Kniga na apstrakti book of abstrcts

part of a health care team, clinical pharmacists are able to closely monitor patient drug therapy and make recommendations on
the selection of the best medication for a patient’s condition, the correct dose and duration of therapy. Pharmacy is a trusted
profession and pharmacists are consistently ranked as one of the most highly trusted professionals because of the care and serv-
ice they provide. However, people’s respect and trust must be deserved by proper services.
Macedonian pharmaceutical bulletin 53 (1,2) 250 (2007)
SPL - 12
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^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION

The Macedonian poison control center - vision or necessity
Z. Kavrakovski, K. Mladenovska, L. Petrusevska-Tozi
Faculty of Pharmacy, University „Ss. Cyril and Methodious“, Vodnjanska 17, Skopje, Macedonia
Poisoning with chemicals, pharmaceuticals, plants and animal toxins is a worldwide phenomenon and has
serious social and economic impact on the health care system. Environmental and industrial poisoning is a signifi-
cant risk in all countries where increasing number of chemicals are being used in the development process. Some of
the countries have already well-established facilities for the prevention and control of the poisoning, some wish to
establish or strengthen their facilities and others like Republic of Macedonia have not yet fully recognized the extent
of this risk. The primary objectives of these poison control centers (PCC) include prevention of poisoning and
improved care of poisoned patients. In developing countries, the main attributes of the PCC are treatment informa-
tion, formal training, accessibility to the laboratory services and availability of antidotes. In the same time, PCC
should accomplish their public health mission through strengthening and expansion of some well-defined roles, such
as toxic-surveillance and environmental health monitoring according to the prevailing and future toxicological prob-
lems. Information center, as a part of the PCC is based on two cornerstones, a well-educated and specifically trained
staff and reliable, updated and easily manageable information sources. 
In order to establish a PCC in the Republic of Macedonia, poison control programmes and guidelines should
be developed as well as toxicovigilance and poison prevention programmes. The programmes have to be focused on
the treatment of harmful effects of chemicals, techniques for decreasing incidence of toxic events, improvement of
outcome and survival, prevention of recurrence, decreasing of unnecessary treatments and costs, providing data on
incidence and most effective therapies, research, staff education and training. The PCC can provide important spe-
cialized services, accessible information and advice to questions regarding poisoning, drug interactions, snake and
insect bites or any other chemical exposure, for the public health care professionals and media, 24 hours a day all year
round via internet network, telephone and facsimile. For these requirements, collaboration between World Federation
of Associations of Clinical Toxicology Centers and Poison Control Centers and its member associations should be
established. Toxicological laboratory services are essential component of the poison control programs. With establish-
ing analytical laboratory services and emerged qualitative and quantitative assays, communication between clinicians
and toxicologists could be improved and thus, morbidity and mortality due to the poisoning can be reduced.
In order to assess the risk for the human health and the environment when exposed to chemicals and the eco-
nomic impact on the sectors other then health as well, it is necessary to establish the poison monitoring system and
toxicological services, which will develop national policy with own chemical safety measures, including network of
centers for chemical urgent response and ensure prompt and adequate diagnosis and treatment of poisoning. Prevention
is the best antidote.
