FIZIOLOGIA (PHYSIOLOGY) 2005; vol. 15, nr. 4 (48)
CONTENTS
1. Editorial: “Fiziologia – Physiology” after 15 years of NEW SERIES
Fr. Schneider, Ioana-Raluca Siska
2. “Fiziologia – Physiology” - after 15 years
M. Sabau
3. A Happy Aniversary: "Fiziologia - Physiology" - At fifteen years of existence
Gh. Benga
4. Review: Behavioral nociceptive testing in mononeuropathies
O.I. Coste, K. Scholich
5. Minireview: Dendritic cells. Therapeutic implications.
Cristian Oancea, Lucian Jiga, Janina Jiga, Carmen Bunu, Florina Mirea, Virgil Păunescu
6. The effects of trazodone subacute administration on analgesy tests in rats
Anca Dana Buzoianu, Ioana Miclutia, Soimita Suciu
7. Role of oxygen reactive species in vulgar psoriasis
Daniela Pop Vornicescu, Adriana Filip, Simona Clichici, Maria Crisan, Adriana Muresan, Nicoleta
Decea
8. Influence of exposure to continual dark and continual light on certain oxidative stress parameters inthe brain
Adriana Filip, Daniela Pop, Simona Clichici, Adela Joanta, Adriana Muresan, A. Miu, C. Login9. Twenty years since the discovery of the first water channel protein by Gheorghe Benga’s group in
Romania
Fr. Schneider
10. Petition for the recognition of Gheorghe Benga as a discoverer of the first water channel proteinin the human red blood cell membrane, several years before Peter Agre (2003 Nobel prize forchemistry)
11. CD31 expression significance in Hodgkin’s disease agressivity
Corina Flangea, Daniela Puscasiu, Elena Potencz, A. Anghel, C. Dogaru, Carmen Tatu, S. Giju
12. Magnesium – between normal involvement and therapeutic uses
M. Nechifor
1. “FIZIOLOGIA – PHYSIOLOGY” AFTER 15 YEARS OF NEW SERIESFrancisc Schneider, Ioana-Raluca Siska
The journal was first published in 1954 and for 19 years represented one of the major journals in thefield of medical fundamental research. It was initiated by a group of outstanding Romanianphysiologists in order to publish original research articles in every aspect of physiology and related
fields. Among the first editors of the journal were prominent members of the Romanian Academy,
Daniel Danielopolu, Grigore Benetato, and Petru Groza, who managed to cover all major researchareas of the Romanian physiology.
The first number of the journal had a prestigious editorial board – Daniel Danielopolu, Gh.
Arsenescu, Gr. Benetato, I. Haulica, I. Nitescu, I. Nitulescu, V. Rascanu, M. Saragea, M. Mozes, St.
Szabo, P. Groza, as well as Professor Marin Popescu from Timisoara. The first issue included several
original articles, such as “Non-specific pharmacodynamic studies” by Daniel Danielopolu. In one of
its issues, Professor Ioan Baciu also published his studies regarding erythropoietin andchronobiology. The last number of the journal issued in 1973 (volume XIX, no.6), had among its
editors distinguished professors, as Petru Groza, Gheorghe Arsenescu, Ioan Baciu, Ion Cotaescu and
Fl. Ulmeanu and included original papers published by Ana Aslan, as well as by a well-known teamof cardiologists leaded by Professor Stefan Gavrilescu from the Institute of Medicine in Timisoara.
Timisoara gathered the circuit of physiological sciences only in the last four and a half decades,
beginning with the initiation of the Institute of Medicine and the publishing of the studies performed
Ilie Georgescu, Marin Popescu, Ion Cotaescu, Mihai Vanghelovici, Maria Mihailescu, Nicolae
Dragomir and Zeno Simon. The Physiology Department of the Victor Babes University of Medicine

and Pharmacy Timisoara became recognized especially for the fundamental and clinical researches
regarding the exercise physiology, bronchomotricity and oxidative stress physiology, and also fororganizing six successful national conferences. The first years of the new millennium added to theabove mentioned themes a new challenging one – stem cell physiology and its potential applications.
In 1991, in view of the rapid developments in physiology research and the need for national andinternational scientific communication, the Physiology Department of the University of Medicine
and Pharmacy Timisoara restarted the editing of Fiziologia in English, with a new title “Fiziologia –Physiology”. Its initiators – Professor Francisc Schneider, chief-editor, and Professor Ana Petroiu
and Dr. Aurelian Vlad as co-chief editors, tried to continue the Romanian tradition in the field ofnormal and pathological physiology. Its rebirth was stormy, and the conditions which led up to its
start continued for a number of years to assist its survival. An important contribution to thecontinuous publication was ensured by several sponsors such as Soros Foundation, Mr. Nicolae
Marcu from Spumotim SA Timisoara and Mr. Mircea Roman from Sanevit SA Arad. In the lastyears, the journal was also supported by Professor Adriana Muresan and the Physiology Department
in Cluj, and last, but not least, by Professor Sabau from Targu-Mures University of Medicine andPharmacy, the president of the Romanian Society of Physiological Sciences.
