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Clinical Toxicology (Philadelphia, Pa.) Apr 2024Guanfacine is a central α-adrenergic receptor agonist that produces drowsiness, bradycardia, hypotension, and occasionally QT interval prolongation. We discuss giant T...
INTRODUCTION
Guanfacine is a central α-adrenergic receptor agonist that produces drowsiness, bradycardia, hypotension, and occasionally QT interval prolongation. We discuss giant T waves associated with guanfacine toxicity.
CASE SUMMARIES
Three patients presented to the hospital with histories and physical findings compatible with guanfacine toxicity. Supratherapeutic concentrations were confirmed in two of them. All three developed QT interval prolongation and giant T waves on the electrocardiogram. Giant T waves occur commonly in patients with acute myocardial infarct and hyperkalemia, as well as rarely with a number of other cardiac and non-cardiac causes.
CONCLUSION
Guanfacine toxicity may cause the novel electrocardiographic finding of 'giant T wave with QT interval prolongation'. Further studies are warranted to investigate the association between the novel electrocardiographic finding and guanfacine toxicity, as well as its diagnostic utility in such cases.
Topics: Humans; Guanfacine; Electrocardiography; Adrenergic alpha-2 Receptor Agonists; Male; Long QT Syndrome; Female; Middle Aged; Adult
PubMed: 38766906
DOI: 10.1080/15563650.2024.2349689 -
Scientific Reports May 2024A series of novel Schiff base derivatives (1-28) of 3,4-dihydroxyphenylacetic acid were synthesized in a multi-step reaction. All the synthesized Schiff bases were...
A series of novel Schiff base derivatives (1-28) of 3,4-dihydroxyphenylacetic acid were synthesized in a multi-step reaction. All the synthesized Schiff bases were obtained in high yields and their structures were determined by HNMR, CNMR, and HR-ESI-MS spectroscopy. Except for compounds 22, 26, 27, and 28, all derivatives show excellent to moderate α-glucosidase inhibition. Compounds 5 (IC = 12.84 ± 0.52 µM), 4 (IC = 13.64 ± 0.58 µM), 12 (IC = 15.73 ± 0.71 µM), 13 (IC = 16.62 ± 0.47 µM), 15 (IC = 17.40 ± 0.74 µM), 3 (IC = 18.45 ± 1.21 µM), 7 (IC = 19.68 ± 0.82 µM), and 2 (IC = 20.35 ± 1.27 µM) shows outstanding inhibition as compared to standard acarbose (IC = 873.34 ± 1.67 µM). Furthermore, a docking study was performed to find out the interaction between the enzyme and the most active compounds. With this research work, 3,4-dihydroxyphenylacetic acid Schiff base derivatives have been introduced as a potential class of α-glucosidase inhibitors that have remained elusive till now.
Topics: Molecular Docking Simulation; Glycoside Hydrolase Inhibitors; alpha-Glucosidases; 3,4-Dihydroxyphenylacetic Acid; Drug Design; Schiff Bases; Hydrazones; Structure-Activity Relationship
PubMed: 38762658
DOI: 10.1038/s41598-024-62034-x -
Medicine May 2024This study was aimed to analyze ocular biometric changes following cycloplegia in pediatric patients with strabismus and amblyopia. Cycloplegia is routinely used to... (Observational Study)
Observational Study
This study was aimed to analyze ocular biometric changes following cycloplegia in pediatric patients with strabismus and amblyopia. Cycloplegia is routinely used to measure refractive error accurately by paralyzing accommodation. However, effects on axial length (AL), anterior chamber depth (ACD), keratometry (Km), and white-to-white distance (WTW) are not well studied in this population. This retrospective study examined 797 patients (1566 eyes) undergoing cycloplegic refraction at a Samsung Kangbuk hospital pediatric ophthalmology clinic from 2010 to 2023. Ocular biometry was measured before and after instilling 1% cyclopentolate and 0.5% phenylephrine/0.5% tropicamide. Patients were categorized by strabismus diagnosis, age, refractive error and amblyopia status. Differences in AL, ACD, Km, WTW, and refractive error pre- and post-cycloplegia were analyzed using paired t tests. ACD (3.44 ± 0.33 vs 3.58 ± 0.29 mm, P < .05) and WTW (12.09 ± 0.42 vs 12.30 ± 0.60 mm, P < .05) increased significantly after cycloplegia in all groups except other strabismus subgroup (Cs) in both parameters and youngest subgroup (G1) in ACD. Refractive error demonstrated a hyperopic shift from -0.48 ± 3.00 D to -0.06 ± 3.32 D (P < .05) in overall and a myopic shift from -6.97 ± 4.27 to -8.10 ± 2.26 in high myopia (HM). Also, AL and Km did not change significantly. In conclusion, cycloplegia impacts ocular biometrics in children with strabismus and amblyopia, significantly increasing ACD and WTW. Refractive error shifts hyperopically in esotropia subgroup (ET) and myopically in high myopia subgroup (HM), eldest subgroup (G3) relating more to anterior segment changes than AL/Km. Understanding cycloplegic effects on biometry is important for optimizing refractive correction in these patients.
