Uporaba vanjskih usluga u istraživanju i razvoju u farmaceutskoj industriji. Mogućnosti i izazovi

Outsourcing of drug discovery processes offers a vast opportunity to scientists to develop and commercialize new and innovative methods and technologies as well as other discoveries that could be of use to pharmaceutical industry. Specifically, this is of special value for investigations that are either too complex or too infrequent to be performed in-house and can be carried out faster and at less overall cost by outsourcing.Uporaba vanjskih usluga u procesu razvoja novih lijekova pruža brojne prilike znanstvenicima za razvijanje i komercijalizaciju inovativnih metoda i tehnologija te otvara put k novim otkrićima, koja se mogu upotrijebiti u farmaceutskoj industriji. To je osobito dragocjeno u istraživanjima koja se u farmaceutskoj industriji rijetko provode ili su presložena da bi se isplatilo njihovo uvođenje u vlastitome laboratoriju. Uporabom vanjskih usluga znanstvenika mnoga se farmaceutska istraživanja mogu provesti brže i djelotvornije

Protective Effects of Met-enkephalin on Alcohol Induced Gastric Lesions

The model of ethanol induced gastric lesions is useful in the evaluation of gastric cytoprotection. We used it to measure cytoprotective effects of two neuropeptides, Met-enkephalin (Peptid-M, LUPEX®) and α-melanocyte stimulating hormone (α-MSH). Both peptides exhibited significant and synergistic cytoprotective effects. The best therapeutic efficacy was obtained with Met-enkephalin and α-MSH mixture 3-5 : 1. Significant cytoprotective action on ethanol induced lesions was also observed by means of two thymus peptide immunomodulators, Thymus Peptide C® and JAN 50®. Thymus Peptide C® exhibited a more significant synergistic effect with Met-enkephalin than JAN 50®. In addition to the cytoprotection of rat gastric mucosa, Met-enkephalin also induced statistically significant and dose dependent Straub tail response versus control in miče. Haloperidol, naloxone and Peptide-D antagonised its effects. NMR spectrospic data supported molecular interaction of Met-enkephalin and haloperidol, while neutralization of Met-enkephalin induced Straub tail response by means of Peptide-D indicated the presence of new non-opioid (naloxone independent) receptor system containing Peptide-D sequence (calpastatin 201-205 aa)

Protective effects of Met-enkephalin on alcohol induced gastric lesions

The model of ethanol induced gastric lesions is useful in the evaluation of gastric cytoprotection. We used it to measure cytoprotective effects of two neuropeptides, Met-enkephalin (Peptid-M, LUPEX(R)) and alpha -melanocyte stimulating hormone (alpha -MSH). Both peptides exhibited significant and synergistic cytoprotective effects. The best therapeutic efficacy was obtained with Met-enkephalin and alpha -MSH mixture 3-5:1. Significant cytoprotective action on ethanol induced lesions was also observed by means of two thymus peptide immunomodulators, Thymus Peptide C(R) and JAN 50(R). Thymus Peptide C(R) exhibited a more significant synergistic effect with Met-enkephalin than JAN 50(R). In addition to the cytoprotection of rat gastric mucosa, Met-enkephalin also induced statistically significant and dose dependent Straub tail response versus control in mice. Haloperidol, naloxone and Peptide-D antagonised its effects. NMR spectrospic data supported molecular interaction of Metenkephalin and haloperidol, while neutralization of Met-enkephalin induced Straub tail response by means of Peptide-D indicated the presence of new non-opioid (naloxone independent) receptor system containing Peptide-D sequence (calpastatin 201-205 aa)

