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K Stoeckel

Publications and source records attributed to K Stoeckel.

65 records · Page 4Linked to original sources
PubMed1977

Role of gangliosides in the uptake and retrograde axonal transport of cholera and tetanus toxin as compared to nerve growth factor and wheat germ agglutinin.

Previous investigations have shown that tetanus toxin is transported retrogradely in all peripheral neurons whereas the transport of NGF is confined to adrenergic and sensory neurons. Other macromolecules with molecular weights and general physiochemical properties similar to NGF and tetanus toxin (e.g., cytochrome C, insulin, horseradish peroxidase and bovine serum albumin) are not transported to a detectable extent if injected in comparable molar concentrations. For tetanus toxin, which is transported in all peripheral neurons, it has be assumed that it's retrograde transport depends on properties common to all neurons. In view of the relatively high ganglioside content of the neurons and the high affinity of tetanus toxin for the trisialoganglioside GT1, we studied the influence of gangliosides on the retrograde transport of tetanus toxin as compared to NGF. We included into the study cholera toxin which is known to have a high affinity for the monosialoganglioside GM1 and wheat germ agglutinatinin, a lectin with specific affinity for glycoproteins with N-acetyl-glucosamine residues. Both cholera toxin and wheat germ agglutinin were transported efficiently in all peripheral neurons. Preincubation of 125I-cholera toxin with monosialoganglioside GM1 completely blocked its retrograde axonal transport. The transport of NGF and wheat germ agglutinin was affected neither by various purified gangliosides nor by a mixture of bovine brain gangliosides. The transport of tetanus toxin was only reduced by 50% both by the trisialoganglioside GT1 and the bovine ganglioside mixture.

Adrenergic Fibers↗
PubMed1976

Selective uptake and retrograde axonal transport of dopamine-beta-hydroxylase antibodies in peripheral adrenergic neurons.

In the present experiments the uptake and retrograde axonal transport of antibodies to dopamine beta-hydroxylase (DBH) in adrenergic neurons was studied. When partially purified labelled antibodies to DBH were injected unilaterally into the vicinity of the adrenergic nerve terminals in the iris, radioactive substances accumulated preferentially in the superior cervical ganglia of the injected. By SDS (sodium dodecyl sulfate) gel electrophoresis and immunoprecipitation it could be shown that the accumulated radioactivity in the superior cervical ganglion represented antibodies to DBH. This retrograde accumulation was greatly reduced by colchicine, axotomy or destruction of the adrenergic nerve terminals by 6-hydroxydopamine. The rate of retrograde transport was the same as that of nerve growth factor (NGF) and tetanus toxin in sympathetic neurons. The retrograde transport of antibodies was confined to sympathetic neurons and could not be detect in either sensory or motor neurons.

Animals↗
PubMed1976

The significance of retrograde axonal transport for the accumulation of systemically administered nerve growth factor (NGF) in the rat superior cervical ganglion.

The present study has shown that after intravenous injection of [125I]NGF the time-course of appearance of radioactivity in all organs studied with the exception of sympathetic and sensory ganglia, roughly paralleled that of the blood. The highest levels were reached immediately after injection, after which the radioactivity decayed rapidly within the firsh hour. By contrast, in the superior cervical ganglion there was a small but significant increase within the first hour. After this the radioactivity remained constant for about 4 h and then increased dramatically (7-fold) when the radioactivity in other tissues had declined to very low levels. Measuring the proportion of radioactivity in the plasma which represents immunologically active NGF, we found that within 30 min after injection all the radioactivity represented unchanged [125I]NGF. After this time the proportion of immunologically active NGF decreased gradually and reached a final level of about 10-15%. Evidence that the radioactivity accumulated in the superior cervical ganglion by retrograde axonal transport represents unchanged [125I]NGF was provided by gel electrophoresis. The results are interpreted as follows: the initial small increase in the sympathetic ganglia may result either from [125I]NGF taken up by short collateral fibres within the ganglion or from a direct accumulation of blood-borne [125I]NGF by the cell bodies of the adrenergic neurones. The dramatic increase occurring after 4 h is caused by the moiety of [125I]NGF reaching the cell body by retrograde axonal transport. This interpretation is supported by autoradiographic studies which showed that 1 h after [125I]NGF injection there was only very sparse labelling of the ganglion, whereas 24 h later virtually all the cell bodies were heavily labelled. Moreover, it could be shown that the lag period between intravenous injection and subsequent accumulation of [125I]NGF in the adrenergic cell bodies was considerably shorter after transection of the postganglionic fibres distal to the cell body [the transected fibres were allowed to regenerate for 7 days] resulting in a reduction of the distance between the site of uptake and accumulation.

