Home About us Contact
|
Home About us Contact | ||
|
|
||
Intraperitoneal
Terms modified by Intraperitoneal Selected AbstractsThe Role of the Vagus Nerve in Mediating the Long-Term Anorectic Effects of LeptinJOURNAL OF NEUROENDOCRINOLOGY, Issue 4 2007C. Sachot Leptin, the product of the obese (ob) gene, is mainly known for its regulatory role of energy balance by direct activation of hypothalamic receptors. Recently, its function in the acute control of food intake was additionally attributed to activation of the vagus nerve to regulate meal termination. Whether vagal afferent neurones are involved in longer term effects of leptin on food intake, however, remains undetermined. Using vagotomised (VGX) rats, we sought to clarify the contributions of vagal afferents in mediating the long-lasting effect of leptin on appetite suppression. Intraperitoneal (i.p.) injection of leptin (3.5 mg/kg) attenuated food intake at 4, 6, 8 and 24 h and body weight at 24 h postinjection in SHAM-operated rats; however, this response was not abrogated by vagotomy. In a separate study using immunohistochemistry, we observed leptin-induced Fos expression in the nucleus tractus solitarii, a brain structure where vagal afferent fibres terminate. This signal was not attenuated in VGX animals compared to the SHAM group. Moreover, leptin treatment led to a similar level of nuclear STAT3 translocation, a marker of leptin signalling, in the hypothalami of SHAM and VGX animals. In addition to the effects of leptin, vagotomy surgery itself resulted in a decrease of 24 h food intake. Analyses of brains from saline-treated VGX animals revealed a significant induction of Fos in the nucleus tractus solitarii and changes in agouti-related peptide and pro-opiomelanocortin mRNA expression in the hypothalamus compared to their SHAM counterparts, indicating that the vagotomy surgery itself induced a modification of brain activity in areas involved in regulating appetite. Collectively, our data suggest that vagal afferents do not constitute a major route of mediating the regulatory effect of leptin on food intake over a period of several hours. [source] Melatonin enhances the rewarding properties of morphine: involvement of the nitric oxidergic pathwayJOURNAL OF PINEAL RESEARCH, Issue 4 2007Noushin Yahyavi-Firouz-Abadi Abstract:, Melatonin has different interactions with opioids including the enhancement of the analgesic effects of morphine and also reversal of tolerance and dependence to morphine. The present study assessed the effect of melatonin on morphine reward in mice using a conditioned place preference (CPP) paradigm. Our data showed that subcutaneous administration of morphine (1,7.5 mg/kg) significantly increased the time spent in the drug-paired compartment in a dose-dependent manner. Intraperitoneal (i.p.) administration of melatonin (1,40 mg/kg) alone did not induce either CPP or conditioned place aversion (CPA), while the combination of melatonin (5,20 mg/kg) and sub-effective dose of morphine (0.5 mg/kg) led to rewarding effect. We further investigated the involvement of the nitric oxidergic pathway in the enhancing effect of melatonin on morphine CPP, by a general nitric oxide synthase inhibitor, NG -nitro- l -arginine methyl ester (l -NAME). l -NAME (1 and 5 mg/kg, i.p.) alone or in combination with morphine (0.5 mg/kg) did not show any significant CPP or CPA. Co-administration of l -NAME (5 mg/kg) with an ineffective combination of melatonin (1 mg/kg) plus morphine (0.5 mg/kg) produced significant CPP that may imply the similarity of action of melatonin and l -NAME and involvement of the nitric oxidergic pathway in this regard. Our results indicate that pretreatment of animals with melatonin enhances the rewarding properties of morphine via a mechanism which may involve the nitric oxidergic pathway. [source] Acute Alcohol Intoxication Increases REDD1 in Skeletal MuscleALCOHOLISM, Issue 5 2008Charles H. Lang Background:, The mechanism by which acute alcohol (EtOH) intoxication decreases basal muscle protein synthesis via inhibition of the Ser/Thr kinase mammalian target of rapamycin (mTOR) is poorly defined. In this regard, mTOR activity is impaired after over expression of the regulatory protein REDD1. Hence, the present study assessed the ability of REDD1 as a potential mediator of the EtOH-induced decrease in muscle protein synthesis. Methods:, The effect of acute EtOH intoxication on REDD1 mRNA and protein was determined in striated muscle of rats and mouse myocytes using an RNase protection assay and Western blotting, respectively. Other components of the mTOR signaling pathway were also assessed by immunoblotting. For comparison, REDD1 mRNA/protein was also determined in the muscle of rats chronically fed an alcohol-containing diet for 14 weeks. Results:, Intraperitoneal (IP) injection of EtOH increased gastrocnemius REDD1 mRNA in a dose- and time-dependent manner, and these changes were associated with reciprocal decreases in the phosphorylation of 4E-BP1, which is a surrogate marker for mTOR activity and protein synthesis. No change in REDD1 mRNA was detected in the slow-twitch soleus muscle or heart. Acute EtOH produced comparable increases in muscle REDD1 protein. The EtOH-induced increase in gastrocnemius REDD1 was independent of the route of EtOH administration (oral vs. IP), the nutritional state (fed vs. fasted), gender, and age of the rat. The nonmetabolizable alcohol tert -butanol increased REDD1 and the EtOH-induced increase in REDD1 was not prevented by pretreatment with the alcohol dehydrogenase inhibitor 4-methylpyrazole. In contrast, REDD1 mRNA and protein were not increased in the isolated hindlimb perfused with EtOH or in C2C12 myocytes incubated with EtOH, under conditions previously reported to decrease protein synthesis. Pretreatment with the glucocorticoid receptor antagonist RU486 failed to prevent the EtOH-induced increase in REDD1. Finally, the EtOH-induced increase in REDD1 was not associated with altered formation of the TSC1,TSC2 complex or the phosphorylation of TSC2 which is down stream in the REDD1 stress response pathway. In contradistinction to the changes observed with acute EtOH intoxication, REDD1 mRNA/protein was not changed in gastrocnemius from chronic alcohol-fed rats despite the reduction in 4E-BP1 phosphorylation. Conclusions:, These data indicate that in fast-twitch skeletal muscle (i) REDD1 mRNA/protein is increased in vivo by acute EtOH intoxication but not in response to chronic alcohol feeding, (ii) elevated REDD1 in response to acute EtOH appears due to the production of an unknown secondary mediator which is not corticosterone, and (iii) the EtOH-induced decrease in protein synthesis can be dissociated from a change in REDD1 suggesting that the induction of this protein is not responsible for the rapid decrease in protein synthesis after acute EtOH administration or for the development of alcoholic myopathy in rats fed an alcohol-containing diet. [source] Stimulated single fiber electromyography in the mouse: Techniques and normative dataMUSCLE AND NERVE, Issue 7 2001Clifton