Flavonoid diosmetin increases ATP levels in kidney cells and relieves ATP depleting effect of ochratoxin A

Diosmetin (DIOS) is a flavone aglycone commonly occurring in citrus species and olive leaves, in addition it is one of the active ingredients of some medications. Based on both in vitro and in vivo studies several beneficial effects are attributed to DIOS but the biochemical background of its action seems to be complex and it has not been completely explored yet. Previous investigations suggest that most of the flavonoid aglycones have negative effect on ATP synthesis in a dose dependent manner. In our study 17 flavonoids were tested and interestingly DIOS caused a significant elevation of intracellular ATP levels after 6- and 12-h incubation in MDCK kidney cells. In order to understand the mechanism of action, intracellular ATP and protein levels, ATP/ADP ratio, cell viability and ROS levels were determined after DIOS treatment. In addition, impacts of different enzyme inhibitors and effect of DIOS on isolated rat liver mitochondria were also tested. Finally, the influence of DIOS on the ATP depleting effect of the mycotoxin, ochratoxin A was also investigated. Our major conclusions are the followings: DIOS increases intracellular ATP levels both in kidney and in liver cells. Inhibition of glycolysis or citric acid cycle does not decrease the observed effect. DIOS-induced elevation of ATP levels is completely abolished by the inhibition of ATP synthase. DIOS is able to completely reverse the ATP-depleting effect of the mycotoxin, ochratoxin A. Most probably the DIOS-induced impact on ATP system does not originate from the antioxidant property of DIOS. Based on our findings DIOS may be promising agent to positively influence ATP depletion caused by some metabolic poisons

Remodeling of Liver and Plasma Lipidomes in Mice Lacking Cyclophilin D

In recent years, several studies aimed to investigate the metabolic effects of non-functioning or absent cyclophilin D (CypD), a crucial regulatory component of mitochondrial permeability transition pores. It has been reported that the lack of CypD affects glucose and lipid metabolism. However, the findings are controversial regarding the metabolic pathways involved, and most reports describe the effect of a high-fat diet on metabolism. We performed a lipidomic analysis of plasma and liver samples of CypD-/- and wild-type (WT) mice to reveal the lipid-specific alterations resulting from the absence of CypD. In the CypD-/- mice compared to the WT animals, we found a significant change in 52% and 47% of the measured 225 and 201 lipid species in liver and plasma samples, respectively. The higher total lipid content detected in these tissues was not accompanied by abdominal fat accumulation assessed by nuclear magnetic resonance imaging. We also documented characteristic changes in the lipid composition of the liver and plasma as a result of CypD ablation with the relative increase in polyunsaturated membrane lipid species. In addition, we did not observe remarkable differences in the lipid distribution of hepatocytes using histochemistry, but we found characteristic changes in the hepatocyte ultrastructure in CypD-/- animals using electron microscopy. Our results highlight the possible long-term effects of CypD inhibition as a novel therapeutic consideration for various diseases

Simplified coronary flow reserve calculations based on three-dimensional coronary reconstruction and intracoronary pressure data

Background: Measurements of fractional flow reserve (FFR) and/or coronary flow reserve (CFR) are widely used for hemodynamic characterization of coronary lesions. The frequent combination of the epicardial and microvascular disease may indicate a need for complex hemodynamic evaluation of coronary lesions. This study aims at validating the calculation of CFR based on a simple hemodynamic model to detailed computational fluid dynamics (CFD) analysis. Methods: Three-dimensional (3D) morphological data and pressure values from FFR measurements were used to calculate the target vessel. Nine patients with one intermediate stenosis each, measured by pressure wire, were included in this study. Results: A correlation was found between the determined CFR from simple equations and from a steady flow simulation (r = 0.984, p < 10−5). There was a significant correlation between the CFR values calculated by transient and steady flow simulations (r = 0.94, p < 10−3). Conclusions: Feasibility was demonstrated of a simple hemodynamic calculation of CFR based on 3D-angiography and intracoronary pressure measurements. A simultaneous determination of both the FFR and CFR values provides the capability to diagnose microvascular dysfunction: the CFR/FFR ratio characterizes the microvascular reserve

A Client-Server Model for Editing ODF Documents on Mobile Devices

Open Document Format (ODF) is a popular office document format accepted by most of modern desktop office suites. The aim of our project is to create a software suite of specialized mobile ODF schemata and editors to provide support of editing ODF-based documents on mobile devices. Number of tests have been carried out with prototype tools focusing on the resource need of transferring, visualizing and editing simple ODF documents. Based on test results we have found that the limited capacity of mobile devices (compared to desktop computers) implies that documents in their original form cannot be handled on mobile devices. In this paper we investigate the methods and background of ODF-based document transfer and edition in a client-server model

Three-dimensional evaluation of the spatial morphology of stented coronary artery segments in relation to restenosis

