Srpsko-albanski odnosi u socijalističkoj Jugoslaviji: protesti na Kosovu i teret sistemske legitimizacije

U ovom radu ćemo nastojati da ispitamo u kojoj meri je egalitaristički rečnik jugoslovenskog socijalizma bio u stanju da ponudi alternativni okvir za interpretaciju savremenih srpsko-albanskih odnosa. Inicijalna hipoteza polazi od toga da je jugoslovenska elita – usled eksperimentalnog karaktera samoupravnog socijalizma koji je podrazumevao određene kompromise sa liberalnim kapitalizmom – bila strukturalno prinuđena da sistematično negira socijalni aspekt demonstracija koje su na Kosovu odvijale tokom 1968, 1981. i 1988 godine. Primenom kritičke analize diskursa na štampane medije (Politika, Večernje novosti i Borba), pokušaćemo da pokažemo kako je vladajuća nomenklatura složene političko-ekonomske aspekte bunta isključivo tretirala kao izraz nacionalizma. Ova diskurzivna strategija je samim akterima sugerisala da je nacionalizam zajednički imenitelj za ekonomsku, političku i etničku jednakost. Krajnje posledice ovakvih diskurzivnih redukcija će biti prikazane kroz analizu medijskog izveštavanja sa demonstracija na Kosovu i mitinga „Bratstva i jedinstva“ u Beogradu 1988. godine, gde je primetno zatvaranje prostora za ne-nacionalističko tumačenje bilo koje vrste socijalnog bunta, ali i postepeno odustajanje aktera od artikulisanja sopstvenog iskustva nepravde u socijalnom ključu

USPOREDBA PRIJEOPERACIJSKIH I POSLIJEOPERACIJSKIH NALAZA HISTOLOŠKIH TIPOVA TUMORA I HISTOLOŠKOG STUPNJA U BOLESNICA S ENDOMETRALNIM KARCINOMOM

Purpose: Our aim was to determine the degree of agreement between preoperative and postoperative histologic type/ subtype and degree of tumor differentiation, and to determine the degree of upgrading and downgrading in relation to preoperative and postoperative histopathologic findings. Methods: We analyzed data on 393 patients. Data included age, preoperative and postoperative histologic type/subtype and histologic grade of tumor. Data on 317 patients were included in statistical processing. Results: Statistical analysis showed moderate agreement between preoperative and postoperative histologic type/subtype of endometrial carcinoma and low degree of agreement between preoperative and postoperative histologic grade of tumor. The lowest agreement in histologic grade was recorded in patients with histologic grade 1 (55.04%), while most accurate agreement was found in patients with grade 3 (73.33%). There was a low degree of agreement between preoperative and postoperative histologic grade in patients with endometrioid adenocarcinoma in both cases. The lowest accuracy in the agreement of histologic grade was in G1, while grades 2 and 3 were similar in the degree of agreement. Conclusions: There is moderate agreement of preoperative and postoperative histologic type/ subtype and low agreement of preoperative and postoperative histologic grade of tumor. The lowest degree of agreement was recorded for preoperatively G1 tumors and highest for preoperatively G3 tumors, which is important because of the clinical significance of tumor histologic grade 3.Namjena: Cilj nam je bio utvrditi stupanj podudaranja između prijeoperacijskog i poslijeoperacijskog histološkog tipa/ podtipa i stupnja diferenciranosti tumora te utvrditi stupanj nadgradnje i podgradnje u odnosu na prijeoperacijski i poslijeoperacijski patohistološki nalaz. Metode: Analizirali smo podatke 393 bolesnice. Podatci su uključivali dob, prijeoperacijski i poslijeoperacijski histološki tip/podtip i histološki stupanj tumora. U statističku obradu uključeno je 317 bolesnica. Rezultati: Statistička analiza pokazala je umjeren stupanj slaganja između prijeoperacijskog i poslijeoperacijskog histološkog tipa/ podtipa karcinoma endometrija te nizak stupanj slaganja između prijeoperacijskog i poslijeoperacijskog histološkog stupnja tumora. Najniži udjel u histološkom stupnju diferenciranosti bio je kod bolesnica s histološkom stupnjem G1 (55,04%), a najtočniji se slagao u skupini bolesnica s G3 (73,33%). U bolesnica s endometroidnim adenokarcinomom u oba slučaja postojao je nizak stupanj slaganja između prijeoperacijskog i poslijeoperacijskog histološkog stupnja. Najniža točnost u slaganju histološke ocjene bila je u G1, dok su stupnjevi 2 i 3 bili po stupnju slaganja slični. Zaključci: Postoji umjereno slaganje prijeoperacijskog i poslijeoperacijskog histološkog tipa/podtipa, a slabo je slaganje prijeoperacijskog i poslijeoperacijskog histološkog stupnja tumora. Najmanji stupanj slaganja utvrđen je za tumore G1 prijeoperacijski, a najviši za tumore G3 prijeoperacijski, što je važno zbog kliničkog značenja tumora histološkog stupnja 3

