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[Individual variation of 90Sr deposition and its variability depending on the genotypic homogeneity of the sample].

Individual peculiarities of 90Sr skeleton deposition in CBA mice were investigated. Differences in the radionuclide accumulation were not more than two times. Sex features in 90Sr deposition were not revealed. The range of individual variability of 90Sr deposition was analyzed in inbred mice in comparison with outbred stock and voles from natural population; it was found that variability in the radionuclide accumulation increased with sample genotypic heterogeneity.

Animals↗

Bronchoalveolar lavage cells and mitotic activity of monocytes and macrophages in rats after long-term intermittent hypoxia.

Long-term (1.5 months) intermittent hypoxia promoted desquamation of bronchial epithelial cells, decreased the relative content of alveolar macrophages and monocytes in bronchoalveolar lavage, stimulated lymphocyte migration to the lungs, and increased the relative content of lymphoid cell in rats. Mitotic activity of monocytes and macrophages decreased against the background of intraalveolar lymphocytosis (lymphocytic alveolitis).

Animals↗

Immunotoxic effects during acute ethylene glycol poisoning.

Experiments on outbred and inbred male CBA mice showed that acute poisoning with ethylene glycol (0.8 LD50) increased mortality from infections, decreased the number of spleen colony-forming units, inhibited antibody formation (mainly to thymus-dependent antigens, and suppressed natural and antibody-dependent cytotoxicity and delayed-type hypersensitivity. Ethylene glycol in concentrations of 10 and 100 mM in vitro inhibited the formation of antibody-producing cells by acting on T and B lymphocytes.

Animals↗

Novel microglomerular structures in the olfactory bulb of mice.

The murine olfactory system consists of two primary divisions: (1) a main olfactory system, in which olfactory sensory neurons (OSNs) located in the main olfactory epithelium (MOE) send their axons to glomeruli in the main olfactory bulb (MOB); and (2) an accessory olfactory system, in which OSNs located in the vomeronasal organ send their axons to glomeruli in the accessory olfactory bulb (AOB). In labeling studies using the lectin Ulex europaeus agglutinin (UEA), we discovered a novel subset of small neuropilar structures in the MOB that are distinct from other glomeruli both in the MOB and AOB. These "microglomeruli" are morphologically similar to MOB glomeruli in many respects: they receive innervation from processes present in the olfactory nerve layer and are isolated from other glomeruli by juxtaglomerular cells; in addition, the compartmental pattern of UEA labeling suggests the presence of UEA (-) processes within their neuropil. Microglomeruli contained processes that express the olfactory marker protein, a marker common to mature OSN axons. However, unlike other glomerular structures, the microglomeruli did not contain neural cell adhesion molecule-labeled processes. Within microglomeruli, UEA(+) processes interdigitated with MAP2(+) dendrites, some of which likely originate from interneurons, as indicated by glutamic acid decarboxylase labeling. Synaptophysin labeling in microglomeruli strongly suggested that synapses occur between UEA(+) processes and dendrites. Anterograde labeling of OSNs, by injection of rhodamine-dextran into one naris, demonstrated that UEA(+) processes in microglomeruli originated in the MOE. The unique morphology, protein expression, and location of microglomeruli have led us to hypothesize that they represent a novel class of glomerular structures in the murine olfactory system.

Animals↗

[Research on genetic variation of heart fatty acid-binding protein gene in ten pig breeds].

The genetic variation of heart fatty acid-binding protein (H-FABP) gene in 561 pigs including Duroc, Landrace, Large Yorkshire, Nanchang white pig, Erhualian, Meishan, Yushan black pig, Leping spotted pig, Jinhua black head-hind pig and Shanggao black head-hind pig were detected by PCR-RFLP with Hinf I, Hae III and Msp I. The results showed as follows: (1) Nanchang white pig presented only HH genotype while other breeds varied at the Hinf I-RFLP site; (2) The exotic breeds including Duroc, Landrace, Large Yorkshire and the native breed Nanchang white pig were proved to be polymorphic while the five Chinese local breeds presented no variation at the Hae III-RFLP site; (3) Among the tested breeds only Duroc presented variation at the Msp I-RFLP site. It is noted that all the Chinese local breeds present as AADD--genotypes.

