Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “rat model”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed2004

Ontogeny of the VATER kidney in a rat model.

By exposing rat fetuses to adriamycin prenatally, a rat model of VATER association has been created. Absence of the fetal bladder is prominent and the kidneys show features of chronic obstruction with hydronephrosis/hydroureter, loss of parenchyma, fewer glomeruli, and less differentiation. The aim of this study was to elucidate this rat model, to determine exactly when the changes in the kidneys develop, hopefully thereby to expand our understanding of congenital obstructive uropathy. Timed-pregnant Sprague-Dawley rats were injected intraperitoneally with adriamycin on days 6-9 of gestation. The control group received saline. Fetuses were recovered on gestational days (GDs) 20, 19, 18, 17, 16, 15, 14, 12, and 10 (total, 120 control, 121 treated). Macroscopic features were determined. Serial sections were then taken and stained with hematoxylin and eosin. Comparisons were made under light microscopy. The metanephric kidney first became apparent at GD12. The development of the control and treated kidneys appeared similar till GD18. Beyond this day, the treated kidneys exhibited increasing degrees of distension of Bowman's capsule, ducts, and subsequently pelvis and ureter. There were fewer levels of glomeruli, which were also less differentiated. Less differentiation was also noted in the medulla, and with time this became thin in comparison to the control kidneys. By GD20, the renal pelvis was grossly dilated with a blunted papilla, and the renal parenchyma was thin. Prenatal exposure of rat fetuses to adriamycin results in kidneys that are chronically obstructed, as the majority of the fetuses show absence of the bladder. Absence of renal dysmorphology until GD18, when urine is first produced, suggests strongly that the effect of adriamycin on the kidney is indirect, via agenesis of the bladder and secondary to backpressure from early urine production. This is a unique, simple, and reliable model of fetal obstructive uropathy and will be very useful to facilitate further investigation into its pathophysiology and to explore new treatment options.

Abnormalities, Drug-Induced↗
PubMed1975

The immunology of large bowel carcinoma in a rat model.

A rat large bowel carcinoma model has been established with close similarities to the immunological features of the corresponding human neoplasms as far as those are presently known: (1) common antigens with tissue-type specificity, (2) expression of immunogenic gut-specific embryonal antigens, (3) cell-mediated immunity present in tumor bearers, whose sera are capable of blocking the lymphocyte effect specifically, and (4) rapid disappearance of the serum blocking activity after tumor excision. It is suggested that this model is therefore particularly suitable for further detailed analysis of the potential function in vivo of tissue-type specific antigens. In addition, this model appears to be applicable to correlating alterations in immune status with tumor course after various modes of intervention such as chemotherapy and immunotherapy alone, or in combination with surgery.

Animals↗
PubMed1997

[Intracerebral grafting of ex vivo transgene muscle cells in rat model of parkinsonism].

The rat model with a unilateral 6-OHDA-induced lesion of the dopaminergic system was used for experimental study on gene therapy for Parkinson's disease (PD). The plasmid pCMVTH (6.04 kb) was constructed as a vector containing the gene of tyrosine hydroxylase (TH) and transferred into cultured primary muscle cells by lipofection ex vivo. After expression of TH was determined in vitro, the intracerebral grafting (ICG) of these genetically modified cells was made in the striatum of PD rat model. The results showed that TH-expressing muscle cells had a long-term survival in the brain and induced a marked decrease in abnormal locomotion and increase in striatal dopamine levels for rat model.

Animals↗
PubMed2001

Characterization of the importance of Staphylococcus epidermidis autolysin and polysaccharide intercellular adhesin in the pathogenesis of intravascular catheter-associated infection in a rat model.

A rat central venous catheter (CVC) infection model was used to assess the importance of the proteinacious autolysin (AtlE) and the polysaccharide intercellular adhesin (PIA) in the pathogenesis of Staphylococcus epidermidis CVC-associated infection. Wild-type (wt) S. epidermidis O-47 was significantly more likely to cause a CVC infection than was either of the isogenic mutant strains (AtlE-negative [O-47mut1] or PIA-negative [O-47mut2]). Bacteria were retrieved from the explanted catheters of 87.5% of rats inoculated with S. epidermidis O-47, compared with 25% of rats challenged with either S. epidermidis O-47mut1 or O-47mut2 (P=.007). Peripheral bacteremia was documented in 75% of rats challenged with S. epidermidis O-47, compared with 12.5% and 25% challenged with O-47mut1 and O-47mut2, respectively (P=.009). Metastatic disease was more common in rats inoculated with wt S. epidermidis, compared with AtlE- or PIA-deficient mutants. These results confirm the importance of initial adherence, associated with AtlE, and biofilm production, mediated by PIA, in the pathogenesis of S. epidermidis experimental CVC infection.

