Statističke metode za usporedbu profila oslobađanja lijeka

Jedna od tehnika usporedbe testnog i referentnog lijeka je usporedba brzine oslobađanja lijeka u nekom relevantnom mediju. U radu su opisane standardne statističke metode (metoda faktora, neparametarska metoda i parametarska metoda) za usporedbu profila oslobađanja testnog i referentnog lijeka. Primjenom metoda (koristeći programski jezik R) na različitim primjerima detaljnije je objašnjena njihova upotreba.One of the techniques for comparison of a test and a reference drug is to compare a dissolution rate of drugs in some dissolution medium. In this thesis, we describe standard statistical methods (factor method, model independent method and model dependent method) for comparison between dissolution profiles of a test and a reference drug. By applying the methods (using programming language R) to different examples we are describing their application in detail

Cell entry strategies of animal viruses

Virusi su obligatni unutarstanični paraziti građeni od nukleinske kiseline (DNA ili RNA) i proteinske kapside, dok je lipidna ovojnica, koju neki virusi posjeduju, porijeklom od domaćinske stanice. Virusi ne posjeduju metabolizam, stoga svi koraci virusnog replikacijskog ciklusa ovise o stanici domaćina koju virus inficira. Virusi su dobro adaptirani na stanicu domaćina i koriste brojne stanične mehanizme koji u stanici imaju ulogu u metaboličkim putevima, transportu tvari, replikaciji genoma ili borbi protiv patogena. Ovaj rad pobliže opisuje strategije ulaska virusa životinja u stanicu. To je prva i često ključna faza kod uspostavljanja produktivne infekcije. Sam proces se može podijeliti na nekoliko koraka: od inicijalnog vezanja za površinu stanice, ulaska u citoplazmu i transporta unutar citoplazme, do početka replikacije, bilo u citoplazmi ili jezgri domaćinske stanice. Uočeno je da su svi koraci uključeni u ulazak virusa u stanicu precizno regulirani, i da postoji izuzetna raznolikost različitih strategija i adaptacija vezanih za taj proces, što je predstavljeno kroz ovaj pregledni rad.Viruses are obligatory intracellular parasites, constituted of a nucleic acid (DNA or RNA) and a protein capside, while a lipid envelope, which some viruses possess, originated from an infected cell. Viruses do not possess metabolism, hence all steps in their replication cycle depend on host cells which are infected by virus. Viruses are well adapted to host cells and make use of numerous cellular mechanisms, which in cell have roles in metabolic pathways, transport of substances, genome replication or fight against pathogens. This paper describes in detail cell entry strategies of animal viruses. That is the first and often crucial phase in establishing a productive infection. The process itself can be divided into several steps: from initial binding to the cell surface, entry into cytoplasm and transport within the cytoplasm, to the beginning of the replication of the viral genome, either in cell nucleus or cytosol. It is observed that all steps included in cell entry are precisely regulated, and that there is a remarkable diversity of different strategies and adaptations regarding that process, which is presented trough this review

Korelacija aktivnosti PAI-1 u plazmi i polimorfizma 4G/5G u genu za PAI-1

Hemostaza 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

The evolution of bipedalism in australopithecines

U ovome seminaru bavim se evolucijom bipedalnog hoda, anatomskim promjenama koje su prethodile njegovom razvoju kao i fosilnim dokazima koji potvrđuju bipedalizam kod australopitecina. Postoji niz teorija koje pokušavaju objasniti zašto i kako je došlo do razvoja bipedalizma, no i dalje ne možemo sa sigurnošću reći da li je ijedna od tih teorija ispravna. Vrlo vjerojatno je do razvoja bipedalnoga hoda došlo kombinacijom više tih teorija. Kako bi moglo doći do pojave bipedalnog hoda, prvo je tijekom evolucije moralo doći do niza anatomskih promjena lokomotornog aparata naših predaka. Tako je došlo do pomicanja foramena magnuma prema bazi lubanje, do promjene u obliku kralježnice prema obliku dvostrukoga slova S kao i pomicanju centra ravnoteže, a također dolazi do promjena u građi kukovlja i naših udova, a prije svega stopala. Iako se bipedalizam prvi put javlja puno prije pojave samih australopitecina (pojavom vrste Sahelanthropus tchadensis), oni se smatraju prvim pravim bipedalnim homininima. Njihov bipedalizam se razlikovao od onoga kakvoga danas poznajemo, no daje nam puno informacija o razvoju uspravnog hoda, kao što su razne anatomske prilagodbe koje su se morale dogoditi da bismo uopće mogli imati uspravan stav, prednost i nedostatci koje smo dobili prelaskom na bipedalizam. Donošenje zaključaka o razvoju bipedalizma i potpuno shvaćanje njegovog razvoja će nam uvelike razjasniti kako je došlo do evolucije današnjega čovjeka i olakšati nam shvaćanje naše prošlosti.In this paper I am dealing with the evolution of bipedalism, the anatomical changes which preceded the development of bipedalism and the fossils that proof bipedalism in australopithecines. There is a series of theories which try to explain why and when the development of bipedalism started, then still we can not know which of the theories are correct. Most likely the evolution of bipedalism is the result of a combination of more of these theories. To come to the evolution of bipedalism first it had to come to a series of anatomical changes in the locomotory system of our ancestors. So it came to the movement of foramen magnum to the base of the cranium, to changes in the shape of the spine to the shape of the double letter S as well as the movement of the center of gravity, also it came to changes in the structure of the hip and limbs, primarily the feet. Although bipedalism occurs much earlier than the appearance of australopithecines (with the appearance of Sahelanthropus tchadensis), they are considered to be the first real bipedal hominins. Their bipedalism is different from the bipedalism we know today, but still it gives us a lot of information of upright gait, as well as a variety of anatomical adaptations that had to happen that have an upright gait, advantages and disadvantages that we got by the transition to bipedalizam. Conclusions about the development of bipedalism and fully understanding its development will help us greatly to clarify how it came to the evolution of modern man and to facilitate our understanding of our past

