Papers by George Theophilidis
Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology, 1997
The neurotoxic action of six pyrethroid insecticides, four type II, (flucythrinate, deltamethrin,... more The neurotoxic action of six pyrethroid insecticides, four type II, (flucythrinate, deltamethrin, fenvalerate, fluvalinate) and two type I (cis- and trans-permethrin) was compared on the isolated sciatic nerve of frog. The nerve was exposed to pyrethroids for 30 min and action potentials were recorded for more than 45 hr after exposure. From the plots of the amplitude of the compound action potential vs time, it was possible to estimate, for each compound, the minimum effective concentration, the concentration which is required to reduce the amplitude of the compound action potential to 50% of its control value (mEC50). Flucythrinate was the most toxic compound, while toxicity decreased in the value: deltamethrin > fenvalerate > fluvalinate > cis-permethrin > trans-permethrin. Low neurotoxicity of cis-permethrin and trans-permethrin (type I pyrethroids) was expected. The neurotoxicity of type I pyrethroids is mainly due to an action at the synapse, which are not present in the frog sciatic nerve preparation. The relative potencies of the four type II compounds agree with their acute toxicity estimated using the LD50.
Toxicology in Vitro, 2007
The eVects on nerve tissue of three dental impression pastes were compared in this study. Two of ... more The eVects on nerve tissue of three dental impression pastes were compared in this study. Two of the impression pastes, Examix and Express 3M, contained vinyl polysiloxane while the other, Xanthopren, did not. An in vitro model based on the isolated sciatic nerve of the frog and rat was used. As an indication of the proper functioning of the Wbres in the nerve, the amplitude of evoked compound action potential (CAP) was monitored continuously. The results clearly showed that the number of active nerve Wbres in the isolated sciatic nerves of either rat or frog exposed directly to impression pastes containing vinyl polysiloxane, decreased much faster than those of the nerves in contact to impression material without vinyl polysiloxane. When the nerve of the frog was exposed to Xanthopren there was a decrease in the CAP to 50% of the control values within 56.87 § 2.42 h (n D 6). This value was called inhibition time to 50%, IT 50 and for Examix it was found to be 9.97 § 1.53 h. When the nerve of the rat was exposed to Xanthopren, the IT 50 was 15.34 § 2.97 h (n D 6) for the Xanthopren and only 2.86 § 1.20 h for Examix and 2.76 § 0.48 h for Express 3M (n D 6). There was no signiWcant diVerence between the action of the last two compounds (P D 0.85). This fast nerve Wbre inactivation could be caused either by the chemical used for the synthesis of the two impression pastes, Examix and Express 3M, or by the unusual constriction of the nerve when it is embedded in the materials with vinyl polysiloxane. There is strong evidence to support the Wrst case, since the incubation of the nerve in the presence of Examix, Express 3M and Xantopren in a way so the nerve was not in contact with the impression pastes, shows a much faster decrease of the CAP in the presence of the Wrst two pastes. The decrease is caused by the death of nerve Wbres, since there is no recovery in the CAP after the removal of Examix from the incubating saline.
Comparative Biochemistry and Physiology Part A: Physiology, 1983
Adaptations to Terrestrial Environments, 1983
Field studies of the behavior of some orthopteran species, found in wheatfields and the bush surr... more Field studies of the behavior of some orthopteran species, found in wheatfields and the bush surrounding them, show that they can be classified according to their behavior into three categories a) insects adapted to live actively on the ground; these are excellent runners, b) species which are able to produce a powerful jump; these are neither good in walking nor in flying and c) insects which are strong fliers (very few species belonging to Acrididae). Since in all these behavior patterns the metathoracic legs and especially the metathoracic extensor tibiae muscle (meta ETi), the jumping muscle, plays an important role, the anatomy and innervation of this muscle was examined in the three categories described above. It seems that in each case the metaETi and also some other morphological and anatomical features of the examined species have been adapted to meet the requirements of their behavior and their environment.
