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Adult Male Wistar Rats (adult + male_wistar_rat)
Selected AbstractsSkeletal muscle HSP72 response to mechanical unloading: influence of endurance trainingACTA PHYSIOLOGICA, Issue 4 2004D. Desplanches Abstract Aims:, It has been shown that increased contractile activity results in heat shock protein 72 (HSP72) accumulation in various skeletal muscles. By contrast, there is no consensus for muscle HSP72 response to muscle disuse for short duration (5,8 days). On the basis of a greater constitutive HSP72 expression in slow-twitch muscles we tested the hypothesis that mechanical unloading for a longer period (2 weeks) would affect this phenotype to a greater extent. Secondly, we evaluated the effects of a physiological muscle heat shock protein (HSP) enhancer (endurance training) on HSP response to unloading and muscle remodelling. Methods:, Adult male Wistar rats were assigned randomly to four groups: (1) sedentary weight-bearing; (2) hindlimb-unloaded (HU) via tail suspension for 2 week; (3) trained on a treadmill (6 week) and (4) trained 6 week and then HU for 2 week. Results:, Unloading resulted in a preferential atrophy of slow muscles [soleus (SOL), adductor longus (AL)] and a slow-to-fast fibre transition with no change in HSP72 level. HSP72 levels were significantly lower in fast muscles [extensor digitorum longus (EDL) and plantaris (PLA)], and did not change with mechanical unloading. Endurance training was accompanied by a small (SOL) or a large (EDL, PLA) increase in HSP72 level with no change in AL. Training-induced accumulation of HSP72 disappeared with subsequent unloading in the SOL and PLA whereas HSP72 content remained elevated in EDL. Conclusion:, The results of this study indicate that (1) after 2 weeks of unloading no change occurred in HSP72 protein levels of slow-twitch muscles despite a slow-to-fast fibre transition; and (2) the training-induced increase of HSP72 content in skeletal muscles did not attenuate fibre transition. [source] Effects of Vigabatrin on Sleep,Wakefulness Cycle in Amygdala-Kindled RatsEPILEPSIA, Issue 2 2000Y. H. Raol Summary: Purpose: Our aim was to study the effect of prolonged administration of vigabatrin (VGB) on sleep-wakefulness cycle in kindled seizure-induced rats. Methods: Adult male Wistar rats were implanted stereotaxically with electrodes for kindling and polysomnography. The rats were divided into two groups, kindled and VGB-treated kindled rats. VGB was administered intraperitonially every day for 21 days, and polysomnographic recordings were taken after doses 1, 7, 14, and 21. The drug effects were evaluated by comparing the records of kindled and drug-treated kindled rats. Results: The VGB-administered kindled rats showed an increase in total sleep time (TST) due to an increase in total non-rapid eye movement (NREM) and light slow-wave sleep stage I (SI) with a decrease in wakefulness. The number of episodes and REM onset latencies were found to be decreased after drug treatment. Conclusions: It can therefore be concluded that VGB has a somnolence-inducing effect and that it might mediate its anti-convulsant effect by altering sleep architecture through sleep-regulating areas. [source] Lamotrigine pharmacokinetic/pharmacodynamic modelling in ratsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2005M.M. Castel-Branco Abstract The aim of this study was to perform a pharmacokinetic/pharmacodynamic (PK/PD) modelling of lamotrigine following its acute administration to rats. Adult male Wistar rats were given 10 mg/kg of lamotrigine intraperitoneally. Plasma and brain samples were obtained at predetermined times over 120 h post-dose and analysed by liquid chromatography. The anticonvulsant profile against maximal electroshock seizure stimulation was determined over 48 h after dosing. As a linear relationship between lamotrigine plasma and brain profiles was observed, only the plasma data set was used to establish the PK/PD relationship. To fit the effect,time course of lamotrigine, the PK/PD simultaneous fitting link model was used: the pharmacokinetic parameters and dosing information were used in the one-compartment first-order model to predict concentrations, which were then used to model the pharmacodynamic data with the sigmoid Emax model, in order to estimate all the parameters simultaneously. The following parameters were obtained: Vd = 2.00 L/kg, kabs = 8.50 h,1, kel = 0.025 h,1, ke0 = 3.75 h,1, Emax = 100.0% (fixed), EC50 = 3.44 mg/L and , = 8.64. From these results, it can be stated that lamotrigine is extensively distributed through the body, its plasma elimination half-life is around 28 h and a lamotrigine plasma concentration of 3.44 mg/L is enough to protect 50% of the animals. When compared with humans, the plasma concentrations achieved with this dose were within the therapeutic concentration range that had been proposed for epileptic patients. With the present PK/PD modelling it was possible to fit simultaneously the time-courses of the plasma levels and the anticonvulsant effect of lamotrigine, providing information not only about the pharmacokinetics of lamotrigine in the rat but also about its anticonvulsant response over time. As this