CONTENTS
1. The involvement and significance of the tyrosine N-terminal residue in nociception processes
Irina M Jaba, D Vasincu, C Neamtu, OC Mungiu
2. The incidence of cardiovascular risk factors in apparently healthy young adults CARDIORISK
study: background and design
Lavinia Noveanu, Georgeta Mihalas, D Duda-Seiman, Adriana Gherbon, Silvia Mancas
3. Brief review: Role of vascular endothelial growth factor (VEGF) in angiogenesis
Daciana Nistor, Ioana Raluca Siska, Daniela Crisnic, Gabriela Tanasie, V Paunescu
4. Thyroid hormones and immobilization
Carmen Tatu, RF Tatu, V Dumitraşcu, Daniela Puşcaşiu, Gabriela Tanasie, Florina Mirea, Fr
Schneider
5. Effects of zopiclone on blood glucose level and serum lipids in streptozotocin –induced diabetes inrats
J Horák, B Cuparencu, Aliz Horák, Cecilia Bobos
6. Angiogenesis significance in renal carcinomas prognostic
Daniela Puscasiu, Carmen Tatu, Doina Verdes, Elena Potencz, RF Tatu, Florina Mirea
7. P53 expression in Hodgkin lymphoma – a tumoral progression index?
Corina Flangea, Daniela Puşcaşiu, Atena Găluşcan, Elena Potencz, A Anghel, C Dogaru, S Gîju8. The influence of coronary risk factors on the progression of aortic stenosis
Elena Ardeleanu, Rodica Mateescu
9. Book review: Chemoinformatics in Drug Discovery
G Mihalas

1. THE INVOLVEMENT AND SIGNIFICANCE OF THE TYROSINE N-TERMINALRESIDUE IN NOCICEPTION PROCESSES
Irina M Jaba, D Vasincu, C Neamtu, OC Mungiu
Faculty of Medicine, “Gr. T. Popa” University of Medicine and Pharmacy, Iasi
Address for correspondence: Dr. Irina Jaba, Department of Pharmacology, University of Medicine and Pharmacy “Gr. T.
Popa” Iasi, 16 University Street, 700115 Iasi, Romania.

ABSTRACTThe aim of this study was to investigate the importance of the amino acid tyrosine (Tyr) for the
analgesic opioid activity. Different groups of mice or rats were treated with: 1) L-tyrosine (i.p. 200
mg/kg), 2) D-tyrosine (i.p. 200 mg/kg), 3) Tyr-Gly-Gly (i.t. 0.5 mg/rat), 4) Gly-Tyr (i.t. 0.5 mg/rat).
Different tests were used to evaluate the anti-nociceptive effect of the substances tested: thermal
nociception (hot plate test, plantar test) and mechanical nociception (analgesymeter test). L-tyrosine,
but not D-tyrosine, administered intraperitoneal produces a significant anti-nociception, blocked byprevious administration of naloxone. Tyr-Gly-Gly, but not Gly-Tyr, elicited analgesic activity
antagonized by naloxone. So, the presumption made in the case of atypical opioid peptides, that
opioid-like activity at the N-terminal sequence, applies for shorter peptides.
Key words: L-tyrosine, D-tyrosine, Tyr-Gly-Gly, Gly-Tyr, anti-nociceptive effect.

