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81.
Gómez-Lechón MJ Ponsoda X Bort R Castell JV 《Alternatives to laboratory animals : ATLA》2001,29(3):225-231
Hepatotoxins can be classified as intrinsic when they exert their effects on all individuals in a dose-dependent manner, and as idiosyncratic when their effects are the consequence of an abnormal metabolism of the drug by susceptible individuals (metabolic idiosyncrasy) or of an immune-mediated injury to hepatocytes (allergic hepatitis). Some xenobiotics are electrophilic, and others are biotransformed by the liver into highly reactive metabolites that are usually more toxic than the parent compound. This activation process is the key to many hepatotoxic phenomena. Mitochondria are a frequent target of hepatotoxic drugs, and the alteration of their function has immediate effects on the energy balance of cells (depletion of ATP). Lipid peroxidation, oxidative stress, alteration of Ca(2+) homeostasis, and covalent binding to cell macromolecules are the molecular mechanisms that are frequently involved in the toxicity of xenobiotics. Against these potential hazards, cells have their own defence mechanisms (for example, glutathione, DNA repair, suicide inactivation). Ultimately, toxicity is the balance between bioactivation and detoxification, which determines whether a reactive metabolite elicits a toxic effect. The ultimate goal of in vitro experiments is to generate the type of scientific information needed to identify compounds that are potentially toxic to man. For this purpose, both the design of the experiments and the interpretation of the results are critical.] 相似文献
82.
1. Elevated proinflammatory cytokines within the central nervous system (CNS) of individuals infected with human immunodeficiency virus (HIV) may contribute to altered CNS processes prior to the onset of AIDS. Most studies of HIV-induced alterations in cytokine expression within the CNS have focused on interleukin (IL)-1 and tumor necrosis factor (TNF).2. We used a ribonuclease protection assay (RPA) to elucidate further the pattern of cytokine mRNA expression in the rat CNS in response to HIV envelope glycoprotein 160 (gp160). Male Sprague–Dawley rats were surgically implanted with a guide cannula directed into a lateral cerebral ventricle. HIV gp160 was injected intracerebroventricularly and rats were sacrificed immediately (time = 0) or at 1, 2, or 4 hr postinjection. Discrete brain regions were dissected, and peripheral glands removed. All tissues were frozen in liquid nitrogen until RNA extraction and assay.3. IL-1, IL-1, TNF-, and TNF mRNAs were constitutively expressed in brain tissues. Central administration of gp160 dramatically increased mRNA expression for IL-1 and TNF in the hypothalamus, hippocampus, brainstem, and cerebellum. Furthermore, although mRNA expression for IL-5, IL-6, and IL-10 was never detected under basal conditions, these mRNAs were increased in brain tissue after administration of gp160. Peak expression in each brain region was detected 2 hr after administration. Multiple cytokine mRNAs were detected in peripheral tissues, but their expression was not altered by central administration of gp160.4. Our results indicate that gp160 induces mRNA expression in brain for cytokines other than IL-1 and TNF. Screening for multiple cytokine mRNA in this manner provides extensive information concerning the particular cytokines that may be involved in HIV-induced pathologies and alterations in CNS processes. 相似文献
83.
Pujol G Baskin TI Casamayor A Cortadellas N Ferrer A Ariño J 《Plant molecular biology》2000,44(4):499-511
The PPX/PP4 Ser/Thr protein phosphatases belong to the type 2A phosphatase subfamily and are present in most eukaryotic organisms. We have previously isolated two closely related DNAs encoding PPX isoforms (PPX-1 and PPX-2) of Arabidopsis thaliana. Here we report the molecular cloning of the genes encoding these proteins. The genes PPX-1 and PPX-2 are composed of eight exons and seven introns located at equivalent positions related to the coding sequences. Whereas the intron-exon organization of the PPX genes is completely different from that of the PP2A-3/PP2A-4 A. thaliana family, specific intron-exon boundaries are conserved among PPX genes from distantly related organisms. Based on GUS expression, both PPX genes show the same spatial and temporal pattern of expression: they are expressed in all the organs and tissues analyzed, and from the earliest stage of development. When PPX proteins were localized to the root in semi-thin methacrylate sections by immunofluorescence, staining was predominantly confined to small organelles, shown to be plastids by co-localization of PPX and ferredoxin. Interestingly, only some ferredoxin-positive plastids were also PPX-positive, and PPX staining was consistently brighter in the epidermis. The localization was confirmed with immunogold and electron microscopy. Our results suggest that, despite its strong sequence conservation, PPX in plants functions differently than in animals. 相似文献
84.