approach can be easily applied to other drugs, it becomes a useful tool for an explanatory comparison between lamotrigine and other antiepileptic drugs. [source] Effects of venlafaxine on ethanol withdrawal syndrome in ratsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2004Esra Sa Abstract The present study was designed to investigate the effects of venlafaxine, a serotonin and noradrenaline reuptake inhibitor (SNRI), on ethanol withdrawal syndrome in rats. Adult male Wistar rats (187,319 g) were used for the study. Ethanol (7.2%, v/v) was given to rats by a liquid diet for 21 days. Control rats were pair-fed an isocaloric liquid diet containing sucrose as a caloric substitute to ethanol. Venlafaxine (5, 10, 20 and 40 mg/kg) and saline were injected to rats intraperitoneally just before ethanol withdrawal. After the 2nd, 4th and 6th hour of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs that included locomotor hyperactivity, agitation, stereotyped behaviour and wet dog shakes were recorded or rated. A second series of injections was given at the 6th hour after the first one, and rats were then tested for audiogenic seizures. Venlafaxine produced some inhibitory effects on locomotor hyperactivity, stereotypic behaviours and wet dog shakes. However, a two-way anova of the data did not indicate any significant effect. It reduced the incidence of the audiogenic seizures at the 6th hour of ethanol withdrawal. Venlafaxine (20 mg/kg) also prolonged the latency of the seizures significantly. Our results suggest that acute venlafaxine treatment has limited beneficial effects on ethanol withdrawal syndrome in rats. [source] Muscarinic receptor blockade in ventral hippocampus and prelimbic cortex impairs memory for socially transmitted food preferenceHIPPOCAMPUS, Issue 5 2009Anna Carballo-Márquez Abstract Acetylcholine is involved in learning and memory and, particularly, in olfactory tasks, but reports on its specific role in consolidation processes are somewhat controversial. The present experiment sought to determine the effects of blocking muscarinic cholinergic receptors in the ventral hippocampus (vHPC) and the prelimbic cortex (PLC) on the consolidation of social transmission of food preference, an odor-guided relational task that depends on such brain areas. Adult male Wistar rats were bilaterally infused with scopolamine (20 ,g/site) immediately after social training and showed impairment, relative to vehicle-injected controls, in the expression of the task measured 24 h after learning. Results indicated that scopolamine in the PLC completely abolished memory, suggesting that muscarinic transmission in this cortical region is crucial for consolidation of recent socially acquired information. Muscarinic receptors in the vHPC contribute in some way to task consolidation, as the rats injected with scopolamine in the vHPC showed significantly lower trained food preference than control rats, but higher than both chance level and that of the PLC-injected rats. Behavioral measures such as social interaction, motivation to eat, neophobia, or exploration did not differ between rats infused with scopolamine or vehicle. Such data suggest a possible differential role of muscarinic receptors in the PLC and the vHPC in the initial consolidation of a naturalistic form of nonspatial relational memory. © 2008 Wiley-Liss, Inc. [source] The Inhibition of Inducible Nitric Oxide Synthase Reverts Arthritic-Induced Decrease in Pituitary Growth Hormone mRNA But Not in Liver Insulin-Like Growth Factor I mRNA ExpressionJOURNAL OF NEUROENDOCRINOLOGY, Issue 12 2003I. Ibáñez De Cáceres Abstract Experimental arthritis induced by Freund-adjuvant administration is a model of chronic inflammation and rheumatoid arthritis associated with a decrease in pituitary growth hormone (GH) and hepatic insulin-like growth factor I (IGF-I) gene expression. Excessive nitric oxide (NO) synthesis by inducible NO synthase (iNOS) has been implicated in the pathogenesis of inflammatory illness. Moreover, NO participates in the regulation of GH secretion at both the hypothalamus and the pituitary. We have examined the role of iNOS activation in producing the changes in the GH-IGF-I axis in arthritic rats. Adult male Wistar rats received aminoguanidine or vehicle from day 20, after adjuvant or vehicle injection, until day 28. Two hours and 30 min after the last aminoguanidine injection, all rats were killed by decapitation. Arthritis increased hypothalamic expression of somatostatin mRNA while it decreased pituitary GH mRNA expression, and both effects were prevented by aminoguanidine administration. In arthritic rats, the parallel decrease in serum IGF-I, and in hepatic IGF-I content and mRNA expression, correlates with the decrease in circulating GH concentrations. Aminoguanidine administration to arthritic rats did not modify either serum GH or serum IGF-I concentrations, or hepatic IGF-I mRNA expression. However, aminoguanidine administration to control rats resulted in a decrease in serum GH concentrations and in a decrease in both hepatic IGF-I mRNA expression and serum IGF-I concentrations. These data suggest that NO mediates the arthritis-induced decrease in GH mRNA expression by acting at a