To investigate the correlations between the three-dimensional (3D) parameters of target coronary artery segments and restenosis after stent implantation. Sixty-four patients after single, cobalt chromium platform stent (27 BM stents and 37 DES) implantation were investigated retrospectively 12 ± 6 months after the index procedure. 3D coronary artery reconstruction was performed before and after the stent implantation using appropriate projections by a dedicated reconstruction software. The curve of the target segment was characterized by the ratio of the vessel length measured at midline (arc: A) and the distance between the edge points of the stent (chord: C): A/C ratio (ACr). Age, diabetes and hyperlipidaemia were taken into account for the statistical evaluation. 22 patients were diagnosed with ISR, while 42 patients without any restenosis served as controls. The two groups did not differ regarding major cardiovascular risk factors, proportion of the treated vessels or the type of stents. Higher initial ACr values were associated with greater straightening of the vessel curvature in all groups (p < 0.001). Significant negative correlations were found in cases of proximal or distal edge bending angles (p < 0.001). Pre-stent edge bending angles < 7° often showed an increase after the stent implantation, while in case of higher initial values, the bending angles generally decreased. Using multivariate logistic regression modelling we found that the pre-stent ACr was an independent predictor of in-stent restenosis (odds ratio for 1% increase of the ACr: 1.08; p = 0.012). Changes of angles at the stent edges following stent implantation correlate with the initial local bending angles. The ACr predispose to chronic shear stress in the vessel wall, which may contribute to the pathological intimal proliferation

Three-dimensional evaluation of the spatial morphology of stented coronary artery segments in relation to restenosis

To investigate the correlations between the three-dimensional (3D) parameters of target coronary artery segments and restenosis after stent implantation. Sixty-four patients after single, cobalt chromium platform stent (27 BM stents and 37 DES) implantation were investigated retrospectively 12 ± 6 months after the index procedure. 3D coronary artery reconstruction was performed before and after the stent implantation using appropriate projections by a dedicated reconstruction software. The curve of the target segment was characterized by the ratio of the vessel length measured at midline (arc: A) and the distance between the edge points of the stent (chord: C): A/C ratio (ACr). Age, diabetes and hyperlipidaemia were taken into account for the statistical evaluation. 22 patients were diagnosed with ISR, while 42 patients without any restenosis served as controls. The two groups did not differ regarding major cardiovascular risk factors, proportion of the treated vessels or the type of stents. Higher initial ACr values were associated with greater straightening of the vessel curvature in all groups (p < 0.001). Significant negative correlations were found in cases of proximal or distal edge bending angles (p < 0.001). Pre-stent edge bending angles < 7° often showed an increase after the stent implantation, while in case of higher initial values, the bending angles generally decreased. Using multivariate logistic regression modelling we found that the pre-stent ACr was an independent predictor of in-stent restenosis (odds ratio for 1% increase of the ACr: 1.08; p = 0.012). Changes of angles at the stent edges following stent implantation correlate with the initial local bending angles. The ACr predispose to chronic shear stress in the vessel wall, which may contribute to the pathological intimal proliferation

Antibacterial and Biofilm Degradation Effects of Hungarian Honeys Linked with Botanical Origin, Antioxidant Capacity and Mineral Content

The aim of the study was to assess the impact of four unifloral honeys on the food-borne pathogens Pseudomonas aeruginosa and Staphylococcus aureus, by analyzing the honeys’ antibacterial and biofilm degradation effects, as well as their antioxidant activity and element content. Linden and milkweed honeys represented light colored honeys, while goldenrod and chestnut honeys the darker ones. The botanical origin of the honeys and the relative frequency of their pollen types were established with melissopalynological analysis. The antioxidant capacities were calculated by two single electron transfer based methods (TRC – Total Reducing Capacity and TEAC – Trolox Equivalent Antioxidant Capacity) and a hydrogen atom transfer based assay (ORAC – Oxygen Radical Absorbance). The amount of four main macro- and two microelements was quantified. The antibacterial activity was determined by minimum inhibitory concentration (MIC) and membrane degradation assays. Furthermore, the biofilm degradation power of the samples was studied as well. The light colored linden honey with the lowest TRC and TEAC, but with the highest ORAC antioxidant activity and high element content showed the best antibacterial and biofilm degradation effects. Meanwhile, the dark colored chestnut honey with significantly higher single electron transfer based antioxidant capacities, with high element content, but lower ORAC showed significantly higher MIC and lower membrane degradation activity than linden honey. In case of biofilm degradation, both honey types gave similarly high inhibitory effect. Goldenrod honey was similarly effective regarding its MIC properties like chestnut honey, but had significantly lower antioxidant potential and ability to disrupt bacterial membranes and biofilms. Milkweed honey was the honey type with the lowest bioactivity and element content. The honeys, unequivocally characterized by their antioxidant characters and element content, displayed different antibacterial and biofilm degradation effects. In addition, some honey traits were found to be good predictors of the antimicrobial potential of honeys: ORAC assay showed correlation with the MIC values of both bacteria, and strict correlation was found between the mineral content and the antibiofilm activity of the studied honeys. Our studies indicate that unifloral honeys, such as linden and chestnut honeys, are plant-derived products with great potential as antimicrobial agents in food preservation, exhibiting remarkable antibacterial activity against food-borne pathogens