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191.
192.
The increased concern about terrorist use of nerve agents prompted us to search for new more effective oximes against tabun and soman poisoning. We investigated the interactions of five bispyridinium oximes: K027 [1-(4-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium) propane dibromide], K048 [1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium) butane dibromide], K033 [1,4-bis(2-hydroxyiminomethylpyridinium) butane dibromide], TMB-4 [1,3-bis(4-hydroxyiminomethylpyridinium) propane dibromide] and HI-6 [(1-(2-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium)-2-oxapropane dichloride)] with human erythrocyte acetylcholinesterase (AChE; E.C. 3.1.1.7) and their effects on tabun- and soman-poisoned mice. All the oximes reversibly inhibited AChE, and the enzyme-oxime dissociation constants were between 17 and 180 microM. Tabun-inhibited AChE was completely reactivated by TMB-4, K027 and K048, with the overall reactivation rate constants of 306, 376 and 673 min(-1)M(-1), respectively. The reactivation of tabun-inhibited AChE by K033 reached 50% after 24h, while HI-6 failed to reactivate any AChE at all. Soman-inhibited AChE was resistant to reactivation by 1mM oximes. All studied oximes protected AChE from phosphorylation with both soman and tabun. In vivo experiments showed that the studied oximes were relatively toxic to mice; K033 was the most toxic (LD50=33.4 mg/kg), while K027 was the least toxic (LD50=672.8 mg/kg). The best antidotal efficacy was obtained with K048, K027 and TMB-4 for tabun poisoning, and HI-6 for soman poisoning. Moreover, all tested oximes showed no cytotoxic effect on several cell lines in concentrations up to 0.8mM. The potency of the oximes K048 and K027 to protect mice from five-fold LD50 of tabun and their low toxicity make these compounds leading in the therapy of tabun poisoning. The combination of HI-6 and atropine is the therapy of choice for soman poisoning. 相似文献
193.
Searching for new potent acetylcholinesterase (AChE; E.C. 3.1.1.7) reactivators (oximes) is a very time-consuming process. At our department, we are able to synthesize more than 50 new AChE reactivators per year. Owing to this fact, we have to select promising reactivators using our in vitro method (potentiometric titration, pH 8 and temperature 25 degrees C; source of cholinesterases, rat brain homogenate; time of inhibition by nerve agents, 30 min; time of reactivation, 10 min) prior to in vivo experiments. For this purpose, we are using two-phase in vitro evaluation of reactivator potency. In the first phase, reactivation potency of all newly synthesized AChE reactivators is tested at two concentrations: 10(-3) M and 10(-5) M. Afterwards, all reactivators achieving reactivation potency over 15% (especially at the concentration 10(-5) M) are tested. The second phase consists of the measurement of the relationship between concentration of the oxime and its reactivation ability. In most cases, the reactivation bell-shaped curve is obtained. The most potent AChE reactivators are selected and provided for further experiments during our development process. 相似文献
194.
Pamela B. Garlick Truman R. Brown Richard H. Sullivan Kamil Ugurbil 《Journal of molecular and cellular cardiology》1983,15(12)
We report here our observations on perfused rat hearts using 31P NMR which show that inorganic phosphate (Pi) is located in two regions of differing pH. From the chemical shifts of the Pi signals and their behaviour under various stimuli we identify one signal (pH 7.0) as coming from the cytosol and suggest that the other (pH 7.38) comes from the mitochondrial matrix space. 相似文献
195.
Kuca K Jun D Cabal J Hrabinova M Bartosova L Opletalova V 《Basic & clinical pharmacology & toxicology》2006,98(4):389-394
Organophosphorus compounds such as nerve agents inhibit, practically irreversibly, cholinesterases by their phosphorylation in the active site of these enzymes. Current antidotal treatment used in the case of acute nerve agent intoxications consists of combined administration of anticholinergic drug (usually atropine) and acetylcholinesterase (AChE, EC 3.1.1.7) reactivator (HI-6, obidoxime, pralidoxime), which from a chemical view is a derivative from the group of pyridinium or bispyridinium aldoximes (commonly called "oxime"). Oximes counteract acetylcholine increase, resulting from AChE inhibition. In the human body environment these compounds are powerful nucleophiles and are able to break down the bond between AChE and nerve agent molecule. This process leads to renewal of enzyme functionality -- to its reactivation. The usefulness of oxime in the reactivation process depends on its chemical structure and on the nerve agent whereby AChE is inhibited. Due to this fact, selection of suitable reactivator in the treatment of intoxications is very important. In our work, we have compared differences in the in vitro inhibition potency of VX and Russian VX on rat, pig and human brain, and subsequently we have tested reactivation of rat brain cholinesterase inhibited by these agents using oxime HI-6, obidoxime, pralidoxime, trimedoxime and methoxime. The results showed that no major differences in the reactivation process of both VX and Russian VX-inhibited cholinesterase. The similarity in reactivation was caused by analogous chemical structure of either nerve agent; and that oxime HI-6 seems to be the most effective reactivator tested, which confirms that HI-6 is currently the most potent reactivator of AChE inhibited by nerve agents. The results obtained in our study should be considered in the future development of new AChE reactivators. 相似文献
196.
