Hamster hearts transplanted to normal Lewis rats and RNU/RNU rats ("nude rats") are rejected at the same tempo but by different mechanisms.
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Eosinophilia in nude rats and nude mice after infection with Fasciola hepatica or injection with its E/S antigens.
Peripheral blood and bone marrow eosinophilia occurred in nude rats and nude mice following F. hepatica infection, with the magnitude of the response in nude rats greater than that in nude mice. Injection of E/S antigens induced eosinophilia in nude rats and a limited eosinophilia in nude mice. Bone marrow eosinophilia was greatly enhanced in Fasciola-infected nude rats, particularly 14 days after infection and later. In nude mice, bone marrow eosinophilia developed soon after infection and persisted for the duration of the experiment, but was not as marked as in nude rats. Bone marrow eosinophils in antigen-injected animals were also elevated, and again this was more marked in nude rats. The number of colonies formed in agar culture from bone marrow cells of both nude rats and nude mice also increased following infection and remained significantly elevated throughout the experiment. Bone marrow colonies in antigen-injected nude rats increased on day 8, while in injected nude mice, the number of colonies rose rapidly following injection with antigens. Thus, nude rats and nude mice develop T-cell-independent eosinophilia, which appears to originate in the bone marrow. The magnitude of eosinophilia is greater in nude rats and it has yet to be determined whether these effects have any relevance to the ability of rats, but not mice, to develop resistance to reinfection with F. hepatica.
Animals↗
Saturable dose-response relationships for melphalan in melanoma treatment by isolated limb infusion in the nude rat.
Nude rats bearing melanomas on their hindlimbs were treated by isolated limb infusion (ILI) with increasing doses (7.5-400 microg/ml) of melphalan. The response of tumours to treatment at the end of the observation period was graded, according to diameter, as complete response (CR), partial response (PR), no change (NC) or progressive disease (PD). No linear relationship between the dose of melphalan and the tumour response was observed. All doses above a threshold of 15 microg/ml achieved a PR or CR. The achievement of CR was not related to increased dose. Two major implications arise from this work. Firstly, the typically two- to three-fold increase in cytotoxic drug concentration given in high dose chemotherapy compared with standard drug concentration may not be sufficient to produce the expected increase in tumour response and possibly survival, and the controversial results of high dose chemotherapy in different studies may thus be explained. Secondly, since an increase in melphalan dose above a certain threshold does not greatly increase tumour response, the use of combination therapies would seem to be more likely to be effective than increased chemotherapeutic drug doses in achieving better tumour responses.
Animals↗
Induction and quantification of hepatic metastases from a human colonic cancer in the nude rat.
Nude rats were injected with human colonic cancer cells (LS 174 T) in the superior mesenteric vein and the extent of hepatic metastases at sacrifice was estimated by visual inspection and computer-based area calculation. After 3 weeks, 5.0 x 10(6) cells caused hepatic metastases in 14/14 rats whereas 0.5 x 10(6) cells failed to produce liver metastases in 4/4 rats (P < 0.001). Injection of 1.0 x 10(7) cells caused portal vein occlusion in 3/5 rats. Extrahepatic tumour growth was rare; lung metastases were observed in four rats, and three rats had local tumour in the abdomen. The average extent of hepatic tumour replacement was 20.2 +/- 4.0%. Injection of embolies or single cells did not affect the incidence or extent of hepatic metastases. The incidence of hepatic metastases was similar in male and female rats, but the extent of hepatic tumour was larger in males (24.6%) than in females (3.2%) (P = 0.005). The pathophysiological similarities to human disease should make this model suitable for diagnostic and therapeutic studies with clinical application.
Animals↗
Infection with Toxoplasma gondii RH and Prugniaud strains in mice, rats and nude rats: kinetics of infection in blood and tissues related to pathology in acute and chronic infection.
