abstract - МЕДИЦИНСКИ УНИВЕРСИТЕТ София

КОНКУРС
за академичната длъжност “професор” в област на висше
образование 7. „Здравеопазване и спорт“ по професионално
направление 7.1. „Медицина“ и научна специалност
“Медицинска биология (Биология на човека)” за нуждите на
Катедрата по биология при Медицински факултет,
Медицински университет, София, обявен в ДВ бр.
31/04.04.2014г. – 17 (2170) и на сайта на МУ, София на
04.04.2014г.
РЕЗЮМЕТА
на научните трудове на доц. д-р Недка Л. Трифонова, дм
публикувани в специализирани научни издания след
придобиване на научната длъжност “доцент”, с които
участва в конкурса
Реферативен бюлетин по Офталмология, година десета, 4, 2003
AНТИТЕЛА СРЕЩУ АЛФА КРИСТАЛИНИ НА
ОЧНАТА ЛЕЩА ПРИ ПАЦИЕНТИ С АЛЕРГИЯ
Н. Трифонова, Св. Калайджиев, Д. Димитрова, Б. Ангелов, М. Стаменова, К.
Николов, М. Балева, W. Breipohl
РЕЗЮМЕ
Субединиците на алфа кристалините се причисляват към групата на стресовите
протеини, известни като heatnshock proteins – Hsps. Съществуват данни за антитела
срещу различини стресови протеини при пациенти с алергии, но няма такива за
алфа кристалините. Цел на настоящото изследване е да се потърсят антитела срещу
алфа кристалините при пациенти с положителни кожно-алергични проби. Чрез
ЕЛИЗА са изследвани серуми на 60 пациенти и 21 кръводарители за наличие на
антитела срещу алфа кристалините и срещу Dermatophagoides pteronissinus
(причинител на алергии). Установена е статистически значима корелация между
реактивността на изследваните серуми срещу двата антигена (Spearman; r=0.756,
P<0,0001), което дава основание да се предположи наличие на общи антигенни
епитопи между тях.
Ключови думи: алфа кристалини, алергия, ЕЛИЗА, Dermatophagoides pteronissinus
Comptes rendus de l’Academie bulgare des Sciences, Vol 56, 2003, No5, pp.95-100
A QUANTITATIVE UTILITY ASSESSMENT OF SOME
BIOPHYSICAL- AND RHEOLOGICAL TESTS USED IN
HYPERTENSION RESEARCH. I. RELEVANCE
ANALYSES OF THE TEST PARAMETERS
S.Stoeff, I.Dikov, M.Vretenarska, S.Jovtchev, N.Trifonova, M.Penev
ABSTRACT
Methodical approaches of electrophoretic mobility (EPM) and aggregation of
erythrocytes and plasma viscosity (PV) as well were subjected to utility assessment for
disclosure reliable tests expedient in a rheological trend of hypertension research.
Metabolic turnover in pregnant state, recently accepted as a transient likeness of
cardiovascular disease in general, is thought to be in charge of rheological decline.
Therefore probing venous blood of healthy pregnants and pre-eclampsia were exploited
for in vitro tests of erythrocyte sedimentaion rate (ESR), zeta sedimentation ratio (ZSR),
EPM and PV. The ZSR seems to be reliable and a satisfactory substitute in clinical
situation for its greater specificity, positive predictive value and the much better
reproducibility than the ESR. By excessive protein level where the HCT- readings are
stable and the sedimentation rates are extremely high, the Westergren method is
recommended as likely better useful. Functional relevance analyses of ESR- and ZSR vs
EPM denote evidence for erythrocyte aggregation in a complex mode added probably by
not yet clarified irreversible aggregation phenomenon due to microcirculatory
disturbances of stasis and ischemia. For the present low sensitivity of PV could be
explained likely by apperance of irreversible protein complexes related also to the
aforementioned microcirculatory settings.
Български офталмологичен преглед, XLVII, 2003, 3, 25-29
ДВУМЕРНА ЕЛЕКТРОФОРЕЗА НА КРИСТАЛИНИТЕ
НА ОЧНАТА ЛЕЩА ПРИ CCFDN СИНДРОМ
(CONGENITAL CATARACT, FACIAL DYSMORPHISM,
NEUROPATHY SYNDROME)
И. Джумерска., А. Пашов, Ив. Търнев, И. Минева, М. Стаменова, И.
Маждракова, С. Чернинкова, Н.Трифонова
РЕЗЮМЕ
Характерен за ромските изолати в България е синдромът CCFDN, при който найранен и постоянен офталмологичен симптом е двустранната зонуларна катаракта. В
предишно наше изследване е установена промяна в относителния дял на трите
основна класа кристалини. С цел анализ на субединиците на всеки от класовете
кристалини е проведена двумерна електрофореза на екстракт от оперативно
отстранената помътняла леща на пациент със CCFDN синдром. Наблюдават се
съществени различия в броя и физикохимичните параметри на полипептидните вериги на
α- и β-кристалините на катарактната леща в сравнение с тези на контролна прозрачна
леща. Причини за наблюдаваните различия биха могли да бъдат допълнителни
посттранслационни модификации на синтезираните полипептидни вериги на
кристалините, дължащи се на променен метаболизъм на очната леща при CCFDN
синдрома.
Ключови думи: CCFDN синдром, двумерна електрофореза, лещени кристалини
Bulgarian review of ophthalmology, XLVII, 2003, 3, 25-29
TWO-DIMENSIONAL ELECTROPHORESIS OF THE
CRYSTALLINS IN EYE LENS OF PATIENTS WITH A
CCFDN SYNDROM (CONGENITAL CATARACT,
FACIAL DYSMORPHISM, NEUROPATHY SYNDROME)
I. Djoumerska, A. Pashov, Iv. Tournev, I. Mineva, M. Stamenova, I. Mazhdrakova,
S. Cherninkova, N. Trifonova
ABSTRACT
The congenital cataract, facial dysmorphism, neuropathy syndrome (CCFDN) is
characteristic for the Gipsy isolates in Bulgaria. A constant finding in the cases with the
CCFDN is binocular zonular cataract. In a previous study we have found a change in the
relative quantity of the three basic classes of crystallins. The aim of the present study is to
analyze the changes in the individual subunits of each of the different classes of
crystallins making use of the high sensitivity of the two-dimensional electrophoresis.
Substantial changes in the polypeptide chains of the alpha and beta crystallins were
observed as compared to normal transparent lens. The cause of the observed differences
could be additional posttranslational modifications of the synthesized polypeptide chains
of the crystallins due to altered metabolism.
Key words: CCFDN syndrome, two-dimensional electrophoresis, lens crystallins
Clinical Hemorheology and Microcirculation, 2004, 30, 439-441
ON THE INTERRELATIONSHIPS BETWEEN
ERYTHROCYTE AGGREGATION, PLASMA VISCISITY
AND THE TOTAL PERIPHERIAL RESISTANCE IN
ARTHERIAL HYPERTENSION
S.Stoeff , M. Vretenarska, N. Stojanova, S. Halacheva, Sv. Jovtchev, M. Tsaneva,
T. Galabova, N. Trifonova, M. Penev
ABSTRACT
A probable conjunction of hemodynamic and rheological variables was tested in
hypertensive patients. Most pronounced correlation was fixed for some indices (sizable in
value for plasma viscosity and small but distinct for blood pressure and ZSR) vs. total
peripheral resistance. These results of a small scale elaboration are encouraging to get up
a study extension.
Key words: Arterial hypertension, blood rheology disturbance, total resistance
Comptes rendus de l’Academie bulgare des Sciences, Vol 58, 2005, No1, pp.85-90
LOCALIZATION OF LOW-MOLECULAR HEAT
SHOCK PROTEIN (sHSP)
I.Mineva, A.Russinova, M.Ahrend, M.Stamenova, N.Trifonova, K.Mainhard,
W.Breipohl
ABSTRACT
Crystallins are major lens proteins with structural role in maintaining the transparency of
the lens. Recently it has been demonstrated that one of its subunits (αB-crystallin) can
prevent the thermally induced aggregation of a diversity of denaturing proteins. This
suggests that αB-crystallin possesses chaperone-like property. AlphaB-crystallin has been
shown to be expressed outside the lens in a number of tissues such as skeletal and cardiac
muscle, skin, brain, and kidney, suggesting that it has a general cellular function. By
using immunohystochemical methods, we demonstrated the presence of αB-crystallin in
human placenta. Using anti- αBcrystallin monospecific serum in sections from early to
late placenta the immunoreaction was observed in the cytoplasm of decidual cells and
syncytiotrophoblast, but the staining intensity strongly increases in the decidual cells of
the late placenta. Strong reaction was also observed in early placenta decidual glandular
epithelium. For the first time studies show that αB-crystallin occurs in most of the cell
types of human placenta and on different stages of its development.
