Public Procurement of Legal Services in Croatia

U prvom dijelu rada analiziraju se odredbe novog Zakona o javnoj nabavi (NN 120/16) koje se primjenjuju na javnu nabavu pravnih usluga u Hrvatskoj te se uspoređuju s pravnim uređenjem važećim do kraja 2016. Prijašnji zakon za javnu je nabavu pravnih usluga predviđao mogućnost provođenja tzv. posebnog postupka, dok novi zakon tu mogućnost otklanja, ali zadržava pregovarački postupak bez prethodne objave poziva na nadmetanje. U drugom dijelu rada analiziraju se podaci o javnim nabavama pravnih usluga u Hrvatskoj u razdoblju 2012.-2016. te se izvode zapažanja o transparentnosti i tržišnoj koncentraciji na tržištu javne nabave pravnih usluga.The paper attempts to present the characteristics of the legal framework governing the public procurement of legal services in Croatia, with a particular view to the processes at the disposal of public and sector contracting authorities. The first part of the paper analyses the provisions of the new Public Procurement Act (Official Gazette 120/16), which apply to the public procurement of legal services in Croatia, and compares these with the legal framework effective until the end of 2016. Because both laws have been harmonised with EU directives, the paper also sets forth the most significant modifications to the public procurement of legal services at EU level. In addition, the paper investigates where the Directorate for the Public Procurement System, the Constitutional Court of Croatia, and the Croatian Bar Association stand with regard to the public procurement of legal services. The previous act governing the public procurement of legal services included the option of the so-called ‘particular procedure’. The new law does not include this option; however, it retains the option of negotiated procedure without prior publication of the contract notice. An analysis of the provisions of the two acts demonstrates that there is no difference between the two types of procedure, which indicates that public and sector contracting entities still have at their disposal the option of conducting a highly non-transparent public procurement process when it comes to legal services. The explanation provided is that these services are specific, and as such are less suited to regular public procurement processes. The second part of the paper presents the statistical analysis results regarding the public procurement of legal services in the period 2012–2016. The aim is to determine process transparency and concentration level in this period; i.e., the level of competition on the market for the public procurement of legal services. In 95% of the cases, the contracting authorities decided to conduct the least transparent process. In the three years under observation a low level of competition was observed, while in two years an oligopoly was observed on the market for the public procurement of legal services

Ameliorating effects of antioxidative compounds from four plant extracts in experimental models of diabetes

Given that oxidative stress plays a major role in pancreatic β-cell dysfunction and ultimate destruction, as well as in different complications of diabetes, therapy with antioxidants has assumed an important place in the management of diabetes. The relatively limited effects of established antioxidant compounds have stimulated efforts to develop new therapeutic strategies, e.g. to increase the endogenous antioxidant defences through pharmacological modulation of key antioxidant enzymes. Plant extracts are gaining popularity in treating diabetes because many substances synthesized by higher plants and fungi possess antioxidant activities and can prevent or protect tissues against the damaging effects of free radicals. This review summarizes experimental models of diabetes and possible mechanisms that lie behind the antioxidative effects of α-lipoic acid (LA), a powerful antioxidant and compound that stimulates cellular glucose uptake, as well as of plant extracts from sweet chestnut (Castanea sativa), edible mushroom (Lactarius deterrimus) and natural products containing β-glucans in the treatment of diabetes. Their roles in preventing pancreatic β-cell death and in ameliorating the effects of severe diabetic complications are discussed.Terapija antioksidansima zauzima značajno mesto u lečenju dijabetesa s obzirom da oksidativni stres u velikoj meri doprinosi narušavanju funkcije i strukture β-ćelija pankreasa kao i razvoju komplikacija u dijabetesu. Zbog ograničenog dejstva postojećih antioksidativnih jedinjenja traga se za novim terapijskim rešenjima u tretmanu dijabetesa, kao što je povećanje endogene antioksidativne zaštite organizma putem farmakološke modulacije ključnih antioksidativnih enzima. Primena biljnih ekstrakata u lečenju dijabetesa postaje sve popularnija. Mnoge supstance koje se nalaze u sastavu viših biljaka i gljiva poseduju antioksidativna svojstva koja mogu da zaštite tkiva od štetnih uticaja slobodnih radikala. U ovom revijalnom radu opisani su eksperimentalni modeli dijabetesa kao i mogući mehanizmi koji leže u osnovi antioksidativnog dejstva α-liponske kiseline (LA), snažnog antioksidansa i jedinjenja koje stimuliše ćelijsku apsorpciju glukoze, kao i biljnih ekstrakata izolovanih iz slatkog kestena (Castanea sativa), jestivih pečuraka (Lactarius deterrimus) i prirodnih proizvoda koji sadrže β-glukan u lečenju dijabetesa. Opisani su njihova uloga u sprečavanju smrti β-ćelija pankreasa kao i blagotvorno dejstvo na komplikacije u dijabetesu.Projekat ministarstva br. 17302