hypothalamic level, but it is not involved in the decrease in hepatic IGF-I mRNA expression. [source] Calcaneal Tendon Regions Exhibit Different MMP-2 Activation After Vertical Jumping and Treadmill RunningTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 10 2009Olga Cristina De Mello Malheiro Abstract Increased activity of matrix metalloproteinases (MMPs) -2 and -9 was found in calcaneal tendon after physical training. However, little attention has been given to the distinct biomechanical and tissue structure of the calcaneal tendon's proximal and distal regions. Herein, we evaluated the effect of two types of physical activities on tendon morphology and matrix metalloproteinase activities in the proximal and distal regions of rat calcaneal tendon, separately. Adult male Wistar rats from control, water-adapted, vertical-jumping, and treadmill-running groups were sacrificed after 1 or 4 days of physical exercise, 6 hr after the end of that day's exercise session. Tendons were processed for histology, morphometry, and gelatin zymography. Tendons from adapted and trained animals showed active secretory cells and increased thickness, cellularity, and blood vessel volume fraction of peritendinous sheath, but without inflammatory process. In the proximal region, both pro- and active MMP-2 were increased after vertical jumping, but only pro-MMP-2 was increased after treadmill running. In contrast, in the distal region, both exercise types increased the activity of pro- and active MMP-2, especially treadmill running, which increased the active MMP-2 by about 11- and eightfold, respectively, after 1 and 4 days of training. No activity of MMP-9 was observed in either tendon region in this study. In conclusion, distal and proximal regions of calcaneal tendon exhibit differential intensities of tissue remodeling after treadmill running or vertical jumping and MMP-2, in the absence of inflammation, plays a major role in this adaptive response. Anat Rec, 2009. © 2009 Wiley-Liss, Inc. [source] Effect of insulin-like growth factor-1 on apoptosis of rat testicular germ cells induced by testicular torsionBJU INTERNATIONAL, Issue 7 2004C. Ozkurkcugil OBJECTIVE To investigate the possible protective role of insulin-like growth factor-1 (IGF-1, reported to have a protective effect in experimental models of hypoxic ischaemia), and the involvement of apoptotic cell death in a model of torsion/detorsion of the rat testis. MATERIALS AND METHODS Adult male Wistar rats were divided into five groups of five rats each. Group 1 underwent a sham operation as a control; in group 2 the testis was twisted and in group 3 then untwisted; in group 4 IGF-1 was injected subcutaneously just before bilateral torsion, and then the right testis removed after 4 h and the left after 24 h; in group 5, IGF-1 was injected immediately after bilateral detorsion and then the testes removed as in group 4. Both testicles were examined histologically, with apoptosis detected using the in situ DNA fragmentation (TUNEL) system, with combined enzymology and immunohistochemistry techniques. RESULTS In groups 2 (torsion) and 3 (detorsion), light microscopy of the testis showed some degenerative changes in the germ cells. Compared to group 1, apoptosis was more significant in group 3 than in the other groups. Group 4 (torsion/IGF-1) had a similar number of apoptotic germ cells as in group 2 (torsion) after 24 h, but fewer than the same group after 4 h. In group 5 (detorsion/IGF-1), apoptosis was reduced by IGF-1 significantly more than in group 3 (P < 0.05). Apoptosis was significantly less in spermatids in group 5 than in group 3 (P < 0.05). CONCLUSIONS IGF-1 seems to lower the levels of germ cell apoptosis, which may be important for protecting the testes from torsion/detorsion injury. Further clinical studies are needed to evaluate this protective effect in testicular torsion/detorsion. [source] Contrasting Effects of Zonisamide and Acetazolamide on Amygdaloid Kindling in RatsEPILEPSIA, Issue 11 2001Koichi Hamada Summary: ,Purpose: Zonisamide (ZNS) and acetazolamide (AZM) are two antiepileptic drugs (AEDs) that differ in clinical efficacy. To elucidate the mechanisms of action of these compounds, we investigated their therapeutic and prophylactic effects in rats by using a kindling model of partial epilepsy. Methods: Electrodes were implanted into the left amygdala of adult male Wistar rats. The animals were stimulated at the afterdischarge threshold until five stage 5 seizures were induced. The generalized seizure threshold was then determined. Therapeutic effects were examined in rats manifesting successive convulsions with near-threshold stimulation. To test prophylactic effects, drugs were administered intraperitoneally before daily kindling stimulation until the animal had a stage 5 seizure or reached day 18. Results: ZNS (10,40 mg/kg; n = 6) suppressed kindled seizures in a dose-dependent manner. Repeated administration for 7 days produced tolerance to anticonvulsive effects. AZM (25,200 mg/kg; n = 7) showed limited therapeutic effect, alleviating only the clonic convulsion in stage 5 seizures and reducing afterdischarge duration. Secondary generalization was not significantly suppressed during repeated treatment (50,200 mg/kg; n = 6). ZNS, 25 or 40 mg/kg (n = 8), significantly retarded seizure development; 15.0 or 17.0 daily stimulations were required to produce a stage 5 seizure. AZM, 50,200 mg/kg (n = 6), also retarded seizure development, with 14.0,14.8 stimulations required. Conclusions: ZNS exhibited modest therapeutic and prophylactic effects, whereas AZM showed mainly prophylactic effects. Hypotheses are presented that may explain the mechanisms of action of these drugs. [source] Methylene blue attenuates lung injury after mesenteric artery clamping/unclampingEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2004A. A. Weinbroum Abstract Background, This controlled, experimental study was designed to assess the effects of intratracheal and intravenous methylene blue on reperfusion lung injury following superior mesenteric artery clamping/unclamping. Materials and methods, Superior mesenteric arteries of 144 anaesthetized adult male Wistar rats (n = 12/group) were clamped for 1 h. Ten minutes before unclamping, methylene blue or its vehicle was administered intratracheally or intravenously, followed by a 3 h-respiratory assessment and postexperimental assessment of survival. Results, Intravenous 3 and 9 mg kg,1 but not higher methylene blue doses, and intratracheal 6-mg kg,1 but not lower doses, significantly (P < 0·05) reduced the 100% increase in plateau pressure, 30% reduction in PO2/FiO2, fourfold augmented bronchoalveolar lavage-retrieved volume and the increased polymorphonuclear leukocytes/bronchoalveolar cells' ratio associated with unclamping of the superior mesenteric artery. Lung tissue polymorphonuclear leukocytes count, total xanthine oxidase activity and wet-to-dry-weight ratio were also normal in these dose-treated groups. These effective regimens were also associated with longer animal survival. Conclusions, Intratracheal methylene blue mitigates lung reperfusion injury following superior mesenteric artery clamping/unclamping at a similar magnitude as an intravenous regimen. This finding is a novel potential use of methylene blue in vivo. [source] Alcohol self-administration acutely stimulates the hypothalamic-pituitary-adrenal axis, but alcohol dependence leads to a dampened neuroendocrine stateEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2008Heather N. Richardson Abstract Clinical studies link disruption of the neuroendocrine stress system with alcoholism, but remaining unknown is whether functional differences in the hypothalamic-pituitary-adrenal (HPA) axis precede alcohol abuse and dependence or result from chronic exposure to this drug. Using an operant self-administration animal model of alcohol dependence and serial blood sampling, we show that long-term exposure to alcohol causes significant impairment of HPA function in adult male Wistar rats. Acute alcohol (voluntary self-administration or experimenter-administered) stimulated the release of corticosterone and its upstream regulator, adrenocorticotropic hormone, but chronic exposure sufficient to produce dependence led to a dampened neuroendocrine state. HPA responses to alcohol were most robust in ,low-responding' non-dependent animals (averaging < 0.2 mg/kg/session), intermediate in non-dependent animals (averaging ,0.4 mg/kg/session), and most blunted in dependent animals (averaging ,1.0 mg/kg/session) following several weeks of daily 30-min self-administration sessions, suggesting that neuroendocrine tolerance can be initiated prior to dependence and relates to the amount of alcohol consumed. Decreased expression of corticotropin-releasing factor (CRF) mRNA expression in the paraventricular nucleus of the hypothalamus and reduced sensitivity of the pituitary to CRF may contribute to, but do not completely explain, neuroendocrine tolerance. The present results, combined with previous studies, suggest that multiple adaptations to stress regulatory systems may be brought about by excessive drinking, including a compromised hormonal response and a sensitized brain stress response that together contribute to dependence. [source] Chronic Hypoxia Induces Prolonged Angiogenesis in Skeletal Muscles of RatEXPERIMENTAL PHYSIOLOGY, Issue 3 2002D. Deveci Skeletal muscle capillarity and fibre cross-sectional area were investigated within and between diaphragm (Diaph), extensor digitorum longus (EDL), soleus (SOL) and tibialis anterior (TA) muscles of control and chronic hypoxic (12% O2 for 6 weeks) adult male Wistar rats (final body mass ,355 g). Cryostat sections were stained for alkaline phosphatase activity to depict all capillaries, and for succinic dehydrogenase to demonstrate regional differences in oxidative capacity within the muscles. Hypoxia-induced angiogenesis occurred in all muscles (P < 0.01), with capillary-to-fibre ratio (C:F) being higher in the more active and oxidative muscles, Diaph (27%) and SOL (26%), than phasically active and glycolytic muscles, TA (21%) and EDL (15%). Diaph, SOL and EDL maintained fibre size, and hence showed an increased capillary density (CD) and reduced intramuscular diffusion distance (DD), whereas TA showed fibre hypertrophy and maintained CD and DD compared to control muscles. The extent of angiogenesis among different regions of muscle