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Untreated Rats (untreated + rat)
Selected AbstractsInfluence of sympathetic and AT1 -receptor blockade on angiotensin II and adrenergic agonist-induced renal vasoconstrictions in spontaneously hypertensive ratsACTA PHYSIOLOGICA, Issue 3 2009M. H. Abdulla Abstract Aim:, This study investigated the influence of angiotensin II (Ang II) receptor and adrenergic blockade on the renal vasoconstrictions caused by Ang II and adrenergic agonists in spontaneously hypertensive rats (SHR). Methods:, Forty-eight SHR were subjected to 7 days of losartan (10 mg kg,1 day,1 p.o.), carvedilol (5 mg kg,1 day,1 p.o.) or losartan + carvedilol (10 mg kg,1 day,1 + 5 mg kg,1 day,1 p.o.). On day 8, the rats were anaesthetized and renal vasoconstrictor experiments performed. One group of rats underwent acute unilateral renal denervation. Results:, There were significant (P < 0.05) reductions in the renal vasoconstrictor responses to noradrenaline, phenylephrine, methoxamine and Ang II after losartan and carvedilol treatments compared with that in untreated rats (all P < 0.05). However, in renally denervated SHR treated with carvedilol, the vasoconstrictor responses to all the vasoactive agents were enhanced compared with those in SHR with intact renal nerves treated with carvedilol. Intact SHR given both losartan and carvedilol showed greater renal vasoconstrictor responses to the vasoactive agents than when given either losartan or carvedilol alone (all P < 0.05). Conclusion:, Carvedilol reduced the vasoconstrictor response to Ang II and all the adrenergic agonists in the presence of the renal nerves, but, following the removal of renal sympathetic activity, carvedilol enhanced the sensitivity of both renal ,1 -adrenoceptors and AT1 receptors to the vasoactive agents. Co-treatment with losartan and carvedilol reduced the renal vasoconstrictor responses to exogenously administered vasoactive agents but to a lesser extent than losartan or carvedilol alone. The results obtained demonstrate an interaction between Ang II receptors and adrenergic neurotransmission in the SHR. [source] Changes in hyporesponsiveness to acute amphetamine and age differences in tyrosine hydroxylase immunoreactivity in the brain over adolescence in male and female ratsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 5 2009Iva Z. Mathews Abstract We investigated hyposensitivity after amphetamine in early (postnatal Day 30; P30) and late (P45) adolescent rats compared to adults (P70) in experiment 1. Locomotor activity was measured for 1,hr after the first (acute) and second (24,hr later) injection of amphetamine (0.5 or 1.5,mg/kg). P30 and P45 rats were transiently hypoactive compared to adults, as indicated by reduced locomotor activity after acute amphetamine and enhanced activity after the second injection in adolescents only. In experiment 2, ovariectomy did not alter locomotor activity during habituation at any age compared to intact rats, and, as for intact adolescents, ovariectomized adolescents continued to be less active after amphetamine than adults, suggesting gonadal immaturity alone cannot account for age differences in experiment 1. However, ovariectomy attenuated the increase in activity after the second treatment. In experiment 3 involving untreated rats, tyrosine hydroxylase immunoreactivity was reduced in P30, P40, and P50 compared to P90 rats in the nucleus accumbens core and the medial prefrontal cortex. Thus, adolescents may have an increased threshold of behavioral activation that can be overcome with either a higher dose or with repeated amphetamine treatment, and may be related to changes in the dopamine system over development. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 51: 417,428, 2009. [source] NGF and GDNF ameliorate the increase in ATF3 expression which occurs in dorsal root ganglion cells in response to peripheral nerve injuryEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2004Sharon Averill Abstract Activating transcription factor-3 (ATF3) is a member of the ATF/CREB transcription factor superfamily and is induced in dorsal root ganglion (DRG) cells after nerve injury. In order to study the regulation of ATF3, we have examined the effect of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) on ATF3 expression. In untreated rats, sciatic nerve transection induced ATF3 immunoreactivity in 82% of L4 DRG cells at 14 days after axotomy. Intrathecal delivery of NGF or GDNF for 2 weeks commencing immediately after injury reduced the ATF3 expression to 35 and 23% of DRG cells, respectively. Cell size analysis indicated that NGF had protected a population of mainly small- to medium-sized cells, but that the GDNF had protected a population