SEARCH · PubMed Health

Results for “RATS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 217 records · Page 12Linked to original sources

PubMed2002

Very high alpha-tocopherol diet diminishes oxidative stress and hypercoagulation in hypertensive rats but not in normotensive rats.

BACKGROUND: Oxidative stress is closely related to cardiovascular diseases, such as atherosclerosis. Increasing dietary antioxidants, such as alpha-tocopherol, may prevent these diseases. However, in some pathologies, such as hypertension, oxidative stress is enhanced, thus alpha-tocopherol requirements may be raised. MATERIAL/METHODS: In eleven-week-old spontaneously hypertensive rats and normotensive Wistar Kyoto rats, we investigated the effects of a four-week very high alpha-tocopherol dietary enrichment (1,200 mg/kg diet, VH) on blood pressure, resistance to free radical aggression, and VLDL+LDL resistance to lipid peroxidation. Platelet aggregation and plasma lipid profile were also investigated. RESULTS: With either diet, hypertensive rats were more protected against oxidative stress than normotensive rats. Their capacity to withstand free radical aggression was better, and their VLDL+LDL particles were less sensitive to lipid peroxidation. In either group, the VH diet did not modify blood pressure values when resistance to free radical aggression was increased, but not the resistance of VLDL+LDL to lipid peroxidation. With the control diet, platelet aggregation was faster and higher in hypertensive rats vs. normotensive rats. It was decreased with the VH diet in hypertensive rats but increased in normotensive rats, when compared to their respective controls. Whatever the diet, plasma triacylglycerol, phospholipid and cholesterol concentrations were lower in hypertensive than in normotensive rats. Only cholesterol concentrations were diminished with the VH diet in hypertensive rats, but not in normotensive rats. CONCLUSIONS: These results indicate that very high alpha-tocopherol dietary amounts decrease cardiovascular risk in hypertensive rats with high oxidative stress, but have less effect on normotensive rats.

Animals↗

PubMed1989

Animal model of anxiety: effect of acute diazepam treatment in the older adult genetically hypertensive rats of Koletsky type and in the older adult rats of Wistar strain.

The experiments were performed in the older adult (10-14 months of age) normotensive rats of Wistar strain and in the genetically hypertensive rats which developed Koletsky; the experiments were performed in both sexes. The behavior of control and diazepam treated rats were traced in the holeboard and in the elevated plus-maze. In the control animals when compared to the normotensive rats of both sexes show increase in total time of locomotor-exploratory activity in holeboard. In control animals the lowest level of directed exploration was found in the genetically hypertensive males. The control genetically hypertensive males show also the highest aversion towards open space and hight in the elevated plus-maze. Diazepam increases directed exploration in the genetically hypertensive rats of both sexes; directed exploration in the normotensive rats is not influenced by diazepam or this drug caused decrease. Diazepam shows no effect in between-session habituation of directed exploration in the normotensive rats of both sexes; in the genetically hypertensive rats under diazepam treatment instead of between-session habituation of directed exploration there appears in the second session elevation of directed exploration. Diazepam treatment alleviates in the first session aversion towards open space and hight in the elevated plus-maze only in the genetically hypertensive rats of both sexes and in the normotensive males. In the second session statistically significant alleviation of aversion towards open space and hight was attained in both strains of rats, in both sexes and under the both doses of diazepam. Considering the different markers of aging, stress plasma corticosterone and/or diazepam induced hypothermia show tighter age dependence in the genetically hypertensive rats than in the normotensive rats of Wistar strain. On the other hand, the effect of diazepam on aversion towards open space and hight show closer age dependence in the latter type of rats.

Age Factors↗

PubMed1994

Dde I restriction fragment length polymorphism of the alpha 2-adrenoceptor gene does not correlate with blood pressure in the F2 generation obtained from crossing stroke-prone spontaneously hypertensive rats and Wistar-Kyoto rats.

