Evolution of liver antioxidant status and iron implication during the development of deoxycorticosterone-saline hypertension in rats

Hypertension is known to be associated with an oxidative stress resulting from an imbalance of antioxidant defense mechanisms in various tissues. The purpose of this study was to investigate the relationship between the increase of arterial blood pressure, measured during the gradual development of experimental hypertension in deoxycorticosterone (DOCA)-salt-treated rats, and an early imbalance of liver antioxidant status. The levels of liver oxidant/antioxidant markers and iron were studied during the induction of hypertension in 3-, 6-, and 8-wk DOCA-salt-treated Sprague-Dawley rats. Hepatic antioxidant defenses were decreased as early as 3 wk of hypertensive treatment: the decrease of peroxidase-reductase-transferase and catalase activities was associated with a significant increase of thiobarbituric acid reactive substances (TBARS) levels. Liver oxidative stress increased until 6 wk, and remained stable at 8 wk of DOCA-salt treatment. Concurrently, liver iron levels were increased at 6 wk and returned to normal values after 8 wk of hypertensive treatment. Iron seems to be an inductor of liver oxidative stress and responsible for the persistent oxidative stress, most likely through secondary free-radical release. Thus, our data (1) confirm that hypertension in DOCA-salt-treated rats might be a free-radical-dependent disease where hepatic oxidant/antioxidant imbalance is obviously involved from the beginning of blood pressure elevation and (2) suggest that the use of suitable iron chelators might reverse liver oxidative stress associated with the increase of blood pressure.     

Electrocoagulation of olive mill wastewaters to enhance biogas production

Objectives

To assess the combination of electrocoagulation and anaerobic co-digestion of olive mill wastewaters (OMWW) with other substrates, such as chicken manure, in a continuous stirred tank reactor for biogas production.

Results

Anaerobic digestion of OMWW treated by electrocoagulation allowed higher production of biogas, up to 0.74 l biogas g^?1 COD introduced compared to untreated or diluted olive mill wastewaters (OMWW) (0.37 and 0.6 l biogas g^?1 COD) respectively. Pretreated OMWW co-digested with chicken manure at different volumic ratios OMWW/manure in a continuous stirred tank reactor under mesophilic conditions revealed that OMWW/manure (7:3 v/v) was optimal for biogas production and process stability.

Conclusion

Anaerobic digestion could achieve promising results in depollution and valorization of OMWW under a continuous stirred tank reactor.

     

Données paléoenvironnementales sur le Vraconnien/Cénomanien de la région de Tébessa (Atlas Saharien,nord-est Algérie). Caractérisation de l’OAE2

The micropalaeontological content of five sections, located in Northeastern Algeria (Saharan Atlas) was investigated by means of washing/counting of microfossils in marly levels, and microfacies analyses of calcareous levels. In these levels of Upper Cretaceous age, hundred species of foraminifera were identified but only about 15 species of ostracoda and about ten of radiolaria. This work allows, first of all, to establish a rather precise stratigraphic frame, in particular by means of studying planktonic foraminifera. Two to five biozones were defined, between the Vraconnian (Th. Appenninica biozone) and the early Turonian (Whiteinella archaeocretacea biozone, then Helvetoglobotruncana Helvetica biozone for certain sections). Secondly, the quantitative analyses led on foraminifera allowed the definition of palaeoenvironment. The ratio P/P+B, generally very high, coupled with a little diversified benthonic microfauna, indicates a calm and deep environment, of external platform or slope type. Furthermore, at numerous levels, various indications give evidence of the existence of a strong surface productivity (presence of upwellings), responsible for the proliferation of radiolaria (late Vraconnian/early Cenomanian especially) or of globular planktonic foraminifera (hedbergellids/heterohelicids); being both associated with low-oxygen deep waters. Two anoxic events were also revealed, the first one at the end of Vraconnian (OAE1d) and the second at the end of Cenomanian (OAE2). This last event in particular was characterized on all the sections, in a more or less detailed way, thanks to the identification of certain indicator: Heterohelix “bloom”, “filament” event, disappearance of rotaliporids, presence of “blackshales” strongly enriched in organic matter (Bahloul levels).     