Macedonian pharmaceutical bulletin 53 (1,2) 251-252 (2007)
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^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION

Centar za kontrola na truewa vo Republika Makedonija
- vizija ili potreba
Z. Kavrakovski, K. Mladenovska, L. Petru{evska-Tozi 
Farmacevtski fakultet, Univerzitet ”Sv. Kiril i Metodij”, 
Vodwanska 17, 1000 Skopje, Republika Makedonija
Trueweto so hemikalii, lekovi, rastitelni i `ivotinski otrovi e svetski fenomen i ima golemo
socijalno i ekonomsko vlijanie vrz zdravstveniot sistem na dr`avata. Odredeni dr`avi imaat dobro orga-
nizirani centri za spre~uvawe i kontrola na truewata, drugi nastojuvaat da gi sozdadat ili da ja podobrat
organizacijata na postoe~kite centri, a odredeni dr`avi, kako R. Makedonija, sé u{te ne go sogledale
celosno rizikot od nekontrolirana primena na hemikalii i soodvetno, potrebata od formirawe na vakvi
centri. Glavni atributi na centrite za kontrola na truewa (CKT) vo razvienite zemji se obrabotka na
informacii, formalna obuka, pristap do laboratoriski kapaciteti i uslugi i raspolo`livost na anti-
doti. Informativniot centar, kako del od CKT vklu~uva dobro obrazuvani eksperti, osposobeni da sobi-
raat, obrabotuvaat i dostavuvaat neophodni informacii za nesakanite slu~uvawa do relevantnite insti-
tucii i javnosta so ocenka na rizicite vrz zdravjeto na lu|eto i vlijanieto vrz `ivotnata sredina.
Za formirawe na CKT neophodno e vospostavuvawe i razvoj na programi i protokoli za spre~uva-
we i kontrola na truewata koi }e bidat naso~eni kon tretmanot na {tetnite efekti predizvikani od
hemikalii, tehnikite za namaluvawe na za~estenosta na truewa, podobruvaweto na ishodot i pre`ivu-
vaweto pri truewe, namaluvaweto na mo`nosta za povtorno slu~uvawe, namaluvaweto na cenata na zdrav-
stvenite uslugi pri truewe, dostapnosta na informaciite i sovetite za nesakanite efekti, vzaemnite
dejstva na hemikaliite i lekovite i najefikasniot tretman. Dobro definiranata uloga na CKT vklu~uva
edukacija i davawe na specijalisti~ki uslugi, informacii i soveti za potrebite na javnosta, nadle`nite
ministerstva, agencii, javnite mediumi, zdravstvenite rabotnici, 24 ~asa na den vo tekot na godinata,
preku internet mre`ata, telefon ili faks.
Toksikolo{kite laboratorii se zna~ajna komponenta vo programite za spre~uvawe i kontrola na
truewata. Toksikolo{ko-hemiskite ispituvawa i sorabotkata me|u doktorite, klini~kite farmacevti
i ekspertite-analiti~ari mo`e da gi namali morbiditetot i mortalitetot predizvikani so truewe. 
So cel da se izvr{i procenka na rizikot vrz zdravjeto na lu|eto i `ivotnata sredina pri izlo`e-
nost na hemikalii i da se utvrdi ekonomskiot efekt vrz ostanatite sferi od `ivotnata sredina neophod-
no e da se vospostavi i razvie sistem za kontrola i spre~uvawe na zagaduvawata {to podrazbira postoja-
no obrazuvawe i usovr{uvawe na ekspertite i stru~nite slu`bi, kako i podigawe na javnata svest za
va`nosta na problemot. 
Za unapreduvawe na rabotata na CKT neophodna e sorabotka i ~lenstvo vo Svetskata federacija
na asocijacii na centrite za klini~ka toksikologija i centrite za kontrola na truewata. Isto taka, treba
da se razvie nacionalna strategija so merki za hemiska za{tita na `ivotnata sredina vo slu£aj na katas-
trofa, sistem od laboratorii za toksikolo{ko-hemiski ispituvawa neophodni za brza i adekvatna dijag-
noza i tretman na trueweto, kako i slu`ba so ekipi za brza reakcija, prevencija i sanacija na {tetite vo
`ivotnata sredina. Preventivata e najdobriot protivotrov.