L. Gooch MD Abstract As the number of new transgenic mouse models of human neuromuscular disease continues to increase, the development of sophisticated electrophysiologic techniques for assessing the peripheral nervous system in these models has become important. Neuromuscular junction (NMJ) dysfunction, in particular, is often not detectable by morphologic or other techniques. To enable sensitive testing of murine NMJ function, we developed and tested a method for stimulated single fiber electromyography (S-SFEMG) in the gastrocnemius muscles of anesthetized mice. Jitter was assessed by measuring the mean consecutive latency difference (MCD) of single fiber responses to sciatic nerve stimulation at 2 HZ. Mean MCD values in normothermic mice were in the range of 6,8 ,s for different strains, with no MCD values exceeding 25 ,s. Reduced core temperature (to 29°,30°C) resulted in increased jitter, whereas intubation and mechanical ventilation of mice did not alter these values. Intraperitoneal and intravenous injection of vecuronium, however, resulted in progressively increased jitter followed by blocking in continuously monitored fibers. These observations validate the utility of S-SFEMG in mice as an index of NMJ function under a variety of physiologic conditions, and suggest that a high safety factor for neuromuscular transmission exists at mouse NMJs. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 941,945, 2001 [source] Inhibitory effect of magnolol on tumour metastasis in micePHYTOTHERAPY RESEARCH, Issue 8 2003Koji Ikeda Abstract It has previously been reported that magnolol, a phenolic compound isolated from Magnolia obovata, inhibited tumour cell invasion in vitro. The purpose of this study was to investigate the antimetastatic effect of magnolol on tumour metastasis in vivo with experimental and spontaneous metastasis models and to clarify the mechanism. The antimetastatic effects of magnolol were evaluated by an experimental liver and spleen metastasis model using L5178Y-ML25 lymphoma, or an experimental and spontaneous lung metastasis model using B16-BL6 melanoma. Intraperitoneal (i.p.) administration of 2 or 10 mg/kg of magnolol signi,cantly suppressed liver and spleen metastasis or lung metastasis. As for the spontaneous lung metastasis model using B16-BL6 melanoma, multiple i.p. administrations of 10 mg/kg of magnolol after and before tumour inoculation signi,cantly suppressed lung metastasis and primary tumour growth. In addition, magnolol signi,cantly inhibited B16-BL6 cell invasion of the reconstituted basement membrane (Matrigel, MG) without affecting cell growth. These data from the in vivo experiments suggest that magnolol possesses strong antimetastatic ability and that it may be a lead compound for drug development. The antimetastatic action of magnolol is considered to be due to its ability to inhibit tumour cell invasion. Copyright © 2003 John Wiley & Sons, Ltd. [source] Effects of repeated injections of fibroblast-stimulating lipopeptide-1 on fever, formation of cytokines, and on the responsiveness to endotoxin in guinea-pigsACTA PHYSIOLOGICA, Issue 1 2009A. Greis Abstract Aims:, We investigated, whether the Toll-like receptors (TLRs)-2/6-agonist fibroblast-stimulating lipopeptide-1 (FSL-1), like the TLR-4 agonist lipopolysaccharide (LPS), induces a state of tolerance. We further tested the influence of repeated pre-treatment with FSL-1 on the animals' responsiveness to LPS. Methods:, Abdominal temperature was recorded in unrestrained guinea-pigs with intra-abdominally implanted radiotransmitters. Circulating concentrations of tumour necrosis factor (TNF) and interleukin-6 (IL-6) were measured with specific bioassays. We tested the effects of intra-arterial (i.a.) or intraperitoneal (i.p.) injections of 100 ,g kg,1 FSL-1, repeated five times at intervals of 3 days. The animals' responses to i.a. or i.p. injections of 10 ,g kg,1 LPS were determined another 3 days later and compared to those of naïve guinea-pigs. Results:, The FSL-1-induced TNF peak was significantly attenuated starting with the third i.a. administration, while fever was unimpaired and the IL-6-peak just tended to decrease. Fever and IL-6 in response to i.a. injections of LPS were identical in both groups, while circulating TNF was higher in naïve compared to FSL-1 pre-treated animals. The effects of repeated i.p. injections of FSL-1 were more pronounced resulting in attenuation of fever as well as circulating TNF and IL-6, the strongest reduction observed after the third stimulation with FSL-1. Repeated i.p. pre-treatment with FSL-1 induced hyporesponsiveness to i.p. administration of LPS compared to naïve animals with regard to fever and especially with regard to LPS-induced formation of cytokines. Conclusions:, There is a development of tolerance to FSL-1 and cross-tolerance between FSL-1 and LPS depending on the route of administration of the respective TLR-2/6 and TLR-4 agonists. [source] A reduction in severe hypoglycaemia in type 1 diabetes in a randomized crossover study of continuous intraperitoneal compared with subcutaneous insulin infusionDIABETES OBESITY & METABOLISM, Issue 11 2009A. Liebl Aim: Continuous intraperitoneal insulin infusion (CIPII) with the DiaPort system using regular insulin was compared to continuous subcutaneous insulin infusion (CSII) using insulin Lispro, to investigate the frequency of hypoglycemia, blood glucose control, quality of life, and safety. Methods: In this open, randomized, controlled, cross-over, multinational, 12-month study, 60 type 1 diabetic patients with frequent hypoglycemia and/or HbA1c > 7.0% with CSII were randomized to CIPII or CSII. The aim was to obtain the best possible blood glucose while avoiding hypoglycemia. Results: The frequency of any hypoglycemia was similar (CIPII 118.2 (SD 82.6) events / patient year, CSII 115.8 (SD 75.7) p = 0.910). The incidence of severe hypoglycemia with CSII was more than twice the one with CIPII (CIPII 34.8 events / 100 patient years, CSII 86.1, p = 0.013). HbA1c, mean blood glucose, and glucose fluctuations were not statistically different. Treatment-related severe complications occurred mainly during CIPII: port infections (0.47 events / patient year), abdominal pain (0.21 events / patient year), insulin underdelivery (0.14 events / patient year). Weight gain was greater with CSII (+ 1.5 kg vs. , 0.1 kg, p = 0.013), quality of life better with CIPII. Conclusions: In type 1 diabetes CIPII with DiaPort reduces the number of severe episodes of hypoglycemia and improves quality of life with no weight gain. Because of complications, indications for CIPII must be strictly controlled. CIPII with DiaPort is an alternative therapy when CSII is not fully successful and provides an easy method of intraperitoneal therapy. [source] Conservative management of duodenal perforation following endoscopic sphincterotomyDIGESTIVE ENDOSCOPY, Issue 2 2005Chee Fook Choong Overall endoscopic retrograde cholangiopancreatography (ERCP) complication rates of 4,10% and mortality rates of 1.5% have been reported. For those patients who fail