Inhibition of AChE by malathion and some structurally similar compounds

Inhibition of bovine erythrocyte acetylcholinesterase (free and immobilized on controlled pore glass) by separate and simultaneous exposure to malathion and malathion transformation products which are generally formed during storage or through natural or photochemical degradation was investigated. Increasing concentrations of malathion, its oxidation product malaoxon, and its isomerisation product isomalathion inhibited free and immobilized AChE in a concentration-dependent manner. K-I, the dissociation constant for the initial reversible enzyme inhibitor-complex, and k(3), the first order rate constant for the conversion of the reversible complex into the irreversibly inhibited enzyme, were determined from the progressive development of inhibition produced by reaction of native AChE with malathion, malaoxon and isomalathion. KI values of 1.3 x 10(-4) M-1, 5.6 x 10(-6) M-1 and 7.2 x 10(-6) M-1 were obtained for malathion, malaoxon and isomalathion, respectively. The IC50 values for free/immobilized AChE, (3.7 +/- 0.2)10(-4) M/(1.6 +/- 0.1)10(-4), (2.4 +/- 0.3)10(-6)/(3.4 +/- 0.1)10(-6) M and (3.2 +/- 0.3)10(-6) M/(2.7 +/- 0.2)10(-6) M, were obtained from the inhibition curves induced by malathion, malaoxon and isomalathion, respectively. However, the products formed due to photoinduced degradation, phosphorodithioic O,O,S-trimethyl ester and O,O-dimethyl thiophosphate, did not noticeably affect enzymatic activity, while diethyl maleate inhibited AChE activity at concentrations GT 10 mM. Inhibition of acetylcholinesterase increased with the time of exposure to malathion and its inhibiting by-products within the interval from 0 to 5 minutes. Through simultaneous exposure of the enzyme to malaoxon and isomalathion, an additive effect was achieved for lower concentrations of the inhibitors (in the presence of malaoxon/isomalathion at concentrations 2 x 10(-7) M/2 x 10(-7) M, 2 x 10(-7) M/3 x 10(-7) M and 2 x 10(-7) M/4.5 x 10(-7)M), while an antagonistic effect was obtained for all higher concentrations of inhibitors. The presence of a non-inhibitory degradation product (phosphorodithioic O,O,S-trimethyl ester) did not affect the inhibition efficiencies of the malathion by-products, malaoxon and isomalathion

Characteristics of prosthetic joint infections due to Enterococcus sp. and predictors of failure: a multi-national study

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Photocatalytic TiO2 Coatings: Effect of Substrate and Template

Transparent TiO2 films with a high photodegradation activity towards an azo dye in aqueous solution were prepared by sol\u2013gel processing. Films on soda\u2013lime glass supports protected with a thin silica barrier layer exhibited better crystallization and monodisperse nanoparticles, higher absorption of light below 370\u2009nm, and higher photocatalytic activity than those films deposited on bare glass supports proving the detrimental effect of interdiffused sodium ions on the development of the anatase nanostructure. The effect of substrate was more pronounced in thinner films (300\u2009nm) than in thicker ones (1200\u2009nm), which were achieved by adding a template (i.e. Pluronic F127) to the sol

The influence of malathion and its decomposition products on free and immobilized acetylcholinesterase

The influence of malathion and its four main degradation products found in irradiated solutions (malaoxon, isomalathion, diethyl maleate and O,O-dimethyl phosphate) on acetylcholinesterase (AChE) of free and immobilized bovine erythrocytes was investigated. The concentration-dependent responses to malathion and related organophosphates, malaoxon and isomalathion, of both AChE bioassays used were obtained. The IC (50) values for free and immobilized AChE (3.7 +/- 0.2) x 10(-4) M/(1.6 +/- 0.1) x 10(-4), (2.4 +/- 0.3) x 10(-6)/(3.4 +/- 0.1) x 10(-6) M, and (3.2 +/- 0.3) x 10(-6) M/(2.7 +/- 0.2) x 10(-6) M were obtained in the presence of malathion, malaoxon and isomalathion, respectively. However, diethyl maleate inhibited AChE activity at concentrations GT = 10 mM, while O,O-dimethyl phosphate did not noticeably affect enzyme activity at all investigated concentrations. The relation between the structure of the compounds and their ability to inhibit enzyme activity was discussed