Реферативен бюлетин по Офталмология, година дванадесета, 6, 2005
СЕРУМНИ АНТИТЕЛА СРЕЩУ КРИСТАЛИНИ НА
ОЧНАТА ЛЕЩА И СПЕРМАТОЗОИДИ ПРИ
ПАЦИЕНТИ С АЛЕРГИЧНИ ЗАБОЛЯВАНИЯ
Н. Трифонова, Д. Димитрова, Б. Ангелов, Св. Калайджиев, М. Балева, Л.
Наков
РЕЗЮМЕ
Цел: Настоящото проучване има за цел изследване на хуморалния имунен отговор
при алергични пациенти срещу намиращи се в имунологична изолация антигени
(алфа кристалини и сперматозоидни антигени).
Материали и методи: Изследвани са 75 серума от алергични пациенти с
положителни кожно-алергични проби срещу различни алергени:
Dermatophagoides pteronissinus (n=32), домашен прах (n=25), животински (пух,
котки, кучета) (n=15), полени (n=11), храни (n=4), лекарства (n=17), и здрави
контроли от кръводарители (n=194) за повишени нива на антитела срещу алфа
кристалини с използването на ЕЛИЗА и срещу сперматозоидни антигени с
използването на желатининов аглутинационен тест на Kibrick (GAT),
аглутинационен тест на Friberg (ТАТ), спермоимобилизиращ (SIT) и ЕЛИЗА. За
статистически анализ на резултатите е използван Soiftwere SPSS7, определено е
ниво на нулевата хипотеза p<0,005.
Резултати: В групата на алергичните пациенти в сравнение с контролната група е
доказана по-висока честота на серуми с повишена концентрация на антитела срещу
алфа кристалини и срещу сперматозоидни антигени. Повишено ниво на серумни
антитела срещу алфа кристалините чрез ЕЛИЗА е установено в 12% от всички
изследвани пациенти и 5% в контролната група, а срещу сперматозоидните – в
различен процент при различните използвани методи: 21% при GAT, 20% при SIT,
21% при ТАТ и7% при ЕЛИЗА срещу съответно 2%, 6%, 16% и 3% в контролната
група.
Изводи: Нашите резултати показват повишен хуморален имунен отговор срещу
сперматозоидни антигени и алфа кристалини при пациенти с алергични
заболявания. Те могат да бъдат обяснени с наличие на кръстосани реакции между
някои алергени и антигени на органи в имунологична изолация.
Ключови думи: алергия, автоантитела, алфа кристалини, спермоантитела,
сперматозоидни антигени, топлинно-шокови протеини (Hsp)
Comptes rendus de l’Academie bulgare des Sciences, Vol 58, 2005, No4, pp.463-468
QUANTITATIVE UTILITY ASSESSMENT OF SOME
BIOPHYSICAL- AND RHEOLOGICAL TESTS USED IN
HYPERTENSION RESEARCH. II. RELATION OF THE
TEST PARAMETERS TO SOME CLINICOLABORATORY INDICES
S.Stoeff, I.Dikov, M.Vretenarska, S.Jovtchev, T.Galabova, N.Trifonova,
A.Mladenova, S.Hadjieva, L.Lambreva, M.Penev
ABSTRACT
Analyses for false values were applied in tests for erythrocyte aggregation and blood
plasma viscosity. In opposite to ESR the ZSR is a satisfactory substitute for clinical
studies of patient’s specimens with low HCT. PV measurements showed the highest rate
of false negative values. The notable meaning of PV data as relevant to a number of a
laboratory test data gives proof of the further effort to find out discernible failings of PV
methodology. ROC curve analyses were an additional support for the validity of the cut
off point of our ESR and ZSR data. We were able also to find reliable proofs that certain
metabolic indices are correlates to our elaborated hemorheological tests.
Comptes rendus de l’Academie bulgare des Sciences, Vol 58, 2005, No3, pp.349-352
ANTIBODIES AGAINST IMMUNOLOGICALLY
SEQUESTERED HUMAN ANTIGENS AND
CORRELATION BETWEEN THEM AND ANTICHLAMYDIAL ANTIBODIES
D.Dimitrova, N.Trifonova, S.Kalaydjiev, B.Anguelov, L.Hristov, K.Nikolov,
T.Boyadjiev, L.Nakov
ABSTRACT
The aim of the present study was to establish whether there exists a correlation between
anti-chlamydial antibody (AChl Ab) titer and anti-lens antibodies (AL Abs) and antisperm antibodies (AS Abs) titer in patients with chlamydial infections in view of the
possibility for induction of chronic eye inflammation or of immune infertility in the
human. The results show no correlation between the presence of AChl Abs and AL Abs
in the sera of patients with intraocular and urogenital inflammation; and a positive
correlation between AChl Abs and AS Abs in agglutination test of Friberg (TAT) and
sperm immobilization test (SIV); and a negative correlation in ELISA for patients with
infections of the urogenital tract. The higher level of AS Abs may be associated with the
inflammatory process with urogenital localization caused by Chlamydia trachomatis .
Comptes rendus de l’Academie bulgare des Sciences, Vol 60, 2007, No4, pp.449-452
LOCALIZATION OF LOW MOLECULAR WEIGHT
STRESS PROTEIN (SHSP) AlphaB-CRYSTALLIN IN
HUMAN THYROID GLAND
I.Mineva, M.Stamenova, S.Popovska, T.Betova, P.Rashev, E.Sapundzhiev,
M.Simeonova, N.Trifonova
ABSTRACT
One of the main members of the mammalian small heat shock protein family are the
subunits of the structure eye lens protein alpha-crystallin. Its subunit alpha B-crystallin is
expressed in some nonlenticular tissues, where it functions as a chaperone under stress
conditions, preventing other cell proteins from aggregation. Synthesis of alpha Bcrystallin is related with the differentiation process during the mammalian embryonic
development. The aim of this study is to investigate the expression and localization of
alpha-crystallins in tissue sections from normal and pathologically changed human
thyroid gland using immunohistochemical methods. Our results show a different level of
positive reaction and specific localization in normal thyroid gland, thyroid struma, thyroid
adenoma and Hashimoto’s thyroiditis. This finding for the different expression of alphacrystallins under pathological conditions probably is related with the cellular
differentiation of these tissues.
Key words: stress proteins, alpha-crystallin, thyroid gland, anti-alpha-crystallin
antibodies, immunohistochemistry
Български офталмологичен преглед, 1, 2007, 49-54
ЕКСПРЕСИЯ НА АНТИГЕНИ НА ОЧНА ЛЕЩА –
АЛФА КРИСТАЛИНИ В ИЗВЪНОЧНИ ТЪКАНИ НА
ЧОВЕШКИ ФЕТУС
Н. Трифонова, Б. Ангелов, П. Рашев, Е. Сапунджиев, И. Бътева, М. Стаменова
РЕЗЮМЕ
Алфа кристаините са основни структурни белтъци на очната леща, съставени от две
субединици αА и αB. Дълго сочени като антигени с висока органна специфичност,
днес алфа кристалините се причисляват към групата на консервативните,
експресиращи се в много видове организми и в различни техни тъкани стресови и
шаперонови молекули. Откриването на високотитърни антитела срещу алфа
кристалините при катаракта и увеити поставя тези белтъци във фокуса на различни
молекулнобиологични и имунобиологични проучвания. В настоящата работа е
изследвана експресията на алфа кристалини в диференцирани тъкани на човешки
фетус. Чрез индиректер имунопероксидазен тест, освен в очна леща, тяхната
експресия е доказана в роговица и ретина, както и в редица извъночни тъкани и
органи – напречно набраздена скелетна мускулатура, миокард, бъбрек, слезка,
тимус, жлезист епител в черва и бял дроб. Резултатите дават основанине да се
предположи отключването на имунен отговор срещу лещата и други очни тъкани в
резултат на извъночна патология.
Ключови думи: очна леща, алфа кристалини, стресови протеини, sHSP,
индиректна имунопероксидазна реакция
Bulgarian review of ophthalmology 1, 2007, 49-54
EXPRESSION OF EYE LENS ANTIGENS – ALPHA
CRYSTALLINS IN EXTRAOCULAR HUMAN FETAL
TISSUES
N.Trifonova, B.Anguelov, P.Rashev, E. Sapundzhiev, I.Buteva, M.Stamenova
ABSTRACT
Eye lens is basically built of alpha crystallins which include two subunits αA and αB.
