Cytotoxic and phytotoxic actions of Heliotropium strigosum.

PubMed

Shah, Syed Majid; Hussain, Sajid; Khan, Arif-Ullah; Shah, Azhar-Ul-Haq Ali; Khan, Haroon; Ullah, Farhat; Barkatullah

2015-05-01

This study describes the cytotoxic and phytotoxic activities of the crude extract of Heliotropium strigosum and its resultant fractions. In brine shrimp toxicology assays, profound cytotoxicity was displayed by ethyl acetate (LD50 8.3 μg/ml) and chloroform (LD50 8.8 μg/ml) fractions, followed by relatively weak crude methanolic extract of H. strigosum (LD50 909 μg/ml) and n-hexane fraction (LD50 1000 μg/ml). In case of phytotoxicity activity against Lemna acquinoctialis, highest phytotoxic effect was showed by ethyl acetate fraction (LD50 91.0 μg/ml), while chloroform fraction, plant crude extract and n-hexane, respectively, caused 50%, 30.76 ± 1.1% and 30.7 ± 1.1% inhibitory action at maximum concentration used, that is, 1000 μg/ml. These data indicates that H. strigosum exhibits cytotoxic and phytotoxic potential, which explore its use as anticancer and herbicidal medicine. The ethyl acetate and chloroform fractions were more potent for the evaluated toxicity effects, thus recommended for isolation and identification of the active compounds. © The Author(s) 2012.

Dependence between LD50 for Rodents and LC50 for Adult Fish and Fish Embryos.

PubMed

Zolotarev, K V; Belyaeva, N F; Mikhailov, A N; Mikhailova, M V

2017-02-01

We revealed empirical dependences between common logarithm of a ratio of rat oral LD 50 to LC a 50 for adult fish and lgP for 50 different chemicals; and common logarithm of a ratio of the oral LD 50 in rodents to LC e 50 for fish embryos and lgP for 30 different chemicals. The dependences were obtained by constructing a trend line between experimental points and calculation of Pearson's R correlation coefficient as a measure of regression significance. These dependences can show the influence of substance lipophilicity on its toxicity for aquatic organisms comparing to mammals.

Acute toxicity of organophosphorus compounds in guinea pigs is sex- and age-dependent and cannot be solely accounted for by acetylcholinesterase inhibition.

PubMed

Fawcett, William P; Aracava, Yasco; Adler, Michael; Pereira, Edna F R; Albuquerque, Edson X

2009-02-01

This study was designed to test the hypothesis that the acute toxicity of the nerve agents S-[2-(diisopropylamino)ethyl]-O-ethyl methylphosphonothioate (VX), O-pinacolyl methylphosphonofluoridate (soman), and O-isopropyl methylphosphonofluoridate (sarin) in guinea pigs is age- and sex-dependent and cannot be fully accounted for by the irreversible inhibition of acetylcholinesterase (AChE). The subcutaneous doses of nerve agents needed to decrease 24-h survival of guinea pigs by 50% (LD(50) values) were estimated by probit analysis. In all animal groups, the rank order of LD(50) values was sarin > soman > VX. The LD(50) value of soman was not influenced by sex or age of the animals. In contrast, the LD(50) values of VX and sarin were lower in adult male than in age-matched female or younger guinea pigs. A colorimetric assay was used to determine the concentrations of nerve agents that inhibit in vitro 50% of AChE activity (IC(50) values) in guinea pig brain extracts, plasma, red blood cells, and whole blood. A positive correlation between LD(50) values and IC(50) values for AChE inhibition would support the hypothesis that AChE inhibition is a major determinant of the acute toxicity of the nerve agents. However, such a positive correlation was found only between LD(50) values and IC(50) values for AChE inhibition in brain extracts from neonatal and prepubertal guinea pigs. These results demonstrate for the first time that the lethal potencies of some nerve agents in guinea pigs are age- and sex-dependent. They also support the contention that mechanisms other than AChE inhibition contribute to the lethality of nerve agents.

[Acute lethal effect of the commercial formulation of the insecticides Imidacloprid, Spinosad y Thiocyclam hidrogenoxalate in Bombus atratus (Hymenoptera: Apidae) workers].

PubMed

Riaño Jiménez, Diego; Cure, José Ricardo

2016-12-01

The effect of insecticides on bees has gained great attention, however, there are few studies that explore this issue on Neotropical bees. Bombus atratus is a neotropical species broadly distributed in Colombia and is considered an important pollinator of both Andean ecosystems and agroecosystems. However, as for many wild bees species, the effect of insecticides on B. atratus is unknow. In this study we determined the acute median lethal dose (LD50) of commercial formulations of insecticides Imidacloprid, Spinosad and Thiocyclam hydrogen oxalate, widely used in Colombia to control several pests of important crops. The LD50 was carried out by oral and contact routes, following and modifying the EPPO and OECD guidelines to perform LD50 on A. mellifera. We evaluated five doses for each route and insecticide, in a total of 25 medium-size workers for each dose by duplicate. Mortality was registered at 24, 48 and 72 hours after the experiment; and data were analyzed with the Probit regression model. For Imidacloprid, contacts and oral LD50 were 0.048 µg/bee and 0.010 µg/bee, respectively. For Thiocyclam hydrogen oxalate, topical and oral LD50 were 0.244 µg/bee and 0.056 µg/bee, respectively. For Spinosad, the oral LD50 corresponded to 0.28 µg/bee; it was not possible to establish the LD50 for the contact route. The Hazard Quotient (HQ) and Index of Relative Toxicity indicated that all three active ingredients are highly toxic. We discussed the risk of the insecticides use on B. atratus, considering their chemical nature.

Using a Hazard Quotient to Evaluate Pesticide Residues Detected in Pollen Trapped from Honey Bees (Apis mellifera) in Connecticut

PubMed Central

Stoner, Kimberly A.; Eitzer, Brian D.

2013-01-01

Analysis of pollen trapped from honey bees as they return to their hives provides a method of monitoring fluctuations in one route of pesticide exposure over location and time. We collected pollen from apiaries in five locations in Connecticut, including urban, rural, and mixed agricultural sites, for periods from two to five years. Pollen was analyzed for pesticide residues using a standard extraction method widely used for pesticides (QuEChERS) and liquid chromatography/mass spectrometric analysis. Sixty pesticides or metabolites were detected. Because the dose lethal to 50% of adult worker honey bees (LD50) is the only toxicity parameter available for a wide range of pesticides, and among our pesticides there were contact LD50 values ranging from 0.006 to >1000 μg per bee (range 166,000X), and even among insecticides LD50 values ranged from 0.006 to 59.8 μg/bee (10,000X); therefore we propose that in studies of honey bee exposure to pesticides that concentrations be reported as Hazard Quotients as well as in standard concentrations such as parts per billion. We used both contact and oral LD50 values to calculate Pollen Hazard Quotients (PHQ = concentration in ppb ÷ LD50 as μg/bee) when both were available. In this study, pesticide Pollen Hazard Quotients ranged from over 75,000 to 0.01. The pesticides with the greatest Pollen Hazard Quotients at the maximum concentrations found in our study were (in descending order): phosmet, Imidacloprid, indoxacarb, chlorpyrifos, fipronil, thiamethoxam, azinphos-methyl, and fenthion, all with at least one Pollen Hazard Quotient (using contact or oral LD50) over 500. At the maximum rate of pollen consumption by nurse bees, a Pollen Hazard Quotient of 500 would be approximately equivalent to consuming 0.5% of the LD50 per day. We also present an example of a Nectar Hazard Quotient and the percentage of LD50 per day at the maximum nectar consumption rate. PMID:24143241

Using a hazard quotient to evaluate pesticide residues detected in pollen trapped from honey bees (Apis mellifera) in Connecticut.

PubMed

Stoner, Kimberly A; Eitzer, Brian D

2013-01-01

Analysis of pollen trapped from honey bees as they return to their hives provides a method of monitoring fluctuations in one route of pesticide exposure over location and time. We collected pollen from apiaries in five locations in Connecticut, including urban, rural, and mixed agricultural sites, for periods from two to five years. Pollen was analyzed for pesticide residues using a standard extraction method widely used for pesticides (QuEChERS) and liquid chromatography/mass spectrometric analysis. Sixty pesticides or metabolites were detected. Because the dose lethal to 50% of adult worker honey bees (LD50) is the only toxicity parameter available for a wide range of pesticides, and among our pesticides there were contact LD50 values ranging from 0.006 to >1000 μg per bee (range 166,000X), and even among insecticides LD50 values ranged from 0.006 to 59.8 μg/bee (10,000X); therefore we propose that in studies of honey bee exposure to pesticides that concentrations be reported as Hazard Quotients as well as in standard concentrations such as parts per billion. We used both contact and oral LD50 values to calculate Pollen Hazard Quotients (PHQ = concentration in ppb ÷ LD50 as μg/bee) when both were available. In this study, pesticide Pollen Hazard Quotients ranged from over 75,000 to 0.01. The pesticides with the greatest Pollen Hazard Quotients at the maximum concentrations found in our study were (in descending order): phosmet, Imidacloprid, indoxacarb, chlorpyrifos, fipronil, thiamethoxam, azinphos-methyl, and fenthion, all with at least one Pollen Hazard Quotient (using contact or oral LD50) over 500. At the maximum rate of pollen consumption by nurse bees, a Pollen Hazard Quotient of 500 would be approximately equivalent to consuming 0.5% of the LD50 per day. We also present an example of a Nectar Hazard Quotient and the percentage of LD50 per day at the maximum nectar consumption rate.

Predictive value of late decelerations for fetal acidemia in unselective low-risk pregnancies.

PubMed

Sameshima, Hiroshi; Ikenoue, Tsuyomu

2005-01-01

We evaluated the clinical significance of late decelerations (LD) of intrapartum fetal heart rate (FHR) monitoring to detect low pH (< 7.1) in low-risk pregnancies. We selected two secondary and two tertiary-level institutions where 10,030 women delivered. Among them, 5522 were low-risk pregnancies. The last 2 hours of FHR patterns before delivery were interpreted according to the guidelines of the National Institute of Child Health and Human Development. The correlation between the incidence of LD (occasional, < 50%; recurrent, > or = 50%) and severity (reduced baseline FHR accelerations and variability) of LD, and low pH (< 7.1) were evaluated. Statistical analyses included a contingency table with chi2 and the Fisher test, and one-way analysis of variance with the Bonferroni/Dunn test. In the 5522 low-risk pregnancies, 301 showed occasional LD and 99 showed recurrent LD. Blood gases and pH values deteriorated as the incidence of LD increased and as baseline accelerations or variability was decreased. Positive predictive value for low pH (< 7.1) was exponentially elevated from 0% at no deceleration, 1% in occasional LD, and > 50% in recurrent LD with no baseline FHR accelerations and reduced variability. In low-risk pregnancies, information on LD combined with acceleration and baseline variability enables us to predict the potential incidence of fetal acidemia.

A Novel Two-Step Hierarchical Quantitative Structure–Activity Relationship Modeling Work Flow for Predicting Acute Toxicity of Chemicals in Rodents

PubMed Central

Zhu, Hao; Ye, Lin; Richard, Ann; Golbraikh, Alexander; Wright, Fred A.; Rusyn, Ivan; Tropsha, Alexander

2009-01-01

Background Accurate prediction of in vivo toxicity from in vitro testing is a challenging problem. Large public–private consortia have been formed with the goal of improving chemical safety assessment by the means of high-throughput screening. Objective A wealth of available biological data requires new computational approaches to link chemical structure, in vitro data, and potential adverse health effects. Methods and results A database containing experimental cytotoxicity values for in vitro half-maximal inhibitory concentration (IC50) and in vivo rodent median lethal dose (LD50) for more than 300 chemicals was compiled by Zentralstelle zur Erfassung und Bewertung von Ersatz- und Ergaenzungsmethoden zum Tierversuch (ZEBET; National Center for Documentation and Evaluation of Alternative Methods to Animal Experiments). The application of conventional quantitative structure–activity relationship (QSAR) modeling approaches to predict mouse or rat acute LD50 values from chemical descriptors of ZEBET compounds yielded no statistically significant models. The analysis of these data showed no significant correlation between IC50 and LD50. However, a linear IC50 versus LD50 correlation could be established for a fraction of compounds. To capitalize on this observation, we developed a novel two-step modeling approach as follows. First, all chemicals are partitioned into two groups based on the relationship between IC50 and LD50 values: One group comprises compounds with linear IC50 versus LD50 relationships, and another group comprises the remaining compounds. Second, we built conventional binary classification QSAR models to predict the group affiliation based on chemical descriptors only. Third, we developed k-nearest neighbor continuous QSAR models for each subclass to predict LD50 values from chemical descriptors. All models were extensively validated using special protocols. Conclusions The novelty of this modeling approach is that it uses the relationships between in vivo and in vitro data only to inform the initial construction of the hierarchical two-step QSAR models. Models resulting from this approach employ chemical descriptors only for external prediction of acute rodent toxicity. PMID:19672406

A novel two-step hierarchical quantitative structure-activity relationship modeling work flow for predicting acute toxicity of chemicals in rodents.

PubMed

Zhu, Hao; Ye, Lin; Richard, Ann; Golbraikh, Alexander; Wright, Fred A; Rusyn, Ivan; Tropsha, Alexander

2009-08-01

Accurate prediction of in vivo toxicity from in vitro testing is a challenging problem. Large public-private consortia have been formed with the goal of improving chemical safety assessment by the means of high-throughput screening. A wealth of available biological data requires new computational approaches to link chemical structure, in vitro data, and potential adverse health effects. A database containing experimental cytotoxicity values for in vitro half-maximal inhibitory concentration (IC(50)) and in vivo rodent median lethal dose (LD(50)) for more than 300 chemicals was compiled by Zentralstelle zur Erfassung und Bewertung von Ersatz- und Ergaenzungsmethoden zum Tierversuch (ZEBET; National Center for Documentation and Evaluation of Alternative Methods to Animal Experiments). The application of conventional quantitative structure-activity relationship (QSAR) modeling approaches to predict mouse or rat acute LD(50) values from chemical descriptors of ZEBET compounds yielded no statistically significant models. The analysis of these data showed no significant correlation between IC(50) and LD(50). However, a linear IC(50) versus LD(50) correlation could be established for a fraction of compounds. To capitalize on this observation, we developed a novel two-step modeling approach as follows. First, all chemicals are partitioned into two groups based on the relationship between IC(50) and LD(50) values: One group comprises compounds with linear IC(50) versus LD(50) relationships, and another group comprises the remaining compounds. Second, we built conventional binary classification QSAR models to predict the group affiliation based on chemical descriptors only. Third, we developed k-nearest neighbor continuous QSAR models for each subclass to predict LD(50) values from chemical descriptors. All models were extensively validated using special protocols. The novelty of this modeling approach is that it uses the relationships between in vivo and in vitro data only to inform the initial construction of the hierarchical two-step QSAR models. Models resulting from this approach employ chemical descriptors only for external prediction of acute rodent toxicity.

Derivation of Human Lethal Doses

DTIC Science & Technology

2006-01-19

1956; Blair, 1961; Mason et al., 1965; Clarke , 1969; Cretney, 1976; Gray et al., 1985). Gordon reported blood level of 5 mg/100ml in a victim. The...LD50 ( Clark et al., 1979). This is a primary source for the value. No LD50 for mouse Clinical Management of Poisoning and Drug Overdose 100 mL...Verschueren (2001) lists an oral LD50 range in various mammalian species as 30-112 mg/kg based on Clark et al., (1966 as cited in Verschueren, 2001

Stroop Color-Word Test: A Screening Measure of Selective Attention to Differentiate LD From Non LD Children.

ERIC Educational Resources Information Center

Lazarus, Philip J.; And Others

1984-01-01

Used the Stroop Color-Word Test to measure selective attention in learning disabled (N=45) and nonLD (N=50) children. Results indicated that LD children have a significant weakness in the process of selective attention compared to the nonLD children. Findings suggested that the Stroop is an effective screening measure. (JAC)

The botulinum neurotoxin LD50 test - problems and solutions.

PubMed

Bitz, Silke

2010-01-01

Apart from the fact that the LD50 test is generally considered a procedure causing severe distress, which alone should result in its immediate deletion, it also conflicts with the EU wide ban on cosmetic testing in animals in the case of Botulinum Neurotoxin (BoNT) testing. The European Pharmacopoeia monograph allows for the use of three alternative methods provided they are validated. However these alternative assays are neither implemented by the manufactures of BoNT products nor are they enforced by the responsible authorities, e.g. by deleting the LD50 from the European Pharmacopoeia. The number of animals used for the testing of BoNT is not officially recorded. However, data from an undercover investigation allow the estimation that the number of mice used in LD50tests for BoNT products is greater than 600,000 per year worldwide.

A novel method for deriving thresholds of toxicological concern for vaccine constituents.

PubMed

White, Jennifer; Wrzesinski, Claudia; Green, Martin; Johnson, Giffe T; McCluskey, James D; Abritis, Alison; Harbison, Raymond D

2016-05-01

Safety assessment evaluating the presence of impurities, residual materials, and contaminants in vaccines is a focus of current research. Thresholds of toxicological concern (TTCs) are mathematically modeled levels used for assessing the safety of many food and medication constituents. In this study, six algorithms are selected from the open-access ToxTree software program to derive a method for calculating TTCs for vaccine constituents: In Vivo Rodent Micronucleus assay/LD50, Benigni-Bossa/LD50, Cramer Extended/LD50, In Vivo Rodent Micronucleus assay/TDLo, Benigni-Bossa/TDLo, and the Cramer Extended/TDLo. Using an initial dataset (n = 197) taken from INCHEM, RepDose, RTECS, and TOXNET, the chemicals were divided into two families: "positive" - based on the presence of structures associated with adverse outcomes, or "negative" - no such structures or having structures that appear to be protective of health. The final validation indicated that the Benigni-Bossa/LD50 method is the most appropriate for calculating TTCs for vaccine constituents. Final TTCs were designated as 18.06 μg/person and 20.61 μg/person for the Benigni-Bossa/LD50 positive and negative structural families, respectively.

Description of histopathological changes induced by the venom of the Persian Gulf Lionfish (Pterois russelli) in a mouse model of multiorgan toxicity.

PubMed

Memar, Bahareh; Jamili, Shahla; Shahbazzadeh, Delavar; Pooshang Bagheri, Kamran

2016-11-01

Pterois russelli is a venomous fish belongs to Scorpaenidae family. Envenomation by the Persian Gulf lionfish is associated with local pain, marked inflammation and local heat. The present study was aimed to document the histopathological changes in liver, heart, lung, kidney and alterations in release of critical enzymes such as LDH, CK. AST, ALT and ALP induced by the administration of various doses of P. russelli venom in a mouse model. LD50 of venom was determined by intravenous injection in Balb/c mice. Histopathological alterations of lung, liver, heart and kidney following injection of one LD50, 1/2 and 1/3 LD50 doses of the venom were evaluated. Simultaneously, release of LDH, CK, AST, ALT and ALP were measured in serum following administration of 1/2 and1/3 LD50 doses of the venom too. LD50 was calculated as 10.5 mg/kg. The level of all enzymes were increased after 3 h and significantly raised after 24 h and rapidly reduced after 48 h. Histological studies showed that one LD50 and 1/2 LD50 doses of the venom induced significant histological alterations in the lungs, liver, heart and kidneys including congestion, hemorrhage, necrosis, apoptosis, edema, and infiltration of inflammatory cells. The results indicate that the venom of P. russelli has nephrotoxic, hepatotoxic, cardiotoxic and pneumotoxic effects in mouse model. Among four examined vital organs, the highest critical events were seen in liver. The findings are useful to give new insight in the fish's venom studies. Gathering the data resulted from this study together will be directed us toward a good aspect concerning the toxicity of potential therapeutic molecules in the venom of lionfish. Copyright © 2016 Elsevier Ltd. All rights reserved.

The effect of dimethoate and pyrantel on vitamin C concentration in the rat liver.

PubMed

Spodniewska, A; Zasadowski, A

2006-01-01

The aim of this study was to determine the content of vitamin C in the liver of rats exposed to dimethoate or pyrantel embonate as well as co-intoxication with both agents. Investigations were carried out in two stages. At each stage, the rats were divided into three experimental groups (I-III) and a control (C) group. In the first stage, rats from group I were administered pyrantel embonate at a two-week interval at a dose of 1/2 LD50, while the animals from group II received dimethoate for 28 days at a dose of 1/25 LD50, and those from group III - both mentioned compounds in an identical manner as in groups I and II. In the second stage, the rats from group I received pyrantel embonate at a dose of 1/5 LD50 for 3 consecutive days, while the animals from group II received dimethoate at a dose of 1/10 LD50 for 5 consecutive days, and those from III received both compounds, but pyrantel was administered on day 3, 4 and 5 of dimethoate administration. The concentration of vitamin C after pyrantel embonate and dimethoate administration was influenced not only by doses of the compounds used but also by the manner of their application (single or co-administration). Dimethoate delivered at a dose of 1/25 LD50 evoked an increase in vitamin C concentration that was observed to continue up to the 14th day after the exposure, whereas when applied at a dose of 1/10 LD50 it increased the vitamin C level only at the 3rd hour. A considerable decrease in the vitamin C level was reported after pyrantel treatment at a dose of 1/5 LD50. In rats from groups where the compounds were co-administered, increased level of vitamin C was observed at both stages of the experiment only in the first period after intoxication, i.e. up to the 6th hour.

High-Throughput, Signature-Tagged Mutagenic Approach To Identify Novel Virulence Factors of Yersinia pestis CO92 in a Mouse Model of Infection

PubMed Central

Ponnusamy, Duraisamy; Fitts, Eric C.; Erova, Tatiana E.; Kozlova, Elena V.; Kirtley, Michelle L.; Tiner, Bethany L.; Andersson, Jourdan A.

2015-01-01

The identification of new virulence factors in Yersinia pestis and understanding their molecular mechanisms during an infection process are necessary in designing a better vaccine or to formulate an appropriate therapeutic intervention. By using a high-throughput, signature-tagged mutagenic approach, we created 5,088 mutants of Y. pestis strain CO92 and screened them in a mouse model of pneumonic plague at a dose equivalent to 5 50% lethal doses (LD50) of wild-type (WT) CO92. From this screen, we obtained 118 clones showing impairment in disseminating to the spleen, based on hybridization of input versus output DNA from mutant pools with 53 unique signature tags. In the subsequent screen, 20/118 mutants exhibited attenuation at 8 LD50 when tested in a mouse model of bubonic plague, with infection by 10/20 of the aforementioned mutants resulting in 40% or higher survival rates at an infectious dose of 40 LD50. Upon sequencing, six of the attenuated mutants were found to carry interruptions in genes encoding hypothetical proteins or proteins with putative functions. Mutants with in-frame deletion mutations of two of the genes identified from the screen, namely, rbsA, which codes for a putative sugar transport system ATP-binding protein, and vasK, a component of the type VI secretion system, were also found to exhibit some attenuation at 11 or 12 LD50 in a mouse model of pneumonic plague. Likewise, among the remaining 18 signature-tagged mutants, 9 were also attenuated (40 to 100%) at 12 LD50 in a pneumonic plague mouse model. Previously, we found that deleting genes encoding Braun lipoprotein (Lpp) and acyltransferase (MsbB), the latter of which modifies lipopolysaccharide function, reduced the virulence of Y. pestis CO92 in mouse models of bubonic and pneumonic plague. Deletion of rbsA and vasK genes from either the Δlpp single or the Δlpp ΔmsbB double mutant augmented the attenuation to provide 90 to 100% survivability to mice in a pneumonic plague model at 20 to 50 LD50. The mice infected with the Δlpp ΔmsbB ΔrbsA triple mutant at 50 LD50 were 90% protected upon subsequent challenge with 12 LD50 of WT CO92, suggesting that this mutant or others carrying combinational deletions of genes identified through our screen could potentially be further tested and developed into a live attenuated plague vaccine(s). PMID:25754198

High-throughput, signature-tagged mutagenic approach to identify novel virulence factors of Yersinia pestis CO92 in a mouse model of infection.

PubMed

Ponnusamy, Duraisamy; Fitts, Eric C; Sha, Jian; Erova, Tatiana E; Kozlova, Elena V; Kirtley, Michelle L; Tiner, Bethany L; Andersson, Jourdan A; Chopra, Ashok K

2015-05-01

The identification of new virulence factors in Yersinia pestis and understanding their molecular mechanisms during an infection process are necessary in designing a better vaccine or to formulate an appropriate therapeutic intervention. By using a high-throughput, signature-tagged mutagenic approach, we created 5,088 mutants of Y. pestis strain CO92 and screened them in a mouse model of pneumonic plague at a dose equivalent to 5 50% lethal doses (LD50) of wild-type (WT) CO92. From this screen, we obtained 118 clones showing impairment in disseminating to the spleen, based on hybridization of input versus output DNA from mutant pools with 53 unique signature tags. In the subsequent screen, 20/118 mutants exhibited attenuation at 8 LD50 when tested in a mouse model of bubonic plague, with infection by 10/20 of the aforementioned mutants resulting in 40% or higher survival rates at an infectious dose of 40 LD50. Upon sequencing, six of the attenuated mutants were found to carry interruptions in genes encoding hypothetical proteins or proteins with putative functions. Mutants with in-frame deletion mutations of two of the genes identified from the screen, namely, rbsA, which codes for a putative sugar transport system ATP-binding protein, and vasK, a component of the type VI secretion system, were also found to exhibit some attenuation at 11 or 12 LD50 in a mouse model of pneumonic plague. Likewise, among the remaining 18 signature-tagged mutants, 9 were also attenuated (40 to 100%) at 12 LD50 in a pneumonic plague mouse model. Previously, we found that deleting genes encoding Braun lipoprotein (Lpp) and acyltransferase (MsbB), the latter of which modifies lipopolysaccharide function, reduced the virulence of Y. pestis CO92 in mouse models of bubonic and pneumonic plague. Deletion of rbsA and vasK genes from either the Δlpp single or the Δlpp ΔmsbB double mutant augmented the attenuation to provide 90 to 100% survivability to mice in a pneumonic plague model at 20 to 50 LD50. The mice infected with the Δlpp ΔmsbB ΔrbsA triple mutant at 50 LD50 were 90% protected upon subsequent challenge with 12 LD50 of WT CO92, suggesting that this mutant or others carrying combinational deletions of genes identified through our screen could potentially be further tested and developed into a live attenuated plague vaccine(s). Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Larvicidal effects of various Euro-Asiatic plants against Culex quinquefasciatus Say larvae (Diptera: Culicidae).

PubMed

Pavela, Roman

2008-02-01

Extracts from 56 species of plants in the Euro-Asiatic region were tested for larvicidal activity against the fourth larval instar of the mosquito Culex quinquefasciatus Say (Diptera: Culicidae). All plant extracts showed larvicidal activity after 24 h of exposure to the plant extracts in a maximal dose of 500 ppm. The extracts of the plants Otanthus maritimus and Ammi visnaga displayed the highest larvicidal effect (LD(50) 7 and 9 ppm, respectively) followed by Acer pseudoplatanus, Humulus japonicus, Acer platanoides, Satureja hortensis, Ocimum basilicum and Thymus vulgaris (LD(50) 23, 25, 28, 28, 32 and 48 ppm respectively). For eight species, the appraisal value of LD(50) was between 51 and 100 ppm, another eight species from 101 to 200 ppm, 15 species from 201 to 500 ppm and for 17 species, low mortality showed no lethal dose (LD(50)>500 ppm).

Persistence of Clostridium botulinum type C toxin in blow fly (Calliphoridae) larvae as a possible cause of avian botulism in spring.

PubMed

Hubálek, Z; Halouzka, J

1991-01-01

Diverse samples were examined at a site of water-bird mortality, caused by Clostridium botulinum type C toxin in southern Moravia (Czechoslovakia). The toxin was detected in high concentrations in mute swan (Cygnus olor) carcasses (less than or equal to 1 x 10(6) LD50/g) as well as in necrophagous larvae and pupae of the blow flies Lucilia sericata and Calliphora vomitoria (less than or equal to 1 x 10(5) LD50/g) collected from them. It was detected in lower concentrations (less than or equal to 1 x 10(3) LD50/g) in other invertebrates (ptychopterid fly larvae, leeches, sow-bugs) associated with these carcasses, and occasionally in water samples (8 LD50/ml) close to the carrion. The toxin was not detected in the samples of water, mud or invertebrates collected at a distance greater than or equal to 5 m from the carcasses. The toxin-bearing larvae of L. sericata and C. vomitoria, containing 80,000 LD50/g of type C toxin, were exposed in the mud at the study site for 131 days from November to March. Although the toxin activity decreased 25-fold and 40-fold in the two samples of maggots exposed during this period, it remained very high (less than or equal to 3,200 LD50/g). Birds ingesting a relatively low number of these toxic larvae (or pupae) in the spring could receive a lethal dose of the toxin.

Acute toxicity and mutagenesis of three metabolites mixture of nitrobenzene in mice.

PubMed

Wang, Guixia; Zhang, Xiuying; Yao, Chunzhu; Tian, Meizhan

2011-03-01

Nitrobenzene is a synthetic compound, more than 95% of which is used in the production of aniline. Nitrobenzene has been demonstrated to be substantially metabolized to p-Nitrophenol, p-Aminophenol and p-Nitroaniline in food animals (e.g., bovines, fowls). There have been no studies on the acute toxicity and the mutagenesis of the mixture of the three metabolites mentioned above. The aim of the present study is to testify the acute toxicity and the mutagenesis of the three metabolites mixture. Seventy Kunming mice (half male, half female) received an intragastric administration exposure to metabolites-containing suspension of 750, 638, 542, 461, 392, 333 mg kg(-1) body weight and 0.5% sodium carboxymethyl cellulose (control), followed by a 14-day observation. The medial lethal dose (LD(50)) concentration for nitrobenzene metabolites mixture in this study was 499.92 mg/kg. Their mutagenic toxicology was studied through micronucleus and sperm abnormality test. Kunming mice were twice intragastrically exposed to 1/5 LD(50), 1/10 LD(50), 1/20 LD(50) mg kg(-1) nitrobenzene metabolites-containing suspension spaced 24-h apart. Cyclophosphamide, pure water and sodium carboxymethyl cellulose served as doses of the positive group, the negative group and the solvent control group, respectively. The incidence of micronucleus and sperm abnormality increased significantly in the 1/5 LD(50) and 1/10 LD(50) group compared with the negative and solvent control group. A dose-related increase in the incidence of micronucleus and sperm abnormality was noted. In conclusion, the three metabolites mixture of nitrobenzene was secondary toxicity and mutagenic substances in mice.

Technetium-99m Pyrophosphate: Comparison of ED50 for Tetany and Acidosis with Acute LD500

DTIC Science & Technology

electrocardiogram and chemical analysis revealed that the hypocalcemic effect occurs at a much lower dosage than for the LD50. Polyphosphate was found to be more...toxic by the LD50 analysis than pyrophosphate. It is emphasized that the hypocalcemic toxic effects should be the determining factor in deciding what...to 1 with regard to the first signs of hypocalcemia by electrocardiographic measurements (i.e., 2 mg/kg). On this basis an injection of no more than 1 mg/kg is recommended to maintain a safety factor of around 10 to 1.

COBALT COMPOUNDS AS ANTIDOTES FOR HYDROCYANIC ACID.

PubMed

EVANS, C L

1964-12-01

The antidotal potency of a cobalt salt (acetate), of dicobalt edetate, of hydroxocobalamin and of cobinamide against hydrocyanic acid was examined mainly on mice and rabbits. All the compounds were active antidotes for up to twice the LD50; under some conditions for larger doses. The most successful was cobalt acetate for rabbits (5xLD50), which was effective at a molar cyanide/cobalt (CN/Co) ratio of 5, but had as a side-effect intense purgation. Hydroxocobalamin was irregular in action, but on the whole was most effective for mice (4.5xLD50 at a molar ratio of 1), and had no apparent side effects. Dicobalt edetate, at molar ratios of up to 2, was more effective for rabbits (3xLD50) than for mice (2xLD50), but had fewer side effects than cobalt acetate. The effect of thiosulphate was to augment the efficacy of dicobalt edetate and, in mice, that of hydroxocobalamin; but, apparently, in rabbits, to reduce that of hydroxocobalamin. Cobinamide, at a molar ratio of 1, was slightly more effective than hydroxocobalamin on rabbits and also less irregular in its action. Cobalt acetate by mouth was effective against orally administered hydrocyanic acid. The oxygen uptake of the body, reduced by cyanide, is rapidly reinstated when one of the cobalt antidotes has been successfully administered.

Acute Toxicity of Permethrin, Deltamethrin, and Etofenprox to the Alfalfa Leafcutting Bee.

PubMed

Piccolomini, Alyssa M; Whiten, Shavonn R; Flenniken, Michelle L; O'Neill, Kevin M; Peterson, Robert K D

2018-05-28

Current regulatory requirements for insecticide toxicity to nontarget insects focus on the honey bee, Apis mellifera (L.; Hymenoptera: Apidae), but this species cannot represent all insect pollinator species in terms of response to insecticides. Therefore, we characterized the toxicity of pyrethroid insecticides used for adult mosquito management (permethrin, deltamethrin, and etofenprox) on a nontarget insect, the adult alfalfa leafcutting bee, Megachile rotundata (F.; Hymenoptera: Megachilidae) in two separate studies. In the first study, the doses causing 50 and 90% mortality (LD50 and LD90, respectively) were used as endpoints and 2-d-old adult females were exposed to eight concentrations ranging from 0.0075 to 0.076 μg/bee for permethrin and etofenprox, and 0.0013-0.0075 μg/bee for deltamethrin. For the second study, respiration rates of female M. rotundata were also recorded for 2 h after bees were dosed at the LD50 values to give an indication of stress response. Results indicated a relatively similar LD50 for permethrin and etofenprox, 0.057 and 0.051 μg/bee, respectively, and a more toxic response, 0.0016 μg/bee for deltamethrin. Comparatively, female A. mellifera workers have a LD50 value of 0.024 μg/bee for permethrin and 0.015 μg/bee for etofenprox indicating that female M. rotundata are less susceptible to topical doses of these insecticides, except for deltamethrin, where both A. mellifera and M. rotundata have an identical LD50 of 0.0016 μg/bee. Respiration rates comparing each active ingredient to control groups, as well as rates between each active ingredient, were statistically different (P < 0.0001). The addition of these results to existing information on A. mellifera may provide more insights on how other economically beneficial and nontarget bees respond to pyrethroids.

[The activity of blood cholinesterase in rats exposed to dimehypo].

PubMed

Wan, Weiguo; Xu, Mailing; Zou, Hejian; Lu, Ailing; Shen, Xinyu; Chen, Yuming

2002-12-01

To determine whether and to what degree the activity of cholinesterase(ChE) is inhibited by dimehypo at different doses of dimehypo [scientific name: 2-dimethylamine-1,3-bi(sodium hyposulfit)]. Rats were dosed with dimehypo or methamidophos orally, and were randomly divided into four subgroups according to the pesticide doses, which were 1/16, 1/8, 1/4 and 1/2 of LD50 respectively(the LD50 of dimethypo and methamidophos is 342 mg/kg and 20 mg/kg respectively). The activity of ChE in blood was determined before and 30 min, 1, 2, 4 and 24 h after exposure. The modified Ellman Method was employed to measure the activity of ChE. 1/16 LD50 dose of dimehypo did not affect the activity of ChE. When the dose increased, the activity of ChE decreased accordingly. 1/2 LD50 dose of dimehypo inhibited the activity of ChE by 35.9% compared with that of control group(P < 0.01). In rats dosed with methamidophos, even 1/16 LD50 dose inhibited the activity of ChE by 42.4% compared with that of control group. When the dose of methamidophos increased, the activity of ChE decreased accordingly. 1/2 LD50 dose of methamidophos inhibited the activity of ChE by 52.9%. The activity of ChE in the rats dosed with dimehypo at various doses was significantly lower than that in the rats dosed with corresponding doses of methamidophos(P < 0.01). Higher doses of dimehypo may inhibit the activity of ChE. However, as compared with methamidophos, dimehypo is a weaker inhibitor of ChE.

Post-hoc analysis showing better clinical response with the loading dose of certolizumab pegol in Japanese patients with active rheumatoid arthritis.

PubMed

Takeuchi, Tsutomu; Yamamoto, Kazuhiko; Yamanaka, Hisashi; Ishiguro, Naoki; Tanaka, Yoshiya; Eguchi, Katsumi; Watanabe, Akira; Origasa, Hideki; Kobayashi, Mariko; Shoji, Toshiharu; Togo, Osamu; Miyasaka, Nobuyuki; Koike, Takao

2016-07-01

To compare the efficacy and safety of certolizumab pegol (CZP) with and without loading dose (LD) in a post-hoc analysis of two Japanese clinical studies. Data from the double-blind trials (DBT) J-RAPID and HIKARI, and their open-label extension (OLE) studies, were used. Patients randomized to CZP 200 mg every 2 weeks (Q2W) groups starting with LD (400 mg Weeks 0/2/4; LD group; J-RAPID: n = 82, HIKARI: n = 116) and patients randomized to placebo groups who subsequently started CZP Q2W without LD in the OLEs (No-LD group; J-RAPID: n = 61, HIKARI: n = 99) were analyzed. Efficacy and pharmacokinetics were assessed during 24 weeks. Adverse events were reported from all studies. In both trials, the LD groups showed more rapid initial ACR20/50/70 kinetics, and maintained higher ACR50/70 responses until 24 weeks, compared with the No-LD groups. Anti-CZP antibody development was less frequent in the LD groups (J-RAPID: 1.2% versus 4.9%; HIKARI: 17.2% versus 27.3%). Similar safety profiles were reported between LD and No-LD groups (any AEs: 281.8 versus 315.7 [J-RAPID], 282.6 versus 321.3 [HIKARI] [incidence rate/100 patient-years]). Despite limitations, including comparing DBT and OLE studies, these results suggest that a CZP LD improves clinical response in active rheumatoid arthritis without altering the safety profile.

Rab5 Isoforms Specifically Regulate Different Modes of Endocytosis in Leishmania.

PubMed

Rastogi, Ruchir; Verma, Jitender Kumar; Kapoor, Anjali; Langsley, Gordon; Mukhopadhyay, Amitabha

2016-07-08

Differential functions of Rab5 isoforms in endocytosis are not well characterized. Here, we cloned, expressed, and characterized Rab5a and Rab5b from Leishmania and found that both of them are localized in the early endosome. To understand the role of LdRab5 isoforms in different modes of endocytosis in Leishmania, we generated transgenic parasites overexpressing LdRab5a, LdRab5b, or their dominant-positive (LdRab5a:Q93L and LdRab5b:Q80L) or dominant-negative mutants (LdRab5a:N146I and LdRab5b:N133I). Using LdRab5a or its mutants overexpressing parasites, we found that LdRab5a specifically regulates the fluid-phase endocytosis of horseradish peroxidase and also specifically induced the transport of dextran-Texas Red to the lysosomes. In contrast, cells overexpressing LdRab5b or its mutants showed that LdRab5b explicitly controls receptor-mediated endocytosis of hemoglobin, and overexpression of LdRab5b:WT enhanced the transport of internalized Hb to the lysosomes in comparison with control cells. To unequivocally demonstrate the role of Rab5 isoforms in endocytosis in Leishmania, we tried to generate null-mutants of LdRab5a and LdRab5b parasites, but both were lethal indicating their essential functions in parasites. Therefore, we used heterozygous LdRab5a(+/-) and LdRab5b(+/-) cells. LdRab5a(+/-) Leishmania showed 50% inhibition of HRP uptake, but hemoglobin endocytosis was uninterrupted. In contrast, about 50% inhibition of Hb endocytosis was observed in LdRab5b(+/-) cells without any significant effect on HRP uptake. Finally, we tried to identify putative LdRab5a and LdRab5b effectors. We found that LdRab5b interacts with clathrin heavy chain and hemoglobin receptor. However, LdRab5a failed to interact with the clathrin heavy chain, and interaction with hemoglobin receptor was significantly less. Thus, our results showed that LdRab5a and LdRab5b differentially regulate fluid phase and receptor-mediated endocytosis in Leishmania. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Characterization and Demonstration of the Value of a Lethal Mouse Model of Middle East Respiratory Syndrome Coronavirus Infection and Disease.

PubMed

Tao, Xinrong; Garron, Tania; Agrawal, Anurodh Shankar; Algaissi, Abdullah; Peng, Bi-Hung; Wakamiya, Maki; Chan, Teh-Sheng; Lu, Lu; Du, Lanying; Jiang, Shibo; Couch, Robert B; Tseng, Chien-Te K

2016-01-01

Characterized animal models are needed for studying the pathogenesis of and evaluating medical countermeasures for persisting Middle East respiratory syndrome-coronavirus (MERS-CoV) infections. Here, we further characterized a lethal transgenic mouse model of MERS-CoV infection and disease that globally expresses human CD26 (hCD26)/DPP4. The 50% infectious dose (ID50) and lethal dose (LD50) of virus were estimated to be <1 and 10 TCID50 of MERS-CoV, respectively. Neutralizing antibody developed in the surviving mice from the ID50/LD50 determinations, and all were fully immune to challenge with 100 LD50 of MERS-CoV. The tissue distribution and histopathology in mice challenged with a potential working dose of 10 LD50 of MERS-CoV were subsequently evaluated. In contrast to the overwhelming infection seen in the mice challenged with 10(5) LD50 of MERS-CoV, we were able to recover infectious virus from these mice only infrequently, although quantitative reverse transcription-PCR (qRT-PCR) tests indicated early and persistent lung infection and delayed occurrence of brain infection. Persistent inflammatory infiltrates were seen in the lungs and brain stems at day 2 and day 6 after infection, respectively. While focal infiltrates were also noted in the liver, definite pathology was not seen in other tissues. Finally, using a receptor binding domain protein vaccine and a MERS-CoV fusion inhibitor, we demonstrated the value of this model for evaluating vaccines and antivirals against MERS. As outcomes of MERS-CoV infection in patients differ greatly, ranging from asymptomatic to overwhelming disease and death, having available both an infection model and a lethal model makes this transgenic mouse model relevant for advancing MERS research. Fully characterized animal models are essential for studying pathogenesis and for preclinical screening of vaccines and drugs against MERS-CoV infection and disease. When given a high dose of MERS-CoV, our transgenic mice expressing hCD26/DPP4 viral receptor uniformly succumbed to death within 6 days, making it difficult to evaluate host responses to infection and disease. We further characterized this model by determining both the ID50 and the LD50 of MERS-CoV in order to establish both an infection model and a lethal model for MERS and followed this by investigating the antibody responses and immunity of the mice that survived MERS-CoV infection. Using the estimated LD50 and ID50 data, we dissected the kinetics of viral tissue distribution and pathology in mice challenged with 10 LD50 of virus and utilized the model for preclinical evaluation of a vaccine and drug for treatment of MERS-CoV infection. This further-characterized transgenic mouse model will be useful for advancing MERS research. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Effects of carbamates on whole blood cholinesterase activity: chemical protection against soman.

PubMed

Heyl, W C; Harris, L W; Stitcher, D L

1980-01-01

The toxicity (LD50) of several carbamates, all reversible inhibitors of cholinesterase (ChE), were determined in male rabbits. These include isopropyl methylphenyl carbamate (IMPC), pyridostigmine, neostigmine, benzpyrinium and physostigmine. When 1/9 of the LD50 of the above carbamates was individually combined with atropine (A) and benactyzine (B), mecamylamine (M) or chloropromazine (CPZ) and administered to rabbits in a pretreatment regimen, most animals could be protected from a 10 LD50 challenge of Soman. If CPZ, M or B was omitted from this regimen, no rabbits survived this challenge of Soman. The protection afforded against Soman was found to be related to reversible inhibition of ChE by the carbamates; reversible ChE inhibition varied with the route of injection and with the physical properties of the carbamate. Oral administration of pyridostigmine, a quaternary carbamate, provided protection for 24 hours. When the pretreatment included four components (pyridostigmine, A, M and B), the LD50 of Soman was raised 30.8 times in rabbits.

Collaborative study to assess the suitability of a candidate International Standard for yellow fever vaccine.

PubMed

Ferguson, Morag; Heath, Alan

2004-12-01

Yellow fever vaccines are routinely assayed by plaque assay. However, the results of these assays are then converted into mouse LD(50) using correlations/conversion factors which, in many cases, were established many years ago. The minimum required potency in WHO Recommendations is 10(3) LD(50)/dose. Thirteen participants from 8 countries participated in a collaborative study whose aim was to assess the suitability of two candidate preparations to serve as an International Standard for yellow fever vaccine. In addition, the study investigated the relationship between the mouse LD(50) test and plaque forming units with a view to updating the WHO recommendations. Plaque assays were more reproducible than mouse assays, as expected. Differences in sensitivities of plaque assays were observed between laboratories but these differences appear to be consistent within a laboratory for all samples and the expression of potency relative to the candidate standard vaccine improved the reproducibility of assays between laboratories. However, the use of potencies had little effect on the between laboratory variability in mouse LD(50) assays. There appears to be a consistent relationship between overall mean LD(50) and plaques titre for all study preparations other than sample E. The slope of the correlation curve is >1 and it would appear that 10(3) LD(50) is approximately equivalent to 10(4) plaque forming units (PFU), based on the overall means of all laboratory results. The First International Standard for yellow fever vaccine, NIBSC Code 99/616, has been established as the First International Standard for yellow fever vaccine by the Expert Committee of Biological Standards of the World Health Organisation. The International Standard has been arbitrarily assigned a potency of 10(4.5) International Units (IU) per ampoule. Manufacturers and National Control Laboratories are including the First International Standard for yellow fever vaccine in routine assays so that the minimum potency in IU of vaccines released for use and which meet the current minimum potency of 10(3) LD(50) in mouse assays, can be determined. These data will be analysed before a review of the WHO requirements, including the minimum potency per dose, is undertaken.

Absence of individual chromosomes and radiation sensitivity of bread wheat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jagathesan, D.; Swaminathan, M. S.

Seeds of twenty different monosomics of bread wheat of the variety Chinese Spring were treated with different doses of x rays to determine LD-50. Dormant seeds with an embryo moisture content of 4 to 5% were irradiated with doses from 5000 to 50000 r. The seeds were sown immediately after irradiation. Germination and survival counts were made 15 days after sowing. The LD-50 rates found are tabulated and show that the monosomics are more radiosensitive than the disonics. Monosomtics for D genome chromosomes have generally a higher LD-50 dosage in comparison with A and B genomes. (J.S.R.)

The connection Between Plasma Protein Binding and Acute Toxicity as Determined by the LD50 Value.

PubMed

Svennebring, Andreas

2016-02-01

Preclinical Research A dataset of three drug classes (acids, bases, and neutrals) with LD50 values in mice was analysed to investigate a possible connection between high plasma protein binding and acute toxicity. Initially, it was found that high plasma protein binding was associated with toxicity for acids and neutrals, but after compensating for differences in lipophilicity, plasma protein binding was found not to be associated with toxicity. The therapeutic index established by the quotient between mouse LD50 and the defined daily dose was unaffected by both lipophilicity and plasma protein binding. © 2015 Wiley Periodicals, Inc.

Oral acute toxic class method: a successful alternative to the oral LD50 test.

PubMed

Schlede, Eva; Genschow, Elke; Spielmann, Horst; Stropp, Gisela; Kayser, Detlev

2005-06-01

The oral acute toxic class method (ATC method) was developed as an alternative to replace the oral LD50 test. The ATC method is a sequential testing procedure using only three animals of one sex per step at any of the defined dose levels. Depending on the mortality rate three but never more than six animals are used per dose level. This approach results in the reduction of numbers of animals used in comparison to the LD50 test by 40-70%. The principle of the oral ATC method is based on the Probit model and it was first evaluated on a biometric basis before a national and subsequently an international ring study were conducted. The results demonstrated an excellent agreement between the toxicity and the animal numbers predicted biometrically and observed in the validation studies. The oral ATC method was adopted as an official test guideline by OECD in 1996 and was slightly amended in 2001. The ATC method has been successfully used in Germany and in 2003 >85% of all tests on acute oral toxicity testing was conducted as oral ATC tests. In member states of the European Union the ATC method is used in the range of 50% of all tests conducted. Meanwhile the oral LD50 test has been deleted by OECD, by the European Union and by the USA, making the use of alternatives to the oral LD50 test mandatory.

Effects of organophosphorus anticholinesterase compounds on brain glucose and energy metabolism. Annual summary report, 1 October 1982-29 February 1984

DOE Office of Scientific and Technical Information (OSTI.GOV)

Medina, M.A.; Miller, A.L.

1984-09-01

The effects of paraoxon and Soman on glucose utilization and of Soman on the levels of intermediary metabolites were investigated in rat brain. The rate of glucose utilization and the levels of intermediary metabolites were determined in six brain areas at varying time periods after administration of 0.5 or 0.8 of the paraoxon or Soman LD50. Behavioral changes were observed only with the 0.8 LD50 dose of both compounds and some of the animals exhibited convulsive activity with this dose of Soman. Brain glucose utilization tended to be decreased by 0.8 LD50 paraoxon and 0.5 LD50 Soman. Some alterations inmore » metabolite levels were observed but these were not consistent and could not be correlated with the rate of glucose utilization. In animals with Soman-induced convulsions, glucose utilization and lactate levels were elevated only in the cortex and thalamus/basal ganglia. ATP, creatine phosphate and glucose levels were decreased in the cortex but not in other brain areas, suggesting the possibility of uncoupling of oxidative phosphorylation. Pretreatment with atropine prevented the behavioral responses and the changes in glucose utilization previously observed with 0.8 Soman LD50. Our results in convulsing animals are similar to those which have been observed with the excitatorytoxins kainic acid and bicuculline.« less

Laboratory Evaluation of Acute Toxicity of the Essential Oil of Allium tuberosum Leaves and Its Selected Major Constituents Against Apolygus lucorum (Hemiptera: Miridae).

PubMed

Shi, Jizhe; Liu, Xinchao; Li, Zhen; Zheng, Yuanyuan; Zhang, Qingwen; Liu, Xiaoxia

2015-01-01

The aim of this research was to evaluate acute toxicity of the essential oil of leaves of Chinese chives, Allium tuberosum Rottler ex Spreng (Asparagales: Alliaceae) and its major constituents against Apolygus lucorum Meyer-Dür (Hemiptera: Miridae). The essential oil of A. tuberosum leaves was obtained by hydrodistillation and analyzed by gas chromatography and gas chromatography-mass spectrometry. The major constituents of the oil were sulfur-containing compounds, including allyl methyl trisulfide (36.24%), diallyl disulfide (27.26%), diallyl trisulfide (18.68%), and dimethyl trisulfide (9.23%). The essential oil of A. tuberosum leaves exhibited acute toxicity against Ap. lucorum with an LD50 value of 20.03 μg per adult. Among the main compounds, diallyl trisulfide (LD50 = 10.13 μg per adult) showed stronger acute toxicity than allyl methyl trisulfide (LD50 = 21.10 μg per adult) and dimethyl trisulfide (LD50 = 21.65 μg per adult). The LD50 value of diallyl disulfide against Ap. lucorum was 28.10 μg per adult. The results indicated that the essential oil of A. tuberosum and its major constituents may have a potential to be developed as botanical insecticides against Ap. lucorum. © The Author 2015. Published by Oxford University Press on behalf of the Entomological Society of America.

Cobalt compounds as antidotes for hydrocyanic acid

PubMed Central

Evans, C. Lovatt

1964-01-01

The antidotal potency of a cobalt salt (acetate), of dicobalt edetate, of hydroxocobalamin and of cobinamide against hydrocyanic acid was examined mainly on mice and rabbits. All the compounds were active antidotes for up to twice the LD50; under some conditions for larger doses. The most successful was cobalt acetate for rabbits (5×LD50), which was effective at a molar cyanide/cobalt (CN/Co) ratio of 5, but had as a side-effect intense purgation. Hydroxocobalamin was irregular in action, but on the whole was most effective for mice (4.5×LD50 at a molar ratio of 1), and had no apparent side effects. Dicobalt edetate, at molar ratios of up to 2, was more effective for rabbits (3×LD50) than for mice (2×LD50), but had fewer side effects than cobalt acetate. The effect of thiosulphate was to augment the efficacy of dicobalt edetate and, in mice, that of hydroxocobalamin; but, apparently, in rabbits, to reduce that of hydroxocobalamin. Cobinamide, at a molar ratio of 1, was slightly more effective than hydroxocobalamin on rabbits and also less irregular in its action. Cobalt acetate by mouth was effective against orally administered hydrocyanic acid. The oxygen uptake of the body, reduced by cyanide, is rapidly reinstated when one of the cobalt antidotes has been successfully administered. PMID:14256807

Acute oral toxicity: variability, reliability, relevance and interspecies comparison of rodent LD50 data from literature surveyed for the ACuteTox project.

PubMed

Hoffmann, Sebastian; Kinsner-Ovaskainen, Agnieszka; Prieto, Pilar; Mangelsdorf, Inge; Bieler, Christian; Cole, Thomas

2010-12-01

The ACuteTox project has aimed to optimise and prevalidate an in vitro testing strategy for predicting human acute toxicity. Ninety-seven reference substances were selected and an in vivo acute toxicity database was compiled. Comprehensive statistical analyses of the in vivo LD50 data to evaluate variability and reliability, interspecies correlation, predictive capacities with regard to EU and GHS toxicity categories, and deduction of performance criteria for in vitro methods is presented. For the majority of substances variability among rodent data followed a log normal distribution where good reproducibility was found. Rat and mouse interspecies comparison of LD50 studies by ordinary regression showed high correlation, with coefficients of determination, ranging between 0.8 and 0.9. Substance specific differences were only significant for warfarin and cycloheximide. No correlation of compound LD50 range with presumed study quality rank (by assigning Klimisch reliability scores) was found. Modelling based on LD50 variability showed that with at least 90% probability ∼54% of the substances would fall into only one GHS category and ∼44% would fall within two adjacent categories. These results could form the basis for deriving a predictive capacity that should be expected from alternative approaches to the conventional in vivo acute oral toxicity test. Copyright © 2010 Elsevier Inc. All rights reserved.

Post-hoc analysis showing better clinical response with the loading dose of certolizumab pegol in Japanese patients with active rheumatoid arthritis

PubMed Central

Takeuchi, Tsutomu; Yamamoto, Kazuhiko; Yamanaka, Hisashi; Ishiguro, Naoki; Tanaka, Yoshiya; Eguchi, Katsumi; Watanabe, Akira; Origasa, Hideki; Kobayashi, Mariko; Shoji, Toshiharu; Togo, Osamu; Miyasaka, Nobuyuki; Koike, Takao

2016-01-01

Abstract Objectives: To compare the efficacy and safety of certolizumab pegol (CZP) with and without loading dose (LD) in a post-hoc analysis of two Japanese clinical studies. Methods: Data from the double-blind trials (DBT) J-RAPID and HIKARI, and their open-label extension (OLE) studies, were used. Patients randomized to CZP 200 mg every 2 weeks (Q2W) groups starting with LD (400 mg Weeks 0/2/4; LD group; J-RAPID: n = 82, HIKARI: n = 116) and patients randomized to placebo groups who subsequently started CZP Q2W without LD in the OLEs (No-LD group; J-RAPID: n = 61, HIKARI: n = 99) were analyzed. Efficacy and pharmacokinetics were assessed during 24 weeks. Adverse events were reported from all studies. Results: In both trials, the LD groups showed more rapid initial ACR20/50/70 kinetics, and maintained higher ACR50/70 responses until 24 weeks, compared with the No-LD groups. Anti-CZP antibody development was less frequent in the LD groups (J-RAPID: 1.2% versus 4.9%; HIKARI: 17.2% versus 27.3%). Similar safety profiles were reported between LD and No-LD groups (any AEs: 281.8 versus 315.7 [J-RAPID], 282.6 versus 321.3 [HIKARI] [incidence rate/100 patient-years]). Conclusions: Despite limitations, including comparing DBT and OLE studies, these results suggest that a CZP LD improves clinical response in active rheumatoid arthritis without altering the safety profile. PMID:26472043

20180311 - Variability of LD50 Values from Rat Oral Acute Toxicity Studies: Implications for Alternative Model Development (SOT)

EPA Science Inventory

Alternative models developed for estimating acute systemic toxicity are generally evaluated using in vivo LD50 values. However, in vivo acute systemic toxicity studies can produce variable results, even when conducted according to accepted test guidelines. This variability can ma...

Variability of LD50 Values from Rat Oral Acute Toxicity Studies: Implications for Alternative Model Development

EPA Science Inventory

Alternative models developed for estimating acute systemic toxicity are generally evaluated using in vivo LD50 values. However, in vivo acute systemic toxicity studies can produce variable results, even when conducted according to accepted test guidelines. This variability can ma...

Statistical considerations in the analysis of data from replicated bioassays

USDA-ARS?s Scientific Manuscript database

Multiple-dose bioassay is generally the preferred method for characterizing virulence of insect pathogens. Linear regression of probit mortality on log dose enables estimation of LD50/LC50 and slope, the latter having substantial effect on LD90/95s (doses of considerable interest in pest management)...

Practical Advice on Calculating Confidence Intervals for Radioprotection Effects and Reducing Animal Numbers in Radiation Countermeasure Experiments

PubMed Central

Landes, Reid D.; Lensing, Shelly Y.; Kodell, Ralph L.; Hauer-Jensen, Martin

2014-01-01

The dose of a substance that causes death in P% of a population is called an LDP, where LD stands for lethal dose. In radiation research, a common LDP of interest is the radiation dose that kills 50% of the population by a specified time, i.e., lethal dose 50 or LD50. When comparing LD50 between two populations, relative potency is the parameter of interest. In radiation research, this is commonly known as the dose reduction factor (DRF). Unfortunately, statistical inference on dose reduction factor is seldom reported. We illustrate how to calculate confidence intervals for dose reduction factor, which may then be used for statistical inference. Further, most dose reduction factor experiments use hundreds, rather than tens of animals. Through better dosing strategies and the use of a recently available sample size formula, we also show how animal numbers may be reduced while maintaining high statistical power. The illustrations center on realistic examples comparing LD50 values between a radiation countermeasure group and a radiation-only control. We also provide easy-to-use spreadsheets for sample size calculations and confidence interval calculations, as well as SAS® and R code for the latter. PMID:24164553

Pathogenicity Of Nosema fumiferanae (Thomson) (Microsporida) In Spruce Budworm, Choristoneura Fumiferana (Clemens), And Implications Of Diapause Conditions

Treesearch

Leah S. Bauer; Gerald L. Nordin

1988-01-01

A standardized bioassay procedure was used to determine median lethal doses (LD 50) of the microsporidium, Nosema fumiferanae (Thom.), on newly molted fourth- and fifth-instar eastern spruce budworm larvae (Choristoneura fumiferana (Clem.)). The LD50 for fifth-instar larva was 1.23 x 10...

Modified tetrahalogenated benzimidazoles with CK2 inhibitory activity are active against human prostate cancer cells LNCaP in vitro.

PubMed

Schneider, Carolin C; Kartarius, Sabine; Montenarh, Mathias; Orzeszko, Andrzej; Kazimierczuk, Zygmunt

2012-07-15

A series of novel CK2 inhibitors, tetrahalogenated benzimidazoles carrying an aminoalkylamino group at position 2, has been prepared by nucleophilic substitution of the respective 2,4,5,6,7-pentabromobenzimidazoles and 2-bromo-4,5,6,7-tetraiodobenzimidazoles. The new derivatives as well as some previously obtained tetrahalogenobenzimidazoles, including 4,5,6,7-tetrabromobenzimidazole (TBI) and 4,5,6,7-tetraiodobenzimidazole (TIBI), were evaluated for activity against the hormone-sensitive human prostate cancer cell line LNCaP. The activity of 2-aminoalkylamino derivatives was notably higher (LD(50) 4.75-9.37 μM) than that of TBI and TIBI (LD(50) ≈ 20 μM). The determination of the LD(50) value identified the 2-aminoethylamino-4,5,6,7-tetraiodobenzimidazole with an additional methyl group at position 1 (6) as the most efficient compound (LD(50): 4.75 ± 1.02 μM). Interestingly, there was no clear correlation between cell viability and apoptosis induction indicating additional cell death mechanisms. Copyright © 2012 Elsevier Ltd. All rights reserved.

Dose and time-dependent effects of cyanide on thiosulfate sulfurtransferase, 3-mercaptopyruvate sulfurtransferase, and cystathionine λ-lyase activities.

PubMed

Singh, Poonam; Rao, Pooja; Bhattacharya, Rahul

2013-12-01

We assessed the dose-dependent effect of potassium cyanide (KCN) on thiosulfate sulfurtransferase (TST), 3-mercaptopyruvate sulfurtransferase (3-MPST), and cystathionine λ-lyase (CST) activities in mice. The time-dependent effect of 0.5 LD50 KCN on cyanide level and cytochrome c oxidase (CCO), TST, 3-MPST, and CST activities was also examined. Furthermore, TST, 3-MPST, and CST activities were measured in stored mice cadavers. Hepatic and renal TST activity increased by 0.5 LD50 KCN but diminished by ≥2.0 LD50. After 0.5 LD50 KCN, the elevated hepatic cyanide level was accompanied by increased TST, 3-MPST, and CST activities, and CCO inhibition. Elevated renal cyanide level was only accompanied by increased 3-MPST activity. No appreciable change in enzyme activities was observed in mice cadavers. The study concludes that high doses of cyanide exert saturating effects on its detoxification enzymes, indicating their exogenous use during cyanide poisoning. Also, these enzymes are not reliable markers of cyanide poisoning in autopsied samples. © 2013 Wiley Periodicals, Inc.

Genetic Validation of Leishmania donovani Lysyl-tRNA Synthetase Shows that It Is Indispensable for Parasite Growth and Infectivity

PubMed Central

Chadha, Sanya; Mallampudi, N. Arjunreddy; Mohapatra, Debendra K.

2017-01-01

ABSTRACT Leishmania donovani is a protozoan parasite that causes visceral leishmaniasis. Increasing resistance and severe side effects of existing drugs have led to the need to identify new chemotherapeutic targets. Aminoacyl-tRNA synthetases (aaRSs) are ubiquitous and are required for protein synthesis. aaRSs are known drug targets for bacterial and fungal pathogens. Here, we have characterized and evaluated the essentiality of L. donovani lysyl-tRNA synthetase (LdLysRS). Two different coding sequences for lysyl-tRNA synthetases are annotated in the Leishmania genome database. LdLysRS-1 (LdBPK_150270.1), located on chromosome 15, is closer to apicomplexans and eukaryotes, whereas LdLysRS-2 (LdBPK_300130.1), present on chromosome 30, is closer to bacteria. In the present study, we have characterized LdLysRS-1. Recombinant LdLysRS-1 displayed aminoacylation activity, and the protein localized to the cytosol. The LdLysRS-1 heterozygous mutants had a restrictive growth phenotype and attenuated infectivity. LdLysRS-1 appears to be an essential gene, as a chromosomal knockout of LdLysRS-1 could be generated when the gene was provided on a rescuing plasmid. Cladosporin, a fungal secondary metabolite and a known inhibitor of LysRS, was more potent against promastigotes (50% inhibitory concentration [IC50], 4.19 µM) and intracellular amastigotes (IC50, 1.09 µM) than were isomers of cladosporin (3-epi-isocladosporin and isocladosporin). These compounds exhibited low toxicity to mammalian cells. The specificity of inhibition of parasite growth caused by these inhibitors was further assessed using LdLysRS-1 heterozygous mutant strains and rescue mutant promastigotes. These inhibitors inhibited the aminoacylation activity of recombinant LdLysRS. Our data provide a framework for the development of a new class of drugs against this parasite. IMPORTANCE Aminoacyl-tRNA synthetases are housekeeping enzymes essential for protein translation, providing charged tRNAs for the proper construction of peptide chains. These enzymes provide raw materials for protein translation and also ensure fidelity of translation. L. donovani is a protozoan parasite that causes visceral leishmaniasis. It is a continuously proliferating parasite that depends heavily on efficient protein translation. Lysyl-tRNA synthetase is one of the aaRSs which charges lysine to its cognate tRNA. Two different coding sequences for lysyl-tRNA synthetases (LdLysRS) are present in this parasite. LdLysRS-1 is closer to apicomplexans and eukaryotes, whereas LdLysRS-2 is closer to bacteria. Here, we have characterized LdLysRS-1 of L. donovani. LdLysRS-1 appears to be an essential gene, as the chromosomal null mutants did not survive. The heterozygous mutants showed slower growth kinetics and exhibited attenuated virulence. This study also provides a platform to explore LdLysRS-1 as a potential drug target. PMID:28875178

Genetic Validation of Leishmania donovani Lysyl-tRNA Synthetase Shows that It Is Indispensable for Parasite Growth and Infectivity.

PubMed

Chadha, Sanya; Mallampudi, N Arjunreddy; Mohapatra, Debendra K; Madhubala, Rentala

2017-01-01

Leishmania donovani is a protozoan parasite that causes visceral leishmaniasis. Increasing resistance and severe side effects of existing drugs have led to the need to identify new chemotherapeutic targets. Aminoacyl-tRNA synthetases (aaRSs) are ubiquitous and are required for protein synthesis. aaRSs are known drug targets for bacterial and fungal pathogens. Here, we have characterized and evaluated the essentiality of L. donovani lysyl-tRNA synthetase ( Ld LysRS). Two different coding sequences for lysyl-tRNA synthetases are annotated in the Leishmania genome database. Ld LysRS-1 (LdBPK_150270.1), located on chromosome 15, is closer to apicomplexans and eukaryotes, whereas Ld LysRS-2 (LdBPK_300130.1), present on chromosome 30, is closer to bacteria. In the present study, we have characterized Ld LysRS-1. Recombinant Ld LysRS-1 displayed aminoacylation activity, and the protein localized to the cytosol. The Ld LysRS-1 heterozygous mutants had a restrictive growth phenotype and attenuated infectivity. Ld LysRS-1 appears to be an essential gene, as a chromosomal knockout of Ld LysRS-1 could be generated when the gene was provided on a rescuing plasmid. Cladosporin, a fungal secondary metabolite and a known inhibitor of LysRS, was more potent against promastigotes (50% inhibitory concentration [IC 50 ], 4.19 µM) and intracellular amastigotes (IC 50 , 1.09 µM) than were isomers of cladosporin (3-epi-isocladosporin and isocladosporin). These compounds exhibited low toxicity to mammalian cells. The specificity of inhibition of parasite growth caused by these inhibitors was further assessed using Ld LysRS-1 heterozygous mutant strains and rescue mutant promastigotes. These inhibitors inhibited the aminoacylation activity of recombinant Ld LysRS. Our data provide a framework for the development of a new class of drugs against this parasite. IMPORTANCE Aminoacyl-tRNA synthetases are housekeeping enzymes essential for protein translation, providing charged tRNAs for the proper construction of peptide chains. These enzymes provide raw materials for protein translation and also ensure fidelity of translation. L. donovani is a protozoan parasite that causes visceral leishmaniasis. It is a continuously proliferating parasite that depends heavily on efficient protein translation. Lysyl-tRNA synthetase is one of the aaRSs which charges lysine to its cognate tRNA. Two different coding sequences for lysyl-tRNA synthetases ( Ld LysRS) are present in this parasite. Ld LysRS-1 is closer to apicomplexans and eukaryotes, whereas Ld LysRS-2 is closer to bacteria. Here, we have characterized Ld LysRS-1 of L. donovani . Ld LysRS-1 appears to be an essential gene, as the chromosomal null mutants did not survive. The heterozygous mutants showed slower growth kinetics and exhibited attenuated virulence. This study also provides a platform to explore Ld LysRS-1 as a potential drug target.

Social Information Processing and Emotional Understanding in Children with LD

ERIC Educational Resources Information Center

Bauminger, Nirit; Edelsztein, Hany Schorr; Morash, Janice

2005-01-01

The present study aimed to comprehensively examine social cognition processes in children with and without learning disabilities (LD), focusing on social information processing (SIP) and complex emotional understanding capabilities such as understanding complex, mixed, and hidden emotions. Participants were 50 children with LD (age range 9.4-12.7;…

Low dose CT perfusion in acute ischemic stroke.

PubMed

Murphy, Amanda; So, Aaron; Lee, Ting-Yim; Symons, Sean; Jakubovic, Raphael; Zhang, Liying; Aviv, Richard I

2014-12-01

The purpose of this investigation is to determine if CT perfusion (CTP) measurements at low doses (LD = 20 or 50 mAs) are similar to those obtained at regular doses (RD = 100 mAs), with and without the addition of adaptive statistical iterative reconstruction (ASIR). A single-center, prospective study was performed in patients with acute ischemic stroke (n = 37; 54% male; age = 74 ± 15 years). Two CTP scans were performed on each subject: one at 100 mAs (RD) and one at either 50 or 20 mAs (LD). CTP parameters were compared between the RD and LD scans in regions of ischemia, infarction, and normal tissue. Differences were determined using a within-subjects ANOVA (p < 0.05) followed by a paired t test post hoc analysis (p < 0.01). At 50 mAs, there was no significant difference between cerebral blood flow (CBF), cerebral blood volume (CBV), or time to maximum enhancement (Tmax) values for the RD and LD scans in the ischemic, infarcted, or normal contralateral regions (p < 0.05). At 20 mAs, there were significant differences between the RD and LD scans for all parameters in the ischemic and normal tissue regions (p > 0.05). CTP-derived CBF and CBV are not different at 50 mAs compared to 100 mAs, even without the addition of ASIR. Current CTP protocols can be modified to reduce the effective dose by 50 % without altering CTP measurements.

Comparison of fluid types for resuscitation after acute blood loss in mallard ducks (Anas platyrhynchos).

PubMed

Lichtenberger, Marla; Orcutt, Connie; Cray, Carolyn; Thamm, Douglas H; DeBehnke, Daniel; Page, Cheryl; Mull, Lori; Kirby, Rebecca

2009-10-01

The purpose of this study was to determine the LD(50) for acute blood loss in mallard ducks (Anas platyrhynchos), compare the mortality rate among 3 fluid resuscitation groups, and determine the time required for a regenerative RBC response. Prospective study. Medical College of Wisconsin Research facility. Eighteen mallard ducks were included for the LD(50) study and 28 for the fluid resuscitation study. Phlebotomy was performed during both the LD(50) and fluid resuscitation studies. Ducks in the fluid resuscitation study received a 5 mL/kg intravenous bolus of crystalloids, hetastarch (HES), or a hemoglobin-based oxygen-carrying solution (HBOCS). The LD(50) for acute blood loss was 60% of total blood volume. This blood volume was removed in the fluid resuscitation study to create a model of acute blood loss. Following fluid administration, 6 birds in the crystalloid group (66%), 4 birds in the HES group (40%), and 2 birds in the HBOCS group (20%) died. No statistical difference in mortality rate was seen among the 3 fluid resuscitation groups. Relative polychromasia evaluated post-phlebotomy demonstrated regeneration starting at 24 hours and continuing through 48 hours. The LD(50) for acute blood loss in mallard ducks was 60% of their total blood volume. Although no statistical difference in mortality rate was appreciated among the 3 fluid resuscitation groups, a trend of decreased mortality rate was observed in the HBOCS group. An early regenerative response was apparent following acute blood loss.

Oral and intraperitoneal LD50 of thymoquinone, an active principle of Nigella sativa, in mice and rats.

PubMed

Al-Ali, Amein; Alkhawajah, Abdul Aziz; Randhawa, Mohammad Akram; Shaikh, Nisar Ahmed

2008-01-01

Thymoquinone is the major active principle of Nigella sativa (N. sativa) and constitutes about 30% of its volatile oil or ether extract. N. sativa oil and seed are commonly used as a natural remedy for many ailments. Using modern scientific techniques, a number of pharmacological actions of N. sativa have been investigated including immunostimulant, anti-inflammatory, anticancer, antioxidant, antihistaminic, antiasthmatic, hypoglycemic, antimicrobial and antiparasitic. There are only few reports regarding the toxicity of thymoquinone. The present study was carried out to determine LD50 of thymoquinone both in mice and rats, orally as well as intraperitoneall, by the method of Miller and Tainter. Autopsy and histopathology of liver, kidney, heart and lungs were also determined. The LD50 in mice after intraperitoneal injection was determined to be 104.7 mg/kg (89.7-119.7, 95% confidence interval) and after oral ingestion was 870.9 mg/kg (647.1-1094.8, 95% confidence interval). Whereas, LD50 in rats after intraperitoneal injection was determined to be 57.5 mg/kg (45.6-69.4, 95% confidence intervals) and after oral ingestion was 794.3 mg/kg (469.8-1118.8, 95% confidence intervals). The LD50 values presented here after intraperitoneal injection and oral gavages are 10-15 times and 100-150 times greater than doses of thymoquinone reported for its anti-inflammatory, anti-oxidant and anti-cancer effects. Thymoquinone is a relatively safe compound, particularly when given orally to experimental animals.

Multiple animal studies for medical chemical defense program in soldier/patient decontamination and drug development. Task order 85-10. Final report, 1 December 1984-1 April 1987

DOE Office of Scientific and Technical Information (OSTI.GOV)

Joiner, R.L.; Harroff, H.H.; Snider, H.

1987-12-04

A rabbit model has been developed and validated for screening noninvasive candidate decontamination systems for their efficacies against topical exposure to the organophosphage chemical surety materiel (CSM), GD, polymer-thickened GD (TGD), and VX. CSM was applied to rabbits in groups of 8 on their clipped dorsa over a range of doses. Dose sites were decontaminated beginning 2 minutes after exposure with both components of the M258A1 standard field kit in the recommended sequence. Replicate LD50s were calculated for each CSM with probit analyses of the doses and lethality rates from replicate studies. A composite LD50 was calculated from the datamore » pooled across replicates for each CSM. The composite LD50 was validated for each CSM by comparing the lethality rate obtained in three replicates of 8 animals each with the population mean of 50 percent. The LD50 values obtained for the three CSM tested produced valid mortality ratios when compared to the population mean. Thus the screen is ready to test candidate decontamination systems. The screen compares the lethality rate obtained from 8 animals each dosed at the established M258A1 LD50 and decontaminated according to the manufacturer's instructions with a candidate system against the population mean of 50 percent. An M258A1-decontaminated control group of 8 animals is included to check for drift via a control chart method. Any candidate decontamination system that is as effective as or more effective than the dual-component M258A1 standard passes the screen and is a candidate for further testing.« less

The extent of linkage disequilibrium in beef cattle breeds using high-density SNP genotypes.

PubMed

Porto-Neto, Laercio R; Kijas, James W; Reverter, Antonio

2014-03-24

The extent of linkage disequilibrium (LD) between molecular markers impacts genome-wide association studies and implementation of genomic selection. The availability of high-density single nucleotide polymorphism (SNP) genotyping platforms makes it possible to investigate LD at an unprecedented resolution. In this work, we characterised LD decay in breeds of beef cattle of taurine, indicine and composite origins and explored its variation across autosomes and the X chromosome. In each breed, LD decayed rapidly and r2 was less than 0.2 for marker pairs separated by 50 kb. The LD decay curves clustered into three groups of similar LD decay that distinguished the three main cattle types. At short distances between markers (<10 kb), taurine breeds showed higher LD (r2=0.45) than their indicine (r2=0.25) and composite (r2=0.32) counterparts. This higher LD in taurine breeds was attributed to a smaller effective population size and a stronger bottleneck during breed formation. Using all SNPs on only the X chromosome, the three cattle types could still be distinguished. However for taurine breeds, the LD decay on the X chromosome was much faster and the background level much lower than for indicine breeds and composite populations. When using only SNPs that were polymorphic in all breeds, the analysis of the X chromosome mimicked that of the autosomes. The pattern of LD mirrored some aspects of the history of breed populations and showed a sharp decay with increasing physical distance between markers. We conclude that the availability of the HD chip can be used to detect association signals that remained hidden when using lower density genotyping platforms, since LD dropped below 0.2 at distances of 50 kb.

Aggressiveness, violence, homicidality, homicide, and Lyme disease

PubMed Central

Bransfield, Robert C

2018-01-01

Background No study has previously analyzed aggressiveness, homicide, and Lyme disease (LD). Materials and methods Retrospective LD chart reviews analyzed aggressiveness, compared 50 homicidal with 50 non-homicidal patients, and analyzed homicides. Results Most aggression with LD was impulsive, sometimes provoked by intrusive symptoms, sensory stimulation or frustration and was invariably bizarre and senseless. About 9.6% of LD patients were homicidal with the average diagnosis delay of 9 years. Postinfection findings associated with homicidality that separated from the non-homicidal group within the 95% confidence interval included suicidality, sudden abrupt mood swings, explosive anger, paranoia, anhedonia, hypervigilance, exaggerated startle, disinhibition, nightmares, depersonalization, intrusive aggressive images, dissociative episodes, derealization, intrusive sexual images, marital/family problems, legal problems, substance abuse, depression, panic disorder, memory impairments, neuropathy, cranial nerve symptoms, and decreased libido. Seven LD homicides included predatory aggression, poor impulse control, and psychosis. Some patients have selective hyperacusis to mouth sounds, which I propose may be the result of brain dysfunction causing a disinhibition of a primitive fear of oral predation. Conclusion LD and the immune, biochemical, neurotransmitter, and the neural circuit reactions to it can cause impairments associated with violence. Many LD patients have no aggressiveness tendencies or only mild degrees of low frustration tolerance and irritability and pose no danger; however, a lesser number experience explosive anger, a lesser number experience homicidal thoughts and impulses, and much lesser number commit homicides. Since such large numbers are affected by LD, this small percent can be highly significant. Much of the violence associated with LD can be avoided with better prevention, diagnosis, and treatment of LD. PMID:29576731

Potential of the insect growth regulator, fluazuron, in the control of Rhipicephalus sanguineus nymphs (Latreille, 1806) (Acari: Ixodidae): determination of the LD95 and LD50.

PubMed

de Oliveira, Patrícia Rosa; Calligaris, Izabela Braggião; Roma, Gislaine Cristina; Bechara, Gervásio Henrique; Pizano, Marcos Aparecido; Camargo Mathias, Maria Izabel

2012-05-01

Conventional pesticides have suffered two main drawbacks: (a) broad spectrum of action and (b) selection of target species resistant to the different active ingredients. Thus compounds that are less harmful to the environment and to human health, more specific and that do not induce resistance need to be developed. One alternative are insect growth regulators, such as fluazuron. The present study examined the efficacy of fluazuron (active ingredient of the acaricide Acatak®) and the sensitivity of Rhipicephalus sanguineus nymphs exposed to different doses of this chemical, and determined the lethal doses of fluazuron: 95% - LD(95) and 50% - LD(50). Different doses of fluazuron were applied in duplicates on the dorsal region of hosts ("pour on"). Distilled water was used in the control group. On the first day after the treatment with fluazuron, hosts were artificially infested with R. sanguineus nymphs. After engorgement, nymphs were removed, placed on Petri dishes, identified, and maintained in BOD incubator for 15days. Dead R. sanguineus nymphs after the treatment with 13 different doses of fluazuron were quantified and the LD(95) was estimated to be 100mg/kg and LD(50), 19.544mg/kg (12.478-22.636), with a confidence interval of 95%. Nymphs of R. sanguineus were sensitive to fluazuron at various levels, indicating that this insect growth regulator (IGR) may be used to control this parasite in this stage of its biological cycle, reducing the significant damage it causes. Copyright © 2012 Elsevier Inc. All rights reserved.

Serological Studies of Types A, B, and E Botulinal Toxins by Passive Hemagglutination and Bentonite Flocculation

PubMed Central

Johnson, H. M.; Brenner, K.; Angelotti, R.; Hall, H. E.

1966-01-01

Johnson, H. M. (Robert A. Taft Sanitary Engineering Center, Cincinnati, Ohio), K. Brenner, R. Angelotti, and H. E. Hall. Serological studies of types A, B, and E botulinal toxins by passive hemagglutination and bentonite flocculation. J. Bacteriol. 91:967–974. 1966.—Formalinized sheep red blood cells (SRBC), sensitized with types A, B, and E botulinal toxoids and toxins by bis-diazotized benzidine (BDB), were tested against A, B, and E antitoxins prepared in horses and rabbits. Type B antitoxin cross-reacted with A toxoid SRBC, but the reciprocal cross-reaction was not observed. E toxin SRBC were specifically agglutinated by E antitoxin. Flocculation of antigen-sensitized bentonite particles was less sensitive in titration of antitoxin than hemagglutination. Also, reciprocal cross-reactions were observed between types A and B antitoxins. Cross-reactions in both serological tests were eliminated by titration of antitoxins in the presence of the heterologous antigens, with no inhibitory effect on the homologous antitoxins. Generally, equine antitoxins were less suitable for agglutinations, especially of antigen-sensitized bentonite particles. Types A, B, and E antitoxins were specifically inhibited by 43, 39, and 245 mouse ld50 of their respective homologous toxins in the hemagglutination-inhibition test. A, B, and E antitoxins were specifically inhibited by 500, 950, and 1,500 mouse ld50 of their respective homologous toxins in bentonite flocculation inhibitions. Formalinized SRBC sensitized with rabbit types A and B antitoxins by BDB were respectively clumped by as little as 0.75 to 1.3 mouse ld50 of A toxin and 2.3 ld50 of B toxin, whereas bentonite particles sensitized by the same antitoxins were specifically clumped by 150 ld50 of A toxin and 630 ld50 of B toxin. E antitoxin sensitization of SRBC or bentonite particles was not successful. Evidence is presented that indicates that the serological procedures are applicable to the detection of botulinal toxins in food. PMID:5326104

Evaluation of potential embryotoxicity and teratogenicity of 42 herbicides, insecticides, and petroleum contaminants to mallard eggs

USGS Publications Warehouse

Hoffman, D.J.; Albers, P.H.

