Cerebellum plus locus coeruleus in tissue culture. II: Development and metabolism of catecholamines

In contrast to locus coeruleus neurons in vivo, dopamine was the predominant catecholamine synthesized, stored, and released by neonatal mouse locus coeruleus cultures which included target cerebellar tissue, and norepinephrine was present in these cultures only at very low levels. Developmentally, norepinephrine increased slightly in the explants during the first 4 days in vitro and declined thereafter to barely detectable levels, whereas dopamine began to rise after 4 days and reached maximal levels by 7 days. Dopamine beta-hydroxylase was present in these cultures throughout maturation. These results suggest that the high ratio of dopamine to norepinephrine in locus coeruleus cultures cannot be attributed to the absence of appropriate target tissue or to a lack of the enzyme, dopamine beta-hydroxylase.     

Lack of effect of omeprazole treatment on steady-state plasma levels of metoprolol

Summary In a randomised double-blind crossover study, seven healthy males were concomitantly given metoprolol 100 mg o. d. as a controlled release formulation, and omeprazole 40 mg o. d. or placebo, for 8 days. Plasma levels of the R- and S-enantiomers of metoprolol were determined on the 8th day of each treatment. The subjects were also characterised by their metabolic capacity to hydroxylate debrisoquine. Concomitant omeprazole treatment had no significant influence on the steady-state plasma levels of the two enantiomers of metoprolol. All subjects were characterised by extensive debrisoquine hydroxylation, i.e. extensive metoprolol metabolism.As metoprolol is metabolised to a great extent by debrisoquine hydroxylase (IID6), it is concluded that concomitant omeprazole treatment will probably have a negligible influence on the metabolism of the relatively large number of drugs mainly metabolised by this isoenzyme of the cytochrome P450 family.     

A library based literacy program for mothers and their preschool children

The program, “Parents as Teachers” was funded by the Library Services and Construction Act, Title VI, from the U.S. Department of Education. This grant was geared toward promoting the literacy of parents through educating them to teach their children. The target population was mothers and their children ages 0-5 living in the Austin neighborhood, a primarily Black, low income neighborhood on the west side of Chicago. Fifteen mothers and twenty-six children volunteered for the project. Pre and post intervention questionnaires were administered to the parents. Parents stated that they had learned the following from the project: 1] how to play games, read books, and make simple toys for children; 2] how children can learn from everyday things; 3] how to observe what children like rather than give them things preferred by the parent. The parents stated that their children had learned the following through the project: 1] to sing new songs, 2] to pick out favorite books, 3] to make arts and crafts projects, 4] to share with other children, 5] to enjoy listening to stories, 6] to love books.     

Lack of relationship between sodium valproate-induced adverse effects and the plasma concentration of its metabolite 2-propylpenten-4-oic acid

Summary The concentrations of valproic acid (VPA) and of its metabolites 3-oxo-VPA and 4-en-VPA were measured in the plasma of 12 selected epileptic patients 1,2,3, and 4 h after administration of a loading dose of VPA. Four of the patients, all on polytherapy, had had short-term adverse effects during chronic VPA treatment, and in them there has been abnormal NH₃-values after a test doese of VPA. Eight patients (4 on monotherapy and 4 on polytherapy) had been free from adverse effects. No significant difference in the VPA, 3-oxo-VPA and 4-en-VPA concentrations was found between the three groups of patients. Accumulation of 4-en-VPA is not involved in the short-term adverse effects and hyperammonaemia induced by VPA.     

Effect of amiodarone on serum T4 and T3 levels in hyperthyroid patients treated with methimazole

Summary We investigated the course of thyroid hormones levels in the serum of hyperthyroid patients acutely treated with amiodarone. Ten patients were treated either with amiodarone, 3 × 400 mg daily for 3 days in addition to methimazole, 3 × 20 mg daily for 10 days (Group I;n=5) or with a placebo plus methimazole at the same doses (Group II;n=5). Basal T₃, T₄ and rT₃ serum concentrations were: 297 ng/dl, 16.6 µg/dl and 507 pg/dl, respectively in Group I and 377 ng/dl, 17.6 µg/dl and 362 pg/dl in Group II (NS). Compared with basal values, the drop in serum T₃ concentration became significant on Day 1 in Group I, but not until day 5 in Group II. The decrease in serum T₃ concentration was significantly higher in Group I than in Group II from Day 1 to Day 7. In Group I, T₄ concentration was significantly lower on Days 2, 4 and 6; the percentage drop in T₄ calculated from the areas under the curves was higher and the T₃/T₄ ratio lower on Days 3–5, 7 and 9; rT₃ was higher on Days 4 and 5 and its rise was significant on Days 1, 3 and 4. During the follow-up period a transient rise in T₄ and T₃ concentrations was observed in two patients in Group I when the methimazole dosage was tapered or stopped because of agranulocytosis. In conclusion, in our hyperthyroid patients, amiodarone in conjunction with methimazole induced a greater fall in T₃ and T₄ than did methimazole alone.     