Being pointed out as highly organ-specific antigens, at present alpha crystallins are added
to the group of the conservative and expressed in a number of tissues stress and
chaperone molecules. The detection of high-titer antibodies against alpha crystallins in
cataract and uveitis puts these proteins in the focus of a range of molecular biological and
immunobiological assays. In our present work, we tested expression of alpha crystallins
in differentiated human fetal tissues. Using indirect immunoperoxidase test, apart from
lens, their expression is also proved in cornea and retina, as well as in a number of
extraocular tissues – striated muscles, myocardium, kidneys, spleen, thymus, glandular
epithelium in intestines and lungs. Our results give basis to presume an onset of immune
response against eye lens and other ocular tissues as a result of extraocular pathology.
Key words: eye lens, alpha crystallins, heat shock proteins, sHSP, indirect
immunoperoxidase test
Ембриология, 2, 2007, 2, 3-8
ЕКСПРЕСИЯ НА НИСКОМОЛЕКУЛНИ СТРЕСОВИ
ПРОТЕИНИ АЛФА-КРИСТАЛИНИ В ЧОВЕШКА
ПЛАЦЕНТА ПРИ РАЗЛИЧНИ ПАТОЛОГИИ
М. Стаменова, С. Поповска, Т, Бетова, П. Рашев, Е. Сапунджиев,
М. Симеонова, Н. Трифонова.
РЕЗЮМЕ
Плацентата е орган с бърз растеж и висока биохимична активност. Тя е особено
чувствителна към негативните фактори на средата. Един от защитните механизми
на клетките към неблагоприятните фактори е синтезата на стресови протеини.
Към групата на нискомолекулните стресови протеини спадат алфа кристалините.
Целта на изследването е да се проследи експресията и локализацията на алфа
кристалините в човешк плацента в норма и патология. Получените резултати
демонстрират наличие на този стресов протеин в нормална плацента, както в
ранните стадии от развитието й (8 – 10 седмици), така и в терминален стадий.
Неговата експресия и локализация е почти непроменена при по-голямата част от
изследваните патологии с изключение на два случая с тежки патологии, налагащи
прекъсване на бременността. Този факт се свързва с участието на алфа
кристалините в процесите на клетъчна пролиферация и диференциация, както и
анти апоптоичната им роля.
Embryology, 2, 2007, 2, 3-8
EXPRESSION OF LOW MOLECULAR WEIGHT
STRESS PROTEINS (sHSPs)
Alpha- CRYSTALLINS IN HUMAN PLACENTA IN
DIFFERENT TYPES OF PATHOLOGY
M.Stamenova, S.Popovska, T.Betova, P.Rashev, E.Sapundzhiev, M.Simeonova,
N.Trifonova
ABSTRACT
The placenta is an organ characterized by fast growth and high levels of biochemical
activity. It is particularly sensitive to negative factors of the surrounding environment.
One of its cells’ defense mechanisms against these negative factors is the stress proteins
synthesis. Alpha-crystallins are a member of the low molecular stress proteins group. The
aim of our work is to study the expression and localization of alpha-crystallins in normal
and pathologically changed human placenta. The results, which we obtained, demonstrate
the presence of this stress protein in normal placenta at early stages, as well as at the final
stage of its development. Its expression and localization are almost constant in most of
the pathologies we have tested, except for two cases with severe pathologies that
demanded termination of the pregnancies. This fact is related to the participation of the
alpha-crystallins in the process of cell proliferation, differentiation and their role in
apoptosis.
2nd Euro Summer School on Biorheology Symposium on Micro Mechanobiology
of Cells, Tissues and Systems, Varna, Bulgaria, September 17-20 2006, published
by Avangard Sofia, 2007, 92 -96.
ASSESSMENT OF VON WILLEBRAND FACTOR AS A
MARKER FOR ENDOTHELIAL DISFUNCTION IN
ARTERIAL HYPERTENSION
Stilian Stoeff, Iliana Buteva, Nedka Trifonova, Maria Stamenova, Milko
Shishenkov, Winrich Breipohl
ABSTRACT
The pathological consequences of endothelial cell dysfunction in arterial hypertension
(AH) are more often threats of thrombotic rather than hemorrhagic complications. von
Willebrand factor (vWF) has been recently revealed to play a crucial role in platelet
thrombosis at sites exposed to high shear stress. The endeavour of the present work was
to accomplish an ELISA for the blood plasma level of vWF. First attempt was made to
explore relation of vWF to C-reactive protein for testing them both as acute phase
reactions of inflammatory process in AH. During statistical processing (Mann-Whitney
test) the vWF level of pregnant women (healthy and with pre-eclampsia) and of subjects
with primary and symptomatic hypertension was significantly increased (P<0.0001,
P<0.001, P=nqs and P<0.01 respectively) versus the vWF level of clinically verified
“healthy” participants (females and males). Spearman correlation test for Prothrombin
time vs. vWF level (including data of all groups together) indicates a constant, small but
statistically significant (P<0.05) inverse relationship as a sign for participation of vWF in
an activated extrinsic coagulation system. The measured vWF levels and the support of
statistical processing perform a validation of vWF-ELISA in the hypertension research.
2nd Euro Summer School on Biorheology Symposium on Micro Mechanobiology
of Cells, Tissues and Systems, Varna, Bulgaria, September 17-20 2006, published
by Avangard Sofia, 2007, 96-99.
A STUDY OF HEMATOLOGICAL INDICES IN
PREGNANCY
Stilian Stoeff, Ivan Dikov, Nedka Trifonova, Sylvia Skelina, Dobrin Kolarov, Tanja
Galabova, Svetoslav Jovtchev, Antoaneta Mladenova, Marin Penev
ABSTRACT
Hemoconcentration in pregnancy tends to be a risk factor for preeclampsia due to its
influence on the flow behaviour of blood in the in the utero-placental region and the
impetus for the blood circulation in the whole body. In a study of arterial hypertension in
preeclampsia were assessed the hematocrit (Hct), the haemoglobin (Hb), the mean
erythrocyte volume (MCV), the leukocyte (LC) and the thrombocyte count (TC). Two
control groups of non-pregnant (NP) and healthy pregnant (HP) women likewise
preeclamptic pregnant (PP) were recruited for blood sampling, conducted after the
regulations of ICSH. Statistical analyses were done using nonparametric comparison
(Mann-Whitney test) of GraphPad InStat programs. A significant increase of Hct in PP
vs. HP (P<0.05) and of LC in PP vs. NP (P<0.0001) as well as decrease of the MCV in
PP vs. NP (P<0.05) were found. In a number of the tested individuals the haematological
indices exceeded the cut off values of the reference ranges in sense of hemorheological
risk for microcirculatory stagnation during pregnancy development.
2nd Euro Summer School on Biorheology Symposium on Micro Mechanobiology
of Cells, Tissues and Systems, Varna, Bulgaria, September 17-20 2006, published
by Avangard Sofia, 2007, 100-103.
OXIDATIVE STRESS IN PRIMARY HYPERTENSION
Stilian Stoeff, Slaven Slaveikow, Svetlana Hadjieva, Tanja Galabova,
Nedka Trifonova, Svetoslav Jovtchev
ABSTRACT
Enhanced lipid peroxidation suggested in the pathogenesis of human hypertension
induced damage has not yet received definite support. To be reported a pilot study for
assessment of malondialdehyde (MDA) in blood plasma from patients with primary
hypertension is the intention of the present work. There will be tested two hypotheses.
First, that it has to be found differences in the MDA level in patients with primary
hypertension vs. normotensive subjects. As second it will be tested for relationship of
MDA levels with indices for blood pressure, lipid profile and uric acid. The study design
encompass clinically verified “healthy” participants (females and males, HS n=12) and
such with essential hypertension (females and males, EH n=13) observing rules for
informed consent. Statistical processing of nonparametric comparison (Mann –Whitney)
and regression analysis tests were performed by GraphPad Instant programs. The MDA
level of the patients with primary hypertension was significantly increased (P<0.05). The
nonparametric correlation test (Spearman r) for MDA levels vs. total cholesterol (TCHL)
and LDL-c of EH indicates moderate significant correlation with r=0.7 (P<0.01) and
r=0.64 (P<0.05) respectively. The statistical significant difference of the measured MDA
levels for HS and EH and the significant correlation of MDA levels especially vs. TCHL
and LDL-c of EH (small patient number n=13) are convincing evidence for the
assumption of enhanced oxidative stress and lipid peroxidation in primary hypertension.
Clinical Hemorheology and microcirculation, 2008, 39, 381-384
QUANTITATIVE EXPEDIENCY ASSESSMENT OF THE ZETA
SEDIMENTATION RATIO AND THE PLASMA VISCOSITY IN
ARTERIAL HYPERTENSION RESEARCH..