varied so as to suggest that muscle fibre size has an additional influence on capillary growth during chronic systemic hypoxia, which is progressive over an extended period of systemic hypoxia. [source] Down-regulation of neurocan expression in reactive astrocytes promotes axonal regeneration and facilitates the neurorestorative effects of bone marrow stromal cells in the ischemic rat brainGLIA, Issue 16 2008Li Hong Shen Abstract The glial scar, a primarily astrocytic structure bordering the infarct tissue inhibits axonal regeneration after stroke. Neurocan, an axonal extension inhibitory molecule, is up-regulated in the scar region after stroke. Bone marrow stromal cells (BMSCs) reduce the thickness of glial scar wall and facilitate axonal remodeling in the ischemic boundary zone. To further clarify the role of BMSCs in axonal regeneration and its underlying mechanism, the current study focused on the effect of BMSCs on neurocan expression in the ischemic brain. Thirty-one adult male Wistar rats were subjected to 2 h of middle cerebral artery occlusion followed by an injection of 3 × 106 rat BMSCs (n = 16) or phosphate-buffered saline (n = 15) into the tail vein 24 h later. Animals were sacrificed at 8 days after stroke. Immunostaining analysis showed that reactive astrocytes were the primary source of neurocan, and BMSC-treated animals had significantly lower neurocan and higher growth associated protein 43 expression in the penumbral region compared with control rats, which was confirmed by Western blot analysis of the brain tissue. To further investigate the effects of BMSCs on astrocyte neurocan expression, single reactive astrocytes were collected from the ischemic boundary zone using laser capture microdissection. Neurocan gene expression was significantly down-regulated in rats receiving BMSC transplantation (n = 4/group). Primary cultured astrocytes showed similar alterations; BMSC coculture during reoxygenation abolished the up-regulation of neurocan gene in astrocytes undergoing oxygen-glucose deprivation (n = 3/group). Our data suggest that BMSCs promote axonal regeneration by reducing neurocan expression in peri-infarct astrocytes. © 2008 Wiley-Liss, Inc. [source] An ultrastructural study of cell death in the CA1 pyramidal field of the hippocapmus in rats submitted to transient global ischemia followed by reperfusionJOURNAL OF ANATOMY, Issue 5 2007Aline De Souza Pagnussat Abstract In the course of ischemia and reperfusion a disruption of release and uptake of excitatory neurotransmitters occurs. This excitotoxicity triggers delayed cell death, a process closely related to mitochondrial physiology and one that shows both apoptotic and necrotic features. The aim of the present study was to use electron microscopy to characterize the cell death of pyramidal cells from the CA1 field of the hippocampus after 10 min of transient global ischemia followed by short reperfusion periods. For this study 25 adult male Wistar rats were used, divided into six groups: 10 min of ischemia, 3, 6, 12 and 24 h of reperfusion and an untouched group. Transient forebrain ischemia was produced using the 4-vessel occlusion method. The pyramidal cells of the CA1 field from rat hippocampus submitted to ischemia exhibited intracellular alterations consistent with a process of degeneration, with varied intensities according to the reperfusion period and bearing both apoptotic and necrotic features. Gradual neuronal and glial modifications allowed for the classification of the degenerative process into three stages: initial, intermediate and final were found. With 3 and 6 h of reperfusion, slight and moderate morphological alterations were seen, such as organelle and cytoplasm edema. Within 12 h of reperfusion, there was an apparent recovery and more ,intact' cells could be identified, while 24 h after the event neuronal damage was more severe and cells with disrupted membranes and cell debris were identified. Necrotic-like neurons were found together with some apoptotic bodies with 24 h of reperfusion. Present results support the view that cell death in the CA1 field of rat hippocampus submitted to 10 min of global transient ischemia and early reperfusion times includes both apoptotic and necrotic features, a process referred to as parapoptosis. [source] Healing patterns in calvarial bone defects following guided bone regeneration in ratsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 9 2002A micro-CT scan analysis Abstract Objective: The objective of this study was to evaluate healing patterns of critical-size calvarial bone defects treated according to principles of guided bone regeneration using micro-CT scan analysis. Specifically, the contribution of bone, periosteum and dura mater to the amount and mineralization of newly formed bone was evaluated. Material and Methods: Surgically induced, critical-size calvarial bone defects in 48 adult male Wistar rats received the following: an occlusive expanded polytetrafluoroethylene (ePTFE) membrane at the exo- and endocranial aspect (OO; n = 12); an occlusive membrane at the exocranial and a perforated membrane at the endocranial aspect (OP; n = 12); a perforated membrane at the exocranial and an occlusive membrane at the