The journal received and published original research papers in all areas of physiology illustrating
new physiological principles or mechanisms, as well as papers on work at the molecular level, at thelevel of the cell membrane, single cells, tissues or organs and systems physiology, with emphasis on
both human and mammalian physiology. The journal reflected most of the experimental and clinicalresearch performed in our country.
In the last two decades, Romanian physiologists became involved in several modern research fields.
Physiologists from Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, leaded byProfessor Adriana Muresan developed a strong centre for the study of oxidative stress. In Craiova,
Professor Valeriu Nestianu was the initiator of neurophysiology, creating a real school in this field.
In Iasi, Professor Ion Haulica, member of the Romanian Academy, one of the pioneers of reninangiotensin system researches in both Romania and Europe initiated a wide research programme inthis area. Another prominent physiologist in Iasi was the initiator of synaptology – Professor V.
Branisteanu.
Last, but not least, in the last 15 years, “Fiziologia-Physiology” became an image of progress inRomanian physiology. Resurrected after a pause of 18 years, the journal aims to present the mostvaluable fundamental studies performed by Romanian scientists. The wide scientific span of thejournal rests on physiology as its keystone. However, the boundaries of physiology have enlarged as
demarcations between concepts and techniques in the physiological, pharmacological, andbiochemical sciences became increasingly blurred. Moreover, theoretical articles on research at any
level of biological organization ranging from molecules to humans fall within the broad scope of thejournal. Papers dealing with topics in other basic sciences that impinge on physiology are also
welcome.
We hope that every paper issued in Fiziologia – Physiology will make not only a solid contribution
to knowledge but will maintain the standard of form and style desired, with succinctness, perfectlucidity and minimum of speculative discussion. The Editors try to remember that it is the labor of
authors, not of editors that sell the journal, and hope that authors still feel that their offerings arewelcomed and treated with sympathy.
2. FIZIOLOGIA-PHYSIOLOGY - after 15 years
Professor Marius Sabau, President of the Romanian Society of Physiological Sciences
FIZIOLOGIA-PHYSIOLOGY, the official journal of the Romanian Society of Physiological
Sciences, is now 15 years old. Resuming the activity of the former Journal of Normal and Pathologic
Physiology interrupted in 1973, the new Physiology "remains open to a broad national andinternational collaboration....reflecting both basic research and applied physiology" as stated in 1991
the first editorial.
Since that time the quality of the journal improved continuously in all respects and was recognizedby the National Council for Scientific Research which placed it among the other important Romanian
medical scientific publications.

The use of English language and the exchanges with other journals offered more accessible
information concerning the activity of Romanian physiologists.
The 48 issues that appeared until now covered a wide area of research in which today's physiologists,
especially the young ones, were involved.
The publication of the summaries of the papers presented at scientific meetings or of the themes ofsuch events, the book reviews contributed to a better information of those interested in scientific or
editorial news.
The words of the senior Romanian physiologist professor Ion Haulică written at the 10th anniversaryof the journal are still valid "Maintaining this course, the journal will continue to prestigiously
represent the physiological sciences in out country, both at the national level and abroad".
Depends only on us to demonstrate that what we publish in our journal represents really the
preoccupations of Romanian physiologists and these are oriented towards the most important
domains of the today's science.
I am convinced that after 15 years, the efforts made by the editorial board headed by Professor
Francisc Schneider, the eminent chief-editor, begin to bear fruits and for that I wish them success.
3. A HAPPY ANIVERSARY:"FIZIOLOGIA - PHYSIOLOGY" AT FIFTEEN YEARS OF EXISTENCE
Gheorghe Benga
Department of Cell and Molecular Biology, "Iuliu Haţieganu" University of Medicine and Pharmacy
Cluj-Napoca, Romania
When a scientist is starting a new journal in the last decade of the last Millennium, someone may
wander if will survive the turn of the Millennium and, if the answer is positive, whether it will be
successful. Such questions are warranted taking into account the great number of scientific journals
already published, particularly in the field of biomedical sciences.
Our distinguished colleague Francisc Schneider was undoubtedly a very courageous man when hestarted "Fiziologia - Physiology" fifteen years ago. There were already many journals of physiology,
however not so many published in the Central and South Eastern Europe. Therefore Professor
Schneider was entitled to start a new journal in this field. On the other hand, Francisc Schneider washimself involved in active research in physiology, as well as in teaching and organization of research.
He has reorganized teaching and research in normal and pathological physiology at the "VictorBabeş" University of Medicine and Pharmacy in Timişoara. Using funding from grants Francisc
Schneider has refurbished and fully equipped the Department of Physiology in Timişoara and has
selected and trained many young very gifted medical students, to become later Professors inTimişoara or elsewhere in the world.