S. Stoeff, Sv. Jovtchev, I. Dikov, D. Kolarov, T. Galabova, N. Trifonova, Sv.
Hadjieva, A. Mladenova, L. Lambreva and M. Penev
ABSTRACT
Accepted method of ESR methodology (the Westergren mode and ZSR mode) and its
alternative the plasma viscosity were tested for diagnostic utility in pregnancy induced
hypertension and pre-eclampsia. The receiver-operating characteristic curve (ROC)
analysis approved moderate diagnostic accuracy for the ESR methodology and supplied
support for its preliminary estimated cutoff values but failed to induce cogent
discernment of pathology by values of plasma viscosity. Likely pathological whole blood
alterations boost the erythrocyte aggregation while the concomitant depletion of
macromolecules degrades plasma viscosity values.
Key words: Pregnancy induced hypertension, ESR methodology, plasma viscosity, ROC
analysis
Реферативен бюлетин по Офталмология, година петнадесета, 4, 2008
АВТОАНТИТЕЛА СРЕЩУ АНТИГЕНИ В
ИМУНОЛОГИЧНА ИЗОЛАЦИЯ ПРИ ПАЦИЕНТИ С
ОЧНИ И УРОГЕНИТАЛНИ ХЛАМИДИЙНИ
ИНФЕКЦИИ
Д. Димитрова, Б. Ангелов, Ч. Еленкова, Св. Калайджиев, Л. Христов, К.
Николов, Т. Бояджиев, Н. Трифонова
РЕЗЮМЕ
Едни от най-често срещаните генитални инфекции, предавани по полов път, с
различни последствия за фертилния статус и с различни ефекти върху тъканите на
окото, са тези, причинени от Chlamydia trachomatis.
Цел на настоящото изследване е да се установи съществува ли корелация между
концентрацията на анти-хламидийните антитела и съответно анти-лещени и
спермоантитела при пациенти с хламидиална инфекция с оглед изясняване
възможността за индукция на хронично очно възпаление или на имунно обусловен
инфертилитет при човека.
Резултатите показват липса на корелация между наличието на анти-хламидиални
антитела и анти-лещени антитела в серумите на пациенти с вътреочни и
урогенитални възпаления, положителна корелация между анти-хламидийни
антитела и спернмоантитела в ТАТ и SIV и негативна корелация в ЕЛИЗА за
пациентите с хламидийни инфекции на урногениталния път. Високата
концентрация на спермоантитела и на анти-лещени антитела се свързва найвероятно с възпалителния процес, причинен от Chlamydia trachomatis.
Ключови думи: Chlamydia trachomatis, автоантитела, спермоантитела, антитела
срещу очна леща, човешко безплодие, възпаление на окото.
Comptes rendus de l’Academie bulgare des Sciences, Vol 62, 2009, No2, pp.285-296
ANTIBODIES AGAINST ALPHA CRYSTALLINS IN
WOMEN WITH REPRODUCTIVE FAILURES
Iliana Buteva-Hristova, Nedka Trifonova, Metodi Genov, Blagovest Bechev,
Maria Stamenova
ABSTRACT
Reproductive failures in women may be caused by decreased ovarian reserve, ovulatory,
cervical, tubal or uterine disorders, infections, systemic illnesses, etc. In some women
there is an immunological conflict between the mother and conceptus due to the presence
of antibodies such as antisperm antibodies, antizona antibodies, antiovarial antibodies,
anti-β2 GPI antibodies, antiphosopholipid antibodies. There are antibodies against other
proteins taking part in reproduction which function is not completely elucidated. Such
proteins are the small heat shock proteins family (sHSP). There are data in the literature
that suggest role of sHSP27 in implantation, decidualization and placentation. Another
protein of this family, alpha-B crystallin, shares the same domain with sHSP27. It is
possible that serum antibodies against alpha crystallins may compromise fertility and lead
to reproductive failures in women. The aim of our study is to test levels of anti-alpha
crystallin antibodies in women with reproductive failures. In order to do this, we tested 50
patient sera from women with reproductive failures, grouped according to their diagnoses.
A negative control group was formed from women who had just delivered healthy babies.
Sera were tested with ELISA and Western blot, and the results were analysed statistically
using SPSS. High levels of anti-alpha crystallin antibodies were found in the sera of
women with unsuccessful IVF, unexplained infertility, habitual and single spontaneous
abortions. These findings suggest that there may be an immunological conflict present
between the mother and the conceptus caused by these antibodies.
Key words: reproductive failures, autoantibodies, small heat shock proteins, anti-alpha
crystallin antibodies
Comptes rendus de l'Academie bulgare des Sciences, Tome 62, No 11, 2009
EXPRESSION OF SMALL HEAT SHOCK PROTEIN aBCRYSTALLIN IN NON-SMALL CELL LUNG CANCER
Radostina Cherneva, .Ognian Georgiev, Danail Petrov, Yanina Slavova, Draga
Toncheva, Blagovest Bechev, Maria Stamenova, Nedka Trifonova
ABSTRACT
AlphaB-crystallin, a small heat shock protein, recently became of major interest because
of its differential expression during tumorigenesis and metastasis in various epithebai
tumours. The purpose of this study was to investigate the expression of alphaB-crystallin
and its biologic significance in non-small cell lung cancer (NSCLC).
Immunohistochemical analysis was performed on a tissue microarray slide containing
samples from 146 NSCLC patients who were operated between 2004 and 2005.
Cytoplasmic and nuclear staining were detected. Squamous cell carcinomas and
adenocarcinomas had a distinctive profile of expression. The cytoplasmic staining of the
tumours, however, related to the local invasion - T-factor (p = 0.044). The nuclear
staining was more commonly detected in advanced stages, and was a biomarker of an
aggressive tumour biology (p = 0.042).
AlphaB -crystallin plays an essential role in NSCLC biology. It has a distinctive profile of
expression in the two major histologic subtypes - squamous cell cancers and
adenocarcinomas. Its nuclear staining is associated with aggressive tumour behaviour.
Key words: aB-crystallin, nuclear expression, NSCLC, biomarker
MEDECINE Oncologie: alpha-crystallin antibodies, NSCLC, biomarker, lymph node
metastasis
Comptes rendus de l'Academie bulgare des Sciences, Tome 62, No 12, 2009
ALPHA-CRYSTALLINE ANTIBODIES IN NON-SMALL
CELL LUNG CANCER PATIENTS
Radostina Cherneva, Ognian Georgiev, Danail Petrov, Yanina Slavova, Draga
Toncheva, Blagovest Bechev, Maria Stamenova, Nedka Trifonova
ABSTRACT
The investigation of biomarkers in peripheral blood of cancer patients makes it useful for
clinical application. The aim of the study was to explore and compare the levels of alphacrystalline antibodies in non-small cell lung cancer patients (NSCLC), high risk chronic
obstructive pulmonary disease (COPD) patients and healthy volunteers. Alpha-crystalline
antibodies were detected with ELISA in 51 NSCLC patients, 38 high risk COPD patients
and 52 age and sex matched healthy volunteers. Alpha-crystalline IgG antibodies differed
significantly between the groups of cancer patients and the healthy volunteers (p <
0.0001). The assay was effective in distinguishing the patients with and without
lymphogenic metastatic spread of the disease (p = 0.054).
The clinical significance of alpha-crystalline antibodies has a modest implication for
screening in high risk groups. Its importance as a marker for molecular staging and lymph
node micrometastasis should be further explored.
MEDECINE Oncologie: alpha-crystalline antibodies, NSCLC, biomarker, lymph node
metastasis
Акушерство и гинекология - Приложение 2, 2010
ИЗСЛЕДВАНЕ НА Д-ДИМЕР ПРИ ПАЦИЕНТКИ С
ХИПЕРТОНИЯ НА БРЕМЕННОСТТА КАТО
ДОПЪЛНИТЕЛЕН РАНЕН ДИАГНОСТИЧЕН
И ПРОГНОСТИЧЕН МАРКЕР ЗА НЕБЛАГОПРИЯТЕН
ПЕРИНАТАЛЕН ИЗХОД
Бътева-Христова И., С. Стоев, Кр. Жекова, М. Шишенков, Н. Трифонова
РЕЗЮМЕ
Хипертензивните усложнения се наблюдават при 7-10% от всички бременности и
заедно с хеморагията и сепсиса спадат към основните три причини за майчина
смъртност в световен мащаб. В литературата са описани над 100 тестa за
прогнозиране или идентифициране на рискови пациенти за развитие на хипертония
на бременността, но на този етап никой не е достатъчно надежден за скрининг
преди поява симптомите, когато вече е късно за лечение и единственото решение се
оказва
родоразрешение,
често
с
цена
живота
или
здравето
на
новороденото.Изхождайки от факта, че ключов момент в съвременните разбирания
за патогенезата на хипертонията на бременността е активацията на ендотела, и че
увреденият (активиран) ендотел секретира вещества които активират системата на
коагулация, ние изследвахме фибрин-деградационния продукт Д-димер като един
допълнителен маркер за хипертензивни усложнения на бременността. Известно е,
че повишени плазмени нива на Д-димер се откриват само когато системата на
коагулация е активирана. В настоящото пилотно проучване изследвахме нивата на
Д-димер в плазмата на здрави бременни и бременни с хипертония. Резултатите са
малко на брой и недостатъчни за да имат статистическа остоверност, но въпреки
това очертават определени тенденции. Здравите бременни жени в трети триместър
имат плазмени нива на Д-димер, ненадвишаващи референтните стойности за
небременни пациенти. При прееклампсия съчетанието от хипертония,
хемоконцентрация и високи стойности на Д-димер е ситуация с много висок риск
от последващо влошаване на микроциркулацията както за майката, така и за плода.
