Biomedical subjects

Zoltan Berente

Publications and source records attributed to Zoltan Berente.

7 recordsLinked to original sources

PubMed2007

In vivo brain edema classification: New insight offered by large b-value diffusion-weighted MR imaging.

PURPOSE: To assess the role of large b-value diffusion weighted imaging (DWI) in the characterization of the physicochemical properties of the water in brain edema under experimental and clinical conditions. MATERIALS AND METHODS: Vasogenic brain edema was induced in mice by means of cold injury. A total of 17 patients with extensive peritumoral brain edema were also investigated. The longitudinal relaxation time (T(1)) and apparent diffusion coefficient (D) were measured in the edematous area both in humans and in mice. D was calculated by using both mono- (D(mono)) and biexponential (D(fast) and D(slow)) approaches in the low and overall range of b-values, respectively. The D values were correlated with the T(1) values. RESULTS: A strong linear correlation was found between T(1) and D(mono) in vasogenic brain edema, both in humans and in mice. After breakdown of D(mono) into fast and slow diffusing components, only D(fast) exhibited a strong correlation with T(1); D(slow) was unchanged in vasogenic brain edema. CONCLUSION: Large b-value DWI can furnish a detailed characterization of vasogenic brain edema, and may provide a quantitative approach for the differentiation of edema types on the basis of the physicochemical properties of the water molecules. Application of the DWI method may permit prediction and follow-up of the effects of antiedematous therapy.

Animals↗

PubMed2005

Osmotic and diffusive properties of intracellular water in camel erythrocytes: effect of hemoglobin crowdedness.

Camel erythrocytes have exceptional osmotic resistance and is believed to be due to augmented water-binding associated with the high hydrophilicity of camel hemoglobin. In practical terms this means that the proportion of osmotically non-removable water in camel erythrocytes is nearly 3-fold greater than that in human erythrocytes (approximately 65 vs approximately 20%). The relationship between water diffusion and the osmotic characteristics of intracellular water is the subject of this report. The amount of osmotically inactive water is 2-fold greater in camel hemoglobin solution in vitro compared to that of human, but water diffusion does not differ in camel and human hemoglobin solutions. However, the evaluation of water diffusion by magnetic resonance measurements in camel erythrocytes revealed approximately 15% lower apparent diffusion coefficient (ADC) compared with human erythrocytes. When human erythrocytes were dehydrated to the level of camel erythrocytes, their osmotic and water diffusion properties were similar. These results show that a lower ADC is associated with a more pronounced increase in osmotically inactive water fraction. It is proposed that increased hemoglobin hydrophilicity allows not only augmented water-binding, but also a closer hemoglobin packaging in vivo, which in turn is associated with slower ADC and increased osmotic resistance.

Animals↗

PubMed2004

Regulation of kinase cascades and transcription factors by a poly(ADP-ribose) polymerase-1 inhibitor, 4-hydroxyquinazoline, in lipopolysaccharide-induced inflammation in mice.

Activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) is involved in numerous pathophysiological conditions. Because PARP-1 knockout mice are resistant to endotoxin-induced shock and inhibitors of the enzyme were reported to have similar beneficial properties, we investigated the effect of 4-hydroxyquinazoline (4-HQN), a potent PARP-1 inhibitor, on the modulation of kinase cascades and the regulation of transcription factors in a rodent septic shock model. T2-weighted magnetic resonance imaging showed the pattern of anatomical localization of the inflammatory response in bacterial lipopolysaccharide (LPS)-treated mice and the anti-inflammatory effect of the PARP-1 inhibitor. We have found that 4-HQN activated the phosphatidylinositol 3 (PI3)-kinase/Akt pathway in lung, liver, and spleen, and down-regulated two elements of the MAP kinase system. Namely, it dramatically attenuated the activation of the LPS-induced extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein (MAP) kinase in a tissue-specific manner. Furthermore, phosphorylation of p90RSK, a downstream target of ERK1/2, showed a similar pattern of down-regulation as did the phosphorylation of ERK1/2 and p38 after LPS and 4-HQN treatment. As a consequence of the aforementioned effects on the kinase pathways, 4-HQN decreased the activation of transcription factor nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP-1) in LPS-induced endotoxic shock. Our results provide evidence for the first time that the beneficial effects of PARP inhibition in endotoxic shock, such as attenuation of NF-kappaB- and AP-1 transcription factor activation, are mediated, at least partially, through the regulation of the PI3-kinase/Akt pathway and MAP kinase cascades.

Animals↗

PubMed2004

The existence of biexponential signal decay in magnetic resonance diffusion-weighted imaging appears to be independent of compartmentalization.

It is generally believed that the apparent diffusion coefficient (ADC) changes measured by diffusion-weighted imaging (DWI) in brain pathologies are related to alterations in the water compartments. The aim of this study was to elucidate the role of compartmentalization in DWI via biexponential analysis of the signal decay due to diffusion. DWI experiments were performed on mouse brain over an extended range of b-values (up to 10,000 mm(-2) s) under intact, global ischemic, and cold-injury conditions. DWI was additionally applied to centrifuged human erythrocyte samples with a negligible extracellular space. Biexponential signal decay was found to occur in the cortex of the intact mouse brain. During global ischemia, in addition to a drop in the ADC in both components, a shift from the volume fraction of the rapidly diffusing component to the slowly diffusing one was observed. In cold injury, the biexponential signal decay was still present despite the electron-microscopically validated disintegration of the membranes. The biexponential function was also applicable for fitting of the data obtained on erythrocyte samples. The results suggest that compartmentalization is not an essential feature of biexponential decay in diffusion experiments.