Macedonian pharmaceutical bulletin 53 (1,2) 251-252 (2007)
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^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION

Reactive Oxigen Species and Defense Systems
Tatjana Kadifkova Panovska
1
,
Svetlana Kulevanova
2
1
Institute of Applied Biochemistry, Faculty of Pharmacy, Vodnjanska 17, 1000 Skopje, R. Macedonia
2
Institute of Pharmacognosy, Faculty of Pharmacy, Vodnjanska 17, 1000 Skopje, R. Macedonia
Although for aerobic organism oxygen is necessary for life, it has been accepted that under certain situa-
tions, oxygen has severely deleterious effects on the human body. Most of the potentially harmful effects of oxygen
are due to the formation and activity of a number of chemical compounds, known as reactive oxygen species (ROS),
which have a tendency to donate oxygen to other substances. Many such reactive species are free radicals and have
a surplus of one or more free-floating electrons rather than having matched pairs and are, therefore, unstable and
highly reactive. Types of free radicals include the hydroxyl radical (OH.), the superoxide radical (O.2), the nitric
oxide radical (NO.) and the lipid peroxyl radical (LOO.).
Reactive oxygen species are formed by several different mechanisms: a) the interaction of ionizing radia-
tion with biological moleculae, b) as unavoidable byproduct of cellular respiration, c) synthesized by dedicated
enzymes in phagocytic cells like neutrophilis and macrophages - NADPH oxodase (in both tipe of phagocytes) and
myeloperoxidase (in neutrophils only), etc.
Strong oxidants like the various ROS can damage other molecules and teh cell structures of which they are
a part. Among the most important of these are the actions of free radicals on the fatty acid side chains of lipids in the
various membranes of the cell, especially mitochondrial membranes (which are directly exposed to the superoxide
anions produced during cellular respiration). Lipid peroxidation is complex process occuring in aerobic cells and
reflects in interaction between molecular oxygen and polyunsaturated fatty acids. This involves formation and prop-
agation of lipid radicals (L.), uptake of oxygen, rearrangement of double bonds, generation of lipid alkoxyl (LO.)
lipid peroxyl (LOO.) radicals, lipid hydroperoxide (LOOH)  as well as variety of degradation products. At least two
paths are known for the formation of lipid peroxide in vivo.One occurs through autooxidation of catecholamine, thi-
ols, quinones, and others, and redox reactions of oxyhemoglobin and myoglobin, and the other from active oxygen
by the action of xanthine oxidase, NADPH oxidase, and other enzymes.
Cells have a variety of defences against the harmful effects of ROS. These include two enzymes: superox-
ide dismutase (SOD), which converts two superoxide anions into a molecule of hydrogen peroxide and one of oxy-
gen, and catalase as well as several small molecules that are antioxidants, such as alpha-tocopherol (vitamin E), uric
acid,  vitamin C, etc. 
Free radical reactions are expected to produce progressive adverse changes that accumulate with age through-
out the body. In the case of disturbed balance between formation of free radicals and antioxidant defense, in the cell
we have oxidative stress and the free radicals can play a role in the development of various diseases. 
Overproductions of ROS have been implicated in the etiology of host degenerative diseases including car-
diovascular diseases, diabetes, cancer, Alzheimer's disease, retinal degeneration, ischemic dementia, and other neu-
rovegetative disorders and aging. In addition, they also play a role not only in acute conditions, such as trauma,
stroke, and infection, but also in physical exercise and stress. 
Macedonian pharmaceutical bulletin 53 (1,2) 253-254 (2007)
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^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION

Reaktivni kislorodni vidovi i odbranbeni sistemi
Tatjana Kadifkova Panovska
1
i Svetlana Kulevanova
2
1
Institut za Primeneta biohemija, Farmacevstki fakultet, Vodwanska 17, 1000 Skopje, R. Makedonija
2
Institut za Farmakognozija, Farmacevstki fakultet, Vodwanska 17, 1000 Skopje, R. Makedonija
Iako za aerobnite organizmi kislorodot e neophoden za `ivot, pod odredeni okolnosti, kislo-
rodot predizvikuva seriozni {tetni efekti vrz ~ove~kiot organizam. Golem broj od potencijalnite
{tetni efekti na kislorodot se posledica na formirawe i aktivirawe na brojni hemiski komponenti,
poznati kako reaktivni kislorodni vidovi (RKV), {to imaat tendencija da doniraat kislorod na drugi
supstancii. Mnogu od reaktivnite vidovi se slobodni radikali koi imaat vi{ok na eden ili pove}e
nespareni elektroni {to gi pravi nestabilni ili visoko reaktivni. Naj~esti slobodni radikali se
hidroksil radikalot (OH.), superoksid radikalot (O.
