficits and increased susceptibility for further injury can accumulate after each repetitive mild TBI. As a potential treatment for restoring cognitive function and daytime sleepiness after injury psychostimulants, including methylphenidate (MPH) that increase levels of NE within the PFC, are being prescribed "off-label". The impact of mild and repetitive mild TBI on the LC-NE system remains limited. Therefore, we determined the extent of LC-NE and arousal dysfunction and response to therapeutic doses of MPH in rats following experimentally induced single and repetitive mild TBI. Microdialysis measures of basal NE efflux from the medial PFC and arousal measures were significantly lower after repetitive mild TBI. Females showed higher baseline PFC-NE efflux than males following single and repetitive mild TBI. In response to MPH challenge, males exhibited a blunted PFC-NE response and persistent arousal levels following repetitive mild TBI. These results provide critical insight into the role of catecholamine system dysfunction associated with cognitive deficits following repeated injury, outcome differences between sex/gender, and lack of success of MPH as an adjunctive therapy to improve cognitive function following injury.
Topics: Animals; Male; Norepinephrine; Female; Rats, Sprague-Dawley; Prefrontal Cortex; Central Nervous System Stimulants; Methylphenidate; Brain Concussion; Rats; Brain Injuries, Traumatic; Locus Coeruleus; Arousal; Microdialysis
PubMed: 38815643
DOI: 10.1016/j.brainres.2024.149040 -
Acta Pharmaceutica (Zagreb, Croatia) Jun 2024Oral solid dosage forms are most frequently administered with a glass of water which empties from the stomach relatively fast, but with a certain variability in its...
Oral solid dosage forms are most frequently administered with a glass of water which empties from the stomach relatively fast, but with a certain variability in its emptying kinetics. The purpose of this study was thus to simulate different individual water gastric emptying (GE) patterns in an glass-bead flow-through dissolution system. Further, the effect of GE on the dissolution of model drugs from immediate-release tablets was assessed by determining the amount of dissolved drug in the samples pumped out of the stomach compartment. Additionally, different HCl solutions were used as dissolution media to assess the effect of the variability of pH of the gastric fluid on the dissolution of three model drugs: paracetamol, diclofenac sodium, and dipyridamole. The difference in fast and slow GE kinetics resulted in different dissolution profiles of paracetamol in all studied media. For diclofenac sodium and dipyridamole tablets, the effect of GE kinetics was well observed only in media, where the solubility was not a limiting factor. Therefore, GE kinetics of co-ingested water influences the drug release from immediate-release tablets, however, in certain cases, other parameters influencing drug dissolution can partly or fully hinder the expression of this effect.
Topics: Gastric Emptying; Drug Liberation; Diclofenac; Water; Solubility; Tablets; Dipyridamole; Acetaminophen; Hydrogen-Ion Concentration; Kinetics; Administration, Oral; Glass
PubMed: 38815199
DOI: 10.2478/acph-2024-0016 -
Environmental Science and Pollution... Jun 2024This study presents a theoretical analysis of the adsorption process of pharmaceutical pollutants, specifically acetaminophen (ATP) and diclofenac (DFC), onto activated...
This study presents a theoretical analysis of the adsorption process of pharmaceutical pollutants, specifically acetaminophen (ATP) and diclofenac (DFC), onto activated carbon (AC) derived from avocado biomass waste. The adsorption isotherms of ATP and DFC were analyzed using a multilayer model, which revealed the formation of two to four adsorption layers depending on the temperature of the aqueous solution. The saturation adsorption capacities for ATP and DFC were 52.71 and 116.53 mg/g, respectively. A steric analysis suggested that the adsorption mechanisms of ATP and DFC involved a multi-molecular process. The calculated adsorption energies (ΔE and ΔE) varied between 12.86 and 22.58 kJ/mol, with the highest values observed for DFC removal. Therefore, the adsorption of these organic molecules was associated with physisorption interactions: van der Waals forces and hydrogen bonds. These findings enhance the understanding of the depollution processes of pharmaceutical compounds using carbon-based adsorbents and highlight the potential of utilizing waste biomass for environmental remediation.
