PITHAGORAS II PROJECT

The research was financed from Ministry of National Education and Religious Affairs and European Union in the frame of Pythagoras Project II

PUBLICATIONS FROM "MEDLINE"

1) Andreou, N. Dabarakis, A. Kagiava, E.K. Kosmidis, A. Geronikaki and G. Theophilidis; "Assessing the effects of three dental impression materials on the isolated sciatic nerve of rat and frog"; Toxicology in Vitro, Volume 21, Issue 1, February 2007, Pages 103-108

http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6TCP-4KRFV3S-1-1&_cdi=5176&_user=604493&_orig=search&_coverDate=02%2F28%2F2007&_sk=999789998&view=c&wchp=dGLzVlz-zSkWz&md5=ba58e3b4126afea92d8c56975f66d185&ie=/sdarticle.pdf

Abstract : The effects 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 fibres in the nerve, the amplitude of evoked compound action potential (CAP) was monitored continuously. The results clearly showed that the number of active nerve fibres 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=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=6) for the Xanthopren and only 2.86+/-1.20 h for Examix and 2.76+/-0.48 h for Express 3M (n=6). There was no significant difference between the action of the last two compounds (P=0.85). This fast nerve fibre 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 first 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 first two pastes. The decrease is caused by the death of nerve fibres, since there is no recovery in the CAP after the removal of Examix from the incubating saline.

2) G. Zafeiridou, A.Geronikaki, C. Papaefthimiou, M. Tryfonos, E. K. Kosmidis, G. Theophilidis; "Assessing the effects of the three herbicides acetochlor,2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and 2,4-dichlorophenoxyacetic acid on the compound action potential of the sciatic nerve of the frog (Rana ridibunda)"; Chemosphere; Volume 65; May 2006; 1040-1048 (Impact factor 2.44)

http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6V74-4JW1208-3-1&_cdi=5832&_user=604493&_orig=search&_coverDate=11%2F30%2F2006&_sk=999349993&view=c&wchp=dGLzVlz-zSkWz&md5=92ba11ab3ae7d881aaf672a87e1a13d6&ie=/sdarticle.pdf

Abstract: To assess the relative toxicity of the herbicides acetochlor and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) on the nervous system, the sciatic nerve of the frog (Rana ridibunda) nerve was incubated in saline inside a specially designed recording chamber. This chamber permits monitoring of the evoked compound action potential (CAP) of the nerve, a parameter that could be used to quantify the vitality of the nerve in normal conditions as well as when the nerve was exposed to the compounds under investigation. Thus, when the nerve was exposed to acetochlor, the EC(50) was estimated to be 0.22mM, while for 2,4,5-T the EC(50) was 0.90mM. Using the identical nerve preparation, the EC(50) of 2,4-D was estimated to be 3.80mM [Kouri, G., Theophilidis, G., 2002. The action of the herbicide 2,4-dichlorophenoxyacetic acid on the isolated sciatic nerve of the frog (Rana ridibunda). Neurotoxicol. Res. 4, 25-32]. The ratio of the relative toxicity for acetochlor, 2,4,5-T and 2,4-D was found to be 1:4:17.2. However, because it is well-known that the action of 2,4-D is dependent on the pH, the relative toxicity of the three compounds was tested at pH 3.3, since it has been found that the sciatic nerve of the frog is tolerant of such a low pH. Under these conditions, the EC(50) was 0.77mM (from 0.22mM at pH 7.2) for acetochlor, 0.20mM (from 0.90mM) for 2,4,5-T and 0.24mM (from 3.80mM at pH 7.2) for 2,4-D. Thus, the relative toxicity of the three compounds changed drastically to 1:0.25:0.31. This change in the relative toxicity is due not only to the increase in the toxicity of 2,4,5-T and 2,4-D at low pH levels, but also to the decrease in the toxicity of acetochlor at pH 3.3.

