Toxic Concentrations (toxic + concentration)

Distribution by Scientific Domains

Selected Abstracts

Synthesis and antiviral activity of new benzothiadiazine dioxide derivatives

Annalisa Tait
A series of 2,1,3- and 1,2,4-benzothiadiazine derivatives were synthesized by alkylation via Mitsunobu reaction and evaluated for their antiviral activity against ADV, HHV-6, Cox-B5 and H-CMV. Most of them were active at micromolar level against one or more viral strains. All the molecules studied are poorly cytotoxic (maximum non toxic concentrations were >25,M), except one compound that presents a higher cytotoxicity (maximum non toxic concentration was 6 ,M). [source]

Protective effects of steroids from Allium chinense against H2O2 -induced oxidative stress in rat cardiac H9C2 cells

Gang Ren
Abstract Allium chinense, a traditional herbal medicine, has been used for the treatment of cardiovascular diseases for hundreds of years. In this study, A. chinense steroids (ACSs) including three steroidal glycosides and their parent aglycones were isolated from the bulbs of A. chinense. For the first time, their cardioprotective effects were evaluated in cultured rat cardiac H9C2 cells by pretreatment with ACSs for 24,h before exposure to 0.2,mm H2O2. The results showed the cell viability decreased markedly when H9C2 cells were incubated with 0.2,mm H2O2 alone for 2,h, while the cell lipid peroxidation (estimated by the excessive production of nitric oxide and malondialdehyde) and intracellular free calcium concentration ([Ca2+]i) increased significantly. The addition of 20,,m (below the toxic concentration) of ACSs notably attenuated the cellular injury induced by H2O2. The effects of ACSs in our experiments were similar to those of nimodipine, a clinically applied calcium channel blocker. Preliminary analysis of the structure,activity relationship indicated that ACSs with a spirostane-type skeleton exhibited stronger protection than that with a furostane-type skeleton, and glycosylation of the steroids could substantially lower the protective activities. The above results suggested the protective effects of steroids originated from A. chinense on the oxidative injury of H9C2 cells and ACSs may have potential for preventing cardiac injuries induced by oxidative stress. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Walker tumor cells express larger amounts of the antiapoptotic protein Bcl-2 and presents higher resistance to toxic concentrations of Ca2+ than the tumor cells K 562

Graziela Milani
Abstract Ca2+ homeostasis was studied in two tumor cell lines (Walker 256 and K 562) previously shown to exhibit different mitochondrial Ca2+ accumulation capacity. When intact, both cells present cytosolic Ca2+ concentrations within the range expected for mammalian cells, as determined through fura-2 fluorescence ratios. In order to study intracellular Ca2+ distribution, digitonin was used to permeabilize the plasma membrane without affecting intracellular organelle structure, as assessed using electron microscopy. Digitonin-permeabilized Walker 256 cells incubated with Ca2+ presented uptake of the cation exclusively through mitochondrial activity. In addition, very large Ca2+ loads were necessary to promote a disruption of Walker 256 mitochondrial membrane potential. K 562 cells presented active Ca2+ uptake through both nonmitochondrial and mitochondrial compartments and suffered disruption of mitochondrial membrane potential at lower Ca2+ loads than Walker 256 mitochondria. The higher Ca2+ resistance in Walker 256 cells could be attributed to Bcl-2 overexpression, as evidenced by immunocytochemical staining. Thus, we correlate natural Bcl-2 overexpression, observed in Walker 256 cells, with higher resistance to mitochondrial Ca2+ overload, as was shown previously in mitochondria from cells transfected with the bcl-2 gene. Drug Dev. Res. 52:508,514, 2001. © 2001 Wiley-Liss, Inc. [source]

Evaluation of methods to remove ammonia interference in marine sediment toxicity tests,

James A. Ferretti
Abstract Ammonia naturally accumulates to high concentrations in nonsurficial marine sediments. It can also interfere and confound interpretation of toxicity from persistent anthropogenic chemicals in tests with laboratory amphipods. Renewal of overlying water has become a standardized procedure to decrease pore-water ammonia. Our objective was to propose an alternative technique for decreasing pore-water ammonia concentrations. Sediment samples with ammonia concentrations of 70 and 155 mg/L were purged of toxic concentrations in pore-water ammonia using the existing procedure of performing two renewals of overlying water per day. A thin-layer technique, which involved increasing the sediment surface area during the purging period, decreased the ammonia concentration by as much as 4.5-fold faster than the conventional purging protocol. Minimal decreases in concentrations of polycyclic aromatic hydrocarbons, heavy metals, and total organic carbon were found among all the purging techniques. Toxicity tests with the marine amphipod Ampelisca abdita suggest that minimizing the time required to purge a sediment of ammonia is critical in maintaining the integrity of the sample. The thin-layer purging technique appears to be an effective method of decreasing pore-water ammonia concentrations in sediments before laboratory toxicity testing with amphipods. [source]

