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Biomedical subjects

C Goetz

Publications and source records attributed to C Goetz.

At least 37 records · Page 2Linked to original sources

Development of the immune system in very low birth weight (less than 1500 g) premature infants: concentrations of plasma immunoglobulins and patterns of infections.

Plasma immunoglobulin concentrations of premature infants of birth weight less than 1500 g were measured longitudinally from birth to 10 months chronological age. Infants were divided into two groups based on gestational age (group I: 25-28 wk; group II: 29-32 wk). In the 1st wk of life, plasma IgG levels correlated with gestational age (r = 0.5, p less than 0.001). At 3 months chronological age, the geometric mean plasma IgG levels were 60 mg/dl in group I and 104 mg/dl in group II infants. Most infants remained hypogammaglobulinemic at 6 months with seven of 11 infants in group I and 13 of 21 infants in group II having plasma IgG levels below 200 mg/dl. In the 1st wk of life, plasma IgM concentrations were 7.6 and 9.1 mg/dl in groups I and II, respectively. They rose to 41.8 and 34.7 by 8 to 10 months of life. Plasma IgA concentrations were comparable for groups I and II in the 1st wk of life (1.2 and 0.6 mg/dl, respectively), but at 1 month of age group I infants had a transient increase in IgA which was not seen in the group II infants (4.5 versus 1.9 mg/dl, respectively, p less than 0.02). This transient elevation in IgA did not correlate with type or route of feeding or amounts of transfused blood. Group I and group II infants had comparable rates of infections prior to discharge from the nursery (p = 0.27). After discharge, the 43 preterm infants followed until 10 months chronological age had a significantly higher incidence of infections than 41 term infants (p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

Biochemical evidence for the 5-HT agonist properties of PAT (8-hydroxy-2-(di-n-propylamino)tetralin) in the rat brain.

In vitro investigations revealed that PAT (8-hydroxy-2-(n-dipropylamino)tetralin) interacted with postsynaptic 5-HT receptors in the rat brain: the drug stimulated 5-HT-sensitive adenylate cyclase in homogenates of colliculi from new-born rats (KAapp 8.6 microM) and inhibited the specific binding of [3H]5-HT to 5-HT1 sites. The PAT-induced inhibition of [3H]5-HT binding showed marked regional differences compatible with a preferential interaction of PAT (IC50 2 nM) with the 5-HT1A subclass. As previously seen with 5-HT agonists, the efficacy of PAT for displacing [3H]5-HT bound to hippocampal membranes was markedly increased by Mn2+ (1 mM) and reduced by GTP (0.1 mM). PAT also affected presynaptic 5-HT metabolism since it inhibited competitively (Ki 1.4 microM) [3H]5-HT uptake into cortical synaptosomes and reduced (in the presence of the 5-HT uptake inhibitor fluoxetine) the K+-evoked release of [3H]5-HT previously taken up or newly synthesized from [3H]tryptophan in cortical or striatal slices. This latter effect was prevented by 5-HT antagonists (methiothepin, metergoline) suggesting that it was mediated by the stimulation of presynaptic 5-HT autoreceptors by PAT. Like 5-HT, PAT counteracted the stimulatory effect of K+-induced depolarization on the synthesis of [3H]5-HT from [3H]tryptophan in cortical slices. It is concluded that PAT is a potent 5-HT agonist acting on both post- and presynaptic 5-HT receptors in the rat brain.

8-Hydroxy-2-(di-n-propylamino)tetralin

Biochemical and functional alterations of central GABA receptors during chronic estradiol treatment.

The characteristics of GABA and benzodiazepine receptors were examined in the hippocampus, striatum and cerebral cortex of female rats at various times (up to 9 months) after the subcutaneous implantation of an estradiol pellet (10 mg). A significant decrease in the Bmax of the high-affinity binding of [3H]muscimol to membranes from these 3 regions was detected as soon as one week after the implantation. Although the characteristics of the high-affinity binding of [3H]flunitrazepam remained unaffected during the whole treatment, the stimulatory effect of GABA (and muscimol) on this binding was significantly reduced by estrogenization. The changes in GABA receptor binding appeared functionally relevant since the elevation of striatal acetylcholine levels normally induced by the peripheral administration of muscimol (5 mg/kg) was significantly lower in estradiol-treated than in control female rats. In contrast to that observed in intact female rats, the implantation of estradiol in hypophysectomized animals did not affect the characteristics of [3H]muscimol binding to hippocampal, striatal and cortical membranes. [3H]muscimol binding was also unchanged in female rats implanted with estradiol and treated chronically with bromocriptine for 3 weeks. Since both hypophysectomy and the chronic administration of bromocriptine suppressed the hyperprolactinemia normally induced by estrogenization, the down-regulation of central GABA receptors very likely involved prolactin in intact animals implanted with 17-beta-estradiol.

Acetylcholine

Long-term local and distal increases in tryptophan hydroxylase activity following intracerebral kainic acid injections in the rat.

The administration of kainic acid (1--2 micrograms) into the right striatum of adult rats resulted in a marked local increase in tryptophan hydroxylase activity (+ 54--106%). This change was significant as soon as on the second day after the treatment and persisted for at least 12 days. In addition, long-lasting elevations of tryptophan hydroxylase activity were also observed in the anterior raphe area, septum and ipsilateral hippocampus and cerebral cortex. In contrast, the intrahippocampal injection of kainic acid (1 microgram) induced a long-term increase in tryptophan hydroxylase activity only in the injected structure. In all cases, the changes in tryptophan hydroxylase activity were associated with significant increases in the Vmax of the enzyme with no alteration of its apparent affinities for tryptophan and the pterin cofactor. Studies of the sensitivity of tryptophan hydroxylase from control and from kainic acid-treated rats to in vitro activating conditions (Ca2+-dependent phosphorylation, partial trypsinization, exposure to sodium dodecyl sulfate) suggest that the intrastriatal injection of the neurotoxin induced a long-lasting activation of the enzyme. These findings indicate that intracerebral injections of kainic acid may be a valuable approach to explore further the mechanisms controlling tryptophan hydroxylase activity in vivo.

Animals

Clonazepam and 5-hydroxytryptophan-induced myoclonic stereotypy.

The effect of clonazepam on a behavioral model of increased whole brain serotonin activity was investigated. While clonazepam induces a moderate elevation of whole brain serotonin, the drug fails to potentiate or inhibit 5-hydroxytryptophan-induced stereotypy in young guinea pigs. These results suggest that despite drug induced alterations in serotonin concentration clonazepam does not hava an effect on the physiologic activity of serotonin and may not exert its pharmacologic activity by influencing serotonin within the brain.

5-Hydroxytryptophan

Levodopa-induced myoclonus.

Twelve parkinsonian patients on long-term levodopa therapy developed intermittent, myoclonic body jerks. The movements consisted of single unilateral or bilateral abrupt jerks of the extremities and occurred most frequently during sleep. Although directly related to daily dosage of levodopa, the myoclonus was specifically blocked by the serotonin antagonist, methysergide. Levodopa-induced myoclonus may be related to intermittent increases of activity of serotonin in the brain and results from levodopa-induced dysregulation of serotonin activity.

5-Hydroxytryptophan