After a few years, when he moved to the "Vasile Goldiş" Western University Arad, also taking theburden of the responsibility of leading the scientific research of the university as Vice-Rector with
scientific affairs, Francisc Schneider brought with him the same high standard of expertise, doubled
by his determination to raise at high levels the teaching and research, not only in physiology andpathophysiology, but in all basic medical sciences at this university. It was very fortunate that
Professor Aurel Ardelean was a very distinguished Rector and was teaching cell and molecularbiology to medical students. Together with other distinguished colleagues, Professors Ardelean andSchneider formed a team determined to bring this new university to international standards in bothteaching and research.
In parallel with all these duties Francisc Schneider found the time to start this new journal 15 years
ago and to act as Editor-in-Chief for so many years. Under his editorial leadership the new journal
grew quite well, became an important one in Romania and in this part of Europe. In the journal were
published many interesting papers, both reviews and original research papers. I am convinced thatsoon the international recognition of "Fiziologia - Physiology" will be accomplished at higher levels.
I was very honored when I was invited to be a member of the Editorial Board of "Fiziologia Physiology" and found it a privilege, since it enabled me to see many of the valuable contributions to
the journal. Fifteen years of publication of any journal is a significant period of time to evaluate its
efficacy. I believe "Fiziologia - Physiology" has proved its great usefulness and reached a stage ofmaturity.

The 15th anniversary of the journal coincides with the 20th anniversary of the discovery in Romaniaof the first water channel protein in the red blood cell membrane by our group in Cluj-Napoca,
Romania. Francisc Schneider was one of the distinguished scientists who supported from the first
moment our struggle for recognition of our priority after the 2003 Nobel Prize in Chemistry wasawarded "for the discovery of water channels". A full story can be found at www.ad-astra.ro/benga
and a summary is presented in this issue by Francisc Schneider.
On the occasion of the 15th anniversary of this journal I wish to Prof. Francisc Schneider good health,and to "Fiziologia - Physiology" the traditional "Many Happy Returns", so that we have the pleasure
to see it published a lot of years from now on, and to continue to enrich the scientific literature withinteresting papers in one of the most dynamic fields of biomedical sciences.
4. BRIEF REVIEW: BEHAVIORAL NOCICEPTIVE TESTING IN MONONEUROPATHIES
Ovidiu I. Coste1,2, Klaus Scholich2
1
Department of Physiology, Victor Babes University of Medicine and Pharmacy Timisoara, Romania
2
Pharmazentrum Frankfurt/ZAFES, Klinikum der Johann Wolfgang Goethe-Universitat Frankfurt,Frankfurt am Main, Germany.
Address for correspondence: Dr. Ovidiu Coste, Pharmazentrum Frankfurt/ZAFES; Klinikum der Johann Wolfgang
Goethe-Universitat Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt/Main, Germany. e-mail: ovidiu_coste@yahoo.com

ABSTRACTThe neuropathic pain syndrome can not be adequately treated with the currently available analgesics,
leading to a loss of life quality for the affected patients. New drugs are proposed continuously andneed to be validated in animal models for neuropathic pain before entering clinical studies. Several
models for neuropathic pain were developed based on various lesions of the sciatic nerve.
Neuropathic pain symptoms such as mechanical allodynia as well as thermal hyperalgesia andallodynia can be observed in the established models. The main symptom of the neuropathic pain
syndrome, spontaneous pain, is still poorly assessed by existing tests and therefore new tests areneeded. The specific behavioral tests used to quantify these symptoms are reviewed.
Key words: neuropathic pain, behavioral nociceptive tests
5. MINI-REVIEW: DENDRITIC CELLS. THERAPEUTIC IMPLICATIONS
Cristian Oancea1, Lucian Jiga2, Janina Jiga3, Carmen Bunu1, Florina Mirea1, Virgil Paunescu1
1
Department of Physiology and Immunology, 2Department of Microsurgery, 3Department of
Hematology, “Victor Babes” University of Medicine and Pharmacy Timisoara
Address for correspondence: Dr. Cristian Oancea, Department of Physiology and Immunology, “Victor Babes”
University of Medicine and Pharmacy Timisoara, 2, E. Murgu Square, 300041 – Timisoara. E-mail: oancea@umft.ro

ABSTRACT
Dendritic cells (DCs) are considered the most powerful antigen presenting cells (APC), having apivotal role both in the initiation of the primary immune response, and in the augmentation of thesecondary immune response. DCs differ from other APC, as B cells, monocytes or macrophages by
their unique capacity to stimulate naive T cells in vivo and in vitro and to induce the immune
response polarization towards a Th1 or Th2 profile. These two types of T lymphocytes response differ
on the basis of cytokines production, and also by the functional effects exerted by Th1 and Th2 cells
after their contact with the antigen. There is evidence to suggest that tumor antigen delivery to thelymphocytes by dendritic cells can stimulate strong cellular immune responses against tumors.
