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Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Connection of mean lymphocyte volume and mean monocyte volume with disease activity in rheumatoid arthritis
Get PDFReumatoidni artritis je kronična autoimuna bolest od koje boluje otprilike I% populacije.
Dijagnostika ove bolesti temelji se na brojnim metodama uključujući radiološke i laboratorijske pretrage te
opću kliničku sliku. Laboratorijska dijagnostika uključuje KKS, upalne parametre (brzina SE, CRP) te
imunološke pretrage na različita antitijela, npr. anti-CCP. Uz pretrage krvi, analizira se i sinovijalna
tekućina. Iako ukupan broj leukocita s podatcima o udjelu pojedinih vrsta leukocita daje vrijednu informaiju
o aktivnosti bolesti, tehnologija VCS pruža informaciju o svakoj pojedinačnoj stanici i stoga biokemičarima
i kliničarima omogućava novi uvid u patofiziologiju upalnog procesa. U ovom radu proučene su vrijednosti
prosječnog volumena limfocita i monocita u definiranju aktivnosti bolesti korištenjem VCS tehnologije
automatskog analizatora na ukupno 140 uzoraka bolesnika i 32 uzorka ispitanika u kontrolnoj skupini.
Analizom podataka dobivena je statistički značajna razlika između vrijednosti MCV Ly i MCV Mo
kontrolne skupine ispitanika i bolesnika s dijagnosticiranim reumatoidnim artritisom te dobra korelacija s
CRP-om i DAS28 kod aktivne bolesti. Također, dobivena je statistički značajna razlika u vrijednostima
MCV Ly i MCV Mo u podskupinama aktivnog reumatoidnog artritisa i remisije bolesti. Uz definiranje
aktivnosti bolesti dobivene su statistički značajno više vrijednosti MCV Ly i MCV Mo kod bolesnika na
terapiji inhibitorima TNF-a u odnosu na bolesnike na terapiji inhibitorima IL-6. Dobiveni rezultati
potvrđuju MCV Ly i MCV Mo kao potencijalne nove biljege aktivnosti bolesti i vrijedna su tema daljnjih
istraživanja u ranoj dijagnostici, praćenju aktivnosti bolesti i terapije u različitim upalnim bolestima
uključujući reumatoidni artritis.Rheumatoid arthritis (RA) is a chronic autoimmune disease with a prevelance of around 1% in the
world. Characterized by joint swelling, joint tenderness, and synovial hyperplasia, inflammatory process
eventually leads to cartilage and bone destruction, severe disability and premature mortality. Differencial
diagnosis is based on multiple diagnostic methods, including laboratory tests, radiography or other imaging
techniques. Along with specific inflammatory markers such as CRP or ESR, laboratory tests include
specific antibodies (anti-CCP) for RA diagnostics. Although total WBC count with cell population data
gives a valuable information about disease activity, VCS technology gives information about each
individua) leukocyte cell population therefore giving biochemists a new insight to the pathology of
inflammatory process. In this masters thesis, the VCS parameters mean lymphocyte volume (MCV Ly) and
mean monocyte volume (MCV Mo) acquired from a Beckman Coulter DxH800 haematology analyzer were
investigated to determine which of them could indicate the activation of inflammatory process in RA. Total number of samples was 140 in the test group and 32 in control group. Out of 140 samples, 34 were patients
with active rheumatoid arthritis and 104 were in remission. The results are as follows: MCV Ly is
significantly increased in patients with RA compared with control group as well as in patients with active
RA compared with those i11 remission. MCV Mo is also sig11ificantly increased in patients RA
compared with control group as well as in patients with active RA compared with those in remission. There
is a positive correlation between MCV Ly a11d MCV Mo and CRP and DAS28 in active rheumatoid
arthritis. MCV Ly a11d MCV Mo are also significantly increased in patients on anti-TNF-a:
with patients on anti-IL-6 drugs. These results indicate that MCV Ly and MCV Mo may have potential for
use in RA, monitoring disease activity as well as efficacy of therapy
Association of the -786 T > C i 894 G > T polymorphisms in the eNOS gene and strokes in children
No full textEndotelna sintaza dušikovog oksida (eNOS) je enzim od iznimne važnosti za vaskularni sustav. Proizvodi dušikov oksid (NO) koji u endotelu djeluje vazodilatacijski, doprinosi regulaciji krvnog tlaka, inhibira agregaciju trombocita i njihovu adheziju na zid krvne žile. eNOS pokazuje zaštitini učinak nakon ishemije mozga jer proizvodi NO koji potiče vazodilataciju i inhibira mikrovaskularnu agregaciju i adheziju. Polimorfizmi eNOS -786 T > C i 894 G > T dovode do smanjene proizvodnje NO ili povećane razgradnje zrelog enzima, stoga su pojedinci koji nose navedene polimorfizme potencijalno pod većim rizikom nepovoljnih vaskularnih događaja. Cilj ovog diplomskog rada bio je istražiti povezanost polimorfizama eNOS i moždanih udara kod djece. Moždani udari kod djece, iako rijetki, danas su u porastu. Ozbiljna su stanja koja u većini slučajeva ostavljaju teški neurološki deficit.