Since mice and rats are the most studied models of experimental toxoplasmosis, the aim of this work was to analyze the outcome of Toxoplasma infection in mice, rats and congenitally athymic nude rats; for this purpose, the parasitic load in different organs and the anatomic-pathological characteristics of infection were investigated in these animals. The data obtained after infection with two different strains and stages of Toxoplasma gondii (RH tachyzoites and Prugniaud cysts) concerned the following organs: brain, mesenteric lymph nodes, blood, spleen, heart, lungs, diaphragm and liver. In Fischer rats, the infection with either the Prugniaud or the RH strains displayed similar characteristics: after a peak in the parasite load, a complete disappearance of parasites was observed, except in the brain of Prugniaud strain-infected rats where toxoplasmas were evidenced throughout the experiment. In OF1 mice, where infection by the RH tachyzoites was lethal, infection with the Prugniaud strain led to survival; the parasitic burden peaked in the different organs and was then undetectable, except in the brain where toxoplasmas were still present during the chronic phase. Like mice, nude rats did not survive to the RH infection. Interestingly, for all the animals the observed histopathological changes in the infected organs, although more or less obvious in the acute phase, were not very severe in almost all cases. For instance, mice, although more susceptible to infection than rats, did not present more severe lesions. They consisted in a discrete inflammation with some focal areas of necrosis in some organs such as brain, liver and heart. Our results support the assumption that rats and nude rats constitute interesting experimental models relevant to either human acute toxoplasmosis, chronic toxoplasmosis, or disseminated toxoplasmosis in AIDS patients.
Acute Disease↗
Prolactin receptors in the hypoprolactinemic male rat (IPL nude rat): measurement in testis and induction in liver.
In order to evaluate the importance of PRL in the regulation of its own receptors, characteristics of specific binding for PRL were studied in membrane preparations from liver and testis of a new hypoprolactinemic male rat, the IPL nude male rat, and this was compared to those found for normal male rats. Under basal conditions, hepatic specific binding of PRL in IPL nude rats, as in normal rats was not detectable. Following castration, it became detectable in both groups, and was 6.99 +/- 0.78% and 6.34 +/- 0.87% for IPL nude and normal rats respectively. Under such conditions, the apparent affinity constant (Ka) and the binding capacity (Nmax) obtained were also similar for both groups (Ka) = 1.36 +/- 0.14.10(9) M-1, Nmax = 102 +/- 14 fmol/mg protein in IPL and Ka = 1.34 +/- 0.28.10(9) M-1, Nmax = 97 +/- 11 fmol/mg protein in normal rats) although a decrease in serum levels of PRL was observed in both groups. This decrease was greater for IPL nude rats. As already reported, estradiol injection following castration was able to further increase the percentage of PRL hepatic specific binding (4 times). Furthermore, our results demonstrated that the affinity constant was significantly increased by estradiol injection in both groups. On the other hand, for testicular PRL binding characteristics, a statistically significant difference was found between IPL nude and normal rats. The PRL specific binding percentage was 7.01 +/- 0.85% for the IPL nude rat and 10.07 +/- 0.64% for the normal rat. By Scatchard analysis, the Ka of testicular membranes for labelled oPRL was similar in both groups, while the capacity differed (Nmax = 9.82 +/- 1.25 fmol/mg protein for IPL nude rat and Nmax = 26.06 +/- 4.39 fmol/mg protein for normal rats). These data established the fact that IPL nude male rats presented characteristics of hepatic PRL receptors similar to those of normal rats, while their testicular oPRL binding significantly differed. These findings therefore suggest that in genetic hypoprolactinemic rats (IPL nude rats), PRL might be more involved in the regulation of testicular PRL receptors than in that of hepatic receptors.
Animals↗
Dissociated estradiol (E2) action on the pituitary-testicular axis in a genetically hypoprolactinemic rat (IPL nude rat).