Така изследването на Д-димер би могло да се окаже информативен бомаркер при
скрининг на рискови бременни и е потенциален допълнителен маркер за прогноза
на перинаталния изход. Необходимо е бъдещо задълбочено изследване, за да се
установят нормите за Д-димер при здрави
бременни и да се оцени стойността на този тест като ранен скрининг на
хипертензивните усложнения на бременността.
A D-DIMER TEST IN PATIENTS WITH PREGNANCY
HYPERTENTION AS AN ADDITIONAL EARLY
DIAGNOSTIC AND PROGNOSTIC MARKER FOR
ADVERSE PERINATAL OUTCOME
Buteva-Hristova I, S. Stoeff, K. Jekova, M. Shishenkov, N. Trifonova
ABSTRACT
Hypertensive disorders account for 7-10% of pregnancy pathology and are one of three
leading causes of maternal mortality, together with sepsis and hemorrhage. Although
more than 100 tests have been suggested so far, there is no reliable method for detection
of women at high risk for pregnancy hypertension before symptoms develop, and at this
point it is often too late for treatment and the only option is delivery, which puts at danger
the neonate’s life and health. Endothelial activation, being considered a central event in
pregnancy hypertension, and consequently damaged endothelial cells activating the
coagulation system, are the grounds we used to study the changes in a fibrin degradation
product D-dimer levels related to this pathology. It is a well known fact that D-dimer
levels rise when the coagulation system is activated. In the present pilot study we tested
D-dimer levels in the blood of healthy pregnant women and pregnant womenwith
hypertension. Our patients are very few in number and not enough for statistical analysis,
yet certain tendencies can be outlined. Healthy pregnant women reveal D-dimer levels not
exceeding the reference range for healthy nonpregnant patients. On the other hand, in
preeclampsia a constellation of hypertension, haemoconcentration and high levels of Ddimer is a high risk situation which leads to impaired microcirculation of the mother and
the fetus. We speculate that a D-dimer test may prove a useful additional marker for
identification of women at high risk for hypertensive disorders and for prognosis of the
perinatal outcome. Further investigation is required in order to set reference range for Ddimer levels in pregnant patients and to elucidate the predicitive value of this test.
European Journal of Cardio-thoracic Surgery 37, 2010, 44-50
EXPRESSION PROFILE OF THE SMALL HEAT-SHOCK
PROTEIN AlphaB-CRYSTALLIN IN OPERATED-ON
NON-SMALL-CELL LUNG CANCER PATIENTS:
CLINICAL IMPLICATION
Radostina Cherneva, Danail Petrov, Ognian Georgiev, Yanina Slavova, Draga
Toncheva, Maria Stamenova, Nedka Trifonova
ABSTRACT
Objective: AlphaB-crystallin, a small heat-shock protein, recently gained major interest
because of its differential expression during tumourigenesis and metastasis in various
epithelial tumours. The purpose of this study was to investigate the expression of alphaB-crystallin and its biologic and prognostic significance in non-small-cell lung cancer
(NSCLC). Methods: Immunohistochemical analysis was performed on a tissue
microarray slide containing samples from 146 NSCLC patients who were operated on
between 2004 and 2005. Results: Cytoplasmic and nuclear staining was detected.
Squamous cell carcinomas and adenocarcinomas had a distinctive profile of expression.
The cytoplasmic staining of the tumours, however, is related to the local invasion - Tfactor (p = 0.044). Nuclear staining was more commonly detected in advanced stages, and
was a biomarker of an aggressive tumour biology (p = 0.042). Kaplan-Meier analysis
showed that patients with positive nuclear staining had shorter overall survival (log-rank
p = 0.002). Using Cox's proportional hazards model, we performed multivariate analyses
to assess the independent prognostic value of nuclear staining. The variables used
included age, histology, gender and stage. AlphaB-crystallin was an independent negative
prognostic factor of survival in addition to clinical stage. Conclusions: AlphaB-crystallin
plays an essential role in NSCLC biology and its nuclear staining is an independent factor
of poor survival. Its clinical application in molecular biologic substaging of NSCLC
patients needs further validation.
Keywords: Alpha-B crystallin; NSCLC; Biomarker; Poor prognosis; Molecular
substaging
№ 61
Interactive Cardiovascular and Thoracic Surgery 10, 2010, 14-17
Work in progress report - Thoracic oncologic
CLINICAL USEFULNESS OF Αlpha-CRYSTALLIN
ANTIBODIES IN NON-SMALL CELL LUNG CANCER
PATIENTS
Radostina Cherneva, Danail Petrov, Ognian Georgiev, Nedka Trifonova
ABSTRACT
The non-invasive approach of finding biomarkers in peripheral blood of cancer patients
makes it useful for clinical application and cancer screening. The aim of the study was to
explore the clinical utility of alpha-crystallin antibodies as markers for diagnosis of nonsmall cell lung cancer (NSCLC) and screening among high-risk groups. Alpha-crystallin
antibodies were detected with enzyme-linked immunosorbent assay (ELISA) in 51
NSCLC patients, 38 high-risk chronic obstructive pulmonary disease (COPD) patients
and 52 age and sex matched healthy volunteers. Alpha-crystallin IgG antibodies differed
significantly between the groups of cancer patients and the healthy volunteers (p<0.001).
A cut-off value of 0.317 discerned NSCLC patients with sensitivity 62%, and specificity
12% among the control group. The assay was effective in distinguishing the patients with
and without lymphogenic metastatic spread of the disease (p=0.045): sensitivity 60%, and
specificity 70%. The clinical significance of this marker has a modest implication in lung
cancer diagnosis and screening in high-risk groups. Its importance as a prognostic marker
or a marker of disease recurrence and lymph node micrometastasis should be further
explored.
Key words: alpha-Crystallin antibodies; NSCLC; Biornarker; Lymph node metastasis
International Journal of COPD, 2012, 7, 633-640
THE ROLE OF SMALL HEAT-SHOCK PROTEIN
ΑlphaB-CRYSTALLIN (HSPB5) IN COPD
PATHOGENESIS
Radostina V Cherneva, Ognian B Georgiev, Daniela S Petrova, Nedka L Trifonova,
Maria Stamenova, Vesela Ivanova, Veselin I Vlasov
ABSTRACT
Background: αB-crystallin (HspB5) is a chaperone whose role as a marker of innate
immunity activation as well as its therapeutic potential have recently been investigated in
several inflammatory diseases: multiple sclerosis, myocardial ischemia, and Guillain–
Barré syndrome.
Aim: The aim of this study is to determine the role of αB-crystallin in chronic obstructive
pulmonary disease (COPD) pathogenesis and inflammation.
Materials: Plasma levels of αB-crystallin were studied in 163 patients: 52 healthy nonCOPD smokers; 20 COPD smokers in Global Initiative for Chronic Obstructive Lung
Disease (GOLD) stages I–II; 43 COPD smokers in GOLD stages III-IV. Forty-eight
patients were diagnosed with acute inflammatory respiratory disease. The plasma levels
of αB-crystallin antibodies were determined by an enzyme-linked immunosorbent assay
(Calbiochem), and were confirmed with Western blotting. Tissue expression of the
protein was compared in three different groups of patients: COPD smokers, COPD
nonsmokers, and in patients with age-related emphysema.
Results: The mean level of anti-αB-crystallin antibodies in non-COPD smokers was
0.291nm. In COPD smokers it was 0.352 nm and, in patients with inflammatory lung
diseases, 0.433 nm. There was a statistically significant difference between COPD
smokers and healthy non-COPD smokers (P = 0.010). The same could be observed
comparing the group of patients with acute inflammation and non-COPD healthy smokers
(P = 0.007). There was no statistically significant difference between patients with
mild/moderate inflammation and those with severe COPD. Tissue detection of the protein
showed that it was significantly overexpressed in COPD smokers in comparison to COPD
nonsmokers and was only slightly expressed in patients with age-related emphysema.
