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Northern Clinics of Istanbul 2023Although hydatid cyst infects many organs, it most commonly involves liver, lungs, and central nervous system. The goal of hydatid cyst treatment is to completely...
Although hydatid cyst infects many organs, it most commonly involves liver, lungs, and central nervous system. The goal of hydatid cyst treatment is to completely eliminate the parasite and to prevent recurrences with minimal mortality and morbidity. The procedure of puncture, aspiration, injection of a scolicidal, and reaspiration (PAIR) of a cyst has been introduced as an alternative to surgical method since it is less invasive and less morbid and is associated with a shorter hospital stay and a lower cost. Herein, we report an 11-year-old girl who developed anaphylaxis during the puncture of a hepatic hydatid cyst. The patient who developed anaphylaxis during the PAIR procedure was administered intravenous adrenaline, methyl prednisolone, and antihistaminic medication. She was intubated and provided assisted ventilation using a mechanic ventilator. The child was extubated 4 h after her admission to the pediatric intensive care unit. During follow-up, the contents of her hepatic hydatid cysts were aspirated through a catheter, followed by their irrigation with 20% sodium chloride and re-aspiration. Then, 97% ethyl alcohol was injected into the cyst cavity to make it collapse. The goal of this report was to draw attention to the rare occurrence of anaphylaxis during the PAIR procedure and to stress that clini-cians should be vigilant for this complication.
PubMed: 38328732
DOI: 10.14744/nci.2022.58260 -
Nature Communications Dec 2023Minor changes to complex structures can exert major influences on synthesis strategy and functional properties. Here we explore two parallel series of picrotoxinin (PXN,...
Minor changes to complex structures can exert major influences on synthesis strategy and functional properties. Here we explore two parallel series of picrotoxinin (PXN, 1) analogs and identify leads with selectivity between mammalian and insect ion channels. These are the first SAR studies of PXN despite its >100-year history and are made possible by advances in total synthesis. We observe a remarkable stabilizing effect of a C5 methyl, which completely blocks C15 alcoholysis via destabilization of an intermediate twist-boat conformer; suppression of this secondary hydrolysis pathway increases half-life in plasma. C5 methylation also decreases potency against vertebrate ion channels (γ-Aminobutyric acid type A (GABA) receptors) but maintains or increases antagonism of homologous invertebrate GABA-gated chloride channels (resistance to dieldrin (RDL) receptors). Optimal 5MePXN analogs appear to change the PXN binding pose within GABARs by disruption of a hydrogen bond network. These discoveries were made possible by the lower synthetic burden of 5MePXN (2) and were illuminated by the parallel analog series, which allowed characterization of the role of the synthetically simplifying C5 methyl in channel selectivity. These are the first SAR studies to identify changes to PXN that increase the GABA-RDL selectivity index.
Topics: Animals; Picrotoxin; Chloride Channels; Receptors, GABA-A; gamma-Aminobutyric Acid; Dieldrin; Methylation; Mammals
PubMed: 38097583
DOI: 10.1038/s41467-023-44030-3 -
Data in Brief Dec 2023Toxicological analysis of the effects of natural compounds is frequently mandated to assess their safety. In addition to more simple cellular systems, more complex...
Toxicological analysis of the effects of natural compounds is frequently mandated to assess their safety. In addition to more simple cellular systems, more complex biological systems can be used to evaluate toxicity. This dataset is comprised of bright-field microscopy images of chicken-embryo blood cells, a complex biological model that recapitulates several features found in human organisms, including circulation in blood stream and biodistribution to different organs. In the presented collection of blood smear images, cells were exposed to the flavonoid quercetin, and the two mutagens methyl methanesulfonate (MMS) and cadmium chloride (CdCl). models offer a unique opportunity to investigate the effects of various substances, pathogens, or cancer treatments on developing embryos, providing valuable insights into potential risks and therapeutic strategies. In toxicology, models allow for early detection of harmful compounds and their impact on embryonic development, aiding in the assessment of environmental hazards. In immunology, these models offer a controlled system to explore the developing immune responses and the interaction between pathogens and host defenses. Additionally, models are instrumental in oncology research as they enable the study of tumor development and response to therapies in a dynamic, rapidly developing environment. Thus, these versatile models play a crucial role in advancing our understanding of complex biological processes and guiding the development of safer therapeutics and interventions. The data presented here can aid in understanding the potential toxic effects of these substances on hematopoiesis and the overall health of the developing organism. Moreover, the large dataset of blood smear images can serve as a resource for training machine learning algorithms to automatically detect and classify blood cells, provided that specific optimized conditions such as image magnification and background light are maintained for comparison. This can lead to the development of automated tools for blood cell analysis, which can be useful in research. Moreover, the data is amenable to the use as teaching and learning resource for histology and developmental biology.
