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Human-Computer Interaction in neurodegenerative diseases
No full textČovjek-računalo interakcije (HCI) igraju ključnu ulogu u razvoju inovativnih
tehnoloških rješenja koja značajno poboljšavaju kvalitetu života osoba s
neurodegenerativnim bolestima, kao što su Alzheimerova bolest,
Parkinsonova bolest i amiotrofična lateralna skleroza (ALS). HCI sustavi,
koji uključuju napredna sučelja prilagođena potrebama pacijenata mogu
pomoći u očuvanju kognitivnih funkcija, olakšati komunikaciju te povećati
autonomiju i neovisnost oboljelih osoba. U medicini, HCI tehnologije se
koriste u raznim oblicima, od jednostavnih softverskih rješenja do
sofisticiranih medicinskih uređaja. Na primjer, duboka moždana stimulacija
(DBS) i Neuralink predstavljaju napredne metode koje omogućavaju
izravnu interakciju s mozgom, čime se značajno poboljšavaju terapijski
ishodi kod neurodegenerativnih bolesti. Osim toga, virtualna stvarnost (VR)
nudi nove mogućnosti za kognitivnu rehabilitaciju i terapiju, omogućujući
simulacije i vježbe koje su prilagođene potrebama pacijenata. Integracija
ovih tehnologija u svakodnevnu medicinsku praksu ne samo da poboljšava
kvalitetu skrbi nego i smanjuje opterećenje na zdravstveni sustav. Stalno
praćenje stanja pacijenata, personalizirana terapija i povećana sposobnost
prilagodbe individualnim potrebama omogućavaju učinkovitije i ciljanije
liječenje. Ovi napretci ukazuju na značajnu transformaciju u pristupu
liječenju neurodegenerativnih bolesti, s potencijalom za daljnji razvoj u
budućnosti.Human-computer interaction (HCI) plays a crucial role in the development
of innovative technological solutions that significantly improve the quality
of life for people with neurodegenerative diseases, such as Alzheimer's
disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). HCI
systems, which include advanced interfaces tailored to the needs of
patients, can help preserve cognitive functions, facilitate communication,
and increase the autonomy and independence of affected individuals. In
medicine, HCI technologies are used in various forms, from simple software
solutions to sophisticated medical devices. For example, deep brain
stimulation (DBS) and Neuralink represent advanced methods that enable
direct interaction with the brain, significantly improving therapeutic
outcomes in neurodegenerative diseases. Additionally, virtual reality (VR)
offers new possibilities for cognitive rehabilitation and therapy, allowing
simulations and exercises tailored to the needs of patients. The integration
of these technologies into everyday medical practice not only improves the
quality of care but also reduces the burden on the healthcare system.
Continuous patient monitoring, personalized therapy, and enhanced
adaptability to individual needs enable more effective and targeted
treatment. These advances indicate a significant transformation in the
approach to treating neurodegenerative diseases, with the potential for
further development in the future
Database (fluorescence microscopy) for a manuscript "BODIPY fluorescent dyes for selective staining of intracellular organelles"
No full textAntimicrobal activity of metabolites of essential oil components
No full textEterična ulja biljaka se od davnina koriste u različite svrhe te je dobro poznato njihovo antimikrobno djelovanje. Mogu se dobiti iz različitih dijelova biljaka, a obilježava ih specifičan, intenzivan miris. Sastoje se od brojnih sekundarnih metabolita različitih svojstava koji su ključni za preživljavanje i prilagodbu biljaka u njihovom okruženju. Zadnjih godina, postoji sve veći interes ljudi za prirodnijim načinima liječenja te je samim time primjena eteričnih ulja i njihovih spojeva u porastu. Zajedničko eteričnim uljima limuna, lavande, i timijana kemotipa timol i linalol te spojevima timolu, karvakrolu i timokinonu je njihova antimikrobna aktivnost prema raznim bakterijama koje izazivaju ozbiljne infekcije kod ljudi. Budući da ključne sastavnice