Home About us Contact
|
Home About us Contact | ||
|
|
||
Challenge Dose (challenge + dose)
Selected AbstractsLactose intolerance: analysis of underlying factorsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2003R. J. Vonk Abstract Background We studied the degree of lactose digestion and orocecal transit time (OCTT) as possible causes for the variability of symptoms of lactose intolerance (LI) in a sample of a population with genetically determined low lactase activity. Methods Lactose digestion index (LDI) was measured by the recently developed 13C-lactose/2H-glucose test. The OCTT was determined using the breath hydrogen test. Based on a 6-h symptom score (SSC) after a challenge dose of 25 g of lactose the subjects were divided into a tolerant group (T: n= 15; SSC = 0) and an intolerant group (IT: n= 28; SSC 1,40). The intolerant group was subdivided according to the severity of symptoms: group ITa (n = 17; mild symptoms without diarrhoea) and group ITb (n = 11; with diarrhoea). Results The LDI was lower in the intolerant group (0·34 ± 0·14) (mean ± SD) than in the tolerant group (0·47 ± 0·14) (P = 0·008). The OCTT of group IT (60, 30,90 min) (median, quartiles) was significantly shorter than that of group T (105, 60,120 min) (P = 0·003) and was positively correlated with the LDI (P = 0·050). In groups ITa and ITb the OCTT (60, 30,90 min; 60, 26,83 min) and LDI (0·30 ± 0·14; 0·39 ± 0·14) were similar. Conclusions Lactose digestion capacity, which is determined by small intestinal lactase activity as well as by OCTT, affects the occurrence of lactose intolerance. However, the major difference in intolerance symptoms is caused by differences in the colonic processing of maldigested lactose. [source] Behavioural sensitization and enhanced dopamine response in the nucleus accumbens after intravenous cocaine self-administration in miceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2003Agustin Zapata Abstract The behavioural effects of cocaine are enhanced in animals with a prior history of repeated cocaine administration. This phenomenon, referred to as sensitization, is also associated with an increase in cocaine-evoked extracellular dopamine levels in the nucleus accumbens. Behavioural and neurochemical sensitization has been demonstrated in rats with a prior history of cocaine self-administration and in those that had received experimenter-administered cocaine. Although it is clear that the repeated non-contingent administration also results in behavioural sensitization in the mouse, the issue of whether behavioural and neurochemical sensitization also occur in this species following intravenous cocaine self-administration has not been assessed. The present study used the technique of in vivo microdialysis in conjunction with operant self-administration to characterize cocaine-evoked locomotor activity and dopamine levels in the nucleus accumbens in mice with a prior history of intravenous cocaine self-administration or those that had received yoked infusions of cocaine. Mice that had received contingent or non-contingent infusions of cocaine exhibited an enhanced behavioural response to cocaine and increased cocaine-evoked dopamine levels in the nucleus accumbens. There was no difference between groups in the magnitude of this effect. Prior exposure to cocaine did not modify baseline dopamine levels in the nucleus accumbens. These data demonstrate that mice with previous cocaine self-administration experience show an enhanced behavioural and dopamine response to cocaine in the nucleus accumbens. Furthermore, control over cocaine infusion does not significantly alter the magnitude of the sensitized behavioural and presynaptic dopamine responses observed in response to a challenge dose of cocaine. [source] Hippocampus modulates the behaviorally-sensitizing effects of nicotine in a rat model of novelty-seeking: Potential role for mossy fibersHIPPOCAMPUS, Issue 10 2007Amrinder S. Bhatti Abstract Present experiments investigate interactions between a rat model of the novelty-seeking phenotype and psychomotor sensitization to nicotine (NIC) in adolescence, and the potential role of hippocampal mossy fibers in mediating the behaviorally-sensitizing effects of NIC. Outbred rats were phenotype-screened as high-responders (HR; locomotor reactivity to novelty score ranking in the upper third of the population) or low-responders (LR; locomotor reactivity to novelty score ranking in the lower third of the population). In Experiment 1, both phenotypes were trained with four NIC injections (at 3-d intervals on postnatal days 33,44), and lidocaine microinfusion was used to temporarily inactivate the hippocampal hilus at each NIC injection. Systemic saline and microinjection of artificial cerebral spinal fluid (CSF) were used as controls. During NIC training, lidocaine inactivation caused augmented locomotor response to NIC in HRs compared to LRs irrespective of injection days. Following 1 week of abstinence, all animals were challenged with a low dose of NIC. During challenge, previously NIC/CSF trained LRs and HRs were divided into two; one half receiving lidocaine inactivation of the hippocampal hilus and the other half receiving CSF control microinjection. Only HRs showed behavioral sensitization to the challenge dose of NIC, which was enhanced with lidocaine inactivation. In Experiment 2, a single NIC exposure was found sufficient to induce sensitization to the challenge