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- ItemSomente MetadadadosAGE DEPENDENCY of the SUSCEPTIBILITY of RATS TO AMINOOXYACETIC ACID SEIZURES(Elsevier B.V., 1992-06-19) Turski, W.; Dziki, M.; Parada, J.; Kleinrok, Z.; Cavalheiro, E. A.; Universidade Federal de São Paulo (UNIFESP)Immature rats are more susceptible to clonic seizures induced by aminooxyacetic acid (AOAA) than mature and senile rats. Highest susceptibility to AOAA seizures was observed in 7-14-day-old rat pups. the lowest susceptibility was recorded in 10-20 month-old rats. AOAA seizures in 14-day-old rats were blocked by clonazepam and valproate, but not by phenobarbital, carbamazepine, diphenylhydantoin, trimethadione or ethosuximide. Morphological analysis of brains from 14-day- and 3-month-old rats which experienced AOAA seizures did not reveal epilepsy-related damage. These observations suggest that immature rat brain is highly prone to convulsions induced by AOAA and that such convulsions are difficult to control by available antiepileptic treatment.
- ItemSomente MetadadadosAUTORADIOGRAPHIC ANALYSIS of D-1 and D-2 DOPAMINERGIC RECEPTORS in RAT-BRAIN AFTER PARADOXICAL SLEEP-DEPRIVATION(Elsevier B.V., 1994-01-01) Nunes, G. P.; Tufik, S.; Nobrega, J. N.; CLARKE INST PSYCHIAT; Universidade Federal de São Paulo (UNIFESP)Previous work had shown that paradoxical sleep deprivation (PSD) results in potentiation of several apomorphine-induced behaviors, leading to the suggestion that PSD induces an upre,oulation of brain dopamine receptors. in this study, quantitative receptor autoradiography was used to verify whether PSD does, in fact, induce alterations in D-1 or D-2 receptor binding, and to investigate the regional brain specificity of such effects. After 96 h of PSD, [H-3]SCH-23390 binding to D-1 receptors was examined in 30 different brain areas of 10 experimental and 10 cage control rats. [H-3]Spiperone was used to label D-2 sites in adjacent tissue sections. Results revealed a 39% increase in [H-3]SCH 23390 binding in the entorhinal cortex of PSD rats (p < 0.05), but no other changes in any of the remaining 29 brain areas examined. in contrast, [H-3]spiperone binding was significantly elevated in the n. accumbens (+45%) and in all subregions of the caudate-putamen (range: +13% to +23%). These results, thus, provide evidence that PSD increases D-2 but not D-1 receptor binding in brain. the present results also suggest that upregulated D-2 receptors can account for the previously reported changes in apomorphine-induced behaviors after PSD.
- ItemSomente MetadadadosChemopreventive Activity of Systemically Administered Curcumin on Oral Cancer in the 4-Nitroquinoline 1-Oxide Model(Wiley-Blackwell, 2015-05-01) Goncalves, Vinicius de Paiva; Ortega, Adriana Alicia C.; Guimaraes, Morgana R.; Curylofo, Fabiana Almeida; Rossa Junior, Carlos; Ribeiro, Daniel Araki [UNIFESP]; Spolidorio, Luis C.; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)Curcumin has therapeutic potential in preventing several types of cancer, including colon, liver, prostate, and breast. the goal of this study was to evaluate the chemopreventive activity of systemically administered curcumin on oral carcinogenesis induced by 4-nitroquinolone-1-oxide (4-NQO). A total of 50 male albino rats, Rattus norvegicus, (Holtzman), were divided into five groups (n = 10 per group). Four of these groups were exposed to 50 ppm 4-NQO in their drinking water ad libitum for 8 or 12 weeks, two groups were treated with curcumin by oral gavage at 30 or 100 mg/kg per day, and one group was treated with corn oil (vehicle) only. the negative control group was euthanized at baseline. Tongues of all animals were removed after euthanasia and used in the subsequent analysis because the tongue is the primary site of carcinogenesis in this model. Descriptive histological analysis and immunohistochemistry for PCNA, Bcl-2, SOCS1 e-3, and STAT3 were performed to assess the oncogenic process. the gene expression of Vimentin, E-cadherin, N-cadherin, or TWIST1 was assessed using RT-qPCR as a representative of epithelial-mesenchymal transition (EMT) events. the administration of curcumin at 100 mg/kg during the 12 weeks markedly decreased the expression of PCNA, Bcl-2, SOCS1 e-3, and STAT3. Curcumin also minimized the cellular atypia under microscopic analysis and diminished the expression of the genes associated with EMT. These findings demonstrate that the systemic administration of curcumin has chemopreventive activity during oral carcinogenesis induced by 4-NQO. J. Cell. Biochem. 116: 787-796, 2015. (C) 2014 Wiley Periodicals, Inc.
