Characterization of the heredity of kininogen deficiency in brown Norway Katholiek strain rats.

Brown Norway rat strain has been studied for mode of inheritance of its congenital deficiency in plasma high molecular weight (HMW)-kininogen and low molecular weight (LMW)-kininogen, and low plasma level of prekallikrein. We examined the genetics of the deficiency by performing a mixed breeding experiment between B/N-Katholiek (B/N-Ka, deficient) and B/N-Kitasato (B/N-Ki, normal) strains. Incidence of the deficiency was judged by the plasma level of HMW-kininogen. Plasma level of HMW-kininogen was around 50% of the normal level in all F1 generations of the hybrid between male B/N-Ka and female B/N-Ki (Exp. 1), and between female B/N-Ka and male B/N-Ki (Exp. 2). Incidence of deficiency (plasma HMW-kininogen level less than 5%) in Exp. 1 was 23.8% in male F2 and 20.0% in female F2 generations. By Exp. 2 also the incidence was 25.0% in male and 30.0% in female F2 generations. There was no significant difference of the incidence between the two experiments or sexes. These results indicate the inheritance of the kininogen-deficiency to be Mendelian autosomal recessive, the same as for the reported cases of human kininogen deficiency. Gel filtration study suggests that prekallikrein in the B/N-Ka plasma may be free form, while that in the B/N-Ki plasma may form complex with HMW-kininogen.     

Consumption of hypoallergenic flour prevents gluten-induced airway inflammation in Brown Norway rats

Brown Norway rats were immunized with gluten, and then fed a diet containing hypoallergenic flour or an amino acid mixture. The rats were then made to inhale a solubilized gluten to induce gluten-specific bronchial asthma. The antibody levels in the serum of rats were measured by ELISA, and cell counts were done on cytospin preparations of bronchoalveolar lavage fluid. Body weight was decreased after allergen challenge in rats fed the amino acid mixture but not in rats fed the hypoallergenic flour. Antibody levels in the serum were significantly lower in rats fed hypoallergenic flour than in those fed the amino acid mixture. Differential cell counts in the bronchoalveolar lavage fluid showed that the numbers of eosinophils, lymphocytes, and neutrophils were significantly lower in rats fed the hypoallergenic flour than in those fed the amino acid mixture. These results suggest that hypoallergenic flour actively suppresses the allergic reactions, probably by inducing oral tolerance.     

Reduction of the RT6.2+ subset of T lymphocytes in brown Norway rats with mercury-induced renal autoimmunity

Chemically induced autoimmunity is a recently recognized environmental hazard that may affect individuals genetically predisposed to autoimmune disease and chronically exposed to certain chemicals. For example, moderate concentrations of mercury may lead to renal autoimmune disease in a small but significant percentage of the exposed population. Mercury also induces autoimmune glomerulonephritis in susceptible Brown Norway (BN) and MAXX inbred strain rats. Autoimmune responses, directed to epitopes of the renal glomerular basement membrane (GBM), are rapid in onset and have a self-limiting course in mercury-treated rats. Both regulatory T cells and idiotype-anti-idiotype network have been implicated in the resolution of this autoimmune process. In our investigations of immune regulation of mercury-induced autoimmune glomerulonephritis, we have used flow cytometry to quantitate lymphocyte subpopulations in the spleen and lymph nodes of mercury-treated and control BN rats. Of particular interest was the RT6+ T cell subset, that appears to have important immunoregulatory properties in a rat model of autoimmune insulin-dependent diabetes mellitus. Spleen and lymph nodes from control BN rats contained 22 and 52%, respectively, RT6+ cells. Spleens from mercury-treated animals contained 21% RT6+ cells on Day 10 of treatment, 13% on Day 17, 16% on Day 24 and 20% on Day 30. Lymph nodes from the same rats had 36% RT6+ cells on Day 10, 23% on Day 17, 29% on Day 24, and 28% on Day 30. The decrease in RT6+ cells correlated inversely with autoimmune responses to GBM, which peaked on Days 17-24 and declined by Day 30. Moreover, autoimmune responses were also associated with elevated RT6-:RT6+ T cell ratios. Similar results were obtained in two additional groups of BN rats, comprising both younger and older animals, sacrificed at Day 18 of mercury treatment. Analysis of other lymphocyte subpopulations demonstrated a decrease of CD4+ and CD5+ cells, whereas B cells as well as CD8+, IL-2 receptor+, and MHC class II+ subsets showed no consistent correlation with the onset or resolution of the autoimmune process. These findings suggest that mercury-induced changes in RT6+ T lymphocytes may be related to the development of renal autoimmune disease in genetically predisposed BN rats.     