3) Moschou Μ, Kosmidis Ε.Κ, Kaloyianni Μ, Geronikaki Μ, Dabarakis Ν, Theophilidis G "In vitro assessment of the neurotoxic and neuroprotective effects of N-acetyl-L-cysteine (NAC) on the rat sciatic nerve fibers"; Toxicology in Vitro; Volume 22; 2008; 267–274 (Impact Factor 2.04).

http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6TCP-4PNM47R-1-1&_cdi=5176&_user=604493&_orig=search&_coverDate=02%2F29%2F2008&_sk=999779998&view=c&wchp=dGLbVlW-zSkWz&md5=299109d439434a274cec65f6b0be7451&ie=/sdarticle.pdf

Abstract: N-acetyl-l-cysteine (NAC), at a concentration of 1–60 mM, has been previously used extensively for protection in a variety of cell cultures against the deleterious effects of various compounds. The results of this in vitro study show that NAC has certain unusual effects on the evoked compound action potential (CAP) of the rat sciatic nerve fibers. Firstly, at concentrations of 5.0, 3.5 and 2.5 mM, concentrations used by others as a protectant for cell cultures, NAC inhibits the action potentials of the sciatic nerve fibers completely in a concentration-dependent manner within a few minutes or hours (2.5 mM). Secondly, the acute inhibitory action of NAC on the CAP of the nerve fibers was not spontaneously reversible, but as soon as NAC was replaced with saline there was a partial (75%) recovery in the function of the nerve fibers. Thirdly, the no observed effect concentration for NAC was estimated to be 1 mM. The paradox is that NAC at 1 mM not only had no effect on the nerve fibers, but it became an excellent neuroprotective compound, giving almost 100% neuroprotection against cadmium-induced neurotoxicity. The results show a possible effect of NAC on voltage-gated sodium and potassium channels. The observed neuroprotective-neurotoxic properties of NAC require careful reconsideration of its use in either in vitro studies or in vivo pharmaceutical applications.

4) Moschou M, Papaefthimiou C, Kagiava A, Antonopoulou E, Theophilidis G. In vitro assessment of the effects of cadmium and zinc on mammalian nerve fibres.

Chemosphere. 2008 Mar 15 (Impact factor 2.44);

http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6V74-4S2VM6X-1-3&_cdi=5832&_user=604493&_orig=search&_coverDate=03%2F17%2F2008&_sk=999999999&view=c&wchp=dGLbVlW-zSkWz&md5=e55ae8a68b23c15b3dac7ad21c44ef8d&ie=/sdarticle.pdf

Abstract: Zinc and cadmium are environmental contaminants that have a wide range of effects on the nervous system, but zinc is also considered to be an important metal in the human body. In this study the effect of CdCl₂ and ZnCl₂, at concentrations of 50,150, 250 and 500 μM, on the nerve fibres of the sciatic nerve of the rat isolated in a three-chamber recording bath were studied. At the same concentrations, CdCl₂ and ZnCl₂ were found to have almost the same inhibitory effect on the compound action potential (CAP) of the nerve fibres. Their concentration–effect curves almost overlap and there was no significant difference in their EC₅₀ which for CdCl₂ is 250.1 ± 18 μM (n = 5) and for ZnCl₂ is 282.2 ± 25 μM (n = 5) correspondingly (P > 0.05). The no-observed-effect concentration (NOEC) was estimated to be 50–100 μM for both metals. The identical inhibitory effect of both metals on the sciatic nerve fibres indicates a common mode of action which is related to their potential to generate reactive oxygen species (ROS).

5) Adamos D.A., Kosmidis E.K. and Theophilidis G. Performance evaluation of PCA-based spike sorting algorithms. Computer Methods and Programs in Biomedicine , vol. 91, Issue 3, Sep 08

Abstract: Deciphering the electrical activity of individual neurons from multi-unit noisy recordings is critical for understanding complex neural systems. A widely used spike sorting algorithm is being evaluated for single-electrode nerve trunk recordings. The algorithm is based on Principal Component Analysis for spike feature extraction. In the neuroscience literature it is generally assumed that the use of the first two or most commonly three principal components is sufficient. We estimate the optimum PCA-based feature space by evaluating the algorithm’s performance on simulated series of action potentials. A number of modifications are made to the open source nev2lkit software to enable systematic investigation of the parameter space. We introduce a new metric to define clustering error considering over-clustering more favorable than under-clustering as proposed by experimentalists for our data. Both the program patch and the metric are available online. Correlated and white Gaussian noise processes are superimposed to account for biological and artificial jitter in the recordings. We report that the employment of more than three principal components is in general beneficial for all noise cases considered. Finally, we apply our results to experimental data and verify that the sorting process with four principal components is in agreement with a panel of electrophysiology experts.