Kliničke karakteristike i liječenje lupusnog nefritisa - preliminarna analiza opservacijskih podataka Nacionalnog referentnog centra

Lupus nephritis (LN) is one of the most severe features of systemic lupus erythematosus (SLE). Data on LN is scarce in the Croatian population. We analysed the characteristics of LN patients diagnosed at our tertiary referral centre. In this retrospective study, we analysed the following features of patients with biopsy-proven LN diagnosed between 2011 and 2020: demographics, renal laboratory parameters, renal histopathology, and treatment. A total of 38 patients were included (30 females; mean age 39±15 years). The most common indication for kidney biopsy was proteinuria (89%). The proportion of LN classes was: class I (2.6%), II (5.3%), III (18.4%), IV (42.1%), V (13.2%), III+V (10.5%), IV+V (5.3%). The median time from SLE diagnosis to histologic confirmation of LN was 1.0 year. All patients were treated with methylprednisolone (MP), 68% received MP pulses. Induction treatment included intravenous (IV) cyclophosphamide (CYC) (71%) (15 patients treated per Euro-Lupus and 9 per the National Institutes of Health regimen), oral CYC (3%), or mycophenolate mofetil (11%). 79% of patients received antimalarials. While there is heterogeneity between different populations, our patient profile was similar to that from other European studies. Further follow-up of this group is necessary to assess outcomes in our population.Lupusni nefritis (LN) je česta i vrlo ozbiljna manifestacija sustavnog eritemskog lupusa (SLE). Još uvijek nema dovoljno podataka o karakteristikama bolesnika s LN u Hrvatskoj. Analizirali smo karakteristike bolesnika s LN koji su liječeni u referentnom centru naše tercijarne ustanove. U ovu retrospektivnu studiju uključili smo bolesnike s biopsijom potvrđenim LN u periodu od 2011. do 2020. godine, analizirali smo demografske podatke, parametre bubrežne funkcije, patohistološki nalaz bioptata bubrega i liječenje. U studiju je uključeno 38 bolesnika (30 žena, prosječna dob 39±15godina). Najčešća indikacija za biopsiju bubrega bila je proteinurija (89%). Raspodjela klasa LN bila je sljedeća: klasa I(2,6 %), II(5,3 %), III(18,4 %), IV(42,1 %), V(13,2 %), III+V(10,5 %), IV+V(5,3 %). Prosječno vrijeme od dijagnoze SLE do histološke potvrde LN bilo je 1,0 godina. Svi bolesnici su liječeni kortikosteroidima, 68 % liječeno je bolusima metilprednizolona. Indukcijska terapija uključivala je parenteralnu primjenu ciklofosfamida (CYC) (71 %) (15 bolesnika liječeno je prema Euro-lupus protokolu, 9 bolesnika prema protokolu Nacionalnog instituta za zdravlje (NIH)), peroralni CYC (3 %) ili mikofenolat mofetil (11 %). Antimalarike je primilo 79 % bolesnika. Unatoč heterogenosti između različitih populacija s LN, profil bolesnika uključen u ovu studiju sličan je ostalim europskim studijama. Daljnje praćenje potrebno je da bi se istražili ishodi u ovoj populaciji

