CONTENTS
1. The dual role of L-arginine in nociceptive processing: L-arginine-kyotorphin szstem versus Larginine-nitric oxide pathway
OC Mungiu, Irina M Jaba, G Manolidis, Dunărea G Ionescu, I Haulică
2. The effects of nitric oxide on airway responsivity in healthy and ovalbumin sensitized rats
Georgeta Mihalaş, Carmen Bunu, Gabriela Tănasie, Ioana Raluca Siska, Lavinia Noveanu
3. Effects of some vasodilators on KCl-induced cardiac arrhythmias. Experiments carried out byintratechal administration in anesthetized rats
Alina Cuprian, B Cuparencu, Vl Şandor4. Mathematical method for cancer-related genes discovery by microarray data analysis
M Roz
5. QSAR for ecotoxicology: the experience of the Timisoara group
A Chiriac, Z Simon, M Olah, Daniela Dascălu, VA Chiriac

1. THE DUAL ROLE OF L-ARGININE IN NOCICEPTIVE PROCESSING: L-ARGININEKYOTORPHIN SZSTEM VERSUS L-ARGININE-NITRIC OXIDE PATHWAY
OC Mungiu, Irina M Jaba, G Manolidis, Dunărea G Ionescu, I Haulică
Faculty of Medicine, “Gr. T. Popa” University of Medicine and Pharmacy, Iasi
Address for correspondence: Department of Pharmacology, Faculty of Medicine, “Gr. T. Popa” , University of Medicine
and Pharmacy, 16 Universitatii Street, 6600 Iasi, Romania

ABSRTACTThe role of L-arginine in nociceptive processing was assessed using different acute pain models: tailflick, hot-plate, algesimetric and writhing assay. Different groups were treated with 1) L-arginine(i.p. 1000 mg/kg, i.t. 1 mg/rat), 2) association of L-NG-nitroarginine methyl ester (L-NAME, i.p. 75
mg/kg, i.t. 0,1 mg/rat) with L-arginine, 3) L-ornithine (i.p. 1000 mg/kg). The 1000 mg/kg i.p. dose ofboth L-arginine and L-ornithine induced an analgesic effect on mice in the hot-plate and writhing
assay, but did not alter the tail-flick latencies. This anti-nociceptive effect was significantly
antagonized by prior subcutaneous administration of naloxone. L-arginine administred i.t. on rats
tends to induce an increase of response latency to nociceptive stimuli for algesimetric and tail-flicktests. These results suggest an antinociceptive action of L-arginine, possible through kyotorphin
system. The antinociceptive effect of L-arginine is increased in association with L-NAME, an nitricoxide (NO) synthase inhibitor, so it appears that the possible pro-nociceptive influences of Larginine mediated through the NO synthase/NO/cGMP cascade are surpassed by the analgesic actionof L-arginine through L-arginine-kyotorphin system.
Key words: L-arginine, nociceptive, processing, nitric oxide synthase, nitric oxide.

2. THE EFFECTS OF NITRIC OXIDE ON AIRWAY RESPONSIVITY IN HEALTHY ANDOVALBUMIN SENSITIZED RATS
Georgeta Mihalaş, Carmen Bunu, Gabriela Tănasie, Ioana Raluca Siska, Lavinia Noveanu
Department of Physiology, University of Medicine and Pharmacy “Victor Babes” Timisoara
Address for correspondence: Department of Physiology, University of Medicine and Pharmacy “Victor Babes”
Timisoara, 2 Eftimie Murgu Square, Timisoara, Romania

ABSTRACT
Objectives: Nitric oxide (NO) donor, glyceryl trinitrate (GTN) and NOS inhibitor Nw-nitro-Larginine (L-NA) were used to investigate the role of NO in airways responsiveness of healthy andasthmatic rats.
Material and method: The experiments were performed on 4 groups or Sprague-Dowley adult rats:group I – control; group II – ovalbumin sensitized rats; group III – ovalbumin sensitized rats treatedwith montelukast, a synthetic leukotriene receptor antagonist; group IV – ovalbumin sensitized rats
treated with glucocorticoids. Tracheal spirals were introduced in organ chambers filled with KrebsHanseleit solution, bubbled with 95% O2 and 5% CO2, at 37o C. isometric force was measured using
a force transducer and the results were recorded using a computerized data acquisition unit. Airways
responsiveness to a muscarinic agonist, acetylcholine, was measured. The bronchodilator action ofNO was evaluated by administration GTN, with or without a previous pre-contraction of thepreparations with acetylcholine. The effect of L-NA was assessed in two situations: after precontraction of the preparations with acethylcholine, and also on the basal tone (incubation of thepreparation with L-NA) followed by administration of the muscarinic agonist.
Results: In ovalbumin-sensitized rats, reduced contractile reactions were noticed, but the basal tone
was significantly higher. In animals treated with either montelukast or glucocorticoids, theimprovement of basal relaxation was correlated with higher acethylcholine-induced contractions.
GTN was a weak bronchodilator, its relaxing action being abolished by ovalbumin sensitization, andrestored after treatment with either montelukast or glucocorticoids. In our experiments, L-NA alone
induced a contractile action in almost all groups, except SO group, in which no contraction wasobserved. Corticotherapy, and especially montelukast augmented the contractile action of L-NA.
Conclusions: Administration of exogenous NO induces weak relaxing effect in all studied animals,
its effect being annulled by ovalbumin sensitization and restored by therapy with either
antileukotrienes or glucocorticoids. Montelukast potentates the contractile effect of the NOS
inhibitor, suggesting that cNOS might play an important role in the development of bronchial
hyperreactivity. Thus, its action seems to be more pronounced compared to that induced bycorticotherapy, which decreases iNOS activity.
Key words: tracheal smooth muscle, Sprague-Dowley rats, ovalbumin, sensitization, nitric oxide.