Conclusion: αB-crystallin is increased in patients with inflammatory lung diseases.
Though unspecific, it could be used in a panel of markers discerning COPD smokers from
healthy nonsmokers. As αB-crystallin is a regulator of innate immunity and a therapeutic
anti-inflammatory agent, its exact role in COPD pathogenesis and therapy should be
explored further.
Key words: COPD, HspB5, chaperonopathology, pathogenesis
Institute of Experimental Morphology and Anthropology with Museum Bulgarian
Anatomical Society
Acta morphologica et anthropologica, 2010, 15, 62-65
EXPRESSION OF SMALL HEAT SHOCK PROTEIN
Alpha-B CRYSTALLINE IN NON-SMALL CELL LUNG
CANCER
R. Cherneva, O, Georgiev, V Vlasov M. Stamenova, N. Trifonova
ABSTRACT
To evaluate the expression profile of the small heat shock protein alphaB-crystallin in
NSCLC and to analyse its correlation with Ki-67 and p53 expression.
Immunohistochemistry with alphaB-crystallin, Ki-67 and p53 was applied on 25 tissue
samples of patients with non-small cell lung cancer.
70% of the samples are positively stained for alpha-B crystallin. Both nuclear and
cytoplasmic staining is observed . Fifty two percent of the tissue samples are positive for
p53 and 40% were positive for Ki-57.
The small heat shock protein alphaB-crystallin is a novel biomarker that is largely
expressed in non-small cell lung cancer. It is not predominantly expressed in any
histologic type. There was a tendency for a more intensive nuclear staining in
adenocarcinomas. AlphaB-crystalline negative cells were positive for Ki- 67 and p53.
Key words: non-small cell lung cancer, p53, Ki-67, alphaB-crystallin.
Int. J.BIO Automation, 2010, 14, 3, 187-196
INVESTIGATION OF THE PROPERTIES OF
COVALENT IMMOBILIZED ANTI-AFLATOXIN B1
ANTIBODY ON MEMBRANES FROM COPOLYMER OF
POLYACRYLAMIDE-POLYACRYLONITRILE
Lyubov Yotova, Nedka Trifonova, Terry Vrabcheva, Vasilka Mironova, Vasilena
Cuchuranova
ABSTRACT
Aflatoxins are toxic secondary metabolites produced by a number of different fungi
(Aspergillus flavis, Aspergillus parasiticus), and can be present in a wide range of blood
and feed commodities. The most used methods for analysis of aflatoxins are thin-layer
chromatography, high-performance liquid chromatography (HPLC), electrochemical
immunoanalysis and microtiter plate enzyme-linked immunosorbent assay (ELISA).
Membranes from copolymer of polyacrylamide- polyacrylonitrile have been prepared.
These membranes were used as a matrix for a covalent binding of polyclonal antiaflatoxin B1 antibody. ELISA was carried out with these membranes to prove successful
immobilization of the antibody. It was done comparative analysis with ELISA between
standard microtitre plate and our membranes with infected peanuts.
Series on Biomechanics, 25, 2010, 1-2, 169-173.
(Peer-reviewed journal edited by the Bulgarian Academy of Sciences).
THE LEUKOCYTE ADHESIVENESS/AGGREGATION
TEST IN ARTERIAL HYPERTENSION RESEARCH
S.Stoeff, Z. Naychov, T. Galabova, N. Trifonova, M. Shishenkov, S. Jovtchev, B.
Bechev, S. Hadjieva, A. Mladenova, M. Penev, M. Vretenarska, E. Rachev
ABSTRACT
The leukocyte adhesiveness/aggregation (LAA) phenomenon, well known like leukergy,
was tested to indicate presumed inflammatory changes in healthy (HP) and pre-eclamptic
pregnancies (PP). Non pregnant patients with essential (EH) and symptomatic
hypertension (SH) were additionally investigated to evaluate the leukergy as a priming
initiation of atherogenic state.
The LLA was significantly increased in HP and PP compared to non pregnant control
persons (NP). There was also significant difference between HP and PP. The LAA in SH
was considerably enhanced compared to NP. For the EH group the raise in LT values was
found not quite significant. C-reactive protein (CRP), fibrinogen (FG) and LDL were
significantly increased in all patient groups. Nonparametric analysis revealed in arterial
hypertension (except PP) low correlation of LAA vs. ZSR, leukocyte count (WCC), total
cholesterol and LDL; likewise there was modest correlation of LAA vs. CRP and FG.
The LAA results allude for systemic low-grade inflammation with additional rheological
impact- microcirculatory worsening of blood fluidity in hypertensive state.
Key words: Arterial hypertension, inflammation, leukergy
Торакална медицина, 4, 2012, 1, 64-77
ИМУНОХИСТОХИМИЧНО ИЗСЛЕДВАНЕ НА
ЕКСПРЕСИЯТА НА НИСКОМОЛЕКУЛНИТЕ
БЕЛТЪЦИ НА СТРЕСА - AlphaB-CRYSTALLIN И
HSP27 ПРИ ПЪРВИЧНИ БЕЛОДРОБНИ КАРЦИНОМИ
Д.М. Маринова, Я.Г. Славова, Н. Трифонова, Вл. Максимов, Д. Петров
.
РЕЗЮМЕ
Белтъците на топлинния стрес – Hsp, са с основна функция да променят
структурата и взаимо-действието между други белтъци. AlphaB-crystallin и Hsp27
са свръхекспресирани при редица тумори при човека и са свързани с
пролиферацията, диференциацията, инвазията, метастазира-нето, клетъчната смърт
и разпознаването от имунната система. Целта на настоящето изследване е да се
проучи експресията на стресовите протеини alphaB-crystallin и Hsp27 при
малигнени епителни белодробни тумори, като се направи опит да се изясни
участието им в канцерогенезата. Изследването включи 105 пациента (72 мъже и 33
жени; средна възраст 56.7Ѓ}12.3 г.), претърпели оперативно лечение за първични
белодробни карциноми – 35 карциноидни тумора (КТ), 20 дребноклетъчни
белодробни карциноми (ДКБК), 10 едроклетъчни невроендокринни карциноми
(ЕКНЕК), 20 аденокарциноми (АК), 20 плоскоклетъчни карциноми (ПК).
Използвани методи: клинико-патологични – хистологичен вид на тумора, Т-статус,
N-статус, pTNM-стадий на болестта; имунохистохимични – експресия на alphaBcrystallin и Hsp27; и статистически за обработка на получената информация. Hsp27
се експресира цитоплазмено при почти всички изследвани белодробни карциноми
(97%), което показва, че този белтък играе основна роля в канцерогенезата им. Поважна в случая се оказва ядрената му експресия, която показва различни нива при
различните белодробни карциноми – най-изразена при ЕКНЕК, ДКБК, ПК и АК
(р<0.001). Hsp27 е потенциална мишена за таргетна терапия при белодробните
карциноми. АlphaB-crystallin се експресира ядрено при 99% от туморите, а
цитоплазмено – при 23%. Наблюдават се статистически значими корелации между
нивата на количествена ядрена експресия на alphaB-crystallin и наличието на
метастази в лимфни възли (р<0.001), стадия (р=0.02), и големината на туморите
(р=0.04). Между нивата на цитоплазмена експресия на маркера и стадия също има
статистическа зависимост – позитивните тумори са по-често в по-ранен стадий,
докато негативните нарастват с покачване на стадия (р<0.001). Тези резултати
водят до заключение за основната роля на нискомолекулните белтъци на топлинния
стрес в канцерогенезата на белодробните карциноми.