Psychological performance in relation to central and peripheral nerve conduction in workers exposed to lead, zinc, and copper

Psychological performance was examined in relation to central and peripheral nerve conduction by means of the Wechsler Adult Intelligence Scale test, short-latency somatosensory-evoked potential (SSEP), and median nerve conduction velocity in 19 male gun-metal foundry workers exposed to lead, zinc, and copper. (Their blood lead concentrations--ie, 16-64 micrograms/dl with a mean of 42--and plasma zinc and copper concentrations were significantly higher than those of control subjects). In these workers, the score of picture completion (psychological performance) was significantly low; indicators of lead absorption, but no indicators of zinc and copper absorption, were significantly correlated with this score. The score of picture completion was significantly correlated with the N11-N13 latency of SSEP (conduction time in the spinobulbar region) in the workers; their N11-N13 latency, together with the N9 and N9-N11 latencies, was significantly prolonged and was significantly correlated with indicators of lead absorption. Furthermore, their maximal motor and sensory conduction velocities of the median nerve were significantly slowed. It is concluded that both psychological performance and central and peripheral nerve conduction may be impaired in lead-exposed workers with BPb's below approximately 60 micrograms/dl.     

The effects of acrivastine (BW825C), diphenhydramine and terfenadine in combination with alcohol on human CNS performance

Summary Two studies were performed to measure the effects of acrivastine (BW825C), an antihistamine, in combination with alcohol on the central nervous system. In one study acrivastine 8 mg, diphenhydramine 50 mg and alcohol 32 ml were administered alone and in combination and compared with placebo. In a second study terfenadine 60 and 120 mg and acrivastine 4 and 8 mg combined with alcohol 32 ml were compared with placebo and alcohol alone. Each study was a double-blind, randomised cross-over design using twelve healthy volunteers. Adaptive tracking, reaction time, body sway, eye movements and subjective effects were measured at intervals after treatments. Acrivastine 8 mg alone did not affect any of these measures in contrast with diphenhydramine. Acrivastine in combination with alcohol caused significantly more impairment of some of the tests than placebo or alcohol alone, but significantly less than diphenhydramine/alcohol, which also affected more tests. In the second study no significant differences were seen between the effects of alcohol alone and combinations of either terfenadine or acrivastine with alcohol.It was concluded that acrivastine 8 mg alone did not impair CNS performance in the tests used. In combination with alcohol significant impairment was seen, but this was less pronounced than after diphenhydramine/alcohol. The second study failed to demonstrate differences between drug/alcohol combinations and alcohol alone confirming that the effect of acrivastine in combination with alcohol is small.     

Visual-auditory interactions in cat superior colliculus: their role in the control of gaze

Superior colliculus cells that respond to a given sensory input (visual or auditory) were influenced by the presence of a stimulus in the other modality. This is a form of sensory-sensory integration which has previously been thought to be involved in initiating the orientation of receptor organs in response to such cues. The present results demonstrate directly that some neurons in cat superior colliculus exhibit premotor discharges which are facilitated when evoked by combinations of visual and auditory stimuli. Other neurons showed sensory interactions which were more difficult to relate directly to orienting behavior; these celpls might have a role in mediating attentional functions.     

A clinically significant interaction between ciprofloxacin and theophylline

Summary We report a case of theophylline toxicity following the co-administration of ciprofloxacin. Total theophylline clearance fell from 2.3 l·h^–1 to 0.8 l·h^–1 when ciprofloxacin was added to the treatment regimen and returned to 2.1 l·h^–1 after ciprofloxacin was discontinued.     

Kinetic and dynamic interactions of oral viqualine and ethanol in man

We have studied the interaction of viqualine, a 5-hydroxytryptamine (5-HT) uptake inhibitor, with ethanol in 16 healthy men aged 20 to 34 years. The subjects were randomly assigned to receive ethanol dosed to maintain blood alcohol concentrations of 17-22 mmol.l-1 (n = 8) or orange juice (n = 8) on each of two test days one week apart and preceded, in random order, by 3 days of viqualine 75 mg bd or placebo. Ethanol had no effect on steady-state viqualine concentrations or the inhibition of 5-HT uptake. Viqualine did not affect acetaldehyde concentrations or cause an aversive alcohol-sensitizing reaction. The deleterious effects of ethanol on word recall, manual tracking, body sway, and self-ratings of intoxication, sedation, and performance were not modified by the presence of viqualine. Within each beverage group performances and self-ratings on viqualine and placebo days were not different. The first dose of viqualine was associated with transient nausea. Viqualine and ethanol do not interact kinetically or dynamically on the variables examined in this study.