OBJECTIVE: A pathogenetic role of altered alpha 2-adrenoceptors in essential hypertension has been suggested, based on studies in humans and animals. To examine the role of the alpha 2-adrenoceptor in genetically hypertensive rats, we compared the alpha 2-adrenoceptor genes of stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats by restriction fragment length polymorphism analysis using human alpha 2-adrenoceptor probes (alpha 2-C10) and Dde I restriction endonuclease, and conducted a genetic cosegregation study. METHOD: Five female WKY rats were bred with five male SHRSP. Eight pairs of F1 rats were mated in brother-sister pairs to yield an F2 population of 84 rats. Systolic blood pressure was determined by tail-cuff sphygmomanometry. Direct arterial blood pressure was taken under ether anaesthesia just before the rats were killed. Southern blots were performed using alpha 2C10 as a probe and the DNA from the F2 generation. RESULTS: A restriction fragment length polymorphism of the SHRSP allele of a 1.6-kb fragment and a WKY rat allele of a 0.9-kb fragment with a common band of 1.3 kb in SHRSP and WKY rats was found, as reported previously. The distribution of the genotype based on restriction fragment length polymorphism conformed to a 1:2:1 ratio in F2 rats, as expected for a Mendelian trait. There was no significant difference in the blood pressure of F2 rats with respect to alpha 2-adrenoceptor genotype. CONCLUSION: This study demonstrated that the alpha 2-adrenoceptor gene restriction fragment length polymorphism distribution is a Mendelian trait in the F2 rats of crossed SHRSP and WKY rats, but failed to show genetic cosegregation of this restriction fragment length polymorphism with blood pressure in this generation.

Alleles↗

PubMed1998

VTA dopamine neuron activity distinguishes alcohol-preferring (P) rats from Wistar rats.

The mesolimbic dopamine (DA) system is innately deficient in rats selectively bred for high alcohol drinking behavior compared with rats selectively bred for low alcohol drinking and unselected rats. In alcohol-preferring (P) rats, compared with alcohol-nonpreferring (NP) rats, this is evidenced by fewer DA neurons in the ventral tegmental area (VTA) projecting to the nucleus accumbens (ACB). Yet, despite this deficiency, DA release in the ACB is similar in P, NP, and Wistar rats. DA release is regulated by DA neuronal activity, and DA neurons fire tonically as well as in bursts. Burst firing has been shown to substantially enhance DA release compared with tonic firing. The present study was designed to test the hypothesis that the remaining VTA DA neurons in P rats have faster firing frequencies and/or burst fire more frequently than VTA DA neurons in Wistar rats. The spontaneous activity of VTA DA neurons was recorded in unanesthetized alcohol-naive P and Wistar rats. A conventional burst analysis on 500 consecutive action potentials revealed that P rats had a significantly (p < 0.05) greater percentage of action potentials in bursts when compared with Wistar rats (P: 50.9%, Wistar: 34.4%). Firing frequency and other burst parameters (burst interspike interval, burst length, interburst interval, and the number of action potentials per burst) did not distinguish the two groups of rats. The increased burst activity in P rats may represent a compensatory mechanism to maintain adequate basal levels of DA despite the deficiency in the mesolimbic DA system.

Alcohol Drinking↗

PubMed2000

NTP Toxicity Studies of Benzyltrimethylammonium Chloride (CAS No. 56-93-9) Administered by Gavage to F344/N Rats, Sprague-Dawley Rats, and B6C3F1 Mice.

