Vascular Endothelial Dysfunction in β-Thalassemia Occurs Despite Increased eNOS Expression and Preserved Vascular Smooth Muscle Cell Reactivity to NO

The hereditary β-thalassemia major condition requires regular lifelong blood transfusions. Transfusion-related iron overloading has been associated with the onset of cardiovascular complications, including cardiac dysfunction and vascular anomalies. By using an untransfused murine model of β-thalassemia major, we tested the hypothesis that vascular endothelial dysfunction, alterations of arterial structure and of its mechanical properties would occur despite the absence of treatments.Vascular function and structure were evaluated ex vivo. Compared to the controls, endothelium-dependent vasodilation with acetylcholine was blunted in mesenteric resistance arteries of β-thalassemic mice while the endothelium-independent vasodilator (sodium nitroprusside) produced comparable vessel dilation, indicating endothelial cell impairment with preserved smooth muscle cell reactivity to nitric oxide (NO). While these findings suggest a decrease in NO bioavailability, Western blotting showed heightened expression of aortic endothelial NO synthase (eNOS) in β-thalassemia. Vascular remodeling of the common carotid arteries revealed increased medial elastin content. Under isobaric conditions, the carotid arteries of β-thalassemic mice exhibited decreased wall stress and softening due to structural changes of the vessel wall.A complex vasculopathy was identified in untransfused β-thalassemic mice characterized by altered carotid artery structure and endothelial dysfunction of resistance arterioles, likely attributable to reduced NO bioavailability despite enhanced vascular eNOS expression

Polar extracts from (Tunisian) Acacia salicina Lindl. Study of the antimicrobial and antigenotoxic activities

<p>Abstract</p> <p>Background</p> <p>Methanolic, aqueous and Total Oligomer Flavonoids (TOF)-enriched extracts obtained from the leaves of <it>Acacia salicina </it>'Lindl.' were investigated for antibacterial, antimutagenic and antioxidant activities.</p> <p>Methods</p> <p>The antimicrobial activity was tested on the Gram positive and Gram negative reference bacterial strains. The Mutagenic and antimutagenic activities against direct acting mutagens, methylmethane sulfonate (MMS) and 4-nitro-o-phenylenediamine (NOPD), and indirect acting mutagens, 2-aminoanthracene (2-AA) and benzo[a]pyrene (B(a)P) were performed with <it>S. typhimurium </it>TA102 and TA98 assay systems. In addition, the enzymatic and nonenzymatic methods were employed to evaluate the anti-oxidative effects of the tested extracts.</p> <p>Results</p> <p>A significant effect against the Gram positive and Gram negative reference bacterial strains was observed with all the extracts. The mutagenic and antimutagenic studies revealed that all the extracts decreased the mutagenicity induced by B(a)P (7.5 μg/plate), 2-AA (5 μg/plate), MMS (1.3 mg/plate) and NOPD (10 μg/plate). Likewise, all the extracts showed an important free radical scavenging activity towards the superoxide anion generated by the xanthine/xanthine oxidase assay system, as well as high Trolox Equivalent Antioxidant Capacity (TEAC), against the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS)⁺• radical. TOF-enriched extract exhibited the highest protective effect against free radicals, direct acting-mutagen and metabolically activated S9-dependent mutagens.</p> <p>Conclusions</p> <p>The present study indicates that the extracts from <it>A. salicina </it>leaves are a significant source of compounds with the antimutagenic and antioxidant activities, and this may be useful for developing potential chemopreventive substances.</p

Corrélations entre méthode de préparation, hauteur de barrière et états d'interface dans les contacts métal-GaAs

Interface states distribution in metal-semiconductor contacts can be determined by studying variations of Schottky diode capacitance as a function of frequency, temperature and forward bias. This method, called Schottky Capacitance Spectroscopy is applied to contacts between Ag, Au, Al and diversely prepared surfaces : cleavage under ultra-high vacuum or controlled gazeous atmosphere, cleavage followed by ion-bombardment, chemical etch, molecular beam epitaxy. So, the rôle played by a great number of physical parameters on interface states distribution and barrier height can be determined. It is established that only the creation of a severely perturbed interfacial zone of a few angströms width can significantly modify the properties of the barrier.La distribution des états d'interface dans un contact métal-semiconducteur peut être déterminée à partir de l'étude du comportement de la capacité dynamique d'une diode Schottky sous polarisation directe en fonction de la fréquence, la température et la tension appliquée. Cette méthode, appelée Spectroscopie de Capacité Schottky est appliquée à des dépôts d'Ag, Au et Al sur des surfaces de GaAs préparées de manières très diverses : clivage sous ultravide ou sous gaz, clivage suivi de bombardement ionique, nettoyage chimique, épitaxie par jets moléculaires. Ceci permet de tester le rôle joué par un grand nombre de paramètres sur la distribution des états d'interface et la hauteur de barrière. On constate que ces propriétés ne sont affectées de manière importante que par la création d'une zone interfaciale fortement perturbée, s'étendant sur plusieurs couches atomiques

