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Prins Maurits Laboratorium TNO (author), Philippens, I.H.C.H.M. (author), Busker, R.W. (author), Wolthuis, O.L. (author), Olivier, B. (author), Bruijnzeel, P.L.B. (author), Melchers, B.P.C. (author)The behavioral and neurophysiological effects of the subchronically administered cholinesterase-inhibitor physostigmine (PHY) (0.025 mg/kg/h) either with or without the muscarinergic antagonist scopolamine (SCO) (0.018 mg/kg/h) were determined in guinea pigs. In contrast to a single injection of PHY, subchronic application by osmotic minipumps...article 1998
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Prins Maurits Laboratorium TNO (author), Wolthuis, O.L. (author), Groen, B. (author), Busker, R.W. (author), van Helden, H.P.M. (author)To investigate at which dose levels undesirable effects started, behavioural performance and several physiological parameters were measured in marmosets (Callithrix Jacchus) after soman (1.75 and 3.5 μg/kg), sarin (3 and 6 μg/kg), physostigmine (10 and 20 μg/kg), and pyridostigmine (200 and 400 μg/kg). Effects on performance were investigated...article 1995
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TNO Pharma (author), Melchers, B.P.C. (author), Philippens, I.H.C.H.M. (author), Wolthuis, O.L. (author)The therapeutic efficacy of the oximes HI-6 and HLo-7 (132.5 μmol/kg), in combination with atropine, in soman- or tabun-intoxicated guinea pigs was compared, particularly with respect to recovery of shuttlebox performance and electroencephalograms (EEGs). After 1.5 x LD50 soman SC, therapy with HI-6 or HLo-7 resulted in survival of 87.5% of the...article 1994
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de Lange, J. (author), van Eck, P. (author), Elliott, G.R. (author), de Kort, W.L.A.M. (author), Wolthuis, O.L. (author), Medisch Biologisch Laboratorium TNO (author)To overcome most of the disadvantages of current models to investigate percutaneous penetration of drugs or toxic substances, a model is proposed here based on the isolated pig ear, which is obtained at the slaughterhouse, and perfused with oxygenated blood from the same pig. To determine the viability of the preparations, we measured glucose...article 1992
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Philippens, I.H.C.H.M. (author), Melchers, B.P.C. (author), de Groot, D.M.G. (author), Wolthuis, O.L. (author)It is known that rats poisoned with near-lethal doses of pinacolyl methylphosphonofluoridate (soman) develop brain lesions, particularly when convulsions are induced. When rats were intoxicated with a LD50 of soman and treated immediately thereafter with a combination of low doses of atropine and diazepam (LOW AS/DZ treatment), large decrements...article 1992
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Philippens, I.H.C.H.M. (author), Melchers, B.P.C. (author), Wolthuis, O.L. (author)Behavioral training of guinea pigs by conventional methods, such as used for rats and mice, appears difficult. Hence, only a few behavioral experiments with guinea pigs have been described in the literature. An active avoidance technique in an automated two-way shuttlebox is described using sound as a conditioned (CS) and a tactile stimulus (a...article 1992
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Wolthuis, O.L. (author), Philippens, I.H.C.H.M. (author), Vanwersch, R.A.P. (author), Medisch Biologisch Laboratorium TNO (author), MBL (author)Several earlier studies showed that, in contrast with DFP, repeated injections with soman did not lead to behavioral tolerance in rats. The reason for the difference between the effects of these two organophosphate cholinesterase inhibitors was not clear and a neurophysiological approach was undertaken. Four experiments (A, B, C and D) were...article 1991
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Prins Maurits Laboratorium TNO (author), Clement, J.G. (author), Benschop, H.P. (author), de Jong, L.P.A. (author), Wolthuis, O.L. (author)The interaction of C(±)P(±)-soman (pinacolyl methylphosphonofluoridate) and its individual stereoisomers with serum carboxylic-ester hydrolase and potentiation of their toxicity by a carboxylic-ester hydrolase inhibitor CBDP (2-(2-methylphenoxy)-4H-1,3,2-benzodioxaphosphorin-2-oxide) was investigated. C(±)P(±)-Soman and the individual...article 1987
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Medisch Biologisch Laboratorium TNO (author), Kulig, B.M. (author), Vanwersch, R.A.P. (author), Wolthuis, O.L. (author)The effects of CNS-active drugs and neurotoxic agents on motor coordination in the rat were studied using a newly developed, automated technique. In this test, a tv/microprocessor-based system was utilized to detect and describe the movement and placement characteristics of one of the rat's hindpaws as the rat placed its paw from one rung to...article 1985
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- Wolthuis, O.L. (author), Vanwersch, R.A.P. (author), Medisch Biologisch Laboratorium TNO (author) article 1984