Andrea Masia Maurizo Ventura Hiroshi Gemma Silviero Sansavini 《Plant Growth Regulation》1998,24(2):127-134
The activity of IAA oxidase (IAAox), peroxidases (POD), and polyphenoloxidases (PPO), as affected by different pre-harvest growth regulator treatments (ABA, AVG, NAA, PDJ), was determined in on-tree ripening apples (cv. Golden Delicious) before and during the ethylene climacteric. The production of ethylene was inhibited by AVG and delayed by NAA, whereas ABA and PDJ treatments caused, in the on-tree remaining fruits, a marked fruit drop and a decrease or a slight increase in ethylene levels respectively. While all treatments reduced POD activity, jasmonate increased IAAox and PPO activity. The inhibitory effect of NAA on all enzyme activity seems related to interference with C2H2 action or to a reduced sensitivity of the fruit abscission zone tissues to the hormone. The observed high fruit drop induced by ABA treatment made it impossible to detect differences in enzyme activity. AVG-treated fruits showed no substantial effects on IAAox and PPO activity in comparison to the control, a finding that seems to be related to a delay in all senescence processes caused by the very low level of the inhibited ethylene production. In control fruits IAAox activity increased during the initial ripening stages and decreased thereafter, POD activity increased throughout ripening and PPO showed little variation. 相似文献
85.
Pablo Cerme?o Gemma Quílez-Badia Andrés Ospina-Alvarez Susana Sainz-Trápaga Andre M. Boustany Andy C. Seitz Sergi Tudela Barbara A. Block 《PloS one》2015,10(2)
We analyzed the movements of Atlantic tuna (Thunnus thynnus L.) in the Mediterranean Sea using data from 2 archival tags and 37 pop-up satellite archival tags (PAT). Bluefin tuna ranging in size from 12 to 248 kg were tagged on board recreational boats in the western Mediterranean and the Adriatic Sea between May and September during two different periods (2000 to 2001 and 2008 to 2012). Although tuna migrations between the Mediterranean Sea and the Atlantic Ocean have been well reported, our results indicate that part of the bluefin tuna population remains in the Mediterranean basin for much of the year, revealing a more complex population structure. In this study we demonstrate links between the western Mediterranean, the Adriatic and the Gulf of Sidra (Libya) using over 4336 recorded days of location and behavior data from tagged bluefin tuna with a maximum track length of 394 days. We described the oceanographic preferences and horizontal behaviors during the spawning season for 4 adult bluefin tuna. We also analyzed the time series data that reveals the vertical behavior of one pop-up satellite tag recovered, which was attached to a 43.9 kg tuna. This fish displayed a unique diving pattern within 16 days of the spawning season, suggesting a use of the thermocline as a thermoregulatory mechanism compatible with spawning. The results obtained hereby confirm that the Mediterranean is clearly an important habitat for this species, not only as spawning ground, but also as an overwintering foraging ground. 相似文献
86.
Rico Fischer Andreas Ensslin Gemma Rutten Markus Fischer David Schellenberger Costa Michael Kleyer Andreas Hemp Sebastian Paulick Andreas Huth 《PloS one》2015,10(4)
Tropical forests are carbon-dense and highly productive ecosystems. Consequently, they play an important role in the global carbon cycle. In the present study we used an individual-based forest model (FORMIND) to analyze the carbon balances of a tropical forest. The main processes of this model are tree growth, mortality, regeneration, and competition. Model parameters were calibrated using forest inventory data from a tropical forest at Mt. Kilimanjaro. The simulation results showed that the model successfully reproduces important characteristics of tropical forests (aboveground biomass, stem size distribution and leaf area index). The estimated aboveground biomass (385 t/ha) is comparable to biomass values in the Amazon and other tropical forests in Africa. The simulated forest reveals a gross primary production of 24 tcha-1yr-1. Modeling above- and belowground carbon stocks, we analyzed the carbon balance of the investigated tropical forest. The simulated carbon balance of this old-growth forest is zero on average. This study provides an example of how forest models can be used in combination with forest inventory data to investigate forest structure and local carbon balances. 相似文献
87.
