Age-dependent tolerance toBaculovirus in last larval instars of the codling moth,Cydia pomonella,L., induced either for pupation or for diapause

Summary LD₅₀ values as well as time-dependent parameters of granulosis virus infections were determined at different times during the last larval instar (L₅) of the codling moth,Cydia pomonella L., induced either for pupation or for diapause. A significant increase of tolerance to virus was found in 48-h-old L₅ induced for pupation, and 24 h later in L₅ induced for diapause.     

The antiviral effect of Keishi-ni-eppi-ichi-to,a tranditional Chinese herbal medicine,on influenza A2(H2N2) virus infection in mice

The antiviral effect of Keishi-ni-eppi-ichi-to (TJS-064), a traditional Chinese herbal medicine, was investigation in mice infected with influenza A₂(H₂N₂) virus. When mice exposed to 5 LD₅₀ dose of the virus were treated orally with a 70 mg/kg dose of TJS-064 1 day before and 1 day and 4 days after the infection, 100% survived over a 25-day experimental period. At the end of this period all the control mice, treated with saline alone, had died; their mean survival time in days (MSD) was 11.2 days. When mice infected with a 10 LD₅₀ dose of the virus were treated with TJS-064, the MSD was >17.4 days and there was a 50% survival rate, while the control group had a MSD of 8.7 days and 0% survival rate. No significant antiviral effect TJS-064 was observed when the agent was administered orally to mice infected with a 100 LD₅₀ or large dose of influenza virus. Pulmonary consolidation, virus titers in lung tissues and HAI titers in sera of infected mice treated with TJS-064 were all significantly lower than those of infected mice treated with saline. Interferon activities were detected in sera of mice treated with the agent at a dose of 100 mg/kg orally. Since viricidal and viristatic activities of the agent against influenza virus were not demonstrated, the antiviral effects of TJS-064 may be expressed through the host's antiviral functions including interferon production.     

Improved treatment of organophosphate intoxication by use of scopolamine or dexetimide

Summary Organophosphate intoxications have been treated by dexetimide plus obidoxime. Rabbits intoxicated by the 50-80fold LD₅₀ of different organophosphates survived. Prophylactic application of dexetimide or scopolamine plus obidoxime increased the LD₅₀ of DFP by a factor up to 180.Supported by the Fraunhofer-Gesellschaft e. V., Munich, BRD     

Blutagglutinierende und toxische Eiweissfraktionen aus Bohnen

Summary Soluble proteins from black beans (Phaseolus vulgaris) have been separated into 4 fractions, one soluble in 1% NaCl-solution and 3 water soluble. The latter were separated by ammonium sulfate fractionation. The haemagglution of these fractions is compared with their toxicity in mice when applied by intraperitoneal injection. The LD₅₀ of the most active fraction was about 50 mg/kg. When used in mice of different strains, the toxicity was not the same while the blood cells were agglutinated by the same final concentration. Crotonoil-induced papilloma-bearing mice were slightly more resistant than normal animals.     

Mechanism of inhibition of IgE-dependent histamine release from rat mast cells by xestobergsterol A from the Okinawan marine spongeXestospongia bergquistia

Histamine release from rat peritoneal mast cells induced by anti-IgE was essentially complete within 4–5 min. Xestobergsterol A and B, which are constituents of the Okinawan marine spongeXestospongia bergquistia Fromont, dose-dependently inhibited anti-IgE-induced histamine release from rat mast cells. The IC₅₀ values of xestobergsterol A and B for histamine release in mast cells activated by anti-IgE were 0.07 and 0.11 M, respectively. Anti-IgE stimulated PI-PLC activity in a mast cell membrane preparation. Xestobergsterol A dose-dependently inhibited the generation of IP3 and membrane-bound PI-PLC activity. Moreover, xestobergsterol A inhibited Ca²⁺-mobilization from intracellular Ca²⁺-stores as well as histamine release in mast cells activated by anti-IgE. On the other hand, xestobergsterol B did not inhibit the membrane-bound and cytosolic PI-PLC activity, IP3 generation or the initial rise in [Ca²⁺]_i in mast cells activated by anti-IgE. These results suggest that the mechanism of inhibition by xestobergsterol A of the initial rise in [Ca²⁺]_i, of the generation of IP3, and of histamine release induced by anti-IgE, was through the inhibition of PI-PLC activity.     

DNA fragmentation in leukocytes following repeated low dose sarin exposure in guinea pigs

