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  • 1
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: An immunization protocol that induces antibodies (Abs) directed to cryptic epitopes of a protein antigen (Ag) reduces the efficacy of vaccines that ideally should induce Abs against native epitopes. We have shown earlier that viral infections concomitant with immunization against a protein tend to shift the Ab specificity toward cryptic epitopes and tend to induce the production of autoantibodies (autoAbs). Here, we show the effects of three adjuvants on the Ab specificity in the absence or presence of a viral infection (lactate dehydrogenase-elevating virus or LDV), with human growth hormone (hGH) being, as before, the protein Ag.Pathogen-free CBA/Ht and BALB/c mice were immunized with hGH in the presence of complete Freund's adjuvant (CFA), monophosphoryl lipid A (MPL) or alum, with the animals being either infected with LDV or not infected with LDV. Conventional and competition enzyme-linked immunosorbent assays (ELISAs) indicated that in noninfected mice, CFA induced higher titres of anti-hGH Ab than did MPL or alum, with the Ab being almost totally directed to cryptic hGH epitopes. Strikingly, CFA plus LDV infection in CBA/Ht mice shifted the specificity of the anti-hGH Ab toward native epitopes, whereas the virus decreased the Ab titre when MPL or alum was used. Our Western blot results showed that 70% of mice immunized with hGH in the presence of any adjuvant produced autoAbs against a variety of tissue Ags. The amount of autoAb and the concentration of Ab to hGH cryptic epitopes did correlate, suggesting a relationship between both kinds of Ab. Significant differences were observed in the various effects of adjuvants and the viral infection between the two mouse strains used in this work.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Chromatography A 46 (1970), S. 125-129 
    ISSN: 0021-9673
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Applied Animal Behaviour Science 42 (1994), S. 145-152 
    ISSN: 0168-1591
    Keywords: Goat ; Labelling ; Maternal behaviour
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 85 (2003), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Oxidative damage is the major responsible for mitochondrial dysfunction during aging and many neurodegenerative diseases with respiratory chain Complex I mostly affected. A down-regulation of the mitochondrial respiratory chain Complex-I subunits ND1 (mitochondrial encoded) in rat total cerebral cortex RNA and 39 kDa (nuclear encoded) in frontal cortex protein extracts was observed at 6, 12 and 28 months of age. However the 39 kDa subunit showed an age-related up-regulation in the parietal cortex and no changes in the cerebellum protein extracts. In frontal and parietal cortex protein extracts a significant reduction of subunit α (nuclear encoded) of FoF1-ATP synthase, with no changes in the cerebellum, were also observed. A similar impairment was found also for mitochondrial adenine nucleotide translocator ANT-1 in total rat cerebral cortex RNA. Any change of subunit synthesis might lead to neuronal dysfunction and increase of ROS.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 347 (1993), S. 371-378 
    ISSN: 1432-1912
    Keywords: Human amnion FL cells ; Noradrenaline ; Uptake2 ; O-methylation ; Papaverine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The uptake and metabolism of 3H-noradrenaline has been examined in the FL cell-line derived originally from human amnion. Cell cultures metabolised 3H-noradrenaline (1.0 μmol/l) to 3H-normetanephrine and, to a lesser extent, to metabolites (not distinguished) of the O-methylated deaminated fraction; primary deaminated metabolites were not detected. 3(H-normetanephrine formation a) was not saturable in the noradrenaline concentration range 0.2–150 μmol/l, b was decreased to 20%–30% of control levels by uptake2 inhibitors (O-methylisoprenaline, 20 and 100 μmol/l; cimetidine, 10 μmol/l; hydrocortisone, 200 μmol/l) and c, was almost insensitive to uptake1 inhibitors (cocaine, 30 μmol/l; desipramine, 3 μmol/l). Uptake of noradrenaline was manifested after 30 minutes as a 6-fold increase in the cell content of the amine following inhibition of catechol-O-methyl transferase, either alone or in conjunction with inhibition of monoamine oxidase. Uptake was decreased maximally to 40% of control levels by O-methylisoprenaline. IC50 values for inhibition of the O-methylisoprenaline-sensitive component of uptake were (in μmol/l): corticosterone (0.3), papaverine (1.1), O-methylisoprenaline (3.0), cimetidine (6.0), (−)noradrenaline (460), and tetraethylammonium (2230). Except for the last agent, for which a comparative value is not available, the IC50's are in good agreement with those for inhibition of uptake2 in the Caki-1 cell-line reported by other investigators. The component of uptake resistant to O-methylisoprenaline was depressed by papaverine (a 50% decrease at 50 μmol/l), but was not affected by the other uptake2 inhibitors or by cocaine (30 μmol/l). It is concluded that the FL cell possesses an extraneuronal metabolising system very similar to the system in tissues such as heart and smooth muscle where transport of noradrenaline into the cell by uptake2 is followed by rapid O-methylation via catechol-O-methyl transferase. The only difference appears to be the absence of saturation of 3H-normetanephrine formation in the FL cell at low micromolar concentrations of 3H-noradrenaline. The presence of a second uptake process is suggested by the inhibitory effect of papaverine on uptake resistant to O-methylisoprenaline; lack of effect of cocaine implies that this second process is not uptake,.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1912
    Keywords: Key words: Human dental pulp – Rabbit dental pulp – Noradrenaline metabolism – 6-Hydroxydopamine – Uptake1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. The study was undertaken to determine the relative roles of neuronal and extraneuronal uptake1 in the metabolism of 3H-noradrenaline in human dental pulp. Rabbit dental pulp was used as a reference since it was already known that normetanephrine (NMN) formation in this tissue utilised extraneuronal uptake1. Slices of pulp were preincubated in the absence and presence of 6-hydroxydopamine (1.6 mmol/l, for 10 or 20 min at pH 4.5) and subsequently incubated with 3H-noradrenaline (0.18 μmol/l for 30 min at pH 7.4).   The principal metabolites formed were normetanephrine in rabbit pulp and deaminated catechols (dihydroxymandelic acid and dihydroxyphenylglycol) in human pulp. In both tissues 6-hydroxydopamine strongly inhibited formation of the deaminated catechols, but was without effect on normetanephrine formation.   It is concluded that: ii)  in vitro 6-hydroxydopamine does not influence the metabolic process which is dependent on extraneuronal uptake1, namely normetanephrine formation in rabbit dental pulp, and ii) the deaminated catechols are largely neuronal in origin in human pulp.   Attention is drawn to an unusual feature of the neuronal metabolism in human pulp, namely the appearance of dihydroxymandelic acid as the principal metabolite.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1912
    Keywords: Human dental pulp ; Rabbit dental pulp ; Noradrenaline metabolism ; 6-Hydroxydopamine ; Uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The study was undertaken to determine the relative roles of neuronal and extraneuronal uptake1 in the metabolism of 3H-noradrenaline in human dental pulp. Rabbit dental pulp was used as a reference since it was already known that normetanephrine (NMN) formation in this tissue utilised extraneuronal uptake,. Slices of pulp were preincubated in the absence and presence of 6-hydroxydopamine (1.6 mmol/l, for 10 or 20 min at pH 4.5) and subsequently incubated with 3H-noradrenaline (0.18 μmol/l for 30 min at pH 7.4). The principal metabolites formed were normetanephrine in rabbit pulp and deaminated catechols (dihydroxymandelic acid and dihydroxyphenylglycol) in human pulp. In both tissues 6-hydroxydopamine strongly inhibited formation of the deaminated catechols, but was without effect on normetanephrine formation. It is concluded that: i) in vitro 6-hydroxydopamine does not influence the metabolic process which is dependent on extraneuronal uptake1, namely normetanephrine formation in rabbit dental pulp, and in human pulp. Attention is drawn to an unusual feature of the neuronal metabolism in human pulp, namely the appearance of dihydroxymandelic acid as the principal metabolite.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1912