Prolactin (PRL) has been reported to be a possible mediator in the estradiol (E2)-induced inhibition of the pituitary-testicular axis. In order to better characterize the role of PRL, we studied the action of chronic hypoprolactinemia on this E2 inhibitory effect, using a genetically hypoprolactinemic rat (IPL nude). Normal and IPL nude adult male rats were injected either with vehicle or with E2 valerianate (4 mg/rat) once a week for 2 weeks. Rats were decapitated 7 days after the last injection. Results showed that E2 increased, similarly in both strains, pituitary weight and serum PRL levels. Serum testosterone values were reduced by 96% in both strains. However, testis weight was significantly reduced by 30% in normal rat, while in IPL nude rat, no significant decrease was observed. PRL binding sites, expressed as fmol/mg protein, were reduced in normal rat by 40%. No decrease was found in IPL nude rat. The dissociated E2 action observed in IPL nude rat suggested that only testicular growth inhibition could be mediated by PRL and confirm that testosterone level decrease could be due to a direct action of E2 on Leydig cells.
Animals↗
Thyroid-hypophyso-hypothalamic axis of the genetically hypoprolactinemic rats (IPL nude rats).
In order to evaluate thyrotropin function in the genetically hypoprolactinemic rat, (IPL nude), we measured by radioimmunoassay TRH hypothalamic content, pituitary TSH content and serum TSH, T3, T4, both in IPL nude and control rats at various times over the 24-hour period. Compared to normal rats, the hypothalamic TRH content in the IPL nude rat showed similar variations during the day, whereas a slight increase was observed during the night characterized by a significant difference at 20.00 h. Pituitary weight and TSH content were doubled in IPL nude rats; however, when expressed as micrograms TSH/micrograms protein or DNA, a significant increase was found only at 17.00 and 20.00 h. Serum TSH and total serum T3, T4 depicted similar variations although they were minute but nonetheless significant modifications, i.e. an increase of TSH at 17.00 and 23.00 h and a decrease of T4 at 11.00 h. However, only FT4 concentrations (and not-FT3) were slightly but significantly decreased in IPL rats over the experimental times. In conclusion, the slight increase in hypothalamic TRH and pituitary TSH contents and the absence of main associated variations of serum TSH, T3 and T4 do not lend support to the hypothesis that TRH could be the cause of the hypoprolactinemia of these rats. On the contrary, the observed thyrotropin axis variations might be rather interpreted as the consequence of it.
Animals↗
beta-Endorphin in genetically hypoprolactinemic rat: IPL nude rat.
Beta-endorphin has been reported to regulate not only stress- and suckling-induced but also basal prolactin secretion. In the aim to better evaluate the endogenous beta-endorphin-prolactin interrelation, we measured beta-endorphin levels in a new rat strain, genetically hypoprolactinemic and characterized by a total lack of lactation: IPL nude rat. Beta-endorphin was measured using a specific anti-h-beta endorphin in plasma and extracts of anterior and neurointermediate lobes of the pituitary, hypothalamus and brain. Pituitary extracts were also chromatographed on Sephadex G50 column. Results obtained showed that in IPL nude females on diestrus and males, the beta-endorphin contents of the neurointermediate lobe was significantly lower than in normal rats, while the values found in the other organs and plasma were similar. However, elution pattern of the anterior pituitary extract from male rats showed greater immunoactivity eluting as I125 h-beta-endorphin than in normal rat; this was not the case for the female rat. These results are consistent with a differential regulation of beta-endorphin levels of anterior and neurointermediate lobe by catecholamines. Moreover they suggest that PRL secretion was more related to neurointermediate beta-endorphin.
Animals↗
Acute and chronic polyarthritis induced by an aqueous form of 6-O-acyl and N-acyl derivatives of N-acetylmuramyl-L-alanyl-D-isoglutamine in euthymic rats and athymic nude rats.