Toxic effects of diazinon and its photodegradation products

The toxic effects of diazinon and its irradiated Solutions were investigated using cultivated human blood cells (lymphocytes and erythrocytes) and skin fibroblasts. Ultra Performance Liquid Chromatography (UPLC)-UV/VIS system was used to monitor the disappearance of starting diazinon during 115-min photodegradation and formation of its by-products (diazoxon and 2-isopropyl-6-methyl-4-pyrimidinol (IMP)) as a function of time Dose-dependent AChE and Na+/K+-ATPase inhibition by diazinon was obtained for all investigated cells Calculated IC50 (72 h) values, in M, were 7 5 x 10(-6)/3 4 x 10(-5), 8.7 x 10(-5)/6.6 x 10(-5), and 3 0 x 10(-5)/4 6 x 10(-5) for fibroblast, erythrocyte and lymphocyte AChE/Na+/K+-ATPase, respectively. Results obtained for reference commercially purified target enzymes indicate similar sensitivity of AChE towards diazinon (IC50 (20 min)-7.8 x 10(-5) M). while diazinon concentrations below 10 mM did not noticeably affect Na+/K+-ATPase activity Besides, diazinon and IMP induced increasing incidence of micronuclei (via clastogenic mode of action) in a dose-dependent manner up to 2 x 10(-6) M and significant inhibition of cell proliferation and increased level of malondialdehyde at all investigated concentrations Although after 15-min diazinon irradiation formed products do not affect purified commercial enzymes activities, inhibitory effect of irradiated solutions on cell enzymes increased as a function of time exposure to UV light and resulted in significant reduction of AChE (LIP to 28-45%) and Na+/K+-ATPase (up to 35-40%) at the end of irradiation period Moreover, photodegradation treatment strengthened prooxidative properties of diazinon as well as its potency to induce cytogenetic damage (C) 2009 Elsevier Ireland Ltd All rights reserved

Characteristics and outcome of 27 elbow periprosthetic joint infection: Results from a 14-year cohort study of 358 elbow prostheses

Abstract Background: Elbow arthroplasty is increasingly performed in patients with rheumatic and posttraumatic arthritis. Data on elbow periprosthetic joint infection (PJI) is limited. We investigated characteristics and outcome of elbow PJI in a 14-year cohort of total elbow arthroplasties in a single center. Methods: Elbow prosthesis, which were implanted between 1994 and 2007 at Schulthess Clinic in Zurich, were retrospectively screened for infection. PJI was defined as periprosthetic purulence, presence of sinus tract or microbial growth. A Kaplan-Meier survival method and Cox proportional hazard analysis was performed. Results: Of 358 elbow prostheses, PJI was identified in 27 (7.5%). The median patient age was 61 (39-82) years, 63% were females. 17 patients (63%) had a rheumatic disorder and 10 (37%) osteoarthritis. Debridement and implant retention was performed in 78%, followed by exchange or removal of the prosthesis (15%) or no surgery (7%).The relapse-free survival (95% confidence interval) was 79% (63% - 95%) after 1 year and 65% (45% - 85%) after 2 years. The outcome after 2 years was significantly better when treated according to the algorithm than in patients which were not (100% versus 33%, p <0.05).In 21 patients treated with debridement and retention, the cure rate was also higher when the algorithm was followed (100% versus 11%, p <0.05). Conclusions: This study suggests that the treatment algorithm developed for hip and knee PJI can be applied to elbow PJI. With proper patient selection and antimicrobial therapy, debridement and retention of the elbow prosthesis is associated with good treatment outcome