IMMUNOHISTOCHEMICAL EXAMINATION OF LOW
WEIGHT HEAT SHOCK PROTEINS – AlphaB
CRYSTALLIN AND Hsp27 – EXPRESSION
IN PRIMARY LUNG CARCINOMAS
D. Marinova, Y. Slavova, N. Trifonova, V. Maksimov, D. Petrov
ABSTRACT
Main function of heat shock proteins (Hsp) is to change the structure and interactions
between other proteins. Overexpression of alphaB-crystallin and Hsp27 is found in
number of tumors and is connected with proliferation, differentiation, invasion,
metastasis, apoptosis and immune recognition. The aim of this study is to investigate the
expression of stress proteins alphaB-crystallin and Hsp27 in malignant epithelial tumors,
as we attempt to clarify their involvement in carcinogenesis. Specimens from surgical
resections of 105 patients (72 men, 33 women; age 56.7Ѓ}12.3) who underwent radical
operation for primary lung cancer were investigated – 35 carcinoid tumors, 20 small cell
lung carcinomas (SCLC), 10 large cell neuroendocrine carcinomas (LCNEC), 20
adenocarcinomas (AC), 20 squamous cell carcinomas (SCC). Methods: clinicopathological – histological type, T-status, N-status, pTNM stage; immunohistochemical
expression of alphaB-crystallin and Hsp27; and statistical. Cytoplasmic expression of
Hsp27 was found in almost every examined lung carcinoma (97%), pointing out the main
role of this protein in their cancerogenesis. Nuclear expression of Hsp27 is more
important with different levels among different lung carcinomas – mostly in LCNEC,
SCLC, SCC, and AC (p<0.001). Hsp27 is a potential target for targeted therapy in lung
cancer. Nuclear expression of alphaB-crystallin is found in 99% of tumors, and
cytoplasmic expression – in 23%. There is a statistically significant correlation between
nuclear expression of alphaB-crystallin and lymph node metastasis р<0.001), stage
(p=0.02), and size of the tumors (p=0.04). There is a statistically significant correlation
between cytoplasmic expression of alphaB-crystallin and stage – expressing tumors are
more often in earlier stage, and negative tumors are more in advanced stage (p<0.001).
We conclude that low weight heat shock proteins play a major role in cancerogenesis of
lung cancer.
Key terms: heat shock
immunohistochemistry
proteins,
lung
cancer,
Hsp27,
alphaB-crystallin,
Series on Biomechanics, Vol.27, 2012, 3-4, 30-33
WHOLE BLOOD VISCOSITY ASSESSMENT IN
ARTERIAL HYPERTENSION: A MATHEMATICAL
APPROACH
S. Stoeff, S. Jovtchev, N. Trifonova
ABSTRACT
Three mathematical models for calculation of whole blood viscosity (WBV) based on data
for hematocrit (Hct),plasma viscosity (PV) or alternatively total plasma protein (TP) were
tested for healthy subjects and drafts with different forms of hypertension. The equation
of J. P. A. Weaver and coauthors was found to give the best statistical significance in
observing alterations in WBV at particular shear rate (208 s-1) from patient with arterial
hypertension of all types studied, cluding the most common type of hypertension - the
essential hypertension. The mathematical approach is an alternative to the expensive and
arduous experimental estimation of WBV recommended worldwide as very important in
evaluation of the total peripheral resistance of the ongoing systemic atherogenesis in
arterial hypertension.
Key words: Arterial hypertension, whole blood viscosity, mathematical approach,
expedient alternative
Comptes rendus de l’Academie bulgare des Sciences, Vol 66, 2013, 2, 281-288
EVALUATION OF THE EXPRESSION OF THE LOW
WEIGHT HEAT SHOCK PROTEIN ΑlphaB CRYSTALLIN IN PULMONARY NEUROENDOCRINE
TUMOURS
Dora M.Marinova, Yanina G.Slavova, Nedka B.Trifonova, Vladimir N.Maksimov,
Dimitar T.Kostadinov, Danail B.Petrov
ABSTRACT
AlphaB–crystallin is a major heat-inducible small heat shock protein, which is supposed
to be implicated in tumour cell proliferation, differentiation, invasion, metastasis and
apoptosis. Still the expression pattern of the phosphorylated on serin 59 form of αB–
crystallin in lung cancer is not yet investigated.
The aim of the present work is to study this pattern in different histological subtypes of
pulmonary neuroendocrine tumours (pNETs).
Surgically resected specimens from 143 patients with pNETs were studied. The
histological subtype, pathological Tumour-Node-Metastasis stage and the
immunohistochemical expression of phosphorylated αB–crystallin were evaluated.
We demonstrated that the nucleus was the major localization site of the protein although
there were some rare cases showing also diffuse cytoplasmic expression. High grade
pNETs (small cell lung carcinoma and large cell neuroendocrine carcinoma) showed
nuclear expression in all cases but most frequently it was in less than 50% of the tumour
cells; cytoplasmic expression was shown in single cases. Just the opposite was observed
in low and intermediate grade pNETs (typical carcinoids and atypical carcinoids) nuclear expression was not seen in all of the cases, but when it was present it was in
almost all tumour cells; the cases expressing phosphorylated αB–crystallin also in the
cytoplasm were mainly typical carcinoids. We demonstrated that cytoplasmic expression
was associated with earlier stage and absence of metastases, which may determine it as a
potential marker for a favourable prognosis in patients.
We conclude that phosphorylated αB–crystallin probably plays a major role in pNETs
biology, it may be associated with tumour grade, it may have a prognostic value, and it
may be used as future target for therapy.
Key words: heat shock proteins, αB–crystallin, pulmonary neuroendocrine tumours
JBUON 2013; 18(4): 915-920
ISSN: 1107-0625, online ISSN: 2241-6293 • www.jbuon.com
STRESS PROTEIN HSP27 EXPRESSION PREDICTS THE
OUTCOME IN OPERATED SMALL CELL LUNG
CARCINOMA AND LARGE CELL NEUROENDOCRINE
CARCINOMA PATIENTS
D. M. Marinova, Y. G. Slavova, N. Trifonova, D. Kostadinov, V. Maksimov, D.
Petrov
ABSTRACT
Purpose: Heat shock protein (Hsp)27 is overexpressed in a range of human cancers and
is implicated in tumor cellproliferation, differentiation, invasion, metastasis, and survival.
The aim of the present study was to determine the prognostic significance of Hsp27
expression in small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma
(LCNEC).
Methods: Surgically resected SCLCs (N=51) and LCNECs (N=15) were studied. The
Hsp27 expression was detected immunohistochemically.
Results: Hsp27 positive immunoreaction in the cytoplasm was observed in 45 (88%)
SCLCs and 14 (93%) LCNECs. Аcombination of cytoplasmic with nuclear Hsp27
expression was observed in 28 (62%) SCLCs and 14 (100%) LCNECs. There was a
correlation between Hsp27 cytoplasmic overexpression and Hsp27 nuclear expression
with patient survival confirmed by Cox multivariate analysis.
Conclusion: We conclude that the higher Hsp27 cytoplasmic expression and nuclear
expression may represent favorable prognostic factors in SCLC and LCNEC.
Key words: heat shock proteins, Hsp27, immunohistochemistry, LCNEC, prognosis,
small cell lung cancer
Comptes rendus de l’Academie bulgare des Sciences, Tome 66, 2013, 3, 451-458
EVALUATION OF THE EXPRESSION OF THE LOW
WEIGHT HEAT SHOCK PROTEIN HSP27 IN
PULMONARY NEUROENDOCRINE TUMOURS
Dora M. Marinova, Yanina G. Slavova, Vladimir N. Maksimov,Nedka L. Trifonova,
Dimitar T. Kostadinov, Danail B. Petrov
ABSTRACT
Hsp27 is overexpressed in a range of human cancers and is implicated in tumour cell
proliferation, differentiation, invasion, metastasis and cell survival. We aim to study
Hsp27 expression in pulmonary neuroendocrine tumours (pNETs).
Surgically resected pNETs (n = 143) were studied. The histological type, the pTNM stage
and the immunohistochemical expression of Hsp27 were evaluated. Hsp27 was found to
be expressed in almost all cases. We demonstrate that tumours with higher per cent
tumour cells with cytoplasmic expression of Hsp27 are smaller, without invasion, low or
intermediate grade of differentiation, at earlier stages, without lymph nodes metastases,
contrary to the nuclear expression of Hsp27, which is found in bigger, locally invasive
high grade tumours at
advanced stages with lymph nodes metastases. We conclude that Hsp27 probably plays a
major role in pNETs biology, it may be associated with tumour grade, and may have a
prognostic value.
Key words: heat shock proteins, Hsp27, pulmonary neuroendocrine tumours
This study was possible with the financial support of the Council for Medical Science,
Medical University of Sofia, Project Contracts No 18-D/2010 and No 1-D/2011.
.
Comptes rendus de l’Academie bulgare des Sciences, Vol 66, 2013, 12, 1777-1784
EXPRESSION OF SMALL HEAT SHOCK PROTEINS
HSP27 AND ΑlphaB-CRYSTALLIN IN HUMAN TUBAL
PREGNANCY
Iliana Buteva-Hristova, Viktor Novachkov, Galen Kurkchiev, Stefan Petrov,
Martin Krupev, Nedka Trifonova, Dimitrina Dimitrova-Dikanarova
ABSTRACT
Small heat shock proteins Hsp27 and αB-crystallin are important for proper embryo
implantation, decidualization and placentation, but little is known about their role in the
occurrence of tubal pregnancy.
In the present report we describe the expression and discuss the possible role of Hsp27
and αB-crystallin in surgically resected oviducts from human tubal pregnancy, 16 cases.
