The interaction of sodium chlorite with phospholipids and glutathione: a comparison of effects in vitro,in mammalian and in microbial cells

In this study the interaction of the preservative sodium chlorite with unsaturated lipids and glutathione was investigated, in comparison with peroxides, sodium hypochlorite, and benzalkonium chloride. The aim was to determine whether the action of sodium chlorite could involve membrane lipid damage or antioxidant depletion, and how this related to toxicity in both mammalian and microbial cells. The treatment of phospholipids with chlorite yielded low levels of hydroperoxides, but sodium chlorite oxidized the thiol-containing antioxidant glutathione to its disulfide form very readily in vitro, with a 1:4 oxidant:GSH stoichiometry. In cultured cells, sodium chlorite also caused a substantial depletion of intracellular glutathione, whereas lipid oxidation was not very prominent. Sodium chlorite had a lower toxicity to ocular mammalian cells than benzalkonium chloride, which could be responsible for the different effects of long-term application in the eye. The fungal cells, which were most resistant to sodium chlorite, maintained higher percentage levels of intracellular glutathione during treatment than the mammalian cells. The results show that sodium chlorite can cause oxidative stress in cells, and suggest that cell damage is more likely to be due to interaction with thiol compounds than with cell membrane lipids. The study also provides important information about the differential resistance of ocular cells and microbes to various preservatives and oxidants.     

Environmental assessment of municipal wastewater discharges: a comparative study of evaluation methods

Purpose

Wastewater treatment plants produce high environmental impacts on receiving water bodies and pose economic burdens on municipalities or industrial facilities. Their overall operational costs and achieved effluent quality depend very much on the influent type, presence of priority pollutants, treatment technology and required effluent quality (for discharge or for recycle/reuse). Life cycle assessment (LCA), environmental impact quantification (EIQ) and water footprint (WF) are important instruments for sustainability assessments applied for products, production and consumption evaluations in connection with natural resources depletion and pollution threats. This study focuses on the environmental assessment of a municipal wastewater treatment plant (MWWTP) discharges by means of these three evaluation methods with the purpose to understand their (methodological) weak and strong points in capturing the impacts. Such a comparative analysis is necessary to understand how the (individual) advantages provided by each of these instruments can be complimentarily used to improve an assessment framework for various stakeholders concerned with water use cycle management (regional water operators, water management authority, public authorities, research entities, societal organizations, etc.).

Methods

The three assessment methodologies (LCA, EIQ, WF) are presented, implemented and critically analysed based on a unitary set of data concerning the MWWTP of Iasi city (a municipality of approx. 300,000 inhabitants situated in the North Eastern region of Romania), the wastewater and river water quality indicators as well as all the other relevant data being collected for the year 2012.

Results and discussion

Although the three methodologies have different principles for environmental impact quantification, the results have shown that most impacts induced to surface waters due to Iasi MWWTP effluents are given by the nutrients (nitrogen and phosphorous compounds), which could induce an eutrophication impact, and to a lesser extent by pollutants responsible for toxicity impacts (such as heavy metals).

Conclusions

Based on the results of this comparative study, a critical analysis of these three methods was realized by considering the data requirements, their development and integration status. Furthermore, the strong and weak points that are relevant for each method implementation and their subsequent use by decision-makers and Water Authorities are discussed, in the context of legislative requirements (including the Water Framework Directive), actual development of regional water operators and stakeholders' interests.

     

Specific [3H]quinuclidinyl benzilate binding activity in Digitonin-solubilized preparations from bovine brain

Receptors for the specific muscarinic radioligand [³H]quinuclidinyl benzilate ([³H]QNB) were solubilized by digitonin from a particulate preparation of bovine brain without significant alteration in binding affinities for muscarinic antagonists. Electron microscopy and sucrose density gradient sedimentation analysis confirmed the solubility of these receptors in aqueous solutions of digitonin. Equilibrium and kinetic studies of [³H]QNB binding to solubilized receptors indicated that binding was stereoselective and was blocked by muscarinic compounds. These tests permit tentative identification of digitonin-solubilized [³H]QNB binding sites as muscarinic acetylcholine receptors. Digitonin-solubilized receptors were homogeneous with respect to sedimentation behavior and binding affinities for agonist and antagonist drugs, unlike membrane-bound receptors. Enzyme digestion studies and treatment with group-specific reagents indicated that muscarinic receptors are proteins whose binding activity could be disrupted by reduction with dithiothreitol or by modification of sulfhydryl residues.     