Topics: Adsorption; Charcoal; Water Pollutants, Chemical; Diclofenac; Pharmaceutical Preparations; Carbon; Acetaminophen
PubMed: 38814558
DOI: 10.1007/s11356-024-33806-9 -
Annals of Medicine Dec 2024Tension-type headache is the most common type of primary headache and results in a huge socioeconomic burden. This network meta-analysis (NMA) aimed to compare the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Tension-type headache is the most common type of primary headache and results in a huge socioeconomic burden. This network meta-analysis (NMA) aimed to compare the efficacy and safety of simple analgesics for the treatment of episodic tension-type headache (ETTH) in adults.
METHODS
We searched the Cochrane Library, PubMed, Web of Science, Embase, Chinese BioMedical Literature database and International Clinical Trials Registry Platform databases for eligible randomized clinical trials reporting the efficacy and/or safety of simple analgesics. A Bayesian NMA was performed to compare relative efficacy and safety. The surface under the cumulative ranking curve (SUCRA) was calculated to rank interventions. PROSPERO registration number: CRD42018090554.
RESULTS
We highlighted six studies including 3507 patients. For the 2 h pain-free rate, the SUCRA ranking was ibuprofen > diclofenac-K > ketoprofen > acetaminophen > naproxen > placebo. All drugs except naproxen reported a higher 2 h pain-free rate than placebo, with a risk ratio (RR) of 2.86 (95% credible interval, CrI: 1.62-5.42) for ibuprofen and 2.61 (1.53-4.88) for diclofenac-K. For adverse events rate, the SUCRA ranking was: metamizol > diclofenac-K > ibuprofen > lumiracoxib > placebo > aspirin > acetaminophen > naproxen > ketoprofen. The adverse event rates of all analgesics were no higher than those of placebo, except for ketoprofen. Moreover, all drugs were superior to placebo in the global assessment of efficacy. In particular, the RR of lumiracoxib was 2.47 (1.57-4.57). Global heterogeneity between the studies was low.
CONCLUSIONS
Simple analgesics are considered more effective and safe as a placebo for ETTH in adults. Our results suggest that ibuprofen and diclofenac-K may be the two best treatment options for patients with ETTH from a comprehensive point of view (both high-quality evidence).
Topics: Humans; Tension-Type Headache; Analgesics; Adult; Network Meta-Analysis; Ibuprofen; Acetaminophen; Bayes Theorem; Treatment Outcome; Diclofenac; Randomized Controlled Trials as Topic; Naproxen; Ketoprofen; Anti-Inflammatory Agents, Non-Steroidal; Female; Male
PubMed: 38813682
DOI: 10.1080/07853890.2024.2357235 -
Scientific Reports May 2024The human microbiome contains genetic information that regulates metabolic processes in response to host health and disease. While acidic vaginal pH is maintained in...
The human microbiome contains genetic information that regulates metabolic processes in response to host health and disease. While acidic vaginal pH is maintained in normal conditions, the pH level increases in infectious vaginitis. We propose that this change in the vaginal environment triggers the biosynthesis of anti-vaginitis metabolites. Gene expression levels of Chryseobacterium gleum, a vaginal symbiotic bacterium, were found to be affected by pH changes. The distinctive difference in the metabolic profiles between two C. gleum cultures incubated under acidic and neutral pH conditions was suggested to be an anti-vaginitis molecule, which was identified as phenylacetic acid (PAA) by spectroscopic data analysis. The antimicrobial activity of PAA was evaluated in vitro, showing greater toxicity toward Gardnerella vaginalis and Candida albicans, two major vaginal pathogens, relative to commensal Lactobacillus spp. The activation of myeloperoxidase, prostaglandin E, and nuclear factor-κB, and the expression of cyclooxygenase-2 were reduced by an intravaginal administration of PAA in the vaginitis mouse model. In addition, PAA displayed the downregulation of mast cell activation. Therefore, PAA was suggested to be a messenger molecule that mediates interactions between the human microbiome and vaginal health.