2. THE INCIDENCE OF CARDIOVASCULAR RISK FACTORS IN APPARENTLYHEALTHY YOUNG ADULTS CARDIORISK STUDY: BACKGROUND AND DESIGN
Lavinia Noveanu1, Georgeta Mihalas1, D Duda-Seiman2, Adriana Gherbon1, Silvia Mancas2
1
Department of Physiology, University of Medicine and Pharmacy “Victor Babes” Timisoara
2
Department of Internal Medicine, Clinical Emergency, Cardiovascular Rehabilitation, University of
Medicine and Pharmacy “Victor Babes” Timisoara
Adrress for correspondence: Dr. Lavinia Noveanu, Department of Physiology, University of Medicine and Pharmacy“Victor Babes”, 300041 Timisoara. E-mail: noveanu@umft.roABSTRACTThe CARDIORISK study comprised one group of 518 apparently healthy young adults, 375 girls and143 boys, with a mean age of 20 ± 2.25 years, who attended the first and the second year study at
University of Medicine and Pharmacy “Victor Babes” Timisoara.
We assessed the CVD risk factors using 4 methods: (a) the questionnaire method, (b) the
measurement of blood pressure, (c) the measurement of several anthropometric parameters, such as
body weight, body height, body mass index (BMI) and waist circumference, and (d) the
measurement of biochemical parameters such as plasma lipid profile (total cholesterol, triglycerides,
HDL-cholesterol, LDL-cholesterol), and fasting plasma glucose.
Great evidence was obtained that certain lifestyles related to tobacco smoking, physical inactivity,
unhealthy diet, and stress had an important incidence in medical young subjects, leading to adversechanges in physiological and biochemical characteristics, that enhance the development of an earlier
atherosclerosis in adulthood.
Key words: cardiovascular risk factors, young adult, blood pressure, dyslipidemia

3. BRIEF REVIEW: ROLE OF VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF)
IN ANGIOGENESIS
Daciana Nistor, Ioana Raluca Siska, Daniela Crisnic, Gabriela Tanasie, V Paunescu
Department of Physiology, University of Medicine and Pharmacy “Victor Babes” Timisoara
Address for correspondence: Dr. Daciana Nistor, Department of Physiology, University of Medicine and Pharmacy“Victor Babes”, 300041 Timisoara. E-mail: daciana_nistor@yahoo.com

ABSTRACT
Angiogenesis is a process of new blood vessel development from preexisting vasculature. It plays anessential role in embryonic development, normal growth of tissues, wound healing, the female
reproductive cycle (ovulation, menstruation and placental development), as well as a major role inmany diseases. Particular interest has focused on cancer, since tumors cannot grow beyond a few
millimeters in size without developing a new blood supply. Angiogenesis is also necessary for the
spread and growth of tumor cell metastases.
VEGF is a key regulator of physiological angiogenesis during embryogenesis, skeletal growth andreproductive functions. VEGF has also been implicated in pathological angiogenesis associated withtumors, intraocular neovascular disorders and other conditions. The biological effects of VEGF are
mediated by two receptor tyrosine kinases (RTKs), VEGFR-1 and VEGFR-2, which differ
considerably in signaling properties. VEGF inhibitors are undergoing clinical testing in several
malignancies and other diseases.
Key words: VEGF, receptor, physiological angiogenesis, pathological angiogenesis.

4. THYROID HORMONES AND IMMOBILIZATION
Carmen Tatu1, RF Tatu2, V Dumitraşcu3, Daniela Puşcaşiu4, Gabriela Tanasie1, Florina Mirea1,
Fr Schneider1
1
Department of Physiology
2 st
1 Department of Orthopedics and Trauma
3
Department of Pharmacology
4
Department of Molecular and Cellular Biology
University of Medicine and Pharmacy “Victor Babes” Timisoara
Address for correspondence: Dr. Carmen Tatu, Department of Physiology, University of Medicine and Pharmacy “Victor
Babes”, Eftimie Murgu Square No. 2, 300041 Timisoara. E-mail: carmentatu@hotmail.com

ABSTRACT
Prolonged immobilization, due to the stress generated by it, leads to different modifications of blood
parameters, including the thyroid hormones.
The purpose of this study is to monitor the variations in thyroid hormones concentration during theimmobilization period.
A group of 15 immobilized patients were taken into this study, who were hospitalize in a specialty
department due to fractures of the inferior members, without suffering from other diseases orcomplications of the fractures. Venous blood samples were taken in the first day of immobilization,
and T4 and TSH determinations were performed. The same determinations were performed in the
14th day of immobilization. A significant increase of T3 was noticed (p<0.05) after theimmobilization period, while the levels of T4 and TSH were not significantly decreased.
The variation of thyroid hormones level during immobilization depends on the period of time thisimmobilization is required. Compared to the increase of thyroid secretion that occurs in short time
immobilization (4-6 days), in long time immobilization (14-25 days), which leads to specific changes
in lipids metabolism, a decrease of thyroid hormones concentration is noticed, which can be
explained by reduced stimulation of thyroid gland, as an adaptive response to the decreased body
physical load.
Key words: immobilization, thyroid hormones, TSH, T3, T4.

