Sket D


Full name : Sket Dusan

First name : Dusan

Mail : Institute of Pathophysiology. Medical School, Zaloska 4, 61105 Ljubljana

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Country : Slovenia

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Phone : (38) 61 310 841

Fax : (38) 61 311 540

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References (15)

Title : N-tert-butyl-alpha-phenylnitrone, a free radical scavenger with anticholinesterase activity does not improve the cognitive performance of scopolamine-challenged rats - Milivojevic_2001_Int.J.Dev.Neurosci_19_319
Author(s) : Milivojevic N , Babic K , Milatovic D , Dettbarn WD , Sket D , Zivin M
Ref : Int J Developmental Neuroscience , 19 :319 , 2001
Abstract : Reversible inhibitors of acetylcholinesterase improve spatial learning and memory in animal models of cognitive impairment. Here we investigate if the beneficial effects of free radical scavenger N-tert-butyl-alpha-phenylnitrone (PBN) on cognitive performance could be explained by its recently discovered anticholinesterase activity. Morris water maze experiment was performed to examine the effect of PBN on the impairment of spatial learning and memory induced by the antagonist of cholinergic muscarinic transmission scopolamine. In situ hybridization histochemistry experiment was performed to study its effects on the induction of immediate early gene expression (c-fos, c-jun) by dopamine D1 receptor agonist SKF-82958 and on the augmentation of the SKF-82958-induced expression of these genes by scopolamine. In both experiments, the effects of PBN were compared to the effects of reversible anticholinesterase physostigmine. We found that physostigmine but not PBN significantly reversed the cognitive impairment in scopolamine-challenged rats, prevented the induction of c-fos and c-jun mRNAs by SKF-82958 and attenuated the augmentation of the SKF-82958-induced expression of these genes by scopolamine. The present experiments did not reveal a significant in vivo anticholinesterase activity of PBN.
ESTHER : Milivojevic_2001_Int.J.Dev.Neurosci_19_319
PubMedSearch : Milivojevic_2001_Int.J.Dev.Neurosci_19_319
PubMedID: 11337201

Title : Application of the nonradioactive in situ hybridization for the localization of acetylcholinesterase mRNA in the central nervous system of the rat\; comparison to the radioactive technique - Kreft_1996_Pflugers.Arch_431_R309
Author(s) : Kreft S , Zajc-Kreft K , Zivin M , Sket D , Grubic Z
Ref : Pflugers Arch , 431 :R309 , 1996
Abstract : In this preliminary report nonradioactive digoxigenine-based and radioactive in situ hybridization procedures for the localization of acetylcholinesterase mRNA were tested and compared in rat brain. General patterns of Ache mRNA localization observed by both techniques did not differ significantly and were practically the same as reported in previous in situ studies on the mammalian brain. Shorter procedure time and avoidance of precautions necessary at work with radioactive materials are major advantages of nonradioactive technique. Under- and over- staining can be prevented by direct examination of coloring reaction. Faint staining in the control experiment with heterologous DNA suggests that proper stringency is essential for the specificity of staining.
ESTHER : Kreft_1996_Pflugers.Arch_431_R309
PubMedSearch : Kreft_1996_Pflugers.Arch_431_R309
PubMedID: 8739388

Title : Comparison between the effects of botulinum toxin-induced paralysis and denervation on molecular forms of acetylcholinesterase in muscles - Sketelj_1993_J.Neurochem_61_501
Author(s) : Sketelj J , Crne-Finderle N , Sket D , Dettbarn WD , Brzin M
Ref : Journal of Neurochemistry , 61 :501 , 1993
Abstract : Velocity sedimentation analysis of acetylcholinesterase (AChE) molecular forms in the fast extensor digitorum longus muscle and in the slow soleus muscle of the rat was carried out on days 4, 8, and 14 after induction of muscle paralysis by botulinum toxin type A (BoTx). The results were compared with those observed after muscle denervation. In addition, the ability of BoTx-paralyzed muscles to resynthesize AChE was studied after irreversible inhibition of the preexistent enzyme by diisopropyl phosphorofluoridate. Major differences were observed between the effects of BoTx treatment and nerve section on AChE in the junctional region of the muscles. A precipitous drop in content of the asymmetric A12 AChE form was observed after denervation, whereas its decrease was much slower and less extensive in the BoTx-paralyzed muscles. Recovery of junctional AChE and of its A12 form after irreversible inhibition of the preexistent AChE in BoTx-paralyzed muscles was nevertheless very slow. It seems that a greater part of the junctional A12 AChE form pertains to a fraction with a very slow turnover that is rapidly degraded after denervation but not after BoTx-produced muscle paralysis. The postdenervation decrease in content of junctional A12 AChE is therefore not primarily due to muscle inactivity. The extrajunctional molecular forms of AChE seem to be regulated mostly by muscle activity because they undergo virtually identical changes both after denervation and BoTx paralysis. The differences observed in this respect between the fast and slow muscles after their inactivation must be intrinsic to muscles.
ESTHER : Sketelj_1993_J.Neurochem_61_501
PubMedSearch : Sketelj_1993_J.Neurochem_61_501
PubMedID: 8336138