Benzyltrimethylammonium chloride is widely used as a solvent for cellulose, a gelling inhibitor in polyester resins, a chemical intermediate, a paint dispersant, and an acrylic dyeing agent. It is also used in plant growth regulator compositions and synthetic processes. The National Institute of Environmental Health Sciences nominated benzyltrimethylammonium chloride for study due to its high production volume and the potential for occupational exposure, as well as the limited information on toxicity of this chemical. Male and female F344/N rats and B6C3F1 mice received benzyltrimethylammonium chloride by gavage for 16 days or 13 weeks. Animals were evaluated for hematology, clinical chemistry, histopathology, neurotoxicity, and reproductive toxicity. Genetic toxicology studies were conducted in Salmonella typhimurium and in mouse peripheral blood erythrocytes. In the 16-day studies, groups of five male and five female rats received 0, 16, 32, 63, 125, or 250 mg benzyltrimethylammonium chloride/kg body weight in deionized water by gavage, 5 days per week for 16 days. Groups of five male and five female mice received 0, 63, 125, 250, 500, or 1,000 mg/kg benzyltrimethylammonium chloride in deionized water by gavage, 5 days per week for 16 days. All rats in the 125 and 250 mg/kg groups, all mice in the 250, 500, and 1,000 mg/kg groups, and one 125 mg/kg female mouse died on day 1 of the studies. Clinical findings observed in 125 mg/kg male and female rats included abnormal breathing, ataxia, lethargy (males only), nasal and eye discharge, and tremors. Salivation was slightly increased in male and female rats in the 63 mg/kg groups. Female mice in the 125 mg/kg group had a significantly greater absolute liver weight than that of the vehicle controls. No gross or microscopic changes observed in rats or mice were considered related to chemical administration. In the 13-week studies, groups of 10 male and 10 female rats and mice received benzyltrimethylammonium chloride in deionized water by gavage at doses of 0, 12.5, 25, 50, or 100 mg/kg, 5 days per week for 13 weeks. Benzyltrimethylammonium chloride generally had little effect on the body weights of rats or mice. Final mean body weights of dosed animals were within 8% (rats) or 3% (mice) of the control group body weights. The deaths of two female rats and one male and one female mouse administered 100 mg/kg were the result of pharmacologic effects on the cardiovascular system. Some cholinergic effects including chromodacryorrhea, lacrimation, salivation, pupillary constriction, altered gait, and mild tremors were observed at nonlethal doses in rats; these effects were accompanied by alterations in body position. No significant target organ toxicity was observed in dosed rats or mice. Benzyltrimethylammonium chloride was not mutagenic in S. typhimurium strain TA97, TA98, TA100, or TA1535, with or without S9 metabolic activation enzymes. However, significant increases in the frequency of micronucleated normochromatic erythrocytes were found in the peripheral blood of male and female mice administered benzyltrimethylammonium chloride by gavage for 13 weeks. Based on the mortality observed in the 16-day and 13-week studies, rats and mice appeared to be equally sensitive to benzyltrimethylammonium chloride. The minimally toxic dose for rats and mice was estimated to be 50 mg/kg.

Journal Article↗

PubMed1983

High, vasopressin-reversible, immunoreactive somatostatin in specific hypothalamic nuclei of rats with diabetes insipidus (Brattleboro rats).

Somatostatin content was studied in brain nuclei and pituitary lobes of homozygous Brattleboro rats lacking vasopressin (DI rats) with and without vasopressin replacement, and their corresponding controls, heterozygous Brattleboro (HZ) rats and Long-Evans (LE) rats. High, vasopressin-reversible, somatostatin levels occurred in DI rats. The changes in somatostatin were localized to the nucleus periventricularis and to brain areas receiving somatostatin projections from this nucleus, including the eminentia mediana. In contrast, vasopressin administration failed to alter somatostatin levels in HZ rats. In brain areas not belonging to the somatostatin periventricular system, the peptide concentration in DI rats was not higher than that of LE controls. High somatostatin levels were present in the intermediate lobe of the pituitary gland. Somatostatin was higher in DI and HZ rats when compared to LE rats. In the posterior pituitary lobe, HZ rats had higher, and DI rats lower, somatostatin than control LE rats. These results suggest that rat brain and pituitary vasopressin and somatostatin systems are interrelated.

Animals↗

PubMed1990

Somatic, endocrine and metabolic changes in controls pair-fed for six weeks to rats with dorsomedial hypothalamic nucleus lesions (DMNL rats).