Topics: Humans; Amblyopia; Strabismus; Retrospective Studies; Male; Female; Child; Biometry; Mydriatics; Child, Preschool; Refraction, Ocular; Cyclopentolate; Refractive Errors; Adolescent; Anterior Chamber; Axial Length, Eye
PubMed: 38758890
DOI: 10.1097/MD.0000000000038143 -
Journal of Insect Physiology Jun 2024Chemical substances are of utmost importance for the biotic interactions between animals and their predators/parasites; many of these semiochemicals are emitted for...
Chemical substances are of utmost importance for the biotic interactions between animals and their predators/parasites; many of these semiochemicals are emitted for defence purposes. One of the most deterrent and toxic biogenic substances we know of is hydrogen cyanide, which can be stored by certain insects, millipedes, centipedes and arachnids in the form of stable and less volatile molecules. The aim of this study was to analyse the biology and chemistry of such a defence mechanism in a geophilomorph centipede (Chilopoda). The cyanogenic secretion of Clinopodes flavidus is discharged from the ventral glands, whose glandular units are located in the space between the cuticle and the trunk muscles and do not extend deep into the segment. In addition to hydrogen cyanide, the ventral secretion contains 2-methylpentanoic acid, benzaldehyde, benzoyl cyanide, 2-methyl branched C-9 carboxylic acid (tentatively identified as 2-methyloctanoic acid), methyl 2-phenylacetate, benzoic acid and mandelonitrile as well as four major proteins with a molecular weight of 150, 66.2, 59 and 55 kDa. The correlation between the presence of ventral glands and guarding with the female's ventral side facing away from the eggs and young indicates a functional link between these two traits. We hope that the specificity of the chemical composition of the ventral secretion could serve as a criterion for chemotaxonomy and that the analysis of more species will help to clarify the phylogenetic relationships within the Geophilomorpha.
Topics: Animals; Female; Hydrogen Cyanide; Chilopoda; Male; Arthropods; Pheromones
PubMed: 38754699
DOI: 10.1016/j.jinsphys.2024.104649 -
Chirality May 2024The absolute configuration of three chiral eugenol derivatives was assigned by a multi-step methodology based on enantioselective HPLC combined with spectroscopic and...
Enantioselective high-performance liquid chromatography combined with spectroscopic methods and theoretical calculations: A valid strategy to determine the absolute configuration of eugenol derivatives.
The absolute configuration of three chiral eugenol derivatives was assigned by a multi-step methodology based on enantioselective HPLC combined with spectroscopic and theoretical calculations. Milligram amounts of enantiopure forms used for stereochemical characterization were isolated by HPLC on the immobilized amylose-based chiral stationary phase Chiralpak IG using normal phase elution conditions. The absolute configuration was indirectly determined for one of the three compounds by H NMR via methoxy-α-trifluoromethyl-α-phenylacetic acid derivatization (Mosher's acid). Comparison of the experimental and predicted electronic circular dichroism spectra confirmed the stereochemical assignment by Mosher's method and extended the absolute configuration assignment to two other chiral compounds.
PubMed: 38747133
DOI: 10.1002/chir.23668 -
The International Journal of... Jun 2024The principle of gain control determines the efficiency of neuronal processing and can be enhanced with pharmacological or brain stimulation methods. It is a key factor...
BACKGROUND
The principle of gain control determines the efficiency of neuronal processing and can be enhanced with pharmacological or brain stimulation methods. It is a key factor for cognitive control, but the degree of how much gain control may be enhanced underlies a physical limit.