Toxicology Mechanisms and Methods, 2013
Abstract Studies have shown that the sciatic nerve epineural sheath acts as a barrier and has a d... more Abstract Studies have shown that the sciatic nerve epineural sheath acts as a barrier and has a delaying effect on the diffusion of local anesthetics into the nerve fibers and endoneurium. The purpose of this work is to assess and to quantify the permeability of the epineural sheath. For this purpose, we isolated the rat sciatic nerve in a three-chamber recording bath that allowed us to monitor the constant in amplitude evoked nerve compound action potential (nCAP) for over 24 h. For nerves exposed to the compounds under investigation, we estimated the IT50 the time required to inhibit the nCAP to 50% of its initial value. For desheathed nerves, the half-vitality time was denoted as IT50(-) and for the ensheath normal nerves as IT50(+). There was no significant difference between the IT50 of desheathed and ensheathed nerves exposed to normal saline. The IT50(-) for nerves exposed to 40 mM lidocaine was 12.1 ± 0.95 s (n=14) and the IT50(+) was 341.4 ± 2.49 s (n=6). The permeability (P) coefficient of the epineural sheath was defined as the ratio IT50(+)/IT50(-). The P coefficient for 40 mM lidocaine and linalool was 28.2 and 3.48, correspondingly, and for 30 mM 2-heptanone was 4.87. This is an indication that the epineural sheath provided a stronger barrier against lidocaine, compared to natural local anesthetics, linalool and 2-heptanone. The methodology presented here is a useful tool for studying epineural sheath permeability to compounds with local anesthetic properties.
SAR and QSAR in Environmental Research, 2003
On the basis of computer prediction of biological activity by PASS and toxicity by DEREK, the mos... more On the basis of computer prediction of biological activity by PASS and toxicity by DEREK, the most prospective 18 alkylaminoacyl derivatives of 3-amino-benzo-[d ]-isothiazole were selected. Their local anesthetic action was assessed using an in vitro preparation of the isolated peroneal nerve of the frog. The local anesthetics action of the compounds was assessed according to the time required for each compound to reduce the amplitude of the evoked compound action potential (CAP). Lidocaine was used as the control compound. The results show that the tested compounds can be divided into three groups: (a) compounds with action similar to lidocaine, (b) compounds with action lower than lidocaine and (c) compounds which block completely the evoked CAP, but after the compound was removed and replaced with normal saline showed no recovery of the potential at all. QSAR studies showed that polarizability, polarity and presence of five-membered rings in molecules have a positive influence on local anesthetic activity, while contributions of aromatic CH and singly bonded nitrogen are negative. Since estimations from PASS probabilities to find local anesthetic activity in the most active compounds were less than 50%, these compounds may be considered as new chemical entities (NCEs).
Pesticide Biochemistry and Physiology, 1997
An in vitro electrophysiological method has been developed for the assessment of synaptic depress... more An in vitro electrophysiological method has been developed for the assessment of synaptic depression in the cercal axons/giant interneurons cholinergic synaptic system of the Locusta migratoria. The evoked compound action potentials generated by the stimulation of the cercal nerve and recorded from the connectives posterior to the metathoracic ganglion in the ventral nerve cord were used to quantify the depression of the synaptic transmission. This in vitro preparation can detect the action of paraoxon, an organophosphate insecticide, on the cercal/giant interneurons synaptic system at nanomolar concentrations. This method is simple, accurate, and sensitive and can be considered as a useful tool for the relatively easy assessment of the neurotoxicity of anticholinesterase chemicals, like organophosphate and carbamate insecticides ᭧1997 Academic Press
Pesticide Biochemistry and Physiology, 1993
ABSTRACT
NeuroToxicology, 2008
Oxaliplatin is a novel chemotherapeutic agent which is effective against advanced colorectal canc... more Oxaliplatin is a novel chemotherapeutic agent which is effective against advanced colorectal cancer, but at the same time causes severe neuropathy in the peripheral nerve fibres, affecting mainly the voltage-gated sodium (Na(+)) channels (VGNaCs), according to literature. In this study the effects of oxaliplatin on the peripheral myelinated nerve fibres (PMNFs) were investigated in vitro using the isolated sciatic nerve of the adult rat. The advantage of this nerve-preparation was that stable in amplitude evoked compound action potentials (CAP) were recorded for over 1000min. Incubation of the sciatic nerve fibres in 25, 100 and 500microM oxaliplatin, for 300-700min caused dramatic distortion of the waveform of the CAP, namely broadening the repolarization phase, repetitive firing and afterhyperpolarization (AHP), related to the malfunction of voltage-gated potassium (K(+)) channels (VGKCs). At a concentration of 5microM, oxaliplatin caused broadening of the repolarization phase of the CAP only, while the no observed effect concentration was estimated to be 1microM. These findings are indicative of severe effects of oxaliplatin on the VGKCs. In contrast, the amplitude and the rise-time of the depolarization of the CAP did not change significantly, a clear indication that the VGNaCs of the particular nerve preparation were not affected by oxaliplatin. The effects of oxaliplatin on the PMNFs were similar to those of 4-aminopyridine (4-AP), a classical antagonist of VGKCs. These similarities in the pattern of action between oxaliplatin and 4-AP combined with the fact that the effects of oxaliplatin were more pronounced and developed at lower concentrations suggest that oxaliplatin acts as a potent VGKCs antagonist.