6) A.Geronikaki, P.Vicini, G. Theophilidis, A. Lagunin, V. Poroikov, N. Dabarakis, H. Modarresi, J.C. Dearden. Evaluation of the local anaesthetic activity of 3-aminobenzo[d]isothiazole derivatives using the rat sciatic nerve model European Journal of Medicine (Submitted for publication )

Abstract: On the basis of computer prediction of biological activity by PASS and toxicity by DEREK, the most promising 32 alkylaminoacyl derivatives of 3-aminobenzo[d]isothiazole were selected for possible local anaesthetic action. This action was evaluated using an in vitro preparation of the isolated sciatic nerve of the rat and compared with lidocaine which was used as a reference compound. QSAR studies showed that the polarizability, polarity and molecular shape of molecules have a positive influence on their local anaesthetic activity, while contributions of aromatic CH and singly bonded nitrogen are negative. Since the estimated PASS probabilities to find local anaesthetic activity in the most active compounds are less than 50%, these compounds may be considered to be possible NCEs.

Conferences

1. Adamos D.A., Kosmidis E.K., TheophilidisG. and Laskaris N. A novel approach to semi-automated spike-sorting based on ISOMAP technique. 21^th Annual Meeting of the Hellenic Society for Neuroscience, Thessaloniki, Greece, November 30-December 1, 2007.

2. Adamos D.A., Kosmidis E.K. and Theophilidis G. Performance evaluation of an unsupervised automatic spike-sorting algorithm. 20th Annual Meeting of the Hellenic Society for Neuroscience, Heraklion, Greece, September 29-October 1, 2006.

3. Kosmidis E.K., Contoyiannis Y.F., Papatheodoropoulos C., Diakonos F.K. and Theophilidis G. Criticality in neurons. 20th Annual Meeting of the Hellenic Society for Neuroscience, Heraklion, Greece, September 29-October 1, 2006.

4. Αραμπατζή Η., Βασιλείου Χ., Παπαευθυμίου Χ., Θεοφιλίδης Γ. (2007). In vivo αξιολόγηση της δράσης του νικοτινικού εντομοκτόνου imidacloprid στον αναπνευστικό ρυθμό του επίμυος. Πρακτικά 29^ου Επιστημονικού Συνεδρίου της Ελληνικής Εταιρίας Βιολογικών Επιστημών (Ε.Ε.Β.Ε.), Καβάλα, 17-19 Μαΐου 2007, 22-23.

5. Arabatzi H., Vasileiou C., Kosmidis E.K., Papaefthimiou C. And Theophilidis, G. In vivo assessment of the activity of the nicotinic insecticide imidacloprid on respiratory rhythm of the rat. 21^th Annual Meeting of the Hellenic Society for Neuroscience, Thessaloniki, Greece, November 30-December 1, 2007.

6. Κωνσταντινίδου Α., Αντωνοπούλου Ε., Παπαευθυμίου Χ. Θεοφιλίδης Γ. (2007). Συγκριτική μελέτη της δράσης της ταυρίνης στη σύσπαση των απομονωμένων κόλπων της καρδιάς σε ψάρι, αμφίβιο και θηλαστικό. Πρακτικά 29^ου Επιστημονικού Συνεδρίου της Ελληνικής Εταιρίας Βιολογικών Επιστημών (Ε.Ε.Β.Ε.), Καβάλα, 17-19 Μαΐου 2007, 210-211.

(ΠΑΡΑΡΤΗΜΑ 5)

7. Adamos D.A., Kagiava A., Kosmidis E.K. and Theophilidis G. Decomposition of recorded compound action potential axon diameter and conduction velocity distribution. 21^th Annual Meeting of the Hellenic Society for Neuroscience, Thessaloniki, Greece, November 30-December 1, 2007.

8. Polyzoidis S.K., Kosmidis E.K., Grigoriadis N., Tascos N., Theophilidis G. An in vivo mouse preparation for estimation of spinal cord conduction velocity. 17^th Meeting of the European Neurological Society. Rhodes, Greece, June 16-20, 2007.

9 . Polyzoidis S., Kosmidis E.K., Grigoriadis N., Tascos N., Milonas I. and Theophilidis G. An in vivo mouse preparation for estimation of the spinal cord conduction velocity. 15^th Conference of the South-East European Society for Neurology and Psychiatry, Thessaloniki, Greece, October 11-14, 2006.