ISC1-encoded inositol phosphosphingolipid phospholipase C is involved in Na+/Li+ halotolerance of Saccharomyces cerevisiae

FEBS JOURNAL, Issue 16 2002
Christian Betz
In Saccharomyces cerevisiae, toxic concentrations of Na+ orLi+ ions induce the expression of the cation-extrusion ATPase gene, ENA1. Several well-studied signal transduction pathways are known correlating high salinity to the transcriptional activation of ENA1. Nevertheless, information on the actual sensing mechanism initiating these pathways is limited. Here, we report that the ISC1 -encoded phosphosphingolipid-specific phospholipase C appears to be involved in stimulation of ENA1 expression and, consequently, in mediating Na+ and Li+ tolerance in yeast. Deletion of ISC1 distinctly decreased cellular Na+ and Li+ tolerance as growth of the ,isc1::HIS5 mutant, DZY1, was severely impaired by 0.5 m NaCl or 0.01 m LiCl. In contrast,K+ tolerance and general osmostress regulation wereunaffected. Isc1, mutant growth with 0.9 m KCl and glycerol accumulation in the presence of 0.9 m NaCl or 1.5 m sorbitol were comparable to that of the wild-type. ENA1 -lacZ reporter studies suggested that the increased salt sensitivity of the isc1, mutant is related to a significant reduction of Na+/Li+ -stimulated ENA1 expression. Correspondingly, Ena1p-dependent extrusion of Na+/Li+ ions was less efficient in the isc1, mutant than in wild-type cells. Itis suggested that ISC1 -dependent hydrolysis of an unidentified yeast inositol phosphosphingolipid represents an early event in one of the salt-induced signalling pathways of ENA1 transcriptional activation. [source]

The effects of fertilization with anaerobic, composted and pelletized sewage sludge on soil, tree growth, pasture production and biodiversity in a silvopastoral system under ash (Fraxinus excelsior L.)

A. A. Rigueiro-Rodríguez
Abstract In silvopastoral systems, tree growth and the composition and productivity of pasture can be modified by management practices such as initial fertilization when tree seedlings are more sensitive to understorey competition. The aim of this study was to compare the effects of fertilization with different types of sewage sludge (anaerobic sludge, composted sludge and pelletized sludge), using different rates of incorporation and mineralization with traditional treatments (with and without mineral fertilizers) on the growth of newly established ash (Fraxinus excelsior L.) and on pasture development, to obtain sustainable management practices that enhance the growth of both components. Soil characteristics, tree growth, sward composition and pasture development were modified differently according to the type of sewage sludge used, and for similar total nitrogen inputs. Anaerobic sludge had a higher initial effect on both tree and pasture productivity. Pelletized sludge sustained better tree and pasture production. Composted sludge was found to be the most appropriate treatment for improving soil characteristics over the long term on sandy soils. It was concluded that pelletized sludge should be promoted because it enhances productivity, allows for better nutrient recovery and is less costly to store and apply compared with anaerobic sludge and composted sludge. No toxic concentrations of Zn or Cu were found in plants or in the soil despite higher concentrations being present in the applied sludge than in soil. [source]

Pulmonary responses and recovery following single and repeated inhalation exposure of rats to polymeric methylene diphenyl diisocyanate aerosols