Key words: dendritic cell, APC, cancer therapy, allergy

6. THE EFFECTS OF TRAZODONE SUBACUTE ADMINISTRATION ON ANALGESYTESTS IN RATS
Anca Dana Buzoianu1, Ioana Miclutia2, Soimita Suciu3
1
Department of Clinical Pharmacology, 2Department of Psychiatry, 3Department of Physiology,“Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Romania
Address for correspondence: Conf. Dr. Anca Buzoianu, Department of Clinical Pharmacology, Iuliu Hatieganu
University of Medicine and Pharmacy Cluj-Napoca, 1, Clinicilor Str., 400006 - Cluj-Napoca, Romania

ABSTRACT
Trazodone is in atypical antidepressant which acts by complexing mechanisms involved in themodulation of pain phenomenon. The aim of this study is to investigate the possible role of trazodone
in the transmission and perception of pain, by studying its subacute administration on analgesic tests
on laboratory animals. The sample was represented by 50 white male rats divided in five groups. The
animals were injected with 2 different doses of trazodone (1 mg/kg, 5 mg/kg), and the association
naloxone-trazodone, and trazodone- ciproheptadine. The analgesia was evaluated by the hot-plate
test and the paw compression using an Ugo Basile analgesy-meter. The results show a clear dose
dependent analgesic effect of trazodone. This analgesic effect of trazodone was diminuated bynaloxone association and also by ciproheptadine administration, suggesting an intervention of opioidand serotoninergic mechanisms.
Key words: analgesy, antidepressants, trazodone
7. ROLE OF OXYGEN REACTIVE SPECIES IN VULGAR PSORIASIS
Daniela Pop Vornicescu1, Adriana Filip2, Simona Clichici2, Maria Crisan1, Adriana Muresan2,
Nicoleta Decea2
1
Dermatology Department “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca
2
Physiology Department “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca
Address for correspondence: Dr. Daniela Pop Vornicescu, Department of Dermatology, Iuliu Hatieganu University of
Medicine and Pharmacy Cluj-Napoca, 1, Clinicilor Str., 400006 - Cluj-Napoca, Romania

ABSTRACT
Although psoriasis is one of the most common dermatoses, the etiopathogenetic mechanisms
involved in this disease have not been yet fully elucidated. The investigations carried out during thelast years had confirmed the role of oxygen reactive species as signal molecules in the activation of T
lymphocytes and in keratinocyte proliferation.
The aim of the present study was to demonstrate the involvement of the redox imbalance in theoccurrence of the disease and especially of its severe forms.
Key words: psoriasis, antioxidants, lipid peroxides, catalase, and hydrogen donor capacity
8. INFLUENCE OF EXPOSURE TO CONTINUE DARK AND CONTINUE LIGHT ON
CERTAIN OXIDATIVE STRESS PARAMETERS IN THE BRAIN
Adriana Filip1, Daniela Pop2, Simona Clichici1, Adela Joanta1, Adriana Muresan1, Andrei Miu3,
Cezar Login1
1
Physiology Department, “Iuliu Haţieganu” Univ. of Medicine and Pharmacy Cluj-Napoca
2
Dermatology Department, “Iuliu Haţieganu” Univ. of Medicine and Pharmacy Cluj-Napoca
3Faculty of Psychology, "Babes-Bolyai" University Cluj-Napoca
Address for correspondence: Dr. Adriana Filip, Department of Physiology, Iuliu Hatieganu University of Medicine andPharmacy Cluj-Napoca, 1, Clinicilor Str., 400006 - Cluj-Napoca, Romania

ABSTRACTThe studies carried out during the last years on the mechanisms involved in brain aging and in thepathogenesis of neurodegenerative diseases discuss more and more on the neuronal effect of the free
radicals. Melatonin, the secretion product of the pineal gland, is an excellent endogenous antioxidant
playing a protecting role against oxidative stress in the nerve tissue. Starting from these data, thestudy aims at investigating the extent to which functional pinealectomy influences the oxidative
stress parameters in the brain and serum of Wistar rats. The animals were divided into three groups:
group 1(n=14)(controls) kept artificially for 3 months, 12 h at dark, 12 h at light; group 2 (n=14) kept
for 3 months at continual light, and group 3 (n=10) kept for 3 months at continual dark. The
experiments were performed in the months March-May. Lipid peroxides (LP) and carbonylated
proteins (CP) were determined as indicators of oxidative stress and for the estimation of theantioxidant states the total SH groupings were assayed. The results obtained demonstrate that the
exposure to light induces the oxidative stress, this effect being especially detected in the serum(serum LP 2.41±0.24 nmoles/ml as against 1.90±0.76 nmoles/ml p<0.001; brain LP 2.36±0.26
nmoles/mg protein as against 2.26±0.28 nmoles/mg protein, p>0.05. Continuous dark intensifies theformation of lipid peroxides, these increasing especially in the serum (serum LP 2.64±0.61
nmoles/ml as against 1.90±0.76 nmoles/ml and brain LP 2.46±0.40 nmoles/mg protein as against
2.26±0.28 nmoles/mg protein p>0.05) possibly due to the reduction of the serum concentration of
total SH groupings (0.16±0.05 μmoles/ml as against 0.21±0.03 μmoles/ml, p<0.01). The level of
total SH groupings in the brain is significantly increased in the conditions of keeping at dark (36 ±9,14 nmoles/mg P as against 16±4, 90 nmoles/mg P, p<0.001), suggesting that the increased melatoninsecretion acts in conjunction with the protecting effect of glutathione and counteracts the formationof the free radicals in the brain.