U ovom istraživanju pronađena je povezanost polimorfizma eNOS -786 T > C i CSVT kod djece prema kodominantnom (p=0,026) i prekodominantnom (p=0,007) modelu nasljeđivanja. Pronađena je i povezanost polimorfizma eNOS 894 G > T i CSVT kod ženske djece prema kodominantnom (p=0,031), dominantnom (p=0,025) i prekodominantnom (p=0,019) modelu. Ovo istraživanje provedeno je na manjoj skupini pacijenata te je potrebno rezultate provjeriti opsežnijim istraživanjima.Endothelial nitric oxide synthase (eNOS) is an enzyme of exceptional importance for the vascular system. It produces nitric oxide (NO), which has a vasodilating effect in the vascular endothelium, contributes to the regulation of blood pressure, inhibits platelet aggregation and their adhesion to the blood vessel wall. Endothelial NO synthase shows a protective effect after cerebral ischemia because it produces NO that promotes vasodilation and inhibits microvascular aggregation and adhesion. The eNOS -786 T > C and 894 G > T polymorphisms lead to reduced NO production or increased degradation of the mature enzyme, so individuals carrying these polymorphisms are potentially at higher risk of adverse vascular events. The aim of this study was to investigate the relationship between eNOS polymorphisms and stroke in children. Strokes in children, although rare, are on the rise today. They are serious conditions that, in most cases, leave a severe neurological deficit.
In this study, an association was found between the eNOS -786 T > C polymorphism and CSVT in children according to the codominant (p = 0,026) and overdominant (p = 0,007) inheritance model. The association of the eNOS 894 G > T polymorphism and CSVT in female children according to the codominant (p = 0,031), dominant (p = 0,025) and overdominant (p = 0,019) inheritance models was also found. This study was performed on a small group of patients and the results need to be verified by more extensive studies
Effect of oral contraceptives on factors of coagulation and fibrinolysis
Get PDFOralni kontraceptivi imaju brojne učinke na organizam žene poput poželjnog smanjenja pojavnosti zloćudnih
bolesti jajnika i endometrija, ali i nepoželjne učinke od kojih je najpoznatiji povišeni trombotički rizik. Činjenica
je da su oralni kontraceptivi jedan od rizika za razvoj trombo-embolijskih bolesti, s relativnim rizikom od 1,15
do 8,5 ovisno o formulaciji pripravka i obliku trombo-embolijske bolesti. Razvoj laboratorijske dijagnostike,
molekularnih ispitivanja i koagulacijskih pretraga, dao je novi zamah istraživanjima povezujući epidemiološke
podatke o trombotičkim rizicima poput pušenja, debljine, dobi, tjelovježbe i drugih s biološkom osnovom.
Istovremeno, razvoj sintetičnih estrogena i progesterona, njihovih doza i kombinacija, dodatan su poticaj
studijama učinka pojedine formulacije na koagulacijski odgovor.
