Radioprotective effect of pyrazolone derivatives]

The intraperitoneal injection of analgin (1000 mg/kg), antipurine (400 mg/kg), amidopyrine (100 mg/kg) 3 hours before the irradiation of mice in a dose of 800 R led to survival of 30 to 45% of the animals (against 12.5% in control) and to increase in the average duration of life of the animals that perished. 80-95% of mice survived the period of "intestinal deaths" (the 7th day after the irradiation) after combined prophylactic use of purasolone derivatives and cystamine before the irradiation of these animals in a dose of 1050 R. The radioprotective effect of pyrasolone derivatives given in therapeutic doses was less pronounced.     

State of the hypothalamo-hypophyseal neurosecretory system of rabbits in anaphylactic shock]

With the aid of morphometric and histochemical methods a study was made of the hypothalamo-hypophyseal neurosecretory system of rabbits in anaphylactic shock. The following occurred in rabbits which survived the shock: an enlargement of the perikarions and reduction in the size of the nuclei and nucleoli of the neurosecretory cells; the content of the neurosecretory substance was increased in the whole neurosecretory system. In rabbits which perished from shock the nuclei and the nucleoli of the neurosecretory cells diminished to a lesser extent, perikarion measurements remained unchanged and the content of the neurosecretory substance in the posterior lobe of the hypophysis fell. Thus, in the animals which survived the shock the processes of synthesis of the neurohormones by the neurosecretory cells were sharply activated, but the secretion of the neurohormones from the posterior lobe of the hypophysis was inhibited; in animals which perished from shock the activation of the hormone formation in the neurosecretory cells was less pronounced, but the processes of the secretion of the neurohormones from the posterior lobe were apparently intensified.     

Action of Na-RNA on infection in mice infected with Shigella flexneri]

Experiments were conducted on albino mice. Experimentally induced dysentery infection proved to become aggravated under the effect of yeast Na-RNA expressed in the increase of the number of animals which fell ill and perished. This phenomenon proved to be based on the acceleration of reproduction of the causative agent, with a simultaneous selection of its virulent clones seen both in vitro and in vivo.     

Resistance of the heart sea urchin Echinocardium cordatum (Echinoidea: Spatangoida) to extreme environmental changes

The ability to survive under extreme environmental conditions was studied in the adults of the heart sea urchin Echinocardium cordatum (Pennant). At seawater temperatures of 13.3 to 14.8°C and salinity of 33.2–33.4‰, being devoid of the possibility to burrow into the sand or eat, some sea urchins died on day 5 and all individuals had perished by the end of day 8. At a temperature of 19°C, the salinity tolerance range of adults was limited to 33–28‰. Only 30 to 20% of sea urchins transferred to a solid substrate survived for 7 days at a salinity of 33 to 24‰, but all of them perished toward the end of day 8.     

Effects of Malaria (Plasmodium berghei) on the Maternal-Fetal Relationship in Mice

Plasmodium berghei infection was more severe in pregnant than in nonpregnant mice. Infection initiated on gestation day 7 resulted in rapidly increasing parasitemia and deaths of all pregnant mice within 12 days, while some nonpregnant mice survived until day 21 postinfection. When mice were infected on gestation day 12 or 14, a proportion of mice died before parturition; but some animals survived to deliver living pups. Reduced birthweights and increased spleen weight to body weight ratios were seen in pups from infected mice as compared with pups from uninfected animals. Histopathological abnormalities of placentae from infected animals included degeneration of the normal labyrinthine architecture and thickening of the trophobast separating maternal and fetal blood vessels.     

Deletion of the alpha(1,3)galactosyl transferase (GGTA1) gene and the prion protein (PrP) gene in sheep

Nuclear transfer offers a cell-based route for producing precise genetic modifications in a range of animal species. Using sheep, we report reproducible targeted gene deletion at two independent loci in fetal fibro-blasts. Vital regions were deleted from the alpha(1,3)galactosyl transferase (GGTA1) gene, which may account for the hyperacute rejection of xenografted organs, and from the prion protein (PrP) gene, which is directly associated with spongiform encephalopathies in humans and animals. Reconstructed embryos were prepared using cultures of targeted or nontargeted donor cells. Eight pregnancies were maintained to term and four PrP-/+ lambs were born. Although three of these perished soon after birth, one survived for 12 days. These data show that lambs carrying targeted gene deletions can be generated by nuclear transfer.     