endocranial aspect (PO; n = 12); and a perforated membrane at the exo- and endocranial aspect (PP; n = 12). The animals were euthanized at 4 weeks for quantitative analysis of bone volume fraction and mineralization in the region of interest (ROI) as well as in the external, middle and central area of the defect using micro-CT. Results: Bone volume fraction ranged from 31.4% (OP) to 24.5% (PP). No differences were found among the groups. Bone volume fraction and mineralization in the middle area were significantly greater in group OP than in group PP, and in the central area in group OO and PO than in group PP. Conclusions: The results of this study suggest that use of occlusive ePTFE membranes enhances bone formation and maturation in the calvarial skeleton. When occlusion of endo- and exocranial tissues was compromised by membrane perforation, impaired bone formation and mineralization were observed. [source] Viral vectors carrying NR1 sequences injected into rat hippocampus interfered with learning and memoryJOURNAL OF NEUROCHEMISTRY, Issue 2002V. Cheli NMDA receptors are relevant to learning and memory as has been shown both by pharmacological and genetic manipulations. Gene knockouts are useful for investigating in vivo functions, but genetic deletions unrestricted in time or region, may lead to developmental defects or death. The challenge is to control expression with temporal and spatial restrictions in the brain. Viral vectors derived from herpes type-1 neurotropic virus are interesting candidates for it. To regulate gene expression of the NMDA receptor NR1 subunit, vectors carrying either sense NR1(+) or antisense NR1(,) sequences and that of the green fluorescent protein (GFP), were constructed. The protein or RNA expression were corroborated in cell culture by GFP autofluorescence, Western blots, immunofluorescence and RT-PCR, and in rat brain, by Western blots and GFP autofluorescence. The vectors were injected into the dorsal hippocampus of adult male Wistar rats. After 6 days each rat was trained and evaluated for both habituation to an open field and inhibitory avoidance to a foot-shock. The rats injected with GFP-NR1(+) vectors showed habituation and learned the inhibitory avoidance, like sham operated rats; while animals injected with GFP-NR1(,) vectors did not. The vectors were useful to modify endogenous gene expression at a defined period, in restricted regions, leading to investigate in vivo functions. NR1 subunit in the hippocampus is involved in mechanisms leading to habituation and to avoidance behaviour, since even a slight change in the availability of NR1 interfered with them. [source] Histometric evaluation of the effect of nicotine administration on periodontal breakdown: an in vivo studyJOURNAL OF PERIODONTAL RESEARCH, Issue 6 2001Francisco H. Nociti Jr The present study investigated the effect of nicotine administration on periodontal breakdown resulting from ligature-induced periodontitis in rats. Twenty adult male Wistar rats were used. After anesthesia, a mandibular first molar was randomly assigned to receive a cotton ligature in the sulcular area while the contralateral tooth was left unligated. The animals were randomly assigned to one of the following treatments, of daily intraperitoneal injections: A , saline solution, B , 0.37 mg of nicotine/kg, C , 0.57 mg of nicotine/kg and D , 0.73 mg of nicotine/kg. Thirty days later, the animals were sacrificed and the specimens routinely processed for serial decalcified sections. Statistical analysis (ANOVA) revealed greater bone loss (p<0.05) in the ligated teeth of animals which received nicotine (groups B/C/D) than in the ligated teeth of animals which received saline solution (group A). In addition, a dose-dependent response was observed among the nicotine groups. A negative effect of nicotine was observed in the unligated teeth of the experimental groups (p<0.05). Therefore, daily administration of nicotine enhanced, in a dose-dependent manner, the effects of local factors in producing periodontal breakdown. Furthermore, the nicotine seemed to have a direct deleterious effect on the periodontal tissues. [source] Pinealectomy reduces hepatic and muscular glycogen content and attenuates aerobic power adaptability in trained ratsJOURNAL OF PINEAL RESEARCH, Issue 1 2007Cristina das Neves Borges-Silva Abstract:, The current study emphasizes the crucial role of the pineal gland on the effects of chronic training in different tissues focusing on carbohydrate metabolism. We investigated the maximal oxygen uptake (aerobic power), muscle and liver glycogen content, and also the enzymes involved in the carbohydrate metabolism of rat adipose tissue. Pinealectomized and sham-operated adult male Wistar rats were distributed into four groups: pinealectomized (PINX) untrained, pinealectomized trained, control untrained and control trained. The maximal oxygen uptake capability was assayed before and after the training protocol by indirect open circuit calorimetry. The rats were killed after 8 wk of training. Blood samples were collected for glucose and insulin determinations. The glycogen content was assayed in the liver and muscle. Maximal activities of epididymal adipose tissue enzymes (hexokinase, pyruvate kinase, lactate dehydrogenase, citrate synthase and malic enzyme) as well as adipocyte size were determined. The exercise training in control animals promoted an increase in the aerobic power and in liver glycogen content but caused a reduction in the malic enzyme activity in adipose tissue. However, PINX trained animals, in contrast to trained controls, showed a decrease in the aerobic power and in liver and muscle glycogen content, as well as an increase in the activity of the adipocyte enzymes involved in carbohydrate metabolism. In conclusion, these data show that the pineal gland integrity is necessary for the homeostatic control of energy metabolism among adipose, muscle and hepatic tissues. The pinealectomized animals showed alterations in adaptive responses of the maximal oxygen uptake to training. Therefore, the pineal gland must be considered an influential participant in the complex adaptation to exercise and is involved in the improvement of endurance capacity. [source] Reduced lipolysis and increased lipogenesis in adipose tissue from pinealectomized rats adapted to trainingJOURNAL OF PINEAL RESEARCH, Issue 2 2005Cristina N. Borges-Silva Abstract:, The current study investigated the effects of chronic training and pinealectomy on the lipogenic and lipolytic activity of adipose tissue. Pinealectomized and sham-operated adult male Wistar rats were distributed in to four subgroups: pinealectomized untrained, pinealectomized trained, control untrained and control trained. At the end of the training period (8 wk) the rats were killed. Blood samples were collected for glucose, insulin and leptin determinations. Peri-epididymal adipocytes were isolated for measurement of in vitro rates of lipolysis and incorporation of substrates (d -[U- 14C]-glucose, l -[U- 14C]-lactate, [2- 14C]-acetate and [1- 14C]-palmitate) into lipids, and samples of epididymal adipose tissue were homogenized for evaluation of glucose-6-phosphate dehydrogenase maximal activity. Pinealectomy resulted in a significantly increased lipolytic capacity in response to isoproterenol and a decrease in circulating leptin levels without affecting the rates of incorporation of different substrates into lipids. However, only in the intact control group did training promote a higher basal and isoproterenol-stimulated lipolysis, increase the incorporation of palmitate (esterification), decrease the incorporation of acetate (lipogenesis) into lipids and diminish circulating leptin levels. These effects of exercise training were not seen in pinealectomized rats. However, pinealectomized trained animals showed a marked reduction in lipolysis and an increased rate of acetate incorporation. In conclusion, we demonstrated for the first time that the pineal gland plays an important role in the regulation of lipid metabolism in such a way that its absence caused a severe alteration in the balance between lipogenesis and lipolysis, which becomes evident with the adaptation to exercise training. [source] Protective effect of melatonin against oxidative stress induced by ligature of extra-hepatic biliary duct in rats: comparison with the effect of S-adenosyl- l -methionineJOURNAL OF PINEAL RESEARCH, Issue 3 2000Pedro Montilla López In the present research, we studied the effect of the administration of melatonin or S-adenosyl- l -methionine (S-AMe) on oxidative stress and hepatic cholestasis produced by double ligature of the extra-hepatic biliary duct (LBD) in adult male Wistar rats. Hepatic oxidative stress was evaluated by the changes in the amount of lipid peroxides and by the reduced glutathione content (GSH) in lysates of erythrocytes and homogenates of hepatic tissue. The severity of the cholestasis and hepatic injury were determined by the changes in the plasma enzyme activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), g-glutamyl-transpeptidase (GGT), and levels of albumin, total bilirubin (TB) and direct bilirubin (DB). Either melatonin or S-AMe were administered daily 3 days before LBD, and for 10 days after biliary obstruction. LDB caused highly significant increases in plasma enzyme activities and in bilirubin and lipid peroxides levels in erythrocytes and hepatic tissue. At the same time, this procedure produced a notable decrease in the GSH pools in these biological media. Both melatonin and S-AMe administration were effective as antioxidants and hepatoprotective substances, although the protective effects of melatonin were superior; it prevented the GSH decrease and reduced significantly the increases in enzyme activities and lipid peroxidation products produced by biliary ligature. S-AMe did not modify the increased GGT activity nor did it decrease greatly the TB levels (43% melatonin vs. 14% S-AMe). However, S-AMe was effective in preventing the loss of GSH in erythrocytes and hepatic tissue, as was melatonin. The obtained data permit the following conclusions. First, the LDB models cause marked hepatic oxidative stress. Second, the participation of free radicals of oxygen in the pathogenecity and severity of cholestasis produced by the acute obstruction of the extra-hepatic biliary duct is likely. Third, the results confirm the function of S-AMe as an antioxidant and