Cilj istraživanja bio je utvrđivanje utjecaja oralnih kontraceptiva na čimbenike zgrušavanja i fibrinolize u
lokalnoj populaciji, ovisno o: količini i hormonalnom sastavu korištenog pripravka, postojanju nasljednih
trombofilija te razlici među ispitanicama u dobivenim vrijednostima aktivnosti čimbenika hemostaze u odnosu
na dodatne čimbenike rizika za trombo-embolijske bolesti.
U istraživanje su uključeni rezultati 195 žena koje su uzimale 6 ciklusa oralnu kontracepciju. Određivani su
čimbenici nasljedne trombofilije (FV Leiden, FIIG20210A i PAI-1 5G/4G) i parametri hemostaze (PV, APTV,
fibrinogen, aPCR, protein C i S, FVIII, antitrombin, plazminogen, inhibitor plazmina, PAI-1 i d-dimeri) mjereni
u 3 vremenske točke: osnovni - prije uzimanja oralne kontracepcije, nakon 3 i nakon 6 ciklusa.
Rezultati istraživanja pokazuju da su pod utjecajem oralnih kontraceptiva promijenjeni svi koagulacijski
parametri osim aktivnosti FVIII. Analizom rezultata formulacija pripravaka, najveće razlike nađene su u
kombinacijama s 20μg EE2 GSD vs DRSP za koagulacijske pretrage protein C i S, plazminogen i PAI-1. U
istraživanju je potvrđena jednaka učestalost trombofilnih mutacija među ispitanicama kao u općoj populaciji.
Polimorfizam PAI-1 5G/4G nije imao utjecaja na aktivnost PAI-1 kod mladih žena, niti je uzimanje oralnih
kontraceptiva imalo učinka na aktivnost PAI-1.
Istraživanje je potvrdilo utjecaj oralne kontracepcije na koagulacijske pretrage, ali i nastojanje sustava
hemostaze za stjecanjem nove točke ravnoteže. Gestageni također utječu na koagulacijski odgovor žena.
Patološke vrijednosti pretraga aktivnosti proteina S i određivanja koncentracije d-dimera mogu pomoći
kliničarima u odluci o nastavku ili prekidu oralne kontracepcije kod žena s drugim visokim rizikom i/ili
sumnjom na trombo-embolijski događaj.Oral contraceptives have numerous effects on women’s body like favorable decrease of prevalence risk for
ovarian and endometrial cancer, but also undesirable increase of thrombotic events. The fact is that oral
contraceptives are one of the reasons for increased risk for venous thromboembolism, with relative risk is 1.15-
8.5, depending on the drug formulation and type of thromboembolic disease. The development of laboratory
diagnostics, molecular tests and coagulation tests, gave a new momentum to the researches linking
epidemiological data on thrombotic risks such as smoking, obesity, age, exercise, and others with a biological
basis. Simultaneously, development of synthetic estrogen and progesterones are an additional stimulus for new
studies of the effect of oral contraceptive formulations on the coagulation response.
The aim of the study was to determine the influence of oral contraceptives on factors of coagulation and
fibrinolysis in the local population, depending on: the amount and composition of used drug, the presence of
hereditary thrombophilia and the difference among study subjects in the obtained values of factors of coagulation
and fibrinolysis in relation to the presence of additional risk factors for thromboembolic diseases.
The study included the data results of 195 women, who took six cycles of oral contraceptives. Tests for
hereditary thrombophilia (FV Leiden, FIIG20210A and PAI-1 5G/4G) were performed, as well as tests of
hemostasis (PT, APTT, fibrinogen, APCR, protein C and S, FVIII, antithrombin, plasminogen, plasmin inhibitor,
PAI-1 and d-dimer) measured at three time points: basic - before taking oral contraceptives after three and after
six cycles of their use.
The results showed that oral contraceptives have changed all measured parameters except activity of FVIII.
Analyzing the results by formulation of drug, the greatest differences were found in combination with 20μg EE2
GSD vs. DRSP for coagulation tests protein C and S, plasminogen and PAI-1. Data confirmed the same
frequency of FV Leiden, FII G2021A i PAI-1 5G/4G among study subjects as in general population.