Effects of alkaline polypeptides, cytomedins, from the kidney tissue on the immunity and hemostasis and the course of Masugi nephritis

In vivo experiment alkaline polypeptide in kidney was established to have anticoagulant effect and increases the expression of receptors on T lymphocytes in burned patients. In the experiment renalin decreases the percentage of perished animals, normalizes the indices of homeostasis and energy metabolism in animals with the developed Mazugi nephritis. In rats, which received renalin, less proliferation of mesangial cells and the absence of balloon dystrophy was found histologically.     

Ethanol antagonism by 5-hydroxymethyl cellular compounds.

The acute intoxicative action of ethanol in mice can be antagonized by the pyrimidine, 5-hydroxymethylcytosine, combined with any of the B₆ vitamin group with exception of pyridoxine. Sleeping time is markedly reduced in standard assays (p<0.01). The antagonist also counteracts a number of after-effects of ethanol. Mice treated with ethanol often show a characteristic syndrome after awakening from narcosis: lethargy, tremor and lack of coordination. These animals die within 72 hours, whereas mice treated with antagonist do not exhibit these symptoms and have a negligible mortality rate in this period. 5-HMC does not appear to alter significantly the metabolism or excretion of alcohol, or its entry into the brain. The action of 5-hydroxymethyl-cytosine and pyridoxal as an antagonist accords with a possible enzymatic mechanism. The reversal of acute ethanol effects by 5-hydroxymethyl-cytosine and pyridoxal may thus result from a competition of their hydroxymethyl groups with the ‘hydroxyethyl’ of ethanol for enzymatic reaction sites.     

Development of the graft versus host reaction and its influence on pregnancy in mice following heparin administration]

The influence of heparin on the graft-versus-host reaction (GVHR) and the peculiarities attending the development of pregnancy in female animals which survived after the GVHR were studied. Preliminary administration of heparin to the recipients prevented their death or increased their life span. An intensification of the GVHR was noted after the administration of heparin to donors or its addition to the transplanted cells. In mice which survived after the GVHR as a result of heparin administration the intrauterine fetuses death and abortions were noted in 60-100% of cases during subsequent pregnancy (3 to 6 months after the cell transplantation). In the case of repeated pregnancies of these female animal pathology of pregnancy was less frequent; however, some of the offspring displayed the rant syndrome. No such disturbances of pregnancy were observed in mice given heparin alone or in those which survived after the transplantation of lymphoid cells only. The sustained pregnancy promoted the intensification of the GVHR induced in the female animals earlier after the heparin administration.     

Toxic activity of Penicillium citrinum metabolites on Mus musculus mice

The aims of this work were to study the influence of secondary metabolites produced by a Penicillium citrinum strain. Mus musculus mice were fed with a diet containing those metabolites to determine both its influence on their development and the pathological and biochemical changes on experimental animals. Male and female including pregnant females, were studied. One group received commercial feed (A.B.) to which the citrinin- producing mould had been added (LF), another received A.B. contaminated with commercial citrinin (LC). The last group received noncontaminated feed (LT). The animals were weighed weekly, and sacrificed after sixty days, so that they could be studied both macro and microscopically. In LF and LT mice, haematological analysis was carried out and hemosiderin was looked for in urine. The diet of the newborne mice, after weaning, was identical to that of their parent. The treated animals (LF and LC) showed morphological alterations, a significant decrease in weight and morphologic alterations and hemosiderin granules were detected in some of their organs. In LT all breeds survived, none of the mice showed neither macro nor microscopic anomalies and had normal biochemical parameters. Fewer breeds in LF survived, male infertility was detected and some of their haematologic parameters were also measurably lower.     

Obtention and Assay of Rabbit Anti-Pseudomonas Serum

Inoculation of rabbits with a nonliving anti-Pseudomonas vaccine induced appreciable levels of agglutinating antibodies against strains of P. aeruginosa included or not included in the vaccine. Serum obtained from vaccinated rabbits was able to confer temporary protection to mice against challenge with homologous or heterologous strains of Pseudomonas. When two or three doses of serum were used, all mice survived the challenge dose for more than 48 hr, but some of the animals died 10 days after challenge. When five doses of serum were used, all mice survived this 10-day period, and even 4 months later they did not show any sign of infection. Serum treatment temporarily inhibited Pseudomonas activity and allowed for the activation of the immunogenic mechanisms of the animals. This was corroborated by the fact that mice treated with three doses of serum and surviving the challenge dose for more than 20 days were immune against a second challenge. Anti-Pseudomonas gamma globulin conferred a lower degree of protection against homologous or heterologous strains of Pseudomonas.     