Keywords: melatonin, light, dark, lipid peroxides, carbonylated proteins, total SH groupings
9. TWENTY YEARS SINCE THE DISCOVERY OF THE FIRST WATER CHANNELPROTEIN BY GHEORGHE BENGA’S GROUP IN ROMANIA
Francisc Scheider
Department of Physiology, “Vasile Goldiş” Western University, Arad, Romania
In 1986, after a decade of systematic studies on water channels in human red blood cells (RBC)
performed at “Iuliu Hatieganu” University of Medicine and Pharmacy in Cluj-Napoca, Romania,
Gheorghe Benga and coworkers discovered the first water channel protein in the human RBC
membrane (8). The presence and location of this water channel protein was detected among
polypeptides migrating in the region of 35-60 kDa on the electrophoretogram of RBC membranes,
labeled with 203Hg-p-chloromercuribenzene sulfonate (PCMBS) under conditions for the specificinhibition of water diffusion. In the landmark publication (8) Benga also indicated the way to further
studies, by purification and reconstitution in lipid vesicles (liposomes). This work was extended (7)and reviewed by Benga in several articles (3-6) including a chapter in a book published in the USA(2).
In 1988, Peter Agre and coworkers, while working on the rhesus blood group antigen at Johns
Hopkins University in Baltimore, USA, serendipitously isolated a new 28 kDa membrane proteinfrom human red blood cells, called CHIP28 (“channel forming integral membrane protein of 28kDa); in addition to the 28 kDa component, this protein had a 35-60 kDa glycosylated component,
the one discovered in 1986 by Benga’s group. Agre and coworkers suggested that "this new protein
may play a role in linkage of the membrane skeleton to the lipid bilayer" (15,21). Only in 1992,
Agre’s group suggested that "it is likely that CHIP28 is a functional unit of membrane water
channels" (19). In this report, they cited a paper of Benga and coworkers from 1983 (9), without
mentioning their landmark 1986 studies (8,7) or any of the reviews (3-6). In 1993 CHIP28 wasrenamed aquaporin 1 (the first water channel protein).
In October 2003, Peter Agre was awarded the Nobel Prize in Chemistry "for the discovery of water
channels". An invited review of the history of the discovery of water channels proteins was publishedby Benga in September 2003, one month before the Nobel Prize for Chemistry was awarded (10).
The seminal contributions from 1986 of the Benga’s group, also mentioned in this review, werecompletely overlooked by the Nobel Prize Committee. No mention of the results of Benga andcoworkers appeared in the historical description of the discovery of aquaporins that joined the prizeannouncement.
It is obvious and overwhelmingly documented from the facts presented above that the first water
channel protein (aquaporin 1) was first discovered by the Romanian scientist Gheorghe Benga andhis group (8), who detected the glycosylated form of the protein (subsequently worked on by Agre’s
group), which they correctly identified as playing the key role in water transport across RBC
membrane.
As discussed by Benga (10) the landmark papers of his group in 1986 (8,7) can be compared with thefirst detection of a child “in utero” by ultrasonography, or with the discovery of The New World of
America; the first man who has “seen” a part of The New Land was Columbus; later, others,
including Amerigo Vespucci (from whom the name derived), have better “seen” larger parts and thecomplexity of the Americas!
After the announcement of the 2003 Nobel Prize in Chemistry was released by Nobel Foundation
Gheorghe Benga received a multitude of spontaneous messages (phone calls, E-mailed messages andfaxed letters) from all over the world. The scientists who sent messages to Gheorghe Bengaconsidered that in fact he and his group have first discovered the first water channel protein in the red
blood cell membranes (the protein later called aquaporin1). As a result Gheorghe Benga wrote a
PETITION for the recognition of his priority, PETITION that is reproduced in this issue. The above
mentioned claim and the PETITION was presented by Gheorghe Benga on October 18th at the 6thInternational Symposium of Molecular Medicine (Hersonissos, Crete, Greece) and immediately
dozens of scientists from a lot of countries have signed in support of his PETITION.
The priority of Gheorghe Benga’s group in the discovery of the first water channel protein has been
mentioned in comments on the 2003 Nobel Prize in Chemistry (11-14, 16-18, 20, 22, 23,). Although
in his Nobel Lecture (1) Agre mentioned twice Benga among “pioneers in water transport field”,
Benga’s publications were not listed among the references.