The Expression of Major Facilitator Superfamily Domain-Containing Protein2a (Mfsd2a) and Aquaporin 4 Is Altered in the Retinas of a 5xFAD Mouse Model of Alzheimer’s Disease

Cerebral amyloid angiopathy (CAA) is characterized by amyloid β (Aβ) accumulation in the blood vessels and is associated with cognitive impairment in Alzheimer’s disease (AD). The increased accumulation of Aβ is also present in the retinal blood vessels and a significant correlation between retinal and brain amyloid deposition was demonstrated in living patients and animal AD models. The Aβ accumulation in the retinal blood vessels can be the result of impaired transcytosis and/or the dysfunctional ocular glymphatic system in AD and during aging. We analyzed the changes in the mRNA and protein expression of major facilitator superfamily domain-containing protein2a (Mfsd2a), the major regulator of transcytosis, and of Aquaporin4 (Aqp4), the key player implicated in the functioning of the glymphatic system, in the retinas of 4- and 12-month-old WT and 5xFAD female mice. A strong decrease in the Mfsd2a mRNA and protein expression was observed in the 4 M and 12 M 5xFAD and 12 M WT retinas. The increase in the expression of srebp1-c could be at least partially responsible for the Mfsd2a decrease in the 4 M 5xFAD retinas. The decrease in the pericyte (CD13+) coverage of retinal blood vessels in the 4 M and 12 M 5xFAD retinas and in the 12 M WT retinas suggests that pericyte loss could be associated with the Mfsd2a downregulation in these experimental groups. The observed increase in Aqp4 expression in 4 M and 12 M 5xFAD and 12 M WT retinas accompanied by the decreased perivascular Aqp4 expression is indicative of the impaired glymphatic system. The findings in this study reveal the impaired Mfsd2a and Aqp4 expression and Aqp4 perivascular mislocalization in retinal blood vessels during physiological (WT) and pathological (5xFAD) aging, indicating their importance as putative targets for the development of new treatments that can improve the regulation of transcytosis or the function of the glymphatic system

The Impact of High-Dose Fish Oil Supplementation on Mfsd2a, Aqp4, and Amyloid-β Expression in Retinal Blood Vessels of 5xFAD Alzheimer’s Mouse Model

In patients with Alzheimer’s disease (AD) and in animal models, the increased accumulation of amyloid β (Aβ) in retinal blood vessels strongly correlates with brain amyloid deposits and cognitive decline. The accumulation of Aβ in blood vessels may result from impaired transcytosis and a dysfunctional ocular glymphatic system in AD. High-dose fish oil (FO) supplementation has been shown to significantly change the expression of major facilitator superfamily domain-containing protein 2a (Mfsd2a), a key regulator of transcytosis, and Aquaporin 4 (Aqp4), an essential component of the glymphatic system in the retinas of WT mice. We examined the expression of Mfsd2a and Aqp4 in the retinas of 4-month-old 5xFAD female mice supplemented with high-dose FO for three weeks. There was a significant increase in Mfsd2a expression in 5xFAD retinas supplemented with FO compared to control 5xFAD mice. Additionally, the increase in Aqp4 expression observed in 4-month-old 5xFAD retinas, indicative of an impaired glymphatic system, was significantly decreased. Simultaneously, Aβ accumulation in 5xFAD retinal blood vessels was reduced following FO supplementation. These findings suggest that high-dose FO supplementation could serve as an adjunct in developing new treatments aimed at improving the regulation of transcytosis or the function of the glymphatic system in the AD retin