1984-01-01

Results are reported for the embryotoxicity of 42 environmental contaminants applied externally to mallard (Anas platyrhynchos) eggs including crude and refined petroleum, and commercial formulations of herbicides and insecticides. Many of the petroleum pollutants were embryotoxic and moderately teratogenic and had LD50s of 0.3 to 5 ?l per egg (~6?90 ?g/g egg). The most toxic was a commercial oil used for control of road dust followed by South Louisiana crude oil, Kuwait crude, no. 2 fuel oil, bunker C fuel oil, and industrial and automotive waste oil. Prudhoe Bay crude, unused crankcase oil, aviation kerosene, and aliphatic hydrocarbon mixtures were less toxic ( LD50s of 18 to over 75 ? l) and less teratogenic. The LD50s of herbicides and insecticides in aqueous emulsion were measured by egg immersion; the most toxic were paraquat and trifluralin (LD50s of about 1.5 Ibs/A; 1.7 kg/ha). Propanil, bromoxynil with MCPA, methyl diclofop, prometon, endrin, sulprofos, and parathion were toxic (LD50s of 7 to 40 Ibs/A; 7.8?44.8 kg/ha), whereas 2,4-D, glyphosate, atrazine, carbaryl, dalapon, dicamba, methomyl, and phosmet were only slightly toxic or not toxic (LD50s of 178 to over 500 Ibs/A; 199?560 kg/ha). Pesticides in nontoxic oil vehicle applied by microliter pipet were up to 18 times more toxic than when applied in water vehicle, which was probably due to better penetration of the pesticide past the eggshell and its membranes. Teratogenic effects and impaired embryonic growth are reported and results discussed in terms of potential hazard at field levels of application. A discussion is provided on the effects of pollutants on the eggs of other species of birds under laboratory and field conditions.

Acute toxicity of some nerve agents and pesticides in rats.

PubMed

Misik, Jan; Pavlikova, Ruzena; Cabal, Jiri; Kuca, Kamil

2015-01-01

Highly toxic organophosphorus compounds (V- and G-nerve agents) were originally synthesized for warfare or as agricultural pesticides. Data on their acute toxicity are rare and patchy. Therefore, there is a need for integrated summary comparing acute toxicity of organophosphates using different administration routes in the same animal model with the same methodology. Based on original data, a summary of in vivo acute toxicity of selected V- and G-nerve agents (tabun, sarin, soman, VX, Russian VX) and organophosphates paraoxon (POX) and diisopropyl fluorophosphate (DFP) in rats has been investigated. Male Wistar rats were exposed to organophosphates in several administration routes (i.m., i.p., p.o, s.c., p.c.). The acute toxicity was evaluated by the assessment of median lethal dose (LD50, mg kg(-1)) 2, 4, and 24 hours post exposure. V-agents were the most toxic presented with LD50 ranged from 0.0082 mg kg(-1) (VX, i.m.) to 1.402 mg kg(-1) (Russian VX, p.o.), followed by G-agents (LD50 = 0.069 mg kg(-1)/soman, i.m./ - 117.9 mg kg(-1)/sarin, p.c./), organophosphate POX and DFP (LD50 = 0.321 mg kg(-1)/POX, i.m./ - 420 mg kg(-1)/DFP, p.c./). Generally, i.m. administration was the most toxic throughout all tested agents and ways of administration (LD50 = 0.0082 mg kg(-1)/VX/ - 1.399 mg kg(-1)/DFP/) whereas p.c. way was responsible for lowest acute toxicity (LD50 = 0.085 mg kg(-1)/VX/ - 420 mg kg(-1)/DFP/). The acute toxicity of selected organophosphorus compounds is summarized throughout this study. Although the data assessed in rats are rather illustrative prediction for human, it presents a valuable contribution, indicating the toxic potential and harmfulness of organophosphates.

Saving two birds with one stone: using active substance avian acute toxicity data to predict formulated plant protection product toxicity.

PubMed

Maynard, Samuel K; Edwards, Peter; Wheeler, James R

2014-07-01

Environmental safety assessments for exposure of birds require the provision of acute avian toxicity data for both the pesticidal active substance and formulated products. As an example, testing on the formulated product is waived in Europe using an assessment of data for the constituent active substance(s). This is often not the case globally, because some countries require acute toxicity tests with every formulated product, thereby triggering animal welfare concerns through unnecessary testing. A database of 383 formulated products was compiled from acute toxicity studies conducted with northern bobwhite (Colinus virginianus) or Japanese quail (Coturnix japonica) (unpublished regulatory literature). Of the 383 formulated products studied, 159 contained only active substances considered functionally nontoxic (median lethal dose [LD50] > highest dose tested). Of these, 97% had formulated product LD50 values of >2000 mg formulated product/kg (limit dose), indicating that no new information was obtained in the formulated product study. Furthermore, defined (point estimated) LD50 values for formulated products were compared with LD50 values predicted from toxicity of the active substance(s). This demonstrated that predicted LD50 values were within 2-fold and 5-fold of the measured formulated product LD50 values in 90% and 98% of cases, respectively. This analysis demonstrates that avian acute toxicity testing of formulated products is largely unnecessary and should not be routinely required to assess avian acute toxicity. In particular, when active substances are known to be functionally nontoxic, further formulated product testing adds no further information and unnecessarily increases bird usage in testing. A further analysis highlights the fact that significant reductions (61% in this dataset) could be achieved by using a sequential testing design (Organisation for Economic Co-operation and Development test guideline 223), as opposed to established single-stage designs. © 2014 The Authors.

Insecticide Activity of Ageratina jahnii and Ageratina pichinchensis (Asteraceae) against Lutzomyia migonei (Diptera: Psychodidae).

PubMed

Torres, Lizzeth; Rojas, Janne; Rondón, Maritza; Morales, Antonio; Nieves, Elsa

2017-01-01

Insects are mostly pathogens transmitters, thus the necessity of finding effective bioinsecticides to combat them. In the present investigation, the insecticide activity of Ageratina jahnii and Ageratina pichinchensis (Asteraceae) essential oils, methanol, and aqueous extracts was evaluated against Lutzomyia migonei (Diptera: Psychodidae) females, Leishmania transmitters, a wide distributed parasitosis in Latin America. All extracts were prepared by maceration at room temperature, and essential oils were obtained by hydrodistillation process. Females of L. migonei were used in the bioassays using the adulticide test in pots. Essential oils from both assayed plant species showed 100% of L. migonei mortality at 48 h of exposure at the concentration of 10 mg/ml. A. jahnii essential oil exhibited the following values, LD 50 = 0.39 mg/ml, LD 90 = 1.57 mg/ml, LD 95 = 2.31 mg/ml, and LD 99 = 4.80 mg/ml while for A. pichinchensis essential oil values were LD 50 = 0.31 mg/ml, LD 90 = 0.99 mg/ml, LD 95 = 1.38 mg/ml, and LD 99 = 2.55 mg/ml. Higher toxicity was observed with A. pichinchensis essential oil against L. migonei , comparing to A. jahnii oil. Two new plant species are being reported, showing bioactive properties against common tropical disease vectors such as L. migonei , hence, opening possibilities to a more environmental friendly control.

Insecticide Activity of Ageratina jahnii and Ageratina pichinchensis (Asteraceae) against Lutzomyia migonei (Diptera: Psychodidae)

PubMed Central

Torres, Lizzeth; Rojas, Janne; Rondón, Maritza; Morales, Antonio; Nieves, Elsa

2017-01-01

Background: Insects are mostly pathogens transmitters, thus the necessity of finding effective bioinsecticides to combat them. In the present investigation, the insecticide activity of Ageratina jahnii and Ageratina pichinchensis (Asteraceae) essential oils, methanol, and aqueous extracts was evaluated against Lutzomyia migonei (Diptera: Psychodidae) females, Leishmania transmitters, a wide distributed parasitosis in Latin America. Materials and Methods: All extracts were prepared by maceration at room temperature, and essential oils were obtained by hydrodistillation process. Females of L. migonei were used in the bioassays using the adulticide test in pots. Results: Essential oils from both assayed plant species showed 100% of L. migonei mortality at 48 h of exposure at the concentration of 10 mg/ml. A. jahnii essential oil exhibited the following values, LD50 = 0.39 mg/ml, LD90 = 1.57 mg/ml, LD95 = 2.31 mg/ml, and LD99 = 4.80 mg/ml while for A. pichinchensis essential oil values were LD50 = 0.31 mg/ml, LD90 = 0.99 mg/ml, LD95 = 1.38 mg/ml, and LD99 = 2.55 mg/ml. Conclusion: Higher toxicity was observed with A. pichinchensis essential oil against L. migonei, comparing to A. jahnii oil. Two new plant species are being reported, showing bioactive properties against common tropical disease vectors such as L. migonei, hence, opening possibilities to a more environmental friendly control. PMID:28553626

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hancock, R.L.

Irradiation effects in the phylum Annelida are almost entirely unknown, nor is it know why the LD/sub 50/30// for amoebae is 100 kr, whereas mammals show LD/sub 50/ doses of approximates 0.5 kr. To shed more light on comparative radiosensitivity, Lumbricus terrestris was irradiated at a rate of 1 kr/min with 250-kr x rays to total doses of 10 to l00 kr. No lethal effect occurs at 45 kr or below in Lumbricus, whereas a definite mortality occurs with 75 kr. All worms died within 2 months after 100 kr. The LD/sub 50/35//and LD/sub 100/67// are approximates 100 kr. Thismore » is in contrast to the mollusk Radix which has a for lethal effects. The annelid Enchytraeus shows no apparent effect after 90 kr. It is suggested that some feature of biological organization, which has up to the present escaped discovery, may hold a clue to the fundamental nature of radiobiological action, and may explain the extremes of radiosensitivity present within a few selected invertebrate types. (BBB)« less

Studies on ’Macaca mulatta’ Infected with Rocky Mountain Spotted Fever

DTIC Science & Technology

1976-09-10

Mountain spotted fever (RMSF) rickettsiae. The LD50 in monkeys of the yolk-sac-grown seed stock was 10 to the 1.35th power plaque-forming units. Blood...acid glycoprotein, haptoglobin and albumin) were measured during a study in 16 male rhesus monkeys to determine the median lethal dose (LD50) of Rocky

40 CFR 261.11 - Criteria for listing hazardous waste.

Code of Federal Regulations, 2010 CFR

2010-07-01

... absence of data on human toxicity, it has been shown in studies to have an oral LD 50 toxicity (rat) of... liter, or a dermal LD 50 toxicity (rabbit) of less than 200 milligrams per kilogram or is otherwise... VIII only if they have been shown in scientific studies to have toxic, carcinogenic, mutagenic or...

40 CFR 261.11 - Criteria for listing hazardous waste.

Code of Federal Regulations, 2011 CFR

2011-07-01

... absence of data on human toxicity, it has been shown in studies to have an oral LD 50 toxicity (rat) of... liter, or a dermal LD 50 toxicity (rabbit) of less than 200 milligrams per kilogram or is otherwise... VIII only if they have been shown in scientific studies to have toxic, carcinogenic, mutagenic or...

Similarities and Differences between Underachievers and Students Labeled Learning Disabled: Identical Twins with Different Mothers.

ERIC Educational Resources Information Center

Ysseldyke, James E.; And Others

School identified learning disabled (LD) fourth graders (N=50) were compared with 49 fourth graders who were underachieving in school (non-LD) but were not identified as LD. Both groups were administered a battery of psychoeducational tests and their performances were compared on all measures. Results indicated considerable similarities between…

Sirc-cvs cytotoxicity test: an alternative for predicting rodent acute systemic toxicity.

PubMed

Kitagaki, Masato; Wakuri, Shinobu; Hirota, Morihiko; Tanaka, Noriho; Itagaki, Hiroshi

2006-10-01

An in vitro crystal violet staining method using the rabbit cornea-derived cell line (SIRC-CVS) has been developed as an alternative to predict acute systemic toxicity in rodents. Seventy-nine chemicals, the in vitro cytotoxicity of which was already reported by the Multicenter Evaluation of In vitro Toxicity (MEIC) and ICCVAM/ECVAM, were selected as test compounds. The cells were incubated with the chemicals for 72 hrs and the IC(50) and IC(35) values (microg/mL) were obtained. The results were compared to the in vivo (rat or mouse) "most toxic" oral, intraperitoneal, subcutaneous and intravenous LD(50) values (mg/kg) taken from the RTECS database for each of the chemicals by using Pearson's correlation statistics. The following parameters were calculated: accuracy, sensitivity, specificity, prevalence, positive predictability, and negative predictability. Good linear correlations (Pearson's coefficient; r>0.6) were observed between either the IC(50) or the IC(35) values and all the LD(50) values. Among them, a statistically significant high correlation (r=0.8102, p<0.001) required for acute systemic toxicity prediction was obtained between the IC(50) values and the oral LD(50) values. By using the cut-off concentrations of 2,000 mg/kg (LD(50)) and 4,225 microg/mL (IC(50)), no false negatives were observed, and the accuracy was 84.8%. From this, it is concluded that this method could be used to predict the acute systemic toxicity potential of chemicals in rodents.

Weather-Dependent Risk for Legionnaires' Disease, United States.

PubMed

Simmering, Jacob E; Polgreen, Linnea A; Hornick, Douglas B; Sewell, Daniel K; Polgreen, Philip M

2017-11-01

Using the Nationwide Inpatient Sample and US weather data, we estimated the probability of community-acquired pneumonia (CAP) being diagnosed as Legionnaires' disease (LD). LD risk increases when weather is warm and humid. With warm weather, we found a dose-response relationship between relative humidity and the odds for LD. When the mean temperature was 60°-80°F with high humidity (>80.0%), the odds for CAP being diagnosed with LD were 3.1 times higher than with lower levels of humidity (<50.0%). Thus, in some regions (e.g., the Southwest), LD is rarely the cause of hospitalizations. In other regions and seasons (e.g., the mid-Atlantic in summer), LD is much more common. Thus, suspicion for LD should increase when weather is warm and humid. However, when weather is cold, dry, or extremely hot, empirically treating all CAP patients for LD might contribute to excessive antimicrobial drug use at a population level.

Chick embryo chorioallantoic membrane (CAM): an alternative predictive model in acute toxicological studies for anti-cancer drugs.

PubMed

Kue, Chin Siang; Tan, Kae Yi; Lam, May Lynn; Lee, Hong Boon

2015-01-01

The chick embryo chorioallantoic membrane (CAM) is a preclinical model widely used for vascular and anti-vascular effects of therapeutic agents in vivo. In this study, we examine the suitability of CAM as a predictive model for acute toxicology studies of drugs by comparing it to conventional mouse and rat models for 10 FDA-approved anticancer drugs (paclitaxel, carmustine, camptothecin, cyclophosphamide, vincristine, cisplatin, aloin, mitomycin C, actinomycin-D, melphalan). Suitable formulations for intravenous administration were determined before the average of median lethal dose (LD50) and median survival dose (SD(50)) in the CAM were measured and calculated for these drugs. The resultant ideal LD(50) values were correlated to those reported in the literature using Pearson's correlation test for both intravenous and intraperitoneal routes of injection in rodents. Our results showed moderate correlations (r(2)=0.42 - 0.68, P<0.005-0.05) between the ideal LD(50) values obtained using the CAM model with LD(50) values from mice and rats models for both intravenous and intraperitoneal administrations, suggesting that the chick embryo may be a suitable alternative model for acute drug toxicity screening before embarking on full toxicological investigations in rodents in development of anticancer drugs.

Chick embryo chorioallantoic membrane (CAM): an alternative predictive model in acute toxicological studies for anti-cancer drugs

PubMed Central

KUE, Chin Siang; TAN, Kae Yi; LAM, May Lynn; LEE, Hong Boon

2015-01-01

The chick embryo chorioallantoic membrane (CAM) is a preclinical model widely used for vascular and anti-vascular effects of therapeutic agents in vivo. In this study, we examine the suitability of CAM as a predictive model for acute toxicology studies of drugs by comparing it to conventional mouse and rat models for 10 FDA-approved anticancer drugs (paclitaxel, carmustine, camptothecin, cyclophosphamide, vincristine, cisplatin, aloin, mitomycin C, actinomycin-D, melphalan). Suitable formulations for intravenous administration were determined before the average of median lethal dose (LD50) and median survival dose (SD50) in the CAM were measured and calculated for these drugs. The resultant ideal LD50 values were correlated to those reported in the literature using Pearson’s correlation test for both intravenous and intraperitoneal routes of injection in rodents. Our results showed moderate correlations (r2=0.42 − 0.68, P<0.005–0.05) between the ideal LD50 values obtained using the CAM model with LD50 values from mice and rats models for both intravenous and intraperitoneal administrations, suggesting that the chick embryo may be a suitable alternative model for acute drug toxicity screening before embarking on full toxicological investigations in rodents in development of anticancer drugs. PMID:25736707

Sensitivity of species to chemicals: dose-response characteristics for various test types (LC(50), LR(50) and LD(50)) and modes of action.

PubMed

Hendriks, A Jan; Awkerman, Jill A; de Zwart, Dick; Huijbregts, Mark A J

2013-11-01

While variable sensitivity of model species to common toxicants has been addressed in previous studies, a systematic analysis of inter-species variability for different test types, modes of action and species is as of yet lacking. Hence, the aim of the present study was to identify similarities and differences in contaminant levels affecting cold-blooded and warm-blooded species administered via different routes. To that end, data on lethal water concentrations LC50, tissue residues LR50 and oral doses LD50 were collected from databases, each representing the largest of its kind. LC50 data were multiplied by a bioconcentration factor (BCF) to convert them to internal concentrations that allow for comparison among species. For each endpoint data set, we calculated the mean and standard deviation of species' lethal level per compound. Next, the means and standard deviations were averaged by mode of action. Both the means and standard deviations calculated depended on the number of species tested, which is at odds with quality standard setting procedures. Means calculated from (BCF) LC50, LR50 and LD50 were largely similar, suggesting that different administration routes roughly yield similar internal levels. Levels for compounds interfering biochemically with elementary life processes were about one order of magnitude below that of narcotics disturbing membranes, and neurotoxic pesticides and dioxins induced death in even lower amounts. Standard deviations for LD50 data were similar across modes of action, while variability of LC50 values was lower for narcotics than for substances with a specific mode of action. The study indicates several directions to go for efficient use of available data in risk assessment and reduction of species testing. Copyright © 2013 Elsevier Inc. All rights reserved.

Levetiracetam in adult patients with and without learning disability: focus on behavioral adverse effects.

PubMed

Brodtkorb, Eylert; Klees, Theresa M; Nakken, Karl O; Lossius, Rasmus; Johannessen, Svein I

2004-04-01

Optimal antiepileptic drug treatment in patients with learning disability (LD) represents a particular challenge. These patients are often unable to report toxicity, and side effects may manifest as behavioral problems. The aim of this open study was to compare efficacy and tolerability of levetiracetam (LEV) in patients with LD and those without LD. One hundred eighty-four consecutive adult patients who received LEV were followed for an average of 8.1 months. Fifty-six patients (30%) had LD. Thirty-nine percent of patients with refractory epilepsy (37% with and 40% without LD) had > 50% seizure reduction. Significantly more behavioral side effects (23% vs 10%) and a tendency toward less reported somatic central nervous side effects were found in the LD group. We conclude that LEV is equally effective and well tolerated in both patients with LD and patients without LD. However, behavioral problems are more frequent in patients with LD, whereas the tendency toward seizure increase is not enhanced.

Remedial Investigation/Feasibility Study Fort Dix U.S. Army Installation Fort Dix, New Jersey

DTIC Science & Technology

1994-01-01

METHOD: PARTICULATE FILTER; GRAVIMETRIC: (NIOSH VOL. Ill I 8583 , NUISANCE DUST (TOTAL)). »OSHA REVOKED THE FINAL RULE LIMITS OF JANUARY 19, 1989 IN...VJ ISO .- i-.i^ !...= : \\J~::— :!__’ii!-!lS . l~>.-- -.^ - ORAL-MCUSE LD50i 5SS0 MO/KG ORAL-rAf-iivifcii i LD50: 750 MG

Phorate can reverse P450 metabolism-based herbicide resistance in Lolium rigidum.

PubMed

Busi, Roberto; Gaines, Todd Adam; Powles, Stephen

2017-02-01

Organophosphate insecticides can inhibit specific cytochrome P450 enzymes involved in metabolic herbicide resistance mechanisms, leading to synergistic interactions between the insecticide and the herbicide. In this study we report synergistic versus antagonistic interactions between the organophosphate insecticide phorate and five different herbicides observed in a population of multiple herbicide-resistant Lolium rigidum. Phorate synergised with three different herbicide modes of action, enhancing the activity of the ALS inhibitor chlorsulfuron (60% LD 50 reduction), the VLCFAE inhibitor pyroxasulfone (45% LD 50 reduction) and the mitosis inhibitor trifluralin (70% LD 50 reduction). Conversely, phorate antagonised the two thiocarbamate herbicides prosulfocarb and triallate with a 12-fold LD 50 increase. We report the selective reversal of P450-mediated metabolic multiple resistance to chlorsulfuron and trifluralin in the grass weed L. rigidum by synergistic interaction with the insecticide phorate, and discuss the putative mechanistic basis. This research should encourage diversity in herbicide use patterns for weed control as part of a long-term integrated management effort to reduce the risk of selection of metabolism-based multiple herbicide resistance in L. rigidum. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Acute toxicity of fipronil to the stingless bee Scaptotrigona postica Latreille.

PubMed

Jacob, Cynthia Renata Oliveira; Soares, Hellen Maria; Carvalho, Stephan Malfitano; Nocelli, Roberta Cornélio Ferreira; Malaspina, Osmar

2013-01-01

Fipronil is an insecticide widely used to control a great number of pests, thus the aim of this study was to determine the lethal dose and lethal concentration (LD(50) and LC(50)) of this insecticide to the stingless bees Scaptotrigona postica Latreille, 1807. The LD(50) and LC(50) values obtained after 24 h of exposition were of 0.54 ng a.i./bee and 0.24 ng a.i./μL diet, respectively. These values were considered highly toxic to stingless bees.

Social Interaction of Children with and without Learning Disabilities in Dyads and Small Groups.

ERIC Educational Resources Information Center

Wiener, Judith; Harris, P. J.

To investigate differences in social behavior between learning disabled (LD) and non-learning disabled (NLD) children in different size groups and to examine the association between children's social behavior and acceptance by their peers, a study was conducted of 44 LD and 50 NLD boys and 7 LD and 13 NLD girls from fourth, fifth, and sixth grade…

49 CFR 173.132 - Class 6, Division 6.1-Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... the particles available for inhalation in the test must have a diameter of 10 microns or less if it is... aerodynamic diameter of that particle-fraction is 10 microns or less. A liquid substance should be tested if a... constituent A, B ... Z in the mixture; T = the oral LD50 values of constituent A, B ... Z; TM = the oral LD50...

49 CFR 173.132 - Class 6, Division 6.1-Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... the particles available for inhalation in the test must have a diameter of 10 microns or less if it is... aerodynamic diameter of that particle-fraction is 10 microns or less. A liquid substance should be tested if a... constituent A, B ... Z in the mixture; T = the oral LD50 values of constituent A, B ... Z; TM = the oral LD50...

49 CFR 173.132 - Class 6, Division 6.1-Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... the particles available for inhalation in the test must have a diameter of 10 microns or less if it is... aerodynamic diameter of that particle-fraction is 10 microns or less. A liquid substance should be tested if a... constituent A, B ... Z in the mixture; T = the oral LD50 values of constituent A, B ... Z; TM = the oral LD50...

Hormone-dependence of sarin lethality in rats: Sex differences and stage of the estrous cycle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Carl D., E-mail: carl.d.smith179.mil@mail.mil; Wright, Linnzi K.M.; Garcia, Gregory E.

Chemical warfare nerve agents (CWNAs) are highly toxic compounds that cause a cascade of symptoms and death, if exposed casualties are left untreated. Numerous rodent models have investigated the toxicity and mechanisms of toxicity of CWNAs, but most are limited to male subjects. Given the profound physiological effects of circulating gonadal hormones in female rodents, it is possible that the daily cyclical fluctuations of these hormones affect females' sensitivity to the lethal effects of CWNAs, and previous reports that included female subjects did not control for the stage of the hormonal cycle. The aim of the current study was tomore » determine the 24-hour median lethal dose (LD{sub 50}) of the CWNA sarin in male, ovariectomized (OVEX) female, and female rats during different stages of the estrous cycle (diestrus, proestrus, and estrus). Additionally, baseline activity levels of plasma acetylcholinesterase, butyrylcholinesterase, and carboxylesterase were measured to determine differences among the groups. Results indicated that females in proestrus had a significantly higher LD{sub 50} of sarin compared to OVEX and estrous females. Although some sex differences were observed in the activity levels of plasma esterases, they were not consistent and likely not large enough to significantly affect the LD{sub 50}s. These results suggest that hormonal cyclicity can influence the outcome of CWNA-related studies using female rodents, and that this variability can be minimized by controlling for the stage of the cycle. Additional research is necessary to determine the precise mechanism of the observed differences because it is unlikely to be solely explained by plasma esterase activity. - Highlights: • The LD{sub 50} of sarin was determined in female rats throughout the stages of the estrous cycle. • Females in proestrus had a significantly higher LD{sub 50} compared to estrous or ovariectomized females. • No sex differences were observed between male and female rats. • It is unlikely that plasma esterase activity underlies the observed differences in LD{sub 50}s.« less

Effects of Starvation on Deltamethrin Tolerance in Bed Bugs, Cimex lectularius L. (Hemiptera: Cimicidae)

PubMed Central

DeVries, Zachary C.; Reid, William R.; Kells, Stephen A.; Appel, Arthur G.

2015-01-01

Bed bugs, Cimex lectularius L., are a major pest in the urban environment. Their presence often results in physical, psychological, and financial distress of homeowners and apartment dwellers. Although many insecticide bioassays have been performed on this pest, little attention has been paid to bed bug feeding status, which is closely linked to metabolism, molting, and mass. Therefore, we evaluated the toxicity of topically applied deltamethrin on insecticide susceptible adult male bed bugs fed 2 d, 9 d, and 21 d prior to testing. When toxicity was evaluated on a “per-bug” basis, there was no difference between 2 d [LD50 = 0.498 (0.316 − 0.692) ng·bug−1] and 9 d [LD50 = 0.572 (0.436 − 0.724) ng·bug−1] starved bugs, while 21 d starved bugs had a significantly lower LD50 [0.221 (0.075 − 0.386) ng·bug−1]. When toxicity was evaluated in terms of body mass, 9 d starved bugs had the highest LD50 values [0.138 (0.102 − 0.176) ng·mg−1], followed by 2 d starved bugs [0.095 (0.060 − 0.134) ng·mg−1], and then 21 d starved bugs [0.058 (0.019–0.102) ng·mg−1]; the LD50 values of 2 d and 9 d starved bugs were significantly different from 21 d starved bugs. These results indicate that feeding status plays an important role in the toxicity of deltamethrin. In addition, the lack of differences between 2 d and 9 d starved bugs indicate that the blood meal itself has little impact on tolerance, but rather it is some physiological change following feeding that confers increased tolerance to bed bugs. PMID:26463068

Molecular Docking Studies of Flavonoids Derivatives on the Flavonoid 3- O-Glucosyltransferase.

PubMed

Harsa, Alexandra M; Harsa, Teodora E; Diudea, Mircea V; Janezic, Dusanka

2015-01-01

A study of 30 flavonoid derivatives, taken from PubChem database and docked on flavonoid 3-O-glucosyltransferase 3HBF, next submitted to a QSAR study, performed within a hypermolecule frame, to model their LD50 values, is reported. The initial set of molecules was split into a training set and the test set (taken from the best scored molecules in the docking test); the predicted LD50 values, computed on similarity clusters, built up for each of the molecules of the test set, surpassed in accuracy the best model. The binding energies to 3HBF protein, provided by the docking step, are not related to the LD50 of these flavonoids, more protein targets are to be investigated in this respect. However, the docking step was useful in choosing the test set of molecules.

Acute toxicity and primary irritancy of alkylalkanolamines.

PubMed

Ballantyne, B; Leung, H W

1996-12-01

The acute handling hazards of several alkylalkanolamines were determined by investigating their potential acute toxicity and primary irritancy. Materials studied were N-methylethanolamine (MEA), N, N, -dimethylethanolamine (DMEA), N, N, -dimethylisopropanolamine (DMIPA), N-methyldiethanolamine (MDEA), and tertbutyldiethanolamine (BDEA). All these alkylalkanolamines were of comparable acute peroral toxicity in the rat (LD50 range 1.48-2.83 ml/kg). By 24 h occluded epicutaneous contact in the rabbit, MEA, DMEA and DMIPA were of moderate acute percutaneous toxicity (LD50 range 1.13-2.0 ml/kg), MDEA was of slight acute percutaneous toxicity (LD50 male 9.85 ml/kg, female 10.90 ml/kg), and BDEA of intermediate toxicity (LD50 6.4 ml/kg). Due to differences in vapor pressure the acute vapor exposure toxicity of the alkylalkanolamines to rats varied; MEA, MDEA and BDEA were of a low order of acute toxicity, and DMIPA was moderately toxic with an LT50 of 3.2 h for a saturated vapor atmosphere exposure. A 4 h-LC50 (rat combined sex) of 1461 ppm was determined for DMEA. All alkylalkanolamines studied, except MDEA, were moderately to markedly irritating and caused variable degrees of skin corrosivity; MDEA caused only transient minor skin irritation. In accord with the skin irritancy results, the eye irritancy from 0.005 ml MEA, DMEA, DMIPA and BDEA was severe, and that from MDEA was slight. Exposure to these compounds has implications for occupational health procedures.

Effects of a chitin binding vicilin from Erythrina velutina seeds on bean bruchid pests (Callosobruchus maculatus and Zabrotes subfasciatus).

PubMed

Teixeira, Fabiano M; Oliveira, Adeliana S; Macedo, Leonardo L P; Santos, Elizeu A; de Sales, Mauricio P

2008-01-01

Erythrina velutina vicilin, EvV, is a dimeric glycoprotein with Mr of 124.6 kDa. EvV was tested for anti-insect activity against bean bruchid larvae. EvV had LD(50) of 0.10% and ED(50) of 0.14% for Z. subfasciatus and LD(50) of 0.26% and ED(50) of 0.19% for C. maculatus. EvV was not digested by bean larvae enzymes until 12 h of incubation, and at 24 h EvV was more resistant to Z. subfasciatus enzymes.

Effects of Text Length on Lexical Diversity Measures: Using Short Texts with Less than 200 Tokens

ERIC Educational Resources Information Center

Koizumi, Rie; In'nami, Yo

2012-01-01

Despite the importance of lexical diversity (LD) in L2 speaking and writing performance, LD assessment measures are known to be affected by the number of words analyzed in the text. This study aims to identify LD measures that are least affected by text length and can be used for the analysis of short L2 texts (50-200 tokens). We compared the…

Sensitization by SR-2508 plus Ro 03-8799

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stone, H.B.; Luu, Y.H.; Lam, K.N.

1986-07-01

The primary toxicity of Ro 03-8799 is a central nervous system toxicity, whereas that of SR-2508 is a peripheral neuropathy. The feasibility of reducing overall toxicity while maintaining maximal radiosensitization by using the two sensitizers together was tested. The LD50/2 of Ro 03-8799 was 0.68 mg/g body wt (mg/gbw) after intravenous (i.v.) administration, and that of SR-2508 was 4.4 mg/gbw after i.v. administration. When both drugs were given together in equitoxic proportions, the LD50/2 was 0.45 mg of Ro 03-8799 plus 2.9 mg of SR-2508/gbw. These doses are 66% of the respective LD50/2 values of the drugs when given separately.more » Radiosensitization was evaluated using in vivo-in vitro assays with EMT6/SF tumors in BALB/c mice. At drug doses between 10 and 60% of the LD50/2, sensitization was generally maximal and similar to that from misonidazole, but there was less sensitization below this dose, both with the drugs given separately and together. If chronic toxicities of these drugs overlap as do the acute toxicities there will be little or no additional benefit from using these drugs in combination, compared to using them separately.« less

Effects of organophosphorus anticholinesterase compounds on brain glucose and energy metabolism. Final summary report, 1 October 1981-29 February 1984

DOE Office of Scientific and Technical Information (OSTI.GOV)

Medina, M.A.; Miller, A.L.

1984-09-01

The effects of Soman and paraoxon on cerebral metabolic rate (CMRg) and the levels of various metabolites in rate brain were investigated. In non-convulsing animals, 0.8 of the paraoxon LD50 and 0.5 of the Soman LD50 tended to lower CMRg. A higher dose of Soman, 0.8-0.95 of the LD50, resulted in convulsive seizures in some but not all of the animals. In convulsing rats the CMRg and lactate levels were elevated primarily in the cortex and thalamus/basal ganglia. Decreased ATP and glucose levels with an elevated CMRg and lactate concentration was observed in the cortex, suggesting that Soman may bemore » uncoupling oxidative phosphorylation. Pretreatment with atropine prevented the behavioral manifestations and the elevated CMRg but not the hyperglycemia produced by an 0.8 LD50 dose of Soman. These results suggest that Soman-induced convulsions are similar to those produced by other central nervous system (CNS) excitatory agents in that only certain brain regions are affected. The use of atropine to block the CNS disturbances produced by Soman appears to be effective also does not result in the extensive depression of CMRg observed with TAB, a mixture of trimedoxime, atropine and benactyzine.« less

LD50 and repellent effects of essential oils from Argentinian wild plant species on Varroa destructor.

PubMed

Ruffinengo, Sergio; Eguaras, Martin; Floris, Ignazio; Faverin, Claudia; Bailac, Pedro; Ponzi, Marta

2005-06-01

The repellent and acaricidal effects of some essential oils from the most typical wild plant species of northern Patagonia, Argentina, on Varroa destructor Anderson & Trueman were evaluated using a complete exposure test. Honey bees, Apis mellifera L., and mites (five specimens of each per dish) were introduced in petri dishes having different oil concentrations (from 0.1 to 25 micro per cage). Survival of bees and mites was registered after 24, 48, and 72 h. An attraction/repellence test was performed using a wax tube impregnated with essential oil and another tube containing wax only. The lowest LD50 values for mites were registered for Acantholippia seriphioides (A. Gray) Mold. (1.27 microl per cage) and Schinus molle L. (2.65 microl per cage) after 24 h, and for Wedelia glauca (Ortega) O. Hoffm. ex Hicken (0.59 microl per cage) and A. seriphioides (1.09 microl per cage) after 72 h of treatment. The oil with the highest selectivity ratio (A. mellifera LD50/V. destructor LD50) was the one extracted from S. molle (>16). Oils of Lippia junelliana (Mold.) Troncoso, Minthostachys mollis (HBK) Grieseb., and Lippia turbinata Grieseb. mixed with wax had repellent properties. None of the oils tested had attractive effects on Varroa mites.

Tityus serrulatus Scorpion Venom: In Vitro Tests and Their Correlation with In Vivo Lethal Dose Assay

PubMed Central

Cajado-Carvalho, Daniela; Galvão, Juliana; Kuniyoshi, Alexandre K.; Carneiro, Patrícia dos Santos; Paes Leme, Adriana Franco; Pauletti, Bianca Alves; Marengo, Eliana Blini; Portaro, Fernanda V.

2017-01-01

Scorpion stings are the main cause of human envenomation in Brazil and, for the treatment of victims, the World Health Organization (WHO) recommends the use of antivenoms. The first step to achieve effective antivenom is to use a good quality venom pool and to evaluate it, with LD50 determination as the most accepted procedure. It is, however, time-consuming and requires advanced technical training. Further, there are significant ethical concerns regarding the number of animals required for testing. Hence, we investigated the correspondence between LD50 results, in vitro assays, and a strong correlation with proteolytic activity levels was observed, showing, remarkably, that proteases are potential toxicity markers for Tityus serrulatus venom. The comparison of reversed-phase chromatographic profiles also has a potential application in venoms’ quality control, as there were fewer neurotoxins detected in the venom with high LD50 value. These results were confirmed by mass spectrometry analysis. Therefore, these methods could precede the LD50 assay to evaluate the venom excellence by discriminating—and discarding—poor-quality batches, and, consequently, with a positive impact on the number of animals used. Notably, proposed assays are fast and inexpensive, being technically and economically feasible in Tityus serrulatus venom quality control to produce effective antivenoms. PMID:29168766

Quantitative structure toxicity relationships for phenols in isolated rat hepatocytes.

PubMed

Moridani, Majid Y; Siraki, Arno; O'Brien, Peter J

2003-05-06

Quantitative structure toxicity relationship (QSTR) equations were obtained to predict and describe the cytotoxicity of 31 phenols using logLD(50) as a concentration to induce 50% cytotoxicity of isolated rat hepatocytes in 2 h and logP as octanol/water partitioning: logLD(50) (microM)=-0.588(+/-0.059)logP+4.652(+/-0.153) (n=27, r(2)=0.801, s=0.261, P<1 x 10(-9)). Hydroquinone, catechol, 4-nitrophenol, and 2,4-dinitrophenol were outliers for this equation. When the ionization constant pK(a) was considered as a contributing factor a two-parameter QSTR equation was derived: logLD(50) (microM)=-0.595(+/-0.051)logP+0.197(+/-0.029)pK(a)+2.665(+/-0.281) (n=28, r(2)=0.859, s=0.218, P<1 x 10(-6)). Using sigma+, the Brown variation of the Hammet electronic constant, as a contributing parameter, the cytotoxicity of phenols towards hepatocytes were defined by logLD(50) (microM)=-0.594(+/-0.052)logP-0.552(+/-0.085)sigma+ +4.540(+/-0.132) (n=28, r(2)=0.853, s=0.223, P<1 x 10(-6)). Replacing sigma+ with the homolytic bond dissociation energy (BDE) for (X-PhOH+PhO.-->X-PhO.+PhOH) led to logLD(50) (microM)=-0.601(+/-0.066)logP-0.040(+/-0.018)BDE+4.611(+/-0.166) (n=23, r(2)=0.827, s=0.223, P<0.05). Hydroquinone, catechol and 2-nitrophenol were outliers for the above equations. Using redox potential and logP led to a new correlation: logLD(50) (microM)=-0.529(+/-0.135)logP+2.077(+/-0.892)E(p/2)+2.806(+/-0.592) (n=15, r(2)=0.561, s=0.383, P<0.05) with 4-nitrophenol as an outlier. Our findings indicate that phenols with higher lipophilicity, BDE, or sigma+ values or with lower pK(a) and redox potential were more toxic towards hepatocytes. We also showed that a collapse of hepatocyte mitochondrial membrane potential preceded the cytotoxicity of most phenols. Our study indicates that one or a combination of mechanisms; i.e. mitochondrial uncoupling, phenoxy radicals, or phenol metabolism to quinone methides and quinones, contribute to phenol cytotoxicity towards hepatocytes depending on the phenol chemical structure.

Immunization with a novel Clostridium perfringens epsilon toxin mutant rETX(Y196E)-C confers strong protection in mice.

PubMed

Yao, Wenwu; Kang, Jingjing; Kang, Lin; Gao, Shan; Yang, Hao; Ji, Bin; Li, Ping; Liu, Jing; Xin, Wenwen; Wang, Jinglin

2016-04-06

Epsilon toxin (ETX) is produced by toxinotypes B and D of Clostridium perfringens. It can induce lethal enterotoxemia in domestic animals, mainly in sheep, goats and cattle, causing serious economic losses to global animal husbandry. In this study, a novel and stable epsilon toxin mutant rETX(Y196E)-C, obtained by substituting the 196th tyrosine (Y196) with glutamic acid (E) and introducing of 23 amino acids long C-terminal peptide, was determined as a promising recombinant vaccine candidate against enterotoxemia. After the third vaccination, the antibody titers against recombinant wild type (rETX) could reach 1:10(5) in each immunized group, and the mice were completely protected from 100 × LD50 (50% lethal dose) of rETX challenge. The mice in 15 μg subcutaneously immunized group fully survived at the dose of 500 × LD50 of rETX challenge and 80% of mice survived at 180 μg (1000 × LD50) of rETX administration. In vitro, immune sera from 15 μg subcutaneously immunized group could completely protect MDCK cells from 16 × CT50 (50% lethal dose of cells) of rETX challenge and protect against 10 × LD50 dose (1.8 μg) of rETX challenge in mice. These data suggest that recombinant protein rETX(Y196E)-C is a potential vaccine candidate for future applied researches.

Toxicity of methyl parathion to bats: Mortality and coordination loss

USGS Publications Warehouse

Clark, D.R.

1986-01-01

The 24-h oral LD50 of methyl parathion (phosphorothioic acid O,O-dimethyl O-(4-nitrophenyl) ester) to little brown bats (Myotis lucifugus) (372 mg/kg) was 8.5 times the LD50 for mice (Mus musculus) (44 mg/kg). However, orally dosed mice either died or appeared behaviorally normal after 2 to 3 h, whereas many dosed bats, although alive at 24 h, could not right themselves when placed on their backs. The oral dose estimated to cause this loss of coordination in 50% of a sample of big brown bats (Eptesicus fuscus) was one-third or less the LD50 of this species. Cholinesterase activity depression in brains of little brown bats was similar whether dosage was oral or dermal. With death as the criterion, bats proved relatively insensitive to methyl parathion in 24-h tests, but considerations of the chemical's potential to cause coordination loss, leading to capture and death by predators, coupled with bats' naturally low reproductive rates, suggest possible injury to exposed bat populations.

A critical role of acute bronchoconstriction in the mortality associated with high-dose sarin inhalation: Effects of epinephrine and oxygen therapies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gundavarapu, Sravanthi; Zhuang, Jianguo; Barrett, Edward G.

Sarin is an organophosphate nerve agent that is among the most lethal chemical toxins known to mankind. Because of its vaporization properties and ease and low cost of production, sarin is the nerve agent with a strong potential for use by terrorists and rouge nations. The primary route of sarin exposure is through inhalation and, depending on the dose, sarin leads to acute respiratory failure and death. The mechanism(s) of sarin-induced respiratory failure is poorly understood. Sarin irreversibly inhibits acetylcholine esterase, leading to excessive synaptic levels of acetylcholine and, we have previously shown that sarin causes marked ventilatory changes includingmore » weakened response to hypoxia. We now show that LD{sub 50} sarin inhalation causes severe bronchoconstriction in rats, leading to airway resistance, increased hypoxia-induced factor-1α, and severe lung epithelium injury. Transferring animals into 60% oxygen chambers after sarin exposure improved the survival from about 50% to 75% at 24 h; however, many animals died within hours after removal from the oxygen chambers. On the other hand, if LD{sub 50} sarin-exposed animals were administered the bronchodilator epinephrine, > 90% of the animals survived. Moreover, while both epinephrine and oxygen treatments moderated cardiorespiratory parameters, the proinflammatory cytokine surge, and elevated expression of hypoxia-induced factor-1α, only epinephrine consistently reduced the sarin-induced bronchoconstriction. These data suggest that severe bronchoconstriction is a critical factor in the mortality induced by LD{sub 50} sarin inhalation, and epinephrine may limit the ventilatory, inflammatory, and lethal effects of sarin. - Highlights: • Inhalation exposure of rats to LD{sub 50} sarin causes death through respiratory failure. • Severe bronchoconstriction is the major cause of sarin-induced respiratory failure. • Transfer of sarin exposed rats to 60% oxygen improves the mortality temporarily. • Epinephrine improves bronchoconstriction and mortality in LD{sub 50} sarin-exposed rats. • Both epinephrine and oxygen moderate the sarin-induced lung inflammatory response.« less

Insecticidal activity of isobutylamides derived from Piper nigrum against adult of two mosquito species, Culex pipiens pallens and Aedes aegypti.

PubMed

Park, Il-Kwon

2012-01-01

The insecticidal activity of Piper nigrum fruit-derived piperidine alkaloid (piperine) and N-isobutylamide alkaloids (pellitorine, guineensine, pipercide and retrofractamide A) against female adults of Culex pipiens pallens and Aedes aegypti was examined. On the basis of 24-h LD(50) values, the compound most toxic to female C. pipiens pallens was pellitorine (0.4 µg/♀) followed by guineensine (1.9 µg/♀), retrofractamide A (2.4 µg/♀) and pipercide (3.2 µg/♀). LD(50) value of chlorpyrifos was 0.03 µg/♀. Against female A. aegypti, the insecticidal activity was more pronounced in pellitorine (0.17 µg/♀) than in retrofractamide A (1.5 µg/♀), guineensine (1.7 µg/♀), and pipercide (2.0 µg/♀). LD(50) value of chlorpyrifos was 0.0014 µg/♀.

Toxicity and developmental defects of different sizes and shape nickel nanoparticles in zebrafish

PubMed Central

Ispas, Cristina; Andreescu, Daniel; Patel, Avni; Goia, Dan V.; Andreescu, Silvana; Wallace, Kenneth N.

2009-01-01

Metallic nanoparticles such as nickel are used in catalytic, sensing and electronic applications, but health and environmental affects have not been fully investigated. While some metal nanoparticles result in toxicity, it is also important to determine whether nanoparticles of the same metal but of different size and shape changes toxicity. Three different size nickel nanoparticle (Ni NPs) of 30, 60, and 100 nm and larger particle clusters of aggregated 60 nm entities with a dendritic structure were synthesized and exposed to zebrafish embryos assessing mortality and developmental defects. Ni NPs exposure was compared to soluble nickel salts. All three 30, 60, and 100 nm Ni NPs are equal to or less toxic than soluble nickel while dendritic clusters were more toxic. With each Ni NP exposure, thinning of the intestinal epithelium first occurs around the LD10 continuing into the LD50. LD50 exposure also results in skeletal muscle fiber separation. Exposure to soluble nickel does not cause intestinal defects while skeletal muscle separation occurs at concentrations well over LD50. These results suggest that configuration of nanoparticles may affect toxicity more than size and defects from Ni NPs exposure occur by different biological mechanisms than soluble nickel. PMID:19746736

Impact of endurance exercise on levodopa-associated cortisol release and force increase in patients with Parkinson's disease.

PubMed

Müller, Thomas; Muhlack, Siegfried

2008-06-01

Levodopa (LD) application improves motor symptoms and reduces cortisol levels in patients with Parkinson's disease (PD). Endurance exercise enhances cortisol release in proportion to the intensity of the effort and thus may counteract the LD associated cortisol decrease. We measured levels of cortisol and LD over an 1-h long interval following administration of soluble 200 mg LD/50 mg benserazide with concomitant maximal grip strength assessment in 16 PD patients under cued conditions during rest and endurance exercise. The motor response, the plasma levels of cortisol and LD did not significantly differ between both conditions. Cortisol concentrations significantly decreased even during exercise. Grip strength only significantly went up during rest. Endurance exercise did not counteract the LD associated decreased cortisol release. Since cortisol improves muscle function, the lack of increase in maximal grip strength following LD administration during exercise may contribute to reduced exercise capacity, which is reported by PD patients.

Acute Oral Toxicity of Tetrodotoxin in Mice: Determination of Lethal Dose 50 (LD50) and No Observed Adverse Effect Level (NOAEL).

PubMed

Abal, Paula; Louzao, M Carmen; Antelo, Alvaro; Alvarez, Mercedes; Cagide, Eva; Vilariño, Natalia; Vieytes, Mercedes R; Botana, Luis M

2017-02-24

Tetrodotoxin (TTX) is starting to appear in molluscs from the European waters and is a hazard to seafood consumers. This toxin blocks sodium channels resulting in neuromuscular paralysis and even death. As a part of the risk assessment process leading to a safe seafood level for TTX, oral toxicity data are required. In this study, a 4-level Up and Down Procedure was designed in order to determine for the first time the oral lethal dose 50 (LD 50 ) and the No Observed Adverse Effect Level (NOAEL) in mice by using an accurate well-characterized TTX standard.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giggleman, M.A.; Fitzpatrick, L.C.; Goven, A.J.

Earthworms, Lumbricus terrestris, exposed for 96 h to filter paper saturated with five nominal concentrations of pentachlorophenol, exhibited a 50% lethal concentration (LC50) of 25.0 {micro}g PCP/cm{sup 2} and corresponding whole worm body burden-based 50% lethal dose (LD50) of 877.7 {micro}g PCP/g dry mass. Linear regression modeling showed that worms increased body concentrations (BC = {micro}g PCP/g dry tissue mass) with increasing exposure concentrations (EC) according to BC = 113.5 + 29.5EC. Phagocytosis of yeast cells by immunoactive coelomocytes was suppressed only at body concentrations (863.3 {micro}g PCP/g dry mass) that approximated the calculated LD50 and overlapped those demonstrating lethality,more » indicating a sharp transition between sublethal and lethal toxicity. An exposure concentration of 15 {micro}g PCP/cm{sup 2} produced significant suppression of phagocytosis of yeast cells by immunoactive coelomocytes. However, the average measured body burden from this group approximated the estimated LD50, indicating a sharp toxic response slope. Exposure to 10 {micro}g PCP/cm{sup 2} with a corresponding body concentration of 501.3 {micro}g PCP/g dry mass did not affect phagocytosis. The importance of body burden data is emphasized.« less

Toxicity of binary chemical munition destruction products: methylphosphonic acid, methylphosphinic acid, 2-diisopropylaminoethanol, DF neutralent, and QL neutralent.

PubMed

Watson, Rebecca E; Hafez, Ahmed M; Kremsky, Jonathan N; Bizzigotti, George O

2007-01-01

This paper reports the toxicity and environmental impact of neutralents produced from the hydrolysis of binary chemical agent precursor chemicals DF (methylphosphonic difluoride) and QL (2-[bis(1-methylethyl)amino]ethyl ethyl methylphosphonite). Following a literature review of the neutralent mixtures and constituents, basic toxicity tests were conducted to fill data gaps, including acute oral and dermal median lethal dose assays, the Ames mutagenicity test, and ecotoxicity tests. For methylphosphonic acid (MPA), a major constituent of DF neutralent, the acute oral LD(50) in the Sprague-Dawley rat was measured at 1888 mg/kg, and the Ames test using typical tester strains of Salmonella typhimurium and Escherichia coli was negative. The 48-h LC(50) values for pH-adjusted DF neutralent with Daphnia magna and Cyprinodon variegatus were > 2500 mg/L and 1593 mg/L, respectively. The acute oral LD(50) values in the rat for QL neutralent constituents methylphosphinic acid (MP) and 2-diisopropylaminoethanol (KB) were both determined to be 940 mg/kg, and the Ames test was negative for both. Good Laboratory Practice (GLP)-compliant ecotoxicity tests for MP and KB gave 48-h D. magna EC(50) values of 6.8 mg/L and 83 mg/L, respectively. GLP-compliant 96-h C. variegatus assays on MP and KB gave LC(50) values of 73 and 252 mg/L, respectively, and NOEC values of 22 and 108 mg/L. QL neutralent LD(50) values for acute oral and dermal toxicity tests were both > 5000 mg/kg, and the 48-h LD(50) values for D. magna and C. variegatus were 249 and 2500 mg/L, respectively. Using these data, the overall toxicity of the neutralents was assessed.

Calocalpe undulata: Contact toxicity of ten insecticides to the larvae

Treesearch

Jacqueline L. Roberson; Marion Page; Nancy L. Gillette

1974-01-01

Ten insecticides were tested against larvae of Calocalpe undulala (L.). The decreasing order of toxicity at LD50 was: bioethanomethrin, phenothrin, pyrethrins, phoxim, tetrachlorvinfos, mexacarbate, carbaryl, phosmet, DDT, and malathion. At LD90,the decreasing order of toxicity was the same, except that...

Colleges or Universities with L.D. Programs.

ERIC Educational Resources Information Center

Association for Children and Adults with Learning Disabilities, Pittsburgh, PA.

The listing describes approximately 50 colleges and universities with programs for learning disabled (LD) students. Descriptions are arranged alphabetically by state and include the college's name, address, telephone number, name of contact person, and brief description. Among services listed are textbooks on cassette; academic, career, and…

Identification of Leishmania donovani Topoisomerase 1 inhibitors via intuitive scaffold hopping and bioisosteric modification of known Top 1 inhibitors

NASA Astrophysics Data System (ADS)

Mamidala, Rajinikanth; Majumdar, Papiya; Jha, Kunal Kumar; Bathula, Chandramohan; Agarwal, Rahul; Chary, M. Thirumala; Mazumdar, H. K.; Munshi, Parthapratim; Sen, Subhabrata

2016-05-01

A library of arylidenefuropyridinediones was discovered as potent inhibitors of Leishmania donovani Topoisomerase 1 (LdTop1) where the active molecules displayed considerable inhibition with single digit micromolar EC50 values. This molecular library was designed via intuitive scaffold hopping and bioisosteric modification of known topoisomerase 1 inhibitors such as camptothecin, edotecarin and etc. The design was rationalized by molecular docking analysis of the compound prototype with human topoisomerase 1 (HTop1) and Leishmania donovani topoisomerase 1(LdTop1). The most active compound 4 displayed no cytotoxicity against normal mammalian COS7 cell line (~100 fold less inhibition at the EC50). Similar to camptothecin, 4 interacted with free LdTop1 as observed in the preincubation DNA relaxation inhibition experiment. It also displayed anti-protozoal activity against Leishmania donovani promastigote. Crystal structure investigation of 4 and its molecular modelling with LdTop1 revealed putative binding sites in the enzyme that could be harnessed to generate molecules with better potency.

Protection of mice against fission neutron irradiation by WR-2721 or WR-151327

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steel, L.K.; Jacobs, A.J.; Giambarresi, L.I.

1987-03-01

Two phosphorothioate compounds, WR-2721 and WR-151327, were examined for their radioprotective efficacies against the effects of fission neutron irradiation in male and female mice. Within sex groups no significant difference in lethality at 30 or 100 days postirradiation was found between WR-2721 or WR-151327 pretreatment. The dose modification factors (DMFs) for male mice treated with either compound were 1.29 (LD50/30) and 1.24 (LD50/100), and those for drug-treated female mice were 1.21 (LD50/30) and 1.19 (LD50/100). Both WR-2721 and WR-151327 were found to be equally radioprotective when compared using DMFs as the end point. WR-151327 (500 mg/kg, ip) was found tomore » be significantly more toxic to both male and female B6D2F1 mice than equimolar amounts of WR-2721. Small but significant sex differences in radioprotection were found: the DMFs for female mice pretreated with either compound were lower than those for similarly treated male mice; the incidence of mortality 31-100 days postexposure in male mice pretreated with WR-151327 was greater than for female mice. In addition, sex differences were noted in drug toxicity. Toxic death in female mice given WR-151327 (500 mg/kg, ip) is 2.6 times more probable than in males.« less

Quantitative determination of biological activity of botulinum toxins utilizing compound muscle action potentials (CMAP), and comparison of neuromuscular transmission blockage and muscle flaccidity among toxins.

PubMed

Torii, Yasushi; Goto, Yoshitaka; Takahashi, Motohide; Ishida, Setsuji; Harakawa, Tetsuhiro; Sakamoto, Takashi; Kaji, Ryuji; Kozaki, Shunji; Ginnaga, Akihiro

2010-01-01

The biological activity of various types of botulinum toxin has been evaluated using the mouse intraperitoneal LD(50) test (ip LD(50)). This method requires a large number of mice to precisely determine toxin activity, and so has posed a problem with regard to animal welfare. We have used a direct measure of neuromuscular transmission, the compound muscle action potential (CMAP), to evaluate the effect of different types of botulinum neurotoxin (NTX), and we compared the effects of these toxins to evaluate muscle relaxation by employing the digit abduction scoring (DAS) assay. This method can be used to measure a broad range of toxin activities the day after administration. Types A, C, C/D, and E NTX reduced the CMAP amplitude one day after administration at below 1 ip LD(50), an effect that cannot be detected using the mouse ip LD(50) assay. The method is useful not only for measuring toxin activity, but also for evaluating the characteristics of different types of NTX. The rat CMAP test is straightforward, highly reproducible, and can directly determine the efficacy of toxin preparations through their inhibition of neuromuscular transmission. Thus, this method may be suitable for pharmacology studies and the quality control of toxin preparations. Copyright 2009 Elsevier Ltd. All rights reserved.

Extensive review of fish embryo acute toxicities for the prediction of GHS acute systemic toxicity categories.

PubMed

Scholz, Stefan; Ortmann, Julia; Klüver, Nils; Léonard, Marc

2014-08-01

Distribution and marketing of chemicals require appropriate labelling of health, physical and environmental hazards according to the United Nations global harmonisation system (GHS). Labelling for (human) acute toxicity categories is based on experimental findings usually obtained by oral, dermal or inhalative exposure of rodents. There is a strong societal demand for replacing animal experiments conducted for safety assessment of chemicals. Fish embryos are considered as alternative to animal testing and are proposed as predictive model both for environmental and human health effects. Therefore, we tested whether LC50s of the fish embryo acute toxicity test would allow effectively predicting of acute mammalian toxicity categories. A database of published fish embryo LC50 containing 641 compounds was established. For these compounds corresponding rat oral LD50 were identified resulting in 364 compounds for which both fish embryo LC50 and rat LD50 was available. Only a weak correlation of fish embryo LC50 and rat oral LD50 was obtained. Fish embryos were also not able to effectively predict GHS oral acute toxicity categories. We concluded that due to fundamental exposure protocol differences (single oral dose versus water-borne exposure) a reverse dosimetry approach is needed to explore the predictive capacity of fish embryos. Copyright © 2014 Elsevier Inc. All rights reserved.

Cultivation, LD(50) determination and experimental model of Streptococcus suis serotype 2 strain HA9801.

PubMed

Zhao, Zhanzhong; Wang, Jian; Liu, Peihong; Zhang, Suhua; Gong, Jianpei; Huang, Xiqin; Li, Bin; Xue, Feiqun

2009-04-01

The effects of nutritional components and submerged culture conditions on colony-forming unit (CFU) counts by Streptococcus suis serotype 2 strain HA9801 in flask culture was investigated, and the optimal medium and cultivation conditions was confirmed by using a 50l bioreactor. The LD(50) values of HA9801 in pigs before and after fermentation were 1.8 x 10(7)CFU, which indicated that the virulence of HA9801 was very stable in the fermentation process. In addition, an experimental model that closely mimics naturally occurring disease in conventional pigs was established.

Determination of the LD50 of acridine orange via intravenous administration in mice in preparation for clinical application to cancer therapy.

PubMed

Nakamura, Tomoki; Kusuzaki, Katsuyuki; Matsubara, Takao; Matsumine, Akihiko; Asanuma, Kunihiro; Satonaka, Haruhiko; Uchida, Atsumasa; Sudo, Akihiro

2014-01-01

We undertook studies to determine the lethal dose 50 (LD50) of acridine orange (AO) using mice in order to confirm the safety of intravenous administration of AO. We used 40 mice and AO was administered once intravenously. General behavior and mortality were continuously observed for 14 days. At the end of the experiment, all animals were sacrificed for subsequent studies. The LD50 for AO in male and female mice was determined to be 32 mg/kg and 36 mg/kg, respectively. Histopathological abnormalities were observed in only one mouse which died three days after the administration of AO. The other nine mice which died immediately after the administration of AO had no pathological findings in major organs. The clinical use of AO can be kept at 1.0 mg/kg or below and, therefore, intravenous administration of AO might be safe for use as cancer therapy. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Disruption of the Putative Vascular Leak Peptide Sequence in the Stabilized Ricin Vaccine Candidate RTA1-33/44-198

DTIC Science & Technology

2013-01-29

Time- dependence of calculated LD50. The data shown in Panel A were submitted to probit analysis to determine the LD50 of ricin at every 0.5-day...degenerate neutrophils and necrotic debris evident; (C) Only a limited region of the epithelium lining a bronchus remains viable (arrowheads); the...quantitative analysis of the dose dependent protective effects of the immunizations. All vaccine doses (2.5, 10 or 40 μg immunogen) resulted in significant

VX Toxicity in the Gottingen Minipig

DTIC Science & Technology

2016-02-01

mouse, and guinea pig ) to determine estimates for differences in lethality based on route of administration. The slope of the dose-response curve was...alter agent toxicity in other species, such as rats (Benke and Murphy, 1975; Karanth and Pope, 2000; Shih et al., 1990) and guinea pigs (Myers and...LD50 is between 8 µg/kg and 16.25 µg/kg (Maxwell, 1992; Shih and McDonough, 1999). In the guinea pig (Dunkin-Hartley) the IM LD50 of VX has been

Subacute Low Dose Nerve Agent Exposure Causes DNA Fragmentation in Guinea Pig Leukocytes

DTIC Science & Technology

2005-10-01

1 SUBACUTE LOW DOSE NERVE AGENT EXPOSURE CAUSES DNA FRAGMENTATION IN GUINEA PIG LEUKOCYTES. Jitendra R. Dave1, John R. Moffett1, Sally M...DNA fragmentation in blood leukocytes from guinea pigs by ‘Comet’ assay after exposure to soman at doses ranging from 0.1LD50 to 0.4 LD50, once per...computer. Data obtained for exposure to soman demonstrated significant increases in DNA fragmentation in circulating leukocytes in CWNA treated guinea pigs as

Acute Oral Toxicity of Tetrodotoxin in Mice: Determination of Lethal Dose 50 (LD50) and No Observed Adverse Effect Level (NOAEL)

PubMed Central

Abal, Paula; Louzao, M. Carmen; Antelo, Alvaro; Alvarez, Mercedes; Cagide, Eva; Vilariño, Natalia; Vieytes, Mercedes R.; Botana, Luis M.

2017-01-01

Tetrodotoxin (TTX) is starting to appear in molluscs from the European waters and is a hazard to seafood consumers. This toxin blocks sodium channels resulting in neuromuscular paralysis and even death. As a part of the risk assessment process leading to a safe seafood level for TTX, oral toxicity data are required. In this study, a 4-level Up and Down Procedure was designed in order to determine for the first time the oral lethal dose 50 (LD50) and the No Observed Adverse Effect Level (NOAEL) in mice by using an accurate well-characterized TTX standard. PMID:28245573

Measuring lexical diversity in narrative discourse of people with aphasia.

PubMed

Fergadiotis, Gerasimos; Wright, Heather H; West, Thomas M

2013-05-01

A microlinguistic content analysis for assessing lexical semantics in people with aphasia (PWA) is lexical diversity (LD). Sophisticated techniques have been developed to measure LD. However, validity evidence for these methodologies when applied to the discourse of PWA is lacking. The purpose of this study was to evaluate four measures of LD to determine how effective they were at measuring LD in PWA. Four measures of LD were applied to short discourse samples produced by 101 PWA: (a) the Measure of Textual Lexical Diversity (MTLD; McCarthy, 2005), (b) the Moving-Average Type-Token Ratio (MATTR; Covington, 2007), (c) D (McKee, Malvern, & Richards, 2000), and (d) the Hypergeometric Distribution (HD-D; McCarthy & Jarvis, 2007). LD was estimated using each method, and the scores were subjected to a series of analyses (e.g., curve-fitting, analysis of variance, confirmatory factor analysis). Results from the confirmatory factor analysis suggested that MTLD and MATTR reflect LD and little of anything else. Further, two indices (HD-D and D) were found to be equivalent, suggesting that either one can be used when samples are >50 tokens. MTLD and MATTR yielded the strongest evidence for producing unbiased LD scores, suggesting that they may be the best measures for capturing LD in PWA.

Linkage disequilibrium between STRPs and SNPs across the human genome.

PubMed

Payseur, Bret A; Place, Michael; Weber, James L

2008-05-01

Patterns of linkage disequilibrium (LD) reveal the action of evolutionary processes and provide crucial information for association mapping of disease genes. Although recent studies have described the landscape of LD among single nucleotide polymorphisms (SNPs) from across the human genome, associations involving other classes of molecular variation remain poorly understood. In addition to recombination and population history, mutation rate and process are expected to shape LD. To test this idea, we measured associations between short-tandem-repeat polymorphisms (STRPs), which can mutate rapidly and recurrently, and SNPs in 721 regions across the human genome. We directly compared STRP-SNP LD with SNP-SNP LD from the same genomic regions in the human HapMap populations. The intensity of STRP-SNP LD, measured by the average of D', was reduced, consistent with the action of recurrent mutation. Nevertheless, a higher fraction of STRP-SNP pairs than SNP-SNP pairs showed significant LD, on both short (up to 50 kb) and long (cM) scales. These results reveal the substantial effects of mutational processes on LD at STRPs and provide important measures of the potential of STRPs for association mapping of disease genes.

Determination of drug toxicity using 3D spheroids constructed from an immortal human hepatocyte cell line.

PubMed

Fey, Stephen J; Wrzesinski, Krzysztof

2012-06-01

Numerous publications have documented that the immortal cells grown in three-dimensional (3D) cultures possess physiological behavior, which is more reminiscent of their parental organ than when the same cells are cultivated using classical two-dimensional (2D) culture techniques. The goal of this study was to investigate whether this observation could be extended to the determination of LD(50) values and whether 3D data could be correlated to in vivo observations. We developed a noninvasive means to estimate the amount of protein present in a 3D spheroid from it is planar area (± 21%) so that a precise dose can be provided in a manner similar to in vivo studies. This avoided correction of the actual dose given based on a protein determination after treatment (when some cells may have lysed). Conversion of published in vitro LC(50) data (mM) for six common drugs (acetaminophen, amiodarone, diclofenac, metformin, phenformin, and valproic acid) to LD(50) data (mg compound/mg cellular protein) showed that the variation in LD(50) values was generally less than that suggested by the original LC(50) data. Toxicological analysis of these six compounds in 3D spheroid culture (either published or presented here) demonstrated similar LD(50) values. Although in vitro 2D HepG2 data showed a poor correlation, the primary hepatocyte and 3D spheroid data resulted in a much higher degree of correlation with in vivo lethal blood plasma levels. These results corroborate that 3D hepatocyte cultures are significantly different from 2D cultures and are more representative of the liver in vivo.

Determination of Drug Toxicity Using 3D Spheroids Constructed From an Immortal Human Hepatocyte Cell Line

PubMed Central

Fey, Stephen J.; Wrzesinski, Krzysztof

2012-01-01

Numerous publications have documented that the immortal cells grown in three-dimensional (3D) cultures possess physiological behavior, which is more reminiscent of their parental organ than when the same cells are cultivated using classical two-dimensional (2D) culture techniques. The goal of this study was to investigate whether this observation could be extended to the determination of LD50 values and whether 3D data could be correlated to in vivo observations. We developed a noninvasive means to estimate the amount of protein present in a 3D spheroid from it is planar area (± 21%) so that a precise dose can be provided in a manner similar to in vivo studies. This avoided correction of the actual dose given based on a protein determination after treatment (when some cells may have lysed). Conversion of published in vitro LC50 data (mM) for six common drugs (acetaminophen, amiodarone, diclofenac, metformin, phenformin, and valproic acid) to LD50 data (mg compound/mg cellular protein) showed that the variation in LD50 values was generally less than that suggested by the original LC50 data. Toxicological analysis of these six compounds in 3D spheroid culture (either published or presented here) demonstrated similar LD50 values. Although in vitro 2D HepG2 data showed a poor correlation, the primary hepatocyte and 3D spheroid data resulted in a much higher degree of correlation with in vivo lethal blood plasma levels. These results corroborate that 3D hepatocyte cultures are significantly different from 2D cultures and are more representative of the liver in vivo. PMID:22454432

[Oral toxicity at 60-days of sacha inchi oil (Plukenetia volubilis L.) and linseed (Linum usitatissimum L.), and determination of lethal dose 50 in rodents].

PubMed

Gorriti, Arilmi; Arroyo, Jorge; Quispe, Fredy; Cisneros, Braulio; Condorhuamán, Martín; Almora, Yuan; Chumpitaz, Víctor

2010-09-01

To evaluate the oral toxicity at 60 days and to determine the lethal dose 50 (LD 50) of raw sacha inchi (Plukenetia volubilis L.) and linseed (Linum ussitatisimum) oils in Holtzman rats and mice of the strain Balb C57 respectively. For the evaluation of the oral toxicity of repeated doses for 60 days, 24 male Holtzman rats were used, divided in three groups of 8 each, the groups were: physiologic saline solution 4 mL/kg (FSS), sacha inchi oil 0.5 mL/kg (SI05) and linseed oil 0.5 mL/kg (L05), during the experiment the body weight was controlled weekly, and signs of toxicity in the research groups, as well as total cholesterol, HDL, glucose, triglycerides and alkaline phosphatase at days 30 and 60 after initiating the experiment. For the evaluation of the LD50 male mice of the Balb C57 strain were used in groups of 10 animals, and they were administered increasing oral doses of raw oils until reaching 1 mL/kg (37 g/kg). The serum parameters in the rats indicated there is no toxicity at 60 days and that the administration of the oils lowered the levels of cholesterol, triglycerides and increased the HDL in comparison with the control group. The LD50 shows that the raw sacha inchi and linseed oils have doses above 37 g/kg of body weight. Sacha inchi and linseed oils are harmless at 60 days and present a LD50 above the 37 g/kg of animal.

Acute and Cumulative Effects of Unmodified 50-nm Nano-ZnO on Mice.

PubMed

Kong, Tao; Zhang, Shu-Hui; Zhang, Ji-Liang; Hao, Xue-Qin; Yang, Fan; Zhang, Cai; Yang, Zi-Jun; Zhang, Meng-Yu; Wang, Jie

2018-01-02

Nanometer zinc oxide (nano-ZnO) is widely used in diverse industrial and agricultural fields. Due to the extensive contact humans have with these particles, it is crucial to understand the potential effects that nano-ZnO have on human health. Currently, information related to the toxicity and mechanisms of nano-ZnO is limited. The aim of the present study was to investigate acute and cumulative toxic effects of 50-nm unmodified ZnO in mice. This investigation will seek to establish median lethal dose (LD50), a cumulative coefficient, and target organs. The acute and cumulative toxicity was investigated by Karber's method and via a dose-increasing method, respectively. During the experiment, clinical signs, mortality, body weights, hematology, serum biochemistry, gross pathology, organ weight, and histopathology were examined. The LD50 was 5177-mg/kg·bw; the 95% confidence limits for the LD50 were 5116-5238-mg/kg·bw. It could be concluded that the liver, kidney, lung, and gastrointestinal tract were target organs for the 50-nm nano-ZnO acute oral treatment. The cumulative coefficient (K) was 1.9 which indicated that the cumulative toxicity was apparent. The results also indicated that the liver, kidney, lung, and pancrea were target organs for 50-nm nano-ZnO cumulative oral exposure and might be target organs for subchronic and chronic toxicity of oral administered 50-nm ZnO.

Endurance exercise modulates levodopa induced growth hormone release in patients with Parkinson's disease.

PubMed

Müller, Thomas; Welnic, Jacub; Woitalla, Dirk; Muhlack, Siegfried

2007-07-11

Acute levodopa (LD) application and exercise release human growth hormone (GH). An earlier trial showed, that combined stimulus of exercise and LD administration is the best provocative test for GH response in healthy participants. Objective was to show this combined effect of LD application and exercise on GH response and to investigate the impact on LD metabolism in 20 previously treated patients with Parkinson's disease (PD). We measured GH- and LD plasma concentrations following soluble 200 mg LD/50 mg benserazide administration during endurance exercise and rest on two separate consecutive days. GH concentrations significantly increased on both days, but GH release was significantly delayed during rest. LD metabolism was not altered due to exercise in a clinical relevant manner. Exercise induced a significant faster LD stimulated GH release in comparison with the rest condition. We did not find the supposed increase of LD induced GH release by endurance exercise. We assume, that only a limited amount of GH is available for GH release in the anterior pituitary following an acute 200 mg LD administration. GH disposal also depends on growth hormone releasing hormone (GHRH), which is secreted into hypothalamic portal capillaries. During the exercise condition, the resulting higher blood pressure supports blood flow and thus GHRH transport towards the GH producing cells in the pituitary. This might additionally have caused the significant faster GH release during exercise.

Australian tiger snake (Notechis scutatus) and mexican coral snake (Micruris species) antivenoms prevent death from United States coral snake (Micrurus fulvius fulvius) venom in a mouse model.

PubMed

Wisniewski, Michael S; Hill, Robert E; Havey, Joshua M; Bogdan, Gregory M; Dart, Richard C

2003-01-01

Wyeth-Ayerst has discontinued production of Antivenin (Micrurus fulvius). Currently, there is no other approved coral snake antivenom available in the United States. This study was a randomized, placebo-controlled and blinded determination of the ability of a Mexican Micrurus (coral snake) antivenom and an Australian Notechis (tiger snake) antivenom to prevent lethality from a United States Micrurus fulvius fulvius venom in a mouse model. Venom dosing was based on an LD50 determined for this experiment. Our comparison groups included: (1) M. f. fulvius venom + Micrurus antivenom, (2) M. f. fulvius venom + Notechis antivenom, (3) M. f. fulvius venom + protein control, (4) 0.9% normal saline + protein control, (5) saline + Notechis antivenom, (6) saline + Micrurus antivenom. Venom dose was 5 times the determined LD50. The antivenom amounts were capable of neutralizing 10 times the venom injected (50 times the LD50). The LD50 of M. f. fulvius venom was determined to be 0.85 mg/kg. All mice in both antivenom test groups were protected from lethality for the entire 24-hour observation period. Six of the 7 mice in the venom test group died, with a survival time of 349 +/- 382 minutes (mean +/- s.d.) after the venom injection. All three groups of control mice survived the entire 24-hour observation period. Mexican Micrurus antivenom and Australian Notechis antivenom provide protection from lethality in mice envenomated with a United States M. f. filvius venom.

Design, synthesis and activity of BBI608 derivatives targeting on stem cells.

PubMed

Zhou, Qifan; Peng, Chen; Du, Fangyu; Zhou, Linbo; Shi, Yajie; Du, Yang; Liu, Dongdong; Sun, Wenjiao; Zhang, Meixia; Chen, Guoliang

2018-05-10

STAT3 plays a vital role in maintaining the self-renewal of tumor stem cells. BBI608, a small molecule identified by its ability to inhibit gene transcription driven by STAT3 and cancer stemness properties, can inhibit stemness gene expression and kill stemness-high cancer cells isolated from a variety of cancer types. In order to improve the pharmacokinetic properties of BBI608 and the antitumor activity, a series of BBI608 derivatives were designed and synthesized here. Most of these compounds were more potent than BBI608 on HepG2 cells, compound LD-8 had the most potent inhibitory activity among them and was 5.4-fold more potent than BBI608 (IC 50  = 11.2 μM), but had considerable activity on normal liver cells L-02. Compounds LD-17 (IC 50  = 3.5 μM) and LD-19 (IC 50  = 2.9 μM) were found to possess significant inhibitory activities and good selectivity. The results showed that compound LD-19 was worthy to investigate further as a lead compound according to its potent inhibitory activity, ideal ClogP value and better water solubility. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Multivariate correlations between properties of metal ions and their acute toxicity in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Turner, J.E.; Williams, M.W.; Hingerty, B.E.

1986-01-01

This paper extends our earlier study of correlations of acute metal-ion toxicity (14-day LD50) in mice and physicochemical properties of the ions. Here we put metal ions into two main groups as defined by Kaiser. Using most of the metals in the periodic system, we find the least redundant linear combinations W/sub i/ of the ionic radius, sum of ionization potentials, atomic weight, Williams softness parameter, and electronegativity for each of Kaiser's two groups. Information is provided so that the W/sub i/ can be evaluated for any metal from these five quantities. For the two groups of metals we thenmore » tested for multivariate correlations between the S/sub i/ having the highest sample variance and our mouse LD50. For our LD50 involving the five metal ions in Kaiser's group (1) the correlation is poor, whereas a good correlation is found for the 14 ions in group (2). 10 refs., 3 tabs.« less

Protection of mice against mixed fission neutron-gamma (n: gamma = 1:1) irradiation by WR-2721, 16,16-dimethyl PGE2, and the combination of both agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steel, L.K.; Walden, T.L. Jr.; Hughes, H.N.

1988-09-01

The survival of mice after whole-body exposure to a modified fission neutron-gamma field (n: gamma = 1:1) was used to examine radiation protection by WR-2721, 16,16-dimethyl PGE2(DiPGE2), and the combination of both agents. Administration of WR-2721 (453 mg/kg) increased the LD50/30 from 5.24 to 7.17 Gy (DMF = 1.37), whereas pretreatment with DiPGE2 (1.6 mg/kg) increased the LD50/30 to 5.77 Gy (dose modification factor (DMF) = 1.10). The combination of 453 mg/kg WR-2721 and 0.4 mg/kg DiPGE2 resulted in an LD50/30 of 7.33 Gy, yielding a DMF of 1.39. However, no significant difference in protection was obtained with the combinationmore » of the two agents compared to that seen with WR-2721 alone.« less

Oral toxicity of p-aminopropiophenone to brushtail possums (Trichosurus vulpecula), dama wallabies (Macropus eugenii), and mallards (Anas platyrhynchos).

PubMed

Fisher, P; O'Connor, C E; Morriss, G

2008-07-01

Development of p-aminopropiophenone (PAPP) as a toxicant for pest predator management in New Zealand and Australia prompted investigation of its toxicity to potential nontarget species. Acute oral toxicity of PAPP in brushtail possums (Trichosurus vulpecula), dama wallabies (Macropus eugenii), and Mallards (Anas platyrhynchos) was estimated in pen trials, carried out between February 2000 and September 2001. The susceptibility of possums (LD50>or=500 mg kg(-1)) and wallabies (LD50 89 mg kg(-1)) to PAPP was low in comparison to noncarnivorous placental mammal species, but ducks (LD50 38 mg kg(-1)) were more susceptible than other bird species. These results suggest that the nontarget hazard to possums and wallabies from PAPP bait applied for pest predator control would be low. However, future development of PAPP as a vertebrate pest control agent should include rigorous assessments of the hazard posed by bait formulations to bird species and provision for delivery techniques that could mitigate exposure of nontarget birds.

Measuring the potency labelling of onabotulinumtoxinA (Botox(®)) and incobotulinumtoxinA (Xeomin (®)) in an LD50 assay.

PubMed

Dressler, Dirk; Mander, Gerd; Fink, Klaus

2012-01-01

The biological potency of botulinum toxin (BT) drugs is determined by a standardised LD50 assay. However, the potency labelling varies vary amongst different BT drugs. One reason for this may be differences in the LD50 assays applied. When five unexpired batches of onabotulinumtoxinA (Botox(®)) and incobotulinumtoxinA (Xeomin(®)) are compared in the Xeomin(®) batch release assay, the potency variability of both BT drugs fell within the range allowed by the European Pharmacopoiea. Statistical analyses failed to detect differences in the potency labelling of both products. Although the existence of a conversion ratio has been questioned recently, our experimental data are in line with previous clinical experience showing that Botox(®) and Xeomin(®) can be compared using a 1:1 conversion ratio. Identical potency labelling allows easy exchange of both BT drugs in a therapeutic setting, and direct comparison of efficacy, adverse effects and costs.

Effects of systemic carbidopa on dopamine synthesis in rat hypothalamus and striatum

NASA Technical Reports Server (NTRS)

Kaakkola, S.; Tuomainen, P.; Wurtman, R. J.; Maennistoe, P. T.

1991-01-01

Significant concentrations of carbidopa (CD) were found in rat hypothalamus, striatum, and in striatal microdialysis efflux after intraperitoneal administration of the drug. Efflux levels peaked one hour after administration of 100 mg/kg at 0.37 microg/kg or about 2 percent of serum levels. Concurrent CD levels in hypothalamus and striatum were about 2.5 percent and 1.5 percent, respectively, of corresponding serum levels. Levels of dopamine and its principal metabolites in striatal efflux were unaffected. The removal of the brain blood by saline perfusion decreased the striatal and hypothalamic CD concentrations only by 33 percent and 16 percent, respectively. In other rats receiving both CD and levodopa (LD), brain L-dopa, dopamine, and 3,4-dihydroxyphenvlacetic acid (DOPAC) levels after one hour tended to be proportionate to LD dose. When the LD dose remained constant, increasing the CD dose dose-dependently enhanced L-dopa levels in the hypothalamus and striatum. However, dopamine levels did not increase but, in contrast, decreased dose-dependently (although significantly only in the hypothalamus). CD also caused dose-dependent decrease in striatal 3-O-methyldopa (3-OMD) and in striatal and hypothalamic homovanillic acid (HVA), when the LD dose was 50 mg/kg. We conclude that, at doses exceedimg 50 mg/kg, sufficient quantities of CD enter the brain to inhibit dopamine formation, especially in the hypothalamus. Moreover, high doses of LD/CD, both of which are themselves catechols, can inhibit the O-methylation of brain catecholamines formed from the LD.

Effects of systemic carbidopa on dopamine synthesis in rat hypothalamus and striatum

NASA Technical Reports Server (NTRS)

Kaakkola, S.; Tuomainen, P.; Wurtman, R. J.; Mannisto, P. T.