Neurotoxicity Research, 2002
The isolated sciatic nerve of the frog was used to assess the effects of the herbicide 2,4-dichlo... more The isolated sciatic nerve of the frog was used to assess the effects of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) on the peripheral nervous system. For each experiment, both sciatic nerves were used. The evoked compound action potentials of the nerves were monitored for over 48 h as an indication of their viability. The viability of nerve incubated in control saline was compared to the viability of the nerve incubated in saline where 2,4-D was diluted. The minimum effective concentration (minEC) of 2,4-D was estimated to be between 2 and 4 mM.
Neuroscience Letters, 1999
In an isolated preparation which consists of the buccal ganglia and the salivary nerve of Helix l... more In an isolated preparation which consists of the buccal ganglia and the salivary nerve of Helix lucorum, neuron B2 can be identi®ed by simultaneously recording the soma spike intracellularly and the axon spike extracellularly from the peripheral salivary nerve. The convulsant drug pentylenetetrazol (PTZ) eliminates the axon spike of the neuron within 1± 5 min after its application while epileptic activity is induced in the soma of the same neuron for hours. It is interesting that almost all nerve activity in the peripheral nerve is blocked by PTZ.
Neuroscience Letters, 2011
Neuroscience, 2000
One of the main principles in neuroscience is that in vertebrate motoneurons and certain interneu... more One of the main principles in neuroscience is that in vertebrate motoneurons and certain interneurons the decision to initiate an action potential is made at the initial segment of the axon, the axon hillock [Kandel E. R. and Schwartz J. H. (1991) In Principles of Neural Science (eds Kandel E. R., Schwartz J. H. and Jessell T. M.), pp. 166-167. Elsevier, New York]. The situation in invertebrate motoneurons is different. The axon has many arborizations near its soma, in the nearby neuropil, and many branches in the target region. The action potentials are generated in the region of the axon in the neuropil and in some cases the trigger zone can be found more than 1 mm apart from the soma [Tauc C. (1962) Aplysia. J. gen. Physiol. 45, 1077-1097]. Thus, it is obvious that, in a neuron, the removal of the trigger zone would cease the spiking activity in the axon. The purpose of this work is to demonstrate that, in snails, there are axons of certain neurons, like neuron B2, which are able to maintain their firing activity after the removal of their cell body and the so-called trigger zone. ᭧ 2000 IBRO.
Journal of Neuroscience Methods, 1984
A simple and easily constructed unit was designed using a buffer amplifier, a programmable transc... more A simple and easily constructed unit was designed using a buffer amplifier, a programmable transconductance amplifier and an active filter. The unit allows extracellular recording and stimulation through the same electrode. Thus in experiments where it is required to stimulate a nerve and record the effects of the stimulation from the same nerve, the stimulating and the recording electrodes can be combined in one.
Journal of Neuroscience Methods, 1989
A method which allows the intracellular staining of physiologically identified muscle fibres is d... more A method which allows the intracellular staining of physiologically identified muscle fibres is described. The possible applications of this method have been discussed.