Title : Efficacy of antidotes against soman poisoning in female physostigmine-protected rats - Sket_1993_Pharmacol.Toxicol_72_25
Author(s) : Sket D
Ref : Pharmacol Toxicol , 72 :25 , 1993
Abstract : Female rats have been found much more sensitive to lethal effects of soman than male rats. Therefore it was of interest to examine the efficacy of different antidotes against soman poisoning in females which are usually not being used in soman poisoning studies. The effects of acetylcholinesterase (AChE) non-reactivating antidotes atropine and diazepam were analyzed in combination with physostigmine prophylaxis against supralethal doses of soman. Physostigmine prophylaxis was much more effective when supplemented by atropine and diazepam therapy, applied at the onset of the first signs of poisoning. The interval between the injection of a supralethal dose of soman and the appearance of signs of poisoning was shorter in physostigmine pretreated animals than in non-pretreated controls poisoned with the same supralethal dose of soman. The prophylactic effect of physostigmine (used at maximal dose) disappeared in about 120 min. The addition of HI-6, an AChE-reactivating oxime, to atropine + diazepam therapy further increased the survival in soman-poisoned and physostigmine-pretreated rats, yielding the highest protective ratio of 6.4. Pretreatment with physostigmine offered marked protection against inhibition of AChE by soman, as shown by enzyme activity determination in different brain regions and in diaphragm muscle. Application of HI-6 in addition to the combination of the above mentioned antidotes even preserved more AChE activity in the skeletal muscle but did not influence inhibition of the enzyme in brain.
ESTHER : Sket_1993_Pharmacol.Toxicol_72_25
PubMedSearch : Sket_1993_Pharmacol.Toxicol_72_25
PubMedID: 93181392

Title : Prevention of diisopropylphosphorofluoridate-induced myopathy by botulinum toxin type A blockage of quantal release of acetylcholine - Sket_1991_Acta.Neuropath_82_134
Author(s) : Sket D , Dettbarn WD , Clinton ME , Misulis KE , Sketelj J , Cucek D , Brzin M
Ref : Acta Neuropathologica , 82 :134 , 1991
Abstract : Botulinum toxin type A (BTx), which blocks quantal and partially reduces spontaneous nonquantal acetylcholine (ACh) release at neuromuscular junctions, was tested for its possible attenuating effect on diisopropylphosphorofluoridate (DFP)-induced muscle lesions. The extent of muscle lesion in extensor digitorum longus and soleus muscle of DFP injected rats with and without BTx pretreatment was evaluated using light and electron microscopic procedures. In parallel experiments, acetylcholinesterase (AChE) activity was measured and the functional state of muscles in experimental groups was determined by electrophysiological methods. The results show that pretreatment with BTx almost completely protects the muscles from DFP-induced spontaneous activity and lesions in spite of critically inhibited synaptic AChE. These results are consistent with the conclusion that the effect is not mediated by direct action of organophosphate on muscle, but by the accumulation of ACh resulting in muscle hyperactivity. Therefore, it is concluded that in conditions of acutely inhibited synaptic AChE, the quantal release of ACh is essential for lesion induction, whereas the spontaneous nonquantal ACh release, which is only partially affected in BTx-blocked nerve endings, seems not to be involved.
ESTHER : Sket_1991_Acta.Neuropath_82_134
PubMedSearch : Sket_1991_Acta.Neuropath_82_134
PubMedID: 1927269

Title : Poster: Effect of botulinum toxin type A on the appearance of organophosphate-induced lesions and AChE recovery in skeletal muscles -
Author(s) : Sket D , Cucek D , Brzin M , Dettbarn WD
Ref : In: Cholinesterases: Structure, Function, Mechanism, Genetics, and Cell Biology , (Massoulie J, Barnard EA, Chatonnet A, Bacou F, Doctor BP, Quinn DM) American Chemical Society, Washington, DC :118 , 1991

