Koncentracije elemenata u tkivima klena (squalus cephalus) iz akumulacija Nacionalnog parka „Tara”

Planinsko područje Tare nalazi se na krajnjem zapadu Srbije. Sa severne i zapadne strane ograničeno je dolinom Drine, sa jugozapada dolinom Rzava, sa juga plitkom kremanskom udolinom koja ga odvaja od zlatiborske površi. Ceo prostor Nacionalnog parka obuhvata: planinu Taru, Crni vrh, Zvezdu, Stolac, kanjon Drine sa Perućcem i okolinu Bajine Bašte. Nacionalni park „Tara“ i njegova uža zaštitna zona raspolaže rekama i potocima koji pripadaju uglavnom gornjim i delimično srednjim pastrmskim regionima. Najznačajnije reke su Rača, Derventa sa pritokama, Brusnički potok sa pritokama, Karaklijski Rzav i Baturski Rzav i reka Jarevac. U Nacionalnom parku „Tara“ formirano je nekoliko veštačkih jezera različitog tipa. Akumulacija „Perućac“ je veštačko jezero nastalo u rečnom koritu reke Drine, njenim pregrađivanjem betonskom branom. Na osnovu lokacije, pripada nizinskom tipu. Akumulacija „Zaovine“ je po lokaciji visinskog tipa, a po načinu nastanka reverzibilna. Nastaje izbacivanjem vode iz akumulacije „Perućac“ i sakupljanja vode od Karakliskog i Baturskog Rzava i drugih manjih pritoka. Akumulacija „Spajići“ je visinska sabirna akumulacija koja nastaje od proceđene vode iz jezera „Zaovine“, te reke Zmajevačke i Popovića potoka. Jezero „Kruščica“ nastaje od Karaklijskog i Baturskog Rzava i koristi se kao pijaća voda (Hegediš, 2012). Ribolovne vode NP „Tara“ naseljava 28 vrsta riba iz sedam familija, a šaranske vrste (Ciprinidae) dominiraju po brojnosti sa 17 vrsta. Klen (Squalius cephalus) je ciprinidna vrsta ribe, široko rasprostranjena u Srbiji južno od Save i Dunava dok je u Vojvodini redak. U Srbiji je popularna sportsko-rekreativna ribolovna vrsta i lovi se različitim tehnikama ribolova. U akumulacijama Zaovine, Spaići i Kruščica klen je najzastupljenija vrsta, dok je i u akumulaciji Perućac prisutan u značajnom broju (Hegediš, 2012). Tokom terenskih istraživanja 2014. godine ispitivan je nivo akumulacije 17 elemenata u tkivima (mišić, jetra, škrge) klena iz četiri akumulacije – Perućac, Zaovine, Spaići i Kruščica. Ribe se nalaze na vrhu lanaca ishrane u vodenoj sredini i često u organizmu akumuliraju velike količine pojedinih teških metala (Yilmaz et al., 2007). Takođe se smatraju i jednim od najosetljivijih akvatičnih organizama na prisustvo toksičnih materija u vodi (Alibabić i sar., 2007). Ribe se često koriste kao bazični organizmi po pitanju pozicije u lancima ishrane, kao i u ishrani ljudi, zbog njihovog potencijala za bioakumulaciju toksičnih materija i njihove osetljivosti na čak i male koncentracije mutagena (Szefer et al., 1990; Višnjić-Jeftić et al., 2010). Jedinke klenova sa Perućca su se na osnovu analize glavnih komponenata (PCA – Principal Components Analysis) izdvajale po višim koncentracijama Cu i Zn u jetri, kao i B i Cu u mišićima; jedinke sa Zaovina se izdvajaju po koncentracijama Sr, Mo, Fe, Cr, Al, Hg u jetri višim nego u jedinkama sa drugih akumulacija, Mn, Sr, Hg, Mo i Cr u mišićima i Al, Sr, Li i Hg u škrgama; jedinke sa akumulacije Kruščica se izdvajaju po koncentracijama Pb, Mn i Ni u jetri, kao i, Mo, Mn, Fe, Pb i Cr u škrgama; jedinke sa akumulacije Spaići su bile grupisane između jedinki sa drugih analiziranih akumulacija, nisu se izdvajale po koncentracijama bilo kog analiziranog elementa u bilo kom tkivu, a najsličnije su bile jedinkama sa Perućca

High Risk First Degree Relatives of Type 1 Diabetics: An Association with Increases in CXCR3 +

We analyzed the level of (a) CXCR3+ (Th1) and CCR4+ (Th2) T memory cells (b) interferon-γ inducible chemokine (IP-10)(Th1) and thymus and activation-regulated chemokine (TARC)(Th2), in 51 first degree relatives (FDRs) of type 1 diabetics (T1D) (17 high risk FDRs (GADA+, IA-2+) and 34 low risk FDRs (GADA−, IA-2−)), 24 recent-onset T1D (R-T1D), and 18 healthy subjects. T memory subsets were analyzed by using four-color immunofluorescence staining and flowcytometry. IP-10 and TARC were determined by ELISA. High risk FDRs showed higher levels of CXCR3+ and lower level of CCR4+ T memory cells compared to low risk FDRs (64.98 ± 5.19 versus 42.13 ± 11.11; 29.46 ± 2.83 versus 41.90 ± 8.58%, resp., P<0.001). Simultaneously, both IP-10 and TARC levels were increased in high risk versus low risk FDRs (160.12 ± 73.40 versus 105.39 ± 71.30; 438.83 ± 120.62 versus 312.04 ± 151.14 pg/mL, P<0.05). Binary logistic regression analysis identified the level of CXCR3+ T memory cells as predictors for high risk FDRs, together with high levels of IP-10. The results imply that, in FDRs, the risk for T1D might be strongly influenced by enhanced activity of Th1 and diminished activity of Th2 autoimmune response