One group of weanling male Sprague-Dawley rats received lesions in the dorsomedial hypothalamic nuclei (DMNL rats), whereas two additional groups of rats were sham-operated (CON). One of these CON groups was allowed to feed ad lib (CON-ADLIB) while the other CON group was pair-fed for 6 weeks to the DMNL rats (CON-PF). Despite eating the same amount of food as DMNL rats. CON-PF animals had consistently lower body weights and also utilized food energy more poorly than DMNL rats. The CON-PF group also had smaller kidneys and less percent liver protein but more epididymal fat pad percent protein than DMNL rats. Whereas plasma glucose concentrations were comparable among the three groups, insulin levels were significantly higher, and free fatty acid levels lower in CON-PF than in DMNL rats. The CON-PF group incorporated less glucose-U-C14 carbon into liver glycogen but more of the tracer into liver lipid than the DMNL group. Glucose carbon was also incorporated more avidly into epididymal fat pad lipid by CON-PF than by DMNL rats. The data not only confirm previous findings in DMNL rats but in addition show that the neurologically intact rats fed the same amount of food that is eaten spontaneously by DMNL rats show somatic and metabolic alterations that suggest that they cannot cope with this low amount of substrate. The normalcy of the DMNL rats, compared to ad lib-fed sham-operated controls, in all metabolic parameters suggests that the low food intake is indeed "normal" for this preparation and may be the reflection of an "organismic" set point.

Animals↗

PubMed2006

Extracellular dopamine levels are lower in the medial prefrontal cortex of alcohol-preferring rats compared to Wistar rats.

Previous studies have identified deficiencies in the mesocorticolimbic dopamine (DA) systems of alcohol-preferring (P) rats. This study uses quantitative microdialysis to compare the extracellular levels of DA in the medial prefrontal cortex (MPF) of P rats and outbred Wistar rats and also compares the effects of systemic ethanol administration on DA levels in the MPF using traditional microdialysis. In experiment 1, male Wistar and P rats were implanted with loop-style microdialysis probes and later perfused at 0.5 microl/min with artificial cerebrospinal fluid for 120 min prior to five baseline (20-min) sample collections. Three concentrations (5, 10, and 20 nM) of DA were then perfused in random order for 100 min each. Samples (20-min) were collected and stored at -70 degrees C until assayed using high performance liquid chromatography/electrochemical detection (HPLC/EC), and the data were analyzed using the quantitative no-net-flux (NNF) method. In experiment 2, male Wistar and P rats were implanted with dialysis probes aimed at the MPF. After collecting four baseline samples, all rats were injected (i.p.) with one dose of either 0.9% saline or 2.0 g/kg ethanol. Microdialysis samples were collected at 20-min intervals and stored at -70 degrees C until analyzed by HPLC/EC. NNF microdialysis yielded significantly (P<.05) lower extracellular DA concentrations in the MPF of P rats compared to Wistar rats (2.0+/-0.4 vs. 4.8+/-0.4 nM, respectively). The extraction fractions were not different between the P and Wistar groups (69+/-3 vs. 65+/-3%, respectively). No significant change in extracellular DA levels was observed in P rats or Wistar rats after either saline or 2g/kg ethanol. The lower extracellular concentrations of DA in the MPF of P rats compared to Wistar rats, without a difference in the extraction fraction, suggest that DA neurotransmission is lower in the MPF of the P rat. This lower DA neurotransmission could be a result of reduced activity of the DA neurons projecting to the MPF, reduced excitatory or increased inhibitory tone occurring locally within the MPF, and/or reduced DA innervation to the MPF. The lack of effect of systemic EtOH administration on extracellular DA levels in the MPF suggests that unlike the mesolimbic DA system, the mesocortical DA system is not responsive to acute EtOH administration.

Alcohol Drinking↗

PubMed2005

GHB-C rats: the control line of GHB-sensitive (GHB-S) and GHB-resistant (GHB-R) rats.