Ex vivo and in vivo antioxidant activity of β-hydroxy-β-arylalkanoic acids

The interplay between oxidative stress and inflammation is implicated in many chronic diseases including Alzheimer`s disease, cardiovascular diseases, diabetes and cancer. Thirteen β-hydroxy-β-arylalkanoic acids were previously synthesized and evaluated for their anti-inflammatory activity. The aim of this study was to asses ex vivo antioxidant activity of synthesized acids, as well as ibuprofen and to identify the compounds with the most promising results for further investigation on their capacity to counteract in vivo oxidative stress triggered by inflammation. The antioxidant potential of tested compounds was evaluated by determining the concentrations of total antioxidative status, total oxidative status, prooxidant antioxidant balance and the total sulfhydryl groups. Z score statistics were used to calculate the summary scores for antioxidative activity, prooxidative activity and oxy score. The tested compounds and ibuprofen demonstrated mild prooxidative activity ex vivo. Seven acids with substituents on one benzene ring exhibited better results than ibuprofen and were selected for in vivo testing. In vivo results demonstrated better antioxidant protection compared to ex vivo results. Compound g which contains nitro group on the benzene ring demonstrated the lowest oxy score, and four compounds exhibited better results than ibuprofen

The Impact of High-Dose Fish Oil Supplementation on Mfsd2a, Aqp4, and Amyloid-β Expression in Retinal Blood Vessels of 5xFAD Alzheimer’s Mouse Model

In patients with Alzheimer’s disease (AD) and in animal models, the increased accumulation of amyloid β (Aβ) in retinal blood vessels strongly correlates with brain amyloid deposits and cognitive decline. The accumulation of Aβ in blood vessels may result from impaired transcytosis and a dysfunctional ocular glymphatic system in AD. High-dose fish oil (FO) supplementation has been shown to significantly change the expression of major facilitator superfamily domain-containing protein 2a (Mfsd2a), a key regulator of transcytosis, and Aquaporin 4 (Aqp4), an essential component of the glymphatic system in the retinas of WT mice. We examined the expression of Mfsd2a and Aqp4 in the retinas of 4-month-old 5xFAD female mice supplemented with high-dose FO for three weeks. There was a significant increase in Mfsd2a expression in 5xFAD retinas supplemented with FO compared to control 5xFAD mice. Additionally, the increase in Aqp4 expression observed in 4-month-old 5xFAD retinas, indicative of an impaired glymphatic system, was significantly decreased. Simultaneously, Aβ accumulation in 5xFAD retinal blood vessels was reduced following FO supplementation. These findings suggest that high-dose FO supplementation could serve as an adjunct in developing new treatments aimed at improving the regulation of transcytosis or the function of the glymphatic system in the AD retina

The high-dose fish oil (FO) supplementation increased Mfsd2a expression in the retina of healthy mice

Mfsd2a is expressed mainly in the endothelial cells and is an essential regulator of blood vessel transcytosis. Therefore, decrease in Mfsd2a expression can be a risk factor for developing leaky blood vessels. Mfsd2a is also the main docosahexaenoic acid (DHA, C22:6n3) transporter. DHA, an omega-3 fatty acid, is one of the main structural lipids of the neuronal and vascular retina, crucial for the normal functioning of photoreceptors (PRs). However, the capacity of the retina to synthesize DHA is limited, and the maintenance of retinal DHA content relies on the uptake from bloodborne lipids. The currently recommended FO doses yielded low PUFAs tissue bioavailability, and supplementation with higher doses has been increasingly recommended. Nevertheless, the effects of higher FO doses on retinal Mfsd2a expression and blood vessels coverage are unknown. Western blot and qPCR analyses showed that high dose FO supplementation increased Mfsd2a expression in the retina. Immunohistochemical analyses of Mfsd2a expression on retinal blood vessels (labeled with 488-conjugated Lycopersicon esculentum, lectin) and subsequent ImageJ analyses revealed 1.32-fold increase in the Mfsd2a retinal blood vessel coverage. In the same time the pericyte blood vessel coverage (CD13+ cells) was not affected with FO supplementation, and the increase in Mfsd2a blood vessel expression is not the result of the increased pericyte coverage. Therefore, the high-dose FO supplementation emerges as the prophylactic fortifier of the retinal blood vessels that can serve either as prophylaxis in the healthy eye or as an adjuvant in developing targeted manipulations of the barrier during diseases.Poster Session: Brain Metabolism & Dietary Intervention

