Toxicology and Pharmacology of Bispyridinium Oximes - Insight into the Mechanism of Action vs Soman Poisoning in vivo

1981 ◽  
Vol 1 (2) ◽  
pp. 193-202 ◽  
Author(s):  
JOHN G. CLEMENT
Keyword(s):  
Mechanism Of Action ◽  
Insight Into

scholarly journals THE MECHANISM OF ACTION OF ANTI-LYMPHOCYTE SERUM

1969 ◽  
Vol 130 (1) ◽  
pp. 49-76 ◽  
Author(s):  
Eugene M. Lance
Keyword(s):  
Mechanism Of Action ◽  
Strong Support ◽  
Reticuloendothelial System ◽  
Selective Ablation ◽  
Subsequent Elution ◽  
Radionuclide Tracer ◽  
Rapid Clearance ◽  
Distribution Studies ◽  
Insight Into

Studies designed to gain insight into the mechanism of action of the active component of antilymphocyte serum were carried out using an antibody eluate prepared from the IgG fraction of anti-lymphocyte serum by absorption and subsequent elution from thymocyte membrane. The resulting antibody eluate was labeled with radionuclide tracer to determine the fate of the antibody in vivo. The result indicated that anti-lymphocytic antibodies are eliminated from recipients extremely rapidly. The mechanism for this rapid clearance appears to depend upon the absorption of antibody molecules onto lymphocyte surfaces and the subsequent clearing and degradation of the antibody-lymphocyte complexes by the reticuloendothelial system. Distribution studies confirm that the major site of antibody-lymphocyte interaction occurs in the periphery with relatively little penetration of antibody within lymphoid organs. Radioautographic studies showed that the pattern of localization within lymphoid and other organs is confined to rather specific areas. These observations are believed to offer strong support for the notion that anti-lymphocyte serum achieves its immunosuppressive effect by bringing about a selective ablation of the population of recirculating lymphocytes.

scholarly journals Functional organization of box C/D RNA-guided RNA methyltransferase

2020 ◽  
Vol 48 (9) ◽  
pp. 5094-5105
Author(s):  
Zuxiao Yang ◽  
Jiayin Wang ◽  
Lin Huang ◽  
David M J Lilley ◽  
Keqiong Ye
Keyword(s):  
Recombinant Proteins ◽  
Mechanism Of Action ◽  
Functional Organization ◽  
Protein Complexes ◽  
Site Specific ◽  
Guide Rnas ◽  
Chaetomium Thermophilum ◽  
Rna Protein Complexes ◽  
Insight Into

Abstract Box C/D RNA protein complexes (RNPs) catalyze site-specific 2′-O-methylation of RNA with specificity determined by guide RNAs. In eukaryotic C/D RNP, the paralogous Nop58 and Nop56 proteins specifically associate with terminal C/D and internal C'/D' motifs of guide RNAs, respectively. We have reconstituted active C/D RNPs with recombinant proteins of the thermophilic yeast Chaetomium thermophilum. Nop58 and Nop56 could not distinguish between the two C/D motifs in the reconstituted enzyme, suggesting that the assembly specificity is imposed by trans-acting factors in vivo. The two C/D motifs are functionally independent and halfmer C/D RNAs can also guide site-specific methylation. Extensive pairing between C/D RNA and substrate is inhibitory to modification for both yeast and archaeal C/D RNPs. N6-methylated adenine at box D/D' interferes with the function of the coupled guide. Our data show that all C/D RNPs share the same functional organization and mechanism of action and provide insight into the assembly specificity of eukaryotic C/D RNPs.

Plasminogen Activation In Vivo upon Intravenous Infusion of DDAVP

1992 ◽  
Vol 67 (01) ◽  
pp. 111-116 ◽  
Author(s):  
Marcel Levi ◽  
Jan Paul de Boer ◽  
Dorina Roem ◽  
Jan Wouter ten Cate ◽  
C Erik Hack
Keyword(s):  
Monoclonal Antibodies ◽  
Plasminogen Activator ◽  
Plasma Levels ◽  
Fold Increase ◽  
Fibrinolytic System ◽  
Plasminogen Activation ◽  
Plasminogen Activator Activity ◽  
Insight Into

