Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system (CNS), characterised by focal destruction of myelin. Although it is evident that the immune system contributes to tissue destruction in MS, it is still unclear as to whether this immune response is a cause or a consequence of the disease process. In addition, there is debate over the contribution of axonal damage to clinical progression. We have described a murine model of relapsing-remitting MS (RR-MS), the most common form of the disease, following immunisation with the myelin component, myelin oligodendrocyte glycoprotein (MOG). We showed that a single injection of a MOG peptide (MOG(35-55)) in NOD/Lt mice induces a paralytic relapsing disease with extensive plaque-like demyelination. This model also mimics many of the immunological features associated with RR-MS. To investigate the relationship between clinical episodes, inflammation, and demyelination/remyelination, we analysed lesions during each attack and remission over the course of the disease, using histological, immunocytochemical, and electron microscopy (EM) techniques. We show that morphological features of lesions in our model resemble those observed in MS. Indeed, severe inflammation and demyelination coincide with the peak of clinical episodes while remissions are characterised by quiescent plaques. Furthermore, axonal damage is evident from the earliest stage of the disease and increases in severity with subsequent relapses. These data establish that in the model of MS-like disease, the peak of clinical episodes coincides with severe inflammation and demyelination and that axonal pathology correlates with clinical progression.

For examination of the title parameters, study was made in which forty healthy male subjects (serum cholesterol concentration 170 309 mg/dL) were fed 0, 200, 400, 600, or 800 mg/day of free plant sterol supplemented in mayonnaise for 4 consecutive weeks. Only the 800 mg/day group significantly reduced serum cholesterol by the paired t-test (Exp.1). Thirtytwo healthy males (serum cholesterol, 184 285 mg/dL) were made to consume plant sterol as ester at 0, 800, 1600, or 2400 mg/day. In all cases at more than 800 mg/day reduction in serum cholesterol was noted though without significant difference with paired t-test results (Exp.2). Subsequent to the mayonnaise consumption, normal diets were resumed for a period of 4 weeks. Total cholesterol showed original values at the end of this period. Plant sterol is thus shown to be a dietary component capable of reducing cholesterol by these results. Fifteen healthy subjects (males 10, females 5) were made to consume free plant sterol supplemented in mayonnaise at 2400 mg/day for 4 consecutive weeks. No change in serum vitamin A or vitamin E levels was observed at 2400 mg consumption. At 2400 mg, a significant increase in serum b-sitosterol was noted though it was markedly less than b-sitosterolemia. Clinical trial results, in all cases, were normal (Exp.3). The minimal effective dose of plant sterol on serum cholesterol concentration would thus appear to be 800 mg/day. At 2400 mg/day in mayonnaise, physiological and biochemical safety markers in serum would not undergo abnormal change.

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