eteričnih ulja brzo metaboliziraju u ljudskom mikrobiomu, gotovo je nemoguće očekivati njihov sistemski učinak. Zbog toga je u ovom istraživanju ispitano djelovanje oralno korištenih eteričnih ulja limuna, lavande i timijana kemotipa timol i linalol te spojeva koji se nalaze u eteričnim uljima: timolu, karvakrolu i timokinonu koji su sastavni dio brojnih farmaceutskih proizvoda. Svrha ovog istraživanja je ispitati antimikrobnu aktivnost i minimalnu inhibitornu koncentraciju (MIK) spomenutih eteričnih ulja i njihovih spojeva na standardnim sojevima - bakterijama Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29212 i Pseudomonas aeruginosa ATCC 27853. Rezultati disk difuzijskih metoda i metoda difuzije u jažicama su pokazali slabije antimikrobne učinke eteričnih ulja u odnosu na testirane spojeve eteričnih ulja i iznenađujuće jak utjecaj metabolita timokinona koji je potrebno dodatno istražiti.From ancient times, the essential oils of plants were used for various purposes since their antimicrobial activity was well known. Oils are obtained from different plant parts and are characterized by a specific, intense smell. They consist of numerous secondary metabolites with different properties that are crucial for the survival and adaptation of plants in their environment. In recent years, people's interest in more natural ways of treatment has increased, therefore essential oils alongside their compounds are on the rise. Essential oils of lemon, lavender, and thyme of the chemotype thymol and linalool and the compounds thymol, carvacrol, and thymoquinone have in common their antimicrobial activity against various bacteria that cause serious infections in humans. Since the key components of essential oils are rapidly metabolized in the human microbiome, it is almost impossible to expect their systemic effect. For this reason, this research examined the effect of orally used essential oils of lemon, lavender and thyme of the chemotype thymol and linalool, as well as the compounds found in essential oils: thymol, carvacrol and thymoquinone, which are integral parts of numerous pharmaceutical products. The purpose of this research is to test the antimicrobial activity alongside minimum inhibitory concentration (MIC) of the mentioned essential oils and their compounds on standard strains - bacteria Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29212 and Pseudomonas aeruginosa ATCC 27853. The results of disk diffusion methods and diffusion methods in wells showed weaker antimicrobial effects of essential oils compared to the tested compounds of essential oils and a surprisingly strong influence of thymoquinone metabolites, which needs to be further investigated
Application of the CETSA method to monitor EGFR stabilization induced by erlotinib binding
No full textCilj ovog rada je dokazati da se testom staničnog termalnog pomaka (engl. cellular thermal shift assay, CETSA) može proučiti interakcija spoja s ciljnim proteinom u stanicama. Razumijevanje mehanizma djelovanja lijeka predstavlja izazov jer je složeno utvrditi njegov afinitet prema različitim ciljevima. CETSA je robusna metoda koja ne zahtijeva kemijsku modifikaciju malih molekula i temelji se na termičkoj stabilizaciji proteina nakon vezanja liganda. Ciljni protein se identificira na temelju promjene u toplinskoj stabilizaciji. U ovom radu će se koristiti modelni protein receptora epidermalnog faktora rasta (engl. epidermal growth factor receptor, EGFR) i lijek iz skupine relativno specifičnih inhibitora tirozin kinaze, erlotinib. Primjenjivost CETSA metode će se ispitati u A431 staničnoj liniji epidermalnog karcinoma te HeLa staničnoj liniji karcinoma vrata maternice. Stanični lizat je bio inkubiran s erlotinibom ili DPBS-om kao kontrolom i zagrijavan na različite temperature kako bi se izazvala denaturacija proteina i identificirali pomaci u stabilnosti. Odrađeni su i eksperimenti koji nisu uključivali inkubaciju s erlotinibom da bi se procijenila temperatura denaturacije EGFR-a. Kako