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Experimental Rat model for Corynebacterium renale-induced pyelonephritis.

The laboratory rat was able to serve as a model for ascending pyelonephritis after implantation of a zinc disk coated with Corynebacterium renale into the urinary bladder because it satisfied three different criteria for infection. The production of an alkaline urine and the presence of significant numbers of C. renale in the kidneys, as well as distinct pyelonephritic lesions as revealed by histological examination, were observed in all rats infected with C. renale. Control rats that harbored sterile disks in their urinary bladders exhibited none of the above effects.

Animals

The Anti-Osteoporosis Effects of Panax japonicus via Downregulation of Inflammatory Factors: A Network Pharmacology and Ovariectomized Rat Model Study.

OBJECTIVE: Osteoporosis is a major and growing public health problem characterized by decreased bone mineral density and destroyed bone microarchitecture. Panax japonicus has been clinically used in the treatment of bone diseases, especially osteoporosis. However, there is a lack of study on the mechanism of osteoporosis treatment with Panax japonicus. MATERIALS AND METHODS: A network pharmacology approach was employed to identify the targets of osteoporosis and Panax japonicus. Cytoscape 3.7.2 and DAVID were used to visualize the pharmacological mechanism of Panax japonicus in treating osteoporosis by building up compound-target and protein-protein interaction (PPI) networks and conducting Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. An ovariectomized SD rat osteoporosis model was used to assess the potential therapeutic effect of Panax japonicus in vivo. The biomechanical properties, pathological changes, inflammatory cytokines, bone density, and bone microstructural parameters in rat bone tissue were carefully measured. The biochemical markers of bone metabolism in serum were detected by Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS AND DISCUSSION: Fifty-two active components and sixty-five target genes of Panax japonicus involved in the treatment of osteoporosis were identified. The PPI network revealed IL-6, TNF, NR3C1, IL-1β, CASP3, ESR1, PGR, and AR to be involved in the treatment of osteoporosis with Panax japonicus. Chikusetsusaponin IVa and Radix ginsenoside-Ro were the main saponins found in Panax japonicus. Panax japonicus was found to exert potent preventive effects on osteoporosis by maintaining biomechanical properties, increasing bone mineral density, and protecting the trabecular microstructure in an ovariectomized rat osteoporosis model. Panax japonicus hindered the initiation of osteoporosis induced by ovariectomy by regulating bone metabolism and downregulating the expression of IL-6 and TNF-α. CONCLUSION: Panax japonicus was found to contain 52 compounds and 65 targets in the treatment of osteoporosis. The administration of Panax japonicus could mitigate osteoporosis in rats induced by ovariectomy, and one of the mechanisms was associated with downregulating the expression of inflammatory factors.

Animals

Rat model for hereditary retinal degeneration.

The disorder in Wag/Rij rats is a spontaneous, bilateral retinal deneration. It is characterized by an early onset, slowly progressive degeneration of the photoreceptor cells leading to destruction of the retina. Degeneration affects both rod cells and cone cells, and to a lesser degree the cells in the inner nuclear layer. The remarkable alterations in the retinal pigment epithelium during the course of the disease suggest a profound change in metabolism and function of the pigment epithelium and implicate a possibility of interaction between the pigment epithelium and the photoreceptors. Since degenerated cells have also been observed in the inner nuclear layers, there is a possibility that Muller's cells are involved in the retinal degeneration. Controlled experiments have demonstrated that the disease is not induced by light damaging effects of the retina, and initial breeding experiments suggest that the disease is inheritable, probably as an autosomal dominant trait. The retinal degeneration in Wag/Rij rats is a new, unique system and it is a potentially very useful animal model of retinitis pigmentosa.

Aging

Biochemical, hematological and histological changes in a fulminant hepatic failure rat model for artificial liver assessment.

Galactosamine-induced fulminant hepatic failure rats have been used as a model for statistical assessment of liver support systems. The present study reports in detail the biochemical, hematological and histological changes in these animals. They have been used to study statistically the effects of ACAC charcoal hemoperfusion, cross-circulation and liver perfusion on long-term survival in fulminant hepatic failure.

Animals

Inhaled vitamin A mitigates hyperoxia-induced acute and chronic lung damage in a neonatal rat model of bronchopulmonary dysplasia.