Enzymic and morphological studies on catalase positive particles from brown fat of cold adapted rats.

Brown adipose tissue of normal and cold-adapted adult rats has been investigated morphologically and cytochemically. In thin-sections catalase-positive particles appear as circular, oval or elongated profiles lying either as single particles or forming groups. Biochemical studies on peroxisomal enzymes show an increase of catalase activity to the tenfold amount after cold adaptation. The tissue is devoid of D-aminoacid oxidase and glycolate oxidase, while low activities of middle-chain-alpha-hydroxyacid oxidases could be detected. The catalase-positive particles were purified by differential and is lower than that of the liver peroxisomes. Enzymic investigations of the fractions render it probably that particles contain carnitine acetyltransferase, whereas they are lacking NAD-dependent glycerophosphate dehydrogenase. The pellets derived from the gradient centrifugation have been checked morphologically for purity. After performing DAB-cytochemistry for identification of the peroxidatic activity of catalase, most of the particles were shown to be structurally intact and homogeneously filled with reaction product.     

Effect of the post-weaning environment on the climbing behaviour of wild and domestic Norway rats

The climbing behaviour of wild and domestic Norway rats (Rattus norvegicus) was compared after early rearing in three post-weaning environments offering different climbing experiences. Wild rats climbed in the test apparatus even when denied early climbing experience; male domestic rats did not. Early climbing experience increased the climbing scores of both stocks but influenced the climbing proficiency of wild rats only. Treatment differences in climbing behaviour may be related to specific motor experiences gained during development and the effect of early experience on the response to a novel environment (test apparatus). Stock differences in climbing behaviour may reflect a general reduction in motor activity among domestic rats and their reduced sensitivity to stimulus change or novelty.     

Pregnancy in the brown Norway rat: a model for investigating the genetics of placentation

The placenta facilitates the exchange of nutrients and wastes in an effort to promote fetal development. Disruptions in the establishment of the placenta and its interactions with the maternal uterus are potential causes of pregnancy failure. In this study we investigated the pregnancy phenotype of two inbred rat strains: the Dahl Salt Sensitive (DSS) strain and the Brown Norway (BN) strain. The DSS strain is reported to have large litters, whereas the BN strain has small litters. Pregnant female rats of each strain were killed on various days of gestation. At the time of killing, the number of viable versus dead and/or resorbing conceptuses was determined. Placental tissues from viable conceptuses were collected and processed for biochemical and histologic analyses. The number of viable conceptuses at Days 8.5 and 18.5 of gestation was significantly greater in DSS versus BN rats. Additionally, the number of resorbing and/or dying conceptuses was significantly greater in the BN strain than in the DSS strain. Maternal responses to pregnancy and elements of placental and fetal development in DSS and BN rats differed. Immunohistologic analysis of placentation and gene expression profiles revealed that trophoblast cell invasion into the uterine mesometrial compartment was significantly less in the BN strain versus the DSS strain. In contrast, the uterine natural killer cell population was reciprocally expanded in the BN strain. The impairment in trophoblast cell invasion in BN rats was associated with a smaller junctional zone compartment of the chorioallantoic placenta. Collectively, the data indicate that BN rats exhibit a unique form of placentation and may represent an excellent model for investigating the genetics of placental development.     