Polymorphism of PAI-1 5G/4G had no influence on PAI-1 activity, nor the use of oral contraceptives.
This study confirmed impact of oral contraceptives on coagulation tests and tendency of hemostasis to
reach new equilibrium. Gestagens also have impact on coagulation response. Pathological test results of protein
S activity and d-dimers may help clinicians in the decision on continuation or discontinuation of oral
contraceptives in women with other high-risk and / or suspected thromboembolic event
Polymorphisms of genes for coagulation and fibrinolysis factors, platelet membrane glycoproteins and intermediate risk factors in children with ischemic stroke
No full textIshemijski moždani udar (IMU) u djece je relativno rijedak poremećaj miješane etiologije koja je nerazjašnjena u približno 30 % slučajeva. Protrombotički poremećaji prepoznati su kao rizični čimbenik za nastanak IMU-a u
djece, ali su potencijalne pozadinske genske varijacije analizirane u oskudnom broju studija u specifičnim populacijama ili u odraslih, dok u djece rijetko ili uopće nisu analizirane. Kako se povezanost protrombotičkih
polimorfizama s IMU-om može razlikovati ovisno o geografskoj i etničkoj pripadnosti ispitivane populacije, a poznato je dodatno povećanje rizika u prisutnosti više od jednoga protrombotičkog rizičnog čimbenika, cilj ovoga istraživanja jest ispitati povezanost pojedinačnih polimorfizama u genima za čimbenike zgrušavanja, glikoproteinima trombocitne membrane i intermedijarne rizične čimbenike te potencijal zajedničke povezanosti s pojavom IMU-a u djece u Hrvatskoj ovisno o tipu, dobi nastanka i lokalizaciji IMU-a. Genotipizacija 21 polimorfizma u 13 gena kandidata provedena je iz uzorka DNA leukocita dobivenih nakon prikupljanja uzoraka ostatne periferne krvi od 185 djece starosne dobi do 18 godina s potvrđenom dijagnozom arterijskog IMU-a ili tromboze venskih sinusa mozga (CSVT) i 185 zdrave djece podudarne po dobi i spolu djeci s IMU-om. Dobiveni rezultati potvrdili su veću zastupljenost dječaka u svim podtipovima bolesti, osim perinatalnog
arterijskog IMU-a i CSVT-a te različite genetičke čimbenike za karakterizaciju različitih podtipova IMU-a u
djece. Na temelju dobivenih rezultata predložen je i algoritam ispitanih genetičkih čimbenika za IMU u djece za razlikovanje rizika nastanka podtipova bolesti te je uspostavljena baza podataka djece s IMU-om u Hrvatskoj. Rezultati predloženog istraživanja proširili su dosadašnja saznanja o potencijalnoj ulozi ispitanih genskih
varijacija u etiologiji IMU-a u djece u Hrvatskoj, ali i u općoj populaciji.Ischemic paediattric stroke (IPS) is a relatively rare disorder of mixed aetiology that is unexplained in
approximately 30% of cases. Prothrombotic disorders are recognized as a risk factor for the development of IPS, but potential genetic variations in prothrombotic risk factors have been analysed in a limited number of studies in
specific populations or in adults, while in children they have been scarcely analysed or they have not been analysed at all. As the association of prothrombotic polymorphisms with IPS can differ depending on the geographic and ethnic categorisation of the population studied, and an additional increased risk is known in the presence of more than one prothrombotic risk factor, the aim of this study is to examine the association of individual polymorphisms in the genes coding clotting factors, platelet membrane glycoproteins and intermediate risk factors, and the potential of their joint association with the occurrence of IPS in children in Croatia depending on the type of IPS, age of onset and localization of the lesion. Genotyping of 21 polymorphisms in 13
candidate genes was performed in a DNA samples obtained from leukocytes after collecting residual peripheral blood samples from 185 children aged up to 18 years with confirmed diagnosis of arterial IPS (AIS) or cerebral venous sinus thrombosis (CSVT) and 185 healthy children matched by age and gender to children with IPS. Obtained results confirmed a higher frequency of AIS in boys and other subtypes, but not in perinatal AIS and CSVT. Also, it has been proven that different subtypes of IPS are caracterised by different genetic factors. Based
on the obtained results, an algorithm of tested genetic risk factors for IPS was proposed to distinguish the risk of subtypes of the disease, which established a database of children with IPS in Croatia. The results of the proposed
research expanded the previous knowledge about the potential role of the examined genetic variations in the aetiology of IPS in Croatia, with translational potential to the adult population
Platelet antigen and P-selectin gene polymorphisms in cerebrovascular disorders in children and adults
Get PDFCerebrovaskularni poremećaji (CVP) su značajan medicinski problem u djece i odraslih. Cilj istraživanja bio je ispitati razlike u učestalostima polimorfizama gena za HPA (-1, -2, -3, -5), PSEL (S290N, N562D, V599L, T715P), mutacija FV G1691A (FVL) i FII G20210A u bolesnika s CVP-om u odnosu na kontrolnu skupinu, te utvrditi njihovu povezanost s bolešću.