Gamma-hydroxybutyric acid (GHB)-sensitive (GHB-S) and GHB-resistant (GHB-R) rats have been selectively bred for their opposite sensitivity to the sedative/hypnotic effect of GHB. This opposite sensitivity has been found to generalize to the GABA(B) receptor agonist, baclofen. A control line [named GHB-control (GHB-C)] has been derived from the foundation stock of GHB-S and GHB-R rats. GHB-C rats have been bred without any evaluation of their sensitivity to GHB. The experiments described here were designed to evaluate the sensitivity of GHB-C rats, from the 13th generation, to the sedative/hypnotic effect of GHB (1 g/kg, i.p.) and baclofen (20 mg/kg, i.p.). All measures (onset, sleep time and r = sleep time/onset) of sensitivity to GHB- and baclofen-induced sedation/hypnosis in GHB-C rats were significantly different from and intermediate to those recorded in GHB-S and GHB-R rats. Furthermore, these values were similar to those recorded in the foundation stock. These results suggest that GHB-C rats may constitute a valid control line for GHB-S and GHB-R rats, representing the "general population" from which GHB-S and GHB-R rats were derived. Furthermore, the relative equidistance of sensitivity to GHB- and baclofen-induced sedation/hypnosis of GHB-C rats from those of GHB-S and GHB-R rats suggests that genetic factors contributes to the development of both sensitivity in GHB-S rats and resistance in GHB-R rats.

Animals↗

PubMed2005

Lower packing density of glial fibrillary acidic protein-immunoreactive astrocytes in the prelimbic cortex of alcohol-naive and alcohol-drinking alcohol-preferring rats as compared with alcohol-nonpreferring and Wistar rats.

BACKGROUND: Low packing density of glial cells, possibly astrocytes, has been described in the prefrontal cortex and hippocampus of "uncomplicated" alcoholics. Astrocytes perform crucial support functions in the processing of neurotransmitters and transfer of energy substrates from blood to cortical neurons. It is still unknown whether attrition in the numbers of astrocytes is only a consequence of prolonged alcohol abuse or also predates the exposure to alcohol in subjects at risk for alcohol dependence. METHODS: We used alcohol-preferring (P) rats exposed ad libitum for 2 or 6 months to either water only or 10% ethanol and alcohol-nonpreferring (NP) rats and nonselected Wistar rats exposed only to water for 2 months. Sections through the rat frontal cortex were immunostained for glial fibrillary acidic protein (GFAP), a specific marker of astrocytes. The packing density of GFAP-immunoreactive (IR) astrocytes and the area fraction of GFAP immunoreactivity were measured in the prelimbic cortex (PLC) using the dissector probe and analysis of binary images of GFAP immunostaining, respectively. RESULTS: The packing density of GFAP-IR astrocytes was significantly lower in both alcohol-naive and alcohol-exposed P rats than in NP rats or Wistar rats. The area fraction of GFAP immunoreactivity was significantly lower in the alcohol-exposed P rats than in NP rats, Wistar rats, and alcohol-naive P rats. CONCLUSION: These results suggest that low density of GFAP-IR astrocytes in the PLC of P rats predates the exposure to alcohol and might be a factor contributing to the increased risk for alcohol dependence. In addition, prolonged free-choice alcohol drinking may reduce the extent of GFAP-IR processes in the PLC of P rats.

Alcohol Drinking↗

PubMed2000

Population structure of rat-derived Pneumocystis carinii in Danish wild rats.

The rat model of Pneumocystis carinii pneumonia is frequently used to study human P. carinii infection, but there are many differences between the rat and human infections. We studied naturally acquired P. carinii in wild rats to examine the relevance of the rat model for human infection. P. carinii DNA was detected in 47 of 51 wild rats and in 10 of 12 nonimmunosuppressed laboratory rats. Evidence for three novel formae speciales of rat-derived P. carinii was found, and these were provisionally named Pneumocystis carinii f. sp. rattus-secundi, Pneumocystis carinii f. sp. rattus-tertii, and Pneumocystis carinii f. sp. rattus-quarti. Our data suggest that low-level carriage of P. carinii in wild rats and nonimmunosuppressed laboratory rats is common and that wild rats are frequently coinfected with more than one forma specialis of P. carinii. We also examined the diversity in the internally transcribed spacer (ITS) regions of the nuclear rRNA operon of Pneumocystis carinii f. sp. carinii by using samples from wild rats and laboratory rats and spore trap samples. We report a lack of variation in the ITS1 and ITS2 regions that is consistent with an evolutionary bottleneck in the P. carinii f. sp. carinii population. This study shows that human- and rat-derived P. carinii organisms are very different, not only in genetic composition but also in population structure and natural history.