1992-01-01

Significant concentrations of carbidopa (CD) were found in rat hypothalamus, striatum, and in striatal microdialysis efflux after intraperitoneal administration of the drug. Efflux levels peaked one hour after administration of 100 mg/kg at 0.37 micrograms/ml, or about 2% of serum levels. Concurrent CD levels in hypothalamus and striatum were about 2.5% and 1.5%, respectively, of corresponding serum levels. Levels of dopamine and its principal metabolites in striatal efflux were unaffected. The removal of the brain blood by saline perfusion decreased the striatal and hypothalamic CD concentrations only by 33% and 16%, respectively. In other rats receiving both CD and levodopa (LD), brain L-dopa, dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels after one hour tended to be proportionate to LD dose. When the LD dose remained constant, increasing the CD dose dose-dependently enhanced L-dopa levels in the hypothalamus and striatum. However dopamine levels did not increase but, in contrast, decreased dose-dependently (although significantly only in the hypothalamus). CD also caused dose-dependent decrease in striatal 3-O-methyldopa (3-OMD) and in striatal and hypothalamic homovanillic acid (HVA), when the LD dose was 50 mg/kg. We conclude that, at doses exceeding 50 mg/kg, sufficient quantities of CD enter the brain to inhibit dopamine formation, especially in the hypothalamus. Moreover, high doses of LD/CD, both of which are themselves catechols, can inhibit the O-methylation of brain catecholamines formed from the LD.

Comparative toxicity effect of bush tea leaves (Hyptis suaveolens) and orange peel (Citrus sinensis) oil extract on larvae of the yellow fever mosquito Aedes aegypti.

PubMed

Amusan, A A S; Idowu, A B; Arowolo, F S

2005-09-01

The ethanolic extracts of the orange peel (Citrus sinensis) and bush tea leaves (Hyptis suaveolens) were compared for their toxicity effect on the larvae of the yellow fever mosquito Aedes aegypti collected from disused tyres beside College of Natural Sciences building University of Agriculture, Abeokuta, Nigeria. Eight graded concentrations, 0.9ppm, 0.8ppm, 0.7ppm, 0.6ppm, 0.5ppm, 0.4ppm, 0.3ppm and 0.2ppm of both plant extracts were tested on the larvae. The mean lethal dose LD10, was 0.15 ppm for C. sinensis, 0.01 for H. suaveolens, while LD50 for C. sinensis was 0.4ppm, H. suaveolens 0.60ppm and LD90 for C. sinensis was 0.9ppm and H. suaveolens was 1.45ppm. LD10 for the control 0.65ppm, LD50 0.9ppm and LD90 2.0 ppm. The extract of C. sinensis peel caused higher mortality rate at concentrations 0.8ppm (95%) and 0.3ppm (90%) of the larvae while the extract of H. suaveolens caused high mortality rate on the larvae at concentrations of 0.9ppm (80%) and 0.3ppm (80%). Significant differences were observed between untreated and treated larvae (exposed to either of the extract) at the various concentrations (P< 0.05).

Vitamin D supplementation in nursing home patients: randomized controlled trial of standard daily dose versus individualized loading dose regimen.

PubMed

Wijnen, Hugo; Salemink, Dayenne; Roovers, Lian; Taekema, Diana; de Boer, Hans

2015-05-01

Supplementation of cholecalciferol 800 IU daily appears to be insufficient to raise vitamin D levels to >75 nmol/l in nursing home (NH) patients. Our objective was to compare the efficacy of an individualized cholecalciferol loading dose (LD) regimen and a daily dose (DD) regimen of cholecalciferol 800 IU in reaching 25-OH vitamin D (25OHD) levels >75 nmol/l. A total of 30 NH patients with 25OHD levels <50 nmol/l were included. Patients were randomized using the minimization method in the LD or DD group. The cholecalciferol LD, calculated with an algorithm based on serum 25OHD level and body weight, was administered in divided doses of 50,000 IU twice a week, followed by a monthly maintenance dose of either 50,000 or 25,000 IU. The DD regimen consisted of cholecalciferol 800 IU daily for 26 weeks. Serum 25OHD, calcium, creatinine, phosphate, and parathyroid hormone were measured, and 2-minute walking test, handgrip strength, and timed get up and go test were assessed at baseline (T 0), after 5 weeks (T 5), 12 weeks (T 12), and 26 weeks (T 26). The primary endpoint was the percentage of patients with 25OHD levels >75 nmol/l at T 5. Secondary endpoints were the proportion of patients with 25OHD levels >75 nmol/l at T 26, safety of LD regimen, and improvement of performance tests with normalization of vitamin D levels. Median baseline 25OHD levels (interquartile range) were comparable between the 14 DD and 16 LD patients: 20.9 (15.9-29.6) and 21.7 (16.4-32.8) nmol/l, respectively. Levels of 25OHD >75 nmol/l at T 5 were reached in 79 % of the 14 LD patients, but in none of the 13 DD patients (p < 0.001). At T 26, 25OHD levels >75 nmol/l were reached in 83 % of the 12 LD patients and in 30 % of the ten DD patients (p < 0.05). Side effects or hypercalcemia were not observed. No improvement of performance tests was observed. In NH patients with severe 25OHD deficiency, an individualized calculated cholecalciferol LD is likely to be superior to a DD of cholecalciferol 800 IU in terms of the ability to rapidly normalize vitamin D levels.

Protection of mice against fission-neutron irradiation by WR-2721 or WR-151327

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steel, L.K.; Jacobs, A.J.; Giambarresi, L.I.

1987-01-01

Two phosphorothioate compounds, WR-2721 and WR-151327, were examined for their radioprotective efficacies against the effects of fission-neutron irradiation in male and female mice. Within sex groups no significant difference in lethality at 30 or 100 days postirradiation was found between WR-2721 or WR-151327 pretreatment. The dose-modification factors (DMFs) for male mice treated with either compound were 1.29 (LD50/30) and 1.24 (LD50/100), and those for drug-treated female mice were 1.21 (LD50/30) and 1.19 (LD50/100). Both WR-2721 and WR-151327 were found to be equally radioprotective when compared using DMFs as the end point. WR-151327 were found to be equally radioprotective when comparedmore » using DMFs as the end point. WR-151327 (500 mg/kg, ip) was found to be significantly more toxic to both male and female B6D2F1 mice than equimolar amounts of WR-2721. Small but significant sex differences in radioprotection were found: the DMFs for female mice pretreated with either compound were lower than those for similarly treated male mice; the incidence of mortality 31-100 days postexposure in male mice pretreated with WR-151327 was greater than for female mice. In addition, sex differences were noted in drug toxicity. Toxic death in female mice given WR-151327 (500 mg/kg, ip) is 2.6 times more probable than in males.« less

Acute and subacute oral toxicity of polychlorinated diphenyl sulfides in mice: determining LD50 and assessing the status of hepatic oxidative stress.

PubMed

Zhang, Xuesheng; Liu, Fu; Chen, Binyuan; Li, Ying; Wang, Zunyao

2012-07-01

Polychlorinated diphenyl sulfides (PCDPSs), a series of dioxin-like compounds, have been detected in various environmental samples. However, information on the toxicity of these compounds is limited. In the present study, the toxic effects of PCDPSs were assessed after acute and subacute exposure in mice. Relationships between acute toxicity, number, and position of substituted Cl atoms were assessed. In the acute study, 11 types of PCDPSs were administered to female Kunming mice by gavage, and median lethal doses (LD50s) were determined by the Karber method. Results indicated that the LD50s of lower substituted PCDPSs were smaller than higher substituted PCDPSs. Substituted positions also influenced the LD50 of PCDPSs. Terminal necropsy showed increased relative liver weights and decreased relative kidney weights. Histological examination of livers demonstrated swollen cells, inflammation, vacuolization, and necrosis. In the 28-d subacute exposure tests, 11 types of PCDPSs were dissolved in corn oil and administered to mice at doses of 1, 10, and 100 mg/kg. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in mouse liver were determined after the exposure period. Results suggested that lower substituted PCDPSs decreased SOD activity in the high-dose groups compared with controls, and MDA level in the 100-mg/kg dose group was significantly increased. In addition, acute toxicity of PCDPSs partly corresponded to the hepatic oxidative damage observed. Copyright © 2012 SETAC.

Myrtaceae Plant Essential Oils and their β-Triketone Components as Insecticides against Drosophila suzukii.

PubMed

Park, Chung Gyoo; Jang, Miyeon; Shin, Eunsik; Kim, Junheon

2017-06-24

Spotted wing drosophila (SWD, Drosophila suzukii (Matsumura), Diptera: Drosophilidae) is recognized as an economically important pest in North America and Europe as well as in Asia. Assessments were made for fumigant and contact toxicities of six Myrtaceae plant essential oils (EOs) and their components to find new alternative types of insecticides active against SWD. Among the EOs tested, Leptospermum citratum EO, consisting mainly of geranial and neral, exhibited effective fumigant activity. Median lethal dose (LD 50 ; mg/L) values of L. citratum were 2.39 and 3.24 for males and females, respectively. All tested EOs except Kunzea ambigua EO exhibited effective contact toxicity. LD 50 (µg/fly) values for contact toxicity of manuka and kanuka were 0.60 and 0.71, respectively, for males and 1.10 and 1.23, respectively, for females. The LD 50 values of the other 3 EOs-L. citratum, allspice and clove bud were 2.11-3.31 and 3.53-5.22 for males and females, respectively. The non-polar fraction of manuka and kanuka did not show significant contact toxicity, whereas the polar and triketone fractions, composed of flavesone, isoleptospermone and leptospermone, exhibited efficient activity with the LD 50 values of 0.13-0.37 and 0.22-0.57 µg/fly for males and females, respectively. Our results indicate that Myrtaceae plant EOs and their triketone components can be used as alternatives to conventional insecticides.

Acute and subacute oral toxicity of periodate salts in rats.

PubMed

Lent, Emily May; Crouse, Lee C B; Eck, William S

2017-02-01

Periodate salts are being developed as potential replacements for perchlorate due to potential health hazards associated with exposure to perchlorate. The aim of this study was to investigate acute and subacute effects of periodate salts in rats. Acute oral toxicity of potassium and sodium periodate was determined using the Sequential Stage-Wise Probit method. The LD 50 for potassium periodate was 732 (95% CI = 539-838, slope = 13.4) and 685 mg/kg (95% CI = 580-809, slope = 10.6) for females and males, respectively. The LD 50 for sodium periodate was 318 (95% CI = 292-347, slope = 24.3) and 741 mg/kg (95% CI = 704-779, slope = 31.2) for females and males, respectively. In the subacute study, rats were administered sodium periodate at five doses (1/16 LD 50 up to LD 50 ) or distilled water for 14-days via oral gavage. Female rats in the 318 mg/kg-day group and male rats in the 185, 370, and 741 mg/kg-day groups exhibited moribundity, kidney toxicity, uremia, and a stress response. BMDL 10 s of 17.2 and 33.7 mg/kg-day were derived for females and males, respectively. Comparison with the NOAEL for perchlorate-induced thyroid toxicity in rats (0.009 mg/kg-day) suggests sodium periodate is less toxic than perchlorate on a subacute basis. Copyright © 2016. Published by Elsevier Inc.

Inter-Judge Agreement in Classifying Students as Learning Disabled.

ERIC Educational Resources Information Center

Epps, Susan; And Others

Eighteen judges with backgrounds in assessment, decision making, and learning disabilities were asked to use an array of information to differentiate learning disabled (LD) and non-learning disabled students. Each judge was provided with forms containing information on 42 test or subtest scores of 50 school-identified LD students and 49 non-LD…

Memory Modality Differences in Children with Attention Deficit Hyperactive Disorder with and without Learning Disabilities.

ERIC Educational Resources Information Center

Webster, Raymond E.; And Others

1996-01-01

Assesses information processing and memory functioning in 50 children diagnosed with Attention Deficit Hyperactive Disorder (ADHD) with and without learning disabilities (LD). Both groups struggled with auditory ordered recall. The ADHD/LD group demonstrated more problems transferring information into short-term and long-term memory stores than…

[Effects of pretreatment of lipid, midazolam and propofol on ropivacaine-induced convulsion and LD50 in rats].

PubMed

Lü, Xiao-lan; Wan, Fu-hong; Zuo, Yun-xia

2012-09-04

To assess the effects of lipid on ropivacaine-induced convulsion and LD50 in rats and compare with those of the traditional anticonvulsants midazolam and propofol. Protocol 1: A total of 120 SD rats (60 males, 60 females), weighing 200-300 g, were randomly assigned into 4 groups with equal males and females: lipid (L), midazolam (M) and propofol (P) and control (C). Rats were pretreated with 10 ml/kg lipid intravenously in group L, saline and 0.23 mg/kg midazolam (10 ml/kg in volume) sequentially in group M, saline and 4 mg/kg propofol (10 ml/kg in volume) in group P and saline 10 ml/kg in group C. Then ropivacaine 44 mg/kg (0.75%) was injected intraperitoneally into each rat. The convulsion rate in each group and the time of convulsion after ropivacaine injection were observed. Meanwhile, the plasma concentration of ropivacaine at the time of convulsion was measured. Protocol 2: Additional 100 male SD rats were used for the measurements of ropivacaine LD50 with different pretreatments including lipid, midazolam, propofol and saline through the up-and-down method. Rats were randomly assigned into 4 groups similarly as protocol 1. The doses of ropivacaine in each group were determined according to our pilot study and 6 dosage levels with the same interval ratio 8.5 was applied in each group. The doses of these pretreatment drugs and administration methods were similarly as protocol 1. The convulsion rate after 44 mg/kg ropivacaine ip injection was 43.3% in group C, 0% in group M, 13.3% in group P and 70% in group L. Lipid increased the convulsion rate significantly. The plasma concentration of ropivacaine at the time of convulsion was 1.65 ± 0.30 µg/kg in group C, 1.73 ± 0.14 µg/kg in group P and 3.45 ± 0.26 µg/kg in group L. The LD50 of ropivacaine in group C was 64.39 mg/kg, 88.40 mg/kg in group M and 90.20 mg/kg in group P and 55.45 mg/kg in group L. Midazolam and propofol not only decrease the convulsion rate of ropivacaine, but also increase its LD50. Lipid not only increases the convulsion rate of ropivacaine, but also decreases its LD50. The application of lipid for the prevention of local anesthetic toxicity has potential risks.

[Clinical correlation of hypnagogic hypersynchrony during sleep in normal children and those with learning disability].

PubMed

Olmos G de Alba, G; Fraire-Martínez, M I; Valenzuela-Romero, R

One of the electroencephalographic (EEG) patterns that can be mistaken for paroxysmal clinical activity, when not taken into account and especially in children, is hypnagogic hypersynchrony (HH). This consists in generalised, paroxysmal, synchronic, symmetrical, slow, high voltage waves lasting 2 8 seconds, which appear in drowsiness and in stage I. It was observed that this pattern often appeared in children with learning disability (LD). AIMS. To correlate clinical data with the presence of HH during sleep in normal children and those with LD. We assessed 180 children between the ages of 6 12 years with normal neurological development, 130 of which suffered LD and 50 who did not have LD. EEG was performed with sleep deprivation, following the International Federation of Clinical Neurophysiology guidelines. The presence or absence of HH, together with its characteristics, was assessed. Of the children with LD, 35.38% displayed HH and of the children without LD, only 4% displayed HH. Since the characteristics of HH in the children with LD were different to previous descriptions, we put forward criteria with which to evaluate those differences. HH appeared more often in children with LD than in normal children. Qualitative, quantitative (p< 0.05) and morphological changes were found in the paroxysmal activity of HH during the stages of sleep in children with LD.

An acute toxicity study of Heliotropium scottae Rendle in mice.

PubMed

Wahome, W M; Muchiri, D J; Mugera, G M

1994-08-01

Twenty-four hour ip median lethal doses (LD50) of freeze-dried aqueous extracts of Heliotropium scottae Rendle leaves and stems in mice were determined and clinical signs noted. The LD50 of the leaf extract was 3.0 g/kg, while that of the stems was 3.5 g/kg. Clinical signs were excitement, prostration, rapid breathing, gasping for breath and death. The signs were the same for both the leaf and stem extracts. It was concluded that both the leaves and stems of H scottae have slight acute toxicity.

Preliminary Problem Definition Study of 48 Munitions Related Chemicals. Volume I. Explosives Related Chemicals

DTIC Science & Technology

1978-04-01

fungicide additive to prevent chemical "peal burn" in citrus fruits, and in the textile industry for improved shrinkproofing, dye...1967 undiluted oral Rabbits, 3 1.6-1.9 L0100 Treon at al., 1943 "young" *.a. oral mice 2.78 24 hr LD50 Caujolle & Caujolls, 1965 undiluted i.p. Mice 1.35...presented in Table IV-10. In general, che acute toxicity of the methylamines to mammals is fairly low with LD50 ’s averaging several hundred mg/kg

Hazards to animals feeding on blackbirds killed with 4-aminopyridine baits

USGS Publications Warehouse

Schafer, E.W.; Brunton, R.B.; Lockyer, Norman F.

1974-01-01

Red-winged blackbirds (Agelaius phoeniceus) killed by ingesting cracked corn baits treated with 3 percent 4-aminopyridine, or by oral doses of 4-aminopyridine, were fed to canines, laboratory rats (Rattus norvegicus), black-billed magpies (Pica pica), and three species of hawks. The test animals consumed the equivalent of up to 3.4 LD50 doses of 4-aminopyridine in single feedings and up to 3.2 LD50 doses a day for 20 days in repeated feedings. None showed any symptoms of intoxication or gross abnormalities at necropsy.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sumarukov, G.V.

Native crickets (Gryllus domesticus L) were irradiated in groups of 20 with Co/sup 60/ gamma rays ln the presence of air and in a nitrogen atmosphere. Separate groups were injected with free cysteine (0.6 mg/g) or with the hydrochloride cysteine salt (0.2 mg/g) as a protective agent, and were irradiated under the same condltions. The LD/sub 50/ dose (dose causing 50% deaths) was taken as a measure of the radio-resistance. A microplatinum electrode (diameter 0.1 mm, length 2 mm), inserted in the hemolymph of the cricket, was used to measure the oxidation-reduction potential Eh, which would vary as a resultmore » of the induced respiratory hypoxia due to lack of oxygen or as a result of the injection of the protective agent. The LD/sub 50/ dose was found to be 4200 r for irradiation in air without use of a protective agent, 6750 r for irradiation in air with the use of cysteine as a protective agent, 9900 r for irradiation in nitrogen with no protective agent, and 11,900 r for irradiation ln nitrogen with cysteine as a protective agent. The protective effects of cysteine, and of the hypoxia induced by replacing air with nitrogen were found to be additive in this case. The redox potential went from +140 millivolts for the unprotected insects (LD/sub 50/ dose of 4200 r) to --185 millivolts for the insects irradiated in nitrogen with the injection of free cysteine (LD/sub 50/ dose of 11,500 r). It is hymothesized that a high concentration of various reducing agents are produced in the cell by removing oxygen and by injection of cysteine, and these reducing agents react with peroxide formed by radlation. As a consequence, there is less damage to vital cell components. (TTT)« less

Characterization of toxin III of the scorpion Leiurus quinquestriatus quinquestriatus: a new type of alpha-toxin highly toxic both to mammals and insects.

PubMed

Kopeyan, C; Mansuelle, P; Martin-Eauclaire, M F; Rochat, H; Miranda, F

1993-01-01

The primary structure of toxin III of Leiurus quinquestriatus quinquestriatus (Lqq III) was elucidated by automatic Edman degradation of the reduced and S-carboxymethylated protein and derived tryptic peptides. Like other scorpion toxins that are active on sodium channels, Lqq III, consisting of 64 amino acids, is a 7 kDa single-chain polypeptide crosslinked by four disulfide bridges. It belongs to the alpha-toxin group, as judged by competition experiments with 125I AaH II for binding to rat brain synaptosomes (K0.5 = 7 x 10(-7) M). Lqq III is the first alpha-toxin to be characterized that is highly toxic to mice [LD50 = 50 micrograms (7.1 nmol)/kg body wt], by subcutaneous injection, insects Blatella germanica [LD50 = 60 ng (8.5 pmol)/g body wt.] and Musca domestica [LD50 = 120 ng (17 pmol)/g body wt]. When tested via the intracerebroventricular route, the toxicity for mice [55 micrograms (8 nmol)/kg] was of the same order as that found by subcutaneous injection, indicating that Lqq III has a higher affinity for peripheral sodium channels that for those of the central nervous system. There are three differences between the sequences of Lqq III and Lqh alpha IT, an alpha-toxin isolated from the venom of Leiurus quinquestriatus hebraeus. These substitutions are found at positions 20, 24, and 64 (Ser-->Ala,Asp-->Glu and His-->Arg, respectively). Surprisingly Lqh alpha IT is only weakly active in mice [LD50 = 5 mg (0.7 mumol)/kg], while in insects its toxicity is similar to that of Lqq III [140 ng (20 pmol)/g body wt blowfly larvae]. These observations are relevant to the definition of scorpion toxin structure-activity relationships.

Safety of high volume lipid emulsion infusion: a first approximation of LD50 in rats.

PubMed

Hiller, David B; Di Gregorio, Guido; Kelly, Kemba; Ripper, Richard; Edelman, Lucas; Boumendjel, Redouane; Drasner, Kenneth; Weinberg, Guy L

2010-01-01

Lipid infusion reverses systemic local anesthetic toxicity. The acceptable upper limit for lipid administration is unknown and has direct bearing on clinical management. We hypothesize that high volumes of lipid could have undesirable effects and sought to identify the dose required to kill 50% of the animals (LD(50)) of large volume lipid administration. Intravenous lines and electrocardiogram electrodes were placed in anesthetized, male Sprague-Dawley rats. Twenty percent lipid emulsion (20, 40, 60, or 80 mL/kg) or saline (60 or 80 mL/kg), were administered over 30 mins; lipid dosing was assigned by the Dixon "up-and-down" method. Rats were recovered and observed for 48 hrs then euthanized for histologic analysis of major organs. Three additional rats were administered 60 mL/kg lipid emulsion and euthanized at 1, 4, and 24 hrs to identify progression of organ damage. The maximum likelihood estimate for LD(50) was 67.72 (SE, 10.69) mL/kg. Triglycerides were elevated immediately after infusion but returned to baseline by 48 hrs when laboratory abnormalities included elevated amylase, aspartate aminotransferase, and serum urea nitrogen for all lipid doses. Histologic diagnosis of myocardium, brain, pancreas, and kidneys was normal at all doses. Microscopic abnormalities in lung and liver were observed at 60 and 80 mL/kg; histopathology in the lung and liver was worse at 1 hr than at 4 and 24 hrs. The LD(50) of rapid, high volume lipid infusion is an order of magnitude greater than doses typically used for lipid rescue in humans and supports the safety of lipid infusion at currently recommended doses for toxin-induced cardiac arrest. Lung and liver histopathology was observed at the highest infused volumes.

In vitro efficacy of essential oils and extracts of Schinus molle L. against Ctenocephalides felis felis.

PubMed

Batista, Lilian C De S O; Cid, Yara P; De Almeida, Ana Paula; Prudêncio, Edlene R; Riger, Cristiano J; De Souza, Marco A A; Coumendouros, Katherine; Chaves, Douglas S A

2016-04-01

Extracts and essential oils from plants are important natural sources of pesticides. These compounds are considered an alternative to control ectoparasites of veterinary importance. Schinus molle, an endemic species of Brazil, produces a high level of essential oil and several other compounds. The aim of this work was to determinate the chemical composition of extracts and essential oils of S. molle and further to evaluate the activity against eggs and adults of Ctenocephalides felis felis, a predominant flea that infests dogs and cats in Brazil. In an in vitro assay, the non-polar (n-hexane) extract showed 100% efficacy (800 µg cm(-2); LD50 = 524·80 µg cm(-2)) at 24 and 48 h. Its major compound was lupenone (50·25%). Essential oils from fruits and leaves were evaluated, and had 100% efficacy against adult fleas at 800 µg cm(-2) (LD50 = 353·95 µg cm(-2)) and at 50 µg cm(-2) (LD50 = 12·02 µg cm(-2)), respectively. On the other hand, the essential oil from fruits and leaves was not active against flea eggs. This is the first study that reports the insecticidal effects of essential oils and extracts obtained from Schinus molle against Ctenocephalides felis felis.

Variability of Performance: A "Signature" Characteristic of Learning Disabled Children?

ERIC Educational Resources Information Center

Fuchs, Douglas; And Others

Two studies were conducted to compare the performance instability of children (grades 3-9) labeled learning disabled/brain injured (LD/BI) to the performance instability of emotionally handicapped (EH) children. In the first study, 50 LD/BI and 37 EH students were measured on three third grade reading passages twice, once within one sitting and…

Potential of crude seed extract of celery, Apium graveolens L., against the mosquito Aedes aegypti (L.) (Diptera: Culicidae).

PubMed

Choochote, Wej; Tuetun, Benjawan; Kanjanapothi, Duangta; Rattanachanpichai, Eumporn; Chaithong, Udom; Chaiwong, Prasong; Jitpakdi, Atchariya; Tippawangkosol, Pongsri; Riyong, Doungrat; Pitasawat, Benjawan

2004-12-01

Crude seed extract of celery, Apium graveolens, was investigated for anti-mosquito potential, including larvicidal, adulticidal, and repellent activities against Aedes aegypti, the vector of dengue haemorrhagic fever. The ethanol-extracted A. graveolens possessed larvicidal activity against fourth instar larvae of Ae. aegypti with LD50 and LD95 values of 81.0 and 176.8 mg/L, respectively. The abnormal movement observed in treated larvae indicated that the toxic effect of A. graveolens extract was probably on the nervous system. In testing for adulticidal activity, this plant extract exhibited a slightly adulticidal potency with LD50 and LD95 values of 6.6 and 66.4 mg/cm2, respectively. It showed repellency against Ae. aegypti adult females with ED50 and ED95 values of 2.03 and 28.12 mg/cm2, respectively. It also provided biting protection time of 3 h when applied at a concentration of 25 g%. Topical application of the ethanol-extracted A. graveolens did not induce dermal irritation. No adverse effects on the skin or other parts of the body of human volunteers were observed during 3 mo of the study period or in the following 3 mo, after which time observations ceased. A. graveolens, therefore, can be considered as a probable source of some biologically active compounds used in the development of mosquito control agents, particularly repellent products.

Ultra-low dose of Mycobacterium tuberculosis aerosol creates partial infection in mice.

PubMed

Saini, Divey; Hopkins, Gregory W; Seay, Sarah A; Chen, Ching-Ju; Perley, Casey C; Click, Eva M; Frothingham, Richard

2012-03-01

A murine low dose (LD) aerosol model is commonly used to test tuberculosis vaccines. Doses of 50-400 CFU (24h lung CFU) infect 100% of exposed mice. The LD model measures progression from infection to disease based on organ CFU at defined time points. To mimic natural exposure, we exposed mice to an ultra-low dose (ULD) aerosol. We estimated the presented dose by sampling the aerosol. Female C57BL/6 mice were exposed to Mycobacterium tuberculosis H37Rv aerosol at 1.0, 1.1, 1.6, 5.4, and 11 CFU presented dose, infecting 27%, 36%, 36%, 100%, and 95% of mice, respectively. These data are compatible with a stochastic infection event (Poisson distribution, weighted R(2)=0.97) or with a dose-response relationship (sigmoid distribution, weighted R(2)=0.97). Based on the later assumption, the ID50 was 1.6CFU presented dose (95% confidence interval, 1.2-2.1). We compared organ CFU after ULD and LD aerosols (5.4 vs. 395CFU presented dose). Lung burden was 30-fold lower in the ULD model at 4 weeks (3.4 vs. 4.8 logs, p<0.001) and 18 weeks (≤3.6 vs. 5.0 logs, p=0.01). Mice exposed to ULD aerosols as compared to LD aerosols had greater within-group CFU variability. Exposure to ULD aerosols leads to infection in a subset of mice, and to persistently low organ CFU. The ULD aerosol model may resemble human pulmonary tuberculosis more closely than the standard LD model, and may be used to identify host or bacterial factors that modulate the initial infection event. Copyright © 2011 Elsevier Ltd. All rights reserved.

Gene Expression in Parp1 Deficient Mice Exposed to a Median Lethal Dose of Gamma Rays.

PubMed

Kumar, M A Suresh; Laiakis, Evagelia C; Ghandhi, Shanaz A; Morton, Shad R; Fornace, Albert J; Amundson, Sally A

2018-05-10

There is a current interest in the development of biodosimetric methods for rapidly assessing radiation exposure in the wake of a large-scale radiological event. This work was initially focused on determining the exposure dose to an individual using biological indicators. Gene expression signatures show promise for biodosimetric application, but little is known about how these signatures might translate for the assessment of radiological injury in radiosensitive individuals, who comprise a significant proportion of the general population, and who would likely require treatment after exposure to lower doses. Using Parp1 -/- mice as a model radiation-sensitive genotype, we have investigated the effect of this DNA repair deficiency on the gene expression response to radiation. Although Parp1 is known to play general roles in regulating transcription, the pattern of gene expression changes observed in Parp1 -/- mice 24 h postirradiation to a LD 50/30 was remarkably similar to that in wild-type mice after exposure to LD 50/30 . Similar levels of activation of both the p53 and NFκB radiation response pathways were indicated in both strains. In contrast, exposure of wild-type mice to a sublethal dose that was equal to the Parp1 -/- LD 50/30 , which resulted in a lower magnitude gene expression response. Thus, Parp1 -/- mice displayed a heightened gene expression response to radiation, which was more similar to the wild-type response to an equitoxic dose than to an equal absorbed dose. Gene expression classifiers trained on the wild-type data correctly identified all wild-type samples as unexposed, exposed to a sublethal dose or exposed to an LD 50/30 . All unexposed samples from Parp1 -/- mice were also correctly classified with the same gene set, and 80% of irradiated Parp1 -/- samples were identified as exposed to an LD 50/30 . The results of this study suggest that, at least for some pathways that may influence radiosensitivity in humans, specific gene expression signatures have the potential to accurately detect the extent of radiological injury, rather than serving only as a surrogate of physical radiation dose.

Anticancer activity of the new photosensitizers: dose and cell type dependence

NASA Astrophysics Data System (ADS)

Gyulkhandanyan, Grigor V.; Ghambaryan, Sona S.; Amelyan, Gayane V.; Ghazaryan, Robert K.; Haroutiunian, Samvel G.; Gyulkhandanyan, Aram G.; Gasparyan, Gennadi H.

2005-04-01

The necessity of researches of antitumor efficiency of new photosensitizers (PS) is explained by the opportunity of their application in photodynamic therapy of tumors. PS, selectively accumulated in cancer cells and activated by the light, generate the active oxygen species that cause apoptosis. Earlier, it was shown that PS chlorin e6 (0.3-0.5 μg/ml) induces rat embryo fibroblast-like cell apoptosis. In present work antitumor activity of the new photosensitizers, water-soluble cationic porphyrins and their metal complexes, is investigated. The dose-dependent destruction of cancer cells was shown on PC-12 (pheochromocytoma, rat adrenal gland) and Jurkat (human lymphoma) cell lines. Meso-tetra-[4-N-(2 `- oxyethyl) pyridyl] porphyrin (TOEPyP) and chlorin e6 possessed the same toxicity at LD50 dose on PC-12 cell line, whereas phototoxicity of TOEPyP was 3 times less compared to chlorin e6(LD50=0.2 and 0.075 μg/ml accordingly). The results have shown weak photosensitizing effect of Zn-and Ag-derivatives of TOEPyP on PC-12 cell line. TOEPyP and Zn-TOEPyP (0.1 - 50 μg/ml) were non-toxic for Jurkat cell line, whereas Ag-TOEPyP was toxic at 10 μg/ml (LD90). TOEPyP and chlorin e6 have shown phototoxic effect in the same dose range (LD50=0.5 and 0.3 μg/ml accordingly). The investigation of toxic and phototoxic effects of the new porphyrins revealed significantly different sensitivity of various cell lines to PSs.

Core body temperature as adjunct to endpoint determination in murine median lethal dose testing of rattlesnake venom.

PubMed

Cates, Charles C; McCabe, James G; Lawson, Gregory W; Couto, Marcelo A

2014-12-01

Median lethal dose (LD50) testing in mice is the 'gold standard' for evaluating the lethality of snake venoms and the effectiveness of interventions. As part of a study to determine the murine LD50 of the venom of 3 species of rattlesnake, temperature data were collected in an attempt to more precisely define humane endpoints. We used an 'up-and-down' methodology of estimating the LD50 that involved serial intraperitoneal injection of predetermined concentrations of venom. By using a rectal thermistor probe, body temperature was taken once before administration and at various times after venom exposure. All but one mouse showed a marked, immediate, dose-dependent drop in temperature of approximately 2 to 6°C at 15 to 45 min after administration. The lowest temperature sustained by any surviving mouse was 33.2°C. Surviving mice generally returned to near-baseline temperatures within 2 h after venom administration, whereas mice that did not survive continued to show a gradual decline in temperature until death or euthanasia. Logistic regression modeling controlling for the effects of baseline core body temperature and venom type showed that core body temperature was a significant predictor of survival. Linear regression of the interaction of time and survival was used to estimate temperatures predictive of death at the earliest time point and demonstrated that venom type had a significant influence on temperature values. Overall, our data suggest that core body temperature is a useful adjunct to monitoring for endpoints in LD50 studies and may be a valuable predictor of survival in venom studies.

Comparative toxicity of diphacinone to northern bobwhite (Colinus virginianus) and American kestrels (Falco sparverius)

USGS Publications Warehouse

Rattner, Barnett A.; Horak, Katherine E.; Warner, Sarah E.; Day, Daniel D.; Johnston, John J.

2010-01-01

The acute oral toxicity of the anticoagulant rodenticide diphacinone was found to be about 20 times greater to American kestrels (LD50=97 mg/kg) than to northern bobwhite (LD50=2,014 mg/kg). Several precise and sensitive clotting assays (prothrombin time, Russell's Viper venom time, thrombin clotting time) were adapted for use in these species, and this combination of assays is recommended to detect effects of diphacinone and other rodenticides on coagulation. Oral administration of diphacinone over a range of doses (sublethal to the extrapolated LD15) prolonged prothrombin time and Russell's Viper venom time within 24 to 48 hrs post-exposure. Prolongation of in vitro clotting time reflects impaired coagulation complex activity and was detected before or at the onset of overt signs of toxicity and lethality. These data will assist in the development of a pharmacodynamic model to assess and predict rodenticide toxicity to non-target avian species.

VX toxicity in the Göttingen minipig.

PubMed

Langston, Jeffrey L; Myers, Todd M

2016-12-15

The present experiments determined the intramuscular LD 50 of VX in male Göttingen minipigs at two stages of development. In pubertal animals (115 days old), the LD 50 of VX was indeterminate, but approximated 33.3μg/kg. However, in sexually mature animals (152 days old), the LD 50 was estimated to be only 17.4μg/kg. Signs of nerve agent toxicity in the Göttingen minipig were similar to those described for other species, with some notable exceptions (such as urticaria and ejaculation). Latencies to the onset of sustained convulsions were inversely related to the administered dose of VX in both ages of minipigs. Additionally, actigraphy was used to quantify the presence of tremor and convulsions and, in some cases, was useful for precisely estimating time of death. The main finding indicates that in minipigs, as in other species, even relatively small differences in age can substantially alter the toxicity of nerve agents. Additionally, actigraphy can serve as a non-invasive method of characterizing the tremors and convulsions that often accompany nerve agent intoxication. Published by Elsevier Ireland Ltd.

Contact Toxicity and Repellency of the Main Components From the Essential Oil of Clausena anisum-olens Against Two Stored Product Insects

PubMed Central

You, Chun Xue; Jiang, Hai Yan; Zhang, Wen Juan; Guo, Shan Shan; Yang, Kai; Lei, Ning; Ma, Ping; Geng, Zhu Feng; Du, Shu Shan

2015-01-01

The essential oil of Clausena anisum-olens (Blanco) Merr. showed strong contact toxicity and repellency against Lasioderma serricorne and Liposcelis bostrychophila adults. The components of the essential oil obtained by hydrodistillation were determined by gas chromatography-mass spectrometry. It was found that the main components were myristicin (36.87%), terpinolene (13.26%), p-cymene-8-ol (12.38%), and 3-carene (3.88%). Myristicin and p-cymene-8-ol were separated by silica gel column chromatography, and their molecular structures were confirmed by means of physicochemical and spectrometric analysis. Myristicin and p-cymene-8-ol showed strong contact toxicity against L. serricorne (LD50 = 18.96 and 39.68 μg per adult) and Li. bostrychophila (LD50 = 20.41 and 35.66 μg per adult). The essential oil acting against the two grain storage insects showed LD50 values of 12.44 and 74.46 μg per adult, respectively. Myristicin and p-cymene-8-ol have strong repellent toxicity to Li. bostrychophila. PMID:26136499

Acute oral toxicities of wildland fire control chemicals to birds

USGS Publications Warehouse

Vyas, N.B.; Spann, J.W.; Hill, E.F.

2009-01-01

Wildland fire control chemicals are released into the environment by aerial and ground applications to manage rangeland, grassland, and forest fires. Acute oral 24 h median lethal dosages (LD50) for three fire retardants (Fire-Trol GTS-R?, Phos-Chek D-75F?, and Fire-Trol LCG-R?) and two Class A fire suppressant foams (Silv-Ex? and Phos-Chek WD881?) were estimated for northern bobwhites, Colinus virginianus, American kestrels, Falco sparverius, and red-winged blackbirds, Agelaius phoeniceus. The LD50s of all chemicals for the bobwhites and red-winged blackbirds and for kestrels dosed with Phos-Chek WD881? and Silv-Ex? were above the predetermined 2000 mg chemical/kg body mass regulatory limit criteria for acute oral toxicity. The LD50s were not quantifiable for kestrels dosed with Fire-Trol GTS-R?, Phos-Chek D-75F?, and Fire-Trol LCG-R? because of the number of birds which regurgitated the dosage. These chemicals appear to be of comparatively low order of acute oral toxicity to the avian species tested.

Acute oral toxicity of sodium cyanide in birds

USGS Publications Warehouse

Wiemeyer, Stanley N.; Hill, E.F.; Carpenter, J.W.; Krynitsky, A.J.

1986-01-01

Sensitivities of six avian species, black vulture (Coragyps atratus), American kestrel (Falco sparverius), Japanese quail (Coturnix japonica), domestic chicken (Gallus domesticus), eastern screech-owl (Otus asio), and European starling (Sturnus vulgaris), to acute poisoning by sodium cyanide (NaCN) were compared by single dose LD50's. Three species, domestic chickens, black vultures, and turkey vultures (Cathartes aura), were dosed with NaCN to determine cyanide residues in those that died and also in survivors, in addition to postmortem fate. Three flesh-eating species (black vulture, American kestrel, and eastern screech-owl; LD50's 4.0-8.6 mg/kg) were more sensitive to NaCN than three species (Japanese quail, domestic chicken, and European starling; LD50's 9.4-21 mg/kg) that fed predominantly on plant material. Elevated concentrations of cyanide were found in the blood of birds that died of cyanide poisoning; however, concentrations in birds that died overlapped those in survivors. Blood was superior to liver as the tissue of choice for detecting cyanide exposure. No gross pathological changes related to dosing were observed at necropsy.

Target-Specificity in Scorpions; Comparing Lethality of Scorpion Venoms across Arthropods and Vertebrates.

PubMed

van der Meijden, Arie; Koch, Bjørn; van der Valk, Tom; Vargas-Muñoz, Leidy J; Estrada-Gómez, Sebastian

2017-10-04

Scorpions use their venom in defensive situations as well as for subduing prey. Since some species of scorpion use their venom more in defensive situations than others, this may have led to selection for differences in effectiveness in defensive situations. Here, we compared the LD 50 of the venom of 10 species of scorpions on five different species of target organisms; two insects and three vertebrates. We found little correlation between the target species in the efficacy of the different scorpion venoms. Only the two insects showed a positive correlation, indicating that they responded similarly to the panel of scorpion venoms. We discuss the lack of positive correlation between the vertebrate target species in the light of their evolution and development. When comparing the responses of the target systems to individual scorpion venoms pairwise, we found that closely related scorpion species tend to elicit a similar response pattern across the target species. This was further reflected in a significant phylogenetic signal across the scorpion phylogeny for the LD 50 in mice and in zebrafish. We also provide the first mouse LD 50 value for Grosphus grandidieri .

Alternative methods for the median lethal dose (LD(50)) test: the up-and-down procedure for acute oral toxicity.

PubMed

Rispin, Amy; Farrar, David; Margosches, Elizabeth; Gupta, Kailash; Stitzel, Katherine; Carr, Gregory; Greene, Michael; Meyer, William; McCall, Deborah

2002-01-01

The authors have developed an improved version of the up-and-down procedure (UDP) as one of the replacements for the traditional acute oral toxicity test formerly used by the Organisation for Economic Co-operation and Development member nations to characterize industrial chemicals, pesticides, and their mixtures. This method improves the performance of acute testing for applications that use the median lethal dose (classic LD50) test while achieving significant reductions in animal use. It uses sequential dosing, together with sophisticated computer-assisted computational methods during the execution and calculation phases of the test. Staircase design, a form of sequential test design, can be applied to acute toxicity testing with its binary experimental endpoints (yes/no outcomes). The improved UDP provides a point estimate of the LD50 and approximate confidence intervals in addition to observed toxic signs for the substance tested. It does not provide information about the dose-response curve. Computer simulation was used to test performance of the UDP without the need for additional laboratory validation.

Effects of pig genotype (Iberian v. Landrace × Large White) on nutrient digestibility, relative organ weight and small intestine structure at two stages of growth.

PubMed

Barea, R; Nieto, R; Vitari, F; Domeneghini, C; Aguilera, J F

2011-02-01

Although the effects of pig genotype on total-tract apparent digestibility (TTAD) have been widely reported in the literature, there is controversial information on the digestive capacity of indigenous breeds compared with lean-type pigs. The strategy of this study was to test the effects of pig genotype and crude protein (CP) supply on performance, digestive utilization of nutrients, relative organ weight and morphometric analysis of the small intestine. Thirty-eight Iberian (IB) and Landrace × Large White (LD) pigs were used. Three pigs per genotype were slaughtered at approximately 15 kg BW. The remaining pigs were fed one of two diets differing in CP content (13% or 17% as fed) using a pair-fed procedure. Feeding level was restricted at 0.8 × ad libitum of IB pigs. Nutrient digestibility and nitrogen (N) balance trials were performed at 30 and 80 kg BW. Four pigs per dietary treatment and genotype were slaughtered at approximately 50 and 115 kg BW. The gastrointestinal tract and the rest of the visceral organs were weighed and samples of the small intestine were taken to carry out histological and histometrical studies. Daily gain and gain-to-feed ratio were higher in LD than in IB pigs during the fattening and growing-fattening periods (P < 0.01). N TTAD was significantly higher for LD pigs at 30 kg BW (P < 0.05), whereas at 80 kg BW we observed greater values for digestibility of organic matter and energy in IB pigs (averaging 1.5%, P < 0.01). Both N retention (NR) and efficiency of NR were increased in LD pigs at 30 and 80 kg BW (30% as mean value). The proportional weight of the small intestine was greater in LD than in IB pigs at 50 and 115 kg BW. Histometry showed that IB presented a lower muscle layer thickness than LD pigs in ileum, irrespective of the BW (P < 0.05). In contrast, LD pigs showed approximately 10% higher ileal villi length and villi-to-crypt ratio than IB pigs at 115 kg BW. CP supply affected to a larger extent the small intestinal micro-anatomical structure of LD pigs at 50 kg BW. In conclusion, our results suggests that although the higher growth rate, NR and efficiency of NR observed in LD pigs might be associated with presumably more efficient structural aspects of the small intestine, the main differences between the two genotypes should be attributed to a larger extent to protein and energy utilization in tissues with consequences for the overall efficiency of energy use.

Virulence of Renibacterium salmoninarum to salmonids

USGS Publications Warehouse

Starliper, C.E.; Smith, D.R.; Shatzer, T.

1997-01-01

Virulence of Renibacterium salmoninarum isolates representing five origins was evaluated in eight salmonid hosts; four origins were of Lake Michigan and the fifth was of the Pacific Northwest. The species type strain, ATCC (American Type Culture Collection) 33209, was also included. Each isolate was grown in a kidney disease medium (KDM2) supplemented with 1 % ATCC 33209 culture metabolite; serial 10-fold dilutions were prepared, and groups of fish were challenged by intraperitoneal injection with 0.1 mL of each dilution. A 70-d observation period followed, and bacterial kidney disease (BKD) was diagnosed by the fluorescent antibody technique. Virulence of isolates was quantified as a dose lethal to 50% of fish (LD50) for each host–isolate challenge. In the first set of experiments, 23 isolates were used to challenge groups of brook trout Salvelinus fontinalis. The mean LD50 was 1.087 x 106 colony-forming units per milliliter (cfu/mL; SD = 2.022 x 106), and the LD50 values ranged from 8.457 x 106 to 2.227 x 104 cfu/mL. Analysis of variance to evaluate the effect of isolate origin on virulence in brook trout revealed no significant difference (F = 1.502; P = 0.243). Susceptibilities of the other salmonid hosts were evaluated by challenge with six isolates of R. salmoninarum representing each origin and the species type strain. For many of the host–isolate challenge combinations, time to death was highly dependent on the dilution (number of bacteria) injected. In general, the isolates MCO4M, B26, and A34 (all of Lake Michigan origin) tended to be more virulent. Also, LD50 values were dispersed throughout a wider range among the more susceptible hosts. Lake trout Salvelinus namaycush, rainbow trout Oncorhynchus mykiss, and brook trout were relatively resistant to challenge with the strains, whereas coho salmon O. kisutch, domestic Atlantic salmon Saltno salar, and chinook salmon O. tshawytscha were relatively susceptible. Another challenge evaluated the effect of washing R. salmoninarum MCO4M cells before injection into brook trout. The calculated LD50 value, 2.009 x 105 cfu/mL, was similar (X2 = 0.878; P = 0.645) to that of the unwashed cells (1.163 x 105 cfu/mL). Furthermore, times to death for successive dilutions were similar regardless of whether or not the cells were washed.

40 CFR 158.630 - Terrestrial and aquatic nontarget organisms data requirements table.

Code of Federal Regulations, 2010 CFR

2010-07-01

... LC50, two avian reproduction studies, two freshwater fish LC50, one freshwater invertebrate EC50, one honeybee acute contact LD50, one freshwater fish early-life stage, one freshwater invertebrate life cycle, and three estuarine acute LC50/EC50 studies -- fish, mollusk and invertebrate. All other outdoor...

Effect of number of lobes and length-diameter ratio on stability of tilted-lobe hydrodynamic journal bearings at zero load

NASA Technical Reports Server (NTRS)

Schuller, F. T.

1975-01-01

Hydrodynamic journal stability tests were conducted with tilted-lobe bearings. The bearings had three, five, and seven lobes and length to diameter (L/D) ratios from 0.2 to 1.0. They were tested in water and MIL-L-7808G oil at 294 K (70 F) at speeds to 5400 rpm with zero load. Stability was not appreciably affected by the number of lobes and decreased with a decrease in L/D ratio. However, a three-tilted-lobe bearing with an offset factor of 0.76 and an L/D of 0.5 was more stable than a three centrally lobed bearing with an offset factor of 0.50 and an L/D of 1.0.

A Theoretical Analysis of the Performance of Learning Disabled Students on the Woodcock-Johnson Psycho-Educational Battery.

ERIC Educational Resources Information Center

Shinn, Mark; And Others

Two studies were conducted to (1) analyze the subtest characteristics of the Woodcock-Johnson Psycho-Educational Battery, and (2) apply those results to an analysis of 50 fourth grade learning disabled (LD) students' performance on the Battery. Analyses indicated that the poorer performance of LD students on the Woodcock-Johnson Tests of Cognitive…

Quantitative relationship between anticapsular antibody measured by enzyme-linked immunosorbent assay or radioimmunoassay and protection of mice against challenge with Streptococcus pneumoniae serotype 4.

PubMed Central

Musher, D M; Johnson, B; Watson, D A

1990-01-01

We have recently shown that a substantial proportion of antibody to pneumococcal polysaccharide as measured by enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay is removed by adsorption with pneumococcal cell wall polysaccharide (CWPS). The present study was undertaken to validate the hypothesis that only serotype-specific antibody that remains after adsorption with CWPS provides protection against pneumococcal infection. Serum samples were obtained from human subjects before and after they had been vaccinated with pneumococcal polysaccharide vaccine. Antibody to Streptococcus pneumoniae serotype 4 was measured by ELISA without adsorption or after adsorption of serum with CWPS. Groups of mice were injected with graded doses of serum and then challenged intraperitoneally with 10, 100, or 1,000 50% lethal doses (LD50) of S. pneumoniae serotype 4. Without adsorption, prevaccination sera from five healthy adults appeared to contain up to 33 micrograms of antibody to S. pneumoniae serotype 4 antigen per ml; adsorption with CWPS removed all detectable antibody, and pretreating mice with up to 0.1 ml of these sera (less than or equal to 3.3 micrograms of antibody) failed to protect them against challenge with 100 LD50. In contrast, postvaccination sera contained 2.9 to 30 micrograms of antibody per ml that was not removed by adsorption. Diluting sera to administer desired amounts of serotype-specific immunoglobulin G showed a significant relationship between protection and antibody remaining after adsorption (P less than 0.05 by linear regression analysis); 150 ng was uniformly protective against 1,000 LD50, and 50 ng was protective against 100 LD50. These studies have, for the first time, quantitated the amount of serotype-specific antibody that protects mice against challenge with S. pneumoniae type 4. In light of these observations, it is necessary to reassess current concepts regarding the presence of antipneumococcal antibody in the unvaccinated population, responses to pneumococcal vaccination, and protective levels of immunoglobulin G. PMID:2254015

Ineffectiveness of 3,4-diaminopyridine as a therapy for type C botulism.

USGS Publications Warehouse

Siegel, L.S.; Price, J.I.

1987-01-01

Clostridium botulinum neurotoxins inhibit acetylcholine release at neuromuscular junctions. Agents stimulating neurotransmitter efflux, such as 3,4-diaminopyridine (3,4-DAP), could be useful for botulism therapy. Treatment with 3,4-DAP (8 mg/kg hourly, beginning 3 hr after toxin injection) failed to increase the survival times of mice receiving 10, 20 or 40 LD50 type C, but did prolong the survival of those receiving 20 LD50 type A. This difference in 3,4-DAP efficacy may reflect variations in the molecular mechanism of action of types A and C botulinum neurotoxins.

Medical Research and Evaluation Facility (MREF) and studies supporting the medical chemical defense program. Determination of the minimum effective pyridostigmine pretreatment dose in monkeys challenged with 5 x LD50 Soman and treated with atropine/2-PAM. Final report, 22 October 1992-31 August 1993

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olson, C.T.; Menton, R.G.; Kiser, R.C.

This task was conducted to determine the minimum dose of pyridostigmine (PYR), and the associated level of erythrocyte acetycholinesterase inhibition (AChE-I), that provides protection from 5 X 48-br GD LD50 of untreated monkeys. Monkeys were injected im with GD and treated with 0.4 mg atropine (ATR) free base and 25.7 mg pralidoxime (2-PAM) per kg BW.

[Alpha competitive structure in children with attention deficit hyperactivity disorder with/without learning disabilities].

PubMed

Sun, Li; Wang, Yu-feng; He, Hua; Chen, Jin

2007-10-18

To explore the alpha competitive structure in children with attention deficit hyperactivity disorder (ADHD) with/without learning disabilities (LD). According to DSM-IV diagnostic criteria, the study involved ADHD children with LD, pure ADHD children and normal controls. Each group consisted of 68 subjects. All subjects were between the ages of 7 and 14 years, and the groups were matched by sex, age and ADHD subtypes. EEG data were recorded during an eye-closed resting period and then were analyzed with EEG-encephaloflutuographic technology (EEG-ET). (1) The pure ADHD children showed significantly more 8 Hz activity (25.84%+/-14.81%) than that of the normal control group (16.50%+/-11.42%, P=0.000); The main frequency of alpha band was 10 Hz in the pure ADHD children, while the energy distribution among alpha components was diffuse. (2) ADHD children with LD showed significantly more 8 Hz and 13 Hz activity (25.11%+/-11.88%, 1.14%+/-1.14%, separately) than that of the normal control (16.50%+/-11.42%, 0.74%+/-0.97%, P=0.000, P=0.009, separately); The dominant probability of 10 Hz (27.80%+/-13.28%) in this group was significantly lower than that of the control group (36.06%+/-17.21%, P=0.011); The energy distribution among alpha components was diffuse in ADHD children with LD, whose main frequency of alpha band was 9 Hz; The entropy value of the ADHD children with LD was significantly higher than that of the control group in the right brain and the left parietal region, temporal region, occipital region (P<0.01). In the right temporal region and right occipital region, the entropy value of the ADHD children with LD was significantly higher than that of the pure ADHD children (P<0.05). The pathogenic mechanisms are different between ADHD children with or without LD. The pure ADHD children show more maturational lag pattern in the central nervous system, while ADHD children with LD have a developmental deviation from normal children, whose brain function is in a lower efficient state.

A longitudinal study on gross motor development in children with learning disorders.

PubMed

Westendorp, Marieke; Hartman, Esther; Houwen, Suzanne; Huijgen, Barbara C H; Smith, Joanne; Visscher, Chris

2014-02-01

This longitudinal study examined the development of gross motor skills, and sex-differences therein, in 7- to 11-years-old children with learning disorders (LD) and compared the results with typically developing children to determine the performance level of children with LD. In children with LD (n=56; 39 boys, 17 girls), gross motor skills were assessed with the Test of Gross Motor Development-2 and measured annually during a 3-year period. Motor scores of 253 typically developing children (125 boys, 112 girls) were collected for references values. The multilevel analyses showed that the ball skills of children with LD improved with age (p<.001), especially between 7 and 9 years, but the locomotor skills did not (p=.50). Boys had higher ball skill scores than girls (p=.002) and these differences were constant over time. Typically developing children outperformed the children with LD on the locomotor skills and ball skills at all ages, except the locomotor skills at age 7. Children with LD develop their ball skills later in the primary school-period compared to typically developing peers. However, 11 year-old children with LD had a lag in locomotor skills and ball skills of at least four and three years, respectively, compared to their peers. Copyright © 2013 Elsevier Ltd. All rights reserved.

Improvement of banana cv. Rasthali (Silk, AAB) against Fusarium oxysporum f.sp. cubense (VCG 0124/5) through induced mutagenesis: Determination of LD50 specific to mutagen, explants, toxins and in vitro and in vivo screening for Fusarium wilt resistance.

PubMed

Saraswathi, M S; Kannan, G; Uma, S; Thangavelu, R; Backiyarani, S

2016-05-01

Shoot tips and in vitro grown proliferating buds of banana cv. Rasthali (Silk, AAB) were treated with various concentrations and durations of chemical mutagens viz., EMS, NaN3 and DES. LD50 for shoot tips based on 50% reduction in fresh weight was determined as 2% for 3 h, 0.02% for 5 h and 0.15% for 5 h, while for proliferating buds, they were 0.6% for 30 min, 0.01% for 2 h and 0.06% for 2 h for the mutagens EMS, NaN3 and DES, respectively. Subsequently, the mutated explants were screened in vitro against fusarium wilt using selection agents like fusaric acid and culture filtrate. LD50 for in vitro selection agents calculated based on 50% survival of explants was 0.050 mM and 7% for fusaric acid and culture filtrate, respectively and beyond which a rapid decline in growth was observed. This was followed by pot screening which led to the identification of three putative resistant mutants with an internal disease score of 1 (corm completely clean, no vascular discolouration). The putative mutants identified in the present study have also been mass multiplied in vitro.

Value of antirabies vaccine with and without serum against severe challenges

PubMed Central

Veeraraghavan, N.; Subrahmanyan, T. P.

1960-01-01

Earlier studies with antirabies serum and vaccine have been extended to determine the value of serum, vaccine, or serum and vaccine combined against rabies challenges of increasing degrees of severity. While serum alone was not found to have any protective effect, vaccine alone was sufficient against mild challenges, the superiority of combined therapy with both serum and vaccine becoming evident at a challenge of about 50 LD50. With challenges of over 300 LD50 no treatment was of any value. It was also found that with a recommended optimum dose of serum, the usual vaccine dose could be halved—a matter of importance in countries with a high incidence of neuroparalytic accidents following administration of nervous tissue vaccine. PMID:13841546

Value of antirabies vaccine with and without serum against severe challenges.

PubMed

VEERARAGHAVAN, N; SUBRAHMANYAN, T P

1960-01-01

Earlier studies with antirabies serum and vaccine have been extended to determine the value of serum, vaccine, or serum and vaccine combined against rabies challenges of increasing degrees of severity. While serum alone was not found to have any protective effect, vaccine alone was sufficient against mild challenges, the superiority of combined therapy with both serum and vaccine becoming evident at a challenge of about 50 LD(50). With challenges of over 300 LD(50) no treatment was of any value. It was also found that with a recommended optimum dose of serum, the usual vaccine dose could be halved-a matter of importance in countries with a high incidence of neuroparalytic accidents following administration of nervous tissue vaccine.

Androgen Receptor Antagonists and Anti-Prostate Cancer Activities of Some Newly Synthesized Substituted Fused Pyrazolo-, Triazolo- and Thiazolo-Pyrimidine Derivatives

PubMed Central

Bahashwan, Saleh A.; Fayed, Ahmed A.; Ramadan, Mohamed A.; Amr, Abd El-Galil E.; Al-Harbi, Naif O.

2014-01-01

A series of substituted pyrazole, triazole and thiazole derivatives (2–13) were synthesized from 1-(naphtho[1,2-d]thiazol-2-yl)hydrazine as starting material and evaluated as androgen receptor antagonists and anti-prostate cancer agents. The newly synthesized compounds showed potent androgen receptor antagonists and anti-prostate cancer activities with low toxicity (lethal dose 50 (LD50)) comparable to Bicalutamide as reference drug. The structures of newly synthesized compounds were confirmed by IR, 1H-NMR, 13C-NMR, and MS spectral data and elemental analysis. The detailed synthesis, spectroscopic data, LD50 values and pharmacological activities of the synthesized compounds are reported. PMID:25421248

Acute and Subacute Toxicity of Safranal, a Constituent of Saffron, in Mice and Rats

PubMed Central

Hosseinzadeh, Hossein; Sadeghi Shakib, Saied; Khadem Sameni, Abbas; Taghiabadi, Elahe

2013-01-01

The acute and sub-acute toxicity of safranal were studied in rat and mice within 2 and 21 days after exposure, respectively. For subacute toxicity, changes in weight as well as biochemical, hematological and pathological parameters were studied. The intraperitoneal LD50 values of safranal were 1.48 mL/kg in male mice, 1.88 mL/kg in female mice and 1.50 mL/kg in male rats. Oral LD50 values were 21.42 mL/kg in male mice, 11.42 mL/kg in female mice and 5.53 mL/kg in male rats. For subacute toxicity, safranal was administered orally to male rats once daily for 21 days. In hematological tests, a significant decrease in RBC counts, hematocrit, hemoglobin and platelets were observed. Safranal decreased cholesterol, triglyceride and alkalin phosphatase. Lactate dehydrogenase and serum urea nitrogen were increased by safranal. Histological studies indicated that safranal did not have any toxic effect on the heart, liver and spleen. However, pathological changes were seen in the kidney and lung. According to LD50 values, safranal was low-toxic in acute intraperitoneal route and practically non-toxic in acute oral administration in both mice and rats. In subacute toxicity, safranal changed some hematological and biochemical parameters. PMID:24250576

2-Alkynoic fatty acids inhibit topoisomerase IB from Leishmania donovani.

PubMed

Carballeira, Néstor M; Cartagena, Michelle; Sanabria, David; Tasdemir, Deniz; Prada, Christopher F; Reguera, Rosa M; Balaña-Fouce, Rafael

2012-10-01

2-Alkynoic fatty acids display antimycobacterial, antifungal, and pesticidal activities but their antiprotozoal activity has received little attention. In this work we synthesized the 2-octadecynoic acid (2-ODA), 2-hexadecynoic acid (2-HDA), and 2-tetradecynoic acid (2-TDA) and show that 2-ODA is the best inhibitor of the Leishmania donovani DNA topoisomerase IB enzyme (LdTopIB) with an EC(50)=5.3±0.7μM. The potency of LdTopIB inhibition follows the trend 2-ODA>2-HDA>2-TDA, indicating that the effectiveness of inhibition depends on the fatty acid carbon chain length. All of the studied 2-alkynoic fatty acids were less potent inhibitors of the human topoisomerase IB enzyme (hTopIB) as compared to LdTopIB. 2-ODA also displayed in vitro activity against Leishmania donovani (IC(50)=11.0μM), but it was less effective against other protozoa, Trypanosoma cruzi (IC(50)=48.1μM) and Trypanosoma brucei rhodesiense (IC(50)=64.5μM). The antiprotozoal activity of the 2-alkynoic fatty acids, in general, followed the trend 2-ODA>2-HDA>2-TDA. The experimental information gathered so far indicates that 2-ODA is a promising antileishmanial compound. Copyright © 2012 Elsevier Ltd. All rights reserved.

QSAR Modeling of Rat Acute Toxicity by Oral Exposure

PubMed Central

Zhu, Hao; Martin, Todd M.; Ye, Lin; Sedykh, Alexander; Young, Douglas M.; Tropsha, Alexander

2009-01-01

Few Quantitative Structure-Activity Relationship (QSAR) studies have successfully modeled large, diverse rodent toxicity endpoints. In this study, a comprehensive dataset of 7,385 compounds with their most conservative lethal dose (LD50) values has been compiled. A combinatorial QSAR approach has been employed to develop robust and predictive models of acute toxicity in rats caused by oral exposure to chemicals. To enable fair comparison between the predictive power of models generated in this study versus a commercial toxicity predictor, TOPKAT (Toxicity Prediction by Komputer Assisted Technology), a modeling subset of the entire dataset was selected that included all 3,472 compounds used in the TOPKAT’s training set. The remaining 3,913 compounds, which were not present in the TOPKAT training set, were used as the external validation set. QSAR models of five different types were developed for the modeling set. The prediction accuracy for the external validation set was estimated by determination coefficient R2 of linear regression between actual and predicted LD50 values. The use of the applicability domain threshold implemented in most models generally improved the external prediction accuracy but expectedly led to the decrease in chemical space coverage; depending on the applicability domain threshold, R2 ranged from 0.24 to 0.70. Ultimately, several consensus models were developed by averaging the predicted LD50 for every compound using all 5 models. The consensus models afforded higher prediction accuracy for the external validation dataset with the higher coverage as compared to individual constituent models. The validated consensus LD50 models developed in this study can be used as reliable computational predictors of in vivo acute toxicity. PMID:19845371

Effectiveness of Donepezil, Rivastigmine, and (±)Huperzine A in Counteracting the Acute Toxicity of Organophosphorus Nerve Agents: Comparison with Galantamine

PubMed Central

Aracava, Yasco; Pereira, Edna F. R.; Akkerman, Miriam; Adler, Michael

2009-01-01

Galantamine, a centrally acting cholinesterase (ChE) inhibitor and a nicotinic allosteric potentiating ligand used to treat Alzheimer's disease, is an effective and safe antidote against poisoning with nerve agents, including soman. Here, the effectiveness of galantamine was compared with that of the centrally active ChE inhibitors donepezil, rivastigmine, and (±)huperzine A as a pre- and/or post-treatment to counteract the acute toxicity of soman. In the first set of experiments, male prepubertal guinea pigs were treated intramuscularly with one of the test drugs and 30 min later challenged with 1.5 × LD50 soman (42 μg/kg s.c.). All animals that were pretreated with galantamine (6–8 mg/kg), 3 mg/kg donepezil, 6 mg/kg rivastigmine, or 0.3 mg/kg (±)huperzine A survived the soman challenge, provided that they were also post-treated with atropine (10 mg/kg i.m.). However, only galantamine was well tolerated. In subsequent experiments, the effectiveness of specific treatment regimens using 8 mg/kg galantamine, 3 mg/kg donepezil, 6 mg/kg rivastigmine, or 0.3 mg/kg (±)huperzine A was compared in guinea pigs challenged with soman. In the absence of atropine, only galantamine worked as an effective and safe pretreatment in animals challenged with 1.0 × LD50 soman. Galantamine was also the only drug to afford significant protection when given to guinea pigs after 1.0 × LD50 soman. Finally, all test drugs except galantamine reduced the survival of the animals when administered 1 or 3 h after the challenge with 0.6 or 0.7 × LD50 soman. Thus, galantamine emerges as a superior antidotal therapy against the toxicity of soman. PMID:19741148

Core Body Temperature as Adjunct to Endpoint Determination in Murine Median Lethal Dose Testing of Rattlesnake Venom

PubMed Central

Cates, Charles C; McCabe, James G; Lawson, Gregory W; Couto, Marcelo A

2014-01-01

Median lethal dose (LD50) testing in mice is the ‘gold standard’ for evaluating the lethality of snake venoms and the effectiveness of interventions. As part of a study to determine the murine LD50 of the venom of 3 species of rattlesnake, temperature data were collected in an attempt to more precisely define humane endpoints. We used an ‘up-and-down’ methodology of estimating the LD50 that involved serial intraperitoneal injection of predetermined concentrations of venom. By using a rectal thermistor probe, body temperature was taken once before administration and at various times after venom exposure. All but one mouse showed a marked, immediate, dose-dependent drop in temperature of approximately 2 to 6 °C at 15 to 45 min after administration. The lowest temperature sustained by any surviving mouse was 33.2 °C. Surviving mice generally returned to near-baseline temperatures within 2 h after venom administration, whereas mice that did not survive continued to show a gradual decline in temperature until death or euthanasia. Logistic regression modeling controlling for the effects of baseline core body temperature and venom type showed that core body temperature was a significant predictor of survival. Linear regression of the interaction of time and survival was used to estimate temperatures predictive of death at the earliest time point and demonstrated that venom type had a significant influence on temperature values. Overall, our data suggest that core body temperature is a useful adjunct to monitoring for endpoints in LD50 studies and may be a valuable predictor of survival in venom studies. PMID:25527024

Quantitative structure-activity relationship modeling of rat acute toxicity by oral exposure.

PubMed

Zhu, Hao; Martin, Todd M; Ye, Lin; Sedykh, Alexander; Young, Douglas M; Tropsha, Alexander

2009-12-01

Few quantitative structure-activity relationship (QSAR) studies have successfully modeled large, diverse rodent toxicity end points. In this study, a comprehensive data set of 7385 compounds with their most conservative lethal dose (LD(50)) values has been compiled. A combinatorial QSAR approach has been employed to develop robust and predictive models of acute toxicity in rats caused by oral exposure to chemicals. To enable fair comparison between the predictive power of models generated in this study versus a commercial toxicity predictor, TOPKAT (Toxicity Prediction by Komputer Assisted Technology), a modeling subset of the entire data set was selected that included all 3472 compounds used in TOPKAT's training set. The remaining 3913 compounds, which were not present in the TOPKAT training set, were used as the external validation set. QSAR models of five different types were developed for the modeling set. The prediction accuracy for the external validation set was estimated by determination coefficient R(2) of linear regression between actual and predicted LD(50) values. The use of the applicability domain threshold implemented in most models generally improved the external prediction accuracy but expectedly led to the decrease in chemical space coverage; depending on the applicability domain threshold, R(2) ranged from 0.24 to 0.70. Ultimately, several consensus models were developed by averaging the predicted LD(50) for every compound using all five models. The consensus models afforded higher prediction accuracy for the external validation data set with the higher coverage as compared to individual constituent models. The validated consensus LD(50) models developed in this study can be used as reliable computational predictors of in vivo acute toxicity.

[Effects of Beauveria bassiana on Myzus persicae and its two predaceous natural enemies].

PubMed

Zhu, Hong; Luo, Xu-mei; Song, Jin-xin; Fan, Mei-zhen; Li, Zeng-zhi

2011-09-01

A Beauveria bassiana strain Bb21 was isolated from naturally infected green peach aphid Myzus persicae (Hemiptera: Aphididae). The effects of the strain on M. persicae and its two predaceous natural enemies Chrysoperla carnea (Neuroptera: Chrysopidae) and Harmonia axyridis (Coleoptera: Coccinellidae) were investigated under laboratory conditions. Bb21 had strong pathogenicity to M. persicae, with the LD50 of 97 conidia x mm(-2) (45-191, 95% confidence interval), but was less pathogenic to the second instar nymph of C. carnea, with the LD50 of 1089 conidia x mm(-2). The LD50 for C. carnea was 10.2 times higher than that for M. persicae. The pathogenicity of Bb21 to H. axyridis was very weak, with a low infection rate of 13% even at a high concentration 5 x 10(8) conidia x mL(-1). The Bb21 at low conidia concentration had less effect on the developmental period and fecundity of the two predaceous natural enemies. However, when applied at the high concentration 5 x 10(8) spores x mL(-1), Bb21 shortened the larval stage of H. axyridis averagely by 1.4 d and decreased the adult emergence rate and fecundity by 33% and 14%, respectively, and shortened the larval stage of C. carnea averagely by 0.7 d and decreased the adult emergence rate and fecundity by 24% and 11%, respectively. Since the LD50 for green peach aphid was much lower than that for the two predaceous natural enemies, and had very low effect on the adult emergence rate and fecundity of the two predators at the concentration recommended for field spray, Bb21 could be applied as a biocontrol agent of M. persicae in the integrated management of pernicious organisms.

Use of butterflies as nontarget insect test species and the acute toxicity and hazard of mosquito control insecticides.

PubMed

Hoang, Tham C; Pryor, Rachel L; Rand, Gary M; Frakes, Robert A

2011-04-01

Honeybees are the standard insect test species used for toxicity testing of pesticides on nontarget insects for the U.S. Environmental Protection Agency (U.S. EPA) under the Federal Insecticide Fungicide and Rodenticide Act (FIFRA). Butterflies are another important insect order and a valued ecological resource in pollination. The current study conducted acute toxicity tests with naled, permethrin, and dichlorvos on fifth larval instar (caterpillars) and adults of different native Florida, USA, butterfly species to determine median lethal doses (24-h LD50), because limited acute toxicity data are available with this major insect group. Thorax- and wing-only applications of each insecticide were conducted. Based on LD50s, thorax and wing application exposures were acutely toxic to both caterpillars and adults. Permethrin was the most acutely toxic insecticide after thorax exposure to fifth instars and adult butterflies. However, no generalization on acute toxicity (sensitivity) of the insecticides could be concluded based on exposures to fifth instars versus adult butterflies or on thorax versus wing exposures of adult butterflies. A comparison of LD50s of the butterflies from this study (caterpillars and adults) with honeybee LD50s for the adult mosquito insecticides on a µg/organism or µg/g basis indicates that several butterfly species are more sensitive to these insecticides than are honeybees. A comparison of species sensitivity distributions for all three insecticides shows that permethrin had the lowest 10th percentile. Using a hazard quotient approach indicates that both permethrin and naled applications in the field may present potential acute hazards to butterflies, whereas no acute hazard of dichlorvos is apparent in butterflies. Butterflies should be considered as potential test organisms when nontarget insect testing of pesticides is suggested under FIFRA. Copyright © 2011 SETAC.

Effectiveness of donepezil, rivastigmine, and (+/-)huperzine A in counteracting the acute toxicity of organophosphorus nerve agents: comparison with galantamine.

PubMed

Aracava, Yasco; Pereira, Edna F R; Akkerman, Miriam; Adler, Michael; Albuquerque, Edson X

2009-12-01

Galantamine, a centrally acting cholinesterase (ChE) inhibitor and a nicotinic allosteric potentiating ligand used to treat Alzheimer's disease, is an effective and safe antidote against poisoning with nerve agents, including soman. Here, the effectiveness of galantamine was compared with that of the centrally active ChE inhibitors donepezil, rivastigmine, and (+/-)huperzine A as a pre- and/or post-treatment to counteract the acute toxicity of soman. In the first set of experiments, male prepubertal guinea pigs were treated intramuscularly with one of the test drugs and 30 min later challenged with 1.5 x LD(50) soman (42 microg/kg s.c.). All animals that were pretreated with galantamine (6-8 mg/kg), 3 mg/kg donepezil, 6 mg/kg rivastigmine, or 0.3 mg/kg (+/-)huperzine A survived the soman challenge, provided that they were also post-treated with atropine (10 mg/kg i.m.). However, only galantamine was well tolerated. In subsequent experiments, the effectiveness of specific treatment regimens using 8 mg/kg galantamine, 3 mg/kg donepezil, 6 mg/kg rivastigmine, or 0.3 mg/kg (+/-)huperzine A was compared in guinea pigs challenged with soman. In the absence of atropine, only galantamine worked as an effective and safe pretreatment in animals challenged with 1.0 x LD(50) soman. Galantamine was also the only drug to afford significant protection when given to guinea pigs after 1.0 x LD(50) soman. Finally, all test drugs except galantamine reduced the survival of the animals when administered 1 or 3 h after the challenge with 0.6 or 0.7 x LD(50) soman. Thus, galantamine emerges as a superior antidotal therapy against the toxicity of soman.

Lethal Effects of Lambda-Cyhalothrin and Demand® CS on Asian Longhorned Beetle, Anoplophora glabripennis (Coleoptera: Cerambycidae): Implications for Population Suppression, Tree Protection, Eradication and Containment

USDA-ARS?s Scientific Manuscript database

We evaluated the 24h contact toxicity of lambda-cyhalothrin for adult Asian longhorned beetle, Anoplophora glabripennis Motschulsky, using topical application. Results showed that beetles are sensitive to lambda-cyhalothrin: the LD50 and LD90 were 0.13639 and 0.78461µg/beetle, respectively. Residual...

Differences in susceptibility of inbred mice to Bacillus anthracis.

PubMed Central

Welkos, S L; Keener, T J; Gibbs, P H

1986-01-01

Animal species differ in their resistance both to infection by Bacillus anthracis and to anthrax toxin. A mouse model was developed to study the basis of the host differences and the pathogenesis of infection. When mice were infected with the virulent B. anthracis strain Vollum 1B, low 50% lethal dose (LD50) values (5 to 30 spores) were found for all 10 strains of inbred mice tested. However, analysis of time-to-death data revealed significant differences among the strains, which could be divided into three groups: most susceptible (A/J and DBA/2J); least susceptible (CBA/J, BALB/cJ, and C57BR/cdJ); and intermediate (the remaining five strains). In contrast, the mice were distinctly susceptible or resistant to lethal infection by the toxigenic, nonencapsulated Sterne vaccine strain. The LD50 for the susceptible A/J and DBA/2J mice was approximately 10(3) spores of the Sterne strain, whereas the remaining eight relatively resistant strains were killed only by 10(6) or more spores. F1 hybrid and backcross studies suggested that resistance to the Sterne strain is determined by a single dominant gene or gene complex. Mice lethally infected with B. anthracis showed an acute course of infection, characterized by extensive gelatinous edema and large concentrations of bacilli in the blood and organs (e.g., 10(9) CFU/g of spleen). The susceptibility of A/J and CBA/J mice to intravenously injected anthrax toxin components appeared to differ from their susceptibility to infection. The toxin LD50 values for both strains were similar. However, CBA/J mice died sooner than did A/J mice, with mean time to death of 0.9 and 3.7 days, respectively, in mice given 4 LD50 of toxin. The mouse model appears to be useful in studies on host resistance to anthrax and on the pathogenesis of the infection. PMID:3081444

EFFECTS OF WHOLE-BODY X IRRADIATION ON THE PRINCIPLE CHEMICAL CONSTITUENTS OF GUINEA-PIG LIVER (in French)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lartique, O.

1960-01-01

In the guinea pig, the LD/sub 50/30/ varies according to the type of vegetables fed in the diet. Following whole body irradiation to a LD/sub 50/30/, deposition of excess neutral fat occurs in the central zone of the liver lobule at the time of the acute phase of the radiation syndrome. A drop in liver glycogen and an increase in liver water are observed concomitantly. These changes are abscopal and transitory effects of x radiation on the liver. X-ray anemia alone is unable to produce a fatty liver in the guinea pig. (auth)

[Acute toxicity of bemithyl and bromithyl].

PubMed

Bugaeva, L I; Spasov, A A; Verovskiĭ, V E; Iezhitsa, I N

2000-01-01

The experiments on rats showed for bemithyl LD50 = 581.48 (350.17-965.57) mg/kg and for bromithyl LD50 = 1750.30 (1463.07-2093.92) mg/kg (males) and 1584.29 (1280.46-1960.22) mg/kg (females). The therapeutic ratios are 4-6 for both drugs, while the toxicity index is 10-15 for bemithyl and 20 <196> 22 for bromithyl. It was established that ergotropic effects prevail in the toxicity of bemithyl administered in the 20-80 mg/kg dose range, while trophotropic effects are dominating at doses above 100 mg/kg. Bromithyl exhibits a dose-dependent trophotropic effect in the entire dose range.

Live Bacterial Physiology Visualized with 5 nm Resolution Using Scanning Transmission Electron Microscopy.

PubMed

Kennedy, Eamonn; Nelson, Edward M; Tanaka, Tetsuya; Damiano, John; Timp, Gregory

2016-02-23

It is now possible to visualize at nanometer resolution the infection of a living biological cell with virus without compromising cell viability using scanning transmission electron microscopy (STEM). To provide contrast while preserving viability, Escherichia coli and P1 bacteriophages were first positively stained with a very low concentration of uranyl acetate in minimal phosphate medium and then imaged with low-dose STEM in a microfluidic liquid flow cell. Under these conditions, it was established that the median lethal dose of electrons required to kill half the tested population was LD50 = 30 e(-)/nm(2), which coincides with the disruption of a wet biological membrane, according to prior reports. Consistent with the lateral resolution and high-contrast signal-to-noise ratio (SNR) inferred from Monte Carlo simulations, images of the E. coli membrane, flagella, and the bacteriophages were acquired with 5 nm resolution, but the cumulative dose exceeded LD50. On the other hand, with a cumulative dose below LD50 (and lower SNR), it was still possible to visualize the infection of E. coli by P1, showing the insertion of viral DNA within 3 s, with 5 nm resolution.

Target-Specificity in Scorpions; Comparing Lethality of Scorpion Venoms across Arthropods and Vertebrates

PubMed Central

Vargas-Muñoz, Leidy J.

2017-01-01

Scorpions use their venom in defensive situations as well as for subduing prey. Since some species of scorpion use their venom more in defensive situations than others, this may have led to selection for differences in effectiveness in defensive situations. Here, we compared the LD50 of the venom of 10 species of scorpions on five different species of target organisms; two insects and three vertebrates. We found little correlation between the target species in the efficacy of the different scorpion venoms. Only the two insects showed a positive correlation, indicating that they responded similarly to the panel of scorpion venoms. We discuss the lack of positive correlation between the vertebrate target species in the light of their evolution and development. When comparing the responses of the target systems to individual scorpion venoms pairwise, we found that closely related scorpion species tend to elicit a similar response pattern across the target species. This was further reflected in a significant phylogenetic signal across the scorpion phylogeny for the LD50 in mice and in zebrafish. We also provide the first mouse LD50 value for Grosphus grandidieri. PMID:28976932

Contact Toxicity and Repellency of the Main Components From the Essential Oil of Clausena anisum-olens Against Two Stored Product Insects.

PubMed

You, Chun Xue; Jiang, Hai Yan; Zhang, Wen Juan; Guo, Shan Shan; Yang, Kai; Lei, Ning; Ma, Ping; Geng, Zhu Feng; Du, Shu Shan

2015-01-01

The essential oil of Clausena anisum-olens (Blanco) Merr. showed strong contact toxicity and repellency against Lasioderma serricorne and Liposcelis bostrychophila adults. The components of the essential oil obtained by hydrodistillation were determined by gas chromatography-mass spectrometry. It was found that the main components were myristicin (36.87%), terpinolene (13.26%), p-cymene-8-ol (12.38%), and 3-carene (3.88%). Myristicin and p-cymene-8-ol were separated by silica gel column chromatography, and their molecular structures were confirmed by means of physicochemical and spectrometric analysis. Myristicin and p-cymene-8-ol showed strong contact toxicity against L. serricorne (LD50 = 18.96 and 39.68 μg per adult) and Li. bostrychophila (LD50 = 20.41 and 35.66 μg per adult). The essential oil acting against the two grain storage insects showed LD50 values of 12.44 and 74.46 μg per adult, respectively. Myristicin and p-cymene-8-ol have strong repellent toxicity to Li. bostrychophila. © The Author 2015. Published by Oxford University Press on behalf of the Entomological Society of America.

Neurotoxicity of Micrurus altirostris (Uruguayan coral snake) venom and its neutralization by commercial coral snake antivenom and specific antiserum raised in rabbits.

PubMed

de Abreu, Valdemir Aparecido; Leite, Gildo Bernardo; Oliveira, Caroline Borja; Hyslop, Stephen; Furtado, Maria de Fatima Domingos; Simioni, Lea Rodrigues

2008-07-01

In this work, we studied the neuromuscular blockade caused by Micrurus altirostris venom (0.1-10 microg/mL) in indirect stimulated chick biventer cervicis and mouse phrenic nerve-diaphragm preparations and the ability of commercial antivenom (Instituto Butantan) and antiserum raised in rabbits to neutralize neurotoxicity and lethality in chicks and mice (LD(50) 0.042 and 0.255 mg/kg), injected i.m. and i.p., respectively, with venom (5 LD(50)):antivenom or antiserum mixtures (n = 6) of 1:1-1:2.5-1:5-1:10-1:20. The venom caused a complete and irreversible neuromuscular blockade in both preparations, inhibited the acetylcholine and carbachol contractures, without interfering on KCl response. The neuromuscular blockade was not Ca(2+) or temperature-dependent and did not affect the response to direct stimulation. Only a venom:antivenom or antiserum ratio of 1:20 neutralized the neuromuscular blockade in vitro and protected chicks and mice against 5 LD(50) of venom. Our results indicated that Micrurus altirostris venom interferes with postsynaptic neurotransmission and that commercial antivenom and rabbit antiserum have low efficacy in neutralizing the neurotoxicity and lethality of this venom.

