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  • Opioids  (2)
  • AIDS-related Kaposi's sarcoma  (1)
  • Chimeric proteins  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 126 (1996), S. 110-114 
    ISSN: 1432-2072
    Keywords: Motivation ; Naloxone ; Opioids ; Sucrose ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The opioid system plays an important role in feeding. In general, opioid agonists typically increase feeding and opioid antagonists decrease feeding in nonfood restricted animals. In food restricted animals the effects of these drugs are substantially reduced. Opioid antagonists have shown a marked effectiveness at reducing consumption of sweet foods. Explanations for this robust effect have typically focused on drug induced changes in taste, taste perception, or palatability. The current study relates the effects of the opioid antagonist naloxone on motivation to obtain different sucrose concentrations to the drug's effects on unrestricted sucrose solution consumption. Changes in motivation to respond were assessed under a progressive ratio reinforcement schedule (PR) which required increased response cost for each successive unit of sucrose solution. Motivation, as measured by the PR, increased as sucrose concentration increased and naloxone produced a dose-dependent decrease in motivation to respond for a given sucrose concentration. Thus, the effectiveness of naloxone was indirectly related to strength of the sucrose concentration. Under unrestricted access to sucrose solutions, naloxone reduced consumption greatest under the higher concentrations. The data suggest at least part of naloxone's effects on sweet tasting food may be mediated through endogenous opioid reward systems that are reflected in measures of motivation.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Key words Discrimination ; Naloxone ; Opioids ; Taste ; Sucrose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The suppression of food intake observed following naloxone administration has often been ascribed to palatability or taste. Unfortunately, many confounds become apparent when attempts are made to isolate such factors in the investigation of ingestive behaviors. In the present study, rats (two groups) were trained to discriminate either a 10% or 5% sucrose solution from water (0.1 ml). These mildly food deprived subjects (95% of free-feeding weight) were trained to press the appropriate lever in a two-lever operant chamber following sampling of sucrose or water; successful responding was reinforced by delivery of a 45 mg grain food pellet. Following random exposure to reduced sucrose concentrations tested under extinction, a sucrose concentration gradient (1.0, 0.5, 0.1, 0.05, 0.01 and 0.005% sucrose solution) was established for both training groups under IP saline administration. Data collected under IP saline were then compared to those collected following random IP naloxone administration (3.0, 1.0, 0.3 and 0.1 mg/kg). No significant differences were observed between the sucrose concentration gradients obtained under saline and those obtained under naloxone, suggesting that the anorectic effect of naloxone is not primarily determined by discrimination of sweet taste.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1569-8041
    Keywords: AIDS-related Kaposi's sarcoma ; interleukin-4
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To define the safety and toxicity of interleukin-4 (IL-4)when administered subcutaneously in patients with AIDS-related Kaposi'ssarcoma (AIDS-KS); to evaluate the effect of IL-4 on immunologic and virologicparameters; and to preliminarily assess the response rate of IL-4 in AIDS-KS. Patients andmethods: Eighteen patients with mucocutaneous, non-visceral AIDS-KS weretreated with IL-4 at a dose of 1 mcg/kg subcutaneously, daily untilunacceptable toxicity or for a maximum period of six months. Twelve(66%) patients had extensive mucocutaneous disease with over 25lesions. Ten patients had received prior systemic chemotherapy. Seventeen hadCD4+ lymphocyte counts less than 200/mm3. Results: The most common adverse effects included headache in78%, fever in 56%, chills in 44%, and edema in44%. Hematologic toxicities consisted of grade 4 neutropenia (less than500/mm3) in 33%, mild anemia in 22%. Transientelevation of liver enzymes was noted in 17%. A transient elevation inCD4+ lymphocyte counts occurred during the first two weeks of therapy. Fourof eleven patients tested showed marked decline in plasma HIV RNA after fourweeks. Partial remission was observed in one patient, lasting six months.Three other patients (17%) had stable disease: 7 weeks in one patient,and 10 weeks in each of the two other patients. Conclusion: Grade 4 neutropenia (absolute neutrophil count〈500/mm3) was the most common hematologic adverse effectwith IL-4 in patients with AIDS-KS. In contrast to in vitro findings,there was a decrease in plasma HIV RNA after four weeks of IL-4 therapy in themajority of patients tested. IL-4 produced minimal anti-tumor effects inAIDS-KS with one partial remission in a patient with CD4 lymphocyte countsover 200/mm3. Further studies of IL-4 in AIDS-KS may beconsidered in patients with better immune status.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1617-4623
    Keywords: Escherichia coli ; Salmonella typhimurium ; SOS mutagenesis ; Chimeric proteins ; UmuC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract UnlikeEscherichia coli, the closely related bacteriumSalmonella typhimurium is relatively unresponsive to the mutagenic effects of DNA-damaging agents. Previous experiments have suggested that these phenotypic differences might result from reduced activity of theS. typhimurium UmuC protein. To investigate this possibility, we have taken advantage of the high degree of homology between the UmuC proteins ofE. coli andS. typhimurium and have constructed a series of plasmid-encoded chimeric proteins. The possibility that the phenotypic differences might be due to differential expression of the respective UmuC proteins was eliminated by constructing chimeric proteins that retained the first 25 N-terminal amino acids of either of the UmuC proteins (and presumably the same translational signals), but substituting the remaining 397 C-terminal amino acids with the corresponding segments from the reciprocal operon. Constructs expressing mostlyE. coli UmuC were moderately proficient for mutagenesis whereas those expressing mostlyS. typhimurium UmuC exhibited much lower frequencies of mutation, indicating that the activity of the UmuC protein ofS. typhimurium is indeed curtailed. The regions responsible for this phenotype were more precisely localized by introducing smaller segments of theS. typhimurium UmuC protein into the UmuC protein ofE. coli. While some regions could be interchanged with few or no phenotypic effects, substitution of residues 212–395 and 396–422 ofE. coli UmuC with those fromS. typhimurium resulted in reduced mutability, while substitution of residues 26–59 caused a dramatic loss of activity. We suggest, therefore, that the primary cause for the poor mutability ofS. typhimurium can be attributed to mutations located within residues 26–59 of theS. typhimurium UmuC protein.
    Type of Medium: Electronic Resource
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