Home About us Contact
|
Home About us Contact | ||
|
|
||
Lethal Dose (lethal + dose)
Kinds of Lethal Dose Selected AbstractsAntibacterial activity of plant extracts from northwestern ArgentinaJOURNAL OF APPLIED MICROBIOLOGY, Issue 6 2007J.R. Soberón Abstract Aims:, To determine the antibacterial and cytotoxic activities of aqueous and ethanolic extracts of northwestern Argentinian plants used in folk medicine. To compare the mentioned activities with those of five commercial antibiotics. To identify the compounds responsible for the antibacterial activity. Methods and Results:, Plant extracts were prepared according to traditional uses in northwestern Argentina. Antibacterial activity was assayed by agar dilution in Petri dishes and broth dilution in 96-well plates. Lethal dose 50 (LD50) was determined by the Artemia salina assay. Phytochemical analysis was performed by sample adsorption on silica gel, thin-layer chromatography (TLC), bioautography and UV-visible spectra. The results showed that Tripodanthus acutifolius aqueous extracts have lower minimal inhibitory concentrations (MIC) (502 and 506 ,g of extracted material (EM) per ml for infusion and decoction, respectively) than cefotaxim MIC (640 ,g ml,1) against Acinetobacterfreundii (303). These data were lower than their LD50. Tripodanthus acutifolius tincture showed lower MIC (110 ,g of EM per ml) and minimal bactericidal concentration (MBC) (220 ,g of EM per ml) than cefotaxim (MIC and MBC of 320 ,g ml,1) for Pseudomonasaeruginosa. This extract also showed a MIC/MBC of 110/220 ,g of EM per ml, lower than oxacillin (MIC/MBC of 160/220 ,g ml,1) for Staphylococcus aureus (ATCC 25923). The cytotoxicity of all extracts were compared with that of commercial antibiotics. Rutin (3,3,,4,,5,7-pentahydroxyflavone 3- , -rhamnosilglucoside), iso -quercitrin (3,3,,4,,5,7-pentahydroxyflavone 3- , -glucoside) and a terpene would be partially responsible for the antibacterial activity of T. acutifolius infusion. Conclusions:,Tripodanthus acutifolius extracts had the ability to inhibit bacterial growth. The antibacterial activity differs with the applied extractive method, and it could be partially attributed to glycoflavonoids. This paper contributes to the knowledge of antibacterial capacity of plants from northwestern Argentina. Significance and Impact of the Study:, These antibacterial activities support further studies to discover new chemical structures that can contribute to alleviate or cure some illnesses. [source] Increased toxicity to invertebrates associated with a mixture of atrazine and organophosphate insecticidesENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2002Troy D. Anderson Abstract This study examined the joint toxicity of atrazine and three organophosphate (OP) insecticides (chlorpyrifos, methyl parathion, and diazinon) exposed to Hyalella azteca and Musca domestica. A factorial design was used to evaluate the toxicity of binary mixtures in which the lethal concentration/lethal dose (LC1/LD1, LC5/LD5, LC15/LD15, and LC50/LD50) of each OP was combined with atrazine concentrations of 0, 10, 40, 80, and 200 ,g/L for H. azteca and 0, 200, and 2,000 ng/mg for M. domestica. Atrazine concentrations (>40 ,g/L) in combination with each OP caused a significant increase in toxicity to H. azteca compared with the OPs dosed individually. Acetylcholinesterase (AChE) activity also was examined for the individual OPs with and without atrazine treatment. Atrazine in combination with each of the OPs resulted in a significant decrease in AChE activity compared with the OPs dosed individually. In addition, H. azteca that were pretreated with atrazine (>40 ,g/L) were much more sensitive to the OP insecticides compared with H. azteca that were not pretreated with atrazine before being tested. Topical exposure to atrazine concentrations did not significantly increase OP toxicity to M. domestica. The results of this study indicate the potential for increased toxicity in organisms exposed to environmental mixtures. [source] The lethal effects of gamma irradiation on larvae of the Huhu beetle, Prionoplus reticularis: a potential quarantine treatment for New Zealand export pine treesENTOMOLOGIA EXPERIMENTALIS ET APPLICATA, Issue 3 2000Philip J. Lester Abstract Gamma irradiation was investigated as a possible method for disinfestation of huhu beetle larvae, Prionoplus reticularis White, in Pinus radiata D. Don. Larvae of four representative size classes were irradiated at six doses, and the lethal dose (LD99) calculated from mortality data 3 days and 10 days post treatment. All larval size classes showed a similar sensitivity to gamma irradiation and required 3677 Gray (Gy) and 2476 Gy for a LD99 3 and 10 days post-treatment, respectively. The penetration of gamma irradiation into pine wood was found to be lowest in freshly cut logs, and decreased linearly at a rate of 0.698 Gy mm,1 of wood. The penetration was greatest in wood that had been stored for 2 years, and decreased 0.512 Gy mm,1 of wood. These results are likely to be correlated with wood moisture content. Gamma irradiation appears to be a potential alternative method to fumigation for quarantine treatment of P. reticularis. [source] Toxicity of oral exposure to 2,4,6-trinitrotoluene in the western fence lizard (Sceloporus occidentalis),ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 5 2008Craig A. McFarland Abstract Contamination of the soil with the explosive 2,4,6-trinitrotoluene (TNT) has been found at military sites, many of which are habitats used by reptiles. To provide data useful in assessing ecological risk for reptilian species, acute, subacute, and subchronic oral toxicity studies were conducted with the western fence lizard (Sceloporus occidentalis). Oral median lethal dose (LD50) values for TNT in corn oil were 1,038 and 1,579 mg/kg of body weight for male and female lizards, respectively. Overt signs of toxicity included chromaturia, abdominal