Sensitivity of some nitrogen fixers and the target pest Fusarium oxysporum to fungicide thiram.

PubMed

Osman, Awad G; Sherif, Ashraf M; Elhussein, Adil A; Mohamed, Afrah T

2012-03-01

This study was carried out to investigate the toxic effects of the fungicide thiram (TMTD) against five nitrogen fixers and the thiram target pest Fusarium oxysporum under laboratory conditions. Nitrogen fixing bacteria Falvobacterium showed the highest values of LD(50) and proved to be the most resistant to the fungicide followed by Fusarium oxysporum, while Pseudomonas aurentiaca was the most affected microorganism. LD(50) values for these microorganisms were in 2-5 orders of magnitude lower in comparison with LD(50) value for Fusarium oxysporum. Thiram was most toxic to Pseudomonas aurentiaca followed by Azospirillum. The lowest toxicity index was recorded for Fusarium oxysporum and Flavobacterium. The slope of the curve for Azomonas, Fusarium oxysporum and Flavobacterium is more steep than that of the other curves, suggesting that even a slight increase of the dose of the fungicide can cause a very strong negative effect. Thiram was more selective to Pseudomonas aurentiaca followed by Azospirillum, Rhizobium meliloti and Azomonas. The lowest selectivity index of the fungicide was recorded for Falvobacterium followed by Fusarium oxysporum. The highest safety coefficient of the fungicide was assigned for Flavobacterium, while Pseudomonas aurentiaca showed the lowest value.

Comparison of intestine and bone marrow radiosensitivity of the BALB/c and the C57BL/6 mouse strains and their B6CF1 offspring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hanson, W.R.; Fry, R.J.; Sallese, A.R.

1987-06-01

The radiosensitivity as measured by LD50/6 or LD50/30 of the F1 hybrid B6CF1 (C57BL/6 X BALB/c) is similar to that of C57BL/6 mice but markedly different from BALB/c. The LD50/6 for BALB/c mice was about 8.8 Gy compared to 16.4 Gy for the B6CF1. The difference in LD50/6 between the parent strains or between BALB/c and the F1 hybrid could not be explained by any differences in crypt cell number, cell cycle time, or transit time. Likewise, the observed differences in the LD50/6 do not appear to result from marked differences in the radiosensitivity of marrow stem cells (CFU-S) sincemore » the D0's for the three genotypes of mice were similar. Also, there were no apparent differences in the red blood cell contents of several enzymes associated with antioxidant defenses. The microcolony assay was used to determine the D0 for the crypt clonogenic cells and the D0 values for 60Co gamma rays were about 0.8 Gy for BALB/c mice and 1.4 Gy for B6CF1 mice. However, the D0 values for JANUS fission neutrons were similar; 0.6 Gy for the BALB/c mice and 0.5 for the B6CF1 mice. A comparison of clonogenic cell kinetics, using prolonged colcemid block to distinguish between slowly and rapidly cycling cells suggest that, normally, the stem cells are slowly cycling in both the BALB/c and the B6CF1 hybrid. However, the stem cells of the B6CF1 appear to go into rapid cell cycle more rapidly than those of the BALB/c following irradiation or prolonged colcemid treatment. The more rapid recovery in intestinal epihelial cell production in the B6CF1 hybrid after irradiation may provide an increased mucosal barrier and may, in part, explain the difference in the response to radiation compared to that in the BALB/c.« less

Radioprotection in depressed metabolic states: The physiology of helium-cold hypothermia

NASA Technical Reports Server (NTRS)

Musacchia, X. J.

1973-01-01

The use of hypothermia as a means of radiation protection was studied on a variety of mammals exposed to 80% helium-20% oxygen atmospheres at low ambient temperatures. Results show that the LD for normothermic animals significantly increased compared with hypothermic animals; similar results were obtained for hibernating mammalians. Pre-exposure of animals to cold temperatures increased their ability to withstand radiation levels close to LD sub 50.

Toxicological deteriorations of two volatile oils of Matricaria chamomilla and Clerodendron inerme on the adult house fly Musca domestica L.

PubMed

Shoukry, I F

1997-12-01

The adult stage of the house fly Musca domestica L. was treated topically with the sublethal doses of LD25, LD50 and LD75 of chamomile, Matricaria chamomilla L. flowers and jasmine, Clerodendron inerme G. leaves oils. Various biological activities of adult stage as well as the amino acids of the treated adults ovaries were determined. Amino acids determinations were achieved on newly emerged flies and on the three and four days old flies. The LD50s. of 76 and 84 ug/fly of the two oils were used for Matricaria chamomilla and Clerodendron inerme oil, respectively. Treatment with the two volatile oils induced serious effects on the biology and biotic potential of Musca domestica. Treatment was significantly increased the acidic and the aromatic amino acids during oogenesis. In contrast the quantity of aliphatic amino acids was significantly decreased while the hydroxy amino acids have inconsistent results. The hydroxy amino acids were remarkably increased in the ovaries during three days of development, and then decreased in the fourth day. Moreover, the concentration of basic and the sulfur amino acids were varied with the two treatments and the amino acid was completely disappeared in the ovaries of the treated flies.

Toxicity of Imidacloprid to the Stingless Bee Scaptotrigona postica Latreille, 1807 (Hymenoptera: Apidae).

PubMed

Soares, Hellen Maria; Jacob, Cynthia Renata Oliveira; Carvalho, Stephan Malfitano; Nocelli, Roberta Cornélio Ferreira; Malaspina, Osmar

2015-06-01

The stingless bee Scaptotrigona postica is an important pollinator of native and cultivated plants in Brazil. Among the factors affecting the survival of these insects is the indiscriminate use of insecticides, including the neonicotinoid imidacloprid. This work determined the toxicity of imidacloprid as the topical median lethal dose (LD50) and the oral median lethal concentration (LC50) as tools for assessing the effects of this insecticide. The 24 and 48 h LD50 values were 25.2 and 24.5 ng of active ingredient (a.i.)/bee, respectively. The 24 and 48 h LC50 values were 42.5 and 14.3 ng a.i./µL of diet, respectively. Ours results show the hazard of imidacloprid and the vulnerability of stingless bees to it, providing relevant toxicological data that can used in mitigation programs to ensure the conservation of this species.

Risk of Disabling Response Fluctuations and Dyskinesias for Dopamine Agonists Versus Levodopa in Parkinson's Disease.

PubMed

Haaxma, Charlotte A; Horstink, Martin W I M; Zijlmans, Jan C; Lemmens, Wim A J G; Bloem, Bastiaan R; Borm, George F

2015-01-01

Response fluctuations and dyskinesias develop during the use of both levodopa (LD) and dopamine agonists (DA), but may not be equally disabling. To compare the risk and time of onset of disabling response fluctuations and dyskinesias (DRFD) among patients with Parkinson's disease (PD) who were initially treated with either LD or DA. Open cohort study of all consecutive de-novo PD patients in routine clinical practice, included over a period of 15 years (median follow-up: 8.1 years, range 1.1-17.7), since embarking on LD or DA. Older patients and patients with more severe PD were started on LD (n = 77), younger patients on a DA (n = 50). Therapy was adjusted according to generally accepted guidelines. The primary endpoints were: the onset of response fluctuations, dyskinesias, and the moment when these complications became disabling (DRFD). LD-starters developed response fluctuations 0.8 years earlier than DA-starters (p = 0.07), while dyskinesias appeared around 2.5 years earlier (p = 0.003). However, the risk and time of onset of DRFD did not differ statistically between the groups (LD-starters: 60% , median interval 7.3 years, DA-starters: 52% , 6.1 years, p = 0.63). DA-starters displayed a 0.19 points lower adjusted mean improvement in motor scores than LD-starters (p = 0.002). Adjustments for age and severity of PD at start of dopaminergic therapy did not change these results. In routine clinical practice, the risk and time of onset of DRFD is comparable for LD-starters versus DA-starters, but motor functioning is worse in DA-starters. These results support the use of LD as initial therapy for PD.

The effect of amphipilic lignin derivatives addition on enzymatic hydrolysis performance of kraft pulp from sorghum bagasse

NASA Astrophysics Data System (ADS)

Fatriasari, Widya; Nugroho Adi, D. T.; Laksana, R. P. B.; Fajriutami, T.; Raniya, R.; Ghozali, M.; Hermiati, E.

2018-03-01

Previously, the chemical characteristics of isolated lignin from Acacia mangium black liquor of kraft pulping was characterized. This lignin was blended with natural rubber latex (NR-L) as adhesive in laminated wood. In addition, lignin has potency for biosurfactant materials by modification of the hydrophobic into hydrophilic properties. Therefore, this study was intended to develop lignin as material for amphipilic lignin derivatives (A-LD) biosurfactant by reacting lignin with epoxilated polyethylene glicol (PEG). A-LD addition in slurries was used to improve the enzymatic hydrolysis (EH) of kraft pulp sweet bagasse sorghum (SSB). The main observation in EH performance was to investigate the effect of lignin isolation method (one and two step) in A-LD and A-LD loading addition on reducing sugar yield (RSY) of SSB kraft pulp. The pulp was hydrolyzed at 50°C and 150 rpm for 72 h with 10 FPU cellulase loading in the shaking incubator. A-LD from one (L1S) and two step (L2S) lignin was added with A-LD loading of 0, 1, 2, 5, and 10% (b/v). The RSY of hydrolyzate has been observed after EH. A-LDs addition in EH of SSB kraft pulp enhanced RSY. L1S worked better in reaction performance with PEDGE compared to L2S and LS. A better performance was showed by PEDGE 500 than that of PEDGE 6000. Generally, the higher A-LDs loading resulted higher RSY. The highest RSY (81.33%) was resulted in addition of 10% A-LD L1S using PEDGE 500. A 5% A-LD loading was more considered to be added in EH because the RSY was comparable with 10% A-LD loading.

Safety of methionine, a novel biopesticide, to adult and larval honey bees (Apis mellifera L.).

PubMed

Weeks, Emma N I; Schmehl, Daniel R; Baniszewski, Julie; Tomé, Hudson V V; Cuda, James P; Ellis, James D; Stevens, Bruce R

2018-03-01

Methionine is an essential/indispensible amino acid nutrient required by adult and larval honey bees (Apis mellifera L. [Hymenoptera: Apidae]). Bees are unable to rear broods on pollen deficient in methionine, and reportedly behaviorally avoid collecting pollen or nectar from florets deficient in methioinine. In contrast, it has been demonstrated that methionine is toxic to certain pest insects; thus it has been proposed as an effective biopesticide. As an ecofriendly integrated pest management agent, methionine boasts a novel mode of action differentiating it from conventional pesticides, while providing non-target safety. Pesticides that minimize collateral effects on bees are desirable, given the economic and ecological concerns about honey bee health. The aim of the present study was to assess the potential impact of the biopesticide methionine on non-target adult and larval honey bees. Acute contact adult toxicology bioassays, oral adult assessments and chronic larval toxicity assessments were performed as per U.S. Environmental Protection Agency (EPA) requirements. Our results demonstrated that methionine fits the U.S. EPA category of practically nontoxic (i.e. lethal dose to 50% mortality or LD 50 > 11µg/bee) to adult honey bees. The contact LD 50 was > 25µg/bee and the oral LD 50 was > 100µg/bee. Mortality was observed in larval bees that ingested DL-methionine (effective concentration to 50% mortality or EC 50 560µg/bee). Therefore, we conclude that methionine poses little threat to the health of the honey bee, due to unlikely exposure at concentrations shown to elicit toxic effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of Systemic Toxicity between Botulinum Toxin Subtypes A1 and A2 in Mice and Rats.

PubMed

Torii, Yasushi; Goto, Yoshitaka; Nakahira, Shinji; Kozaki, Shunji; Kaji, Ryuji; Ginnaga, Akihiro

2015-06-01

The adverse events caused by botulinum toxin type A (subtype A1) product, thought to be after-effects of toxin diffusion after high-dose administration, have become serious issues. A preparation showing less diffusion in the body than existing drugs has been sought. We have attempted to produce neurotoxin derived from subtype A2 (A2NTX) with an amino acid sequence different from that of neurotoxin derived from subtype A1 (A1NTX). In this study, to investigate whether A2NTX has the potential to resolve these issues, we compared the safety of A2NTX, a progenitor toxin derived from subtype A1 (A1 progenitor toxin) and A1NTX employing the intramuscular lethal dose 50% (im LD50) in mice and rats and the compound muscle action potential (CMAP) in rats. Mouse im LD50 values for A1 progenitor toxin and A2NTX were 93 and 166 U/kg, respectively, and the rat im LD50 values were 117 and 153 U/kg, respectively. In the rat CMAP test, the dose on the contralateral side, which caused a 50% reduction in the CMAP amplitude, that is, CMAP-TD50 , was calculated as 19.0, 16.6 and 28.7 U/kg for A1 progenitor toxin, A1NTX and A2NTX, respectively. The results indicate that A2NTX is safer than A1 progenitor toxin and A1NTX. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Inorganic and organic mercury chloride toxicity to Coturnix: Sensitivity related to age and quantal assessment of physiologic responses

USGS Publications Warehouse

Hill, E.F.

1982-01-01

The toxicities of mercuric chloride (HgCl(,2)) and methylmercuric chloride (CH(,3)HgCl) were compared for coturnix (Coturnix coturnix japonica) from hatching to adulthood. Comparisons were based on: (1) Median lethal dosages (LD50) derived by administering single peroral and single intramuscular dosages of mercury, (2) median lethal concentrations (LC50) derived by feeding mercury for 5 days, (3) median toxic concentrations (TC50) derived by feeding mercury 9 weeks and measuring plasma enzyme activity, plasma electrolytes, and other blood constituents, and (4) transient changes of various blood chemistries following a single peroral dose of mercury. Acute peroral and intramuscular LD50s for HgCl(,2) and CH(,3)HgCl increased by two- to threefold for coturnix chicks from hatching to 4 weeks of age. Concomitantly, the LC50s also increased, but the important difference between test procedures was that with both single dose routes of exposure the toxicity ratios, i.e., HgCl(,2)/CH(,3)HgCl, at each age were about 2 to 2.5 compared to about 100 for the LC50s. For example, at 2 weeks of age the peroral LD50s for HgCl(,2) and CH(,3)HgCl were 42 and 18 mg/kg; the dietary LC50s were 5086 and 47 ppm for HgCl(,2) and CH(,3)HgCl. The 9 week feeding trial was not associated with gross effects from either HgCl(,2) at 0.5 to 32 ppm or CH(,3)HgCl at 0.125 to 8 ppm. However, subtle responses were detected for the plasma enzymes aspartate aminotransferase, lactate dehydrogenase, and ornithine carbamoyl transferase and could be quantified by probit analysis. This quantal procedure was based on establishment of a normal value for each enzyme and classing outliers as respondents. A 'hazard index' based on the TC50 for an enzyme divided by the LD50 or LC50 was introduced. The single oral dosages of HgCl(,2) and CH(,3)HgCl showed that ratios of alanine aminotransferase, lactate dehydrogenase, and orinthine carbamoyl transferase for the liver and kidneys of adult coturnix were opposite from that accepted for mammals. It was concluded that a chronic study of sublethal responses of young birds should be required in addition to the current toxicity screens used for regulatory purposes.

Inorganic and organic mercury chloride toxicity to Coturnix: sensitivity related to age and quantal assessment of physiologic responses

USGS Publications Warehouse

Hill, E.F.

1981-01-01

The toxicities of mercuric chloride (HgCl(,2)) and methylmercuric chloride (CH(,3)HgCl) were compared for coturnix (Coturnix coturnix japonica) from hatching to adulthood. Comparisons were based on: (1) Median lethal dosages (LD50) derived by administering single peroral and single intramuscular dosages of mercury, (2) median lethal concentrations (LC50) derived by feeding mercury for 5 days, (3) median toxic concentrations (TC50) derived by feeding mercury 9 weeks and measuring plasma enzyme activity, plasma electrolytes, and other blood constituents, and (4) transient changes of various blood chemistries following a single peroral dose of mercury. Acute peroral and intramuscular LD50s for HgCl(,2) and CH(,3)HgCl increased by two- to threefold for coturnix chicks from hatching to 4 weeks of age. Concomitantly, the LC50s also increased, but the important difference between test procedures was that with both single dose routes of exposure the toxicity ratios, i.e., HgCl(,2)/CH(,3)HgCl, at each age were about 2 to 2.5 compared to about 100 for the LC50s. For example, at 2 weeks of age the peroral LD50s for HgCl(,2) and CH(,3)HgCl were 42 and 18 mg/kg; the dietary LC50s were 5086 and 47 ppm for HgCl(,2) and CH(,3)HgCl. The 9 week feeding trial was not associated with gross effects from either HgCl(,2) at 0.5 to 32 ppm or CH(,3)HgCl at 0.125 to 8 ppm. However, subtle responses were detected for the plasma enzymes aspartate aminotransferase, lactate dehydrogenase, and ornithine carbamoyl transferase and could be quantified by probit analysis. This quantal procedure was based on establishment of a normal value for each enzyme and classing outliers as respondents. A 'hazard index' based on the TC50 for an enzyme divided by the LD50 or LC50 was introduced. The single oral dosages of HgCl(,2) and CH(,3)HgCl showed that ratios of alanine aminotransferase, lactate dehydrogenase, and orinthine carbamoyl transferase for the liver and kidneys of adult coturnix were opposite from that accepted for mammals. It was concluded that a chronic study of sublethal responses of young birds should be required in addition to the current toxicity screens used for regulatory purposes.

Desiccation and Mortality Dynamics in Seedlings of Different European Beech (Fagus sylvatica L.) Populations under Extreme Drought Conditions.

PubMed

Bolte, Andreas; Czajkowski, Tomasz; Cocozza, Claudia; Tognetti, Roberto; de Miguel, Marina; Pšidová, Eva; Ditmarová, Ĺubica; Dinca, Lucian; Delzon, Sylvain; Cochard, Hervè; Ræbild, Anders; de Luis, Martin; Cvjetkovic, Branislav; Heiri, Caroline; Müller, Jürgen

2016-01-01

European beech (Fagus sylvatica L., hereafter beech), one of the major native tree species in Europe, is known to be drought sensitive. Thus, the identification of critical thresholds of drought impact intensity and duration are of high interest for assessing the adaptive potential of European beech to climate change in its native range. In a common garden experiment with one-year-old seedlings originating from central and marginal origins in six European countries (Denmark, Germany, France, Romania, Bosnia-Herzegovina, and Spain), we applied extreme drought stress and observed desiccation and mortality processes among the different populations and related them to plant water status (predawn water potential, ΨPD) and soil hydraulic traits. For the lethal drought assessment, we used a critical threshold of soil water availability that is reached when 50% mortality in seedling populations occurs (LD50SWA). We found significant population differences in LD50SWA (10.5-17.8%), and mortality dynamics that suggest a genetic difference in drought resistance between populations. The LD50SWA values correlate significantly with the mean growing season precipitation at population origins, but not with the geographic margins of beech range. Thus, beech range marginality may be more due to climatic conditions than to geographic range. The outcome of this study suggests the genetic variation has a major influence on the varying adaptive potential of the investigated populations.

Microstructure and Ultrastructure Alterations in the Pallium of Immature Mice Exposed to Cadmium.

PubMed

Yang, X F; Han, Q G; Liu, D Y; Zhang, H T; Fan, G Y; Ma, J Y; Wang, Z L

2016-11-01

The aim of this study was to investigate microstructure and ultrastructure alterations in the pallium of immature mice exposed to cadmium. Forty immature mice were randomly divided into control, 1/100 LD 50 (1.87 mg/kg, low), 1/50 LD 50 (3.74 mg/kg, medium), and 1/25 LD 50 (7.48 mg/kg, high) dose groups. After oral cadmium exposure for 40 days, the pallium of mice was obtained for microstructure and ultrastructure studies. The results showed that both microstructure and ultrastructure alterations of the pallium were observed in all treated mice and the most obvious alterations were in the high dose group. Microstructural analysis showed seriously congested capillary in the pia mater of the pallium in the high cadmium group. Meanwhile, vacuolar degenerate or karyopyknosis presented in some neurocytes, capillary quantity, and the number of apoptotic cells increased, some neurocytes became hypertrophy, the pia mater separated from the cortex, and local hemorrhage and accompanied inflammatory cell infiltration were also observed. Ultrastructural analysis showed that rough endoplasmic reticulum was expanded, heterochromatin marginalized, perinuclear space distinctly broadened, swelling and vacuolization mitochondria appeared, synapse was swelling, presynaptic and postsynaptic membranes presented fusion, and most of mitochondrial cristae were ambiguous. The results indicated that cadmium exposure for 40 days induced dose-dependent microstructure and ultrastructure alterations in pallium of immature mice.

Orthene? toxicity to little brown bats (Myotis lucifugus): Acetylcholinesterase inhibition, coordination loss, and mortality

USGS Publications Warehouse

Clark, D.R.; Rattner, B.A.

1987-01-01

The 24-h LD50 of Orhene (active ingredient acephate, acetylphosphoramidothioic acid o,s-dimethyl ester, CAS 30560-19-1) to little brown bats (Myotis lucifugus) was high (> 1,500 mg acephate/kg) and at least several times greater than the LD50 for mice (Mus musculus) (720 mg/kg). Twenty-four hours after dosing, all surviving mice appeared behaviorally normal, but 9 of 30 surviving bats could not right themselves when placed on their backs. When dead and incapacitated bats were combined to calculate an ED50 (median effective dose), the resultant estimate (687 mg/kg) did not differ (p > 0.05) from the LD50 for mice. Serum cholinesterase (ChE) activity in control bats was 3.2 times greater than in mice. The relationship between the naturally high level of ChE and the relative tolerance of bats to organophosphorus insecticides is unexplained. Toxicity of Orthene was clearly less than that reported elsewhere for methyl parathion (phosphorothioic acid o,o-dimethyl o-[4-nitrophenyl] ester, CAS 298-00-0). This finding may be useful in selection of a chemical for agricultural use, but conclusions about the safety of Orthene to this bat species, or to others, must remain tentative until confirmed by studies under field conditions. Because bats are long-lived with low reproductive rates and slow recruitment, any additional mortality in the wild could be critical to population survival.

Morbidity and mortality reduction by supplemental vitamin A or beta-carotene in CBA mice given total-body gamma-radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seifter, E.; Rettura, G.; Padawer, J.

Male CBA mice received graded doses (450-750 rad) of total-body gamma-radiation (TBR) from a dual-beam /sup 137/Cs irradiator. Commencing directly after TBR, 2 days later, or 6 days later, groups of mice received supplemental vitamin A (Vit A) or beta-carotene (beta-Car), compounds previously found to reduce radiation disease in mice subjected to partial-body X-irradiation. Given directly after TBR, supplemental Vit A decreased mortality, evidenced by increases in the radiation dose required to kill 50% of the mice within 30 days (LD50/30). In one experiment, Vit A increased the LD50/30 from 555 to 620 rad; in another experiment, Vit A increasedmore » the dose from 505 to 630 rad. Similarly, in a third experiment, supplemental beta-Car increased the LD50/30 from 510 to 645 rad. Additionally, each compound increased the survival times, even of those mice that died within 30 days. In addition to reduction of mortality and prolongation of survival time, supplemental Vit A moderated weight loss, adrenal gland hyperemia, thymus involution, and lymphopenia--all signs of radiation toxicity. Delaying the supplementation for 2 days after irradiation did not greatly reduce the efficacy of Vit A; however, delaying supplementation for 6 days decreased its effect almost completely.« less

Toxicity Profile of a Nutraceutical Formulation Derived from Green Mussel Perna viridis

PubMed Central

Joseph, Deepu; Chakkalakal, Selsa J.

2014-01-01

The short-term (acute) and long-term (subchronic) toxicity profile, mean lethal dose 50 (LD50), and no-observed-adverse-effect level (NOAEL) of a nutraceutical formulation developed from green mussel Perna viridis, which showed in vitro and in vivo anti-inflammatory properties, were evaluated in the present study. The formulation was administered to the male and female Wistar rats at graded doses (0.5, 1.0, and 2.5 g/kg body weight) for two weeks of acute toxicity study and 0.5, 1.0, and 2.0 g/kg body weight for 90 days in subchronic toxicity study. The LD50, variations in clinical signs, changes in body weight, body weight, food/water consumption, organ weight (liver, kidney, spleen, and brain), hematology, serum chemistry, and histopathological changes were evaluated. The LD50 of the formulation was 5,000 mg/kg BW. No test article related mortalities as well as change in body weight, and food and water consumption were observed. No toxicity related significant changes were noted in renal/hepatic function, hematological indices, and serum biochemical parameters between the control and treated groups. Histopathological alterations were not observed in the vital organs of rats. The subchronic NOAEL for the formulation in rats is greater than 2000 mg/kg. This study demonstrated that the green mussel formulation is safe to consume without any adverse effects in the body. PMID:24995298

Dermal and inhalation acute toxic class methods: test procedures and biometric evaluations for the Globally Harmonized Classification System.

PubMed

Holzhütter, H G; Genschow, E; Diener, W; Schlede, E

2003-05-01

The acute toxic class (ATC) methods were developed for determining LD(50)/LC(50) estimates of chemical substances with significantly fewer animals than needed when applying conventional LD(50)/LC(50) tests. The ATC methods are sequential stepwise procedures with fixed starting doses/concentrations and a maximum of six animals used per dose/concentration. The numbers of dead/moribund animals determine whether further testing is necessary or whether the test is terminated. In recent years we have developed classification procedures for the oral, dermal and inhalation routes of administration by using biometric methods. The biometric approach assumes a probit model for the mortality probability of a single animal and assigns the chemical to that toxicity class for which the best concordance is achieved between the statistically expected and the observed numbers of dead/moribund animals at the various steps of the test procedure. In previous publications we have demonstrated the validity of the biometric ATC methods on the basis of data obtained for the oral ATC method in two-animal ring studies with 15 participants from six countries. Although the test procedures and biometric evaluations for the dermal and inhalation ATC methods have already been published, there was a need for an adaptation of the classification schemes to the starting doses/concentrations of the Globally Harmonized Classification System (GHS) recently adopted by the Organization for Economic Co-operation and Development (OECD). Here we present the biometric evaluation of the dermal and inhalation ATC methods for the starting doses/concentrations of the GHS and of some other international classification systems still in use. We have developed new test procedures and decision rules for the dermal and inhalation ATC methods, which require significantly fewer animals to provide predictions of toxicity classes, that are equally good or even better than those achieved by using the conventional LD(50)/LC(50) methods. In order to cope with rather narrow dose/concentration classes of the GHS we have, as in our previous publications, combined the outcome of all results that can be obtained during testing for the allocation to one of the defined toxicity classes of the GHS. Our results strongly recommend the deletion of the dermal LD(50) and the inhalation LC(50) test as regulatory tests and the adoption of the dermal and inhalation ATC methods as internationally accepted alternatives.

SU-F-18C-06: Prospective Patient Evaluation of Iterative Reconstruction in Radiation Oncology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Price, R; Vance, S; Cattaneo, R

2014-06-15

Purpose: This work incorporates iterative reconstruction (IR) into a dose reduction study to characterize image quality metrics, delineation, and dosimetric assessment, with the goal of reducing imaging dose in Radiation Oncology. Methods: Three-dimensional noise power spectrum (NPS) analysis characterized noise magnitude/texture (120 kVp, 50–200 mAs, IR levels 1–6 yielding noise reduction of 0.89–0.55 compared to filtered backprojection (FBP)). Task-specific Modulation Transfer Functions (MTFtask) were characterized across varied subject contrasts. A prospective dose reduction study (500 to 150 mAs) was conducted for 12 patients (43 inter-fraction CTs) for high-dose rate brachytherapy. Three physicians performed qualitative image assessment between full-dose FBP (FD-FBP,more » 500 mAs), low-dose FBP (LD-FBP, 150–250 mAs), and low-dose IRL5-6 (LD-IR) scans for image noise, cuff/bladder interface detectability, spatial resolution, texture, and segmentation confidence. Comparisons between LD-FBP and LD-IR were conducted for the following metrics: delineation (bladder and rectum evaluated via overlap indices (OI) and Dice similarity coefficients (DSC)), noise, boundary changes, dose calculation, and digitally reconstructed radiographs (DRRs). Results: NPS showed ∼50% reduction in noise magnitude and ∼0.1 1/mm spatial frequency shift with IRL6. The largest MTFtask decrease between FBP and IR was 0.08 A.U. Qualitative patient image evaluation revealed LD-IR was equivalent or slightly worse than FD-FBP, and superior to LD-FBP for all metrics except low contrast interface and texture. The largest CT number discrepancy from FBP occurred at a bone/tissue interface using IRL6 (−1.2 ± 4.9 HU (range: −17.6 – 12.5 HU)). No significant contour differences (OIs and DSCs = 0.85 – 0.95) and dose calculation discrepancy (<0.02%) were observed. DRRs preserved anatomical detail and demonstrated <2% difference in intensity between LD-FBP and LD-IRL6. Conclusion: While phantom analysis showed slight noise texture differences with IR, patient results revealed that image quality, contouring ability, and dosimetric parameters were not adversely affected, thus support integrating IR into treatment planning. Research supported in part by a grant from Philips HealthCare.« less

Photosynthetically supplemental lighting for vegetable crop production with super-bright laser diode

NASA Astrophysics Data System (ADS)

Hu, Yongguang; Li, Pingping; Shi, Jintong

2007-02-01

Although many artificial light sources like high-pressure sodium lamp, metal halide lamp, fluorescent lamp and so on are commonly used in horticulture, they are not widely applied because of the disadvantages of unreasonable spectra, high cost and complex control. Recently new light sources of light-emitting diode (LED) and laser diode (LD) are becoming more and more popular in the field of display and illumination with the improvement of material and manufacturing, long life-span and increasingly low cost. A new type of super-bright red LD (BL650, central wavelength is 650 nm) was selected to make up of the supplemental lighting panel, on which LDs were distributed with regular hexagon array. Drive circuit was designed to power it and adjust light intensity. System performance including temperature rise and light intensity distribution under different vertical/horizontal distances were tested. Photosynthesis of sweet pepper and eggplant leaf under LD was measured with LI-6400 to show the supplemental lighting effects. The results show that LD system can supply the maximum light intensity of 180 μmol/m2 •s at the distance of 50 mm below the panel and the temperature rise is little within 1 °C. Net photosynthetic rate became faster when LD system increased light intensity. Compared with sunlight and LED supplemental lighting system, LD's promotion on photosynthesis is in the middle. Thus it is feasible for LD light source to supplement light for vegetable crops. Further study would focus on the integration of LD and other artificial light sources.

Induction of P450 genes in Nilaparvata lugens and Sogatella furcifera by two neonicotinoid insecticides.

PubMed

Yang, Yuan-Xue; Yu, Na; Zhang, Jian-Hua; Zhang, Yi-Xi; Liu, Ze-Wen

2018-06-01

Nilaparvata lugens and Sogatella furcifera are two primary planthoppers on rice throughout Asian countries and areas. Neonicotinoid insecticides, such as imidacloprid (IMI), have been extensively used to control rice planthoppers and IMI resistance consequently occurred with an important mechanism from the over-expression of P450 genes. The induction of P450 genes by IMI may increase the ability to metabolize this insecticide in planthoppers and increase the resistance risk. In this study, the induction of P450 genes was compared in S. furcifera treated with IMI and nitromethyleneimidazole (NMI), in two planthopper species by IMI lethal dose that kills 85% of the population (LD 85 ), and in N. lugens among three IMI doses (LD 15 , LD 50 and LD 85 ). When IMI and NMI at the LD 85 dose were applied to S. furcifera, the expression changes in most P450 genes were similar, including the up-regulation of nine genes and down-regulation of three genes. In terms of the expression changes in 12 homologous P450 genes between N. lugens and S. furcifera treated with IMI at the LD 85 dose, 10 genes had very similar patterns, such as up-regulation in seven genes, down-regulation in one gene and no significant changes in two genes. When three different IMI doses were applied to N. lugens, the changes in P450 gene expression were much different, such as up-regulation in four genes at all doses and dose-dependent regulation of the other nine genes. For example, CYP6AY1 could be induced by all IMI doses, while CYP6ER1 was only up-regulated by the LD 50 dose, although both genes were reported important in IMI resistance. In conclusion, P450 genes in two planthopper species showed similar regulation patterns in responding to IMI, and the two neonicotinoid insecticides had similar effects on P450 gene expression, although the regulation was often dose-dependent. © 2017 Institute of Zoology, Chinese Academy of Sciences.

Radiation dose in neoadjuvant chemoradiation therapy for esophageal cancer: patterns of care and outcomes from the National Cancer Data Base.

PubMed

Haque, Waqar; Verma, Vivek; Butler, E Brian; Teh, Bin S

2018-02-01

Neoadjuvant chemoradiotherapy (CRT) for locally advanced esophageal cancer (EC) may utilize a wide variety of RT doses, without clear consensus to date. This study evaluated national practice patterns between lower dose (LD) (40-41.4 Gy) or higher dose (HD) (50-50.4 Gy) therapy, in addition to differences in survival and postoperative events. The National Cancer Data Base (NCDB) was queried [2004-2013] for patients with newly-diagnosed cT1a-T4aN0/N+M0 EC that received neoadjuvant CRT followed by esophagectomy. Multivariable logistic regression determined factors predictive of receiving LD RT. Kaplan-Meier analysis evaluated overall survival (OS), and Cox proportional hazards modeling determined variables associated with OS. Propensity score matching assessed groups in a balanced manner while reducing indication biases. Altogether, 5,025 patients met inclusion criteria; 257 (5%) received LD RT, while 4,768 (95%) received HD RT. LD RT was more likely delivered at academic centers (P=0.038), in more recent years (2009-2013, P=0.011), and to squamous cell carcinomas (P=0.001). HD RT tended to be administered with higher T stage as well as node-positive disease (P<0.05). The median OS in the LD and HD cohorts was 39.0 vs. 35.6 months (P=0.072), and 39.0 vs. 42.7 months after propensity matching (P=0.812). Dose did not independently correlate with OS on multivariate analysis (P=0.069), but treatment at academic centers correlated with improved OS (P=0.028). There were no differences between groups in the rates of 30-day readmission (P=0.182), 30-day mortality (P=0.314), or length of postoperative hospital stay (P=0.665), but the LD group experienced lower 90-day mortality (P=0.007). Although neoadjuvant LD CRT has been underutilized for EC in the United States, it is rising in more recent years. Dose did not significantly impact survival before or after propensity matching, nor did it independently predict for survival. Treatment at academic facilities independently correlated with higher survival, which has implications for patient counseling.

Semiconductor laser applications in rheumatology

NASA Astrophysics Data System (ADS)

Pascu, Mihail-Lucian; Suteanu, S.

1996-01-01

Two types of laser diode (LD) based equipment for rheumatology are introduced. The first is a portable device which contains single LD emitting at 890 nm laser pulses (time full width 100 nsec) of reprate tunable within (0.5 - 1.5) kHz; the laser beam average power is 0.7 mW at 1 kHz reprate. The second is computer controlled, contains one HeNe laser and 5 LD allowing 6 modes of patient irradiation (placebo effect evaluation included). HeNe laser works in cw at 632.8 nm; the LD works each as described for the portable equipment. HeNe and LD beams are superposed so that HeNe laser spot in the irradiation plane has a 60 mm diameter and the LD spots covers a 50 mm diameter disc centered on the HeNe laser spot. Clinical applications using the second type of equipment are reported; 1287 patients were treated between October 1991 and October 1994. Female/male ratio was 4:1 and their age distribution was between 18 and 85 years. The average number of exposures was 10 and the mean exposure time was 7 minutes. Studies were made on the treatment of rheumatoid arthritis, seronegative arthritis, degenerative joint diseases, abarticular rheumatism, osteoporosis pain and pains and edema after fractures.

Detection-gap-independent optical sensor design using divergence-beam-controlled slit lasers for wearable devices

NASA Astrophysics Data System (ADS)

Yoon, Young Zoon; Kim, Hyochul; Park, Yeonsang; Kim, Jineun; Lee, Min Kyung; Kim, Un Jeong; Roh, Young-Geun; Hwang, Sung Woo

2016-09-01

Wearable devices often employ optical sensors, such as photoplethysmography sensors, for detecting heart rates or other biochemical factors. Pulse waveforms, rather than simply detecting heartbeats, can clarify arterial conditions. However, most optical sensor designs require close skin contact to reduce power consumption while obtaining good quality signals without distortion. We have designed a detection-gap-independent optical sensor array using divergence-beam-controlled slit lasers and distributed photodiodes in a pulse-detection device wearable over the wrist's radial artery. It achieves high biosignal quality and low power consumption. The top surface of a vertical-cavity surface-emitting laser of 850 nm wavelength was covered by Au film with an open slit of width between 500 nm and 1500 nm, which generated laser emissions across a large divergence angle along an axis orthogonal to the slit direction. The sensing coverage of the slit laser diode (LD) marks a 50% improvement over nonslit LD sensor coverage. The slit LD sensor consumes 100% more input power than the nonslit LD sensor to obtain similar optical output power. The slit laser sensor showed intermediate performance between LD and light-emitting diode sensors. Thus, designing sensors with multiple-slit LD arrays can provide useful and convenient ways for incorporating optical sensors in wrist-wearable devices.

Highly reliable 637-639 nm red high-power LDs for displays

NASA Astrophysics Data System (ADS)

Nishida, Takehiro; Shimada, Naoyuki; Ono, Kenichi; Yagi, Tetsuya; Shima, Akihiro

2010-02-01

Higher power laser diodes (LDs) with a wavelength of 637-639nm are strongly demanded as a light source of display applications because luminosity factor of laser light is relatively high. In order to realize reliable high power operation, we have optimized LD structure, focusing on improvement of power saturation and sudden degradation. As a result, 40μm-wide broad-area (BA) LDs with window-mirror structure have been designed. We fabricated two kinds of single emitter LDs of 1.0mm cavity and 1.5mm cavity. The single LD is installed in conventional φ5.6 mm TO-CAN package. The 1.0mm LD showed very high wall plug efficiency (WPE) of 33% at 25 ºC (23% at 45 ºC) in the power range of around 300mW (30 lm). High output power of 600mW (60 lm) is realized by the 1.5mm LD. Both LDs have operated for over 1,000 hours without any degradation. Estimated mean time to failure (MTTF) is 10,000 hours. In addition, we fabricated an array LD consisting of 20 emitters (BA-LD structure), which shows reliable CW operation of 8W (at junction temperature of 50 ºC) for 10,000 hours.

Hypothalamic Ventricular Ependymal Thyroid Hormone Deiodinases Are an Important Element of Circannual Timing in the Siberian Hamster (Phodopus sungorus)

PubMed Central

Bolborea, Matei; Wilson, Dana; Mercer, Julian G.; Ebling, Francis J. P.; Morgan, Peter J.; Barrett, Perry

2013-01-01

Exposure to short days (SD) induces profound changes in the physiology and behaviour of Siberian hamsters, including gonadal regression and up to 30% loss in body weight. In a continuous SD environment after approximately 20 weeks, Siberian hamsters spontaneously revert to a long day (LD) phenotype, a phenomenon referred to as the photorefractory response. Previously we have identified a number of genes that are regulated by short photoperiod in the neuropil and ventricular ependymal (VE) cells of the hypothalamus, although their importance and contribution to photoperiod induced physiology is unclear. In this refractory model we hypothesised that the return to LD physiology involves reversal of SD expression levels of key hypothalamic genes to their LD values and thereby implicate genes required for LD physiology. Male Siberian hamsters were kept in either LD or SD for up to 39 weeks during which time SD hamster body weight decreased before increasing, after more than 20 weeks, back to LD values. Brain tissue was collected between 14 and 39 weeks for in situ hybridization to determine hypothalamic gene expression. In VE cells lining the third ventricle, expression of nestin, vimentin, Crbp1 and Gpr50 were down-regulated at 18 weeks in SD photoperiod, but expression was not restored to the LD level in photorefractory hamsters. Dio2, Mct8 and Tsh-r expression were altered by SD photoperiod and were fully restored, or even exceeded values found in LD hamsters in the refractory state. In hypothalamic nuclei, expression of Srif and Mc3r mRNAs was altered at 18 weeks in SD, but were similar to LD expression values in photorefractory hamsters. We conclude that in refractory hamsters not all VE cell functions are required to establish LD physiology. However, thyroid hormone signalling from ependymal cells and reversal of neuronal gene expression appear to be essential for the SD refractory response. PMID:23637944

Extent of Linkage Disequilibrium in the Domestic Cat, Felis silvestris catus, and Its Breeds

PubMed Central

Alhaddad, Hasan; Khan, Razib; Grahn, Robert A.; Gandolfi, Barbara; Mullikin, James C.; Cole, Shelley A.; Gruffydd-Jones, Timothy J.; Häggström, Jens; Lohi, Hannes; Longeri, Maria; Lyons, Leslie A.

2013-01-01

Domestic cats have a unique breeding history and can be used as models for human hereditary and infectious diseases. In the current era of genome-wide association studies, insights regarding linkage disequilibrium (LD) are essential for efficient association studies. The objective of this study is to investigate the extent of LD in the domestic cat, Felis silvestris catus, particularly within its breeds. A custom illumina GoldenGate Assay consisting of 1536 single nucleotide polymorphisms (SNPs) equally divided over ten 1 Mb chromosomal regions was developed, and genotyped across 18 globally recognized cat breeds and two distinct random bred populations. The pair-wise LD descriptive measure (r 2) was calculated between the SNPs in each region and within each population independently. LD decay was estimated by determining the non-linear least-squares of all pair-wise estimates as a function of distance using established models. The point of 50% decay of r2 was used to compare the extent of LD between breeds. The longest extent of LD was observed in the Burmese breed, where the distance at which r2 ≈ 0.25 was ∼380 kb, comparable to several horse and dog breeds. The shortest extent of LD was found in the Siberian breed, with an r2 ≈ 0.25 at approximately 17 kb, comparable to random bred cats and human populations. A comprehensive haplotype analysis was also conducted. The haplotype structure of each region within each breed mirrored the LD estimates. The LD of cat breeds largely reflects the breeds’ population history and breeding strategies. Understanding LD in diverse populations will contribute to an efficient use of the newly developed SNP array for the cat in the design of genome-wide association studies, as well as to the interpretation of results for the fine mapping of disease and phenotypic traits. PMID:23308248

Extent of linkage disequilibrium in the domestic cat, Felis silvestris catus, and its breeds.

PubMed

Alhaddad, Hasan; Khan, Razib; Grahn, Robert A; Gandolfi, Barbara; Mullikin, James C; Cole, Shelley A; Gruffydd-Jones, Timothy J; Häggström, Jens; Lohi, Hannes; Longeri, Maria; Lyons, Leslie A

2013-01-01

Domestic cats have a unique breeding history and can be used as models for human hereditary and infectious diseases. In the current era of genome-wide association studies, insights regarding linkage disequilibrium (LD) are essential for efficient association studies. The objective of this study is to investigate the extent of LD in the domestic cat, Felis silvestris catus, particularly within its breeds. A custom illumina GoldenGate Assay consisting of 1536 single nucleotide polymorphisms (SNPs) equally divided over ten 1 Mb chromosomal regions was developed, and genotyped across 18 globally recognized cat breeds and two distinct random bred populations. The pair-wise LD descriptive measure (r(2)) was calculated between the SNPs in each region and within each population independently. LD decay was estimated by determining the non-linear least-squares of all pair-wise estimates as a function of distance using established models. The point of 50% decay of r(2) was used to compare the extent of LD between breeds. The longest extent of LD was observed in the Burmese breed, where the distance at which r(2) ≈ 0.25 was ∼380 kb, comparable to several horse and dog breeds. The shortest extent of LD was found in the Siberian breed, with an r(2) ≈ 0.25 at approximately 17 kb, comparable to random bred cats and human populations. A comprehensive haplotype analysis was also conducted. The haplotype structure of each region within each breed mirrored the LD estimates. The LD of cat breeds largely reflects the breeds' population history and breeding strategies. Understanding LD in diverse populations will contribute to an efficient use of the newly developed SNP array for the cat in the design of genome-wide association studies, as well as to the interpretation of results for the fine mapping of disease and phenotypic traits.

Cellular but not humoral antibacterial activity of earthworms is inhibited by Aroclor 1254.

PubMed

Roch, P; Cooper, E L

1991-12-01

Earthworms, Eisenia fetida andrei and Lumbricus terrestris, exposed to Aroclor 1254, followed by infestation with Aeromonas hydrophila, elicited two types of responses. First, in E. fetida, there was no change in the LD50 nor in the in vitro antibacterial growth capacity of cell-free coelomic fluid. Thus, Aroclor exerts no influence on antibacterial proteins nor on the chloragogue cells responsible for their release. Second, in L. terrestris, both a high LD50 value and no antibacterial activity indicate that A. hydrophila was not pathogenic. The 10(4) times higher sensitivity of exposed L. terrestris suggests that Aroclor inhibits leukocyte activity since E. fetida eliminates nonpathogenic bacteria by a cellular mechanism.

LD-cladding-pumped 50 pm linewidth Tm 3+ -doped silica fiber laser.

PubMed

Yunjun, Zhang; Baoquan, Yao; Youlun, Ju; Hui, Zhou; Yuezhu, Wang

2008-05-26

We report on a Tm(3+)-doped fiber laser source operating at 1936.4 nm with a very narrow linewidth (50 pm) laser output. Up to 2.4 W cw laser power was obtained from an 82 cm long Tm(3+)-doped multimode-core fiber cladding pumped by a 792 nm laser diode (LD). The fiber laser cavity included a high-reflective dichroic and a low-reflective FBG output coupler. The multimode fiber Bragg grating (FBG) transmission spectrum and output laser spectrum were measured. By adjusting the distance between the dichroic and the Tm(3+)-doped fiber end, the multipeak laser spectrum changed to a single-peak laser spectrum.

EFFECTS OF GAMMA RADIATION ON TWO DECAPOD CRUSTACEANS, PALAEMONETES PUGIO AND UCA PUGNAX

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rees, G.H.

1962-03-01

Experiments are described that were undertaken with the objective of determining the lethal dosages of gamma radiation, particularly the doses at which 50% succumb (LD/sub 50/), for 2 decapod crustaceans. (Pub. Health Eng. Abstr.)

An Interlaboratory Validation of the Radiation Dose Response Relationship (DRR) for H-ARS in the Rhesus Macaque.

PubMed

Thrall, Karla D; Love, Ruschelle; OʼDonnell, Kyle C; Farese, Ann M; Manning, Ronald; MacVittie, Thomas J

2015-11-01

The Medical Countermeasures against Radiological Threats (MCART) consortium has established a dose response relationship for the hematopoietic acute radiation syndrome (HARS) in the rhesus macaque conducted under an individualized supportive care protocol, including blood transfusions. Application of this animal model as a platform for demonstrating efficacy of candidate medical countermeasures is significantly strengthened when the model is independently validated at multiple institutions. The study reported here describes implementation of standard operating procedures at an institute outside the consortium in order to evaluate the ability to establish an equivalent radiation dose response relationship in a selected species. Validation of the animal model is a significant component for consideration of the model protocol as an FDA-recommended drug development tool in the context of the "Animal Rule." In the current study, 48 male rhesus macaques (4-8 kg) were exposed to total-body irradiation (TBI) using 6 MV photon energy at a dose rate of approximately 0.8 Gy min. Results show that onset and duration of the hematological response, including anemia, neutropenia, and thrombocytopenia, following TBI ranging from 6.25 to 8.75 Gy correlate well with previously reported findings. The lethality values at 60 d following TBI were estimated to be 6.88 Gy (LD30/60), 7.43 Gy (LD50/60), and 7.98 Gy (LD70/60). These values are equivalent to those published previously of 7.06 Gy (LD30/60), 7.52 Gy (LD50/60), and 7.99 Gy (LD70/60); the DRR slope (p = 0.68) and y-intercepts show agreement along the complete dose range for HARS. The ability to replicate the previously established institutional lethality profile (PROBIT) and model outcomes through careful implementation of defined procedures is a testament to the robustness of the model and highlights the need for consistency in procedures.

Radioprotective effect of polyethylene glycol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shaeffer, J.; Schellenberg, K.A.; Seymore, C.H.

1986-07-01

Polyethylene glycol of molecular weight 400 (PEG-400) had a radioprotective effect of about 20% against lethality when given ip 20 min prior to single or fractionated X-ray doses to the head and neck. Dose modification factors (DMF) based on LD50/15 values ranged from 1.14 to 1.24. A similar DMF of 1.12 based on LD50/30 values was obtained using single doses of whole-body X irradiation. Mice given head and neck irradiation had significantly reduced rectal temperatures (31.3 +/- 3.0/sup 0/C) 9 days post irradiation compared with unirradiated controls (35.4 +/- 0.6/sup 0/C). No such reduction was observed when PEG-400 was givenmore » with radiation (36.3 +/- 0.9/sup 0/C). PEG-400 also lessened, but not significantly, the frequency of shivering in irradiated animals. Histopathologic examination of the oral structures demonstrated only marginal protection by PEG-400. Estimation of the alpha/beta ratio from LD50 data on head and neck-irradiated mice yielded values of 4.4 +/- 1.9 (95% confidence limits) Gy without PEG-400 and 7.9 +/- 1.4 Gy with PEG-400. Since it is a non-thiol radioprotector, PEG-400 may be more useful when combined with more conventional thiol-containing radioprotectors.« less

Intra-strain dioxin sensitivity and morphometric effects in swim-up rainbow trout (Oncorhynchus mykiss)

USGS Publications Warehouse

Carvalho, Paulo S. M.; Noltie, Douglas B.; Tillitt, D.E.

2004-01-01

Inter and intra-specific differences in sensitivity of early life stage salmonids to 2,3,7,8-TCDD exposure have been reported, but intra-strain differences have not been found in the literature. Our results indicate that intra-strain variability in terms of embryo mortality (LD50) is small in Eagle Lake strain of rainbow trout, LD50 values ranging from 285 to 457 pg TCDD egg g−1. These results confirm Eagle Lake as a less sensitive strain within rainbow trout, and do not indicate overlap with reported LD50 values for brook or lake trout. Our results also demonstrate that although generalized edema in regions including the yolk-sac are frequently associated with mortality following dioxin exposure, not all edematous fish die. We detected dose-dependent decreases in cranial length, eye diameter, mass, and total length (P<0.05) in viable swim-up rainbow trout. These effects are presumed to indicate more subtle dose-dependent disruptions of the viteline vein vasculature and, therefore, in access to energy sources. A tendency for dose-dependent decrease in liver glycogen reserves concurred with previous results on salmonids and with the well described TCDD-induced alterations in intermediate metabolism of rats and chicken embryos (wasting syndrome). This syndrome could be contributing to the reduced growth that we observed.

Virulence and genotypes of white spot syndrome virus infecting Pacific white shrimp Litopenaeus vannamei in north-western Mexico.

PubMed

Ramos-Paredes, J; Grijalva-Chon, J M; Ibarra-Gámez, J C

2017-03-01

White spot syndrome virus (WSSV) has caused substantial global economic impact on aquaculture, and it has been determined that strains can vary in virulence. In this study, the effect of viral load was evaluated by infecting Litopenaeus vannamei with 10-fold serial dilution of tissue infected with strain WSSV Mx-H, and the virulence of four WSSV strains from north-western Mexico was assessed along with their variable number of tandem repeat (VNTR) genotypes in ORF75, ORF94 and ORF125. The LD 50 of the Mx-H strain was a dilution dose of 10 -7.5 ; the mortality titre was 10 9.2 LD 50 per gram. In shrimp injected with 10 2.5 to 10 6.5 LD 50 , no significant virulence differences were evident. Using mortality data, the four WSSV strains grouped into three virulence levels. The Mx-F strain (intermediate virulence) and the Mx-C strain (high virulence) showed more genetic differences than those observed between the Mx-G (low-virulence) and Mx-H (high-virulence) strains, in ORF94 and ORF125. The application of high-viral-load inocula proved useful in determining the different virulence phenotypes of the WSSV strains from the Eastern Pacific. © 2017 John Wiley & Sons Ltd.

Radiation-induced mutations in sweet cherry (Prunus avium L. ) cvs Napoleon and Bing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saamin, S.

1987-01-01

Experiments were conducted using gamma radiation to determine radiosensitivities of main and accessory buds, to increase the proportion of mutant tissue, and to determine the type of damage and mode of recovery in irradiated shoot spices of sweet cherry cvs Napoleon and Bin. Survival, growth, and the types of mutations of V/sub 1/ (primary) shoots and V/sub 2/ plants were observed. LD/sub 50/ values, based on survival of forced buds were about 5kR for both acute and fractionated irradiation in air, 5.5kR for acute exposure in water, and 6kR for fractionated dose in water. 0.39-0.69 accessory buds/site on non-irradiated Napoleonmore » had forced after 30 days in the glasshouse. In the Bing field experiment with main buds, the LD/sub 50/ for both acute and fractionated irradiation in air was 3.5kR. In water, the LD/sub 50/ was 5kR for acute treatment and 6.5kR for fractionated dose. The overall mutation frequency in Napoleon V/sub 2/ shoots derived from main buds was 7.6%: 0.04% growth-reduced mutants, 0.4% total leaf mutants, and7.1% partial leaf mutants.« less

Effect of exposure routes on the relationships of lethal toxicity to rats from oral, intravenous, intraperitoneal and intramuscular routes.

PubMed

Ning, Zhong H; Long, Shuang; Zhou, Yuan Y; Peng, Zi Y; Sun, Yi N; Chen, Si W; Su, Li M; Zhao, Yuan H

2015-11-01

The lethal toxicity values (log 1/LD(50)) of 527 aliphatic and aromatic compounds in oral, intravenous, intramuscular and intraperitoneal routes were used to investigate the relationships of log 1/LD(50) from different exposure routes. Regression analysis shows that the log 1/LD(50) values are well correlated between intravenous and intraperitoneal or intramuscular injections. However, the correlations between oral and intravenous or intraperitoneal routes are relatively poor. Comparison of the average residuals indicates that intravenous injection is the most sensitive exposure route and oral administration is the least sensitive exposure route. This is attributed to the difference in kinetic process of toxicity testing. The toxic effect of a chemical can be similar or significantly different between exposure routes, depending on the absorption rates of chemicals into blood. Inclusion of hydrophobic parameter and fractions of ionic forms can improve the correlations between intravenous and intraperitoneal or oral routes, but not between intraperitoneal and oral routes. This is due to the differences of absorption rate in different exposure environments from different routes. Several factors, such as experimental uncertainty, metabolism and toxic kinetics, can affect the correlations between intravenous and intraperitoneal or oral routes. Copyright © 2015 Elsevier Inc. All rights reserved.

Kill curve analysis and response of first generation Capsicum annuum L. B12 cultivar to ethyl methane sulfonate.

PubMed

Arisha, M H; Liang, B-K; Muhammad Shah, S N; Gong, Z-H; Li, D-W

2014-11-28

Pepper seeds (Capsicum annuum L.) var. B12 were mutagenized by four presoaking treatments in ten concentrations of ethyl methane sulfonate (EMS) to determine the sensitivity of the first generation (M1) to mutagens. The spectrum of mutations and induced variability for various quantitative traits, including germination, percent plant height, injury occurrence, survival ratio, first three fruits weight, and number of seeds per first fruit, were observed in the M1 generation. Our results indicated that all of the test parameters decreased with increasing EMS concentration, except for seedling injury. There were significant differences in germination ratio, LD50, plant height, percent injury, and survival ratio among the tested presoaking treatment. The LD50 was 1% EMS in seeds that were not presoaked (T1) and seeds presoaked for 12 h before treating with EMS (T3). In contrast, the LD50 was 0.5% EMS in seeds presoaked for 6 h (T2) and seeds presoaked in water for 6 h then incubated at 28°C for 12 h before EMS treatment (T4). Five dwarf plants were observed in mutagenized seeds without presoaking as compared to control seeds (at the maturity stage of the control plant).

Striking LD50 variation associated with fluctuations of CYP2E1-positive cells in hepatic lobule during chronic CCl4 exposure in mice.

PubMed

Irie, Hiroshi; Asano-Hoshino, Anshin; Sekino, Yoshihisa; Nogami, Makoto; Kitagawa, Tomoyuki; Kanda, Hiroaki

2010-04-01

Intraperitoneal injection of serially diluted carbon tetrachloride (CCl(4)) from 0.2 to 2.0 ml/kg produced an LD(50) value of 0.46 ml/kg in the normal mouse. Following repeated administration of 0.2 ml/kg CCl(4) twice a week for 1 and 3 months, the LD(50) values were over 2.0 and 0.72 ml/kg, respectively. A single administration of 0.2 ml/kg CCl(4) induced, within 24 h, apoptotic death of liver cells in the centrilobular zone 3 that were observed positive in cytochrome P450 2E1 (CYP2E1). However, after repeated exposure to 0.2 ml/kg twice a week for 1 month, cells in the centrilobular area were almost completely replaced with CYP2E1-negative cells. These cells were tolerant to CCl(4). After 3 months of exposure, a considerable number of CYP2E1-positive hepatocytes were observed throughout the periportal zone 1 and intermediate zone 2. Thus, fluctuations in CYP2E1-positive cells during chronic exposure to low doses of CCl(4) induced tolerance, which can be partially lost after prolonged CCl(4) exposure.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harris, L.W.; Talbot, B.G.; Lennox, W.J.

A pretreatment for organophosphorus (OP) anticholinesterase (e. g. , soman) intoxication should prevent lethality and convulsions (CNV) at 2 LD50s and be behavioral-decrement-free when given alone. Behavioral-deficit-free pretreatment regimens (PRGs) for guinea pigs consisted of Physostigmine (0.15 mg/kg, im) and adjunct. Adjuncts MG/KG, IM tested were akineton 0.25, aprophen 8, trihexyphenidyl 2, atropine 16, azaprophen 51, BENACTYZINE 1.25, cogentin 4, dextromethorphan 7.5, ethopropazine 12, kemadrin 11, MEMANTINE 5, promethazine 5, scopolamine 0.081 AND CONTROL 2. PRGs were given 30 min before soman (60 ug/kg, sc; 2 LD50S) or other OP agents. Animals were then observed and graded for signs ofmore » intoxication, including CNV at 7 time points and at 24 hr. Physostigmine alone reduced the incidence of CNV and lethality induced by 2 LD50s of soman by 42 and 60%, respectively. All of the PRGs tested abolished lethality and 12 shortened recovery time to 2 hr or less. Also, PRGs including azaprophen or atropine prevented CNV. When selected PRGs were tested against intoxication by sarin, tabun or VX, the efficacy was generally superior to that for soman. The data show that several PRGs are effective against soman intoxication in guinea pigs. Pretreatment, physostigmine, anticholinesterases, soman (GD).« less

5W intracavity frequency-doubled green laser for laser projection

NASA Astrophysics Data System (ADS)

Yan, Boxia; Bi, Yong; Li, Shu; Wang, Dongdong; Wang, Dongzhou; Qi, Yan; Fang, Tao

2014-11-01

High power green laser has many applications such as high brightness laser projection and large screen laser theater. A compact and high power green-light source has been developed in diode-pumped solid-state laser based on MgO doped periodically poled LiNbO3 (MgO:PPLN). 5W fiber coupled green laser is achieved by dual path Nd:YVO4/MgO:PPLN intra-cacity frequency-doubled. Single green laser maximum power 2.8W at 532nm is obtained by a 5.5W LD pumped, MgO:PPLN dimensions is 5mm(width)×1mm(thickness)×2mm(length), and the optical to optical conversion efficiency is 51%. The second LD series connected with the one LD, the second path green laser is obtained using the same method. Then the second path light overlap with the first path by the reflection mirrors, then couple into the fiber with a focus mirror. Dual of LD, Nd:YVO4, MgO:PPLN are placed on the same heat sink using a TEC cooling, the operating temperature bandwidth is about 12°C and the stablity is 5% in 96h. A 50×50×17mm3 laser module which generated continuous-wave 5 W green light with high efficiency and width temperature range is demonstrated.

Effect of the As-Forged and Heat-Treated Microstructure on the Room Temperature Anisotropic Ductile Fracture of Inconel 718

NASA Astrophysics Data System (ADS)

Teimouri, Javad; Hosseini, Seyed Rahman; Farmanesh, Khosro

2018-05-01

The purpose of the present work was to investigate the effect of primary carbides and the δ-phase on the anisotropic ductile fracture of Inconel 718 in the forging process. Inconel 718 alloys were prepared by VIM + VAR processes with various carbon contents (0.009 and 0.027 wt.%). Then, the alloys were forged and annealed at temperatures of 980 and 1030 °C. The room temperature mechanical anisotropy of the alloys was evaluated at the longitudinal direction (LD) and transverse direction (TD). Tensile and impact tests were used to characterize the mechanical properties of the specimens. The microstructural characterization and the fractography of the alloys were carried out by FE-SEM. The obtained results showed that the fracture strain and the impact energy in the TD were 30-50% lower than the LD. The fracture was accelerated by the δ-phase, leading to the reduction of impact energy in the longitudinal and the lateral directions up to 50%. The low-carbon alloy indicated similar characteristics in both the LD and the TD. Aligned carbides changed the fracture path from a zigzag path in the LD to a fibrous path in the TD, while the δ-phase created a flat fracture path. The shear lip area ratio in the tensile fracture cross section was decreased by reducing ductility.

Effect of the As-Forged and Heat-Treated Microstructure on the Room Temperature Anisotropic Ductile Fracture of Inconel 718

NASA Astrophysics Data System (ADS)

Teimouri, Javad; Hosseini, Seyed Rahman; Farmanesh, Khosro

2018-04-01

The purpose of the present work was to investigate the effect of primary carbides and the δ-phase on the anisotropic ductile fracture of Inconel 718 in the forging process. Inconel 718 alloys were prepared by VIM + VAR processes with various carbon contents (0.009 and 0.027 wt.%). Then, the alloys were forged and annealed at temperatures of 980 and 1030 °C. The room temperature mechanical anisotropy of the alloys was evaluated at the longitudinal direction (LD) and transverse direction (TD). Tensile and impact tests were used to characterize the mechanical properties of the specimens. The microstructural characterization and the fractography of the alloys were carried out by FE-SEM. The obtained results showed that the fracture strain and the impact energy in the TD were 30-50% lower than the LD. The fracture was accelerated by the δ-phase, leading to the reduction of impact energy in the longitudinal and the lateral directions up to 50%. The low-carbon alloy indicated similar characteristics in both the LD and the TD. Aligned carbides changed the fracture path from a zigzag path in the LD to a fibrous path in the TD, while the δ-phase created a flat fracture path. The shear lip area ratio in the tensile fracture cross section was decreased by reducing ductility.

LC and LD50 values of Bacillus thuringiensis Serovar japonensis strain buibui toxin to Oriental beetle and northern masked chafer larvae (Coleoptera: Scarabaeidae).

PubMed

Mashtoly, Tamer A; El-Zemaity, Mohamed El-Said; Hussien, Mohamed I; Alm, Steven R

2009-10-01

Bacillus thuringiensis serovar japonensis strain Buibui has the potential to be an important control agent for pest scarabs. Bioassays were designed to test B. t. japonensis against two of the major turf and ornamental scarab pests infesting turfgrasses and ornamentals and to serve as a basis for further tests against other scarab pests. LC and LD50 values of B. t. serovarjaponensis strain Buibui toxin and spores were determined by four different bioassays for the oriental beetle, Anomala orientalis (Waterhouse), and northern masked chafer, Cyclocephala borealis Arrow. Oriental beetle larvae were bioassayed in autoclaved and nonautoclaved soil from where they were collected (Kingston, RI [native]), in nonautoclaved soil from where the northern masked chafer larvae were collected (Groton, CT [foreign]), and per os. Northern masked chafer larvae were bioassayed in autoclaved and nonautoclaved soil from where they were collected (Groton, CT [native]), in nonautoclaved soil from where the oriental beetle larvae were collected (Kingston, RI [foreign]) and per os. LC50 values of 3.93 microg toxin/g autoclaved native soil, 1.80 microg toxin/g nonautoclaved native soil, and 0.42 microg toxin/g nonautoclaved foreign soil and an LD50 value of 0.41 microg per os were determined at 14 d forA. orientalis. LC50 values of 588.28 microg toxin/g autoclaved native soil, 155.10 microg toxin/g nonautoclaved native soil, 265.32 microg toxin/g nonautoclaved foreign soil, and LD50 of 5.21 microg per os were determined at 14 d (soils) and 10 d (per os) for C. borealis. There were significant differences in LC50 values for oriental beetles in autoclaved, nonautoclaved native soil and nonautoclaved foreign soil. There were significant differences in LCo values for northern masked chafers in autoclaved and nonautoclaved native soil. B. t. japonensis can be applied now for control of oriental beetles at rates that are economically competitive with synthetic chemicals. If we can determine the component of nonautoclaved soil that enhances the activity of toxin, it may be possible to lower the rates of toxin needed for control to more economical levels for more difficult to control species such as the northern masked chafer.

[The establishment of the immortalized mouse brain microvascular pericytes model and its preliminary application in screening of cerebrovascular toxicants].

PubMed

Zhao, H P; Gao, Y F; Xia, D; Zhao, Z Q; Wu, S; Wang, X H; Liu, H X; Xiao, C; Xing, X M; He, Y

2018-05-06

Objective: To establish the immortalized mouse brain microvascular pericytes model and to apply to the cerebrovascular toxicants screening study. Methods: Brain pericytes were isolated from 3 weeks of mice by tissue digestion. Immortalized pericyte cell line was constructed by infecting with LT retrovirus. Monoclone was selected to purify the immortalized pericyte cell line. The pericyte characteristics and purity were explored by immunocytochemistry. Cell proliferation was measured by using the Pomega MTS cell Proliferation Colorimetric Assay Kit. Pericytes were treated with 0, 160, 320, 640, 1 280, 2 560 μmol/L lead acetate, 0, 5, 10, 20, 40, 80 μmol/L cadmium chloride and 0, 5, 10, 20, 40, 80 μmol/L sodium arsenite in 24 hours. Cell toxicity of each group was determined by MTS assay, median lethal dose (LD(50)) was calculated in linear regression. Results: Mouse brain pericytes were successfully isolated by tissue separation and enzyme digestion method. After immortalized by LT retroviruses, monoclone was selected and expanded to establish pericyte cell line. The brain pericytes exhibited typical long spindle morphology and positive staining for α-SMA and Vimentin. The proliferation of brain pericytes cell lines was very slowly, and the doubling time was about 48 hours. The proliferation of immortalized brain pericytes cell lines was very quickly, and the doubling time was about 24 hours. After lead acetate, cadmium chloride and sodium arsenite treatment for 24 hours respectively, gradual declines in cell viability were observed. The LD(50) of lead acetate was 2 025.0 μmol/L, the LD(50) of cadmium chloride was 36.6 μmol/L, and the LD(50) of sodium arsenite was 33.2 μmol/L. Conclusion: The immortalized mouse brain microvascular pericyte model is established successfully by infecting with LT retrovirus, and can be applied to screen cerebrovascular toxicants. The toxicity of these toxicants to immortalized mouse brain microvascular pericyte is in sequence: sodium arsenite,cadmium chloride, lead acetate.

High-Throughput Screening of Australian Marine Organism Extracts for Bioactive Molecules Affecting the Cellular Storage of Neutral Lipids

PubMed Central

Rae, James; Fontaine, Frank; Salim, Angela A.; Lo, Harriet P.; Capon, Robert J.; Parton, Robert G.; Martin, Sally

2011-01-01

Mammalian cells store excess fatty acids as neutral lipids in specialised organelles called lipid droplets (LDs). Using a simple cell-based assay and open-source software we established a high throughput screen for LD formation in A431 cells in order to identify small bioactive molecules affecting lipid storage. Screening an n-butanol extract library from Australian marine organisms we identified 114 extracts that produced either an increase or a decrease in LD formation in fatty acid-treated A431 cells with varying degrees of cytotoxicity. We selected for further analysis a non-cytotoxic extract derived from the genus Spongia (Heterofibria). Solvent partitioning, HPLC fractionation and spectroscopic analysis (NMR, MS) identified a family of related molecules within this extract with unique structural features, a subset of which reduced LD formation. We selected one of these molecules, heterofibrin A1, for more detailed cellular analysis. Inhibition of LD biogenesis by heterofibrin A1 was observed in both A431 cells and AML12 hepatocytes. The activity of heterofibrin A1 was dose dependent with 20 µM inhibiting LD formation and triglyceride accumulation by ∼50% in the presence of 50 µM oleic acid. Using a fluorescent fatty acid analogue we found that heterofibrin A1 significantly reduces the intracellular accumulation of fatty acids and results in the formation of distinct fatty acid metabolites in both cultured cells and in embryos of the zebrafish Danio rerio. In summary we have shown using readily accessible software and a relatively simple assay system that we can identify and isolate bioactive molecules from marine extracts, which affect the formation of LDs and the metabolism of fatty acids both in vitro and in vivo. PMID:21857959

The natural flavonoid silybin improves the response to Photodynamic Therapy of bladder cancer cells.

PubMed

Gándara, L; Sandes, E; Di Venosa, G; Prack Mc Cormick, B; Rodriguez, L; Mamone, L; Batlle, A; Eiján, A M; Casas, A

2014-04-05

Photodynamic Therapy (PDT) is an anticancer treatment based on photosensitisation of malignant cells. The precursor of the photosensitiser Protoporphyrin IX, 5-aminolevulinic acid (ALA), has been used for PDT of bladder cancer. Silybin is a flavonoid extracted from Silybum marianum, and it has been reported to increase the efficacy of several anticancer treatments. In the present work, we evaluated the cytotoxicity of the combination of ALA-PDT and silybin in the T24 and MB49 bladder cancer cell lines. MB49 cells were more sensitive to PDT damage, which was correlated with a higher Protoporphyrin IX production from ALA. Employing lethal light doses 50% (LD50) and 75% (LD75) and additional silybin treatment, there was a further increase of toxicity driven by PDT in both cell lines. Using the Chou-Talalay model for drug combination derived from the mass-action law principle, it was possible to identify the effect of the combination as synergic when using LD75, whilst the use of LD50 led to an additive effect on MB49 cells. On the other hand, the drug combination turned out to be nearly additive on T24 cells. Apoptotic cell death is involved both in silybin and PDT cytotoxicity in the MB49 line but there is no apparent correlation with the additive or synergic effect observed on cell viability. On the other hand, we found an enhancement of the PDT-driven impairment of cell migration on both cell lines as a consequence of silybin treatment. Overall, our results suggest that the combination of silybin and ALA-PDT would increase PDT outcome, leading to additive or synergistic effects and possibly impairing the occurrence of metastases. Copyright © 2014 Elsevier B.V. All rights reserved.

Lethal factor is not required for Bacillus anthracis virulence in guinea pigs and rabbits.

PubMed

Levy, Haim; Weiss, Shay; Altboum, Zeev; Schlomovitz, Josef; Rothschild, Nili; Blachinsky, Eran; Kobiler, David

2011-11-01

The major virulence factor of Bacillus anthracis is the tripartite anthrax toxin, comprising the protective antigen (PA), lethal factor (LF) and edema factor (EF). The LF of B. anthracis is a metalloprotease that has been shown to play an important role in pathogenicity. Deletion of this gene (lef) in the Sterne strain was reported to dramatically reduce the pathogenicity of this strain in mice, and was reported to be as dramatic as the deletion of PA. We evaluated the effect on pathogenicity of the lef deletion in the fully virulent Vollum strain in guinea pigs and NZW rabbits by either subcutaneous injection or intranasal instillation. In guinea pigs, no major differences between the mutant strain and the wild type could be detected in the LD(50) or mean time to death values. On the other hand, the lef deletion caused death of 50-70% of all rabbits infected with the mutant spores at doses equivalent or higher than the wild type LD(50). The surviving rabbits, which were infected with spore doses higher than the wild type LD(50), developed a protective immune response that conferred resistance to challenge with the wild type strain. These findings may indicate that the mutant lacking the LF is capable of host colonization which causes death in 50-70% of the animals and a protective immune response in the others. These results indicate that unlike the data obtained in mice, the LF mutation does not abolish B. anthracis pathogenicity. Copyright © 2011 Elsevier Ltd. All rights reserved.

Oral LD50 toxicity modeling and prediction of per- and polyfluorinated chemicals on rat and mouse.

PubMed

Bhhatarai, Barun; Gramatica, Paola

2011-05-01

Quantitative structure-activity relationship (QSAR) analyses were performed using the LD(50) oral toxicity data of per- and polyfluorinated chemicals (PFCs) on rodents: rat and mouse. PFCs are studied under the EU project CADASTER which uses the available experimental data for prediction and prioritization of toxic chemicals for risk assessment by using the in silico tools. The methodology presented here applies chemometrical analysis on the existing experimental data and predicts the toxicity of new compounds. QSAR analyses were performed on the available 58 mouse and 50 rat LD(50) oral data using multiple linear regression (MLR) based on theoretical molecular descriptors selected by genetic algorithm (GA). Training and prediction sets were prepared a priori from available experimental datasets in terms of structure and response. These sets were used to derive statistically robust and predictive (both internally and externally) models. The structural applicability domain (AD) of the models were verified on 376 per- and polyfluorinated chemicals including those in REACH preregistration list. The rat and mouse endpoints were predicted by each model for the studied compounds, and finally 30 compounds, all perfluorinated, were prioritized as most important for experimental toxicity analysis under the project. In addition, cumulative study on compounds within the AD of all four models, including two earlier published models on LC(50) rodent analysis was studied and the cumulative toxicity trend was observed using principal component analysis (PCA). The similarities and the differences observed in terms of descriptors and chemical/mechanistic meaning encoded by descriptors to prioritize the most toxic compounds are highlighted.

The effects of stage-specific selection on the development of benzimidazole resistance in Haemonchus contortus in sheep.

PubMed

Taylor, M A; Hunt, K R; Goodyear, K L

2002-10-16

Resistance to the benzimidazole (BDZ) class of anthelmintics in nematodes of sheep has become a common and global phenomenon. The rate at which the selection process and development of resistance occurs is influenced by a number of factors. Of these, the effects of stage-specific exposures to anthelmintic were investigated with a BDZ-resistant strain of Haemonchus contortus (HCR) over five parasite generations. Sheep were infected at each generation with the HCR strain and were treated with thiabendazole (TBZ), either 5 days post-infection (p.i.) (larval line), 21 days p.i. (adult line), or left untreated (no selection line). Additionally eggs from each generation were exposed to TBZ (egg line). Geometric worm burdens were calculated from post-mortem worm counts, both at the start of the study, and after the final selection studies for each of the selection lines. Egg hatch assays (EHAs) were also conducted throughout the study. All data relating to worm burdens and EHAs for each generation were analysed by linear regression to produce dose titration curves and lethal dose(50) (LD(50)) values for each of the selection lines. Over the five generations, LD(50) values on dose-response were increased and worm survival occurred at higher dose rates of TBZ irrespective of the parasite stage exposed to treatment. A similar picture was seen with ED(50) values, which showed a fluctuating but generally upward trend for each of the three selection lines. In contrast, LD(50) and ED(50) values were decreased in the no selection line, indicating some degree of reversion albeit to levels still considered to be BDZ-resistant.

Risk Factors for Clinician-Diagnosed Lyme Arthritis, Facial Palsy, Carditis, and Meningitis in Patients From High-Incidence States

PubMed Central

Kwit, Natalie A; Max, Ryan; Mead, Paul S

2018-01-01

Abstract Background Clinical features of Lyme disease (LD) range from localized skin lesions to serious disseminated disease. Information on risk factors for Lyme arthritis, facial palsy, carditis, and meningitis is limited but could facilitate disease recognition and elucidate pathophysiology. Methods Patients from high-incidence states treated for LD during 2005–2014 were identified in a nationwide insurance claims database using the International Classification of Diseases, Ninth Revision code for LD (088.81), antibiotic treatment history, and clinically compatible codiagnosis codes for LD manifestations. Results Among 88022 unique patients diagnosed with LD, 5122 (5.8%) patients with 5333 codiagnoses were identified: 2440 (2.8%) arthritis, 1853 (2.1%) facial palsy, 534 (0.6%) carditis, and 506 (0.6%) meningitis. Patients with disseminated LD had lower median age (35 vs 42 years) and higher male proportion (61% vs 50%) than nondisseminated LD. Greatest differential risks included arthritis in males aged 10–14 years (odds ratio [OR], 3.5; 95% confidence interval [CI], 3.0–4.2), facial palsy (OR, 2.1; 95% CI, 1.6–2.7) and carditis (OR, 2.4; 95% CI, 1.6–3.6) in males aged 20–24 years, and meningitis in females aged 10–14 years (OR, 3.4; 95% CI, 2.1–5.5) compared to the 55–59 year referent age group. Males aged 15–29 years had the highest risk for complete heart block, a potentially fatal condition. Conclusions The risk and manifestations of disseminated LD vary by age and sex. Provider education regarding at-risk populations and additional investigations into pathophysiology could enhance early case recognition and improve patient management. PMID:29326960

[Value of condensation and rarefaction click evoked action potential latency difference in the diagnosis of Meniere's disease].

PubMed

Wang, Z; Shao, X; Yan, W; Lin, H

2000-06-01

To study the value of condensation and rarefaction clicks evoked action potential (AP) latency difference (LD) in diagnosis of Meniere's disease. AP was recorded with ECochG in controls (50 ears) and patients with Meniere's disease(90 ears) and sensorineural hearing loss(SNHL) of other origins(60 ears). LD was calculated and analyzed. LD in patients with Meniere's disease was (0.30 +/- 0.15) ms, which was significantly larger than that of controls(0.18 +/- 0.07) ms and of patients with SNHL of other origins(0.20 +/- 0.10) ms (P < 0.01). In the group of Meniere's disease, LD in patients with the mild and moderate hearing impairment was larger than those with severe hearing loss(P < 0.01) and LD in patients with low tone or high tone auditory sensation curve was larger than those with flat auditory sensation curve(P < 0.01). Positive rate was 4/60(6.7%) in other SNHL patients and 58/90(64.0%) in Meniere's disease group respectively. The increase in condensation and rarefaction click evoked AP latency difference can be an objective parameter in diagnosis of Meniere's disease.