Title : Attenuation of soman-induced lesions of skeletal muscle by acetylcholinesterase reactivating and non-reactivating antidotes - Dekleva_1989_Acta.Neuropath_79_183
Author(s) : Dekleva A , Sket D , Sketelj J , Brzin M
Ref : Acta Neuropathologica , 79 :183 , 1989
Abstract : It has been reported recently that some oximes reactivating acetylcholinesterase (AChE) exhibit concomitant ganglion-blocking effects which presumably could contribute independently to their powerful antidotal action in organophosphate inhibitor (OPI) poisoning, thus mimicking some unrelated substances which are effective antidotes without reactivating AChE. This raises the question whether OPI-induced muscle lesions, like some other symptoms could also be attenuated by oximes and other antidotes in the absence of AChE reactivation. To test this possibility, the oxime HI-6 was applied at increasing time intervals after the injection of soman until and beyond the point when soman-AChE complex becomes completely "aged" and not capable of reactivation. As the examples of OPI antidotes which do not reactivate AChE, the muscarinic antagonist atropine and the ganglion-blocking agent hexamethonium were also tested on possible attenuation of muscle lesions. The proportions of fibers with lesions, AChE inhibition and muscle fasciculations in experimental groups relative to the controls treated with soman only were evaluated. The results show that HI-6 can attenuate lesions only if AChE is partially reactivated and muscle fasciculations are permanently eliminated. However, atropine does not affect either AChE inhibition or muscle fasciculations and is also ineffective in counteracting the lesions in spite of its potency as an effective general antidote. Hexamethonium also does not affect AChE inhibition, but abolishes fasciculations and effectively attenuates muscle lesions. The latter findings reveal the existence of lesion-protecting mechanisms unrelated to AChE reactivation, which if further elucidated might become potentially relevant for additional treatment in OPI poisoning.
ESTHER : Dekleva_1989_Acta.Neuropath_79_183
PubMedSearch : Dekleva_1989_Acta.Neuropath_79_183
PubMedID: 2596267

Title : Iso-OMPA-induced potentiation of soman toxicity in rat correlates with the inhibition of plasma carboxylesterases - Grubic_1988_Arch.Toxicol_62_398
Author(s) : Grubic Z , Sket D , Brzin M
Ref : Archives of Toxicology , 62 :398 , 1988
Abstract : Recently, the question was raised as to why iso-OMPA, generally known as a selective irreversible inhibitor of butyrylcholinesterase (BuChE), potentiates soman toxicity in rats but not in mice. Mice are known to have higher carboxylesterase (CarbE) and lower BuChE activity in plasma than rat. It could be hypothesized that it is the iso-OMPA inhibition of plasma CarbE, and not of BuChE, which is responsible for potentiation of soman toxicity in iso-OMPA-pretreated rats. In order to test this hypothesis two doses of iso-OMPA were administered to rats prior to soman. The two doses were selected in such a way that both were high enough to inhibit more than 90% of plasma BuChE activity; plasma CarbE activity, however, was only slightly inhibited by the lower and substantially by the higher dose of iso-OMPA. Our results demonstrate that iso-OMPA-induced potentiation of soman toxicity correlates with the inhibition of CarbE and not with the inhibition of BuChE activity in rat plasma. Relative resistance of mice to iso-OMPA-induced potentiation of soman toxicity could therefore be explained by a higher proportion of CarbE activity remaining uninhibited after iso-OMPA pretreatment. By having their active centers unoccupied, CarbE molecules can bind soman and reduce its concentration in neuronal tissue and motor end-plates.
ESTHER : Grubic_1988_Arch.Toxicol_62_398
PubMedSearch : Grubic_1988_Arch.Toxicol_62_398
PubMedID: 3242452