Journal of Neuroscience Methods, 1998
An in vitro model for the study of the axonal transport of herpes simplex virus-1 (HSV-1) in the ... more An in vitro model for the study of the axonal transport of herpes simplex virus-1 (HSV-1) in the nerve fibres of the sciatic nerve of the frog Rana ridibunda, has been developed. The nerve was placed along a three-chambered bath consisting of three isolated chambers arranged in series: the stimulating, perfusion and recording chambers. The HSV-1 inoculum was placed in the stimulating chamber, where the proximal part of the isolated sciatic nerve was immersed. HSV-1 was detected after 24-36 h in the recording chamber, where the distal part of the nerve was immersed in Dulbecco's Modified Eagle Medium (DMEM), indicating an axonal transport speed of 46-60 mm/day. The evoked maximum compound action potentials generated in the stimulating chamber was monitored continuously in the recording chamber as an indication of the viability of the nerve during axonal transport. The in vitro method presented here is a useful tool for the pharmacological study of various parameters, e.g. drugs diluted in the perfusion chamber, ionising radiation and temperature, which may affect the axonal transport or other properties of HSV-1.
Journal of Morphology, 1989
... Seven of them, the vil l-7 (lev-els A, B, and C in Fig. ... 2C,D). They originate posteri-orl... more ... Seven of them, the vil l-7 (lev-els A, B, and C in Fig. ... 2C,D). They originate posteri-orly from the pVIF and insert to the ventral body cuticle, except for vep 1 that inserts on the longitudinal fold. Muscles vep 1 and 3 run ob-... Scale bar: 0.50 mm for AD and 0.25 mm for E. Page 6. ...
Journal of Insect Physiology, 1990
The firing pattern of the locust mesothoracic femoral motoneurones during passive extension of th... more The firing pattern of the locust mesothoracic femoral motoneurones during passive extension of the tibia (resistance reflexes) has been examined. Of the flexor excitors, some are activated only by very fast tibia1 movements producing a few spikes. Others produce a discharge which lasts as long as the imposed tibia1 extension. The flexor slow motoneurones are the only spontaneously active neurones and their frequency increases and remains high as long as the tibia1 extension lasts. The inhibitors remain silent during active tibia1 flexion (or extension) and they are active only during maintained extension. From the mesothoracic extensor tibiae motor axons, the slow extensor tibiae fires during tibia1 flexion and the inhibitor during tibia1 extension. The fast extensor tibiae is silent during tibia1 movement. The activity of the femoral motoneurones was also studied in a tethered locust walking on a treadmill. First, the similarities in the firing motor pattern between a deafferented and a normal walking leg were established and then the activity of the flexor tibiae motoneurones, recorded from a deafferented leg of a walking locust, was analysed. A modification in the resistance reflexes during the active stage of the animal was also demonstrated. The resistance reflexes seemed to become assistant reflexes during walking.
Journal of Applied Entomology, 2008
Two pesticides, the insecticide imidacloprid and the herbicide acetochlor, were evaluated for the... more Two pesticides, the insecticide imidacloprid and the herbicide acetochlor, were evaluated for their insecticidal and genotoxic effects in Drosophila melanogaster. Their insecticidal effects were assessed by calculating LC50 values after acute or chronic exposure of larvae and adults to different concentrations of the test compounds. After acute exposure, the LC50 of imidacloprid was 7.59 × 10−5 M for larvae and 1.43 × 10−4 M for adults, and after chronic exposure, it was 2.67 × 10−5 M and 6.09 × 10−5 M for larvae and adults, respectively. On the contrary, the herbicide acetochlor showed no acute or chronic insecticidal effect against either larvae or adults, even at very high concentrations (8 × 10−3 M). For the evaluation of genotoxic properties of the two pesticides, the Somatic Mutation and Recombination Test in D. melanogaster was used. Our results suggest that neither imidacloprid nor acetochlor exhibits mutagenic or recombinogenic activity at applicable concentrations.
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Papers by George Theophilidis