enlargement, and tremors. A 14-d subacute study followed in which male lizards were orally dosed with TNT (corn oil) at 0, 33, 66, 132, 263, 525, and 1,050 mg/kg of body weight each day. Clinical signs of toxicity, while similar to the LD50 study, were more subtle and noted in lizards receiving TNT amounts of at least 66 mg/kg/d. Chromaturia was an early consistent sign, often preceding the onset of adverse effects. Male lizards in the 60-d subchronic study were dosed at 0, 3, 15, 25, 35, and 45 mg/kg/d with nearly complete survival (>90%) for lizards in all treatments. Changes in food consumption and body weight were observed at 35 and 45 mg/kg/d. Alterations in hematological end points; blood chemistries (albumin, total protein, alkaline phosphatase, calcium); kidney, spleen, and liver weights; and adverse histopathology were observed in lizards exposed at 25 to 45 mg/kg/d. Testosterone concentration, sperm count, and motility were variable between treatments. Although not significant, incidences of hypospermia and testicular atrophy were observed in some individuals. Together, these data suggest a lowest-observed-adverse effect level of 25 mg/kg/d and a no-observed-adverse effect level of 15 mg/kg/d in S. occidentalis. [source] Dose-related effects following oral exposure of 2,4-dinitrotoluene on the western fence lizard, Sceloporus occidentalisENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2008Jamie G. Suski Abstract 2,4-dintitrotoluene (2,4-DNT) is an explosive frequently found in the soil of military installations. Because reptiles can be common on these sites, ecological risk assessments for compounds such as 2,4-DNT could be improved with toxicity data specific to reptiles. Western fence lizards, Sceloporus occidentalis, were used to develop a laboratory toxicity model for reptiles. A hierarchical approach was used; acute to subchronic studies were conducted to provide toxicity data relevant to short- and long-term exposures. First, a modified median lethal dose (LD50) study was conducted on male and female lizards using a stage-wise probit model. The LD50 was 577 mg/kg for female and 380 mg/kg for male lizards. Subsequently, a subacute experiment was conducted to further assess 2,4-DNT toxicity to male lizards and to define exposure levels for a longer term, subchronic study. The subchronic study was conducted for 60 consecutive days; male lizards were exposed to 0, 9, 15, 25, 42, 70 mg/kg/d. Dose-dependent mortality was observed in the three highest dose groups (25, 42, and 70 mg/kg/d); all other animals survived the study duration. Benchmark dose model calculations based on mortality indicated a 5% effect level of 15.8 mg/kg/d. At study termination, a gross necropsy was performed, organ weights were taken, and blood was collected for clinical and hematological analysis. Body weight, kidney weight, food consumption, postdose observations, and blood chemistries all were found to be significantly different from controls at doses above 9 mg/kg/d. Also, preliminary results suggest behavioral observations, and reduced food consumption may be a sensitive indicator of toxicity. The present study indicates Sceloporus occidentalis is suitable for evaluating toxicity of compounds to reptilian species. [source] Effect of in vitro and in vivo organotin exposures on the immune functions of murray cod (Maccullochella peelii peelii)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2007Andrew J. Harford Abstract Murray cod (Maccullochella peelii peelii) is an iconic native Australian freshwater fish and an ideal species for ecotoxicological testing of environmental pollutants. The species is indigenous to the Murray-Darling basin, which is the largest river system in Australia but also the ultimate sink for many environmental pollutants. The organotins tributyltin (TBT) and dibutyltin (DBT) are common pollutants of both freshwater and marine environments and are also known for their immunotoxicity in both mammals and aquatic organisms. In this study, TBT and DBT were used as exemplar immunotoxins to assess the efficiency of immune function assays (i.e., mitogen-stimulated lymphoproliferation, phagocytosis in head kidney tissue, and serum lysozyme activity) and to compare the sensitivity of Murray cod to other fish species. The organotins were lethal to Murray cod at concentrations previously reported as sublethal in rainbow trout (i.e., intraperitoneal [i.p.] lethal dose to 75% of the Murray cod [LD75] = 2.5 mg/kg DBT and i.p. lethal dose to 100% of the Murray cod [LD100] = 12.5 mg/kg TBT and DBT). In vivo TBT exposure at 0.1 and 0.5 mg/kg stimulated the phagocytic function of Murray cod (F = 6.89, df = 18, p = 0.004), while the highest concentration of 2.5 mg/kg TBT decreased lymphocyte numbers (F = 7.92, df = 18, p = 0.02) and mitogenesis (F = 3.66, df = 18, p = 0.035). Dibutyltin was the more potent immunosuppressant in Murray cod, causing significant reductions in phagocytic activity (F = 5.34, df = 16, p = 0.013) and lymphocyte numbers (F = 10.63, df = 16, p = 0.001). [source] Effects of methamidophos on the predating behavior of Hylyphantes graminicola (Sundevall) (Araneae: Linyphiidae)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2007Lingling Deng Abstract The effects of an organophosphorous insecticide, methamidophos, on the pest control potential of the spider Hylyphantes graminicola (Sundevall) (Araneae: Linyphiidae) were investigated in the laboratory with the fruit flies (Drosophila melanogaster Meigen). The influence of methamidophos on predation by H. graminicola was very obvious in female spiders, which preyed on fewer prey in the 8 h after exposure to the insecticide but subsequently recovered. On the other hand, the predation rates in male spiders were not affected by the insecticide within 24 h of treatment. However, a 10% lethal dose (LD10) of methamidophos resulted in an enhanced predation rate per day for male spiders, whereas a 50% lethal dose