of both small and large cells. This effect was confirmed by double labelling for P2X3, CGRP and 200 kDa neurofilament, markers for small peptide-poor cells, peptide-rich cells and large cells, respectively. Thus GDNF reduced the percentage of ATF3-immunoreactive P2X3 cells from 70 to 4%, and the percentage of ATF3-immunoreactive neurofilament cells from 63 to 24%. NGF was less effective than GDNF in reducing ATF3 expression in these cell types, but reduced the percentage of ATF3-immunoreactive CGRP cells from 10% to <,1%. These results show that ATF3 expression in specific populations of DRG cells can be modulated by exogenous supplementation of specific trophic factors, and suggest that ATF3 expression may normally be induced by the loss of target-derived NGF and GDNF. [source] Down-regulation of pathogenic autoantibody response in a slowly progressive Heymann nephritis kidney disease modelINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 6 2004Arpad Z. Barabas Summary In the present article, we describe an antigen-specific down-regulation of a pathogenic autoantibody (aab)-mediated disease process in an experimental autoimmune kidney disease in rats called slowly progressive Heymann nephritis (SPHN). This autoimmune disease is initiated and maintained by pathogenic immunoglobulin G (IgG) autoantibodies (aabs), which cause an immune-complex (IC) glomerulonephritis associated with proteinuria. We achieved down-regulated pathogenic aab response in SPHN rats by injections of an IC containing the native nephritogenic antigen and specific high-titred nonpathogenic IgM aabs, in antigen excess. The injected IC increased the level of circulating nonpathogenic IgM aabs; the increased levels of specific IgM aabs in turn facilitated the removal of the injected altered nephritogenic and liberated autoantigens from the renal tubules and greatly diminished the production of pathogenic aabs and the build up of immune deposits in the glomeruli. While animals treated early had advantages over rats whose kidney disease was well established before treatment; animals treated late into the disease still manifested noticeable improvements in similar areas, i.e. with lessened proteinuria, kidney lesion reduction and a decreased pathogenic aab response. At the end of the experiment at 29 weeks, 80% of all the treated rats had insignificantly low levels of circulating IgG aabs, indicating cessation of pathogenic aab production and corresponding termination of the disease process. In contrast, most untreated rats with the kidney disease still had high levels of circulating pathogenic aabs at the end of the experiment, which maintained disease progression. [source] A comparative study of the preventative effects exerted by three probiotics, Bifidobacterium lactis, Lactobacillus casei and Lactobacillus acidophilus, in the TNBS model of rat colitisJOURNAL OF APPLIED MICROBIOLOGY, Issue 4 2007L. Peran Abstract Aims:, The intestinal anti-inflammatory effects of three probiotics with immunomodulatory properties, Lactobacillus casei, Lactobacillus acidophilus and Bifidobacterium lactis, were evaluated and compared in the trinitrobenzenesulphonic acid (TNBS) model of rat colitis. Methods and Results:, Colitis was induced in rats by intracolonic administration of 10 mg of TNBS dissolved in 0·25 ml of 50% ethanol. Each probiotic was administered orally (5 × 108 CFU suspended in 0·5 ml of skimmed milk) for 3 weeks, starting 2 weeks before the administration of TNBS. Colonic damage was evaluated histologically and biochemically 1 week after TNBS instillation. The results obtained revealed that all probiotics assayed showed intestinal anti-inflammatory effects, macroscopically evidenced by a significant reduction in the colonic weight/length ratio. Only B. lactis showed a lower incidence of diarrhoea in comparison with untreated rats. Biochemically, all probiotics restored colonic glutathione levels, depleted as a consequence of the oxidative stress of the inflammatory process. Bifidobacterium lactis treatment reduced colonic tumour necrosis factor (TNF)-, production, and inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) expression; L. acidophilus administration reduced colonic leukotriene B4 production and iNOS expression and L. casei intake was associated with a decrease in colonic COX-2 expression. Conclusion:, The three probiotics assayed have shown intestinal anti-inflammatory activity in the TNBS model of rat colitis, although each probiotic shows its own anti-inflammatory profile. Significance and Impact of the Study:, These probiotics could be considered as potential adjuvants in the treatment of inflammatory bowel disease, although more studies are required in order to demonstrate their efficacy