Benga’s claim is presented on the web site of the Ad Astra Association (www.ad-astra.ro/benga)
where a full story can be seen. The recognition of Gheorghe Benga as a discoverer of the first water
channel protein from the human RBC membrane is growing. Thousands of science-related
professionals from hundreds of academic and research units, as well as participants in several
international scientific events, have signed as supporters of the priority of Benga’s group in the
discovery of the first water channel, as can be seen at www.ad-astra.ro/benga/support.
The above mentioned facts were also presented by Gheorghe Benga in 2003-2005 in invited lecturesat over 30 international scientific events and in dozens of seminars at many European, Americanand Japanese universities, as well as at some World conferences (24, 25), steering favorable
reactions.

10. PETITION FOR THE RECOGNITION OF GHEORGHE BENGA, AS A DISCOVERER
OF THE FIRST WATER CHANNEL PROTEIN IN THE HUMAN RED BLOOD CELLMEMBRANE, SEVERAL YEARS BEFORE PETER AGRE (2003 NOBEL PRIZE FORCHEMISTRY)TO THE NOBEL COMMITTEE
TO THE SCIENTIFIC &TO ALL AUTHORITIES& ROYAL SWEDISH ACADEMY ACADEMIC COMMUNITY IN ROMANIAOF SCIENCES
AND MASS-MEDIASTOCKHOLM, SWEDEN
WORLDWIDEIn 1986, Benga and coworkers (1) clearly demonstrated for the first time the presence and location ofa water channel protein in the human red blood cell (RBC) membrane among polypeptides migratingin the region of 35-60 kDa on the electrophoretogram of RBC membranes, labeled with 203Hg-pchloromercuribenzene sulfonate (PCMBS) under conditions for the specific inhibition of water
diffusion. I suggested that a minor membrane component that binds PCMBS is involved in watertransport and also indicated the way in which the specific protein could be further characterized: by
purification and reconstitution in liposomes. In the same year the labeling experiments wereconfirmed and extended (2) and in the following 2-3 years I described the novelty of our work inseveral reviews (3-8).
In 1988, Agre and coworkers purified a new protein from the RBC membrane (9), nick-named
CHIP28 (channel-forming integral membrane protein of 28 kDa) (10). However, in addition to the 28
kDa component, the protein had a 35-60 kDa glycosylated component, i.e, the one we detected as thebinding site of PCMBS under conditions for the inhibition of water transport across the RBC
membrane (1,2). They suggested that CHIP28 may play a role in the linkage of the membraneskeleton to the lipid bilayer (9).
In 1990, Parker first suggested in personal discussion to Agre that the novel protein might be thewater channel, and in 1992 1Agre and coworkers (11), based on Windager’s suggestion to use oocyte
expression as a mechanism to study water transporters, found that oocytes from Xenopus laevis
microinjected with in vitro-transcribed CHIP28 RNA exhibited increased osmotic water
permeability. The water permeability was inhibited by mercuric chloride, therefore, it was suggested
that CHIP28 is a functional unit of membrane water channels. By reconstitution in liposomes it was
shown that CHIP28 is a water channel itself rather than a water channel regulator. In 1993 CHIP28
was renamed aquaporin 1.
It is obvious and overwhelmingly documented from the facts presented above that the first water
channel protein (aquaporin 1) was first discovered in 1986 by Benga et al. (1,2). He described one ofits essential components (a molecular weight of 35-60 kDa for the glycosylated component) and theway to distinguish it from other proteins (reconstitution in liposomes and measurement of water
permeability). Aquaporin 1 was first purified in 1988 and its water transport property was identified
in 1992 by Agre and coworkers (9, 11). It is also obvious that what we identified by labelingexperiments is the same protein that Agre and coworkers later purified, since they mentioned (11)that “the characteristics of CHIP28 are consistent with other known features of water channels, e.g.
CHIP28 proteins in intact RBCs are impervious to proteolytic digestion (9, 10), as are water channels(12)”.
As Agre and coworkers cited our 1983 paper (12) it is very surprising that they never cited ourlandmark 1986 papers (1,2); in contrast they referred only to work by other American scientists who
pointed to a non-specific “pore” that allowed for permeation of anions, cations, nonelectrolytes andwater (13). In contrast, we strongly argued all the time that there were indeed water channels in the
RBC membrane and indicated the way in which specific water channel proteins could be further
characterized by purification and reconstitution in liposomes.
I continued to be very active in the field, by achieving the purification of aquaporin 1 and developing
a new procedure for its quantification by densitometry of silver stained gel (14). Over the last
decade, we have characterized the water permeability of RBCs from over 30 species (reviewed in ref.
15, 16); we reported a positive correlation between the water permeability values of RBCs frommaternal venous blood and fetal RBCs isolated from cord blood taken at delivery. This points to a
genetic basis for the determination of RBC water permeability (17).
