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Sažeci 2. Hrvatskog kongresa medicinske biokemije SEKCIJSKA PREDAVANJA CATECHOLAMINES, ENDORPHINS, BIOACTIVE PEPTIDES AND STRESS S4/3 O. Zinder Rambam Medical Center Haifa, Israel The human response to stress is a complex physiological event involving numerous neuronal and metabolic pathways. The perception of stress, vvhether physical or psychological, triggers the activation of a cascade of events usually initiated at the level of the hypothalamus. This series occurs via secretion of a number of peptide molecules which act as releasing or inhibiting factors in the continuation of the stress response cascade. These peptides include CRF (Corticotropin Releasing Factor), PRF (Prolactin Releasing Factor), TRF (Thyrotrophic Releasing Factor) and others. These compounds flow through the neural pathways in the brain and activate secretion of hormones (Prolactin, TSH, GH, others), trophic substances (ACTH) and peptide precursors such as POMC (Pro-opio-melano-cortin), from the pituitary gland. While POMC acts as a narent compound, stimulated by CRF to be secreted and broken down to ACTH, P-lipoprotein and MSH, the other secretory products of the pituitary have an immediate and profound effect on peripheral tissues, e.g. stimulation of cortisol secretion by the adrenal gland. Endorphines, the endogenous opiates are released via POMC cleavage, and exert their effect mainly within the central nervous system, binding to pain receptors and inhibiting their response. Catecholamines are quickly released in the brain, the sympathic nervous system, and from the adrenal medulla, in response to stress. The regulatory activities of the catecholamines in maintaining blood glucose levels, providing free fatty acids as metabolic fuel, and adjusting cardiovascular pressures, are key factors in maintenance of physiological homeostasis. The adrenal medulla also contains very large amounts of enkephaline (as well as other active peptides) which are co-stored together with epinephrine and not with norepinephrine. Secretion from the adrenal medulla following stimulation by acetylcholine shows preferential release of norepinephrine, vvhile basal secretion is mainly epinephrine. The mechanism of secretion, its physiological consequences, the clinical relevance and diagnostic importance in measurement of these regulatory compounds, and their action on peripheral tissues will be discussed. 54 BIOCHEMIA MEDICA god. 6, br. 1, 1996.
SEKCIJSKA PREDAVANJA Sažeci 2, Hrvatskog kongresa medicinske biokemije S4/4 CISTIČNA FIBROZA: OD GENA DO GENSKE TERAPIJE N. Canki-Klain Neurološka klinika Medicinskog fakulteta, Zagreb Cistična fibroza (CF) je najčešća potencijalno letalna autosomna recesivna bolest u bijelaca s poprečnom učestalošću 1:2500 novorođenčadi. Sam naziv ukazuje na osnovno patološko anatomsko obilježje kojeg čine cistične tvorbe egzokrinih žlijezda nastale zbog začepljenja njihovih izvodnih kanala gustom sluzi što sekundarno prati infekcija i bujanje vezivnog tkiva. Premda se CF prvenstveno očituje na razini egzokrinih žlijezda, bolest više ili manje zahvaća sve stanice u tijelu, a najčešći simptomi potječu sa strane dišnog, probavnog i spolnog sustava. Otkriće CF gena 1989. godine epohalnog je značenja za medicinsku genetiku. Izolacija i identifikacija CF gena te definiranje građe i funkcije genskog proizvoda nazvanog CFTR ("cistično fibrozni transmembranski regulator provodljivosti") rezultat su novog znanstvenog pristupa već uspješno iskušanog na primjeru Duchenneove mišićne distrofije 1987. godine. Taj postupak prvotno poznat pod nazivom "obrnuta" ("reverse") genetika, danas sve više zamjenjuje novi naziv "položajno kloniranje". Revolucionarno otkriće FC gena znatno je doprinijelo poboljšanoj i ranoj dijagnostici bolesti, otkriću zdravih heterozigota, sigurnijem prenatalnom otkrivanju bolesnih plodova te omogućilo bolje razumijevanje patofiziološkoga procesa čime je otvoren put genskoj terapiji. Ispitivanja koja su još u tijeku imaju za cilj ustanoviti međusobne odnose građe i funkcije normalnog i oštećenog genskog proizvoda, utvrditi doprinos različitih mutacija na heterogenost fenotipa bolesnika te odrediti strategije za rješenje molekularnih nenormalnosti u CF epitelu. Tim istraživanjima je od 1992. godine pridružen transgenični životinjski model. Genska terapija na čovjeku započeta 1993. godine polako napreduje, ali ne zaboravimo taj kompleksni zahvat zahtijeva savršenu koordinaciju stručnjaka različitih profila od staničnih biologa, molekularnih genetičara, fiziologa, imunologa, toksikologa, virusologa, bakteriologa i drugih do kliničara. BIOCHEMIA MEDICA god. 6, br. 1, 1996 55
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