in humans. [source] Effect of ursodeoxycholic acid treatment on the expression and function of multidrug resistance-associated protein 2 in rat intestineJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2009Ryoko Yumoto Abstract Effect of ursodeoxycholic acid (UDCA) treatment on the expression and function of intestinal multidrug resistance-associated protein (Mrp) 2 was examined in rats. When rats were orally administered 0.5% UDCA solution for 6 days, mRNA and protein levels of Mrp2 in the intestine were increased about twofold compared with those in untreated rats. In in vitro everted sac study, Mrp2-mediated efflux of 2,4-dinitrophenyl-S-glutathione (DNP-SG) to the mucosal surface was shown to be increased by UDCA treatment. In vivo intestinal exsorption clearance of DNP-SG was also increased by UDCA treatment. In addition, in situ intestinal absorption of methotrexate, a substrate of Mrp2, was decreased by the treatment. These results indicate that the expression and function of intestinal Mrp2 is up-regulated by oral administration of UDCA. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2822,2831, 2009 [source] Intraepidermal innervation and tail nerve conduction velocity in neurotoxicity models: results of a correlation study in normal and pathological conditionsJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2004M Borgna Animal models of human diseases affecting the peripheral nervous system are widely used to assess the pathogenesis of neurotoxicity and to compare the effect of new agents. Several behavioural, pathological and neurophysiological methods have been used, and each has advantages and disadvantages. A major goal in the study of neurotoxicity would be to assess the damage in the same way in animal models and in humans. In this study we correlated the neurophysiological results obtained in normal rats and in rats treated with cisplatin 2 mg/kg q3d × 8 with the density of intraepidermal fibers (IEF) obtained in skin biopsy specimens. The aim was to investigate the possible role of a minimally invasive procedure such as skin biopsy as an alternative method to assess the peripheral neurotoxicity of antineoplastic drugs. The nerve conduction velocity (NCV) in the tail nerve was assessed in thirty-six young adult female Wistar rats which were left untreated, or treated with erythropoietin (EPO), cisplatin (CDDP) or EPO + CDDP. CDDP and CDDP + EPO-treated rats had a significantly reduced NCV vs. age-matched untreated rats. At sacrifice, skin specimens were obtained. The density of IEF was calculated by 2 independent blinded examiners and the correlation existing between NCV and IEF was highly significant (r = 0.670, p < 0.001). This preliminary result suggests that IEF should be evaluated in other animal models and might represent a useful tool to study peripheral neurotoxicity also in humans. [source] Inflammatory Pain Reduction In Rats By Local Treatment With oATP, A Selective Inhibitor Of P2X7 ATP ReceptorJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2001G Dell'Antonio Peptide neurotransmitters, as substance P or ATP, are released during inflammatiory processes by the nerve endings of sensory fibers. ATP is also released from the cytoplasm of damaged cells at the site of inflammation. It acts at the level of many P2X subtypes of purinoreceptors. The receptor for extracellular ATP named P2Z/P2X7 is selectively blocked by the periodate oxidized ATP (oATP). We have hypothesized that P2X subunits present on peripheral sensory nerve terminals, able to initiate a nociceptive signal, could be blocked by local treatment with oATP, so inducing pain relief. Male inbred Fisher rats weighing about 250 g were used. Unilateral inflammation into rat hind paw was induced by intraplantar injection of Freund's complete adjuvant (FCA). The following signs of inflammation, from 3 to 48 h after FCA injection, were detected: increased paw volume, increased paw temperature and hyperalgesia. The latter was evaluated using an algesiometric test wich measured the paw pressure threshold (PPT, expressed in g). We treated some rats, bearing paw inflammation by 12 h, with local injection of 56 ,M oATP. We showed a significant reduction of hyperalgesia in treated rats (PPT = 190 ± 2.3 in inflamed paw of oATP treated vs. PPT = 60 ± 1.6 in inflamed paw of untreated rats, at 60 min following oATP innoculation). We showed also that treatment with oATP was more efficient than treatment with diclofenac in reducing local inflammatory pain (PPT expressed as percentage of the maximum possible effect = 60 ± 0.5, at 120 min following intraplantar administration of oATP, vs. 25 ± 1.9 at the same time following intraplantar administration of diclofenac). The use of polyclonal antibody