conservative therapy, a mortality rate of almost 50% has been reported. This has led some authors to recommended early operation in all duodenal perforations. We report two cases of duodenal perforations following endoscopic sphincterotomy. Perforation was suspected immediately post-ERCP in one case and, in the second case, perforation was evident during ERCP and a biliary stent was inserted. Both of the patients were managed conservatively with bowel rest, nasogastric suction, analgesia and intravenous antibiotics. Although abdominal XR and CT showed extensive intraperitoneal and retroperitoneal gas, both of the patients made an uneventful recovery without surgical management. Based on our experience and literature review, routine surgery is not required in patients with duodenal perforations following endoscopic sphincterotomy. Surgery should be considered in any patients with clinical signs of sepsis, abscess or fluid collection in the retroperitoneum or peritoneum, documented ERCP perforation with cholelithiasis, choledocholithiasis or retained hardware. There are currently no strong data to support the benefits of early routine surgery and management should be tailored individually according to the patient's clinical condition and response to therapy. [source] Monoamine oxidase inhibition and neuroprotection by N1 -propargylphenelzineDRUG DEVELOPMENT RESEARCH, Issue 1 2001B. Duff Sloley Abstract The ability of N1 -propargylphenelzine and related N1 -propargylhydrazines to inhibit monoamine oxidase-A (MAO-A) and -B (MAO-B) and to prevent N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4)-induced noradrenergic neurotoxicity was examined. N1 -Propargylphenelzine strongly inhibited MAO-A and MAO-B in in vitro assays using rat brain or liver as the enzyme source. In ex vivo studies in rats, both intraperitoneal and oral administration of N1 -propargylphenelzine strongly inhibited brain and liver MAO-A and MAO-B. The extent of ex vivo MAO inhibition and increased levels of noradrenaline and 5-hydroxytryptamine by N1 -propargylphenelzine was comparable to that of phenelzine. Unlike phenelzine, however, N1 -propargylphenelzine did not elevate ,-aminobutryic acid (GABA) concentrations in rat brain. A single intraperitoneal administration of N1 -propargylphenelzine to mice, 1 week prior to sacrifice, reduced DSP-4-induced depletion of noradrenaline in the hippocampus. The brains of N1 -propargylphenelzine-treated mice from the DSP-4 neurotoxicity experiments had normal MAO-B activity, but MAO-A was significantly inhibited; this was in contrast to animals that had received (,)-deprenyl, who showed normal MAO-A activity but a decrease of MAO-B. The present results indicate that N1 -propargylphenelzine may be a useful neuroprotective compound with a long-term in vivo propensity to inhibit MAO-A. Drug Dev. Res. 53:15,21, 2001. © 2001 Wiley-Liss, Inc. [source] Transplacental mutagenicity of N -ethyl- N -nitrosourea at the hprt locus in T-lymphocytes of exposed B6C3F1 miceENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2001Hillary E. Sussman Abstract Previous studies have compared age-related differences in total mutagenic burden in mice of differing age (preweanling, weanling, or young adult) after single intraperitoneal (i.p.) injections of ethylnitrosourea (ENU). The purpose of the present investigation was to determine the effects of time elapsed since treatment on the frequency of hprt mutant T-cells (Mf) from mice treated transplacentally with single acute vs. multiple split doses of ENU. To this end, pregnant C57BL/6 mice (n = 13,16/group), which had been bred to C3H males, were given i.p. injections of 40 mg ENU/kg bw in a single dose on day 18 of gestation, in a split dose of 6 mg ENU/kg bw on days 12 through 18 of gestation, or DMSO vehicle alone. Groups of pups were necropsied on days 10, 13, 15 (single dose only), 17, 20, 40, and 70 postpartum for T-cell isolations and hprt Mf measurements using the T-cell cloning assay. The time required to reach maximum Mfs in T-cells isolated from thymus of transplacentally treated animals was 2 weeks, the same time span as previously observed after ENU treatment of adult, weanling, and preweanling mice. Mfs in T-cells isolated from spleens of control animals averaged 2.1 ± 0.3 (SE) × 10,6. In spleens of mice treated transplacentally with ENU in a single dose, Mfs reached a maximum at 15 days postpartum [84.7 ± 15.8 (SE) × 10,6] and decreased to lower but still elevated levels at 40 days postpartum. In spleens of mice treated transplacentally with ENU in a split dose, Mfs reached a maximum at 13 days postpartum [74.0 ± 16.3 (SE) × 10,6] and decreased to background levels at 40 days postpartum. The areas under the curves describing the change in hprt Mfs over time for ENU-treated vs. control mice estimate the mutagenic potency for transplacental single- and split-dose exposures to be 1.9 and 0.8 × 103, respectively. Comparison of the mutagenic potency estimates for mice exposed to ENU in utero to 4-week-old mice given a similar dose of the same lot number of ENU indicates that the mouse is more susceptible to ENU-induced mutagenesis during fetal life. Environ. Mol. Mutagen. 38:30,37, 2001 © 2001 Wiley-Liss, Inc. [source] Oral toxicity of the cyanobacterial toxin cylindrospermopsin in mice: Long-term exposure to low dosesENVIRONMENTAL TOXICOLOGY, Issue 6 2006A. Sukenik Abstract The hepatotoxin cylindrospermopsin, a sulfated-guanidinium alkaloid with substituted dioxypyrimidine (uracil) moiety, was isolated from several cyanobacteria species. The acute toxicity of cylindrospermopsin was well established based on intraperitoneal and oral exposure; however, only a few long-term subacute exposure studies were performed to permit a reliable guideline value for cylindrospermopsin in drinking water. In the study reported herein, female and male mice were exposed to cylindrospermopsin in their drinking water. Cylindrospermopsin-containing, Aphanizomenon ovalisporum (cyanobacterium)-free medium was provided as the only source of drinking water, whereas a control group was given a fresh medium for cyanobacteria as drinking water. Over a period of 42 weeks, experiment groups were exposed to cylindrospermopsin concentration, gradually increased from 100 to 550 ,g L,1 (daily exposure ranged between 10 and 55 ,g kg,1 day,1). Body and organ weights were recorded, and serum and hematology analyses were performed 20 and 42 weeks after the beginning of the experiment. The most pronounced effect of cylindrospermopsin was elevated hematocrit levels in both male and female mice after 16 weeks of exposure to cylindrospermopsin. The observed changes in the hematocrit level were accompanied by deformation of red blood cells, which were changed into acanthocyte. Based on these results, a daily cylindrospermopsin dose of 20 ,g kg,1 day,1 (equivalent to 200 ,g L,1) is proposed as the lowest-observed-adverse-effect level for both male and female mice. © 2006 Wiley Periodicals, Inc. Environ Toxicol 21: 575,582, 2006. [source] Effect of in vitro and in vivo organotin exposures on the