eNOS Protects from Atherosclerosis Despite Relevant Superoxide Production by the Enzyme in apoE−/− Mice

All three nitric oxide synthase (NOS) isoforms are expressed in atherosclerotic plaques. NOS enzymes in general catalyse NO production. However, under conditions of substrate and cofactor deficiency, the enzyme directly catalyse superoxide formation. Considering this alternative chemistry, the effects of NOS on key events in spontaneous hyperlipidemia driven atherosclerosis have not been investigated yet. Here, we evaluate how endothelial nitric oxide synthase (eNOS) modulates leukocyte/endothelial- (L/E) and platelet/endothelial- (P/E) interactions in atherosclerosis and the production of nitric oxide (NO) and superoxide by the enzyme. Intravital microscopy (IVM) of carotid arteries revealed significantly increased L/E-interactions in apolipoproteinE/eNOS double knockout mice (apoE(-/-)/eNOS(-/-)), while P/E-interactions did not differ, compared to apoE(-/-). eNOS deficiency increased macrophage infiltration in carotid arteries and vascular cell adhesion molecule-1 (VCAM-1) expression, both in endothelial and smooth muscle cells. Despite the expression of other NOS isoforms (inducible NOS, iNOS and neuronal NOS, nNOS) in plaques, Electron Spin Resonance (ESR) measurements of NO showed significant contribution of eNOS to total circulating and vascular wall NO production. Pharmacological inhibition and genetic deletion of eNOS reduced vascular superoxide production, indicating uncoupling of the enzyme in apoE(-/-) vessels. Overt plaque formation, increased vascular inflammation and L/E- interactions are associated with significant reduction of superoxide production in apoE(-/-)/eNOS(-/-) vessels. Therefore, lack of eNOS does not cause an automatic increase in oxidative stress. Uncoupling of eNOS occurs in apoE(-/-) atherosclerosis but does not negate the enzyme's strong protective effects

Primjena i kompozicija individualiziranih zaštitnih elemenata linijske grafike u projektiranju novčanica

Proces stvaranja novčanica je dugotrajan i složen, što rezultira kompleksnim rješenjima koja predstavljaju pravo remek djelo grafike. Novčanice su prožete brojnim detaljima i prenose različite informacije koje se analiziraju u teorijskom dijelu rada. Prvotno se postavljaju kriteriji po kojima se izrađuje detaljna analiza velikog broja zaštitnih i konceptualnih elemenata na primjerima novčanica. Time je prikazan okvirni povijesni pregled razvoja novčanica i utjecaji kojima je bio izložen. Analizira se međuovisnost dizajna o sigurnosnim značajkama, te se ispituje razina informiranosti javnosti o zaštitama na novčanicama. Zaključuje se koje metode zaštite su najučinkovitije, te kako šira javnost najčešće provjerava autentičnost novčanica. U eksperimentalnom dijelu rada se na temelju donesenih zaključaka iz teorijskog dijela izrađuje prototip novčanice koja je u najvećoj mjeri prožeta individualiziranim PostScript programskim rješenjima elemenata linijske grafike (rozete, mikrotekst, zaštitne linije, brojevi apoena), a od ostalih zaštita modeliran je individualizirani raster transformacijom matematičkog izraza u PostScript programski kod. Sve ostale zaštite tipične za novčanice simulirane su alatima za rastersku i vektorsku grafiku. U radu se ispituje utjecaj kompozicije zaštitnih elemenata na prepoznavanje autentičnosti novčanica, te efikasnost samih individualiziranih programskih rješenja

The role of liver transplantation techniques in the surgical management of advanced renal urothelial carcinoma with or without inferior vena cava thrombus

Purpose: Standard radical nephrectomy for large masses is significantly facilitated by liver transplantation techniques, which have been successfully employed over the last ten years at our institution. Large and locally-advanced urothelial carcinoma of the kidney with or without extension into the inferior vena cava is rare. The purpose of this study was to present the surgical management of large and locally-advanced urothelial tumors arising from the renal pelvis using liver transplantation techniques and to evaluate patient outcome. Materials and Methods: Diagnostic work-up and surgical management of 4 patients with large and locally-advanced renal urothelial carcinoma were retrospectively reviewed. Two out of four patients with urothelial carcinoma presented with inferior vena cava thrombus. Mean tumor size was 11.6 cm. All patients underwent surgery, 2 patients with the presumed diagnosis of renal cell cancer. Liver transplantation techniques were an integral part in all radical nephrectomies. Results: No intraoperative complications and postoperative mortality occurred. Mean operative time was 7.5 hours, estimated blood loss was 1.5 L, and an average of 4.8 units of blood was transfused intraoperatively. Three patients succumbed to cancer recurrence at a mean postoperative time of 6.3 months; 1 patient is still alive 24 months after surgery. Conclusions: Large and locally-advanced renal masses of urothelial origin can be successfully removed by a combination of radical nephrectomy with liver transplantation techniques. Since long-term outcome of such patients has been poor, accurate preoperative diagnosis is essential to consider neoadjuvant treatment and to plan nephroureterectomy