Association between Ag1-CA Alleles and Severity of Autosomal Recessive Proximal Spinal Muscular Atrophy

The gene for autosomal recessive proximal spinal muscular atrophy (SMA) has been mapped to an 850-kb interval on 5q11.2-q13.3, between the centromeric D5S823 and telomeric D5S557 markers. We report a new complex marker, Ag1-CA, that lies in this interval, whose primers produce one, two, or rarely three amplification-fragment-length variants (AFLVs) per allele. Class I chromosomes are those which amplify a single AFLV allele, and class II chromosomes are those which amplify an allele with two or three AFLVs. Ag1-CA shows highly significant allelic association with type I SMA in both the French Canadian (Hôpital Sainte-Justine [HSJ]) and American (Ohio State University [OSU]) populations (P<.0001). Significant association between the Ag1-CA genotype and disease severity was also observed. Type I patients were predominantly homozygous for class I chromosomes (P=.0003 OSU; P=.0012 HSJ), whereas the majority of type II patients were heterozygous for class I and II chromosomes (P=.0014 OSU; P=.001 HSJ). There was no significant difference in Ag1-CA genotype frequencies between type III patients (P=.5 OSU; P=.25 HSJ) and the paired normal chromosomes from both carrier parents. Our results indicate that Ag1-CA is the most closely linked marker to SMA and defines the critical candidate-gene region. Finally, we have proposed a model that should be taken into consideration when screening candidate SMA genes.     

Ecology of bottom biocoenoses in the possjet bay (the Sea of Japan) and the peculiarities of their distribution in connection with physical and chemical conditions of the habitat

Summary 1. By employing autonomous diving techniques, direct observations on the biocoenoses of the upper marine zones were carried out. The population of each biotope was studied quantitatively in areas from 100 m² to 1/10 or 1/100 m² depending on size and density of the organisms studied.2. The quality and quantity of bottom organisms depend not only on the nature of the ground, other physico-chemical environmental factors or the quantity of food available, but also on the biocoenotic background, i. e. conditions created by aggregations of certain species whose presence create additional, new niches.3. In estuaries and lagoons, salinity greatly affects biocoenosis composition. The effect of salinity changes increases from phytal and epifauna to infauna elements, a fact which may be associated with the relatively higher salinity inside the bottom substratum.4. The most highly effective force in determining distribution, composition and biogeographical structure of biocoenoses is the water temperature (absolute values as well as fluctuations).5. In half-closed areas of bays the patchiness of biocoenoses tends to increase and the territories occupied become smaller. These changes may be associated with (a) higher fluctuations of physico-chemical conditions, (b) their increased variety and (c) accelerated succession.6. There is the closest connection between the distribution of organisms and the position of the layers of definite water masses in the system of vertical marine zones. In the Bay of Possjet the low border of the particular vertical zone lies at a depth of 5 m (0 to 5 m); its location is determined by the position of the upper layer of the surface Japanese marine water mass.7. When carrying out biogeographical studies, in addition to comparing similar vertical zones, one should consider bionomically similar areas.

---

Ökologie der Bodenbiozönosen in der Posjet-Bucht (Japanisches Meer) und die Besonderheiten ihrer Verbreitung in Verbindung mit physikalischen und chemischen Bedingungen des Habitats

Kurzfassung Verbreitung und Zusammensetzung der Fauna und Flora der reichbesiedelten, oberen marinen Wasserzonen sind nur ungenügend bekannt, weil große Forschungsschiffe mit geeigneten Einrichtungen zum Sammeln und zur Datenverarbeitung in küstennahen Gewässern wegen der geringen Wassertiefe nicht arbeiten können. Die Anwendung autonomer Tauchausrüstungen hat es uns ermöglicht, direkte Beobachtungen an litoralen Biozönosen durchzuführen. Je nach Größe und Besiedlungsdichte der angetroffenen Organismen haben wir Areale von 100 m² bis zu 1/100 m² untersucht. Qualität und Quantität der Boden-organismen hängen nicht nur von der Beschaffenheit des Untergrundes ab, sondern auch von physiko-chemischen Umweltfaktoren sowie vom Nahrungsangebot und dem biozönotischen Hintergrund (biotischen Faktoren). In Ästuarien und Lagunen beeinflußt der Salzgehalt in starkem Maße die artliche Zusammensetzung der Biozönose, wobei der Salzgehaltseinfluß in der Endofauna geringer ist als im Phytal und bei der Epifauna — ein Umstand, der vermutlich mit dem relativ höheren Salzgehalt innerhalb des Bodens zusammenhängt. Verbreitung, Komposition und biographische Struktur der Biozönosen werden primär von der Wassertemperatur (absolute Intensität und Fluktuationsmuster) beeinflußt. In halb abgeschlossenen Meeresbuchten und flachen Litoralgebieten neigen die Biozönosen immer mehr zu kleinflächigen Verbreitungsmustern. Diese Veränderungen hängen möglicherweise zusammen mit (a) intensiveren Fluktuationen der physiko-chemischen Verhältnsse, (b) deren zunehmende Variabilität und (c) beschleunigter Sukzession. Die Verbreitung der Organismen ist sehr eng gebunden an die Positionen bestimmter Wassermassen. Bei der Durchführung biogeographischer Studien sollten — zusätzlich zu Vergleichen ähnlicher Vertikalzonen — bionomisch ähnliche Gebiete analysiert werden. Die Einwanderung von Warmwasserorganismen von einer Warmwasserzone in die andere erfolgt vermutlich während Perioden, in denen die intermediären Gebiete starken Oberflächenerwärmungen ausgesetzt sind.