bi se odredila najučinkovitija koncentracija erlotiniba, analizirani su profili stabilnosti EGFR-a pri različitim koncentracijama erlotiniba na temperaturi denaturacije EGFR-a. Za sva ispitivanja provedene su SDS PAGE i Western blot analiza kako bi se odredila prisutnost i ekspresija specifičnih proteina u uzorcima. Intenzitet signala odgovora količini prisutnog proteina, a rezultati su normalizirani prema kontroli, beta-aktinu. Toplinski pomaci za EGFR uočeni su nakon vezanja erlotiniba. U A431 i HeLa staničnom lizatu, protein EGFR je najstabilniji na 55 °C, što ukazuje na to da ga erlotinib učinkovito štiti od denaturacije na toj temperaturi. Ovi rezultati sugeriraju da vezanje erlotiniba stabilizira EGFR, čime se sprječava denaturacija proteina pri višim temperaturama.The aim of this study is to demonstrate that the cellular thermal shift assay (CETSA) can be used to investigate the interaction between a compound and its target protein in cells. Understanding the mechanism action of a drug is challenging, as it is complex to determine its affinity for various potential targets. CETSA is a robust method that does not require chemical modifications of small molecules and is based on the thermal stabilization of proteins after ligand binding. The target protein is identified based on changes in thermal stability. In this study, the model protein used is the epidermal growth factor receptor (EGFR) and the drug from the group of relatively specific tyrosine kinase inhibitors, erlotinib. The applicability of the CETSA method will be tested in the A431 epidermal carcinoma cell line and the HeLa cervical carcinoma cell line. The cell lysate was incubated with erlotinib or DPBS as a control and heated to different temperatures to induce protein denaturation and identify shifts in stability. Experiments that did not include incubation with erlotinib were also conducted to assess the denaturation temperature of EGFR. To determine the most effective concentration of erlotinib, the stability profiles of EGFR were analysed at different erlotinib concentrations at the denaturation temperature od EGFR. SDS-PAGE and Western blot were performed for all experiments to assess the presence and expression of specific proteins in the samples. Signal intensity corresponds to the amount of protein present, and results were normalized to the control, beta-actin. Thermal shifts for EGFR were observed after erlotinib binding. In A431 and HeLa cell lysates, EGFR was most stable at 55°C, indicating that erlotinib effectively protects it from denaturation at that temperature. These results suggest that erlotinib binding stabilizes EGFR, thereby preventing protein denaturation at higher temperatures
Antimikrobna i prebiotska aktivnost Pilosella hoppeane
No full textAntimicrobial resistance (AMR) poses a critical global health challenge, with Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus faecalis among the top pathogens causing AMR-related deaths. This study explores the antimicrobial and prebiotic potential of Pilosella officinarum and three Pilosella hoppeana extracts (collected in June, July, and August 2023) against these pathogens and their prebiotic impact on Lactobacillus casei. Using broth microdilution assays, we evaluated the antimicrobial activity of water and ethanol extracts and their prebiotic effects compared to inulin, GOS, and FOS. Ethanol extracts showed greater antibacterial activity than water extracts. Notably, Pilosella officinarum ethanol extracts were effective against S. aureus, E. faecalis, and P. aeruginosa, while Pilosella hoppeana August extracts targeted only P. aeruginosa. None of the extracts demonstrated prebiotic activity on L. casei. These findings suggest Pilosella species as promising antimicrobial agents, particularly against P. aeruginosa.Antimikrobna rezistencija (AMR) predstavlja ozbiljan globalni zdravstveni izazov, pri čemu su Staphylococcus aureus, Pseudomonas aeruginosa i Enterococcus faecalis među vodećim patogenima