The analogs of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), 6-O-stearoyl-MDP (L18-MDP), and N-(N-acetylmuramyl-L-alanyl-D-isoglutaminyl)-N-stearoyl-L-lysine (MDP-Lys-L18) and N-(2-tetradecylhexadecanoyl)-MDP (B30-MDP) induced acute polyarthritis in both euthymic rats and in athymic nude rats after a single or multiple systemic administrations of their aqueous forms; water-in-oil emulsions did not induce acute polyarthritis. MDP and the adjuvant-active analogs MDP-O-nBu (MDP butyl ester), N-(3-hydroxy-2-docosylhexacosanoyl)-MDP (BH48-MDP) and the adjuvant-inactive analogs [L18-MDP (L)] or MDP-Lys-L18 (L), which is 6-O-stearoyl-N-acetylmuramyl-L-alanyl-L-isoglutamine, or N-(N-acetylmuramyl-L-alanyl-L-isoglutaminyl)-N-stearoyl-L-lysine, did not induce disease, at the dosages used. Histological examination of the acute exudative inflammatory reactions around joints revealed hypertrophy of both synovial villi and tendon sheath, infiltration of polymorphonuclear leukocytes (PMN) and fibrin deposition of the affected joint spaces. Most of these lesions rapidly subsided after cessation of the adjuvant injections. During multiple systemic injections of acyl-MDPs, this acute arthritis became chronic in euthymic rats but not in athymic nude rats; the chronic polyarthritis consisted of mononuclear cell infiltration and proliferation of the connective tissue growth and severe new bone formation of the shaft of the bone. It remains uncertain whether chronic polyarthritis results from the repeated flare of acute inflammatory reactions to the continuing stimulation of the adjuvants or whether it may require some immunologic process to such exogenous substances as bacterial fragments or autoantigens modified by exogenous substances such as type II collagen.
Acetylmuramyl-Alanyl-Isoglutamine↗
Adenoviral vector-mediated gene expression in the nervous system of immunocompetent Wistar and T cell-deficient nude rats: preferential survival of transduced astroglial cells in nude rats.
In the present paper, we examined the effect of the adenoviral vector dosage, the role of T cells, and the influence of the presence of replication-competent adenovirus (RCA) in adenoviral vector stocks, on the efficacy of adenoviral vector-directed transgene expression in the facial nucleus of immunocompetent Wistar and athymic nude rats. A small number of motor neurons and glial cells was transduced at low dosages of viral vector (1 x 10(6) pfu) and in the absence of RCA, and transgene-expressing cells persisted throughout the 3-week period of observation. Intraparenchymal infusion of 2 x 10(7) pfu of a recombinant adenoviral vector free of RCA was required for optimal transduction of facial motor neurons. In Wistar rats, a biphasic immune response occurred at higher dosages of the vector (5 x 10(6) and 2 x 10(7) pfu) that was characterized by early infiltration of macrophages and the occurrence of T cells during the second week after injection of the vector. The immune response was associated with the loss of transduced neural cells. In nude rats, administration of an adenoviral vector free of RCA resulted in a macrophage response comparable to that in the Wistar rat and long-term survival of transduced astroglial cells. However, transduced motor neurons degenerated according to a similar time course as observed in Wistar rats. Small amounts of RCA (2 x 10(5) pfu) injected with 2 x 10(7) pfu recombinant viral vector particles resulted in an accelerated T cell response and a rapid elimination of transduced cells within 1 week in Wistar rats, whereas in nude rats transgene expression continued during this period. Taken together, these observations suggest that at the high viral vector loads necessary to achieve optimal transduction of the facial nucleus, T cells play a role in the degeneration of adenoviral vector-transduced astroglial cells. The adverse effects on neurons appear to be due to the observed inflammatory response or to direct adenoviral vector toxicity.
Adenoviridae↗
Growth of rat-mouse hybridomas in nude mice and nude rats.