The objective of this study was to determine levels of DNA fragmentation in blood leukocytes and parietal cortex from guinea pigs following repeated lowlevel exposure to the chemical warfare nerve agent (CWNA) sarin. Guinea pigs were injected (s.c.) once a day for 10 days with saline, or 0.1, 0.2, or 0.4 LD₅₀ (50% mean lethal dose) sarin dissolved in sterile physiological saline. Blood and parietal cortex was collected after injection at 0, 3, and 17 days recovery and evaluated for DNA fragmentation using single-cell gel electrophoresis (Comet assay). Cells were imaged using comet analysis software and three parameters of DNA fragmentation measured: tail length, percent DNA in the tail, and tail moment arm. Repeated low-dose exposure to sarin produced a dose-dependent response in leukocytes at 0 and 3 days post-exposure. There was a significant increase in all measures of DNA fragmentation at 0.2 and 0.4 LD₅₀, but not at 0.1 LD₅₀. There was no significant increase in DNA fragmentation in any of the groups at 17 days post-exposure. Sarin did not produce a systematic dose-dependent response in parietal cortex at any of the time points. However, significant increases in DNA fragmentation at 0.1 and 0.4 LD₅₀ were observed at 0 and 3 days post-exposure. All measures of DNA fragmentation in both leukocytes and neurons returned to control levels by 17 days post-exposure, indicating a small and non-persistent increase in DNA fragmentation following repeated low-level exposure to sarin. Received 23 July 2007; received after revision 23 August 2007; accepted 3 September 2007 Research was conducted in compliance with the Animal Welfare Act, and other Federal statutes and regulation relating to animals and experiments involving animals and adheres to the principles stated in the Guide for the Care and Use of Laboratory Animals, NIH publication 85-23. The views of the authors do not purport to reflect the position of the Department of the Army or the Department of Defense (para 4-3), AR 360–365.     

Expression ofPseudomonas phosphotriesterase activity in the fall armyworm confers resistance to insecticides

Summary The gene encoding for the phosphotriesterase (opd) fromPseudomonas diminuta has been subcloned into a baculovirus expression system. Functional enzyme is produced when the recombinant baculovirus is used to infect either culturedSpodoptera frugiperda sf9 cells or the larval stage of the fall armyworm. The LD₅₀ for paraoxon toxicity was found to increase 280-fold in the larvae after infection with the recombinant baculovirus and expression of the functional phosphotriesterase.This work was supported by the Army Research Office (DAAL03-87-K-0017) and the Texas Advanced Technology Program. F.M.R. is the recipient of NIH Research Career Development Award DK-01366.     

DNA fragmentation in leukocytes following subacute lowdose nerve agent exposure

The objective of the present study was to determine levels of DNA fragmentation in blood leukocytes from guinea pigs by single-cell gel electrophoresis (comet assay) after exposure to the chemical warfare nerve agent (CWNA), soman, at doses ranging from 0.1 LD₅₀ to 0.4 LD₅₀, once per day for either 5 or 10 days. Post-exposure recovery periods ranged from 0 to 17 days. Leukocytes were imaged from each animal, and the images analyzed by computer. Data obtained for exposure to soman demonstrated significant increases in DNA fragmentation in circulating leukocytes in CWNA-treated guinea pigs compared with saline-injected control animals at all doses and time points examined. Notably, significantly increased DNA fragmentation was observed in leukocytes 17 days after cessation of soman exposure. Our findings demonstrate that leukocyte DNA fragmentation assays may provide a sensitive biomarker for low-dose CWNA exposure.Received 29 July 2003; accepted 14 August 2003     

The LD50 value of tetraethyl lead

Zusammenfassung Im Hinblick auf den offensichtlichen Mangel eines LD₅₀-Wertes für Bleitetraethyl wurde bei intragastrischer Applikation im Rattenversuch der Wert 14,18 mg/kg (Spielraum 12,62–15,93) ermittelt.

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Funded in part by National Science Grant No. GI-4.     

Chemical structure and biological activity ofo-disubstituted derivatives of benzene

Zusammenfassung Es wurden die i.v. LD₅₀ einer Gruppeo-disubstituierter Benzolderivate, welche alle Kombinationen der erwähnten Substituenten enthielt, bestimmt. Die quantitative Korrelation zwischen chemischer Struktur und biologischer Aktivität wird in einer Gleichung gefasst.     

Acute toxicity of folic acid in mice

Summary The toxicity of folic acid (PGA) was studied in different inbred strains of mice. LD₅₀ values of PGA by the i.p. route showed a unique toxicity pattern. In some strains, convulsions, ataxia and weakness were observed. Histopathological study in strains S/RVCri, BDF₁, DBA/2 and DBA/2fNCri showed acute renal tubular necrosis.Acknowledgment. The authors thank Ms N. Hasgekar for her technical assistance     

Chemical structure and biological activity ofp-disubstituted derivatives of benzene

Zusammenfassung Es wurden die i.v. LD₅₀ einer Gruppep-disubstituierter Benzolderivate, welche alle Kombinationen der erwähnten Substituenten enthielten, in Polyvinylpyrrolidonlösungen bestimmt. Der Zusammenhang zwischen der chemischen Struktur dieser Verbindungsklasse und ihrer biologischen Aktivität konnte mit einer vorgeschlagenen Gleichung beschrieben werden.     

Vergleichende Untersuchungen über die Toxizität der Ca- und Zn(II)-Chelate der Diäthylentriaminpentaessigsäure

Summary The lethal effect of daily intraperitoneal administrations of Ca-DTPA and Zn(II)-DTPA was studied in mice. Due to recovery processes, single chelate doses are non-additive and the cumulative LD₅₀ increases with decreasing daily dosage. At a given number of administrations, Zn(II)-DTPA is 2.5 times less toxic than Ca-DTPA. However, if the daily dosage is kept constant and the number of administrations variable, Zn(II)-DTPA is 30 times less toxic.     