reduced the predation rate. In addition, it was shown that the functional response of H. graminicola to the fruit fly was a type II response, and the type of functional response of insecticide-treated females changed from type II to type I, with no change in the response of male spiders. The attack rate of males treated with the LD10 dosage of insecticide was significantly higher than the controls, which suggests that the insecticide stimulates the performance of spiders. Prey utilization of males treated with low doses of insecticide was lower than the control, which indicates that the insecticide did not result in these spiders eating more prey, but killing more. [source] Effects of an organophosphorous insecticide on survival, fecundity, and development of Hylyphantes graminicola (Sundevall) (Araneae: Linyphiidae)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 11 2006Lingling Deng Abstract The effects of an organophosphorous insecticide, methamidophos, on fecundity and development of the spider Hylyphantes graminicola (Sundevall) (Araneae: Linyphiidae) were assessed under laboratory conditions. Susceptibility of adults of both sexes to the insecticide and its influence on fecundity of females and development of offspring were investigated. At 48 h after topical application in adults, the median lethal dose (LD50) and 10% lethal dose (LD10) were 0.35 and 0.12 ,g/spider, respectively, for males and 0.52 and 0.16 ,g/spider, respectively, for females. Methamidophos had detrimental effects on fecundity of females; number of eggs per clutch, total egg mass, and clutch size decreased significantly. The hatching rate of eggs from LD10-treated females was slightly higher than the rate in the controls, but the hatching rate of eggs from LD50-treated females was lower than the rate in the controls. However, no significant differences were observed in hatching time and development time across treatments. Development time of spiderlings from LD50-treated females was significantly longer than the time in the controls, and body sizes of the first spiderlings from insecticide-treated females were larger than those in the controls. However, matured offspring were smaller than those in the controls. It was concluded that methamidophos has long-term effects on H. graminicola, and that this may affect the development of spider populations in the field. [source] Influence of dietary 2,4,6-trinitrotoluene exposure in the northern bobwhite (Colinus virginianus)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2002Robert M. Gogal Jr. Abstract The risk to wildlife from exposure to the explosive, 2,4,6-trinitrotoluene (TNT) has been a concern at numerous military installations where it has been found in the soil. To date, no published data are available describing effects of TNT exposure in an avian species. Subchronic dietary exposure to TNT was therefore evaluated in a species of management concern at military installations, the northern bobwhite (Colinus virginianus). Adult male and female quail (n = 5/sex/dose) were given commercial feed containing 3,000, 1,500, 750, and 100 mg/kg TNT for 90 d following the determination of an acute lethal dose and a 14-d range finding study. Dietary TNT intake caused a dose-dependent decrease in total red blood cell counts, packed cell volume, total plasma protein, blood prolymphocytes, and blood lymphocytes. An increased trend in late apoptotic/necrotic blood leukocytic cells was also observed in TNT-exposed birds, as was hemosiderosis in the liver. With the exception of hemosiderosis, these trends were statistically significant yet of questionable biological significance. Since treatment-related responses in this preliminary study were variable, a conservative interpretation is suggested. However, since these treatments had concentrations that were a log-fold or more than doses in similar studies using mammals, these data suggest that northern bobwhite are less sensitive to oral exposures of TNT than mammals. [source] Chronic liver disease in murine hereditary tyrosinemia type 1 induces resistance to cell deathHEPATOLOGY, Issue 2 2004Arndt Vogel The murine model of hereditary tyrosinemia type 1 (HT1) was used to analyze the relationship between chronic liver disease and programmed cell death in vivo. In healthy fumarylacetoacetate hydrolase deficient mice (Fah -/- ), protected from liver injury by the drug 2-(2- nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), the tyrosine metabolite homogentisic acid (HGA) caused rapid hepatocyte death. In contrast, all mice survived the same otherwise lethal dose of HGA if they had preexisting liver damage induced by NTBC withdrawal. Similarly, Fah -/- animals with liver injury were also resistant to apoptosis induced by the Fas ligand Jo-2 and to necrosis-like cell death induced by acetaminophen (APAP). Molecular studies revealed a marked up-regulation of the antiapoptotic heat shock proteins (Hsp) 27, 32, and 70 and of c-Jun in hepatocytes of stressed mice. In addition, the p38 and Jun N-terminal kinase (JNK) stress-activated kinase pathways were markedly impaired in the cell-death resistant liver. In conclusion, these results provide evidence that chronic liver disease can paradoxically result in cell death resistance in vivo. Stress-induced failure of cell death programs may lead to an accumulation of damaged cells and therefore enhance the risk for cancer as observed in HT1 and other chronic liver diseases. (HEPATOLOGY 2004;39:433,443.) [source] Induction of a protective capsular polysaccharide antibody response to a multiepitope DNA vaccine encoding a peptide mimic of meningococcal serogroup C capsular polysaccharideIMMUNOLOGY, Issue 2 2003Deborah M. Prinz Summary Systemic infection by encapsulated organisms, such as Neisseria meningitidis, is a major cause of morbidity and mortality worldwide, especially in individuals less than 2 years of age. Antibodies directed at the capsular polysaccharide are