Athymic (nude) mice and rats were inoculated intraperitoneally with rat-mouse hybridoma cells secreting monoclonal antibodies to rat MHC class I antigens in order to improve the yield of antibodies. Pristane priming and subsequent intraperitoneal injection of the hybridoma cells in to nude mice yielded ascites which contained antibody in high concentration (10-15 mg/ml). Complete Freund's adjuvant, mineral oil, pristane or antibody-antigen complexes were used to induce ascites in nude rats, but only pristane priming did so consistently. The hybridoma cells in the ascitic fluid failed to secrete antibody, although they contained intracellular antibody. However, when the pristane-primed nude rats received 250-500 rads of total body radiation prior to injection with the hybridoma cells, they produced large amounts of antibody. When the nude rats were splenectomized and injected with the hybridoma cells, they also produced antibody in high titers. There was no in vitro inhibition of antibody formation by the hybridoma cells cultured in medium containing 15% serum from nude rats, but co-culture of the hybridoma cells with splenic lymphocytes from normal or nude rats markedly inhibited antibody production. These results indicate that the defect in antibody secretion by the hybridoma cells in the ascites of nude rats is due to the presence of radiation-sensitive suppressor cells in the spleen.
Animals↗
Steroid regulation of gonadotropins in genetically hypoprolactinemic females (IPL nude rats).
IPL nude females present an absence of lactation with hypoprolactinemia. While males present a slight but significant decrease in serum testosterone and gonadotropins, females show normal values of estradiol, progesterone, LH and FSH during all estrus cycle stages. In this work, we observed that the postovariectomy rise of LH and FSH was significantly lower in the IPL nude females. We studied also the effect of acute (1 injection of 25 micrograms/rat E2Bz) or long-term (E2Bz capsule for 8 days) estradiol benzoate (E2Bz) treatment, with or without progesterone injection (5 mg/rat) in ovariectomized (OVX) IPL and normal females. The sensitivity of gonadotropins to E2 negative feedback is decreased in the IPL nude rats, result in agreement with previous reports and which could be linked to both hypoprolactinemia and decreased beta-endorphin observed in the IPL nude rat. The responsiveness of LH to LHRH was also tested in OVX and OVX + E2Bz or OVX + E2B + P treated. In OVX females responsiveness of LH to LHRH was similar in IPL nude to that of normal females. However, LH responsiveness in acute and long-term steroid-treated OVX IPL nude was significantly depressed. Since the mechanism whereby PRL interacts with steroids to modify gonadotropin secretion is still unexplained, IPL nude rat could be a good model to study it.
Animals↗
Basophils and eosinophils in three strains of rats and in athymic (nude) rats following infection with the nematodes Nippostrongylus brasiliensis or Trichinella spiralis.
A previous report showed that infection with the nematode Nippostrongylus brasiliensis stimulates a basophilia as well as an eosinophilia in the blood of August rats. The present study shows that blood levels of basophils and eosinophils were increased in two other rat strains, one inbred and one outbred, after infection with N. brasiliensis, and infection of two inbred rat strains with Trichinella spiralis also stimulated a basophilia as well as an eosinophilia. No increase occurred in basophils or eosinophils in athymic (nude) rats infected with N. brasiliensis, although both these cell types were found in the blood of control, specific pathogen free, nude rats in numbers comparable to those in specific pathogen free, heterozygote controls of the same strain. Rat basophils usually have few granules and in blood smears often appear as if they were partly degranulated. Basophils from uninfected nude rats contained more negative than positive staining granules compared with basophils from parasitized heterozygotes. The possession of small numbers of granules which vary in their reaction to stains of the Romanowski type is a normal feature of rat basophils in blood smears. Consequently rat basophils differ in these respects from those of other species.
Animals↗
Conjunctivitis in the nude rat (rnu/rnu).
Nude rats are susceptible to similar eye problems to those suffered by nude mice, notably conjunctivitis leading to periorbital abscesses. Pasteurella pneumotropica has been isolated from the conjunctiva. The condition can be alleviated by washing the eyes of mildly affected rats with warm water. More severe cases respond to treatment with ampicillin. Conjunctivitis has not appeared in a germ-free colony of nude rats.
Animals↗
Growth of human digestive-tumour xenografts in athymic nude rats.