Ukupno je ispitano 300 bolesnika s CVP-om (ishemijski moždani udar-iCVI, TIA) (djece-100, odraslih-200) i 200 ispitanika kontrolne skupine (djece-100, odraslih-100), uz podatke za odrasle o standardnim čimbenicima rizika. Polimorfizmi HPA genotipizirani su PCR-SSP-om i PCR-om u stvarnom vremenu, PSEL-a PCR-SSP-om, a FVL i FII G20210A PCR-RFLP-om.
U Hrvata alelne učestalosti HPA odgovaraju podacima za Europljane. Multivarijantnom regresijskom analizom u odraslih potvrđena je povezanost anamneze, hipertenzije, šećerne bolesti i alkoholizma s CVP-om, ali ne s alelom HPA-2b. U djece značajno je učestaliji genotip HPA-5a/b i alel HPA-5b u oboljelih od TIA-e u odnosu na iCVI, a u djece s genotipom GA ili s alelom A FVL, 5 puta je veća vjerojatnost oboljenja od CVP-a. Značajno učestaliji genotip GA i alel A FVL dobiven je u djece u odnosu na odrasle s CVP-om, te iCVI-om. Pomoć u predviđanju CVP-a u odraslih imaju anamneza, hipertenzija, šećerna bolest i alkoholizam, a u djece FVL.Cerebrovascular disorders (CVD) are a significant medical problem in children and adults. The aim of this research was to examine differences in the frequency of gene polymorphisms for HPA (-1, -2, -3, -5), PSEL (S290N, N562D, V599L, T715P), FV G1691A (FVL) and FII G20210A mutations in patients with CVD as compared to the control group, and to determine their correlation with the disease.
The research included 300 patients with CVD (ischemic stroke-iCVI, TIA) (children-100, adults-200), 200 control subjects (children-100, adult-100), as well as data for standard risk factors for adults. HPA polymorphisms were genotyped using PCR-SSP and real-time PCR, PSEL by PCR-SSP, and the FVL and FII G20210A by PCR-RFLP.