anti P2X7 receptor to perform immunohistochemical analysis of inflamed tissue, showed a reduction of receptor expression at the level of nerve endings in sections obtained from rat paw treated with oATP with respect to sections obtained from untreated rats. Such an effect was independent on the recruitment of immunocytes in inflamed tissue. Our results demonstrate that ATP exerts a key role in the pathophysiology of peripheral inflammation and that oATP may be effective in treating inflammatory pain. [source] The antiulcer activity of Garcinia cambogia extract against indomethacin-induced gastric ulcer in ratsPHYTOTHERAPY RESEARCH, Issue 1 2002P. Mahendran Abstract Garcinia cambogia extract is a herbal preparation that has been suggested as useful in the treatment of gastrointestinal disorders. In the present study this drug was tested for its antiulcerogenic effect. Oral pretreatment with Garcinia cambogia fruit extract (1,g/kg body wt/day) for 5, 10 or 15 days protected the gastric mucosa against the damage induced by indomethacin (20,mg/kg body wt). The volume and acidity of the gastric juice decreased in the pretreated rats. The glycoprotein levels of the gastric contents which were decreased in the untreated rats, maintained near normal levels in the pretreated rats. Protein which was elevated in the gastric juice of untreated rats, showed near normal levels in the pretreated rats. Garcinia cambogia was able to decrease the acidity and to increase the mucosal defence in the gastric areas, thereby justifying its use as an antiulcerogenic agent. Copyright © 2002 John Wiley & Sons, Ltd. [source] Effects of antisense interleukin-5 gene transferred by recombinant adeno-associated virus to allergic ratsRESPIROLOGY, Issue 1 2010Daxiong ZENG ABSTRACT Background and objective: The accumulation of eosinophils in airways is an important characteristic of asthma. The process is primarily mediated by interleukin-5 (IL-5) secreted by Th2 lymphocytes. This study explored a new approach to asthma therapy in which allergic rats were transfected with the IL-5 antisense gene delivered by the recombinant adeno-associated virus (rAAV-ASIL-5). Methods: The viral vector rAAV-ASIL-5 was constructed and the IL-5 antisense gene transfected into allergic rats. The levels of IL-5, IgE, eotaxin and eosinophilic cationic protein (ECP) in sera and bronchoalveolar lavage fluid (BALF) were measured by ELISA. The inflammatory responses in lung tissues were evaluated by histological study. Results: The levels of IL-5 protein in serum and BALF were significantly decreased in the allergic rats treated with rAAV-ASIL-5 (P < 0.05). Serum ovalbumin-specific IgE was reduced in treated rats compared with untreated rats (P < 0.05). rAAV-ASIL-5 treatment also reduced eosinophils in the peripheral blood and BALF, as well as the ECP and eotaxin levels in serum and BALF (P < 0.05). There was significantly less inflammation in the lungs of rAAV-ASIL-5-treated rats than in those of untreated rats. No obvious pathological damage to the kidneys and livers of the rats treated with rAAV was observed. Conclusions: Treatment with rAAV-ASIL-5 inhibited the accumulation of eosinophils and airway inflammation in the rat model of allergic asthma by suppressing IL-5 production. These results suggest that rAAV-ASIL-5-based gene therapy may be used for the treatment of allergic asthma. [source] Growth Factors and Their Receptors in the Middle Ear Mucosa During Otitis Media,THE LARYNGOSCOPE, Issue 3 2002Sean D. Palacios MD Abstract Objective The hyperplastic response of the middle ear mucosa during bacterial otitis media is thought to be mediated by the actions of growth factors and their respective receptors. The purpose of the study was to explore the expression of growth factors known to stimulate epithelial cells in other systems, as well as their receptors, in the middle ear mucosa during otitis media. Study Design Expression of mRNA growth factors and receptors was measured over time after inoculation of the rat middle ear with bacteria. Methods The middle ears of 12 male Sprague-Dawley rats were injected with 105/mL Haemophilus influenzae strain 3655 (nontypeable, biotype II). Three rats were killed at 6, 24, 48, and 72 hours. Three untreated rats were also killed to serve as negative controls. The middle ear mucosa samples were surgically removed and homogenized. Reverse transcription-polymerase chain reaction was performed on each sample with primers for rat epidermal growth factor, epidermal growth factor receptor (ErbB), heparin binding epidermal-like growth factor, hepatocyte growth factor, hepatocyte growth factor receptor, keratinocyte growth factor, betacellulin, amphiregulin, and neuregulin-,. Results Hepatocyte growth