Regional brain distribution of [18F]GBR 13119, a dopamine uptake inhibitor, in CD-1 and C57BL/6 mice

We have examined the regional brain distribution of [18F]GBR 13119 (18F: beta +, T1/2 = 110 min), a dopamine uptake inhibitor, in CD-1 and C57BL/6 mice. High levels of binding are observed in the striatum of both species, with striatum/cerebellum ratios of 3-4 at 60 min after injection of the radiotracer. Striatum radioactivity and striatum/cerebellum ratios are more than 50% reduced in C57BL/6 mice treated chronically with the neurotoxin MPTP. We conclude mice are an appropriate model for the in vivo study of the dopamine uptake system, and that [18F]GBR 13119 may be a suitable in vivo marker for degeneration of striatal dopaminergic neurons.     

A GABAergic projection from the pretectum to the dorsal lateral geniculate nucleus in the cat.

To study the projection from the pretectum to the lateral geniculate nucleus, we placed wheat-germ agglutinin conjugated to horseradish peroxidase into the lateral geniculate nuclei of six cats, allowed this marker to be retrogradely transported by afferent axons to their parent somata in the pretectum, and revealed the label in these cells with stabilized tetramethylbenzidine histochemistry. In three cases we made large pressure injections that completely infiltrated the lateral geniculate nucleus and extended into neighboring thalamic nuclei; in the other three we made smaller iontophoretic injections largely confined to the A- and C-laminae of the lateral geniculate nucleus. In both types of injection we found labeled pretectal cells mainly in the nucleus of the optic tract but also found some cells labeled in the olivary pretectal nucleus and the posterior pretectal nucleus. After one of the larger injections we analysed both sides of the pretectum and found that 11% of the labeled cells were located contralaterally and were distributed in the same three nuclei. We analysed only the ipsilateral side in the remaining five cats. In those five experiments we also immunohistochemically stained the pretectal sections with an antibody directed against the neurotransmitter, GABA. Of the retrogradely labeled pretectal cells, 40% were also labeled for GABA, and those were similar in soma size (350 microns 2 in cross-sectional area) to those labeled only with the retrograde marker (331 microns 2). GABA-positive cells not labeled by retrograde transport were smaller (246 microns 2) than either of these other cells populations. These results indicate that at least 40% of the cells involved in the projection from the pretectum to the lateral geniculate nucleus are GABAergic. We suggest that this extrathalamic projection may serve to inhibit thalamic GABAergic cells. This, in turn, would disinhibit geniculate relay cells, thereby facilitating the geniculate relay of retinal information to cortex.     

Distribution of selenium in human milk

The present studies were designed to characterize selenium distribution in human milk. These studies reveal that most selenium in human milk is protein bound. Percentage dialyzable selenium varied proportionally with total selenium content of milk but not with stage of lactation. Neither rate of freezing nor frozen storage of samples for one month influenced distribution profiles. At least nine selenoproteins were detected in dialyzed milk samples following molecular sieve (Sephadex) chromatography. Glutathione peroxidase accounted for approximately 15-30% of selenium found in milk. Approximately half of peroxidase activity in human milk was associated with selenium dependent glutathione peroxidase activity.     

D-chiro-inositol metabolism in diabetes mellitus.

D-chiro-inositol is a rare inositol isomer present in inositol phosphoglycans which are proposed mediators of insulin action. To study D-chiro-inositol metabolism in diabetes mellitus, a sensitive and specific assay was developed using negative-ion chemical ionization gas chromatography/mass spectrometry. Median urinary D-chiro-inositol excretion, which was 2.1 mumol/day in nondiabetics, was substantially increased to 12 mumol/day in non-insulin-dependent diabetes (P < 0.0001) and to 74 mumol/day in insulin-dependent diabetes (P < 0.0001). Urinary D-chiro-inositol was strongly correlated with fasting plasma glucose (r = 0.568, P < 0.0001), glycated hemoglobin (r = 0.529, P < 0.0001), and urinary glucose (r = 0.368, P = 0.01). The renal clearance of D-chiro-inositol was selectively elevated in both non-insulin-dependent and insulin-dependent diabetes when compared with the clearances of L-chiro-inositol or myo-inositol and exceeded the glomerular filtration rate in 71% of the diabetics but in none of the nondiabetics. In poorly controlled diabetic patients insulin treatment reduced urinary D-chiro-inositol losses by 63% and increased plasma levels by 8.8-fold. The metabolism of D-chiro-inositol is abnormal in diabetes and appears to be influenced by short- and long-term metabolic control.