PubMed: 37876742
DOI: 10.1016/j.dib.2023.109673 -
Turkish Journal of Pharmaceutical... Nov 2023Parabens, which are p-hydroxybenzoic acid esters, are used as preservatives in personal care products, pharmaceuticals, and food because of their antimicrobial activity....
Ultrasound- and Vortex-Assisted Dispersive Liquid-Liquid Microextraction of Parabens from Personal Care Products and Urine, Followed by High-Performance Liquid Chromatography.
OBJECTIVES
Parabens, which are p-hydroxybenzoic acid esters, are used as preservatives in personal care products, pharmaceuticals, and food because of their antimicrobial activity. However, they are also classified as suspected endocrine disruptors and carcinogens. In the present study, we aimed to optimize an ultrasound and vortex-assisted dispersive liquid-liquid microextraction (DLLME) procedure for the simultaneous extraction of methyl, ethyl, isopropyl, propyl, isobutyl, and butyl parabens from personal care products and urine.
MATERIALS AND METHODS
The extraction solvent type, extraction solvent volume, disperser solvent volume, sodium chloride concentration, ultrasonication time, and vortex application time were evaluated to obtain optimum recoveries by ultrasound and vortex-assisted DLLME. Parabens were detected using a validated high performanc-liquid chromatography (HPLC) method with fluorescence detection. Method validation was performed by examining linearity, the limit of detection, limit of quantification, accuracy, and precision.
RESULTS
The limits of detection and quantification of the HPLC method were between 0.09-0.18 μg/mL and 0.28-0.54 μg/mL, respectively. Precision was examined as the relative standard deviation, which was 0.22-1.81% and 1.12-2.03% for intra- and interday studies. Recovery percentages were higher than 96.00%. Samples of two paraben-free personal care products and synthetic urine were spiked with the analyses at 0.02 μg/mL and were successfully analyzed using the developed procedure with recovery values higher than 82.00%.
CONCLUSION
The proposed procedure provided quantification of selected parabens at 20 ng/mL in analyzed personal care products and urine matrices with good precision and accuracy.
PubMed: 37933823
DOI: 10.4274/tjps.galenos.2022.42387 -
The Science of the Total Environment Aug 2023The effects of non-insecticidal agrochemicals on pest natural predators remain largely unexplored except bees and silkworm. The herbicide quizalofop-p-ethyl (QpE),...
The effects of non-insecticidal agrochemicals on pest natural predators remain largely unexplored except bees and silkworm. The herbicide quizalofop-p-ethyl (QpE), fungicide thiophanate-methyl (TM), and plant growth regulator mepiquat chloride (MC) have been extensively applied as non-insecticidal agrochemicals. Here, we systematically evaluated multiple effects of these 3 non-insecticidal agrochemicals on three generations of Propylea japonica, an important agroforestry predatory beetle, including the effects on its development, reproduction, enterobacteria, and transcriptomic response. The results showed that QpE exhibited a hormetic effect on P. japonica, thus significantly increasing the survival rate of generation 2 (F2) females, generation 3 (F3) females, and F3 males and body weight of F3 males. However, three successive generations exposed to TM and MC had no significant effect on longevity, body weight, survival rate, pre-oviposition period, and fecundity of P. japonica. Additionally, we investigated the effects of MC, TM, and QpE exposure on gene expression and gut bacterial community of F3 P. japonica. Under MC, TM, and QpE exposure, the overwhelming genes of P. japonica (99.90 %, 99.45 %, and 99.7 %) remained unaffected, respectively. Under TM and MC exposure, differentially expressed genes (DEGs) were not significantly enriched in any KEGG pathway, indicating TM and MC did not significantly affect functions of P. japonica, but under QpE exposure, the expression levels of drug metabolism-related genes were down-regulated. Although QpE treatment did not affect gut dominant bacterial community composition, it significantly increased relative abundances of detoxification metabolism-related bacteria such as Wolbachia, Pseudomonas and Burkholderia in P. japonica. However, TM and MC had no significant effect on the gut bacterial community composition and relative abundance in P. japonica. This study revealed for the first time the mechanism by which P. japonica might compensate for gene downregulation-induced detoxification metabolism decline through altering symbiotic bacteria under QpE exposure. Our findings provide reference for the rational application of non-insecticidal agrochemicals.
