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PubMedDate not supplied

[The protective effect of alpha-tocopherol characterized by erythron system indices in rats with chronic nitrite intoxication].

The effect of alpha-tocopherol administered in a dose of 15 and 150 mg/kg on the erythron system was studied in rats subjected to chronic nitrite intoxication. The chronic poisoning with sodium nitrite led to three-phase changes in the concentration of erythrocytes (RBC count) and hemoglobin and to activation of the erythropoiesis and erythrophagocytosis processes. The introduction of alpha-tocopherol on the background of intoxication with sodium nitrite prevents from the development of erythropenia, causes erythrocytosis (in large doses), decreases the degree of cytoarchitectonic changes, and reduces the erythropoiesis and erythrophagocytosis activity.

Animals↗

PubMedDate not supplied

[Anti-enterovirus and immunostimulating activity of the polyphenol complex extracted from Pethaphylloides fruticosa (L.) O. Schwarz].

Studied within the present case study was the antiviral and viricidal activity of the water-soluble polyphenol complex, obtained from Penthaphylloides fruticosa (L.) O. Schwarz, in respect to Enteroviruses Coxsackie B. The complex had a low toxicity and high chemotherapeutic index when introduced experimentally in the cell culture. The therapeutic effect of the water-soluble extract was detected in an experimental infection of newborn mice caused by Coxsackievirus B3. The interferongenic and immunostimulating action of the drug were demonstrated. The results obtained are in favor of further research of the extract as of a promising antiviral drug.

Adjuvants, Immunologic↗

PubMedDate not supplied

[New acellular pertussis vaccine, containing glucosaminylmuramyldipeptide].

As shown in this work, the synthetic immunomodulator glucosaminylmuramyldipeptide (GMDP) can be included into acellular pertussis vaccine (APV). The optimal doses of GMDP, ranging from 0.001 to 0.0001 microg, have been found. These doses enhance the protective activity of APV, especially its low-active doses. GMDP decrease the manifestations of toxic, anaphylactogenic and pyrogenic properties of APV, which may lead to the decrease of the antigenic load of APV on the body of the vaccines and thus to lessening the side-effects of vaccination. GMDP has been shown to considerably increase, in comparison with common pertussis vaccine and APV, the percentage of phagocytizing leukocytes by day 14. The immunization of mice with APV with and without GMDP in doses of 0.01 and 0.001 microg leads to a change in T-lymphocyte/B-lymphocyte ratio in the population of spleen lymphocytes.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMedDate not supplied

[Influence of the activation of the immune system cells on the parameters of lipid metabolism in macrophages].

The influence of tumor necrosis factor a (TNF-alpha) and media, conditioned by activated macrophages and lymphocytes and containing a complex of biologically active compounds (including cytokines), on the parameters of lipid metabolism in macrophages was studied. The addition of recombinant TNF-alpha and immunocompetent cell-conditioned media to mouse peritoneal macrophages culture stimulated labelled oleate incorporation into cholesterol esters and triglycerides, as well as labelled glycerine incorporation into cholesterol esters, but inhibited labelled cholesterol incorporation into cholesterol esters. One of the mechanisms of the influence of activated immunocompetent cells on cholesterol metabolism in macrophages was, supposedly, the stimulation of sphigmomyelinase activity by a complex of anti-inflammatory cytokines produced by these cells on their activation.

Animals↗

PubMed2004

Tissue distribution and elimination of selected chlorinated naphthalenes.

OBJECTIVES: Polychlorinated naphthalenes are widespread, persistent environmental pollutants. Commercial products are generally mixtures of several congeners and range from thin liquids to hard waxes of high melting point. The higher chlorinated naphthalene products are used as impregnants for condensers and capacitors and dipping encapsulating compounds in electronics. The aim of this study was to investigate the disposition of penta- and tetrachloronaphthalene in rats following a single intraperitoneal administration. MATERIALS AND METHODS: Experiments were performed on male Outbred Wist rats with body weight of 200-250 g. Both compounds labeled with tritium, were given intraperitoneally in a single dose of 10 mg/kg body weight. Blood and selected tissues distribution of 3H-radioactivity as well as urine and feces excretion from 0 to 336 h were traced following the administration. RESULTS: After 120 h about 70% of the given dose was excreted in feces. Feces proved to be the main route of tritium excretion; only about 6% were excreted in urine within 120 h. In all the examined tissues, the highest 3H concentrations were found in the fat tissue, liver, kidneys and adrenals. CONCLUSIONS: Following calculations of the balance of total tritium excreted and stored, it was found out that both chloronaphthalenes belong to compounds of slow turnover rate in the rat body, and especially in the case of repeated exposure they might accumulate in the body.