Animals↗

PubMed1991

The disappearance rate of human versus rat intermediate density lipoproteins from rat liver perfusion.

The aim of this work was to compare the disappearance rate of human and rat intermediate density lipoproteins (IDL) using the rat liver perfusion system. Human and rat IDL were produced in vitro by incubating human or rat very low density lipoproteins (VLDL) with either rat post-heparin plasma (method I) or a resolubilized isopropanol precipitate of rat post-heparin plasma (method II). With both methods, the degree of triacylglycerol lipolysis was approximately 55%. The different preparations of IDL were labelled with 125I and added to perfusates of rat livers. The disappearance rates of 125I-labelled IDL were monitored by measuring the radioactivity associated with apolipoprotein (apo) B in the perfusate during a 15-min period. Both human and rat IDL prepared with method I had an increased apoE to apoC ratio as compared with their native counterparts. Furthermore, human IDL had a significantly higher apoE to apoC ratio than rat IDL. However, when IDL were produced in the absence of exchangeable apolipoproteins (method II), no change in the apoE to apoC ratios was observed for the transformation of VLDL to IDL and the ratios were similar for human and rat IDL. Despite these differences, human IDL were always removed at a lower rate than rat IDL. The only striking difference between the two types of IDL made by method II was that the apoB100 to apoB48 ratio was considerably higher in human than in rat IDL. These results suggest that the apoB100 to apoB48 ratio is likely to be responsible for the observed differences in liver uptake between rat and human IDL.

Animals↗

PubMedDate not supplied

Prepubertal rats are more resistant to ischemic renal injury and recover more rapidly than adult rats.

Bilateral clamping of renal pedicles during 60, 75 or 90 min was used to characterize the evolution of ischemic acute renal failure (ARF) in prepubertal rats. To verify the existence of age-conditioned differences in the evolution of ARF, adult rats were exposed to 40, 60 or 75 min of clamping. After 7 days, survival rate was significantly better in young than adult rats for identical times of clamping (89 vs. 35% for 60 min and 69 vs. 35% for 75 min). Young rats largely died within the first 24 h following ischemia while the risk of death extended until the 4th day after ischemia in adult rats. Peak values of serum urea nitrogen and creatinine were observed on the 1st and 3rd day after ischemia in young and adult rats, respectively. In young rats, these markers of renal function returned to normal on days 5 and 6 whereas they remained elevated at the end of the study in adult animals. Growth curves of young rats paralleled those of sham-operated animals from the 3rd day of clamping whereas adult rats did not even reach the initial weight at the end of the study. Analysis of kidneys obtained 7 days after clamping revealed more severe histopathological lesions in adult rats as well as a higher proliferative activity (10-40 times the value of sham-operated animals versus 2-4 times the control value in young rats). Our findings indicate that kidneys from young rats are more resistant to ischemia and recover more quickly from the ischemic insult. Therefore, the experimental model of ischemic ARF is clearly different in young and adult rats.

Acute Kidney Injury↗

PubMed1988

Localization of 7B2, neuromedin B, and neuromedin U in specific cell types of rat, mouse, and human pituitary, in rat hypothalamus, and in 30 human pituitary and extrapituitary tumors.