koji uzrokuju smrti povezane s AMR-om. Ovo istraživanje ispituje antimikrobni i prebiotički potencijal Pilosella officinarum i tri ekstrakta Pilosella hoppeana (prikupljenih u lipnju, srpnju i kolovozu 2023.) protiv ovih patogena te njihov prebiotički učinak na Lactobacillus casei. Koristeći test mikrorazrjeđivanja bujona, procijenili smo antimikrobnu aktivnost vodenih i etanolnih ekstrakata te njihov prebiotički učinak u usporedbi s inulinom, GOS-om i FOS-om. Etanolni ekstrakti pokazali su veću antibakterijsku aktivnost od vodenih. Ekstrakti Pilosella officinarum u etanolu bili su učinkoviti protiv S. aureus, E. faecalis i P. aeruginosa, dok su ekstrakti Pilosella hoppeana prikupljeni u kolovozu bili učinkoviti samo protiv P. aeruginosa. Nijedan ekstrakt nije pokazao prebiotičku aktivnost na L. casei. Ovi rezultati ukazuju na potencijal vrsta Pilosella kao izvora učinkovitih antimikrobnih sredstava, osobito protiv P. aeruginosa
Association between methylenetetrahydr ofolate reductase gene polymorphisms and multiple sclerosis
No full textMultipla skleroza (MS) kronična je autoimuna bolest s
neurodegenerativnim posljedicama, koju karakteriziraju upalna područja,
demijelinizacija i degeneracija aksona. Etiologija ove bolesti još uvijek nije
u potpunosti razjašnjena zbog kompleksne veze između okolišnih
čimbenika, genetske predispozicije i virusne infekcije pri čemu ovi faktori
u većoj ili manjoj mjeri mogu igrati ulogu u riziku za razvoj bolesti te nisu
međusobno isključivi. Jedan od gena asociran s podložnošću za MS je
MTHFR gen. Polimorfne varijante gena, MTHFR C677T i MTHFR A1298C,
rezultiraju reduciranom aktivnošću enzima kodiranog pripadnim genom.
Time je narušen balans metabolizma folata i metionina, što uzrokuje
povećane razine neurotoksičnog homocisteina i slobodnih radikala, koji
oštećuju mijelin te smanjene razine S-adenozilmetiona neophodnog za
remijelinizaciju. Dosadašnja istraživanja u različitih populacija pokazala su
nedosljednosti u rezultatima u pokušaju da povežu polimorfizme s
predispozicijom za MS. Ovo istraživanje provedeno je PCR-RFLP metodom
na 200 MS bolesnika i 200 kontrolnih ispitanika u svrhu definiranja uloge
MTHFR polimorfizama u predispoziciji za MS i kliničkoj ekspresiji bolesti.
Obradom rezultata otkriveno je da polimorfizmi MTHFR C677T i MTHFR
A1298C ne pridonose povećanom riziku za MS. Međutim, pronađena je
povezanost između prisustva T alela MTHFR C677T polimorfizma i
povećanog progresijskog indeksa bolesti te potencijalan utjecaj C alela
MTHFR A1298C polimorfizma na trajanje bolesti. Analiza međudjelovanja
između polimorfizama ukazuje na povećan rizik od obolijevanja za osobe s
kombinacijom genotipova CC/AC i moguć smanjen rizik za one s CC/CC
kombinacijom. Zaključno, ispitivani polimorfizmi ne pridonose podložnosti
za MS, ali mogu modificirati eskpresiju bolesti što se mora uzeti s
rezervom obzirom na ograničen broj ispitanika s pojedinim kombinacijama
polimorfizama.Multiple sclerosis (MS) is a chronic autoimmune disease with
neurodegenerative consequences, characterized by inflammatory areas,
demyelination and axonal degeneration. The etiology of this disease is still
not fully elucidated due to the complex relationship between
environmental factors, genetic predisposition and viral infection, whereby
these factors can play a role in the risk for the development of the disease
to a greater or lesser extent and are not mutually exclusive. One of the
genes associated with susceptibility to MS is the MTHFR gene. Polymorphic
gene variants, MTHFR C677T and MTHFR A1298C, result in reduced
activity of the enzyme encoded by the corresponding gene. This disrupts
the balance of folate and methionine metabolism, which causes increased
levels of neurotoxic homocysteine and free radicals, which damage myelin,
and reduced levels of S-adenosylmethione, necessary for remyelination.
Previous studies in different populations have shown inconsistencies in the
results in an attempt to link polymorphisms with a predisposition to MS.
