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L-arginine intake effect on adenin nucleotide metabolism in rat parenchymal and reproductive tissues
Gordana Kocić, J. Nikolić, Tatjana Jevtović, Dušan Sokolović, H. Kocić, T. Cvetković, Miloš Pavlović, Avrelija Cencič, D. Stojanovic, 2012, izvirni znanstveni članek

Opis: L-arginine is conditionally essential amino acid, required for normal cell growth, protein synthesis, ammonia detoxification, tissue growth and general performance, proposed in the treatment of men sterility and prevention of male impotence. The aim of the present paper was to estimate the activity of the enzymes of adenine nucleotide metabolismČ 5' -nucleotidase ( 5'-NU), adenosine deaminase (ADA), AMP deaminase, and xanthine oxidase (XO), during dietary intake of L-arginine for a period of four weeks of male Wistar rats. Adenosine concentration in tissues is maintained by the relative activities of the adenosine-producing enzyme, 5' -NU and the adenosine-degrading enzyme-ADA adenosine deaminase. Dietary L-arginine intake directed adenine nucleotide metabolism in liver, kidney, and testis tissue toward the activation of adenosine production, by increased 5' -NU activity and decreased ADA activity. Stimulation of adenosine accumulation could be of importance in mediating arginine antiatherosclerotic, vasoactive, immunomodulatory, and antioxidant effects. Assuming that the XO activity reflects the rate of purine catabolism in the cell, while the activity of AMP deaminase is of importance in ATP regeneration, reduced activity of XO, together with the increased AMP-deaminase activity, may suggest that adenine nucleotides are presumably directed to the ATP regenerating process during dietary L-arginine intake.
Ključne besede: biochemistry
Objavljeno: 15.06.2017; Ogledov: 30; Prenosov: 0
.pdf Polno besedilo (1,16 MB)

Skin cancer and its treatment
Kristjan Orthaber, Matevž Pristovnik, Kristijan Skok, Barbara Perić, Uroš Maver, 2017, pregledni znanstveni članek

Opis: The life expectancy in the Western world is increasing for a long time, which is the courtesy of a higher life standard, a more thorough hygiene, and, of course, the progress of modern medicine. Nevertheless, one of the illnesses that still proves to be a great challenge regardless of the recent advancements in medicine is cancer. Skin cancer is, according to theWorld Health Organization, the most common malignancy for the white population.The beginning of the paper offers a brief overview of the latest available information concerning epidemiology, aetiology, diagnostics, and treatment options for skin cancer, whereas the rest of the article deals with modern approaches to skin cancer treatment, highlighting recent development of nanotechnology based treatment approaches. Among these, we focus especially on the newest nanotechnological approaches combined with chemotherapy, a field which specialises in target specificity, drug release control, and real time monitoring with the goal being to diminish unwanted side effects and their severity, achieving a cheaper treatment and a generally more efficient chemotherapy. The field of nanotechnology is a rapidly developing one, judging by already approved clinical studies or by new theranostic agents that combine both the therapeutic and diagnostic modalities.
Ključne besede: skin cancer, treatment, nanotechnology, nanotechnological methods
Objavljeno: 14.06.2017; Ogledov: 48; Prenosov: 0
.pdf Polno besedilo (1,56 MB)

Age-related differences in percentages of regulatory and effector T lymphocytes and their subsets in healthy individuals and characteristic STAT1/STAT5 signalling response in helper T lymphocytes
Marija Holcar, Aleš Goropevšek, Alojz Ihan, Tadej Avčin, 2015, izvirni znanstveni članek