Animals↗

PubMed2005

Eradication of enteric helicobacters in Mongolian gerbils is complicated by the occurrence of Clostridium difficile enterotoxemia.

Outbred Mongolian gerbils from a United States commercial source were examined for colonization with naturally occurring enterohepatic Helicobacter spp. Helicobacter spp. were identified in the cecum and colon by culture and by using genus-specific primers in polymerase chain reaction (PCR) assays. Nutritionally balanced triple-antibiotic wafers (containing amoxicillin, metronidazole, and bismuth) used previously to eliminate helicobacter infections in mice were administered in an attempt to eradicate the naturally occurring novel helicobacters in the gerbils. After 7 days of antibiotic treatment, two of the experimental animals died due to Clostridium difficile-associated enterotoxemia. However, at 3 weeks after antibiotic cessation, the surviving three animals had no Helicobacter spp. in the cecum or colon according to PCR analysis. Eradication of Helicobacter spp. using dietary administration of antibiotics was complicated by the presence of toxin-producing C. difficile. An alternate method to develop helicobacter-free gerbils (such as Caesarian rederivation) may be necessary.

Animals↗

PubMed2005

Therapeutic effect of subcurative dose praziquantel on Schistosoma mansoni infected mice and resistance to challenge infection after treatment.

The therapeutic effect of a subcurative dosage of praziquantel (PZQ) on Schistosoma mansoni infected mice and resistance to challenged worm infection after treatment were assessed and compared with conventional treatment using a curative dosage of PZQ. S. mansoni infected mice were treated with PZQ at a curative dosage (600 mg kg(-1)) or a subcurative dosage (300 mg kg(-1)) at 9 weeks after infection. Untreated mice and non-infected mice were added as controls. The therapeutic effect of the drug was evaluated in terms of the mortality of mice after treatment, and the parasitological and pathological findings in mice sacrificed at 1 week, 1 month, or 3 months after treatment. Another sample of mice was not killed but challenged with S. mansoni cercariae at 1 week, 1 month, or 3 months after treatment. Resistance to re-infection was evaluated by the extent of challenged worm reduction. In conclusion, there was no significant difference in mortality, or parasitological and pathological findings between mice treated with PZQ at the two dosages. However, resistance to challenged worm infection was more sustained in the group treated with subcurative dose PZQ, especially at 3 months after treatment.

Animals↗

PubMed2005

[Change in pain reaction by combined action of nitric oxide modulators and low intensity electromagnetic field].

In experiments on mice with the tonic pain caused by introduced of 5% of formalin in hindpaw, are quantitatively measure changes of painful behavioural reaction (PBR) values under action low intensity electromagnetic field (EMF) and substances that modulate activity of NO-synthase system, and at both of these action also. Such substances were used: in quality inhibitor NO-synthase--Nw-nitro-L-arginin (L-NAME), donors NO--sodium nitroprusside (SNP) and sodium nitrite (SN). Influence of the EMF completely eliminated effect of the L-NAME and SN in concentration of 0.5 mM/l, and also SNP in concentration 5 mcM/l on the painful reaction. The assumption that neurogenetics and NO- ergic mechanisms are basis of the systems analgesic effects of the low intensity electromagnetic fields. Mechanisms of modulation of painful behavioural reaction and other behavioural displays of animals under condition EMF and NO are discussed.

Animals↗

PubMed2006

[Microsatellite DNA monitoring in inbred cultivation of outbred rats].

Microsatellite DNA was used to monitor the gene inheritance of successive generations of rats. It is useful in selective breeding to quickly bring genes to homozygosity and to shorten the cultivation periods of new inbreeding of rats. Thirty microsatellite DNA loci were PCR amplified to analyze the DNA polymorphism in generational crosses between the outbred Wistar and SD rats. Rats in F generations with a moderate to high coefficient of similarity with the female F0 SD rats were crossed. All loci in the F2 generation were heterozygous and polymorphic. By F9, 27 loci have become homozygotic, with a homozygosity rate of 90%. The coefficient of similarity tended to increase at a rate of 6%-20% with each successive generation. Skin grafting confirmed no rejection among the F9 generation of rats. Therefore we have established a novel method for rapid cultivation of inbred rats.

Animals↗

PubMedDate not supplied

Inhibition of large intestinal cancers by celecoxib using a serial sacrifice technique.