SummaryInfusion of desamino-d-arginine vasopressin (DDAVP) results in an increase in plasma plasminogen activator activity. Whether this increase results in the generation of plasmin in vivo has never been established.A novel sensitive radioimmunoassay (RIA) for the measurement of the complex between plasmin and its main inhibitor α2 antiplasmin (PAP complex) was developed using monoclonal antibodies preferentially reacting with complexed and inactivated α2-antiplasmin and monoclonal antibodies against plasmin. The assay was validated in healthy volunteers and in patients with an activated fibrinolytic system.Infusion of DDAVP in a randomized placebo controlled crossover study resulted in all volunteers in a 6.6-fold increase in PAP complex, which was maximal between 15 and 30 min after the start of the infusion. Hereafter, plasma levels of PAP complex decreased with an apparent half-life of disappearance of about 120 min. Infusion of DDAVP did not induce generation of thrombin, as measured by plasma levels of prothrombin fragment F1+2 and thrombin-antithrombin III (TAT) complex.We conclude that the increase in plasminogen activator activity upon the infusion of DDAVP results in the in vivo generation of plasmin, in the absence of coagulation activation. Studying the DDAVP induced increase in PAP complex of patients with thromboembolic disease and a defective plasminogen activator response upon DDAVP may provide more insight into the role of the fibrinolytic system in the pathogenesis of thrombosis.

scholarly journals Plant-Derived Extracellular Vesicles: Current Findings,Challenges, and Future Applications

Membranes ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 411
Author(s):  
Nader Kameli ◽  
Anya Dragojlovic-Kerkache ◽  
Paul Savelkoul ◽  
Frank R. Stassen
Keyword(s):  
Human Health ◽  
Extracellular Vesicles ◽  
Preliminary Results ◽  
In Vivo Experiments ◽  
Health And Disease ◽  
Conducting Research ◽  
Protocol Standardization ◽  
Insight Into

In recent years, plant-derived extracellular vesicles (PDEVs) have gained the interest of many experts in fields such as microbiology and immunology, and research in this field has exponentially increased. These nano-sized particles have provided researchers with a number of interesting findings, making their application in human health and disease very promising. Both in vitro and in vivo experiments have shown that PDEVs can exhibit a multitude of effects, suggesting that these vesicles may have many potential future applications, including therapeutics and nano-delivery of compounds. While the preliminary results are promising, there are still some challenges to face, such as a lack of protocol standardization, as well as knowledge gaps that need to be filled. This review aims to discuss various aspects of PDEV knowledge, including their preliminary findings, challenges, and future uses, giving insight into the complexity of conducting research in this field.

scholarly journals A Molecular Insight into the Synergistic Mechanism of Nigella sativa (Black Cumin) with β-Lactam Antibiotics against Clinical Isolates of Methicillin-Resistant Staphylococcus aureus

2021 ◽  
Vol 11 (7) ◽  
pp. 3206
Author(s):  
Lorina I. Badger-Emeka ◽  
Promise Madu Emeka ◽  
Hairul Islam M. Ibrahim
Keyword(s):  
Staphylococcus Aureus ◽  
Mechanism Of Action ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Nigella Sativa ◽  
Synergistic Effects ◽  
Diffusion Method ◽  
Methicillin Resistant ◽  
Cell Wall Disruption ◽  
Time Kill ◽  
Insight Into

Methicillin-resistant Staphylococcus aureus (MRSA) infection is detrimental to hospitalized patients. With diminishing choices of antibiotics and the worry about resistance to colistin in synergistic combined therapy, there are suggestions for the use of herbal derivatives. This investigation evaluated the synergistic effects of Nigella sativa (NS) in combination with beta-lactam (β-lactam) antibiotics on extreme drug-resistant (XDR) MRSA isolates. NS concentrations of 10, 7.5, 5.0, 2.5, 1.0, and 0.1 µg/mL, alone and in combination with β-lactam antibiotics, were used to determine the antimicrobial susceptibility of MRSA isolates by the well diffusion method. Time–kill assays were performed using a spectrophotometer, with time–kill curves plotted and synergism ascertained by the fractional inhibitory concentration (FIC). Scanning and transmission electron microscopy were used to gain insight into the mechanism of action of treated groups. Isolates were inhibited by the NS concentrations, with differences in the zones of inhibition being statistically insignificant at p < 0.05. There were statistically significant differences in the time–kill assay for the MRSA isolates. In addition, NS combined with augmentin showed better killing than oxacillin and cefuroxime. The mechanism of action shown by the SEM and TEM results revealed cell wall disruption, which probably created interference that led to bacterial lysis.

scholarly journals Human umbilical cord mesenchymal stem cell-derived exosomal miR-27b attenuates subretinal fibrosis via suppressing epithelial–mesenchymal transition by targeting HOXC6

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dongli Li ◽  
Junxiu Zhang ◽  
Zijia Liu ◽  
Yuanyuan Gong ◽  
Zhi Zheng
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Umbilical Cord ◽  
Mechanism Of Action ◽  
Epithelial Mesenchymal Transition ◽  
Human Umbilical Cord ◽  
Mesenchymal Transition ◽  
Rpe Cells ◽  
Subretinal Fibrosis