hepatoprotector. Finally, melatonin is far more potent and provides superior protection as compared to S-AMe. Considering the decrease in oxidative stress and the intensity of cholestasis, these findings have interesting clinical implications for melatonin as a possible therapeutic agent in biliary cholestasis and parenchymatous liver injury. [source] Enhanced conditioned inhibitory avoidance by a combined extract of Zingiber officinale and Ginkgo bilobaPHYTOTHERAPY RESEARCH, Issue 4 2002B. Topic Abstract Previous work has shown that intragastric administration of Zingicomb®, a preparation consisting of Zingiber officinale and Ginkgo biloba extracts, has anxiolytic-like properties. The aim of the present study was to assess the effects of acute treatment with this preparation on inhibitory avoidance learning. The influence of pre-trial administered Zingicomb (ZC) on inhibitory avoidance conditioning was investigated in adult male Wistar rats, with a one-trial step-through avoidance task. The animals were treated intragastrically with either vehicle, 0.5, 1, 10 or 100,mg/kg ZC 60,min prior to the acquisition trial. When tested 24,h after training, rats which had received 10,mg/kg ZC exhibited significantly longer step-through latencies than vehicle treated animals. This result, thus, demonstrates the beneficial effects of Zingicomb on conditioned inhibitory avoidance. Unlike conventional anxiolytic drugs, such as the benzodiazepines, which tend to have amnesic properties, this phytopharmacon is a potent anxiolytic agent which, additionally, can facilitate performance on a learning task, indicating promising clinical applications. Copyright © 2002 John Wiley & Sons, Ltd. [source] GSM modulated radiofrequency radiation does not affect 6-sulfatoxymelatonin excretion of ratsBIOELECTROMAGNETICS, Issue 8 2003József Bakos Abstract In this study, the effect of exposure to 900 and 1800 MHz GSM-like radiofrequency radiation upon the urinary 6-sulfatoxymelatonin (6SM) excretion of adult male Wistar rats was studied. Seventy-two rats were used in six independent experiments, three of which were done with 900 MHz and the other three with 1800 MHz. The exposures were performed in a gigahertz transverse electromagnetic mode (GTEM) cell. The power densities of radiation were 100 and 20 ,W/cm2 at 900 and 1800 MHz frequency, respectively. The carrier frequency was modulated with 218 Hz, as in the GSM signal. The animals were exposed for 2 h between 8:00 AM and noon daily during the 14 day exposure period. The urine of rats was collected from 12:00 AM to 8:00 AM, collecting from exposed and control animal groups on alternate days. The urinary 6SM concentration was measured by 125I radioimmunoassay and was referred to creatinine. The combined results of three experiments done with the same frequency were statistically analyzed. Statistically significant changes in the 6SM excretion of exposed rats (n,=,18) compared to control group (n,=,18) were not found either at 900 or 1800 MHz. Bioelectromagnetics 24:531,534, 2003. © 2003 Wiley-Liss, Inc. [source] The effect of Phyllanthus niruri on urinary inhibitors of calcium oxalate crystallization and other factors associated with renal stone formationBJU INTERNATIONAL, Issue 9 2002A.M. Freitas Objective,To evaluate the effect of an aqueous extract of Phyllanthus niruri (Pn), a plant used in folk medicine to treat lithiasis, on the urinary excretion of endogenous inhibitors of lithogenesis, citrate, magnesium and glycosaminoglycans (GAGs). Materials and methods,The effect of chronic (42 days) administration of Pn (1.25 mg/mL/day, orally) was evaluated in a rat model of urolithiasis induced by the introduction of a calcium oxalate (CaOx) seed into the bladder of adult male Wistar rats. The animals were divided into four groups: a sham control (16 rats); a control+Pn (six); CaOx+water instead of Pn (14); and CaOx+Pn (22). Plasma and urine were collected after 42 days of treatment for biochemical analysis and the determination of urinary excretion of citrate, magnesium and GAGs. The animals were then killed and the calculi analysed. Results,The creatinine clearance or urinary and plasma concentrations of Na+, K+, Ca2+, oxalate, phosphate and uric acid were unaffected by Pn or the induction of lithiasis. Treatment with Pn strongly inhibited the growth of the matrix calculus and reduced the number of stone satellites compared with the group receiving water. The calculi were eliminated or dissolved in some treated animals (three of 22). The urinary excretion of citrate and magnesium was unaffected by Pn treatment. However, the mean (sd) urinary concentration of GAGs was significantly lower in rats treated with CaOx+Pn, at 5.64 (0.86) mg/g creatinine, than when treated with CaOx + water, at 11.78 (2.21) mg/g creatinine. In contrast, the content of GAGs in the calculi was higher in the CaOx + Pn rats, at 48.0 (10.4) g/g calculus, than in the CaOx + water group, at 16.6 (9.6) g/g calculus. Conclusion,These results show that Pn has an inhibitory effect on crystal growth, which is independent of changes in the urinary excretion of citrate and Mg, but might be related to the higher incorporation of GAGs into the calculi. [source] | |||||||||||||||||||||||||