Flavonoidi kao inhibitori Lck i Fyn kinaza

Phosphorylation of tyrosine residues constitutes a unique signaling pathway involved in regulation of most cellular processes responding to different extracellular stimuli. The enzymes that carry out this modification are tyrosine kinases. These enzymes enable the transfer of γ-phosphate from ATP to the phenol –OH group of tyrosine on protein substrates. Development of specific and potent protein kinase inhibitors is important not only for treatment of diseases, but also as a tool to investigate the physiological roles of protein kinases. Flavonoids are biologically active polyphenol compounds naturally occurring in many plants. They are recognized as inhibitors of Fyn and Lck protein kinases, two representatives of the Src family of non receptor kinases involved in T-cell signaling transport. In the described experiments, the inhibitory activity of flavonoids on Fyn and Lck kinases was monitored by the ELISA method. Myricetin showed the highest inhibitory effect, and no ATP-competitive mechanism of inhibition was observed on Fyn tyrosine kinase. The affinity of human Fyn and Lck for two different substrates, polypeptide polymer Poly Glu:Tyr (4:1) and peptide M3-01, was also tested.Tirozinska fosforilacija predstavlja jedinstveni mehanizam prijenosa signala primljenoga iz okoline do stanič ne jezgre koja će odgovoriti na podražaj. Velika skupina enzima odgovorna za provo|enje ove modifikacije poznata je pod jedinstvenim nazivom tirozinske kinaze. One omogućuju prijenos -fosfata ATP-a na –OH skupinu tirozina supstrata. Lck i Fyn su dvije nereceptorske Src tirozinske kinaze, koje su važne komponente regulacije aktivnosti T-limfocita. Rezultati ispitivanja flavonoida, biološki aktivnih polifenolnih spojeva prirodno prisutnih u mnogim biljkama, upućuju na njihov inhibitorni učinak na proteinske kinaze Fyn i Lck. Najveću inhibiciju pokazao je miricetin, a pri ispitivanju mehanizma inhibicije Fyn kinaze nije ustanovljena kompeticija s ATP-om. Ispitivanje potencijalne inhibicijske aktivnosti flavonoidnih spojeva prema kinazama Fyn i Lck, provedeno je ELISA metodom. Pri tome je uspore|en afinitet ispitivanih enzima prema supstratima s različitim brojem skupina podložnih fosforilaciji, odnosno prema polipeptidnome polimeru glutaminske kiseline i tirozina Poly Glu:Tyr (4:1) i M3-01 peptidu. Razvoj učinkovitih kinaznih inhibitora važan je ne samo za prevenciju i liječenje mnogih bolesti već i za bolje razumijevanje uloge proteinskih kinaza u organizmu

Koštani morfogenetski proteini (BMP): Od otkrića do razvoja nove autologne koštane naprave koja se sastoji od rekombinantnog humanog BMP6 u autolognom krvnom ugrušku kao nosaču