Animals↗
PubMed1975

Specificity of retrograde transport of nerve growth factor (NGF) in sensory neurons: a biochemical and morphological study.

In previous studies it has been shown that nerve growth factor (NGF) is taken up with a high selectivity by adrenergic nerve terminals and is transported retrogradely to the perikaryon11,22. It was the aim of the present experiments to investigate whether the sensory neurons exhibit the same high degree of selectivity for retrograde transport throughout the whole life cycle, although it is known that their dramatic response to NGF is confined to a short period of ontogenetic development. Unilateral injection of [125I]NGF into the forepaw of adult rats was followed by a preferential accumulation of radioactivity in the sensory ganglia (C6-C7) of the injected side. However, this preferential accumulation was not detectable earlier than 6 h after injection and reached a maximum (ratio between injected and non-injected side, 5:1) after 11-16 h. Transection of the plexus brachialis abolished and local administration of colchicine prior to that of [125I]NGF greatly reduced the preferential accumulation of radioactivity in the ganglia of the injected side. The rate of retrograde transport of NGF in sensory neurons was calculated to be 13 mm/h which is about 5 times faster than that in adrenergic neurons. The selectivity of this retrograde transport was demonstrated by the fact that injection of 125I-labeled bovine serum albumin and cytochrome c did not result in a preferential accumulation of radioactivity in the sensory ganglia of the injected side. Light microscopic autoradiography revealed heavily labeled cells in the sensory ganglia (C6-C7) of the injected side after administration of [125I]NGF into the forepaw. Only cells belonging to the large cell type were labeled. Prolonged (7 mug/g/day over 5 days) injection of NGF into the forepaw of 10-day-old rats did not result in a hypertropic response of the sensory neurons as far as can be judged from morphometric studies at the light microscopic level.

Age Factors↗
PubMed1975

Biological importance of retrograde axonal transport of nerve growth factor in adrenergic neurons.

Previous studies have shown that nerve growth factor (NGF) produces a selective induction of tyrosine hydroxylase (TH) in peripheral adrenergic neurons and that NGF is transported retrogradely with a high selectivity from the adrenergic nerve terminals to the perikaryon. In order to investigate the biological importance of retrograde NGF transport, the following experiments have been performed; (a) effect of NGF on TH activity in superior cervical ganglia (SCG) after unilateral injection into the anterior eye chamber and the submaxillary gland; and (b) effect of systemic injection of NGF on TH activity in SCG after blockage of retrograde axonal transport by axotomy. After unilateral injection of NGF into the anterior eye chamber and submaxillary gland of both 8-10-day-old rats and adult mice, the increase in TH activity in the SCG was considerably larger on the injected than on the non-injected side although the adrenergic neurons supplying the two organs do not account for more than 25% of the total number of adrenergic neurons in the SCG. A direct diffusion mechanism could be excluded by the fact that unilateral local injection of [125 I] produced no significant side difference in the accumulation of radioactivity in the SCG 2 after injection whereas after 14 h there was a several-fold difference between the injected and non-injected side. Moreover, the nodose ganglia which are located very close to the SCG exhibited no statistically significant difference in the accumulation of radioactivity at any time. Forty-eight hours after subcutaneous injections of 10 mg/kg of NGF the increase in TH activity of the SCG amounted to 154% on the intact side and to 92% on the axotomized side. However, these experiments do not permit decisions about the extent the axotomy, as such, impaired the response to NGF. It is concluded that the biological effect of NGF results to a considerable extent, from the moiety which reaches the cell body by retrograde transport from the nerve terminals.

