Veterinary medicine - Repository of PHD, master's thesis
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Životinje u službi znanosti: nevidljivi junaci medicinskih otkrića : Noć knjige 2025. godine
No full textEksperimenti na životinjama dio su biomedicinskih istraživanja već tisućama godina. Zbog anatomskih i fizioloških sličnosti između ljudi i životinja, osobito sisavaca, određeni lijekovi, cjepiva i terapije najprije se ispituju na životinjskim modelima. Razumijevanje načina funkcioniranja ljudskog organizma i povezane spoznaje koje su dovele do iznimnog napretka medicinske prakse izravni su rezultat takvih istraživanja.
Zanimljivo je istaknuti da se čak 188 od ukupno 225 Nobelovih nagrada za fiziologiju i medicinu temelji na rezultatima ostvarenim upravo na životinjskim modelima.
Kako su se tijekom povijesti razvijala istraživanja na životinjama? U kojim područjima kliničke medicine ne bismo mogli napredovati bez takvih eksperimenata? Koje se životinje koriste, uzgajaju li se posebno za te svrhe? Kako je regulirano njihovo korištenje i pod kojim zakonskim okvirom? I na kraju – hoće li biomedicinska istraživanja u budućnosti biti moguća bez korištenja životinjskih modela?
Na ova, kao i brojna druga pitanja pokušat će odgovoriti Središnja medicinska knjižnica Medicinskog fakulteta Sveučilišta u Zagrebu svojim programom „Životinje u službi znanosti: nevidljivi junaci medicinskih otkrića“. Osim u sklopu Noći knjige 23. travnja, programom će se simbolično obilježiti i Svjetski dan eksperimentalnih životinja, 24. travnja, kojim se nastoji podići svijest o eksperimentiranju na životinjama
Frequency and type of renal damage in children and young adults with haemophilia A and B
No full textUvod: Stupanj bubrežnog oštećenja u djece i mladih odraslih ispitanika s hemofilijom nepoznat je i nedovoljno istražen. Svrha ovog rada je istražiti učestalost bubrežnog oštećenja u ispitanika s hemofilijom A/B laboratorijskim, ultrazvučnim i metodama nuklearno medicinske dijagnostike. Svi su ispitanici bili bez simptoma bubrežnog oštećenja s normalnim vrijednostima kreatinina i ureje.
Metode: U istraživanje je uključeno 73 muška ispitanika s hemofilijom A ili B. Od toga 34 mlađih do 18 godina i 39 odraslih muškaraca do 32 godine liječenih u KBC Zagreb. Metode procjene bubrežnog oštećenja bile su ultrazvuk bubrega, dinamička scintigrafija bubrega, mjerenje korigiranog klirensa kreatinina, cistatina C, eritropoetina i procjena tubularne funkcije bubrega pomoću parametara iz 24-satnog urina (kreatinin, klirens kreatinina, proteinurija, kalciurija, natriurija, kaliurija, magnezurija).
Rezultati: Najveća učestalost poremećene bubrežne funkcije utvrđena je mjerenjem radioizotopnog klirensa s 99m Tc-DTPA i to u 45,3% ispitanika. Mjerenjem poremećaja tubularne funkcije nađeno je odstupanje od normale u 36,9 % ispitanika, a povišeni cistatin C utvrđen je u 17,4 % ispitanika. UZV analizom urotrakta morfološko oštećenje bilo je prisutno u 7,5% ispitanika. U svega 6,3% ispitanika bio je snižen klirens kreatinina. Statistički je značajna povezanost morfološkog oštećenja bubrega s prisutnim inhibitorima na FVIII/FIX. Oštećenje je prisutno u 4,9 % bolesnika bez i 33,3 % bolesnika s inhibitorima. Osim toga, statistički je značajna povezanost morfološkog oštećenja s tipom terapije i prisutno je u 40% bolesnika na „ostaloj terapiji“.
Zaključak: Kao najbolja metoda za procjenu pa i najmanjeg otklona bubrežne funkcije od normale u djece i mladih odraslih s hemofilijom utvrđena je metoda dinamičke scintigrafije bubrega. Mjerenje DTPA iGF i u našem istraživanju potvrdilo je ranije dokazanu visoku osjetljivost i specifičnost.. Analizom ROC krivulje vidi se kako različite metode procjene bubrežnog oštećenja ne posjeduju dobra diskriminatorna svojstva za prepoznati ispitanike s poremećenim DTPA iGF.Introduction: The extent of kidney damage in children and young adults with haemophilia is not well studied and a lot is still unknown. The aim of this study is to evaluate the incidence of kidney damage in subjects with haemophilia A/B using laboratory, ultrasound, and nuclear medicine diagnostic methods. None of the subjects had renal damage symptoms and all of them had normal creatinine and urea values.