The distributions of three novel peptides, 7B2, neuromedin B, and neuromedin U, in rat, mouse, and human pituitaries, rat hypothalamus, and 30 human pituitary tumors were investigated with immunocytochemistry. Immunoreactivity for 7B2 was present in rat, mouse, and human gonadotropes, in intermediate lobe cells and posterior lobe nerve fibers in rats and mice, in rat hypothalamus (particularly in the median eminence), and in eight human pituitary gonadotropinomas. In gonadectomized rats, larger, more numerous LH beta- and 7B2-immunoreactive gonadotropes were seen than in controls. Extractable 7B2-like immunoreactivity was elevated but not significantly so in gonadectomized rat pituitaries [males: castrated, 37.4 +/- 4.3 (mean +/- SE); controls, 26.9 +/- 4.3; females: ovariectomized, 27.2 +/- 2.7; controls, 19.1 +/- 2.2 pmol/gland]. Neuromedin B immunoreactivity was found in normal rat and mouse thyrotropes and weakly in "thyroidectomy" cells in hypothyroid rats, in which extractable pituitary neuromedin B was significantly depleted (thyroidectomized, 87.0 +/- 14.0; methimazole-treated, 82.0 +/- 11.4; control, 230.7 +/- 25.6 fmol/gland). Hyperthyroid rat pituitaries showed increased TSH beta and neuromedin B immunoreactivities and neuromedin B content (TRH-treated, 385.2 +/- 30.2; T4-treated, 352.6 +/- 20.2; control, 230.7 +/- 25.6 fmol/gland). Neuromedin U immunoreactivity occurred in corticotropes of all species, in rat and mouse intermediate lobe, and throughout the rat hypothalamus, with immunoreactive cell bodies in the arcuate nucleus. Neuromedin U-immunoreactive cells were present in six of six human pituitary and five of six human extrapituitary corticotropinomas. In adrenalectomized rats, corticotropes were larger and more numerous than in controls, but extractable anterior pituitary neuromedin U-like immunoreactivity was not raised (adrenalectomized, 3.30 +/- 0.45; control, 3.32 +/- 0.27 pmol/gland). Our findings suggest that 7B2, neuromedin B, and neuromedin U may be involved in pituitary function.

Animals↗

PubMed2005

Rat PXR reporter-gene activity correlates with the induction of CYP3A in rat precision-cut liver slices.

Recent studies have suggested that both constitutive androstane receptor (CAR) and pregnane X-receptor (PXR) are involved in the induction of rat liver microsomal cytochrome P-450 (CYP) 2B and 3A through a mechanism called cross-talk. In this study we intend to determine if a PXR-reporter gene assay could be used for the prediction of CYP3A and/or CYP2B induction in rats. The induction of rat CYP2B and CYP3A by nineteen structurally diverse compounds was evaluated by using rat precision-cut liver slices and a rat PXR reporter-gene system. Induction of CYP2B and CYP3A mRNAs in rat liver slices was quantified by real-time polymerase chain reaction. Rat PXR activation was measured by induction of luciferase activity in rat PXR reporter-gene system. Linear regression analysis of the fold of induction of mRNA in liver slices and the fold of luciferase activity in rat PXR reporter-gene system shows that a reasonable correlation (r2 = 0.6) exists between the CYP3A induction and the rat PXR activation. A much lower correlation was observed between CYP2B induction and the rat PXR activation (r2 = 0.1). The results from this study suggest that the PXR may play a major role in the induction of rat CYP3A, but not CYP2B. Therefore, the PXR-reporter gene assay may be useful in a high-throughput screening to predict CYP3A induction in rats.

Animals↗

PubMed1994

Comparison of retinal lesions in alloxan-diabetic rats and galactose-fed rats.

Galactose-fed rats develop a retinal microvascular disease, but retinopathy has not been found to develop reproducibly in diabetic rats. We sought to determine which retinal lesions can be reproducibly produced by long-term diabetes in rats, the extent to which the capillary lesions in diabetic rats and galactosemic rats are similar, and whether the retinopathy induced by 50% galactose can be reproduced satisfactorily by a lower concentration of galactose. Alloxan-diabetic rats and rats fed either a 50% galactose diet or a 30% galactose diet were killed after comparable durations of study (18 to 22 months). Rats fed 50% galactose showed greater than normal frequency of retinal pericyte ghosts and acellular capillaries, and thickening of capillary basement membranes by 18 months of galactosemia. Rats eating 30% galactose developed similar retinal lesions, and tended to be healthier than rats fed 50% galactose. Diabetes of 1 1/4 years or more likewise resulted in retinal pericyte ghosts, acellular capillaries and thickened capillary basement membrane. IRMAs and other vascular abnormalities were not reproducibly demonstrated at this duration of study, and saccular microaneurysms were not seen in any groups. In a number of diabetic rats, the severity of diabetes diminished spontaneously (after 1 to 1 1/2 years of insulin deficiency), thus making it essential that glycemia be systematically monitored. Both diabetic rats and experimentally galactosemic rats develop microvascular lesions that are consistent with at least the early stages of diabetic retinopathy, and these models should be useful to screen potential therapies for their ability to inhibit the development of retinopathy.