Joanne D. Kilgour
Abstract Acute and repeated inhalation exposures (for 28 days) to polymeric methylene diphenyl diisocyanate (PMDI) were performed in rats. Investigations were made at the end of exposures and after 3, 10 and 30 days of recovery following single acute exposures and after 30 days of recovery following 28 days of exposure. Acute exposures to 10, 30 or 100 mg m,3 PMDI produced clinical signs in all animals that were consistent with exposure to irritant aerosols. An exposure concentration-related body weight loss and increase in lung weight were seen post-exposure, with complete recovery by day 8. The time course of changes in the lung over the initial days following exposure consisted of a pattern of initial toxicity, rapid and heavy influx of inflammatory cells and soluble markers of inflammation and cell damage, increased lung surfactant, a subsequent recovery and epithelial proliferative phase and, finally, a return to the normal status quo of the lung. During these stages there was evidence for perturbation of lung surfactant homeostasis, demonstrated by increased amounts of crystalline surfactant and increased number and size of lamellar bodies within type II alveolar cells. Repeated exposure over 28 days to the less toxic concentrations of 1, 4 or 10 mg m,3 PMDI produced no clinical signs or body weight changes, but an increase in lung weight was seen in animals exposed to 10 mg m,3, which resolved following the 30-day recovery period. Other effects seen were again consistent with exposure to irritant aerosols, but were less severe than those seen in the acute study. Analysis of bronchoalveolar lavage fluid revealed similar changes to those seen in the acute study. At both 10 and 4 mg m,3 PMDI increased numbers of ,foamy' macrophages in lung lavage cell pellet correlated with the increased phospholipid content of the pellet. Changes in lung lavage parameters and electron microscopic evidence again suggested perturbations in surfactant homeostasis. Histologically, bronchiolitis and thickening of the central acinar regions was seen at 10 and 4 mg m,3, reflecting changes in cell proliferation in the terminal bronchioles and centro-acinar regions. Almost all effects seen had recovered by day 30 post-exposure. Both acute and subacute studies demonstrate rapid recovery of effects in the lung following exposure to PMDI, with no progression of these effects even at concentrations higher than those shown to produce tumours in a chronic study. These findings add weight to the hypothesis that pulmonary tumours seen following chronic exposure to PMDI are most likely due to a combination of the chronic irritant effects of repeated exposure, coupled with the presence of insoluble polyureas formed by polymerization of PMDI (found in studies reported here and previous chronic studies), and therefore acute or short-term exposures to PMDI are likely to be of little concern for long-term pulmonary health. Copyright © 2002 John Wiley & Sons, Ltd. [source]

Why are very large herbivores absent from Australia?

A new theory of micronutrients
Abstract Aim We propose a Megacatalyst Theory, based on the pivotal role of the micronutrients iodine (I), cobalt (Co) and selenium (Se), in answer to the body size anomaly of herbivores on different continents, and the previously unexplained absence of megaherbivores in certain environments. Location It is anomalous that megaherbivores are absent from Australia while present in even dry and nutrient-poor parts of southern Africa, and that they have been exterminated from the Americas, but not south-east Asia. Methods We hypothesize that I, Co and Se are micronutrients in quantity, but megacatalysts in effect, determining maximum body size and pace of life, hence whether energy is used by animals or fire. The Megacatalyst Theory suggests that the greater the reproductive rate and brain size relative to body size, the greater the probable demand for I, Co and Se. Results Balanced supply of I, Co and Se, within narrow tolerances, is elusive because of disparate cycles: I gravitates towards the sea, whereas Co and Se are concentrated in ultramafics and organic shales, respectively. Sufficiency of these micronutrients, at less than toxic concentrations, is vital for rapid metabolism and growth, particularly of the nervous system. Iodine controls thermogenesis, Co controls the gut fermentation supplying herbivores, and Se controls biochemical damage where both processes occur rapidly. The supply of Co allows vegetation to be metabolized instead of combusted, by promoting digestion of fibre by gut microbes. Herbivores demand I, Co and Se in greater concentrations than palatable plants necessarily contain, as an increasing proportion of energy is fermented from fibre with increasing body size. Economy of scale is limited by loss of I in urine (partly compensated by thyroid size), Co in faeces (partly compensated by gut compartments), and Se both ways. Main conclusions The larger the herbivore species, the more it may depend on supplementation in order to survive predation by humans. As body mass increases, Co becomes deficient before I, because it is essential for rumination, and cannot be absorbed by the skin. Moderate uplift of a fairly flat landscape sustainably supplies I from mineralized springs, and Co from rocks (and Se from both), avoiding the excess of I in the sea and the excess of Co on high mountains. Iodine and Se leached to groundwater under dry climates are inaccessible to herbivores on a continent as flat as Australia, where even kangaroos have limited fecundity and intelligence compared to southern African ruminants of similar body mass. Where springs and associated earth-licks were available in the late Pleistocene, megaherbivores could evolve to survive the era of domestication. [source]

Synthesis and antiviral activity of new benzothiadiazine dioxide derivatives

Annalisa Tait
A series of 2,1,3- and 1,2,4-benzothiadiazine derivatives were synthesized by alkylation via Mitsunobu reaction and evaluated for their antiviral activity against ADV, HHV-6, Cox-B5 and H-CMV. Most of them were active at micromolar level against one or more viral strains. All the molecules studied are poorly cytotoxic (maximum non toxic concentrations were >25,M), except one compound that presents a higher cytotoxicity (maximum non toxic concentration was 6 ,M). [source]

The small heat shock protein Hsp27 protects cortical neurons against the toxic effects of ,-amyloid peptide