Enhanced Hepatic apoA-I Secretion and Peripheral Efflux of Cholesterol and Phospholipid in CD36 Null Mice

CD36 facilitates oxidized low density lipoprotein uptake and is implicated in development of atherosclerotic lesions. CD36 also binds unmodified high and very low density lipoproteins (HDL, VLDL) but its role in the metabolism of these particles is unclear. Several polymorphisms in the CD36 gene were recently shown to associate with serum HDL cholesterol. To gain insight into potential mechanisms for these associations we examined HDL metabolism in CD36 null (CD36^−/−) mice. Feeding CD36^−/− mice a high cholesterol diet significantly increased serum HDL, cholesterol and phospholipids, as compared to wild type mice. HDL apolipoproteins apoA-I and apoA-IV were increased and shifted to higher density HDL fractions suggesting altered particle maturation. Clearance of dual-labeled HDL was unchanged in CD36^−/− mice and cholesterol uptake from HDL or LDL by isolated CD36^−/− hepatocytes was unaltered. However, CD36^−/− hepatocytes had higher cholesterol and phospholipid efflux rates. In addition, expression and secretion of apoA-I and apoA-IV were increased reflecting enhanced PXR. Similar to hepatocytes, cholesterol and phospholipid efflux were enhanced in CD36^−/− macrophages without changes in protein levels of ABCA1, ABCG1 or SR-B1. However, biotinylation assays showed increased surface ABCA1 localization in CD36^−/− cells. In conclusion, CD36 influences reverse cholesterol transport and hepatic ApoA-I production. Both pathways are enhanced in CD36 deficiency, increasing HDL concentrations, which suggests the potential benefit of CD36 inhibition.     

Inflammatory responses of a macrophage/epithelial cell co-culture model to mono and mixed infections with Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia

Accumulated evidence points to Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia as three major etiologic agents of chronic periodontitis. Epithelial cells and macrophages play a major role in the host response to periodontopathogens, and the secretion of inflammatory mediators and matrix metalloproteinases (MMPs) by these host cells is believed to contribute to periodontal tissue destruction. The aim of this study was to investigate the inflammatory response of a macrophage/epithelial cell co-culture model following mono or mixed infections with the above three periodontopathogens. An in vitro co-culture model composed of epithelial-like transformed cells (HeLa cell line) and macrophage-like cells (phorbol myristic acid-differentiated U937 monocytic cell line) was challenged with whole cells or lipopolysaccharides (LPS) of P. gingivalis, T. denticola, and T. forsythia, individually and in combination. Following stimulation, the production of interleukin-1 beta (IL-1beta), IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), regulated on activation normal T cell expressed and secreted (RANTES), prostaglandin E2 (PGE2), and MMP-9 were quantified by enzyme-linked immunoassays. We observed that mono or mixed infections of the co-culture model induced the secretion of IL-1beta, IL-6, IL-8, PGE2, and MMP-9. P. gingivalis and T. forsythia induced an increase in RANTES secretion, whereas T. denticola alone or in combination resulted in a significant decrease in RANTES levels. All LPS challenges induced an increase in chemokine, MMP-9, and PGE2 production. No synergistic effect on the production of cytokines, chemokines, PGE2, and MMP-9 was observed for any of the bacterial or LPS mixtures tested. This study supports the view that P. gingivalis, T. denticola, and T. forsythia may induce high levels of pro-inflammatory mediators and MMP-9 in periodontal lesions, thus contributing to the progression of periodontitis.     

