PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “rat model”

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 55 records · Page 3Linked to original sources
PubMed1979

Organ and tumor specificity of colon mucoprotein antigen in a rat model.

We purified a high-molecular-weight colon mucoprotein antigen (CMA) from normal F344 rat colon and from a transplantable dimethylhydrazine-induced colon carcinoma. Chemical analysis of the mucins showed similar amino acid and carbohydrate compositions. This finding was in contrast to the major differences that occurred in the composition of human CMA as a consequence of neoplasia. Immunohistochemical techniques were used in an examination of organ and tumor specificities. A New Zealand White rabbit antiserum against purified normal rat CMA, appropriately absorbed, detected a normal colon-specific determinant(s). The organ-specific determinant was lost as a consequence of neoplasia. However, a new tumor-specific determinant was then detected. CMA may have a potential role as an organ-specific marker of the neoplastic process.

Amino Acids↗
PubMed2026

Effects of Intravenously Administered Plasma from Exercise-Trained Donors on Mitochondrial Respiration in a Rat Model of Alzheimer's Disease.

PURPOSE: Dysfunction of mitochondria is observed early in Alzheimer's disease (AD), possibly driving the pathogenesis of the disease. This study aims to assess whether plasma from exercise-trained donors can enhance mitochondrial function in a transgenic AD model and to gain insight into the proteomic profile of the donor plasma. METHODS: Male McGill-R-Thy1-APP rats (n = 3 per treatment group) were treated at either an early preplaque stage (2.2 months) or a later stage (5.2 months) with plasma from exercise-trained donors (ExPlas), sedentary donors (SedPlas), or saline. The rats received 14 transfusions over 6&#x2009;wk. Mitochondrial respiration was assessed in cornu ammonis (CA), dentate gyrus (DG), gastrocnemius, and left ventricle using high-resolution respirometry. Proteomic analyses were performed in donor blood using mass spectrometry. RESULTS: In early-stage AD rats, ExPlas improved hippocampal mitochondrial respiration. Compared with saline, CA oxidative phosphorylation (OXPHOS) capacity for complex I increased by +30.8 pmol O2&#xb7;s-1&#xb7;mg-1 (P < 0.001) and CI+II by +37.8 pmol O2&#xb7;s-1&#xb7;mg-1 (P < 0.001). Compared with SedPlas, CA OXPHOS for CI increased by +16.9 pmol O2&#xb7;s-1&#xb7;mg-1 (P = 0.01) and CI+II by +23.8 pmol O2&#xb7;s-1&#xb7;mg-1 (P = 0.007). In DG, similar improvements were only seen compared with saline. In CA, but not DG, of later-stage rats, ExPlas produced smaller but significant increases in CI and CI+II OXPHOS compared with saline, but no significant differences compared with SedPlas. No changes were observed in muscle or heart. Proteomics revealed enrichment of complement and platelet-related pathways in ExPlas. CONCLUSIONS: This proof-of-concept study shows that exercise-trained donor plasma enhances hippocampal mitochondrial respiration in early-stage AD rats and, to a lesser extent, in later-stage AD rats. The proteomic profile of the exercise-trained donor plasma indicates a role of altered complement and platelet functions.

Animals↗
PubMedDate not supplied

Nomifensine chronopharmacology, schedule-shifts and circadian temperature rhythms in di-suprachiasmatically lesioned rats--modeling emotional chronopathology and chronotherapy.

Some emotional disorders are associated with alterations of biological rhythm characteristics ('echronism'). Chronotherapy aims empirically to 1. optimize the kind and timing of conventional psychopharmacologic treatment and, need be, to use such old or new molecules in the rational endeavor to 2. correct (disease-determining) rhythm alteration directly. With respect to the first aim, a reduction by timing of undesired pharmacodynamic effects, as well as an amplification of empirically desired ones, can be dramatically illustrated by circadian rhythms in tolerance to many drugs affecting the central nervous system of rodents. A more rational approach is aimed at correcting ecchronism. The new antidepressant drug, nomifensine, achieves this task in rats with bilateral suprachiasmatic lesions, exhibiting in the telemetered core temperature an echronism of varying degrees. In this model system for the chronobiotic treatment of ecchronism, the properly timed administration of nomifensine speeds the adjustment of bilaterally (suprachiasmatically) lesioned rats to a shift in the synchronizing light-dark schedule. With methodologic provisions, notably for treatment timed by pertinent marker rhythms, nomifensine deserves clinical tests in psychochronotherapy.