factor and epidermal growth factor receptor primers demonstrated polymerase chain reaction products of the expected size that were not displayed in the normal middle ear mucosa. Keratinocyte growth factor and hepatocyte growth factor receptor demonstrated polymerase chain reaction products at all time points tested. Betacellulin and neuregulin-, products were present at all time points except 72 hours after infection. Conclusions The results of the study support a role for growth factors in the middle ear mucosa during otitis media. These bioactive ingredients contribute to mucosal hyperplasia. [source] In vivo microfocal computed tomography and micro,magnetic resonance imaging evaluation of antiresorptive and antiinflammatory drugs as preventive treatments of osteoarthritis in the ratARTHRITIS & RHEUMATISM, Issue 9 2010Michael D. Jones Objective To determine whether treatment with an antiresorptive drug in combination with an antiinflammatory drug reduces periarticular bone and soft tissue adaptations associated with the progression of posttraumatic secondary osteoarthritis (OA). Methods We used in vivo microfocal computed tomography (micro-CT) to map bony adaptations and in vivo micro,magnetic resonance imaging (micro-MRI) to examine joint inflammation in a rat model of surgically induced OA secondary to knee triad injury. We examined the arthroprotective effects of the bisphosphonates alendronate and risedronate and the nonsteroidal antiinflammatory drug (NSAID) meloxicam. Results Micro-CT revealed reduced levels of periarticular trabecular bone loss in animals with knee triad injury treated with the bisphosphonate drugs alendronate or risedronate, or the NSAID meloxicam, compared with untreated animals. Alendronate treatment reduced bony osteophyte development. While risedronate as a monotherapy did not positively impact osteophytogenesis, combination therapy with risedronate and meloxicam reduced osteophyte severity somewhat. Micro-MRI revealed an increased, diffuse water signal in the epiphyses of untreated rats with knee triad injury 8 weeks after surgery, suggestive of a bone marrow lesion,like stimulus. In contrast, meloxicam-treated rats showed a significant reduction in fluid signal compared with both bisphosphonate-treated groups 8 weeks after surgery. Histologic analysis qualitatively confirmed the chondroprotective effect of both bisphosphonate treatments, showing fewer degradative changes compared with untreated rats with knee triad injury. Conclusion Our findings indicate that select combinations of bisphosphonate and NSAID drug therapy in the early stages of secondary OA preserve trabecular bone mass and reduce the impact of osteophytic bony adaptations and bone marrow lesion,like stimulus. Bisphosphonate and NSAID therapy may be an effective disease-modifying drug regimen if administered early after the initial injury. [source] Effect of in vivo and in vitro ethanol on adrenergic and purinergic responses of the bisected rat vas deferens to low and high frequency pulsesAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 4 2001C. Boselli 1 This study investigates the effect of acute in vivo and in vitro ethanol administration on the contractions evoked electrically and by exogenous noradrenaline and ,,,-methylene-ATP in the rat bisected vas deferens. 2 In vivo ethanol treatment (3 g kg,1, i.p.) significantly potentiated the early purinergic (phase I) and the delayed adrenergic (phase II) phases evoked by single-pulse stimulation of the epididymal portion of the rat vas deferens, leaving unaffected both phases in the prostatic portion. In vitro 50 mM ethanol significantly depressed phase I leaving unaffected phase II in both portions from untreated rats. In vitro ethanol significantly depressed phase I in the epididymal portion from in vivo ethanol treated animals and potentiated phase II in both portions. 3 In vivo ethanol treatment (3.0 g kg,1, i.p.) selectively impaired the response to noradrenaline only in the prostatic portion of rat vas deferens while it was devoid of any action on ,,,-methylene-ATP contractions. Ethanol 50 mMin vitro was devoid of any action on the response to exogenous noradrenaline and ,,,-methylene-ATP in both tissues. 4 In vivo ethanol treatment slightly but significantly increased the phasic response in the epididymal portion to trains of stimuli (2,30 Hz). In vitro 50 mM ethanol was ineffective against the phasic and tonic contractions elicited by the tetanus in both portions. 