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I Sažeci 2. Hrvatskog kongresa medicinske biokemije SEKCIJSKA PREDAVANJA S4/1 NOVEL OBSERVATIONS ON NITRIC OXIDE BIOLOGY: AMINO ACID TRANSPORT AND THE IMMUNE SYSTEM C.A.R. Boyd Department of Human Anatomy, University of Oxford, Oxford, UK Nitric oxide (NO) has unexpectedly been found to have a critical role in cell signalling, for example in the brain, in the immune response, in cardiovascular and reproductive physiology. When the biosynthetic pathways of NO production are activated, production of NO can cause important clinical problems (e.g. septic shock). The cationic amino acids arginine, lysine and histidine were shown more than 20 years ago to be transported in animal cells by a system (called y + ) which was characterised by its independence of extracellular sodium ions and its ability to translocate in addition to these three amino acids some neutral amino acids (e.g. homoserine) in the presence of sodium. Over the last 5 years there have been three major developments. The molecular identification of system y + as being via the CAT family of gene products (having twelve transmembrane domains) which have 3 characterized gene products (CAT1, CAT2A, CAT2B); the realisation that in addition to y + there are transporters of very high affinity for a broader range of amino acids as substrates (systems y + L, b + 0 ) which are clearly distinct from system y + ; and the understanding that arginine delivery, required as the substrate for NO biosvnthesis, may be rate-limiting for NO production, i.e. that the rate of cationic amino acid transport across the plasma membrane may regulate NO production. Recent experiments show transport of arginine to be a potential site for the regulation of tissue-specific NO production and thus a target for therapeutic intervention for pathological circumstances associated with abnormalities resulting from stimulated NO production. Results of preliminary work on sepsis patients will be reviewed with respect to observed alterations in cationic amino acids transport found in human peripheral blood mononuclear cells. 52 BIOCHEMIA MEDICA god. 6, br. 1, 1996.
SEKCIJSKA PREDAVANJA Sažeci 2. Hrvatskog kongresa medicinske biokemije S4/2 ULOGA KOŠTANIH MORFOGENETSKIH PROTEINA U REGENERACIJI KOSTI I BUBREGA S. Vukičević Zavod za anatomiju Medicinskog fakulteta, Zagreb Koštani morfogenetski proteini (BMPs) članovi su TGF-(3 superobitelji i otkriveni su na temelju svoje sposobnosti da uzrokuju stvaranje kosti na ektopičnom mjestu. Predklinička istraživanja ukazala su na lokalnu djelotvornost BMPs u liječenju defekata dugih kosti, u kraniofacijalnoj rekonstrukcijskoj kirurgiji i liječenju paradentoze. Klinički pokusi su u tijeku, a preliminarni rezultati su potvrdili predklinička istraživanja. Nedavno otkriveni hrskavični morfogenetski proteini (CDMPs) važni su za razvoj hrskavice i kosti okrajina, a mutacija u CDMP-1 genu uzrokuje Hunter-Thompsonovu hondrodisplaziju. Osim u stvaranju nove kosti, BMPs djeluju i kao signalne molekule u razvoju okrajina, zubi, epifizne ploče i bubrega. Jedan od članova BMP obitelji, osteogeni protein-1 (BMP-7) ključanje za razvoj metanefričkog mezenhima i njegovih derivata u razvitku bubrega čovjeka i miša. Miševi s nefunkcionalnim BMP-7 genom umiru unutar 24 sata nakon okota zbog zatajenja bubrega. Prva predklinička istraživanja uloge OP-1 u bolestima bubrega ukazala su da profilaktička i terapijska primjena OP-1 u štakora s akutnim zatajenjem bubrega zbog okluzije bubrežne arterije znatno poboljšava biokemijske i tkivne parametre bubrežne funkcije. U životinja s kroničnim zatajenjem bubrega OP-1 sprečava brzo propadanje funkcije glomerula i smanjuje mortalitet. Otkrivanje mehanizama kojima OP-1 (BMP-7) pospješuje regeneraciju kosti i očuvanje bubrežnih funkcija bitno će doprinijeti razumijevanju procesa cijeljenja i prevencije bolesti. BIOCHEMIA MEDICA god. 6, br. 1, 1996 53
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