2
), azot oksid radikalot (NO.) i lipid peroksil
radikalot (LOO.). 
Reaktivnite kislorodni vidovi se formiraat so nekolku razli~ni mehanizmi: a) interakcija na
jonizirano zra~ewe so biolo{ki molekuli, b) kako neizbe`en sporeden produkt na kleto~noto di{ewe,
v) sinteza vo fagocitnite kletki kako {to se neutrofilite i makrofagite, posreduvana so enzimite
NADPH oksidaza (vo dvata vida fagociti) i mieloperoksidaza (samo vo neutrofilite), itn.  
Silnite oksidansi kako {to se RKV mo`at da o{tetat drugi molekuli i kleto~ni strukturi.
Edno od najva`nite dejstva na slobodnite radikali e vlijanieto vrz strani~kite sinxiri na masnite
kiselini na lipidite {to se del od kleto~nite membrani, osobeno mitohondrijalnite membrani (koi se
direktno izlo`eni na superoksid anjonot produciran vo tek na kleto~noto di{ewe). Lipidnata perok-
sidacija e kompleksen proces koj se odviva vo aerobnite kletki i ja odrazuva interakcijata pome|u mole-
kularniot kislorod i polinezasitenite masni kiselini.
 Procesot opfa}a sozdavawe i {irewe na
lipidni radikali (L.), fa}awe na kislorod, preureduvawe na dvojnite vrski, generirawe na lipid alkok-
sil (LO.)i lipid peroksil (LOO.) radikali, lipidni peroksidi (LOOH)  kako i razli~ni degradacioni
produkti. Formiraweto na lipidnite peroksidi
   in vivo mo`e da se odviva na dva na~ina: preku avtook-
sidacija na kateholamini, tioli, kinoni, i dr., i redoks reakcii na oksihemoglobin i mioglobin i so
vlijanie na ksantin oksidaza, NADPH oksidaza i drugi enzimi vrz aktiven kislorod.
Kletkite poseduvaat razli~ni odbranbeni sistemi za {tetnite efekti na RKV. Vo prv red se
dvata enzimi: superoksid dismutaza (SOD), koj preveduva dva superoksid anjoni vo molekula na vodoro-
den peroksid i molekul na kislorod i katalaza, kako i pove}e mali molekuli koi se antioksidansi, kako
alfa-tokoferol (vitamin E), uri~na kiselina, vitamin C itn.
Reakciite na slobodnite radikali predizvikuvaat nesakani promeni koi se akumuliraat vo orga-
nizmot so tek na vremeto. Koga se poremetuva ramnote`ata pome|u formiraweto na slobodnite radika-
li i antioksidativnata odbrana, vo kletkite se slu~uva oksidativen stres i slobodnite radikali mo`at
da igraat uloga za razvoj na razli~ni bolesti.
Prekomernata produkcija na RKV e povrzana so etiologijata na degenerativnite bolesti kako {to
se kardiovaskularnite zaboluvawa, dijabetes, kancer, Alchajmerova bolest, degeneracija na retinata, is-
hemi~na demencija i drugi nervnodegenerativni poremetuvawa kako i stareewe. Isto taka, tie igraat ulo-
ga ne samo vo akutni sostojbi kako trauma, mozo~en udar i infekcija, tuku i pri fizi~ki ve`bi i stres.