dose of NIC in HRs, and concurrently an enlarged supra-pyramidal mossy fiber (SP-MF) terminal field. The increase in the SP-MF volume in HRs was greater with repeated NIC training. In both single and repeated NIC training cases, a significant positive morphobehavioral correlation was observed between challenge NIC-induced locomotion and the SP-MF terminal field volume. These findings suggest that the HR hippocampal mossy fibers are vulnerable to neuroadaptive alterations induced by NIC, which may be a substrate for the observed behavioral vulnerability to NIC. © 2007 Wiley-Liss, Inc. [source] Effects of chronic paroxetine treatment on dialysate serotonin in 5-HT1B receptor knockout miceJOURNAL OF NEUROCHEMISTRY, Issue 1 2003A. M. Gardier Abstract The role of serotonin (5-HT)1B receptors in the mechanism of action of selective serotonin re-uptake inhibitors (SSRI) was studied by using intracerebral in vivo microdialysis in conscious, freely moving wild-type and 5-HT1B receptor knockout (KO 5-HT1B) mice in order to compare the effects of chronic administration of paroxetine via osmotic minipumps (1 mg per kg per day for 14 days) on extracellular 5-HT levels ([5-HT]ext) in the medial prefrontal cortex and ventral hippocampus. Basal [5-HT]ext values in the medial prefrontal cortex and ventral hippocampus, ,,20 h after removing the minipump, were not altered by chronic paroxetine treatment in both genotypes. On day 15, in the ventral hippocampus, an acute paroxetine challenge (1 mg/kg i.p.) induced a larger increase in [5-HT]ext in saline-pretreated mutant than in wild-type mice. This difference between the two genotypes in the effect of the paroxetine challenge persisted following chronic paroxetine treatment. Conversely, in the medial prefrontal cortex, the paroxetine challenge increased [5-HT]ext similarly in saline-pretreated mice of both genotypes. Such a challenge produced a further increase in cortical [5-HT]ext compared with that in saline-pretreated groups of both genotypes, but no differences were found between genotypes following chronic treatment. To avoid the interaction with raphe 5-HT1A autoreceptors, 1 µm paroxetine was perfused locally through the dialysis probe implanted in the ventral hippocampus; similar increases in hippocampal [5-HT]ext were found in acutely or chronically treated wild-type mice. Systemic administration of the mixed 5-HT1B/1D receptor antagonist GR 127935 (4 mg/kg) in chronically treated wild-type mice potentiated the effect of a paroxetine challenge dose on [5-HT]ext in the ventral hippocampus, whereas systemic administration of the selective 5-HT1A receptor antagonist WAY 100635 did not. By using the zero net flux method of quantitative microdialysis in the medial prefrontal cortex and ventral hippocampus of wild-type and KO 5-HT1B mice, we found that basal [5-HT]ext and the extraction fraction of 5-HT were similar in the medial prefrontal cortex and ventral hippocampus of both genotypes, suggesting that no compensatory response to the constitutive deletion of the 5-HT1B receptor involving changes in 5-HT uptake capacity occurred in vivo. As steady-state brain concentrations of paroxetine at day 14 were similar in both genotypes, it is unlikely that differences in the effects of a paroxetine challenge on hippocampal [5-HT]ext are due to alterations of the drug's pharmacokinetic properties in mutants. These data suggest that there are differences between the ventral hippocampus and medial prefrontal cortex in activation of terminal 5-HT1B autoreceptors and their role in regulating dialysate 5-HT levels. These presynaptic receptors retain their capacity to limit 5-HT release mainly in the ventral hippocampus following chronic paroxetine treatment in mice. [source] Abuse liability of intravenous buprenorphine/naloxone and buprenorphine alone in buprenorphine-maintained intravenous heroin abusersADDICTION, Issue 4 2010Sandra D. Comer ABSTRACT Background Sublingual buprenorphine is an effective maintenance treatment for opioid dependence, yet intravenous buprenorphine misuse occurs. A buprenorphine/naloxone formulation was developed to mitigate this misuse risk. This randomized, double-blind, cross-over study was conducted to assess the intravenous abuse potential of buprenorphine/naloxone compared with buprenorphine in buprenorphine-maintained injection drug users (IDUs). Methods Intravenous heroin users (n = 12) lived in the hospital for 8,9 weeks and were maintained on each of three different sublingual buprenorphine doses (2 mg, 8 mg, 24 mg). Under each maintenance dose, participants completed laboratory sessions during which the reinforcing and subjective effects of intravenous placebo, naloxone, heroin and low and high doses of buprenorphine and buprenorphine/naloxone were examined. Every participant received each test dose under the three buprenorphine maintenance dose conditions. Results Intravenous buprenorphine/naloxone was self-administered less frequently than buprenorphine or heroin (P < 0.0005). Participants were most likely to self-administer drug intravenously when maintained on the lowest sublingual buprenorphine dose. Subjective ratings of ,drug liking' and ,desire to take the drug again' were lower for buprenorphine/naloxone than for buprenorphine or heroin (P = 0.0001). Participants reported that they would pay significantly less money for buprenorphine/naloxone than for buprenorphine or heroin (P < 0.05). Seven adverse events