5. EFFECTS OF ZOPICLONE ON BLOOD GLUCOSE LEVEL AND SERUM LIPIDS IN
STREPTOZOTOCIN –INDUCED DIABETES IN RATS
J Horák1, B Cuparencu2, Aliz Horák3, Cecilia Bobos4
1
Department of Pharmaceutical Pharmacology, Faculty of Medicine and Pharmacy, University of
Oradea2
Department of Medical Pharmacology, Faculty of Medicine and Pharmacy, University of Oradea
3
Institute of Oncology “Ion Chiricuţă” Cluj-Napoca
4
University of Medicine and Pharmacy “Iuliu Haţieganu” Cluj-Napoca
Address for correspondence: Prof. Dr. József Horák, 3400, Cluj-Napoca, No. 7 Ion Andreescu Street, Apt. 3

ABSTRACTIn rats with streptozotocin-induced diabetes (65mg/kg, i.v., repeated for five days), the blood glucose
level, serum total cholesterol, serum triglycerides and free glycerol were increased, whereas the freefatty acids (FFA) level was decreased, zopiclone (2.5 mg/kg – 5.0 mg/kg – 10.0 mg/kg i.p., for fivedays) very significantly decreased blood glucose and serum lipids level, elevated by theadministration of streptozotocin. In the same time, zopiclone increased the level of FFA. It ishypothesized that the anti-diabetic effects of benzodiazepines and zopiclone are due to thestimulation of peripheral type of benzodiazepine receptors.
Key words: rats, streptozotocin, diabetes, zopiclone, blood glucose, serum lipids.

6. ANGIOGENESIS SIGNIFICANCE IN RENAL CARCINOMAS PROGNOSTIC
Daniela Puscasiu1, Corina Flangea2, Carmen Tatu3, Doina Verdes1, Elena Potencz, RF Tatu4,
Florina Mirea3
1
Department of Molecular and Cellular Biology
2
Department of Biochemistry3
Department of Physiology
4 st
1 Department of Orthopedics and Trauma
University of Medicine and Pharmacy “Victor Babes” Timisoara
Address for correspondence: Dr. Daniela Puscasiu, Department of Molecular and Cell Biology, University of Medicine
and Pharmacy “Victor Babes” 300041 Timisoara. E-mail: danielapuscasiu@yahoo.com

ABSTRACT
Angiogenesis represents one of the important factors of tumor proliferation (8). Theoretically, an
intense neovascularization allows a rapid tumor growth, while the decrease of angiogenesis process
will reduce or even stop the neoplazic growth (5).
In our study we tried to establish a correlation between tumor angiogenesis and the prognostic ofrenal carcinomas. A number of 43 patients were monitored, which had operated renal tumors, in the
Department of Urology of the County Hospital 1 Timisoara. The surgical treatment performed wastotal nefrectomy. The surgical excision pieces were processed by the Morphopathology Laboratoryof County Hospital 1 Timisoara and the Histopathology Laboratory of the Department ofMorphopathology from University of Medicine and Pharmacy “Victor Babes” Timisoara. In order toreveal the angiogenesis, the tissue samples were processed by usual methods (paraffin inclusion,
several sections were made, hematoxylin-eosin staining), and by special methods ofimmunohistochemistry for CD31, using CD31 DACO monoclonal antibody; for revealing we usedthe DACO peroxidase system LSAB2, the chromogen being DAB.
From the 43 tumors, 9 of them were well differentiated in G1, 27 of them in G2, and 7 tumors wereweakly differentiated in G3. The relative vascular density determined by microscopy, showed thehighest values in case of G1renal carcinomas, of 27.35. The lowest vascular density, of 4.95, wasachieved for the less differentiated carcinomas. For G2 tumors, the relative vascular density was
11.98. The relative vascular density assessed by immunohistochemical reaction to CD31, indicatesan inverse proportionality between the tumor differentiation degree and vascular density (13).
Key words: angiogenesis, neovascularization, renal carcinoma, immunohistochemistry.

