Targeting the superoxide/nitric oxide ratio by L-arginine and SOD mimic in diabetic rat skin

AbstractSetting the correct ratio of superoxide anion (O2•-) and nitric oxide (•NO) radicals seems to be crucial in restoring disrupted redox signaling in diabetic skin and improvement of •NO physiological action for prevention and treatment of skin injuries in diabetes. In this study we examined the effects of L-arginine and manganese(II)-pentaazamacrocyclic superoxide dismutase (SOD) mimic – M40403 in diabetic rat skin. Following induction of diabetes by alloxan (blood glucose level ≥12 mMol l −1) non-diabetic and diabetic male Mill Hill hybrid hooded rats were divided into three subgroups: (i) control, and receiving: (ii) L-arginine, (iii) M40403. Treatment of diabetic animals started after diabetes induction and lasted for 7 days. Compared to control, lower cutaneous immuno-expression of endothelial NO synthase (eNOS), heme oxygenase 1 (HO1), manganese SOD (MnSOD) and glutathione peroxidase (GSH-Px), in parallel with increased NFE2-related factor 2 (Nrf2) and nitrotyrosine levels characterized diabeti..

Heteropentanuclear Oxalato-Bridged nd-4f (n=4, 5) Metal Complexes with NO Ligand: Synthesis, Crystal Structures, Aqueous Stability and Antiproliferative Activity

A series of heteropentanuclear oxalate-bridged Ru(NO)-Ln (4d-4f) metal complexes of the general formula (nBu(4)N)(5)[Ln{RuCl3(-ox)(NO)}(4)], where Ln=Y (2), Gd (3), Tb (4), Dy (5) and ox=oxalate anion, were obtained by treatment of (nBu(4)N)(2)[RuCl3(ox)(NO)] (1) with the respective lanthanide salt in 4:1 molar ratio. The compounds were characterized by elemental analysis, IR spectroscopy, electrospray ionization (ESI) mass spectrometry, while 1, 2, and 5 were in addition analyzed by X-ray crystallography, 1 by Ru K-edge XAS and 1 and 2 by (CNMR)-C-13 spectroscopy. X-ray diffraction showed that in 2 and 5 four complex anions [RuCl3(ox)(NO)](2-) are coordinated to Y-III and Dy-III, respectively, with formation of [Ln{RuCl3(-ox)(NO)}(4)](5-) (Ln=Y, Dy). While Y-III is eight-coordinate in 2, Dy-III is nine-coordinate in 5, with an additional coordination of an EtOH molecule. The negative charge is counterbalanced by five nBu(4)N(+) ions present in the crystal structure. The stability of complexes 2 and 5 in aqueous medium was monitored by UV/Vis spectroscopy. The antiproliferative activity of ruthenium-lanthanide complexes 2-5 were assayed in two human cancer cell lines (HeLa and A549) and in a noncancerous cell line (MRC-5) and compared with those obtained for the previously reported Os(NO)-Ln (5d-4f) analogues (nBu(4)N)(5)[Ln{OsCl3(ox)(NO)}(4)] (Ln=Y (6), Gd (7), Tb (8), Dy (9)). Complexes 2-5 were found to be slightly more active than 1 in inhibiting the proliferation of HeLa and A549 cells, and significantly more cytotoxic than 5d-4f metal complexes 6-9 in terms of IC50 values. The highest antiproliferative activity with IC50 values of 20.0 and 22.4M was found for 4 in HeLa and A549 cell lines, respectively. These cytotoxicity results are in accord with the presented ICP-MS data, indicating five- to eightfold greater accumulation of ruthenium versus osmium in human A549 cancer cells

Modelovanje energetskih ušteda u procesu osmotske dehidratacije svinjskog mesa u melasi

The goal of the presented research is defining energy savings mathematical models of the osmotic dehydration process of pork meat in sugar beet molasses and analysing the effects of applied technological parameters in the process. Quantity of saved energy in the process of osmotic dehydration ranged from 891,57 to 1770,92 kJ•kg-1 meat. In this paper developed mathematical models of energy savings in the process of pork meat osmotic dehydration are presented. Time of the process was the most influential technological parameter on developed models, than osmotic solution concnetration, and temperature of the process was the least influential technological parameter. Maximal value of the energy savings was achived in the process of osmotic dehydration of pork meat at the temperature of 20°C, after five hours of the process in sugar beet molasses of the maximal concentration. Presented results indicate on low energy profile of osmotic dehydration process which, by utilisation of molassses as an osmotic medium, even more contributes to the ecological properites of the process.Cilj prezentovanog istraživanja je definisanje matematičkih modela energetskih ušteda u procesu osmotske dehidratacije svinjskog mesa u melasi šećerne repe i analiziranje uticaja primenjenih tehnoloških parametara. Ušteđena količina toplote u procesu osmotske dehidratacije kretala se u opsegu od 891,57 do 1770,92 kJ•kg-1 mesa. U radu su prikazani razvijeni matematički modeli energetskih ušteda u procesu osmotske dehidratacije svinjskog mesa u melasi. Kao najuticajniji tehnološki parametar na razvijene matematičke modele pokazalo se vreme procesa, pa zatim koncentracija osmostskog rastvaora i na kraju temperatura procesa. Maksimalna vrednost uštede količine toplote ostvarena je u procesu osmotske dehidratacije svinjskog mesa na temperaturi procesa od 20°C, nakon 5 časova procesa u melasi šećerne repe maksimalne koncentracije. Rezultati prikazani u ovom istraživanju ukazuju na niskoenergetski profil procesa osmotske dehidratacije koji upotrebom melase kao osmotskog rastvora još više doprinosi ekološkom karakteru procesa