Animals↗
PubMed1999

Preliminary study on the relationship between osteoporosis and trace elements with rat models.

Thirty rats were divided randomly into five groups and fed with different feeds. They were killed after 2 mo. Right thighs of these rats were taken as samples. Bone mineral densities of these samples were measured by the double-energy x-ray bone mineral densitometer, and trace elements contents of the samples were analyzed by neutron activation analysis. Results of the experiments showed that some elements were well correlated with others, and there were obvious variances between some elements of the normal group and those of other four groups.

Absorptiometry, Photon↗
PubMed1994

Pectoralis major muscle free flap in rat model.

The rat pectoralis muscle can serve as a vascularized, innervated muscle flap model. The muscle, consisting of superficialis and profundus portions, is supplied by separate neurovascular systems. The vessels to pectoralis profundus (averaging 0.3 mm in diameter) can be taken in continuity with the axillary vessels (averaging 11 mm in diameter), which are used for transplantation. The profundus portion of muscle weighed an average of 1.8 g, and the average pedicle length was 0.9 cm. Nine of 11 transplanted muscles were viable, with intact circulation at 72 hours. An example of muscle transplantation for tissue defect coverage was attempted. The pectoralis profundus transplant was technically reliable, and the muscle bulk and contour could allow biochemical and functional studies.

Abdominal Muscles↗
PubMed1986

Inheritance and site of expression of genes controlling susceptibility to mammary cancer in an inbred rat model.

An inbred rat model for genetically controlled susceptibility to chemically induced mammary cancer has been established. Wistar-Furth (W/Fu) rats were found to be more susceptible to 7,12-dimethylbenz(a)anthracene-induced mammary tumors than were Fischer (F344) rats. The susceptibilities of various F1, F2, and backcross generations of these strains were examined for susceptibility to 7,12-dimethylbenz(a)anthracene-induced mammary tumors. The data suggest that susceptibility is inherited as a dominant trait. Both a single locus autosomal model and an X-linked model have been ruled out. However, the data support the hypothesis that complete susceptibility is controlled by any one of a group of independently segregating genes; i.e., any one gene of this group is both necessary and sufficient to induce maximal susceptibility. It is not known if these genes are identical or different. In order to identify the role of these genes we asked if they were expressed in the mammary epithelial cells themselves or elsewhere in the rat. Chimeric animals were produced by transplanting mammary cells from either W/Fu or F344 rats into the white interscapular fat pad of female W/Fu X F344 F1 rats. One month after transplantation the animals were treated with 7,12-dimethylbenz(a)anthracene and then palpated weekly for tumor development at the graft site. Tumors developed more rapidly and in greater total frequency at sites grafted with W/Fu mammary cells. This result suggests that the genes controlling inherited susceptibility are expressed in the mammary cells. The role of these genes is now under investigation. We have thus far shown that they do not control carcinogen metabolism or activation.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1995

cDNA structure, alternative splicing and exon-intron organization of the predisposing tuberous sclerosis (Tsc2) gene of the Eker rat model.

The Eker rat hereditary renal carcinoma (RC) is an excellent example of a Mendelian dominant predisposition to a specific cancer in an experimental animal. We recently reported that a germline insertion in the rat homologue of the human tuberous sclerosis gene (TSC2) gives rise to the dominantly inherited cancer in the Eker rat model. We now describe the entire cDNA (5375 bp without exons 25 and 31) and genomic structure of the rat Tsc2 gene. The deduced amino acid sequence (1743 amino acids) shows 92% identity to the human counterpart. Surprisingly, there are a great many (> or = 41) coding exons with small sized introns spanning only approximately 35 kb of genomic DNA. Two alternative splicing events [involving exons 25 (129 bp) and 31 (69 bp)] make for a complex diversity of the Tsc2 product. The present determination of the Tsc2 gene and establishment of strong conservation between the rat and man provide clues for assessing unknown gene functions apart from that already predicted from the GTPase activating proteins (GAP3) homologous domain and for future analysis of intragenic mutations in tumors using methods such as PCR-SSCP and for insights into diverse phenotypes between species.