shown to be protective against disease by inducing complement-dependent bactericidal activity. The current polysaccharide vaccine has been shown to be poorly immunogenic in high-risk groups and this is probably related to its T-independent properties. An alternative approach to eliciting a T-dependent serum immunoglobulin G (IgG) antibody response to encapsulated pathogens is DNA vaccination. We assessed the immunogenicity of a multiepitope DNA vaccine encoding a T-cell helper epitope and a peptide mimic of N. meningitidis serogroup C. The DNA construct induced a significant anti-polysaccharide antibody response that was bactericidal. Mice immunized with the DNA construct were subsequently protected against challenge with a lethal dose of N. meningitidis serogroup C. [source] Metabolism of the mesoionic compound (MI-D) by mouse liver microsome, detection of its metabolite In Vivo, and acute toxicity in miceJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 6 2009Silvia Romão Abstract The mesoionic derivative 4-phenyl-5-[4-nitrocinnamoyl]-1,3,4-thiadiazolyl-2-phenylamine chloride (MI-D) has antitumoral and anti-inflammatory effects. In this study, we present aspects of its metabolism and toxicity in mice. MI-D was metabolized in vitro by liver microsome, generating a main product with a much shorter retention time than MI-D in high-performance liquid chromatography (HPLC) analysis but with a spectrum similar to that of the original molecule. Mass spectrometry with electrospray ionization in positive mode analysis of the purified compound by HPLC indicated that the product of metabolism has four additional hydroxyl groups (m/z = 465) compared with MI-D (m/z = 401). The HPLC analyses of plasma and urine samples from mice treated with MI-D showed the presence of the metabolite product. The kinetic parameters Km (19.5 ± 4.5 ,M) and Vmax [1.5 ± 0.4 units of fluorescence/(100 ,g of microsomal protein/mL/s)] were estimated, confirming the metabolism of MI-D and indicating that the reaction follows Michaelis-Menten kinetics. Acute toxicity was established on the basis of an estimation of mean lethal dose (LD-50; 181.2 mg/kg) and histopathological analysis of animals that survived the LD-50 test. Abdominal adhesions, inflammatory foci, and formation of granulomas were observed. Altogether, the results contribute to the advancement of research in support of MI-D as a future chemotherapeutic drug. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:394,405, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20303 [source] Assessment of Rhodamine B for labelling the plague reservoir Rattus rattus in MadagascarAFRICAN JOURNAL OF ECOLOGY, Issue 3 2010Soanandrasana Rahelinirina Abstract The black rat is the main plague reservoir in rural foci in Madagascar, inside the villages as well as in the cultivated areas around. We have evaluated the potentialities of mass-marking of rats, using baits containing Rhodamine B (RB) in order to get a tool to study the movements of rats and to understand the spread of plague. Laboratory experiments demonstrated that: (i) rats were more attracted by the rodent granules and peanut butter; (ii) incorporation of RB in baits did not reduce their appetence; (iii) RB lasted for 60 days in rat vibrissae and 180 days in rat hairs; and (iv) consumption of baits during a week was under the lethal dose. Field tests have been realized comparatively among 24 highland villages where plague is endemic, in different contexts: baits inside houses or around the village, baits with and without RB, rats captured 1, 2 and 3 months after the marking. No negative effect of the RB on population dynamics of rats or fleas on them was observed. The effectiveness of the marking was comparable between males and females. This technique of collective marking appears very valuable for monitoring rat movements in plague foci. Résumé Le rat noir est le principal réservoir de la peste dans les foyers ruraux de Madagascar, dans les villages comme dans les zones cultivées environnantes. Nous avons évalué les potentialités de marquage en masse de rats avec des appâts contenant de la Rhodamine B (RB) afin de disposer d'un outil pour étudier les déplacements des rats et de comprendre la dispersion de la peste. Les expériences en laboratoire ont montré que : (i) les rats étaient plus attirés par les granulés pour rongeurs et le beurre de cacahuète; (ii) l'adjonction de RB dans les appâts ne réduisait pas leur appétence; (iii) la RB persistait pendant 60 jours dans les vibrisses des rats, et 180 jours dans leurs poils; et (iv) la consommation des appâts pendant une semaine restait en dessous de la dose létale. Des tests sur le terrain dans 24 villages des hauts plateaux où la peste est endémique étaient réalisés dans différents contextes: appâts dans les maisons et autour des villages, appâts avec ou sans RB, rats capturés un, deux ou trois mois après le marquage. Aucun effet négatif de la RB sur la dynamique de population des rats ou des puces qui les parasitent n'a été observé. L'efficacité du marquage était comparable chez les mâles et les femelles. Cette technique de marquage collectif apparaît très intéressante pour suivre les déplacements des rats dans les foyers de peste. [source] Production and Stability Studies of a Neurotoxin Produced by Clostridium sp.JOURNAL OF FOOD SCIENCE, Issue 3 2006ABSTRACT: A neurotoxigenic Clostridium sp. (RKD) isolated from intestine of decaying fish produced a neurotoxin that was neutralized by botulinum antitoxin (A+B+E) when tested by mouse protection bioassay. An amplicon of expected size (approximately 700 bp) was generated with primers specific for BoNT/B. Toxin was maximally released in the culture supernatant in the late stationary phase and was dependent on media composition. Growth was optimal in trypticase peptone yeast-extract glucose (TPYG) medium in a pH range of 7.5 to 8.0 and at a temperature between 35°C to 40°C while toxin production was