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Wolthuis, O.L. (author), Medisch Biologisch Laboratorium TNO (author)The effects of etiracetam, a structural analogue or piracetam, were investigated in rats on Y-maze discrimination acquisition, on open field behavior, on one-trial passive avoidance learning and on shuttlebox acquisition and extinction. The results indicate that this drug significantly enhances acquisition and may improve retention without...article 1981
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Wolthuis, O.L. (author), Benschop, H.P. (author), Berends, F. (author), Medisch Biologisch Laboratorium TNO (author)Anaesthetized, atropinized rats were posioned with 6x LD50 soman (1,2,2-trimethylpropyl methylphosphonofluoridate). Purified acetylcholinesterase, injected i.v. 75 min later, was rapidly inhibited, presumably by soman stored in a 'depot' from which it was gradually released. Existence of a depot is supported by the effect of a soman-simulator (...article 1981
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Tanger, H.J. (author), Vanwersch, R.A.P. (author), Wolthuis, O.L. (author), Medisch Biologisch Laboratorium TNO (author)A method is described whereby open field behaviour of rats can be automatically registered using a TV camera, a video converter, an X-Y recorder and a papertape puncher. Use is made of the scanning properties of the TV camera to obtain the X and Y coordinates of the rat's position and to print this position on an X-Y recorder to obtain the...article 1978
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Wolthuis, O.L. (author), Kepner, L.A. (author), Medisch Biologisch Laboratorium TNO (author)The bisquarternary mono-oxime HI-6, and to a lesser extent HS-6, caused functional recovery of neuromuscular transmission in vivo and in vitro when given 60 min after soman, i.e. when the soman-cholinesterase (AChE) complex is said to be fully 'aged'. Atropinised rats, with the tracheas intubated, received 4 x LD50 soman i.v. and were kept alive...article 1978
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Kepner, L.A. (author), Wolthuis, O.L. (author), Medisch Biologisch Laboratorium TNO (author)The bisquaternary mono-oximes HS-6 and HI-6 may both be considered as potential therapeutic agents for soman intoxication. It has been found that HI-6 was superior to an equal dose of HS-6 in the treatment of soman intoxication in mice and rats. Not only did HI-6 protect against higher levels of soman, but also fewer 'delayed deaths' were seen...article 1978
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Wolthuis, O.L. (author), Clason-van der Wiel, H.J. (author), Visser, R.P.L.S. (author), Medisch Biologisch Laboratorium TNO Chemisch Laboratorium TNO (author)Atropinised anaesthetised rats were injected i.v. with 4, 6 or 8 x LD50 of the organophosphorous anticholinesterase soman. Subsequent treatment with one dose of HS 6 (100 mg/kg, i.v.) delayed respiratory failure by 1 h or more; a further postponement was obtained when an additional HS 6 infusion was given. At the same infusion rate, HS 6 blood...article 1976
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Wolthuis, O.L. (author), Knook, D.L. (author), Nickolson, V.J. (author), Medisch Biologisch Laboratorium TNO (author)Spontaneous motor activity and physically undemanding conditioned suppression of drinking behavior were assessed in rats of 3, 12, 18 or 30 months (M) age. Initial spontaneous motor activity of 12 M rats was as low as that of 30 M rats and both were significantly lower than that of 3 M rats. The performance of 3, 12 and 18 M rats were similar to...article 1976
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Nickolson, V.J. (author), Wolthuis, O.L. (author), Medisch Biologisch Laboratorium TNO (author)The effects of Piracetam, Naftidrofuryl and methamphetamine on several parameters of cerebral energy metabolism have been studied. At variance with some reports in the literature neither Piracetam nor Naftidrofuryl affected the cerebral contents of adenine nucleotides and, accordingly, both substances were without effect on the adenylate energy...article 1976
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Nickolson, V.J. (author), Wolthuis, O.L. (author), Medisch Biologisch Laboratorium TNO (author)The effect of Piracetam on rat cerebral protein metabolism in vivo and in vitro was studied. It was found that the drug stimulates the uptake of labelled leucine by cerebral cortex slices, has no effect on the incorporation of leucine into cerebral protein, neither in slices nor in vivo, but inhibits the breakdown of newly formed protein in...article 1976
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Wolthuis, O.L. (author), de Wied, D. (author), Medisch Biologisch Laboratorium TNO Chemisch Laboratorium TNO (author)Averaged visual evoked responses (VER) in cortical area 17 were recorded one hour after the administration of 7-l-phe ACTH(4-10) or 7-d-phe ACTH(4-10) to artificially ventilated rats, paralysed with gallamine. In addition, the effects of these peptides on spontaneous motor behavior were analyzed. The results show that the latencies of all VER...article 1976