Our landmark papers in 1986 can be compared with the first detection of a child “in utero” byultrasonography, since we discovered one of the essential components of the “aquaporin child” (amolecular weight of 35-60 kDa for the glycosylated component); we have also indicated the way torecognize him after birth (among other children of his group!): placing the isolated children in acertain environment and asking them to perform the same task (one should read: reconstitution
studies in liposomes and measurement of water permeability), like aligning athletes for a running
test. This was the only certain way to know that the child is really the fastest runner and not just one
that is helping (by various means) another child to be the fastest runner. A “new child” was observedin 1988 by Agre and coworkers; however only in 1992 the child we first detected was recognized ashaving the predicted qualities.
Looking in retrospect, asking the crucial question, when was the first water channel protein,aquaporin 1, discovered, a fair and clear cut answer would be: the first water channel protein, now
called aquaporin 1, was identified or “seen” in situ in the human RBC membrane by Benga andcoworkers in 1986, It was again “seen” when it was by chance purified by Agre and coworkers in1988 and was again identified when its main feature, the water transport property, was found by
Agre and coworkers in 1992.

If a comparison with the discovery of The New World of America is made, the first man who has“seen” a part, very small indeed, of The New Land was Columbus; later, others, including Amerigo
Vespucci (from whom the name derived), have better “seen” a larger part of the new Continent andin the subsequent years many explorers discovered the complexity of the Americas!
I presented the complete history of the discovery of water channel proteins in an invited review (18)that was published one month before the Nobel Prize for Chemistry was awarded to Peter Agre for“the discovery of water channel proteins”. It appears that our seminal contribution in 1986 wasgrossly overlooked by Peter Agre and also by the Nobel Committee. It is another example of
mistakes in awarding Nobel Prizes, when a scientist who made the very first landmark contribution
to a discovery is left aside. This is my case in regard with the discovery of the first water channel
protein in the human RBC membrane.
For any scientist in the world dedicated to the truth and justice there is only one conclusion: Dr
Benga’s initial discovery must be properly credited by the Nobel Prize Committee.
The daily newspaper “Adevarul de Cluj” (19), this should be emphasized, has mentioned and put
together for the first time the two names Benga and Agre and the possibility of awarding to bothscientists the Nobel Prize for the discovery of aquaporin 1.
11. CD31 EXPRESSION SIGNIFICANCE IN HODGKIN’S DISEASE AGRESSIVITY
Corina Flangea1, Daniela Puscasiu2, Elena Potencz3, Andrei Anghel1, Constantin Dogaru1,
Carmen Tatu4, Sorin Giju5
1
Biochemistry Department, 2Molecular and Cell Biology Department, 3Pathology Department,
4
Physiology Department “Victor Babes” University of Medicine and Pharmacy Timisoara, 5Central
Laboratory Timisoara County
Address for correspondence: Dr. Corina Flangea, Department of Biochemistry, “Victor Babes” university of Medicine
and Pharmacy, 2, Eftimie Murgu Square, 300041, Timisoara, Romania

ABSTRACTIn most cases malignant tumor aggressivity is followed by angiogenesis estimation which has anactive role in tumoral mass spread and growth, because most vascularized tumors are the mostaggressive.
Between January 2000-June 2004, 63 cases of classical Hodgkin’s disease hospitalized in
Hematology Department of City Hospital Timisoara were studied. CD31expression estimation was
performed by immunohistochemical qualitative appreciation.
The monoclonal antibody was clone JC70A and the visualization system was LSABPeroxidase/DAB.
In our study, the rich vascularized CD31 positive cases were in stage IV and presented tumoral cells
in their lumen, confirming the hematological dissemination pathway described in the literature. In a
relative high number of cases, the existence of vessels without walls is observed only in mixed
cellularity and lymphocyte depletion lymphomas, indicating a high tumor aggressivity.
Key words: classical Hodgkin’s lymphoma, CD31, tumor aggressivity
12. MAGNESIUM – BETWEEN NORMAL INVOLVEMENT AND THERAPEUTIC USES
Mihai Nechifor
Department of Pharmacology, Gr.T. Popa University of Medicine and Pharmacy Iasi, Romania
Address of correspondence: Prof. Mihai Nechifor, Pharmacology Department, University of Medicine and Pharmacy“Gr. T. Popa” Iaşi, 16, Universitatii Str., 700115 Iasi, Romania

Between the 3rd and the 5th of November 2005, Bucharest was the host of the “5th National Congressof Magnesium”, its main theme being Magnesium in therapeutics - modern concepts.
The Symposium was organized by the Romanian Society for the Study of Magnesium and took placein the main building of Romanian Academy Library. It revealed the strong connection between

fundamental and applicative Romanian research and its alignment to the international trends andpreoccupations in the related fields.