Alternative Splicing↗
PubMed1994

Hypouricemic and uricosuric actions of AA-193 in a hyperuricemic rat model.

In normal rats, consecutive administrations of AA-193 for 7 days maintained the dose-dependent uricosuric activity without significant changes of the plasma urate level. In clearance studies, AA-193 produced an increase in the fractional excretion of urate (FEua) namely an inhibition of the net urate reabsorption in the nephron, which was probably dependent on the plasma concentration of the agent. During in vitro studies, 1 mmol/L AA-193 had no effect on liver uricase activity and 0.2 mmol/L AA-193 did not inhibit xanthine dehydrogenase activity. Therefore, it is unlikely that AA-193 at physiologic doses has a significant effect on either the production or degradation of urate. To assess the hypouricemic effect of AA-193 derived from its uricosuric effect, we used uricase-inhibited rats produced by oxonate feeding. In the hyperuricemic rat model, consecutive administrations of AA-193 for 7 days increased urate excretion and decreased the plasma urate level. We conclude that AA-193 has a hypouricemic effect caused by increases in urate excretion in hyperuricemic rats.

Animals↗
PubMed1996

Presence of potent transcriptional activation domains in the predisposing tuberous sclerosis (Tsc2) gene product of the Eker rat model.

The Eker rat hereditary renal carcinoma is an excellent example of Mendelian dominant predisposition to a specific cancer in an experimental animal. We recently reported that a germline insertion in the rat homologue of the human tuberous sclerosis gene (TSC2) gives rise to dominantly inherited cancer in the Eker rat model, as well as a tumor suppressor nature for the Tsc2 gene function. We also showed a strong conservation between the rat and human gene products. The molecular function of the Tsc2 gene product (called "tuberin" in the human case) is not yet understood, although it contains a short amino acid sequence homologous to ras family GTPase-activating proteins (Rap1GAP). Here, we describe transcriptional activation domains (AD1 and AD2) in the carboxyl terminus of the Tsc2 product (in exons 30 and 32 and exon 41, respectively). The Eker insertional mutation (intron 30) disrupts their transcriptional activity. Whereas a COOH-terminal truncated Tsc2 protein was localized in the nucleus, the full-length protein is found predominantly in the perinuclear region of cytoplasm. The present demonstration of transcriptional activation domains in the Tsc2 gene provides clues for studying its role in renal carcinogenesis.

Amino Acid Sequence↗
PubMedDate not supplied

A new mechanism of serum creatine phosphokinase elevation in strangulated small bowel obstruction: an experimental rat model.

An experimental rat model was used to investigate the mechanisms of serum creatine phosphokinase (CPK) elevation in strangulated small bowel obstruction. Two models were used: a strangulated ileus model with the bowel lumen and blood flow obstructed simultaneously, and a control ileus model with only the bowel lumen occluded. The experiments demonstrated that CPK was released into the blood when the mesenteric blood flow was restored, and that CPK was released into the intestinal lumen in the strangulated ileus model but not the control ileus model. CPK activity in the mucosal layer of the strangulated ileus model was significantly decreased compared with that in the control ileus model. Purified CPK injected into the intestinal lumen was absorbed by the healthy intestine. These results suggest a new mechanism of serum CPK elevation in strangulated small bowel obstruction in which serum CPK is elevated with a significant decrease in mucosal CPK. Strangulated bowel content including mucosal CPK may be reabsorbed by the healthy distal intestine when bowel obstruction is incomplete.

Animals↗
PubMed1994

Thyroxine pretreatment and halothane administration alter Ca2+ transport and transmembrane potential in rat liver mitochondria. An additional mechanism for halothane-induced liver damage in the hyperthyroid rat model.

Male rats pretreated with thyroid hormones and exposed to halothane in non-hypoxic conditions develop acute liver damage. In order to investigate the mechanisms leading to liver damage in this animal model, the effects of thyroxine (T4) pretreatment and halothane administration on Ca2+ transport and transmembrane potential were studied in isolated rat liver mitochondria. Five-day T4-pretreatment reduced the mitochondrial Ca2+ loading capacity and increased the rate of Ca2+ cycling across the mitochondrial membrane. Halothane administration further increased Ca2+ cycling and produced a time- and dose-dependent loss of transmembrane potential which was more pronounced in mitochondria from T4-pretreated rats than in euthyroid animals. When mitochondria from T4-pretreated rats were incubated in the presence of the Ca2+ chelator EGTA, membrane potential was well preserved. In contrast, when Ca2+ concentration in the extramitochondrial medium was increased, mitochondria deenergization occurred earlier. These findings confirm that alterations in Ca2+ transport and mitochondrial function can be interrelated events and suggest that a Ca(2+)-dependent, halothane-induced loss of transmembrane potential could participate in generating acute liver damage in hyperthyroid rats exposed to halothane in non-hypoxic conditions.