- ItemSomente MetadadadosDECREASED MUSCARINIC RECEPTOR-BINDING in RAT-BRAIN AFTER PARADOXICAL SLEEP-DEPRIVATION - AN AUTORADIOGRAPHIC STUDY(Elsevier B.V., 1994-05-09) Nunes, G. P.; Tufik, S.; Nobrega, J. N.; CLARKE INST PSYCHIAT; Universidade Federal de São Paulo (UNIFESP)Previous work demonstrated that paradoxical sleep deprivation (PSD) leads to a decrease in yawning behavior elicited by cholinergic agonists, suggesting that a downregulation of cholinergic muscarinic receptors may occur after PSD. More recent work using intracerebral injections of muscarinic agonists has suggested a critical role for M2 receptors in paradoxical sleep. in this study [H-3]AF-DX 384 was used to investigate the effects of PSD on M2-type cholinergic receptors throughout the brain using quantitative autoradiography. After 96 h of paradoxical sleep deprivation, [3H]AF-DX 384 binding was generally reduced throughout the brain, and significantly so in the olfactory tubercle (-20%), n. accumbens (-23%), frontal caudate-putamen (-16%), islands of Callejas (-20%), piriform cortex (-24%), lateral (-26%) and medial (-24%) septum, anteromedial (-19%), ventrolateral (-22%), and lateral geniculate (-15%) nuclei of thalamus, deep layers of the superior colliculus (-15%), entorhinal cortex (-12%) and subiculum (-23%). [H-3]AF-DX 384 binding was reduced in pontine structures, but not to a higher degree than in other brain areas. the observed downregulation of M2-type muscarinic receptors after PSD may be causally related to the previously reported decrease in cholinergically induced behaviors after PSD.
- ItemSomente MetadadadosEFFECT OF AGE ON ANTINOCICEPTIVE EFFECTS OF ELEVATED PLUS-MAZE EXPOSURE(Assoc Bras Divulg Cientifica, 1992-01-01) Frussa-Filho, Roberto [UNIFESP]; Otoboni, JR; Giannotti, A. D.; Amaral, ACS; Conceição, Isaltino Marcelo da [UNIFESP]; FDN MUNICIPAL ENSINO SUPER MARILIA; Universidade Federal de São Paulo (UNIFESP)It has been suggested that anxiety may be a critical factor in certain forms of non-opioid environmental analgesia. Furthermore, age has been reported to increase the anxiety levels in rats as measured in the elevated plus-maze. In the present investigation 10 young (3 months), 10 middle-aged (14-16 months) and 10 old (28-30 months) male Wistar tats were tested by the tail withdrawal assay of nociception before (baseline), and at 0 (T1) and 10 (T2) min after a 5-min exposure to the elevated plus-maze apparatus. Only old rats presented an increase in tail withdrawal latencies after elevated plus-maze exposure, even though this effect was statistically significant only immediately after exposure to the apparatus (baseline = 2.5 +/- 0.3 s; T1 = 3.8 +/- 0.3 s; T2 = 3.3 +/- 0.4 s). The results indicate that exposure to the elevated plus-maze induces a rapidly reversed and age-dependent antinociception in rats. They are also consistent with the proposed greater sensitivity of old rats to anxiogenic effects of the plus-maze.
- ItemSomente MetadadadosEFFECTS of STRESS ON DRUG-INDUCED YAWNING - CONSTANT VS INTERMITTENT STRESS(Elsevier B.V., 1995-07-01) Tufik, S.; Nathan, C. D.; Neumann, B.; Hipolide, D. C.; Lobo, L. L.; Demedeiros, R.; Troncone, LRP; Braz, S.; Suchecki, D.; Universidade Federal de São Paulo (UNIFESP)Experiment 1 tested whether chronic exposure to immobilization, foot shock or forced swimming would result in suppression of apomorphine, pilocarpine-, and physostigmine-induced yawning. Immobilization caused suppression of yawning, whereas foot shock and swimming resulted in increased number of yawns. Since interstressor interval was long in the two latter stressors, animals could have recovered and the increase in yawning could be due to the last (acute) exposure to stress. in Experiment 2 we recorded the number of yawns induced by pilocarpine in animals exposed to 1 h of swimming or foot shock. No differences between control and acutely stressed animals were detected. These results suggest that yawning is differently altered by constant and intermittent stressors (i.e., diminished by constant and increased by intermittent stress).