optimum at 37°C (3 to 4 × 103 minimum lethal dose per milliliter) without any protease treatment. There was no correlation between growth and toxin production when cells were grown in media containing different concentrations of NaCl (0% to 5%). Toxin in the culture supernatant was more stable (50% reduction at 50°C in 90 min) than the partially purified fraction. Toxicity was destroyed gradually after increasing the number of freeze-thaw cycles and was almost completely inactivated after 5 cycles. It was completely inactivated by overnight treatment of 1 N NaOH while it retained 1.5% activity with a similar treatment with 1 N HCl. [source] Electronic structure and biological activity of chosen DDT-type insecticides studied by 35Cl-NQRMAGNETIC RESONANCE IN CHEMISTRY, Issue 2 2009Maciej Jad Abstract A correlation between the electronic structure and biological activity of chosen dichlorodiphenyltrichloroethane (DDT)-type insecticides: 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane, 1,1-dichloro-2,2-bis(4-chlorophenyl)ethane, 2,2-bis(p-chlorophenyl)-1,1-dichloroethylene, 2,2-bis(4-chlorophenyl)ethanoic acid and 4,4,-dichlorobenzophenone (used in agriculture) has been analysed on the basis of the 35Cl-nuclear quadrupole resonance (NQR) spectroscopy. The 35Cl-NQR resonance frequencies measured at 77 K have been correlated with the lethal dose (LD50) parameter that characterises the biological activity of these insecticides. Copyright © 2008 John Wiley & Sons, Ltd. [source] In vivo distribution and metabolisation of 14C-imidacloprid in different compartments of Apis mellifera LPEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 11 2004Séverine Suchail Abstract In vivo distribution of the neonicotinoid insecticide, imidacloprid, was followed during 72 h in six biological compartments of Apis mellifera L: head, thorax, abdomen, haemolymph, midgut and rectum. Honeybees were treated orally with 100 µg of 14C-imidacloprid per kg of bee, a dose close to the median lethal dose. Elimination half-life of total radioactivity in honeybee was 25 h. Haemolymph was the compartment with the lowest and rectum that with the highest level of total radioactivity during the whole study, with a maximum 24 h after treatment. Elimination half-life of imidacloprid in whole honeybee was 5 h. Imidacloprid was readily distributed and metabolised only by Phase I enzymes into five metabolites: 4/5-hydroxy-imidacloprid, 4,5-dihydroxy-imidacloprid, 6-chloronicotinic acid, and olefin and urea derivatives. The guanidine derivative was not detected. The urea derivative and 6-chloronicotinic acid were the main metabolites and appeared particularly in midgut and rectum. The olefin derivative and 4/5-hydroxy-imidacloprid preferentially occurred in head, thorax and abdomen, which are nicotinic acetylcholine receptor-rich tissues. Moreover, they presented a peak value around 4 h after imidacloprid ingestion. These results explain the prolongation of imidacloprid action in bees, and particularly the differences between rapid intoxication symptoms and late mortality. Copyright © 2004 Society of Chemical Industry [source] Effect of diphacinone on blood coagulation in Spermophilus beecheyi as a basis for determining optimal timing of field bait applicationsPEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 7 2002Desley A Whisson Abstract The effect was determined of a single dose of 2,mg,kg,1 diphacinone on three blood-clotting parameters [Prothrombin Time (PT), Partial Thromboplastin Time (PTT), and Protein Induced by Vitamin K Absence or Antagonists (PIVKA)] over a 120-h period in California ground squirrels, Spermophilus beecheyi. Diphacinone resulted in elevated PT, PTT and PIVKA within 24,h of squirrels receiving the dose. The most significant change was observed 72,h after dosing. As time following diphacinone dosing increased, there was higher individual variation in blood-clotting time. We suggest that increasing the interval between field bait applications should still result in squirrel mortality but reduce the potential for secondary hazards that may occur when squirrels have the opportunity to consume more than one lethal dose of diphacinone. © 2002 Society of Chemical Industry [source] Effect of green tea and (-)-epigallocatechin gallate on ethanol-induced toxicity in HepG2 cellsPHYTOTHERAPY RESEARCH, Issue 5 2008Sang Il Lee Abstract Despite the continuing reports supporting the hepatoprotective effects of green tea against ethanol intoxication, there remain controversies regarding the active compound(s) and molecular mechanism. These issues were addressed in the present study using cultured HepG2 cells exposed to a lethal dose of ethanol. Gamma-glutamyl transferase (GGT) was chosen as a marker of ethanol toxicity because it is widely used in clinics. When the cells were treated with ethanol at various concentrations, there was a dose-dependent increase of GGT activity in the culture media and loss of cell viability. Pretreatment of the cells with green tea extract attenuated the changes significantly. Among the green tea constituents, (-)-epigallocatechin gallate (EGCG) attenuated the ethanol cytotoxicity effectively, whereas l -theanine and caffeine had no effects. The ethanol cytotoxicity was also attenuated by alcohol dehydrogenase inhibitor 4-methyl pyrazol and GGT inhibitor acivicin as well as by thiol modulators such as S -adenosyl- l -methionine, N -acetyl- l -cysteine and glutathione. EGCG failed to prevent the intracellular glutathione loss caused by ethanol, but it appeared to be a strong GGT inhibitor. Therefore the cytoprotective effects of green tea could be attributed to the inhibition of GGT activity by EGCG. This study suggests that GGT inhibitors including EGCG may provide a novel strategy for attenuating ethanol-induced liver damage. Copyright © 2008 John Wiley & Sons, Ltd. [source] Preventative antiinflammatory effect of potamogetonan, a pectin from the common pondweed