Tubes from a case of uterine pregnancy followed by hysterectomy at 6 gestational weeks
were used as a control. Immunohistochemical expression of Hsp27, αB-crystallin and
their phosphorylated forms (p-Hsp27, p-αB-crystallin) was read at light microscopy. αBcrystallin is found moderately expressed predominantly apically and inside the cilia in
tubal pregnancy, far from the implantation site and inside the whole epithelial cells
cytoplasm at the implantation site. The same protein is evenly distributed inside the
cytoplasm in the control case. p-αB-crystallin and Hsp27 are moderately to strongly
expressed in the tubal epithelial cells’ cytoplasm in both tubal pregnancy and uterine
pregnancy; p-Hsp27’s expression is found negative in all tubal pregnancy and positive in
the cilia in the uterine pregnancy.
We hypothesize that p-Hsp27 interacts with the motor protein dynein and αB-crystallin
functions to protect the tubulin subunits in the cilia. Different stress factors lead to
changes in the expression and the localization of these small heat shock proteins which
most probably interferes with proper ciliary function and allows tubal pregnancy to occur.
Key words: Hsp27, αB-crystallin, human tubal pregnancy
Comptes rendus de l’Academie bulgare des Sciences, Vol 67, 2014 ,3, .367-372
IMMUNOHISTOCHEMICAL STUDY OF HSP27 IN
HUMAN EMBRYOS
Iliana Hristova, Viktor Novachkov, Stefan Petrov, Ilia Vatev,
Dimitrina Dimitrova-Dikanarova, Dora Marinova, Yanina Slavova,
Nedka Trifonova
ABSTRACT
Expression of heat shock proteins (Hsp) is necessary for optimal running of the
mammalian embryo development. Despite the growing interest in small Hsps' role in
human embryo development, their importance is not fully elucidated.
The aim of our work is to describe the expression of a member of the sHsp-Hsp27
(phosphorylated and nonphosphorylated) in human embryos, aged from 5 to 12 gestation
weeks.
In order to detect expression and localization of Hsp27 we have immunostained parafin
embeded tissue sections from patients with elective abortions which contain embryos ( n
=34). Results were read at light microscopy, using a semiquantitative 4-stage scale.
Protein expression is documented over a short time-frame, in a stagedependent manner.
Hsp27 appears early in the cytoplasm of mesenchymal cells, while p-Hsp27 does not
appear in the embryos. As gestation age advances, expression becomes more
uncoordinated in different tissues.
Our observations give us the ground to hypothesize that the protein plays an important
role in the processes of cell division, apoptosis and diferentiation during embryo
development.
Key words: human embryos, Hsp27, small heat shock proteins
Учебни помагала
ИЗБРАНИ МЕТОДИ ЗА ДНК, ЛИПИДЕН И
БЕЛТЪЧЕН АНАЛИЗ. ТОМ III БЕЛТЪЧЕН
АНАЛИЗ 2005, pp 65 (на български и на английски език)
Авторски колектив: Р. Комса Пенкова, К. Ковачева, С. Ангелова, М.
Симеонова, Y Carpentier, J. Winand, I. Dupont, O. Scruel, W. Breipohl, M.
Ahrend, M. Aргирова, А. Савов, Н. Трифонова, М. Стаменова, С.
Калайджиев и А. Пашов
Ръководството е изработено в хода на изпълнение на: Leonardo da Vinci
Pilot Project № BG/00/B/F/PP/132100 ”Improving of Practical Skills in
Molecular Biology and Analytical Biochemistry in Medical Training”.
Предназначено е за студенти и специализанти от България, Германия и
Белгия в курсове по биохимия, биотехнологии и имунология. В
ръководството са включени следните методи за белтъчен анализ:
Протеомен анализ; физикохимични методи – полиакриламидна
електрофореза и изоелектрично фокусиране; имунологични методи,
методи за изолиране и пречистване на белтъци.
FOOD
SAFETY.
EXPOSURE
TO
TOXIC
ENVIRONMENT. CHAPTER 6, MODULE 32.1. IN:
TRAINING MEDICAL DOCTORS AND STUDENTS
IN NUTRITION, STUDY MANUAL EDUCTIONAL
MODULES, 2005, v. 2: 88-98.
Stavreva M, Ed van Klink, I. Buteva, N. Trifonova
Ръководството е изработено по Leonardo da Vinci Pilot Project BG-03-BF-PP-166039, “Life Long Learning System: Nutrition at the Level of
Molecular Medicine”. Ръководството е предназначено за лекари и
студенти. Модул 32.1. е посветен на световно значим проблем безопасността на храните. Дава се определение за безопасна храна и
основните термини по безопасност на храните,
дискотират се
рисковите храни, критериите за оценка на безопасна храна,
представени са петте ключа ключа на Световната здравна организация
за безопасна храна.
РЪКОВОДСТВО ПО ИМУНОХИМИЧНИ МЕТОДИ
ЗА СТУДЕНТИ ПО МЕДИЦИНА
под редакцията на Н. Трифонова и М. Стаменова, рецензент Ив.
Буланов, от модул по Имунобиология, организиран 2006 г. от Катедрата
по биология при МФ, МУ – София
Авторски колектив: Д. Димитрова, Ив. Младенов, М. Стаменова,
Н. Трифонова, П. Mинчева, Р. Пенкова, Св. Калайджиев, Цв. Маринова
ПРИМЕРНИ ТЕСТОВЕ ПО МЕДИЦИНСКА
БИОЛОГИЯ В: БИОЛОГИЯ - УЧЕБНИК ЗА
МЕДИЦИНСКИТЕ УНИВЕРСИТЕТИ ПОД
РЕДАКЦИЯТА НА ИЛИЯ ВАТЕВ, СОФИЯ, РЕКО,
2006 г.
Авторски колектив: Велев В, В. Дамянова, С. Делимитрева, Д.
Димитрова, Р. Живкова, М. Маркова, И. Младенов, А. Тошев, Н.
Трифонова, В. УзуновВатев И, В. Велев, П. Георгиева, В. Дамянова, С.
Делимитрева, Д. Димитрова, Р. Живкова, Ц. Маринова, М. Маркова, И.
Младенов, Н. Трифонова, А. Тошев, В. Узунов, К. Хаджииванова.
ТЕСТОВА ПО БИОЛОГИЯ, ПАРАЗИТОЛОГИЯ И
СРАВНИТЕЛНА АНАТОМИЯ ЗА СТУДЕНТИ ПО
МЕДИЦИНА, СТОМАТОЛОГИЯ И ФАРМАЦИЯ
ОТ МЕДИЦИНСКИТЕ УНИВЕРСИТЕТИ, СОФИЯ,
РЕКО, 2009 г.
Авторски колектив: Ватев И, В. Велев, П. Георгиева, В. Дамянова, С.
Делимитрева, Д. Димитрова, Р. Живкова, Ц. Маринова, М. Маркова, И.
Младенов, Н. Трифонова, А. Тошев, В.Узунов, К. Хаджииванова.
ИМУНОХИМИЧНИ И БИОТЕХНОЛОГИЧНИ
МЕТОДИ, УНИВЕРИСИТЕТСКО ИЗДАТЕЛСТВО
ХТМУ, ПОД РЕДАКЦИЯТА НА Н. ТРИФОНОВА,
Л. ЙОТОВА И М. СТАМЕНОВА, РЕЦЕНЗЕНТ ИВ.
БУЛАНОВ, СОФИЯ 2013
Авторски колектив: Илия Ватев, Д. Димитрова, Ив. Младенов, Л.
Йотова, Св. Калайджиев, Д. Маринкова, П. Минчева, И. Младенова, М.
Стаменова, Н. Трифонова, Р. Трифонова
РЪКОВОДСТВО ЗА ПРАКТИЧЕСКИ
УПРАЖНЕНИЯ ПО БИОЛОГИЯ ЗА СТУДЕНТИ
ПО МЕДИЦИНА, ДЕНТАЛНА МЕДИЦИНА И
ФАРМАЦИЯ, ПОД РЕДАКЦИЯТА НА Д.
ДИМИТРОВА И М. МАРКОВА, РЕЦЕНЗЕНТ М.
СТАМЕНОВА, СОФИЯ, РЕКО, 2014
Авторски колектив: И. Буланов, И. Ватев, В. Дамянова, С. Делимитрева,
Д. Димитрова – Диканарова, Р. Живкова, Р. Коларова – Колева, В.
Лазаров, Ц. Маринова, М. Маркова, Л. Мархолев, П. Минчева, И.
Младенов, В. Николова, З. Сабит, Н. Трифонова, В. Узурова, И.
Чакърова

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