were reported; most were mild and transient. Conclusions These data suggest that although the buprenorphine/naloxone combination has intravenous abuse potential, that potential is lower than it is for buprenorphine alone, particularly when participants received higher maintenance doses and lower buprenorphine/naloxone challenge doses. Buprenorphine/naloxone may be a reasonable option for managing the risk for buprenorphine misuse during opioid dependence treatment. [source] Salmonella enteritidis temperature-sensitive mutants protect mice against challenge with virulent Salmonella strains of different serotypesFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2000M.Magdalena Gherardi Abstract The protection conferred by temperature-sensitive mutants of Salmonella enteritidis against different wild-type Salmonella serotypes was investigated. Oral immunization with the single temperature-sensitive mutant E/1/3 or with a temperature-sensitive thymine-requiring double mutant (E/1/3T) conferred: (i) significant protection against the homologous wild-type Salmonella strains; (ii) significant cross-protection toward high challenge doses of S. typhimurium. Significant antibody levels against homologous lipopolysaccharide and against homologous and heterologous protein antigens were detected in sera from immunized mice. Moreover, a wide range of protein antigens from different Salmonella O serotypes were recognized by sera from immunized animals. Besides, primed lymphocytes from E/1/3 immunized mice recognized Salmonella antigens from different serotypes. Taken together, these results indicate that temperature-sensitive mutants of S. enteritidis are good candidates for the construction of live vaccines against Salmonella. [source] Characterization of serum and mucosal antibody responses and relative per cent survival in rainbow trout, Oncorhynchus mykiss (Walbaum), following immunization and challenge with Flavobacterium psychrophilumJOURNAL OF FISH DISEASES, Issue 12 2002B R LaFrentz Abstract Serum and mucosal antibody responses of juvenile rainbow trout, Oncorhynchus mykiss, were characterized by enzyme-linked immunosorbent assay (ELISA) following immunization with various preparations of formalin-killed Flavobacterium psychrophilum cells. The protective nature of these preparations was then determined by immunizing rainbow trout fry and challenging with the bacterium. Juvenile rainbow trout immunized intraperitoneally (i.p.) with formalin-killed F. psychrophilum emulsified with Freund's complete adjuvant (FCA), and i.p. with formalin-killed F. psychrophilum either with or without culture supernatant generated significant serum antibody responses by 6 and 9 weeks, respectively. Significant mucosal antibody responses were detected by 9 weeks only in fish immunized i.p. with killed F. psychrophilum/FCA. Following immunization and bacterial challenge of rainbow trout fry, protective immunity was conferred in F. psychrophilum/FCA and saline/FCA groups with relative per cent survival values of up to 83 and 51, respectively. Significant protection was not observed in treatment groups immunized by immersion or i.p. without adjuvant at the challenge doses tested. Results suggest that stimulation of non-specific immune factors enhances the ability of fish to mount a protective immune response, but specific antibody appears necessary to provide near complete protection. In this study, an ELISA was developed to monitor anti- F. psychrophilum antibody production in trout. The relationship of such responses to protective immunity suggests that future vaccination strategies against coldwater disease may require stimulation of both the innate and adaptive arms of the immune response. [source] Effect of different challenge doses after repeated citalopram treatment on extracellular serotonin level in the medial prefrontal cortex: In vivo microdialysis studyPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 5 2008Ihoko Muraki md Aims:, In order to elucidate the relevance between the delayed onset of clinical efficacy of selective serotonin re-uptake inhibitors (SSRI) and extracellular 5-HT levels in the medial prefrontal cortex, the present study compared the ability of low-dose (3 mg/kg) and high-dose (30 mg/kg) citalopram to increase extracellular 5-HT levels in the medial prefrontal cortex following repeated citalopram treatment using in vivo microdialysis. Methods:, An SSRI, citalopram, was given 10 mg/kg, s.c. twice daily for 6 days and once on the seventh day in rats. On the eighth day, rats received a single injection of citalopram (3 or 30 mg/kg s.c.), and extracellular 5-HT levels were assessed in the medial prefrontal cortex of rats using in vivo brain microdialysis. Results:, There was no significant difference in basal extracellular 5-HT levels between the repeated citalopram group and the repeated saline group. The low-challenge dose of citalopram (3 mg/kg) produced significantly greater increases (170,200% at each time point) in the repeated citalopram group than in the repeated saline group (150%). The high-challenge dose of citalopram (30 mg/kg), however, increased extracellular 5-HT levels by 200,250% of basal levels in the repeated citalopram group, which was similar to the increases in the repeated saline group. Conclusions:, Repeated SSRI treatment enhances the effect of low-dose SSRI on extracellular 5-HT levels but not that of high-dose SSRI. [source] | |||||||||||||