Korelacija između koncentracije receptora 2 faktora nekroze tumora u serumu i destrukcije parodoncijuma kod bolesnika sa dijabetes melitusom tip 2 - studija preseka

Introduction: The role of tumor necrosis factor-α (TNFα) is well documented in pathogenesis of chronic periodontitis (CP) and type 2 diabetes (T2D). Considering short half-life of TNFα, tumor necrosis factor receptor-2 (TNFR2) is used as prosperous surrogate marker of TNFα activity. Objective The aim was to detect TNFR2 serum concentration and correlate it with periodontal destruction in patients with diagnosed T2D and nondiabetics. Methods The study included 85 patients divided into three groups: T2D + CP (group T2D, n = 34); nondiabetics + CP (Group PD, n = 27); and healthy controls (group HC, n = 24). T2D was diagnosed according to WHO criteria (2013) and periodontitis was diagnosed using International Workshop for a Classification of Periodontal Diseases and Conditions criteria (1999). TNFR2 level was measured by enzyme-linked immunosorbent assay (ELISA). Results There was no difference in TNFR2 level among the groups (Kruskal-Wallis, p = 0.482). Significant correlation (Pearson's correlation coefficient) was observed between clinical attachment loss (CAL) and TNFR2 concentration in PD group (rp = -0.460, p = 0.016). In T2D group, correlations were observed between TNFR2 concentration and CaL (rp = 0.363, p = 0.005) and periodontal inflamed surface area (PISA) (rp = 0.345, p = 0.046) and periodontalepithelial surface area (PESA) (rp = 0.578, p = 0.000). Conclusion Higher concentration of TNFR2 was associated with higher CAL, PESA, and PISA scores in T2D group. Contrary to that, nondiabetics with higher values of CAL exhibited lower concentration of TNFR2, presenting potential protective effect on periodontal destruction. These results imply that diabetes may alter TNFR2 secretion originated from periodontium.Uvod: Uloga faktora nekroze tumora-alfa (TNFα) dokazana je u patogenezi hronične parodontopatije (HP) i dijabetesa melitusa tipa 2 (DM tip 2). S obzirom na to da je poluživot TNFα veoma kratak, receptor 2 faktora nekroze tumora (TNFR2) koristi se kao marker aktivnosti TNFα. Cilj rada Cilj ovog rada je određivanje koncentracije TNFR2 u serumu i koreliranje sa parametrima destrukcije parodoncijuma kod zdravih i ispitanika sa dijagnostikovanim DM tip 2. Metode rada U studiju je uključeno 85 pacijenata podeljenih u tri grupe: DM tip 2 + HP (DM grupa, n = 34), zdravi ispitanici + HP (PD grupa, n = 27) i zdrave kontrole (ZK grupa, n = 24). Dijagnoza DM tip 2 postavljena je na osnovu kriterijuma SZO (2013), dok je dijagnoza HP postavljena na osnovu kriterijuma Internacionalne radionice za klasifikaciju stanja i oboljenja parodoncijuma (1999). Koncentracija TNFR2 merena je ELISA metodom. Rezultati Koncentracija serumskog TNFR2 nije se razlikovala među grupama (Kraskal-Volis, p = 0,482). Postoji značajna korelacija (Pirson) između nivoa pripojnog epitela (NPE) i koncentracije TNFR2 u PD grupi (rp = -0,460, p = 0,016). U DM tip 2 grupi, statistički značajna korelacija uočena je između koncentracije TNFR2 i NPE (rp = 0,363, p = 0,005), kao i parametara uticaja inflamacije iz parodoncijuma na sistemsko zdravlje - PISA (rp = 0,345, p = 0,046) i PESA (rp = 0,578, p = 0,000). Zaključak Kod pacijenata sa dijabetesom veće koncentracije TNFR2 odgovaraju većim vrednostima NPE, PESA i PISA. Nasuprot tome, kod sistemski zdravih ispitanika sa HP veće vrednosti NPE su povezane sa manjim koncentracijama TNFR2, što bi moglo govoriti o potencijalnoj zaštitnoj ulozi ovog citokina na destrukciju parodoncijuma. Rezultati govore da dijabetes može uticati na sekreciju TNFR2 iz parodoncijuma