Postweaning environmental and social factors influencing the onset and expression of agonistic behavior in Norway rats

Two studies were conducted to determine the importance of the postweaning environment and social milieu in regulating the expression of intraspecific aggression in Norway rats. In Experiment 1, male rats were housed either individually or in pairs at 21 days of age. In addition, one-half of the singly housed and paired animals were given experiences with intruders during maturation. At 85 days of age, all animals were given a brief intruder test and then removed from their postweaning environment and provided individually with homecages for a two week period until tested for aggression toward intruders. Results of intruder tests given during maturation indicated agonistic exchanges appeared earlier and more frequently in cages housing a single resident than cages with cohabiting males. However, agonistic exchanges between singly reared residents and intruders had detrimental consequences in adulthood especially under long-term combat situations. That is, although individually reared animals, with early fighting experiences, were capable of initiating intraspecific aggression, such individuals were unable to defend their homecage over a long period of time as evidenced by the high number of wounds and tendency to lose body weight during adult fighting.In Experiment 2, male Norway rats were reared in pairs from 21 days of age and identified as dominant or subordinate on the basis of intracolony social interactions shown during maturation. At 80 days of age, animals were paired with individually reared males in an unfamiliar cage for a 20 day period and examined for agonistic behavior toward intruders at 100 days of age. Group-reared subordinate males exhibited defensive behavior during confrontations with individually reared animals and incurred more wounds and lost more body weight than their cohabiting partner. In addition, subordinate males showed significantly fewer offensive postures toward intruders than individually reared cohabitants. In contrast, group-reared dominant animals did not differ from individually reared males in display of agonistic patterns, in number of wounds, and body weight changes during the period of cohabitation. These findings demonstrate that early rearing factors have pronounced effects on agonistic behavior. Animals experiencing defeat during development are more likely to lose agonistic confrontations in unfamiliar territory than either animals dominant in their early social interactions or animals without the experience of winning or losing agonistic encounters. These results have implications for the understanding of agonistic behavior and predicting outcomes of animal contests, and reveal important differences in agonistic experiences among animals reared in groups.     

Early postprandial low-grade inflammation after high-fat meal in healthy rats: possible involvement of visceral adipose tissue

In the postprandial period, low-grade inflammation may contribute to vascular endothelial dysfunction, a hallmark of atherogenesis. Little is known about the involvement of the adipose tissue in the initiation of the postprandial inflammatory response such as obtained after a high-saturated fat meal (HFM). In the present study, we first studied the time course of appearance of systemic inflammation after a HFM in healthy rats, and then we investigated whether a HFM activates the inflammatory signaling in the visceral adipose tissue, with a focus on the key component, nuclear factor-κB (NF-κB).Two hours after the HFM, plasma IL-6 and PAI-1, but not plasma C-reactive protein and soluble intracellular adhesion molecule-1, showed a marked, transient increase. These changes were specific to the postprandial state as not observed after a control water load. Neutrophils count and activation markers CD11B and CD62L, assessed by flow cytometry, also rose significantly 2 h after the HFM, while remaining steady after the control. At the same time, the HFM decreased significantly B-cell count and expression of the activation marker CD62L. Interestingly, at the same early time after the HFM, in the visceral adipose tissue, there was a 2.2-fold increase in the activation of NF-κB (p65) in nuclear extract and an increase in IL-6 mRNA.As far as we know, this is the first study evidencing an acute, postprandial activation of inflammation in visceral adipose tissue. This early activation of NF-κB pathway after a HFM may play a triggering role in the initiation of the complex postprandial proatherogenic phenotype.     

Salmonella spp. in the working environment of sewage treatment plants in Oslo, Norway.

The presence of Salmonella spp. was investigated at three sewage treatment plants in Oslo, Norway. Salmonella bacteria were isolated from floor surfaces and areas with hand contact in the treatment plant, from floor surfaces and areas with hand contact in the treatment plant, from floor surfaces in the changing rooms, and in one case from floor surfaces in an eating room. The sewage sludge contained from 140 to 140,000 Salmonella spp. per 100 g dry weight. Raw and treated sewage contained an average of 130 and 3 of these bacteria per 100 ml, respectively. There was poor correlation between the pattern of serotypes isolated from the sewage works and the patterns of those which were registered among the population of Oslo during the investigation. Neither enteropathogenic bacteria nor parasite eggs were found in fecal samples from employees at the plant. The health significance of the presence of Salmonella spp. in the environment of sewage workers is discussed.     