Opis: The dynamic process of the development of the immune system can in itself result in age-related immune malfunctions. In this study, we analysed lymphocyte subsets in the peripheral blood of 60 healthy donors, divided into groups of children, adolescents, and adults, focusing on effector (Teff) and regulatory (Treg) T lymphocytes and STAT1/STAT5 signalling response in helper T lymphocytes (Th) in adults, using flow cytometry. Our results demonstrate a decrease in the percentage of total Tregs and an increase in the percentage of total Teffs with age and a consequential immense increase in the Teff/Treg ratio. The increase of Teffs was most apparent in Th1, Th1Th17, and Th17CD161- subsets. Significant Th lymphocyte STAT1 expression differences were observed between children and adolescents, which were associated with the decrease in activated Tregs. Higher expression of STAT1 was found in FoxP3hi than in FoxP3low Th lymphocytes, while significant IL-2 induced STAT5 phosphorylation differences were found among the subsets of Th lymphocytes in adults. Our study demonstrates age-related changes in circulating Teff and Treg, as well as significant differences in STAT5/STAT1 signalling among FoxP3+ Th lymphocytes, providing new advances in the understanding of immunosenescence.
Ključne besede: T lymphocytes, age-related differences, immune system
Objavljeno: 14.06.2017; Ogledov: 55; Prenosov: 0
.pdf Polno besedilo (2,39 MB)

Intermittent chemotherapy and erlotinib for nonsmokers or light smokers with advanced adenocarcinoma of the lung
Matjaž Zwitter, Mirjana Rajer, Viljem Kovač, Izidor Kern, Martina Vrankar, Uroš Smrdel, 2011, izvirni znanstveni članek

Opis: Background. Intermittent application of chemotherapy and tyrosine kinase inhibitors may avoid antagonism between the two classes of drugs. This hypothesis was tested in a Phase II clinical trial. Patients and Methods. Eligible patients were nonsmokers or light smokers, chemo-naïve, with metastatic adenocarcinoma of the lung. Treatment: 4 to 6 cycles of gemcitabine 1250 mg/m2 on days 1 and 4, cisplatin 75 mg/m2 on day 2, and erlotnib 150 mg daily on days 5–15, followed by erlotinib as maintenance. Results. 24 patients entered the trial. Four pts had grade 3 toxicity. Complete remission (CR) and partial remission (PR) were seen in 5 pts and 9 pts, respectively (response rate 58%). Median time to progression (TTP) was 13.4 months and median overall survival (OS) was 23 months. When compared to patients with negative or unknown status of EGFR mutations, 8 patients with EGFR gene activating mutations had significantly superior experience: 4 CR and 4 PR, with median TTP 21.5 months and OS 24.2 months (P < .05). Conclusions. Intermittent schedule with gemcitabine, cisplatin and erlotinib has mild toxicity. For patients who are positive for EGFR gene activating mutations, this treatment offers excellent response rate, time to progression and survival.
Ključne besede: smokers, nonsmokers, cancer treatment, lung cancer, chemotherapy, erlotinib
Objavljeno: 14.06.2017; Ogledov: 48; Prenosov: 0
.pdf Polno besedilo (2,30 MB)

Single nucleotide polymorphisms as prognostic and predictive factors of adjuvant chemotherapy in colorectal cancer of stages I and II
Matej Horvat, Uroš Potočnik, Katja Repnik, Rajko Kavalar, Borut Štabuc, 2016, pregledni znanstveni članek

Opis: Colorectal cancer (CRC) is a highly heterogeneous disease regarding the stage at time of diagnosis and there is special attention regarding adjuvant chemotherapy in unselected patients with stage I and stage II. The clinicohistologically based TNM staging system with emphasis on histological evaluation of primary tumor and resected regional lymph nodes remains the standard of staging, but it has restricted sensitivity resulting in false downward stage migration. Molecular characteristics might predispose tumors to a worse prognosis and identification of those enables identifying patients with high risk of disease recurrence. Suitable predictive markers also enable choosing the most appropriate therapy. The current challenge facing adjuvant chemotherapy in stages I and II CRC is choosing patients with the highest risk of disease recurrence who are going to derive most benefit without facing unnecessary adverse effects. Single nucleotide polymorphisms (SNPs) are one of the potential molecular markers that might help us identify patients with unfavorable prognostic factors regarding disease initiation and recurrence and could determine selection of an appropriate chemotherapy regimen in the adjuvant and metastatic setting. In this paper, we discuss SNPs of genes involved in the multistep processes of cancerogenesis, metastasis, and the metabolism of chemotherapy that might prove clinically significant.
Ključne besede: single nucleotide polymorphism, colorectal cancer, adjuvant chemotherapy
Objavljeno: 14.06.2017; Ogledov: 28; Prenosov: 0
.pdf Polno besedilo (1,27 MB)

Hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in patients with recurrent variceal hemorrhage
Peter Popović, Andrej Zore, Katarina Šurlan Popović, Manca Garbajs, Pavel Skok, 2013, izvirni znanstveni članek

Opis: Purpose.The purpose of this study was to determine the incidence and predictors of hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) and endoscopic therapy (ET) in the elective treatment of recurrent variceal hemorrhage. Methods. Seventy patients were treated with elective TIPS and fifty-six patients with ET. Median observation time was 46.28 months in the TIPS group and 42.31 months in the ET group. Results. 30 patients (42.8%) developed clinically evident portosystemic encephalopathy in TIPS group and 20 patients (35.6%) in ET group. The difference between the groups was not statistically significant (P=0.542; X2 test). The incidence of new or worsening portosystemic encephalopathy was 24.3% in TIPS group and 10.7% in ET group. Multivariate analysis showed that ET treatment (P=0.031), age of >65 years (P=0.022), pre-existing HE (P=0.045), and Childs class C (P=0.051) values were independent predictors for the occurrence of HE. Conclusions. Procedure related HE is a complication in a minority of patients treated with TIPS or ET. Patients with increased age, preexisting HE, and higher Child-Pugh score should be carefully observed after TIPS procedure because the risk of post-TIPS HE in these patients is higher.
Ključne besede: veins, dilated veins, rebleeding, portacaval encephalopathy, liver, cirrhosis, portal hypertension, transjugular intrahepatic portosystemic shunt
Objavljeno: 14.06.2017; Ogledov: 53; Prenosov: 0
.pdf Polno besedilo (1,18 MB)

Quantitative evaluation of growth plates around the knees of adolescent soccer players by diffusion-weighted magnetic resonance imaging
Zmago Krajnc, Mitja Rupreht, Matej Drobnič, 2015, izvirni znanstveni članek

Opis: Purpose. To quantitatively evaluate growth plates around the knees in adolescent soccer players utilizing the diffusion-weighted MR imaging (DWI). Methods. The knees and adjacent growth plates of eleven 14-year-old male soccer players were evaluated by MRI before (end of season´s summer break) and after two months of intense soccer training. MRI evaluation was conducted in coronal plane by PD-FSE and DWI. All images were screened for any major pathological changes. Later, central growth plate surface area (CGPSA) was measured and the apparent diffusion coefficient (ADC) values were calculated in two most central coronal slices divided into four regions: distal femur medial (DFM), distal femur lateral (DFL), proximal tibia medial (PTM), and proximal tibia lateral (PTL). Results. No gross pathology was diagnosed on MRI. CGPSA was not significantly reduced: DFM 278 versus 272, DFL 265 versus 261, PTM 193 versus 192, and PTL 214 versus 210. ADC decrease was statistically significant only for PTM: DFM 1.27 versus 1.22, DFL 1.37 versus 1.34, PTM 1.13 versus 1.03 (p=0.003), and PTL 1.28 versus 1.22. Conclusions. DWI measurements indicate increased cellularity in growth plates around knees in footballers most prominent in PTM after intense training. No detectable differences on a standard PD-FSE sequence were observed.
Ključne besede: soccer, adolescent, quantitative magnetic resonance, knee
Objavljeno: 14.06.2017; Ogledov: 35; Prenosov: 1
.pdf Polno besedilo (1,92 MB)

Predictors of mortality and prehospital monitoring limitations in blunt trauma patients
Vitka Vujanović, Tine Pelcl, Matej Strnad, Miljenko Križmarić, Vesna Borovnik Lesjak, 2015, izvirni znanstveni članek