Macedonian pharmaceutical bulletin 53 (1,2) 253-254 (2007)
SPL - 14
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^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION

Classification of endocrine disrupters using supervised 
self-organizing maps
Ksenija Mickova Dimitrova
1
, Lidija Petrushevska-Tozi
2
, Igor Kuzmanovski
3
, Zoran Kavrakovski
2
1
Promedika DOO, Mito Hadzivasilev Jasmin 50/5,1000 Skopje, Macedonia
2
Faculty of Pharmacy, Vodnjanska 17, 1000 Skopje, Macedonia 
3
Institut za hemija, PMF, Univerzitet “Sv. Kiril i Metodij”, P.O. Box 162, 1001 Skopje, Macedonia
Endocrine-disrupting chemicals (ED) present an increasing concern because of their adverse effects on human
and wildlife. The effects on humans include reproductive and developmental disruptions, cancer, altered immune,
nervous system and thyroid function. The information about biological activity obtained from in vitro and in vivo
tests is exploited in theoretical studies of the relationship between chemical structure and biological activity. Alternative
methods, i.e. computer-based prediction and modeling systems for specific toxicological endpoints, based on the
achievements of the structure-activity relationship studies, are becoming widespread because of the increasing need
for screening a large number of chemicals for their adverse biological activity. Due to this reason here we present a
novel approach for development of classification models for prediction of endocrine-disrupting activity.
In this study classification models are developed using nonlinear projection algorithm supervised self-organ-
izing maps for data set consisting of 107 chemicals extracted from the report of the European Union Commission.
The chemicals belong to four classes defined in the EU Commission report: literature evidence for ED, potential ED,
uncertain evidence for non-ED and certain evidence for non-ED.
The selection of the optimal parameters of the classification models as well as the most suitable descriptors
for them was performed using genetic algorithms. Additionally, during the optimization using genetic algorithms
our newly developed approach for adjustment of the relative importance of descriptors was applied. 
The classification models were validated using 10-fold cross validation. After several repetitions of the opti-
mization procedure a number of models with acceptable prediction performances were found. The best model is able
to correctly classify 72,9 % of chemicals into four classes. 
Using the approach for adjustment of the relative importance we are able to find the descriptors most suit-
able for classification purposes (and the properties of molecules they represent), as well as the descriptors that con-
tribute more in separation of the molecules into these four classes.
Macedonian pharmaceutical bulletin 53 (1,2) 255-256 (2007)
PP - 124
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FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION

Klasifikacija na hemikalii koi ja poremetuvaat funkcijata 
na endokriniotsistem so upotreba na samoorganizirani mapi 
Ksenija Mickova Dimitrova
1
, Lidija Petru{evska-Tozi
2
, 
Igor Kuzmanovski
3
, Zoran Kavrakovski2
1
Promedika DOO, Mito Haxivasilev Jasmin 50/5, 1000 Skopje, Makedonija
2
Farmacevtski fakultet, Vodwanska 17, 1000 Skopje, Makedonija
3
Institut za hemija, PMF, Univerzitet „Sv. Kiril i Metodij“, P. fah 162, 1001 Skopje, Makedonija
Ispituvaweto na hemikaliite koi ja poremetuvaat normalnata funkcija na endokriniot sistem
(ES) pretstavuva golem interes bidej}i istite mo`e da predizvikaat nesakani efekti vrz zdravjeto na
lu|eto i `iviot svet. Efektite vrz lu|eto osven poremetuvawe na reprodukcijata i razvojot, vklu~uvaat
pojava na kancer, poremetuvawe na imunolo{kiot, na nervniot sistem, kako i na funkcijata na tiroid-
nata `lezda. Podatocite za biolo{kata aktivnost dobieni od in vitro i in vivo studii se koristat vo teo-
retski studii za relacii pome|u hemiskata struktura i biolo{kata aktivnost. Upotrebata na alterna-
tivnite metodi kako kompjutersko predviduvawe i modelirawe na toksikolo{kite efekti bazirani na
struktura-aktivnost relacii e zgolemena poradi potrebata za testirawe na golem broj hemikalii. Zatoa
vo ovoj trud e pretstaven nov priod za razvoj na modeli za klasifikacija na hemikaliite koi ja poreme-
tuvaat funkcijata na ES.