5 It is concluded that ethanol treatment affects purinergic and adrenergic pathways of transmission possibly leading to a disruption of physiological contractions necessary to seminal emission. [source] Effect of Tiagabine and Topiramate on Porphyrin Metabolism in an in vivo Model of PorphyriaBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2001Jan Krijt Information on the porphyrogenic activity of new antiepileptic drugs is still limited. In the presented study, the effects of tiagabine and topiramate on porphyrin metabolism were evaluated in an in vivo model of porphyria. Administration of the protoporphyrinogen oxidase inhibitor oxadiazon (12.5 mg/kg/day) for four days to male Wistar rats caused a partial block of porphyrin biosynthesis, thus mimicking the condition of quiescent variegate porphyria. Administration of phenobarbital (75 mg/kg/day) to oxadiazon-pretreated rats increased liver porphyrin content, liver porphobilinogen content (means 480 nmol/g, control less than 20 nmol/g) and urinary excretion of porphobilinogen (means 1000 ,mol/l, control less than 20 ,mol/l). Tiagabine (75 mg/kg/day) and topiramate (75 mg/kg/day) increased liver porphobilinogen content (means 33 and 53 nmol/g respectively) and urinary porphobilinogen concentration (240 and 490 ,mol/l respectively). Similar results were obtained in oxadiazon-treated BALB/c mice. In untreated rats, tiagabine and topiramate caused a moderate increase of hepatic pentoxyresorufin-O-dealkylase activity (approximately 100 and 200 pmol/min./mg respectively, controls 15 pmol/min./mg). These data demonstrate that administration of tiagabine or topiramate to oxadiazon-treated animals can provoke a condition resembling an acute porphyric attack and suggest that administration of these drugs to patients with suspected porphyria should be avoided. However, 5-day administration of both tiagabine and topiramate (75 mg/kg) is considerably less porphyrogenic than phenobarbital administered at the same dose. [source] Pharmacodynamics of glucose regulation by methylprednisolone.BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2009II. normal rats Abstract A physiologic pharmacodynamic model was developed to jointly describe the effects of methylprednisolone (MPL) on adrenal suppression and glycemic control in normal rats. Six groups of animals were given MPL intravenously at 0, 10 and 50,mg/kg, or by subcutaneous 7 day infusion at rates of 0, 0.1 and 0.3,mg/kg/h. Plasma concentrations of MPL, corticosterone (CST), glucose and insulin were determined at various times up to 72,h after injection and 336,h after infusion. The pharmacokinetics of MPL was described by a two-compartment model. A circadian rhythm for CST was found in untreated rats with a stress-altered baseline caused by handling, which was captured by a circadian harmonic secretion rate with an increasing mesor. All drug treatments caused CST suppression. Injection of MPL caused temporary increases in glucose over 4,h. Insulin secretion was thereby stimulated yielding a later peak around 6,h. In turn, insulin can normalize glucose. However, long-term dosing caused continuous hyperglycemia during and after infusion. Hyperinsulinemia was achieved during infusion, but diminished immediately after dosing despite the high glucose concentration. The effects of CST and MPL on glucose production were described with a competitive stimulation function. A disease progression model incorporating reduced endogenous glucose uptake/utilization was used to describe glucose metabolism under different treatments. The results exemplify the roles of endogenous and exogenous hormones in mediating glucose dynamics. The pharmacokinetic/pharmacodynamic model is valuable for quantitating diabetogenic effects of corticosteroid treatments and provides mechanistic insights into the hormonal control of the metabolic system. Copyright © 2009 John Wiley & Sons, Ltd. [source] Neuroprotective effect of chronic lithium treatment against hypoxia in specific brain regions with upregulation of cAMP response element binding protein and brain-derived neurotrophic factor but not nerve growth factor: comparison with acute lithium treatmentBIPOLAR DISORDERS, Issue 3 2008N Omata Objectives:, We evaluated the neuroprotective effect of chronically or acutely administered lithium against hypoxia in several brain regions. Furthermore, we investigated the contribution of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and cAMP response element binding protein (CREB) to the neuroprotective effect of lithium. Methods:, Brain slices were prepared from rats that had been treated chronically or acutely with lithium. The cerebral glucose metabolic rate (CMRglc) before and after hypoxia loading to brain slices was measured using the dynamic positron autoradiography technique with [18F]2-fluoro-2-deoxy- d -glucose. The changes of expression of proteins were investigated using Western blot analysis. Results:, Before hypoxia loading, the CMRglc did not differ between