Methods: We included 73 male subjects with haemophilia A or B. Among them, 34 were minors, while 39 were young adults, all treated in UHC Zagreb. To estimate renal damage ultrasound, dynamic renal scintigraphy, corrected creatinine clearance, cystatin C, erythropoietin, and 24 urine excretion to evaluate tubular renal function were performed. All subjects were examined, and blood samples and 24-hour urine were collected (creatinine, creatinine clearance, proteinuria, calcuria, natriuria, kaliuria, magnesuria).
Results: The highest prevalence of impaired renal function was determined by measuring the radioisotope clearance with 99m Tc-DTPA in 45,3% of the subjects. Tubular function measurement discovered a deviation in 36,9% of subjects, and elevated cystatin C was found in 17,4% of subjects. Urinary tract imaging damage showed morphological abnormalities in 7,5% of subjects. Only 6,3% of the subjects had decreased creatinine clearance. There was a statistically significant association between morphological kidney damage and the presence of FVIII/FIX inhibitors. Damage was present in 4,9% of patients without and 33,3% of patients with inhibitors. Additionally, there was a statistically significant association between morphological damage with the type of therapy and was present in 40% of patients treated with "other" therapy. Conclusion: Dynamic renal scintigraphy was established as the best method for assessing even the smallest renal function deviation in children and young adults with haemophilia. DTPA iGF measurement was also in our research shown to be highly sensitive and specific. The ROC curve analyses showed that the different methods of kidney damage assessment do not have good discriminatory characteristics for recognizing subjects with impaired DTPA iGF
Heavily pretreated patient with nodal marginal zone lymphoma successfully treated with mosunetuzumab
No full textRegenerative effect of oral mucosa stem cells on hypoxia damaged neurons in vitro
No full textRegenerativna medicina je moderna disciplina koja jedan dio svojih uspjeha temelji na terapijskom učinku matičnih stanica i molekula koje one izlučuju. Ipak, mnoge vrste matičnih stanica se teško dobivaju ili je njihova primjena povezana s etičkim nedoumicama, pa je pronalaženje lako dostupnih izvora stanica važno za daljnji napredak. Ovo istraživanje je opisalo novu populaciju matičnih stanica, dobivenu biopsijom oralne sluznice, nazvanih ljudske matične stanice oralne sluznice (hOMSC). Nakon što smo usporedbom različitih protokola uspostavili postupak kojim dobivamo dovoljnu količinu homogenih stanica koje su
diferencijacijom oblikovale strukture tipične za nezrele ektodermalne stanice, testiranjem različitih biljega smo ovu populaciju definirali kao značajno pozitivnu na nestin i CD166, uz mjerljivu prisutnost OCT4, SOX2, CD90, CD40 i SNAIL2. Testiranje njihove otpornosti na anoksiju je otkrilo kako oralne matične stanice bolje preživljavaju u odnosu na iPSC. Također, hOMSC izlučuju regenerativne molekule BDNF, VEGF i NGF što je ovisilo o duljini kontakta s neuronima. Isto tako je pokazano kako oralne matične stanice povećavaju preživljenje ljudskih neurona oštećenih manjkom kisika. Sve navedeno ukazuje kako je ovo istraživanje uspostavilo protokol dobivanje stanične populacije iz razmjerno lako dostupnog izvora koja ima značajan potencijal u liječenju ishemijski oštećenog živčanog tkiva.Regenerative medicine is a contemporary discipline that relies part of its success on the therapeutic effects of stem cells and the molecules they secrete. However, many types of stem cells are difficult to obtain or are associated with ethical concerns, making the identification of easily accessible cell sources crucial for further advancement. This study describes a novel population of stem cells, obtained through oral mucosa biopsy, referred to as human oral mucosa stem cells (hOMSC). By comparing different protocols, we established a method to obtain enough of homogeneous cells that differentiate into structures typical of immature ectodermal cells. Through marker analysis, this population was characterized as significantly positive for nestin and CD166 with a measurable expression of OCT4, SOX2, CD90, CD40, and SNAIL2. Testing their resistance to anoxia revealed that oral stem cells exhibit substantial resilience under extreme conditions compared to iPSC. Additionally, hOMSC secretes essential regenerative molecules: BDNF, VEGF, and NGF. The duration of contact with neurons modulates the secretion levels of these molecules. It was also demonstrated that oral stem cells enhance the survival of human neurons subjected to hypoxic damage. These findings indicate that this study has established a protocol for deriving a cell population from an easily accessible source with significant potential for treating ischemic neural tissue damage
Nucelotide polymorphism rs531564 of pri-miR-124 gene in patients with primary sclerosing cholangitis and inflammatory bowel disease
No full textUpalne bolesti crijeva (UBC) kronične su imunosno posredovane bolesti genski predisponiranih osoba, čija etiopatogeneza nije potpuno razjašnjena. Posebno se ističe fenotip UBC-a kod pacijenata s primarnim sklerozirajućim kolangitisom (PSC). UK i CB u tih bolesnika dominantno zahvaćaju kolon, karakteristično su blažeg tijeka, ali uz povišen rizik razvoja kolorektalnog karcinoma, a i drugih malignih bolesti. Rezultati naše kohorte bolesnika su u skladu s dosad publiciranim podacima u literaturi.