This research was conducted using the PCR-RFLP method on 200 MS
patients and 200 control subjects in order to define the role of MTHFR
polymorphisms in the predisposition to MS and the clinical expression of
the disease. Processing the results revealed that the MTHFR C677T and
MTHFR A1298C polymorphisms do not contribute to an increased risk for
MS. However, an association was found between the presence of the T
allele of the MTHFR C677T polymorphism and an increased disease
progression index, and the potential influence of the C allele of the MTHFR
A1298C polymorphism on the duration of the disease. Analysis of the
interaction between polymorphisms indicates an increased risk of the
disease for people with the combination of CC/AC genotypes and a
possible reduced risk for those with the CC/CC combination. In conclusion,
the studied polymorphisms do not contribute to susceptibility to MS, but
they can modify the expression of the disease, which must be taken with
caution considering the limited number of subjects with certain
combinations of polymorphisms
Računalna evaluacija derivata benzimidazola kao inhibitora MEK
No full textCancer is a condition where certain body cells uncontrollably multiply and invade
other parts of the body. The study deals with molecular interactions within the
Raf/Ras/MEK/ERK signalling pathway with the MEK1 as a focal point. The main goal
of this study is to investigate diarylbenzimidazole derivatives as potential MEK1 inhibitors. The study evaluates 15 drug candidates designed to target the MEK1 receptor, an important biomolecule in cancer progression. The aim is to determine
their effectiveness and binding affinities through various analyses, including docking, molecular dynamics simulations and free binding energy calculations. To provide
insights into the structural stability and dynamic behavior of the drug-receptor complexes, several parameters were calculated (RMSD, RMSF, RoG, SASA). Compounds
L05, L15 and referent Trametinib showed the best docking fit with the MEK 1 kinase.
Based on the experimental values molecular dynamics and free binding energy, L15
is a potential drug candidate. Next step is to experimentally validate the obtained
computational results of potential drug candidates.Rak je stanje u kojem se određene tjelesne stanice nekontrolirano umnožavaju i
napadaju druge dijelove tijela. Studija se bavi međumolekulskim interakcijama unutar signalizacijskog puta Raf/Ras/MEK/ERK, s MEK1 proteinom kao fokalnom točkom.
Glavni cilj ove studije je istražiti 15 derivata diarilbenzimidazola kao potencijalne inhibitore MEK1 receptora, važne molekule u progresiji raka. Cilj je utvrditi njihovu
učinkovitost i afinitete vezanja kroz različite analize, uključujući molekularno prijanjanje, simulacije molekularne dinamike te izračune slobodne energije vezanja. Strukturalna stabilnost kompleksa te interkacije kompleksa receptor-ligand potvrđena je
praćenjem raznih parametara (RMSD, RMSF, RoG, SASA). Rezultati molekularnog prijanjanja indiciraju najjače veze između MEK1 i spojeva L05, L15 te referentnog Trametiniba. Na temelju rezultata molekularne dinamike i izračuna slobodne energije,
L15 je potencijalni kandidat za lijek. Sljedeći korak je eksperimentalna validicija dobivenih rezultata računalne analize potencijalnih kandidata za lijek
Synthesis of thiazole-amide derivatives of theophylline-7-acetic acid to evaluate their biological effects
No full textU sklopu ovog rada reakcijom amidacije pripravljeni su derivati teofilin-7-
octene kiseline: a) tiazolni derivati 1-2, b) benzo[d]tiazolni derivati 3-6 i c)
4-feniltiazolni derivati 7-15. Strukture spojeva potvrđene su
spektroskopijom 1H NMR kao i spektrometrijom masa. In silico PASS
analizom predviđeni su farmakološki učinci i biološke mete. Većina spojeva
prema predviđanju bi trebala posjedovati djelovanje na transkripcijski
faktor STAT, cAMP fosfodiesterazu ili posjedovati nootropno djelovanje.As part of this work, theophylline-7-acetic acid derivatives were prepared
by te amidation reaction : a) thiazole derivatives 1-2, b) benzo[d]thiazole
derivatives 3-6, c) 4-phenylthiazole derivatives 7-15. The structures of the
prepared compounds were elucidated by 1H NMR spectroscopy and mass
spectrometry. Pharmacological effects and potential biological targets of
novel compounds have been predicted by in silico analysis (PASS). Most
compounds are predicted to have activity on transcription factor STAT, cAM
phosphodiesterase, or posses nootropic activity
Design of linear and cyclic catalytic peptides
No full textPozadina: Enzimi su proteini koji ubrzavaju kemijske reakcije stvaranjem povoljnih uvjeta za pretvorbu supstrata u produkte. Enzimi su velike makromolekule građene od aminokiselina povezanih peptidnim vezama. Peptidi, koji su također sastavljeni od aminokiselina, su manji i jednostavniji od proteina i mogu imati katalitička svojstva.