Symposium’s programme consisted of four oral communication sessions and the course “Magnesium2005”, where Professor Corneliu Zeana, Dr. Paul Porr, Professor I. Gutiu, Professor Mihai
Nechifor, Dr. Manole Cojocaru have presented interesting lectures. The meeting also included amini-symposium organised by the firm Sanofi-Aventis, where Dr. C. Chira presented thecommunication: “MagneB6 – the Synergism between Magnesium and B6 Vitamin”.
The “5th National Congress of Magnesium” was organized by the Romanian Society for the Study ofMagnesium 6 years after the initiation of the Society, marking the ascending trend of its activity(president: Paul Porr). The same Society managed to organize the VIIIth European Magnesium
Congress at Cluj-Napoca in 2004, as well as a large palette of events with international participation,
including the “Magnesium Symposium” organized in Iasi in 2002.
The Romanian Society for the Study of Magnesium is quite young, but in Romania magnesium
research has a tradition of more than four decades, its major centers being Cluj, Iaşi and Bucharest.
Most of the papers presented at the Symposium came from these three universitary centers.
The national course “Magnesium 2005” approached largely theoretical and practical interest themes.
Professor I. Gutiu presented a lecture entitled “Magnesium, menopause and coronary heartdisease”, revealing the links between the impairment of magnesium metabolism after menopause andthe cardiovascular risk factors and coronary disease. Dr. Manole Cojocaru has revealed theinterrelations between magnesium and some hormones, and Professor Corneliu Zeană has
thoroughly presented the relationship between magnesium deficiency and mitral valve prolapse, as
well as the relationship between magnesium and cardiac arrhythmias. Professor Mihai Nechifor
spoke about the implications of magnesium in reproduction, detailing magnesium implications in
reproduction in case of both sexes. Our experimental data revealed that magnesium reduces benign
testosterone-induced prostate hypertrophy in animals and suggest that magnesium supplementation
may be beneficial in preventing or reducing benign prostate hypertrophy.
Dr. Paul Porr presented the relation between magnesium deficiency and digestive apparatus
pathology.
Other aspects discussed during the meeting were the possibility of existence of some correlations
between plasmatic and tissue concentration of magnesium and juvenile hypertension (Dr. A. Balla,
Odorheiul Secuiesc) and the possible connections between hypovitaminosis D and magnesium levelin elderly population (the last paper was presented by Dr. Otilia Voroniuc in Iasi and was performedin cooperation with Toronto University.)
Regarding the correlation between the tissue and plasmatic concentrations of magnesium and adultessential arterial hypertension, the latest published meta-analysis revealed its lack of existence (23trials agree that there is no correlation and only 3-4 sustain that low cellular or plasmatic magnesium
levels is associated with adult hypertension pathology). The trials about juvenile arterial hypertension
are fewer and the conclusions are not clear. This is an aria in which some extensive studies can be
performed relatively easy in Romanian pediatric hospitals.
Dr. Nicolae Ilinca (Bucharest) tackled the problem of some possible correlations between
intracellular magnesium levels and atopic dermatitis and Dr. Sorina Scipor (Bucharest) showed data
regarding the existence of the correlation between magnesium concentrations and alopecia.
Both absolute concentration and the ratio between magnesium and other cations were changed inneoplasms (original papers communicated by Dr. Marilena Cristea – Bucharest, and Dr. Irina
Gradinaru and other contribuitors in Iasi.
The Mg2+/Ca2+ salivary ratio in patients with malignant tumors of the oral cavity was significantly
higher than in normal subjects and patients with benign tumors of the oro-facial aria.
Other original papers stated the importance of magnesium level assessment in cardiovascularpathology (Dr. Isabela Silosi and Dr. Manole Cojocaru), the correlation between magnesium levels
during pregnancy and the new born health (Dr. Victoria Papadopol – Iasi), the correlation between
magnesium level, dental health and the atherogenic risk factors. (Professor I.A. Gutiu, Bucuresti).
Unquestionably, the current state of knowledge regarding magnesium implications in the pathogenyof some diseases improves continuously, enlarging the area of magnesium therapeutical indications.
More data strongly emphasize that in living organisms there are numerous interrelations betweencations and that cations behave like a system. Cations actions cannot be accurately understood unless
regarding these as a whole.
Professor Corneliu Zeana, the president of the symposium, had a prominent role in the organizationof the symposium, providing an adequate scientific programme and optimal conditions for
symposium proceedings. In Romania, the magnesium research registered an indisputably improveafter the establishment of the SRCM and these results succeeded to make the Romanian research inthis field also renowned outside the borders of our country. We hope that both healthy and sickpeople will benefit from the scientific efforts made in this scientific area.
Recently the research about magnesium diversified and this cation (together with calcium) remains
one of the most studied non-proteic substance in the living world. The intracellular magnesium
dosing became more and more precise. The holistic view over the cation’s role in the living world
and particularly in the human body, as well as the understanding of cellular compartimentation as
being essential to life, open new perspectives for magnesium research and broadens magnesium
therapeutical indications.