Topics: Female; Animals; Phenylacetates; Vagina; Mice; Humans; Chryseobacterium; Candida albicans; Symbiosis; Hydrogen-Ion Concentration; Gardnerella vaginalis; Disease Models, Animal; Vaginitis
PubMed: 38806600
DOI: 10.1038/s41598-024-62947-7 -
Bioresource Technology Jul 2024This study explored a direct feeding of expanded polystyrene as the sole diet for breeding Tenebrio molitor larvae. Temperature and relative humidity were manipulated to...
This study explored a direct feeding of expanded polystyrene as the sole diet for breeding Tenebrio molitor larvae. Temperature and relative humidity were manipulated to evaluate polystyrene biodegradation efficiency, survival rate, and formation of micro-polystyrene residue. Efficient conditions were at temperature of 25 °C with a humidity of 65 ± 5 %. Comparative metabolomic and metabolic-metabolic network analyses was performed for visualizing detailed pathway. Possibility of forming 4 (p)-hydroxyphenylacetic acid from phenylacetic acid with further conversion to 4-methylphenol, 4-hydroxybenzaldehyde, and 4-hydroxybenzoate could be seen as a side chain route for further biodegrading process. Key species identified in the gut of T. molitor larvae included Citrobacter sp., Serratia marcescens, Klebsiella aerogenes, and Klebsiella oxytoca. Pseudomonas aeruginosa was detected only under an anaerobic condition whereas Acinetobacter sp. was present only under an aerobic condition. These results demonstrate the potential to decrease micro-polystyrene by optimizing breeding conditions and biodegradation process of polystyrene.
Topics: Animals; Tenebrio; Polystyrenes; Biodegradation, Environmental; Larva; Gastrointestinal Microbiome; Bacteria
PubMed: 38801953
DOI: 10.1016/j.biortech.2024.130895 -
Journal of Pharmacological and... 2024Receptor occupancy is an indicator of antipsychotic efficacy and safety. It is desirable to simultaneously determine the occupancy of multiple brain receptors as an...
Development of simultaneous determination of dopamine 2, histamine 1, and muscarinic acetylcholine receptor occupancies by antipsychotics using liquid chromatography with tandem mass spectrometry.
Receptor occupancy is an indicator of antipsychotic efficacy and safety. It is desirable to simultaneously determine the occupancy of multiple brain receptors as an indicator of the efficacy and central side effects of antipsychotics because many of these drugs have binding affinities for various receptors, such as dopamine 2 (D), histamine 1 (H), and muscarinic acetylcholine (mACh) receptors. The purpose of this study was to develop a method for the simultaneous measurement of multiple receptor occupancies in the brain by the simultaneous quantification of unlabeled tracer levels using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Rats were pre-administered with a vehicle, displacer, or olanzapine, and mixed solutions of raclopride, doxepin, and 3-quinuclidinyl benzilate (3-QNB) were administered (3, 10, and 30 μg/kg). The brain tissue and plasma tracer concentrations were quantified 45 min later using LC-MS/MS, and the binding potential was calculated. The highest binding potential was observed at 3 μg/kg raclopride, 10 μg/kg doxepin, and 30 μg/kg 3-QNB. Tracer-specific binding at these optimal tracer doses in the cerebral cortex was markedly reduced by pre-administration of displacers. D, H and mACh receptor occupancy by olanzapine increased in a dose-dependent manner, reaching 70-95%, 19-43%, and 12-45%, respectively, at an olanzapine dose range of 3-10 mg/kg. These results suggest that simultaneous determination of in vivo D, H, and mACh receptor occupancy is possible using LC-MS/MS.