methodological approach

The present study provides molecular insight into the effect of thymol and carvacrol on the oxidative damage caused to myofibrillar proteins by a hydroxyl-radical generating system (HAGS). An innovative model system was designed, in which gels, prepared with increasing levels of myofibrillar proteins, were oxidized by a HRGS (Fe3+ /H2O2, 60 degrees C and 7 days) in the presence of lipids. The molecular affinity between myofibrillar proteins and both terpenes, as well as their effect on the oxidative stability of the gel systems, were studied using a nondestructive and solvent-free procedure based on fluorescence spectroscopy. Carvacrol displayed more affinity than thymol for establishing chemical interactions with protein residues. Both terpenes exhibited a significant antioxidant potential against the generation of lipid-derived volatile carbonyls and against the formation of protein crosslinking. This procedure may be applied to meat products to assess the effectiveness of a given antioxidant additive without size reduction or sample processing

Protective Effect of Astaxanthin on Primary Retinal Cells of the Gerbil Psammomys Obesus Cultured in Diabetic Milieu

Astaxanthin is a major marine carotenoid with powerful antioxidant and neuroprotective properties. The in vitro protective effect of astaxanthin in adult retinal cells of the type-2 diabetic model Psammomys obesus in hyperglycemic conditions was investigated. Primary retinal cells were cultured in normal (5 mM) or high concentrations of glucose (25 and 40 mM) for 5 days and treated with 1-20 μM astaxanthin for the last 48 h of culturing. Mitochondrial dehydrogenase activity and cell viability were assessed using MTT test and trypan blue exclusion dye. Retinal cells were characterized by immunohistochemistry. The results showed that mitochondrial function increased significantly (P&lt;0.05) with 5-20 μM astaxanthin in 25-40 mM glucose. At 10 μM astaxanthin, cell viability recovered to 78.51±5.81% and 54.37±9.64% of control in 25 and 40 mM, respectively. Neurons and glial cells expression were enhanced in elevated glucose conditions. These finding suggest that astaxanthin exerted neuroprotection against high glucose induced- retinal damage. Practical Applications: The xanthophyll astaxanthin is found in many marine food sources such as shrimp. The cytoprotective and antioxidant capacity of astaxanthin in retinal disease has been pointed out and presented as a promising therapeutic strategy. The present study shows that astaxanthin can interfere with hyperglycemia-induced retinal cell death and that primary retinal culture of Psammomys obesus may represent an effective system to explore astaxanthin antioxidant mechanisms in diabetic retinopathy

Chemical Composition and Cytotoxic Activity of Eucalyptus torquata Luehm. and Eucalyptus salmonophloia F. Muell. Trunk Bark Essential Oils against Human SW620 and MDA-MB-231 Cancer Cell Lines

In recent years, there has been a growing interest in the screening of natural active ingredients from Eucalyptus essential oils because of their evident importance in practical utility and their undeniable therapeutic properties. Based on this, the aim of the present study was to investigate the chemical profile of the essential oils of the trunk bark of Eucalyptus torquata Luehm. (ETEO), and E. salmonophloia F. Muell. (ESEO), growing in Tunisia. The in vitro cytotoxic properties of the extracted EOs were also evaluated against two human cancer cell lines: breast carcinoma cell lines MDA-MB-231 and colorectal cancer cell lines SW620. The analysis by gas chromatography coupled with mass spectrometry (GC/MS) led to the identification of 32 compounds from the ETEO, with the dominant constituents being the monoterpenes trans-myrtanol (73.4 %) and myrtenol (4.7 %), and the apocarotene (E)-β-ionone (3.9 %). In the case of ESEO, 29 compounds were identified with trans-myrtanol (25.0 %), decanoic acid (22.1 %), nonanoic acid (9.8 %), γ-elemene (6.5 %), γ-maaliene (5.5 %), and α-terpineol (5.3 %) as the main components. The cytotoxicity of EOs against the two chosen cell lines was tested using Crystal Violet Staining (CVS) assay and 5-fluorouracil as a reference drug. The two EOs exhibited a significant dose-dependent inhibition against the viability of the used cell lines. Their inhibitory effects were particularly observed towards SW620 colon carcinoma cells with IC50 values of 26.71±1.22 and 22.21±0.85 μg/mL, respectively, indicating that both oils were more cytotoxic for SW620 cells compared to MDA-MB-231 one