RATIONALE: Prevention of bronchopulmonary dysplasia (BPD) remains a critical unmet need. OBJECTIVES: We continued evaluating aerosolized vitamin A in a neonatal rat hyperoxia-injury model of BPD, testing whether lung-targeted inhalation yields superior outcomes compared to enteral or intramuscular (IM) delivery. METHODS: Rat pups were exposed to continuous 95% hyperoxia for seven days to induce lung damage. Vitamin A was administered from post-natal day (PD) 1-7 by inhalation, enteral or IM dosing. Persisting effectiveness of inhaled vitamin A was examined at PD 21, dwelling in normoxia after all interventions were discontinued at PD 7. MEASUREMENTS AND MAIN RESULTS: Comprehensive analyses include alveolar morphometrics, in vivo pulmonary function testing, assessment of hepatic vitamin A level, and quantitating gene and protein expression of relevant biomarkers of lung maturation, inflammation and damage/repair, employing singlex and multiplexed assays and whole-genome gene expression. CONCLUSIONS: Inhaled vitamin A suppressed hyperoxia-induced lung damage, with key hallmarks of BPD, including lung morphometrics and biomarkers associated with lung damage and inflammation, being effectively indistinguishable from healthy controls at both PD 7 and 21, Natural reparative processes were enhanced, with normal alveolarization and pulmonary function at PD 21. Despite raising hepatic vitamin A levels, enteral dosing was ineffective in restoring alveolar morphology at PD 7. Consistent with previous reporting, IM dosing yielded modest effect at PD 7 but with little evidence of benefit to pulmonary function at PD 21. Observation of dose-dependent effects with aerosolized vitamin A strengthens the evidence of the benefits of lung-targeted delivery, supporting further development of inhaled vitamin A as a BPD preventive strategy.

Journal Article

A rat model for study of bilirubin conjugation by a cultured cell/ artificial capillary liver assist device.

The Gunn rat, congenitally lacking the conjugating enzyme glucuronyl transferase, provides an animal model for the study of bilirubin conjugation by an extracorporeal liver assist device (LAD) composed of cultured cells and artificial capillaries. Rat hepatoma cells of the H4-II-E cell line able to form conjugated bilirubin glucuronide from bilirubin were grown to tissue density by circumfusion culture of the LAD before symbiotic hemoperfusion experiments lasting up to 24 hours. Rat bile was analyzed by thin layer chromatography for bilirubin glucuronide which was formed by the device and then excreted by the rat.

Acrylic Resins

A rat model of chronic respiratory infection with Pseudomonas aeruginosa.

Chronic, nonlethal, pulmonary infection of rats by Pseudomonas aeruginosa can be initiated by intratracheal inoculation of 10(4) bacteria enmeshed in agar beads. The number of bacteria recoverable from the lung increased to approximately 10(6) within 3 days and remained at that number during 35 days of observation. Histologic examination of the infected lungs revealed lesions resembling those seen in lung tissue of humans with acute or chronic nonbacteremic, Pseudomonas aeruginosa pneumonia, including the presence of goblet-cell hyperplasia, focal areas of necrosis, and acute and chronic inflammatory infiltrate. This model should be useful for investigating the interactions between microbial virulence factors and host defense mechanisms.

Animals

Immunopotentiation and antiviral chemotherapy in a suckling rat model of herpesvirus encephalitis.

Encephalitis was induced in 10-day-old Wistar rats by intraperitoneal injection of approximately 100 50% tissue culture infective doses of herpes simplex virus type 2. Treatment regimens included immunopotentiation with levamisole and combined therapy with levamisole and an antiviral agent, adenine arabinoside. Rats treated with levamisole alone had significantly higher rates of survival than placebo-treated controls 14 days after injection of virus. Combination therapy with levamisole and adenine arabinoside prolonged survival, but there was no significant difference between treated animals and controls given placebo. Because adenine arabinoside inhibits the beneficial effect of levamisole in this model, antiviral chemotherapy in conjunction with immunopotentiation should be used with caution in humans. Further studies will be necessary to determine the value of immunopotentiation therapy in the treatment of life-threatening viral infections.

Animals

Rat model of acute heatstroke mortality.

A total of 252 untrained, unacclimatized, and unanesthetized laboratory rats weighing between 485 and 545 g were fasted and either run to exhaustion at 5, 20, 23, or 26 degrees C or were restrained and heated at an ambient temperature of 41.5 degrees C. The incidence of mortality associated with a wide range of work-induced hyperthermias was compared to the lethality of equivalent heat loads in the absence of physical effort. The severity of hyperthermia was calculated in degree-minutes above a base-line core temperature of 40.4 degrees C. The LD25's of run-exhausted versus restrained-heated rats were 16.8 and 30.1 deg-min, respectively. Survivors had a faster cooling rate than fatalities, but run-exhausted survivors had a slower cooling rate than restrained-heating survivors. Results indicate that 1) both the incidence of mortality and the survival time can be predicted from the severity of core heating, 2) work-related factors contribute to an increased rate of heatstroke death at low thermal loads, and 3) retrospectively, both heat-sensitive and heat-resistant groups were identified.

