Inhibition of experimental autoimmune neuritis by the immunomodulator linomide.

Experimental autoimmune neuritis (EAN) is an animal model that shares clinical, pathological and electrophysiological features with the human disease Guillain-Barre syndrome. The synthetic immunomodulatory substance linomide has been successfully used to prevent the development of several experimental autoimmune models in laboratory animals and has been proved to be beneficial in modulating the course of multiple sclerosis in humans. In the present study we demonstrate that oral administration of linomide prevents the development of clinical and histopathological signs of EAN in Lewis rats, inoculated with the P2 (60-70) synthetic peptide. The immunomodulatory effect of linomide on this experimental model of disease was associated with marked apoptosis of lymphocytes in thymus and spleen early after starting the treatment. Furthermore, a downregulation of the endothelial expression of the adhesion molecules ICAM-1 at the target site and LFA-1 on lymphocytes could also contribute to the absence of inflammatory cells in the neuraxis.

Linomide activates the adrenocortical axis in the rat: inhibition of experimental autoimmune encephalomyelitis by linomide is not related to the increase of corticosterone.

Linomide is a synthetic compound that affects various immunological functions and inhibits experimental autoimmune encephalomyelitis (EAE). In the present study we evaluated the effect of linomide on the HPA axis functions under basal and stress-induced conditions and examined whether the effect of linomide on the HPA axis is involved in linomide-induced amelioration of EAE in rats. Linomide caused a significant increase of serum ACTH and corticosterone (CS). The adrenocortical response to various stress modalities as well as the negative feedback exerted by glucocorticoids was not affected. The marked reduction of thymus weight following linomide treatment was abrogated in adrenalectomized rats. The induction of EAE in adrenalectomized rats was completely inhibited by linomide treatment. These results suggest that the increased CS levels induced by linomide are responsible for the decrease in thymus weight but do not play a role in the therapeutic effect of this drug in EAE.

Structural changes in aging bone: osteopenia in the proximal femurs of female mice.

A computerized image analysis system was used to quantitate age-related changes in the structure of the proximal femur in CW-1 female mice, ranging from 3 to 32 months of age. Morphological findings revealed a progressive thinning of bone trabeculae within the femoral head, accompanied by the development of marrow cavities in the cortical bone of the femoral neck and in the subchondral bone. As a result, the compact bone in senescent mice acquired an appearance similar to trabecular bone. Quantitative image analysis revealed a similarity in the pattern of changes in the three types of bone: cortical, trabecular, and subchondral. Bone density increased from 3 to 12 months of age and subsequently declined. A similar pattern was noted for the changes in the thickness of the cortical and the subchondral bone. Regression analysis revealed that the changes with age fitted a second-order model; thus it was possible to predict the age of maximal values for each parameter. Hence, the age of maximal bone density for cortical, trabecular, and subchondral bone was 12.3, 14.8, and 18.0 months, respectively. The rate of bone loss after 12 months was most prominent for trabecular bone (1.47% per month), so that by 32 months of age its overall mass had declined by 57% in comparison to peak values seen at 12 months of age (p less than 0.001). The density of the subchondral and cortical bones decreased at a slower rate (0.6% to 0.8% per month) and at the age of 32 months their values had decreased by 12% to 18% in comparison to those at 12 months (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)