Animals↗

[Construction of linkage map of chromosomes 1 and 3 in large white x Meishan reference family].

A three-generation family of pigs has been constructed by using three Large White boars and seven sows of Meishan pigs as parents. In this family, five F1 males and twenty-three F1 females were intercrossed to generate 147 F2 offspring. According to the pig linkage map of USDA-MARC, eight and nine microsatellite markers selected on chromosomes 1 and 3 were chosen to span the entire chromosomes. The members of this family were genotyped. The characterization of these microsatellites was shown that they were polymorphic and could be used to construct linkage map and detect quantitative trait loci (QTLs). Linkage analyses were performed using the CRI-MAP software package. The lengths of the sex-averaged linkage map were 182.3 cM and 180.2 cM on chromosomes 1 and 3, respectively. There were some differences between the linkage maps in this study and of USDA-MARC. The linkage map of chromosome 1 in female was found to be shorter than in male, and the contrary was on chromosome 3.

Animals↗

[Effect of dermorphin analogs on thermoregulation of rats under various thermal conditions].

We studied the influence of dermorphin (dermorphin) analogs with stereochemical modification of the amino acid residue proline in position 6 (Pro6), Tyr-D-Ala-Phe-Gly-Tyr-Hyp-Ser-NH2, Tyr-D-Ala-Phe-Gly-Tyr-[D-Pro]-Ser-NH2, Tyr-D-Ala-Phe-Gly-Tyr-[dehydro-Pro]-Ser-NH2, and Tyr-D-Ala-Phe-Gly-Tyr-[D-dehydro-Pro]-Ser-NH2, after their intraperitoneal injection at 0.5 mg/kg dose in the cold (4-7 degrees C), thermoneutral (27-28 degrees C), and hot (31-33 degrees C) environment. Stereochemical modifications of amino acid residue Pro6 proved to induce specific changes in the thermoregulatory effect of the peptide. Substitution of DPro6 for Pro6 has the most dramatic consequences: it considerably attenuates the thermoregulatory effect of dermorphin in the cold environment, cancels it in the hot environment, and inverts the dermorphin-specific thermoregulatory response in thermoneutral conditions. The data obtained indicate the important role of Pro6 residue in realization of this physiological activity of dermorphins.

Animals↗

Protective immunity induced by the anti-idiotypic monoclonal antibody NP30 of Schistosoma japonicum.

OBJECTIVE: To investigate the protective immunity induced by the anti-idiotypic monoclonal antibody NP30 of Schistosoma japonicum in mice. METHODS: An orthogonal table L(16) (4 x 2(12)) was selected as the experimental design. Eight-week-old Kunming outbred mice (male and female) were randomly divided into 16 experimental groups and 2 control groups. Control groups were injected with SP2/0 ascites intraperitoneally. Mice from each group were infected with 100 +/- 2 cercariae of Schistosoma japonicum in the abdominal skin and were sacrificed on the thirtieth day postchallenge. Adult worms were recovered and counted by perfusion of the left ventricle-portal vein. The SP2/0 ascites injected mice were used as controls and the percentage of protection was calculated. RESULTS: Active immunization of mice with NP30 could produce protection levels ranging from 22.36% to 50.46% depending on the different immunity protocols. The best immunization protocol was established from the results. CONCLUSIONS: Active immunization with NP30 can induce a degree of protection to infection with Schistosoma japonicum cercariae and NP30 is a potential vaccine candidate against Schistosoma japonicum.

Analysis of Variance↗

[Effect of structural changes of Pro6 in dermorphin molecule on its antinociceptive activity].