Synergistic effect of low-dose cucurbitacin B and low-dose methotrexate for treatment of human osteosarcoma

PubMed Central

Goff, Catherine; Iwanski, Gabriela B.; Forscher, Charles; Doan, Ngan B.; Said, Jonathan W.; Koeffler, H. Phillip

2016-01-01

We investigated the use of cucurbitacin B, a plant-derived tetracyclic triterpenoid, as a single agent or in combination with methotrexate (MTX) for human osteosarcoma (OS) treatment. Cucurbitacin B showed antiproliferative activity against seven human OS cell lines in vitro accompanying G2/M cell cycle arrest, apoptosis, and inhibition of ERK, Akt, and mTOR proteins. Cucurbitacin B in combination with MTX synergistically inhibited OS cell growth in vitro. Low-dose cucurbitacin B (LD-CuB, 0.5 mg/kg body weight) or low-dose MTX (LD-MTX, 150 mg/kg) failed to decrease the size of human OS xenografts in nude mice. However, combined therapy at identical concentrations inhibited tumor growth by 62% vs. LD-CuB and 81% vs. LD-MTX (p < 0.001). Strikingly, the effect persisted even when the dose of MTX was decreased by two thirds (VLD-MTX, 50 mg/kg). In conclusion, cucurbitacin B alone or in combination with MTX shows promising antiproliferative activity against human OS. PMID:21440986

Evaluation of the Lethal Potency of Scorpion and Snake Venoms and Comparison between Intraperitoneal and Intravenous Injection Routes

PubMed Central

Oukkache, Naoual; Jaoudi, Rachid El; Ghalim, Noreddine; Chgoury, Fatima; Bouhaouala, Balkiss; Mdaghri, Naima El; Sabatier, Jean-Marc

2014-01-01

Scorpion stings and snake bites are major health hazards that lead to suffering of victims and high mortality. Thousands of injuries associated with such stings and bites of venomous animals occur every year worldwide. In North Africa, more than 100,000 scorpion stings and snake bites are reported annually. An appropriate determination of the 50% lethal doses (LD50) of scorpion and snake venoms appears to be an important step to assess (and compare) venom toxic activity. Such LD50 values are also commonly used to evaluate the neutralizing capacity of specific anti-venom batches. In the present work, we determined experimentally the LD50 values of reference scorpion and snake venoms in Swiss mice, and evaluated the influence of two main venom injection routes (i.e., intraperitoneal (IP) versus intravenous (IV)). The analysis of experimental LD50 values obtained with three collected scorpion venoms indicates that Androctonus mauretanicus (Am) is intrinsically more toxic than Androctonus australis hector (Aah) species, whereas the latter is more toxic than Buthus occitanus (Bo). Similar analysis of three representative snake venoms of the Viperidae family shows that Cerastes cerastes (Cc) is more toxic than either Bitis arietans (Ba) or Macrovipera lebetina (Ml) species. Interestingly, the venom of Elapidae cobra snake Naja haje (Nh) is far more toxic than viper venoms Cc, Ml and Ba, in agreement with the known severity of cobra-related envenomation. Also, our data showed that viper venoms are about three-times less toxic when injected IP as compared to IV, distinct from cobra venom Nh which exhibited a similar toxicity when injected IP or IV. Overall, this study clearly highlights the usefulness of procedure standardization, especially regarding the administration route, for evaluating the relative toxicity of individual animal venoms. It also evidenced a marked difference in lethal activity between venoms of cobra and vipers, which, apart from the nature of toxins, might be attributed to the rich composition of high molecular weight enzymes in the case of viper venoms. PMID:24926799

Desiccation and Mortality Dynamics in Seedlings of Different European Beech (Fagus sylvatica L.) Populations under Extreme Drought Conditions

PubMed Central

Bolte, Andreas; Czajkowski, Tomasz; Cocozza, Claudia; Tognetti, Roberto; de Miguel, Marina; Pšidová, Eva; Ditmarová, Ĺubica; Dinca, Lucian; Delzon, Sylvain; Cochard, Hervè; Ræbild, Anders; de Luis, Martin; Cvjetkovic, Branislav; Heiri, Caroline; Müller, Jürgen

2016-01-01

European beech (Fagus sylvatica L., hereafter beech), one of the major native tree species in Europe, is known to be drought sensitive. Thus, the identification of critical thresholds of drought impact intensity and duration are of high interest for assessing the adaptive potential of European beech to climate change in its native range. In a common garden experiment with one-year-old seedlings originating from central and marginal origins in six European countries (Denmark, Germany, France, Romania, Bosnia-Herzegovina, and Spain), we applied extreme drought stress and observed desiccation and mortality processes among the different populations and related them to plant water status (predawn water potential, ΨPD) and soil hydraulic traits. For the lethal drought assessment, we used a critical threshold of soil water availability that is reached when 50% mortality in seedling populations occurs (LD50SWA). We found significant population differences in LD50SWA (10.5–17.8%), and mortality dynamics that suggest a genetic difference in drought resistance between populations. The LD50SWA values correlate significantly with the mean growing season precipitation at population origins, but not with the geographic margins of beech range. Thus, beech range marginality may be more due to climatic conditions than to geographic range. The outcome of this study suggests the genetic variation has a major influence on the varying adaptive potential of the investigated populations. PMID:27379105

Protective Efficacy of the Conserved NP, PB1, and M1 Proteins as Immunogens in DNA- and Vaccinia Virus-Based Universal Influenza A Virus Vaccines in Mice

PubMed Central

Wang, Wenling; Li, Renqing; Deng, Yao; Lu, Ning; Chen, Hong; Meng, Xin; Wang, Wen; Wang, Xiuping; Yan, Kexia; Qi, Xiangrong; Zhang, Xiangmin; Xin, Wei; Lu, Zhenhua; Li, Xueren; Bian, Tao; Gao, Yingying; Tan, Wenjie

2015-01-01

The conventional hemagglutinin (HA)- and neuraminidase (NA)-based influenza vaccines need to be updated most years and are ineffective if the glycoprotein HA of the vaccine strains is a mismatch with that of the epidemic strain. Universal vaccines targeting conserved viral components might provide cross-protection and thus complement and improve conventional vaccines. In this study, we generated DNA plasmids and recombinant vaccinia viruses expressing the conserved proteins nucleoprotein (NP), polymerase basic 1 (PB1), and matrix 1 (M1) from influenza virus strain A/Beijing/30/95 (H3N2). BALB/c mice were immunized intramuscularly with a single vaccine based on NP, PB1, or M1 alone or a combination vaccine based on all three antigens and were then challenged with lethal doses of the heterologous influenza virus strain A/PR/8/34 (H1N1). Vaccines based on NP, PB1, and M1 provided complete or partial protection against challenge with 1.7 50% lethal dose (LD50) of PR8 in mice. Of the three antigens, NP-based vaccines induced protection against 5 LD50 and 10 LD50 and thus exhibited the greatest protective effect. Universal influenza vaccines based on the combination of NP, PB1, and M1 induced a strong immune response and thus might be an alternative approach to addressing future influenza virus pandemics. PMID:25834017

Protective Efficacy of the Conserved NP, PB1, and M1 Proteins as Immunogens in DNA- and Vaccinia Virus-Based Universal Influenza A Virus Vaccines in Mice.

PubMed

Wang, Wenling; Li, Renqing; Deng, Yao; Lu, Ning; Chen, Hong; Meng, Xin; Wang, Wen; Wang, Xiuping; Yan, Kexia; Qi, Xiangrong; Zhang, Xiangmin; Xin, Wei; Lu, Zhenhua; Li, Xueren; Bian, Tao; Gao, Yingying; Tan, Wenjie; Ruan, Li

2015-06-01

The conventional hemagglutinin (HA)- and neuraminidase (NA)-based influenza vaccines need to be updated most years and are ineffective if the glycoprotein HA of the vaccine strains is a mismatch with that of the epidemic strain. Universal vaccines targeting conserved viral components might provide cross-protection and thus complement and improve conventional vaccines. In this study, we generated DNA plasmids and recombinant vaccinia viruses expressing the conserved proteins nucleoprotein (NP), polymerase basic 1 (PB1), and matrix 1 (M1) from influenza virus strain A/Beijing/30/95 (H3N2). BALB/c mice were immunized intramuscularly with a single vaccine based on NP, PB1, or M1 alone or a combination vaccine based on all three antigens and were then challenged with lethal doses of the heterologous influenza virus strain A/PR/8/34 (H1N1). Vaccines based on NP, PB1, and M1 provided complete or partial protection against challenge with 1.7 50% lethal dose (LD50) of PR8 in mice. Of the three antigens, NP-based vaccines induced protection against 5 LD50 and 10 LD50 and thus exhibited the greatest protective effect. Universal influenza vaccines based on the combination of NP, PB1, and M1 induced a strong immune response and thus might be an alternative approach to addressing future influenza virus pandemics. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Adenovirus-mediated human paraoxonase1 gene transfer to provide protection against the toxicity of the organophosphorus pesticide toxicant diazoxon.

PubMed

Duysen, E G; Parikh, K; Aleti, V; Manne, V; Lockridge, O; Chilukuri, N

2011-03-01

Human paraoxonase1 (hPON1) is a potential therapeutic against the toxicity of organophosphorus (OP) pesticides and chemical warfare nerve agents. We tested whether PON1 gene transfer using adenovirus provides protection against the toxicity of the OP diazoxon. Using an adenovirus construct containing hPON1 gene, we showed elevated levels of recombinant hPON1 in vitro in 293A cells and in vivo in mice. The recombinant enzyme was secreted by 293A cells into culture medium and into the systemic circulation of mice. Western blotting revealed that the virally expressed hPON1 had the expected molecular weight of 45 kDa. Recombinant hPON1 in mice was in complex with mouse high-density lipoprotein (HDL) and migrated more slowly than endogenous hPON1 in the human HDL complex. Mice injected with adenovirus expressed PON1 at 600-3480 U ml(-1) on day 5 post-treatment, which is 8-50-fold above endogenous. Six mice expressing hPON1 survived 2LD(50) doses of diazoxon. Four of the six mice survived a second dose of diazoxon (for a total of 4LD(50)) administered 24 h later. In contrast, none of the three mice in the control group survived one 2LD(50) dose. These results show that hPON1 in mice functions as a prophylactic and offers significant protection against lethal doses of diazoxon.

Delisting toxicity evaluation of HTH and oxone(trade name) decontaminated VX. Final report, July 1989-March 1990

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manthei, J.H.; Heitkamp, D.H.; Buettner, L.C.

1992-07-01

The acute percutaneous (bare skin) LD50 was determined for EA 2192 in the rabbit. Also established were the effective doses (ED50s) for the major toxic signs observed. Dermal, Department of Transportation (DOT), tests with rabbits indicated that VX/HTH decontaminated waste is a Class B poison after being aged only 24 hr following initiation of the decontamination procedure. The same reaction, when allowed to age through about 2 half-lives (28-30 days), was no longer a Class B poison and was nonhazardous by Code of Maryland Regulations (COMAR) toxicity criteria. The DOT tests with OXONE decontaminated/neutralized VX showed this solution to bemore » less than a Class B poison by all three routes of administration (rat oral, rat inhalation, and rabbit dermal) after only 24-hr aging and a nonhazardous material by COMAR toxicity criteria.... vx, Rat, Half-life, ED50, EA 2192, Rabbit, COMAR, Decontaminated/Neutralized, HTH, OXONE, LD50.« less

Testicular and spermatotoxic effects of quinalphos in rats.

PubMed

Pant, N; Srivastava, S P

2003-01-01

Testicular and spermatotoxic effects were investigated in rats exposed to technical-grade quinalphos (70%) at dose levels of 0.52 mg kg(-1) (1/50th ld(50)) or 1.04 mg kg(-1) body weight (1/25th ld(50)) for 5 days a week for 60 days. The activities of marker testicular enzymes such as sorbitol dehydrogenase (SDH) and acid phosphatase were significantly decreased but those of lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (gamma-GT) and beta-glucuronidase were significantly increased in a dose-dependent manner. This particular pattern in the activity of testicular-cell-specific enzymes, a decrease in sperm motility and total epididymal sperm count and an increase in abnormal sperm suggest damage to germ cells and Sertoli cells. The testicular and spermatotoxic effects observed in rats may be due to the pesticide quinalphos or its metabolites. Copyright 2003 John Wiley & Sons, Ltd.

Efficacy of a type C botulism vaccine in green-winged teal.

PubMed

Rocke, T E; Samuel, M D; Swift, P K; Yarris, G S

2000-07-01

We tested the efficacy of a single dose of Botumink toxoid for protecting wild green-winged teal (Anas crecca) during botulism epizootics caused by Clostridium botulinum type C. We challenged control and immunized ducks with four different doses of type C botulinum toxin to determine the LD50 for this species and to evaluate vaccine protection. Fewer immunized ducks were affected with botulism than control ducks, indicating that a single dose of Botumink toxoid could increase the survival of ducks during epizootics. However, the frequency of immunized ducks with signs of botulism increased with the challenge dose of botulinum toxin. Even at doses of botulinum toxin approximately 2 to 4 green-winged teal LD50, about 50% of the immunized ducks were affected. We believe an improved vaccine or a better delivery system is required to justify immunization of wild birds for experimental survival studies.

Efficacy of a type C botulism vaccine in green-winged teal

USGS Publications Warehouse

Rocke, T.E.; Samuel, M.D.; Swift, P.K.; Yarris, G.S.

2000-01-01

We tested the efficacy of a single dose of Botumink toxoid for protecting wild green-winged teal (Anas crecca) during botulism epizootics caused by Clostridium botulinum type C. We challenged control and immunized ducks with four different doses of type C botulinum toxin to determine the LD50 for this species and to evaluate vaccine protection. Fewer immunized ducks were affected with botulism than control ducks, indicating that a single dose of Botumink toxoid could increase the survival of ducks during epizootics. However, the frequency of immunized ducks with signs of botulism increased with the challenge dose of botulinum toxin. Even at doses of botulinum toxin approximately 2 to 4 green-winged teal LD50, about 50% of the immunized ducks were affected. We believe an improved vaccine or a better delivery system is required to justify immunization of wild birds for experimental survival studies.

Proceedings of the NATO Radiological Human Response Subject Matter Expert Review Meeting, 26 June 2008, Albuquerque, New Mexico, United States of America

DTIC Science & Technology

2009-08-01

the proposed general casualty estimation process. The next two briefings described the technical details of the development and content of the...Forces Radiobiological Research Institute (AFRRI) Dr. Gene McClellan, Applied Research Associates (ARA) COL John Mercier, AFRRI Dr. Kyle Millage...marrow damage occurs; lethality ranges from LD50/60 to LD99/60; death occurs within 3.5 to 6 weeks with the radiation injury alone but is accelerated

In vitro cytotoxicity testing of 30 reference chemicals to predict acute human and animal toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barile, F.A.; Arjun, S.; Borges, L.

1991-03-11

This study was conducted in cooperation with the Scandinavian Society of Cell Toxicology, as part of the Multicenter Evaluation for In Vitro Cytotoxicity (MEIC), and was designed to develop an in vitro model for predicting acute human and animal toxicity. The technique relies on the ability of cultured transformed rat lung epithelial cells (L2) to incorporate radiolabled amino acids into newly synthesized proteins in the absence or presence of increasing doses of the test chemical, during a 24-hr incubation. IC50 values were extrapolated from the dose-response curves after linear regression analysis. Human toxic blood concentrations estimated from rodent LD50 valuesmore » suggest that our experimental IC50's are in close correlation with the former. Validation of the data by the MEIC committee shows that our IC50 values predicted human lethal dosage as efficient as rodent LD50's. It is anticipated that this and related procedures may supplement or replace currently used animal protocols for predicting human toxicity.« less

Web-based Interspecies Correlation Estimation

EPA Science Inventory

Web-ICE estimates acute toxicity (LC50/LD50) of a chemical to a species, genus, or family from the known toxicity of the chemical to a surrogate species. Web-ICE has modules to predict acute toxicity to aquatic (fish and invertebrates) and wildlife (birds and mammals) taxa for us...

REGRESSION ON MEDIANS OF PROBABILITY DISTRIBUTIONS

EPA Science Inventory

The median is a fundamental parameter in the area of lifetime and survival statistics. n toxicodynamics the LD50, lethal dose that results in 50% mortality, is frequently used. he median is also used to describe the incidence of cancer and other disease states. Factors such as nu...

Testing of selected pharmacological agents for capturing waterfowl [Annual Progress Report

USGS Publications Warehouse

Cline, D.R.

1970-01-01

The response of game-farm mallards (Frost strain) to seven pharmacological immobilizing agents was evaluated in Phase I of a planned four-phase study. A limited amount of testing was also done with wild mallards. Single dosages were administered to determine the mean effective dose (ED50) and mean lethal dose (LD50), The therapeutic index, or safety factor (LD50/ED50), and palatability were also established. Optimum dosage rates of compounds administered orally on baits were not considered in this phase of the study. Compounds were-administered by intubation and calculated in terms of mg/kg. All except one compound produced narcosis within 5 minutes at the effective dose rate.Immobilization periods for the seven compounds ranged from 7-24 minutes, and recovery periods from 1.0-6.5 hours. Such wide variations in actions of the compounds can be attributed to a compound's rate of absorption, the ease with which it passes the blood-brain barrier, its solubility in tissues, and its rate of metabolism in the liver and kidneys. Length of both the immobilization and recovery periods were extended when dosages were increased. There was no delayed mortality among survivors with any of the seven compounds at either the ED50 or LD50. Females were generally more sensitive to the anesthetizing agents than males. The ED50 for wild mallards was substantially higher than that for the experimental game-farm birds for the two compounds on which this was tested.Tribromoethanol (Avertin of Winthrop Laboratories) satisfied all test criteria an Phase I and will be subjected to more intensive investigation in ensuing tests. Thiopental sodium (Pentothal of Amdal Company) and pentobarbital sodium (Nembutal of Abbott Laboratories) were judged to be marginal. Although their therapeutic indexes were good (5.00), recovery periods were prolonged and toxic convulsions occurred at medium to high dose rates as the LD50 was approached.Alpha-chloralose (Fisher Scientific) proved least promising of the seven compounds, mainly because of its unacceptable therapeutic index (2.25) and because it possesses prolonged induction and recovery periods. Two new experimental drugs, methoxymol and metomidate (Pitman-Moore), appeared effective and safe when administered by intubation but produced a taste aversion when added to bait. Rejection because of taste was also a problem with secobarbital (Seconal of Elanco Products), and its therapeutic index of 2.75 was unacceptable. Monitoring of heart and respiratory rates, and body temperature by telemetry showed promise as a technique for determining physiological response to drug action.

A rapid non invasive L-DOPA-¹³C breath test for optimally suppressing extracerebral AADC enzyme activity - toward individualizing carbidopa therapy in Parkinson’s disease.

PubMed

Modak, Anil; Durso, Raymon; Josephs, Ephraim; Rosen, David

2012-01-01

Peripheral carbidopa (CD) levels directly impact on central dopamine (DA) production in Parkinson disease (PD) through extracerebral inhibition of dopa decarboxylase (AADC) resulting in an increase in levodopa (LD) bioavailability. Recent data suggests that higher CD doses than those presently used in PD treatment may result in improved clinical response. Optimizing CD doses in individual patients may, therefore, result in ideal individualized treatment. A single center, randomized, double-blind study was carried out recruiting 5 Parkinson’s disease (PD) patients already on LD/CD and 1 treatment näve PD patient using stable isotope labeled LD-1-¹³C as a substrate for a noninvasive breath test to evaluate individual AADC enzyme activity. Each patient was studied five times, receiving 200 mg LD-¹³C at each visit along with one of five randomized CD doses (0, 25, 50, 100 and 200 mg). The metabolite ¹³CO₂ in breath was measured for evaluating AADC enzyme activity and plasma metabolite levels for LD-¹³C and homovanillic acid (HVA) were measured for 4 hours. HVA in plasma and ¹³CO₂ in breath are metabolic products of LD. We found a significant positive correlation of ¹³CO₂ DOB AUC0-240 with serum HVA AUC0-240 following the oral dose of LD-1-¹³C for all 5 doses of CD (r² = 0.9378). With increasing inhibition of AADC enzyme activity with CD, we observed an increase in the plasma concentration of LD.We found an inverse correlation of the 13CO2 DOB AUC with serum LD-¹³C AUC. Our studies indicate the optimal dose of CD for maximal suppression of AADC enzyme activity can be determined for each individual from ¹³CO₂ generation in breath. The LD-breath test can be a useful noninvasive diagnostic tool for evaluation of AADC enzyme activity using the biomarker ¹³CO₂ in breath, a first step in personalizing CD doses for PD patients.

Radiation dose in neoadjuvant chemoradiation therapy for esophageal cancer: patterns of care and outcomes from the National Cancer Data Base

PubMed Central

Haque, Waqar; Verma, Vivek; Butler, E. Brian

2018-01-01

Background Neoadjuvant chemoradiotherapy (CRT) for locally advanced esophageal cancer (EC) may utilize a wide variety of RT doses, without clear consensus to date. This study evaluated national practice patterns between lower dose (LD) (40–41.4 Gy) or higher dose (HD) (50–50.4 Gy) therapy, in addition to differences in survival and postoperative events. Methods The National Cancer Data Base (NCDB) was queried [2004–2013] for patients with newly-diagnosed cT1a-T4aN0/N+M0 EC that received neoadjuvant CRT followed by esophagectomy. Multivariable logistic regression determined factors predictive of receiving LD RT. Kaplan-Meier analysis evaluated overall survival (OS), and Cox proportional hazards modeling determined variables associated with OS. Propensity score matching assessed groups in a balanced manner while reducing indication biases. Results Altogether, 5,025 patients met inclusion criteria; 257 (5%) received LD RT, while 4,768 (95%) received HD RT. LD RT was more likely delivered at academic centers (P=0.038), in more recent years (2009–2013, P=0.011), and to squamous cell carcinomas (P=0.001). HD RT tended to be administered with higher T stage as well as node-positive disease (P<0.05). The median OS in the LD and HD cohorts was 39.0 vs. 35.6 months (P=0.072), and 39.0 vs. 42.7 months after propensity matching (P=0.812). Dose did not independently correlate with OS on multivariate analysis (P=0.069), but treatment at academic centers correlated with improved OS (P=0.028). There were no differences between groups in the rates of 30-day readmission (P=0.182), 30-day mortality (P=0.314), or length of postoperative hospital stay (P=0.665), but the LD group experienced lower 90-day mortality (P=0.007). Conclusions Although neoadjuvant LD CRT has been underutilized for EC in the United States, it is rising in more recent years. Dose did not significantly impact survival before or after propensity matching, nor did it independently predict for survival. Treatment at academic facilities independently correlated with higher survival, which has implications for patient counseling. PMID:29564174

The H-ARS Dose Response Relationship (DRR): Validation and Variables.

PubMed

Plett, P Artur; Sampson, Carol H; Chua, Hui Lin; Jackson, William; Vemula, Sasidhar; Sellamuthu, Rajendran; Fisher, Alexa; Feng, Hailin; Wu, Tong; MacVittie, Thomas J; Orschell, Christie M

2015-11-01

Manipulations of lethally-irradiated animals, such as for administration of pharmaceuticals, blood sampling, or other laboratory procedures, have the potential to induce stress effects that may negatively affect morbidity and mortality. To investigate this in a murine model of the hematopoietic acute radiation syndrome, 20 individual survival efficacy studies were grouped based on the severity of the administration (Admn) schedules of their medical countermeasure (MCM) into Admn 1 (no injections), Admn 2 (1-3 injections), or Admn 3 (29 injections or 6-9 oral gavages). Radiation doses ranged from LD30/30 to LD95/30. Thirty-day survival of vehicle controls in each group was used to construct radiation dose lethality response relationship (DRR) probit plots, which were compared statistically to the original DRR from which all LDXX/30 for the studies were obtained. The slope of the Admn 3 probit was found to be significantly steeper (5.190) than that of the original DRR (2.842) or Admn 2 (2.009), which were not significantly different. The LD50/30 for Admn 3 (8.43 Gy) was less than that of the original DRR (8.53 Gy, p < 0.050), whereas the LD50/30 of other groups were similar. Kaplan-Meier survival curves showed significantly worse survival of Admn 3 mice compared to the three other groups (p = 0.007). Taken together, these results show that stressful administration schedules of MCM can negatively impact survival and that dosing regimens should be considered when constructing DRR to use in survival studies.

Functional sequelae following bilateral mastectomy and immediate reconstruction with latissimus dorsi flap: medium-term follow-up.

PubMed

Paolini, Guido; Amoroso, Matteo; Pugliese, Pierfrancesco; Longo, Benedetto; Santanelli, Fabio

2014-04-01

Arm morbidity following unilateral Latissimus Dorsi (LD) flap harvest is controversial and bilateral harvest is considered potentially disabling. Arm and shoulder disability was investigated in patients undergoing bilateral mastectomy and immediate LD flap reconstruction. Thirty consecutive bilateral immediate reconstructions with denervated LD flaps, performed between 2005-2009, were retrospectively analyzed. Patients were assessed for arm function by conducting the Disability of Arm, Shoulder and Hand (DASH) test, between 12-51 months after surgery (mean 23 months). Disability scores ranged from 1-100%, with 1-25% being regarded as mild dysfunction, 26-50% as moderate dysfunction, 51-75% as severe dysfunction, and 76-100% as total dysfunction. A statistical analysis was performed using the Fisher exact test and the multivariate linear regression model for variables. The Global Mean Dash score was 14.8%. Twenty-four patients presented a mild functional deficit (< 25%), while six presented a moderate one (< 50%). Five of them presented a score < 40%, while only one patient presented a score of 49.1%. Higher scores were significantly associated (p < 0.001) with major postoperative complications and lower ones with re-innervated LD flaps (p < 0.01). An insignificant functional impairment was noted in most patients, while a moderate-to-severe one was noted only in the group with complications. Greater impairment is observed in the heavy activities. The DASH test is a useful tool in terms of informing patients and helping the surgeon to choose the best surgical option.

Repeated exposure to sublethal doses of the organophosphorus compound VX activates BDNF expression in mouse brain.

PubMed

Pizarro, Jose M; Chang, Wenling E; Bah, Mariama J; Wright, Linnzi K M; Saviolakis, George A; Alagappan, Arun; Robison, Christopher L; Shah, Jinesh D; Meyerhoff, James L; Cerasoli, Douglas M; Midboe, Eric G; Lumley, Lucille A

2012-04-01

The highly toxic organophosphorus compound VX [O-ethyl S-[2-(diisopropylamino)ethyl]methylphosphonate] is an irreversible inhibitor of the enzyme acetylcholinesterase (AChE). Prolonged inhibition of AChE increases endogenous levels of acetylcholine and is toxic at nerve synapses and neuromuscular junctions. We hypothesized that repeated exposure to sublethal doses of VX would affect genes associated with cell survival, neuronal plasticity, and neuronal remodeling, including brain-derived neurotrophic factor (BDNF). We examined the time course of BDNF expression in C57BL/6 mouse brain following repeated exposure (1/day × 5 days/week × 2 weeks) to sublethal doses of VX (0.2 LD(50) and 0.4 LD(50)). BDNF messenger RNA expression was significantly (p < 0.05) elevated in multiple brain regions, including the dentate gyrus, CA3, and CA1 regions of the hippocampal formation, as well as the piriform cortex, hypothalamus, amygdala, and thalamus, 72 h after the last 0.4 LD(50) VX exposure. BDNF protein expression, however, was only increased in the CA3 region of the hippocampus. Whether increased BDNF in response to sublethal doses of VX exposure is an adaptive response to prevent cellular damage or a precursor to impending brain damage remains to be determined. If elevated BDNF is an adaptive response, exogenous BDNF may be a potential therapeutic target to reduce the toxic effects of nerve agent exposure.

Comparative study of the fungicide Benomyl toxicity on some plant growth promoting bacteria and some fungi in pure cultures.

PubMed

Elslahi, Randa H; Osman, Awad G; Sherif, Ashraf M; Elhussein, Adil A

2014-03-01

Six laboratory experiments were carried out to investigate the effect of the fungicide Benomyl on pure cultures of some plant growth promoting bacteria (PGPB) and some fungi. The highest LD50 was recorded for Bacillus circulans and proved to be the most resistant to the fungicide, followed by Azospirillum braziliense, while Penicillium sp. was the most affected microorganism. LD50 values for the affected microorganisms were in 21-240 orders of magnitude lower in comparison with the LD50 value for Azospirillum braziliense. The results indicate a strong selectivity for Benomyl against Rhizobium meliloti and Penicillium sp. when compared to other microorganisms tested. The highest safety coefficient was recorded for Bacillus circulans followed by Azospirillum braziliense, while Rhizobium meliloti, showed the lowest safety coefficient value compared to other bacteria. The lowest toxicity index was recorded for Bacillus circulans and Azospirillum braziliense. The slope of the curves for Bacillus sp. and Rhizobium meliloti was steeper than that of the other curves, suggesting that even a slight increase of the dose of the fungicide can cause a very strong negative effect. In conclusion, Benomyl could be applied without restriction when using inocula based on growth promoting bacteria such as symbiotic nitrogen fixers (Rhizobium meliloti), non-symbiotic nitrogen fixers (Azospirillum braziliense) or potassium solibilizers (Bacillus circulans), given that the fungicide is applied within the range of the recommended field dose.

Large Dataset of Acute Oral Toxicity Data Created for Testing ...

EPA Pesticide Factsheets

Acute toxicity data is a common requirement for substance registration in the US. Currently only data derived from animal tests are accepted by regulatory agencies, and the standard in vivo tests use lethality as the endpoint. Non-animal alternatives such as in silico models are being developed due to animal welfare and resource considerations. We compiled a large dataset of oral rat LD50 values to assess the predictive performance currently available in silico models. Our dataset combines LD50 values from five different sources: literature data provided by The Dow Chemical Company, REACH data from eChemportal, HSDB (Hazardous Substances Data Bank), RTECS data from Leadscope, and the training set underpinning TEST (Toxicity Estimation Software Tool). Combined these data sources yield 33848 chemical-LD50 pairs (data points), with 23475 unique data points covering 16439 compounds. The entire dataset was loaded into a chemical properties database. All of the compounds were registered in DSSTox and 59.5% have publically available structures. Compounds without a structure in DSSTox are currently having their structures registered. The structural data will be used to evaluate the predictive performance and applicable chemical domains of three QSAR models (TIMES, PROTOX, and TEST). Future work will combine the dataset with information from ToxCast assays, and using random forest modeling, assess whether ToxCast assays are useful in predicting acute oral toxicity. Pre

Aluminum Trichloride Induces Hypertension and Disturbs the Function of Erythrocyte Membrane in Male Rats.

PubMed

Zhang, Qiuyue; Cao, Zheng; Sun, Xudong; Zuang, Cuicui; Huang, Wanyue; Li, Yanfei

2016-05-01

Aluminum (Al) is the most abundant metal in the earth's crust. Al accumulates in erythrocyte and causes toxicity on erythrocyte membrane. The dysfunction of erythrocyte membrane is a potential risk to hypertension. The high Al content in plasma was associated with hypertension. To investigate the effect of AlCl3 on blood pressure and the function of erythrocyte membrane, the rats were intragastrically exposed to 0, 64(1/20 LD50), 128(1/10 LD50), and 256(1/5 LD50) mg/kg body weight AlCl3 in double distilled water for 120 days, respectively. Then, we determined the systolic and mean arterial blood pressures of rats, the osmotic fragility, the percentage of membrane proteins, the activities of Na(+)/K(+)-ATPase, Mg(2+)-ATPase, Ca(2+)-ATPase, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-pX), and malondialdehyde (MDA) content of the erythrocyte membrane in this experiment. The results showed that AlCl3 elevated the systolic and mean arterial blood pressure of rats, increased the osmotic fragility, decreased the percentage of membrane protein, inhibited the activities of Na(+)/K(+)-ATPase, Mg(2+)-ATPase, Ca(2+)-ATPase, CAT, SOD and GSH-pX, and increased the MDA content of erythrocyte membrane. These results indicate that AlCl3 may induce hypertension by disturbing the function of erythrocyte membrane.

Fumigant toxicity of basil oil compounds and related compounds to Thrips palmi and Orius strigicollis.

PubMed

Kim, Kwang-Ho; Yi, Chang-Geun; Ahn, Young-Joon; Kim, Soon Il; Lee, Sang-Guei; Kim, Jun-Ran

2015-09-01

This study was aimed at assessing the fumigant toxicity to adult Thrips palmi (a serious insect pest) and Orius strigicollis (a beneficial predator insect) of basil (Ocimum basilicum) essential oil compounds and structurally related compounds using vapour-phase toxicity bioassays. Against adult T. palmi, linalool (LD50 0.0055 mg cm(-3) ) was the most toxic fumigant and was 15.2-fold more effective than dichlorvos (0.0837 mg cm(-3) ). Strong fumigant toxicity was also observed in pulegone (0.0095 mg cm(-3) ), (±)-camphor (0.0097 mg cm(-3) ) and 1,8-cineole (0.0167 mg cm(-3) ). Moderate toxicity was produced by camphene, 3-carene, (-)-menthone, (+)-α-pinene, (+)-β-pinene, α-terpineol and (-)-α-thujone (0.0215-0.0388 mg cm(-3) ). Against adult O. strigicollis, dichlorvos (LD50 9.0 × 10(-10) mg cm(-3) ) was the most toxic fumigant, whereas the LD50 values of these compounds ranged from 0.0127 to >0.23 mg cm(-3) . Based upon the selective toxicity ratio, the compounds described are more selective than dichlorvos. The basil oil compounds described merit further study as potential insecticides for control of T. palmi in greenhouses because of their generally lower toxicity to O. strigicollis and their greater activity as a fumigant than dichlorvos. © 2014 Society of Chemical Industry.

[Pharmacological analysis of the effect of natural double-helical nucleic acids on the detoxifying function of the liver].

PubMed

Masycheva, V I; Morozova, E N; Nadolinnaia, I G

1988-10-01

The effect of interferon inductors i.e. double stranded RNAs from S. cerevisiae and phage F6 on the liver detoxicating function was studied on noninbred albino mice. The liver detoxicating function was tested by duration of hexenal sleep. It was shown that intraperitoneal administration of the yeast and phage RNAs in doses of 1/5 LD50 for three times led to increasing of the narcotic sleep duration in the animals by 65 and 207 per cent, respectively. The effect was of the dose-dependent nature. The doses not inducing reliable inhibition of hexenal metabolism were equal to 1/10 LD50 for the yeast dsRNA and 1/27 LD50 for the phage dsRNA. The inhibitory effect of the dsRNAs was retained for 2-3 days after discontinuation of the drug use. When the dsRNAs were administered simultaneously with nembutal, an inductor of the liver microsomal enzymes, the dsRNAs eliminated its inducing effect. Simultaneous administration of alpha-tocopherol lowered the dsRNA effect on hexenal metabolism. The findings suggested that the dsRNA inhibitory effect on the liver detoxicating function was grounded on the mechanisms associated with inhibition of syntheses and activation of lipid peroxidation specific of the monooxygenase system under the action of the dsRNAs.

Estimation of reliability of predictions and model applicability domain evaluation in the analysis of acute toxicity (LD50).

PubMed

Sazonovas, A; Japertas, P; Didziapetris, R

2010-01-01

This study presents a new type of acute toxicity (LD(50)) prediction that enables automated assessment of the reliability of predictions (which is synonymous with the assessment of the Model Applicability Domain as defined by the Organization for Economic Cooperation and Development). Analysis involved nearly 75,000 compounds from six animal systems (acute rat toxicity after oral and intraperitoneal administration; acute mouse toxicity after oral, intraperitoneal, intravenous, and subcutaneous administration). Fragmental Partial Least Squares (PLS) with 100 bootstraps yielded baseline predictions that were automatically corrected for non-linear effects in local chemical spaces--a combination called Global, Adjusted Locally According to Similarity (GALAS) modelling methodology. Each prediction obtained in this manner is provided with a reliability index value that depends on both compound's similarity to the training set (that accounts for similar trends in LD(50) variations within multiple bootstraps) and consistency of experimental results with regard to the baseline model in the local chemical environment. The actual performance of the Reliability Index (RI) was proven by its good (and uniform) correlations with Root Mean Square Error (RMSE) in all validation sets, thus providing quantitative assessment of the Model Applicability Domain. The obtained models can be used for compound screening in the early stages of drug development and prioritization for experimental in vitro testing or later in vivo animal acute toxicity studies.

Web-based Interspecies Correlation Estimation (Web-ICE) for Acute Toxicity: User Manual Version 3.1

EPA Science Inventory

Predictive toxicological models are integral to ecological risk assessment because data for most species are limited. Web-based Interspecies Correlation Estimation (Web-ICE) models are least square regressions that predict acute toxicity (LC50/LD50) of a chemical to a species, ge...

WEB-BASED INTERSPECIES CORRELATION ESTIMATION (WEB-ICE) FOR ACUTE TOXICITY: USER MANUAL V2

EPA Science Inventory

Predictive toxicological models are integral to environmental risk Assessment where data for most species are limited. Web-based Interspecies Correlation Estimation (Web-ICE) models are least square regressions that predict acute toxicity (LC50/LD50) of a chemical to a species, ...

A preliminary safety evaluation of polyhexamethylene guanidine hydrochloride.

PubMed

Asiedu-Gyekye, Isaac Julius; Mahmood, Seidu Abdulai; Awortwe, Charles; Nyarko, Alexander Kwadwo

2014-01-01

Polyhexamethylene guanidine hydrochloride (PHMGH) is used worldwide as an antimicrobial agent with broad spectra of activity and also for treating pool water. This non-GLP preliminary study aims at investigating in a subchronic toxicity study possible effects at supra-optimal doses of this biocide. Both acute and subchronic toxicity studies were conducted. LD(50) for PHMGH was estimated to be 600 mg/kg (ie LC(50) 2 ml of 7.5% solution) when administered as a single dose by gavage via a stomach tube in accordance with the expected route of administration. The acute studies showed that the median lethal dose (LD(50)) of 600 mg/kg was accompanied by signs of neurotoxicity. Haematological and biochemical parameters of subchronic toxicity studies were non-significant. Subchronic doses of 0.006 mg/kg, 0.012 mg/kg and 0.036 mg/kg were administered. 20% of the animals at a dose of 0.006 mg/kg and 0.036 mg/kg showed mild degrees of hydropic changes in proximal tubules while 10% of animals at all the doses had their liver tissues showing local areas of mild pericentral hepatocytes degeneration. PHMGH did not produce any major organ defect with regard to the kidney, heart, and liver. The LD(50) was much higher than the recommended dosage by a factor of about 50,000. The recommended residual concentration is far less than the median lethal dose using rats as test subjects. These results could serve as a basis for investigating the full toxicological profile if it is to be used for the treatment of raw water to make it potable. © The Author(s) 2014.

Differential regulation of duplicate light-dependent protochlorophyllide oxidoreductases in the diatom Phaeodactylum tricornutum

DOE PAGES

Hunsperger, Heather M.; Ford, Christopher J.; Miller, James S.; ...

2016-07-01

Diatoms (Bacilliariophyceae) encode two light-dependent protochlorophyllide oxidoreductases (POR1 and POR2) that catalyze the penultimate step of chlorophyll biosynthesis in the light. Algae live in dynamic environments whose changing light levels induce photoacclimative metabolic shifts, including altered cellular chlorophyll levels. We hypothesized that the two POR proteins may be differentially adaptive under varying light conditions. Using the diatom Phaeodactylum tricornutum as a test system, differences in POR protein abundance and por gene expression were examined when this organism was grown on an alternating light:dark cycles at different irradiances; exposed to continuous light; and challenged by a significant decrease in light availability.more » As a result, for cultures maintained on a 12h light: 12h dark photoperiod at 200μEm –2 s –1 ( 200L/D), both por genes were up-regulated during the light and down-regulated in the dark, though por1 transcript abundance rose and fell earlier than that of por2. Little concordance occurred between por1 mRNA and POR1 protein abundance. In contrast, por2 mRNA and POR2 protein abundances followed similar diurnal patterns. When 200L/D P. tricornutum cultures were transferred to continuous light ( 200L/L), the diurnal regulatory pattern of por1 mRNA abundance but not of por2 was disrupted, and POR1 but not POR2 protein abundance dropped steeply. Under 1200μEm –2 s –1 ( 1200L/D), both por1 mRNA and POR1 protein abundance displayed diurnal oscillations. A compromised diel por2 mRNA response under 1200L/D did not impact the oscillation in POR2 abundance. When cells grown at 1200L/D were then shifted to 50μEm –2 s –1 (50L/D), por1 and por2 mRNA levels decreased swiftly but briefly upon light reduction. Thereafter, POR1 but not POR2 protein levels rose significantly in response to this light stepdown.« less

Efficacy evaluation of physostigmine and anticholinergic adjuncts as a pretreatment for nerve agent intoxication. (Reannouncement with new availability information)

DOE Office of Scientific and Technical Information (OSTI.GOV)

von Bredow, J.; Corcoran, K.; Maitland, G.

1991-12-31

Pretreatment of nonhuman primates with physostigmine (Phy) and scopolamine or physostigmine and trihexyphenidyl 25 min before exposure to 2 LD50 soman im resulted in complete survival without convulsions or loss of consciousness. When identically pretreated animals were challenged with 5 LD50s of soman followed by atropine and 2-PAM therapy 1 min later, all animals experienced a loss of consciousness for approximately 10 min followed by functional recovery within an additional 20 min. These findings indicated that a pretreatment regimen composed of Phy and cholinolytic is capable of protecting primates from an absolute lethal dose of soman with rapid recovery frommore » incapacitation. Physostigmine, nerve agent pretreatment, cynomolgus monkeys soman (GD).« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walton, B.T.

The toxicity of acridine to Acheta domesticus (L.) was determined to evaluate the potential for this pollutant from synthetic fuels production to affect insect populations. Acridine was highly toxic to cricket eggs but not toxic to nymphs or adults. An LD/sub 50/ for eggs = 7.4 ..mu..g/g was calculated from the LC/sub 50/ = 15.1 +- 0.61 ppM. The 24-h LD/sub 10/ of acridine to nymphal crickets was > 332 ..mu..g/g. Male and female crickets consumed up to 1.0% of their weight in acridine over an 18-day period with no significant effect on mortality, weight gain, digestibility of food, ormore » fecundity. Percent hatch of eggs from treated crickets (81.0 +- 6.7) was not significantly different from controls (77.2 +- 5.1).« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walton, B.T.

The toxicity of acridine to Acheta domesticus (L.) was determined to evaluate the potential for this pollutant from synthetic fuels production to affect insect populations. Acridine was highly toxic to cricket eggs but not toxic to nymphs or adults. An LD/sub 50/ for eggs = 7.4 ..mu..g/g was calculated from the LC/sub 50/ = 15.1 +- 0.61 ppM. The 24-h LD/sub 10/ of acridine to nymphal crickets was >332 ..mu..g/g. Male and female crickets consumed up to 1.0% of their weight in acridine over an 18-day period with no significant effect on mortality, weight gain, digestibility of food, or fecundity.more » Percent hatch of eggs from treated crickets (81.0 +- 6.7) was not significantly different from controls (77.2 +- 5.1).« less

Estimating Risk of Hematopoietic Acute Radiation Syndrome in Children.

PubMed

Adams, Tim G; Sumner, Louise E; Casagrande, Rocco

2017-12-01

Following a radiological terrorist attack or radiation accident, the general public may be exposed to radiation. Historically, modeling efforts have focused on radiation effects on a "reference man"-a 70-kg, 180-cm-tall, 20- to 30-y-old male-which does not adequately reflect radiation hazard to special populations, particularly children. This work examines the radiosensitivity of children with respect to reference man to develop a set of parameters for modeling hematopoetic acute radiation syndrome in children. This analysis was performed using animal studies and the results verified using data from medical studies. Overall, the hematopoietic system in children is much more radiosensitive than that in adults, with the LD50 for children being 56% to 91% of the LD50 of adults, depending on age.

Blood-brain barrier penetration of novel pyridinealdoxime methiodide (PAM)-type oximes examined by brain microdialysis with LC-MS/MS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Okuno, Sou; Sakurada, Koichi; Ohta, Hikoto

2008-02-15

To develop a new reactivator of inhibited acetylcholinesterase (AChE) that can easily penetrate the blood-brain barrier (BBB), BBB penetration of 6 known and novel pyridinealdoxime methiodide (PAM)-type oximes (alkylPAMs) with relatively high reactivation activities was examined by in vivo rat brain microdialysis with liquid chromatography-mass spectrometry (LC-MS/MS). The 50% lethal dose (LD{sub 50}) of alkylPAMs was intravenously determined for Wistar rats, then the limit of detection, quantification range and linearity of the calibration curve of the alkylPAMs in dialysate and blood were determined by LC-MS/MS. Following 10% LD{sub 50} intravenous administration of the alkylPAMs, 4-[(hydroxyimino) methyl]-1-(2-phenylethyl) pyridinium bromide (4-PAPE) andmore » 4-[(hydroxyimino) methyl]-1-octylpyridinium bromide (4-PAO) appeared in the dialysate. Striatal extracellular fluid/blood concentration ratios were 0.039 {+-} 0.018 and 0.301 {+-} 0.183 (mean {+-} SEM), respectively, 1 h after treatment. This is the first report of BBB penetration of 4-PAPE, and the concentration ratio was smaller than that of 2-PAM.The mean BBB penetration of 4-PAO was approximately 30%, indicating that intravenous administration of 4-PAO may be effective for the reactivation of blocked cholinesterase in the brain. However, the toxicity of 4-PAO (LD{sub 50}; 8.89 mg/kg) was greater than that of 2-PAM. Further investigation is required to determine the effects of these alkylPAMs in organophosphate poisoning.« less

An antiapoptotic Bcl-2 family protein index predicts the response of leukaemic cells to the pan-Bcl-2 inhibitor S1

PubMed Central

Zhang, Z; Liu, Y; Song, T; Xue, Z; Shen, X; Liang, F; Zhao, Y; Li, Z; Sheng, H

2013-01-01

Background: Bcl-2-like members have been found to be inherently overexpressed in many types of haematologic malignancies. The small-molecule S1 is a BH3 mimetic and a triple inhibitor of Bcl-2, Mcl-1 and Bcl-XL. Methods: The lethal dose 50 (LD50) values of S1 in five leukaemic cell lines and 41 newly diagnosed leukaemia samples were tested. The levels of Bcl-2 family members and phosphorylated Bcl-2 were semiquantitatively measured by western blotting. The interactions between Bcl-2 family members were tested by co-immunoprecipitation. The correlation between the LD50 and expression levels of Bcl-2 family members, alone or in combination, was analysed. Results: S1 exhibited variable sensitivity with LD50 values ranging >2 logs in both established and primary leukaemic cells. The ratio of pBcl-2/(Bcl-2+Mcl-1) could predict the S1 response. Furthermore, we demonstrated that pBcl-2 antagonised S1 by sequestering the Bak and Bim proteins that were released from Mcl-1, andpBcl-2/Bak, pBcl-2/Bax and pBcl-2/Bim complexes cannot be disrupted by S1. Conclusion: A predictive index was obtained for the novel BH3 mimetic S1. The shift of proapoptotic proteins from being complexed with Mcl-1 to being complexed with pBcl-2 was revealed for the first time, which is the mechanism underlying the index value described herein. PMID:23558901

Development of Derivatives of 3, 3′-Diindolylmethane as Potent Leishmania donovani Bi-Subunit Topoisomerase IB Poisons

PubMed Central

Sengupta, Souvik; Mandal, Madhumita; Jaisankar, Parasuraman; D'Annessa, Ilda; Desideri, Alessandro; Majumder, Hemanta K.

2011-01-01

Background The development of 3, 3′-diindolyl methane (DIM) resistant parasite Leishmania donovani (LdDR50) by adaptation with increasing concentrations of the drug generates random mutations in the large and small subunits of heterodimeric DNA topoisomerase I of Leishmania (LdTOP1LS). Mutation of large subunit of LdTOP1LS at F270L is responsible for resistance to DIM up to 50 µM concentration. Methodology/Principal Findings In search of compounds that inhibit the growth of the DIM resistant parasite and inhibit the catalytic activity of mutated topoisomerase I (F270L), we have prepared three derivatives of DIM namely DPDIM (2,2′-diphenyl 3,3′-diindolyl methane), DMDIM (2,2′-dimethyl 3,3′-diindolyl methane) and DMODIM (5,5′-dimethoxy 3,3′-diindolyl methane) from parent compound DIM. All the compounds inhibit the growth of DIM resistant parasites, induce DNA fragmentation and stabilize topo1-DNA cleavable complex with the wild type and mutant enzyme. Conclusion The results suggest that the three derivatives of DIM can act as promising lead molecules for the generation of new anti-leishmanial agents. PMID:22174820

Genome-wide linkage disequilibrium and past effective population size in three Korean cattle breeds.

PubMed

Sudrajad, P; Seo, D W; Choi, T J; Park, B H; Roh, S H; Jung, W Y; Lee, S S; Lee, J H; Kim, S; Lee, S H

2017-02-01

The routine collection and use of genomic data are useful for effectively managing breeding programs for endangered populations. Linkage disequilibrium (LD) using high-density DNA markers has been widely used to determine population structures and predict the genomic regions that are associated with economic traits in beef cattle. The extent of LD also provides information about historical events, including past effective population size (N e ), and it allows inferences on the genetic diversity of breeds. The objective of this study was to estimate the LD and N e in three Korean cattle breeds that are genetically similar but have different coat colors (Brown, Brindle and Jeju Black Hanwoo). Brindle and Jeju Black are endangered breeds with small populations, whereas Brown Hanwoo is the main breeding population in Korea. DNA samples from these cattle breeds were genotyped using the Illumina BovineSNP50 Bead Chip. We examined 13 cattle breeds, including European taurines, African taurines and indicines, and hybrids to compare their LD values. Brown Hanwoo consistently had the lowest mean LD compared to Jeju Black, Brindle and the other 13 cattle breeds (0.13, 0.19, 0.21 and 0.15-0.22 respectively). The high LD values of Brindle and Jeju Black contributed to small N e values (53 and 60 respectively), which were distinct from that of Brown Hanwoo (531) for 11 generations ago. The differences in LD and N e for each breed reflect the breeding strategy applied. The N e for these endangered cattle breeds remain low; thus, effort is needed to bring them back to a sustainable tract. © 2016 Stichting International Foundation for Animal Genetics.

Legionnaires' Disease in Hotels and Passenger Ships: A Systematic Review of Evidence, Sources, and Contributing Factors.

PubMed

Mouchtouri, Varvara A; Rudge, James W

2015-01-01

Travel-associated Legionnaires' disease (LD) is a serious problem, and hundreds of cases are reported every year among travelers who stayed at hotels, despite the efforts of international and governmental authorities and hotel operators to prevent additional cases. A systematic review of travel-associated LD events (cases, clusters, outbreaks) and of environmental studies of Legionella contamination in accommodation sites was conducted. Two databases were searched (PubMed and EMBASE). Data were extracted from 50 peer-reviewed articles that provided microbiological and epidemiological evidence for linking the accommodation sites with LD. The strength of evidence was classified as strong, possible, and probable. Three of the 21 hotel-associated events identified and four of nine ship-associated events occurred repeatedly on the same site. Of 197 hotel-associated cases, 158 (80.2%) were linked to hotel cooling towers and/or potable water systems. Ship-associated cases were most commonly linked to hot tubs (59/83, 71.1%). Common contributing factors included inadequate disinfection, maintenance, and monitoring; water stagnation; poor temperature control; and poor ventilation. Across all 30 events, Legionella concentrations in suspected water sources were >10,000 cfu/L, <10,000 cfu/L, and unknown in 11, 3, and 13 events, respectively. In five events, Legionella was not detected only after repeated disinfections. In environmental studies, Legionella was detected in 81.1% of ferries (23/28) and 48.9% of hotels (587/1,200), while all 12 cruise ships examined were negative. This review highlights the need for LD awareness strategies targeting operators of accommodation sites. Increased standardization of LD investigation and reporting, and more rigorous follow-up of LD events, would help generate stronger, more comparable evidence on LD sources, contributing factors, and control measure effectiveness. © 2015 International Society of Travel Medicine.

Late diagnosis of influenza in adult patients during a seasonal outbreak.

PubMed

Choi, Seong-Ho; Chung, Jin-Won; Kim, Tark; Park, Ki-Ho; Lee, Mi Suk; Kwak, Yee Gyung

2018-03-01

Due to advances in diagnostic techniques, clinicians are more frequently performing influenza diagnostic tests and referring to their test results ahead of the administration of neuraminidase inhibitors (NAIs). To investigate the clinical significance of the time from symptom onset to laboratory diagnosis, we reviewed the clinical characteristics of adult patients with influenza who had an early laboratory diagnosis (ED) or a late laboratory diagnosis (LD) at one of four tertiary care centers during a seasonal outbreak of influenza. Clinical data were collected from 1,405 adults during the 2013 to 2014 influenza season. A patient was regarded as receiving an ED or LD if he/she received an influenza diagnostic test at 0 to 1 or 4 to 7 days after symptom onset, respectively. Early NAI therapy and late NAI therapy were defined as the administration of NAI ≤ 2 or > 2 days after symptom onset, respectively. Nearly half of the patients (47.0%) received an ED (n = 661), whereas 13.5% (n = 190) received a LD. Patients with a LD had initial symptoms of cough, sputum production, and dyspnea and experienced pneumonia, antibiotic therapy, hospitalization, and admission to the intensive care unit more often than those with an ED. NAI therapy and early NAI therapy were less frequent in patients with a LD than those with an ED. Of the analyzed baseline characteristics, age ≥ 50 years, influenza B infection, and diagnosis using a polymerase chain reaction test were significantly associated with a LD. LD was associated with inappropriate antiviral therapy and complicated presenting features in adult patients with seasonal influenza. ED of influenza should be emphasized, especially for older adults.

Extent of genome-wide linkage disequilibrium in Australian Holstein-Friesian cattle based on a high-density SNP panel.

PubMed

Khatkar, Mehar S; Nicholas, Frank W; Collins, Andrew R; Zenger, Kyall R; Cavanagh, Julie A L; Barris, Wes; Schnabel, Robert D; Taylor, Jeremy F; Raadsma, Herman W

2008-04-24

The extent of linkage disequilibrium (LD) within a population determines the number of markers that will be required for successful association mapping and marker-assisted selection. Most studies on LD in cattle reported to date are based on microsatellite markers or small numbers of single nucleotide polymorphisms (SNPs) covering one or only a few chromosomes. This is the first comprehensive study on the extent of LD in cattle by analyzing data on 1,546 Holstein-Friesian bulls genotyped for 15,036 SNP markers covering all regions of all autosomes. Furthermore, most studies in cattle have used relatively small sample sizes and, consequently, may have had biased estimates of measures commonly used to describe LD. We examine minimum sample sizes required to estimate LD without bias and loss in accuracy. Finally, relatively little information is available on comparative LD structures including other mammalian species such as human and mouse, and we compare LD structure in cattle with public-domain data from both human and mouse. We computed three LD estimates, D', Dvol and r2, for 1,566,890 syntenic SNP pairs and a sample of 365,400 non-syntenic pairs. Mean D' is 0.189 among syntenic SNPs, and 0.105 among non-syntenic SNPs; mean r2 is 0.024 among syntenic SNPs and 0.0032 among non-syntenic SNPs. All three measures of LD for syntenic pairs decline with distance; the decline is much steeper for r2 than for D' and Dvol. The value of D' and Dvol are quite similar. Significant LD in cattle extends to 40 kb (when estimated as r2) and 8.2 Mb (when estimated as D'). The mean values for LD at large physical distances are close to those for non-syntenic SNPs. Minor allelic frequency threshold affects the distribution and extent of LD. For unbiased and accurate estimates of LD across marker intervals spanning < 1 kb to > 50 Mb, minimum sample sizes of 400 (for D') and 75 (for r2) are required. The bias due to small samples sizes increases with inter-marker interval. LD in cattle is much less extensive than in a mouse population created from crossing inbred lines, and more extensive than in humans. For association mapping in Holstein-Friesian cattle, for a given design, at least one SNP is required for each 40 kb, giving a total requirement of at least 75,000 SNPs for a low power whole-genome scan (median r2 > 0.19) and up to 300,000 markers at 10 kb intervals for a high power genome scan (median r2 > 0.62). For estimation of LD by D' and Dvol with sufficient precision, a sample size of at least 400 is required, whereas for r2 a minimum sample of 75 is adequate.

Analysis of volatile combustion products and a study of their toxicological effects.

NASA Technical Reports Server (NTRS)

Seader, J. D.; Einhorn, I. N.; Drake, W. O.; Mihlfeith, C. M.

1972-01-01

An experimental program was conducted to study the thermochemical, flammability and toxicological characteristics of uncoated and coated polyisocyanurate foams. The coatings used were fluorinated copolymer and an intumescent material. Combustion and pyrolysis gases were analyzed by gas chromatography and mass spectrometry. The LD-50 and LD-100 tests were performed on Sprague-Dawley rats housed in an environmental chamber. The isocyanurate foam, fluorinated-copolymer-coated foam, and the intumescent-coated foam were found to have excellent flammability and insulation characteristics, although smoke development was substantial.

Imaging the Laguna del Maule Volcanic Field, central Chile using magnetotellurics: Evidence for crustal melt regions laterally-offset from surface vents and lava flows

NASA Astrophysics Data System (ADS)

Cordell, Darcy; Unsworth, Martyn J.; Díaz, Daniel

2018-04-01

Magnetotelluric (MT) data were collected at the Laguna del Maule volcanic field (LdMVF), located in central Chile (36°S, 70.5°W), which has been experiencing unprecedented upward ground deformation since 2007. These data were used to create the first detailed three-dimensional electrical resistivity model of the LdMVF and surrounding area. The resulting model was spatially complex with several major conductive features imaged at different depths and locations around Laguna del Maule (LdM). A near-surface conductor (C1; 0.5 Ωm) approximately 100 m beneath the lake is interpreted as a conductive smectite clay cap related to a shallow hydrothermal reservoir. At 4 km depth, a strong conductor (C3; 0.3 Ωm) is located beneath the western edge of LdM. The proximity of C3 to the recent Pleistocene-to-Holocene vents in the northwest LdMVF and nearby hot springs suggests that C3 is a hydrous (>5 wt% H2O), rhyolitic partial melt with melt fraction >35% and a free-water hydrothermal component. C3 dips towards, and is connected to, a deeper conductor (C4; 1 Ωm). C4 is located to the north of LdM at >8 km depth below surface and is interpreted as a long-lived, rhyolitic-to-andesitic magma reservoir with melt fractions less than 35%. It is hypothesized that the deeper magma reservoir (C4) is providing melt and hydrothermal fluids to the shallower magma reservoir (C3). A large conductor directly beneath the LdMVF is not imaged with MT suggesting that any mush volume beneath LdM must be anhydrous (<2 wt% H2O), low temperature and low melt fraction (<25%) in order to go undetected. The presence of large conductors to the north has important implications for magma dynamics as it suggests that material may have a significant lateral component (>10 km) as it moves from the deep magma reservoir (C4) to create small, ephemeral volumes of eruptible melt (C3). It is hypothesized that there may be a north-south contrast in physical processes affecting the growth of melt-rich zones since major conductors are imaged in the northern LdMVF while no major conductors are detected beneath the southern vents. The analysis and interpretation of features directly beneath the lake is complicated by the surface conductor C1 which attenuates low-frequency signals. The attenuation from C1 does not affect C3 or C4. At 1 km depth directly beneath LdM, a weak conductor (C2; <10 Ωm) is imaged but is not required by the data. Forward modeling tests show that a relatively large (30 km3), high melt fraction (>50%), silicic reservoir with 5 wt% H2O at 2 to 5 km depth beneath the inflation center is not supported by the MT data. However, a smaller (10 km3) eruptible volume could go undetected even with relatively high melt fraction (>50%). The location of large melt regions to the north has important implications for long-term volcanic hazards at LdMVF as well as other volcanoes as it raises the possibility that the vent distribution is not always indicative of the location of deeper source regions of melt.

A Comparative Study of Pathways to Care for Children with Specific Learning Disability and Mental Retardation

PubMed Central

Chakraborty, Suhash; Kommu, John Vijay Sagar; Srinath, Shoba; Seshadri, Shekhar P.; Girimaji, Satish C.

2014-01-01

Context: Early intervention in specific learning disability (SpLD) results in better outcome and prevents comorbidity. Understanding the pathways is therefore important. Aims: To study and compare the pathways to care for children with SpLD and mental retardation (MR) before reaching a tertiary care center. Settings and Design, Material and Methods: A cross-sectional study was conducted for pathways to care of two groups: SpLD and MR with 50 children in each group from 8 to 16 years. MINI-KID for comorbidity and Goldberg's pathway to care instrument was used. The groups were divided into early contact (up to three carers) and late contact (more than three carers) and compared. Statistical Analysis: Data were analyzed using Statistical Packages for Social Sciences (SPSS) version 10.0 software. Results: Majority (n = 24 or 48%) of SpLD children visited “others” (teachers, neighbors, relatives, and guardians of fellow classmates) as first carer. Allopathic practitioners were the first choice for MR children (n = 31 or 62%). Six children (12%) in SpLD group and 10 of MR (20%) group have seen either traditional practitioner or healer as first carer. Maximum referral to the tertiary center in both groups was done by others (62% in SpLD and 56% in MR group). Early contacts in SpLD group belonged to younger age group (P = 0.01). While comparing both groups on the basis of early and late contact, mother's education was found to be significant in early contact group (P = 0.036) and having comorbidity was significant among late contacts (P = 0.038). Conclusions: The pathways to care for SpLD children are more or less similar to MR children whose parents recognize MR late. Both the groups visit multiple carers including traditional healers substantiating the strong belief for supernatural causation of developmental disorders in India. PMID:24701006

Sensitivity of species to chemicals: dose-response characteristics for various test types (coldbloodedLC50, cold-blooded LR50 and warm-blooded LD50) and modes of action

EPA Science Inventory

While sensitivity of model species to common toxicants has been addressed, a systematic analysis of inter-species variability for different test types, modes of action and species is as yet lacking. Hence, the aim of the present study was to identify similarities and differences ...

9 CFR 113.101 - Leptospira Pomona Bacterin.

Code of Federal Regulations, 2011 CFR

2011-01-01

... young adult hamsters, each weighing 50 to 90 grams, with 0.25 ml of the diluted bacterin either... least 10 but not more than 12 additional hamsters from the same group as unvaccinated controls. (3... intraperitoneally with a suspension of virulent Leptospira pomona organisms, using a dose of 10-10,000 hamster LD50...

9 CFR 113.101 - Leptospira Pomona Bacterin.

Code of Federal Regulations, 2010 CFR

2010-01-01

... young adult hamsters, each weighing 50 to 90 grams, with 0.25 ml of the diluted bacterin either... least 10 but not more than 12 additional hamsters from the same group as unvaccinated controls. (3... intraperitoneally with a suspension of virulent Leptospira pomona organisms, using a dose of 10-10,000 hamster LD50...

40 CFR Appendix A to Part 300 - The Hazard Ranking System

Code of Federal Regulations, 2011 CFR

2011-07-01

... control groups. For HRS purposes, the response considered is cancer. [milligrams toxicant per kilogram...-2Containment factor values for surface water migration pathway. 4-3Drainage area values. 4-4Soil group... a group of exposed organisms. The LC50 is used in the HRS in assessing acute toxicity. LD 50 (lethal...

40 CFR Appendix A to Part 300 - The Hazard Ranking System

Code of Federal Regulations, 2012 CFR

2012-07-01

... control groups. For HRS purposes, the response considered is cancer. [milligrams toxicant per kilogram...-2Containment factor values for surface water migration pathway. 4-3Drainage area values. 4-4Soil group... a group of exposed organisms. The LC50 is used in the HRS in assessing acute toxicity. LD 50 (lethal...

Pharmacological activity and toxicity of some neurotropic agents under conditions of experimental hypodynamia

NASA Technical Reports Server (NTRS)

Kirichek, L. T.

1980-01-01

The indices of pharmacological range, risk coefficients, ED50, LD50, the size of the area of toxic activity, and maximal tolerated and absolute lethal doses were compared in hypodynamic mice. The pharmacological activity of the test neurotropic agents exhibiting a central action underwent change, but their toxicity remained unchanged.

Evaluation of Acute toxicity of Lambda Cyhalothrin in Mus musculus L.

PubMed

Tomar, Monika; Kumar, Ajay; Kataria, Sudhir Kumar

2015-08-01

Lambda Cyhalothrin (LCT) is a type II synthetic pyrethroid widely used in agriculture, home pest control and protection of food stuff. Here, we evaluated its toxicity on biochemical parameters (Total protein, Acetyl cholinesterase, RNA and DNA) and liver histological alteration in mice after 24 h of oral administration @ 25, 50 and 75% of LD50 i.e.; 26.49 mg/kg/body wt. Distilled water (DW) and Cyclophosphamide (CP @ 40 mg/kg/body wt.) were used as negative and positive control; respectively. LCT treated mice showed significant decrease in total protein (P < 0.01), acetyl cholinesterase (P < 0.001) and DNA (P < 0.001) in a dose dependent manner. On the contrary, RNA content showed significant increase (P < 0.01) at 50% of LD50 of LCT. Histological observations of the mice liver showed vascular congestion and hepatocyte degeneration with 6.63 mg/kg/body wt. of LCT; and accumulation of RBCs with sinusoid degeneration and wide necrotic area with pyknosis with 13.25 and 19.88 mg/kg/body wt., respectively. The results demonstrated LCT induced biochemical changes and hepatotoxicity in female mice.

Toxicity and hazard of vanadium to mallard ducks (Anas platyrhynchos) and Canada geese (Branta canadensis).

PubMed

Rattner, Barnett A; McKernan, Moira A; Eisenreich, Karen M; Link, William A; Olsen, Glenn H; Hoffman, David J; Knowles, Kathy A; McGowan, Peter C

2006-02-01

A recent Canada goose (Branta canadensis) die-off at a petroleum refinery fly ash pond in Delaware was attributed to vanadium (V) toxicity. Because of the paucity of V toxicity data for wild birds, a series of studies was undertaken using the forms of V believed to have resulted in this incident. In 7-d single oral dose trials with mallard drakes (Anas platyrhynchos), the estimated median lethal dose (LD50) for vanadium pentoxide was 113 mg/kg body weight, while the LD50 for sodium metavanadate was 75.5 mg/kg. Sodium metavanadate was found to be even more potent (LD50 = 37.2 mg/kg) in male Canada geese. The most distinctive histopathological lesion of both forms of V was lympho-granulocytic enteritis with hemorrhage into the intestinal lumen. Vanadium accumulation in liver and kidney was proportional to the administered dose, and predictive analyses based on these data suggest that V concentrations of 10 microg/g dry weight (dw) in liver and 25 microg/g dw in kidney are associated with mortality (>90% confidence that exposure is >LD50) in mallards acutely exposed to sodium metavanadate. Chronic exposure to increasing dietary concentrations of sodium metavanadate (38.5 to 2651 ppm) over 67 d resulted in V accumulation in liver and kidney (25.2 and 13.6 microg/g dw, respectively), mild intestinal hemorrhage, blood chemistry changes, and evidence of hepatic oxidative stress in mallards, although some of these responses may have been confounded by food avoidance and weight loss. Dietary exposure of mallards to 250 ppm sodium metavanadate for 4 wk resulted in modest accumulation of V in liver and kidney (<5 microg/g dw) and mild intestinal hemorrhage. Based on these data and other observations, it is unlikely that chronic low-level dietary exposure to V poses a direct lethal hazard to wildlife. However, point sources, such as the V-laden fly ash pond encountered by geese at the petroleum refinery in Delaware, may pose a significant hazard to water birds.

Toxicity and hazard of vanadium to mallard ducks (Anas platyrhynchos) and Canada geese (Branta canadensis)

USGS Publications Warehouse

Rattner, Barnett A.; McKernan, Moira A.; Eisenreich, Karen M.; Link, William A.; Olsen, Glenn H.; Hoffman, David J.; Knowles, K.A.; McGowan, Peter C.

2006-01-01

A recent Canada goose (Branta canadensis) die-off at a petroleum refinery fly ash pond in Delaware was attributed to vanadium (V) toxicity. Because of the paucity of V toxicity data for wild birds, a series of studies was undertaken using the forms of V believed to have resulted in this incident. In 7-d single oral dose trials with mallard drakes (Anas platyrhynchos), the estimated median lethal dose (LD50) for vanadium pentoxide was 113 mg/kg body weight, while the LD50 for sodium metavanadate was 75.5 mg/kg. Sodium metavanadate was found to be even more potent (LD50 = 37.2 mg/kg) in male Canada geese. The most distinctive histopathological lesion of both forms of V was lympho-granulocytic enteritis with hemorrhage into the intestinal lumen. Vanadium accumulation in liver and kidney was proportional to the administered dose, and predictive analyses based on these data suggest that V concentrations of 10 μg/g dry weight (dw) in liver and 25 μg/g dw in kidney are associated with mortality (>90% confidence that exposure is >LD50) in mallards acutely exposed to sodium metavanadate. Chronic exposure to increasing dietary concentrations of sodium metavanadate (38.5 to 2651 ppm) over 67 d resulted in V accumulation in liver and kidney (25.2 and 13.6 μg/g dw, respectively), mild intestinal hemorrhage, blood chemistry changes, and evidence of hepatic oxidative stress in mallards, although some of these responses may have been confounded by food avoidance and weight loss. Dietary exposure of mallards to 250 ppm sodium metavanadate for 4 wk resulted in modest accumulation of V in liver and kidney (<5 μg/g dw) and mild intestinal hemorrhage. Based on these data and other observations, it is unlikely that chronic low-level dietary exposure to V poses a direct lethal hazard to wildlife. However, point sources, such as the V-laden fly ash pond encountered by geese at the petroleum refinery in Delaware, may pose a significant hazard to water birds.

An in vitro and in vivo evaluation of the efficacy of recombinant human liver prolidase as a catalytic bioscavenger of chemical warfare nerve agents.

PubMed

Rezk, Peter E; Zdenka, Pierre; Sabnekar, Praveena; Kajih, Takwen; Mata, David G; Wrobel, Chester; Cerasoli, Douglas M; Chilukuri, Nageswararao

2015-01-01

In this study, we determined the ability of recombinant human liver prolidase to hydrolyze nerve agents in vitro and its ability to afford protection in vivo in mice. Using adenovirus containing the human liver prolidase gene, the enzyme was over expressed by 200- to 300-fold in mouse liver and purified to homogeneity by affinity and gel filtration chromatography. The purified enzyme hydrolyzed sarin, cyclosarin and soman with varying rates of hydrolysis. The most efficient hydrolysis was with sarin, followed by soman and by cyclosarin {apparent kcat/Km [(1.9 ± 0.3), (1.7 ± 0.2), and (0.45 ± 0.04)] × 10(5 )M(-1 )min(-1), respectively}; VX and tabun were not hydrolyzed by the recombinant enzyme. The enzyme hydrolyzed P (+) isomers faster than the P (-) isomers. The ability of recombinant human liver prolidase to afford 24 hour survival against a cumulative dose of 2 × LD50 of each nerve agent was investigated in mice. Compared to mice injected with a control virus, mice injected with the prolidase expressing virus contained (29 ± 7)-fold higher levels of the enzyme in their blood on day 5. Challenging these mice with two consecutive 1 × LD50 doses of sarin, cyclosarin, and soman resulted in the death of all animals within 5 to 8 min from nerve agent toxicity. In contrast, mice injected with the adenovirus expressing mouse butyrylcholinesterase, an enzyme which is known to afford protection in vivo, survived multiple 1 × LD50 challenges of these nerve agents and displayed no signs of toxicity. These results suggest that, while prolidase can hydrolyze certain G-type nerve agents in vitro, the enzyme does not offer 24 hour protection against a cumulative dose of 2 × LD50 of G-agents in mice in vivo.

The effect of 7,8-methylenedioxylycoctonine-type diterpenoid alkaloids on the toxicity of methyllycaconitine in mice.

PubMed

Welch, K D; Panter, K E; Gardner, D R; Green, B T; Pfister, J A; Cook, D; Stegelmeier, B L

2008-10-01

Larkspur plants contain numerous norditerpenoid alkaloids, which include the 7,8-methylenedioxylycoctonine (MDL)-type alkaloids and the N-(methylsuccinimido)anthranoyllycoctonine (MSAL)-type alkaloids. The MSAL-type alkaloids are generally much more toxic (typically >20 times). Toxicity of many tall larkspurs, such as Delphinium barbeyi, has been attributed to its large concentration of MSAL-type alkaloids, including methyllycaconitine (MLA). However, the norditerpenoid alkaloids found in the greatest concentrations in most D. barbeyi populations are either deltaline or 14-O-acetyldictyocarpine (14-OAD), both less toxic MDL-type alkaloids. Although the individual toxicities of MLA, 14-OAD, and deltaline have been determined, the impact (additive or antagonistic) that large concentrations of deltaline or 14-OAD in the plant have on the toxicity of MLA is unknown. Consequently, the effect of MDL-type alkaloids on the toxicity of MLA was compared by using median lethal dose (LD(50)) and toxicokinetic profiles of the brainand muscle from mice receiving i.v. administration of these alkaloids, individually or in combination, at ratios of 1:1, 1:5, and 1:25 MLA to MDL-type alkaloids. The LD(50) for MLA alone was 4.4 +/- 0.7 mg/kg of BW, whereas the coadministration of MLA and deltaline at 1:1, 1:5, and 1:25 resulted in an LD(50) of 2.7, 2.5, and 1.9 mg/kg of BW, respectively. Similarly, the coadministration of MLA and 14-OAD at 1:1, 1:5, and 1:25 resulted in an LD(50) of 3.1, 2.2, and 1.5 mg/kg of BW, respectively. Coadministration of mixtures did not result in increased MLA bioavailability or alterations in clearance from the brain and muscle. Consequently, the increased toxicity of the mixtures was not a result of increased MLA bioavailability (based on the maximum concentrations observed) or alterations in MLA clearance from the brain and muscle, because these were unchanged. These results demonstrate that MDL-type alkaloids have an additive effect on MLA toxicity in mice and may also play a role in the overall toxicity of tall larkspur plants in cattle.

High-dose versus low-dose local anaesthetic for transversus abdominis plane block post-Caesarean delivery analgesia: a meta-analysis.

PubMed

Ng, S C; Habib, A S; Sodha, S; Carvalho, B; Sultan, P

2018-02-01

The optimal local-anaesthetic (LA) dose for transversus-abdominis-plane (TAP) block is unclear. In this meta-analysis, we aimed to determine whether TAP blocks for Caesarean delivery (CD) with low-dose (LD) LA demonstrated non-inferiority in terms of analgesic efficacy, compared with high-dose (HD) LA. A literature search was performed for randomised controlled trials examining the analgesic efficacy of TAP blocks vs control after CD. The different dosing used in these studies was classified as HD or LD (bupivacaine equivalents >50 or ≤50 mg per block side, respectively). The pooled results of each dose group vs control were indirectly compared using the Q test. The primary outcome was 24 h opioid consumption. Secondary outcomes included 6 and 24 h postoperative pain scores, time to first analgesia, 6 h opioid consumption, opioid-related side-effects, and maternal satisfaction. Fourteen studies consisting of 770 women (389 TAP and 381 control) were included. Compared with controls, the 24 h opioid consumption (milligram morphine equivalents) was lower in HD [mean difference (MD) 95% confidence interval (CI) -22.41 (-38.56, -6.26); P=0.007; I 2 =93%] and LD [MD 95% CI -16.29 (-29.74, -2.84); P=0.02; I 2 =98%] TAP groups. However, no differences were demonstrated between the HD and LD groups (P=0.57). There were also no differences between the HD and LD groups for the 6 h opioid consumption, time to first analgesia, 6 and 24 h pain scores, postoperative nausea and vomiting, pruritus, and maternal satisfaction. Low-dose TAP blocks for Caesarean delivery provide analgesia and opioid-sparing effects comparable with the high-dose blocks. This suggests that lower doses can be used to reduce local anaesthetic toxicity risk without compromising the analgesic efficacy. Copyright © 2017 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Lean diabetes in middle-aged adults: A joint analysis of the German DIVE and DPV registries.

PubMed

Hartmann, Bettina; Lanzinger, Stefanie; Bramlage, Peter; Groß, Felix; Danne, Thomas; Wagner, Siegfried; Krakow, Dietmar; Zimmermann, Artur; Malcharzik, Christian; Holl, Reinhard W

2017-01-01

To assess differences in demographics, treatment and outcome of lean (LD) compared to overweight and obese people with diabetes clinically classified as type 2 diabetes mellitus (T2DM). We combined data from the German DIVE (Diabetes Versorgungs-Evaluation) and DPV (Diabetes-Patienten-Verlaufsdokumentation) databases to produce a large cohort of people with T2DM. The characteristics of people with Body Mass Index (BMI) <25 kg/m2, ≥25-30 kg/m2 and ≥30 kg/m2 aged 30 to 50 years were compared, including demographics, cardiovascular (CV) risk factors, comorbidities and outcomes. A total of 37,870 people were included in the analysis, 3,191 of these (8.4%) had a BMI < 25 kg/m2. LD reported more nicotine (41.6% of 2,070 vs. 38.1% of 6,070 and 33.4% of 16,823; P<0.001)and alcohol consumption (12.0% of 1,282, 10.3% of 3,594 and 6.6% of 9,418; P<0.001)compared to overweight and obese people. More LD were treated with insulin in comparison to the other subgroups (short acting insulin 33.1% of 3,191 vs. 28.4% of 9,234 and 28.0% of 25,445; P <0.001; long acting insulin 31.3% of 3,191 vs. 28.9% of 9,234 and 29.3% of 25,445; P = 0.043). Regression models adjusted for age, gender and diabetes duration showed a 2.50 times higher odds ratio (OR) for hypoglycemia and a 2.52 higher OR for mortality in LD compared to the BMI subgroup ≥30 kg/m2. LD is associated with an increased risk of hypoglycaemia and death. Patients are characterized by male gender, lifestyle habits as smoking and alcohol consumption while cardiovascular comorbidities are less important. In comparison to patients of the other weight groups they are treated with insulin more often and considerably less with metformin.

Crotalidae polyvalent immune Fab (ovine) antivenom is effective in the neutralization of South American viperidae venoms in a murine model.

PubMed

Richardson, William H; Tanen, David A; Tong, Tri C; Betten, David P; Carstairs, Shaun D; Williams, Saralyn R; Cantrell, Frank L; Clark, Richard F

2005-06-01

Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV) is used in the treatment of symptomatic crotaline envenomations in North America. Unlike Antivenin (Crotalidae) Polyvalent, which is approved for treatment of crotaline envenomation in North and South America, FabAV is manufactured using only venoms from crotaline snakes native to the United States. This study was designed to evaluate the efficacy of FabAV in the neutralization of venom from 2 South American crotaline snakes: Crotalus durissus terrificus (tropical rattlesnake) and Bothrops atrox (fer-de-lance). A randomized, blinded, placebo-controlled murine model of intraperitoneal venom injection was used. Venom potency was determined in preliminary median lethal dose (LD 50) dosing studies. Study animals were then divided into 7 groups: (1) C durissus terrificus venom (Sigma-Aldrich Co.)+FabAV, (2) C durissus terrificus venom (Sigma-Aldrich Co.)+0.9% normal saline solution, (3) C durissus terrificus venom (Biotoxins Inc.)+FabAV, (4) C durissus terrificus venom (Biotoxins Inc.)+normal saline solution, (5) B atrox venom+FabAV, (6) B atrox venom+normal saline solution, and (7) FabAV+normal saline solution. Twice the estimated LD 50 was the chosen venom dose, and the amount of FabAV injected was 10 times the amount needed for venom neutralization. Statistical analysis included Fisher's exact test and log-rank testing to compare survival rates and times. The venom LD 50 was found in preliminary studies to be 0.9 mg/kg and 1.35 mg/kg for the C durissus terrificus venom obtained from Sigma-Aldrich Co. and Biotoxins Inc., respectively. The LD 50 for B atrox venom was 5.0 mg/kg. All animals receiving venom only and saline solution died. Animals receiving FabAV together with either venom survived to the end of the 24-hour observation period ( P <.001). Comparison of survival times between groups demonstrated a significant difference in time to death between venom-only control groups and the FabAV+venom groups (P <.001). All animals in the FabAV+normal saline solution group survived to the conclusion of the study. FabAV, when premixed with venom, decreases lethality in a murine model of intraperitoneal venom injection of the South American pit vipers, C durissus terrificus and B atrox .

The Madagascar hissing cockroach as a novel surrogate host for Burkholderia pseudomallei, B. mallei and B. thailandensis.

PubMed

Fisher, Nathan A; Ribot, Wilson J; Applefeld, Willard; DeShazer, David

2012-06-22

Burkholderia pseudomallei and Burkholderia mallei are gram-negative pathogens responsible for the diseases melioidosis and glanders, respectively. Both species cause disease in humans and animals and have been designated as category B select agents by the Centers for Disease Control and Prevention (CDC). Burkholderia thailandensis is a closely related bacterium that is generally considered avirulent for humans. While it can cause disease in rodents, the B. thailandensis 50% lethal dose (LD50) is typically ≥ 104-fold higher than the B. pseudomallei and B. mallei LD50 in mammalian models of infection. Here we describe an alternative to mammalian hosts in the study of virulence and host-pathogen interactions of these Burkholderia species. Madagascar hissing cockroaches (MH cockroaches) possess a number of qualities that make them desirable for use as a surrogate host, including ease of breeding, ease of handling, a competent innate immune system, and the ability to survive at 37°C. MH cockroaches were highly susceptible to infection with B. pseudomallei, B. mallei and B. thailandensis and the LD50 was <10 colony-forming units (cfu) for all three species. In comparison, the LD50 for Escherichia coli in MH cockroaches was >105 cfu. B. pseudomallei, B. mallei, and B. thailandensis cluster 1 type VI secretion system (T6SS-1) mutants were all attenuated in MH cockroaches, which is consistent with previous virulence studies conducted in rodents. B. pseudomallei mutants deficient in the other five T6SS gene clusters, T6SS-2 through T6SS-6, were virulent in both MH cockroaches and hamsters. Hemocytes obtained from MH cockroaches infected with B. pseudomallei harbored numerous intracellular bacteria, suggesting that this facultative intracellular pathogen can survive and replicate inside of MH cockroach phagocytic cells. The hemolymph extracted from these MH cockroaches also contained multinuclear giant cells (MNGCs) with intracellular B. pseudomallei, which indicates that infected hemocytes can fuse while flowing through the insect's open circulatory system in vivo. The results demonstrate that MH cockroaches are an attractive alternative to mammals to study host-pathogen interactions and may allow the identification of new Burkholderia virulence determinants. The importance of T6SS-1 as a virulence factor in MH cockroaches and rodents suggests that the primary role of this secretion system is to target evasion of the innate immune system.

Novel potent pyridoxine-based inhibitors of AChE and BChE, structural analogs of pyridostigmine, with improved in vivo safety profile.

PubMed

Strelnik, Alexey D; Petukhov, Alexey S; Zueva, Irina V; Zobov, Vladimir V; Petrov, Konstantin A; Nikolsky, Evgeny E; Balakin, Konstantin V; Bachurin, Sergey O; Shtyrlin, Yurii G

2016-08-15

We report a novel class of carbamate-type ChE inhibitors, structural analogs of pyridostigmine. A small library of congeneric pyridoxine-based compounds was designed, synthesized and evaluated for AChE and BChE enzymes inhibition in vitro. The most active compounds have potent enzyme inhibiting activity with IC50 values in the range of 0.46-2.1μM (for AChE) and 0.59-8.1μM (for BChE), with moderate selectivity for AChE comparable with that of pyridostigmine and neostigmine. Acute toxicity studies using mice models demonstrated excellent safety profile of the obtained compounds with LD50 in the range of 22-326mg/kg, while pyridostigmine and neostigmine are much more toxic (LD50 3.3 and 0.51mg/kg, respectively). The obtained results pave the way to design of novel potent and safe cholinesterase inhibitors for symptomatic treatment of neuromuscular disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dehydroleucodine, a Sesquiterpene Lactone from Gynoxys verrucosa, Demonstrates Cytotoxic Activity against Human Leukemia Cells.