3. EFFECTS OF SOME VASODILATORS ON KCL-INDUCED CARDIAC
ARRHYTHMIAS.
EXPERIMENTS
CARRIEDOUTBY
INTRATECHAL
ADMINISTRATION IN ANESTHETIZED RATS
Alina Cuprian1, B Cuparencu2, Vl Şandor3
1
Linacre College, Oxford, UK2
Department of Pharmacology, university of Oradea
3
Department of Pharmacology, University of Medicine and Pharmacy, Cluj-Napoca
Address for correspondence: Prof. Dr. B Cuparencu, 27 Horea Street, 3400 Cluj-Napoca, Romania

ABSTRACTIn pentobarbital-anesthetized rats, the intrathecal (i.t.) administration of KCl induces bradycardia andcardiac arrhythmias. Vinpocetine, dipyridamole, and papaverine given i.t. had a small effect on theslowing down of the heart rate, but they blocked quasicompletely the cardiac arrhythmias.
Key words: rats, intratechal, heart rate, arrhythmias, KCl, dipyridamole, papaverine, vinpocetine.

4. MATHEMATICAL METHOD FOR CANCER-RELATED GENES DISCOVERY BY
MICROARRAY DATA ANALYSIS
MA RozDecision Systems Group, Harvard University, Boston, USA
Address for correspondence: Mugur Roz, Decision Systems Group, Harvard University, USA. E-mail:mroz@dsg.harvard.edu

ABSTRACTIn this paper we introduce a new mathematical method for selecting cancer-informative genes frommicroarray data. Usually, genes of interest are selected by ranking genes according to a test statistic
and then choose the top genes. However, the main problem with this approach is that most statisticaltests assume a normal distribution of the data, which is frequently not the case. To identify cancerrelated genes, it would be ideal to have distinct but still highly informative genes. One of the mostvaluable techniques currently utilized is discriminate analysis (supervised learning). A key issue toimprove the classification performance is to find the genes that are most likely to contribute to theseparation of the types (classes) of tissues (or diseases), because not all the genes are needed for thediscriminant analysis. In this paper, we introduce a new method for gene selection, based on thetheory of sets. The method substantially improves the performance of the acute leukemia
classification based on microarray data (presented in Golub et al.), using both symbolic andsubsymbolic machine learning algorithms.
Key words: cancer-related genes, microarray data analysis, featutre selection, machine learning.

5. QSAR FOR ECOTOXICOLOGY: THE EXPERIENCE OF THE TIMISOARA GROUP
A Chiriac, Z Simon1, M Olah1, Daniela Dascălu, VA Chiriac
Department of Chemistry, Faculty of Chemistry-Biology-Geography, West University of Timisoara
1Institute of Chemistry of the Romanian Academy, Timisoara
Address for correspondence: Professor Adrian Chiriac, Department of Chemistry, Faculty of Chemistry-BiologyGeography, West University of Timisoara, 16 Pestalozzi Street, 1900 Timisoara, Romania. E-mail: achiriac@cbg.uvt.ro

ABSTRACTAn enormous number of organic and inorganic chemicals are potential pollutants, due both to theirtoxicity, and to high persistence in nature. A non-specific action is observed for large classes ofsubstances (alcohols, aldehydes, etc.) determined largely by hydrophobicity, but several pollutants
act upon specific receptors. The interest for QSAR studies in this domain is obvious.
The Timisoara group of QSAR has performed Hansch type QSAR studies for the toxicity on
mammals of organophosphorus pesticides already in the seventies. In the last ten years, QSAR
studies were performed on a large series of mutagenic aromatic amines, using a modified, classical
MLR-method such as to include also inactive substances. Another QSAR study by the MLR method,combined also with PLS, was performed for a large series of inorganic cations, with an attempt tointroduce also nontoxic cations. 3D-QSAR methods, namely MTD and PLS variant of MTD wereperformed for a series of over 70 polyhalogenated derivatives of dibenzoxine and diphenyl.
The studied substances interact with specific receptors. The QSAR results are modest for the seriesof mutagenic aromatic amines and especially for the series of inorganic cations; different molecules(ions) of these series probably act upon different receptors. The results are very good for the series ofpolyhalogenated aromatic derivatives; their toxicity is probably based upon interaction with the same
receptor.
Key words: QSAR studies, MTD-method, polyhalogenated derivatives, mutagenic aromatic amines,
inorganic pollutants.