    Keywords: Rabbit dental pulp ; Ear artery ; Noradrenaline uptake ; Metabolism ; Cocaine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Incisor pulp from the rabbit metabolises exogenous noradrenaline in concentrations between 0.12 and 1.2 μmol/l mainly to NMN. Effects of chronic sympathetic denervation indicated that in incisor pulp the NMN is extraneuronal in origin, and that DOPEG and DOMA formation, as well as a major part of the noradrenaline which accumulates in the tissue, are associated with the sympathetic nerves. NMN formation was unaffected by hydrocortisone 210 μmol/l, but was strongly inhibited by cocaine 30 μmol/l. These effects contrasted with those in the rabbit ear artery, where NMN formation was increased by cocaine 30 μmol/l and decreased by hydrocortisone 210 μmol/l. In COMT-inhibited denervated pulp, cocaine inhibited the accumulation of noradrenaline. Monoamine fluorescence histochemistry of pulp exposed to noradrenaline 50 μmol/l indicated that cocaine-sensitive uptake occurred in fibroblasts. It is concluded that O-methylation of noradrenaline in dental pulp involves prior uptake of the amine by a process resembling uptake, but which is distinguished from uptake1 by its extraneuronal location.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 346 (1992), S. 166-172 
    ISSN: 1432-1912
    Keywords: Dental pulp ; Noradrenaline ; Extraneuronal uptake1 ; O-methylation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The extraneuronal removal and disposition of noradrenaline in rabbit dental pulp was examined in view of earlier evidence that the tissue possessed an extra-neuronal uptake process resembling neuronal uptake1. Pulp, which had been depleted of sympathetic nerves by homolateral superior cervical ganglionectomy, was incubated in vitro with 3H-noradrenaline in low concentrations (0.025 or 0.18 μmol/l). When the metabolising enzymes (monoamine oxidase, catechol-O-methyl transferase) were active, 3H retention by the denervated pulp, as indicated by the 3H content after the tissue had been washed for 30 min following incubation with 3H-noradrenaline, was less than 30% of that of the innervated pulp. When the enzymes were inhibited, retention rose to approximately 30% of that of the innervated pulp. Analysis of the time course of the 3H efflux indicated that the 3H-noradrenaline in the denervated pulp had accumulated in a single compartment characterised by a t1/2 for efflux of several hours. Accumulation did not occur under Na+-free conditions, and was inhibited by desipramine (IC50 〈 0.03 μmol/l) and by substrates of neuronal uptake1. Mean IC50, values of the latter were very similar to those for inhibition of neuronal uptake1 and comprised (in μmol/l): (+)amphetamine (0.29), dopamine (0.31), tyramine (0.39), (−)noradrenaline (0.70), (−)adrenaline (1.50), 5-hydroxytryptamine (20) and bretylium (35). Uptake2 inhibitors were less active (O-methyl isoprenaline, IC50 = 60 μmol/l) than uptake1 inhibitors, or were without inhibitory effects at the concentrations tested (hydrocortisone, 210 μmol/l; 2-methoxy oestrone, 10 μmol/l). The effects of Na+ omission, of (+)amphetamine, and of O-methylisoprenaline on 3H-normetanephrine formation (measured in the absence of catechol-O-methyl transferase inhibition) matched their effects on 3H-noradrenaline accumulation. The results provide strong support for the presence in rabbit dental pulp of extraneuronal uptake1 which is linked with catechol-O-methyl transferase in the removal of noradrenaline.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 44 (1993), S. 477-480 
    ISSN: 1432-1041
    Keywords: Ibopamine ; thymoxamine ; mydriasis ; antagonism ; gonism ; adverse events
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of thymoxamine 0.5% solution and of a placebo solution (mannitol) on the mydriasis induced by ibopamine 1% solution were evaluated in 8 healthy volunteers and 12 patients with eye diseases. One drop of ibopamine was instilled into each eye and 30 min later 1 drop of thymoxamine was instilled into one eye and 1 drop of placebo into the contralateral eye. Pupillary diameter was measured before and 30 min after the instillation of ibopamine, immediately before the treatment with thymoxamine and placebo and 30, 60 and 90 min after the instillation of thymoxamine or of placebo. Within 30 min of treatment, ibopamine had produced a statistically and clinically significant mydriatic effect. In eyes treated with thymoxamine, prompt reversal of mydriasis was observed, the baseline diameter being observed within 60 min. No difference in the time-course of the mydriatic effect was detected between healthy subjects and patients. The pupillary response to thymoxamine was not influenced by the colour of the iris. The tolerability of ibopamine and of thymoxamine was good. No local or systemic adverse events were seen or reported.
    Type of Medium: Electronic Resource
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