- ItemSomente MetadadadosEFFECTS OF THE IMMUNOSUPPRESSANT FK506 ON A PENETRATING KERATOPLASTY REJECTION MODEL IN THE RAT(Lippincott-raven Publ, 1993-07-01) Nishi, Mauro [UNIFESP]; Herbort, C. P.; Matsubara, M.; Morishita, Y.; Nishimura, M.; Nieda, M.; Mori, Satomi [UNIFESP]; Mochizuki, M.; UNIV LAUSANNE; UNIV TOKYO; KURUME UNIV; Universidade Federal de São Paulo (UNIFESP)Purpose. The immunosuppressive effects of FK506 on allogeneic corneal transplantation were tested in a rat model.Methods. Inbred-strain Lewis rats were used as recipients, and Fisher rats were used as donors. Intraperitoneal injection of FK506 (0.3, 1.0, and 3.0 mg/kg per day) was administered for 2 weeks, and the grafts were inspected by clinical evaluation. Mixed lymphocyte culture assay, using lymphocytes from recipients of penetrating keratoplasty as responder cells and irradiated splenocytes from naive Fisher or Brown Norway as stimulator cells, was used to identify allogeneic stimulation. The rejection process was studied by histology and immunohistochemistry.Results. The rat strain combination developed 100% graft rejection in about 2 weeks after the penetrating keratoplasty. FK506 prolonged the graft survival in a dose-dependent manner, as observed by clinical evaluation. In mixed lymphocyte culture assay, Lewis rats that had been primed to allogeneic stimulation at the time of cornea transplantation presented significant proliferation to Fisher stimulator splenocytes. FK506 suppressed this primed lymphocyte proliferation. Immunohistochemical and histologic studies confirmed the clinical evaluations. Untreated rat corneas, at the second postoperative week, presented a large number of helper/inducer T cells, macrophages, IL-2 receptor-expressing cells, and Ia-antigen-expressing cells. In the same period, FK506-treated rats appeared normal and had no cellular infiltration. Corneas rejected after FK506 cessation had less intense cell infiltration than the control corneas.Conclusions. These data indicate that FK506 prolonged the corneal graft survival and can be a potentially useful drug in the immunotherapeutic arsenal to suppress corneal graft rejection.
- ItemSomente MetadadadosREVERSIBLE EFFECTS of ACUTE and LONG-TERM ADMINISTRATION of DELTA-9-TETRAHYDROCANNABINOL (THC) ON MEMORY in the RAT(Elsevier B.V., 1991-08-01) Nakamura, Ester Miyuki [UNIFESP]; Da Silva, Eroy Aparecida [UNIFESP]; Concilio, Germana Valéria [UNIFESP]; Wilkinson, D. Adrian; Masur, Jandira [UNIFESP]; ADDICT RES FDN; Universidade Federal de São Paulo (UNIFESP)A study was designed to develop a measure of both acute and chronic effects of THC administration on memory in the rat. Errors in an 8-arm radial maze, before and after two delay intervals (5 s and 1 h, introduced between the fourth and the fifth arm choice), constituted the principal dependent measures. the first experiment involved testing the animals shortly after administration of 1.25 mg/kg THC. the drug did not affect performance in the pre-delay tests, although a significant effect was observed after the 5-s delay but not after 1-h delay. in the second experiment, 5 mg/kg THC or saline were administered 6 days/week for 90 days. Testing was conducted 18 h after each drug administration. During chronic administration the pre-delay performance did not differ between groups but the post-delay performance of the THC group deteriorated in a gradual manner, relative to their controls, in both the 5-s and 1-h delay conditions. After discontinuation of drug administration, the differences between groups reversed only after 30 days.The results provided evidence that both acute and chronic administration of THC affected working-memory in the radial arm maze test, although it did not interfere with the general cues of the task (reference memory). Chronic drug effects on memory were reversible after prolonged abstinence. Thus, the 8-arm radial maze task proved to be a useful measure of THC effects on memory and could be further used to investigate more thoroughly the mechanisms involved in such drug effects. in addition, since hippocampal formation is involved in learning and memory processes, it was hypothesized that THC effects on memory could be mediated by a hippocampal dysfunction.
- ItemSomente MetadadadosSUPPRESSION OF PILOCARPINE-INDUCED STATUS EPILEPTICUS AND THE LATE DEVELOPMENT OF EPILEPSY IN RATS(Springer, 1995-01-01) Lemos, Tadeu [UNIFESP]; Cavalheiro, Esper Abrão [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Status epilepticus (SE) has been related to subsequent development of epilepsy. The present work was aimed at elucidating the relationship between the duration of pilocarpine- (PILO)-induced SE and the subsequent development of epilepsy in rats. The latency for the appearance of the first spontaneous seizure, the frequency of spontaneous seizures, the cell density in the hippocampal formation and the density of supragranular neo-Timm staining were monitored. At 30 min, 1, 2 and 6 h after the beginning of SE, animals were treated with diazepam plus pentobarbital. In non-treated rats, SE remitted spontaneously. Animals exhibiting 30 min of PILO-induced SE did not develop spontaneous seizures. Hippocampal cell counts and the density of neo-Timm staining in these animals were similar to those observed in control rats. In the other groups longer SE durations were related to: shorter latency for the appearance of the first spontaneous seizure, increased number of the spontaneous recurrent seizures, severe cell loss in the hippocampal formation, or increased supragranular neo-Timm staining. These data suggest that more than 30 min of SE is required to produce hippocampal damage with subsequent synaptic reorganization of the messy fibre pathway that could account for SRSs observed in the PILO model of epilepsy.