the lithium-treated and untreated groups. After hypoxia loading, the CMRglc of the untreated group was significantly lower than that before hypoxia loading. However, the CMRglc of the chronic lithium treatment group recovered in the frontal cortex, caudate putamen, hippocampus and cerebellum, but not in the thalamus. In contrast, the CMRglc of the acute lithium treatment group did not recover in any analyzed brain regions. After chronic lithium treatment, the levels of expression of BDNF and phospho-CREB were higher than those of untreated rats in the frontal cortex, but not in the thalamus. However, the expression of NGF did not change in the frontal cortex and thalamus. Conclusions:, These results demonstrated that lithium was neuroprotective against hypoxia only after chronic treatment and only in specific brain regions, and that CREB and BDNF might contribute to this effect. [source] Rebound phenomenon in tissue plasminogen activator activity of parietal peritoneum after anastomosing colon in rats with bacterial peritonitisBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2000M. M. P. J. Reijnen Background This study aimed to measure the fibrinolytic response, which plays a role in adhesion and abscess formation, of the parietal peritoneum to surgery in the presence and absence of bacterial peritonitis. Methods In 48 male Wistar rats bacterial peritonitis was induced using caecal ligation and puncture (CLP). Some 24 h after CLP (day 0), 12 rats were killed and biopsies were taken from the parietal peritoneum. The remaining 36 rats were reoperated whereby the ligated caecum was resected followed by resection of a 1-cm segment of the descending colon and end-to-end anastomosis. Thirty additional rats underwent resection of a 1-cm segment and anastomosis of the descending colon without any previous procedure. One-third of the rats were killed on days 1, 3 and 7 after anastomosing the colon, and biopsies were taken from the parietal peritoneum. From ten untreated rats, biopsies were taken for measurement of baseline levels. All biopsies were homogenized and tissue plasminogen activator (tPA) activity was measured using an enzyme-linked immunosorbent assay. Results Some 24 h after inducing peritonitis (day 0), tPA activity was significantly (P < 0·0001) decreased compared with baseline levels. One day after anastomosis in rats with peritonitis, tPA activity was in the same range as baseline values, while tPA activity was significantly increased on days 3 and 7 after anastomosis, in comparison to baseline levels (P = 0·0002). There was no significant difference in tPA activity compared with baseline levels 1, 3 and 7 days after anastomosing colon in normal rats. Conclusion In rats with bacterial peritonitis, tPA activity in the parietal peritoneum was depressed after 24 h; 24,48 h after inducing peritonitis, tPA activity increased, reaching supranormal levels at days 3,7. Surgery alone does not influence tPA activity of the parietal peritoneum. © 2000 British Journal of Surgery Society Ltd [source] Elevated Expression of Interleukins in Lung Adenocarcinomas Induced by N -Nitrosobis(2-hydroxypropyl)amine in RatsCANCER SCIENCE, Issue 10 2000Toshifumi Tsujiuchi The expression of interleukins (ILs) in lung adenocarcinomas induced by N -nitrosobis(2-hydroxypropyl)amine (BHP) in rats was investigated using a multiprobe RNase protection assay (RPA) followed by densitometric quantification. Male Wistar rats, 6 weeks old, were given 2000 ppm BHP in their drinking water for 12 weeks and maintained without further treatment until they were killed at week 25. Total RNAs were extracted from 14 individual adenocarcinomas and 2 specimens of normal lung tissue of untreated rats. In adenocarcinomas, elevated expression of IL-1, (6/14), IL-1, (14/14), IL-3 (7/14), IL-4 (11/14), IL-5 (9/14), IL-6 (11/14) and IL-10 (8/14) was observed, compared with normal lung tissues. In contrast, no expression of IL-2 was detected in any case. The results suggest that preferential expression of these ILs and their complex networks may contribute to the development and progression of lung adenocarcinomas induced by BHP in rats. [source] NBD-cholesterol incorporation by rat macrophages and lymphocytes: a process dependent on the activation state of the cellsCELL BIOCHEMISTRY AND FUNCTION, Issue 1 2004Érica P. Portioli Silva Abstract The time-course of incorporation of NBD-cholesterol by macrophages (Ma) and lymphocytes (LY) obtained from untreated and thioglycollate-injected (thio) rats was investigated. NBD-cholesterol incorporation was also examined in Ma obtained from untreated rats and stimulated in vitro by lipopolysaccharide (LPS) and phorbol-myristate acetate (PMA). The same measurement was performed in LY