Cilj: Glavna svrha ovoga rada je istraživanje promjena svojstva katalize i samoorganizacije kod peptida koje proizlaze iz izmjena aminokiselina.
Metode: Tehnike koje su korištene su sinteza na čvrstom nosaču, tekuća kromatografija, masena spektrometrija, infracrvena spektroskopija, katalitički kinetički test i računalna simulacija molekularne dinamike.
Rezultati: Dva linearna i dva ciklička peptida su sintetizirana i karakterizirana. Strukture sintetiziranih peptida su kromatografski potvrđene što dokazuje mogućnost ciklizacije oktapeptida na čvrstom nosaču. Linearni peptidi formiraju supramolekularne strukture u obliku β-ploče sa cinkom. Daljnja analiza peptida sa katalitičkim kinetičkim testom je potrebna za dokazivanje njihovih katalitičkih svojstava.
Zaključak: Kombinacija računalnih i laboratorijskih tehnika je koristan alat u dizajnu peptida. Dizajn katalitičkih peptida relativno je novo polje proučavanja, stoga ovaj rad ima za cilj steći detaljnija saznanja o području.Background: Enzymes are proteins that help speed up chemical reactions by creating favourable environment for the conversion of substrates into products. Enzymes are large macromolecules composed of amino acids connected with peptide bonds. Peptides, which are also made up of amino acids, are smaller and easier to synthesize than proteins and can display catalytic properties.
Aim: The main purpose of this thesis is to explore the changing of self-assembly and catalytic properties of peptides by introducing amino acid alterations.
Methods: Techniques used are solid phase peptide synthesis, liquid chromatography, mass spectrometry, infrared spectroscopy, catalytic kinetic assay and computational molecular dynamics simulation.
Results: Two linear and two cyclic peptides were synthesized and characterized. The chromatography data validates the synthesized peptides which proves the possibility of octapeptide on-resin cyclization. Linear peptides formed supramolecular β-sheet-like structures with zinc. Further analysis of the peptides using the catalytic kinetic assay in needed to confirm their catalytic properties.
Conclusions: The combination of computational and laboratory techniques is a useful tool in peptide design. Catalytic peptide design is a newly emerging field of study and for this reason, this thesis aims to obtain a better understanding of the matter
Uloga meloksikama u proteinuriji kod ozljede kralježnične moždine
No full textBACKGROUND: Spinal cord injury (SCI) resulting from trauma to spinal
column leads to changes in organ function above and below the level of
the injury. There are many preclinical animal models of SCI which
recapitulate different forms and degrees of injury occurring in human
population. SCI procedure carried out in preclinical animal models usually
involves some surgical manipulation of spinal cord or vertebral column
and therefore requires analgesic treatment in order to ensure optimal
recovery. Non-steroid anti-inflammatory (NSAID) drugs such as
meloxicam or carprofen are generally used to alleviate surgical pain in
animal models of SCI. Since SCI leads to a multitude of changes in organs
which handle metabolism and excretion of drugs, one needs to choose
appropriate analgesic agent with minimal side effect profile. Previously we
have observed increased mortality in animals which received meloxicam
as part of the analgesic regiment following SCI surgery. The mortality was
likely due to the suboptimal effects of the drug on the bladder function
which is compromised by SCI. Therefore, the purpose of this study was
to: (i) investigate the mechanism via which administration of meloxicam
contributes towards the adverse outcomes following induction of
experimental SCI in rats, and to (ii) determine the gender differences in
response to SCI and in the response to the drug administration.