immune functions of murray cod (Maccullochella peelii peelii)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2007Andrew J. Harford Abstract Murray cod (Maccullochella peelii peelii) is an iconic native Australian freshwater fish and an ideal species for ecotoxicological testing of environmental pollutants. The species is indigenous to the Murray-Darling basin, which is the largest river system in Australia but also the ultimate sink for many environmental pollutants. The organotins tributyltin (TBT) and dibutyltin (DBT) are common pollutants of both freshwater and marine environments and are also known for their immunotoxicity in both mammals and aquatic organisms. In this study, TBT and DBT were used as exemplar immunotoxins to assess the efficiency of immune function assays (i.e., mitogen-stimulated lymphoproliferation, phagocytosis in head kidney tissue, and serum lysozyme activity) and to compare the sensitivity of Murray cod to other fish species. The organotins were lethal to Murray cod at concentrations previously reported as sublethal in rainbow trout (i.e., intraperitoneal [i.p.] lethal dose to 75% of the Murray cod [LD75] = 2.5 mg/kg DBT and i.p. lethal dose to 100% of the Murray cod [LD100] = 12.5 mg/kg TBT and DBT). In vivo TBT exposure at 0.1 and 0.5 mg/kg stimulated the phagocytic function of Murray cod (F = 6.89, df = 18, p = 0.004), while the highest concentration of 2.5 mg/kg TBT decreased lymphocyte numbers (F = 7.92, df = 18, p = 0.02) and mitogenesis (F = 3.66, df = 18, p = 0.035). Dibutyltin was the more potent immunosuppressant in Murray cod, causing significant reductions in phagocytic activity (F = 5.34, df = 16, p = 0.013) and lymphocyte numbers (F = 10.63, df = 16, p = 0.001). [source] Possible mechanisms for the anticonvulsant activity of fructose-1,6-diphosphateEPILEPSIA, Issue 2008Janet L. Stringer Summary Fructose-1,6-diphosphate (FDP), an intracellular metabolite of glucose, has anticonvulsant activity in several models of acute seizures in laboratory animals. The anticonvulsant effect of FDP is most likely due to a direct effect since intraperitoneal and oral administration results in significant increases in brain levels. A number of mechanisms have been proposed for this action of FDP. One possibility is that peripheral administration of FDP results in changes in brain metabolism that are anticonvulsant. Glucose can be metabolized through the glycolytic or pentose phosphate pathway. There is evidence that the pentose phosphate pathway is more active in the brain than in other tissues, and that, in the presence of elevated levels of FDP, the majority of glucose is metabolized by the pentose phosphate pathway. The pentose phosphate pathway generates NADPH, which is used to reduce glutathione. The reduced form of endogenous glutathione has been shown to have anticonvulsant activity. Taken together, the data suggest a hypothesis that exogenously administered FDP gets into the brain and astrocytes where it increases the flux of glucose through the pentose phosphate pathway, generating additional NADPH for the reduction of glutathione. [source] Corticothalamic Modulation during Absence Seizures in Rats: A Functional MRI AssessmentEPILEPSIA, Issue 9 2003Jeffrey R. Tenney Summary:,Purpose: Functional magnetic resonance imaging (fMRI) was used to identify areas of brain activation during absence seizures in an awake animal model. Methods: Blood-oxygenation-level,dependent (BOLD) fMRI in the brain was measured by using T2*-weighted echo planar imaging at 4.7 Tesla. BOLD imaging was performed before, during, and after absence seizure induction by using ,-butyrolactone (GBL; 200 mg/kg, intraperitoneal). Results: The corticothalamic circuitry, critical for spike,wave discharge (SWD) formation in absence seizure, showed robust BOLD signal changes after GBL administration, consistent with EEG recordings in the same animals. Predominantly positive BOLD changes occurred in the thalamus. Sensory and parietal cortices showed mixed positive and negative BOLD changes, whereas temporal and motor cortices showed only negative BOLD changes. Conclusions: With the BOLD fMRI technique, we demonstrated signal changes in brain areas that have been shown, with electrophysiology experiments, to be important for generating and maintaining the SWDs that characterize absence seizures. These results corroborate previous findings from lesion and electrophysiological experiments and show the technical feasibility of noninvasively imaging absence seizures in fully conscious rodents. [source] Anticonvulsant Profile and Teratogenicity of N -methyl-tetramethylcyclopropyl Carboxamide: A New Antiepileptic DrugEPILEPSIA, Issue 2 2002Nina Isoherranen Summary: ,Purpose: The studies presented here represent our efforts to investigate the anticonvulsant activity of N -methyl-tetramethylcyclopropyl carboxamide (M-TMCD) and its metabolite tetramethylcyclopropyl carboxamide (TMCD) in various animal (rodent) models of human epilepsy, and to evaluate their ability to induce neural tube defects (NTDs) and neurotoxicity. Methods: The anticonvulsant activity of M-TMCD and TMCD was determined after intraperitoneal (i.p.) administration to CF#1 mice, and either oral or i.p. administration to Sprague,Dawley rats. The ability of M-TMCD and TMCD to block electrical-, chemical-, or sensory-induced seizures was examined in eight animal models of epilepsy. The plasma and brain concentrations of M-TMCD and TMCD were determined in the CF#1 mice after i.p. administration. The induction of NTDs by M-TMCD and TMCD was evaluated after a single i.p. administration at day 8.5 of gestation in a highly inbred mouse strain (SWV) that is susceptible to valproic acid,induced neural tube defects. Results: In mice, M-TMCD afforded protection against maximal electroshock (MES)-induced, pentylenetetrazol (Metrazol)-induced, and bicuculline-induced seizures, as well as against 6-Hz "psychomotor" seizures and sound-induced seizures with ED50 values of 99, 39, 81, 51, and 10 mg/kg, respectively. In rats, M-TMCD effectively prevented MES- and Metrazol-induced seizures and secondarily generalized seizures in hippocampal kindled rats (ED50 values of 82, 45, and 39 mg/kg, respectively). Unlike M-TMCD, TMCD was active only against Metrazol-induced seizures in mice and rats (ED50 values of 57 and 52 mg/kg, respectively). Neither M-TMCD nor TMCD was found to induce NTDs in SWV mice. Conclusions: The results obtained in this study show that M-TMCD is a broad-spectrum anticonvulsant drug that does not induce NTDs and support additional studies to evaluate its full therapeutic potential. [source] Analysis of clinical outcomes and prognostic factors of neoadjuvant chemoradiotherapy combined with surgery: intraperitoneal versus extraperitoneal rectal cancerEUROPEAN JOURNAL OF CANCER CARE, Issue 3 2006E. BENZONI md Neoadjuvant chemoradiotherapy (CRT) is a widely purposed and performed treatment for rectal cancer. Downstaging effects possibly enhance the rate of curative surgery and may enable sphincter preservation in low-lying tumours. The current study examines