     

The Role of Propagating and Localized Surface Plasmons for SERS Enhancement in Periodic Nanostructures

Periodic arrays of plasmonic nanopillars have been shown to provide large, uniform surface-enhanced Raman scattering (SERS) enhancements. We show that these enhancements are the result of the combined impact of localized and propagating surface plasmon modes within the plasmonic architecture. Here, arrays of periodically arranged silicon nanopillars of varying sizes and interpillar gaps were fabricated to enable the exploration of the SERS response from two different structures; one featuring only localized surface plasmon (LSP) modes and the other featuring LSP and propagating (PSP) modes. It is shown that the LSP modes determine the optimal architecture, and thereby determine the optimum diameter for the structures at a given incident. However, the increase in the SERS enhancement factor for a system in which LSP and PSP cooperatively interact was measured to be over an order of magnitude higher and the peak in the diameter dependence was significantly broadened, thus, such structures not only provide larger enhancement factors but are also more forgiving of lithographic variations.     

A Comparison of the Effects of Ocular Preservatives on Mammalian and Microbial ATP and Glutathione Levels

The aim of this study was to investigate the mechanism of action of the preservative sodium chlorite (NaClO²), and the relationship with intracellular glutathione depletion. A detailed comparison of the dose responses of two cultured ocular epithelial cell types and four species of microorganism was carried out, and comparisons were also made with the quaternary ammonium compound benzalkonium chloride (BAK), and the oxidant hydrogen peroxide (H²O²). The viability of mammalian and microbial cells was assessed in the same way, by the measurement of intracellular ATP using a bioluminescence method. Intracellular total glutathione was measured by reaction with 5,5′-dithiobis-2-nitrobenzoic acid in a glutathione reductase-dependent recycling assay. BAK and H²O² caused complete toxicity to conjunctival and corneal epithelial cells at ～25?ppm, in contrast to NaClO², where >100?ppm was required. The fungi Candida albicans and Alternaria alternata had a higher resistance to NaClO² than the bacteria Staphyloccus aureus and Pseudomonas aeruginosa, but the bacteria were extremely resistant to H²O². NaClO² caused substantial depletion of intracellular glutathione in all cell types, at concentrations ranging from <10?ppm in Pseudomonas, 25–100?ppm in epithelial cells, to >500?ppm in fungal cells. The mechanisms of cytotoxicity of NaClO², H²O² and BAK all appeared to differ. NaClO² was found to have the best balance of high antibacterial toxicity with low ocular toxicity. The lower toxicity of NaClO² to the ocular cells, compared with BAK and H²O², is in agreement with fewer reported adverse effects of application in the eye.     

Mechanisms of resistance to BCR-ABL and other kinase inhibitors

In this article, we are reviewing the molecular mechanisms that lead to kinase inhibitor resistance. As the oncogenic BCR-ABL kinase is the target of the first approved small-molecule kinase inhibitor imatinib, we will first focus on the structural and mechanistic basis for imatinib resistance. We will then show ways how next generations of BCR-ABL inhibitors and alternative targeting strategies have helped to offer effective treatment options for imatinib-resistant patients. Based on these insights, we discuss commonalities and further mechanisms that lead to resistance to other kinase inhibitors in solid tumors. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases (2012).     

Amaranth oil reduces accumulation of 4-hydroxynonenal-histidine adducts in gastric mucosa and improves heart rate variability in duodenal peptic ulcer patients undergoing Helicobacter pylori eradication

Helicobacter pylori-induced oxidative stress in gastric mucosa (GM) is a milieu for the development of chronic gastritis, duodenal peptic ulcer (DPU), gastric cancer, and a number of extragastric diseases. Because our previous study revealed the accumulation of the protein adducts of lipid peroxidation product 4-hydroxynonenal (HNE) in GM, which persists after eradication of H. pylori, the aim of the study was to test whether Amaranth oil supplementation in addition to standard anti-Helicobacter treatment could prevent such accumulation of HNE in GM in H. pylori-positive DPU patients. Seventy-five patients were randomly split into two groups: group 1 – standard treatment (n?=?39) and group 2 – standard treatment with additional supplementation of 1?ml of concentrated oil from amaranth seeds (Amaranthus cruenthus L., n?=?36). Clinical analysis, including endoscopy with biopsies from antrum and corpus of the stomach were performed before and after the treatment, as was heart rate variability (HRV) recorded, as parameter of systemic, extragastric pathophysiological alterations in DPU patients. Improvement of clinical, endoscopic and histologic manifestations, and successful ulcer healing were observed in both the groups. Moreover, supplementation of amaranth oil in addition to standard anti-H. pylori treatment significantly reduced accumulation of HNE-histidine adducts in GM and increased HRV in DPU patients (p?相似文献