In this serial sacrifice experiment, celecoxib (C) was administered at a 0.1% dose level, in the diet of female Swiss Webster CFW outbred mice. The animals also received either 1,2-dimethylhydrazine dihydrochloride (1,2-DMH) as ten weekly subcutaneous (s.c.) injections at 20 microg/g body weight or physiological saline (PS) as ten weekly s.c. injections at 0.01 ml/g body weight. Subsequently, the mice were sacrificed at 26 weeks or 35 weeks after the first injection of 1,2-DMH or PS. The number of mice with large intestinal tumors and the total number of these tumors were: Group 1 (1,2-DMH), 29 and 438; Group 2 (C + 1,2-DMH), 18 and 64; and Group 3 (PS), 1 and 1, in the mice sacrificed at 26 weeks. The corresponding tumor incidences in the mice sacrificed at 35 weeks were: Group 1 (1,2-DMH), 30 and 323; Group 2 (C + 1,2-DMH), 23 and 134; and Group 3 (PS), 0 and 0. Histopathologically, the tumors were diagnosed as polypoid adenomas and adenocarcinomas of the cecum, colon and rectum. Celecoxib treatment inhibited the development of large intestinal cancers in mice sacrificed at 26 or 35 weeks after the first injection of the carcinogen.

1,2-Dimethylhydrazine↗

PubMedDate not supplied

[Adaptation of different modifications of enzyme immunoassay and immune blot assay to assess the candidate vaccine HIVREPOL against HIV/AIDS].

A preclinical trial of the vaccine HIVREPOL provided a complex of methods for assessing the identity and specific activity of vaccines against HIVIAIDS. The identity of "HIVREPOL" has been assessed by indirect enzyme immunoassay (EIA): the vaccine specifically binds the antibodies of the sera from HIV-infected individuals. Immune blot assay was the most informative method for assessing the identity of the candidate vaccine. The sera from HIVREPOL-vaccinated mice recognized the proteins gp41, p24, p55 of cultured HIV1 on "New-Lay-Blot1" strips. The bands corresponding to p24 were revealed in the line blots "Blot-HIV-1/2+O" and "INNO-LIA-HIV-Confirmation". The specific activity of the HIVREPOL vaccine was confirmed from the reactivity of sera of the mice vaccinated with recombinant proteins of the immunosorbents available in EIA test systems for the detection of HIV antibodies. Competitive EIA established the antigen-binding activity of sera from HIVREPOL-vaccinated mice against the native reference HIV-1 antigen.

AIDS Vaccines↗

PubMed2004

To enrich or not to enrich: providing shelter does not complicate handling of laboratory mice.

Environmental enrichment (EE) is used in laboratory animal housing to provide stimuli exceeding those of barren cages and is intended to improve the welfare of captive animals. It is argued that when laboratory mice can routinely retreat in sheltering objects when humans are present, they do not habituate to humans and continue to shy away, thereby increasing the time needed for husbandry and testing procedures. To this date very limited research has been carried out to determine whether providing EE in the form of shelter interferes with the habituation of mice to humans and thus complicates catching and handling them. We housed 20 FVB (inbred) and 20 NMRI (outbred) male mice in standard cages and another 20 FVB and 20 NMRI male mice in cages enriched with two PVC conduits. When the mice were 10 weeks old, measurements of food and water consumption, weight, latency of catching, and a behavior score in response to handling during a sham subcutaneous injection were performed weekly for 4 consecutive weeks. Food and water consumption and weight were influenced by strain, but the presence of EE in the home cage did not affect these parameters as much. Outbred mice ate, drank, and weighed more than did the inbred animals, but they did not significantly gain weight during the course of the 4 testing weeks. Cage enrichment in the form of PVC conduits decreased the time needed to catch outbred animals and did not increase the time needed to catch mice from the inbred strain. Furthermore, no differences in resistance to being held during the sham injection could be detected between animals from the enriched versus non-enriched group. These results indicate that EE in the form of sheltering objects does not complicate catching or handling mice and that allowing access to enrichment in the laboratory cage, which has been shown to have positive effects on welfare, does not interfere with the management or cost of laboratory animals.

Animal Husbandry↗

PubMed2005

NIH Swiss and Black Swiss mice have retinal degeneration and performance deficits in cognitive tests.

