ARTreat Project: Three-Dimensional Numerical Simulation of Plaque Formation and Development in the Arteries

Atherosclerosis is a progressive disease characterized by the accumulation of lipids and fibrous elements in arteries. It is characterized by dysfunction of endothelium and vasculitis, and accumulation of lipid, cholesterol, and cell elements inside blood vessel wall. In this study, a continuum-based approach for plaque formation and development in 3-D is presented. The blood flow is simulated by the 3-D Navier-Stokes equations, together with the continuity equation while low-density lipoprotein (LDL) transport in lumen of the vessel is coupled with Kedem-Katchalsky equations. The inflammatory process was solved using three additional reaction-diffusion partial differential equations. Transport of labeled LDL was fitted with our experiment on the rabbit animal model. Matching with histological data for LDL localization was achieved. Also, 3-D model of the straight artery with initial mild constriction of 30% plaque for formation and development is presented

Ascorbate mediates the non-enzymatic reduction of nitrite to nitric oxide

Nitric oxide (NO•) generated by nitric oxide synthases is involved in many physiological and pathophysiological processes. However, non-enzymatic formation of NO• also occurs in vivo. Here we investigated the production of NO• from nitrite, as facilitated by ascorbate, over the pH range of 2.4–7.4. Using a nitric oxide electrode, we observed at low pH a rapid generation of NO• from nitrite and ascorbate that slows with increasing pH. The formation of NO• was confirmed by its reaction with oxyhemoglobin. In the ascorbate/nitrite system a steady-state level of NO• was achieved, suggesting that a futile redox cycle of nitrite-reduction by ascorbate and NO•-oxidation by dioxygen was established. However, at pH-values of around 7 and greater, the direct reduction of nitrite by ascorbate is very slow; thus, this route to the non-enzymatic production of NO• is not likely to be significant process in vivo in environments having a pH around 7.4. The production of nitric oxide by nitrite and ascorbate would be important only in areas of lower pH, e.g. stomach/digestive system, sites of inflammation, and areas of hypoxia such as tumor tissue. In patients receiving very large doses of ascorbate delivered by intravenous infusion, plasma levels of ascorbate on the order of 20 - 30 mM can be achieved. After infusion, levels of nitrate and nitrite in plasma were unchanged. Thus, in blood and tissue that maintain a pH of about 7.4, the reduction of nitrite to nitric oxide by ascorbate appears to be insignificant, even at very large, pharmacological levels of ascorbate

Beyond H2S and NO Interplay: Hydrogen Sulfide and Nitroprusside React Directly to Give Nitroxyl (HNO). A New Pharmacological Source of HNO

Hydrogen sulfide (H2S) has been increasingly recognized as an important signaling molecule that regulates both blood pressure and neuronal activity. Attention has been drawn to its interactions with another gasotransmitter, nitric oxide (NO). Here, we provide evidence that the physiological effects observed upon the application of sodium nitroprusside (SNP) and H2S can be ascribed to the generation of nitroxyl (HNO), which is a direct product of the reaction between SNP and H2S, not a consequence of released NO subsequently reacting with H2S. Intracellular HNO formation has been confirmed, and the subsequent release of calcitonin gene related peptide from a mouse heart has been demonstrated. Unlike with other thiols, SNP reacts with H2S in the same way as rhodanese, i.e, the cyanide transforms into a thiocyanate. These findings shed new light on how H2S is understood to interact with nitroprusside. Additionally, they offer a new and convenient pharmacological source of HNO for therapeutic purposes.FAU Erlangen-Nuremberg (Emerging Field Initiative: Medicinal Redox Inorganic Chemistry); DAAD; Serbian Ministry of Education and science [OI 173014

Etude d'échange de solvant sur des composés demi- sandwich du Ru(II) et sur Rh24+