MATERIALS AND METHODS: 29 12 weeks old Wistar rats were used in
the present study. All animals were subjected to T3 SCI and received
either
meloxicam (1mg/kg) or vehicle control administered
subcutaneously once a day for three days following the surgery. Urine
was collected once a day for three days and protein concentration was
determined using Bradford Assay. Animals were euthanized 72 hours after
the injury. Organs, tissues and blood were collected for future analyses.
RESULTS: Both female and male animals exhibited hematuria following
SCI. However, the proportion of female animals which exhibited
hematuria following SCI was significantly less than male animals.
Furthermore, male animals exhibited proteinuria while female animals
were less affected. Finally, meloxicam administration tended to increase
protein concentration in urine 72 hours following spinal cord injury.
CONCLUSION: These data suggest that there are significant gender
differences in response to experimental SCI in Wistar rats. Furthermore,
due to the effect of SCI on renal and urinary physiology, utility of
meloxicam for alleviating pain following SCI in male Wistar rats may be
suboptimal and other NSAIDs should be used.POZADINA: Ozljeda kralježnične moždine (OKM) uzrokovana traumom
dovodi do promjena u funkciji organa iznad i ispod područja ozljede.
Pretklinički modeli životinja OKM koji prikazuju različite oblike i stupnjeve
ozljede do kojih dolazi u ljudima su brojni. Postupak OKM u pretkliničkim
životinjskim modelima obično uključuje kiruršku manipulaciju kralježnične
moždine ili kralježnice i stoga zahtjeva tretman analgetikom kako bi se
osigurao najpovoljniji oporavak. Obično se koriste nesteroidni protuupalni
lijekovi (NSAID) kao što su meloksikam ili karprofen za ublažiti bol nakon
kirurškog zahvata u OKM modelima životinja. OKM dovodi do mnogih
promjena u organima koji sudjeluju u metabolizmu i izlučivanju lijekova i
zato je potrebno izabrati prikladan analgetski agens sa minimalnim
mogućim nuspojavama. Prethodno smo uvidjeli povećanu smrtnost u
životinjama koje su primale meloksikam kao analgetik nakon što su
podvrgnute operaciji OKM. Stoga, cilj ovog istraživanja je bio: (i) istražiti
mehanizam kojim administracija meloksikama pridonosi nepovoljnim
ishodima uslijed indukcije eksperimentalne OKM u štakorima i (ii) odrediti
razlike između spolova prema odgovoru na OKM i odgovoru na
administraciju lijeka.
MATERIJALI I METODE: U ovome je istraživanju korišteno 29 Wistar
štakora stara 12 tjedana. Sve su životinje bile podvrgnute operaciji
ozljede T3 kralješka te su primile meloksikam (1mg/kg) ili kontrolu koji su
potkožno administrirani jednom dnevno tri dana uslijed operacije.
Mokraća je prikupljana jednom dnevno tri uzastopna dana, a
koncentracija proteina je određena pomoću Bradford eseja. Životinje su
eutanazirane 72 sata nakon ozljede. Organi, tkiva i krv su prikupljeni za
daljnja istraživanja.
REZULTATI: Obje ženske i muške jedinke su doživjele hematuriju uslijed
OKM. Međutim, omjer ženskih životinja koje su doživjele hematuriju
uslijed OKM je značajno manji u odnosu na muške životinje. Nadalje,
koncentracija proteina u mokraći je značajno manja u ženkama u odnosu
na mužjake. Administracijom meloksikama se povećala koncentracija
proteina u mokraći 72 sata nakon operacije OKM.
ZAKLJUČAK: Ovi podatci nalažu da postoje značajne razlike u odgovoru
na eksperimentalnu OKM između muških i ženskih Wistar štakora.
Nadalje, radi utjecaja OKM na renalnu i urinarnu fiziologiju, upotreba
meloksikama za ublažavanje boli uslijed OKM u muškim Wistar štakorima
nije povoljna i drugi bi se NSAID-ovi trebali upotrijebiti