Alloxan↗

PubMedDate not supplied

Expression of crisp-1 mRNA splice variants in the rat epididymis, and comparative analysis of the rat and mouse crisp-1 gene regulatory regions.

The rat Crisp-1 gene encodes Protein DE (acidic epididymal glycoprotein; AEG), a glycoprotein secreted by the epididymal epithelium that associates with maturing sperm and has been implicated in the process of sperm-egg fusion. Previous characterization of the Crisp-1 messenger RNA in the rat epididymis has demonstrated the presence of 3 splice variants (Klemme et at, 1999). This study was undertaken to determine if expression of the Crisp-1 splice variants in the rat epididymis is region-specific and correlates with the region-specific pattern of synthesis of the D and E forms of the Crisp-1 protein. Expression of each of the splice variants was shown by RNase protection assays to be under the control of androgens, but they are not differentially regulated either within the epididymal segments or along the length of the organ. The reported structure of the mouse Crisp-1 gene does not include an exon that is equivalent to the rat exon 1, suggesting that the rat splice variants cannot exist in the mouse and may be specific to the rat. Furthermore, the mouse transcription start site is situated in a different region of the gene than in the rat. In this study, a comparison of the mouse and rat genes in the region flanking the mouse exon 1 and the rat exon 2 (within the rat intron 1) shows greater than 80% sequence identity, including the conservation of several putative androgen receptor binding sites. In addition, the rat gene is shown to have a corrupted TATA box in intron 1 that corresponds to the TATA box located in the mouse gene. These observations explain the preferential transcription for the mouse gene in this region, while the predominant start site for the rat gene is 5' of the upstream exon 1. Although an exon corresponding to the rat exon 1 has not been found in the mouse gene, reverse transcription-polymerase chain reaction experiments using mouse epididymal RNA suggest that such an exon exists in the mouse gene and is transcribed at low frequency.

Alternative Splicing↗

PubMed1992

[Effects of ethanol intake by the mother rat on learning ability and behavior of offspring rats].

The effects of ethanol intake by the mother rat were studied in five groups of Fischer strain rats; we observed learning ability and behavior of offspring rats using a maze with eight radial arms. I The ethanol free-intake groups (F-) were given a 10% aqueous solution of ethanol, classified by length of ethanol exposure. The mother rats were exposed to ethanol from a young age. The offspring were classified as follows: A. to the delivery (F-DEL), B. to the lactation period (F-NURS), C. to the lactation period, and after weaning, the offspring was continuously exposed to the maze experiment (F-CON). II The ethanol compulsory-intake group (P-DEL) was given a 20% aqueous solution of ethanol, 2 ml/100 g b.w., for the first time on the first day of pregnancy. The solution was given orally once a day through gestation. III The control group was not exposed to ethanol. Radial arm maze observations were made on offspring rats during a total of 30 trials, and we made the following findings: 1) The number of trials required for fulfilling learning criterion was significantly large in F-DEL and F-NURS male rats groups relative to the controls; that is, F-DEL and F-NURS were slow in learning. The number of rats which did not fulfill the learning criterion was significantly large in F-DEL and F-NURS male rats groups, relative to the controls. 2) In all groups running time was shortened with training time, it was result of acclimation to the device and of practice to catch and eating feed. In female rats of the F-DEL and F-NURS groups, running time was not shortened with the training, relative to the control. 3) The behavior of the rats in the F-CON group differed from those in the other groups: The number of well-performed trials was significantly large in F-CON rats group relative to control. They seemed to lack carefulness, and the number of times they failed to eat the feeds even though they succeeded in selecting the correct arm, was significantly large in F-CON female rats group, relative to the controls, in the final 10 trials. Their motion was abrupt and they ran at extraordinarily high speeds. 4) The number of trials required for fulfilling learning criterion was significantly large in the P-DEL rats relative to the controls.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