Bajgar J Bartosova L Fusek J Jun D Kuca K 《Arhiv za higijenu rada i toksikologiju》2006,57(4):391-395
Protection experiments were conducted using different doses of equine serum butyrylcholinesterase (Eq BuChE) as pretreatment in rats. Cholinesterase activities were determined in blood [whole blood, red blood cells (RBC) acetylcholinesterase (AChE), and plasma BuChE] before and after sarin inhalation exposure in untreated rats and those pretreated with Eq BuChE. Brain AChE activity was also determined in the frontal cortex, basal ganglia and pontomedullar areas following exposure. Dose-dependent increases in plasma BuChE activity and no changes in the RBC and brain AChE activities were demonstrated following i.p. injection of different amounts of Eq BuChE. Decreases in plasma BuChE activity and RBC and brain AChE activities were observed in control rats following sarin inhalation exposure. In rats pretreated with Eq BuChE this inhibition was lower than in control animals. These results demonstrate protective effects of Eq BuChE pretreatment in rats intoxicated with sublethal concentrations of sarin by inhalation. 相似文献
197.
Bekas M Pachocki KA Rózycki Z Wieprzowski K Fabiszewska E 《Roczniki Państwowego Zak?adu Higieny》2006,57(1):81-90
The aim of mammography examination is to discover as soon as possible any structural changes in a breast tissue. Every X-ray examination exposure the patient to the radiation as it takes place in mamnography images might be a cause of cancer. In this publication the dynamics growth of mammnography units number in Poland in years 1995,1997 and 2002 has been analyzed. The distribution of mammography units in Poland has been examined. The places of mammography units exploitation in regard to the type of health service institution has been determined. In this publication the manufacturers and the age of mammography units as a prerequisite to determine whether the specified mammography unit complies with the actual requirements in radiation protection regulations have been taken into consideration. The mammography laboratory equipment for providing quality control and the method of developing X-ray films has been also analyzed. It has been ascertained that about 25 % of mammography units do not comply with current technical requirements and they should be withdrawn from exploitation. However, it should be pointed out that there were only 554 mammography units in Poland at the end of year 2002. Their unequal distribution do not provide satisfactory availability to examinations for patients. As a result of this, the principal method of withdrawing them from exploitation should be replacing the time-worn the X-ray apparatuses with the new ones. 相似文献
198.
To treat bone loss that is induced by disease or wounds, bone grafts are commonly used. In dentistry, guided tissue regeneration is effective in the treatment of periodontal diseases. However, bone resorption after implantation is a major problem with the bone graft and guided tissue regeneration technique. This study examines a cell pellet culture system without exogenous scaffolds for bone regeneration. First, we examined the effect of ascorbic acid on cells. Transmission electron microscopic observation revealed that cells formed a three-dimensional structure of multiple cell layers after 5 weeks of culturing in medium containing 50 microg/ ml ascorbic acid with the medium changed every 7 days. A single cell pellet was produced by centrifuging cells that were gathered from 10 tissue culture dishes. Van Gieson staining and collagen type I immunostaining showed that the pellet contained collagen fibers and cells that adhered to the collagen fibers. Several of these cell pellets were implanted subcutaneously on the backs of nude mice for 6 weeks. Histology and immunohistochemistry results indicated new bone formation, vascular invasion, and insular areas of calcification. Bone tissue was surrounded by osteoblasts. The appearance of new bone formation is similar to that seen in intramembranous ossification. The present pellet system is reliable and might solve problems of bone resorption after implantation. 相似文献
199.
200.
Sucu HK Gökmen M Bezircioglu H Tektaş S 《Journal of neurosurgical sciences》2006,50(3):71-4; discussion 74
Contralateral acute complications such as acute epi/subdural hematomas can be encountered after evacuation of a chronic subdural hematoma, though they are rare. We found only one case of chronic subdural hematoma following the surgery for contralateral chronic subdural hematoma, have been published in English language literature. A 73-year-old male admitted to our hospital with a right-sided subdural hematoma. The subdural hematoma was evacuated through a burr-hole. A left-sided subdural higroma appeared after operation and turned into classical subdural hematoma in the course of time. After evacuation of contralateral chronic subdural hematoma, the patient recovered completely. All stages of the development of contralateral chronic subdural hematomas were shown by serial computed tomograms. It was suggested that traumatic chronic subdural hematomas develop from mostly subdural higromas. If contralateral subdural higroma is seen after surgical evacuation of a chronic subdural hematoma, the possibility of development of contralateral chronic subdural hematoma must be kept on mind. 相似文献