Smatra se da miR imaju važnu ulogu u navedenoj patogenezi. Uloga miR-124 posebno je istražena, pokazujući važnost u održavanju integriteta crijevne barijere i regulaciji proinflamatornih citokina, a SNP (rs531564) gena povezan je s njezinom ekspresijom.
Cilj ovog ispitivanja bio je prvi put u ovoj populaciji analizirati učestalost genotipa navedenog SNP-a.
Nismo uspjeli pokazati značajne razlike u genotipu između ispitivane (UBC/PSC) i kontrolne skupine (UBC). Genotip GG numerički je učestaliji u bolesnika s UBC-om u odnosu na PSC, ali razlike nisu bile statistički značajne. Nije pronađena značajna razlika po genotipu za kliničke ili demografske varijable osim za bolesnike s UK-om, gdje su ispitanici s genotipom GC bili značajno mlađi te su mlađi započinjali biološku terapiju u odnosu na ispitanike s genotipom GG. Potrebna su daljnja, multicentrična istraživanja na većem uzorku kako bi se potvrdili ovi nalazi.Inflammatory bowel diseases (IBD) are chronic, immunologically mediated diseases of genetically predisposed individuals, whose etiopathogenesis is not fully understood. The phenotype of IBD in patients with primary sclerosing cholangitis (PSC) is particularly notable. Ulcerative colitis (UC) and Crohn's disease (CD) in these patients predominantly affect the colon and are characteristically milder in course but with an increased risk of developing colorectal cancer as well as other malignancies. The results from our cohort of patients are consistent with previously published data in the literature.
It is believed that microRNAs (miRNAs) play an important role in the aforementioned pathogenesis. The role of miR-124 has been particularly studied, showing its importance in maintaining intestinal barrier integrity and regulating pro-inflammatory cytokines, with the SNP (rs531564) gene being associated with its expression.
The aim of this study was to analyze, for the first time in this population, the frequency of genotypes of the mentioned SNP.
We did not show significant differences in genotype between the study group (IBD/PSC) and the control group (IBD). The GG genotype was numerically more prevalent in patients with IBD compared to PSC, but the differences were not statistically significant. No significant difference was found by genotype for clinical or demographic variables except for UC patients, where participants with the GC genotype were significantly younger and started biological therapy earlier compared to the GG genotype. Further multicentric studies on larger samples are needed to confirm these findings
Controversies in treating nutcracker syndrome
No full textNutcracker syndrome (NCS) is a relatively uncommon vascular condition characterized by compression of the left renal vein (LRV), resulting in a variable spectrum of nonspecific symptoms, including hematuria, flank pain, varicocele, and pelvic congestion syndrome. NCS can be classified into anterior and posterior types regarding the origin of LRV compression: anterior NCS occurs when LRV is compressed between the aorta and superior mesenteric artery, whereas posterior NCS involves LRV compression between the aorta and the spine. Despite advancements in diagnostic modalities, including Doppler ultrasound, computed tomography, magnetic resonance imaging, and invasive techniques like phlebography, there is still no globally accepted diagnostic algorithm, leading to inconsistencies in diagnosis. Moreover, due to the lack of standardized treatment guidelines, the optimal management of anterior NCS remains a topic of debate. While conservative management is usually recommended in the pediatric population, invasive treatments—including surgical options like LRV transposition and renal autotransplantation, as well as interventional radiology procedures like stenting, present challenges such as stent migration, restenosis, and long-term material durability. Nevertheless, the emergence of 3D-printed stents offers potential improvements in patient-specific treatment, particularly in the pediatric population, yet their clinical efficacy and safety remain under investigation. This brief communication addresses the current discussions regarding anterior NCS management, emphasizing the need for standardized diagnostic algorithms, a multidisciplinary approach, and continued technological advancements to refine treatment possibilities and strategies. Further research is critical to resolve these controversies and establish a consensus on best practices
Comparable outcomes after busulfan- or treosulfan-based conditioning for allo-HSCT in children with ALL: results of FORUM