Bárbara Pérez-K?hler Francisca García-Moreno Yves Bayon Gemma Pascual Juan Manuel Bellón 《PloS one》2015,10(5)
Introduction
Presoaking meshes for hernia repair with antiseptics prior to implantation could decrease the adhesion of microorganisms to the material surface and reduce the risk of antibiotic resistances. In this work, we evaluate chlorhexidine and allicin (natural antiseptic not yet tested for these purposes) against vancomycin as antiseptics to be used in the pretreatment of a heavyweight polypropylene mesh using an in vitro model of bacterial contamination.Methods
Solutions of saline, vancomycin (40 µg/mL), allicin (1,000 µg/mL), chlorhexidine (2%-0.05%) and the combination allicin-chlorhexidine (900 µg/mL-0.05%) were analyzed with agar diffusion tests in the presence of 106 CFU Staphylococcus aureus ATCC25923. Additionally, sterile fragments of Surgipro (1 cm2) were soaked with the solutions and cultured onto contaminated agar plates for 24/48/72 h. The antimicrobial material DualMesh Plus was utilized as positive control. At every time, the inhibition zones were measured and the bacterial adhesion to the mesh surface quantified (sonication, scanning electron microscopy). Cytotoxicity of the treatments was examined (alamarBlue) using rabbit skin fibroblasts.Results
The largest zones of inhibition were created by allicin-chlorhexidine. Chlorhexidine was more effective than vancomycin, and allicin lost its effectiveness after 24 h. No bacteria adhered to the surface of the DualMesh Plus or the meshes soaked with vancomycin, chlorhexidine and allicin-chlorhexidine. On the contrary, saline and allicin allowed adherence of high loads of bacteria. Vancomycin had no toxic effects on fibroblasts, while allicin and chlorhexidine exerted high toxicity. Cytotoxicity was significantly reduced with the allicin-chlorhexidine combination.Conclusions
The use of antiseptics such as chlorhexidine, alone or combined with others like allicin, could represent an adequate prophylactic strategy to be used for hernia repair materials because soaking with these agents provides the mesh with similar antibacterial properties to those observed after soaking with vancomycin, similar to the effect of DualMesh Plus. 相似文献88.
Kim Y. C. Fung Bruce Tabor Michael J. Buckley Ilka K. Priebe Leanne Purins Celine Pompeia Gemma V. Brierley Trevor Lockett Peter Gibbs Jeanne Tie Paul McMurrick James Moore Andrew Ruszkiewicz Edouard Nice Timothy E. Adams Antony Burgess Leah J. Cosgrove 《PloS one》2015,10(3)
Background
The majority of colorectal cancer (CRC) cases are preventable by early detection and removal of precancerous polyps. Even though CRC is the second most common internal cancer in Australia, only 30 per cent of the population considered to have risk factors participate in stool-based test screening programs. Evidence indicates a robust, blood-based, diagnostic assay would increase screening compliance. A number of potential diagnostic blood-based protein biomarkers for CRC have been reported, but all lack sensitivity or specificity for use as a stand-alone diagnostic. The aim of this study was to identify and validate a panel of protein-based biomarkers in independent cohorts that could be translated to a reliable, non-invasive blood-based screening test.Principal Findings
In two independent cohorts (n = 145 and n = 197), we evaluated seven single biomarkers in serum of CRC patients and age/gender matched controls that showed a significant difference between controls and CRC, but individually lack the sensitivity for diagnostic application. Using logistic regression strategies, we identified a panel of three biomarkers that discriminated between controls and CRC with 73% sensitivity at 95% specificity, when applied to either of the two cohorts. This panel comprised of Insulin like growth factor binding protein 2 (IGFBP2), Dickkopf-3 (DKK3), and Pyruvate kinase M2(PKM2).Conclusions
Due to the heterogeneous nature of CRC, a single biomarker is unlikely to have sufficient sensitivity or specificity for use as a stand-alone diagnostic screening test and a panel of markers may be more effective. We have identified a 3 biomarker panel that has higher sensitivity and specificity for early stage (Stage I and -II) disease than the faecal occult blood test, raising the possibility for its use as a non-invasive blood diagnostic or screening test. 相似文献89.
Mar Abril-Gil Alba Garcia-Just Trinitat Cambras Francisco J Pérez-Cano Cristina Castellote àngels Franch Margarida Castell 《Experimental biology and medicine (Maywood, N.J.)》2015,240(10):1373-1377
The release of mediators by mast cells triggers allergic symptoms involving various physiological systems and, in the most severe cases, the development of anaphylactic shock compromising mainly the nervous and cardiovascular systems. We aimed to establish variables to objectively study the anaphylactic response (AR) after an oral challenge in an allergy model. Brown Norway rats were immunized by intraperitoneal injection of ovalbumin with alum and toxin from Bordetella pertussis. Specific immunoglobulin (Ig) E antibodies were developed in immunized animals. Forty days after immunization, the rats were orally challenged with the allergen, and motor activity, body temperature and serum mast cell protease concentration were determined. The anaphylaxis induced a reduction in body temperature and a decrease in the number of animal movements, which was inversely correlated with serum mast cell protease release. In summary, motor activity is a reliable tool for assessing AR and also an unbiased method for screening new anti-allergic drugs. 相似文献
90.