PubMed

Ordóñez, Paola E; Sharma, Krishan K; Bystrom, Laura M; Alas, Maria A; Enriquez, Raul G; Malagón, Omar; Jones, Darin E; Guzman, Monica L; Compadre, Cesar M

2016-04-22

The sesquiterpene lactones dehydroleucodine (1) and leucodine (2) were isolated from Gynoxys verrucosa, a species used in traditional medicine in southern Ecuador. The activity of these compounds was determined against eight acute myeloid leukemia (AML) cell lines and compared with their activity against normal peripheral blood mononuclear cells. Compound 1 showed cytotoxic activity against the tested cell lines, with LD50 values between 5.0 and 18.9 μM. Compound 2 was inactive against all of the tested cell lines, demonstrating that the exocyclic methylene in the lactone ring is required for cytotoxic activity. Importantly, compound 1 induced less toxicity to normal blood cells than to AML cell lines and was active against human AML cell samples from five patients, with an average LD50 of 9.4 μM. Mechanistic assays suggest that compound 1 has a similar mechanism of action to parthenolide (3). Although these compounds have significant structural differences, their lipophilic surface signatures show striking similarities.

Aerogenic vaccination with a Burkholderia mallei auxotroph protects against aerosol-initiated glanders in mice.

PubMed

Ulrich, Ricky L; Amemiya, Kei; Waag, David M; Roy, Chad J; DeShazer, David

2005-03-14

Burkholderia mallei is an obligate mammalian pathogen that causes the zoonotic disease glanders. Two live attenuated B. mallei strains, a capsule mutant and a branched-chain amino acid auxotroph, were evaluated for use as vaccines against aerosol-initiated glanders in mice. Animals were aerogenically vaccinated and serum samples were obtained before aerosol challenge with a high-dose (>300 times the LD50) of B. mallei ATCC 23344. Mice vaccinated with the capsule mutant developed a Th2-like Ig subclass antibody response and none survived beyond 5 days. In comparison, the auxotrophic mutant elicited a Th1-like Ig subclass antibody response and 25% of the animals survived for 1 month postchallenge. After a low-dose (5 times the LD50) aerosol challenge, the survival rates of auxotroph-vaccinated and unvaccinated animals were 50 and 0%, respectively. Thus, live attenuated strains that promote a Th1-like Ig response may serve as promising vaccine candidates against aerosol infection with B. mallei.

[Influence of Leukodeplated Blood Transfusion on Cellular Immunity of Acute Leukemia Patients].

PubMed

Lu, Ya-Lan; Zhang, Xin; Wang, Yu-Fang; Ke, Shan-Dong; Ke, Jin-Yong; Liu, Geng-Fu; Chen, Shi-Ming

2016-08-01

To study the influence of leukodeplated blood transfusion on cellular immunity of patients with acute leuemia, so as to provide support for application of leuko-deplated blood transfusion in clinic. A total of 100 AL patients from January 2012 to December 2015 were chosen, and were divided into 2 groups: leukodeplated blood transfusion group(50 cases) and routine blood transfusion group(RBT) as control (50 cases). The effective rate, side effects, peripheral blood T cells and expression level of TLR2 and TLR4 were compared between 2 groups. The expression levels CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+) of TLR2 and TLR4 in control group were (52.18±2.14)%, （27.28±1.19）%,（24.21±1.65）%,1.22±0.18,0.62±0.04 and 0.57±0.05, respectively, after treatment; while these indicators in LdBT group were （52.18±2.14）%,（30.97±2.01）%,（27.08±1.55）%,1.39±0.24,0.91±0.06 and 0.87±0.07, respectively, and above-mentioned indicators in LdBT group were significantly higher than those in control group（P<0.05）. Compared with these indicators before treatment, CD3(+), CD4(+), CD8(+) and CD4(+)/CD8(+) in the patients increased significantly（P<0.05）. The efficiency was 92.00% (46/50) in LdBT group, and 84.00% (42/50) in control group, without statistically significant difference（P>0.05）. The rate of side effects in study group was 6% (3/50), 18% (9/50) in control group, with statistically significance difference （P<0.05）. Leukodeplated blood transfusion can improve the cellular immunity of AL patients, and reduce the rate of side effects.

An egg injection method for assessing early life stage mortality of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls in rainbow trout, (Oncorhynchus mykiss)

USGS Publications Warehouse

Walker, M.K.; Hufnagle, L.C.; Clayton, M.K.; Peterson, R.E.

1992-01-01

To characterize the risk that polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls (PCBs) pose to salmonid early life stage survival, we developed a method to expose rainbow trout (Oncorhynchus mykiss) eggs to graded doses of PCDD, PCDF, and PCB congeners, using 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a prototype. Rainbow trout eggs were injected 24–50 h post-fertilization with 0.2 μl of 50 mM phosphatidylcholine (PC) liposomes (control) or 0.2 μl of 5–7 graded doses of TCDD incorporated into 50 mM PC liposomes. Injection volume never exceeded 0.6% egg volume. Immediately following injection, the injection site was sealed with Super glue®, resulting in 92–97% of TCDD dose retained by the egg. Following both egg injection and waterborne egg exposure. TCDD toxicity in rainbow trout was manifested by half-hatching mortality but predominantly by sac fry mortality associated with hemorrhages, pericardial edema, and yolk sac edema. TCDD LD50s, following injection and waterborne exposure of rainbow trout eggs, were 421 (331–489) and 439 (346–519) pg TCDD/g egg (LD50, 95% fiducial limits), respectively. As in rainbow trout, TCDD toxicity in lake trout (Salvelinus namaycush) following the same two routes of exposure was manifested by half-hatching mortality but predominantly by sac fry mortality preceded by hemorrhages and yolk sac edema. LD50s, based on the dose of TCDD in lake trout eggs, were 47 (21–65) and 65 (60–71) pg/g following injection and waterborne exposure, respectively. The egg injection method is ideal for assessing the relationship between early life stage mortality in rainbow trout and graded egg doses of individual PCDD, PCDF, or PCB congeners.

Chemical constituents and insecticidal activities of the essential oil from Amomum tsaoko against two stored-product insects.

PubMed

Wang, Ying; You, Chun-Xue; Wang, Cheng-Fang; Yang, Kai; Chen, Ran; Zhang, Wen-Juan; Du, Shu-Shan; Geng, Zhu-Feng; Deng, Zhi-Wei

2014-01-01

The aim of this research was to determine the chemical constituents and toxicities of the essential oil derived from Amomum tsaoko Crevost et Lemarie fruits against Tribolium castaneum (Herbst) and Lasioderma serricorne (Fabricius). Essential oil of A. tsaoko was obtained from hydrodistillation and was investigated by gas chromatography-mass spectrometry (GC-MS). GC-MS analysis of the essential oil resulted in the identification of 43 components, of which eucalyptol (23.87%), limonene (22.77%), 2-isopropyltoluene (6.66%) and undecane (5.74%) were the major components. With a further isolation, two active constituents were obtained from the essential oil and identified as eucalyptol and limonene. The essential oil and the two isolated compounds exhibited potential insecticidal activities against two storedproduct insects. Limonene showed pronounced contact toxicity against both insect species (LD50 = 14.97 μg/adult for T. castaneum; 13.66 μg/adult for L. serricorne) and was more toxic than eucalyptol (LD50 = 18.83 μg/adult for T. castaneum; 15.58 μg/adult for L. serricorne). The essential oil acting against the two species of insects showed LD50 values of 16.52 and 6.14 μg/adult, respectively. Eucalyptol also possessed strong fumigant toxicity against both insect species (LC50 = 5.47 mg/L air for T. castaneum; 5.18 mg/L air for L. serricorne) and was more toxic than limonene (LC50 = 6.21 mg/L air for T. castaneum; 14.07 mg/L air for L. serricorne), while the crude essential oil acting against the two species of insects showed LC50 values of 5.85 and 8.70 mg/L air, respectively. These results suggested that the essential oil of A. tsaoko and the two compounds may be used in grain storage to combat insect pests.

Further Characterization of the Mitigation of Radiation Lethality by Protective Wounding

PubMed Central

Dynlacht, Joseph R.; Garrett, Joy; Joel, Rebecca; Lane, Katharina; Mendonca, Marc S.; Orschell, Christie M.

2017-01-01

There continues to be a major effort in the United States to develop mitigators for the treatment of mass casualties that received high-intensity acute ionizing radiation exposures from the detonation of an improvised nuclear device during a radiological terrorist attack. The ideal countermeasure should be effective when administered after exposure, and over a wide range of absorbed doses. We have previously shown that the administration of a subcutaneous incision of a defined length, if administered within minutes after irradiation, protected young adult female C57BL/6 mice against radiation-induced lethality, and increased survival after total-body exposure to an LD50/30 X-ray dose from 50% to over 90%. We refer to this approach as “protective wounding”. In this article, we report on our efforts to further optimize, characterize and demonstrate the validity of the protective wounding response by comparing the response of female and male mice, varying the radiation dose, the size of the wound, and the timing of wounding with respect to administration of the radiation dose. Both male and female mice that received a subcutaneous incision after irradiation were significantly protected from radiation lethality. We observed that the extent of protection against lethality after an LD50/30 X-ray dose was independent of the size of the subcutaneous cut, and that a 3 mm subcutaneous incision is effective at enhancing the survival of mice exposed to a broad range of radiation doses (LD15–LD100). Over the range of 6.2–6.7 Gy, the increase in survival observed in mice that received an incision was associated with an enhanced recovery of hematopoiesis. The enhanced rate of recovery of hematopoiesis was preceded by an increase in the production of a select group of cytokines. Thus, a thorough knowledge of the timing of the cytokine cascade after wounding could aid in the development of novel pharmacological radiation countermeasures that can be administered several days after the actual radiation exposure. PMID:28437188

Design of Mini Latissimus Dorsi Flap Based on Thoracodorsal Vascular Patterns.

PubMed

Elzawawy, Ehab Mostafa; Kelada, Melad Naim; Al Karmouty, Ahmed Farouk

2018-06-01

Latissimus dorsi (LD) flap has been used for reconstructive purposes in oncoplastic breast surgery. Using large part of the muscle as a flap leads to a residual functional loss. Muscle sparing and mini LD flaps can be used with no functional sequelae. However, the design of such flap presents a challenge. Twenty cadavers were dissected on both sides to identify the different vascular patterns of the thoracodorsal (TD) pedicle. The vessels were counted, and the following measurements were taken: diameter, length, distance from inferior angel of scapula, and vertebral level. Data were collected and entered into the personal computer. Statistical analysis was done using (SPSS/version 20) software. Five vascular patterns of TD pedicle were found. Type 1: a long vertically descending pedicle giving 3 to 4 transverse medial branches to LD in 40%. Type 2: a short pedicle terminating into 1 to 2 serratus anterior collaterals and 1 to 2 transverse lateral branches to LD in 10%. Type 3: a long vertically descending pedicle giving 2 to 3 small lateral branches to upper part of LD and terminating into medial and lateral branches in the lower part of LD in 10%. Type 4: a short pedicle that gives 4 to 5 terminal branches to LD, one of them is a long vertically descending branch to lower part of LD in 20%. Type 5: a short pedicle that terminates into a transverse medial and a long vertical branch to LD in 20%. The classically described pattern of TD pedicle (type 5) was found in 20% of cases, whereas the most commonly found pattern was type 1. This means that the pattern of TD branching is unpredictable, and a preoperative ultrasound is essential to define the existing pattern and plan the best LD flap design for each patient. In types 1 and 5, the flap can be designed using the transverse medial branch or branches. In type 2, one of the lateral transverse branches can be used. In types 3, 4, and 5, the long descending vertical branch can be used. It has a sizeable diameter (1.80.23 mm), length (12.31.64 cm), and can be located 6.50.96 cm below the inferior angle of scapula.

Polysaccharides induce radioprotection of murine hemopoietic stem cells and increase the LD50/30 days

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maisin, J.R.; Kondi-Tamba, A.; Mattelin, G.

1986-02-01

Intravenous administration of 60 mg/kg of a polysaccharide (MNR, MNZ, GLP/BO4, GLP/BO5) significantly decreases the mortality of mice exposed to a single dose of X rays. The dose reduction factors (DRF) obtained for MNZ, MNR, GLP/BO4, and GLP/BO5 given intraperitoneally 15 min before exposure were 2.16, 1.93, 1.80, and 1.94, respectively. The DRF was not increased when MNZ or GLP/BO4 were combined with injection of AET before X-ray exposure. The LD50 for the CFUs exposed in vivo in mice was 1.13 Gy for the treated mice and 0.75 Gy for the nontreated mice. This corresponds to a DRF of 1.6.more » The DRF calculated from the slope is 1.27.« less

Deriving allowable daily intakes for systemic toxicants lacking chronic toxicity data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Layton, D.W.; Mallon, B.J.; Rosenblatt, D.H.

1987-03-01

The lack of human toxicological data for most chemical compounds makes it difficult to quickly assess health risks associated with exposure to contaminants at hazardous waste sites. It would therefore be advantageous to have a technique for estimating acceptable daily intakes (ADIs) of potentially toxic substances based on more widely available animal toxicity data. This article focuses on the use of LD50 data to derive provisional ADIs, and it suggests multiplying oral LD50 values (expressed in mg/kg of body wt) by a factor in the range of 5 X 10(-6) to 1 X 10(-5) day-1 to convert them to suchmore » ADIs. It is emphasized that these interim ADI values are no substitute for toxicity testing, but that such testing would most likely result in higher ADI estimates.« less

Protection by butyrylcholinesterase against organophosphorus poisoning in nonhuman primates. (Reannouncement with new availability information)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Broomfield, C.A.; Maxwell, D.M.; Solana, R.P.

1991-12-31

Butyrylcholinesterase (BuChE) was examined as an in vivo exogenous scavenger for highly toxic organophosphorus (OP) poisons. Protection studies with equine BuChE were carried out in rhesus monkeys trained to perform a Serial Probe Recognition task. The pharmacokinetics of equine BuChE administered i.v. in rhesus monkeys revealed an elimination T1/2 of -620 hr. Animals given 503 nmol of BuChE i.v. and then challenged with 220 to 260 nmol of soman (two LD50; a lethal dose in untreated animals) all survived with no clinical signs of OP poisoning. Serial Probe Recognition performance was depressed after enzyme administration and at 1 hr postsoman.more » However, all monkeys performed the task at base-line levels at 8 hr after soman and throughout the remainder of the experimental period. Two different monkeys each were given two doses of sarin, 183 nmol/ dose (one LD50) after 460 nmol of BuChE. No signs were observed. A third group of monkeys given 253 or 340 nmol (three and four LD50, respectively) of soman after 460 nmol of BuChE required 1 mg/kg of atropine i.v. 1 0 min postsoman, but recovered completely within 24 hr. Our results indicate that BuChE has the required properties to function as a biological scavenger to protect against the pharmacological and behavioral toxicity of OP poisons. Exogenous scavenger, butyrylcholinesterase, nerve agent.« less

Effects of 3,3{prime},4,4{prime},5-pentachlorobiphenyl (PCB 126), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), or an extract derived from field-collected cormorant eggs injected into double-crested cormorant (Phalacrocorax auritus) eggs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Powell, D.C.; Aulerich, R.J.; Powell, J.F.

1997-07-01

Double-crested cormorant (Phalacrocorax auritus) eggs were injected with either 3,3{prime},4,4{prime},5-pentachlorobiphenyl (PCB 126), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), or an extract derived from field-collected double-crested cormorant eggs. These compounds were injected into the yolks of cormorant eggs from an isolated colony on Lake Winnipegosis, Manitoba, Canada. Upon hatching, chicks were necropsied. The brain, bursa, heart, liver, and spleen were removed and weighed. An approximate median lethal dose (LD50) of 158 {micro}g/kg egg was determined for PCB 126, which is 69 times greater than the LD50 determined for the chicken (Gallus domesticus) in a previous study. A significantly greater mortality occurred at the highest dosemore » of TCDD when compared to the vehicle control. However, the mortality data did not provide sufficient information for the determination of an LD50. The cormorant egg extract did not adversely affect hatchability. No significant increases were observed in the incidence of developmental abnormalities, including pronounced edema, in any of the treatment groups, nor were there any relevant effects on body and organ weights. Based on the results from this study, the cormorant appears to be considerably less sensitive to polyhalogenated diaromatic hydrocarbons than the chicken, which has been the typical species used for egg injection studies.« less

Decreased pneumotoxicity of deuterated 3-methylindole: bioactivation requires methyl C-H bond breakage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huijzer, J.C.; Adams, J.D. Jr.; Yost, G.S.

1987-08-01

The bioactivation of the pulmonary toxin 3-methylindole has been postulated to proceed via the formation of an imine methide. To test this hypothesis, the toxicity in mice of 3-methylindole has been compared to the toxicity of its perdeuteromethyl analog. Deuteration of the methyl group should slow the rate of production of the corresponding imine methide and diminish the toxicity of deutero-3-methylindole, if C-H bond breakage occurs prior to or during the rate-determining step. In agreement with this hypothesis, deutero-3-methylindole was synthesized and was shown to be significantly less toxic (LD50 735 mg/kg) than 3-methylindole (LD50 578 mg/kg). Both compounds producedmore » the same lesion at the LD50 dose, bronchiolar damage and mild alveolar edema, indicating that deuteration of 3-methylindole did not change the pathologic process. However, at a much lower dose (25 mg/kg), 3-methylindole produced a mild bronchiolar lesion whereas deutero-3-methylindole did not damage lung tissue. Additionally, administration of deutero-3-methylindole caused less pulmonary edema compared to 3-methylindole, as assessed by increased wet lung weights. Finally, the depletion of pulmonary glutathione by deutero-3-methylindole was considerably slower than depletion by 3-methylindole. The electrophilic imine methide has been postulated to be the intermediate which binds with and depletes glutathione. Therefore, the evidence presented here supports the involvement of an imine methide as the primary reactive intermediate in 3-methylindole-mediated pneumotoxicity.« less

DRDE-07 and its analogues as promising cytoprotectants to nitrogen mustard (HN-2)--an alkylating anticancer and chemical warfare agent.

PubMed

Sharma, Manoj; Vijayaraghavan, R; Gautam, Anshoo

2009-08-10

Nitrogen mustard (HN-2), also known as mechlorethamine, is an alkylating anticancer agent as well as blister inducing chemical warfare agent. We evaluated the cytoprotective efficacy of amifostine, DRDE-07 and their analogues, and other antidotes of mustard agents against HN-2. Administration of 1 LD(50) of HN-2 (20mg/kg) percutaneously, decreased WBC count from 24h onwards. Liver glutathione (GSH) level decreased prominently and the maximum depletion was observed on 7th day post-HN-2 administration. Oxidised glutathione (GSSG) level increased significantly at 24h post-administration and subsequently showed a progressive decrease. Hepatic malondialdehyde (MDA) level and percent DNA damage increased progressively following HN-2 administration. The spleen weight decreased progressively and reached a minimum on 3-4 days with subsequent increase. The antidotes were administered repeatedly for 4 and 8 days after percutaneous administration of single sublethal dose (0.5 and 0.25 LD(50)) of HN-2. Treatment with DRDE-07, DRDE-30 and DRDE-35 significantly protected the changes in spleen weight, WBC count, GSH, GSSG, MDA and DNA damage following HN-2 administration (0.5 and 0.25 LD(50)). There was no alteration in the transaminases (AST and ALT), and alkaline phosphatase (ALP) activities, neither with HN-2 nor with antidotes. The present study shows that HN-2 is highly toxic by percutaneous route and DRDE-07, DRDE-30 and DRDE-35 can partially protect it.

Effects of 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), or an extract derived from field-collected cormorant eggs injected into double-crested cormorant (Phalacrocorax auritus) eggs

USGS Publications Warehouse

Powell, Debra C.; Aulerich, Richard J.; Meadows, John C.; Tillitt, Donald E.; Powell, Jon F.; Restum, Janelle C.; Stromborg, Kenneth L.; Giesy, John P.; Bursian, Steven J.

1997-01-01

Double-crested cormorant (Phalacrocorax auritus) eggs were injected with either 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), or an extract derived from field-collected double-crested cormorant eggs. These compounds were injected into the yolks of cormorant eggs from an isolated colony on Lake Winnipegosis, Manitoba, Canada. Upon hatching, chicks were necropsied. The brain, bursa, heart, liver, and spleen were removed and weighed. An approximate median lethal dose (LD50) of 158 μg/kg egg was determined for PCB 126, which is 69 times greater than the LD50 determined for the chicken (Gallus domesticus) in a previous study. A significantly greater mortality occurred at the highest dose of TCDD (4.0 μg/kg egg) when compared to the vehicle control. However, the mortality data did not provide sufficient information for the determination of an LD50. The cormorant egg extract did not adversely affect hatchability. No significant increases were observed in the incidence of developmental abnormalities, including pronounced edema, in any of the treatment groups, nor were there any relevant effects on body and organ weights. Based on the results from this study, the cormorant appears to be considerably less sensitive to polyhalogenated diaromatic hydrocarbons than the chicken, which has been the typical species used for egg injection studies.

Fenitrothion: an alternative insecticide for the control of deltamethrin-resistant populations of Triatoma infestans in northern Argentina.

PubMed

Germano, M; Picollo, M I; Spillmann, C; Mougabure-Cueto, G

2014-03-01

Deltamethrin-based campaigns to control Triatoma infestans (Klug) (Hemiptera: Reduviidae) have decreased in success as a result of the development of insecticide resistance. We compared the in vitro effects of the pyrethroid deltamethrin and two doses of the organophosphate fenitrothion, presented on different materials, on T. infestans from La Esperanza, Argentina. Laboratory tests demonstrated a decrease in susceptibility to deltamethrin in the field population [LD50 : 30.32 nanograms per insect (ng/i)] compared with the reference population (LD50 : 0.13 ng/i), giving a high resistance ratio of 233.42. By contrast, similar susceptibility to fenitrothion was assessed in both the field and reference populations (LD50 : 21.65 ng/i and 21.38 ng/i, respectively). The effectiveness of the formulated insecticides varied according to the surfaces to which they were applied. The application of fenitrothion formulations to glass or brick resulted in mortality of 90-100%. The application of fenitrothion formulations to wood or mud caused mortality in the range of 6.7-56.7%. Resistant insects presented low mortality when exposed to the deltamethrin formulation and high mortality when exposed to fenitrothion formulations. Moreover, the insecticides demonstrated residual activity only when applied to glass. The present work demonstrates that fenitrothion is an alternative to pyrethroids for the management of deltamethrin-resistant insects in La Esperanza. However, this effectiveness is not sustained over time. © 2013 The Royal Entomological Society.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Bingzhen; Shen, Chunzi; Yang, Liu

Carbon disulfide (CS{sub 2}) may lead to spontaneous abortion and very early pregnancy loss in women exposed in the workplace, but the mechanism remains unclear. We designed an animal model in which gestating Kunming strain mice were exposed to CS{sub 2} via i.p. on gestational day 4 (GD4). We found that the number of implanted blastocysts on GD8 was significantly reduced by each dose of 0.1 LD{sub 50} (157.85 mg/kg), 0.2 LD{sub 50} (315.7 mg/kg) and 0.4 LD{sub 50} (631.4 mg/kg). In addition, both the level of DNA damage and apoptosis rates of endometrial cells on GD4.5 were increased, showedmore » definite dose–response relationships, and inversely related to the number of implanted blastocysts. The expressions of mRNA and protein for the Bax and caspase-3 genes in the uterine tissues on GD4.5 were up-regulated, while the expressions of mRNA and protein for the Bcl-2 gene were dose-dependently down-regulated. Our results indicated that DNA damage and apoptosis of endometrial cells were important reasons for the loss of implanted blastocysts induced by CS{sub 2}. - Highlights: • We built an animal model of CS2 exposure during blastocyst implantation. • Endometrial cells were used in the comet assay to detect DNA damage. • CS2 exposure caused DNA damage and endometrial cell apoptosis. • DNA damage and endometrial cell apoptosis were responsible for embryo loss.« less

Fumigant toxicity of cassia and cinnamon oils and cinnamaldehyde and structurally related compounds to Dermanyssus gallinae (Acari: Dermanyssidae).

PubMed

Na, Young Eun; Kim, Soon-Il; Bang, Hea-Son; Kim, Byung-Seok; Ahn, Young-Joon

2011-06-10

The toxicity of two cassia oils, four cinnamon oils and (E)-cinnamaldehyde and (E)-cinnamic acid and 34 structurally related compounds to adult Dermanyssus gallinae (De Geer) collected from a poultry house was examined using a vapour-phase mortality bioassay. Results were compared with those of dichlorvos, a conventional acaricide. The cassia and cinnamon oils (cinnamon technical, cinnamon #500, cassia especial, cassia true, cinnamon bark and cinnamon green leaf) exhibited good fumigant toxicity (LD(50), 11.79-26.40 μg cm(-3)). α-Methyl-(E)-cinnamaldehyde (LD(50), 0.45 μg cm(-3)) and (E)-cinnamaldehyde (0.54 μg cm(-3)) were the most toxic compounds and the toxicity of these compounds was comparable to that of dichlorvos (0.30 μg cm(-3)). Potent fumigant toxicity was also observed in allyl cinnamate, ethyl-α-cyanocinnamate, (E)-2-methoxylcinnamic acid and (Z)-2-methoxylcinnamic acid (LD(50), 0.81-0.92 μg cm(-3)). Structure-activity relationships indicate that structural characteristics, such as types of functional groups and carbon skeleton rather than vapour pressure parameter, appear to play a role in determining toxicity. The essential oils and compounds described merit further study as potential acaricides for the control of D. gallinae populations as fumigants with contact action due to global efforts to reduce the level of highly toxic synthetic acaricides in the agricultural environment. Copyright © 2011. Published by Elsevier B.V.

9 CFR 113.102 - Leptospira Icterohaemorrhagiae Bacterin.

Code of Federal Regulations, 2011 CFR

2011-01-01

... each of at least 10 but not more than 12 young adult hamsters, each weighing 50 to 90 grams, with 0.25... recommendations for use. (2) Controls. Retain at least 10 but not more than 12 additional hamsters from the same... icterohaemorrhagiae organisms, using a dose of 10-10,000 hamster LD50 as determined by titration. (4) Post-challenge...

9 CFR 113.102 - Leptospira Icterohaemorrhagiae Bacterin.

Code of Federal Regulations, 2010 CFR

2010-01-01

... each of at least 10 but not more than 12 young adult hamsters, each weighing 50 to 90 grams, with 0.25... recommendations for use. (2) Controls. Retain at least 10 but not more than 12 additional hamsters from the same... icterohaemorrhagiae organisms, using a dose of 10-10,000 hamster LD50 as determined by titration. (4) Post-challenge...

9 CFR 113.104 - Leptospira Grippotyphosa Bacterin.

Code of Federal Regulations, 2011 CFR

2011-01-01

... each of at least 10 but not more than 12 young adult hamsters, each weighing 50 to 90 grams, with 0.25... recommendations for use. (2) Controls. Retain at least 10 but not more than 12 additional hamsters from the same... organisms, using a dose of 10-10,000 hamster LD50 as determined by titration. (4) Post-challenge period...

9 CFR 113.104 - Leptospira Grippotyphosa Bacterin.

Code of Federal Regulations, 2010 CFR

2010-01-01

... each of at least 10 but not more than 12 young adult hamsters, each weighing 50 to 90 grams, with 0.25... recommendations for use. (2) Controls. Retain at least 10 but not more than 12 additional hamsters from the same... organisms, using a dose of 10-10,000 hamster LD50 as determined by titration. (4) Post-challenge period...

Sensitivity of shovelnose sturgeon (Scaphirhynchus platorynchus) and pallid sturgeon (S. albus) early life stages to 3,30,4,40,5-pentachlorobiphenyl and 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure

USGS Publications Warehouse

Buckler, Justin; Candrl, James S.; McKee, Michael J.; Papoulias, Diana M.; Tillitt, Donald E.; Galat, David L.

2015-01-01

Concern exists that polychlorinated biphenyls (PCBs) may be contributing to the current decline of shovelnose sturgeon (Scaphirhynchus platorynchus) and the US federally endangered pallid sturgeon (Scaphirhynchus albus). Waterborne exposures with newly fertilized eggs were used to assess developmental and morphological effects of 2 of the most potent aryl hydrocarbon receptor (AhR) agonists, 3,3′,4,4′,5-pentachlorobiphenyl (PCB-126) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), on early life stage shovelnose and pallid sturgeon. No dose-related effects of PCB-126 were observed on percent development or hatch in either species at concentrations as high as 1711 ng/g egg. Effects of TCDD on percent development were not assessed in shovelnose sturgeon. However, percent development was not affected by TCDD in pallid sturgeon, and percent hatch was unaffected by TCDD doses as high as 60 ng/g egg to 81 ng/g egg in either species. Morphological pathologies such as yolk sac edema and craniofacial deformities were typical of AhR agonist exposure and were similar in both species. Calculated PCB-126 50% lethal dose (LD50, 95% fiducial limits) values were 196 ng/g egg (188–203 ng/g) for shovelnose and 159 ng/g egg (122–199 ng/g) for pallid sturgeon. Likewise, calculated TCDD LD50 values were 13 ng/g egg (11–15 ng/g) for shovelnose and 12 ng/g egg (10–14 ng/g) for pallid sturgeon. These LD50 values are among the highest recorded in early life stage fish, suggesting that early life stage Scaphirhynchus sturgeon may be comparatively insensitive to AhR agonists.

Subcellular localization patterns and their relationship to photodynamic activity of pyropheophorbide-a derivatives.

PubMed

MacDonald, I J; Morgan, J; Bellnier, D A; Paszkiewicz, G M; Whitaker, J E; Litchfield, D J; Dougherty, T J

1999-11-01

To determine if subcellular localization is important to photodynamic therapy (PDT) efficacy, an in vitro fluorescence microscopy study was conducted with a congeneric series of pyropheophorbide-a derivatives in human pharyngeal squamous cell carcinoma (FaDu) cells and murine radiation-induced fibrosarcoma (RIF) mutant cells. In the FaDu cells the octyl, decyl and dodecyl ether derivatives localized to the lysosomes at extracellular concentrations less than needed to produce a 50% cell kill (LD50). At extracellular concentrations equal or greater than the LD50 the compounds localized mainly to mitochondria. The propyl, pentyl, hexyl and heptyl ether derivatives localized mainly to the mitochondria at all concentrations studied. This suggested that mitochondria are a sensitive PDT target for these derivatives. Similar experiments were performed with two Photofrin-PDT resistant RIF cell lines, one of which was found to be resistant to hexyl ether derivative (C6) mediated-PDT and the other sensitive to C6-PDT relative to the parent line. At extracellular concentrations of C6 below the LD50 of each cell line, the mutants exhibited lysosomal localization. At concentrations above these values the patterns shifted to a mainly mitochondrial pattern. In these cell lines mitochondrial localization also correlated with PDT sensitivity. Localization to mitochondria or lysosomes appeared to be affected by the aggregation state of the congeners, all of which are highly aggregated in aqueous medium. Monomers apparently were the active fraction of these compounds because equalizing the extracellular monomer concentrations produced equivalent intracellular concentrations, photoxicity and localization patterns. Compounds that were mainly aggregates localized to the lysosomes where they were rendered less active. Mitochondria appear to be a sensitive target for pyropheophorbide-a-mediated photodamage, and the degree of aggregation seems to be a determinant of the localization site.

Toxicity status and antiulcerative potential of Sansevieria trifasciata leaf extract in Wistar rats.

PubMed

Ighodaro, Osasenaga Macdonald; Adeosun, Abiola Muhammad; Ojiko, Barinemene Francis; Akorede, Abeeb Taiwo; Fuyi-Williams, Oyindamola

2017-01-01

The lethal dose 50% (LD 50 ) and antiulcerative potentials of Sansevieria trifasciata (ST) leaf extract were investigated. LD 50 was determined through two routes of administration (intraperitoneal [i.p] and oral [p.o]) using the method of Lorke. The antiulcerative activity was evaluated in indomethacin-induced ulcer model (40 mg/kg body weight [BW], i.p, single dose) against a reference drug, cimetidine (100 mg/kg BW, p.o). ST was assessed at two different doses (200 and 400 mg/kg BW, p.o). Treatments were done twice daily at 8 h interval for 7 days before indomethacin administration. The i.p LD 50 was determined as 774.60 mg/kg BW and oral administration of the extract at 18,000 mg/kg BW dosage did not cause any negative behavioral changes in the animals, and no mortality was recorded after 24 h of the experiment. ST-pre-treated animals showed some improvement against indomethacin-induced ulceration. The extract curtailed indomethacin-induced reduction in gastric volume (36.1%), free acidity (55.3%), total acidity (35.6%) while minimizing the increase in pH by 13.3%. Moreover, the extract showed 17.92% and 14.96% ulcer protective ability at 200 and 400 mg/kg BW, respectively. The phytochemical analysis of ST extract revealed the presence of phytoconstituents such as glycosides, saponins, flavonoids, terpenoids, alkaloids, tannins, anthraquinone, and glycosides. ST apparently has a promising antiulcerative potential, and is safe for use in folk medicine. This valuable medicinal property is probably due to the array of important phytochemicals contained in the plant as observed in this study. However, a further study involving bioassay-guided identification of the main antiulcerative compound in ST is required to establish the use of the plant as a viable antiulcerative agent.

Acute toxicity and sublethal effects of myclobutanil on respiration, flight and detoxification enzymes in Apis cerana cerana.

PubMed

Han, Wensu; Wang, Yajun; Gao, Jinglin; Wang, Shijie; Zhao, Shan; Liu, Junfeng; Zhong, Yihai; Zhao, Dongxiang

2018-05-01

Myclobutanil is currently used on the flowering plants. Little is known about how Apis cerana cerana respond to myclobutanil exposure. Hence, the acute toxicity of myclobutanil and its sublethal effects on respiration, flight and detoxification enzymes [7-ethoxycoumarin O-deethylase (ECOD) and glutathione S-transferases (GSTs)] in A. cerana cerana were investigated. The results indicated that formulation grade myclobutanil showed moderate toxicity to A. cerana cerana either contact (LD 50 =4.697μg/bee) or oral (LD 50 =2.154μg/bee) exposure. Sublethal dose of myclobutanil significantly reduced the respiration rate of workers at 24h and 48h regardless of the exposure method. However, myclobutanil didn't significantly affect the take-off flight. After nurse bees exposure to the dose (LD 5 ) of formulation-grade myclobutanil, ECOD activity was significantly induced when compared with control, but GST activity didn't change. In the forager bees, no enzyme markers response was obtained in this test. From the present study we can infer that myclobutanil disturb respiration and P450-mediated detoxification of the individual bees of A. cerana cerana. Thus, myclobutanil may has risk for A. cerana cerana, it should be cautiously used. Copyright © 2017. Published by Elsevier Inc.

Differential Regulation of Duplicate Light-Dependent Protochlorophyllide Oxidoreductases in the Diatom Phaeodactylum tricornutum

PubMed Central

Hunsperger, Heather M.; Cattolico, Rose Ann

2016-01-01

Background Diatoms (Bacilliariophyceae) encode two light-dependent protochlorophyllide oxidoreductases (POR1 and POR2) that catalyze the penultimate step of chlorophyll biosynthesis in the light. Algae live in dynamic environments whose changing light levels induce photoacclimative metabolic shifts, including altered cellular chlorophyll levels. We hypothesized that the two POR proteins may be differentially adaptive under varying light conditions. Using the diatom Phaeodactylum tricornutum as a test system, differences in POR protein abundance and por gene expression were examined when this organism was grown on an alternating light:dark cycles at different irradiances; exposed to continuous light; and challenged by a significant decrease in light availability. Results For cultures maintained on a 12h light: 12h dark photoperiod at 200μE m−2 s−1 (200L/D), both por genes were up-regulated during the light and down-regulated in the dark, though por1 transcript abundance rose and fell earlier than that of por2. Little concordance occurred between por1 mRNA and POR1 protein abundance. In contrast, por2 mRNA and POR2 protein abundances followed similar diurnal patterns. When 200L/D P. tricornutum cultures were transferred to continuous light (200L/L), the diurnal regulatory pattern of por1 mRNA abundance but not of por2 was disrupted, and POR1 but not POR2 protein abundance dropped steeply. Under 1200μE m−2 s−1 (1200L/D), both por1 mRNA and POR1 protein abundance displayed diurnal oscillations. A compromised diel por2 mRNA response under 1200L/D did not impact the oscillation in POR2 abundance. When cells grown at 1200L/D were then shifted to 50μE m−2 s−1 (50L/D), por1 and por2 mRNA levels decreased swiftly but briefly upon light reduction. Thereafter, POR1 but not POR2 protein levels rose significantly in response to this light stepdown. Conclusion Given the sensitivity of diatom por1/POR1 to real-time light cues and adherence of por2/POR2 regulation to the diurnal cycle, we suggest that POR1 supports photoacclimation, whereas POR2 is the workhorse for daily chlorophyll synthesis. PMID:27367227

Chemical Constituents and Insecticidal Activities of Ajania fruticulosa Essential Oil.

PubMed

Liang, Jun-Yu; Guo, Shan-Shan; You, Chun-Xue; Zhang, Wen-Juan; Wang, Cheng-Fang; Geng, Zhu-Feng; Deng, Zhi-Wei; Du, Shu-Shan; Zhang, Ji

2016-08-01

The insecticidal activity and chemical constituents of the essential oil from Ajania fruticulosa were investigated. Twelve constituents representing 91.0% of the essential oil were identified, and the main constituents were 1,8-cineole (41.40%), (+)-camphor (32.10%), and myrtenol (8.15%). The essential oil exhibited contact toxicity against Tribolium castaneum and Liposcelis bostrychophila adults with LD50 values of 105.67 μg/adult and 89.85 μg/cm(2) , respectively. The essential oil also showed fumigant toxicity against two species of insect with LC50 values of 11.52 and 0.65 mg/l, respectively. 1,8-Cineole exhibited excellent fumigant toxicity (LC50  = 5.47 mg/l) against T. castaneum. (+)-Camphor showed obvious fumigant toxicity (LC50  = 0.43 mg/l) against L. bostrychophila. Myrtenol showed contact toxicity (LD50  = 29.40 μg/cm(2) ) and fumigant toxicity (LC50  = 0.50 mg/l) against L. bostrychophila. 1,8-Cineole and (+)-camphor showed strong insecticidal activity to some important insects, and they are main constituents of A. fruticulosa essential oil. The two compounds may be related to insecticidal activity of A. fruticulosa essential oil against T. castaneum and L. bostrychophila. © 2016 Wiley-VHCA AG, Zürich.

Stoichiometric and catalytic scavengers as protection against nerve agent toxicity: a mini review.

PubMed

Lenz, David E; Yeung, David; Smith, J Richard; Sweeney, Richard E; Lumley, Lucille A; Cerasoli, Douglas M

2007-04-20

Currently fielded treatments for nerve agent intoxication promote survival, but do not afford complete protection against either nerve agent-induced motor and cognitive deficits or neuronal pathology. The use of human plasma-derived butyrylcholinesterase (HuBuChE) to neutralize the toxic effects of nerve agents in vivo has been shown to both aid survival and protect against decreased cognitive function after nerve agent exposure. Recently, a commercially produced recombinant form of human butyrylcholinesterase (r-HuBuChE; PharmAthene Inc.) expressed in the milk of transgenic goats has become available. This material is biochemically similar to plasma-derived HuBuChE in in vitro assays. The pharmacokinetic characteristics of a polyethylene glycol coated (pegylated) form of r-HuBuChE were determined in guinea pigs; the enzyme was rapidly bioavailable with a half-life (t(1/2)) and pharmacokinetic profile that resembled that of plasma-derived huBuChE. Guinea pigs were injected with 140mg/kg (i.m.) of pegylated r-HuBuChE 18h prior to exposure (sc) to 5.5xLD(50) VX or soman. VX and soman were administered in a series of three injections of 1.5xLD(50), 2.0xLD(50), and 2.0xLD(50), respectively, with injections separated by 2h. Pretreatment with pegylated r-HuBuChE provided 100% survival against multiple lethal doses of VX and soman. Guinea pigs displayed no signs of nerve agent toxicity following exposure. Assessments of motor activity, coordination, and acquisition of spatial memory were performed for 2 weeks following nerve agent exposure. There were no measurable decreases in motor or cognitive function during this period. In contrast, animals receiving 1.5xLD(50) challenges of soman or VX and treated with standard atropine, 2-PAM, and diazepam therapy showed 50 and 100% survival, respectively, but exhibited marked decrements in motor function and, in the case of GD, impaired spatial memory acquisition. The advances in this field have resulted in the decision to select both the plasma-derived and the recombinant form of BuChE for advanced development and transition to clinical trials. Efforts have now been expanded to identify a catalytic protein capable of not only binding, but also rapidly hydrolyzing the standard threat nerve agents. Recent work has focused on paraoxonase-1 (PON1), a naturally occurring human serum enzyme with the capacity to catalyze the hydrolysis of nerve agents, albeit too slowly to afford dramatic protection. Using rational design, several amino acids involved in substrate binding have been identified and site-directed mutations have revealed that residue H115 plays an important role in binding. In addition, the stereospecificity of PON1 for the catalytic hydrolysis of soman has been examined. The enzyme exhibits a slight stereospecificity for the C+P+ isomer of soman, which is due more to preferential binding than to selective hydrolysis of this isomer. The results suggest that it may be possible to engineer a mutant form of PON1 with enhanced activity and stereospecificity for the most toxic nerve agent isoforms.

Reactions of methamidophos with mammalian cholinesterase.

DOT National Transportation Integrated Search

1978-07-01

The lethality of methamidophos, a phosphoramidothioate, to rats (i.p. LD50, 15 mg/kg), is similar to that of such potent organophosphate compounds as parathion and paraoxon. Certain distinctive features of its chemical structure, and reported failure...

Combined ionizing radiation and thermal injury in the rat. Evaluation of early excision and closure of the burn wound

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hirsch, E.F.; Vezina, R.; Corbett, S.

1990-01-01

The present study was undertaken to establish an animal model of combined whole-body irradiation and thermal injury and to determine the effectiveness of early excision and closure of the burn wound in such a model. Whole-body irradiation over a range of doses resulted in a predictable mortality rate, with an LD50/30 of 783 rad with 95% confidence limits of 737 and 823 rad. A controlled 10% body surface area full-thickness thermal injury resulted in no deaths in 30 animals. When combined with a standard nonlethal 10% thermal injury, varying doses of whole-body irradiation resulted in widely differing LD50/30 values inmore » three separate cohorts of rats. Excision and closure of a 10% burn 24 hours after exposure to 200 rads did not improve survival.« less

THE RADIOSENSITIVITY OF BIRDS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kushnuruk, V.A.

1962-01-01

ABS>Earlier reports suggest that the radiosensitivity of birds varies according to the systematic position of the species in question. To study this question in greater detail, birds belonging to different species were exposed to x rays and the LD/sub 50/ for 30 days recorded. During exposure, the birds were kept in a small cage but could move freely. Five different species were investigated: the greenfinch (Chloris chloris L.), goldfinch (Carduelis carduelis L.), linnet (Acantis cannabina L.), house sparrow (Passer domesticus), and the canary (Serinus canarina L.). It appeared that the radiosensitivity of the birds moved within a fairly narrow rangemore » quite independently of the species. The LD/ sub 50/ for 30 days varied in the 5 species in question between 400 and 625 r. All birds showed disorders of the coordination of movements, in the reflex governing the picking of food, in flight, and in perching. (OTS)« less

Acute toxicity of diazinon is similar for eight stocks of bobwhite

USGS Publications Warehouse

Hill, E.F.; Camardese, M.B.; Heinz, G.H.; Spann, J.W.; DeBevec, A.B.

1984-01-01

Nine-week-old bobwhite (Colinus virginianus) from eight different game farms were tested for their sensitivity to an acute oral exposure of technical-grade diazinon (phosphorothioic acid O, O-diethyl-O-[6-methyl- 2-(1 -methylethy 1)-4-pyrimidinyl]ester). Extraneous variables associated with interlaboratory differences in husbandry were eliminated by incubating eggs and rearing chicks to test age for all stocks simultaneously in the same facilities at the Patuxent Wildlife Research Center. Under this single set of conditions, the responses of the eight stocks of bobwhite to diazinon were statistically inseparable, with LD50 values varying from 13 mg/kg (95% confidence interval, 8-21 mg/kg) to 17 mg/kg (95% confidence interval, 11-25 mg/kg). The pooled LD50 for the eight stocks was 14.7 mg/kg (95% confidence interval,13.1-16.5 mg/kg).

Development of an acceptable factor to estimate chronic end points from acute toxicity data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Venman, B.C.; Flaga, C.

1985-12-01

Acceptable daily intake (ADI) values are routinely developed for threshold toxicants from NOAELs determined from human or animal chronic or subchronic data. These NOAELs are then divided by appropriate uncertainty factors ranging from 10 to 1000 depending on the quality of the data. However, for the vast majority of chemicals used industrially, adequate toxicity data needed to use this process are not available. Thus, a procedure to estimate a chronic toxicity endpoint from acute toxicity data, such as an oral rat LD50, becomes necessary. An acute-to-chronic application factor of 0.0001 was developed, which when multiplied by an oral LD50 formore » an individual chemical, yields a surrogate chronic NOAEL. This figure can then be used to estimate an acceptable daily exposure for humans. The process used to estimate this application factor is detailed.« less

Optimization of the scan protocols for CT-based material extraction in small animal PET/CT studies

NASA Astrophysics Data System (ADS)

Yang, Ching-Ching; Yu, Jhih-An; Yang, Bang-Hung; Wu, Tung-Hsin

2013-12-01

We investigated the effects of scan protocols on CT-based material extraction to minimize radiation dose while maintaining sufficient image information in small animal studies. The phantom simulation experiments were performed with the high dose (HD), medium dose (MD) and low dose (LD) protocols at 50, 70 and 80 kVp with varying mA s. The reconstructed CT images were segmented based on Hounsfield unit (HU)-physical density (ρ) calibration curves and the dual-energy CT-based (DECT) method. Compared to the (HU;ρ) method performed on CT images acquired with the 80 kVp HD protocol, a 2-fold improvement in segmentation accuracy and a 7.5-fold reduction in radiation dose were observed when the DECT method was performed on CT images acquired with the 50/80 kVp LD protocol, showing the possibility to reduce radiation dose while achieving high segmentation accuracy.

Allometric scaling: analysis of LD50 data.

PubMed

Burzala-Kowalczyk, Lidia; Jongbloed, Geurt

2011-04-01

The need to identify toxicologically equivalent doses across different species is a major issue in toxicology and risk assessment. In this article, we investigate interspecies scaling based on the allometric equation applied to the single, oral LD (50) data previously analyzed by Rhomberg and Wolff. We focus on the statistical approach, namely, regression analysis of the mentioned data. In contrast to Rhomberg and Wolff's analysis of species pairs, we perform an overall analysis based on the whole data set. From our study it follows that if one assumes one single scaling rule for all species and substances in the data set, then β = 1 is the most natural choice among a set of candidates known in the literature. In fact, we obtain quite narrow confidence intervals for this parameter. However, the estimate of the variance in the model is relatively high, resulting in rather wide prediction intervals. © 2010 Society for Risk Analysis.

Alum adjuvanted rabies DNA vaccine confers 80% protection against lethal 50 LD50 rabies challenge virus standard strain.

PubMed

Garg, Rajni; Kaur, Manpreet; Saxena, Ankur; Prasad, Rajendra; Bhatnagar, Rakesh

2017-05-01

Rabies is a serious concern world-wide. Despite availability of rabies vaccines for long; their efficacy, safety, availability and cost effectiveness has been a tremendous issue. This calls for improvement of rabies vaccination strategies. DNA vaccination has immense potential in this regard. The DNA vaccine pgp.LAMP-1 conferred 60% protection to BALB/c mice against 20 LD 50 rabies challenge virus standard (CVS) strain challenge. Upon supplementation with Emulsigen-D, the vaccine formulation conferred complete protection against lethal challenge. To assess the feasibility of this vaccine formulation for human use, it was tested along with other FDA approved adjuvants, namely, Alum, Immuvac, Montanide ISA720 VG. Enhanced immune response correlated with high IgG antibody titer, Th2 biased response with a high level of rabies virus neutralizing antibodies (RVNAs) and IgG1/IgG2a ratio >1, observed upon alum supplementation of the rabies DNA vaccine. The total IgG antibody titer was 2IU/ml and total RVNA titer was observed to be 4IU/ml which is eight times higher than the minimum protective titer recommended by WHO. Furthermore, it conferred 80% protection against challenge with 50 LD 50 of the rabies CVS strain, conducted in compliance with the potency test for rabies recommended by the National Institutes of Health (NIH), USA. Previously, we have established pre-clinical safety of this vaccine as per the guidelines of Schedule Y, FDA as well as The European Agency for evaluation of Medicinal Products. The vaccine showed no observable toxicity at the site of injection as well as at systemic level in Wistar rats when administered with 10X recommended dose. Therefore, supplementation of rabies DNA vaccine, pgp.LAMP-1 with alum would lead to development of a non-toxic, efficacious, stable and affordable vaccine that can be used to combat high numbers of fatal rabies infections tormenting developing countries. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation of 2 methods for sodium intake assessment in cardiac patients with and without heart failure: the confounding effect of loop diuretics.

PubMed

Arcand, JoAnne; Floras, John S; Azevedo, Eduardo; Mak, Susanna; Newton, Gary E; Allard, Johane P

2011-03-01

Twenty-four-hour urine collections are considered the optimal method for sodium intake assessment. Whether a diagnosis of heart failure (HF) or the use of loop diuretic (LD) therapy for HF compromises the validity of 24-h urine collections as a surrogate marker for sodium intake is unknown. The objective was to determine the strength of association between 24-h urine collections and food records for sodium intake assessment in non-HF cardiac patients and in HF patients stratified by LD usage. Food records and 24-h urine collections were simultaneously completed for 2 consecutive days. Correlation coefficients and the Bland-Altman method of agreement described the relation between the techniques. Non-HF cardiac patients (n = 96; mean ± SD age: 65 ± 11 y), HF patients who were not taking an LD (n = 47; 62 ± 11 y), and HF patients who were taking an LD (n = 62; age: 60 ± 12 y) were included. Correlation coefficients for sodium intake between food records and urine collections were r = 0.624 (P < 0.001) for non-HF cardiac patients and r = 0.678 (P < 0.001) for HF patients who were not taking an LD. However, no significant association (r = 0.132, P = 0.312) was observed for HF patients who were taking LDs. The 95% limits of agreement between the non-HF cardiac patients and the HF patients who were not taking LDs were similar but were ≈50% wider for HF patients who were taking LDs. For the assessment of sodium intake, food records agree well with 24-h urine collections in non-HF patients with cardiovascular disease and in HF patients who are not receiving LD but not for HF patients who are taking LDs. Therefore, food records may provide a better estimate of sodium intake in HF patients who are receiving LD therapy.

Reducing dosing frequency of carbidopa/levodopa: double-blind crossover study comparing twice-daily bilayer formulation of carbidopa/levodopa (IPX054) versus 4 daily doses of standard carbidopa/levodopa in stable Parkinson disease patients.

PubMed

Hinson, Vanessa K; Goetz, Christopher G; Leurgans, Sue; Fan, Wenqing; Nguyen, Tiffany; Hsu, Ann

2009-01-01

We compared IPX054, a bilayer tablet of immediate- and extended-release carbidopa/levodopa (CD/LD) given twice daily to standard CD/LD given 4 times daily in patients with stable Parkinson disease (PD). Twelve PD patients with no or mild fluctuations on CD/LD 25/100 mg 4 times daily were randomized to a double-blind crossover comparison with IPX054 (50/200 mg) twice daily. At the end of each 2-week treatment, patients were video recorded while performing a modified Unified Parkinson's Disease Rating Scale motor examination and Rush Dyskinesia Rating Scale at 30-minute intervals over 8.5 hours. The primary outcome measure was the number of videotape epochs rated as "ON" without troublesome dyskinesia by a blinded observer (Wilcoxon signed rank tests). The 9 men and 3 women had a mean age of 69 years and mean PD duration of 6 years. IPX054 and CD/LD showed no significant differences in the primary outcome measure (mean number of video epochs rated as ON without troublesome dyskinesia; P = 0.14). The mean time to ON was improved with IPX054 (P = 0.014), and the mean modified Unified Parkinson's Disease Rating Scale scores slightly favored IPX054 (14.4 vs 16.9; P = 0.052). Mean Rush Dyskinesia Rating Scale scores were not significantly different between IPX054 and CD/LD (0.45 vs 0.69; P = 0.25). No patient developed troublesome dyskinesias. In stable PD patients, no difference was detected between twice-daily treatment with IPX054 and CD/LD given 4 times daily. In this group, substitution with IPX054 reduced dosing frequency while maintaining CD/LD efficacy. In clinical practice, this ease of administration may offer improved treatment compliance.

Glycyrrhizic acid attenuates growth of Leishmania donovani by depleting ergosterol levels.

PubMed

Dinesh, Neeradi; Neelagiri, Soumya; Kumar, Vinay; Singh, Sushma

2017-05-01

In the present study, glycyrrhizic acid (GA) the main component of Glycyrrhiza glabra was evaluated for its efficacy as antileishmanial agent and its mode of action explored. GA inhibits promastigotes and intracellular amastigotes in a dose dependent manner at an IC 50 value of 34 ± 3.0 μM and 20 ± 4.2 μM respectively. GA was non-toxic against THP-1 macrophage host cell line. GA was found to inhibit recombinant Leishmania donovani HMG-CoA reductase (LdHMGR) enzyme at the half-maximum inhibitory concentration of 24 ± 4.3 μM indicating the sensitivity and specificity of GA towards the enzyme. However, GA could cause only 30% reduction in HMGR activity when measured in Leishmania promastigotes treated with 34 μM of GA. Interestingly western blot analysis revealed fivefold reduced HMGR expression in GLA treated promastigotes. To further study the mode of action of GA, we used transgenic parasites overexpressing LdHMGR. Results indicated that ∼2 fold resistance was exhibited by LdHMGR overexpressing promastigotes to GA with an IC 50 value of 74 μM compared to the wild type parasite. This explained the specific binding of GA to LdHMGR enzyme. There was ∼2 fold depletion in ergosterol levels in wild type promastigotes compared to the HMGR overexpressors. This data was further validated by exogenous supplementation of GA treated cells with ergosterol and 40% reversal of growth inhibition was observed. The results obtained suggested that GA kills the parasite by affecting sterol biosynthetic pathway, especially by inhibiting the L. donovani HMGR and altering ergosterol levels. The finding from the current study shows that GA is a potential antileishmanial chemotherapeutic agent. Copyright © 2017 Elsevier Inc. All rights reserved.

Neutralization of crotaline snake venoms from Central and South America by antivenoms produced in Brazil and Costa Rica.

PubMed

Bogarín, G; Morais, J F; Yamaguchi, I K; Stephano, M A; Marcelino, J R; Nishikawa, A K; Guidolin, R; Rojas, G; Higashi, H G; Gutiérrez, J M

2000-10-01

A study was performed on the ability of antivenoms, produced in Brazil and Costa Rica, to neutralize lethal, hemorrhagic and coagulant activities of the venoms of 16 species of Central and South American snakes of the subfamily Crotalinae. Neutralization of lethality was studied by two different methods routinely used in the quality control of antivenoms at Instituto Butantan (IB) and Instituto Clodomiro Picado (ICP). Both antivenoms neutralized the majority of the venoms studied, but the values of effective doses 50% (ED(50)) differed markedly depending on the method used. In general, higher potencies were obtained with the method of ICP, where a challenge dose corresponding to 4 LD(50)s is used, than with the method of IB, where a challenge dose of 5 LD(50)s is employed. All venoms induced hemorrhagic activity in the mouse skin test, which was effectively neutralized by the two antivenoms. All venoms, except those of Porthidium nasutum and Bothriechis lateralis, induced coagulation of human plasma in vitro and both antivenoms were effective in the neutralization of this activity. In conclusion, our results provide evidence of an extensive cross reactivity between these antivenoms and Central and South American crotaline snake venoms.

Synthetic bioactive novel ether based Schiff bases and their copper(II) complexes

NASA Astrophysics Data System (ADS)

Shabbir, Muhammad; Akhter, Zareen; Ismail, Hammad; Mirza, Bushra

2017-10-01

Novel ether based Schiff bases (HL1- HL4) were synthesized from 5-chloro-2-hydroxy benzaldehyde and primary amines (1-amino-4-phenoxybenzene, 4-(4-aminophenyloxy) biphenyl, 1-(4-aminophenoxy) naphthalene and 2-(4-aminophenoxy) naphthalene). From these Schiff bases copper(II) complexes (Cu(L1)2-Cu(L4)2)) were synthesized and characterized by elemental analysis and spectroscopic (FTIR, NMR) techniques. The synthesized Schiff bases and copper(II) complexes were further assessed for various biological studies. In brine shrimp assay the copper(II) complexes revealed 4-fold higher activity (LD50 3.8 μg/ml) as compared with simple ligands (LD50 12.4 μg/ml). Similar findings were observed in potato disc antitumor assay with higher activities for copper(II) complexes (IC50 range 20.4-24.1 μg/ml) than ligands (IC50 range 40.5-48.3 μg/ml). DPPH assay was performed to determine the antioxidant potential of the compounds. Significant antioxidant activity was shown by the copper(II) complexes whereas simple ligands have shown no activity. In DNA protection assay significant protection behavior was exhibited by simple ligand molecules while copper(II) complexes showed neutral behavior (neither protective nor damaging).

The chalcone derivative Chana 1 protects against amyloid β peptide-induced oxidative stress and cognitive impairment.

PubMed

Kwak, Jieun; Kim, Mi-Jeong; Choi, Kyung-Chul; Choi, Hyo-Kyung; Jun, Woojin; Park, Hyun-Jin; Lee, Yoo-Hyun; Yoon, Ho-Geun

2012-07-01

Alzheimer's disease (AD) is the most common neurodegenerative disease to cause dementia in the elderly. Amyloid β (Aβ)-peptide induced oxidative stress causes the initiation and progression of AD. Recently, new chalcone derivatives termed the Chana series were synthesized. Among them, Chana 1 showed high free radical scavenging activity (72.5%), as measured by a DPPH (1,1-diphenyl-2-picrylhydrazyl) assay. In this study, we investigated the effect of Chana 1 against Aβ-induced cytotoxicity and cognitive deficits. Additionally, we sought to estimate the lethal dose, 50% (LD50) of Chana 1 in mice using an acute oral toxicity test. We found that Chana 1 significantly protected against Aβ-induced neuronal cell death in PC12 cells. Oral administration of Chana 1 at a dose of 50 mg/kg body weight/day significantly improved Aβ-induced learning and memory impairment in mice, as measured in Y-maze and passive avoidance tests. In acute toxicity tests, the LD50 in mice was determined to be 520.44 mg/kg body weight. The data are valuable for future studies and suggest that Chana 1 has therapeutic potential for the management of neurodegenerative disease.

QTLs for heading date and plant height under multiple environments in rice.

PubMed

Han, Zhongmin; Hu, Wei; Tan, Cong; Xing, Yongzhong

2017-02-01

Both heading date and plant height are important traits related to grain yield in rice. In this study, a recombinant inbred lines (RILs) population was used to map quantitative trait loci (QTLs) for both traits under 3 long-day (LD) environments and 1 short-day (SD) environment. A total of eight QTLs for heading date and three QTLs for plant height were detected by composite interval mapping under LD conditions. Additional one QTL for heading date and three QTLs for plant height were identified by Two-QTL model under LD conditions. Among them, major QTLs qHd7.1, qHd7.2 and qHd8 for heading date, and qPh1 and qPh7.1 for plant height were commonly detected. qHd7.1 and qHd7.2 were mapped to small regions of less than 1 cM. Genome position comparison of previously cloned genes with QTLs detected in this study revealed that qHd5 and qPh3.1 were two novel QTLs. The alleles of these QTLs increasing trait values were dispersed in both parents, which well explained the transgressive segregation observed in this population. In addition, the interaction between qHd7.1 and qHd8 was detected under all LD conditions. Multiple-QTL model analysis revealed that all QTLs and their interactions explained over 80% of heading date variation and 50% of plant height variation. Two heading date QTLs were detected under SD condition. Of them, qHd10 were commonly identified under LD condition. The difference in QTL detection between LD and SD conditions indicated most heading date QTLs are sensitive to photoperiod. These findings will benefit breeding design for heading date and plant height in rice.

Differential response to alcohol in light and moderate female social drinkers.

PubMed

Evans, S M; Levin, F R

2004-05-01

Individuals who are moderate drinkers are at increased risk to abuse alcohol. Moreover, women are more vulnerable than men to the adverse consequences of alcohol consumption and recent data indicate that the drinking pattern in women is becoming more similar to that of men. However, few studies have determined whether female moderate drinkers (MD) show a differential response to the subjective and performance effects of alcohol, compared to female light drinkers (LD). Fifteen female MD who consumed an average of 34.7 drinks/month were compared to 15 female LD who consumed an average of 6.7 drinks/month. None of the participants had a first-degree family history of alcoholism or substance abuse. The acute effects of alcohol (0, 0.25, 0.50, 0.75 mg/kg) were evaluated using a double-blind, placebo-controlled outpatient design. Drug effects were assessed using a full range of performance measures, subjective-effects questionnaires and observer ratings. Alcohol impaired performance in a dose-related manner on all performance tasks for both groups of females. However, MD were less impaired than LD on balance and Digit Symbol Substitution Test (DSST). This reduced response was also evident from the observer ratings, with MD being viewed as less impaired by alcohol than LD. While ratings of Drug Liking increased in both groups of women on the ascending limb of the breath alcohol curve, alcohol was disliked by LD on the descending limb and LD reported increased ratings of Bad Drug Effects following the high dose of alcohol. The reduced performance impairment, coupled with the positive subjective effects and relative absence of adverse subjective effects, suggestive of behavioral tolerance, could result in a progression towards increased alcohol consumption among moderate female social drinkers.

In-silico screening and validation of high-affinity tetra-peptide inhibitor of Leishmania donovani O-acetyl serine sulfhydrylase (OASS).

PubMed

Kant, Vishnu; Vijayakumar, Saravanan; Sahoo, Ganesh Chandra; Chaudhery, Shailendra S; Das, Pradeep

2018-02-07

OASS is a specific enzyme that helps Leishmania parasite to survive the oxidative stress condition in human macrophages. SAT C-terminal peptides in several organisms, including Leishmania, were reported to inhibit or reduce the activity of OASS. Small peptide and small molecules mimicking the SAT C-terminal residues are designed and tested for the inhibition of OASS in different organisms. Hence, in this study, all the possible tetra-peptide combinations were designed and screened based on the docking ability with Leishmania donovani OASS (Ld-OASS). The top ranked peptides were further validated for the stability using 50 ns molecular dynamic simulation. In order to identify the better binding capability of the peptides, the top peptides complexed with Ld-OASS were also subjected to molecular dynamic simulation. The docking and simulation results favored the peptide EWSI to possess greater advantage than previously reported peptide (DWSI) in binding with Ld-OASS active site. Also, screening of non-peptide inhibitor of Asinex Biodesign library based on the shape similarity of EWSI and DWSI was performed. The top similar molecules of each peptides were docked on to Ld-OASS active site and subsequently simulated for 20 ns. The results suggested that the ligand that shares high shape similarity with EWSI possess better binding capability than the ligand that shares high shape similarity with DWSI. This study revealed that the tetra-peptide EWSI had marginal advantage over DWSI in binding with Ld-OASS, thereby providing basis for defining a pharmacophoric scaffold for the design of peptidomimetic inhibitors as well as non-peptide inhibitors of Ld-OASS.

Assessment of antiradiation drug effectiveness to fission neutron irradiation. Annual report September 1981-August 1982

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sigdestad, C.P.

1982-09-01

This report describes the assays of various compounds for their toxicity and anti-radiation efficacy following exposure to either Co-60 or fission neutron irradiation. The chemicals covered in this report are: WR 347, WR 1065, WR 2529, WR 2721, WR 3689, WR 44923, WR 109342, WR 151327 and WR 168643. The drugs and their respective dose modification factors (DMF) for fission neutron gastrointestinal lethality (LD50-6) following intraperitoneal administration are, in decreasing order of effectiveness: WR 44923 (1.77), WR 2529 (1.47), WR 1065 (1.42), WR 2721 (1.39), WR 16843 (1.23). Following per os (P. O.) administration of the drug, the DMF's formore » the LD50-6 are: WR 109342 (1.47), WR 3689 (1.36), and WR 168643 (1.31). For hematopoietic neutron radiation lethality (LD50-30) the DMF's are: following i.p. administration, WR 2529 (1.04); WR 151327 (1.34), WR 168643 (1.25), WR 44923 (1.22), WR 2721 (1.20), WR 1065 (1.04); following P. O. administration, WR 168643 (1.38), WR 109342 (1.21), WR 3689 (1.04). Using an intestinal microcolony assay system the following drugs provided the listed DMF's against neutron radiation after i.p. injection: WR 3689 (1.24), WR 2721 (1.15), WR 44923 (1.14), and WR 347 (1.05). The protective effects against neutron radiation using an endogenous spleen colony assay and i.p. administration were: WR 3689 (1.18), WR 2529 (1.15), WR 2721 (1.10), WR 44923 (1.02) and WR 347 (0.94).« less

Toxicity and mechanism of action of bromethalin: a new single-feeding rodenticide

DOE Office of Scientific and Technical Information (OSTI.GOV)

van Lier, R.B.; Cherry, L.D.

1988-11-01

Bromethalin is a new rodenticide for the control of commensal rodents. Doses in excess of the LD50 (2 mg/kg in rats) will cause death within 8-12 hr and it is preceded by one to three episodes of clonic convulsions with death usually due to respiratory arrest. Multiple low doses or sublethal intoxication yields hind leg weakness and loss of tactile sensation in rodents. Histopathology of the brain and spinal cord of these animals revealed a spongy degeneration of the white matter which was shown upon ultramicroscopic examination to be intramyelenic edema. No inflammation or cellular destruction of neuronal tissue wasmore » noted. LD50 values ranged from 1.8 mg/kg in the cat to approximately 13 mg/kg in rabbits. The only apparent nonsusceptible species was the guinea pig which could tolerate doses in excess of 1000 mg/kg without effect. Identification of the desmethyl metabolite was demonstrated in the blood and liver of treated animals by comparison of chromatographic retention times to that of a reference standard, but direct mass spectral identification was unsuccessful in part due to the low dose which could be administered. Therefore, the metabolism of bromethalin was studied by indirect means. Animals were pretreated with three inducers of microsomal drug metabolism: phenobarbital, 3-methylcholanthrene (3MC), and Aroclor 1254 (Aroclor) and one inhibitor, SKF-525A. Pretreated mice or rats were given an LD50 dose of bromethalin or the desmethyl analog and the percentage of surviving animals was determined.« less

Mitigation of the hematopoietic and gastrointestinal acute radiation syndrome by octadecenyl thiophosphate, a small molecule mimic of lysophosphatidic acid.

PubMed

Deng, Wenlin; Kimura, Yasuhiro; Gududuru, Veeresh; Wu, Wenjie; Balogh, Andrea; Szabo, Erzsebet; Thompson, Karin Emmons; Yates, C Ryan; Balazs, Louisa; Johnson, Leonard R; Miller, Duane D; Strobos, Jur; McCool, W Shannon; Tigyi, Gabor J

2015-04-01

We have previously demonstrated that the small molecule octadecenyl thiophosphate (OTP), a synthetic mimic of the growth factor-like mediator lysophosphatidic acid (LPA), showed radioprotective activity in a mouse model of total-body irradiation (TBI) when given orally or intraperitoneally 30 min before exposure to 9 Gy γ radiation. In the current study, we evaluated the effects of OTP, delivered subcutaneously, for radioprotection or radiomitigation from -24 h before to up to +72 h postirradiation using a mouse TBI model with therapeutic doses at around 1 mg/kg. OTP was injected at 10 mg/kg without observable toxic side effects in mice, providing a comfortable safety margin. Treatment of C57BL/6 mice with a single dose of OTP over the time period from -12 h before to +26 h after a lethal dose of TBI reduced mortality by 50%. When administered at +48 h to +72 h postirradiation (LD50/30 to LD100/30), OTP reduced mortality by ≥34%. OTP administered at +24 h postirradiation significantly elevated peripheral white blood cell and platelet counts, increased crypt survival in the jejunum, enhanced intestinal glucose absorption and reduced endotoxin seepage into the blood. In the 6.4-8.6 Gy TBI range using LD50/10 as the end point, OTP yielded a dose modification factor of 1.2. The current data indicate that OTP is a potent radioprotector and radiomitigator ameliorating the mortality and tissue injury of acute hematopoietic as well as acute gastrointestinal radiation syndrome.

Neutralization Capacity of Monovalant Antivenom Against Existing Lethal Scorpions in the Turkish Scorpiofauna

PubMed Central

Ozkan, Ozcan; Yağmur, Ersen Aydın

2017-01-01

In this study, Mesobuthus gibbosus and Mesobuthus eupeus eupeus venom samples were compared for lethality, in-vivo effects and proteins. Neutralization capacity of monovalent Androctonus crassicauda antivenom (RSHA anti-Ac) was tested against the lethal effects of the venoms. Venom was obtained from mature scorpions by electrical stimulation of the telson. The lethality of the venom and potency of Horse RSHA anti-Ac were determined in Swiss mice. The protein profiles of the scorpion venoms were analysed by NuPAGE® 4–12% gradient Bis-Tris gel followed by Coomassie blue staining. Western blotting was performed to determine immunogenic compounds in the venom samples. The median lethal doses of M. e. eupeus, M.gibbosus scorpion and A.crassicauda venoms were determined to be 1.92 mg/kg by i.v. injection route, 0.67 mg/kg and 0.24 mg/kg by s.c. injection route, respectively. A.crassicauda (Olivier, 1807) venom was used as control. One millilitre of the RSHA anti-Ac neutralises 23 LD50 of M. e. eupeus, 32 LD50 of M.gibbosus and 42 LD50 of A. crassicauda venom in mice. Analysis of electrophoresis indicates that three scorpion venoms posses low molecular weight proteins. Immunoblotting indicated that RSHA anti-Ac strongly reacted with both the specific venom and Mesobuthus species venoms which have antigenic similarity. The result of our study showed that M.e. eupeus and M.gibbosus could be medically important scorpions for humans, particullary children. The RSHA anti-Ac can be used in the treatment of envenomation by M. e.eupeus and M.gibbosus scorpion stings. PMID:28979319

Prophylaxis with human serum butyrylcholinesterase protects guinea pigs exposed to multiple lethal doses of soman or VX.

PubMed

Saxena, Ashima; Sun, Wei; Fedorko, James M; Koplovitz, Irwin; Doctor, Bhupendra P

2011-01-01

Human serum butyrylcholinesterase (Hu BChE) is currently under advanced development as a bioscavenger for the prophylaxis of organophosphorus (OP) nerve agent toxicity in humans. It is estimated that a dose of 200mg will be required to protect a human against 2×LD(50) of soman. To provide data for initiating an investigational new drug application for the use of this enzyme as a bioscavenger in humans, we purified enzyme from Cohn fraction IV-4 paste and initiated safety and efficacy evaluations in mice, guinea pigs, and non-human primates. In mice, we demonstrated that a single dose of enzyme that is 30 times the therapeutic dose circulated in blood for at least four days and did not cause any clinical pathology in these animals. In this study, we report the results of safety and efficacy evaluations conducted in guinea pigs. Various doses of Hu BChE delivered by i.m. injections peaked at ∼24h and had a mean residence time of 78-103h. Hu BChE did not exhibit any toxicity in guinea pigs as measured by general observation, serum chemistry, hematology, and gross and histological tissue changes. Efficacy evaluations showed that Hu BChE protected guinea pigs from an exposure of 5.5×LD(50) of soman or 8×LD(50) of VX. These results provide convincing data for the development of Hu BChE as a bioscavenger that can protect humans against all OP nerve agents. Published by Elsevier Inc.

Supralethal poisoning by any of the classical nerve agents is effectively counteracted by procyclidine regimens in rats.

PubMed

Myhrer, Trond; Mariussen, Espen; Enger, Siri; Aas, Pål

2015-09-01

A treatment regimen consisting of HI-6, levetiracetam, and procyclidine (termed the triple regimen) has previously been shown to work as a universal therapy against soman poisoning in rats, since it has capacities to function as both prophylactic and therapeutic measure. The purpose of the present study was to examine whether the triple regimen may have antidotal efficacy against intoxication by other classical nerve agents than soman. The treatment was given 1 and 5 min after exposure to a supralethal dose of nerve agents, and the results showed that the triple regimen successfully prevented or terminated seizures and preserved the lives of rats exposed to 5×LD50 of soman, sarin, cyclosarin, or VX, but solely 3×LD50 of tabun was managed by this regimen. To meet the particular antidotal requirements of tabun, the triple regimen was reinforced with obidoxime and was made to a quadruple regimen that effectively treated rats intoxicated by 5×LD50 of tabun. The rats recovered very well and the majority gained pre-exposure body weight within 7 days. Neuropathology was seen in all groups regardless of whether the rats seized or not. The most extensive damage was produced by sarin and cyclosarin. Differentiation between the nerve agents' potency to cause lesions was probably seen because the efficacious treatments ensured survival of supralethal poisoning. A combination of 2 oximes and 2 anticonvulsants may be a prerequisite to counteract effectively high levels of poisoning by any classical nerve agent. Copyright © 2015 Elsevier Inc. All rights reserved.

Repellant and insecticidal activities of shyobunone and isoshyobunone derived from the essential oil of Acorus calamus rhizomes.

PubMed

Chen, Hai-Ping; Yang, Kai; Zheng, Li-Shi; You, Chun-Xue; Cai, Qian; Wang, Cheng-Fang

2015-01-01

It was found that the essential oil of Acorus calamus rhizomes showed insecticidal activity. The aim of this study was to determine the chemical composition of the essential oil from A. calamus rhizomes, evaluate insecticidal and repellant activity against Lasioderma serricorne (LS) and Tribolium castaneum (TC), and to isolate any insecticidal constituents from the essential oil. Essential oil from A. calamus was obtained by hydrodistillation and analyzed by gas chromatography (GC) flame ionization detector and GC-mass spectrometry. The insecticidal and repellant activity of the essential oil and isolated compounds was tested using a variety of methods. The main components of the essential oil were identified to be isoshyobunone (15.56%), β-asarone (10.03%), bicyclo[6.1.0]non-1-ene (9.67%), shyobunone (9.60%) and methylisoeugenol (6.69%). Among them, the two active constituents were isolated and identified as shyobunone and isoshyobunone. The essential oil showed contact toxicity against LS and TC with LD50 values of 14.40 and 32.55 μg/adult, respectively. The isolated compounds, shyobunone and isoshyobunone also exhibited strong contact toxicity against LS adults with LD50 values of 20.24 and 24.19 μg/adult, respectively, while the LD50 value of isoshyobunone was 61.90 μg/adult for TC adults. The essential oil, shyobunone and isoshyobunone were strongly repellent (98%, 90% and 94%, respectively, at 78.63 nL/cm(2), after 2 h treatment) against TC. The essential oil, shyobunone and isoshyobunone possessed insecticidal and repellant activity against LS and TC.

Prevalence and features of peripheral neuropathy in Parkinson's disease patients under different therapeutic regimens.

PubMed

Mancini, F; Comi, C; Oggioni, G D; Pacchetti, C; Calandrella, D; Coletti Moja, M; Riboldazzi, G; Tunesi, S; Dal Fante, M; Manfredi, L; Lacerenza, M; Cantello, R; Antonini, A

2014-01-01

Recent reports suggest increased frequency of peripheral neuropathy (PN) in Parkinson's disease (PD) patients on levodopa compared with age-matched controls particularly during continuous levodopa delivery by intestinal infusion (CLDII). The aim of this study is to compare frequency, clinical features, and outcome of PN in PD patients undergoing different therapeutic regimens. Three groups of consecutive PD patients, 50 on intestinal levodopa (CLDII), 50 on oral levodopa (O-LD) and 50 on other dopaminergic treatment (ODT), were enrolled in this study to assess frequency of PN using clinical and neurophysiological parameters. A biochemical study of all PN patients was performed. Frequency of PN of no evident cause was 28% in CLDII, 20% in O-LD, and 6% in ODT patients. Clinically, 71% of CLDII patients and all O-LD and ODT PN patients displayed a subacute sensory PN. In contrast, 29% of CLDII patients presented acute motor PN. Levodopa daily dose, vitamin B12 (VB12) and homocysteine (hcy) levels differed significantly in patients with PN compared to patients without PN. Our findings support the relationship between levodopa and PN and confirm that an imbalance in VB12/hcy may be a key pathogenic factor. We suggest two different, possibly overlapping mechanisms of PN in patients on CDLII: axonal degeneration due to vitamin deficiency and inflammatory damage. Whether inflammatory damage is triggered by vitamin deficiency and/or by modifications in the intestinal micro-environment should be further explored. Proper vitamin supplementation may prevent peripheral damage in most cases. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Intercostal NMJ Assay: a new alternative to the conventional LD50 assay for the determination of the therapeutic potency of botulinum toxin preparations.

PubMed

Huber, Alexander; France, Richard M; Riccalton-Banks, Lisa; McLaren, Jane; Cox, Helen; Quirk, Robin A; Shakesheff, Kevin M; Thompson, David; Panjwani, Naveed; Shipley, Sarah; Pickett, Andy

2008-05-01

Therapeutic botulinum neurotoxin type A preparations have found an increasing number of clinical uses for a large variety of neuromuscular disorders and dermatological conditions. The accurate determination of potency in the clinical application of botulinum toxins is critical to ensuring clinical efficacy and safety, and is currently achieved by using a lethal dose (LD50) assay in mice. Ethical concerns and operational constraints associated with this assay have prompted the development of alternative assay systems that could potentially lead to its replacement. As one such alternative, we describe the development and evaluation of a novel ex vivo assay (the Intercostal Neuromuscular Junction [NMJ] Assay), which uses substantially fewer animals and addresses ethical concerns associated with the LD50 assay. The assay records the decay of force from electrically-stimulated muscle tissue sections in response to the toxin, and thus combines the important mechanisms of receptor binding, translocation, and the enzymatic action of the toxin molecule. Toxin application leads to a time-related and dose-related reduction in contractile force. A regression model describing the relationship between the applied dose and force decay was determined statistically, and was successfully tested as able to correctly predict the potency of an unknown sample. The tissue sections used were found to be highly reproducible, as determined through the innervation pattern and the localisation of NMJs in situ. Furthermore, the efficacy of the assay protocol to successfully deliver the test sample to the cellular target sites, was critically assessed by using molecular tracer molecules.

Skin notation in the context of workplace exposure standards

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scansetti, G.; Piolatto, G.; Rubino, G.F.

1988-01-01

In the establishment of workplace exposure standards, the potential for cutaneous absorption is taken into consideration through the addition of skin notation to the relevant substance. In the TLVs Documentation (ACGIH, 1986) dermal lethal dose to 50% (LD50) or human data are the bases for the assignment of skin notation to 91 of 168 substances. For the other substances, the skin attribution seems to be based on undocumented statements in 24 (14.5%), skin effects in 13 (8%), and analogy in 7 (4%), while in the remaining 33 (20%) any reference is lacking as to the basis for notation of themore » cutaneous route of entry. Furthermore, since the established cut-off value of 2 g/kg is sometimes bypassed when a notation is added or omitted, the use of dermal LD50 is perplexing. Given the relevance of the skin notation for the validation of threshold limit values (TLVs) in the workplace, a full examination and citation of all available scientific data are recommended when establishing the TLV of substances absorbable through the skin.« less

Experimental milk-borne transmission of Powassan virus in the goat.

PubMed

Woodall, J P; Roz, A

1977-01-01

A lactating goat with a 74-day-old kid was inoculated with 10(3) mouse 50% lethal dose (LD50) of Powassan virus. No ensuing viremia could be detected, but virus was secreted in the milk on postinoculation days 7 through 15, with a titer of 10(5) LD50/ml on day 12. Neutralizing antibody was found in the serum on days 22 through 36 and in the milk on day 36. The offspring was not inoculated but was allowed to continue feeding on its mother's milk. It developed neutralizing antibody by day 22. Since the kid was past the age when it could resorb antibody from the milk, its serum antibody was evidence of active infection. Neither animal showed any clinical sign of illness. A serum survey of 499 goats in New York State showed that 9 had neutralizing antibodies to Powassan virus. These immune goats came from widely scattered localities, including counties where human cases have been confirmed. The findings suggest the possibility of milk-borne transmission of Powassan virus from goat to man.

Field evaluation of the efficacy of fenbendazole in captive wild ruminants.

