At 1, 2, and 4 weeks after unilateral premotor and motor cortex ablation in rats, a significant and lasting decrease in glutamate levels in the ipsilateral versus contralateral striatum was observed. A significant corresponding fall in aspartate was seen only after 1 week. In contrast, there was a large increase in the striatal concentrations of lysine, threonine, alanine, and glutamine 1 week after the cortical ablation. This correlates with the extensive glial proliferation in the deafferented ipsilateral striatum. Four weeks after cortical ablation the GABA concentration was significantly increased. There was no decrease in other putative transmitters (dopamine, serotonin, acetylcholine, glycine and taurine), nor was a glutamate decrease observed in the hippocampus or in the hypothalamus, which do not receive direct premotor and motor cortical inputs. Both biochemical and morphological evidence for a minor contralateral cortico-striatal projection was obtained. Correlating with the fall in glutamate, ultrastructural observations indicated the degeneration of two types of striatal synapses, i.e., those of the axo-spinous type III and of the axo-dendritic type VII. Frontal cortex ablation clearly affects, in opposite directions, the metabolism of various striatal amino acids but not that of acetylcholine and the monoamine transmitters. The results strongly support the view that glutamate is the transmitter of the cortico-striatal fibers.

In relapsing-remitting MS subjects, serum iron concentration correlated significantly with age at diagnosis (r=0.49; p=0.008). In Caucasian female MS subjects, serum iron and ferritin concentrations were significantly lower than in matched controls. In a 6-month pilot study, 12 subjects taking a regimen of nutritional supplements designed to promote myelin regeneration, improved significantly neurologically as measured by the Kurzke EDSS (Total Score means 3.50 to 2.45, 29.9%; p=0.021). These were significantly improved (p=0.002) compared to 6 control group patients taking multivitamins (Kurzke Score increased by 13.9% from 4.83 to 5.50). Both groups had significantly reduced homocysteine concentrations at 6 months, suggesting that methylation is necessary but not sufficient for myelin regeneration.

Thus far, our search for molecular carbonaceous remnants, specifically indicative of biogenic processes, has been epitomized by the isolation and identification of isoprenoid alkanes in a number of ancient sediments of various geologic types ranging from several million to over 2.7 billion years in age.'-3 We have felt that the isoprenoid alkanes could serve as "biological markers" in our quest for evidence of life among geologically well-characterized ancient shales and oils, and more specifically in carbonaceous chondrites.Earlier we reported preliminary studies on the oil shale from the Green River Formation (Eocene age, about 52 X 106 years) at Rifle, Colorado.' 2 These results, which paralleled those of Cummins and Robinson,4 established the biological history of this Cenozoic rock from the very uneven distribution of the n-alkanes and from the presence of large proportions of isoprenoid alkanes [C16-, C18-isoprenoid; C19isoprenoid (pristane); C20-isoprenoid (phytane)].We wish to report now the isolation and identification of the C27-, C28-, and C29steranes and a C3o-pentacyclic triterpane from the branched-cyclic alkane fraction of the Green River Shale. Separation of the branched-cyclic alkane fraction (extraction from shale previously described in detail2) into its individual components was achieved by an initial programed gas-liquid chromatographic run to 3000 (3% SE-30 on Gaschrom Z, 100-120 mesh, 10 ft X 1/4 in. s.s. column, program rate 40 per min) in which peaks were collected and in turn rechromatographed isothermally at temperatures ranging from 2600 to 280°(1% SE-30 on Gaschrom Z, 100-120 mesh, 10 ft X 1/4 in. s.s. column). Mass spectra of these collected samples were determined in a direct inlet system of a modified C.E.C. 21-103C mass spectrometer.' A preliminary mass spectral examination of the fractions collected as indicated in Figure 1 from a programed run revealed the molecular weights which are listed in Table 1 for the major components. From the subsequent isothermal separations, a homologous series of compounds were isolated which display mass spectral fragmentation patterns characteristic of the saturated, tetracyclic sterane carbon skeleton

Isolation of the C(9) and C(10) isoprenoid carboxylic acids, the C(12) to C(18)alpha,omega-dicarboxylic acids, and the 2-methyl 1,n-dicarboxylic acids (n is 13, 15, and 16) from organic extract of the Colorado Green River shale (Eocene) is reported. Separation was achieved by column and gas-liquid chromatographic techniques and structural identification of individual components, by mass spectrometry.