the clinical outcomes in patients enrolled in a neoadjuvant CRT-surgery protocol for rectal cancer, distinguishing between intraperitoneal and extraperitoneal cancer. From 1994 to 2003, 58 patients with a primary diagnosis of rectal cancer were enrolled in a single-centre, not randomized study based on 5-week sessions of radiotherapy associated with a 30-day protracted venous 5-FU infusion followed by surgical resection. The study population was divided into two groups according to the localization of the tumour: 18 intraperitoneal and 40 extraperitoneal (EPt). Fifty-eight patients were treated with neoadjuvant CRT and surgery. Overall mortality rate was 25.9%, no deaths were recorded during hospitalization; 10 patients (all EPt) died because of recurrence. Significant differences in disease-free survival and overall survival rates were found between intraperitoneal vs. extraperitoneal tumours (P = 0.006), both intraperitoneal vs. extraperitoneal tumours N0 (P = 0.04 and P < 0.05) and intraperitoneal vs. extraperitoneal tumours N+ (P < 0.05). We diagnosed all local recurrence and liver metastasis in extraperitoneal tumours (t = 0.02 and t = 0.04), and only one case of lung metastasis arose from intraperitoneal cancer. Extraperitoneal tumours could be more aggressive than intraperitoneal ones, spreading more precociously, and/or less responsive to the neoadjuvant CRT because of their localization rather than biological differences. Aside from lymph node status, the location of the tumour with respect to the peritoneum border, is also a prognostic factor of survival in rectal cancer treated by neoadjuvant CRT and surgery. [source] Arsenic trioxide is effective in the treatment of multiple myeloma in SCID miceEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2004Philippe Rousselot Abstract: Objectives :,Pharmacological concentrations of arsenic trioxide (ATO) and organic arsenic melarsoprol induce apoptosis in malignant plasma cells. In an attempt to further document the interest of the arsenic in vivo, we treated severe combined immunodeficient (SCID) mice transplanted with human myeloma cells by ATO or melarsoprol. Methods :,Fifty-two SCID mice were irradiated before intraperitoneal (i.p.) injection of plasma cells from five myeloma patients. Engraftment was assessed by serial measurement of the human monoclonal immunoglobulin G (HuMIgG) concentration in mouse serum. Treatment with ATO (10 ,g/g i.p. 5 d a week), melarsoprol (30 ,g/g i.p. 5 d a week) or phosphate buffer saline was started when a sustained growth of the tumor cells was demonstrated. Results :,Seventeen mice developed the human tumor. A significant decrease in HuMIgG amounts was observed in three of five mice of the ATO group, including two that achieved an apparent complete remission persisting up to 5 months after ATO discontinuation. In these mice, no human plasma cells were detected in tissue samples collected postmortem. Soluble human interleukin-6 receptor amount, measured in mice sera as a surrogate marker of the plasma cell proliferation, varied in parallel with HuMIgG concentration. A significant difference in survival was observed between control and ATO treated mice (113 and 158 d, respectively; P = 0.01) whereas no difference could be evidenced in control and melarsoprol groups. Conclusion :,Present study confirms in vivo the in vitro effects of ATO on myeloma cells. Delayed relapses were observed suggesting that prolonged or maintenance therapy has to be considered in future clinical trials. Whether or not this will translate into clinically relevant effect of the drug in myeloma patients deserves further consideration. [source] PRECLINICAL STUDY: Route of administration affects the ability of naltrexone to reduce amphetamine-potentiated brain stimulation reward in ratsADDICTION BIOLOGY, Issue 4 2009Mark S. Todtenkopf ABSTRACT Opioid receptor antagonism has been shown to attenuate behavioral and neurochemical effects of amphetamine in humans and rodents. The effects of acute (oral or subcutaneous) or extended-release naltrexone (XR-NTX) were tested on the reward-enhancing effects of amphetamine using the intracranial self-stimulation (ICSS) paradigm. Acute exposure to drugs of abuse reduces the locus of rise (LOR) in the ICSS procedure, reflecting enhanced brain stimulation reward (BSR). Rats were treated once a day with naltrexone orally (PO; 5.0 mg/kg) or subcutaneously (SC; 0.5 mg/kg) for four consecutive days and tested with D-amphetamine (0.5 mg/kg, intraperitoneal) in the ICSS paradigm 30 minutes later on days 1 and 4. Separate groups of rats received XR-NTX (50 mg/kg, SC) or placebo microspheres (similar mass to XR-NTX, SC) on day 0 and tested with D-amphetamine in the ICSS paradigm on days 4, 14, 21, 28 and 41 after administration. Naltrexone plasma concentrations were determined for each amphetamine testing session using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). In rats pretreated with naltrexone acutely, amphetamine-potentiated BSR did not differ from vehicle-pretreated rats on either day 1 or day 4 (25,30% decrease in LOR). In XR-NTX-pretreated rats, amphetamine-potentiated BSR was reduced by 64 and 70% on days 4 and 14, respectively, compared to placebo microsphere-treated controls. This effect dissipated by day 21. Naltrexone plasma concentrations were comparable across all treatment groups (14,30 ng/ml) on days 1, 4 and 14. In summary, an extended-release formulation of naltrexone results in significant attenuation of psychostimulant-enhanced BSR that is not observed with acute naltrexone. [source] PRECLINICAL STUDY: Circadian regulation of central ethanol sensitivity by the mPer2 geneADDICTION BIOLOGY, Issue 3 2009Stéphanie Perreau-Lenz ABSTRACT The effect of alcohol is known to vary with the time of the day. Although initially it was suggested that this phenomenon may be due to diurnal differences in ethanol metabolism, more recent studies were contradicting. In the present study, we therefore first set out in assessing the diurnal variations in ethanol sensitivity in mice analysing, concurrently, ethanol elimination rates. Ethanol-induced (3.5 g/kg; intraperitoneal) loss of righting reflex (LORR) duration was thus determined at several Zeitgeber time (ZT) points (ZT5, 11, 17 and 23) in C57BL/6N mice. In parallel, the corresponding ethanol elimination rates were also assessed. The results display the existence of a distinct diurnal rhythm in LORR duration peaking at ZT11, whereas no differences could be observed regarding the elimination rates of alcohol. Successively, we checked the involvement of the clock genes mPer1 and mPer2 in conveying this rhythm in sensitivity, testing LORR and hypothermia at the peak and trough previously observed (ZT5 and ZT11). Per1Brdm1 mice demonstrate a similar diurnal pattern as control mice, with enhanced LORR durations at ZT11. In contrast, Per2Brdm1 mice did not exhibit a temporal variation to the depressant effects of ethanol with respect to LORR, revealing a constant high sensitivity to ethanol. The present study reveals a central role of the mPer2 gene