Title : Effect of HI-6, applied into the cerebral ventricles, on the inhibition of brain acetylcholinesterase by soman in rats - Sket_1986_Neuropharmacol_25_103
Author(s) : Sket D , Brzin M
Ref : Neuropharmacology , 25 :103 , 1986
Abstract : When applied to rats (intraperitoneally) immediately after subcutaneous injection of soman (120 micrograms/kg) HI-6 (100 mg/kg) protected about 40% of the activity of acetylcholinesterase (AChE) in the motor end plate region of the diaphragm but did not protect AChE in the brain. However, a partial protection of AChE in brain against inhibition by soman was obtained in anaesthetized, atropinized rats by the oxime injected into the cerebral ventricle 5 min before parenteral exposure to soman. The AChE activity in brain of rats pretreated with HI-6, analyzed 60 min after the injection of soman was between 10 and 19%, while that in non-protected animals did not exceed 1% of the control. The degree of protection of AChE in brain was dose-dependent. Large doses of HI-6 (greater than or equal to 100 micrograms) were tolerated by animals because of the pentobarbital anaesthesia which counteracted the lethal action of HI-6. The rate of "aging" of AChE in brain inhibited by soman was analyzed by intracerebroventricular injection of 200 micrograms of HI-6 at different time intervals after the subcutaneous injection of soman. A statistically-significant reactivation of inhibited AChE activity in brain was demonstrated when HI-6 was applied up to 20 min after soman. The protection and reactivation by HI-6 of both AChE in brain and AChE in muscle end plates in poisoning with soman appear to be quite similar.
ESTHER : Sket_1986_Neuropharmacol_25_103
PubMedSearch : Sket_1986_Neuropharmacol_25_103
PubMedID: 3951676

Title : Cholinesterases in skeletal muscle and sympathetic ganglia -
Author(s) : Brzin M , Klinar B , Sketelj J , Kiauta T , Grubic Z , Sket D
Ref : In: Cholinesterases, fundamental and applied aspects : proceedings of the Second International Meeting on Cholinesterases , (Brzin M, Barnard EA, Sket D, Eds) De Gruyter :259 , 1984

Title : Poster 72. The effect of HI-6 on soman induced muscle lesions -
Author(s) : Dekleva A , Sket D , Sketelj J , Brzin M
Ref : In: Cholinesterases, fundamental and applied aspects : proceedings of the Second International Meeting on Cholinesterases , (Brzin M, Barnard EA, Sket D, Eds) De Gruyter , 1984

Title : Poster 78. HI-6 against inhibition of AChE in the rat brain -
Author(s) : Sket D , Brzin M
Ref : In: Cholinesterases, fundamental and applied aspects : proceedings of the Second International Meeting on Cholinesterases , (Brzin M, Barnard EA, Sket D, Eds) De Gruyter , 1984

Title : Poster 79. Some aspects of AChE reactivation by HI-6 alter soman poisoning in the rat -
Author(s) : Sket D , Sketelj J , Klinar B , Brzin M
Ref : In: Cholinesterases, fundamental and applied aspects : proceedings of the Second International Meeting on Cholinesterases , (Brzin M, Barnard EA, Sket D, Eds) De Gruyter , 1984

Title : Poster 48. Does nerve cell produce and release only one transmitter? -
Author(s) : Pavlin R , Sket D
Ref : In: Cholinesterases, fundamental and applied aspects : proceedings of the Second International Meeting on Cholinesterases , (Brzin M, Barnard EA, Sket D, Eds) De Gruyter , 1984

Title : Presynaptic modulation of activity and molecular forms of acetylcholinesterase in the rat superior cervical ganglion during early postnatal development - Klinar_1983_J.Neurosci.Res_9_437
Author(s) : Klinar B , Sketelj J , Sket D , Brzin M
Ref : Journal of Neuroscience Research , 9 :437 , 1983
Abstract : Preganglionic nerve trunk of the rat superior cervical ganglion was transected shortly after birth in order to evaluate the influence of preganglionic nerves on the development of acetylcholinesterase and choline acetyltransferase in ganglionic neurons. In spite of an early decentralization, specific activity of acetylcholinesterase in the ganglion is increasing during the first 3 wk of life until it is about equal to the activity which remains in the superior cervical ganglion decentralized in an adult animal. Thus, the preganglionic nerves, which per se contribute the presynaptic fraction of total ganglionic AChE activity in normal innervated ganglia, apparently exert no significant regulatory effect on the specific activity of the fraction of acetylcholinesterase affiliated with the developing ganglionic cells. However, the absence of innervation during development is strongly reflected in the pattern of acetylcholinesterase molecular forms. The activity of the 16 S molecular form of AChE remains high in the developing superior cervical ganglion, decentralized at birth, in contrast to the substantial absolute and relative decrease of specific activity of this form during development of a normally innervated ganglion. A high proportion of 16 S AChE probably reflects a shift of decentralized immature ganglion nerve cells toward a cholinergic character. In accordance with this assumption, choline acetyltransferase activity in early decentralized ganglia is significantly higher than that in the ganglia decentralized in adult animals.
ESTHER : Klinar_1983_J.Neurosci.Res_9_437
PubMedSearch : Klinar_1983_J.Neurosci.Res_9_437
PubMedID: 6308273