Simulation of the interactions of predatoryTyphlodromus mites with the European red mite,Panonychus ulmi (Koch)

Interactions of Typhlodromus mites and their prey, the European red mite, in orchard settings were examined through computer simulation. In particular, the consequences of very slow dispersal by the predators, compared with the weather-dependent higher rates of prey dispersal, were elucidated. In simulations of the interactions of the predator and its prey, both dispersal and temperature strongly affected the available supply of juvenile prey, and thus could determine whether the predators on an individual tree survived or perished.     

The anamnestic neutralizing antibody response is critical for protection of mice from challenge following vaccination with a plasmid encoding the Japanese encephalitis virus premembrane and envelope genes.

For Japanese encephalitis (JE), we previously reported that recombinant vaccine-induced protection from disease does not prevent challenge virus replication in mice. Moreover, DNA vaccines for JE can provide protection from high challenge doses in the absence of detectable prechallenge neutralizing antibodies. In the present study, we evaluated the role of postchallenge immune responses in determining the outcome of JE virus infection, using mice immunized with a plasmid, pcDNA3JEME, encoding the JE virus premembrane (prM) and envelope (E) coding regions. In the first experiment, 10 mice were vaccinated once (five animals) or twice (remainder) with 100 micrograms of pcDNA3JEME. All of these mice showed low (6 of 10) or undetectable (4 of 10) levels of neutralizing antibodies. Interestingly, eight of these animals showed a rapid rise in neutralizing antibody following challenge with 10,000 50% lethal doses of JE virus and survived for 21 days, whereas only one of the two remaining animals survived. No unimmunized animals exhibited a rise of neutralizing antibody or survived challenge. Levels of JE virus-specific immunoglobulin M class antibodies were elevated following challenge in half of the unimmunized mice and in the single pcDNA3JEME-immunized mouse that died. In the second experiment, JE virus-specific primary cytotoxic T-lymphocyte (CTL) activity was detected in BALB/c mice immunized once with 100 micrograms of pcDNA3JEME 4 days after challenge, indicating a strong postchallenge recall of CTLs. In the third experiment, evaluation of induction of CTLs and antibody activity by plasmids containing portions of the prM/E cassette demonstrated that induction of CTL responses alone were not sufficient to prevent death. Finally, we showed that antibody obtained from pcDNA3JEME-immunized mice 4 days following challenge could partially protect recipient mice from lethal challenge. Taken together, these results indicate that neutralizing antibody produced following challenge provides the critical protective component in pcDNA3JEME-vaccinated mice.     

Effectiveness of phosphomycin and its combinations with amikacin and cefotaxime in experimental plague infection]

When administered intramuscularly in doses of 8 and 16 mg/mouse, phosphomycin was highly active in the treatment of albino mice with experimental plague infection (80-100-percent protection of the animals from death). Combinations of phosphomycin with cefotaxime in inefficient or not sufficiently efficient doses had a synergistic effect. When the albino mice were treated with combinations of phosphomycin and amikacin, the percentage of the survived animals significantly increased in comparison to that after the use of the antibiotics alone.     

Detection of Toxoplasma gondii by polymerase chain reaction in sera of acutely infected mice

The presence of Toxoplasma gondii DNA was detected in sera of acutely infected mice by polymerase chain reaction. Adult mice were inoculated intraperitoneally with 5 x 10(3) T. gondii RH strain tachyzoites. Five mice were killed every 3 hr from 3 to 21 hr post infection (PI) and every day from 1 to 7 days PI. Toxoplasma gondii DNA was first detected in 60% of the infected mice 18 hr PI and in 100% of the animals 21 hr PI and from 1 to 7 days PI. No mice survived longer than 7 days.     