in inhibiting alcohol sensitivity at the beginning of the inactive phase. [source] PRECLINICAL STUDY: Pavlovian drug discrimination with bupropion as a feature positive occasion setter: substitution by methamphetamine and nicotine, but not cocaineADDICTION BIOLOGY, Issue 2 2009Jamie L. Wilkinson ABSTRACT Bupropion can serve as a discriminative stimulus (SD) in an operant drug discrimination task, and a variety of stimulants substitute for the bupropion SD. There are no reports, however, of bupropion functioning as a Pavlovian occasion setter (i.e. feature positive modulator). The present experiment seeks to fill this gap in the literature by training bupropion in rats as a feature positive modulator that disambiguates when a light will be paired with sucrose. Specifically, on bupropion (10 mg/kg intraperitoneal) sessions, offset of 15-second cue lights were followed by brief delivery of liquid sucrose; saline sessions were similar except no sucrose was available. Rats readily acquired the discrimination with more conditioned responding to the light on bupropion sessions. Bupropion is approved for use as a smoking cessation aid, and more recently has drawn attention as a potential pharmacotherapy for cocaine and methamphetamine abuse. Accordingly, after discrimination training, we tested the ability of cocaine (1,10 mg/kg), methamphetamine (0.1 to 1 mg/kg) and nicotine (0.00625 to 0.2 mg/kg) to substitute for the bupropion feature. Nicotine (0.05 mg/kg) and methamphetamine (0.3 mg/kg) substituted fully for bupropion; cocaine did not substitute. These results extend previous research on shared stimulus properties between bupropion and other stimulants to a Pavlovian occasion setting function. Further, this is the first report of nicotine and methamphetamine substitution for bupropion. The overlap in stimulus properties might explain the effectiveness of bupropion as a smoking cessation aid and highlight the possible utility of bupropion for treatment of stimulant use disorder. [source] Effect of a dose of ethanol on acute tolerance and ethanol consumption in alcohol drinker(UChB) and non-drinker (UChA) ratsADDICTION BIOLOGY, Issue 3 2002Lutske Tampier Acute tolerance that develops within minutes of ethanol exposure appears to influence the apparent acute behavioral sensitivity of laboratory animals to ethanol actions. The existence of a correlation between voluntary ethanol consumption and the speed of acquiring acute tolerance has been proposed. In the present paper we investigated the effect of an acute dose of ethanol on tolerance development and on ethanol voluntary consumption in our two selected bred strains, UChA (low ethanol drinker) and UChB (high ethanol drinker) rats. Acute tolerance developed to motor impairment induced by a dose of ethanol of 2.3 g/kg. administered intraperitoneally was evaluated by the tilting plane test. Voluntary ethanol consumption was compared in rats receiving the ethanol dose, to rats receiving a saline intraperitoneal (i.p.) injection. The results show that UChB rats receiving an intoxicating dose of ethanol develop more tolerance and they significantly increased their ethanol consumption compared to the same line that received a saline injection, while no change in acute tolerance and voluntary ethanol consumption were obtained in UChA rats. In conclusion, a possible mechanism by which UChB rats drink high amounts of ethanol appears to be the development of tolerance to the pharmacological effects of ethanol. [source] Intrathecally applied flurbiprofen produces an endocannabinoid-dependent antinociception in the rat formalin testEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2003Mehmet Ates Abstract It is generally accepted that the phospholipase-A2 -cyclooxygenase-prostanoids-cascade mediates spinal sensitization and hyperalgesia. However, some observations are not in line with this hypothesis. The aim of the present work was to investigate whether different components of this cascade exhibit nociceptive or antinociceptive effects in the rat formalin test. Intrathecal (i.th.) injection of prostaglandin E2 (PGE2) induced a dose-dependent antinociceptive effect on the formalin-induced nociception. Furthermore, thimerosal, which inhibits the reacylation of arachidonic acid thereby enhancing arachidonic acid levels, had an antinociceptive effect rather than the expected pronociceptive effect when given i.th. While the phospholipase A2 inhibitor methyl arachidonyl fluorophosphonate (MAFP; i.th.) had a significant antinociceptive effect, its analogue palmitoyl trifluoromethyl ketone (PTFMK; i.th.) had no significant effect on the formalin-induced nociception. However, MAFP, but not PTFMK, showed a cannabinoid CB1 agonistic effect as shown by the inhibition of electrically evoked contractions of the vas deferens isolated from CB1 wild-type mice but not of that from CB1 knockout mice. The antinociceptive effect of MAFP was completely reversed by the CB1 receptor antagonist AM-251 (i.th.), thus attributing such effect to its CB1 agonistic effect. Moreover, the antinociceptive effect of the cyclooxygenase inhibitor, flurbiprofen (i.th.) was reversed by the co-administration of AM-251, but not by PGE2. Finally. the combination of phenylmethylsulfonyl fluoride (PMSF; intraperitoneal), which inhibits the degradation of anandamide through the inhibition of fatty acid amidohydrolase, with thimerosal (i.th.) produced a profound CB1 -dependent antinociception. The present results show that endocannabinoids play a major role in mediating flurbiprofen-induced antinociception at the spinal level. [source] Route of Administration Differentially Affects Fevers Induced by Gram-Negative and Gram-Positive Pyrogens in RabbitsEXPERIMENTAL PHYSIOLOGY, Issue 3 2002T. Cartmell We have investigated the febrile responses of New Zealand White rabbits to a Gram-negative pyrogen (bacterial lipopolysaccharide (LPS) from Salmonella typhosa), commonly associated with systemic infection, and a Gram-positive pyrogen (Staphylococcus aureus), more frequently associated with superficial soft tissue infection, each administered via one of four different routes (intravenous, intramuscular, subcutaneous or intraperitoneal) at each of three different doses (LPS: 0.1, 1 and 10 ,g kg,1; S. aureus: 1.5 × 107, 1.5 × 108 and 1.5 × 109 cell walls kg,1). Intravenous administration of LPS evoked rapid, dose-dependent biphasic fever. Injection of LPS by the other routes also evoked dose-dependent fever. However, these fevers were monophasic, had increased latency of onset, and were of lower amplitude. It is important to note that a dose of approximately 10 and 100 times that of the standard intravenous dose was required to produce a similar peak rise in temperature when administered subcutaneously and intraperitoneally, respectively. Intravenous injection of the highest dose of S. aureus evoked dose-dependent biphasic fever, with short latency of onset, which was very similar to that induced by intravenous LPS. At lower doses, intravenous S. aureus induced monophasic fever. No fever occurred when the same doses