Potamogeton natans L.PHYTOTHERAPY RESEARCH, Issue 7 2007Sergey V. Popov Abstract The pectic polysaccharide named potamogetonan (PN) was obtained using extraction of the leaves and stems of the common pondweed Potamogeton natans L. by an aqueous ammonium oxalate. The purified potamogetonan PN-300 was obtained using membrane ultrafiltration of PN and proved to be pectin with a molecular weight of 300 kDa. The capacity of potamogetonan PN-300 to prevent inflammation was assessed using a carrageenan paw edema test in mice. Oral administration of PN-300 24 h prior to induction of inflammation was found to reduce edema formation in a dose-related manner. The maximal effect of PN-300 was observed at 1 h after carrageenan injection (60% reduction of footpad swelling) and was comparable to that of indomethacin. The delayed edema (5 h) was less affected by pre-administration of PN-300 (33% reduction). PN-300 was found to improve the survival of mice subjected to a lethal dose of LPS. The anti-endotoxemic effect of PN-300 was shown to be mediated by decreased TNF- , and IL-1, and increased IL-10 production. Thus, a pectin named potamogetonan PN-300 was isolated from P. natans and was shown to possess a preventive antiinflammatory effect following oral administration. Copyright © 2007 John Wiley & Sons, Ltd. [source] The evaluation of the radioprotective effect of chyavanaprasha (an ayurvedic rasayana drug) in mice exposed to lethal dose of , -radiation: a preliminary studyPHYTOTHERAPY RESEARCH, Issue 1 2004Ganesh Chandra Jagetia Abstract The effect of various doses of 50% ethanolic extract of chyavanaprasha (an Ayurvedic rejuvenating herbal preparation) was studied on the survival of mice exposed to 10 Gy of , -radiation. Treatment with chyavanaprasha, consecutively for ,ve days before irradiation, delayed symptoms of radiation sickness and onset of mortality when compared with the non-drug treated irradiated controls. All doses of chyavanaprasha provided a signi,cant protection against gastrointestinal (GI) death (death of animals within 10 days after exposure to radiation), however, highest protection against GI death was observed for 15 mg/kg chyavanaprasha. Chyavanaprasha also provided a signi,cant protection against the bone marrow death after 10 to 40 mg/kg. However, the best protection was seen for 15 mg/kg, where the highest number of survivors was observed at the end of 30 days post-irradiation. The drug was non-toxic up to a dose of 6 g/kg b. wt., the highest drug dose that could be tested. Our study demonstrates that chyavanaprasha can provide good radioprotection at a very low non-toxic dose. Copyright © 2004 John Wiley & Sons, Ltd. [source] Stability of some commonly measured blood-chemistry variables in juvenile salmonids exposed to a lethal dose of the anaesthetic MS-222AQUACULTURE RESEARCH, Issue 11 2006James L Congleton First page of article [source] Toxicity Profile of Lisdexamfetamine Dimesylate in Three Independent Rat Toxicology StudiesBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2007Suma Krishnan The toxicity profile of orally administered LDX has been evaluated in rats. In an acute study, LDX doses of 60 mg/kg and higher caused increased motor activity. At 1000 mg/kg, one rat died and another was euthanized. In a 7-day repeat-dose study, all rats dosed with LDX (14 per dose group for each sex) showed increased activity; 10 male rats and 11 female rats at 300 mg/kg/day and 3 female rats at 100 mg/kg/day were euthanized because of self-mutilation and 1 male rat at 300 mg/kg/day was found dead. In a 28-day study, only rats at 80 mg/kg showed signs of self-mutilation and thin body condition. In both the 7- and 28-day studies, LDX caused significant changes in some blood chemistry parameters (e.g. blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase) and organ weights (e.g. particularly heart, liver, brain, and spleen). Overall, no apparent treatment-related histopathologic changes were observed. Toxicokinetic assessments indicated that as the dose of LDX was increased, rats were exposed to increasing levels of LDX and d -amphetamine. The extent of exposure to LDX and d -amphetamine increased after repeated-dose in the 28-day study. The findings of the repeat-dose studies indicate that the toxicity profile in rats administered LDX orally is comparable to that for d -amphetamine; however, the apparent lethal dose of LDX in rats is more than five times higher than the LD50 of orally administered d -amphetamine, supporting a putative protective effect of conjugating amphetamine with lysine. [source] Assessment of Acute Respiratory and Cardiovascular Toxicity of Casiopeinas in Anaesthetized DogsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2007Marco Leal-García Considering therapeutic dose ranges from 3.6 to 18 mg/m2 for the former and 1.2 to 3 mg/m2 for the latter, true therapeutic margin of safety varies from 4.7 to 23.6 mg/m2 and from 20 to 50 mg/m2, respectively. For both casiopeinas intravenous administration of the corresponding lethal dose in 100 ml of 5% dextrose solution in a time period of 30 min. induced death after an almost uneventful latency time period of 30,50 min. Then, after an apparently sudden onset, changes in blood gases indicated respiratory distress (PO2 from 82.5% to 26.5% for casiopeina III-ia and from 88.6% to 37.5% for casiopeina IIgly; end-tidal CO2 from 38 to 8.1 mmHg for the first and from 35.1 to 11.2 mmHg for the second, this was almost simultaneously confirmed by the onset of tachypnoea (from 16 to almost 60 breaths/min. for both casiopeinas) and by a drop in arterial blood pressure (from 117 to 51 mmHg for casiopeina III-ia and from 108 to 49 mmHg for casiopeina IIgly). Reflex tachycardia occurs at the beginning of intravenous administration followed by bradycardia a few minutes later (from 158 to 63 beats/min. for casiopeina III-ia and from 148 to 56 beats/min. for casiopeina IIgly). Finally, cardiac arrest occurred