Hippocampal structural changes associated with diabetes-related cognitive impairments are well described, but their molecular background remained vague. We examined whether/how diabetes alters molecular basis of energy metabolism in hippocampus readily after diabetes onset, with special emphasis on its redox-sensitivity. To induce diabetes, adult Mill Hill hybrid hooded rats received a single alloxan dose (120 mg/kg). Both non-diabetic and diabetic groups were further divided in two subgroups receiving (i) or not (ii) superoxide dismutase (SOD) mimic, [Mn(II)(pyane)Cl-2] for 7 days, i.p. Treatment of the diabetic animals started after blood glucose level >= 12 mM. Diabetes decreased protein levels of oxidative phosphorylation components: complex III and ATP synthase. In contrast, protein amounts of glyceraldehyde-3-phosphate dehydrogenase, pyruvate dehydrogenase, and hypoxia-inducible factor-1 alpha - the key regulator of energy metabolism in stress conditions, were higher in diabetic animals. Treatment with SOD mimic restored/increased the levels of oxidative phosphorylation components and returned hypoxia-inducible factor-1 alpha to control level, while diabetes-induced up-regulation of glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase, was additionally stimulated. To conclude, our results provide insight into the earliest molecular changes of energy-producing pathways in diabetes that may account for structural/functional disturbance of hippocampus, seen during disease progression. Also, data suggest [Mn(II)(pyane)Cl-2] as potential therapeutic agent in cutting-edge approaches to threat this widespread metabolic disorder. (C) 2013 Elsevier Inc. All rights reserved.Ministry of Education, Science and Technological Development of the Republic of Serbia [173054, 173055

The effects of superoxide dismutase mimic on energy metabolism in hippocampus of diabetic rats

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The effects of superoxide dismutase mimic on energy metabolism in hippocampus of diabetic rats

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Manganese (II) pentaazamacrocyclic SOD mimic improves functional status of human sperm mitochondria: involvement of iNO

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Manganese (II) pentaazamacrocyclic SOD mimic improves functional status of human sperm mitochondria: involvement of iNO

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Is Manganese (II) Pentaazamacrocyclic Superoxide Dismutase Mimic Beneficial for Human Sperm Mitochondria Function and Motility?

Mitochondria play an important role in sperm cell maturation and function. Here, we examined whether (and how) changes in sperm redox milieu affect the functional status of sperm mitochondria, that is, sperm functionality. Compared with the control, incubation in Tyrode's medium for 3 h, under noncapacitating conditions, decreased sperm motility, the amount of nitric oxide ((NO)-N-center dot), the number of MitoTracker (R) Green FM (MT-G) positive mitochondria, and the expression of complexes I and IV of the mitochondrial respiratory chain. In turn, superoxide dismutase (SOD) mimic (M40403) treatment restored/increased these parameters, as well as the expression of endothelial nitric oxide synthase, manganese SOD, and catalase. These data lead to the hypothesis that M40403 improves mitochondrial functional state and motility of spermatozoa, as well as (NO)-N-center dot might be involved in the observed effects of the mimic. Antioxid. Redox Signal. 18, 170-178.Ministry of Education and Science of the Republic of Serbia [173054]; University of Erlangen-Nurember

Is Manganese (II) Pentaazamacrocyclic Superoxide Dismutase Mimic Beneficial for Human Sperm Mitochondria Function and Motility?

Mitochondria play an important role in sperm cell maturation and function. Here, we examined whether (and how) changes in sperm redox milieu affect the functional status of sperm mitochondria, that is, sperm functionality. Compared with the control, incubation in Tyrode's medium for 3 h, under noncapacitating conditions, decreased sperm motility, the amount of nitric oxide ((NO)-N-center dot), the number of MitoTracker (R) Green FM (MT-G) positive mitochondria, and the expression of complexes I and IV of the mitochondrial respiratory chain. In turn, superoxide dismutase (SOD) mimic (M40403) treatment restored/increased these parameters, as well as the expression of endothelial nitric oxide synthase, manganese SOD, and catalase. These data lead to the hypothesis that M40403 improves mitochondrial functional state and motility of spermatozoa, as well as (NO)-N-center dot might be involved in the observed effects of the mimic. Antioxid. Redox Signal. 18, 170-178.Ministry of Education and Science of the Republic of Serbia [173054]; University of Erlangen-Nurember