Animals↗
PubMedDate not supplied

Metabolic alterations of toxic and nonessential elements by the treatment of Sempervivum tectorum extract in a hyperlipidemic rat model.

A hyperlipidemic rat model was used to examine the therapeutic effect of Sempervivum tectorum plant extract on the metabolic alterations of Al, As, B, Ba, Cd, Hg, Ni, Pb, and Ti in the liver and bile. Hyperlipidemia was produced by lipogenic diet and alcohol and verified by morphological investigation of the liver with the aid of light and an electron microscope. Element concentration in the liver and bile were determined by inductively coupled plasma optical emission spectrometry (ICP-OES). The concentration values in the liver higher than the detection limit (Al, Ba, Ni, Ti) were unambiguous. Significant differences were found for the four groups at p < 0.05 level (ANOVA). A significant difference was observed between Al and B concentration in the bile fluids of the 4 groups (p < 0.05). The excretion of Al and Ti into the bile fluid increased significantly (p < 0.05). Following the administration of S. tectorum extract to rats with hyperlipidemia, the excretion of Al, B and Ba increased, whereas the excretion of Ti decreased significantly (p < 0.05). The favorable action of the extract (protecting the liver in hyperlipidemic rats) was verified by morphological studies, and its detoxicating property was shown by the elimination of Al, Ba, Ni, and Ti from the liver.

Administration, Oral↗
PubMed1995

Topical immunoglobulin is an effective therapy for parainfluenza type 3 in a cotton rat model.

A cotton rat model was used to test the efficacy of topical immunotherapy against parainfluenza type 3 (PIV3) infection. On day 3 after experimental infection with 10(5.5) pfu of PIV3, animals were treated with 2-fold dilutions of convalescent cotton rat serum or with one of two purified human immunoglobulin preparations; all three had moderate titers of anti-PIV3 neutralizing antibody (range, 1:200-1:1000). Therapy with high concentrations of all three preparations resulted in significant reductions of > or = 2 logs (> or = 100-fold) of pulmonary virus titers compared with titers for control animals. Little or no reduction in virus titers were seen in nasal tissues.

Administration, Topical↗
PubMed1996

Combination of PS-15, epiroprim, or pyrimethamine with dapsone in prophylaxis of Toxoplasma gondii and Pneumocystis carinii dual infection in a rat model.

In a rat model of dual infection, we studied such dihydrofolate reductase (DHFR) inhibitors as PS-15 (25 mg/kg of body weight), epiroprim (100 mg/kg), and pyrimethamine (3 mg/kg) alone or in combination with various doses of dapsone (50, 25, or 5 mg/kg) for the prevention of pneumocystosis and toxoplasmosis. Rats latently infected with Pneumocystis carinii were immunosuppressed by corticosteroids for 7 weeks, and the drugs were administered from the initiation of the corticosteroid treatment. At week 5, the rats were inoculated intraperitoneally with the RH strain of Toxoplasma gondii. Infections were monitored by the counting of P. carinii cysts in lung homogenates and the titration of T. gondii in organs by quantitative culture and an indirect immunofluorescence assay. Fourteen of the 15 untreated rats died after T. gondii challenge, with P. carinii infection in the lungs and T. gondii infection in the lungs, liver, spleen, and brain. Of the three tested DHFR inhibitors, only PS-15 exhibited anti-P. carinii activity; none prevented toxoplasmosis in 100% of the rats. After the DHFR inhibitors were combined with dapsone (50 or 25 mg/kg), both pneumocystosis and toxoplasmosis were completely prevented. On the basis of these results, PS-15 and epiroprim combined with dapsone are candidates for use for the prevention of both pneumocystosis and toxoplasmosis.

Animals↗
PubMed2002

Cell death in the early adriamycin rat model.

