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Clinical Pharmacokinetics Apr 2022Tedizolid is an oxazolidinone antibiotic with high potency against Gram-positive bacteria and currently prescribed in bacterial skin and skin-structure infections. The... (Review)
Review
Tedizolid is an oxazolidinone antibiotic with high potency against Gram-positive bacteria and currently prescribed in bacterial skin and skin-structure infections. The aim of the review was to summarize and critically review the key pharmacokinetic and pharmacodynamic aspects of tedizolid. Tedizolid displays linear pharmacokinetics with good tissue penetration. In in vitro susceptibility studies, tedizolid exhibits activity against the majority of Gram-positive bacteria (minimal inhibitory concentration [MIC] of ≤ 0.5 mg/L), is four-fold more potent than linezolid, and has the potential to treat pathogens being less susceptible to linezolid. Area under the unbound concentration-time curve (fAUC) related to MIC (fAUC/MIC) was best correlated with efficacy. In neutropenic mice, fAUC/MIC of ~ 50 and ~ 20 induced bacteriostasis in thigh and pulmonary infection models, respectively, at 24 h. The presence of granulocytes augmented its antibacterial effect. Hence, tedizolid is currently not recommended for immunocompromised patients. Clinical investigations with daily doses of 200 mg for 6 days showed non-inferiority to twice-daily dosing of linezolid 600 mg for 10 days in patients with acute bacterial skin and skin-structure infections. In addition to its use in skin and skin-structure infections, the high pulmonary penetration makes it an attractive option for respiratory infections including Mycobacterium tuberculosis. Resistance against tedizolid is rare yet effective antimicrobial surveillance and defining pharmacokinetic/pharmacodynamic targets for resistance suppression are needed to guide dosing strategies to suppress resistance development.
Topics: Animals; Anti-Bacterial Agents; Humans; Mice; Microbial Sensitivity Tests; Organophosphates; Oxazoles; Oxazolidinones; Tetrazoles
PubMed: 35128625
DOI: 10.1007/s40262-021-01099-7 -
Current Medicinal Chemistry 2017Human exposure to insecticides raises serious public health concerns worldwide. Insecticides constitute a wide-ranging heterogeneous group of chemicals, most of which... (Review)
Review
BACKGROUND
Human exposure to insecticides raises serious public health concerns worldwide. Insecticides constitute a wide-ranging heterogeneous group of chemicals, most of which target the nervous system and disrupt neurometabolism and/or neurotransmission. Although the acute effects of insecticide poisoning in humans are well documented, the chronic and long-term effects remain difficult to investigate.
OBJECTIVES AND METHOD
We sought to review the present state-of-knowledge of acute, chronic, neurodevelopmental and neurological consequences of human exposure to insecticides.
RESULTS
Animal and epidemiologic studies indicate cognitive, behavioral and psychomotor alterations in mammals chronically exposed to insecticides. Parkinson's and Alzheimer's diseases, amyotrophic lateral sclerosis, and depression, have been regularly associated with insecticide exposure. Clinical studies, supported by experiments on animal models, demonstrate the neurotoxic impact of insecticide exposure during the period of cerebral development, the developing brain being particularly vulnerable to the action of insecticides. Moreover, detoxifying systems that are highly polymorph lead to great inter-individual variability in susceptibility to the neurotoxic effects of insecticides.
CONCLUSION
Studies on mild chronic exposure to insecticides suggest significant involvement in the pathogenesis of multifactorial neurological diseases. However, the tardive appearance of neurodegenerative disorders and the large variability of inter-individual susceptibility to neurotoxicants make it difficult to assess the relative contribution of insecticide exposure. Close vigilance should therefore be exercised with regard to possible exposure to insecticides, particularly during the period of cerebral development.
Topics: Animals; Genetic Predisposition to Disease; Humans; Insecticides; Nervous System; Neurodegenerative Diseases; Neurons; Organophosphates
PubMed: 28552054
DOI: 10.2174/0929867324666170526122654 -
ChemMedChem Jun 2020Phosphoantigens (pAgs) are small phosphorus-containing molecules that stimulate Vγ9Vδ2 T cells with sub-nanomolar cellular potency. Recent work has revealed that these... (Review)
Review
Phosphoantigens (pAgs) are small phosphorus-containing molecules that stimulate Vγ9Vδ2 T cells with sub-nanomolar cellular potency. Recent work has revealed that these compounds work through binding to the transmembrane immunoglobulin butyrophilin 3A1 (BTN3A1) within its intracellular B30.2 domain. Engagement of BTN3A1 is critical to the formation of an immune synapse between cells that contain pAgs and the Vγ9Vδ2 T cells. This minireview summarizes the structure-activity relationships of pAgs and their implications to the mechanisms of butyrophilin 3 activation leading to Vγ9Vδ2 T cell response.