Procena sadržaja metala i elemenata u tkivima 4 komercijalne vrste riba iz Dunava kod Beograda

Cilj ovog istraživanja je bio da se proceni akumulacija elemenata u četiri komercijalne vrste riba na dva lokaliteta na Dunavu, u Beogradu. U ovom istraživanju, određene su koncentracije 11 elemenata (As, Cd, Cr, Co, Cu, Fe, Hg, Mn, Ni, Se, i Zn) u tkivima mišića, jetre i škrga sledećih vrsta: mrena (Barbus barbus), deverika (Abramis brama), štuka (Esox lucius) i smuđ (Sander lucioperca). Rezultati su ukazali da je distribucija metala i elemenata u tragovima u različitim tkivima specifična za vrstu. Koncentracije As, Cd, Fe, Hg, i Zn u mišićima riba su bile ispod maksimalno dozvoljenih koncentracija MDK, utvrđenih od strane EU i Republike Srbije. Na osnovu dobijenih rezultata, neophodno je uspostaviti program stalnog monitoringa na Dunavu u Beogradskom regionu

The Impact of the International Cooperation On Familial Hypercholesterolemia Screening and Treatment: results from the ScreenPro FH Project

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Different aspect of sustainable use of fish resources in Serbia for the period 2006-2017

Ovaj rad ima za cilj da ustanovi koja je uloga zakona u dobrom upravljanju ribolovnim resursima. Zaštita i održivo korišćenje ribljeg fonda u Srbiji regulisano je istoimenim zakonom, a odvija se na 17 ribarskih područja i 29 ribarskih područja u zaštićenim prirodnim dobrima. Na 17 osnovnih ribarskih područja upravljaju „javna preduzeća“ ili privatne firme u statusu „doo“. Kod većih područja, posebno u Vojvodini, postoji više upravljača za jedno ribarsko područje. U zaštićenim prirodnim dobrima upravljači su ujedno i korisnici ribljeg fonda. U periodu od 2006. do 2017. godine Zakon o zaštiti i održivom korišćenju ribljeg fonda menjan je u dva navrata: 2009. i 2014. godine. Podzakonska akta su takođe podložna vrlo čestim promenama. U radu se prate efekti promene zakonske regulative na broj rekre ativnih i profesionalnih ribolovaca, broj ribočuvara i trendove u ulovima. Osnovni trendovi su da broj rekreativnih ribolovaca u navedenom periodu opada, broj profesionalnih riba ra stagnira, dok broj ribočuvara raste. Ulov ima tendenciju opadanja za sve vrste koje se statististički prate (šaran, som, smuđ i deverika od autohtonih vrsta, i babuška i tolstolobik od alohtonih). Odnos ulova u rekreativnom i komercijalnom ribolovu pokazuje značajne promene u poslednjih desetak godina: osim za tolstolobika, kod koga dominira komer cijalni ulov, kod ostalih vrsta je došlo do zamene u smislu da rekreativni ulov preuzima dominaciju u poslednjih nekoliko godin

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

mTOR Inhibitor Therapy and Metabolic Consequences: Where Do We Stand?

mTOR (mechanistic target of rapamycin) protein kinase acts as a central integrator of nutrient signaling pathways. Besides the immunosuppressive role after solid organ transplantations or in the treatment of some cancers, another promising role of mTOR inhibitor as an antiaging therapeutic has emerged in the recent years. Acute or intermittent rapamycin treatment has some resemblance to calorie restriction in metabolic effects such as an increased insulin sensitivity. However, the chronic inhibition of mTOR by macrolide rapamycin or other rapalogs has been associated with glucose intolerance and insulin resistance and may even provoke type II diabetes. These metabolic adverse effects limit the use of mTOR inhibitors. Metformin is a widely used drug for the treatment of type 2 diabetes which activates AMP-activated protein kinase (AMPK), acting as calorie restriction mimetic. In addition to the glucose-lowering effect resulting from the decreased hepatic glucose production and increased glucose utilization, metformin induces fatty acid oxidations. Here, we review the recent advances in our understanding of the metabolic consequences regarding glucose metabolism induced by mTOR inhibitors and compare them to the metabolic profile provoked by metformin use. We further suggest metformin use concurrent with rapalogs in order to pharmacologically address the impaired glucose metabolism and prevent the development of new-onset diabetes mellitus after solid organ transplantations induced by the chronic rapalog treatment

Report from the 3rd Cardiovascular Outcome Trial (CVOT) Summit of the Diabetes & Cardiovascular Disease (D&CVD) EASD Study Group

Abstract The 3rd Cardiovascular Outcome Trial Summit of the Diabetes & Cardiovascular Disease EASD Study Group was held on the 26–27 October 2017 in Munich. As in 2015 and 2016, this summit was organised in light of recently completed and published CVOTs on diabetes, aiming to serve as a reference meeting for in-depth discussions on the topic. Amongst others, the CVOTs EXSCEL, DEVOTE, the CANVAS program and the ACE-trial, which released primary outcome results in 2017, were discussed. Trial implications for diabetes management and recent perspectives of diabetologists, cardiologists, endocrinologists, nephrologists and general practitioners were highlighted. The clinical relevance of cardiovascular outcome trials and its implications regarding reimbursement were compared with real-world studies. The 4th Cardiovascular Outcome Trial Summit will be held in Munich 25–26 October 2018 (http://www.dcvd.org)