Protective effect of Shigyaku-to,a traditional Chinese herbal medicine,on the infection of herpes simplex virus type 1 (HSV-1) in mice

The antiviral activity of Shigyaku-to (TJS-109), a traditional Chinese herbal medicine, was investigated in mice infected with herpes simplex virus type 1 (HSV-1). TJS-109 is a combination of the medicinal plant extracts fromZingiberis siccatum rhizoma,Aconiti tuber andGlycyrrhizae radix in a specific proportion. Mice infected with a 10 LD₅₀ dose of HSV-1 were treated with TJS-109 orally at doses of 1.25 to 20 mg/kg 2 days before, and 1 and 4 days after the infection. The treated groups had 80% (1.25 mg/kg), 40% (5 mg/kg) and 23% (20 mg/kg) mortality rates 25 days after the infection as compared with a 100% mortality rate in control mice treated with saline. When HSV-1 infected mice (recipients) received CD8⁺T cell fractions derived from spleens of mice treated with TJS-109 (donors), 70% of recipients survived, as compared with 0% survivors in the groups of mice treated with saline, B cell fractions, CD4⁺ T cell fractions or macrophage-enriched fractions prepared from the same donors. TJS-109 did not show any virucidal activities against HSV-1 or any virostatic activities on the growth of HSV-1 in Vero cells. These results suggest that TJS-109 protected mice exposed to lethal amounts of HSV-1 through the activation of CD8⁺ T cells.     

Effects of histones on embryonic cells

Zusammenfassung Der Einfluss vom Kalbsthymus Histon (CTH) und seines diazotierten Derivatives (DCTH) auf Vitalität und Zelldifferenzierung verschiedener Gewebe des Hühnerembryos wurde geprüft. Die LD₅₀ für CTH wurde bei 25µg/ml der Zellsuspensionen festgestellt. Es wurden keine bedeutenden Änderungen in der Differenzierung der embryonalen Gewebe in Kulturen bei sublethalen Konzentrationen gefunden.     

Activity of precocene analogs onLocusta migratoria migratorioides (R. and F.)

Summary Several analogs of precocene have been synthesized and evaluated as potential inhibitors of juvenile hormone onLocusta migratoria. Only 5,7-dimethoxy-2,2-dimethylchromene was active; its ED₅₀ and LD₅₀ were measured and compared to those of precocene I and II.Acknowledgments. This work was supported by grants from the Natural Sciences and Engineering Research Council of Canada and the Ministère de l'Education du Québec. We are grateful to Gaston Grégoire for rearing the insects.     

Effects of L-lysine administration on certain aspects of ascorbic acid metabolism in weanling rats

Summary L-lysine administration to male weanling rats at a dose of 110.4 mg (25% LD₅₀) per 100 g body weight per day for 15 days reduced the liver total ascorbic acid level. The biosynthesis as well as the degradation of L-ascorbic acid was diminished under these conditions. The fall in liver total ascorbic acid level after L-lysine administration was ascribed to its reduced synthesis.Acknowledgment. The authors are thankful to the Council of Scientific and Industrial Research, India, for providing Junior Research Fellowships to Miss J. Basu and Miss K. Sen Gupta.     

Circadian variation of diazepam acute toxicity in mice

Summary The LD₅₀ of i.p. injected diazepam was determined every 4 h over a 24-h period in albino mice adapted to a 12-h dark/12-h light programmed illumination cycle. Results show that diazepam is more toxic during the light phase of the cycle than during the dark phase and demonstrate circadian variation in the toxicity of the compound in mice.     

Selective susceptibility to nanosecond pulsed electric field (nsPEF) across different human cell types

Tumor ablation by nanosecond pulsed electric fields (nsPEF) is an emerging therapeutic modality. We compared nsPEF cytotoxicity for human cell lines of cancerous (IMR-32, Hep G2, HT-1080, and HPAF-II) and non-cancerous origin (BJ and MRC-5) under strictly controlled and identical conditions. Adherent cells were uniformly treated by 300-ns PEF (0–2000 pulses, 1.8 kV/cm, 50 Hz) on indium tin oxide-covered glass coverslips, using the same media and serum. Cell survival plotted against the number of pulses displayed three distinct regions (initial resistivity, logarithmic survival decline, and residual resistivity) for all tested cell types, but with differences in LD₅₀ spanning as much as nearly 80-fold. The non-cancerous cells were less sensitive than IMR-32 neuroblastoma cells but more vulnerable than the other cancers tested. The cytotoxic efficiency showed no apparent correlation with cell or nuclear size, cell morphology, metabolism level, or the extent of membrane disruption by nsPEF. Increasing pulse duration to 9 µs (0.75 kV/cm, 5 Hz) produced a different selectivity pattern, suggesting that manipulation of PEF parameters can, at least for certain cancers, overcome their resistance to nsPEF ablation. Identifying mechanisms and cell markers of differential nsPEF susceptibility will critically contribute to the proper choice and outcome of nsPEF ablation therapies.