Opis: This study aimed at determining predictors of in-hospital mortality and prehospital monitoring limitations in severely injured intubated blunt trauma patients. We retrospectively reviewed patients' charts. Prehospital vital signs, Injury Severity Score (ISS), initial Glasgow Coma Scale (GCS), Revised Trauma Score (RTS), arterial blood gases, and lactate were compared in two study groups: survivors (n=40) and nonsurvivors (n=30). There were no significant differences in prehospital vital signs between compared groups. Nonsurvivors were older (P=0.006), with lower initial GCS (P<0.001) and higher ISS (P<0.001), along with higher lactate (P<0.001) and larger base deficit (BD; P=0.006 ), whereas RTS (P=0.001) was lower in nonsurvivors. For predicting mortality, area under the curve (AUC) was calculated: for lactate 0.82 (P<0.001), for ISS 0.82 (P<0.001), and for BD 0.69 (P=0.006). Lactate level of 3.4mmol/L or more was 82% sensitive and 75% specific for predicting in-hospital death. In a multivariate logistic regression model, ISS (P=0.037), GCS (P=0.033), and age (P=0.002) were found to be independent predictors of in-hospital mortality. The AUC for regression model was 0.93 (P<0.001). Increased levels of lactate and BD on admission indicate more severe occult hypoperfusion in nonsurvivors whereas vital signs did not differ between the groups.
Ključne besede: vital signs, nonsurvivors, survivors
Objavljeno: 14.06.2017; Ogledov: 30; Prenosov: 0
.pdf Polno besedilo (1,30 MB)

Genski polimorfizem rastnih faktorjev in citokinov pri proliferativni vitreoretinopatiji
Xhevat Lumi, 2016, doktorsko delo/naloga