We studied effect of dermorphin (H-Tyr-DAla-Phe-Gly-Tyr-Pro-Ser-NH2) and its analogs with modified amino acid residue proline in position 6, H-Tyr-DAla-Phe-Gly-Tyr-[DPro]-Ser-NH2, H-Tyr-DAla-Phe-Gly-Tyr-[dehydro-Pro]-Ser-NH2, and H-Tyr-DAla-Phe-Gly-Tyr-[D-dehydro-Pro]-Ser-NH2, on nociception in the tail-flick and hot plate tests after intraperitoneal injection. Replacement of LPro with the stereoisomer DPro as well as Pro dehydration (LdHPro) was shown to increase antinociceptive activity. Replacement of LdHPro with DdHPro cancelled the activity in the tail-flick test. All three dermorphin analogs retained antinociceptive activity in the hot plate test; however, the effect of dermorphin was more pronounced.

Analgesics↗

Identification of hypoglycemia in mice as a surrogate marker of ricin toxicosis.

PURPOSE: In an effort to develop a non-lethal model of ricin toxicosis, we studied the biochemical effects of the administration of ricin in mice. METHODS: Mice received an intraperitoneal injection of ricin toxin, after which a panel of 21 biochemical parameters was determined. Effect of ricin administration on blood glucose concentration was studied in greater detail. To determine whether results of biochemical analyses correlated with therapeutic manipulations known to protect against ricin toxicosis, the effect of immunization on blood glucose values after ricin administration was studied. RESULTS: Of the biochemical parameters studied, only blood glucose and amylase values were affected by ricin administration. Because blood glucose concentration can be easily and instantaneously measured on 25 to 50 microl of blood, using handheld instruments, this parameter was further evaluated. A dose- and time-related decrease in blood glucose concentration was documented. Mice immunized with ricin had smaller changes in blood glucose concentration than did non-immunized animals after ricin administration. CONCLUSION: Blood glucose concentration may be used as a surrogate for lethal challenge as a measure of ricin toxicosis after its systemic administration.

Animals↗

Some observations on the pharmacological properties of ivermectin during treatment of a mite infestation in mice.

Ivermectin has become one of the most widely used drugs for the treatment of parasitic infections in laboratory rodents. Despite its wide popularity, little has been published regarding its pharmacokinetic properties in mice. We made use of a routine mite control treatment in a conventional animal unit to gain some knowledge of these properties. Numerous inbred, outbred, and transgenic lines of mice were being treated with ivermectin in the drinking water (32 mg/L) for a chronic Myocoptes infestation. A sample of mice from different cages and rooms was culled at various time intervals to check levels of ivermectin in blood. In addition, cellophane tape impressions of fur were obtained from mice undergoing treatment to monitor the effectiveness of ivermectin in controlling the mite infestation. Results showed that ivermectin levels rose sharply in the serum of treated mice and gradually fell once treatment was discontinued. Maximum levels detected at the end of a 10-day period of treatment were 90 ng/ml. Once treatment was discontinued, serum levels of the drug were undetectable after 7 days. In addition, treatment with ivermectin proved very effective in reducing parasite burdens in the colony. Results were in line with known pharmacological properties of ivermectin in other species. Nevertheless, it was worth noting that serum levels can vary markedly depending on various factors, something to be taken into account when considering treatment of mice, especially transgenics.

Administration, Oral↗

Comparison of cytotoxicity and radical scavenging activity between tea extracts and Chinese medicines.

Three hot water extracts of black tea, green tea and powdered green tea and five Chinese medicines (Shosaiko-tou, Orengedoku-tou, Goshuyu-tou, Choto-san, Keishininjinn-tou) were investigated for their ability to modify nitric oxide (NO) production by lipopolysaccharide (LPS)-stimulated mouse macrophage-like Raw 264.7 cells, and for their cytotoxicity, radical intensity and scavenging activity. All eight materials significantly reduced the extracellular concentration of NO in the LPS-stimulated Raw 264.7 cells. ESR spectroscopy shows that tea extracts, which had higher cytotoxicity, generated higher amounts of radicals, and more efficiently scavenged O2- (generated by hypoxanthine-xanthine oxidase reaction), hydroxyl radical (generated by Fenton reaction) and NO (generated by 1-hydroxyl-2-oxo-3-(N-3-methyl-3-aminopropyl)-3-methyl-1-triazene) than Chinese medicines. Close association between the radical intensity and radical scavenging activity suggests their bimodal (anti-oxidant and pro-oxidant) action. Pretreatment of mice with tea extracts significantly reduced the lethality of Escherichia coli-infection. All tea extracts showed no apparent anti-HIV activity. The present study demonstrates, for the first time, several attractive features of tea extracts in comparison with Chinese medicines, suggesting the possible application of the tea extracts for radical-mediated diseases.