Animals↗
PubMedDate not supplied

New analogs of trimethoprim.

Possible goals and recent developments in the field of antimicrobial 2,4-diamino-5-benzylpyrimidines are discussed. Three analogs of trimethoprim--all bearing different substituents at position 4 of the benzyl moiety and one also having the methoxy groups replaced by ethoxy substituents--are characterized in some detail. These analogs exhibit physicochemical properties different from those of trimethoprim and are potent inhibitors of several dihydrofolate reductases. Because they differ from trimethoprim in lipophilicity, their in vitro activity, spectrum of activity, and pharmacokinetic properties also differ from those of trimethoprim. These differences are judged to be the reason for enhanced in vivo efficacy against several experimental infections. Distinct pharmacokinetic differences observed in dogs include a longer elimination half-life and a larger volume of distribution. These favorable properties indicate the potential value of further studies in humans.

Animals↗
PubMedDate not supplied

Prospective comparison of ceftriaxone and cefotaxime for the short-term treatment of bacterial meningitis in children.

The effectiveness and safety of ceftriaxone and cefotaxime in the short-term treatment of primary bacterial meningitis were compared using a prospective, randomized, multicenter study design. Children between the ages of 6 weeks and 16 years received either ceftriaxone as a single dose (100 mg/kg on the first day followed by 75 mg/kg/day) or cefotaxime as four divided doses (200 mg/kg/day) for 4-7 days. A total of 82 patients (44 ceftriaxone, 38 cefotaxime) with documented bacteria in the CSF were studied. In patients receiving ceftriaxone, full recovery occurred in 79.5% while a further 13.7% recovered with neurologic sequelae. Full recovery was observed in 71.1% of children treated with cefotaxime with sequelae in a further 23.6% (no statistically significant differences between drugs). The time to clinical improvement and resolution of fever (3-4 days) was also similar for both drugs. All but 1 of the 82 patients studied had negative CSF cultures within 24 h of the beginning of therapy consistent with the excellent penetration into the CSF (trough concentrations of 2.7 mg/l for both drugs at the end of therapy). No differences were observed in the incidence of clinically significant adverse events. Ceftriaxone and cefotaxime are both effective in the treatment of bacterial meningitis. Ceftriaxone offers an advantage in case of administration since it is administered as a single daily dose.

Adolescent↗
PubMedDate not supplied

Age-associated changes in ceftriaxone pharmacokinetics.

Ceftriaxone pharmacokinetic parameters were compiled from recent publications. The subjects (27 female, 93 male) were from 1 day to 92 years old and appeared to have normal renal and hepatic function. In 1- to 8-day-old neonates, the half-life averaged 19 hours; it declined to 6.3 hours in 1- to 6-year-old subjects and then increased gradually throughout the remainder of the life-span to 14 hours in 75- to 92-year-old subjects. The age-associated changes in half-life appeared to result from changes in systemic clearance. The fraction of the dose eliminated renally averaged 70% in neonates and declined throughout childhood to 40 to 60% in adults, in whom it was age invariant. No clinically significant differences between males and females were detected in ceftriaxone kinetic parameter values. Plasma protein binding of ceftriaxone (100 mg/L) was about 70% in neonates and it increased throughout childhood to the adult value of 90 to 95%. To achieve a given free concentration of ceftriaxone, the same dosage per unit surface area can be used for children and adults, provided glomerular filtration and biliary secretion function are normal for age. Dosage should be reduced by as much as a factor of 5 in neonates less than 1 week of age and perhaps by a factor of 2 in the very old.

Adolescent↗