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.     

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.     

Increase in the survival time of mice exposed to ionizing radiation by a new class of free radical scavengers

Summary N-acyl dehydroalanines react with and scavenge mainly superoxide radical and hydroxyl radical (HO^.). The ortho-methoxyphenylacetyl dehydroalanine derivative, indexed as AD-20, protects mice against damage resulting from total body X-irradiation, as measured by the increase in their survival time. AD-20 increases the LD₅₀ at 30 days from 6.1 to 7.3 Gy in animals exposed to a wide range of X-rays (6 to 10 Gy). The dose reduction factor (D R F) of AD-20 is 1.20. We postulate that such radioprotective effect may result from its free radical scavenging activity.     

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     

Über die Wirkung von rac-endo-2-Bornanamin und von verwandten Verbindungen gegen Influenza A2-Virus Asia

Summary rac-endo-2-Bornanamine (1) shows good activity against infections with influenza A₂ virus (Asia) in mice. None of 41 derivatives or analogues was superior to compound1.     

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.     

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     

The influence of cold or isolation stress on resistance of mice to West Nile virus encephalitis

Summary The effect of cold or isolation stress on mortality rate and brain virus level were investigated in mice infected with West Nile virus (WNV). Exposure of mice for 5 min/day to cold water (1±0.5°C) for 8–10 days resulted in 92% mortality as compared to 47% in control mice (p<0.001). Mice housed in individual cages (isolation stress) were also more susceptible to WN viral infection, as shown by increased mortality rate reaching 85% as compared to 50% in mice housed 6 per cage (p<0.01). Cold or isolation stress increased blood brain and spleen virus levels as early as 2 days after inoculation. After 8 days of isolation or cold stress, mice inoculated with WNV had 8.9 and 9.0 log₁₀ plaque forming units in the brain, respectively, as compared to 6.9 in the control (p<0.01–0.001). Furthermore, lymphoid organs such as spleen and thymus showed severe mass loss. These data suggest that physical or non-physical stress situations enhance WNV encephalitis by accelerating virus proliferation and increase mortality in mice.     

Acute toxicity of dimethylnitrosamine in the presence of inhibitors of DMN demethylase

Summary The LD₅₀ of DMN was determined in groups of mice in the presence of inhibitors of DMN demethylase. Piperonyl butoxide, dibutylnitrosamine and nitrososarcosine had no effect on the acute toxicity of DMN. Diethylnitrosamine and DMN were markedly synergistic. All mice treated with 100 mg/kg diethylnitrosamine and 10.7 mg/kg DMN died. These results suggest that DMN demethylase may not be involved in theaacute toxicity of DMN.We thank Dr.D. B. Couch, Mr.E. J. Greene and Dr.A. E. Munson for their technical assistance.     

Ulteriori dati sull'attività dei derivati triazinici nelle infezioni da virus

Summary A number of 2-amino-4-morpholinyl-s-triazine derivatives has been synthetized by the authors, and the activity of these compounds has been tested against some viral infections in laboratory animals.Among these substances, the compounds having the NH₂ group free or monosubstituted, and the 6-CH group unsubstituted, revealed an interesting protective activity in Swiss albino mice infected with influenza virus type B.The compound 2-morpholinyl-4-acetylamino-s-triazine, able to protect the animals when administered by oral route and non-toxic, has been tried in viral diseases in human beings.     

The influence of lithium on serum ceruloplasmin

Summary Serum ceruloplasmin oxidase activity did not change in mice treated orally for 120 days with Li₂CO₃ (0.58 mEq/kg/day). After a single i.p. injection of LiCl (20 mEq/kg), a significant activation of ceruloplasmin was observed.R. R. A. is working with a research grant from the Conselho Nacional de Pesquisas (National Research Council of Brasil).     

Die Hämagglutination des Influenzavirus A2-Hongkong

Summary A₂-Hongkong influenza virus does not agglutinate the erythrocytes of the cow, the calf, the horse, the pony and the spiny mouse at room temperature, while the A₂-Asia influenza virus causes agglutination. At a temperature of 4 °C A₂-Hongkong was able to agglutinate the erythrocytes of all species examined except those of the spiny mouse. Whether the A₂-Hongkong virus does or does not agglutinate the erythrocytes of the chicken, the donkey, the goat, the spiny mouse and the horse at room temperature could depend on the speed of elution.     

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.     

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.     

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     

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.     

Quantitative cytophotometric analyses of mesenteric mast cell granulation in acute soman intoxicated rats

Summary Effects of the organophosphate neurotoxin soman on rat mesenteric mast cell granule content were determined using scanning-integrating microdensitometric analysis of individual cell metachromasia. Mast cell degranulation was evidenced both with sublethal (0.5 LD₅₀) and lethal (1.5 LD₅₀) dosages and as early as 3–10 min post-injection. These data indicate a possible contribution of mast cell autacoids in the genesis of organophosphate-induced respiratory and circulatory collapse.Supported by U.S. Army Medical Research and Development Command Contract DAMD-17-81-C-1202.     

Encephalomyocarditis (EMC) virus-induced diabetes mellitus prevented byCorynebacterium parvum in mice

Summary Corynebacterium parvum prevented the development of encephalomyocarditis virus-induced diabetes in mice, when it was given 3–14 days before the virus infection. This treatment inhibited virus replication in the pancreas of the infected mice at an early stage of the infection.