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Biomedical subjects

F Hefti

Publications and source records attributed to F Hefti.

At least 235 records · Page 13Linked to original sources
PubMed1981

[The treatment of Scheuermann's kyphosis with the Milwaukee brace (author's transl)].

The application of the Milwaukee brace during adolescence is indicated not only in scoliosis, but also in severe forms of Scheuermann's kyphosis. In Basel between 1970 and 1979, 55 patients with severe thoracic kyphosis were treated with the Milwaukee brace. 45 of these patients were followed for a longer period of time. The results of the measurements of the kyphotic angles and of the angles of the wedges vertebral bodies are presented in detail. In those children who were followed to adulthood an average curvature correction from 40 degrees to 32 degrees was found. This represents a correction exceeding 50%, if a physiological angle of 25 degrees is presumed. Also, measurements showed erection of the wedged vertebral bodies after completion of growth. Consequently, the use of the Milwaukee brace for rigid thoracic kyphosis of more than 35 degrees in adolescents is advised.

Adolescent↗
PubMed1981

Aromatic L-amino acid decarboxylase in rat corpus striatum: implications for action of L-dopa in parkinsonism.

We studied the distribution of aromatic L-amino acid decarboxylase (AAAD) activity in striatal compartments of rats. After near-total destruction of nigrostriatal dopaminergic neurons, 15 to 20% of the initial enzyme activity remained. Striatal enzyme activity remained unchanged after destruction of serotoninergic terminals by electrolytic raphe lesions. Combined raphe-nigrostriatal lesions or nigrostriatal lesions alone produced similar decreases in striatal decarboxylase. Intrastriatal injection of kainic acid (which selectively destroys striatal interneurons and efferent neurons and also induces marked glial proliferation) reduced activity by 20%. Only 7% of initial striatal activity (perhaps localized in capillaries) remained after combined nigrostriatal-kainic acid lesions. These findings indicate that after degeneration of dopaminergic terminals, striatal interneurons and efferent neurons, but not serotonergic terminals of glia, contain an important fraction of the residual AAAD. This compartment may be the site of enzymatic conversion of exogenous L-dopa to dopamine in the parkinsonian striatum.

Animals↗
PubMed1981

Cardiovascular effects of a novel vasoactive antihypertensive agent, Ro 12-4713.

Ro 12-4713, an oxadiazolopyrimidine derivative, lowered blood pressure of conscious spontaneously hypertensive rats and renal hypertensive dogs in a dose-dependent manner from 10 to 100 mg/kg p.o. The antihypertensive effect was slow in onset, had a long duration of action and was not subject to the development of tachyphylaxis. Ro 12-4713 did not influence blood pressure in conscious normotensive rats, cats and dogs. Several observations suggest that metabolites formed from the inactive parent compound are responsible for the cardiovascular effects. A hemodynamic analysis in anesthetized dogs showed that Ro 12-4713 lowered blood pressure and peripheral vascular resistance. These effects were associated with an increase in cardiac output and flow in various vascular beds as well as with an increase in myocardial contractility. This pattern of hemodynamic activity together with the absence of effects on the autonomic neuroeffector system allow the classification of Ro 12-4713 as a vasoactive antihypertensive agent like e.g. hydralazine or minoxidil. However, in contrast to other vasoactive antihypertensives, Ro 12-4713 virtually did not produce tachycardia or water and sodium retention. Ro 12-4713 may represent a considerable improvement in current vasodilator antihypertensive therapy.

Animals↗
PubMed1981

The site of dopamine formation in rat striatum after L-dopa administration.

Unilateral nigrostriatal lesions produced by injecting 6-hydroxydopamine stereotaxically into both the substantia nigra and the medial forebrain bundle reduced striatal tyrosine hydroxylase activity and dopamine (DA) concentrations by 95% (compared with the intact, contralateral striata) but lowered dopa decarboxylase (DDC) activity by only 80%. L-Dopa administration increased DA concentrations in both lesioned and unlesioned sides; absolute increases were higher in control striata and pretreatment with carbidopa (an inhibitor of peripheral DDC) amplified the increases on both sides. Animals given both of the above lesions plus intrastriatal kainic acid injections exhibited a further reduction in DDC activity, i.e., to only 6% of the activity measured in intact, contralateral striata. Kainic acid lesions alone reduced striatal DDC activity by 20%, without affecting striatal tyrosine hydroxylase activity or DA concentrations, and diminished DA formation from exogenous L-dopa. These observations indicate that DA formation from exogenous L-dopa within the striatum occurs mainly, but not exclusively, within DA terminals. Some DA formation persists after most DA neurons have been destroyed; it may occur within kainic acid-sensitive striatal interneurons or efferent neurons. The DA formed outside DA neurons is apparently able to stimulate postsynaptic DA receptors and to mediate some of the behavioral effects of L-dopa, since L-dopa continued to induce circling behavior in animals with unilateral nigrostriatal lesions, even when these lesions approached totality.

Animals↗
PubMed1980

Decarboxylation of exogenous L-DOPA in rat striatum after lesions of the dopaminergic nigrostriatal neurons: the role of striatal capillaries.

In rats with unilateral nigrostriatal lesions, L-DOPA-induced dopamine increases in ipsilateral striata were further enhanced after inhibition of DOPA decarboxylase in cerebral microvessels by carbidopa. DOPA levels were similar, but dopamine increases in lesioned striata were smaller, after carbidopa and DOPA (100 mg/kg) than after DOPA alone (500 mg/kg). These findings suggest that after degeneration of dopaminergic terminals, striatal decarboxylation of exogenous DOPA occurs partly, but not exclusively, in tbe capillaries.

Animals↗
PubMed1980

Partial lesions of the dopaminergic nigrostriatal system in rat brain: biochemical characterization.

Various doses of 6-hydroxydopamine injected into the rat substantia nigra produced partial, dose-dependent lesions of the dopaminergic nigrostriatal tract. The resulting reduction in striatal dopamine concentrations and tyrosine hydroxylase activities tended to be proportional, allowing these measurements to serve as indices for lesion severity in any particular animal. Lesions destroying two-thirds or more of the nigrostriatal neurons accelerated dopamine's synthesis in, and release from, surviving neurons, as indicated by increased striatal levels of the dopamine metabolites dihydroxyphenylacetic acid and homovanillic acid. Formation of these metabolites was also enhanced in dendrites of dopaminergic neurons in the substantia nigra. Supersensitivity of striatal postsynaptic receptors, as judged by induction of rotational behavior after apomorphine or L-DOPA administration, occurred when 90% or more of the nigrostriatal neurons had been destroyed. In contrast, rotational behavior could be induced by amphetamine in animals with only 50% of these neurons destroyed.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1980

Nonaminergic striatal neurons convert exogenous L-dopa to dopamine in parkinsonism.

In intact striatum, the enzyme dopa decarboxylase is localized predominantly in dopaminergic nerve terminals. In Parkinson disease, loss of dopaminergic neurons is associated with massive depletion of striatal decarboxylase activity. Nevertheless, efficacy of exogenous L-dopa in parkinsonism is generally believed to result from its enzymatic decarboxylation to dopamine in the corpus striatum. It has previously been suggested that, after degeneration of nigrostriatal pathways, decarboxylation of administered L-dopa may occur mainly at such striatal sites as surviving dopaminergic terminals, serotonergic neurons, or capillaries; but currently available data do not favor these hypotheses. Recent experimental studies indicate that a substantial amount of decarboxylase activity is localized in striatal interneurons or efferent neurons that may not normally synthesize monoamines. We propose that after depletion of dopaminergic terminals, these nonaminergic striatal neurons may contain a large fraction of residual dopa decarboxylase activity and may represent an important locus for conversion of administered dopa to functional dopamine in the parkinsonian corpus striatum.

Corpus Striatum↗
PubMed1980

The decarboxylation of DOPA in the parkinsonian brain: in vivo studies on an animal model.

The site of decarboxylation of exogenously administered L-DOPA was studied in corpora striata of rats with near-total unilateral nigrostriatal lesions. After DOPA administration, the absolute increases in dopamine (DA) levels were lower in lesioned than in unlesioned striata, suggesting that, in the intact striatum, a major part of exogenous DOPA is decarboxylated in DA neurons. DOPA can also be decarboxylated outside DA neurons, however, as shown by our finding that relatively higher DOPA decarboxylase than tyrosine hydroxylase activity or DA concentration remains in striata after the nigrostriatal lesions. Also, the percentage increases in DA formation after DOPA administration were much higher in lesioned than in control striata. Rats with both raphé and nigrostriatal lesions failed to exhibit further reductions in striatal DOPA decarboxylase activity or diminished biochemical or behavioral (turning behavior) reactions to DOPA. Inhibition of the DOPA decarboxylase contained in brain capillary endothelial cells did not abolish DA formation in lesioned striata or circling behavior after DOPA administration. These findings all suggest an additional cell type in the striatum as the site of DOPA's decarboxylation in the absence of DA neurons.

Animals↗
PubMed1980

Regional tyrosine levels in rat brain after tyrosine administration.

Endogenous tyrosine concentrations varied two-fold among various rat brain regions, tending to be highest in brain stem structures. Administration of L-tyrosine (100 mg/kg) increased tyrosine concentrations in all brain areas; high relative increases were observed in areas with low initial tyrosine concentrations and vice versa, resulting in a more uniform distribution of tyrosine in the brain. Largest relative increases were observed in cortex and hippocampus. Tyrosine concentrations in all areas reached maximal levels 1 hour after tyrosine was given and declined gradually over the next 3 hours. The results suggest that tyrosine's effects on catecholamine synthesis and release might be amplified in cortex and hippocampus, where highest relative increases in tyrosine concentrations were observed.

Animals↗
PubMed1980

Circling behavior in rats with partial, unilateral nigro-striatal lesions: effect of amphetamine, apomorphine, and DOPA.

Partial, unilateral lesions of the nigro-striatal tract were produced in rats by injecting various quantities of 6-hydroxydopamine into the substantia nigra. The extent of each animal's lesion was estimated by comparing tyrosine hydroxylase activities in its lesioned and control striata. L-DOPA and apomorphine induced contralateral (i.e., away from the lesion) circling behavior only in rats in which more than 90% of the nigro-striatal system had been destroyed. In contrast, d-amphetamine caused turning in the ipsilateral direction when as few as 50% of the nigro-striatal neurons had been destroyed.

Amphetamine↗
PubMed1980

Antihypertensive (2-aminoethyl)thiourea derivatives. 2.

Starting with 2,6-dichlorophenyl isothiocyanate, 1-(2-aminoethyl)-2-cyano-3-(2,6-dichlorophenyl)guanidine (2) was prepared in three steps. In contrast to the corresponding thiourea 1, this compound was essentially inactive as an antihypertensive agent.

Animals↗
PubMed1980

Tyrosine administration increases striatal dopamine release in rats with partial nigrostriatal lesions.

Partial, unilateral nigrostriatal lesions of varying severity were produced in rats by injecting graded doses of 6-hydroxydopamine into the substantia nigra. Formation of the dopamine metabolites dihydroxyphenylacetic acid and homovanillic acid in each surviving nigrostriatal neuron (estimated by the ratios of dihydroxyphenylacetic acid to dopamine and homovanillic acid to dopamine in the striatum) increased significantly when dopamine concentrations in striata containing lesions had been reduced to 25% or less of control values, but remained unchanged in rats with less severe lesions. These findings suggest that, in rats with severe damage of nigrostriatal dopaminergic neurons, surviving neurons increase their firing rates and accelerate dopamine synthesis and release. In rats that had lesions and enhanced striatal dopamine release, but not in rats with lesser lesions (i.e., which reduced ipsilateral dopamine concentrations by less than 75%), administration of tyrosine (250 mg/kg) caused further significant increases in formation of dihydroxyphenylacetic acid and homovanillic acid. These findings provide further evidence that tyrosine availability can enhance dopamine synthesis in and release from nigrostriatal neurons if the firing rates of these neurons are accelerated.

3,4-Dihydroxyphenylacetic Acid↗