Swiss mice are among the most commonly used outbred strains in biomedical research. Because prior knowledge of the baseline phenotypes of mouse strains will allow informed selection of strains for particular experiments, we sought to characterize the behavior of two previously untested outbred Swiss strains--NIH Swiss and Black Swiss--in the two most widely used paradigms for evaluating the cognitive abilities of mice. Unlike the C57BL/6J and C57BL/6J-Tyr(c-2J) controls, animals of both outbred Swiss strains were unable to demonstrate learning in the Morris water maze and contextual fear conditioning paradigms. A polymerase chain reaction assay revealed that all of the NIH Swiss and Black Swiss mice tested were homozygous for the recessive retinal degeneration 1 mutation of the Pde6b gene. Histological examination of NIH Swiss and Black Swiss mouse eyes confirmed the presence of retinal degeneration, which causes visual image blindness. These findings indicate that NIH Swiss and Black Swiss mice are visually im paired and thus may be unsuitable for use in some experiments.

Animals↗

PubMed1993

Toxicity testing and genetic quality control.

The genetic background of animals plays a major role in the outcome of toxicity tests. The use animals with a defined and standardized genetic variation as opposed to animals from an outbred strain may improve the quality of the tests and may reduce the numbers of animals to be used. In order to achieve this, animals from distantly related inbred strain (and their F1 hybrids) should be matched up in test and control groups (block design). The genetic distance between strains can be estimated by comparing the genetic profiles of strains which have been characterized for a set of monogenic marker genes. The establishment of the genetic strain profiles is also necessary when selecting the marker genes which are to be used for the genetic quality control of inbred strains. DNA markers, in particular the highly polymorphic SSLP's (microsatellites) are the most appropriate ones for this purpose.

Animals↗

PubMed1992

Outcome of herpes simplex virus type 2 infection in guinea pigs.

Factors that influence the outcome of genital herpes simplex virus (HSV) infection were explored in a guinea pig model. The viral inoculum required to establish infection in 50% of animals (ID50) was similar for inbred (strain 2) and outbred (Hartley) guinea pigs. However, the viral inoculum required to produce clinical disease in 50% of the animals (CD50) was 10 times greater for strain 2 compared to Hartley animals. HSV infection of both inbred and outbred animals was more likely to result in death of weanling than adult animals. The duration and severity of genital disease and the magnitude of vaginal viral replication were similar for strain 2 and Hartley animals in both young and adult animals. The lethal dose for 50% of animals (LD50) was 100-fold greater than the CD50 for Hartley animals, but the LD50 and the CD50 were equal in strain 2 guinea pigs. Viral cultures of homogenized neural tissues from infected animals revealed that HSV ascended to the level of the temporal cortex in strain 2 guinea pigs while virus was never recovered above the lumbar spinal cord in Hartley animals. Endogenous peripheral blood mononuclear cell-mediated cytolytic activity against HSV-infected targets was greater prior to HSV inoculation in survivors compared to animals that died. A fatal outcome of genital HSV-2 may relate to the failure to limit CNS viral replication. Death is more common among guinea pigs that have low endogenous HSV-directed natural killer activity, such as occurs among strain 2 and young animals whether inbred or outbred.

Administration, Intravaginal↗

PubMed1993

Genetic variation within and between strains of outbred Swiss mice.

The aim of this survey was to measure levels of genetic variation within and between 5 different strains of outbred Swiss mice. Ten to 15 animals from each strain (NIH, Q(S), ARC, IMVS and STUD) were typed, using allozyme electrophoresis, at 10 gene loci: Mod-1, Idh-1, Gpi-I, Es-1, Es-3, Hbb, Pep-3, Gr-1, Got-2 and Pgm-1. Polymorphic variation in at least one of the 5 strains was detected at all 10 loci. The proportion of polymorphic loci ranged from 0.3 (NIH) to 0.8 (IMVS) with a mean of 0.52. Average expected heterozygosities ranged from 0.08 (NIH) to 0.37 (IMVS) with a mean of 0.21. The inbred strain SWR was, as expected, homozygous at all 10 loci. The amount of allelic substitution between pairs of strains was quantified using Nei's genetic distance, and a dendrogram based on these genetic distances showed a close overall similarity in its branching pattern to the known genealogy of the strains. This survey showed that a considerable degree of genetic variation persists in the 5 strains examined, a level of variation similar to that previously detected by Rice and O'Brien (1980) in 3 other outbred Swiss strains.

Animals↗

PubMed2002

Strain variation of immature female rats in response to various superovulatory hormone preparations and routes of administration.