Opis: Proliferativna vitreoretinopatija (PVR) predstavlja rast membran na površini mrežnice ter med mrežnico in steklovino pri bolnikih z regmatogenim odstopom mrežnice. Je najbolj pogost razlog za neuspeh pri zdravljenju bolnikov z odstopom mrežnice. Zaradi PVR imajo ti bolniki tudi slabši funkcionalni izid zdravljenja. Klinične raziskave kažejo, da kljub uspešnemu anatomskem zdravljenju bolniki nepojasnjeno izgubljajo tako centralni kot tudi periferni vid. Zaradi prizadetosti centralnega dela mrežnice, rumene pege, se poslabšata tako vidna ostrina kot tudi barvni vid. Zaradi okvare ostalih delov mrežnice imajo ti bolniki začasne ali trajne izpade vidnega polja. Številni dejavniki na celični in molekularni ravni so odgovorni za poslabšanje vida pri teh bolnikih. Morfološke analize rumene pege, narejene s pomočjo optične koherenčne tomografije (OCT), so pokazale, da je osip notranjih in zunanjih segmentov fovealnih fotoreceptorjev značilen pojav pri bolnikih s slabo vidno funkcijo po odstopu mrežnice. Zadnja desetletja so bile objavljene številne raziskave, ki nakazujejo na vpletenost rastnih dejavnikov in citokinov v patogenezi PVR. Skupaj s hipotezo rastnih dejavnikov se je porodilo vprašanje o vplivu genetskih dejavnikov na proces celjenja ran in na pojav PVR. Določanje genetskih determinant v povezavi s PVR se je pričelo v zadnjih desetih letih. V do sedaj objavljenih raziskavah je že bila dokazana povezava med posameznimi polimorfizmi enega nukleotida v genih TGFB1, SMAD7, p53, MDM2 in TNF in PVR, ki pa je ozko omejena samo na nekaj evropskih populacij. V naši raziskavi smo se osredotočili na klinične in genetske dejavnike PVR. Vrednotili smo funkcionalne plati rehabilitacije vidne funkcije bolnikov kot tudi morfološke spremembe, ki vplivajo na končni izid kirurškega zdravljenja. Poleg funkcionalnih preiskav, kot so vidna ostrina, barvni vid in vidno polje, smo v naši raziskavi analizirali tudi s pomočjo OCT pridobljene morfološke parametre: centralno debelino mrežnice (CRT) in skupno prostornino rumene pege (TMV). Analizirali smo vidno ostrino, barvni vid, vidno polje, stopnjo PVR, število operacij, očesni tlak, CRT in TMV za vse bolnike skupaj in za vsako skupino posebej. Pri vseh bolnikih, vključenih v raziskavo, smo ugotavljali, ali stopnja PVR vpliva na končno vidno ostrino. Analizirali smo, ali je barvni vid povezan s končno vidno ostrino. Prav tako smo pod drobnogled vzeli vprašanje o morebitni povezavi CRT in TMV z vidno ostrino in barvnim vidom, saj številna poročila kažejo, da so subklinične morfološke spremembe v rumeni pegi pomemben dejavnik za funkcionalno rehabilitacijo bolnikov po odstopu mrežnice. V raziskavo smo vključili 191 bolnikov z odstopom mrežnice, ki smo jih razdelili v 2 skupini: 113 bolnikov, pri katerih se je pojavila PVR (PVR skupina), in 78 bolnikov brez PVR (kontrolna skupina). Bolniki iz PVR skupine so imeli slabšo povprečno preoperativno vidno ostrino (0,13) v primerjavi s kontrolno skupino (0,28). Statistično pomembna razlika med skupinami je bila tudi glede postoperativne vidne ostrine. Povprečna postoperativna vidna ostrina bolnikov s PVR je bila slabša kot pri ostalih bolnikih z odstopom mrežnice. Zaradi relativno omejenega števila preiskovancev smo za genetsko analizo in v namen doseganja praga za ugotavljanje statistično značilnih povezav raziskavo za posamezne gene razširili na 261 primerov. Naša raziskava je pokazala statistično pomembne razlike v porazdelitvi genotipov med bolniki s PVR in kontrolnimi bolniki pri SNP-jih znotraj ali v bližini genov IL6, TGFB1 in IL10. V tej raziskavi nismo ugotovili povezanosti med SNP-ji znotraj ali v bližini genov za CCL2, FGF2, IL1A, IL2, JAK3, LTA, p53, PDGFRA, SMAD7, in TNF ter PVR, s čimer nismo potrdili do sedaj dognanih povezav med SNP-ji in PVR. Primerjali smo tudi razporeditev genotipov med kontrolno skupino 96 slovenskih krvodajalcev in bolnikov iz PVR skupine pri 4 SNP-jih v genih IL1A, IL2, LTA ter TNF.
Ključne besede: proliferativna vitreoretinopatija, odstop mrežnice, genski polimorfizem, rastni dejavniki, citokini, vidna ostrina
Objavljeno: 08.06.2017; Ogledov: 122; Prenosov: 8
.pdf Polno besedilo (7,91 MB)

Neinvazivno merjenje akceleracije kontrakcije levega prekata z doplersko ehokardiografijo
Igor Krajnc, 2017, doktorsko delo/naloga