Bone Morphogenetic Proteins (BMPs) are growth and differentiation factors within the TGFβ superfam- ily of proteins. They induce ectopic and orthotopic endochondral bone formation and are involved in the regulation of cell proliferation, differentiation, apoptosis and mesenchymal-epithelial interactions in critical morphogenetic processes of tissues beyond bone. BMP2 and BMP7 osteogenic devices have been approved for enhancing healing in patients with long bone defects and anterior spinal fusion proce- dures. However, due to a high price and various serious adverse events including heterotopic ossifica- tion, retrograde ejaculation and pain their clinical use have been limited. In this review we discuss the BMP discovery, biology and their use in clinical studies with particular reference to the newly developed BMP6 based autologous bone graft substitute (ABGS). A novel ABGS consisting of an autologous bone coagulum (ABC) carrier with dispersed BMP6 to initiate the differentiation of mesenchymal cells into endochondral bone. The ABC met the conditions for an optimal delivery system for BMP6 due to han- dling simplicity, without an immunogenic and inflammatory response at the implantation site. Addition of allograft or synthetic ceramics to ABGS demonstrated in animal models significantly increased volume and better microarchitecture of the newly formed bone. The first clinical study was conducted in patients with distal radial fractures (Phase I study) and the second in patients undergoing high tibial osteotomy (Phase I/II study) and no serious adverse events have been observed. Finally, in the ongoing OSTEO- proSPINE study ABGS enforced with allograft bone is evaluated in patients with chronic back pain due to degenerative disc diseases. The novel ABGS bone mimetic is a major breakthrough and contribution to bone biology and regenerative medicine of skeletal repair.Koštani morfogenetski proteini (BMP) čine grupu čimbenika rasta i diferencijacije unutar TGFβ nado- bitelji. Oni induciraju stvaranje ektopične i ortotopične endohondralne kosti te su uključeni u regulaciju stanične proliferacije, diferencijacije, apoptoze i mezenhimalno-epitelne interakcije u važnim tkivnim morfogenetskim procesima izvan koštanog sustava. Koštane naprave koje sadrže BMP2 i BMP7 pro- tein odobrene su za poboljšanje koštanog cijeljenja kod pacijenata s defektima dugih cjevastih kostiju i kod prednje spinalne fuzije kralježnice. Međutim, zbog visoke cijene i mnogobrojnih nuspojava koje su uključivale pojavu heterotopičnih osifikacija, retrogradnu ejakulaciju i bol, njihova je klinička prim- jena ograničena. U ovom smo preglednom radu raspravili otkriće BMP molekula, njihovu biologiju i primjenu u kliničkim studijama s posebnim osvrtom na nedavno otkrivenu novu autolognu koštanu napravu (ABGS) koja sadrži BMP6. Novi ABGS sastoji se od nosača autolognog koaguluma (ABC) s otopljenim BMP6 koji je ključan za pokretanje diferencijacije mezenhimalnih stanica u smjeru stvaranja endohondralne kosti. ABC je ispunio sve potrebne uvjete za formulaciju optimalnog nosača za BMP6 isključivo zbog jednostavnosti priprave i primjene te odsustva imunogenog i upalnog odgovora na mjestu implantacije. Uz dodatak alografta ili sintetičke keramike što je potvrđeno na životinjskim modelima došlo je do značajnog povećanja volumena te poboljšanja mikroarhitekture novonastale kosti. Prvo kliničko ispitivanje provedeno je na pacijentima s distalnim prijelomima radijusa (faza I studije), a drugo na pacijentima koji su podvrgnuti visokoj osteotomiji tibije (faza I/II studije) bez uočenih ozbiljnih nuspojava. Trenutno je u tijeku studija OSTEOproSPINE u kojoj se testira učinkovitost ABGS u kom- binaciji s koštanim alograftom u bolesnika s kroničnim bolovima u leđima uzrokovanim degenerativnim promjenama intervertebralnog diska. Nova ABGS koštana naprava značajna je prekretnica i napredak u području koštane biologije te regenerativne medicine koštanog sustava

Institucijska potpora u ostvarivanju prava intelektualnog vlasništva

Izlaganje na konferenciji MICC 2016 - Intelektualno vlasništvo u biomedicini s tematikom institucijskih potpor

Institucijska potpora u ostvarivanju prava intelektualnog vlasništva

Izlaganje na konferenciji MICC 2016 - Intelektualno vlasništvo u biomedicini s tematikom institucijskih potpor

Ured za znanost i transfer tehnologije Medicinskoga fakulteta: aktivnosti i zadaće

Izlaganje na konferenciji MICC 2011 - Upravljati znanjem na tematiku Ured za znanost i transfer tehnologije Medicinskoga fakultet

Ured za znanost i transfer tehnologije Medicinskoga fakulteta: aktivnosti i zadaće

Izlaganje na konferenciji MICC 2011 - Upravljati znanjem na tematiku Ured za znanost i transfer tehnologije Medicinskoga fakultet

Priprema, prijava i evaluacija EU projekata

Izlaganje na konferenciji MICC 2015 na tematiku izrade EU projekata u biomedicin