Topics: Antigens, CD; Binding Sites; Butyrophilins; Humans; Intraepithelial Lymphocytes; Ligands; Molecular Structure; Organophosphates; Protein Binding; Protein Domains; Structure-Activity Relationship
PubMed: 32453919
DOI: 10.1002/cmdc.202000198 -
Molecules (Basel, Switzerland) Feb 2020Biomimetic molecular design is a promising approach for generating functional biomaterials such as cell membrane mimetic blood-compatible surfaces, mussel-inspired... (Review)
Review
Biomimetic molecular design is a promising approach for generating functional biomaterials such as cell membrane mimetic blood-compatible surfaces, mussel-inspired bioadhesives, and calcium phosphate cements for bone regeneration. Polyphosphoesters (PPEs) are candidate biomimetic polymer biomaterials that are of interest due to their biocompatibility, biodegradability, and structural similarity to nucleic acids. While studies on the synthesis of PPEs began in the 1970s, the scope of their use as biomaterials has increased in the last 20 years. One advantageous property of PPEs is their molecular diversity due to the presence of multivalent phosphorus in their backbones, which allows their physicochemical and biointerfacial properties to be easily controlled to produce the desired molecular platforms for functional biomaterials. Polyphosphodiesters (PPDEs) are analogs of PPEs that have recently attracted interest due to their strong affinity for biominerals. This review describes the fundamental properties of PPDEs and recent research in the field of macromolecular bone therapeutics.
Topics: Animals; Biocompatible Materials; Biomimetic Materials; Bone Regeneration; Calcification, Physiologic; Cell Differentiation; Esters; Humans; Materials Testing; Nanoparticles; Organophosphates; Osteoblasts
PubMed: 32050545
DOI: 10.3390/molecules25030758 -
Dental Materials Journal Mar 2017This study aimed to evaluate the bond strength of a resin cement to yttria-stabilized tetragonal zirconia polycrystals (Y-TZPs) treated with three different phosphate...
This study aimed to evaluate the bond strength of a resin cement to yttria-stabilized tetragonal zirconia polycrystals (Y-TZPs) treated with three different phosphate functional monomers containing primers by measuring the water contact angle. Seventy Y-TZP discs were divided into seven experimental groups (n=10), including an untreated (control) group. Specimens were treated with one of the following monomers: MDP (MD), GPDM (GP), and Phenyl-P (PP). After primer application and air drying, half the treated specimens were ultrasonically cleaned in ethanol for 2 min (MD-e, GP-e, and PP-e), and contact angles were measured. The tensile bond strength test was performed after storage for 24 h in 37°C water. The contact angle on the MD-e surface (64°) was significantly higher than that on the Con, GP-e, and PP-e surfaces (51°-52°). The application of the MDP-containing primer resulted in significantly higher bond strength between Y-TZP ceramics and a resin cement.
Topics: Dental Bonding; Dental Stress Analysis; Materials Testing; Organophosphates; Resin Cements; Shear Strength; Surface Properties; Yttrium; Zirconium
PubMed: 28111385
DOI: 10.4012/dmj.2016-060 -
Journal of Dental Research Oct 2006Among functional monomers used in contemporary dental adhesives, 10-methacryloyloxydecyl dihydrogen phosphate (MDP) has been found to interact chemically with...
Among functional monomers used in contemporary dental adhesives, 10-methacryloyloxydecyl dihydrogen phosphate (MDP) has been found to interact chemically with hydroxyapatite (HAp) most intensively and stably. This effect was thought to be the basis of the superior bonding effectiveness of MDP-based self-etch adhesives to enamel/dentin. To elucidate fully the chemical interaction and reactivity of MDP with HAp, we used (31)P CP-MAS NMR spectroscopy and powder x-ray diffraction. In an aqueous ethanol solution, Ca ions were leached from HAp to form, at short term, a MDP-calcium salt (CaMHP(2)) layered structure on the HAp surface. When MDP was allowed to interact for longer time (< 24 hrs), CaHPO(4).2H(2)O precipitated on top of this MDP-calcium salt layered structure. In conclusion, the intense chemical interaction of MDP with HAp must be ascribed to superficial dissolution of HAp induced by the MDP adsorption and subsequent deposition of MDP-calcium salt with a solubility lower than that of CaHPO(4).2H(2)O.
