Inhibition of ache by malathion and some structuraly similar compounds

Inhibition of bovine serum acetylcholinesterase by in vitro exposure to malathion, malaoxon, isomalathion and diethyl maleate was investigated to elucidate the mechanism of the enzyme interaction with structurally similar organophosphorus compounds. IC50 (half maximum inhibitory concentrations) were determined by Hill analysis of experimentally obtained inhibition curves. The values (2.87 ± 0.24)x10-6 M, (2.65±0.61)x10-6M, (3.01±0.36)x10-4 M and (5.69 ±0.7)x10-2 M were obtained for malaoxon, isomalathion, malathion and their hydrolysis product diethyl maleate, respectively. The relationship between the structure of the compounds and their potency to inhibit the enzyme activity was discussed.Physical chemistry 2006 : 8th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 26-29 September 200

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

Supercritical carbon dioxide extraction of four medicinal mediterranean plants

With everyday advances in the field of pharmaceuticals, medicinal plants have high priority regarding the introduction of novel synthetic compounds by the usage of environmentally friendly extraction technologies. Herein, a supercritical CO2 extraction method was implemented in the analysis of four plants (chamomile, St. John’s wort, yarrow, and curry plant) after which the non-targeted analysis of the chemical composition, phenolic content, and antioxidant activity was evaluated. The extraction yield was the highest for the chamomile (5%), while moderate yields were obtained for the other three plants. The chemical composition analyzed by gas chromatographyhigh-resolution mass spectrometry (GC-HRMS) and liquid chromatography-high-resolution mass spectrometry (LC-HRMS) demonstrated extraction of diverse compounds including terpenes and terpenoids, fatty acids, flavonoids and coumarins, functionalized phytosterols, and polyphenols. Voltammetry of microfilm immobilized on a glassy carbon electrode using square-wave voltammetry (SWV) was applied in the analysis of extracts. It was found that antioxidant activity obtained by SWV correlates well to 1,1-diphenyl-2-picrylhidrazine (DPPH) radical assay (R2 = 0.818) and ferric reducing antioxidant power (FRAP) assay (R2 = 0.640), but not to the total phenolic content (R 2 = 0.092). Effective results were obtained in terms of activity showing the potential usage of supercritical CO2 extraction to acquire bioactive compounds of interest

Should the dilated ascending aorta be repaired at the time of bicuspid aortic valve replacement?

OBJECTIVES Bicuspid aortic valve (BAV) is the most common congenital valvular abnormality and frequently presents with accelerated calcific aortic valve disease, requiring aortic valve replacement (AVR) and thoracic aortic aneurysm and dissection. Supporting evidence for Association Guidelines of aortic dimensions for aortic resection is sparse. We sought to determine whether concurrent repair of dilated or aneurysmal aortic disease during AVR in patients with BAV substantially improves morbidity and mortality outcomes. METHODS Mortality and reoperation outcomes of 1301 adults with BAV and dilated aorta undergoing AVR-only surgery were compared to patients undergoing AVR with aortic resection (AVR-AR) using Cox proportional hazards modelling and patient matching. RESULTS Clinically important differences in patient characteristics, aortic valve function and aortic dimensions were identified between cohorts. Event rates were low, with rates of reoperation and death within 1 year of only 1.8% and 5.4%, respectively, and no aortic dissection observed during follow-up. There were no significant differences in reoperation or mortality outcomes between the AVR-only and AVR-AR cohorts. Age, aortic dimension or a combination thereof was not associated with better or worse outcomes after each AVR-AR compared with AVR. CONCLUSIONS We conclude AVR-only and AVR-AR surgery have low morbidity and mortality and have utility over a wide range of age and aortic sizes. Our results do not provide support for the 45-mm aortic dimension recommended in the current guidelines for aortic resection while performing AVR or any other specific dimension

The association between ambient exposure to organophosphates and Parkinson's disease risk

OBJECTIVES: There is a general consensus that pesticides are involved in the etiology of Parkinson’s disease (PD), although associations between specific pesticides and the risk of developing Parkinson’s disease have not been well studied. This study examines the risk of developing PD associated with specific organophosphate pesticides and their mechanisms of toxicity. METHODS: This case-control study uses a geographic information system (GIS)-based exposure assessment tool to estimate ambient exposure to 36 commonly used organophosphates (OPs) from 1974-1999. All selected OPs were analyzed individually and also in groups formed according to their presumed mechanisms of toxicity. RESULTS: The study included 357 incident PD cases and 752 population controls living in the Central Valley of California. Ambient exposure to each OP evaluated separately increased the risk of developing PD. However, most participants were exposed to combinations of OPs rather than a single pesticide. Risk estimates for OPs grouped according to different presumed functionalities and toxicities were similar and did not allow us to distinguish between them. However, we observed exposure-response patterns with exposure to an increasing number of OPs. CONCLUSIONS: This study adds strong evidence that OPs are implicated in the etiology of idiopathic PD. However, studies of OPs at low doses reflective of real-world ambient exposure are needed to determine the mechanisms of neurotoxicity