Animals

Alpha 1-antitrypsin deficiency and increased susceptibility to elastase-induced experimental emphysema in a rat model.

Administration of 200 mg of D-galactosamine/kg intraperitoneally to rats produced a decrease in the serum concentrations of trypsin and elastase inhibitory capacities. Induction of emphysema by intravenous injection of pancreatic elastase resulted in significantly increased severity of the disease in the animals depleted of alpha 1-antitrypsin. The degree of severity of the disease determined by mean linear intercept suggested a correlation with trypsin and elastase inhibitory capacities at the time of elastase injection.

Animals

Inhibition of cis-platinum nephrotoxicity by diethyldithiocarbamate rescue in a rat model.

The nephrotoxic effects of cis-dichlorodiammineplatinum(II) (NSC-119875) administered to male F344 rats at the median lethal dose (LD50; 7.5 mg/kg) were inhibited by treatment with sodium diethyldithiocarbamate (500 or 750 mg/kg) between 1 and 4 hr after cis-platinum administration. Those animals receiving cis-platinum alone had mean serum blood urea nitrogen levels of 234 mg/dl at the time of maximal toxicity (day 5); kidney sections revealed large areas of degeneration and necrosis. When dithiocarbamate rescue was carried out after cis-platinum treatment, mean blood urea nitrogen levels were in the range 56-95 mg/dl; kidney sections were grossly normal with a barely discernible band of degeneration at the corticomedullary junction. Gastrointestinal toxicity was observed in greater than 95% of the cis-platinum-treated rats but was totally absent in those receiving subsequent rescue treatment. A significant decrease in weight loss was also observed in the dithiocarbamate-rescued rats. Based on the chemistry of platinum-sulfur interactions and the observed time-dependence of the rescue treatment, it is suggested that dithiocarbamate exerts its effects via competitive chelation and removal of platinum coordinated to protein-bound sulfhydryl groups of the kidney tubule cells.

Animals

Hepatic reticuloendothelial function in the sub-totally nephrectomized rat model of chronic uremia.

The chronic uremic condition was induced in male Wistar rats by long term maintenance of the animals following sequential sub-total and contralateral nephrectomies. Hepatic reticuloendothelial (RES) activity was estimated by non-invasive measurement of blood clearance rates and hepatic uptake of 99Tcm sulfur colloid administered intravenously. The blood half-time, and the blood clearance rate constants for normals and chronic uremics were 78 +/- 10 s and 49.5 +/- 5 s, and 7.51 +/- 1.04 x 10(-3) s-1 and 10.81 +/- 1.17 x 10(-3) s-1 respectively. The normal hepatic uptake rate constant was 9.03 +/- 1.25 x 10(-3) s-1, compared with a uremic uptake rate constant of 14.34 +/- 1.51 s-1. Measurement of total liver radioactivity upon termination, 15 min after injection, showed significantly increased total uptake in uremia, whereas no change in spleen radioactivity was observed. The clinical implications of these data are discussed.

Animals

Subcutaneous isoproterenol: a convenient rat model for early detection of myocardial necrosis.

The uptake of Tc-99m pyrophosphate was studied in rat myocardial lesions produced by a single subcutaneous injection of isoproterenol (10--50 mg/kg of body weight). The uptake in the whole heart of treated rats is directly proportional to the isoproterenol dose. The Tc-99m PPi uptake measured at various times after lesion initiation parallels the myocardial calcium concentration changes. This model is useful for screening radiopharmaceuticals, and may also be suitable for studying early uptake in myocardial infarcts.

Animals

Virulence of Streptococcus mutans: an antibiotic-suppressed rat model for studies of pathogenesis.

This investigation describes a simple and effective method of antibiotic suppression of the total indigenous microbiol flora of rats. Specifically, the results of this study demonstrate that: (1) antibiotics which inhibit microbial growth of oral and fecal cultures from individual rats are effective in suppressing the indigenous flora of 95% of these rats when provided as dietary supplements; (2) S mutans 6715 colonized 95% of the antibiotic-suppressed animals while only 50% of the untreated rat pups yielded S mutans following challenge with a single inoculum of this micro-organism; and (3) significant smooth surface caries developed in S mutans-infected rats within 20 days when provided caries-promoting Diet 305, while noninfected, antibiotic-suppppressed offspring remained essentially caries-free.

Ampicillin

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

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

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