Antioxidant status in plasma, erythrocytes and platelets following the use of antihemostatic drugs and vasodilatation supplements

U istraživanju se pratila promjena antioksidativnog statusa u plazmi, trombocitima i eritrocitima krvi štakora nakon primjene antihemostatskih lijekova i vazodilatacijskih suplemenata zasebno i u kombinaciji. U pokusu je bilo 9 skupina pod tretmanom i jedna kontrolna skupina. Skupine pod tretmanom bile su skupine: 1. Ginko, 2. Vulkan, 3. Salicilna kiselina , 4. Varfarin, 5. Vulkan+varfarin, 6. Vulkan + salicilna kiselina, 7. Ginko + varfarin, 8. Ginko + salicilna te 9. Ginkalert. Uz 9 skupina pod tretmanom bila je i kontrolna skupina 0. Životinje su tretirane kroz razdoblje od 28 dana, prema preporučenom toksikološkom protokolu OECD 407 nakon čega su žrtvovane i uzeti uzorci krvi. Nakon centrifugiranja i odvajanja komponenti krvi izmjereni su markeri antioksidativnog sustava: superoksid dismutazu (SOD), glutation (GSH), katalazu (CAT) te malondialdehid (MDA). Ovo istraživanje je potvrdilo da postoji niz mogućih interakcija između vazodilatacijskih suplemenata i primjene antihemostatskih lijekova, koje dovode do velikih promjena u antioksidativnom statusu organizma. Stoga je potrebno ograničiti istovremenu primjenu antihemostatika i vazodilatacijskih suplemenata prehrani kako bi spriječili moguće štetne posljedice.The study monitored the changes in antioxidant status of plasma, platelets and red blood cells of rat blood after administration of antihemostatic drugs and vasodilating supplements alone and in combination. The experiment was composed of 9 groups under treatment and one control group. The groups under treatment were the groups: 1. Ginkgo, 2. Vulkan, 3. Salicilna, 4. Warfarin, 5. Vulkan+warfarin, 6. Vulkan+salicilna, 7. Ginko + warfarin, 8. Ginko + and 9. Ginkalert. Nine groups under treatment and the control group animals were treated over a period of 28 days, according to the recommended OECD 407 toxicological protocol. The animals were sacrificed and blood samples were taken. After centrifugation and separation of blood components the markers of antioxidant system, superoxide dismutase (SOD), glutathione (GSH), catalase (CAT) and malondialdehyde (MDA) were measured. This research has confirmed that there are a number of possible interactions between applying vasodilating supplements and antihemostatic drugs, which led to big changes in the antioxidant status of the organism. Obtained results suggest it is necessary to confine the simultaneous application of antihemostatic drugs and vasodilating supplements in order to prevent possible harmful effects

TVORBA STOPLJENICA

Along with neologisms, formed by established and well-documented word formation patterns in the Croatian language, recent years have seen a rise in (electronic) media language of words formed by blending parts of existing words which do not necessarily count as morphemes, the latter being a basic criterion for distinguishing compounds from blends. Blending has thus become a handy way of forming neologisms, particularly in marketing, due to their innovative and exclusive nature, well suited to attract the viewers (aromagija, slastistika, sprinternet). Since the word formation patterns and elements in question are not inherent to Croatian, the paper aims to determine whether the number of blends in Croatian grows by direct transfer of foreign words, or if the particular pattern of word formation is reproduced and adapted to the linguistic system of Croatian. Furthermore, the paper shall define the structure of blends based on the corpus compiled from Croatian printed and electronic media, list registers these most frequently appear in, and elaborate on the basic incentives for their creation.Uz neologizme koji u hrvatskom jeziku nastaju već utvrđenim i opisanim tvorbenim načinima, posljednjih je godina u jeziku (elektroničkih) medija primijećen sve veći broj riječi koje nastaju stapanjem dijelova postojećih riječi koji nisu nužno morfemi što ujedno predstavlja i osnovnu razliku između složenice i stopljenice. Stapanje se dakle nametnulo kao prikladan način tvorbe neologizama posebno u reklamama jer svojom ekskluzivnošću i inovativnošću privlače pozornost gledatelja (aromagija, slastistika, sprinternet). Budući da je riječ o hrvatskome jeziku neautohtonim tvorbenim formantima i obrascima, u radu će se nastojati utvrditi povećava li se broj stopljenica u hrvatskome jeziku izravnim preuzimanjem stranih riječi ili se taj tvorbeni obrazac reproducira te prilagođuje hrvatskomu jezičnom sustavu. Nadalje, utvrdit će se struktura stopljenica iz korpusa koji je prikupljen iz hrvatskih tiskanih i elektroničkih medija, popisati registri u kojima se one najčešće pojavljuju te objasniti najčešći razlozi nastanka