of S. aureus were administered by any other route. We conclude that any of the four routes may be used for the study of LPS-induced fever, provided that the doses are adjusted. However, studies of S. aureus -induced fever, and detection of contamination with either pyrogen, requires intravenous injection. [source] High-dose methylprednisolone influences the physiology and virulence of Candida albicans ambiguously and enhances the candidacidal activity of the polyene antibiotic amphotericin B and the superoxide-generating agent menadioneFEMS YEAST RESEARCH, Issue 2 2007Ágnes Gyetvai Abstract Although exposure of Candida albicans cells to high-dose (4 mM) methylprednisolone stimulated microbial growth, germination rate in serum and phospholipase release, it also promoted the recognition of C. albicans cells by polymorphonuclear leukocytes. Pretreatment of C. albicans cells with methylprednisolone did not result in any increase in the pathogenicity of the fungus in intraperitoneal and intravenous mouse assays. Therefore, the virulence of C. albicans is unlikely to increase in patients treated with comparably high-dose methylprednisolone on skin and mucosal membranes. Methylprednisolone treatments also increased the production of conjugated dienes and thiobarbituric acid-reactive substances, and the menadione sensitivity of C. albicans cells, which can be explained by a significant decrease in the specific activities of several antioxidant enzymes. The combination of methylprednisolone with oxidants, e.g. in topical applications, may be of clinical importance when the predisposition to candidiasis is high. Methylprednisolone treatments negatively affected membrane fluidity and decreased the antifungal effects of both the polyene antibiotic nystatin and the ergosterol biosynthesis inhibitor lovastatin, and also enhanced the deleterious effects of the polyene antimycotic amphotericin B on C. albicans cells. These corticosteroid,polyene drug interactions should be considered in the treatment of C. albicans infections in patients with prolonged topical application of corticosteroids. [source] Efficient generation of human hepatocytes by the intrahepatic delivery of clonal human mesenchymal stem cells in fetal sheep,HEPATOLOGY, Issue 6 2007Jason Chamberlain Alternative methods to whole liver transplantation require a suitable cell that can be expanded to obtain sufficient numbers required for successful transplantation while maintaining the ability to differentiate into hepatocytes. Mesenchymal stem cells (MSCs) possess several advantageous characteristics for cell-based therapy and have been shown to be able to differentiate into hepatocytes. Thus, we investigated whether the intrahepatic delivery of human MSCs is a safe and effective method for generating human hepatocytes and whether the route of administration influences the levels of donor-derived hepatocytes and their pattern of distribution throughout the parenchyma of the recipient's liver. Human clonally derived MSCs were transplanted by an intraperitoneal (n = 6) or intrahepatic (n = 6) route into preimmune fetal sheep. The animals were analyzed 56,70 days after transplantation by immunohistochemistry, enzyme-linked immunosorbent assay, and flow cytometry. The intrahepatic injection of human MSCs was safe and resulted in more efficient generation of hepatocytes (12.5% ± 3.5% versus 2.6% ± 0.4%). The animals that received an intrahepatic injection exhibited a widespread distribution of hepatocytes throughout the liver parenchyma, whereas an intraperitoneal injection resulted in a preferential periportal distribution of human hepatocytes that produced higher amounts of albumin. Furthermore, hepatocytes were generated from MSCs without the need to first migrate/lodge to the bone marrow and give rise to hematopoietic cells. Conclusion: Our studies provide evidence that MSCs are a valuable source of cells for liver repair and regeneration and that, by the alteration of the site of injection, the generation of hepatocytes occurs in different hepatic zones, suggesting that a combined transplantation approach may be necessary to successfully repopulate the liver with these cells. (HEPATOLOGY 2007.) [source] Contribution of NR2A and NR2B NMDA subunits to bidirectional synaptic plasticity in the hippocampus in vivoHIPPOCAMPUS, Issue 11 2006Christopher J. Fox Abstract It has recently been proposed that activation of the NR2A subunit results in Long-term potentiation (LTP) induction, whereas activation of the NR2B subunit results in long-term depression (LTD) induction. The present study undertakes to replicate these findings in vivo to determine if a role for specific subunits in synaptic plasticity can be shown in the intact brain. Field recordings were made from the CA1 subfield of the hippocampus using Schaffer collateral stimulation in anesthetized male Sprague-Dawley rats. Antagonists of the N -methyl- D -aspartate receptors NR2A and NR2B subunits were administered by either intraperitoneal (i.p.) or intrahippocampal (i.h.) injections to assess their involvement in LTP (100 Hz stimuli) and LTD (200 Paired-burst stimuli). i.h. injection of Ro25,6981 (100 ,M) significantly attenuated hippocampal LTP expression and completely blocked LTD expression. When administered i.p., Ro25,6981 (6 mg/kg) again blocked LTD, but did not significantly diminish the expression of LTP. When NVP-AAM077 was administered i.h. (80 ,M) both LTP and LTD were completely abolished. The administration of this compound i.p. (1.2 mg/kg) also significantly attenuated LTP, but did not affect LTD. These data suggest that both NR2A and NR2B subunits can play roles in LTP and LTD in the hippocampus in vivo. © 2006 Wiley-Liss, Inc. [source] Effect of mucosal and systemic immunization with virus-like particles of severe acute respiratory syndrome coronavirus in miceIMMUNOLOGY, Issue 2 2010Baojing Lu Summary Nasal administration has emerged as a promising and attractive route for vaccination, especially for the prophylaxis of respiratory diseases. Our previous studies have shown that severe acute respiratory syndrome coronavirus (SARS-CoV) virus-like particles (VLPs) can be assembled using a recombinant baculovirus (rBV) expression system and such VLPs induce specific humoral and cellular immune responses in mice after subcutaneous injection. Here, we investigated mucosal immune responses to SARS-CoV VLPs in a mouse model. Mice were immunized in parallel, intraperitoneally or intranasally, with VLPs alone or with VLPs plus cytosine,phosphate,guanosine (CpG). Immune responses, including the production of SARS-CoV-specific serum immunoglobulin G (IgG) and secretory immunoglobulin A (sIgA), were determined in mucosal secretions and tissues. Both immunizations induced SARS-CoV-specific IgG, although the levels of IgG in groups immunized via the intraperitoneal (i.p.) route were higher. sIgA was detected in saliva in groups immunized intranasally but not in groups immunized intraperitoneally. CpG had an adjuvant effect on IgA production in genital tract washes when administered intranasally but only