METHODS
To investigate whether methylphenidate (MPH) and transcranial direct current stimulation (tDCS) share common underlying mechanisms and cognitive effects, we administered MPH and anodal tDCS (atDCS) over the right inferior frontal gyrus both separately and combined, while healthy adult participants (n = 104) performed a response selection and inhibition task. The recorded EEG data were analyzed with a focus on theta band activity, and source estimation analyses were conducted.
RESULTS
The behavioral data show that MPH and atDCS revealed interactive effects on the ability to inhibit responses. Both MPH and atDCS modulated task-related theta oscillations in the supplementary motor area when applied separately, making a common underlying mechanism likely. When both stimulation methods were combined, there was no doubling of effects in the supplementary motor area but a shift to inferior frontal areas in the cortical network responsible for theta-driven processing.
CONCLUSIONS
The results indicate that both MPH and atDCS likely share a common underlying neuronal mechanism, and interestingly, they demonstrate interactive effects when combined, which are most likely due to the physical limitations of gain control increases. The current study provides critical groundwork for future combined applications of MPH and non-invasive brain stimulation.
Topics: Humans; Transcranial Direct Current Stimulation; Male; Female; Adult; Young Adult; Methylphenidate; Inhibition, Psychological; Theta Rhythm; Electroencephalography; Central Nervous System Stimulants; Prefrontal Cortex; Motor Cortex
PubMed: 38742426
DOI: 10.1093/ijnp/pyae023 -
Analytical Methods : Advancing Methods... May 2024The non-steroidal anti-inflammatory drug (NSAID) diclofenac (DCF) is an important environmental contaminant occurring in surface waters all over the world, because,...
The non-steroidal anti-inflammatory drug (NSAID) diclofenac (DCF) is an important environmental contaminant occurring in surface waters all over the world, because, after excretion, it is not adequately removed from wastewater in sewage treatment plants. To be able to monitor this pollutant, highly efficient analytical methods are needed, including immunoassays. In a medical research project, monoclonal antibodies against diclofenac and its metabolites had been produced. Based on this monoclonal anti-DCF antibody, a new indirect competitive enzyme-linked immunosorbent assay (ELISA) was developed and applied for environmental samples. The introduction of a spacer between diclofenac and the carrier protein in the coating conjugate led to higher sensitivity. With a test midpoint of 3 μg L and a measurement range of 1-30 μg L, the system is not sensitive enough for direct analysis of surface water. However, this assay is quite robust against matrix influences and can be used for wastewater. Without adjustment of the calibration, organic solvents up to 5%, natural organic matter (NOM) up to 10 mg L, humic acids up to 2.5 mg L, and salt concentrations up to 6 g L NaCl and 75 mg L CaCl are tolerated. The antibody is also stable in a pH range from 3 to 12. Cross-reactivity (CR) of 1% or less was determined for the metabolites 4'-hydroxydiclofenac (4'-OH-DCF), 5-hydroxydiclofenac (5-OH-DCF), DCF lactam, and other NSAIDs. Relevant cross-reactivity occurred only with an amide derivative of DCF, 6-aminohexanoic acid (DCF-Ahx), aceclofenac (ACF) and DCF methyl ester (DCF-Me) with 150%, 61% and 44%, respectively. These substances, however, have not been found in samples. Only DCF-acyl glucuronide with a cross-reactivity of 57% is of some relevance. For the first time, photodegradation products were tested for cross-reactivity. With the ELISA based on this antibody, water samples were analysed. In sewage treatment plant effluents, concentrations in the range of 1.9-5.2 μg L were determined directly, with recoveries compared to HPLC-MS/MS averaging 136%. Concentrations in lakes ranged from 3 to 4.4 ng L and were, after pre-concentration, determined with an average recovery of 100%.
Topics: Diclofenac; Antibodies, Monoclonal; Water Pollutants, Chemical; Enzyme-Linked Immunosorbent Assay; Anti-Inflammatory Agents, Non-Steroidal; Environmental Monitoring; Wastewater
PubMed: 38742423
DOI: 10.1039/d3ay01333b -
Journal of Hazardous Materials Jul 2024The capacity for organic micropollutant removal in granular activated carbon (GAC) filters for wastewater treatment changes over time. These changes are in general...