Treatment of streptozotocin-induced diabetic rats with Castanea sativa and Lactarius deterrimus extracts decreases liver damage by initiating activation of the Akt prosurvival kinase

Diabetes is the most important non-infectious disease affecting 5% of the general population. Different plant and mushroom extracts with hypoglycemic and antioxidant properties have been used traditionally as antidiabetic herbal medicines. The aim of this study was to study the in vivo effect of extracts obtained from the edible mushroom, Lactarius deterrimus (Ld), and chestnut, Castanea sativa (Cs), on the alleviation of liver damage in streptozotocin (STZ)-induced diabetic rats. The extracts were applied, either alone or in combination, for four weeks, starting from the last day of STZ administration. Diabetic rats treated with the extracts exhibited reduced hyperglycemia and lower hepatic oxidative stress. Extract treatment decreased the level of O-linkage of N-acetylglucosamine modified superoxide dismutase, catalase and NF-κB. Masson trichrome staining showed a decrease in collagen fiber deposition in the liver. Immunoblot analysis revealed the activation of the prosurvival Akt kinase after extract application. The obtained results revealed that the hyperglycemia-reducing and antioxidant effects of the Ld and Cs extracts suppressed cytotoxic signaling pathways, attenuating the negative effects of diabetes on the liver. The examined extracts are beneficial in the prevention of liver damage and could be considered for prediabetes and diabetes management after a definitive phytochemical description of extract constituents and subsequent evaluation in preclinical and clinical studies

Ameliorating effects of antioxidative compounds from four plant extracts in experimental models of diabetes

Given that oxidative stress plays a major role in pancreatic β-cell dysfunction and ultimate destruction, as well as in different complications of diabetes, therapy with antioxidants has assumed an important place in the management of diabetes. The relatively limited effects of established antioxidant compounds have stimulated efforts to develop new therapeutic strategies, e.g. to increase the endogenous antioxidant defences through pharmacological modulation of key antioxidant enzymes. Plant extracts are gaining popularity in treating diabetes because many substances synthesized by higher plants and fungi possess antioxidant activities and can prevent or protect tissues against the damaging effects of free radicals. This review summarizes experimental models of diabetes and possible mechanisms that lie behind the antioxidative effects of α-lipoic acid (LA), a powerful antioxidant and compound that stimulates cellular glucose uptake, as well as of plant extracts from sweet chestnut (Castanea sativa), edible mushroom (Lactarius deterrimus) and natural products containing β-glucans in the treatment of diabetes. Their roles in preventing pancreatic β-cell death and in ameliorating the effects of severe diabetic complications are discussed.Terapija antioksidansima zauzima značajno mesto u lečenju dijabetesa s obzirom da oksidativni stres u velikoj meri doprinosi narušavanju funkcije i strukture β-ćelija pankreasa kao i razvoju komplikacija u dijabetesu. Zbog ograničenog dejstva postojećih antioksidativnih jedinjenja traga se za novim terapijskim rešenjima u tretmanu dijabetesa, kao što je povećanje endogene antioksidativne zaštite organizma putem farmakološke modulacije ključnih antioksidativnih enzima. Primena biljnih ekstrakata u lečenju dijabetesa postaje sve popularnija. Mnoge supstance koje se nalaze u sastavu viših biljaka i gljiva poseduju antioksidativna svojstva koja mogu da zaštite tkiva od štetnih uticaja slobodnih radikala. U ovom revijalnom radu opisani su eksperimentalni modeli dijabetesa kao i mogući mehanizmi koji leže u osnovi antioksidativnog dejstva α-liponske kiseline (LA), snažnog antioksidansa i jedinjenja koje stimuliše ćelijsku apsorpciju glukoze, kao i biljnih ekstrakata izolovanih iz slatkog kestena (Castanea sativa), jestivih pečuraka (Lactarius deterrimus) i prirodnih proizvoda koji sadrže β-glukan u lečenju dijabetesa. Opisani su njihova uloga u sprečavanju smrti β-ćelija pankreasa kao i blagotvorno dejstvo na komplikacije u dijabetesu.Projekat ministarstva br. 17302