Aphid clonal resistance to a parasitoid fails under heat stress

Parasitoid virulence and host resistance are complex interactions depending on metabolic rate and cellular activity, which in aphids additionally implicate heritable secondary symbionts among the Enterobacteriaceae. As performance of the parasitoid, the aphid host and its symbionts may differentially respond to temperature, the success or failure of aphid parasitism is difficult to predict when temperature varies. We tested the hypothesis that resistance of the pea aphid Acyrthosiphon pisum to the parasitoid Aphidius ervi, which is linked to aphid secondary symbionts, may depend on temperature in several resistant and non-resistant aphid clonal lineages of different geographic origin and of known bacterial symbiosis, using experiments in controlled environments. Complete immunity to A. ervi at 20 degrees C in three different aphid clones whose symbiosis is characterized by the possession of Hamiltonella defensa reversed to high susceptibility at 25 degrees C and especially 30 degrees C, suggesting that the aphid's immune responses to the establishment and early development of the parasitoid is strongly reduced at moderately high temperatures. There was no evidence that a pea aphid control genotype that was susceptible to A. ervi at 20 degrees C could become more resistant as temperature increases, as has been suggested for insect fungal pathogens. By contrast, our results suggest that aphid clonal resistance to A. ervi and related parasitoids is characteristic of cool temperature conditions, similar to various other fitness attributes of aphids. Based on evidence that H. defensa symbionts characterized all three A. ervi resistant pea aphid clones studied, but was absent in control aphids that remained susceptible at all temperatures, we suggest that secondary symbiosis plays a key role in the heat sensitivity of aphid clonal resistance. Our study may also indicate that aphid natural control of variably susceptible host populations by aphid parasitoids is more likely at moderate to high temperatures.     

Effect of periodontopathogen lipopolysaccharides and proinflammatory cytokines on CD46, CD55, and CD59 gene/protein expression by oral epithelial cells

Membrane-anchored complement regulatory proteins (CRPs), including CD46, CD55, and CD59, protect host cells from complement attack. In the present study, we investigated whether periodontopathogen lipopolysaccharide and proinflammatory cytokines modulate CRP gene/protein expression in human oral epithelial cells. The lipopolysaccharide of Treponema denticola and Tannerella forsythia were the most potent for increasing the gene expression of CD55 and CD59, and to a lesser extent CD46, after a 48-h stimulation. An lipopolysaccharide-induced upregulation of epithelial cell-surface CRP was also demonstrated. The stimulation of epithelial cells with lipopolysaccharide was associated with interleukin-6 (IL-6) and IL-8 secretion. Although these two cytokines had no effect on CD46 and CD55 gene expression in epithelial cells, IL-1β and tumor necrosis factor-α induced a significant upregulation. The cell-surface expression of CRP was also increased by the stimulation of epithelial cells with cytokines. The CD46, CD55, and CD59 gene/protein expression was upregulated by periodontopathogen lipopolysaccharide and proinflammatory cytokines. It can be hypothesized that, when faced with bacterial challenges and inflammatory conditions associated with active periodontal sites, oral epithelial cells may respond by increasing CRP gene/protein expression to avoid cell lysis by the complement system, which is activated during periodontitis.     

Towards better digital pathology workflows: programming libraries for high-speed sharpness assessment of Whole Slide Images

Background

Since microscopic slides can now be automatically digitized and integrated in the clinical workflow, quality assessment of Whole Slide Images (WSI) has become a crucial issue. We present a no-reference quality assessment method that has been thoroughly tested since 2010 and is under implementation in multiple sites, both public university-hospitals and private entities. It is part of the FlexMIm R&D project which aims to improve the global workflow of digital pathology. For these uses, we have developed two programming libraries, in Java and Python, which can be integrated in various types of WSI acquisition systems, viewers and image analysis tools.

Methods

Development and testing have been carried out on a MacBook Pro i7 and on a bi-Xeon 2.7GHz server. Libraries implementing the blur assessment method have been developed in Java, Python, PHP5 and MySQL5. For web applications, JavaScript, Ajax, JSON and Sockets were also used, as well as the Google Maps API. Aperio SVS files were converted into the Google Maps format using VIPS and Openslide libraries.

Results

We designed the Java library as a Service Provider Interface (SPI), extendable by third parties. Analysis is computed in real-time (3 billion pixels per minute). Tests were made on 5000 single images, 200 NDPI WSI, 100 Aperio SVS WSI converted to the Google Maps format.

Conclusions

Applications based on our method and libraries can be used upstream, as calibration and quality control tool for the WSI acquisition systems, or as tools to reacquire tiles while the WSI is being scanned. They can also be used downstream to reacquire the complete slides that are below the quality threshold for surgical pathology analysis. WSI may also be displayed in a smarter way by sending and displaying the regions of highest quality before other regions. Such quality assessment scores could be integrated as WSI's metadata shared in clinical, research or teaching contexts, for a more efficient medical informatics workflow.