Quinolone therapy in the prevention of mortality after irradiation

The effect of oral therapy with three quinolones (ofloxacin, ciprofloxacin, and pefloxacin) in the prevention of postirradiation bacteremia and mortality was tested in B6D2F1 mice given 9.5 Gy 60Co gamma radiation. Only 8 of 60 (13%) untreated mice survived for 30 days, compared to 47 of 60 (78%) mice treated with ofloxacin, 44 of 60 (74%) mice treated with ciprofloxacin, and 42 of 60 (70%) mice treated with pefloxacin (P less than 0.05). The organisms recovered from the mice were Streptococcus spp. and Enterobacteriaceae. More Enterobacteriaceae were recovered from the livers of untreated animals than from the mice treated with the quinolones. However, no reduction in the number of Streptococcus spp. was noted in the animals given quinolones when compared to controls. This study shows that quinolones prolonged survival and decreased systemic spread of Enterobacteriaceae up to 30 days after exposure of mice to lethal irradiation.     

Tyrosine hydroxylase activity in Venezuelan equine encephalomyelitis virus infection

In rats inoculated with the Venezuelan equine encephalomyelitis (VEE) virus, a significant decrease was found in the tyrosine hydroxylase activity of neostriatum, midbrain, and hypothalamus during the acute phase of the infection. In animals that survived the acute infection, we observed no changes in the enzymatic activity in the same regions studied. Our findings suggest a vulnerability of the dopaminergic and noradrenergic pathways to the infection produced by VEE virus.     

Selective treatment of leukemia L1210 with combination of deoxycytidine and lethal doses of cytosine arabinoside]

Oral administration of deoxycytidine simultaneously with intraperitoneal injections of toxic doses of cytosine arabinosidetomice with advanced L1210 leukemia diminished the toxic effects preventing drug death of these mice. They developed a marked antitumor effect. The mean survival time of these mice was considerably extended as compared to that of untreated animals or those given one of these drugs alone. At the optimum schedule of treatment about 23% of the mice survived over 60 days. Deoxycytidine protection reduced the antileukemic effect of cytosine arabinoside administered in nontoxic doses. The deoxycytidine plus cytosine arabinose combination was ineffective in the treatment of transplantable myeloid leukemia in mice.     

Herpes simplex virus type 2 UL24 gene is a virulence determinant in murine and guinea pig disease models

A herpes simplex virus type 2 (HSV-2) UL24 beta-glucuronidase (UL24-betagluc) insertion mutant was derived from HSV-2 strain 186 via standard marker transfer techniques. Cell monolayers infected with UL24-betagluc yielded cytopathic effect with syncytium formation. UL24-betagluc replicated to wild-type viral titers in three different cell lines. UL24-betagluc was not virulent after intravaginal inoculation of BALB/c mice in that all inoculated animals survived doses up to 400 times the 50% lethal dose (LD50) of the parental virus. Furthermore, few UL24-betagluc-inoculated mice developed any vaginal lesions. Intravaginal inoculation of guinea pigs with UL24-betagluc at a dose equivalent to the LD50 of parental virus (approximately 5 x 10(3) PFU) was not lethal (10/10 animals survived). Although genital lesions developed in some UL24-betagluc-inoculated guinea pigs, both the overall number of lesions and the severity of disease were far less than that observed for animals infected with parental strain 186.     

TPA (12-O-tetradecanoyl-phorbol-13-acetate) as a carcinogen for mouse skin. A positive dose-response relationship

In order to study a possible dose/response relationship in the tumorigenic effect of 12-O-tetradecanoyl-phorbol-13-acetate (TPA), groups of hairless mice were treated topically on the back skin with different doses and treatment schedules of TPA in acetone. A group of 104 mice (56 M/48 F) received a single application of 20 nmol TPA; 80 mice (32 M/48 F) received 2 X 20 nmol TPA at 3 day intervals; 95 mice (48 M/47 F) received five applications; and 32 mice (16 M/16 F) received 50 applications of 20 nmol TPA twice weekly. Two groups of 32 mice (16 M/16 F) were painted topically on the back skin twice weekly with doses of 17 and 10 nmol TPA, respectively, in each application for 60 weeks or until the animals died. All applications were given in 0.1 ml reagent grade acetone. A control group was treated twice weekly with acetone alone for 60 weeks. Long-term application of 17 nmol TPA was toxic to the animals, and only 20% survived 10 months. Doses of 10 nmol TPA twice weekly were less toxic, and 80% of the animals survived 14 months. The other doses were fairly non-toxic. The results were assessed statistically by accepted methods for tumor rates and yields, respectively. There was a significant tumor incidence after the higher doses of TPA and a clear dose-response relationship. This further strengthens the evidence that TPA is a complete carcinogen, and not merely a promoter.