Topics: Female; Male; Animals; Bees; Coleoptera; Bacteria; Risk Assessment
PubMed: 37156379
DOI: 10.1016/j.scitotenv.2023.163931 -
Frontiers in Chemistry 2024In this study, choline chloride/urea was used as a green deep eutectic solvent in the three-component reaction of hydrazine/phenylhydrazine, malononitrile, and aromatic...
Choline chloride/urea as a green and efficient deep eutectic solvent in three-component and four-component synthesis of novel pyrazole and pyrano[2,3-c] pyrazole derivatives with antibacterial and antifungal activity.
In this study, choline chloride/urea was used as a green deep eutectic solvent in the three-component reaction of hydrazine/phenylhydrazine, malononitrile, and aromatic aldehydes for synthesizing pyrazole derivatives, and in the four-component reaction of methyl/ethyl acetoacetate, hydrazine/phenylhydrazine, malononitrile, and aromatic aldehydes for synthesizing pyrano[2,3-c]pyrazole derivatives. Elemental analysis, H, and C NMR spectroscopy were used to confirm the structure of the synthesized pyrazole and pyrano[2,3-c] pyrazole derivatives. The antimicrobial effects of the synthesized pyrazole and pyrano[2,3-c] pyrazole derivatives were investigated. In antimicrobial tests, instructions from clinical and laboratory standards institutes were used. Antimicrobial study was done on pathogenic gram-positive and gram-negative species, and specialized aquatic strains and fungal species. Using choline chloride/urea, novel pyrazole derivatives and pyrano[2,3-c]pyrazole derivatives were synthesized, and other derivatives were synthesized with higher efficiency in less time than some previously reported methods. MIC (minimum inhibitory concentration) and MBC (minimum bactericidal concentration) obtained for derivatives were higher than some antibiotic drugs. Synthesis and reports of new derivatives of pyrazole and pyrano[2,3-c]pyrazole, and investigation and reports of their antimicrobial properties on gram-positive, gram-negative, and specialized aquatic and fungal species are among the novel and important findings of this study.
PubMed: 38435668
DOI: 10.3389/fchem.2024.1342784 -
Pharmaceuticals (Basel, Switzerland) Nov 2023The design, synthesis, and evaluation of novel non-steroidal anti-inflammatory drugs (NSAIDs) with better activity and lower side effects are big challenges today. In...
The design, synthesis, and evaluation of novel non-steroidal anti-inflammatory drugs (NSAIDs) with better activity and lower side effects are big challenges today. In this work, two 5-acetamido-2-hydroxy benzoic acid derivatives were proposed, increasing the alkyl position (methyl) in an acetamide moiety, and synthesized, and their structural elucidation was performed using H NMR and C NMR. The changes in methyl in larger groups such as phenyl and benzyl aim to increase their selectivity over cyclooxygenase 2 (COX-2). These 5-acetamido-2-hydroxy benzoic acid derivatives were prepared using classic methods of acylation reactions with anhydride or acyl chloride. Pharmacokinetics and toxicological properties were predicted using computational tools, and their binding affinity (kcal/mol) with COX-2 receptors ( and ) was analyzed using docking studies (PDB ID 4PH9, 5KIR, 1PXX and 5F1A). An in-silico study showed that 5-acetamido-2-hydroxy benzoic acid derivates have a better bioavailability and binding affinity with the COX-2 receptor, and in-vivo anti-nociceptive activity was investigated by means of a writhing test induced by acetic acid and a hot plate. PS3, at doses of 20 and 50 mg/kg, reduced painful activity by 74% and 75%, respectively, when compared to the control group (20 mg/kg). Regarding the anti-nociceptive activity, the benzyl showed reductions in painful activity when compared to acetaminophen and 5-acetamido-2-hydroxy benzoic acid. However, the proposed derivatives are potentially more active than 5-acetamido-2-hydroxy benzoic acid and they support the design of novel and safer derivative candidates. Consequently, more studies need to be conducted to evaluate the different pharmacological actions, the toxicity of possible metabolites that can be generated, and their potential use in inflammation and pain therapy.
PubMed: 38004449
DOI: 10.3390/ph16111584 -
Journal of Enzyme Inhibition and... Dec 2023A series of 4-methyl-1,2,3-benzoxathiazine-2,2-dioxides with various substituents in 5, 6 or 7 positions was obtained from corresponding 2'-hydroxyacetophenones in their...