CXC Chemokine Ligand 12 Protects Pancreatic β-Cells from Necrosis through Akt Kinase-Mediated Modulation of Poly(ADP-ribose) Polymerase-1 Activity

The diabetes prevention paradigm envisages the application of strategies that support the maintenance of appropriate β-cell numbers. Herein we show that overexpression of CXC chemokine ligand12 (CXCL12) considerably improves the viability of isolated rat Langerhans islet cells and Rin-5F pancreatic β-cells after hydrogen peroxide treatment. In rat islets and wt cells hydrogen peroxide treatment induced necrotic cell death that was mediated by the rapid and extensive activation of poly(ADP-ribose) polymerase-1 (PARP-1). In contrast, CXCL12-overexpressing cells were protected from necrotic cell death as a result of significantly reduced PARP-1 activity. CXCL12 downstream signalling through Akt kinase was responsible for the reduction of PARP-1 activity which switched cell death from necrosis to apoptosis, providing increased protection to cells from oxidative stress. Our results offer a novel aspect of the CXCL12-mediated improvement of β-cell viability which is based on its antinecrotic action through modulation of PARP-1 activity

Beneficial effects of α-lipoic acid in diabetes- and drug- induced liver injury

This review summarizes the effects of α-lipoic acid (LA) on liver damage and complications in diabetes and drug toxicity. LA is a naturally occurring dithiol compound that plays an essential role in mitochondrial metabolism in its protein-bound form. In contrast, free LA in supplements has diverse biological actions, and its antioxidant effect is its most studied and important activity. Due to its strong antioxidant potential, LA could have a promising role in the treatment of pathologies resulting from an imbalance in redox homeostasis. This includes diabetes, which produces deleterious effects on many organs, including the liver. In diabetes specifically, LA prevents β-cell destruction, enhances glucose uptake, and its antioxidant effects may be particularly useful in slowing down the development of diabetic complications. Diabetes-related liver damage is a serious complication in which oxidative stress is the main contributor to tissue injury. Oxidative stress is regarded as one of the main pathological mechanisms underlying liver pathologies provoked by other insults, such as drug toxicity, where LA could also be a useful agent in therapeutic intervention. However, before wider application of LA in a clinical setting, experimental and clinical research needs to be extended