7. P53 EXPRESSION IN HODGKIN LYMPHOMA – A TUMORAL PROGRESSIONINDEX?
Corina Flangea1, Daniela Puşcaşiu2, Atena Găluşcan3, Elena Potencz4, A Anghel1, S Gîju5,
Carmen Tatu6
1
University of Medicine and Pharmacy “Victor Babeş” Timişoara, Biochemistry Department
2
University of Medicine and Pharmacy “Victor Babeş” Timişoara, Molecular and Cell Biology
Department
3
University of Medicine and Pharmacy “Victor Babeş” Timişoara, Community Preventive Dental
Medicine and Oral Health Department
4
University of Medicine and Pharmacy “Victor Babeş” Timişoara, Pathology Department
5County Hospital No. 1 Timisoara, Central Laboratory
6
University of Medicine and Pharmacy “Victor Babeş” Timişoara, Department of Physiology
Address for correspondence: Dr. Corina Flangea, Department of Biochemistry, University of Medicine and Pharmacy“Victor Babes” 300041 Timisoara. E-mail: flangea corina@yahoo.com

ABSTRACTP53 protein suffers mutations at malignant cells level, becoming stable and accumulating at thesecells level, thus, could be revealed by immunohistochemical methods. 64 hospitalized in Hematology
Department of City Hospital Timişoara cases of Hodgkin’s disease were studied. The p53 expression
was immunohistochemical semi quantitative evaluated using clone DO7 as monoclonal antibody and
LSAB2-Peroxidase/DAB system for visualization.
In our study, p53 expression isn’t associated with disease progression, nor with histological type,because weak positive (-/+) interval into were situated the majority of cases is irrelevant for all
histological type or stage association. Depending by literature data too, we recommend giving up to
p53 expression determination including as tumor proliferation index in Hodgkin’s lymphomas.
Keywords: Hodgkin’s lymphoma, p53, tumor progression.

8. THE INFLUENCE OF CORONARY RISK FACTORS ON THE PROGRESSION OF
AORTIC STENOSISElena Ardeleanu1, Rodica Mateescu2
1
Department of Family Medicine
2
Department of Physiology
University of Medicine and Pharmacy “Victor Babes” Timisoara
Address for correspondence: Prof. Dr. Elena Ardeleanu, Family Medicine Department, University of Medicine andPharmacy “Victor Babes”, 300041 Timisoara

ABSTRACTThe aim of the present study was to identify the prevalence of aortic valve abnormalities in an elderlygroup, the clinical factors associated with degenerative aortic valve disease and to analyze theinfluence of the risk factors of atherosclerosis on the progression of mild aortic stenosis.
The study was made on 386 elderly patients (age over 65 years), of which there are 218 men (60%)
and 168 women (40%). 270 cases (70%) had normal valves, 95 cases ( 25 %) presented aortic
sclerosis and 19 cases (5%) aortic stenosis (3 severe AS and 16 mild AS).
The progression of mild aortic stenosis (increase in peak systolic gradient across the aortic
valve/year) was studied on 16 patients with mild aortic stenosis. Progression was statisticalsignificant associated to age, current cigarette smoking, systemic hypertension, diabetes mellitus,
high LDL and low HDL cholesterol.
The patients with LDL cholesterol ≥125 mg/dl received treatment with statins. The statins reduced
the mean serum LDL cholesterol from 182 ± 20 to 116 ± 11 mg/dl (p <0.001), increased the mean
serum HDL cholesterol from 41 ± 9 to 45 ± 9 mg/dl (p<0.001) and reduced the mean serum
triglycerides from 135 ± 45 to 118 ± 40 mg/dl (p<0.001).
The conclusion of the study is that mild aortic stenosis is influenced by the following independentrisk factors: smoking (p<0.0001), hypertension (p<0.0001), LDL cholesterol ≥ 125 mg% (p<0.001),
HDL cholesterol ≤ 35 mg (p<0.001), diabetes mellitus (p<0.001) and the use of statins (inverse
association, p < 0.001).
Key words: aortic stenosis, progression, coronary risk factors.