The adriamycin rat model (ARM) exhibits many features of the VACTERL association. Adriamycin is a cytotoxic drug used in cancer chemotherapy. Although its exact mode of action is not clear, it is presumed to have a similar cytotoxic role in the developing embryo. Lysotracker red (LT) is a dye that stains phagolysosomes and apoptotic bodies and allows entire rodent embryos to be stained for apoptosis. We hypothesised that there was increased cell death in adriamycin-exposed embryos. To investigate this hypothesis, adriamycin (1.75 mg/kg) was given intraperitoneally to rats on days 7, 8, and 9 of pregnancy. A control group was given saline on the same schedule. Embryos were recovered at 3, 12, 24, and 48 h following the last dose and also at term (21 days) to confirm that the usual incidence of congenital anomalies found in the ARM was obtained in our animal model. Embryos were embedded in resin, sectioned, and studied by light microscopy. Embryos from the 3-h and 24-h groups were studied using LT and confocal microscopy to search for evidence of apoptosis. All term newborns (100%) from the adriamycin-treated group demonstrated the typical abnormalities found in the ARM, i.e., oesophageal atresia, multiple gastrointestinal atresias, vertebral malformations, absent tails, ureterohydronephrosis, etc. In the 9.5-day adriamycin group there was no difference in appearance between the experimental and control embryos. Specifically, no cellular debris or increased cell turnover indicative of adriamycin cytotoxicity was observed in the experimental group. At day 10.5, 90% of embryos from two separate litters had evidence of notochordal distortion and tethering to the gut or gut-tube abnormalities. These findings were not observed in the control embryos. Confocal microscopy and LT examination of the embryos from litters killed at 3 and 24 h following the last dose of adriamycin demonstrated no evidence of increased cell death in adriamycin-exposed embryos compared to control embryos. The absence of significant apoptosis in the developing embryos in the immediate period following administration of adriamycin suggests that the teratogenic effect of adriamycin is not caused by cell death.

Abnormalities, Drug-Induced↗
PubMed2000

Mapping and determination of the cDNA sequence of the Erc gene preferentially expressed in renal cell carcinoma in the Tsc2 gene mutant (Eker) rat model.

The Eker rat develops hereditary renal carcinomas (RCs) due to two hit mutations of the tumor suppressor gene, Tsc2. We previously identified using representational difference analysis (RDA), four genes that were expressed more abundantly in an Eker rat RC cell line than in normal kidney tissue. One gene, Erc (expressed in renal carcinoma) showed sequence homology to the mouse and human megakaryocyte potentiating factor (MPF)/mesothelin gene. The present study determines the full sequence of the cDNA and the exon-intron structure of the rat Erc gene and maps its locus in the chromosome by fluorescence in situ hybridization. Rat Erc and its human homologue were localized in chromosomes 10q12-21 and 16p13.3, respectively, both of which coincided with the locus of the Tsc2/TSC gene. We also found that Erc was expressed at higher levels in primary RCs compared with the normal kidney of the Eker rat. Erc may be related to carcinogenesis in the Tsc2 gene mutant (Eker) rat model.

Amino Acid Sequence↗
PubMed2002

Strain specific differences in a cardio-pulmonary resuscitation rat model.

An asphyxial cardiac arrest rat model, originally developed for Sprague-Dawley rats, was transferred to a Wistar rat model. Several strain specific life support adjustments, i.e. ventilator settings, anaesthesia, and drug requirements, were necessary to stabilize the model for Wistar rats. Despite these arrangements numerous resuscitation related variables appeared different. Three groups were evaluated and compared: a temperature monitored Wistar group 1 (n=34), a temperature controlled Wistar group 2 (n=26) and a temperature controlled Sprague-Dawley group 3 (n=7). Overall, Wistar rats seem to have more sensitive cardio-circulatory system evidenced by a more rapid development of cardiac arrest (164 vs. 201 s), requiring higher adrenaline/epinephrine doses (10 vs. 5 microg/kg) and requiring more time for recovery after resuscitation (i.e. for return of blood pressure and blood gases). Without strict temperature control (as in groups 2+3 rats) group 1 rats went into spontaneous mild to moderate hypothermia during the first 24 h after restoration of spontaneous circulation (ROSC). Spontaneous hypothermia delayed the development of overall visible CA1 neuronal damage 24-48 h, but did not prevent it; therefore the model seemed to be suitable for future studies. Neuronal damages in the CA1 region in Wistar rats appeared to be more as shrunken cell bodies and pyknotic nuclei before resorption took place, whereas in Sprague-Dawley rats appeared in the same region.

Animals↗