Prolonged Zaleplon Treatment Increases the Expression of Proteins Involved in GABAergic and Glutamatergic Signaling in the Rat Hippocampus

Zaleplon is a positive allosteric modulator of the γ-aminobutyric acid (GABA)A receptor approved for the short-term treatment of insomnia. Previous publications on zaleplon have not addressed the proteins involved in its mechanism of action but have mostly referred to behavioral or pharmacological studies. Since both GABAergic and glutamatergic signaling have been shown to regulate wakefulness and sleep, we examined the effects of prolonged zaleplon treatment (0.625 mg/kg for 5 days) on these systems in the hippocampus of male Wistar rats. Western blot and immunohistochemical analyses showed that the upregulated components of GABAergic signaling (glutamate decarboxylase, vesicular GABA transporter, GABA, and α1 subunit of the GABAA receptor) were accompanied by increased protein levels in the glutamatergic system (vesicular glutamate transporter 1 and NR1, NR2A, and NR2B subunits of N-methyl-d-aspartate receptor). Our results, showing that zaleplon enhances GABA neurotransmission in the hippocampus, were not surprising. However, we found that treatment also increased glutamatergic signaling. This could be the result of the downregulation of adenosine A1 receptors, important modulators of the glutamatergic system. Further studies are needed to investigate the effects of the zaleplon-induced increase in hippocampal glutamatergic neurotransmission and the possible involvement of the adenosine system in zaleplon’s mechanism of action

Improvement of lipid metabolism regulation by low-intensity exercise in fructose-fed rats

Excessive dietary fructose consumption in parallel with limited physical activity contributes to the global increase in prevalence of metabolic disorders. Metabolic syndrome represents a collection of cardiometabolic risk factors that includes obesity, insulin resistance, hypertension, and dyslipidemia, and it is undoubtedly linked to increased risk for two global maladies, type 2 diabetes, and cardiovascular diseases. Fructose-rich diet is accompanied by the development of insulin resistance in the heart, and it could change the use of cardiac energy substrates towards increased fatty acid (FA) uptake, and catabolism. Exercise may be beneficial in prevention and treatment of the metabolic syndrome. The aim of this study was to analyse the impact of low-intensity exercise on protein expression of nuclear transcription factors involved in regulating FA β- oxidation in a heart of fructose fed rats. Male Wistar rats were divided into control group, and two groups that received 10% fructose for 9 weeks, one which was sedentary and one which was additionally exposed to low intensity exercise. The protein expression of important transcriptional regulators of fatty acid β-oxidation PPARα, and FOXO1, and coregulators Lipin1, PGC-1, and SIRT1 are analyzed in cardiac lysate and/or nuclear fraction by Western blot. Gene expression of ACADL, the enzyme that catalyzes the initial step of mitochondrial β-oxidation, was quantified by real-time PCR. Fructose-rich diet decreased nuclear PPARα compared to control. Exercise increased nuclear PPARα, nuclear FOXO1, lysate PGC1, and nuclear Lipin1 in fructose-fed rats compared to sedentary fructose-fed rats. Exercise increased lysate PPARα, lysate and nuclear FOXO1, lysate PGC1, lysate and nuclear SIRT1, and nuclear Lipin1 in fructose-fed rats compared to control. In conclusion, running at low intensity is accompanied by increased expression of key regulators of fatty acid oxidation. The results indicate that exercise achieves its effect by increasing the nuclear content of PPARα, Lipin1, and FOXO1