The allelic frequencies of HPA in Croats correspond to the data for Europeans. Multivariate regression analysis in adults confirmed the correlation between family history, hypertension, diabetes and alcoholism with CVD, but not with the HPA-2b allele. In children, HPA-5a/b genotype and HPA-5b allele is significantly more frequent in patients with TIA as compared to iCVI, and in children with GA genotype or with A allele FVL, there is a 5 times higher likelihood of CVD disease. Significantly more frequent GA genotype and A allele FVL was obtained in children than in adults with CVD and iCVI. Help in predicting CVD in adults is provided by family history, hypertension, diabetes and alcoholism, and in children by FVL
Association of procoagulant and fibrinolytic factors with thrombin potential and hemophilia A phenotype
Get PDFHemofilija A je rijetki nasljedni poremećaj zgrušavanja krvi koji nastaje zbog manjka FVIII u cirkulaciji i dijeli
se na teški, srednje teški i blagi oblik. Kod teškog oblika bolesti javljaju se spontana krvarenja, koja su kod
blažih oblika rijetka. Literaturni podaci ukazuju na heterogenost kliničkog izražaja hemofilije A. Cilj ovog
istraživanja bio je utvrditi mogući utjecaj drugih prokoagulacijskih i fibrinolitičkih čimbenika, osim FVIII, na
endogeni trombinski potencijal i na klinički izražaj bolesti. Ispitana je vrijednost analize reakcijske krivulje
APTV-a i analize stvaranja trombina u dijagnostici hemofilije A jer se ovim metodama mjeri ukupni hemostatski
potencijal plazme. Dobiveni rezultati potvrđuju povećanu aktivnost fibrinolitičkog sustava kod hemofilije A u
odnosu na zdravu populaciju, koja je izraženija kod teškog oblika bolesti. Pojačana fibrinoliza kod bolesnika s
težom kliničkom slikom nije nedvojbeno potvrđena. Potvrđena je vrijednost analize reakcijske krivulje APTV-a
u dijagnostici hemofilije A. Pokazana je dobra korelacija sa standardnim laboratorijskim metodama i kliničkim
pokazateljima te dobro razlikovanje stupnja bolesti. Jednostavnost i cijena metode, koja zahtijeva samo mjerenje
APTV-a, dodatne su prednosti. Ispitivanjem analize stvaranja trombina dobivena je slabija korelacija sa
standardnim laboratorijskim metodama i kliničkim pokazateljima, te slabije razlikovanje stupnja bolesti. U
postojećoj izvedbi metoda nije primjenjiva u rutinskoj laboratorijskoj dijagnostici hemofilije A.Hemophilia A is a rare X-linked bleeding disorder characterized by decreased FVIII activity, and is classified as
severe, moderate or mild. The clinical phenotype of severe hemophilia A consists of spontaneous bleeding
episodes that are rare in non-severe types. Heterogeneity in bleeding pattern has been observed, but mechanisms
are poorly understood. The aim of this study was to identify whether activities of common prothrombotic and
fibrinolytic factors are associated with clinical phenotypes. New laboratory methods were evaluated that assess
overall clotting function, clot waveform analysis and thrombin generation test. Results showed enhanced
fibrinolytic activity in patients as compared to healthy subjects, as well as in severe hemophilia A patients
compared to those with mild disease. The enhanced fibrinolytic activity in patients with severe phenotype was
not confirmed with certainity. By using waveform analysis, good correlation was obtained to standard laboratory
methods and clinical parameters, as well as good discrimination of disease severity. Simplicity and cost benefit
of this method make this approach a promising tool for assessing coagulation in hemophilia patients. The
correlation to routine laboratory methods and clinical parameters in thrombin generation test was weaker and this
method did not fulfill the goals expected for a routine laboratory method
Korelacija aktivnosti PAI-1 u plazmi i polimorfizma 4G/5G u genu za PAI-1
Get PDFHemostaza obuhvaća složene, međusobno povezane sustave čija je zadaća održati fluidnost krvi u tekućem stanju u krvožilnom sustavu, ali i omogućiti brzo stvaranje krvnog ugruška nakon ozljede krvne žile. Zgrušavanje i fibrinoliza, dvije ključne komponente hemostaze, moraju biti strogo kontrolirane. Inhibitor aktivatora plazminogena 1 (PAI-1) je jedan od faktora kontrole fibrinolize. Uloga ovog serpina je spriječiti aktivaciju plazminogena u plazmin inhibirajući njegove aktivatore tkivni aktivator plazminogena (tPA) i urokinazu (uPA). Na aktivnost PAI-1 utječe polimorfizam 4G/5G koja se javlja u promotorskoj regiji gena za PAI-1. Homozigoti 4G/4G će imati veću aktivnost PAI-1 od homozigota 5G/5G. Osim toga, na aktivnost