PubMed

Goossens, E; Dorny, P; Vercammen, F; Vercruysse, J

2005-11-05

The efficacy of in-feed fenbendazole at a dose rate of 7.5 mg/kg bodyweight for three consecutive days was assessed in five Arabian oryx (Oryx leucoryx), six scimitar-horned oryx (Oryx dammah), 14 slender-horned gazelles (Gazella leptoceros), eight Soay sheep (Ovis aries aries soay), 13 alpine ibex (Capra ibex ibex), six red deer (Cervus elaphus hippelaphus) and 11 Nelson's elk (Cervus elaphus nelsoni) kept in five herds in a zoo. The efficacy was assessed by means of repeated faecal egg count reduction (fecr) tests and in vitro egg hatch assays. Fenbendazole was highly effective against nematodes in five of the seven species, consistently reducing egg shedding by more than 90 per cent. In the egg hatch assays of the five herds, 50 per cent inhibition of hatching (ld50) was observed at a concentration of thiabendazole below 0.1 microg/ml. In the Arabian oryx and alpine ibex the efficacy of fenbendazole was less than 90 per cent, and the ld50 in the egg hatch assays was between 0.1 and 0.2 microg/ml thiabendazole.

Experimental Escherichia coli peritonitis in immunosuppressed mice: the role of specific and non-specific immunity.

PubMed

Vuopio-Varkila, J

1988-01-01

An experimental Escherichia coli septicaemia-peritonitis model was adapted to immunosuppressed mice. The mice were made neutropenic by a sublethal dose of cyclophosphamide, which resulted in a 100-fold increase in their susceptibility to intraperitoneal injection of E. coli O18:K1. A lethal infection could be prevented by passive immunisation with anti-K1 capsular or anti-O18 LPS antibodies but not with anti-J5 bacterial antibodies. The anti-K1 and anti-O18 antisera were able to increase the LD50 of the E. coli challenge by factors of 50 and 5, respectively. The role of non-specific, lipopolysaccharide (LPS)-mediated resistance to infection was also investigated in this model, in which only long-living phagocytic cells such as macrophages are believed to be functional. Pretreatment of mice with LPS was shown to prevent growth of the bacterial challenge in the peritoneal cavity and blood and to result in a five-fold increase in the LD50 of the challenge strain. These findings suggest an important role for macrophages as effector cells in defence against E. coli infection.

Cheap streak camera based on the LD-S-10 intensifier tube

NASA Astrophysics Data System (ADS)

Dashevsky, Boris E.; Krutik, Mikhail I.; Surovegin, Alexander L.

1992-01-01

Basic properties of a new streak camera and its test results are reported. To intensify images on its screen, we employed modular G1 tubes, the LD-A-1.0 and LD-A-0.33, enabling magnification of 1.0 and 0.33, respectively. If necessary, the LD-A-0.33 tube may be substituted by any other image intensifier of the LDA series, the choice to be determined by the size of the CCD matrix with fiber-optical windows. The reported camera employs a 12.5- mm-long CCD strip consisting of 1024 pixels, each 12 X 500 micrometers in size. Registered radiation was imaged on a 5 X 0.04 mm slit diaphragm tightly connected with the LD-S- 10 fiber-optical input window. Electrons escaping the cathode are accelerated in a 5 kV electric field and focused onto a phosphor screen covering a fiber-optical plate as they travel between deflection plates. Sensitivity of the latter was 18 V/mm, which implies that the total deflecting voltage was 720 V per 40 mm of the screen surface, since reversed-polarity scan pulses +360 V and -360 V were applied across the deflection plate. The streak camera provides full scan times over the screen of 15, 30, 50, 100, 250, and 500 ns. Timing of the electrically or optically driven camera was done using a 10 ns step-controlled-delay (0 - 500 ns) circuit.

The acute toxicity of the death camas (Zigadenus species) alkaloid zygacine in mice, including the effect of methyllycaconitine coadministration on zygacine toxicity.

PubMed

Welch, K D; Panter, K E; Gardner, D R; Stegelmeier, B L; Green, B T; Pfister, J A; Cook, D

2011-05-01

Death camas (Zigadenus spp.) is a common poisonous plant on foothill rangelands in western North America. The steroidal alkaloid zygacine is believed to be the primary toxic component in death camas. Poisonings on rangelands generally occur in the spring when death camas is abundant, whereas other more desirable forage species are limited in availability. In most cases where livestock are poisoned by plants in a range setting, there is more than one potential poisonous plant in that area. One common poisonous plant that is often found growing simultaneously in the same area as death camas is low larkspur (Delphinium nuttallianum). Consequently, the objectives of this study were to conduct acute toxicity studies in mice and to determine if coadministration of low larkspur will exacerbate the toxicity of death camas. We first characterized the acute toxicity of zygacine in mice. The LD(50) of zygacine administered intravenously (i.v.) and orally was 2.0 ± 0.2 and 132 ± 21 mg/kg, respectively. The rate of elimination of zygacine from whole blood was determined to be 0.06 ± 0.01/min, which corresponds to an elimination half-life of 13.0 ± 2.7 min. The i.v. LD(50) of total alkaloid extracts from a Utah and a Nevada collection were 2.8 ± 0.8 and 2.2 ± 0.3 mg/kg, respectively. The i.v. LD(50) of methyllycaconitine (MLA), a major toxic alkaloid in low larkspur, was 4.6 ± 0.5 mg/kg, whereas the i.v. LD(50) of a 1:1 mixture of MLA and zygacine was 2.9 ± 0.7 mg/kg. The clinical signs in mice treated with this mixture were very similar to those of mice treated with zygacine alone, including the time of onset and death. These results suggest that there is an additive effect of coadministering these 2 alkaloids i.v. in mice. The results from this study increase knowledge and understanding regarding the acute toxicity of death camas. As combined intoxications are most likely common, this information will be useful in further developing management recommendations for ranchers and in designing additional experiments to study the toxicity of death camas to livestock.

The development of response surface pathway design to reduce animal numbers in toxicity studies

PubMed Central

2014-01-01

Background This study describes the development of Response Surface Pathway (RSP) design, assesses its performance and effectiveness in estimating LD50, and compares RSP with Up and Down Procedures (UDPs) and Random Walk (RW) design. Methods A basic 4-level RSP design was used on 36 male ICR mice given intraperitoneal doses of Yessotoxin. Simulations were performed to optimise the design. A k-adjustment factor was introduced to ensure coverage of the dose window and calculate the dose steps. Instead of using equal numbers of mice on all levels, the number of mice was increased at each design level. Additionally, the binomial outcome variable was changed to multinomial. The performance of the RSP designs and a comparison of UDPs and RW were assessed by simulations. The optimised 4-level RSP design was used on 24 female NMRI mice given Azaspiracid-1 intraperitoneally. Results The in vivo experiment with basic 4-level RSP design estimated the LD50 of Yessotoxin to be 463 μg/kgBW (95% CI: 383–535). By inclusion of the k-adjustment factor with equal or increasing numbers of mice on increasing dose levels, the estimate changed to 481 μg/kgBW (95% CI: 362–566) and 447 μg/kgBW (95% CI: 378–504 μg/kgBW), respectively. The optimised 4-level RSP estimated the LD50 to be 473 μg/kgBW (95% CI: 442–517). A similar increase in power was demonstrated using the optimised RSP design on real Azaspiracid-1 data. The simulations showed that the inclusion of the k-adjustment factor, reduction in sample size by increasing the number of mice on higher design levels and incorporation of a multinomial outcome gave estimates of the LD50 that were as good as those with the basic RSP design. Furthermore, optimised RSP design performed on just three levels reduced the number of animals from 36 to 15 without loss of information, when compared with the 4-level designs. Simulated comparison of the RSP design with UDPs and RW design demonstrated the superiority of RSP. Conclusion Optimised RSP design reduces the number of animals needed. The design converges rapidly on the area of interest and is at least as efficient as both the UDPs and RW design. PMID:24661560

CYTOTOXIC, α-CHYMOTRYPSIN AND UREASE INHIBITION ACTIVITIES OF THE PLANT Heliotropium dasycarpum L.

PubMed

Ghaffari, Muhammad Abuzar; Chaudhary, Bashir Ahmed; Uzair, Muhammad; Ashfaq, Khuram

2016-01-01

The aim of this study was to investigate Cytotoxic, α-Chymotrypsin and Urease inhibition activities of the plant Heliotropium dasycarpum . Dichloromethane and methanol extracts of the plant were evaluated for cytotoxic, α-Chymotrypsin and Urease inhibition by using in vivo Brine Shrimp lethality bioassay and in vitro enzymatic inhibition assays respectively. The methanol extract of the plant exhibited significant cytotoxic activity. Out of 30 brine shrimp larvae, 2 (6%), 26 (86%) and 28 (93%) larvae were survived at concentration of 1000μg/ml, 100μg/ml and 10μg/ml respectively with LD50; 215.837. Similarly 21 (70%), 25 (83%), 29 (96%) larvae were survived of dichloromethane plant extract with LD50; 6170.64. The methanol and dichloromethane extract exhibited 10.50±0.18% and 41.51±0.15% α-chymotrypsin enzyme inhibition respectively with IC 50 values of greater than 500 μmol. The methanol extract showed 24.39±0.21% Urease enzyme inhibition with IC 50 values of greater than 400 μmol While dichloromethane extract has 11.46±0.09% enzyme inhibition with IC 50 values of greater than 500 μmol. The results clearly indicated that Heliotropium dasycarpum has cytotoxic potential and enzyme inhibition properties. Further study is needed to screen out antitumor and anti-ulcerative agents.

CYTOTOXIC, α-CHYMOTRYPSIN AND UREASE INHIBITION ACTIVITIES OF THE PLANT Heliotropium dasycarpum L.

PubMed Central

Ghaffari, Muhammad Abuzar; Chaudhary, Bashir Ahmed; Uzair, Muhammad; Ashfaq, Khuram

2016-01-01

Background: The aim of this study was to investigate Cytotoxic, α-Chymotrypsin and Urease inhibition activities of the plant Heliotropium dasycarpum. Materials & Methods: Dichloromethane and methanol extracts of the plant were evaluated for cytotoxic, α-Chymotrypsin and Urease inhibition by using in vivo Brine Shrimp lethality bioassay and in vitro enzymatic inhibition assays respectively. Results: The methanol extract of the plant exhibited significant cytotoxic activity. Out of 30 brine shrimp larvae, 2 (6%), 26 (86%) and 28 (93%) larvae were survived at concentration of 1000μg/ml, 100μg/ml and 10μg/ml respectively with LD50; 215.837. Similarly 21 (70%), 25 (83%), 29 (96%) larvae were survived of dichloromethane plant extract with LD50; 6170.64. The methanol and dichloromethane extract exhibited 10.50±0.18% and 41.51±0.15% α-chymotrypsin enzyme inhibition respectively with IC50 values of greater than 500 μmol. The methanol extract showed 24.39±0.21% Urease enzyme inhibition with IC50 values of greater than 400 μmol While dichloromethane extract has 11.46±0.09% enzyme inhibition with IC50 values of greater than 500 μmol Conclusion: The results clearly indicated that Heliotropium dasycarpum has cytotoxic potential and enzyme inhibition properties. Further study is needed to screen out antitumor and anti-ulcerative agents. PMID:28480379

The Hematopoietic Syndrome of the Acute Radiation Syndrome in Rhesus Macaques: A Systematic Review of the Lethal Dose Response Relationship.

PubMed

MacVittie, Thomas J; Farese, Ann M; Jackson, William

2015-11-01

Well characterized animal models that mimic the human response to potentially lethal doses of radiation are required to assess the efficacy of medical countermeasures under the criteria of the U.S. Food and Drug Administration "animal rule." Development of a model requires the determination of the radiation dose response relationship and time course of mortality and morbidity across the hematopoietic acute radiation syndrome. The nonhuman primate, rhesus macaque, is a relevant animal model that may be used to determine the efficacy of medical countermeasures to mitigate major signs of morbidity and mortality at selected lethal doses of total body irradiation. A systematic review of relevant studies that determined the dose response relationship for the hematopoietic acute radiation syndrome in the rhesus macaque relative to radiation quality, dose rate, and exposure uniformity has never been performed. The selection of data cohorts was made from the following sources: Ovid Medline (1957-present), PubMed (1954-present), AGRICOLA (1976-present), Web of Science (1954-present), and U.S. HHS REPORT (2002 to present). The following terms were used: Rhesus, total body-irradiation, total body x irradiation, TBI, irradiation, gamma radiation, hematopoiesis, LD50/60, Macaca mulatta, whole-body irradiation, nonhuman primate, NHP, monkey, primates, hematopoietic radiation syndrome, mortality, and nuclear radiation. The reference lists of all studies, published and unpublished, were reviewed for additional studies. The total number of hits across all search sites was 3,001. There were a number of referenced, unpublished, non-peer reviewed government reports that were unavailable for review. Fifteen studies, 11 primary (n = 863) and four secondary (n = 153) studies [n = 1,016 total nonhuman primates (NHP), rhesus Macaca mulatta] were evaluated to provide an informative and consistent review. The dose response relationships (DRRs) were determined for uniform or non-uniform total body irradiation (TBI) with 250 kVp or 2 MeV x radiation, Co gamma radiation and reactor- and nuclear weapon-derived mixed gamma: neutron-radiation, delivered at various dose rates from a total body, bilateral, rotational, or unilateral exposure aspect. The DRRs established by a probit analysis vs. linear dose relationship were characterized by two main parameters or dependent variables: a slope and LD50/30. Respective LD50/30 values for studies that used 250 kVp x radiation (five primary studies combined, n = 338), 2 MeV x radiation, Co gamma radiation, and steady-state reactor-derived mixed gamma:neutron radiation for total body uniform exposures were 521 rad [498, 542], 671 rad [632, 715], 644 rad [613, 678], and 385 rad [357, 413]. The respective slopes were steep and ranged from 0.738 to 1.316. The DRR, LD50/30 values and slopes were also determined for total body, non-uniform, unilateral, pulse-rate exposures of mixed gamma:neutron radiation derived at reactor and nuclear weapon detonations. The LD50/30 values were, respectively, 395 rad [337, 432] and 412 rad [359, 460]. Secondary data sets of limited studies that did not describe a DRR were used to support the mid-to-high lethal dose range for the H-ARS and the threshold dose range for the concurrent acute GI ARS. The available evidence provided a reliable and extensive database that characterized the DRR for the H-ARS in young rhesus macaques exposed to 250 kVp uniform total body x radiation without the benefit of medical management. A less substantial but consistent database demonstrated the DRR for total body exposure of differing radiation quality, dose rate and non-uniform exposure. The DRR for the H-ARS is characterized by steep slopes and relative LD50/30 values that reflect the radiation quality, exposure aspect, and dose rate over a range in time from 1954-2012.

[A comparative study on characterizations of genetic recombination hotspots in PPARG gene between Kirgiz and Uyghur ethnic groups in Xinjiang].

PubMed

Zohra, Rozi; Song, M S; Iliham, Nizam; Dolikun, Mamatyusupu

2016-08-16

To investigate the characterizations of genetic recombination hotspots and linkage disequilibrium (LD) patterns in peroxisome proliferative activated receptor gamma (PPARG) gene in Kirgiz and Uyghur ethnic groups. Blood samples were collected from 100 Kirgiz (50 healthy controls and 50 patients with type 2 diabetes mellitus) residents in Halajun County, Artux City, Kizilsu Kirgiz Autonomous Prefecture, Xinjiang in August 2013, and 50 healthy Uyghur residents in Hotan Prefecture of Xinjiang Uygur Autonomous Region in May 2012.Thirty-one tagSNPs in PPARG gene were genotyped using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS) method.The recombination hotspots and LD patterns within the PPARG gene were estimated by analyzing the SNP genotying data using the Hotspot Fisher program and Haploview software, respectively. Eighteen tagSNPs (rs1151999, rs1175540, rs1875796, rs1899951, rs2292101, rs2921190, rs2938397, rs2959272, rs2959273, rs2972162, rs3856806, rs4135247, rs4135275, rs709151, rs4135354, rs6805419, rs17036700 and rs4135304) were same with relatively higher recombination rates between the patients with type 2 diabetes mellitus (T2DM) and healthy controls of Kirgiz ethnic group, and healthy controls of Uyghur ethnic group.Five haplotype blocks with LD coefficient D' value of 1, indicating no genetic recombination occurred within the region, were observed in the healthy controls of Kirgiz ethnic groups, whereas five haplotype blocks with LD coefficient D' value less than 1 were observed in the Kirgiz patients with T2DM, indicating historical recombination events occurred within the region.Four haplotype blocks with LD coefficient D' value of 1 were observed in the Uyghur healthy controls, indicating no genetic recombination occurred within the region.There were significantly different recombination hotspot profiles between the Kirgiz, Uyghur, Utah residents with Northern and Western European ancestry (CEU), Yoruban in Ibadan, Nigeria (YRI) and Han Chinese in Beijing (CHB) and Japanese in Tokyo (JPT) samples.There are six recombination hotspots in the HapMap profile of genetic recombination.The last 5 SNPs within the PPARG gene were shown with lower recombination rates in the Kirgiz, whereas no recombination hotspot was found in the Uyghur. Variable recombination rates may be present in certain chromosome region between patients and healthy controls within the same or between the different ethnic groups.There may be presence of recombination hotspots of ethnic specificity and with variable recombination rates.

Control of human filarial vector, Culex quinquefasciatus Say 1823 (Diptera: Culicidae) through bioactive fraction of Cayratia trifolia leaf.

PubMed

Chakraborty, Sumanta; Singha, Someshwar; Bhattacharya, Kuntal; Chandra, Goutam

2013-12-01

To investigate the mosquito larvicidal activity of Cayratia trifolia (L.) Domin (Vitaceae: Vitales) (C. trifolia) which is distributed in many parts of India with medicinal properties as vector control is facing threat due to the emergence of resistance to synthetic insecticides. Young and mature leaves of C. trifolia were investigated for larvicidal activity against 3rd instars larvae of Culex quinquefasciatus in different seasons throughout the year. The active fractions were extracted using six different solvents in a non-polar to polar fashion viz petroleum-ether, benzene, chloroform: methanol (1:1 v/v), acetone, absolute alcohol and distilled water. Dose dependent mortality was recorded against each solvent extract. Determination of LD50 and LD90 were executed through log-probit analysis using the most bioactive fraction. The fluctuations in mortality were statistically co-related through ANOVA analyses concerning different seasons and types of leaves as random variables. Justification of larvicidal activity was established through student's t-test. Costing effects were evaluated on the non-target water fauna under laboratory conditions. Thin layer chromatographic techniques were performed for phytochemical analysis and categorization of chemical personality of the active fractions using the most effective solvent extract following standard methods. Significant variations in mortality rate were noted with respect to the type of leaves (mature and senescence), concentration of leaf extract and between seasons. The water extract among all the solvent extracts was found to induce cent percent mortality at 50 mg/L in test mosquito species within 24 h with a LD50 and LD90 value of 10.70 mg/L and 27.64 mg/L respectively. No significant mortality was recorded in non-target water population. Chromatographic analyses of the water extract revealed the presence of steroids, triterpene glycosides, essential oil, phenolics and diterpenes as secondary phytochemicals. Water extract of C. trifolia leaf promised as a cost effective and potent larvicidal agent against Culex quinquefasciatus. Copyright © 2013 Asian Pacific Tropical Biomedical Magazine. Published by Elsevier B.V. All rights reserved.

Low-Dose Involved-Field Radiation in the Treatment of Non-Hodgkin Lymphoma: Predictors of Response and Treatment Failure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Russo, Andrea L., E-mail: alrusso@partners.org; Chen, Yu-Hui; Martin, Neil E.

Purpose: To investigate clinical and pathologic factors significant in predicting local response and time to further treatment after low-dose involved-field radiation therapy (LD-IFRT) for non-Hodgkin lymphoma (NHL). Methods and Materials: Records of NHL patients treated at a single institution between April 2004 and September 2011 were retrospectively reviewed. Low-dose involved-field radiation therapy was given as 4 Gy in 2 fractions over 2 consecutive days. Treatment response and disease control were determined by radiographic studies and/or physical examination. A generalized estimating equation model was used to assess the effect of tumor and patient characteristics on disease response. A Cox proportional hazardsmore » regression model was used to assess time to further treatment. Results: We treated a total of 187 sites in 127 patients with LD-IFRT. Histologies included 66% follicular, 9% chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma, 10% marginal zone, 6% mantle cell lymphoma (MCL), and 8% other. Median follow-up time was 23.4 months (range, 0.03-92.2 months). The complete response, partial response, and overall response rates were 57%, 25%, and 82%, respectively. A CLL histology was associated with a lower response rate (odds ratio 0.2, 95% confidence interval 0.1-0.5, P=.02). Tumor size, site, age at diagnosis, and prior systemic therapy were not associated with response. The median time to first recurrence was 13.6 months. Those with CLL and age ≤50 years at diagnosis had a shorter time to further treatment for local failures (hazard ratio [HR] 3.63, P=.01 and HR 5.50, P=.02, respectively). Those with CLL and MCL had a shorter time to further treatment for distant failures (HR 11.1 and 16.3, respectively, P<.0001). Conclusions: High local response rates were achieved with LD-IFRT across most histologies. Chronic lymphocytic leukemia and MCL histologies and age ≤50 years at diagnosis had a shorter time to further treatment after LD-IFRT.« less

Oral administration of leaf extracts of Momordica charantia affect reproductive hormones of adult female Wistar rats

PubMed Central

Adewale, Osonuga Odusoga; Oduyemi, Osonuga Ifabunmi; Ayokunle, Osonuga

2014-01-01

Objective To determine the effect of graded doses of aqueous leaf extracts of Momordica charantia on fertility hormones of female albino rats. Methods Twenty adult, healthy, female Wistar rats were divided into four groups: low dose (LD), moderate dose (MD) and high dose (HD) groups which received 12.5 g, 25.0 g, 50.0 g of the leaf extract respectively and control group that was given with water ad libatum. Result Estrogen levels reduced by 6.40 nmol/L, 10.80 nmol/L and 28.00 nmol/L in the LD, MD and HD groups respectively while plasma progesterone of rats in the LD, MD and HD groups reduced by 24.20 nmol/L, 40.8 nmol/L and 59.20 nmol/L respectively. Conclusion Our study has shown that the antifertility effect of Momordica charantia is achieved in a dose dependent manner. Hence, cautious use of such medication should be advocated especially when managing couples for infertility. PMID:25183143

Determination of the Effects of Medium Composition on the Monochloramine Disinfection Kinetics of Nitrosomonas europaea by the Propidium Monoazide Quantitative PCR and Live/Dead BacLight Methods ▿

PubMed Central

Wahman, David G.; Schrantz, Karen A.; Pressman, Jonathan G.

2010-01-01

Various medium compositions (phosphate, 1 to 50 mM; ionic strength, 2.8 to 150 meq/liter) significantly affected Nitrosomonas europaea monochloramine disinfection kinetics, as determined by the Live/Dead BacLight (LD) and propidium monoazide quantitative PCR (PMA-qPCR) methods (lag coefficient, 37 to 490 [LD] and 91 to 490 [PMA-qPCR] mg·min/liter; Chick-Watson rate constant, 4.0 × 10−3 to 9.3 × 10−3 [LD] and 1.6 × 10−3 to 9.6 × 10−3 [PMA-qPCR] liter/mg·min). Two competing effects may account for the variation in disinfection kinetic parameters: (i) increasing kinetics (disinfection rate constant [k] increased, lag coefficient [b] decreased) with increasing phosphate concentration and (ii) decreasing kinetics (k decreased, b increased) with increasing ionic strength. The results support development of a standard medium for evaluating disinfection kinetics in drinking water. PMID:20952645

A comparative study on the relationship between various toxicological endpoints in Caenorhabditis elegans exposed to organophosphorus insecticides.

PubMed

Rajini, P S; Melstrom, Paul; Williams, Phillip L

2008-01-01

The toxicity of 10 organophophorus (OP) insecticides-acephate, dimethoate, dichlorvos, dicrotophos, monocrotophos, methamidophos, phosphamidon, omethoate, phosdrin, and trichlorfon-was evaluated in Caenorhabditis elegans using lethality, movement, and acetylcholinesterase (AChE) activity as the endpoints after a 4-hr- exposure period. The OP insecticides tested showed LC50 values ranging from 0.039 mM (for dichlorovs) to 472.8 mM (for methamidophos). The order of toxicity for lethality and movement was not significantly different when tested using the rank order correlation coefficient. AChE activity was markedly affected by all the OP insecticide exposures that caused significant inhibition in movement, indicating that the mechanism of toxicity of OP insecticides in C. elegans is the same as in higher animals. All OP insecticides induced greater than 50% inhibition of AChE at the lowest tested OP insecticide concentration resulting in inhibition in movement. While a significant correlation was evident between LC50 values in C. elegans and the LD50 values in rats for the 10 OP insecticides studied, a correlation was not evident between EC50 values in C. elegans and LD50 values in rats. Overall, the two endpoints, LC50 and movement, were more reliable and easier to perform than measurement of AChE activity in C. elegans for determining the toxicity of OP insecticides. Further, ranking of these endpoints with respect to the OP insecticides studied indicates that these parameters in C. elegans are predictive of OP insecticides mammalian neurotoxicity.

Students classified as LD who received course substitutions for the college foreign language requirement: a replication study.

PubMed

Sparks, Richard L; Philips, Lois G; Javorsky, James

2002-01-01

This replication study examined whether 158 college students classified as learning disabled (LD) who were granted course substitutions for the foreign language (FL) requirement would display significant cognitive and academic achievement differences when grouped by levels of IQ-achievement and achievement-achievement discrepancy and by level of performance on an FL aptitude test (Modern Language Aptitude Test; MLAT), phonological/orthographic processing measures, and in FL courses. The results showed that there were few differences among groups with differing levels of IQ-achievement or achievement-achievement discrepancy (i.e., < 1.0 SD, 1.0-1.49 SD, and > 1.50 SD) on MLAT and American College Testing (ACT) scores, graduating grade point average (GPA), or college FL GPA. The results also showed that between groups who scored at or above versus below the 15th percentile (i.e., < 1.0 SD) on the MLAT, there were no differences on measures of graduating GPA, college FL GPA, native language skill, ACT score, and Verbal IQ. Demographic findings showed that 44% of these petition students met a minimum IQ-achievement discrepancy criterion (> or = 1.0 SD) for classification as LD. These findings suggest that many traditional assumptions about LD and FL learning are likely to be false.

Students classified as LD and the college foreign language requirement: a quantitative analysis.

PubMed

Sparks, R L; Philips, L; Ganschow, L; Javorsky, J

1999-01-01

This study was conducted to determine whether students classified as learning disabled (LD) who were permitted to substitute courses for the college foreign language (FL) requirement at one university would display significant cognitive and academic achievement differences when grouped by level of discrepancy between IQ and achievement, by discrepancy between achievement according to different measures, and by level of performance on phonological-orthographic processing measures, on the Modern Language Aptitude Test (MLAT), and in FL courses. Results showed that there were no differences among students with different levels of discrepancy (i.e., < 1.0 SD, 1.0-1.49 SD, and > 1.50 SD) on MLAT and American College Testing (ACT) scores, graduating grade point average (GPA) or college FL GPA. Results also showed that among students who scored below versus at or above the 25th percentile on phonological-orthographic processing measures, there were no differences on measures of IQ, ACT, MLAT, and GPA, as well as most measures of academic achievement. Implications for the use of the LD label to grant FL course substitutions or waivers, use of the MLAT in the diagnostic and course substitution/waiver process, and the validity and reliability of traditional criteria for the classification as LD are discussed.

9 CFR 121.13 - Restricted experiments.

Code of Federal Regulations, 2014 CFR

2014-01-01

... naturally, if such acquisition could compromise the control of disease agents in humans, veterinary medicine... such acquisition could compromise the control of disease agents in humans, veterinary medicine, or... of select toxins lethal for vertebrates at an LD[50] body weight) resulting from, the...

9 CFR 121.13 - Restricted experiments.

Code of Federal Regulations, 2013 CFR

2013-01-01

... naturally, if such acquisition could compromise the control of disease agents in humans, veterinary medicine... such acquisition could compromise the control of disease agents in humans, veterinary medicine, or... of select toxins lethal for vertebrates at an LD[50] body weight) resulting from, the...

ESTIMATION OF CHEMICAL TOXICITY TO WILDLIFE SPECIES USING INTERSPECIES CORRELATION MODELS

EPA Science Inventory

Ecological risks to wildlife are typically assessed using toxicity data for relataively few species and with limited understanding of differences in species sensitivity to contaminants. Empirical interspecies correlation models were derived from LD50 values for 49 wildlife speci...

Toxic responses of medaka, d-rR strain, to polychlorinated naphthalene mixtures after embryonic exposure by in ovo nanoinjection: A partial life-cycle assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Villalobos, S.A.; Papoulias, D.M.; Meadows, J.

2000-02-01

Polychlorinated naphthalenes (PCNs) are organic compounds with some chemical properties and uses similar to polychlorinated biphenyls. Polychlorinated naphthalenes have been detected in biota from certain aquatic environments. The toxicities of several PCN technical mixtures (Halowax) to medaka (Oryzias latipes) were determined by use of an embryo nanoinjection method. Medaka eggs (early gastrula) were injected with 0.5 nl of triolein (vehicle control) or 0.5 nl of four to five graded doses (0.3--30 ng/egg) of Halowax 1014, Halowax 1013, or Halowax 1051 in triolein. Following exposure, embryos developed, and fry were reared to sexual maturity (4 months), at which time they weremore » euthanized. Responses were evaluated as early life stage (ELS) and early adult life stage (EALS) assessments. For ELS, lethality and sublethal alterations in embryos and larvae (<16 d old), such as craniofacial, cardiovascular, and myoskeletal deformities and abnormal or delayed hatch, were monitored for the first 9 d, and a dose severity index was computed. The EALS assessment examined the survival of 16-d-old larvae until early adulthood (123 {+-} 3 d old), including gonadosomatic index (GSI) and morphometry. Halowax 1014 was found to be the most toxic mixture (LD50 4.2 ng/egg), whereas Halowax 1013 and 1051 were significantly less toxic (LD50s could not be determined). The gonadosomatic index of females was significantly less in fish dosed with Halowax 1014 or 1051. The LD50 for medaka embryos nanoinjected with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is about 0.75 pg/egg. Thus, Halowax 1014 was 5,585-fold less potent than TCDD. For Halowax 1014, ELS assessments accurately predicted the results of EALS assessments.« less

Acute and subacute toxicity of 10B-paraboronophenylalanine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taniyama, K.; Fujiwara, H.; Kuno, T.

1989-07-01

The acute and subacute toxicities of 10B-paraboronophenylalanine (10B-BPA) were investigated in the rat, according to the Good Laboratory Practice Standard for safety studies on drugs in Japan. In the acute toxicity test of 10B-BPA, LD50 values of acidic 10B-BPA for intraperitoneal and subcutaneous injections were 640 mg/kg for male and 710 mg/kg for female rats, and more than 1,000 mg/kg for male and female rats, respectively. The LD50 values of neutral 10B-BPA for intraperitoneal and subcutaneous injections were more than 3,000 mg/kg for male and female rats. The difference in LD50 values between acidic and neutral 10B-BPA may be attributedmore » to the acidity of material. From the subacute toxicity test, in which the rats were injected daily subcutaneously for 28 days, the following toxic effects of 10B-BPA were observed. Increase in ketone level in the urine was induced in all rats treated with 10B-BPA. High dose of 10B-BPA (1,500 mg/kg) induced increase in spleen weight and reticulocyte count, and decrease in hemoglobin count, thereby suggesting that 10B-BPA causes hemolysis. Increases in the leukocyte count and the ratio of neutrophils and lymphocytes were also observed in rats treated with a high dose of 10B-BPA. This may be attributed to local reactions at the injection site. There were no significant differences in the findings between control rats and rats treated with a low dose of 10B-BPA (300 mg/kg). Thus, low doses of neutral 10B-BPA may be available for use as a drug.« less

Endocrine disrupting pesticides impair the neuroendocrine regulation of reproductive behaviors and secondary sexual characters of red munia (Amandava amandava).

PubMed

Pandey, Surya Prakash; Tsutsui, Kazuyoshi; Mohanty, Banalata

2017-05-01

The exposure effects of two endocrine disrupting pesticides (EDPs), mancozeb/MCZ and imidacloprid/IMI of the group dithiocarbamate and neonicotinoid respectively, on reproductive behaviors and secondary sexual characters have been studied in a seasonally breeding wildlife bird, red munia (Amandava amandava). Adult male birds were exposed to both the pesticides individually (0.25% LD 50 of each) as well as co-exposed (MIX-I: 0.25% LD 50 of each and MIX-II: 0.5% LD 50 of each) through food for 30d in preparatory (July-August) and breeding (September-October) phase of reproductive cycle. Singing and pairing patterns started decreasing from 2nd week to complete disappearance during 4th week of pesticides exposures at both the phases of reproductive cycles. Similar trend was observed in the disappearance of spots on the plumage as well as color of both plumage and beak which turned black/gray from red. Pesticides caused impairment of the lactotropic as well as hypothalamic-pituitary-testicular (HPT) axes as there was increased plasma PRL and decreased LH, FSH and testosterone levels. Testicular expressions of GnRH and androgen receptor/AR were significantly decreased but that of GnIH significantly increased as compared to control. Significant differences among individually- and co-exposed groups were also present. Abnormalities in sexual behaviors and secondary sexual characteristics could be linked to inhibition of HPT axis and/or direct toxicity at the level of hypothalamus, pituitary and testis. In addition, pesticide-induced hyperprolactinemia as well as impaired thyroid hormones might have also affected maintenance of reproductive behaviors. On co-exposures, the more distinct impairments might be due to cumulative toxicity of pesticides. Copyright © 2017 Elsevier Inc. All rights reserved.

Cardiovascular effects of equinatoxin III from the sea anemone Actinia equina (L.).

PubMed

Suput, D; Frangez, R; Bunc, M

2001-09-01

Equinatoxin III is the most hemolytic, and the least lethal of the three basic proteins isolated from the sea anemone Actinia equina (L.). Its LD50 in mice is 83 microg/kg. Preliminary results on Wistar rats have suggested cardiorespiratory arrest as a putative cause of death, but the mechanism of its action has not yet been studied. So far only equinatoxin II has been investigated more thoroughly. As equinatoxin II is less lythic, but more toxic, than equinatoxin III (its LD50 in mice=35 microg/kg), it may be assumed that haemolysis with a consequent rise in plasma potassium level is not the major factor in the lethality of equinatoxins. To assess the relative contribution of hyperkalemia in the lethality of the toxin in rat, the effects of equinatoxin III were compared to the effects of hyperkalemia caused by the injection of KCl giving the same final concentration of K+ in the plasma as that observed after an i.v. injection of 3LD50 of equinatoxin III. As coronary vasoconstriction may be an important mechanism of the cardiotoxic action of equinatoxins, the effect of EqT III on isolated porcine coronary arteries was studied by measurements of smooth muscle tension in the presence of 1-100 nM equinatoxin III. The results revealed that animals survive the elevated K+ plasma concentration caused by an i.v. application of KCl. This suggests that equinatoxin III induced haemolysis is not the major mechanism of equinatoxin III lethality. However, equinatoxin III increases the potassium induced contractions of coronary smooth muscle for 289+/-29%, suggesting that coronary vasoconstriction may be an important factor in the cardiotoxic effects of equinatoxin III.

A comparison of the reactivating and therapeutic efficacy of two novel bispyridinium oximes (K727, K733) with the oxime HI-6 and obidoxime in sarin-poisoned rats and mice.

PubMed

Kassa, Jiri; Sepsova, Vendula; Matouskova, Lenka; Horova, Anna; Musilek, Kamil

2015-03-01

The ability of two novel bispyridinium oximes K727 and K733 and currently available oximes (HI-6, obidoxime) to reactivate sarin-inhibited acetylcholinesterase and to reduce acute toxicity of sarin was evaluated. To investigate the reactivating efficacy of the oximes, the rats were administered intramuscularly with atropine and oximes in equitoxic doses corresponding to 5% of their LD50 values at 1 min after the intramuscular administration of sarin at a dose of 24 µg/kg (LD50). The activity of acetylcholinesterase was measured at 60 min after sarin poisoning. The LD50 value of sarin in non-treated and treated mice was assessed using probit-logarithmical analysis of death occurring within 24 h after intramuscular administration of sarin at five different doses. In vivo determined percentage of reactivation of sarin-inhibited rat blood, diaphragm and brain acetylcholinesterase showed that the potency of both novel oximes K727 and K733 to reactivate sarin-inhibited acetylcholinesterase roughly corresponds to the reactivating efficacy of obidoxime. On the other hand, the oxime HI-6 was found to be the most efficient reactivator of sarin-inhibited acetylcholinesterase. While the oxime HI-6 was able to reduce the acute toxicity of sarin >3 times, both novel oximes and obidoxime decreased the acute toxicity of sarin <2 times. Based on the results, we can conclude that the reactivating and therapeutic efficacy of both novel oximes K727 and K733 is significantly lower compared to the oxime HI-6 and, therefore, they are not suitable for the replacement of the oxime HI-6 for the antidotal treatment of acute sarin poisoning.

[The activity of blood cholinesterase in rats exposed to dimethypo after drug intervention].

PubMed

Wan, Weiguo; Xu, Mailing; Zou, Hejian; Lu, Ailing; Shen, Xinyu; Chen, Yuming

2002-12-01

To investigate the activity of ChE in rats poisoned by dimehypo and then treated with pralidoxime methylchloride or unithiol. Rats were divided into control group (dimehypo); intervention groups [dimehypo plus pralidoxime methylchloride or dimehypo plus unithiol (sodium dimercaptopropanesulphonate)]. Rats were dosed with 4 different doses of dimehypo: 1/16, 1/8, 1/4 and 1/2 of LD50 respectively(the LD50 of dimehypo is 342 mg/kg). After being poisoned with dimehypo orally, rats were immediately injected intramuscularly with pralidoxime methylchloride or unithiol. The activity of ChE in blood was detected before and 1/2, 1, 2, 4 and 24 h after poisoning in dimehypo and intervention groups. The ChE activity of four dose subgroups at 1 h after poisoning were (1.04 +/- 0.21), (0.84 +/- 0.12), (0.71 +/- 0.12), (0.66 +/- 0.07) U/ml respectively; the ChE activity of pralidoxime methylchloride intervention groups were (1.01 +/- 0.18), (1.17 +/- 0.11), (1.01 +/- 0.04), (1.03 +/- 0.12) U/ml respectively; and the ChE activity of unithiol intervention groups were (1.15 +/- 0.15), (1.26 +/- 0.27), (1.08 +/- 0.08), (1.04 +/- 0.12) U/ml respectively. The inhibited ChE in blood was recovered by either treatment with pyraldoxime methylchloride or unithiol. These two drugs had similar effects of recovering the activity of ChE(P > 0.05), but at higher doses(1/4 and 1/2 of LD50) the effects of both were not so good. Pralidoxime methylchloride and unithiol could partly recover the activity of ChE inhibited by dimehypo.

Toxic responses of medaka, D-rR strain, to polychlorinatednaphthalene mixtures after embryonic exposure by in ovo nanoinjection: A partial life-cycle assessment

USGS Publications Warehouse

Villalobos, Sergio A.; Papoulias, Diana M.; Meadows, John C.; Blankenship, Alan L.; Pastva, Stephanie D.; Kannan, Kurunthachalam; Hinton, D.E.; Tillitt, Donald E.; Giesy, John P.

2000-01-01

Polychlorinated naphthalenes (PCNs) are organic compounds with some chemical properties and uses similar to polychlorinated biphenyls. Polychlorinated naphthalenes have been detected in biota from certain aquatic environments. The toxicities of several PCN technical mixtures (Halowax) to medaka (Oryzias latipes) were determined by use of an embryo nanoinjection method. Medaka eggs (early gastrula) were injected with 0.5 nl of triolein (vehicle control) or 0.5 nl of four to five graded doses (0.3-30 ng/egg) of Halowax 1014, Halowax 1013, or Halowax 1051 in triolein. Following exposure, embryos developed, and fry were reared to sexual maturity (4 months), at which time they were euthanized. Responses were evaluated as early life stage (ELS) and early adult life stage (EALS) assessments. For ELS, lethality and sublethal alterations in embryos and larvae ( < 16 d old), such as craniofacial, cardiovascular, and myoskeletal deformities and abnormal or delayed hatch, were monitored for the first 9 d, and a dose severity index was computed. The EALS assessment examined the survival of 16-d-old larvae until early adulthood (123 ?? 3 d old), including gonadosomatic index (GSI) and morphometry. Halowax 1014 was found to be the most toxic mixture (LD50 4.2 ng/egg), whereas Halowax 1013 and 1051 were significantly less toxic (LD50s could not be determined). The gonadosomatic index of females was significantly less in fish dosed with Halowax 1014 or 1051. The LD50 for medaka embryos nanoinjected with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is about 0.75 pg/egg. Thus, Halowax 1014 was 5,585-fold less potent than TCDD. For Halowax 1014, ELS assessments accurately predicted the results of EALS assessments.

Predation and behavioral changes in the neotropical lacewing Chrysoperla externa (Hagen) (Neuroptera: Chrysopidae) exposed to lambda-cyhalothrin.

PubMed

Luna, René Fernando; Bestete, Luziani Rezende; Torres, Jorge Braz; da Silva-Torres, Christian Sherley Araújo

2018-05-24

Pyrethroid insecticides are widely recommended against various defoliating pest species, but usually lack efficacy against sucking pests such as aphids, which are preferred prey of lacewing larvae. Interaction of pyrethroids and lacewings are likely to occur in fields infested by both defoliating and sap-sucking pests and should provide a complementary control. Therefore, our study aimed to estimate dose-mortality curves and behavioral changes by Chrysoperla externa exposed to lambda-cyhalothrin. We tested the susceptibility of two populations from different locations and insecticide history exposure through topical application. Based on the LD 50 -calculated, the population exhibiting the greater LD 50 was exposed to resistance enhancement (Sel) by treating larvae once for seven successive generations. The population with lower LD 50 was kept without selection (Nsel). Subsequently, walking, predation and oviposition behavioral after exposure to dried insecticide residues were investigated. After seven generations with insecticide selection, the resistance rations between Sel and Nsel populations were 5.85- and 9.37-fold higher for larvae and 3.38- and 2.75-fold higher for adults, respectively. Selected females caged in partially treated arenas laid similar eggs number on both treated and untreated surfaces, while Nsel females laid fewer eggs on treated surfaces. Insecticide repellency was not observed in either population, although irritability was observed for Nsel larvae. Selected larvae confined on fully and partially treated surfaces walked further, for a longer time, and with greater speeds compared to Nsel larvae. Furthermore, Sel and Nsel larvae had reduced predation rates when confined on treated surfaces, and Nsel larvae consumed less prey than Sel larvae. Results indicate changes in susceptibility, behavior, and predation rate of C. externa following exposure to lambda-cyhalothrin.

Evaluating health risks from occupational exposure to pesticides and the regulatory response.

PubMed Central

Woodruff, T J; Kyle, A D; Bois, F Y

1994-01-01

In this study, we used measurements of occupational exposures to pesticides in agriculture to evaluate health risks and analyzed how the federal regulatory program is addressing these risks. Dose estimates developed by the State of California from measured occupational exposures to 41 pesticides were compared to standard indices of acute toxicity (LD50) and chronic effects (reference dose). Lifetime cancer risks were estimated using cancer potencies. Estimated absorbed daily doses for mixers, loaders, and applicators of pesticides ranged from less than 0.0001% to 48% of the estimated human LD50 values, and doses for 10 of 40 pesticides exceeded 1% of the estimated human LD50 values. Estimated lifetime absorbed daily doses ranged from 0.1% to 114,000% of the reference doses developed by the U.S. Environmental Protection Agency, and doses for 13 of 25 pesticides were above them. Lifetime cancer risks ranged from 1 per million to 1700 per million, and estimates for 12 of 13 pesticides were above 1 per million. Similar results were obtained for field workers and flaggers. For the pesticides examined, exposures pose greater risks of chronic effects than acute effects. Exposure reduction measures, including use of closed mixing systems and personal protective equipment, significantly reduced exposures. Proposed regulations rely primarily on requirements for personal protective equipment and use restrictions to protect workers. Chronic health risks are not considered in setting these requirements. Reviews of pesticides by the federal pesticide regulatory program have had little effect on occupational risks. Policy strategies that offer immediate protection for workers and that are not dependent on extensive review of individual pesticides should be pursued. Images Figure 1. PMID:7713022

[Nephrotoxicity of Aristolochia manshuriensis and aristolochic acids in mice].

PubMed

Ding, Xiao-shuang; Liang, Ai-hua; Wang, Jin-hua; Xiao, Yong-qing; Wu, Zi-lun; Li, Chun-ying; Li, Li; He, Rong; Hui, Lian-qiang; Liu, Bao-yan

2005-07-01

The acute toxic effects of Aristolochia manshuriensis (GMT) and the total aristolochic acids (TA) were compared in mice with aristolochic acid A (AA) as the dose standard. The dose relationship of the renal toxicity induced by Aristolochia manshuriensis was determined. A single dose of GMT extract or TA was given intragastrically to mice at different doses. LD50 values, the blood levels of BUN, Cr and ALT were measured. A histomorphological study was also performed in livers and kidneys of mice. LD50 value of GMT extract was 4.4 g x kg(-1) which was equivalent to 40 mg x kg(-1) as calculated by the content of AA in GMT extract, and this value was comparable with LD50 obtained from TA given intragastrically in mice (equivalent to 33 mg x kg(-1) of AA for male and 37 mg x kg(-1) for female). GMT extract caused a significant increase in blood BUN and Cr and an obvious morphological change in kidney in a dose-dependent manner at doses of AA 4.5 mg x kg(-1) and above. Liver damage, characterized by both an increase in blood level of AST and histomorphological change, was observed at doses of AA 25 mg x kg(-1) and above. All changes were in proportion to the doses of AA. GMT causes both renal and liver toxicity. The dose leading to nephrotoxicity is much lower than that inducing hepatatoxicity. Aristolochic acids existed in GMT are the main toxic components to cause renal toxicity which is a crucial cause to result in death. The lethality and nephrotoxicity of GMT is in proportion to the doses of AA.

Structure-activity models of oral clearance, cytotoxicity, and LD50: a screen for promising anticancer compounds

PubMed Central

Boik, John C; Newman, Robert A

2008-01-01

Background Quantitative structure-activity relationship (QSAR) models have become popular tools to help identify promising lead compounds in anticancer drug development. Few QSAR studies have investigated multitask learning, however. Multitask learning is an approach that allows distinct but related data sets to be used in training. In this paper, a suite of three QSAR models is developed to identify compounds that are likely to (a) exhibit cytotoxic behavior against cancer cells, (b) exhibit high rat LD50 values (low systemic toxicity), and (c) exhibit low to modest human oral clearance (favorable pharmacokinetic characteristics). Models were constructed using Kernel Multitask Latent Analysis (KMLA), an approach that can effectively handle a large number of correlated data features, nonlinear relationships between features and responses, and multitask learning. Multitask learning is particularly useful when the number of available training records is small relative to the number of features, as was the case with the oral clearance data. Results Multitask learning modestly but significantly improved the classification precision for the oral clearance model. For the cytotoxicity model, which was constructed using a large number of records, multitask learning did not affect precision but did reduce computation time. The models developed here were used to predict activities for 115,000 natural compounds. Hundreds of natural compounds, particularly in the anthraquinone and flavonoids groups, were predicted to be cytotoxic, have high LD50 values, and have low to moderate oral clearance. Conclusion Multitask learning can be useful in some QSAR models. A suite of QSAR models was constructed and used to screen a large drug library for compounds likely to be cytotoxic to multiple cancer cell lines in vitro, have low systemic toxicity in rats, and have favorable pharmacokinetic properties in humans. PMID:18554402

Structure-activity models of oral clearance, cytotoxicity, and LD50: a screen for promising anticancer compounds.

PubMed

Boik, John C; Newman, Robert A

2008-06-13

Quantitative structure-activity relationship (QSAR) models have become popular tools to help identify promising lead compounds in anticancer drug development. Few QSAR studies have investigated multitask learning, however. Multitask learning is an approach that allows distinct but related data sets to be used in training. In this paper, a suite of three QSAR models is developed to identify compounds that are likely to (a) exhibit cytotoxic behavior against cancer cells, (b) exhibit high rat LD50 values (low systemic toxicity), and (c) exhibit low to modest human oral clearance (favorable pharmacokinetic characteristics). Models were constructed using Kernel Multitask Latent Analysis (KMLA), an approach that can effectively handle a large number of correlated data features, nonlinear relationships between features and responses, and multitask learning. Multitask learning is particularly useful when the number of available training records is small relative to the number of features, as was the case with the oral clearance data. Multitask learning modestly but significantly improved the classification precision for the oral clearance model. For the cytotoxicity model, which was constructed using a large number of records, multitask learning did not affect precision but did reduce computation time. The models developed here were used to predict activities for 115,000 natural compounds. Hundreds of natural compounds, particularly in the anthraquinone and flavonoids groups, were predicted to be cytotoxic, have high LD50 values, and have low to moderate oral clearance. Multitask learning can be useful in some QSAR models. A suite of QSAR models was constructed and used to screen a large drug library for compounds likely to be cytotoxic to multiple cancer cell lines in vitro, have low systemic toxicity in rats, and have favorable pharmacokinetic properties in humans.

Study on characterization, pathogenicity and histopathology of disease caused by Aeromonas hydrophila in gourami (Osphronemus gouramy)

NASA Astrophysics Data System (ADS)

Rozi; Rahayu, K.; Daruti, D. N.; Stella, M. S. P.

2018-04-01

This study aims to determine the bacterial pathogens that cause disease of the gourami in Blitar (East Java) and Yogyakarta (Central Java), Indonesia. A total of 50 fish samples taken randomly gourami in pond farmers in seventh different locations. There were 18 isolates were isolated and then test Koch’s postulates were injected 0.1 ml/fish intraperitoneally to gourami. Characterization is done by using the biochemical tests. Pathogenicity test carried out on 3 isolates of Aeromonas spp. with intraperitoneal injection at a dose of 104-108 CFU/fish, the value of Lethal Dosage 50 (LD50) using the method Dragstedt Behrens. After the treatment, spleen and kidney samples were processed for histopathological analysis. The all of identified bacteria were 5 isolates Aeromonas hydrophila. Isolates of A. hydrophila in a row AH3 was virulen to gourami with LD50 (4.53 x 106 CFU/fish), while isolate AH4 and AH5 (2.903 x 108, 1.319 x 109 CFU/fish) not be avirulen. Koch’s postulates; 3 isolates are pathogenic with mortality of 40-100 % and 2 are non-pathogenic isolates with a mortality of 0 %. Clinically; ulcers, haemorhagic at the base of the fins, body, mouth and exophthalmia. Histopathologically indecated spleen necrosis, piknosis, necrosis and inflammatory cells in kidney.

Comparative acute toxicity of shale and petroleum derived distillates.

PubMed

Clark, C R; Ferguson, P W; Katchen, M A; Dennis, M W; Craig, D K

1989-12-01

In anticipation of the commercialization of its shale oil retorting and upgrading process, Unocal Corp. conducted a testing program aimed at better defining potential health impacts of a shale industry. Acute toxicity studies using rats and rabbits compared the effects of naphtha, Jet-A, JP-4, diesel and "residual" distillate fractions of both petroleum derived crude oils and hydrotreated shale oil. No differences in the acute oral (greater than 5 g/kg LD50) and dermal (greater than 2 g/kg LD50) toxicities were noted between the shale and petroleum derived distillates and none of the samples were more than mildly irritating to the eyes. Shale and petroleum products caused similar degrees of mild to moderate skin irritation. None of the materials produced sensitization reactions. The LC50 after acute inhalation exposure to Jet-A, shale naphtha, (greater than 5 mg/L) and JP-4 distillate fractions of petroleum and shale oils was greater than 5 mg/L. The LC50 of petroleum naphtha (greater than 4.8 mg/L) and raw shale oil (greater than 3.95 mg/L) also indicated low toxicity. Results demonstrate that shale oil products are of low acute toxicity, mild to moderately irritating and similar to their petroleum counterparts. The results further demonstrate that hydrotreatment reduces the irritancy of raw shale oil.

Gene and noncoding RNA regulation underlying photoreceptor protection: microarray study of dietary antioxidant saffron and photobiomodulation in rat retina

PubMed Central

Zhu, Yuan; Valter, Krisztina; Bisti, Silvia; Eells, Janis; Stone, Jonathan

2010-01-01

Purpose To identify the genes and noncoding RNAs (ncRNAs) involved in the neuroprotective actions of a dietary antioxidant (saffron) and of photobiomodulation (PBM). Methods We used a previously published assay of photoreceptor damage, in which albino Sprague Dawley rats raised in dim cyclic illumination (12 h 5 lux, 12 h darkness) were challenged by 24 h exposure to bright (1,000 lux) light. Experimental groups were protected against light damage by pretreatment with dietary saffron (1 mg/kg/day for 21 days) or PBM (9 J/cm2 at the eye, daily for 5 days). RNA from one eye of four animals in each of the six experimental groups (control, light damage [LD], saffron, PBM, saffronLD, and PBMLD) was hybridized to Affymetrix rat genome ST arrays. Quantitative real-time PCR analysis of 14 selected genes was used to validate the microarray results. Results LD caused the regulation of 175 entities (genes and ncRNAs) beyond criterion levels (p<0.05 in comparison with controls, fold-change >2). PBM pretreatment reduced the expression of 126 of these 175 LD-regulated entities below criterion; saffron pretreatment reduced the expression of 53 entities (50 in common with PBM). In addition, PBM pretreatment regulated the expression of 67 entities not regulated by LD, while saffron pretreatment regulated 122 entities not regulated by LD (48 in common with PBM). PBM and saffron, given without LD, regulated genes and ncRNAs beyond criterion levels, but in lesser numbers than during their protective action. A high proportion of the entities regulated by LD (>90%) were known genes. By contrast, ncRNAs were prominent among the entities regulated by PBM and saffron in their neuroprotective roles (73% and 62%, respectively). Conclusions Given alone, saffron and (more prominently) PBM both regulated significant numbers of genes and ncRNAs. Given before retinal exposure to damaging light, thus while exerting their neuroprotective action, they regulated much larger numbers of entities, among which ncRNAs were prominent. Further, the downregulation of known genes and of ncRNAs was prominent in the protective actions of both neuroprotectants. These comparisons provide an overview of gene expression induced by two neuroprotectants and provide a basis for the more focused study of their mechanisms. PMID:20844572

NEUTRALIZATION OF TWO NORTH AMERICAN CORAL SNAKE VENOMS WITH UNITED STATES AND MEXICAN ANTIVENOMS

PubMed Central

Sánchez, Elda E.; Lopez-Johnston, Juan C.; Rodríguez-Acosta, Alexis; Pérez, John C.

2009-01-01

Elapid snakes throughout the world are considered very lethal containing neurotoxic venoms that affect the nervous system. When humans are envenomated it is considered a serious medical emergency, and antivenom is the main form of treatment considered, in spite of the fact that some patients may only survive under intensive therapy treatment such as respiratory support. Coral snakes are part of the family Elapidae and envenomations by these snakes are very low (< 2% of total snakebites) in most countries from southeastern United States to Argentina. In the United States there are only two species of coral snakes of medical importance which belong to the Micrurus genera: Micrurus fulvius fulvius (Eastern coral snake) and M. tener tener (Texas coral snake). In 2006, Wyeth pharmaceutical notified customers that the production of the North American Coral Snake Antivenin (NACSA) in the U.S. was discontinued and adequate supplies were available to meet historical needs through the end of October 2008; and therefore, it is of utmost important to consider other antivenoms as alternatives for the treatment of coral snake envenoming. One logical alternative is the coral snake antivenom, Coralmyn, produced by the Mexican company, Bioclon. In order to compare neutralization between NACSA and Coralmyn antivenoms with the North American coral snake venoms, the venom lethal doses (LD50) and antivenom effective doses (ED50) were determined in 18–20 g, female, BALB/c mice. Additionally, venom comparisons were determined through a non reduced SDS-PAGE for M. f. fulvius, M. t. tener and the Mexican coral snake venom, M. nigrocinctus nigrocinctus. Coralmyn antivenom was able to effectively neutralize 3 LD50 doses of all venom from both M. t. tener and M. f. fulvius, while Wyeth antivenom only neutralized M. f. fulvius venom and was not effective in neutralizing 3 LD50 doses of M. t. tener venom. Coralmyn is effective in the neutralization of both clinically important coral snake venoms in the U.S. PMID:18054059

Neutralization of two North American coral snake venoms with United States and Mexican antivenoms.

PubMed

Sánchez, Elda E; Lopez-Johnston, Juan C; Rodríguez-Acosta, Alexis; Pérez, John C

2008-02-01

Elapid snakes throughout the world are considered very lethal, containing neurotoxic venoms that affect the nervous system. When humans are envenomated it is considered a serious medical emergency, and antivenom is the main form of treatment considered, in spite of the fact that some patients may only survive under intensive therapy treatment such as respiratory support. Coral snakes are part of the family Elapidae and envenomations by these snakes are very low (<2% of total snakebites) in most countries from southeastern United States to Argentina. In the United States, there are only two species of coral snakes of medical importance that belong to the Micrurus genera: Micrurus fulvius fulvius (Eastern coral snake) and Micrurus tener tener (Texas coral snake). In 2006, Wyeth pharmaceutical notified customers that the production of the North American coral snake antivenin (NACSA) in the US was discontinued and adequate supplies were available to meet historical needs through the end of October 2008; and therefore, it is of utmost important to consider other antivenoms as alternatives for the treatment of coral snake envenoming. One logical alternative is the coral snake antivenom, Coralmyn, produced by the Mexican company, Bioclon. In order to compare neutralization between NACSA and Coralmyn antivenoms with the North American coral snake venoms, the venom lethal doses (LD(50)) and antivenom effective doses (ED(50)) were determined in 18-20 g, female, BALB/c mice. Additionally, venom comparisons were determined through a non-reduced SDS-PAGE for M.f.fulvius, M.t.tener and the Mexican coral snake venom, Micrurus nigrocinctus nigrocinctus. Coralmyn antivenom was able to effectively neutralize three LD(50) doses of all venom from both M.t.tener and M.f.fulvius, while Wyeth antivenom only neutralized M.f.fulvius venom and was not effective in neutralizing three LD(50) doses of M.t.tener venom. Coralmyn is effective in the neutralization of both clinically important coral snake venoms in the US.

Toxicity status and antiulcerative potential of Sansevieria trifasciata leaf extract in Wistar rats

PubMed Central

Ighodaro, Osasenaga Macdonald; Adeosun, Abiola Muhammad; Ojiko, Barinemene Francis; Akorede, Abeeb Taiwo; Fuyi-Williams, Oyindamola

2017-01-01

Aims: The lethal dose 50% (LD50) and antiulcerative potentials of Sansevieria trifasciata (ST) leaf extract were investigated. Materials and Methods: LD50 was determined through two routes of administration (intraperitoneal [i.p] and oral [p.o]) using the method of Lorke. The antiulcerative activity was evaluated in indomethacin-induced ulcer model (40 mg/kg body weight [BW], i.p, single dose) against a reference drug, cimetidine (100 mg/kg BW, p.o). ST was assessed at two different doses (200 and 400 mg/kg BW, p.o). Treatments were done twice daily at 8 h interval for 7 days before indomethacin administration. Results: The i.p LD50 was determined as 774.60 mg/kg BW and oral administration of the extract at 18,000 mg/kg BW dosage did not cause any negative behavioral changes in the animals, and no mortality was recorded after 24 h of the experiment. ST-pre-treated animals showed some improvement against indomethacin-induced ulceration. The extract curtailed indomethacin-induced reduction in gastric volume (36.1%), free acidity (55.3%), total acidity (35.6%) while minimizing the increase in pH by 13.3%. Moreover, the extract showed 17.92% and 14.96% ulcer protective ability at 200 and 400 mg/kg BW, respectively. The phytochemical analysis of ST extract revealed the presence of phytoconstituents such as glycosides, saponins, flavonoids, terpenoids, alkaloids, tannins, anthraquinone, and glycosides. Conclusions: ST apparently has a promising antiulcerative potential, and is safe for use in folk medicine. This valuable medicinal property is probably due to the array of important phytochemicals contained in the plant as observed in this study. However, a further study involving bioassay-guided identification of the main antiulcerative compound in ST is required to establish the use of the plant as a viable antiulcerative agent. PMID:28512605

Development of biomarkers of exposure to xenobiotics in the honey bee Apis mellifera: application to the systemic insecticide thiamethoxam.

PubMed

Badiou-Bénéteau, Alexandra; Carvalho, Stephan M; Brunet, Jean-Luc; Carvalho, Geraldo A; Buleté, Audrey; Giroud, Barbara; Belzunces, Luc P

2012-08-01

This study describes the development of acetylcholinesterase (AChE), carboxylesterases (CaE1, CaE2, CaE3), glutathion-S-transferase (GST), alkaline phosphatase (ALP) and catalase (CAT) as enzyme biomarkers of exposure to xenobiotics such as thiamethoxam in the honey bee Apis mellifera. Extraction efficiency, stability under freezing and biological variability were studied. The extraction procedure achieved good recovery rates in one extraction step and ranged from 65 percent (AChE) to 97.3 percent (GST). Most of the enzymes were stable at -20°C, except ALP that displayed a slight but progressive decrease in its activity. Modifications of enzyme activities were considered after exposure to thiamethoxam at the lethal dose 50 percent (LD(50), 51.16 ng bee(-1)) and two sublethal doses, LD(50)/10 (5.12 ng bee(-1)) and LD(50)/20 (2.56 ng bee(-1)). The biomarker responses revealed that, even at the lowest dose used, exposure to thiamethoxam elicited sublethal effects and modified the activity of CaEs, GST, CAT and ALP. Different patterns of biomarker responses were observed: no response for AChE, an increase for GST and CAT, and differential effects for CaEs isoforms with a decrease in CaE1 and CaE3 and an increase in CaE2. ALP and CaE3 displayed contrasting variations but only at 2.56 ng bee(-1). We consider that this profile of biomarker variation could represent a useful fingerprint to characterise exposure to thiamethoxam in the honey bee A. mellifera. This battery of honey bee biomarkers might be a promising option to biomonitor the health of aerial and terrestrial ecosystems and to generate valuable information on the modes of action of pesticides. Copyright © 2012 Elsevier Inc. All rights reserved.

Protection against soman and sarin exposure by transdermal physostigmine and scopolamine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meshulam, Y.; Davidovici, R.; Levy, A.

1993-05-13

The purpose of this study was to evaluate the prophylactic efficacy of physostigmine (physo), administered via sustained release (SR) methods, with and without scopolamine, against soman and sarin exposure in guinea-pigs. Transdermal physo pad (3 sq cm/kg; 60-80 ug/sq cm), containing a vehicle based on propionic acid, was applied onto the dorsal back of the animals, 24 hours before exposure to the cholinesterase (ChE) inhibitors. At the time of exposure, physo concentrations in brain and plasma were 3.6 ng/g and 4.1 ng/ml respectively. Brain and whole blood ChE activity were inhibited to 70% and 57% of their original activity. Transdermalmore » physo by itself protected up to 70% of the animals exposed to 1.5 LD(50) of soman or sarin (100% mortality was recorded in the control group). Combining transdermal physo with Scopoderm (by Ciba Geigy Inc.) provided full protection against 1.5 LD(50).« less

In the search for new anticancer drugs XII. Synthesis and biological evaluation of spin labeled nitrosoureas.

PubMed

Sosnovsky, G; Li, S W

1985-04-15

The spin labeled nitrosourea 1-(2-chloroethyl)-3-(1-oxyl-2,2,6,6- tetramethyl-piperidinyl)-1-nitrosourea (SLCNU, 4) and its analogues 5-7 were synthesized either by a regio-selective method or by a conventional route via the nitrosation of the spin labeled intermediates (11a-e). Nitrosation of the ureas 11a-e with dinitrogen tetraoxide resulted in better yields than those obtained with sodium nitrite. The nitrosoureas 4-8 were tested for their anticancer activity against the lymphocytic leukemia P388 in mice. Thus, either at the equal molar dose or at the dose of equal toxicity level, the SLCNU (4) was found to be more active than the clinically used CCNU (1). Unlike CCNU (1) whose LD50 is 56 mg/kg, the SLCNU (4) possesses a low toxicity (LD50 123 mg/kg). Therefore, SLCNU (4) is a promising new entry into the nitrosourea class of anticancer drugs.

Comparative investigation of Umbellularia californica and Laurus nobilis leaf essential oils and identification of constituents active against Aedes aegypti.

PubMed

Tabanca, Nurhayat; Avonto, Cristina; Wang, Mei; Parcher, Jon F; Ali, Abbas; Demirci, Betul; Raman, Vijayasankar; Khan, Ikhlas A

2013-12-18

Umbellularia californica (California bay laurel) and Laurus nobilis (Mediterranean bay laurel) leaves may be mistaken or used as a substitute on the market due to their morphological similarity. In this study, a comparison of anatomical and chemical features and biological activity of both plants is presented. L. nobilis essential oil biting deterrent and larvicidal activity were negligible. On the other hand, U. californica leaf oil showed biting deterrent activity against Aedes aegypti . The identified active repellents was thymol, along with (-)-umbellulone, 1,8-cineole, and (-)-α-terpineol. U. californica essential oil also demonstrated good larvicidal activity against 1-day-old Ae. aegypti larvae with a LD50 value of 52.6 ppm. Thymol (LD50 = 17.6 ppm), p-cymene, (-)-umbellulone, and methyleugenol were the primary larvicidal in this oil. Umbellulone was found as the principal compound (37%) of U. californica essential oil, but was not present in L. nobilis essential oil. Umbellulone mosquito activity is here reported for the first time.

Galleria mellonella larvae allow the discrimination of toxic and non-toxic chemicals.

PubMed

Allegra, Enrico; Titball, Richard W; Carter, John; Champion, Olivia L

2018-05-01

The acute toxicities of 19 chemicals were assessed using G. mellonella larvae. The results obtained were compared against LD50 values derived from in vitro cytotoxicity tests and against in vivo acute oral LD50 values. In general, cell culture systems overestimated the toxicity of chemicals, especially low toxicity chemicals. In contrast, toxicity testing in G. mellonella larvae was found to be a reliable predictor for low toxicity chemicals. For the 9 chemicals tested which were assigned to Globally Harmonised System (GHS) category 5, the toxicity measured in G. mellonella larvae was consistent with their GHS categorisation but cytotoxicity measured in 3T3 or NHK cells predicted 4 out of 9 chemicals as having low toxicity. A more robust assessment of the likely toxicity of chemicals in mammals could be made by taking into account their toxicities in both cell cultures and in G. mellonella larvae. Copyright © 2018 Elsevier Ltd. All rights reserved.

QSTR of the toxicity of some organophosphorus compounds by using the quantum chemical and topological descriptors.

PubMed

Senior, Samir A; Madbouly, Magdy D; El massry, Abdel-Moneim

2011-09-01

Quantum chemical and topological descriptors of some organophosphorus compounds (OP) were correlated with their toxicity LD(50) as a dermal. The quantum chemical parameters were obtained using B3LYP/LANL2DZdp-ECP optimization. Using linear regression analysis, equations were derived to calculate the theoretical LD(50) of the studied compounds. The inclusion of quantum parameters, having both charge indices and topological indices, affects the toxicity of the studied compounds resulting in high correlation coefficient factors for the obtained equations. Two of the new four firstly supposed descriptors give higher correlation coefficients namely the Heteroatom Corrected Extended Connectivity Randic index ((1)X(HCEC)) and the Density Randic index ((1)X(Den)). The obtained linear equations were applied to predict the toxicity of some related structures. It was found that the sulfur atoms in these compounds must be replaced by oxygen atoms to achieve improved toxicity. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effect of treatment with interferon-gamma and concanavalin A on the course of infection of mice with Salmonella typhimurium strain LT-2

NASA Technical Reports Server (NTRS)

Gould, Cheryl L.; Sonnenfeld, Gerald

1987-01-01

The effect of pretreatment of mice with 34 units/day, for five days, of interferon-gamma (IFN-gamma) on the course of infection with LD50 of Salmonella typhimurium strain LT-2 was assessed, using two IFN preparations: (1) a hybridoma supernatant fluid containing concanavalin-A-induced IFN-gamma activity and (2) pure murine IFN-gamma produced by recombinant DNA technology. The hybridoma supernatant-treated Salmonella-infected mice were found to die faster than mice treated only with Salmonella. Pure murine IFN-gamma was found to protect infected mice significantly, with 95 percent of mice surviving LD50 infection. In contrast, the Salmonella-infected mice treated with hybridoma supernatant were found to die faster than the Salmonella-infected untreated controls. Mice treated with concanavalin A alone prior to infection with S. typhimurium died more quickly than the untreated infected controls, suggesting that contamination with concanavalin A had a detrimental effect on mice survival.

Absence of circannual toxicity of parathion to starlings

USGS Publications Warehouse

Rattner, B.A.; Grue, C.E.

1990-01-01

Ambient temperature and season have been observed to influence the toxicity of several environmental pollutants in homeotherms. The circannual toxicity of ethyl parathion (EP) was examined in adult European starlings (Sturnus vulgaris). Groups of birds housed in outdoor pens received oral doses of EP (20-150 mg/kg body weight) in fall, winter, spring and summer (temperature range -3.3 to 36.7?C). The median lethal dosage (LD50), and brain and plasma cholinesterase inhibition, were found to be quite similar among seasons. There was some suggestion that EP may have been more toxic during hot weather (winter versus summer LD50 estimate [95% confidence interval]:160 [114-225] vs. 118 [102-136] mg/kg; P<0.10). In view of previous reports in which ambient temperature extremes and harsh weather have enhanced organophosphorus insecticide toxicity to birds, it is concluded that circannual toxicity studies should include measures of sensitivity (acute oral exposure) and vulnerability (dietary exposure) to better predict responses of free-ranging birds

Single oral dose toxicity test of platycodin d, a saponin from platycodin radix in mice.

PubMed

Lee, Won-Ho; Gam, Cheol-Ou; Ku, Sae-Kwang; Choi, Seong-Hun

2011-12-01

The object of this study was to evaluate the single oral dose toxicity of platycodin D, a saponin from the root of Platycodon grandiflorum in male and female mice. Platycodin D was administered to female and male mice as an oral dose of 2000, 1000, 500, 250 and 125 mg/kg (body wt.). Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after treatment, upon necropsy, organ weight and histopathology of 14 principle organs were examined. As the results, no platycodin D treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principle organs were detected up to 2000 mg/kg in both female and male mice. Therefore, LD50 (50% lethal dose) and approximate LD of playtcodin D after single oral treatment in female and male mice were considered over 2000 mg/kg - the limited dosages recommended by KFDA Guidelines [2009-116, 2009], respectively.

Radiation-induced hemopoietic death in mice as a function of photon energy and dose rate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gengozian, N.; Taylor, T.; Jameson, H.

1986-03-01

Radiation-induced hemopoietic death was measured in mice exposed to photons of four different energies: 250-kVp X rays, /sup 60/Co gamma rays (1.25 MeV), and 6- and 25-MV photons from a linear accelerator. For each radiation source, the lethal dose which killed 50% of the population in 30 days (LD50/30) associated with the hemopoietic syndrome was determined in groups of mice exposed to graded doses from 600 to 1150 cGy at dose rates of 20, 40, and 80 cGy/min. The calculated LD50/30 values for 25 and 6 MV were significantly different from each other at all exposure rates while no differencemore » was observed between 6 MV and /sup 60/Co. Using /sup 60/Co gamma rays as the standard, the relative biologic effectiveness was as follows: 250 kVp greater than 25 MV greater than 6 MV = /sup 60/Co. The data suggest that there may be a greater damage to tissue within the marrow cavities following exposure to very high megavoltage radiation, a factor which must be considered with the increasing utilization of linear accelerators in the clinic and laboratory.« less

Toxicity of non-pyrethroid insecticides against Triatoma infestans (Hemiptera: Reduviidae).

PubMed

Carvajal, Guillermo; Mougabure-Cueto, Gastón; Toloza, Ariel Ceferino

2012-08-01

Triatoma infestans (Klug) is the main vector of Chagas disease, which is a public health concern in most Latin American countries. The prevention of Chagas disease is based on the chemical control of the vector using pyrethroid insecticides. In the last decade, different levels of deltamethrin resistance have been detected in certain areas of Argentina and Bolivia. Because of this, alternative non-pyrethroid insecticides from different chemical groups were evaluated against two T. infestans populations, NFS and El Malá, with the objective of finding new insecticides to control resistant insect populations. Toxicity to different insecticides was evaluated in a deltamethrin-susceptible and a deltamethrin-resistant population. Topical application of the insecticides fenitrothion and imidacloprid to first nymphs had lethal effects on both populations, producing 50% lethal dose (LD50) values that ranged from 5.2-28 ng/insect. However, amitraz, flubendiamide, ivermectin, indoxacarb and spinosad showed no insecticidal activity in first instars at the applied doses (LD50 > 200 ng/insect). Fenitrothion and imidacloprid were effective against both deltamethrin-susceptible and deltamethrin-resistant populations of T. infestans. Therefore, they may be considered alternative non-pyrethroid insecticides for the control of Chagas disease.

Evaluation of YadC protein delivered by live attenuated Salmonella as a vaccine against plague.

PubMed

Sun, Wei; Olinzock, Joseph; Wang, Shifeng; Sanapala, Shilpa; Curtiss, Roy

2014-03-01

Yersinia pestis YadB and YadC are two new outer membrane proteins related to its pathogenicity. Here, codon-optimized yadC, yadC810 (aa 32-551), or yadBC antigen genes delivered by live attenuated Salmonella strains are evaluated in mice for induction of protective immune responses against Y. pestis CO92 through subcutaneous or intranasal challenge. Our findings indicate that mice immunized with Salmonella synthesizing YadC, YadC810, or YadBC develop significant serum IgG responses to purified recombinant YadC protein. For subcutaneous challenge (approximately 230 LD50 of Y. pestis CO92), mice immunized with Salmonella synthesizing YadC or YadC810 are afforded 50% protection, but no protection by immunization with the Salmonella strain synthesizing YadBC. None of these antigens provided protection against intranasal challenge (approximately 31 LD50 of Y. pestis CO92). In addition, subcutaneous immunization with purified YadC810 protein emulsified with alum adjuvant does not elicit a protective response against Y. pestis administered by either challenge route. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

An interspecies correlation model to predict acute dermal toxicity of plant protection products to terrestrial life stages of amphibians using fish acute toxicity and bioconcentration data.

PubMed

Weltje, Lennart; Janz, Philipp; Sowig, Peter

2017-12-01

This paper presents a model to predict acute dermal toxicity of plant protection products (PPPs) to terrestrial amphibian life stages from (regulatory) fish data. By combining existing concepts, including interspecies correlation estimation (ICE), allometric relations, lethal body burden (LBB) and bioconcentration modelling, an equation was derived that predicts the amphibian median lethal dermal dose (LD 50 ) from standard acute toxicity values (96-h LC 50 ) for fish and bioconcentration factors (BCF) in fish. Where possible, fish BCF values were corrected to 5% lipid, and to parent compound. Then, BCF values were adjusted to an exposure duration of 96 h, in case steady state took longer to be achieved. The derived correlation equation is based on 32 LD 50 values from acute dermal toxicity experiments with 15 different species of anuran amphibians, comprising 15 different PPPs. The developed ICE model can be used in a screening approach to estimate the acute risk to amphibian terrestrial life stages from dermal exposures to PPPs with organic active substances. This has the potential to reduce unnecessary testing of vertebrates. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effect of exercise and time on the height and width of the medial longitudinal arch following the modified reverse-6 and the modified augmented low-dye taping procedures.

PubMed

Cornwall, Mark W; McPoil, Thomas G; Fair, Austin

2014-10-01

No evidence exits regarding the magnitude of the change in foot posture following the "modified reverse-6" (MR6) taping procedure, either alone or in combination with the "low-dye" (LD) taping technique. The purpose of this study was to investigate the change in the height and width of the midfoot after application of the MR6 and the MR6 plus the LD (MR6+LD) taping technique and determine how long those changes last. Eleven individuals (2 female and 9 male) were recruited for this study and were tested under each of two experimental conditions, the MR6 and the MR6+LD taping technique. The order of testing for the two conditions was randomly determined. For each condition, the height and width of the midfoot at 50% of each subject's foot length was initially measured and then again immediately following the application of the tape. These measurements were repeated four hours later immediately prior to running two miles on a treadmill, again immediately after running, and finally after another four hours. The dorsal arch height increased significantly with both the MR6 and MR6+LD taping, but only the MR6+LD remained statistically greater after four hours, a bout of exercise and again at the end of the day. The mean width of the midfoot significantly decreased with both taping procedures. The change in the width of the midfoot remained significantly decreased in both taping conditions after exercise and throughout the day. Both taping procedures are able to significantly change the height and width of the medial longitudinal arch of the foot, but the change lasted longer when the two taping procedures were combined. Level 3, Prospective Cohort Study.

Influenza Infection Control Practices in Labor and Delivery Units During the 2009 H1N1 Influenza Pandemic

PubMed Central

Williams, Jennifer L.; Mersereau, Patricia W.; Ruch-Ross, Holly; Zapata, Lauren B.; Ruhl, Catherine

2015-01-01

Objective To assess the presence and usefulness of written policies and practices on infection control consistent with the Center for Disease Control and Prevention’s (CDC) guidance in hospital labor and delivery (L&D) units during the 2009 H1N1 influenza pandemic. Setting Online survey. Participants Of 11,845 eligible nurses, 2,641 (22%) participated. This analysis includes a subset of 1,866 nurses who worked exclusively in L&D units. Methods A cross-sectional descriptive evaluation was sent to 12,612 members from the Association of Women’s Health, Obstetric, and Neonatal Nurses (AWHONN) who reported working in labor, delivery, postpartum, or newborn care settings during the 2009 H1N1 influenza pandemic. Results Respondents (73.8%) reported that CDC guidance was very useful for infection control in L&D settings during the pandemic. We assessed the presence of the following infection control written policies, consistent with CDC’s guidance in hospital L&D units, during the 2009 H1N1 influenza pandemic and their rate of implementation most of the time: questioning women upon arrival about recent flu-like symptoms (89.4%, 89.9%), immediate initiation of antiviral medicines if flu suspected or confirmed (65.2%, 49%), isolating ill women from healthy women immediately (90.7%, 84.7%), ask ill women to wear masks during L&D (67%, 57.7%), immediately separating healthy newborns from ill mothers (50.9%, 42.4%), and bathing healthy infants when stable (58.4%, 56.9%). Reported written policies for five of the six practices increased during the pandemic. Five of six written policies remained above baseline after the pandemic. Conclusions Respondents considered CDC guidance very useful. The presence of written policies is important for the implementation of infection control practices by L&D nurses. PMID:24020478

Platelet reactivity in response to loading dose of atorvastatin or rosuvastatin in patients with stable coronary disease before percutaneous coronary intervention: The STATIPLAT randomized study.

PubMed

Godino, Cosmo; Pavon, Anna Giulia; Mangieri, Antonio; Salerno, Anna; Cera, Michela; Monello, Alberto; Chieffo, Alaide; Magni, Valeria; Cappelletti, Alberto; Margonato, Alberto; Colombo, Antonio

2017-08-01

The acute effects of statin loading dose (LD) on platelet reactivity in patients with chronic stable angina (CSA) are not completely clear. We hypothesized that LDs of atorvastatin and rosuvastatin have different pharmacodynamic acute effects on platelet aggregability in CSA patients with baseline normal platelet reactivity while on dual antiplatelet therapy (DAPT). From September 2011 to February 2014, all consecutive CSA patients on chronic DAPT (aspirin and clopidogrel) were evaluated before elective percutaneous coronary intervention (PCI). An initial assessment of platelet reactivity in response to thrombin receptor agonist, ADP, and ASP (respectively, indicative of the response to clopidogrel and aspirin) was performed with impedance aggregometry. Patients with high platelet reactivity to ADP test (area under the curve >47) were excluded. The remaining patients were randomized into 3 treatment groups: Group A, atorvastatin LD 80 mg; Group B, rosuvastatin LD 40 mg; and Group C, no statin LD (control group). A second assessment of platelet reactivity was performed ≥12 hours after statin LD. 682 patients were screened and 145 were randomized into the 3 groups. At baseline and after statin LD, no significant difference was found in platelet reactivity in response to 3 different agonists between the 3 groups. Subgroup analysis showed that platelet reactivity to ADP test was significantly lower in patients chronically treated with low-dose statins (n = 94) compared with statin-naïve patients (n = 51; 15.32 ± 1.50 vs 18.59 ± 1.30; P = 0.007). Loading dose of atorvastatin (80 mg) or rosuvastatin (40 mg) did not induce significant variation in platelet reactivity in CSA patients with baseline reduced platelet reactivity as in chronic DAPT. Our data confirm that chronic concomitant treatment with low-dose statins and clopidogrel resulted in significantly lower platelet reactivity compared with clopidogrel alone. © 2017 Wiley Periodicals, Inc.