Antigen-induced airway inflammation in the Brown Norway rat results in airway smooth muscle hyperplasia.

Asthma is characterized by chronic airways inflammation, airway wall remodeling, and airway hyperresponsiveness (AHR). An increase in airway smooth muscle has been proposed to explain a major part of AHR in asthma. We have used unbiased stereological methods to determine whether airway smooth muscle hyperplasia and AHR occurred in sensitized, antigen-challenged Brown Norway (BN) rats. Ovalbumin (OA)-sensitized BN rats chronically exposed to OA aerosol displayed airway inflammation and a modest level of AHR to intravenously administered ACh 24 h after the last antigen challenge. However, these animals did not show an increase in smooth muscle cell (SMC) number in the left main bronchus, suggesting that short-lived inflammatory mechanisms caused the acute AHR. In contrast, 7 days after the last aerosol challenge, there was a modest increase in SMC number, but no AHR to ACh. Addition of FCS to the chronic OA challenge protocol had no effect on the degree of inflammation but resulted in a marked increase in both SMC number and a persistent (7-day) AHR. These results raise the possibility that increases in airway SMC number rather than, or in addition to, chronic inflammation contribute to the persistent AHR detected in this model.     

Pulmonary inflammation alters the lung disposition of lipophilic amine indicators.

Many lipophilic amine compounds are rapidly extracted from the blood on passage through the pulmonary circulation. The extent of their extraction in normal lungs depends on their physical-chemical properties, which affect their degree of ionization, lipophilicity, and propensity for interacting with blood and tissue constituents. The hypothesis of the present study was that changes in the tissue composition that occur during pulmonary inflammation would have a differential effect on the pulmonary extraction of lipophilic amines having different properties. If so, measurement of the extraction patterns for a group of lipophilic amines, having different physical-chemical properties, might provide a means for detecting and identifying lung tissue abnormalities. To evaluate this hypothesis, we measured the pulmonary extraction patterns for four lipophilic amines, [(14)C]diazepam, [(3)H]alfentanil, [(14)C]lidocaine, and [(14)C]codeine, along with two hydrophilic compounds, (3)HOH and [(14)C]phenylethylamine, after the bolus injection of these indicators into the pulmonary artery of isolated lungs from normal rabbits and from rabbits with pulmonary inflammation induced by an intravenous injection of complete Freund's adjuvant. The pulmonary extraction patterns, parameterized using a previously developed mathematical model, were, in fact, differentially altered by the inflammatory response. For example, the tissue sequestration rate, k(seq) (ml/s), per unit (3)HOH accessible extravascular lung water volume significantly increased for diazepam and lidocaine, but not for codeine and alfentanil. The results are consistent with the above hypothesis and suggest the potential for using lipophilic amines as indicators for detection and quantification of changes in lung tissue composition associated with lung injury and disease.     

Infectious disease in animal metapopulations: the importance of environmental transmission

Motivated by an array of infectious diseases that threaten wildlife populations, a simple metapopulation model (subpopulations connected by animal movement) is developed, which allows for both movement-based and environmental transmission. The model demonstrates that for a range of plausible parameterizations of environmental transmission, increased movement rate of animals between discrete habitats can lead to a decrease in the overall proportion of sites that are occupied. This can limit the ability of the rescue effect to ensure locally extinct populations become recolonized and can drive metapopulations down in size so that extinction by mechanisms other than disease may become more likely. It further highlights that, in the context of environmental transmission, the environmental persistence time of pathogens and the probability of acquiring infection by environmental transmission can affect host metapopulations both qualitatively and quantitatively. Additional spillover sources of infection from alternate reservoir hosts are also included in the model and a synthesis of all three types of transmission, acting alone or in combination, is performed revealing that movement-based transmission is the only necessary condition for a decline in the proportion of occupied sites with increasing movement rate, but that the presence of other types of transmission can reverse this qualitative result. By including the previously neglected role of environmental transmission, this work contributes to the general discussion of when dispersal by wild animals is beneficial or detrimental to populations experiencing infectious disease.     