Animals↗
PubMed1977

Glucagon and insulin binding to liver membranes in a partially nephrectomized uremic rat model.

To investigate the role of glucagon and insulin receptor binding in the glucagon hypersensitivity and insulin resistance which characterize the glucose intolerance of uremia, liver plasma membranes were prepared from control rats (blood urea nitrogen [BUN] 15+/-1 mg/100 ml, creatinine 0.7+/-0.2 mg/100 ml), and from 70% nephrectomized rats (BUN 30+/-2 mg/100 ml, creatinine 2.2+/-0.2 mg/100 ml), and from 90% nephrectomized rats (BUN 46+/-3 mg/100 ml, creatinine 4.20+/-0.7 mg/100 ml), 4 wk after surgery. As compared to controls, the 90% nephrectomized rats had significantly higher levels of plasma glucose (95+/-4 vs. 125+/-11 mg/100 ml), plasma insulin (28+/-9 vs. 52+/-11 muU/ml), and plasma glucagon (28+/-5 vs. 215+/-18 pg/ml). Similar, but less marked, elevations were observed in the 70% nephrectomized animals. In liver plasma membranes from nephrectomized rats, specific binding of (125)I-glucagon was increased by 80-120%. Furthermore, glucagon (2 muM)-stimulated adenylate cyclase activity in nephrectomized rats was twofold higher than in controls. In contrast, fluoridestimulated adenylate cyclase activity was similar in both groups of rats. In marked contrast to glucagon binding, specific binding of (125)I-insulin to liver membranes from nephrectomized rats was reduced by 40-50% as compared to controls. Data analysis suggested that the changes in both glucagon and insulin binding are a consequence of alterations in binding capacity rather than changes in affinity. Liver plasma membranes from nephrectomized rats degraded (125)I-glucagon and (125)I-insulin to the same extent as control rats. THESE RESULTS DEMONSTRATE THAT: (a) the 70 and 90% nephrectomized rats simulate the hyperglycemia, hyperinsulinemia, and hyperglucagonemia observed in clinical uremia; (b) in these animals specific binding of glucagon to liver membranes is increased and is accompanied by higher glucagon-stimulated adenylate cyclase activity; and (c) specific binding of insulin is markedly decreased. These findings thus provide evidence of oppositely directed, simultaneous changes in glucagon and insulin receptor binding in partially nephrectomized rats. Such changes may account for the hypersensitivity to glucagon and may contribute to resistance to insulin observed in the glucose intolerance of uremia.

Adenylyl Cyclases↗
PubMed1977

Studies on the lissamine green distribution in three model rat tumors.

In order to gain knowledge on the extent of distribution of chemotherapeutical agents through the blood systems of various tumors, we studied as an indicator the lissamine green concentrations in various tumor segments after different exposure times. As model tumors we used the autochthonic benzpyrene fibrosarcoma and the transplantable tumors Walker and Yoshida in Sprague-Dawley rats. Remarkable differences in the providing blood vessel were observed.

Animals↗
PubMed1979

The evaluation of tiodonium chloride as an antiplaque and anticaries agent. III. Evaluation of the antiplaque potential of tiodonium chloride utilizing a rat model.

Tiodonium chloride (4-chlorophenyl-2-thienyliodonium chloride), when used in a twice daily mouthrinse at a concentration of 0.3% for either one or four weeks, inhibited dental plaque formation in rats that had been inoculated with Streptococcus mutans 6715-15 and Actinomyces viscosus T-6. Mouthrinses containing 0.1 and 0.2% tiodonium chloride were also effective in inhibiting plaque, but not as consistently as the 0.3% level.

Actinomyces↗
PubMed2025

Contribution of the Brain-Gut-Microbiome Axis to Intergenerational Abnormalities in a Rat Model of Perioperative Neurocognitive Disorder.