The capacity for organic micropollutant removal in granular activated carbon (GAC) filters for wastewater treatment changes over time. These changes are in general attributed to changes in adsorption, but may in some cases also be affected by biological degradation. Knowledge on the degradation of organic micropollutants, however, is scarce. In this work, the degradation of micropollutants in several full-scale GAC and sand filters was investigated through incubation experiments over a period of three years, using C-labeled organic micropollutants with different susceptibilities to biological degradation (ibuprofen, diclofenac, and carbamazepine), with parallel 16S rRNA gene sequencing. The results showed that the degradation of diclofenac and ibuprofen in GAC filters increased with increasing numbers of bed volumes when free oxygen was available in the filter, while variations over filter depth were limited. Despite relatively large differences in bacterial composition between filters, a degradation of diclofenac was consistently observed for the GAC filters that had been operated with high influent oxygen concentration (DO >8 mg/L). The results of this comprehensive experimental work provide an increased understanding of the interactions between microbial composition, filter material, and oxygen availability in the biological degradation of organic micropollutants in GAC filters.
Topics: Diclofenac; Water Pollutants, Chemical; Ibuprofen; Filtration; Biodegradation, Environmental; Carbamazepine; Charcoal; Bacteria; RNA, Ribosomal, 16S; Oxygen; Waste Disposal, Fluid; Water Purification
PubMed: 38733780
DOI: 10.1016/j.jhazmat.2024.134449 -
BMC Biotechnology May 2024Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, and it leads to irreversible inflammation in intra-articular joints. Current treatment approaches...
BACKGROUND
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, and it leads to irreversible inflammation in intra-articular joints. Current treatment approaches for RA include non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), corticosteroids, and biological agents. To overcome the drug-associated toxicity of conventional therapy and transdermal tissue barrier, an injectable NSAID-loaded hydrogel system was developed and explored its efficacy.
RESULTS
The surface morphology and porosity of the hydrogels indicate that they mimic the natural ECM, which is greatly beneficial for tissue healing. Further, NSAIDs, i.e., diclofenac sodium, were loaded into the hydrogel, and the in vitro drug release pattern was found to be burst release for 24 h and subsequently sustainable release of 50% drug up to 10 days. The DPPH assay revealed that the hydrogels have good radical scavenging activity. The biocompatibility study carried out by MTT assay proved good biocompatibility and anti-inflammatory activity of the hydrogels was carried out by gene expression study in RAW 264.7 cells, which indicate the downregulation of several key inflammatory genes such as COX-2, TNF-α & 18s.
CONCLUSION
In summary, the proposed ECM-mimetic, thermo-sensitive in situ hydrogels may be utilized for intra-articular inflammation modulation and can be beneficial by reducing the frequency of medication and providing optimum lubrication at intra-articular joints.
Topics: Hydrogels; Animals; Mice; Arthritis, Rheumatoid; RAW 264.7 Cells; Anti-Inflammatory Agents, Non-Steroidal; Extracellular Matrix; Diclofenac; Drug Liberation
PubMed: 38724967
DOI: 10.1186/s12896-024-00856-3 -
Bulletin of Experimental Biology and... Mar 2024A bradykinin B receptors antagonist PAV-0056, an 1,4-benzodiazepin-2-one derivative, intragastrically administrated to mice at doses of 0.1 and 1 mg/kg causes analgesia...
A bradykinin B receptors antagonist PAV-0056, an 1,4-benzodiazepin-2-one derivative, intragastrically administrated to mice at doses of 0.1 and 1 mg/kg causes analgesia in the "formalin test" not inferior to that of diclofenac sodium (10 mg/kg) and tramadol (20 mg/kg). PAV-0056 at doses of 0.1 and 10 mg/kg has no anxiolytic and central muscle relaxant effects in mice and does not damage the gastric mucosa in rats. Based on the results of the conditioned place preference test, PAV-0056 also does not induce addiction in mice.
Topics: Animals; Mice; Rats; Male; Analgesics; Diclofenac; Tramadol; Psychotropic Drugs; Bradykinin; Anti-Anxiety Agents; Bradykinin B1 Receptor Antagonists; Rats, Wistar; Gastric Mucosa; Pain Measurement
PubMed: 38724817
DOI: 10.1007/s10517-024-06071-6