Topics: Animals; Tandem Mass Spectrometry; Rats; Male; Antipsychotic Agents; Chromatography, Liquid; Receptors, Dopamine D2; Rats, Sprague-Dawley; Receptors, Muscarinic; Receptors, Histamine H1; Olanzapine; Brain; Benzodiazepines; Raclopride; Doxepin; Quinuclidinyl Benzilate; Dose-Response Relationship, Drug
PubMed: 38797366
DOI: 10.1016/j.vascn.2024.107518 -
Chemosphere Jul 2024In recent years, the concentrations of cadmium (Cd) and diclofenac (DCF) in water have frequently exceeded the standard; however, the toxic effects of these two...
In recent years, the concentrations of cadmium (Cd) and diclofenac (DCF) in water have frequently exceeded the standard; however, the toxic effects of these two pollutants on grass carp under single and combined exposure are unknown. In this study, the concentrations of pollutants in different tissues were detected, and the toxicities of the two pollutants to grass carp under different exposure conditions were compared based on growth traits, biochemical responses, gut microbiome, and transcriptomes. Based on these findings, the brain showed the lowest levels of Cd and DCF accumulation. Oxidative stress and pathological damage were observed in the brain and intestines. Changes in the structure and abundance of the gut microflora affect the synthesis of neurotransmitters, such as GABA and steroids. Differentially expressed genes in the brain were enriched in circadian rhythm functions. The expression of PER, CLOCK,1L-1β, 1L-17, and other genes are related to the abundance of Akkermansia, which indicates that the disorder of gut microflora will affect the normal circadian rhythm of the brain. All indices in the recovery group showed an increasing trend. Overall, the toxicity of Cd and DCF showed antagonism, and a single exposure had a stronger effect on gut microorganisms and circadian rhythm, which provided a scientific basis for exploring the comprehensive effects of different pollutants.
Topics: Animals; Carps; Gastrointestinal Microbiome; Cadmium; Water Pollutants, Chemical; Diclofenac; Transcriptome; Oxidative Stress; Brain
PubMed: 38797211
DOI: 10.1016/j.chemosphere.2024.142428 -
International Journal of Biological... Jun 2024Metal-organic frameworks are emerging inorganic-organic hybrid materials that can be self-assembled from metal ions and organic ligands via coordination bonds. These...
Metal-organic frameworks are emerging inorganic-organic hybrid materials that can be self-assembled from metal ions and organic ligands via coordination bonds. These materials possess large specific surface area, tunable pore structure, abundant active center, diversity of functional groups as well as high mechanical and thermal stability which promote their applications in adsorption and catalysis studies. In this study, NH-MIL-53(Al/Zr) was prepared and embedded into sodium alginate gel spheres (NH-MIL-53(Al/Zr)-SA) and its adsorption properties towards TC and DCF in solution were investigated. According to XRD and FTIR analysis, the structure of the raw material was not changed after making the gel spheres. The maximum adsorption towards TC (pH =3) and DCF (pH =5) reached 98.5 mg·g and 192 mg·g, respectively. The process was consistent with Langmuir and Freundlich, suggesting that there was both monolayer and multilayer adsorption which infers the presence of physical adsorption (intra-particle diffusion) and non-homogeneous chemical adsorption. The thermodynamic parameters showed that the adsorption process was a spontaneous entropy increasing reaction. The regeneration rate of spent NH-MIL-53(Al/Zr)-SA could still reach 99.1 % after three cycles, indicating good regeneration performance. This study can provide a basis for the application of NH-MIL-53(Al/Zr)-SA in wastewater treatment.
Topics: Alginates; Adsorption; Diclofenac; Metal-Organic Frameworks; Tetracycline; Gels; Water Pollutants, Chemical; Thermodynamics; Water Purification; Kinetics; Hydrogen-Ion Concentration; Zirconium
PubMed: 38795565
DOI: 10.1016/j.ijbiomac.2024.132637