9. BOOK REVIEW: CHEMOINFORMATICS IN DRUG DISCOVERY
Tudor I Oprea
Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA, 2004, xxii + 493 pp. ISBN 3-52730753-2, Vol 23 in series Methods and Principles in Medicinal Chemistry;
Series editors: R Mannhold, H Kubinyi, G Folkers
Intersection between two large domains, chemistry and informatics, is as old as information
technology itself. There were created many data bases comprising an enormous amount of
information about many chemical compounds and dedicated software for applications in chemistrywere developed. However, the term “chemoinformatics” is quite new, being introduced in 1998 by
Franck Brown, who defined it as “the mixing of information resources relevant in the drug discovery
process, to transform data into information and information into knowledge for the intended purposeof making better decisions faster in the area of drug lead identification and organization”.
Chemoinformatics has a central concept: chemical information and the definition presented above
intends to cover all possible operations related to it: design, creation, organization, storage, retrieval,analysis, visualization and use. The present volume on “Chemoinformatics in Drug Discovery”
covers all these important aspects in a systematic manner.
The editor, Tudor Oprea, is now Professor of Biochemistry and Molecular Biology at University of
New Mexico School of Medicine in Albuquerque. He did his studies in Timisoara and had his Ph.D.
thesis supervised by Francisc Schneider. He was a post-doctoral fellow at Washington University
and Los Alamos National Laboratory, and then worked six years for Astra Zeneca in Sweden. In
2002 he received the Hansch Award from the QSAR and Modeling Society. With such a soundbackground in both medicine and chemistry and a solid experience in research, he put his fingerprint
on this volume not only as author but also by arranging hierarchically the chapters, driving the reader

in an attractive way from the theoretical background in the first part to the practical applications inlast part.
The book starts with an excellent introduction by Garland Marshall followed by four sections. The
first one is focused on Virtual Screening and lead discovery, covering aspects of screening set
design, algorithmic engines and pharmacophore-based virtual screening. The second section, Hit andLead Discovery refers to various performant in silico technologies. In the third section, Databases
and Libraries, data collection and mining using chemical databases are discussed in the context ofchemical libraries. Finally, in the last section, Chemoinformatics Applications, specific applications
and examples are collected, bringing together industrial and academic perspectives. The volumeconcludes with another excellent account, by Dan Abraham, on drug discovery.
We can trace across the book, as a red thread, the progression from hit identification to leadgeneration, then to lead optimization up to candidate drug nomination. A large variety ofchemoinformatics tools and strategies serve this purpose. All these new procedures underline theprogress in preclinical drug discovery process as well as its needs for novel technologies and for
integrated informatics support. The huge span, from atomic level in drug-receptor binding up topharmacokinetics profiling, is likely to lead towards a better path for drug discovery.
The book is written in an excellent academic style. Even the level is advanced; it is accessible also
from introductory level. The transition between chapters is smoth and the contents cover a large
variety of items, being recommended not only to biochemists, pharmacologists and bioinformaticians
but also to researchers in neighboring fields.
I join the opinion of the series editors who remarked Tudor Oprea’s enthusiasm to organize thevolume and work with such a fine selection of authors from several research centers in USA,
Germany, France, UK, Switzerland, Sweden and Romania.
George I Mihalas
Department of Biophysics and Medical Informatics“Victor Babes” University of Medicine and Pharmacy
Timisoara, Romania