no later than 25 min. towards the end of these events lung oedema appeared as fluid dripping from the endotracheal tube. Death occurred in a mean of 15 ± 5 min. S.D. from the beginning of the end of the latency period. For both casiopeina's data allow the speculation that lung oedema is caused by a joined toxicity to the lung capillary bed, and particularly to the heart. Carvedilol premedication for 8 days delayed the outcome of lung oedema by approximately 8 hr but could not prevent it. [source] MORAL FICTIONS AND MEDICAL ETHICSBIOETHICS, Issue 9 2010FRANKLIN G. MILLER ABSTRACT Conventional medical ethics and the law draw a bright line distinguishing the permitted practice of withdrawing life-sustaining treatment from the forbidden practice of active euthanasia by means of a lethal injection. When clinicians justifiably withdraw life-sustaining treatment, they allow patients to die but do not cause, intend, or have moral responsibility for, the patient's death. In contrast, physicians unjustifiably kill patients whenever they intentionally administer a lethal dose of medication. We argue that the differential moral assessment of these two practices is based on a series of moral fictions , motivated false beliefs that erroneously characterize withdrawing life-sustaining treatment in order to bring accepted end-of-life practices in line with the prevailing moral norm that doctors must never kill patients. When these moral fictions are exposed, it becomes apparent that conventional medical ethics relating to end-of-life decisions is radically mistaken. [source] Kinetics and Efficacy of an Organophosphorus Hydrolase in a Rodent Model of Methyl-parathion PoisoningACADEMIC EMERGENCY MEDICINE, Issue 7 2010Chip Gresham MD ACADEMIC EMERGENCY MEDICINE 2010; 17:736,740 © 2010 by the Society for Academic Emergency Medicine Abstract Objectives:, Organophosphorus (OP) pesticides exert a tremendous health burden, particularly in the developing world. Limited resources, the severity of intentional OP ingestions, and a paucity of beneficial therapies all contribute to the morbidity and mortality of this broad class of chemicals. A novel theoretical treatment for OP poisoning is the use of an enzyme to degrade the parent OP in the circulation after poisoning. The aims of this study were to determine the pharmacokinetics and efficacy of an OP hydrolase (OpdA) in a rodent model of severe methyl-parathion poisoning. Methods:, Two animal models were used. First, Wistar rats were administered two different doses of the hydrolase (0.15 and 1.5 mg/kg), and the ex vivo hydrolytic activity of plasma was determined by a fluorometric method. Second, an oral methyl-parathion animal poisoning model was developed to mimic severe human poisoning, and the efficacy of postpoisoning OpdA (as measured by survival to 4 and 24 hours) was determined. Results:, The half-life of OpdA in the Wistar rat was dependent on the dose administered and ranged between 45.0 and 57.9 minutes. The poisoning model of three times the lethal dose to 50% of the population (3 × LD50) of methyl-parathion resulted in 88% lethality at 4 and 24 hours. Using a single dose of 0.15 mg/kg OpdA 10 minutes after poisoning resulted in 100% survival at 4 hours (p = 0.001 vs. placebo), but 0% at 24 hours postpoisoning (p = NS vs. placebo). Conclusions:, The OP hydrolase OpdA exhibits pharmacokinetics suitable for repeated dosing and increases short-term survival after severe methyl-parathion poisoning. [source] Survivin as a Radioresistance Factor in Pancreatic CancerCANCER SCIENCE, Issue 11 2000Koichi Asanuma We examined whether survivin acts as a constitutive and inducible radioresistance factor in pancreatic cancer cells. Using a quantitative TaqMan reverse transcription-polymerase chain reaction for survivin mRNA in five pancreatic cancer cell lines, we found an inverse relationship between survivin mRNA expression and radiosensitivity. PANC-1 cells, which had the highest survivin mRNA levels, were most resistant to X-irradiation; MIAPaCa-2 cells, which showed the least survivin mRNA expression, were the most sensitive to X-irradiation. Our results suggested that survivin could act as a constitutive radioresistance factor in pancreatic cancer cells. To determine whether radioresistance is enhanced by induction of survivin expression by irradiation, PANC-1 and MIAPaCa-2 cells were subjected to sublethal doses of X-irradiation followed by a lethal dose. Survivin mRNA expression was increased significantly in both PANC-1 and MIAPaCa-2 cell lines by pretreatment with a sublethal dose of X-irradiation, as was cell survival after exposure to the lethal dose. In this system, enzymatic caspase-3 activity was significantly suppressed in cells with acquired resistance. These results suggest that survivin also acts as an inducible radioresistance factor in pancreatic cancer cells. Survivin, then, appears to enhance radioresistance in pancreatic cancer cells; inhibition of survivin mRNA expression may improve the effectiveness of radiotherapy. [source] Preconditioning protects the retinal pigment epithelium cells from oxidative stress-induced cell deathACTA OPHTHALMOLOGICA, Issue 1 2009Rajesh K. Sharma Abstract. Purpose:, The cytotoxic effects of oxidative stress, which play an important role in ocular diseases, are well known. In this study, we investigated the effect of non-lethal doses of oxidative stress on various cell functions, namely cell viability, cell attachment and cell migration in a widely used retinal pigment epithelium (RPE) cell line (ARPE-19). Methods:, A single exposure to various concentrations of hydrogen peroxide (H2O2) was used to establish a dose response for H2O2 -induced cell death. Other cellular responses, such as changes in cell attachment and migration, were monitored after exposure to increasing doses. Finally, the effects of preconditioning cells with increasing non-lethal doses of H2O2, with and without a subsequent