No full textThe superiority of total body irradiation (TBI)-based vs chemotherapy conditioning for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with acute lymphoblastic leukemia (ALL) has been established in the international, prospective phase-3 FORUM study, randomizing 417 patients aged 4-18 years in complete remission (CR), who received allo-HSCT from HLA-matched sibling or unrelated donors. Because of the unavailability of TBI in some regions and to accommodate individual contraindications, this study reports the prespecified comparison of outcomes of patients receiving busulfan (BU)- or treosulfan (TREO)-based regimens from 2013 to 2018. Overall, 180 and 128 patients received BU/thiotepa (THIO)/fludarabine (FLU) or TREO/THIO/FLU, respectively. Data were analyzed as of February 2023, with a median follow-up of 4.2 years (range, 0.3-9.1). 3-year overall survival was 0.71 (BU, 95% confidence interval [0.64-0.77]) and 0.72 (TREO, [0.63-0.79]) and 3-year event-free survival was 0.60 (BU, [0.53-0.67]) and 0.55 (TREO, [0.46-0.63]). The 3-year cumulative incidence of relapse (BU, 0.31 [0.25-0.38]; TREO, 0.36 [0.27-0.44]); and nonrelapse mortality (BU, 0.08 [0.05-0.13]; TREO, 0.09 [0.05-0.15]) were comparable. One case of fatal veno-occlusive disease occurred in each group. No significant differences in acute and chronic graft-versus-host disease (GVHD) or 3-year GVHD-free and relapse-free survival (BU, 0.48 [0.41-0.55]; TREO, 0.45 [0.37-0.54]) were recorded. Outcomes for patients in first and second CR were similar irrespective of the regimen. In conclusion, BU/THIO/FLU or TREO/THIO/FLU regimens can be an alternative to TBI for patients with ALL aged >4 years with contraindications or lack of access to TB
Epidemiological and Entomological Study After the Possible Re-Emergence of Dengue Fever in Croatia, 2024
No full textAutochthonous dengue cases have been continuously recorded in Europe in the past two decades. The first autochthonous dengue case in Croatia was reported in 2010 on the Pelješac Peninsula, while imported cases were recorded continuously thereafter. In 2024, dengue re-emerged in Croatia. An epidemiological and entomological study was conducted after receiving information on dengue virus (DENV) infection in a German tourist probably acquired on Dugi Otok Island in Croatia in May 2024. Serum samples were collected from 30 residents of the Veli Rat region where the patient had stayed. In addition, mosquitoes were collected in the same area. Human samples were tested for the presence of DENV antibodies (ELISA and IFA) and DENV RNA (RT-qPCR), while mosquito samples were tested for DENV RNA (RT-qPCR). DENV IgM or IgG antibodies were found in 8 serum samples, while no one sample was RT-qPCR positive. No cross-reactivity with flaviviruses was detected in seropositive samples, supporting DENV infection. One patient was classified as a confirmed dengue case (IgG seroconversion in paired serum samples) and five as probable cases (IgM detection in a single serum sample). One additional patient, sampled only once, was IgG seropositive. Two of the seropositive individuals reported fever and rash three weeks before testing. The re-emergence of dengue in Croatia highlights the need for continuous monitoring of DENV circulation in both humans and vectors
Quiescent cells maintain active degradation-mediated protein quality control requiring proteasome, autophagy, and nucleus-vacuole junctions
No full textMany cells spend a major part of their life in quiescence, a reversible state characterized by a distinct cellular organization and metabolism. In glucose-depleted quiescent yeast cells, there is a metabolic shift from glycolysis to mitochondrial respiration, and a large fraction of proteasomes are reorganized into cytoplasmic granules containing disassembled particles. Given these changes, the operation of protein quality control (PQC) in quiescent cells, in particular the reliance on degradation-mediated PQC and the specific pathways involved, remains unclear. By examining model misfolded proteins expressed in glucose-depleted quiescent yeast cells, we found that misfolded proteins are targeted for selective degradation requiring functional 26S proteasomes. This indicates that a significant pool of proteasomes remains active in degrading quality control substrates. Misfolded proteins were degraded in a manner dependent on the E3 ubiquitin ligases Ubr1 and San1, with Ubr1 playing a dominant role. In contrast to exponentially growing cells, the efficient clearance of certain misfolded proteins additionally required intact nucleus-vacuole junctions (NVJ) and Cue5-independent selective autophagy. Our findings suggest that proteasome activity, autophagy, and NVJ-dependent degradation operate in parallel. Together, the data demonstrate that quiescent cells maintain active PQC that relies primarily on selective protein degradation. The necessity of multiple degradation pathways for the removal of misfolded proteins during quiescence underscores the importance of misfolded protein clearance in this cellular state