[Similar sensitivity of neurotoxic esterase from rat and chicken brain to the effect of o-alkyl-o-alkylchloroformiminophenylphosphonates].
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Biomedical subjects
Publications and source records attributed to I V Filonenko.
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Based on epizootological and epidemiological investigations in the Vologda province since 1958 till 2000, the combined territorial and temporal manifestations of natural foci of diseases was revealed. A natural focus occupies a complex of biotopes, and in different time the focus is activated in different areas, such as a river plain, marsh, meadow-field, and forest. Most commonly an activation of the natural focus appears in a border zone of three biotopes, namely, a forest, meadow-field, and river plain. A dependence of activation of various natural foci upon local climate conditions and fluctuations of micromammalian host number are considered.
The paper presents data on the diagnostic use of three-dimensional (3-D) ultrasound visualization, analyzes earlier existing and new ultrasound diagnostic technologies, and shows it expedient to apply them in ophthalmologic practice. A hundred and forty-six healthy individuals and 52 patients (60 eyes) with different diseases of the eye and orbital cavity (chorioidal melanoma, facial angiomatosis, retinal detachment, vitreoretinal changes, etc.) were examined. The results of the studies and the analysis of the data available in the literature on this problem allow the authors to state that 3-D ultrasound diagnostic technologies can detect occult masses undetectable during conventional visual and ultrasound studies and define the topography of the dislocation of structurally complicated changes in the tunics of the eyeball.
The results of 48 surgeries (refraction epikeratoplasty) for aphakia, high ametropia, and keratoconus evidence the efficacy of such operation in the afore-said conditions. Further studies are necessary to elucidate the pathogenesis of complications, improve the technique of surgery and technology of the transplant preparation in order to make it more safe and improve its functional results.
The results of experimental and clinical trials of a new type of transplantation of the cornea, stromaplasty, have shown the possibility of a blunt detachment from Descemet's membrane and removal of the deep lamellae of recipient's stroma, followed by replacement of the defect with a through allotransplant. Further studies are necessary to validate this first successful surgery and to objectively assess the prospects of such surgery.
The results of keratometry of 13 allotransplants have confirmed the rightfulness of the employed methods for calculation of the parameters of biolenses for epikeratophakia. For clinical application the initial intumescence should be taken into consideration, as well as the donor tissue thickening during its freezing for working on a lathe.
In order to validate a rodent biochemical model of delayed neurotoxicity of organophosphates (OP) inhibition of rat and hen brain neurotoxic esterase (NTE) by some dichlorovinyl phosphates and phosphonates was studied in vitro and in vivo. It was shown that compounds investigated exhibited the similar inhibitory potency to NTE from both species in vitro, in addition rat and hen NTE showed the same sensitivity to variation of the structure of OP inhibitors. A good correlation was found between pI50 estimated with enzymes from rat and hen trains: r2 = 0.951, n = 18, p < or = 0.05. NTE activities were also measured in rat and hen brains after acute administration of various dosages of potent axonopathic compound dipropyldichlorovinyl phosphate. The results obtained indicate that difference in species susceptibility to neurotoxic action of OP, in particular the absence of ataxia in rats, is not caused by difference in target enzyme sensitivity to axonopathic organophosphates.
Acetylcholinesterase (AChE) and neuropathy target esterase (neurotoxic esterase, NTE) are two major target enzymes for organophosphorus (OP) esters. The relative potency of an OP ester to react with AChE or with NTE in vitro correlates with its relative potency in vivo to cause acute toxicity (death) or organopohosphate-induced delayed neurotoxicity (OPIDN). On this basis extrapolation from in vitro to in vivo data now seems justifiable to predict risk of OPIDN. The kinetics of NTE and AChE inhibition by experimental pesticides of the general formula (RO)2P(O)ON=CClCH2Cl, where R = methyl, ethyl, isopropyl, propyl, isobutyl, butyl, pentyl, has been studied. Compounds with short R (methyl, ethyl) were shown to be far more potent inhibitors of AChE than NTE. Both anti-NTE activity, selectivity for NTE and, correspondingly, the propensity of compounds to cause OPIDN rise with increasing their hydrophobicity. A high value of ki(NTE)/ki(AChE) for R = pentyl suggests that this compound would have the potential to cause OPIDN at doses lower than the LD50. A quantitative structure-activity relationships (QSAR) analysis indicated that NTE and AChE have different structural and electronic requirements for their respective OP inhibitors.