BACKGROUND: The brain-gut-microbiome (BGM) axis is a communication network through which the brain and gastrointestinal microbiota interact via neural, hormonal, immune, and gene expression mechanisms. Gut microbiota dysbiosis is thought to contribute to neurocognitive disorders, including perioperative neurocognitive disorder, and to various metabolic abnormalities. Recently, the authors reported that sevoflurane induces neurocognitive deficits in exposed rats as well as their future offspring, with male offspring being particularly affected (intergenerational perioperative neurocognitive disorder). In this study, the authors examined in the same animals whether the intergenerational effects of sevoflurane involve abnormalities in the BGM axis, and whether they are mitigated by paternal pretreatment with either the Na + -K + -Cl - (NKCC1) Cl - transporter inhibitor bumetanide or the glucocorticoid receptor inhibitor RU486, as previously demonstrated for neurocognitive deficits. METHODS: Male Sprague-Dawley rats (F0 generation) were exposed to 2.1% sevoflurane for 3&#x2009;h on postnatal days 56, 58, and 60 (F0M_S group). Before each sevoflurane exposure, distinct experimental groups of F0 males received bumetanide (F0M_BS group) or RU486 (F0M_RS group). These males were mated on postnatal day 90 to produce offspring (F1 generation). Gut microbiota were profiled using 16S rRNA gene sequencing, and brain changes analyzed via RNA sequencing of hippocampal samples. RESULTS: F1 male offspring of F0M_S sires exhibited heightened corticosterone responses to stress, increased inflammatory markers, altered hippocampal transcriptomes, gut microbiota dysbiosis, elevated serum low-density lipoprotein cholesterol levels, and increased body weight. The only abnormality observed in F1 females was a shift in microbial diversity. F0M_S displayed profound alterations in hippocampal transcriptome, while microbial diversity was the only parameter affected in their gut microbiota. Bumetanide or RU486 mitigated most abnormalities, except increased body weight in F1 males. CONCLUSIONS: Paternal sevoflurane exposure in rats induces BGM axis abnormalities, particularly in male offspring, despite the absence of direct anesthetic exposure. Pretreatment with bumetanide or RU486 showed therapeutic efficacy.

Animals↗
PubMed1977

Enzymic differentiation of human liver: comparison with the rat model.

The quantitative pattern of enzymes in the second trimester human fetal liver is significantly different from that of adult liver. For some 20 enzymes, the activity quotient (AQ, i.e., activity of immature liver divided by that in adult liver) is appreciably different from 1.0. Most of the enzymes increase their concentrations with age but, as one would expect, some contribute to differentiation by diminishing in amount. In developing human liver the concentrations of the various enzymes tend to change in the same direction as they do in rat liver. Those that increase in rat liver have been classified into three main clusters, according to whether their rise begins on about the 17th day of gestation (B), the first neonatal day (C), or just before weaning (D), respectively. The distribution of these enzymes among these three clusters correlates with their AQ's in the human fetal liver. In general, enzymes with AQ around 0.5 belong to cluster (B) in rat liver whereas those with 0-0.16 belong to cluster C or D. Gross malformations resulting from the teratogenic action of drugs, hormones, or vitamins on the early embryo attract much attention. The harmful impacts of such agents at late stages of gestation are less spectacular. They may be more frequent, however, and manifest themselves in permanent inadequacies in metabolism or growth with a tendency to succumb to minor childhood diseases. The underlying causes may not be mirrored in the cytocomposition or even the subcellular morphology of autopsy specimens. Only deviations from the organ characteristic quantitative pattern of gene products would provide sensitive enough indictors of the metabolic lesions and of the aberrant aspects of differentiation that were responsible for them. In both the presence and absence of detectable morphologic abnormalities, the study of enzymes, this most varied and largest class of specific chemical constituents, would greatly extend the resolving power of the usual diagnostic procedures postmortem.

Animals↗
PubMed1978

Immunologic studies of prostatic cancer using the R3327 rat model.

We report herein on the destruction by cryosurgery of the Dunning R3327 adenocarcinoma grown in the prostate. Tumors less than 1,000 mm.3 were destroyed by a single freezing procedure within 2 to 4 weeks, whereas tumors greater than 1,000 mm.3 could not be destroyed completely. We also have been able to demonstrate antibody and cellular immune responses to antigens on the R3327 cells. Species, organ and tumor specific antigens were identified by xenogeneic antiserum produced in the rabbit, while major and minor antigens were identified by alloantisera produced in the rat. Tumor antigens were characterized by a variety of in vitro and in vivo immune responses. In addition to the rabbit xenoantisera used in cytotoxicity assays, mixed lymphocyte tumor interaction produced a demonstrable in vitro immune response, lymphocytes from rats immunized with tumor cells were cytotoxic to radiolabeled tumor cells in culture, rats immunized with tumor cells in adjuvant demonstrated protection against subsequent challenge and immunological stimulation of lymph nodes draining the site of tumor cell inoculation was demonstrated by an increase in lymphocyte trapping. Clearing, the R3327 tumor system in the rat is suitable for immunological studies of prostatic cancer.