from untreated rats stimulated by addition of LPS and concanavalin A (Con A) into the culture medium. Thio-treated Ma showed high fluorescence intensity after 1,h of incubation with NBD-cholesterol. Ma submitted concomitant to LPS and NBD-cholesterol showed low fluorescence intensity, as well as Ma stimulated with PMA. Ma from untreated and LPS pre-treated rats showed a similar time-course of incorporation. LY from thio-treated rats showed lower incorporation of NBD-cholesterol in comparison to LY from untreated rats. Incorporation was reduced when LPS was added concomitantly with NBD-cholesterol. On the other hand, LY pre-treated with LPS for 48,h showed a very high incorporation of NBD-cholesterol. Con A treatment did not cause a significant effect on NBD-cholesterol incorporation. The findings presented herein led us to conclude that the uptake of NBD-cholesterol by Ma and LY is markedly affected by the activation state of the cells. Copyright © 2003 John Wiley & Sons, Ltd. [source] Toxicity testing of the VEGF inhibitors bevacizumab, ranibizumab and pegaptanib in rats both with and without prior retinal ganglion cell damageACTA OPHTHALMOLOGICA, Issue 5 2010Sebastian Thaler Abstract. Purpose:, To evaluate the effects of intravitreally introduced vascular endothelial growth factor (VEGF) inhibitors in rat eyes with healthy retinal ganglion cells (RGC) and into others with N-methyl-D-aspartate (NMDA)-induced RGC damage. Methods:, Bevacizumab, ranibizumab and pegaptanib were intravitreally injected each at two different concentrations. Respective vehicles of the three substances served as controls. In a different group, additionally a rat anti-VEGF antibody was injected after NMDA treatment. Retrogradely labelled RGC were counted on retinal wholemounts 1 week or 2 months after intravitreal introduction of the VEGF inhibitors. Electron microscopy (EM) was performed on normal rat eyes 2 months after introduction of the VEGF inhibitors. Results:, RGC counts in healthy rat eyes were essentially unchanged from those of the control animals after the administration of both low and high concentrations of bevacizumab, ranibizumab or pegaptanib. Compared to the other two substances, however, high doses of pegaptanib and its respective vehicle significantly decreased RGC after 1 week and led to a marked increase of mitochondrial swelling in EM. In eyes with NMDA-induced RGC damage, no changes of RGC numbers were detected after rat anti-VEGF antibody or bevacizumab, ranibizumab and pegaptanib at both tested concentrations. Conclusions:, Even at higher doses, bevacizumab and ranibizumab showed no toxic effects on RGC in vivo in either untreated rats or in the NMDA-induced RGC damage model. Also a rat anti-VEGF antibody showed no adverse effects after NMDA. Anti-VEGF therapy therefore appears safe even for eyes with additional excitotoxic RGC damage. Potential harm from the pegaptanib carrier solution at very high local concentrations cannot be excluded. [source] PROTECTIVE EFFECTS OF ICARIIN ON COGNITIVE DEFICITS INDUCED BY CHRONIC CEREBRAL HYPOPERFUSION IN RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2009Rui-Xia Xu SUMMARY 1Icariin is a major constituent of flavonoids derived from the Chinese medicinal herb Epimedium revicornum Maxim. The aim of the present study was to investigate whether icariin has protective effects on learning ability and memory in a rat model of chronic cerebral hypoperfusion. 2Chronic cerebral hypoperfusion was induced by permanent ligation of the common carotid artery in Wistar rats for 4 months. One month after permanent artery occlusion, rats were adminitered icariin at doses of 0, 30, 60 or 120 mg/kg per day, p.o., for 3 months. Neurobehavioural and neurobiochemical parameters were examined to evaluate the effects of icariin on cognitive deficits induced by chronic cerebral hypoperfusion. 3The Morris water maze test revealed that learning ability and memory were severely impaired in untreated rats, but were significantly improved in icariin-treated rats. Icariin treatment also ameliorated chronic cerebral hypoperfusion-induced oxidative stress in the brain, as evidenced by reduced malondialdehyde formation and maintained superoxide dismutase activity. In addition, the decreased hippocampal levels of acetylcholine, acetylcholinesterase and choline acetyltransferase associated with chronic cerebral hypoperfusion were significantly prevented by icariin treatment. 4In conclusion, icariin protects against cognitive deficits induced by chronic cerebral hypoperfusion in rats. These effects appear to be mediated through its anti-oxidant effects, as well as its effects on the circulatory and cholinergic systems. 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