Protection of hamsters by Venezuelan equine encephalitis virus candidate vaccine V3526 against lethal challenge by mosquito bite and intraperitoneal injection.

In an attempt to improve the current live, attenuated vaccine (TC-83) for Venezuelan equine encephalitis virus (VEEV), specific mutations associated with attenuation of VEEV in rodent models were inserted into a full-length cDNA clone of the Trinidad donkey strain of VEEV by site-directed mutagenesis. Because some viruses have been reported to be more pathogenic when introduced by mosquito bite than the same virus introduced by needle inoculation, there were concerns that the presence of mosquito saliva, or changes in the virus caused by replication in a mosquito, might allow the virus to overcome the protective effects of prior vaccination with V3526. Therefore, we determined if hamsters vaccinated with V3526 were protected from challenge with the virulent Trinidad donkey strain of VEEV. All non-vaccinated hamsters died after intraperitoneal challenge or after being fed on by VEEV-inoculated Aedes taeniorhynchus. In contrast, hamsters vaccinated with V3526 were resistant to intraperitoneal challenge and infection by VEEV-infected Ae. taeniorhynchus. Therefore, the V3526 candidate vaccine elicits protection against VEEV infection by mosquito bite.

The effect of steroids and ammonium chloride acidosis on phosphoenolpyruvate carboxykinase in rat kidney cortex. II. The kinetics of enzyme induction

The kinetics of the induction of rat kidney phosphoenolpyruvate carboxykinase activity after triamcinolone and ammonium chloride administration have been investigated with a view to the further differentiation of the two processes. The half-life of kidney phosphoenolpyruvate carboxykinase activity, as measured from the decay curve after a single dose of triamcinolone, is approximately 1.4 hr. This compares with a half-life for the enzyme from acidotic kidney of approximately 3.4 hr. Analysis of the data indicates that the induction of phosphoenolpyruvate carboxykinase activity by triamcinolone may be attributed to an increase in de novo protein synthesis. Induction by acidosis is qualitatively distinct and is partly attributed to a reduction in the rate of decay of phosphoenolpyruvate carboxykinase activity. The activities of the gluconeogenic enzymes glucose-6-phosphotase, fructose-1,6-diphosphotase and phosphoenolpyruvate carboxykinase in both liver and kidney have been measured in animals separately treated with triamcinolone and ammonium chloride. Triamcinolone significantly increases the activities of liver phosphoenolpyruvate carboxykinase, kidney glucose-6-phosphatase, and kidney phosphoenolpyruvate carboxykinase only; ammonium chloride stimulates a 200 percent increase in kidney phosphoenolpyruvate carboxykinase, but has no effect on the other enzymes. The induction processes whereby triamcinolone increases phosphoenolpyruvate carboxykinase activities in liver and kidney differ qauntitatively. (AU

Studies on hypoglycin toxicity in rats. I. Changes in hepatic ultrastructure

Hypoglycin is a toxic amino acid found in the unripe ackee fruit. The ackee is a popular item of diet in Jamaica and has been proposed as a cause of the so-called vomiting sickness. Hypoglycin is thought to act by inhibiting the oxidation of long-chain fatty acids, uncoupling oxidative phosphorylation, and interfering with gluconeogenesis. Hypoglycin was given intraperitoneally to rats in a dose of 10 mg/100 g, and samples of liver taken at hourly intervals up to 5 hr were studied with the electron microscope and compared with controls. The major ultrastructural findings in the hypoglycin-treated rats were progressive mitochondrial swelling with loss of granules and pallor of the matrix, followed by incorporation into autophagic vacuoles. These findings correlate well with the reported biochemical mechanisms.(AU)

The teratogenicity of barbital sodium in mice

The teratogenic activity of sodium barital in pregnant mice of the Rockfeller strain was investigated. A high incidence of foetal resorption and congenital malformations were observed following the i.p. administration of the barbiturate. (Summary)

Alizarin red in the study of the apposition and resorption of bone

Alizarin red is given intraperitoneally in dosages of 50-200 mg per kg. It stains visibly only one generation of bone. Its deposition is studied in gross specimens and in undecalcified sections, and is controlled by comparison with serial decalcified sections. Apposition of white bone can be followed in relation to red bone on periosteal surfaces (where it presents appearances corresponding to different growth rates), on endosteal surfaces, in osteons, and in the interstitial compaction of cancellous bone. Red surfaces may be sites of deposition, stasis, or resorption. Measurements may be made from red lines, provided microscopic control is available. Removal of red bone implies resorption. It is closely correlated with the presence of osteoclaasts in control sections and with areas of surface pitting grossly. Resorbing surfaces may be precicely delimited by studing a graded series of animals. Whole surfaces or zones of stained bone are seen to drift to other situations, undergoing resorptive dissolution or consolidating anew as they move relative to the newer layers. The usefullness of the dye lies in its simplicity of administration, its ready visibility, and the fact that its persistence in bone enables the fate of areas of bone to be followed over long periods. The preparation of undecalcified sections is a problem common to many other techniques