The purpose of this study was to examine the response of rats of different genetic backgrounds to various superovulatory hormonal treatments. Immature Sprague Dawley (SD), FBNF1, and F344 female rats (30 to 35 days of age) were used for this study as representatives of outbred, hybrid, and inbred strains respectively. Animals from each strain were allocated into four groups of hormone treatments as follows: 1) 30 IU pregnant mare serum gonadotrophin (PMSG) intraperitoneally (i.p.) followed 52 h later with 25 IU human chorionic gonadotrophin (HCG) i.p.; 2) 15 IU PMSG i.p. followed 52 h later with 7.5 IU HCG i.p.; 3) 1.0 IU follicle stimulating hormone (FSH) daily via Alzet mini-pumps for 60 h; and 4) 1.0 IU FSH daily via Alzet mini-pumps for 54 h followed by 10 mg luteinizing hormone (LH). The efficacies of the hormone treatments were evaluated using the following criteria: % mated, % ovulated, total oocytes per female, and % fertilized. The % mated of SD rats treated with PMSG(30)+HCG(25) was significantly higher (P < 0.05) than that of animals treated with PMSG(15)+HCG(7.5); in addition, the total oocytes per female was significantly higher (P < 0.05) for SD animals receiving PMSG(30)+HCG(25) than all other treatments. The % ovulated of SD rats was significantly lower (P < 0.05) in response to FSH alone as compared to all other treatments. The % ovulated for FBNF1 rats was significantly greater (P < 0.05) in response to both PMSG+HCG treatments as compared to FSH and FSH+LH. The % ovulated and % fertilized were significantly lower (P < 0.05) in F344 rats treated with FSH alone as compared to all other treatments. F344 rats produced significantly (P < 0.05) more oocytes per female in response to both PMSG+HCG treatments as compared to FSH and FHS+LH. The % ovulated of SD and F344 rats were significantly higher (P < 0.05) than that of FBNF1 rats in response to FSH and FSH+LH. SD rats produced a significantly greater (P < 0.05) number of oocytes per female than did FBNF1 rats in response to PMSG(30)+HCG(25) and a significantly greater (P < 0.05) number of oocytes per female as compared to those of FBNF1 and F344 rats in response to FSH and FSH+LH. The % fertilized of SD and FBNF1 rats were significantly higher (P < 0.05) than that of F344 rats in response to PMSG(15)+HCG(7.5). Our study demonstrates that treatment with PMSG+HCG is an effective method of eliciting superovulatory responses according to most criteria examined. We have also shown that outbred (SD) rats generally produced more oocytes per female in response to hormonal stimulation than did inbred and hybrid rats. Our results indicate that different strains of rats have various degrees of hormone sensitivity and response to different superovulation protocols.

Animals↗

PubMed2005

Strain differences in superovulatory response, embryo development and efficiency of transgenic rat production.

The differences between rat strains in superovulation response, in vitro and in vivo development of preimplantation embryos and overall transgenic efficiency was studied. The protocols for induction of superovulation using single injections of pregnant mare's serum gonadotropin (PMSG) or minipumps with follicle stimulating hormone (FSH) were compared in Lewis (LEW), Wistar-Kyoto (WKY), and stroke-prone spontaneously hypertensive rats (SHRSP) or Sprague-Dawley (SD) and Wistar rats as representative inbred or outbred strains, respectively. The percentage of mated animals with positive superovulatory response was similar in all strains (60.0-100%). The mean number of ova per donor was not dependent on the kind of hormonal treatment used within each rat strain. In general, females from outbred SD and Wistar rats were more responsive to hormonal treatments than animals from inbred rat strains. In addition, SD female rats produced a significantly higher number of embryos per female in response to PMSG-treatment compared to all other strains. Between the inbred strains, SHRSP was the most effective for superovulation. In vitro development of intact zygotes to the blastocyst stage was not different between SD, Wistar and SHRSP rats. In contrast, in vitro development of WKY zygotes was significantly less efficient than in other strains. However, 2-cell stage embryos in vivo produced from SD, SD x Wistar and WKY animals showed no difference in competence to develop to blastocyst stage in vitro. The proportion of offspring developing after oviduct transfer of intact zygotes was similar in all strains (44.0-56.4%) with the exception of WKY rats (35.9%). We also compared the survival rate after injection, ability of manipulated zygotes to develop to term and overall transgenic efficiency in various rat strains. SD and SHRSP zygotes survived after microinjection better than the WKY and Lewis zygotes. No differences were found in the efficiency of transgene integration per newborn in different strains ranging from 5.7 to 16.7%. The results of this study demonstrate that different rat strains have varying responses to superovulation, sensitivity to microinjection, capability to develop in vitro until blastocyst stage or in vivo to term after transfer to foster mothers. Despite these differences all studied strains can be used for efficient transgenic rat production.

Animals↗