exposure to lethal doses of H2O2, were determined. Results:, The optimum dose for inducing cell death in ARPE-19 cells was between 900 and 1000 ,m H2O2. Preconditioning the cells with 1, 10 and 50 ,m of H2O2 provided a dose-dependent protection against cell death induced by a lethal dose (900,1000 ,m) of H2O2. Preconditioning with higher doses caused cells to become more susceptible to the cytotoxic effects of the lethal dose. Although H2O2 increased cell attachment in lower doses, it induced a dose-dependent inhibition of cell attachment to the substrate in higher doses. H2O2 did not affect cell migration in sub-lethal doses. Conclusion:, Preconditioning RPE cells with limited exposure to non-lethal oxidative stress confers significant protection against subsequent H2O2 -induced cell death. It also affects cell attachment in a dose-specific manner. This finding may help in understanding the pathogenesis of diseases in which oxidative stress plays an important role and in determining the suitability of certain treatment strategies, in particular RPE transplantation in the treatment of age-related macular degeneration. [source] Ziprasidone, Diazepam, or the Combination for Prevention of Cocaine Toxicity in a Mouse ModelACADEMIC EMERGENCY MEDICINE, Issue 8 2007Nathan R. Cleveland MD BackgroundAcute cocaine poisoning is a common problem in the United States. Sedation with benzodiazepines is the standard treatment, but animal studies have suggested that ziprasidone is also protective. ObjectivesTo assess whether the combination of these two medications would offer more protection than either treatment alone. MethodsThis was a randomized, blinded, placebo-controlled trial in CF-1 mice. The authors administered intraperitoneal injections of 2 mg/kg diazepam (group D), 4 mg/kg ziprasidone (group Z), the same dose of both drugs (group DZ), or saline 15 minutes before intraperitoneal administration of 105 mg/kg cocaine (an estimated lethal dose to 70%). The number of animals with seizures and apparent lethality over the following 30 minutes was recorded. ResultsAll treatments increased survival relative to placebo (relative risk: D = 2.6, Z = 2.3, DZ = 2.9) and decreased seizures (relative risk: D = 0.5, Z = 0.3, DZ = 0.02). ConclusionsThis study suggests that diazepam and ziprasidone have efficacy for preventing lethality from cocaine poisoning in an animal model but that the combination offers little addition to either therapy alone. However, the combination may be more effective for prevention of cocaine-induced seizures. [source] Stereospecific activity of two glutamate analogsCHIRALITY, Issue 9 2004Juan Manuel Araujo Alvarez Abstract Two glutamic acid analogs, (+)-(S)- and (,)-(R)-4-(2,2-diphenyl-1,3,2-oxazaborolidin-5-oxo)propionic acid ((+)-(S)- and (,)-(R)-Trujillon, respectively), were prepared. The stereospecific activity of their pharmacological properties was studied. The median convulsant dose (CD50) and median lethal dose (LD50) were analyzed in female Swiss Webster mice and their effects in vivo on unitary electrical activity in globus pallidus neurons were elucidated in male Wistar rats. Compounds were characterized by 1H, 13C, and 11B nuclear magnetic resonance. The LD50 of (+)-(S)-Trujillon was 449.08 mg/kg and it increased spontaneous motor activity, while with (,)-(R)-Trujillon there was no mortality up to 1,000 mg/kg and it decreased spontaneous motor activity. The CD50 in experiments with (+)-(S)-Trujillon was 199.34 mg/kg. Unitary recording in globus pallidus neurons showed i.v. administration (+)-(S)-Trujillon (50 mg/kg) increased frequency 79.0 ± 23.0% in relation to basal response. (,)-(R)-Trujillon and (+)-(S)-glutamate (50 mg/kg each) did not provoke changes in spontaneous basal firing. Local infusion of (+)-(S)-Trujillon (1 nMol) increased spontaneous firing in most neurons tested by 269.0 ± 83.0% in relation to basal values. Intrapallidal infusion of (,)-(R)-Trujillon (1 nMol) and saline solution did not cause statistically significant changes in globus pallidus spiking. Results showed that (+)-(S)-Trujillon crosses the blood,brain barrier and has stereospecific activity. Chirality 16:586,591, 2004. © 2004 Wiley-Liss, Inc. [source] Lipophilicity affects the pharmacokinetics and toxicity of local anaesthetic agents administered by caudal blockCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1-2 2004Alejandro A Nava-Ocampo Summary 1.,Drugs administered into the epidural space by caudal block are cleared by means of a process potentially affected by the lipophilic character of the compounds. 2.,In the present study, we examined the relationship between the octanol,water partition coefficient (log Poct) and the time to reach the maximum plasma drug concentration (tmax) of lignocaine, bupivacaine and ropivacaine administered by caudal block in paediatric patients. We also examined the relationship between log Poct and the toxicity of these local anaesthetic agents in experimental models. The tmax and toxicity data were obtained from the literature. 3.,Ropivacaine, with a log Poct of 2.9, exhibited a tmax of 61.6 min. The tmax of lignocaine, with a log Poct of 2.4, and bupivacaine, with a log Poct of with 3.4, were approximately 50% shorter than ropivacaine. At log Poct of approximately 3.0, the toxicity of these local anaesthetic agents was substantially increased. The relationship between log Poct and the convulsive effect in dogs was similar to the relationship between log Poct and the lethal dose in sheep. 4.,With local anaesthetic agents, it appears that the relationship between log Poct and drug transfer from the epidural space to the blood stream is parabolic, being the slowest rate of transference at log Poct 3.0. Toxicity, due to plasma availability of these local anaesthetic agents, seems to be increased at log Poct equal or higher than 3.0 secondary to the highest transfer from plasma into the central nervous system. [source] | |||||||||||||||||||