The role of targeted (epi)genetic modifications in potential diabetes therapy

U osnovi dijabetesa se nalazi smanjen broj beta ćelija endokrinog pankreasa, njihovo poremećeno funkcionisanje ili gubitak identiteta u procesu dediferencijacije. Jedna od aktuelnih strategija za potencijalnu primenu u terapiji dijabetesa je i direktno ćelijsko reprogramiranje kojim bi se nadomestio nedostatak funkcionalnih beta ćelija i insulina u organizmu. Ovaj pravac u istraživanjima podrazumeva transdiferencijaciju somatskih ćelija poreklom iz različitih organa u ćelije koje proizvode insulin kroz modulaciju ekspresije transkripcionih faktora koji su ključni za održavanje ćelijskog identiteta. U ovom poglavlju biće predstavljena aktuelna istraživanja koja podrazumevaju ćelijsko reprogramiranje uz pomoć novih sintetičkih alata koji imaju ulogu da dirigovano uvode izmene u (epi)genom sa posebnim osvrtom na CRISPR/Cas9 sistem i njegove modifikacije. Alfa ćelije endokrinog pankreasa predstavljaju atraktivan izvor ćelija za potencijalnu terapiju dijabetesa zato što dele zajedničko poreklo sa beta ćelijama, imaju visok nivo plastičnosti kao i zbog bliske pozicioniranosti koja obezbeđuje prirodno okruženje pogodno za njihovo preživljavanje. Jedna od nedavnih studija je podrazumevala upotrebu EpiCRISPR sistema za ciljano uvođenje metilacije u okviru promotora gena Arx u alfa ćelijama pankreasa miša u cilju njihove transdiferencijacije. Uvedene izmene na nivou epigenoma su dovele do pokretanja ekspresije insulina u alfa ćelijama pankreasa miša i inicijacije procesa njihove transdiferencijacije u ćelije koje produkuju insulin.Diabetes is caused by a reduced number of beta cell mass, impaired functioning, or loss of beta cell identity through the dedifferentiation process. Direct cellular reprogramming is one of the current strategies in the potential diabetes therapy, which would replace the lack of functional beta cells and regulate insulin levels. This research approach involves the transdifferentiation of somatic cells from several organs into insulin-producing cells by modulating the expression pattern of transcription factors responsible for maintaining cellular identity. This chapter will present current research involving cellular reprogramming using the new synthetic tools that have ability to introduce targeted (epi)genetic modifications. Special attention will be paid to the CRISPR/Cas9 system and its modifications. Pancreatic alpha cells represent an attractive cell source for potential diabetes therapy because they share a common origin with beta cells, have a high level of plasticity, and provide a natural environment suitable for cell survival because of their close placement. One of the recent studies involved the use of the EpiCRISPR system for targeted DNA methylation within the Arx gene promoter in murine pancreatic alpha cells. The introduced changes at the epigenetic level led to the initiation of insulin expression in the alpha cells of the mouse pancreas and the initiation of their transdifferentiation process into insulin-producing cells

Effets motivationnels et sommatifs de l'évaluation par réussite-échec à paliers

Résumé à la fin des ptiesÉgalement disponible en version papierTitre de l'écran-titre (visionné le 3 mars. 2010)Comprend des bibliogr

Centaurium erythraea extract mediates prosurvival pathways and insulin expression in STZ-treated beta-cells

Diabetes is characterized by hyperglycaemia resulting from a deficiency in insulin secretion and/or action leading to severe diabetic complications. Despite numerous efforts, recovery and maintenance of functional beta-cells is still an unresolved task in diabetes therapy. Considering anti-diabetic properties of medicinal herb Centaurium erythraea Rafn (CE), this study aimed to analyze protective effects of the CE extract on Rin-5F beta-cell line exposed to diabetogenic agent streptozotocin (STZ). Cytoprotective concentration of CE extract (0.25 mg/mL) and IC50 dose of STZ (12mM) were determined using cell viability assay (MTT). The level of insulin mRNA and the concentration of insulin released from beta-cells in a culture medium were analyzed by RT-qPCR and ELISA, respectively. Activity of Akt, ERK and p38 kinases, as well as nuclear levels of islet-enriched Pdx1 and MafA proteins were assessed by Western blot analysis. In comparison to STZ-treated cells, CE extract/STZ co-treatment increased viability of Rin- 5F cells for 12%. STZ-treated beta-cells displayed reduced mRNA level of insulin to 63% and reduced insulin secretion to 76% in comparison to controls, while application of CE extract improved insulin mRNA level to 77% and insulin secretion to 90% of the control level. Improved viability and functionality of beta-cells could be ascribed to a CE extractmediated modulation of the activities of pro-survival Akt, ERK and p38 kinases and Pdx- 1 and MafA factors involved in regulation of beta-cell proliferation and insulin expression/secretion. The results of this study suggest that CE extract promotes proliferative and pro-survival pathways in beta-cells and improves their functional properties