Animals↗

PubMed2004

Functional analyses of placental protein 13/galectin-13.

Placental protein 13 (PP13) was cloned from human term placenta. As sequence analyses, alignments and computational modelling showed its conserved structural and functional homology to members of the galectin family, the protein was designated galectin-13. Similar to human eosinophil Charcot-Leyden crystal protein/galectin-10 but not other galectins, its weak lysophospholipase activity was confirmed by 31P-NMR. In this study, recombinant PP13/galectin-13 was expressed and specific monoclonal antibody to PP13 was developed. Endogenous lysophospholipase activity of both the purified and also the recombinant protein was verified. Sugar binding assays revealed that N-acetyl-lactosamine, mannose and N-acetyl-glucosamine residues widely expressed in human placenta had the strongest binding affinity to both the purified and recombinant PP13/galectin-13, which also effectively agglutinated erythrocytes. The protein was found to be a homodimer of 16 kDa subunits linked together by disulphide bonds, a phenomenon differing from the noncovalent dimerization of previously known prototype galectins. Furthermore, reducing agents were shown to decrease its sugar binding activity and abolish its haemagglutination. Phosphorylation sites were computed on PP13/galectin-13, and phosphorylation of the purified protein was confirmed. Using affinity chromatography, PAGE, MALDI-TOF MS and post source decay, annexin II and beta/gamma actin were identified as proteins specifically bound to PP13/galectin-13 in placenta and fetal hepatic cells. Perinuclear staining of the syncytiotrophoblasts showed its expression in these cells, while strong labelling of the syncytiotrophoblasts' brush border membrane confirmed its galectin-like externalization to the cell surface. Knowing its colocalization and specific binding to annexin II, PP13/galectin-13 was assumed to be secreted to the outer cell surface by ectocytosis, in microvesicles containing actin and annexin II. With regard to our functional and immunomorphological results, PP13/galectin-13 may have special haemostatic and immunobiological functions at the lining of the common feto-maternal blood-spaces or developmental role in the placenta.

Amino Acid Sequence↗

PubMed2003

Decrease of the inflammatory response and induction of the Akt/protein kinase B pathway by poly-(ADP-ribose) polymerase 1 inhibitor in endotoxin-induced septic shock.

The lack of efficacy of anti-inflammatory drugs, anti-coagulants, anti-oxidants, etc. in critically ill patients has shifted interest towards developing alternative treatments. Since inhibitors of the nuclear enzyme poly-(ADP-ribose) polymerase (PARP) were found to be beneficial in many pathophysiological conditions associated with oxidative stress and PARP-1 knock-out mice proved to be resistant to bacterial lipopolysaccharide (LPS)-induced septic shock, PARP inhibitors are candidates for such a role. In this study, the mechanism of the protective effect of a potent PARP-1 inhibitor, PJ34 was studied in LPS-induced (20mg/kg, i.p.) septic shock in mice. We demonstrated a significant inflammatory response by magnetic resonance imaging in the dorsal subcutaneous region, in the abdominal regions around the kidneys and in the inter-intestinal cavities. We have found necrotic and apoptotic histological changes as well as obstructed blood vessels in the liver and small intestine. Additionally, we have detected elevated tumor necrosis factor-alpha levels in the serum and nuclear factor kappa B activation in liver of LPS-treated mice. Pre-treating the animals with PJ34 (10mg/kg, i.p.), before the LPS challenge, besides rescuing the animals from LPS-induced death, attenuated all these changes presumably by activating the phosphatidylinositol 3-kinase-Akt/protein kinase B cytoprotective pathway.

Animals↗

PubMed2002

2,2,5,5-Tetramethylpyrroline-based compounds in prevention of oxyradical-induced myocardial damage.

Reactive oxygen species have been known to play a major role in a wide variety of pathophysiologic processes. A new compound, H-2545, based on a 2,2,5,5-tetramethyl-3-pyrroline-3-carboxamide structure, has been reported to exhibit antiarrhythmic function as well as favorable antioxidant properties. Studies were performed in an isolated rat heart model to measure the efficacy of H-2545 and its metabolite, H-2954, in preventing ischemia-reperfusion and hydrogen peroxide-induced oxidative myocardial damage: lipid peroxidation, protein oxidation, activity of respiratory complexes, NAD, and high-energy phosphate metabolism. The cardioprotective effects of examined compounds were compared with that of a well-known water-soluble vitamin E analog, Trolox. To determine whether the antioxidant property of H-2545 is due to the pyrroline ring, the scavenger effects of mexiletine and HO-2434 (mexiletine substituted with a pyrroline group) were compared. The results showed that H-2545 decreased significantly the ischemia-reperfusion-induced thiobarbituric acid reactive substance (TBARS) formation, the protein oxidation and ssDNA break formation in perfused rat hearts. H-2545 decreased the NAD loss in postischemic hearts. The activity of respiratory complexes, myocardial energy metabolism, and functional myocardial recovery were also improved during reperfusion by adding H-2545 to the perfusion medium. H-2954 exerted significantly lower protection against ischemia-reperfusion-induced myocardial injury than H-2545, and it was comparable to that of Trolox. Both H-2545 and H-2954 are highly effective against H O -induced oxidative myocardial cell damage. The findings show that substitution of mexiletine with a 2,2,5,5-tetramethyl-pyrroline group (HO-2434) increased its antioxidant and cardioprotective effects. In conclusion, these results suggest that sterically hindered pyrroline derivatives accumulating in membranes can be highly effective at preventing oxidative myocardial cell damage.

Animals↗