A series of 4-methyl-1,2,3-benzoxathiazine-2,2-dioxides with various substituents in 5, 6 or 7 positions was obtained from corresponding 2'-hydroxyacetophenones in their reaction with sulphamoyl chloride. 6- and 7-aryl substituted 4-methyl-1,2,3-benzoxathiazine-2,2-dioxides were obtained from aryl substituted 2'-hydroxyacetophenonesprepared from 4- or 5-bromo-2'-hydroxyacetophenones via two-step protocol. 4-Methyl-1,2,3-benzoxathiazine-2,2-dioxides were investigated as inhibitors of four human (h) carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, off-target cytosolic hCA I and II, and target transmembrane, tumour-associated hCA IX and XII. Twenty derivatives of 4-methyl-1,2,3-benzoxathiazine 2,2-dioxide were obtained. With one exception (compound), they mostly act as nanomolar inhibitors of target hCA IX and XII. Basically, all screened compounds express none or low inhibitory properties towards off-target hCA I. hCA II is inhibited in micromolar range. Overwhelming majority of 4-methyl-1,2,3-benzoxathiazine 2,2-dioxides express excellent selectivity towards CA IX/XII over hCA I as well as very good selectivity towards CA IX/XII over hCA II.
Topics: Humans; Structure-Activity Relationship; Carbonic Anhydrase Inhibitors; Carbonic Anhydrase IX; Carbonic Anhydrases; Antigens, Neoplasm; Neoplasms; Isoenzymes; Molecular Structure
PubMed: 36718988
DOI: 10.1080/14756366.2023.2170370 -
F1000Research 2023Altered sensory processing is a pervasive symptom in individuals with Autism Spectrum Disorders (ASD); people with Phelan McDermid syndrome (PMS), in particular, show...
Altered sensory processing is a pervasive symptom in individuals with Autism Spectrum Disorders (ASD); people with Phelan McDermid syndrome (PMS), in particular, show reduced responses to sensory stimuli. PMS is caused by deletions of the terminal end of chromosome 22 or point mutations in People with PMS can present with an array of symptoms including ASD, epilepsy, gastrointestinal distress, and reduced responses to sensory stimuli. People with PMS are often medicated to manage behaviors like aggression and/or self-harm and/or epilepsy, and it remains unclear how these medications might impact perception/sensory processing. Here we test this using zebrafish mutant PMS models that likewise show reduced sensory responses in a visual motor response (VMR) assay, in which increased locomotion is triggered by light to dark transitions. We screened three medications, risperidone, lithium chloride (LiCl), and carbamazepine (CBZ), prescribed to people with PMS and one drug, 2-methyl-6-(phenylethynyl) pyridine (MPEP) tested in rodent models of PMS, for their effects on a sensory-induced behavior in two zebrafish PMS models with frameshift mutations in either the N- or C- termini. To test how pharmacological treatments affect the VMR, we exposed larvae to selected drugs for 24 hours and then quantified their locomotion during four ten-minute cycles of lights on-to-off stimuli. We found that risperidone normalized the VMR in models. LiCl and CBZ had no effect on the VMR in any of the three genotypes. MPEP reduced the VMR in wildtype (WT) to levels seen in models but caused no changes in either model. Finally, mutants showed resistance to the seizure-inducing drug pentylenetetrazol (PTZ), at a dosage that results in hyperactive swimming in WT zebrafish. Our work shows that the effects of drugs on sensory processing are varied in ways that can be highly genotype- and drug-dependent.
Topics: Animals; Humans; Chromosomes, Human, Pair 22; Nerve Tissue Proteins; Risperidone; Zebrafish; Chromosome Disorders; Disease Models, Animal; Lithium Chloride; Carbamazepine; Perception
PubMed: 37868296
DOI: 10.12688/f1000research.127830.2 -
Chemistry (Weinheim An Der Bergstrasse,... Nov 2023A metal-free natural dye has been developed to selectively convert methane to methyl trifluoroacetate (CH TFA) using visible light, probably due to the formation of a...
A metal-free natural dye has been developed to selectively convert methane to methyl trifluoroacetate (CH TFA) using visible light, probably due to the formation of a chloride-bridged dimer undergoing fast intra-complex charge transfer.
PubMed: 37503795
DOI: 10.1002/chem.202301796