Abstract Background and aim Subretinal fibrosis resulting from neovascular age-related macular degeneration (nAMD) is one of the major causes of serious and irreversible vision loss worldwide, and no definite and effective treatment exists currently. Retinal pigmented epithelium (RPE) cells are crucial in maintaining the visual function of normal eyes and its epithelial–mesenchymal transition (EMT) is associated with the pathogenesis of subretinal fibrosis. Stem cell-derived exosomes have been reported to play a crucial role in tissue fibrosis by transferring their molecular contents. This study aimed to explore the effects of human umbilical cord-derived mesenchymal stem cell exosomes (hucMSC-Exo) on subretinal fibrosis in vivo and in vitro and to investigate the anti-fibrotic mechanism of action of hucMSC-Exo. Methods In this study, human umbilical cord-derived mesenchymal stem cells (hucMSCs) were successfully cultured and identified, and exosomes were isolated from the supernatant by ultracentrifugation. A laser-induced choroidal neovascularization (CNV) and subretinal fibrosis model indicated that the intravitreal administration of hucMSC-Exo effectively alleviated subretinal fibrosis in vivo. Furthermore, hucMSC-Exo could efficaciously suppress the migration of retinal pigmented epithelial (RPE) cells and promote the mesenchymal–epithelial transition by delivering miR-27b-3p. The latent binding of miR-27b-3p to homeobox protein Hox-C6 (HOXC6) was analyzed by bioinformatics prediction and luciferase reporter assays. Results This study showed that the intravitreal injection of hucMSC-Exo effectively ameliorated laser-induced CNV and subretinal fibrosis via the suppression of epithelial–mesenchymal transition (EMT) process. In addition, hucMSC-Exo containing miR-27b repressed the EMT process in RPE cells induced by transforming growth factor-beta2 (TGF-β2) via inhibiting HOXC6 expression. Conclusions The present study showed that HucMSC-derived exosomal miR-27b could reverse the process of EMT induced by TGF-β2 via inhibiting HOXC6, indicating that the exosomal miR-27b/HOXC6 axis might play a vital role in ameliorating subretinal fibrosis. The present study proposed a promising therapeutic agent for treating ocular fibrotic diseases and provided insights into the mechanism of action of hucMSC-Exo on subretinal fibrosis.

scholarly journals Effect of ethanol and cocaine on [11C]MPC-6827 uptake in SH-SY5Y cells

2021 ◽  
Author(s):  
Naresh Damuka ◽  
Miranda Orr ◽  
Paul W. Czoty ◽  
Jeffrey L. Weiner ◽  
Thomas J. Martin ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Ex Vivo ◽  
Neuroblastoma Cells ◽  
Proper Function ◽  
Brain Functions ◽  
Biodistribution Studies ◽  
Positron Emission ◽  
Vitro Binding

AbstractMicrotubules (MTs) are structural units in the cytoskeleton. In brain cells they are responsible for axonal transport, information processing, and signaling mechanisms. Proper function of these processes is critical for healthy brain functions. Alcohol and substance use disorders (AUD/SUDs) affects the function and organization of MTs in the brain, making them a potential neuroimaging marker to study the resulting impairment of overall neurobehavioral and cognitive processes. Our lab reported the first brain-penetrant MT-tracking Positron Emission Tomography (PET) ligand [11C]MPC-6827 and demonstrated its in vivo utility in rodents and non-human primates. To further explore the in vivo imaging potential of [11C]MPC-6827, we need to investigate its mechanism of action. Here, we report preliminary in vitro binding results in SH-SY5Y neuroblastoma cells exposed to ethanol (EtOH) or cocaine in combination with multiple agents that alter MT stability. EtOH and cocaine treatments increased MT stability and decreased free tubulin monomers. Our initial cell-binding assay demonstrated that [11C]MPC-6827 may have high affinity to free/unbound tubulin units. Consistent with this mechanism of action, we observed lower [11C]MPC-6827 uptake in SH-SY5Y cells after EtOH and cocaine treatments (e.g., fewer free tubulin units). We are currently performing in vivo PET imaging and ex vivo biodistribution studies in rodent and nonhuman primate models of AUD and SUDs and Alzheimer's disease.

An insight into the determination of size and number concentration of silver nanoparticles in blood using single particle ICP-MS (spICP-MS): Feasibility of application to samples relevant to in vivo toxicology studies

2021 ◽  
Author(s):  
Isabel Abad-Álvaro ◽  
Diego Leite ◽  
Dorota Bartczak ◽  
Susana Cuello ◽  
Beatriz Gomez-Gomez ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Single Particle ◽  
Number Concentration ◽  
Biological Matrices ◽  
Icp Ms ◽  
Toxicological Studies ◽  
Insight Into

Toxicological studies concerning nanomaterials in complex biological matrices usually require a carefully designed workflow that involves handling, transportation and preparation of a large number of samples without affecting the nanoparticle...

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