Michael King
Abstract Neurofibrillary tangles and amyloid plaques are considered to be hallmarks of Alzheimer's disease (AD), and the toxic effects of amyloid-, peptide (A,) lead to activation of stress-related signaling and neuronal loss. The small heat shock protein Hsp27 is reported to be increased in AD brains and to accumulate in plaques, but whether this represents a potentially protective response to stress or is part of the disease process is not known. We hypothesized that increased expression of Hsp27 in neurons can promote neuronal survival and stabilize the cytoskeleton in the face of A, exposure. By using neonatal rat cortical neurons, we investigated the potential role of Hsp27 in neuronal cultures in the presence or absence of A,. We initially tested whether a heat stress (HS) would be sufficient to induce endogenous Hsp27 expression. HS not only did not result in neuronal Hsp27 up-regulation but made the cells more vulnerable to A, exposure. We then used cDNA transfection to overexpress EGFP-Hsp27 (or the empty vector) in cultures and then assessed neuronal survival and growth. Transfected neurons appeared healthy and had robust neuritic outgrowth. A, treatment induced significant cell death by 48,72 hr in nontransfected and empty-vector-expressing cultures. In contrast, cultures expressing Hsp27 did not display significant apoptosis. Our results show that Hsp27-expressing neurons were selectively protected against the deleterious effects of A, treatment; neuronal degeneration was prevented, and A,-induced alterations in mitochondrial size were attenuated. We also demonstrate that Hsp27 expression can enhance neurite growth in cortical neurons compared with control vector-transfected cells. Overall, our study provides new evidence that Hsp27 can provide a protective influence in primary cortical neurons in the face of toxic concentrations of amyloid. © 2009 Wiley-Liss, Inc. [source]

Effects of wastewater irrigation on soil and cabbage-plant (brassica olerecea var. capitate cv. yalova-1) chemical properties

Fatih M. Kiziloglu
Abstract The use of wastewater for irrigation is increasingly being considered as a technical solution to,minimize soil degradation and to restore nutrient contents of soils. The aim of this study is to increase fertility and minimize degradation of soils irrigated with wastewater exposed to different purification treatments. A field experiment was conducted to investigate the effects of control and irrigation with wastewater, which had undergone different purification treatments, on macro- and micronutrient distribution within the soil profile and nutrient contents of cabbage (Brassica olerecea var. Capitate cv. Yalova-1) in Erzurum, Turkey. Wastewater irrigation and preliminary treatment,wastewater irrigation significantly affected soil chemical properties especially at 0,30,cm soil depth and plant nutrient contents after one year. Application of wastewater increased soil salinity, organic matter, exchangeable Na, K, Ca, Mg, plant-available P, and micro-elements and decreased soil pH. Wastewater increased also yield and N, P, K, Fe, Mn, Zn, Cu, B, and Mo contents of cabbage plants. Undesirable side effects were not observed in plant heavy-metal contents, due to salinity and toxic concentrations of metals from the application of wastewater to soil. [source]


Gary O. Graening
ABSTRACT: Subterranean ecosystems harbor globally rare fauna and important water resources, but ecological processes are poorly understood and are threatened by anthropogenic stresses. Ecosystem analyses were conducted from 1997 to 2000 in Cave Springs Cave, Arkansas, situated in a region of intensive land use, to determine the degree of habitat degradation and viability of endangered fauna. Organic matter budgeting quantified energy flux and documented the dominant input as dissolved organic matter and not gray bat guano (Myotis grisescens). Carbon/nitrogen stable isotope analyses described a trophic web of Ozark cavefish (Amblyopsis rosae) that primarily consumed cave isopods (Caecidotea stiladactyla), which in turn appeared to consume benthic matter originating from a complex mixture of soil, leaf litter, and anthropogenic wastes. Septic leachate, sewage sludge, and cow manure were suspected to augment the food web and were implicated in environmental degradation. Water, sediment, and animal tissue analyses detected excess nutrients, fecal bacteria, and toxic concentrations of metals. Community assemblage may have been altered: sensitive species-grotto salamanders (Typhlotriton spelaeus) and stygobro-mid amphipods,were not detected, while more resilient isopods flourished. Reduction of septic and agricultural waste inputs may be necessary to restore ecosystem dynamics in this cave ecosystem to its former undisturbed condition. [source]

Lipid resuscitation in a carnitine deficient child following intravascular migration of an epidural catheter,

ANAESTHESIA, Issue 2 2010
G. K. Wong
Summary A child with cerebral palsy and carnitine deficiency developed ventricular arrhythmias with loss of cardiac output during elective surgery under general anaesthesia with concomitant epidural analgesia. Sinus rhythm was restored on administration of adrenaline, but hypotension persisted despite resuscitation. Bolus administration of 0.8,1 (20 ml) lipid emulsion resulted in rapid improvement in cardiac output. Blood samples taken before and after the lipid bolus did not demonstrate toxic concentrations of bupivacaine. This case suggests that carnitine deficiency may increase susceptibility to bupivacaine cardiotoxicity. [source]