Topics: Adsorption; Calcium; Dentin-Bonding Agents; Durapatite; Magnetic Resonance Spectroscopy; Methacrylates; Organophosphates; Resin Cements; Solubility; Tooth Demineralization; X-Ray Diffraction
PubMed: 16998137
DOI: 10.1177/154405910608501014 -
Chemical Reviews Jun 2020The formation of organophosphate molecules by prebiotic processes relies on nonenzymatic synthesis. Given the centrality of phosphorylated biomolecules in metabolic,... (Review)
Review
The formation of organophosphate molecules by prebiotic processes relies on nonenzymatic synthesis. Given the centrality of phosphorylated biomolecules in metabolic, structural, and replicative processes, it is highly likely that such nonenzymatic synthesis had to occur early in Earth's history. This Review collects and uses thermodynamic data to constrain processes that may have produced organophosphates and evaluates both the plausibility of reactants and the likelihood that environments conducive to phosphorylation were present. The energy required to phosphorylate organics is ∼15 kJ/mol, requiring either very low water activities or reactive inorganic phosphorus compounds. Thermodynamics permits evaluating phosphorylation environments for both plausibility and novelty and shows that several routes would have been available to form these potentially key reagents. Building from phosphate monoesters to diesters may have enabled the synthesis of nucleic acids, perhaps opening a way into the RNA world.
Topics: Evolution, Chemical; Nucleic Acids; Organophosphates; Phosphorylation; Thermodynamics
PubMed: 31736304
DOI: 10.1021/acs.chemrev.9b00492 -
Organic & Biomolecular Chemistry Jan 2020Through the combined action of palladium catalysts and chiral phosphoric acids (CPAs) a variety of catalytic asymmetric reactions have been realized during the past... (Review)
Review
Through the combined action of palladium catalysts and chiral phosphoric acids (CPAs) a variety of catalytic asymmetric reactions have been realized during the past decade, including allylation, alkene functionalization, and C-H activation. This review surveys key examples across these various reaction types and examines the different mechanisms by which CPAs can affect stereoinduction in these reaction systems.
Topics: Catalysis; Organic Chemicals; Organophosphates; Palladium; Stereoisomerism
PubMed: 31907504
DOI: 10.1039/c9ob02205h -
Clinical Infectious Diseases : An... Jan 2014
Review
Topics: Anti-Bacterial Agents; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Organophosphates; Oxazoles; Oxazolidinones
PubMed: 24343826
DOI: 10.1093/cid/cit658 -
Frontiers in Endocrinology 2024Organophosphate esters (OPEs) may interfere with thyroid function, but the relationship between OPEs and thyroid disease remains unclear. This study aims to elucidate...
Association between urinary organophosphate ester metabolite exposure and thyroid disease risk among US adults: National Health and Nutrition Examination Survey 2011-2014.
BACKGROUND
Organophosphate esters (OPEs) may interfere with thyroid function, but the relationship between OPEs and thyroid disease remains unclear. This study aims to elucidate the relationship between OPEs exposure and thyroid disease risk in the general population in the United States.
METHOD
Data were obtained from the 2011-2014 National Health and Nutrition Examination Survey cycle. All participants were tested for seven OPE metabolites in their urine and answered questions about whether they had thyroid disease through questionnaires. Logistic regression was employed to analyze the association between exposure to individual OPE metabolites and thyroid disease. Weighted Quantile Sum (WQS) regression modeling was utilized to assess exposure to mixed OPE metabolites and risk of thyroid disease. Bayesian kernel machine regression(BKMR) models to analyze the overall mixed effect of OPE metabolites.
RESULT
A total of 2,449 participants were included in the study, 228 of whom had a history of thyroid disease. Bis(1,3-dichloro-2-propyl) phos (BDCPP), Diphenyl phosphate (DPHP) and Bis(2-chloroethyl) phosphate (BCEP) were the top three metabolites with the highest detection rates of 91.75%, 90.77% and 86.57%, respectively. In multivariate logistic regression models, after adjustment for confounding variables, individuals with the highest tertile level of BCEP were significantly and positively associated with increased risk of thyroid disease (OR=1.57, 95% CI=1.04-2.36), using the lowest tertile level as reference. In the positive WQS regression model, after correcting for confounding variables, mixed exposure to OPE metabolites was significantly positively associated with increased risk of thyroid disease (OR=1.03, 95% CI=1.01-1.06), with BCEP and DPHP having high weights. In the BKMR model, the overall effect of mixed exposure to OPE metabolites was not statistically significant, but univariate exposure response trends showed that the risk of thyroid disease decreased and then increased as BCEP exposure levels increased.
CONCLUSION
The study revealed a significant association between exposure to OPE metabolites and an increased risk of thyroid disease, with BCEP emerging as the primary contributor. The risk of thyroid disease exhibits a J-shaped pattern, whereby the risk initially decreases and subsequently increases with rising levels of BCEP exposure. Additional studies are required to validate the association between OPEs and thyroid diseases.
Topics: Adult; Humans; United States; Nutrition Surveys; Bayes Theorem; Flame Retardants; Organophosphates; Thyroid Diseases; Phosphates; Esters
PubMed: 38405137
DOI: 10.3389/fendo.2024.1329247