Opis: Uvod Ehokardiografska meritev iztisnega deleža (EF) levega prekata predstavlja večinoma dober in uporaben označevalec sistolične funkcije levega prekata (LP), vendar s pomembnimi omejitvami. Uporaba doplerskih tehnik nam omogoča natančno merjenje hitrosti krvi v srčnih votlinah in hitrosti miokarda, vključno z meritvami trajanja posameznih časovnih intervalov. Cilji Cilj naše raziskave je bil, da s pomočjo doplerske ehokardiografije, natančneje s sintezo pulznega in tkivnega doplerja, izmerimo pospešek krčenja LP pri zdravih preiskovancih in pri simptomatičnih bolnikih s kroničnim srčnim popuščanjem (SP). Upoštevaje pospešek krčenja LP in dimenzije LP smo izračunali indeks akceleracije levega prekata 1 (AccLV1) in indeks akceleracije levega prekata 2 (AccLV2). Indeks AccLV1 je premosorazmeren z doseženo maksimalno hitrostjo v času iztisa v iztočnem delu LP (Vmax LVOT) v cm/s in obratno sorazmeren s časovnim intervalom (dt) od začetka izovolumetrične kontrakcije LP do dosežene maksimalne hitrosti v LVOT, merjenim v sekundah in s končnim diastoličnim volumnom LP (EDV) v mililitrih. Indeks AccLV2 pa je premosorazmeren z V max LVOT in obratno sorazmeren s dt in s končnim diastoličnim premerom LP (LVEDD), merjenim v cm. Oba indeksa imata potencial doplerskih pokazateljev globalne sistolične disfunkcije, oziroma okvare LP. V nadaljevanju raziskave smo oba indeksa primerjali s standardno oceno sistolične funkcije LP z merjenjem EF. Bolniki in metode V prospektivno, opazovalno raziskavo smo vključili 121 preiskovancev, 76 (62,8 %) zdravih preiskovancev in 45 (37,2 %) bolnikov z znanim kroničnim SP. Pri vseh smo opravili standardne ehokardiografske meritve in izračunali AccLV1 po formuli: AccLV1=Vmax LVOT / dt x EDV [cm/s2 ml] in AccLV2 po formuli: AccLV2=Vmax LVOT / dt x LVEDD [1/s2]. Preiskovance smo nato opazovali dve leti in spremljali pojav končnih opazovanih dogodkov, ki kažejo na poslabšanje SP. Rezultati Celotni vzorec preiskovancev je zajemal 65 (53,7 %) moških in 56 (46,3 %) žensk, od teh je bilo v skupino zdravih uvrščenih 76 preiskovancev (46,1 % moških), v skupino bolnikov pa 45 preiskovancev (66,7 % moških). Med zdravimi in bolniki smo ugotovili statistično pomembno razliko v povprečnih vrednostih EF (65,4 ± 6,7 % vs 38,6 ± 18,0 %; p < 0,001), AccLV1 (12,1 ± 2,8 cm/s2 ml vs 4,4 ± 2,1 cm/s2 ml; p < 0,001) in AccLV2 (217,8 ± 43,8 1/s2 vs 110,5 ± 43,7 1/s2; p < 0,001). ROC krivulja, ki ločuje zdrave preiskovance od bolnikov s kroničnim SP, ne glede na pridruženo MR, je pokazala višje vrednosti AUC za AccLV1 in AccLV2 v primerjavi z EF (0,996 vs 0,897 in 0,969 vs 0,897). V skupini bolnikov smo prav tako potrdili nekoliko močnejšo korelacijo indeksov AccLV1 in AccLV2 s funkcijskim razredom po NYHA (r = - 0,657; p < 0,001 in r = - 0,569; p < 0,001), glede na korelacijo EF z NYHA (r = - 0,539 p < 0,001). V toku dve-letnega opazovanja smo pri 16 preiskovancih ugotovili končne opazovane dogodke. Vseh zabeleženih dogodkov je bilo 31 in vsi v skupini bolnikov. Določeni preiskovanci so doživeli končni opazovani dogodek, čeprav so imeli EF nad povprečjem EF preiskovancev brez zapleta (nad 58,1 %). Noben preiskovanec ni doživel končni opazovani dogodek, če je njegov indeks AccLV1 presegel povprečje indeksa AccLV1 preiskovancev brez zapleta (nad 10,1 cm/s2 ml ) ali če je njegov indeks AccLV2 znašal nad povprečjem indeksa AccLV2 preiskovancev brez zapleta (nad 190,1 /s2). Zaključek Z izračunom indeksov AccLV1 in AccLV2 lahko v primerjavi z meritvami EF z večjo natančnostjo razlikujemo med zdravimi in bolniki s simptomatičnim SP, prav tako vrednosti AccLV1 in AccLV2 dobro, oziroma bolje kot EF, korelirajo s funkcijskim razredom NYHA v skupini bolnikov. Oba indeksa nakazujeta prav tako boljšo napovedno vrednost za klinično poslabšanje SP v primerjavi z EF.
Ključne besede: levi prekat, funkcija, dopler, kontrakcija, akceleracija
Objavljeno: 08.06.2017; Ogledov: 66; Prenosov: 9
.pdf Polno besedilo (2,42 MB)

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