Preclinical and first-in-human evaluation of PRX-105, a PEGylated, plant-derived, recombinant human acetylcholinesterase-R

DOE Office of Scientific and Technical Information (OSTI.GOV)

Atsmon, Jacob; Sackler Faculty of Medicine, Tel Aviv University; Brill-Almon, Einat

PRX-105 is a plant-derived recombinant version of the human ‘read-through’ acetylcholinesterase splice variant (AChE-R). Its active site structure is similar to that of the synaptic variant, and it displays the same affinity towards organophosphorus (OP) compounds. As such, PRX-105 may serve as a bio-scavenger for OP pesticides and chemical warfare agents. To assess its potential use in prophylaxis and treatment of OP poisoning we conducted several preliminary tests, reported in this paper. Intravenous (IV) PRX-105 was administered to mice either before or after exposure to an OP toxin. All mice who received an IV dose of 50 nmol/kg PRX-105, 2more » min before being exposed to 1.33 × LD{sub 50} and 1.5 × LD{sub 50} of toxin and 10 min after exposure to 1.5 × LD{sub 50} survived. The pharmacokinetic and toxicity profiles of PRX-105 were evaluated in mice and mini-pigs. Following single and multiple IV doses (50 to 200 mg/kg) no deaths occurred and no significant laboratory and histopathological changes were observed. The overall elimination half-life (t{sub ½}) in mice was 994 (± 173) min. Additionally, a first-in-human study, to assess the safety, tolerability and pharmacokinetics of the compound, was conducted in healthy volunteers. The t{sub ½} in humans was substantially longer than in mice (average 26.7 h). Despite the small number of animals and human subjects who were assessed, the fact that PRX-105 exerts a protective and therapeutic effect following exposure to lethal doses of OP, its favorable safety profile and its relatively long half-life, renders it a promising candidate for treatment and prophylaxis against OP poisoning and warrants further investigation. - Highlights: • PRX-105 is a PEGylated plant-derived recombinant human acetylcholinesterase-R. • PRX-105 is a promising bio-scavenger for organophosphorous toxins at lethal doses. • PRX-105 was shown to protect animals both prophylactically and post-poisoning. • First-in-human study exhibited its safety, tolerability and pharmacokinetics. • Toxicokinetic animal studies have shown a favorable safety profile.« less

Evaluation of the Insecticidal Efficacy of Wild Type and Recombinant Baculoviruses.

PubMed

Popham, Holly J R; Ellersieck, Mark R; Li, Huarong; Bonning, Bryony C

2016-01-01

A considerable amount of work has been undertaken to genetically enhance the efficacy of baculovirus insecticides. Following construction of a genetically altered baculovirus, laboratory bioassays are used to quantify various parameters of insecticidal activity such as the median lethal concentration (or dose) required to kill 50 % of infected larvae (LC50 or LD50), median survival of larvae infected (ST50), and feeding damage incurred by infected larvae. In this chapter, protocols are described for a variety of bioassays and the corresponding data analyses for assessment of the insecticidal activity of baculovirus insecticides.

Phosalone-induced inflammation and oxidative stress in the colon: Evaluation and treatment.

PubMed

Ghasemi-Niri, Seyedeh Farnaz; Maqbool, Faheem; Baeeri, Maryam; Gholami, Mahdi; Abdollahi, Mohammad

2016-06-07

To investigate the side effects of phosalone on intestinal cells and to evaluate benefits of ellagic acid (EA) as a remedy. In order to conduct an in vivo study, a rat model was used. The rats were divided into ten groups based on the materials used in the experiment and their dosage. The first group was fed normally. The second group was administered EA through gavage. Next Four groups were given (1/3, 1/5, 1/10, 1/20) LD50 phosalone; an organophosphorus compound. The last four groups received (1/3, 1/5, 1/10, 1/20) LD50 phosalone and of EA. After one month, the rats were sacrificed and their colon cells were examined to evaluate the level of inflammation, proteins and oxidative stress markers. The results of this research show that phosalone elevates oxidative stress and changes the level of tumor necrosis factor-a (TNF-α), interlukin-6β (IL-6β) and nuclear factor (NF)-κB proteins. EA administration reduced phosalone toxicity and changed oxidative stress and inflammatory markers for all phosalone doses. Overall changes in reduction of TNF-α (230.47 ± 16.55 pg/mg protein vs 546.43 ± 45.24 pg/mg protein, P < 0.001), IL-6β (15.85 ± 1.03 pg/mg protein vs 21.55 ± 1.3 pg/mg protein, P < 0.05), and NF-κB (32.47 ± 4.85 pg/mg protein vs 51.41 ± 0.71 pg/mg protein, P < 0.05) manifest that the efficacy of EA is more viable for 1/3 LD50 dose of phosalone. Furthermore, EA is effective to counteract the negative outcomes of oxidative stress. When EA was used to treat 1/3 LD50 of phosalone's side effects, it improved the level of AChE activity (48.5% ± 6% vs 25% ± 7%, P < 0.05), TTM (0.391 ± 0.008 mmol/L vs 0.249 ± 0.032 mmol/L, P < 0.05), FRAP (46.04 ± 5.005 μmol/L vs 18.22 ± 1.9 μmol/L, P < 0.01) and MPO (0.222 ± 0.019 U/mg protein vs 0.387 ± 0.04 U/mg protein, P < 0.05). This research highlights that EA is effective to alleviate the side effects of phosalone by reducing the level of oxidative stress and inflammatory proteins.

Phosalone-induced inflammation and oxidative stress in the colon: Evaluation and treatment

PubMed Central

Ghasemi-Niri, Seyedeh Farnaz; Maqbool, Faheem; Baeeri, Maryam; Gholami, Mahdi; Abdollahi, Mohammad

2016-01-01

AIM: To investigate the side effects of phosalone on intestinal cells and to evaluate benefits of ellagic acid (EA) as a remedy. METHODS: In order to conduct an in vivo study, a rat model was used. The rats were divided into ten groups based on the materials used in the experiment and their dosage. The first group was fed normally. The second group was administered EA through gavage. Next Four groups were given (1/3, 1/5, 1/10, 1/20) LD50 phosalone; an organophosphorus compound. The last four groups received (1/3, 1/5, 1/10, 1/20) LD50 phosalone and of EA. After one month, the rats were sacrificed and their colon cells were examined to evaluate the level of inflammation, proteins and oxidative stress markers. RESULTS: The results of this research show that phosalone elevates oxidative stress and changes the level of tumor necrosis factor-a (TNF-α), interlukin-6β (IL-6β) and nuclear factor (NF)-κB proteins. EA administration reduced phosalone toxicity and changed oxidative stress and inflammatory markers for all phosalone doses. Overall changes in reduction of TNF-α (230.47 ± 16.55 pg/mg protein vs 546.43 ± 45.24 pg/mg protein, P < 0.001), IL-6β (15.85 ± 1.03 pg/mg protein vs 21.55 ± 1.3 pg/mg protein, P < 0.05), and NF-κB (32.47 ± 4.85 pg/mg protein vs 51.41 ± 0.71 pg/mg protein, P < 0.05) manifest that the efficacy of EA is more viable for 1/3 LD50 dose of phosalone. Furthermore, EA is effective to counteract the negative outcomes of oxidative stress. When EA was used to treat 1/3 LD50 of phosalone’s side effects, it improved the level of AChE activity (48.5% ± 6% vs 25% ± 7%, P < 0.05), TTM (0.391 ± 0.008 mmol/L vs 0.249 ± 0.032 mmol/L, P < 0.05), FRAP (46.04 ± 5.005 μmol/L vs 18.22 ± 1.9 μmol/L, P < 0.01) and MPO (0.222 ± 0.019 U/mg protein vs 0.387 ± 0.04 U/mg protein, P < 0.05). CONCLUSION: This research highlights that EA is effective to alleviate the side effects of phosalone by reducing the level of oxidative stress and inflammatory proteins. PMID:27275092

Acute toxicity of methanol in the folate-deficient acatalasemic mouse.

PubMed

Smith, E N; Taylor, R T

1982-01-01

Formate acidosis is the chief measurable biochemical characteristic of acute methanol toxicity in man. Its marked elevation in the blood stream of primates has been proposed to account for their much greater susceptibility versus rodents to methanol poisoning. Therefore, a study was undertaken to assess whether folic acid deficient (FAD) mice which accumulate formate are much more sensitive to the lethal effects of this alcohol than folic acid sufficient (FAS) mice. Moreover, because some formate is oxidized by catalase-H2O2 in rodents, but not in primates, we also compared the urinary excretion and blood plasma accumulation of formate and the methanol sensitivity of acatalasemic mice. Methanol-dosed C57BL/6Csb (acatalasemic) mice exhibit slightly lower LD50S than CSa (normal catalase) mice, irrespective of their folate state. CSb-FAD mice excreted much more formate and developed higher plasma formate concentrations (11-17 mM) than identically dosed CSa-FAD animals (6 mM). However, in no instance did a folate deficiency produce a large reciprocal decrease in the oral or i.p. LD50 that would be expected from a huge increase (greater than 10-fold) in the 24-h blood plasma formate level. A low methionine (0.2%) intake did not decrease the oral methanol LD50 of CSb-FAD mice, although excess dietary methionine (1.8%) did lower it from 7.1 to 6.4 g/kg. Methanol treated (4 g/kg) Csb-FAD mice excreted 30.8-48.2% of the oral dose as urinary formate, depending on the level of dietary methionine. Csb-FAS and -FAD mice which were given 2 g/kg sodium formate orally (LD50 = 4.7 and 3.7 g/kg) cleared this dose from the blood within 24 h and excreted 58% and 76% of it, respectively, in the urine. Our results indicate that the plasma formate concentration does not correlate well with methanol lethality in Csb-FAS vs. -FAD mice. In addition, urinary excretion, not oxidation, is the primary means by which mice, and probably rats, eliminate high levels of blood formate. Since the Csb-FAD mouse attains high plasma formate levels and low blood pH-values similar to those which have been reported for methanol poisoned monkeys, it appears to be of value as an inexpensive small animal model for further studies of lethal methanol toxicity and the contribution of formate to this process.

Central Acetylcholinesterase Reactivation by Oximes Improves Survival and Terminates Seizures Following Nerve Agent Intoxication

DTIC Science & Technology

2009-01-01

activity ; GB = sarin; im = intramuscular; ip = intraperitoneal; LD50 = median lethal dose 50%; MINA = monoisonitrosoacetone; MMB-4 = methoxime; OP...inhibited acetylcholinesterase (AChE) activity . We have studied the capability of the tertiary oximes monoisonitrosoacetone (MINA) and diacetylmonoxime...of 20, 26, 35, 46 and 60 mg/kg, there were 0, 9, 17, 60, and 75%, respectively, of animals never exhibited EEG seizure activity with 43, 64, 75, 90

Radioadaptive Cytoprotective Pathways in the Mouse Retina

NASA Technical Reports Server (NTRS)

Zanello, Susana B.; Wotring, V.; Theriot, C.; Ploutz-Snyder, R.; Zhang, Y.; Wu, H.

2010-01-01

Exposure to cosmic radiation implies a risk of tissue degeneration. Radiation retinopathy is a complication of radiotherapy and exhibits common features with other retinopathies and neuropathies. Exposure to a low radiation dose elicits protective cellular events (radioadaptive response), reducing the stress of a subsequent higher dose. To assess the risk of radiation-induced retinal changes and the extent to which a small priming dose reduces this risk, we used a mouse model exposed to a source of Cs-137-gamma radiation. Gene expression profiling of retinas from non-irradiated control C57BL/6J mice (C) were compared to retinas from mice treated with a low 50 mGy dose (LD), a high 6 Gy dose (HD), and a combined treatment of 50 mGy (priming) and 6 Gy (challenge) doses (LHD). Whole retina RNA was isolated and expression analysis for selected genes performed by RTqPCR. Relevant target genes associated with cell death/survival, oxidative stress, cellular stress response and inflammation pathways, were analyzed. Cellular stress response genes were upregulated at 4 hr after the challenge dose in LHD retinas (Sirt1: 1.5 fold, Hsf1: 1.7 fold, Hspa1a: 2.5 fold; Hif1a: 1.8 fold, Bag1: 1.7). A similar trend was observed in LD animals. Most antioxidant enzymes (Hmox1, Sod2, Prdx1, Cygb, Cat1) and inflammatory mediators (NF B, Ptgs2 and Tgfb1) were upregulated in LHD and LD retinas. Expression of the pro-survival gene Bcl2 was upregulated in LD (6-fold) and LHD (4-fold) retinas. In conclusion, cytoprotective gene networks activation in the retina suggests a radioadaptive response to a priming irradiation dose, with mitigation of the deleterious effects of a subsequent high dose exposure. The enhancement of these cytoprotective mechanisms has potential value as a countermeasure to ocular alterations caused by radiation alone or in combination with other factors in spaceflight environments.

[Insecticidal action of synthetic girgensohnine analogues and essential oils on Rhodnius prolixus (Hemiptera: Reduviidae)].

PubMed

Cuadros, Juliana; Carreño, Aurora L; Kouznetsov, Vladimir V; Duque, Jonny E

2017-03-29

The alkaloid girgensohnine has been used as a natural model in the synthesis of new alkaloid-like alpha-aminonitriles with insecticidal effect against disease vectors. To evaluate the biocide activity of girgensohnine analogues and essential oils of Cymbopogon flexuosus, Citrus sinensis and Eucalyptus citriodora in stage I and stage V Rhodnius prolixus nymphs. We used a topical application model in tergites and sternites, as well as exposure to treated surfaces with different exploratory doses of each of the molecules and essential oils to determine the lethal doses (LD50 and LD95). Analogue 3 showed the highest insecticidal activity with 83.3±16.7% of mortality when applied on tergites, 38.9±4.8% on sternites and 16.7±0% on treated surfaces in stage I nymphs at 72 hours (h) and 500 mg.L-1. In stage V nymphs, the compounds induced mortality only in sternums (11.1±9.6% for analogue 6 and 5.5±4.7% for analogues 3 and 7 at 72 h and 1500 mg.L-1). The lethal doses for molecule 3 on tergites in stage I nymphs were LD50 225.60 mg.L-1 and LD95 955.90 mg.L-1. The insecticidal effect of essential oils was observed only in stage I nymphs, with 11.1±4.8% for C. flexuosus when applied in sternites, while using exposure to surfaces treated it was 5.6±4.8% for C. sinensis applied on tergites and 8.3±0% on sternites at 72 h and 1000 mg.L-1. Synthetic girgensohnine analogues, and C. flexuosus and C. sinensis essential oils showed insecticidal activity in R. prolixus. Analogue 3 showed the greatest insecticidal activity among all molecules and oils evaluated under our laboratory conditions.

Toxicity of Cypermethrin and Chlorpyrifos Against German Cockroach [ Blattella germanica (Blattaria: Blattellidae)] Strains from Hamadan, Iran.

PubMed

Nazari, Mansour; Motlagh, Behrouz Alipourian; Nasirian, Hassan

German cockroach has relatively short life cycle and reproduce rapidly. It is the most common medically and public health pest. As a result, it is essential to combat this pest. Cypermethrin and chlorpyrifos are used by private companies in Hamadan to control Blattella germanica. It seems necessary to determine its susceptibility levels to these insecticides. The aim of this study was to determine the susceptibility levels of B. germanica strains to cypermethrin and chlorpyrifos in Hamadan. In this study, the German cockroach strains were collected from two hospitals (Fatemiyeh and Atiyeh) in Hamadan and transfered to the insectarium. The cockroach strains were reared under the same laboratory condition. Then their sensitivity levels were considered to 1, 2, 4, 8 and 16 mg m -2 for cypermethrin and 0.82, 1.65, 3.31, 6.63, 9.945 and 13.26 mg m -2 for chlorpyrifos using surface contact method. Results based on insecticide treated doses, B. germanica strains showed different percent mortality to the insecticides ranged from 13.3-100. The LD 50 and LD 90 and regression lines of the treated insecticides against German cockroach strains indicate that Fatemiyeh Hospital strain is more susceptible to the treated insecticides than Atiyeh Hospital strain. The LD 50 and LD 90 of chlorpyrifos are also lower than cypermethrin, indicated that chlorpyrifos is more effective than cypermethrin against German cockroach. As the slopes of the regression lines are observed mild in this study indicate that the population of the cockroach strains is very heterogeneous. It can be a symbol of insecticides resistance to cypermethrin and chlorpyrifos. As chlorpyrifos and cypermethrin insecticides are also used for residual spraying by private companies and the doses which provide more than 90% mortality are below the WHO recommended insecticide doses. Therefore, chlorpyrifos and cypermethrin insecticides can be used for B. germanica control in Hamadan within regular monitoring and preventive measures of resistance.

Autophagy is an important event for low-dose cytarabine treatment in acute myeloid leukemia cells.

PubMed

Chen, Liyun; Guo, Pei; Zhang, Yunxiang; Li, Xiaoyang; Jia, Peimin; Tong, Jianhua; Li, Junmin

2017-09-01

Cytarabine (Ara-c) has been an important agent in acute myeloid leukemia (AML) treatment for more than 40 years. While, the mechanisms underlying low dose cytarabine (LD Ara-c) is poorly understood. In this study, we investigated the therapeutic effect of LD Ara-C in vitro. U937 and HEL cell lines were treated with increasing dose of Ara-C and showed growth inhibition rates in a time and dose-dependent manner. Treatment with LD Ara-C (50nM) induced a time-dependent increase in expression of microtubule-associated protein light chain 3 (LC3) and beclin1, but degradation of sequestosome1 (p62) in both U937 and HEL cells. Characteristic of autophagosomes appeared after 24h treatment. Meanwhile, deregulation of Akt-mTOR pathway was also detected. When cultured in presence of autophagy inhibitors, autophagy and differentiation was reversed, and cell growth inhibition was also attenuated. Similar phenomenon could also be seen when beclin1 expression was down-regulated. Taken together, we concluded that LD Ara-C can induce autophagy in AML cells and appeared to play an important role in differentiation and death. Down-regulation of Akt-mTOR pathway is involved in these processes. We suggest that cytarabine-induced autophagy is not a pro-survival mechanism, but accounts for its antineoplastic effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dark nights reverse metabolic disruption caused by dim light at night.

PubMed

Fonken, L K; Weil, Z M; Nelson, R J

2013-06-01

The increasing prevalence of obesity and related metabolic disorders coincides with increasing exposure to light at night. Previous studies report that mice exposed to dim light at night (dLAN) develop symptoms of metabolic syndrome. This study investigated whether mice returned to dark nights after dLAN exposure recover metabolic function. Male Swiss-Webster mice were assigned to either: standard light-dark (LD) conditions for 8 weeks (LD/LD), dLAN for 8 weeks (dLAN/dLAN), LD for 4 weeks followed by 4 weeks of dLAN (LD/dLAN), and dLAN for 4 weeks followed by 4 weeks of LD (dLAN/LD). After 4 weeks in their respective lighting conditions both groups initially placed in dLAN increased body mass gain compared to LD mice. Half of the dLAN mice (dLAN/LD) were then transferred to LD and vice versa (LD/dLAN). Following the transfer dLAN/dLAN and LD/dLAN mice gained more weight than LD/LD and dLAN/LD mice. At the conclusion of the study dLAN/LD mice did not differ from LD/LD mice with respect to weight gain and had lower fat pad mass compared to dLAN/dLAN mice. Compared to all other groups dLAN/dLAN mice decreased glucose tolerance as indicated by an intraperitoneal glucose tolerance test at week 7, indicating that dLAN/LD mice recovered glucose metabolism. dLAN/dLAN mice also increased MAC1 mRNA expression in peripheral fat as compared to both LD/LD and dLAN/LD mice, suggesting peripheral inflammation is induced by dLAN, but not sustained after return to LD. These results suggest that re-exposure to dark nights ameliorates metabolic disruption caused by dLAN exposure. Copyright © 2013 The Obesity Society.

Tolerance of house fly, Musca domestica L. (Diptera: Muscidae) to dichlorvos (76% EC) an insecticide used for fly control in the tsunami-hit coastal villages of southern India.

PubMed

Srinivasan, R; Jambulingam, P; Gunasekaran, K; Boopathidoss, P S

2008-02-01

The Directorate of Public Health (DPH), Tamil Nadu, in southern India employed spraying of dichlorvos (76% EC) for quick elimination of fly concentrations in the tsunami-hit coastal villages at the concentration of 304g (a.i.)/10,000m(2). However, nuisance of house flies remained high particularly in temporary shelters and centralized relief kitchens. Susceptibility of house fly, Musca domestica to dichlorvos was determined in the laboratory to provide information for an effective management of this pest. Various concentrations of dichlorvos (76% EC) viz., 0.1, 0.2, 0.4, 0.6 and 0.8microg (a.i.) per fly, were tested using topical application against F(1) progenies of house flies collected 12 months after insecticide applications from different habitats in the tsunami-hit coastal villages. Fly mortality was recorded at 24h post treatment. Parallel controls were maintained for comparison. Mortality of the house flies varied between 17.5% and 100% and increased with an increase in dosage of the insecticide. Mortality was >80% at 0.6 and 0.8microg (a.i.) per fly. The LD(50) of dichlorvos tested against flies collected from different villages varied from 0.218microg (a.i.) to 0.235microg (a.i.) per fly and the LD(90) varied from 0.574microg (a.i.) to 0.639microg (a.i.) per fly. House flies collected from a rural village, Thirukanur that had never been exposed for insecticide treatment in the past one decade, when tested, the mortality varied between 92.5% and 100% and increased with concentration of dichlorvos. Mortality was >90% from 0.2microg (a.i.) per fly and the LD(50) was 0.0399microg (a.i.)/fly, while the LD(90) was 0.1604microg (a.i.)/fly. The LD(90) values of the flies collected from the tsunami-hit villages were 3.5-3.9 times higher than that of the flies collected from Thirukanur. Fly abundance remained high in tsunami-hit villages with no marked reduction, suggesting that the flies had developed tolerance to dichlorvos. It is suggested that for an effective management of these resistant populations changing insecticides, application of unrelated insecticide, together with an appropriate environmental sanitation measure is necessary to keep the population under check.

Factors associated with late diagnosis of HIV infection and missed opportunities for earlier testing.

PubMed

Gullón, Alejandra; Verdejo, José; de Miguel, Rosa; Gómez, Ana; Sanz, Jesús

2016-10-01

Late diagnosis (LD) of human immunodeficiency virus (HIV) infection continues to be a significant problem that increases disease burden both for patients and for the public health system. Guidelines have been updated in order to facilitate earlier HIV diagnosis, introducing "indicator condition-guided HIV testing". In this study, we analysed the frequency of LD and associated risk factors. We retrospectively identified those cases that could be considered missed opportunities for an earlier diagnosis. All patients newly diagnosed with HIV infection who attended Hospital La Princesa, Madrid (Spain) between 2007 and 2014 were analysed. We collected epidemiological, clinical and immunological data. We also reviewed electronic medical records from the year before the HIV diagnosis to search for medical consultations due to clinical indicators. HIV infection was diagnosed in 354 patients. The median CD4 count at presentation was 352 cells/mm(3). Overall, 158 patients (50%) met the definition of LD, and 97 (30.7%) the diagnosis of advanced disease. LD was associated with older age and was more frequent amongst immigrants. Heterosexual relations and injection drug use were more likely to be the reasons for LD than relations between men who have sex with men. During the year preceding the diagnosis, 46.6% of the patients had sought medical advice owing to the presence of clinical indicators that should have led to HIV testing. Of those, 24 cases (14.5%) were classified as missed opportunities for earlier HIV diagnosis because testing was not performed. According to these results, all health workers should pursue early HIV diagnosis through the proper implementation of HIV testing guidelines. Such an approach would prove directly beneficial to the patient and indirectly beneficial to the general population through the reduction in the risk of transmission.

Validation of an Open-Source Tool for Measuring Carotid Lumen Diameter and Intima-Media Thickness.

PubMed

Manterola, Hugo Luis; Lo Vercio, Lucas; Díaz, Alejandro; Del Fresno, Mariana; Larrabide, Ignacio

2018-05-14

In low- and middle-income regions, a relatively large number of deaths occur from cardiovascular disease or stroke. Carotid intima-media thickness (cIMT) and carotid lumen diameter (cLD) are strong indicators of cardiovascular event risk and stenosis severity, respectively. The interactive open-source software described here, Cimtool, is based on active contours for measuring these indicators in clinical practice and thus helping in preventive diagnosis and treatment. Cimtool was validated using carotid phantoms and real images obtained using ultrasound. Expert users measured cIMT and cLD in regular practice and also with Cimtool. The results obtained with Cimtool were then compared with the results for the manual approach in terms of measurement agreement, time spent on the measurements and usability. Intra-observer variability when using Cimtool was also analyzed. Statistical analysis revealed strong agreement between the manual method and Cimtool (p > 0.01 for cIMT and cLD). The correlation coefficient for both cIMT and cLD measurements was r > 0.9. Moreover, this software allowed the users to spend considerably less time on each measurement (3.5 min per study versus 50 s with Cimtool on average). An open-source, interactive, validated tool for measuring cIMT and cLD clinically was thus developed. Compared with the manual approach, Cimtool's straightforward measurement flow allows the user to spend less time per measurement and has less standard deviation. The coefficients of variation for measurements and intra-observer variability were lower than those reported for recent automated approaches, even with low-quality images. Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

Perioperative lumbar drain utilization in transsphenoidal pituitary resection.

PubMed

Alharbi, Shatha; Harsh, Griffith; Ajlan, Abdulrazag

2018-01-01

To evaluate lumbar drain (LD) efficacy in transnasal resection of pituitary macroadenomas in preventing postoperative cerebrospinal fluid (CSF) leak, technique safety, and effect on length of hospital stay. We conducted a retrospective data review of pituitary tumor patients in our institution who underwent surgery between December 2006 and January 2013. All patients were operated on for complete surgical resection of pituitary macroadenoma tumors. Patients were divided into 2 groups: group 1 received a preoperative drain, while LD was not preoperatively inserted in group 2. In cases of tumors with suprasellar extension with anticipation of high-flow leak, LD was inserted after the patient was intubated and in a lateral position. Lumbar drain was used for 48 hours, and the drain was removed if no leak was observed postoperatively. In documented postoperative CSF leak patients with no preoperative drain, the leak was treated by LD trial prior to surgical reconstruction. Cases in which leak occurred 6 months postoperatively were excluded. Our study population consisted of 186 patients, 99 women (53%) and 87 men (47%), with a mean age of 50.3+/-16.1 years. Complications occurred in 7 patients (13.7%) in group 1 versus 21 (15.5%) in group 2 (p=0.72). Postoperative CSF leak was observed in 1 patient (1.9%) in group 1 and 7 (5%) in group 2 (Fisher exact test=0.3). Length of hospital stay was a mean of 4.7+/-1.9 days in group 1 and a mean of 2.7+/-2.4 days in group 2 (p<001). The most common reason to extend hospital stay was management of diabetes insipidus. Although LD insertion is generally considered safe with a low risk of complications, it increases the length of hospitalization. Minor complications include headaches and patient discomfort.

Two Automated Techniques for Carotid Lumen Diameter Measurement: Regional versus Boundary Approaches.

PubMed

Araki, Tadashi; Kumar, P Krishna; Suri, Harman S; Ikeda, Nobutaka; Gupta, Ajay; Saba, Luca; Rajan, Jeny; Lavra, Francesco; Sharma, Aditya M; Shafique, Shoaib; Nicolaides, Andrew; Laird, John R; Suri, Jasjit S

2016-07-01

The degree of stenosis in the carotid artery can be predicted using automated carotid lumen diameter (LD) measured from B-mode ultrasound images. Systolic velocity-based methods for measurement of LD are subjective. With the advancement of high resolution imaging, image-based methods have started to emerge. However, they require robust image analysis for accurate LD measurement. This paper presents two different algorithms for automated segmentation of the lumen borders in carotid ultrasound images. Both algorithms are modeled as a two stage process. Stage one consists of a global-based model using scale-space framework for the extraction of the region of interest. This stage is common to both algorithms. Stage two is modeled using a local-based strategy that extracts the lumen interfaces. At this stage, the algorithm-1 is modeled as a region-based strategy using a classification framework, whereas the algorithm-2 is modeled as a boundary-based approach that uses the level set framework. Two sets of databases (DB), Japan DB (JDB) (202 patients, 404 images) and Hong Kong DB (HKDB) (50 patients, 300 images) were used in this study. Two trained neuroradiologists performed manual LD tracings. The mean automated LD measured was 6.35 ± 0.95 mm for JDB and 6.20 ± 1.35 mm for HKDB. The precision-of-merit was: 97.4 % and 98.0 % w.r.t to two manual tracings for JDB and 99.7 % and 97.9 % w.r.t to two manual tracings for HKDB. Statistical tests such as ANOVA, Chi-Squared, T-test, and Mann-Whitney test were conducted to show the stability and reliability of the automated techniques.

PHOTOACTIVATED POLYCYCLIC AROMATIC HYDROCARBON TOXICITY IN MEDAKA (ORYZIAS LATIPES) EMBRYOS: RELEVANCE TO ENVIRONMENTAL RISK IN CONTAMINATED SITES

EPA Science Inventory

The hazard for photoactivated toxicity of polycyclic aromatic hydrocarbons (PAHs) has been clearly demonstrated; however, to our knowledge, the risk in contaminated systems has not been characterized. To address this question, a median lethal dose (LD50) for fluoranthene photoa...

7 CFR 1737.50 - Review of completed loan application.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 3017); (3) A market survey called the Area Coverage Survey (ACS); (4) The plan and associated costs for the proposed construction, called the Loan Design (LD); (5) Evidence that the borrower is... determine that the system design is acceptable to RUS, that the design is technically correct, that the cost...

7 CFR 1737.50 - Review of completed loan application.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 3017); (3) A market survey called the Area Coverage Survey (ACS); (4) The plan and associated costs for the proposed construction, called the Loan Design (LD); (5) Evidence that the borrower is... determine that the system design is acceptable to RUS, that the design is technically correct, that the cost...

7 CFR 1737.50 - Review of completed loan application.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 3017); (3) A market survey called the Area Coverage Survey (ACS); (4) The plan and associated costs for the proposed construction, called the Loan Design (LD); (5) Evidence that the borrower is... determine that the system design is acceptable to RUS, that the design is technically correct, that the cost...

7 CFR 1737.50 - Review of completed loan application.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 3017); (3) A market survey called the Area Coverage Survey (ACS); (4) The plan and associated costs for the proposed construction, called the Loan Design (LD); (5) Evidence that the borrower is... determine that the system design is acceptable to RUS, that the design is technically correct, that the cost...

7 CFR 1737.50 - Review of completed loan application.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 3017); (3) A market survey called the Area Coverage Survey (ACS); (4) The plan and associated costs for the proposed construction, called the Loan Design (LD); (5) Evidence that the borrower is... determine that the system design is acceptable to RUS, that the design is technically correct, that the cost...

Prediction of pesticide acute toxicity using two-dimensional chemical descriptors and target species classification

EPA Science Inventory

Previous modelling of the median lethal dose (oral rat LD50) has indicated that local class-based models yield better correlations than global models. We evaluated the hypothesis that dividing the dataset by pesticidal mechanisms would improve prediction accuracy. A linear discri...

Consensus Modeling of Oral Rat Acute Toxicity

EPA Science Inventory

An acute toxicity dataset (oral rat LD50) with about 7400 compounds was compiled from the ChemIDplus database. This dataset was divided into a modeling set and a prediction set. The compounds in the prediction set were selected so that they were present in the modeling set used...

Toxicity of Pesticides. Agrichemical Fact Sheet 2.

ERIC Educational Resources Information Center

Hock, Winand K.

This fact sheet gives the acute oral and dermal toxicity (LD 50) of over 250 pesticides in lab animals. The chemicals are categorized as fungicides, herbicides, insecticides, or miscellaneous compounds. One or more trade names are given for each pesticide. In addition, a brief explanation of toxicity determination is given. (BB)

Toxicity of selected insecticides applied to western spruce budworm

Treesearch

Jacqueline L. Robertson; Nancy L. Gillette; Melvin Look; Barbara A. Lucas; Robert L. Lyon

1975-01-01

The contact toxicity of 100 insecticides to last stage larvae of Choristoneura occidentalis Freeman was tested by topical application in a 10-yr series of screening experiments. Pyrethroids were generally the most toxic group of chemicals tested. Compounds more toxic than the standard, mexacarbate, at Ld50 were:...

Alternative Placements: Does a Difference Exist in the LD Populations?

ERIC Educational Resources Information Center

Olson, Judy; Midgett, Jeanice

1984-01-01

The performance of learning disabled male elementary students in self-contained classes (N=35) and resource rooms (N=50) was compared on five diagnostic tests and factors of retention, chronological age, and behavior. Results indicated a difference only in the intelligence factor between the groups. (Authors)

State Learning Disability Eligibility Criteria: A Comprehensive Review

ERIC Educational Resources Information Center

Maki, Kathrin E.; Floyd, Randy G.; Roberson, Triche

2015-01-01

For many decades, discussions regarding the definition and identification of learning disabilities have been contentious; one result is the varied practices across states and school districts. This study reviewed learning disability (LD) regulations and guidelines from the 50 United States and the District of Columbia that were employed during…

The botulinum toxin LD50 potency assay - another chapter, another mystery.

PubMed

Pickett, Andy

2012-09-01

Observers of the potency assay used for botulinum toxin were greeted last year with the news that one company had an alternative, non-animal alternative in place. But all was not as it seemed from the press release, and over a year later, information is still lacking.

16 CFR 1700.14 - Substances requiring special packaging.

Code of Federal Regulations, 2014 CFR

2014-01-01

...) Aspirin. Any aspirin-containing preparation for human use in a dosage form intended for oral... following: (i) Effervescent tablets containing aspirin, other than those intended for pediatric use, provided the dry tablet contains not more than 15 percent aspirin and has an oral LD-50 in rats of 5 grams...

16 CFR 1700.14 - Substances requiring special packaging.

Code of Federal Regulations, 2012 CFR

2012-01-01

...) Aspirin. Any aspirin-containing preparation for human use in a dosage form intended for oral... following: (i) Effervescent tablets containing aspirin, other than those intended for pediatric use, provided the dry tablet contains not more than 15 percent aspirin and has an oral LD-50 in rats of 5 grams...

16 CFR § 1700.14 - Substances requiring special packaging.

Code of Federal Regulations, 2013 CFR

2013-01-01

...) Aspirin. Any aspirin-containing preparation for human use in a dosage form intended for oral... following: (i) Effervescent tablets containing aspirin, other than those intended for pediatric use, provided the dry tablet contains not more than 15 percent aspirin and has an oral LD-50 in rats of 5 grams...

16 CFR 1700.14 - Substances requiring special packaging.

Code of Federal Regulations, 2011 CFR

2011-01-01

...) Aspirin. Any aspirin-containing preparation for human use in a dosage form intended for oral... following: (i) Effervescent tablets containing aspirin, other than those intended for pediatric use, provided the dry tablet contains not more than 15 percent aspirin and has an oral LD-50 in rats of 5 grams...

16 CFR 1700.14 - Substances requiring special packaging.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) Aspirin. Any aspirin-containing preparation for human use in a dosage form intended for oral... following: (i) Effervescent tablets containing aspirin, other than those intended for pediatric use, provided the dry tablet contains not more than 15 percent aspirin and has an oral LD-50 in rats of 5 grams...

Effects of a chitin-binding vicilin from Enterolobium contortisiliquum seeds on bean bruchid pests (Callosobruchus maculatus and Zabrotes subfasciatus) and phytopathogenic fungi (Fusarium solani and Colletrichum lindemuntianum).

PubMed

Moura, Fabiano T; Oliveira, Adeliana S; Macedo, Leonardo L P; Vianna, André L B R; Andrade, Lucia B S; Martins-Miranda, A S; Oliveira, Jose T A; Santos, Elizeu A; de Sales, Mauricio P

2007-01-24

Chitin-binding vicilin from Enterolobium contortisiliquum seeds was purified by ammonium sulfate followed by gel filtration on Sephacryl 300-SH and on Sephacryl 200-SH. The vicilin, called EcV, is a dimeric glycoprotein composed of 1.03% carbohydrates and a Mr of 151 kDa, consisting of two subunits of Mr of 66.2 and 63.8 kDa. The EcV homogeneity was confirmed in a PAGE where it was observed to be a unique acid protein band with slow mobility in this native gel. E. contortisiliquum vicilin (EcV) was tested for anti-insect activity against C. maculatus and Zabrotes subfasciatus larvae and for phytopathogenic fungi, F. solani and C. lindemuntianum. EcV was very effective against both bruchids, producing 50% mortality for Z. subfasciatus at an LD50 of 0.43% and affected 50% of the larvae mass with an ED50 of 0.65%. In artificial diets given to C. maculatus, 50% of the larvae mass was affected with an ED50 of 1.03%, and larva mortality was 50% at LD50 of 1.11%. EcV was not digested by midgut homogenates of C. maculatus and Z. Subfasciatus until 12 h of incubation, and at 24 h EcV was more resistant to Z. subfasciatus larval proteases. The binding to chitin present in larvae gut associated to low EcV digestibility could explain its lethal effects. EcV also exerted an inhibitory effect on the germination of F. solani at concentrations of 10 and 20 microg mL-1. The effect of EcV on fungi is possibly due to binding to chitin-containing structures of the fungal cell wall.

GTPase Sar1 regulates the trafficking and secretion of the virulence factor gp63 in Leishmania.

PubMed

Parashar, Smriti; Mukhopadhyay, Amitabha

2017-07-21

Metalloprotease gp63 ( Leishmania donovani gp63 (Ldgp63)) is a critical virulence factor secreted by Leishmania However, how newly synthesized Ldgp63 exits the endoplasmic reticulum (ER) and is secreted by this parasite is unknown. Here, we cloned, expressed, and characterized the GTPase LdSar1 and other COPII components like LdSec23, LdSec24, LdSec13, and LdSec31 from Leishmania to understand their role in ER exit of Ldgp63. Using dominant-positive (LdSar1:H74L) and dominant-negative (LdSar1:T34N) mutants of LdSar1, we found that GTP-bound LdSar1 specifically binds to LdSec23, which binds, in turn, with LdSec24(1-702) to form a prebudding complex. Moreover, LdSec13 specifically interacted with His 6 -LdSec31(1-603), and LdSec31 bound the prebudding complex via LdSec23. Interestingly, dileucine 594/595 and valine 597 residues present in the Ldgp63 C-terminal domain were critical for binding with LdSec24(703-966), and GFP-Ldgp63 L594A/L595A or GFP-Ldgp63 V597S mutants failed to exit from the ER. Moreover, Ldgp63-containing COPII vesicle budding from the ER was inhibited by LdSar1:T34N in an in vitro budding assay, indicating that GTP-bound LdSar1 is required for budding of Ldgp63-containing COPII vesicles. To directly demonstrate the function of LdSar1 in Ldgp63 trafficking, we coexpressed RFP-Ldgp63 along with LdSar1:WT-GFP or LdSar1:T34N-GFP and found that LdSar1:T34N overexpression blocks Ldgp63 trafficking and secretion in Leishmania Finally, we noted significantly compromised survival of LdSar1:T34N-GFP-overexpressing transgenic parasites in macrophages. Taken together, these results indicated that Ldgp63 interacts with the COPII complex via LdSec24 for Ldgp63 ER exit and subsequent secretion. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Mechanisms of action of (meth)acrylates in hemolytic activity, in vivo toxicity and dipalmitoylphosphatidylcholine (DPPC) liposomes determined using NMR spectroscopy.

PubMed

Fujisawa, Seiichiro; Kadoma, Yoshinori

2012-01-01

We investigated the quantitative structure-activity relationships between hemolytic activity (log 1/H(50)) or in vivo mouse intraperitoneal (ip) LD(50) using reported data for α,β-unsaturated carbonyl compounds such as (meth)acrylate monomers and their (13)C-NMR β-carbon chemical shift (δ). The log 1/H(50) value for methacrylates was linearly correlated with the δC(β) value. That for (meth)acrylates was linearly correlated with log P, an index of lipophilicity. The ipLD(50) for (meth)acrylates was linearly correlated with δC(β) but not with log P. For (meth)acrylates, the δC(β) value, which is dependent on the π-electron density on the β-carbon, was linearly correlated with PM3-based theoretical parameters (chemical hardness, η; electronegativity, χ; electrophilicity, ω), whereas log P was linearly correlated with heat of formation (HF). Also, the interaction between (meth)acrylates and DPPC liposomes in cell membrane molecular models was investigated using (1)H-NMR spectroscopy and differential scanning calorimetry (DSC). The log 1/H(50) value was related to the difference in chemical shift (ΔδHa) (Ha: H (trans) attached to the β-carbon) between the free monomer and the DPPC liposome-bound monomer. Monomer-induced DSC phase transition properties were related to HF for monomers. NMR chemical shifts may represent a valuable parameter for investigating the biological mechanisms of action of (meth)acrylates.

Mechanisms of Action of (Meth)acrylates in Hemolytic Activity, in Vivo Toxicity and Dipalmitoylphosphatidylcholine (DPPC) Liposomes Determined Using NMR Spectroscopy

PubMed Central

Fujisawa, Seiichiro; Kadoma, Yoshinori

2012-01-01

We investigated the quantitative structure-activity relationships between hemolytic activity (log 1/H50) or in vivo mouse intraperitoneal (ip) LD50 using reported data for α,β-unsaturated carbonyl compounds such as (meth)acrylate monomers and their 13C-NMR β-carbon chemical shift (δ). The log 1/H50 value for methacrylates was linearly correlated with the δCβ value. That for (meth)acrylates was linearly correlated with log P, an index of lipophilicity. The ipLD50 for (meth)acrylates was linearly correlated with δCβ but not with log P. For (meth)acrylates, the δCβ value, which is dependent on the π-electron density on the β-carbon, was linearly correlated with PM3-based theoretical parameters (chemical hardness, η; electronegativity, χ; electrophilicity, ω), whereas log P was linearly correlated with heat of formation (HF). Also, the interaction between (meth)acrylates and DPPC liposomes in cell membrane molecular models was investigated using 1H-NMR spectroscopy and differential scanning calorimetry (DSC). The log 1/H50 value was related to the difference in chemical shift (ΔδHa) (Ha: H (trans) attached to the β-carbon) between the free monomer and the DPPC liposome-bound monomer. Monomer-induced DSC phase transition properties were related to HF for monomers. NMR chemical shifts may represent a valuable parameter for investigating the biological mechanisms of action of (meth)acrylates. PMID:22312284

New chrodrimanin congeners, chrodrimanins D-H, from YO-2 of Talaromyces sp.

PubMed

Hayashi, Hideo; Oka, Yuki; Kai, Kenji; Akiyama, Kohki

2012-01-01

Four new meroterpenoids, named chrodrimanins D-G (4-7), and one known compound, renamed chrodrimanin H (8), were isolated from okara (the insoluble residue of whole soybean) that had been fermented with the YO-2 strain of Talaromyces sp. Their structures were elucidated by spectroscopic methods. Chrodrimanins D (4), E (5), and F (6) showed insecticidal activity against silkworms with respective LD(50) values of 20, 10, and 50 µg/g of diet.

R&D of Energetic Ionic Liquids

DTIC Science & Technology

2011-11-01

Ammonia 3-6 H2O balance Properties LMP-103S AF - M315E Hydrazine Ispvac,lbf sec/lbm (e = 50:1 Pc = 300 psi) 252 (theor.) 235 (del) 266...Distribution A: Public Release, Distribution unlimited. AF - M315E is US Air Force IL-Based Monopropellant •Significant physical property and performance...6 Toxicity Assessment of AF - M315E Toxicity Testing Results PROPERTY AF - M315E HYDRAZINE LD50 (rat), mg/kg 550 60 Dermal Irritation (rabbit

Evaluation of Caenorhabditis elegans as an acute lethality and a neurotoxicity screening model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, P.L.

1988-01-01

This investigation evaluated C. elegans as a lethality and neurotoxicity screening model. The lethality experiments were performed in both agar and an aquatic medium. The salts of 8 metals (Hg, Be, Al, Cu, Zn, Pb, Cd, and Sr) were used in the agar studies and the salts of 14 metals (Ag, Hg, Cu, Be, Al, Pb, Cr, As, Tl, Zn, Cd, Ni, Sr, and Sb) were used in the aquatic tests. In each of these tests an LC50 value was determined. The data from the agar plates were compared to the published mammalian oral LD50 values for salts of themore » same metals. Within this set of chemicals C. elegans was found to be a predictor of mammalian acute lethality, generating LC50 values parallel to the rat and mouse LD50 values. The aquatic data were compared to data from EPA Ambient Water Quality Criteria documents. C. elegans was found to be less sensitive than Daphnia but generally more sensitive than the other invertebrate organisms that are presently used. The neurotoxicity testing also was performed in both agar and an aquatic media. The testing in agar was conducted with the salts of 4 metals (Cu, Be, Pb, and Hg) and 2 organophosphate pesticides (malathion and vapona). The studies in an aquatic medium tested the salts of 4 metals (Cu, Be, Pb, and Hg).« less

Low-Dose Radiation 3D Intraoperative Imaging: How Low Can We Go? An O-Arm, CT Scan, Cadaveric Study.

PubMed

Sarwahi, Vishal; Payares, Monica; Wendolowski, Stephen; Maguire, Kathleen; Thornhill, Beverly; Lo, Yungtai; Amaral, Terry D

2017-11-15

MINI: The objective of this study was to evaluate the accuracy and reliability of pedicle screw placement using O-Arm at dosages below the manufactured recommended dose. O-Arm at reduced dose showed a 90% accuracy when compared with computed tomography; however, about 30% medial breaches were misclassified. Cadaveric study. The objective was to evaluate O-Arm's ability at low-dose (LD) settings to assess intraoperative screw placement. Accurate placement of pedicle screws is crucial because of proximity to vital structures. Malposition of screws may result in significant morbidity and potential mortality. O-arm provides real-time, intraoperative imaging of patient's anatomy and provides higher accuracy in scoliosis surgeries, avoiding risk to vital structures. We hypothesize using LD or ultra-low doses (ULDs) to obtain intraoperative images allow for accurate assessment of screw placement, both minimizing radiation exposure and preventing screw misplacement. Eight cadavers were instrumented with pedicle screws bilaterally from T1 to S1. Screws were randomly placed using O-arm navigation into three positions: contained within the bone, OUT-anterior/lateral, and OUT-medial. O-arm images were obtained at three dosage settings: LD (kVp120/mAs125-lowest manufacturer recommended), very-low dose (VLD) (kVp120/mAs63), and ULD (kVp120/mAs39). Computed tomography (CT) scan was performed using institution's LD protocol (kVp100/mAs50) and gross dissection to identify screw positions. LD, VLD, ULD, and CT for identifying "IN" screws relative to gross dissection had, a mean (standard deviation) sensitivity of 84.2% (±5.7), specificity of 76.1% (±9.3), and accuracy of 79.9% (±3.1) from all three observers. Across the three observers, the interobserver agreement was 0.67 (0.61-0.72) for LD, 0.74 (0.69-0.79) for VLD, 0.61 (0.56-0.66) for ULD, and 0.79 (0.74-0.84) for CT. Effective doses of radiation (mSV) for LD O-arm scan was 2.16, VLD 1.08, ULD 0.68, and our LD CT protocol was 1.05. Accuracy of pedicle screw placement is similar for O-arm at all doses and CT compared to gross dissection. Interobserver reliability was substantial for VLD and CT. Approximately 30% of medial screw breaches are, however, misclassified. ULD and VLDs can be used for intraoperative navigation and evaluation purposes within these limitations. N/A.

New ribosome-inactivating proteins with polynucleotide:adenosine glycosidase and antiviral activities from Basella rubra L. and bougainvillea spectabilis Willd.

PubMed

Bolognesi, A; Polito, L; Olivieri, F; Valbonesi, P; Barbieri, L; Battelli, M G; Carusi, M V; Benvenuto, E; Del Vecchio Blanco, F; Di Maro, A; Parente, A; Di Loreto, M; Stirpe, F

1997-12-01

New single-chain (type 1) ribosome-inactivating proteins (RIPs) were isolated from the seeds of Basella rubra L. (two proteins) and from the leaves of Bougainvillea spectabilis Willd. (one protein). These RIPs inhibit protein synthesis both in a cell-free system, with an IC50 (concentration causing 50% inhibition) in the 10(-10) M range, and by various cell lines, with IC50S in the 10(-8)-10(-6) M range. All three RIPs released adenine not only from rat liver ribosomes but also from Escherichia coli rRNA, polyadenylic acid, herring sperm DNA, and artichoke mottled crinkle virus (AMCV) genomic RNA, thus being polynucleotide:adenosine glycosidases. The proteins from Basella rubra had toxicity to mice similar to that of most type 1 RIPs (Barbieri et al., 1993, Biochim Biophys Acta 1154: 237-282) with an LD50 (concentration that is 50% lethal) < or = 8 mg.kg-1 body weight, whilst the RIP from Bougainvillea spectabilis had an LD50 > 32 mg.kg-1. The N-terminal sequence of the two RIPs from Basella rubra had 80-93% identity, whereas it differed from the sequence of the RIP from Bougainvillea spectabilis. When tested with antibodies against various RIPs, the RIPs from Basella gave some cross-reactivity with sera against dianthin 32, and weak cross-reactivity with momordin I and momorcochin-S, whilst the RIP from Bougainvillea did not cross-react with any antiserum tested. An RIP from Basella rubra and one from Bougainvillea spectabilis were tested for antiviral activity, and both inhibited infection of Nicotiana benthamiana by AMCV.

Behavioral Effects and Tunneling Responses of Eastern Subterranean Termites (Isoptera: Rhinotermitidae) Exposed to Chlorantraniliprole-Treated Soils.

PubMed

Saran, Raj K; Ziegler, Melissa; Kudlie, Sara; Harrison, Danielle; Leva, David M; Scherer, Clay; Coffelt, Mark A

2014-10-01

Intrinsic toxicities of chlorantraniliprole, fipronil, and imidacloprid were evaluated with topical applications on worker termites. Worker termites were exposed to substrates treated with formulated chlorantraniliprole to study contact toxicity, tunneling, and postexposure behaviors. The intrinsic toxicities (LD50, ng/termite) of chlorantraniliprole (1.25, 0.96, and 0.44) and fipronil (0.12, 0.11, and 0.13) at 11 d were similar for workers from three termite colonies. Imidacloprid toxicity (LD50) values were highly variable among the workers from three different colonies, values at 11 d ranging from 0.7 to 75 ng/termite. Termite workers exposed to sand and soils treated with chlorantraniliprole at 50 ppm exhibited delayed mortality and, for most of the exposure times, it took >5 d to observe 90-100% mortality in termite workers. Exposure to chlorantraniliprole-treated sand (50 ppm) for as little as 1 min stopped feeding and killed 90-100% of the workers. Tunneling (≈ 2 h) in different soil types treated with chlorantraniliprole at 50 ppm, even those with high organic matter (6.3%) and clay content (30%), caused immediate feeding cessation in worker termites and mortality in the next 7-14 d. Worker termites exposed for 1 and 60 min to sand treated with chlorantraniliprole (50 ppm) were able to walk normally for 4 h after exposure in most cases. Delayed toxicity, increased aggregation, and grooming were observed in exposed termites and discussed in the context of horizontal transfer effects within termite colonies. © 2014 Entomological Society of America.

Reversible Nuclear-Lipid-Droplet Morphology Induced by Oleic Acid: A Link to Cellular-Lipid Metabolism

PubMed Central

Lagrutta, Lucía C.; Montero-Villegas, Sandra; Layerenza, Juan P.; Sisti, Martín S.; García de Bravo, Margarita M.

2017-01-01

Neutral lipids—involved in many cellular processes—are stored as lipid droplets (LD), those mainly cytosolic (cLD) along with a small nuclear population (nLD). nLD could be involved in nuclear-lipid homeostasis serving as an endonuclear buffering system that would provide or incorporate lipids and proteins involved in signalling pathways as transcription factors and as enzymes of lipid metabolism and nuclear processes. Our aim was to determine if nLD constituted a dynamic domain. Oleic-acid (OA) added to rat hepatocytes or HepG2 cells in culture produced cellular-phenotypic LD modifications: increases in TAG, CE, C, and PL content and in cLD and nLD numbers and sizes. LD increments were reversed on exclusion of OA and were prevented by inhibition of acyl-CoA synthetase (with Triacsin C) and thus lipid biosynthesis. Under all conditions, nLD corresponded to a small population (2–10%) of total cellular LD. The anabolism triggered by OA, involving morphologic and size changes within the cLD and nLD populations, was reversed by a net balance of catabolism, upon eliminating OA. These catabolic processes included lipolysis and the mobilization of hydrolyzed FA from the LD to cytosolic-oxidation sites. These results would imply that nLD are actively involved in nuclear processes that include lipids. In conclusion, nLD are a dynamic nuclear domain since they are modified by OA through a reversible mechanism in combination with cLD; this process involves acyl-CoA-synthetase activity; ongoing TAG, CE, and PL biosynthesis. Thus, liver nLD and cLD are both dynamic cellular organelles. PMID:28125673

Environmental Assessment for Lock and Dam 21 Major Rehabilitation, Marion County, Missouri and Adams County, Illinois.

DTIC Science & Technology

1987-02-01

Stout floater 1 (Anodonta grandis grandis) Wabash pig toe 6 1 (Fusconaia flava) Fragile pape-shell 1 (Leptodea f-agilis) Three-horned warty back 1...LD21-U2 Arsenic <.01 <.01 Barium <.1 <.1 Cadmium .003 .002 Chromium (+3) <.05 <.05 Chromium (+6) <.05 <.05 Copper <.01 <.01 Cyanide <.01 <.01 Lead .03...60 >60 Cadmium * * >6 Chromium ញ 25-75 >75 Copper ញ 25-50 >50 Cyanide ɘ.10 0.10-0.25 >0.25 Lead ម 40-60 >60 Mercury ** - - Nickel ង 20-50 >50

Prioritization of the Oral (Ingestive) Hazard of Industrial Chemicals

DTIC Science & Technology

2011-10-28

NY) Volume(issue)/page/year: UR-154,1951 47 Imidacloprid #(E3) 138261-41-3 (changed) LD50 - Lethal dose, 50 percent kill Oral Rodent - rat 410 mg/kg...51-5 30.00 3.00 0.00 5.00 5.00 13.00 11.00 50 Potassium fluoride #(T3) 7789-23-3 245.00 2.00 0.00 5.00 5.00 12.00 14.00 51 Imidacloprid #(E3) 138261-41...T3) 950-37-8 49 Dimethoate #(T3) 60-51-5 50 Potassium fluoride #(T3) 7789-23-3 51 Imidacloprid #(E3) 138261-41-3 (changed) 52 Kerosene #(T3) 8008-20

Linkage disequilibrium, persistence of phase, and effective population size in Spanish local beef cattle breeds assessed through a high-density single nucleotide polymorphism chip.

PubMed

Cañas-Álvarez, J J; Mouresan, E F; Varona, L; Díaz, C; Molina, A; Baro, J A; Altarriba, J; Carabaño, M J; Casellas, J; Piedrafita, J

2016-07-01

Linkage disequilibrium (LD) and persistence of phase are fundamental approaches for exploring the genetic basis of economically important traits in cattle, including the identification of QTL for genomic selection and the estimation of effective population size () to determine the size of the training populations. In this study, we have used the Illumina BovineHD chip in 168 trios of 7 Spanish beef cattle breeds to obtain an overview of the magnitude of LD and the persistence of LD phase through the physical distance between markers. Also, we estimated the time of divergence based on the persistence of the LD phase and calculated past from LD estimates using different alternatives to define the recombination rate. Estimates of average (as a measure of LD) for adjacent markers were close to 0.52 in the 7 breeds and decreased with the distance between markers, although in long distances, some LD still remained (0.07 and 0.05 for markers 200 kb and 1 Mb apart, respectively). A panel with a lower boundary of 38,000 SNP would be necessary to launch a successful within-breed genomic selection program. Persistence of phase, measured as the pairwise correlations between estimates of in 2 breeds at short distances (10 kb), was in the 0.89 to 0.94 range and decreased from 0.33 to 0.52 to a range of 0.01 to 0.08 when marker distance increased from 200 kb to 1 Mb, respectively. The magnitude of the persistence of phase between the Spanish beef breeds was similar to those found in dairy breeds. For across-breed genomic selection, the size of the SNP panels must be in the range of 50,000 to 83,000 SNP. Estimates of past showed values ranging from 26 to 31 for 1 generation ago in all breeds. The divergence among breeds occurred between 129 and 207 generations ago. The results of this study are relevant for the future implementation of within- and across-breed genomic selection programs in the Spanish beef cattle populations. Our results suggest that a reduced subset of the SNP panel would be enough to achieve an adequate precision of the genomic predictions.

Antimalarial efficacy of Albizia lebbeck (Leguminosae) against Plasmodium falciparum in vitro & P. berghei in vivo.

PubMed

Kalia, Shagun; Walter, Neha Sylvia; Bagai, Upma

2015-12-01

Albizia lebbeck Benth. (Leguminosae) has long been used in Indian traditional medicine. The current study was designed to test antimalarial activity of ethanolic bark extract of A. lebbeck (EBEAL). EBEAL was prepared by soxhlet extraction and subjected to phytochemical analysis. The extract was evaluated for its in vitro antimalarial activity against Plasmodium falciparum chloroquine (CQ) sensitive (MRC2) and CQ resistant (RKL9) strains. Cytotoxicity (CC 50 ) of extract against HeLa cells was evaluated. Median lethal dose (LD 50 ) was determined to assess safety of EBEAL in BALB/c mice. Schizonticidal (100-1000 mg/kg) and preventive (100-750 mg/kg) activities of EBEAL were evaluated against P. berghei. Curative activity (100-750 mg/kg) of extract was also evaluated. Phytochemical screening revealed presence of alkaloids, flavonoids, phenols, saponins, terpenes and phytosterols. The extract exhibited IC 50 of 8.2 µg/ml (MRC2) and 5.1 µg/ml (RKL9). CC 50 of extract on HeLa cell line was calculated to be >1000 µg/ml. EBEAL showed selectivity indices (SI) of >121.9 and >196.07 against MRC2 and RKL9 strains of P. falciparum, respectively. LD 50 of EBEAL was observed to be >5 g/kg. Dose-dependent chemosuppression was observed with significant ( p<0.001) schizonticidal activity at 1000 mg/kg with ED 50 >100 mg/kg. Significant (P<0.001) curative and repository activities were exhibited by 750 mg/kg concentration of extract on D7. The present investigation reports antiplasmodial efficacy of EBEAL in vitro against P. falciparum as evident by high SI values. ED 50 of <100 mg/kg against P. berghei categorizes EBEAL as active antimalarial. Further studies need to be done to exploit its antiplasmodial activity further.

Mucuna pruriens in Parkinson Disease: A Kinetic-Dynamic Comparison With Levodopa Standard Formulations.

PubMed

Contin, Manuela; Lopane, Giovanna; Passini, Andrea; Poli, Ferruccio; Iannello, Carmelina; Guarino, Maria

2015-01-01

We compared levodopa (LD) kinetic-dynamic profile of a dose of LD/aromatic amino acid decarboxylase peripheral inhibitors versus a nominally equivalent dose of a commercial Mucuna pruriens (Mucuna) seeds extract in 2 patients with Parkinson disease chronically taking LD standard combined with self-prescribed Mucuna. Patients were challenged with a fasting morning dose of 100 mg LD/25 mg carbidopa (patient 1) or benserazide (patient 2) versus 100 mg LD from Mucuna capsules in 2 different sessions, after a 12-hour standard LD formulations' washout. They underwent kinetic-dynamic LD monitoring based on LD dose intake and simultaneous serial assessments of plasma drug concentrations and motor test performances. Quantitative analysis of LD in Mucuna capsules was also performed. Levodopa bioavailability was markedly lower after Mucuna administration compared with LD standard formulations: in patient 1, peak plasma LD concentration (Cmax) decreased from 2.0 to 1.0 mg/L and the area under the plasma concentration time curve from 137 to 33.6 mg/L per minute; in patient 2, Cmax was 0.7 mg/L after LD/benserazide and nearly undetectable after Mucuna. In patient 1, impaired LD bioavailability from Mucuna resulted in reduced duration and overall extent of drug response compared with LD/carbidopa. In patient 2, no significant subacute LD motor response was observed in either condition. Quantitative analysis of Mucuna formulation confirmed the 100 mg LD content for the utilized capsules. Our results show an impaired LD bioavailability from Mucuna preparation, as expected by the lacking aromatic amino acid decarboxylase inhibitors coadministration, which might explain the suggested lower dyskinetic potential of Mucuna compared with standard LD formulations.

Contact toxicity of twenty insecticides applied to Symmerista canicosta

Treesearch

Jacqueline L. Robertson; Robert L. Lyon; Fay L. Shon; Nancy L. Gillette

1972-01-01

Twenty insecticides were tested by topical application on mixed groups of 4th- and 5th -stage larvae of Symmerista canicosta Franclemont. Four exceeded DDT in toxicity at LD50 but only resmethrin was significantly mor toxic. Most of the compounds showed unusually high toxicities. Twelve, listed in decreasing order of toxicity...

NAPHTHALENE TOXICITY IN CD-1 MICE: GENERAL TOXICOLOGY AND IMMUNOTOXICOLOGY

EPA Science Inventory

The purpose of this study was to evaluate the acute and subchronic toxicity, and effects on immune function, of naphthalene (NAP) in random-bred CD-1 mice. The acute oral LD50 of this compound was 533 and 710 mg/kg in male and female mice, respectively. Fourteen- and ninety-day d...

Glyphosate-Resistant Goosegrass. Identification of a Mutation in the Target Enzyme 5-enolpyruvylshikimate-3-phosphate Synthase

USDA-ARS?s Scientific Manuscript database

The spontaneous occurrence of resistance to the herbicide glyphosate in weed species has been an extremely infrequent event, despite over 20 years of extensive use. Recently, a glyphosate-resistant biotype of goosegrass (Eleusine indica) was identified in Malaysia exhibiting an LD50 value approxima...

Acute Oral Toxicity (LD(50)) of CHF1 in Rats.

DTIC Science & Technology

1982-04-01

had moderate hydronephrosis . Another animal in group 6 and one in group 4 had gray streaks in the cortical parenchyma which were probably incidental...considered to be a post mortem change. *Number of rats affected/number of rats in the group. 21 APPENDIX A-2 (cont.) Unilateral hydronephrosis was observed in

40 CFR 156.85 - Non-target organisms.

Code of Federal Regulations, 2012 CFR

2012-07-01

... streams. Do not contaminate water by cleaning of equipment or disposal of wastes.” ... oral LD50 of 100 mg/kg or less, the statement, “This pesticide is toxic to wildlife” is required. (2... or less, the statement, “This pesticide is toxic to fish” is required. (3) If a pesticide intended...

40 CFR 156.85 - Non-target organisms.

Code of Federal Regulations, 2014 CFR

2014-07-01

... streams. Do not contaminate water by cleaning of equipment or disposal of wastes.” ... oral LD50 of 100 mg/kg or less, the statement, “This pesticide is toxic to wildlife” is required. (2... or less, the statement, “This pesticide is toxic to fish” is required. (3) If a pesticide intended...

40 CFR 156.85 - Non-target organisms.

Code of Federal Regulations, 2013 CFR

2013-07-01

... streams. Do not contaminate water by cleaning of equipment or disposal of wastes.” ... oral LD50 of 100 mg/kg or less, the statement, “This pesticide is toxic to wildlife” is required. (2... or less, the statement, “This pesticide is toxic to fish” is required. (3) If a pesticide intended...

9 CFR 113.66 - Anthrax Spore Vaccine-Nonencapsulated.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) Forty-two susceptible guinea pigs from the same source each weighing 400 to 500 grams, shall be used as... conducted. The guinea pigs used as vaccinates shall be injected as recommended on the label with a... and controls shall each be challenged with not less than 4,500 guinea pig LD50 of a virulent...

Intramodal and Intermodal Functioning of Normal and LD Children

ERIC Educational Resources Information Center

Heath, Earl J.; Early, George H.

1973-01-01

Assessed were the abilities of 50 normal 5-to 9-year-old children and 30 learning disabled 7-to 9-year-old children to recognize temporal patterns presented visually and auditorially (intramodal abilities) and to vocally produce the patterns whether presentation was visual or auditory (intramodal and cross-modal abilities). (MC)

Central nervous system radiation syndrome in mice from preferential 10B(n, alpha)7Li irradiation of brain vasculature

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slatkin, D.N.; Stoner, R.D.; Rosander, K.M.

1988-06-01

Ionizing radiations were directed at the heads of anesthetized mice in doses that evoked the acute central nervous system (CNS) radiation syndrome. Irradiations were done using either a predominantly thermal neutron field at a nuclear reactor after intraperitoneal injection of 10B-enriched boric acid or 250-kilovolt-peak x-rays with and without previous intraperitoneal injection of equivalent unenriched boric acid. Since 10B concentrations were approximately equal to 3-fold higher in blood than in cerebral parenchyma during the reactor irradiations, more radiation from alpha and 7Li particles was absorbed by brain endothelial cells than by brain parenchymal cells. Comparison of the LD50 dose formore » CNS radiation lethality from the reactor experiments with the LD50 dose from the x-ray experiments gives results compatible with morphologic evidence that endothelial cell damage is a major determinant of acute lethality from the CNS radiation syndrome. It was also observed that boric acid is a low linear energy transfer radiation-enhancement agent in vivo.« less

Chernobyl doses. Volume 1. Analysis of forest canopy radiation response from multispectral imagery and the relationship to doses. Technical report, 29 July 1987-30 September 1993

DOE Office of Scientific and Technical Information (OSTI.GOV)

McClennan, G.E.; Anno, G.H.; Whicker, F.W.

1994-09-01

This volume of the report Chernobyl Doses presents details of a new, quantitative method for remotely sensing ionizing radiation dose to vegetation. Analysis of Landsat imagery of the area within a few kilometers of the Chernobyl nuclear reactor station provides maps of radiation dose to pine forest canopy resulting from the accident of April 26, 1986. Detection of the first date of significant, persistent deviation from normal of the spectral reflectance signature of pine foliage produces contours of radiation dose in the 20 to 80 Gy range extending up to 4 km from the site of the reactor explosion. Themore » effective duration of exposure for the pine foliage is about 3 weeks. For this exposure time, the LD50 of Pinus sylvestris (Scotch pine) is about 23 Gy. The practical lower dose limit for the remote detection of radiation dose to pine foliage with the Landsat Thematic Mapper is about 5 Gy or 1/4 of the LD50.« less

In vivo screening of candidate pretreatment compounds against cyanide using mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kiser, R.C.; Olson, C.T.; Menton, R.G.

1993-05-13

An in vivo screening procedure was established at Battelle's Medical Research and Evaluation Facility (MREF) to evaluate the efficacy of candidate pretreatment compounds in mice challenged with the blood agent, sodium cyanide (NaCN). Male albino mice of ICR outbred stock weighing between 22.5 and 27.5 g are challenged by intramuscular (i.m.) injection, at a volume of 0.5 mL/kg, of a dose of NaCN twice the LD50 of untreated mice as determined on that day of testing. Candidate drugs are tested at fractions of their LD50 or their limit of solubility in the most optimum vehicle and given intraperitoneally (i.p.) tomore » separate groups of mice at either 60 or 15 min prior to NaCN challenge. Sodium thiosulfate (1000 mg/kg)/sodium nitrite (100 mg/kg) controls are injected i.p. only at 60 min prior to challenge. A test compound is deemed effective if, at any of three concentrations tested, or at either pretreatment time, it is statistically more efficacious in preventing lethality than is a negative control substance (candidate compound vehicle).« less

Huperzine a as a pretreatment candidate drug against nerve agent toxicity. (Reannouncement with new availability information)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grunwald, J.; Raveh, L.; Doctor, B.P.

1994-12-31

Huperzine A (HUP) is a naturally-occurring, potent, reversible inhibitor of acetylcholinesterase (AChE) that crosses the blood-brain barrier. To examine its ability to protect against nerve agent poisoning, HUP was administered i.p. to mice, and the s.c. LD50 of soman was determined at various time intervals after pretreatment. Results were compared to those obtained for animals treated with physostigmine. A protective ratio of approximately 2 was maintained for at least 6 hr after a single injection of HUP, without the need for any post-challenge drug therapy. By contrast, pretreatment with physostigmine increased the LD50 of soman by 1.4- to 1.5-fold formore » only up to 90 min. The long-lasting antidotal efficacy displayed by HUP correlated with the time course of the blood-AChE inhibition. The results suggest that the protection of animals by HUP from soman poisoning was achieved by temporarily sequestering the active site region of the physiologically important AChE.« less

Biochemical effects of three chlorinated phenols in rat liver

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kitchin, K.T.; Brown, J.L.

1988-01-01

The hepatic biochemical effects of four chlorinated oxygen containing environmental contaminants were determined. Two oral doses of 1/5 the LD50 of 2,4-dichlorophenoxyacetic acid, 2,4,5-trichlorophenol, 2,4,6-trichlorophenol and 2,3,4,6-tetrachlorophenol were given 21 and 4 hours before sacrifice to adult female rats. Although 2,4,6-trichlorophenol is a carcinogen in lifetime rodent studies, no evidence was found for DNA damage in rat liver or the white cells of rat blood. Similiarly no compound related changes were found in serum alanine aminotransferase, hepatic glutathione or cytochrome P-450 content. A dose of 193 mg/kg/day (slightly over the published rat LD50) of 2,3,4,6-tetrachlorophenol increased 5-fold the activity ofmore » hepatic ornithine decarboxylase. As 2,4,6-trichlorophenol did not damage DNA or induce hepatic ornithine decarboxylase (a marker of carcinogenic promotion) in the study, no explanation is apparent why this molecule is a carcinogen in rodent lifetime exposures and structurally related congeners are not.« less

Estimation of maximum tolerated dose for long-term bioassays from acute lethal dose and structure by QSAR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gombar, V.K.; Enslein, K.; Hart, J.B.

1991-09-01

A quantitative structure-activity relationship (QSAR) model has been developed to estimate maximum tolerated doses (MTD) from structural features of chemicals and the corresponding oral acute lethal doses (LD50) as determined in male rats. The model is based on a set of 269 diverse chemicals which have been tested under the National Cancer Institute/National Toxicology Program (NCI/NTP) protocols. The rat oral LD50 value was the strongest predictor. Additionally, 22 structural descriptors comprising nine substructural MOLSTAC(c) keys, three molecular connectivity indices, and sigma charges on 10 molecular fragments were identified as endpoint predictors. The model explains 76% of the variance and ismore » significant (F = 35.7) at p less than 0.0001 with a standard error of the estimate of 0.40 in the log (1/mol) units used in Hansch-type equations. Cross-validation showed that the difference between the average deleted residual square (0.179) and the model residual square (0.160) was not significant (t = 0.98).« less

Fulminant hyperammonaemia induced by thiopental coma in rats.

PubMed

Ivnitsky, Jury Ju; Rejniuk, Vladimir L; Schäfer, Timur V; Malakhovsky, Vladimir N

2006-07-25

Fulminant hyperammonaemia as a threshold effect of coma-inducing dose of sodium thiopental has been revealed in rats. Blood ammonia content increased progressively after the introduction of 1.0 LD(50) (but not 0.8 LD(50)) of sodium thiopental three times in 3h and five times in 18h. The urinary ammonia excretion was not impaired while the volatilization of ammoniac from the body of ST-treated rats was higher, giving evidence of the augmentation of ammonia production. Blood urea increased by one third despite of insignificant alterations of haematocrit and blood creatinine. Ammonia hyperproduction in the digestive tract could result from gastrointestinal stasis, which has been verified by roentgenography and confirmed by correlation of hyperammonaemia with the stool retardation. In thiopental coma rats the slope of a dose-dependent increase of the blood ammonia and the blood urea after the intraperitoneal injection of ammonium acetate did not exceed that in intact animals. So the ammonia hyperproduction in the digestive tract could be the main contributing cause of fulminant hyperammonaemia in rats with thiopental coma and thus be involved into pathogenesis of the coma.

The relationship between total cholinesterase activity and mortality in four butterfly species

USGS Publications Warehouse

Bargar, Timothy A.

2012-01-01

The relationship between total cholinesterase activity (TChE) and mortality in four butterfly species (great southern white [Ascia monuste], common buckeye [Junonia coenia], painted lady [Vanessa cardui], and julia butterflies [Dryas julia]) was investigated. Acute contact toxicity studies were conducted to evaluate the response (median lethal dose [LD50] and TChE) of the four species following exposure to the organophosphate insecticide naled. The LD50 for these butterflies ranged from 2.3 to 7.6 μg/g. The average level of TChE inhibition associated with significant mortality ranged from 26 to 67%, depending on the species. The lower bounds of normal TChE activity (2 standard deviations less than the average TChE for reference butterflies) ranged from 8.4 to 12.3 μM/min/g. As a percentage of the average reference TChE activity for the respective species, the lower bounds were similar to the inhibition levels associated with significant mortality, indicating there was little difference between the dose resulting in significant TChE inhibition and that resulting in mortality.

Application of enhanced membrane bioreactor (eMBR) to treat dye wastewater.

PubMed

Rondon, Hector; El-Cheikh, William; Boluarte, Ida Alicia Rodriguez; Chang, Chia-Yuan; Bagshaw, Steve; Farago, Leanne; Jegatheesan, Veeriah; Shu, Li

2015-05-01

An enhanced membrane bioreactor (eMBR) consisting of two anoxic bioreactors (ARs) followed by an aerated membrane bioreactor (AMBR), UV-unit and a granular activated carbon (GAC) filter was employed to treat 50-100 mg/L of remazol blue BR dye. The COD of the feed was 2334 mg/L and COD:TN:TP in the feed was 119:1.87:1. A feed flow rate of 5 L/d was maintained when the dye concentration was 50 mg/L; 10 L/d of return activated sludge was recirculated to each AR from the AMBR. Once the biological system is acclimatised, 95% of dye, 99% of COD, 97% of nitrogen and 73% of phosphorus were removed at a retention time of 74.4 h. When the effluent from the AMBR was drawn at a flux rate of 6.5 L/m(2)h, the trans-membrane pressure reached 40 kPa in every 10 days. AMBR effluent was passed through the UV-unit and GAC filter to remove the dye completely. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Construction and characterization of a gspL mutant of avian pathogenic Escherichia coli].

PubMed

Fan, Guobo; Han, Yue; Zhang, Yuxi; Han, Xiangan; Wang, Shaohui; Bai, Hao; Meng, Qingmei; Qi, Kezong; Ding, Chan; Yu, Shengqing

2015-01-04

To study the role of gspL gene in avian pathogenic Escherichia coli. The gspL mutant of Avian pathogenic Escherichia coli (APEC) was constructed by homologous recombination assay. The growth characteristics, the ability of adhesion and invasion to DF1 cells, the virulence genes transcription level and median lethal dose (LD50) were analyzed between the gspL mutant strain and the wild strain. Compared with the wild strain, the mutant strain had no significant difference in the growth status. However, its ability of adhesion and invasion was significantly lower. The transcription of genes pfs, fyuA, iss and vat increased obviously, the tsh decreased and the transcription level of luxS, ibeA, stx2f and ompA had no significant change. LD50 showed that the gspL mutant strain had 12-fold increase in virulence. The deletion of gspL gene could abate the ability of adhesion and invasion, regulate and control some virulence gene transcription level, enhance the virulence of APEC. The results show that the gspL gene play roles in pathogenicity of APEC.

Study on development of Vipera lebetina snake anti-venom in chicken egg yolk for passive immunization

PubMed Central

Zolfagharian, Hossein; Dounighi, Naser Mohammadpour

2015-01-01

Chicken egg yolk antibodies against Vipera lebetina venom were evaluated for their antivenom potential. White leghorn hens were immunized with detoxified V. lebetina venom (γ-irradiated venom). The detoxified venom (200 μg) was mixed with an equal volume of complete Freund's adjuvant and was injected intramuscularly into the hens. The antibodies showed high activity (1.6 LD50/mL) in egg yolks after 12 d of venom injection. The eggs were collected after 12 days, and the egg yolks were removed and washed with purified water to remove any contamination with egg whites. The purification was performed using a method described by Maya Devi et al., followed by gel filtration (Sephadex G-50). The purity and molecular weight of antivenom antibodies (IgY) were determined using electrophoresis, and the molecular weight was found to be approximately 185 kDa. The potency of IgY was 6 LD50/mL (mice), i.e., 1 mL of IgY could neutralize 43.8 μg of standard V. lebetina venom). Our results showed that chicken egg yolk antibodies were effective in neutralizing the lethality and several pharmacological effects of V. lebetina venom and could be used for developing effective antivenom. PMID:25700656

Inhibition of para-Hydroxyphenylpyruvate Dioxygenase by Analogues of the Herbicide Nitisinone As a Strategy to Decrease Homogentisic Acid Levels, the Causative Agent of Alkaptonuria.

PubMed

Laschi, Marcella; Bernardini, Giulia; Dreassi, Elena; Millucci, Lia; Geminiani, Michela; Braconi, Daniela; Marzocchi, Barbara; Botta, Maurizio; Manetti, Fabrizio; Santucci, Annalisa

2016-04-05

Alkaptonuria (AKU) is a rare multisystem metabolic disease caused by deficient activity of homogentisate 1,2-dioxygenase (HGD), which leads to the accumulation of homogentisic acid (HGA). Currently, there is no treatment for AKU. The sole drug with some beneficial effects is the herbicide nitisinone (1), an inhibitor of p-hydroxyphenylpyruvate dioxygenase (4-HPPD). 1 has been used as a life-saving drug in infants with type I tyrosinemia despite severe side effects due to the buildup of tyrosine. Four clinical trials of nitisinone to treat AKU have shown that 1 consistently decreases HGA levels, but also caused the accumulation of tyrosine in blood serum. Moreover, the human preclinical toxicological data for 1 are incomplete. In this work, we performed pharmacodynamics and toxicological evaluations of 1, providing the first report of LD50 values in human cells. Intracellular tyrosinemia was also evaluated. Three additional 4-HPPD inhibitors with a more favorable profile than that of 1 in terms of IC50, LD50, and tyrosine accumulation were also identified among commercially available compounds. These may be promising starting points for the development of new therapeutic strategies for the treatment of AKU. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Resistance to pyrethroid insecticides in house flies, Musca domestica L., (Diptera: Muscidae) collected from urban areas in Punjab, Pakistan.

PubMed

Khan, Hafiz Azhar Ali; Akram, Waseem; Fatima, Ammara

2017-12-01

House flies are one of the major public health pests in urban settings. People usually use insecticides containing pyrethroids for the management of house flies; however, there is a lack of information on pyrethroid resistance in house flies from urban areas. In the present study, resistance to four pyrethroids (beta-cyfluthrin, deltamethrin, permethrin, transfluthrin) was assessed in house flies collected from urban areas of Punjab, Pakistan. Significant levels of resistance to all the pyrethroids were found in different strains of house flies. The resistance ratios (RRs) at the median lethal dose (LD 50 ) level were in the range of 5.25- to 11.02-fold for beta-cyfluthrin, 7.22- to 19.31-fold for deltamethrin, 5.36- to 16.04-fold for permethrin, and 9.05- to 35.50-fold for transfluthrin. Pairwise comparison of the log LD 50 s revealed a highly significant correlation (p < 0.01) between deltamethrin and permethrin, suggesting the possibility of a cross-resistance mechanism. The results revealed the occurrence of pyrethroid resistance in house flies from urban areas of Punjab. Regular resistance monitoring surveys and integrated approaches for the management of house flies are needed to retain the efficacy of these insecticides for a longer period of time.

Antinociceptive and Anti-Inflammatory Activities of Leaf Methanol Extract of Cotyledon orbiculata L. (Crassulaceae).

PubMed

Amabeoku, George J; Kabatende, Joseph

2012-01-01

Leaf methanol extract of C. orbiculata L. was investigated for antinociceptive and anti-inflammatory activities using acetic acid writhing and hot-plate tests and carrageenan-induced oedema test in mice and rats, respectively. C. orbiculata (100-400 mg/kg, i.p.) significantly inhibited acetic acid-induced writhing and significantly delayed the reaction time of mice to the hot-plate-induced thermal stimulation. Paracetamol (300 mg/kg, i.p.) significantly inhibited the acetic acid-induced writhing in mice. Morphine (10 mg/kg, i.p.) significantly delayed the reaction time of mice to the thermal stimulation produced with hot plate. Leaf methanol extract of C. orbiculata (50-400 mg/kg, i.p.) significantly attenuated the carrageenan-induced rat paw oedema. Indomethacin (10 mg/kg, p.o.) also significantly attenuated the carrageenan-induced rat paw oedema. The LD(50) value obtained for the plant species was greater than 4000 mg/kg (p.o.). The data obtained indicate that C. orbiculata has antinociceptive and anti-inflammatory activities, justifying the folklore use of the plant species by traditional medicine practitioners in the treatment of painful and inflammatory conditions. The relatively high LD(50) obtained shows that C. orbiculata may be safe in or nontoxic to mice.

Evaluating of the Anticonvulsant Gabapentin against Nerve Agent-Induced Seizures in a Guinea Pig Model

DTIC Science & Technology

2010-07-01

from Cutter Labs, Inc. (Berkeley, CA). Pyridostigmine bromide was obtained from Hoffmann- La Roche, Inc. (Nutley, NJ), and pyridine-2-aldoxime... Pyridostigmine bromide was prepared in sterile water to a concentration of 0.052 mg/ml. Atropine sulfate (4 mg/ml) and 2-PAM (50 mg/ml) were prepared in...activity. After a week recovery, animals were pretreated with pyridostigmine 30 min prior to subcutaneous soman challenge (56 ug/kg; 2 X LD50