Animals↗

Assessment of retinal degeneration in outbred albino mice.

Evaluation of a pharmaceutical's safety includes assessment of the potential for ophthalmologic toxicity. These nonclinical studies commonly use various outbred stocks of mice. Pretest indirect ophthalmoscopic examinations in the commonly used outbred stock Hsd:ICR(CD-1) indicated that retinal degeneration was a problem in this particular outbred stock of mice. This prompted the authors to examine other stocks of outbred mice routinely used in the performance of nonclinical safety studies. Groups of mice were observed over a 13-week period to determine the progression and changing incidence of retinal degeneration. Light intensity in the room and caging was measured during the study, and it was determined that light did not play a direct role in the progression of the retinal degeneration observed during the study. Histomorphologic examination of the mouse eyes was performed at the end of the study to confirm the presence of retinal degeneration observed after ophthalmoscopic examination. The incidence of retinal atrophy in the various outbred stocks of mice was: Crl:CFW(SW)BR (98.3%), Tac(SW)fBR (80%), Tac:Icr:Ha(ICR)fBR (75%), Hsd:ICR(CD-1) (43.3%), and Crl:CF-1BR (3.0%). Retinal atrophy was not observed in the following outbred mice stocks: Crl:CD-1(ICR)BR, HsdWin:CFW1, and Hsd:NSA(CF-1). On the basis of these findings, it is highly recommended that pretest ophthalmologic screening be performed on mice to obviate pre-existing conditions from confounding or invalidating nonclinical study results.

Animals↗

Rodent vendor apparent source of mouse parvovirus in sentinel mice.

Mouse parvovirus (MPV) has been increasingly prevalent in laboratory animal facilities, and the source of infection often can be difficult to determine. After 4 years of sporadic MPV detected in our sentinel mice and continual failure to identify index cases in colony mice, we developed a regimen to house newly arrived vendor mice in large sterile cages with a high stocking density. Some of these mice were retained in isolation after the remaining mice were deployed as sentinels. After detecting MPV seropositive sentinel mice 4 weeks after introduction to the mouse colonies in one facility, the remaining naïve mice that had been previously housed with those sentinels also tested positive for MPV, despite never having been exposed to colony mice. These results suggest that commercially bred mice intended for use as sentinels may, in fact, arrive at animal facilities already infected with MPV. Depending upon numerous factors, including the health surveillance methods used, it is possible that a low prevalence of MPV may exist undetected at rodent vendors.

Animals↗

[Experimental study on the effect of low molecular DNA from salmon milt on hemopoiesis].

Biological activity of low molecular DNA isolated from salmon milt was studied. When administered subcutaneously to mice with with acute experimental radiation disease in a course dose of 10 mg/kg, it showed a therapeutic effect, stimulated hemopoiesis, increased the survival rate and the average life span of the animals. Moreover, its marked effect on the humoral immunity was observed.

Acute Disease↗

[Ladasten induces the expression of genes regulating dopamine biosynthesis in various structures of rat brain].

The effect of ladasten (50 mg/kg) on the activity of tyrosine hydrolase (TH) and DOPA-decarboxylase (DDC) gene expression and on the content of dopamine and L-DOPA in the striatum and hypothalamus in rat brain was studied depending on the duration of drug action. In the initial stage (first hours) of the drug action, the dopaminergic effects are related to an increase in the dopamine release. The observed accumulation of L-DOPA and dopamine is correlated with the transcription activity of genes studied. This leads to a conclusion that the pharmacological activity of ladasten is related to activation of de novo synthesis of TH and DDC. There is a certain difference in the ladasten action upon the TH and DDC gene expression of the key enzymes in hypothalamus and striatum of rat brain.

Adamantane↗