Correlation between Cholinesterase and Paraoxonase 1 Activities:Case Series of Pesticide Poisoning Subjects.

INTRODUCTION: Acute exposure to pesticide due to suicidal poisoning is the most extensive cause of pesticide exposure, compared with all other causes including agricultural or industrial exposure. Organophosphate (OP) and carbamate group of pesticides can inhibit acetylcholinesterase; on the other hand, paraoxonase1 can detoxify organophosphate poisoning by hydrolyzing organophosphate metabolites. METHODS: We have compared the serum paraoxonase1 status and cholinesterase activity of subjects who attempted to commit suicide by consuming OP pesticide. Cholinesterase and paraoxonase1 activity were measured spectrophotometrically using butyrylthiocholine and phenyl acetate as substrates, respectively. RESULTS: A positive correlation was found between serum paraoxonase1 activity and cholinesterase activity among pesticide consumed subjects. CONCLUSION: Our results suggest that subjects with higher paraoxonase1 activity may have a better chance of detoxifying the lethal effect of acute organophosphate poisoning.

Effect of sequential hole enlargement on cortical bone temperature during drilling of 6.2-mm-diameter transcortical holes in the third metacarpal bones of horse cadavers.

OBJECTIVE: To compare the bone temperature and final hole dimensions associated with sequential overdrilling (SO) and single 6.2-mm drill bit (S6.2DB) methods used to create transcortical holes in the third metacarpal bones (MCIIIs) of horse cadavers. SAMPLE: 60 MCIIIs from 30 horse cadavers. PROCEDURES: In phase 1, hole diameter, tap insertion torque, peak bone temperature, and postdrilling bit temperature for 6.2-mm-diameter holes drilled in the lateral or medial cortical region of 12 MCIIIs via each of three 2-bit SO methods with a single pilot hole (diameter, 3.2, 4.5, or 5.5 mm) and the S6.2DB method were compared. In phase 2, 6.2-mm-diameter transcortical holes were drilled via a 2-bit SO method (selected from phase 1), a 4-bit SO method, or a S6.2DB method at 1 of 3 locations in 48 MCIIIs; peak bone temperature during drilling, drill bit temperature immediately following drilling, and total drilling time were recorded for comparison. RESULTS: Hole diameter or tap insertion torque did not differ among phase 1 groups. Mean ± SD maximum bone temperature increases at the cis and trans cortices were significantly less for the 4-bit SO method (3.64 ± 2.01°C and 8.58 ± 3.82°C, respectively), compared with the S6.2DB method (12.00 ± 7.07°C and 13.19 ± 7.41°C, respectively). Mean drilling time was significantly longer (142.9 ± 37.8 seconds) for the 4-bit SO method, compared with the S6.2DB method (49.7 ± 24.3 seconds). CONCLUSIONS AND CLINICAL RELEVANCE: Compared with a S6.2DB method, use of a 4-bit SO method to drill transcortical holes in cadaveric equine MCIIIs resulted in smaller bone temperature increases without affecting hole accuracy.

Homology modeling of human serum paraoxonase1 and its molecular interaction studies with aspirin and cefazolin.

Human serum paraoxonase1 (HuPON1) belongs to the family of A-esterases (EC.3.1.8.1). It is associated with HDL particle and prevents atherosclerosis by cleaving lipid hydroperoxides and other proatherogenic molecules of oxidized low density lipoproteins (LDL). Since the precise structure of HuPON1 is not yet available, the structure-function relationship between HuPON1 and activators/inhibitors is still unknown. Therefore, a theoretical model of HuPON1 was generated using homology modelling and precise molecular interactions of an activator aspirin and an inhibitor cefazolin with PON1 were studied using Autodock software. The ligand binding residues were found to be similar to the predicted active site residues. Both cefazolin and aspirin were found to dock in the vicinity of the predicted active sites of PON1; cefazolin bound at residues N166, S193 and Y71, while aspirin at residues N309, I310 and L311. Binding region in the PON1 by prediction (3D2GO server) and docking studies provide useful insight into mechanism of substrate and inhibitor binding to the enzyme active site.