The athymic nude rat rnu/rnu has been established as an in vivo model for the acceptance of human digestive-tumour xenografts. We report the successful xenografting of 7/12 (58%) primary explants from patients with digestive cancer. Successful xenografting also occurred in 21/25 (84%) pancreatic tumours derived from a pancreatic exocrine adenocarcinoma (GER) maintained in cell culture; 2 of those have been successfully passaged in nude rats. The simultaneous implantation of these tumours into nude mice led to an almost identical take rate. Passage of one colonic and one pancreatic xenograft from nude rats into nude mice, and transplantation back into nude rats, increased the take rates. The critical period for the establishment of primary tumour growth was usually 28-42 days. The xenografts maintained histological and cytological characteristics of the primary explants or of the original tumour from which the cell line derived. The karyotype of the cell line was also maintained in the solid tumour. Three murine tumours were successfully grown as xenografts. Despite their immunoincompetence, the rats in this study showed no increased morbidity or mortality when kept in conventional conditions, compared with animals housed in isolators. The athymic nude rat will become a valuable complementary tool to the nude mouse for the establishment and maintenance of human digestive tumours and for surgical and serial serological studies.
Adenocarcinoma↗
Immune responses to Legionella pneumophila in athymic nude rats.
Athymic nude rats (rnu) were immunized intraperitoneally with the attenuated Phil I strain (serogroup 1) of Legionella pneumophila. These rats developed a humoral immune response, including the IgG class, that was of comparable magnitude to that seen in their non-nude littermates. When the rats were challenged ip with a dose of the virulent strain LD-8 (also serogroup 1) that proved to be lethal in non-immune rnu-rats, none of them developed any signs of disease, but survived well for the observation period of 2 weeks. However, it was impossible by adoptive transfer of lymphocytes from immunized inbred PVG donors to protect non-immune syngeneic rats from the lethality of the LD-8. These results together with previous data (16) indicate that specific antibodies, present in the animal at the time of infection, protect effectively against a lethal dose of L. pneumophila in this experimental system.
Agglutination Tests↗
Acquired immunity to Trichophyton mentagrophytes in thymus-grafted or peritoneal exudate cell-injected nude rats.
Congenitally athymic "nude" (RNU/RNU) rats were grafted with syngeneic neonatal thymus glands and 30 days later cutaneously inoculated with Trichophyton mentagrophytes. Nude rats and thymus-grafted nude rats were susceptible to infection with T. mentagrophytes but only thymus-grafted nude rats cleared the dermatophytosis. Clearance of the fungal infection took twice as long (approximately 60 days) in thymus-grafted nude rats when compared with heterozygous euthymic (+/RNU) controls (approximately 35 days). Following clearance of the primary dermatophytosis, peritoneal exudate cells (PEC) were adoptively transferred from either thymus-grafted or heterozygous rats to nude rats. Eight of 12 PEC-recipient nude rats acquired the capacity to resolve T. mentagrophytes-induced dermatophytosis (mean clearance time was approximately 40 days). All heterozygous (+/RNU) rats, thymus-grafted nude rats (4/4), and 8 of 12 PEC-recipient nude rats, which had cleared a primary dermatophytosis also expressed delayed-type hypersensitivity and elevated serum antibody titers to trichophytin antigen. These results demonstrate that immunity to T. mentagrophytes can be acquired in congenitally athymic nude rats following thymus grafting or injection of PEC from syngeneic +/RNU rats; however, injection of PEC from trichophytin-sensitized +/RNU donor rats to nude recipient rats did not result in transfer of specific adoptive immunity to T. mentagrophytes. Interestingly, PEC transfer from non-sensitized +/RNU rats was comparable to thymus grafting in effecting clearance of T. mentagrophytes dermatophytosis. These results suggest that acquired immunity to T. mentagrophytes in the rat is T cell-dependent, and that the absence of functional T lymphocytes and not an epithelial defect results in chronic dermatophytosis in the nude rat.
Animals↗