affected IgA production in faeces samples when administered intraperitoneally. In addition, IgA was also detected in mucosal tissues from the lung and intestine, while CpG induced an increased level of IgA in the intestine. Most importantly, neutralization antibodies were detected in sera after i.p. and intranasal (i.n.) immunizations. Secretions in genital tract washes from the i.n. group also showed neutralization activity. Furthermore, VLPs that were administered intraperitoneally elicited cellular immune responses as demonstrated by enzyme-linked immunospot (ELISPOT) assay analyses. In summary, our study indicates that mucosal immunization with rBV SARS-CoV VLPs represent an effective means for eliciting protective systemic and mucosal immune responses against SARS-CoV, providing important information for vaccine design. [source] Induction of an antitumour adaptive immune response elicited by tumour cells expressing de novo B7-1 mainly depends on the anatomical site of their delivery: the dose applied regulates the expansion of the responseIMMUNOLOGY, Issue 4 2003Silvia Sartoris Summary De novo expression of costimulatory molecules in tumours generally increases their immunogenicity, but does not always induce a protective response against the parental tumour. This issue was addressed in the mouse Sp6 hybridoma model, comparing different immunization routes (subcutaneous, intraperitoneal and intravenous) and doses (0·5 × 106 and 5 × 106 cells) of Sp6 cells expressing de novo B7-1 (Sp6/B7). The results can be summarized as follows. First, de novo expression of B7-1 rendered Sp6 immunogenic, as it significantly reduced the tumour incidence to ,15% with all delivery routes and doses tested, whereas wild-type Sp6 was invariably tumorigenic (100% tumour incidence). Second, long-lasting protection against wild-type Sp6 was mainly achieved when immunization with Sp6/B7 was subcutaneous: a dose of 0·5 × 106 Sp6/B7 cells elicited protection that was confined to sites in the same anatomical quarter as the immunizing injection. Repeated injections of the same dose extended protection against wild-type Sp6 to other anatomical districts, as well as a single injection of a 10-fold higher dose (5 × 106 cells). Finally, Sp6-specific cytotoxic T-lymphocyte activity was detected in draining lymph nodes, and the splenic expansion of Sp6-specific cytotoxic T-lymphocyte precursors quantitatively correlated with the dose of antigen. We conclude that activation of a protective immune response against Sp6 depends on the local environment where the immunogenic form of the ,whole tumour cell antigen' is delivered. The antigen dose regulates the anatomical extent of the protective response. [source] Eine erweiterte Evaluation der Neurolept-Anästhesie für Meerschweinchen mit einer Analyse gemischt-exspiratorischer Gase während Spontanatmung.JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 1-2 2004Wirkung des Fastens auf das kardiorespiratorische System und den Metabolismus Zusammenfassung Das beatmete Meerschweinchen wurde oft für neurophysiologische und respiratorische Studien eingesetzt. Diese Spezies ist auch für eine Evaluation künstlicher Sauerstoffträger, entwickelt aus Hämoglobin, geeignet, weil seine Sauerstoff-Hämoglobin-Bindung der des Menschen sehr ähnlich ist. Andererseits ist eine Narkose dieser Tiere wegen kardio-respiratorischer Depression mit herkömmlichen Verfahren schwierig. Bewährt hat sich die folgende intraperitoneal zu verabreichende Neurolept-Anästhesie: 0,2 mg Fentanyl (Janssen/D), 10 mg Droperidol (Janssen/D) sowie 400 mg Urethan in 10 ml isotonischer Natriumchlorid-Lösung pro kg Körpergewicht. Unser neues Tier-Modell ermöglicht, mit einem speziellen Ventilsystem den Gasaustausch unter Spontanatmung, kardiovaskuläre wie auch Blutgaswerte und damit den Säure-Basen-Status zu messen. Die vitalen Parameter der Tiere, blieben über mehr als 6 Stunden stabil und nahe bei Werten wacher Tiere, insbesondere der mittlere arterielle Blutdruck. Deswegen ist diese etablierte Neurolept-Anästhesie des Meerschweinchens für Forschungszweck zu bevorzugen. Nüchterne Tiere zeigten signifikant erniedrigte Blut-pH- (7,345 bzw. 7,401) sowie Herzfrequenz- (244 bzw. 277 min,1) und Ventilationswerte (167 bzw. 205 ml/min) im Vergleich zu nicht nüchternen Tieren. Summary An Extended Evaluation of a Neuroleptanesthesia for the Guinea Pig with Analysis of Mixed Expiratory Gases during Spontaneous Breathing. Effects of Fasting on the Cardiorespiratory System and Metabolism The artificially ventilated guinea pig was frequently used for neurophysiological and respiratory studies. This species is also preferable for an evaluation of hemoglobin based artificial oxygen carriers, because its oxygen hemoglobin binding is very similar to that of man. But the narcosis of this animal-species is very difficult, because of cardiorespiratory depression induced by conventional procedures. The following intraperitoneal administered neuroleptanesthesia was proved in guinea pigs: 0,2 mg Fentanyl (Janssen/D), 10 mg Droperidol (Janssen/D) and 400 mg Urethan in 10 ml isotonic sodium chloride solution per kg body weight. Our new animal model with a special valve system enables to assess the gas exchange under spontaneous breathing, cardiovascular and the acid-base parameters. The vital parameters of animals were stable over 6 hours and very close to those of awake animals, especially the arterial average blood pressure. For that reason, this established neuroleptanesthesia of guinea pigs is preferable for research purpose. The fasted animals show significantly decreased values of arterial blood pH (7,345 vs. 7,401), of heart frequency (244 vs. 277 min,1), and of ventilation value (167 vs. 205 ml/min) compared to non-fasted animals. [source] Infectious gastroenteritis caused by Vibrio harveyi (V. carchariae) in cultured red drum, Sciaenops ocellatusJOURNAL OF APPLIED ICHTHYOLOGY, Issue 1 2003P.-C. Liu Summary An outbreak of serious mortality among the cultured red drum Sciaenops ocellatus (L.) characterized by a swollen intestine containing transparent yellow fluid (ascites and gastroenteritis) occurred in July 2000 in Taiwan. A motile strain Rd 0700 was isolated from head kidney and/or the intestinal yellow fluid on tryptone soya agar (TSA) supplemented with 2% (w/v) NaCl and/or thiosulfate citrate bile salt (TCBS) sucrose agar plates. Applying biochemical characteristics, this strain was characterized and identified as Vibrio harveyi (V. carchariae). The bacteria could be re-isolated from kidney, liver, and the transparent yellow fluid of swollen intestine of fish after bacterial challenge. The LD50 values of the organism and its extracellular products (ECP) were 2.9×107 colony forming units (CFU) and 3.85 ,g protein g,1 fish body weight, respectively. All moribund/dead fish exhibited gastroenteritis except those killed within 12 h. This is a first report showing that intraperitoneal (i.p.) injection of the ECP from V. carchariae is lethal to red drum and can reproduce gastroenteritis in the fish. [source] | ||||||||||||||||||||||||||||||||||||||||