Evaluation of water, sucrose and minerals effective diffusivities during osmotic treatment of pork in sugar beet molasses

Effective diffusivities of water, sucrose and minerals in osmotic treatment of pork cubes (M. triceps brachii) were calculated using Response Surface Methodology (RSM), with respect to temperature (20, 35 and 50°C) and concentration of sugar beet molasses, (60, 70 and 80 mass%). The numerical solution of Fick's law for unsteady-state mass transfer in a perfect cube configuration was used to calculate the effective diffusivities of water, sucrose and minerals (Na, K, Ca and Mg). Zugarramurdi and Lupin's model was used to predict the equilibrium condition, which has shown to be appropriate for water loss and solute uptake during osmotic treatment. Effective diffusivity of water was found to be in the range of 6.95×10-10-8.03×10-10 m2 s-1, the sucrose effective diffusivity was between 6.39×10-10 and 8.25×10-10 m2 s-1, while diffusivities for minerals (m2 s-1) were in the range: 6.34×10-10-8.82×10-10 for Na, 6.27×10-10-7.43×10-10 for K, 6.44×10-10-8.94×10-10 for Ca and 3.47×10-10-5.66×10-10 for Mg.Metoda odzivne površine (Response Surface Methodology - RSM) je korišćena pri matematičkom modelovanju i izračunavanju vrednosti prividne (efektivne) difuzije vode, saharoze i minerala tokom osmotskog tretmana kockica svinjskog mesa (M. triceps brachii), na temperaturi 20, 35 i 50°C i pri koncentracijama osmotskog rastvora (melasa šećerne repe) od 60, 70 i 80 mas.%. Numeričko rešavanje Fikovog (Fick) zakona o prenosu mase, pri nestacionarnim uslovima, za idealnu kocku je korišćeno za izračunavanje efektivnog koeficijenta difuzije vode, saharoze i minerala (Na, K, Ca and Mg). Sadržaj vlage i minerala je izmeren u tri ponavljanja. Korišćen je model Cuguramurdija (Zugarramurdi) i Lupina (Lupin) za predviđanje ravnotežnih uslova i ispostavilo se da je taj model pogodan za izračunavanje gubitka vlage i priraštaja suve materije tokom procesa osmotskog tretmana. Metoda odzivnih površina, koje se široko koristi za modelovanje i kontrolu procesa u prehrambenoj industriji, a u ovom radu je korišćena za predviđanje efektivnog koeficijenta difuzije vode, saharoze i minerala, pri određenoj temperaturi imerzije i koncentraciji melase šećerne repe. Matematički modeli koji su dobijeni na osnovu eksperimentalnih podataka obrađuju kompleksne nelinearne relacije sa interakcijama između procesnih promenljivih. Dobijene vrednosti efektivne difuzivnosti (m2 s-1) za vodu bili su u rasponu od 6,95×10-10 do 8,03×10-10, za efektivnu difuzivnost saharoze bili su između 6,39×10-10 i 8,25×10-10, dok su difuzivnosti za minerale bile u opsezima: 6,34×10-10-8,82×10-10 (Na), 6,27×10-10- -7,43×10-10 (K), 6,44×10-10-8,94×10-10 (Ca) i 3,47×10-10-5,66×10-10 (Mg). Korišćenjem razvijenih matematičkih modela dobijene su vrednosti efektivnih koeficijenata difuzije, sa tačnošću izraženom preko koeficijenata determinacije (r2) za Dw, DSuc, DNa. DK, DCa i DMg, i to: 0,993; 0,998; 0,999; 0,992; 0,999 i 0,998, redom. Širok opseg procesnih promenljivih veličina razmatranih u formiranju ovih modela, kao i njihova laka implementacija u tabelarnim proračunima, čini ove modele veoma praktičnim za projektovanje i kontrolu procesa

Anthropogenetic Variability in the Group of Individuals with Febrile Seizures: Population-Genetic Study

Febrile seizures (FS) are the most common neurological disorder in childhood and are a great stress for parents due to their dramatic clinical appearance. Using test for determination of homozygously recessive characteristics in humans (HRC test) we analyzed presence, distribution, and individual combination of 20 selected genetically controlled morphophysiological traits among FS patients (N=121) and control (N=121) to determine a possible deviation in the homozygosity level and genetic loads in the group of affected children and whether there is a predisposition to the occurrence of FS. The results of our study show a statistically significant difference in the mean values of the HRC tested (x¯HRC/20 CN = 3.2 ± 0.2; x¯HRC/20 FS = 4.6 ± 0.2, t= 5.74 , p< 0.0001), as well as in the distribution and variability of two studied samples (VC=55,3%, VFS= 39,6%), which indicates a complex polygenic difference among the tested groups of subjects. The differences in the degree of genetic homozygosity and variability are also present between the genders (t Cf/FSf = 4.12; t Cm/FSm = 3.98; p <0.0001) (VCf=56.9%, VFSf= 39.3%; VCm=54.1%, VFSm=40.1%). Obtained results indicate the enlargement of recessively homozygous genetic loads in the group of children with FS which may represent some kind of predisposition for expressivity of this type of seizures