Vo ovoj trud se razvieni modeli za klasifikacija, so upotreba na samoorganizirani mapi treni-
rani so nadgleduvano u~ewe, za mno`estvo od 107 hemikalii ekstrahirani od izve{tajot na Komisijata
na Evropskata unija. Hemikaliite se podeleni vo ~etiri klasi: literaturen podatok za poremetuvawe
na ES, potencijalna aktivnost na poremetuvawe na ES, nesiguren podatok deka nema aktivnost na poreme-
tuvawe na ES i siguren podatok deka nema aktivnost na poremetuvawe na ES.
Za odbirawe na optimalnite parametri na modelite i deskriptorite najpogodni za klasifikaci-
ja koristeni se genetski algoritmi. Vo tekot na optimizacijata na modelite so genetskite algoritmi
koristena e novorazviena postapka za opredeluvawe na relativnite va`nosti na deskriptorite.
Vo modelite za klasifikacija koristena e 10-kratna vkrstena validacija, a po pove}epati pov-
torena optimizacija dobeni se modeli so prifatlivi performansi. Najdobriot model to~no klasifi-
cira 72,9 % od hemikaliite vo ~etirite klasi.
So upotreba na postapkata za opredeluvawe na relativnite va`nosti na deskriptorite, gi utvr-
divme najpogodnite deskriptori za klasifikacija (i osobinite na molekulite koi tie gi pretstavuvaat),
kako i koi deskriptori najmnogu pomagaat vo klasifikacijata.
Macedonian pharmaceutical bulletin 53 (1,2) 255-256 (2007)
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Urinary proteins in febrile conditions of non renal origin
Svetlana Cekovska
1
, Snezhana Palchevska 
2
, Velibor Tasik
2
, Petar Korneti
1
1
Institute of medical and experimetal biochemistry, Medical faculty, 50 Divizija 6, Skopje, R. of Macedonia
2
Clinic of children diseases, Medical Faculty, Vodnjanska 17, Skopje, R. of Macedonia
The study included examination of several basic parameters related to urinary protein excretion in subjects
with febrile conditions of non renal origin.
Second morning urine samples excreted from 30 children with febrile conditions of non renal origin and 24
healthy children, all at age of 2-7 years, were analysed.
Concentration of total urinary proteins, P/C ratio and concentration of catalytic activity of the enzyme 
N-acetyl-
β-D-glucosaminidase (β-NAG) were determined for each subject included in the study. Electrophoretic
separation of urinary proteins was also performed by applying thin layer sodium dodecyl sulphate poliacrylamide
gel electrophoresis (SDS-PAGE). Total urinary proteins were determined with the method by Meulemans. Creatinine
concentration in urine was determined with the method by Jaffe and the activity of the enzyme 
β-NAG with spec-
trophotometric method by Horak. Electrophoretic separation was done by using 4-22% gradient gels (for Multiphor
II system) stained with Coomassie Blue R-250.
Colmogorov-Smirnov test has shown that there were highly statistical significant differences concerning all
investigated parameters between subjects with febrile conditions of non-renal origin and controls (p< 0,002 for total
urinary proteins, p < 0,001 for P/C ratio and p < 0,001 for 
β-NAG).
Values for total urinary proteins, P/C ratio and the activity of enzyme 
β-NAG represent mean arithmetic
value of examination during two consequent days with increased body temperature (> of 38oC) in examined chil-
dren. Highest values for P/C ratio and for the concentration of catalytic activity of enzyme 
β-NAG were detected in
children with virus infection of upper respiratory roads. After administration of therapy and decrease of body tem-
perature fast decreasing of all investigated parameters were detected, reaching the values characteristic for healthy
children after three days.
In the examinees with increased body temperature of non-renal origin a characteristic electrophoretic pro-
file was noticed with apparent albumin fraction and apparent fractions of low molecular proteins. Electrophoretic
profiles returned to normal having characteristics of healthy persons after administration of therapy and decrease of
body temperature.
The results have shown that proteinuria which is detected in febrile conditions of non-renal origin is func-
tional and transitory.
Macedonian pharmaceutical bulletin 53 (1,2) 257-258 (2007)
PP - 125
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^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION