Nuclear Medicine Technology and other Health Applications
Project Title:
16,
Treatment and Biochemical Dissection of Parkinsonism and
Allied Conditions
Technical Progress in FY 1973:
RX-01-03-(a)
(Cont'd.)
These studies (and others) were facilitated by the development of an
automated ergometer,
for the fast,
simple,
and quantitative assessment of
changes of the neurological state in parkinsonism,
The changes in output
of work correlated with the neurological changes determined with a con-
ventional scoring system.
Studies on cerebrospinal fluid
(CSF)
showed Levodopa and dopamine to
be present only after levodopa administration and not in control patients;
however,
effects,
their levels did not correlate with dose, improvement or sideWhen L-dopa was given with pyridoxine, the level of levodopa
in the CSF dropped and correlated with a loss of therapeutic efficacy.
However, a more convenient biochemical marker for the effect of pyridoxine
is the determination of urinary dopamine.
Thus, the usefulness of CSF
analyses in following the treatment of parkinsonism is questioned. Animal
experiments are proposed to develop methods applicable to brain biopsies.
In order to maximize the chemical information one can obtain from these
biopsies a method was developed to analyze biopsy samples of brain for
manganese and catecholamines,
This micro-method combines nondestructive
Neutron activation analysis for manganese with spectrofluoremetric determina-
tion of dopa and dopamine in the same sample.
Reaction of cats given 200
and 400 mg/kg (i.p.) of saline or levodopa were scored.
The animals were
then anesthetized for sampling the caudate, the hypothalamus, the corpus
callosum, the frontal white and frontal gray cortex.
Administration of
levodopa was found to increase the concentration of dopa and dopamine in
all areas studied.
In the caudate area the level of dopamine showed a high
correlation with behavioral scores.
Ranking of control animals according
to dopamine concentration in the caudate had a coefficient of 0.8 with
their ranking by manganese concentration in this nucleus.
Manganese levels
in the hypothalamus appeared to correlate with those of dopamine,
Upon
completion of this phase of the study regional brain samples from living
cats will be obtained stereotactically in preparation for studies in
appropriate human subjects,
In other studies on interactions between levodopa and manganese, young
mice (three weeks of age) showed both higher responses to levodopa and
faster turnover of manganese than adult animals, implying correlations
between the two.
Data obtained on newborn mice, their mothers, and mice of
variowg ages, include:
1) concentration of Mn in embryonic liver is about 1/6
that of the adult and remains at that level until the 12th postpartum
day; BFat day 18 liver Mn peaks to 11.8 + 2.5 ug/g dry weight (adult
3.0 pg/g) in offspring from mothers fed purina chow, in contrast to off-
spring from mothers fed milk; 3) the peak persisted between days 17 and
19, followed by a slow decline to adult levels at about 5 weeks; 4) Mn-54
was not eliminated from the whole body between birth and the l8thday of life,
5)
one week old mice injected with radiomanganese incorporated 0.3% of the
(See Continuation Sheet)
bi 19198
RX-40