Adenocarcinoma↗
PubMed1978

Pharmacological studies on experimental nephritic rats. (4) Improvement of hyperlipemic models in rats utilizing anti-rat kidney rabbit serum and effects of anti-hyperlipemic agents on serum lipid levels.

Three hyperlipemic models in rats were compared regarding serum lipid levels and known anti-hyperlipemic agents were tested for their effects on the hyperlipemia. In rats fed a cholesterol diet (group A), only serum cholesterol level resulted in a marked increase as compared with normal level. In animals given a large dose (0.7 ml/100 g body weight, i.v.) of anti-kidney serum (group B), extremely high elevations of serum total lipid, phospholipid, triglyceride and cholesterol levels were observed. In animals given a small dose (0.3 ml/100 g body weight, i.v.) of anti-kidney serum and fed the cholesterol diet (group C), elevations of these serum lipids except for triglyceride were not only greater than in group B, but also synergistic. On the contrary, serum triglyceride level and proteinuria were less in group C than in group B. Furazabol, clofibrate the beta-sitosterol given orally for 7 days at doses of 1,100 and 500 mg/kg/day, respectively were clearly effective on the hyperlipemia of group C, without affecting the proteinuria. Furthermore, this model was more sensitive to these anti-hyperlipemic agents than groups A and B. From the above results, group C would seem to be an adequate and effective experimental hyperlipemic model.

Animals↗
PubMed1977

Biochemical characteristics of different forms of protein-energy malnutrition: an experimental model using young rats.

I. In three separate experiments, four groups of five to eight young male rats were fed either (i) a high-protein diet, for which the net dietary protein:total metabolizable energy ratio (NDp:E) was 0-1 (HP diet); or (ii) a low-protein diet, for which NDp:E was 0-04 (LP diet). In both these groups, food intake was ad lib. In group (iii) the HP diet was given in an amount approximately equal to that taken by the LP group fed ad lib. (HP-restricted). In group (iv) rats were fasted for 48 h after receiving the HP diet (HP-fasted). Each experiment lasted 4 weeks. 2. In the LP and HP-restricted groups, food intake was about 50% of that of the HP rats, while body-weight, after 4 weeks on diet was about 35% and 55% of that of HP rats, for LP and HP-restricted respectively. Both groups of malnourished rats gained some weight during the experiment. 3. Measurements of oral glucose tolerance and plasma insulin levels were made in the fourth week. LP and HP-restricted rats both showed low fasting insulin levels and low insulin to glucose ratios during the glucose tolerance tests; the LP rats were more seriously affected. 4. At the end of the fourth week the rats were killed and blood, liver and gastrocnemius muscle were analysed. LP rats showed specifically and consistently low values for haemoglobin and plasma protein concentration, and low activities of hepatic glucose-6-phosphatase (EC 3-1-3-9) and of alanine aminotransferase (EC 2.6.1.2) in liver and muscle. The activity of hepatic aspartate aminotransferase (EC 2.6.1.1) was, if anything, increased. The plasma amino acid concentrations and ratios showed a specific fall in branched-chain amino acids. Liver fat concentration was consistently elevated. The HP-restricted rats had normal values for haemoglobin, plasma protein andliver fat, and near-normal values for plasma amino acids. Hepatic alanine aminotransferase showed increased activity compared with HP rats, but muscle alanine aminotransferase showed reduced activity. The HP-fasted rats had increased haemoglobin, plasma protein and liver fat concentration, and very low liver glycogen concentrations. Hepatic alanine aminotransferase activity was elevated. Plasma alanine concentration was specifically reduced. 5. The results are consistent with suppression of gluconeogenesis, liver dysfunction and essential amino acid deprivation in LP rats. These biochemical changes found in rats on a low intake of a diet of low protein and high carbohydrate value are similar to those found in kwashiorkor. An equally low intake of a diet of good protein value (HP-restricted) led to marginally better growth, accompanied by biochemical signs of increased gluconeogenesis, analogous to those reported for nutritional marasmus. This nutritional state was not biochemically identical with that of acute fasting. 6. The results are discussed in terms of the consistency of the rat model, and its contribution to understanding biochemical changes found in infant malnutrition.

Amino Acids↗