Heterogeneity in the performance of outbred sprague-dawley rats in an elevated-plus maze test: A possible animal model for anxiety disorder

A wide variation in the performance of inbred rats measured in the elevated plus maze test suggests a possible genetic basis for anxiety response (AR). To gain further insight into the role of genetics in AR, we have characterized AR in male outbred S-D rats. Rats were placed in the black compartment (BC) facing the wall opposite the aperture and time needed for the animal to exit BC was noted. All rats underwent 3 successive trials 1–1.5 hrs apart. Naive rats showed a wide variation in their AR in trial 1(mean = 89 ± 19 sec, range = 5–360 sec). Sixty-eight % of the rats exhibiting low AR exited BC in <30sec, whereas 16% stayed in for the entire 360 sec (high AR). On successive testing, there was a progressive increase in AR which reached to max on second trial (Trial 1: 89±19, Trial 2: 171± 23, Trial 3: 210± 22 sec, p<0.0001). The time spent in BC on successive trials increased for most rats ($\text{33}\text{44}$), decreased for some ($\text{2}\text{44}$), showed min to no change ($\text{5}\text{44}$) or erratic response ($\text{4}\text{44}$) for others. In conclusion wide variation in the AR in outbred rats could be exploited to study genetic and neurochemical mechanisms of anxiety.     

Liporotein particles in the jejunal mucosa of fetal rats.

The jejunal mucosa of fetal rats contains particles of the same size, electron density and distribution as particles identified by others in adult jejunum as very low density lipoprotein particles. These particles are first seen in 19-day fetuses at which time the jejunal mucosa is still relatively undifferentiated and formation of villi is just beginning. They become progressively more abundant during the last 3 days of gestation as differentiation proceeds and are seen in virtually all absorptive cells in the apical third of jejunal villi of fetuses at term.     

Pulmonary surfactant and inflammation in septic adult mice: role of surfactant protein A.

Surfactant alterations, alveolar cytokine changes, and the role of surfactant protein (SP)-A in septic mice were investigated. Sepsis was induced via cecal ligation and perforation (CLP). Septic and sham mice were euthanized at 0, 3, 6, 9, 12, 15, and 18 h after surgery. Mice deficient in SP-A and mice that overexpressed SP-A were euthanized 18 h after surgery. In wild-type, sham-operated mice, surfactant pool sizes were similar at all time points, whereas in the CLP groups there was a significant decrease in small-aggregate surfactant pool sizes beginning 6 h after CLP. Interleukin-6 concentrations in bronchoalveolar lavage fluid from septic animals increased from 6 to 18 h after surgery. Identical surfactant alterations and concentrations of cytokines were observed in septic mice that were SP-A deficient or that overexpressed SP-A. In conclusion, alterations of pulmonary surfactant and alveolar cytokines occur simultaneously, 6 h after a systemic insult. In addition, we did not detect a role for SP-A in regulating surfactant phospholipid pool sizes or pulmonary inflammation in septic mice.     

Food habits and foraging of the brown bear Ursus arctos in central south Norway

Analysis of 134 excrement samples from the brown bear Ursus arctos L in boreal forests m central south Norway found volumes to be largest for Vaccinium spp, herbage Empetrum spp, and Formicidae The most important plant material in volume uptake were herbage, leaves, and mosses, closely followed by berries and seeds All together, plant material amounted to c 85% by volume, Formicidae to c 8%, and domestic sheep to c 7% These values were radically changed by applying correction factors for different nutritional value of food items The importance of large mammals then increased substantially, while the importance of herbage was reduced There was a drastic shift in food composition through the seasons Formicidae and flowers of deciduous trees were prevalent in spring, herbage in early summer, Vaccinium spp and sheep in late summer, and Vaccinium spp and Empetrum spp in autumn