10. A.Geronikaki, P.Vicini, G. Theophilidis, A. Lagunin, V. Poroikov, N. Dabarakis, H. Modarresi, J.C. Dearden. Assessing the local anesthetic activity of derivatives of 3-amino-1,2-[d]benzoisothiazoles on the sciatic nerve of rat model European Journal of Medicine (Έχει υποβληθεί για δημοσίευση)

11. Καγιαβά Α., Βακαλοπούλου Μ., Νταμπαράκης Ν., Γερονικάκη Α., Θεοφιλίδης Γ., Αξιολόγηση της νευροπροστατευτικής δράσης του οξυγόνου στο απομονωμένο ισχιακό νεύρο του αρουραίου και μελέτη του ρόλου της θερμοκρασίας, 19^ο Συνέδριο της Ελληνικής Εταιρείας για τις Νευροεπιστήμες, Πρακτικά Συνεδρίου σελ. 125-126, 30 Σεπτεμβρίου-2 Οκτωβρίου 2005, Πάτρα-Ελλάδα

12. Καγιαβά Α. και Θεοφιλίδης Γ., In vitro αξιολόγηση της ανοχής του ισχιακού νεύρου του αρουραίου σε συνθήκες υποξίας και ανοξίας, 29^ο Ετήσιο Συνέδριο της ΕΕΒΕ, Πρακτικά Συνεδρίου σελ. 126-127, Μάιος 17-19 2997, Καβάλα-Ελλάδα

13. Καγιαβά Α., In vitro αξιολόγηση της ανοχής του ισχιακού νεύρου του επίμυος σε συνθήκες υποξίας και ανοξίας, ΑΠΘ, Τμήμα Βιολογίας, Μεταπτυχιακή διπλωματική εργασία, 2007

14. Α. Kagiava, A. Tsingotjidou, T. Poutahidis, N. Foroglou and G. Theophilidis; "Evaluation of the regeneration in the three main nerve branches of the rat sciatic nerve"; 5^th Forum of European Neuroscience; July 8-12, 2006, Vienna-Austria

15. Kagiava A., Tsingotjidou A., Emmanouilides C., Kosmidis E.K.and Theophilidis G.; "Assessment of oxaliplatin-induced acute neurotoxicity on the peripheral nervous system using the isolated sciatic nerve of the rat"; 20^th Annual Meeting of the Hellenic Society for Neuroscience; Page 58; September 29-October 1 2006, Crete-Greece

16. Kagiava A, Tsingotjidou A., Emmanouilides C., Theophilidis G.; "Oxaliplatin:an anticancer drug inducing severe neuropathy by affecting the voltage- gated potassium channels in the nerve fibers of the peripheral nervous system"; 21^st Annual Meeting of the Hellenic Society for Neuroscience; Pages 108-109; November 30-December 1 2007, Thessaloniki-Greece

17. Ιωάννης Ζαλαχώρας, Δέσποινα Βώκου και Γεώργιος Θεοφιλίδης., Συγκριτική μελέτη της επίδρασης πέντε τερπενικών ουσιών(λιναλοόλη, φεγχόνη, π-κυμένιο, α-πινένιο, κινεόλη) στο σύνθετο δυναμικό ενέργειας του ισχιακού νεύρου του βατράχου, 29^ο Ετήσιο Συνέδριο της ΕΕΒΕ, Πρακτικά Συνεδρίου σελ. 98-99, Μάιος 17-19 2997, Καβάλα-Ελλάδα

18. Zalachoras I., Vokou D. and Theophilidis G., "Assessing in vitro the local anesthetic action of the terpens linalool and fenchone using the isolated sciatic nerve of the frog",

Natural Products in Drug Discovery and Development, 4-5 December 2007, Munich, Germany

19. Zalachoras I., Vokou D. and Theophilidis G., "Assessing in vitro the local anesthetic action of the terpens linalool and fenchone using the isolated sciatic nerve of the frog",

V^thInternational Symposium on Wild Fauna, 22-27 September 2007, Chalkidiki, Greece (Προφορική Παρουσίαση, που δημοσιεύθηκε στα Πρακτικά του Συνεδρίου)

Contact person

G.Theophilidis (Prof. Ph.D.)

Aristotle University, School of Biology,

Department of Zoology, Lab. Animal Physiology,

Thessalonniki, Greece 54 124

Tel.: 00302310 998261, Fax: 0030 2310 998269

e-mail: theophil@bio.auth.gr