PAI-1 djeluju brojni drugi faktori uključujući spol, doba dana, pretilost, inzulin i glukokortikoide. U ovom istraživanju utvrđivali smo ovisnost aktivnosti PAI-1 o prisutnosti polimorfizma 4G/5G u uzorcima plazme 60 ispitanika. Također je ispitana razlika u aktivnosti PAI-1 između muškaraca i žena. Genotip se određivao uređajem za PCR u stvarnom vremenu LightCycler 2.0 (Roche, Švicarska), a aktivnosti funkcionalnim testom na automatskom koagulacijskom analizatoru Behring Coagulation Timer koristeći komplet reagencija Berichrom PAI (Siemens Medical Solutions, Njemačka). Pokazan je trend (p=0.092) veće
aktivnosti PAI-1 kod muškaraca, kao što je i očekivano. Nije dokazana statistički značajna razlika u aktivnosti PAI-1 između pojedinih genotipova. Taj neočekivan rezultat objašnjava se malim brojem ispitanika, te ne uzimanjem u obzir ostalih faktora koji utječu na aktivnost PAI-1 kao što su dob, vrijeme uzorkovanja, pretilost, inzulin i glukokortikoidi.Hemostasis consists of complex and interrelated systems whose task is to maintain blood fluidity in the vascular system, while allowing the rapid formation of solid blood clots in the prevention of hemorrhage after a blood vessel injury. The balance between coagulation and fibrinolysis, two key components of hemostasis, has to be strictly controlled. Plasminogen activator inhibitor-1 (PAI-1) is a serpin that prevents the conversion of plasminogen to plasmin by inhibiting its activators - urokinase (uPA) and tissue plasminogen activator (tPA). The PAI-1 gene has a common polymorphism 4G/5G which is located in the promoter region and it affects the activity of PAI-1. People who are homozygotes 4G/4G have a higher plasma PAI-1 activity. Other factors such as age, circadian rhythm, obesity, insulin and glucocorticoids can
also influence plasma PAI-1 activity. The aim of this study was to determine the correlation between the 4G/5G polymorphism and the plasma PAI-1 activity in plasma samples of 60 subjects. Additionally, we compared the activities of plasma PAI-1 of female and male subjects. The genotype was determined using the LightCycler 2.0 real-time PCR system (Roche, Switzerland). The activity was determined using the automated hemostasis analyzer Behring Coagulation Timer with the Berichrom PAI test kit (Siemens Medical Solutions, Germany). A trend was found (p=0.092) which confirmed the premise of a higher activity in male patients. A statistically significant difference in the activities between genotypes was not found. This unexpected result can be explained taking into account the small sample size and not considering the other influential factors (age, circadian rhythm, obesity, insulin, glucocorticoids) whilst selecting subject samples
Morfološke i citogenetičke promjene, razina ekspresije WT1 te duplikacija gena FLT3 u novootkrivenim akutnim mijeloičnim leukemijama sa znacima mijelodisplazije [Morphologic and cytogenetic alterations, level of WT1 expression, and duplication of FLT3 gene in de novo acute myeloid leukaemia with myelodysplasia-related changes]
No full textAML with myelodysplasia related-changes (AML-MRC) is considered as high-risk
leukaemia. AML-MRC is associated with higher age and unfavorable cytogenetics. FLT3
gene mutations occur in one third of patients with AML. It is unknown weather they are
linked to AML-MRC. The WT1 gene can act both as a tumor-suppressor gene and an
oncogene.
The aim of this study was to set scoring criteria for dysgranulocytopoiesis,
dyseryhrocytopoiesis and dysmegakaryocytopoiesis, to compare morphologic alterations
with cytogenetic abnormalities, to asses the expression of WT1 and frequency of FLT3-ITD
and relate them to morphologic alterations and cytogenetic abnormalities in patients with
AML-MRC.
No association between severe dysplastic changes and unfavorable karyotypes was
found. Scoring dysplastic changes has not been demonstrated to be a good predictor of
cytogenetic abnormalities. Positive correlation between trilineage dysplasia and
overexpression of WT1 gene was found. No relationship was found between severe
morphological alterations and FLT3-ITD mutation or between FLT3-ITD and unfavorable
cytogenetics.
The hypothesis that morphologic alterations in de novo diagnosed AML with
myelodysplasia related-changes are stronger in patients with unfavorable cytogenetics, FLT3-
ITD mutation and overexpression of the WT1 gene was not confirmed
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