In vitro cysteine reactivates organophosphate insecticide dichlorvos-inhibited human cholinesterases

Objectives: Organophosphate [OP] pesticides inhibit both red blood cell [RBC] and plasma cholinesterases [ChEs]. Oximes, especially pralidoxime [2-PAM], are widely used as antidotes to treat OP poisoning. In addition, N-acetylcysteine [NAC] is sometimes used as an adjuvant antidote. The current study aimed to assess the feasibility of using NAC as a single therapeutic agent for OP poisoning in comparison to in vitro 2-PAM

Methods: This study was carried out at the Razi Drug Research Center of Iran University of Medical Sciences, Tehran, Iran, between April and September 2014. A total of 22 healthy human subjects were recruited and 8 mL citrated blood samples were drawn from each subject. Dichlorvos-inhibited blood samples were separately exposed to low and high doses [final concentrations of 300 and 600 micro mol.L[-1], respectively] of 2-PAM, NAC and cysteine. Plasma and RBCs were then separated by centrifugation and their ChE activity was measured using spectrophotometry

Results: Although cysteine-and not NAC-increased the ChE activity of both plasma and RBCs over those of dichlorvos, it did not increase them over those of a high dose of 2-PAM

Conclusion: These results suggest that the direct reactions of 2-PAM and cysteine with dichlorvos and the reactivation of phosphorylated ChEs occurr via an associative stepwise addition-elimination process. High therapeutic blood concentrations of cysteine are needed for the elevation of ChE activity in plasma and RBCs; however, both this agent and NAC may still be effective in the reactivation of plasma and RBC ChEs

Functional treatment comparing with immobilization after acute ankle sprain

Ankle injuries are among the most prevalent injuries with which a physician may encounter. In this study, the efficiency of the functional treatment was compared with the immobilization treatment in healing the acute ankle sprain. This clinical trial study was carried out on 100 male patients whose ankle sprain had been diagnosed by Yasuj Shahid Beheshti Hospital. Using block allocation randomization method and regardless of damage degree, patients were divided into two groups, functional method [1st group] or immobilization with plaster [2nd group], for treatment. Several variables such as range of motion, pain intensity, inflammation, joint tenderness and returning to work after 2, 6 and 12 weeks were examined. After two weeks, the average pain intensity in the first group [33.2 +/- 3.2] has been decreased compared to the second group [55 +/- 1.2], which showed a significant difference between the two groups [p<0.05]. The average ankle range of motion in the first and second groups was 29.08 +/- 1.2 degrees and 20.4 +/- 2.2 degrees, respectively which had been increased significantly in the first group compared to the second group [p<0.03]. Similarly, a considerable difference was observed in decreased inflammation and tenderness in the first group compared to the second one. In acute ankle sprains, the functional treatment is better than the immobilization treatment in alleviating pain, inflammation and improving the range of joint motion

Human coagulated plasma as a natural and low cost matrix for in vitro angiogenesis

Angiogenesis, the development of new blood vessels, is an important process in tissue development and wound healing, but becomes pathologic when associated with solid tumor growth, proliferative retinopathies, and rheumatoid arthritis. Accurate and reliable qualification of neovascular [angiogenic] response, both in vitro and in vivo, is an essential requirement for the study of new blood vessel growth. The complexity of currently used three-dimensional in vitro angiogenesis systems makes it difficult to approve material in its models. Capillary-like structure occurs on basement membrane components such as collagen and/or laminin, while in other models, CLS formation occurs on transitional matrices such as fibrin. To solve this problem, we were interested in developing an angiogenesis system which allows rapid and reliable quantification of three-dimensional neovessel formation in vitro. Human bone marrow endothelial cells were seeded on gelatin-coated microcarriers and suspended in a solution of platelet-poor plasma which was induced to polymerize by addition of calcium chloride. In this way, microcarriers were entrapped in three-dimensional coagulated plasma. Within a few hours, endothelial cells begin to leave these supporting microcarries and migrate into the coagulated-plasma matrix and formed CLS within 48-72 hours. We developed a convenient angiogenesis in vitro system which allows reliable quantification of capillary formation in a three-dimensional environment