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Biomedical subjects

Lea Glass-Marmor

Publications and source records attributed to Lea Glass-Marmor.

5 recordsLinked to original sources

Chronotherapy using corticosteroids for multiple sclerosis relapses.

BACKGROUND: The activity of the immune system displays a circadian rhythm. In diseases characterised by aberrant immune activity, chronotherapy (a treatment regimen tailored to diurnal body rhythms) may increase the efficiency, safety and tolerability of drugs. AIM: To compare the outcomes of intravenous corticosteroid administration during the day or night, for treatment of acute multiple sclerosis relapses. METHODS: 17 patients with multiple sclerosis were included in the study. Clinical assessment of disability was performed at trial entry, and at days 7 and 30 from the initiation of treatment. Adverse events and preference of night-time versus daytime treatment were assessed at the end of the treatment course. RESULTS: After night-time treatment, clinical recovery was significantly (p<0.001) enhanced and the mean number of side effects was significantly (p = 0.007) lower. Furthermore, most patients expressed a preference for night-time versus daytime treatment. CONCLUSIONS: The study suggests a potential benefit for implementation of chronotherapy using steroid treatment for acute multiple sclerosis relapse, with implications for other immune-mediated disorders.

Acute Disease↗

Modulation of matrix metalloproteinase-9 (MMP-9) secretion in B lymphopoiesis.

The matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade the extracellular matrix, thus involved in cellular migration. The extent and role of MMPs secretion in primary non-transformed B cells, and specifically during early stages of development in the bone marrow (BM), has been barely unveiled. Herein, we investigated the secretion of MMP-9 during B lymphopoiesis and its modulation in response to different mitogens and cytokines. To do so, we used our BM culture system and well-studied mutated mouse models to isolate the different B cell populations. Our results show that MMP-9 is spontaneously secreted throughout B lymphopoiesis, and that the level of secreted MMP-9 is developmentally regulated. Using reverse transcription-PCR, we found that IFNbetaR is expressed throughout B cell development, while tumor necrosis factor (TNF)-alphaR-p55 and IFNgammaR expressions are initiated only at the pre-B stage. We found that TNFalpha stimulates MMP-9 secretion in transitional cells, whereas IFNs suppress MMP-9 secretion in immature cells. LPS and phorbol 12-myristate 13-acetate suppressed MMP-9 secretion in transitional cells, whereas LPS and concanavalin A stimulated MMP-9 secretion in mature B cells. We conclude that B lymphocyte development is accompanied with MMP-9 secretion and the developing cells are competent to modify this secretion upon different immune stimuli.

Animals↗

Serum anti-Glc(alpha1,4)Glc(alpha) antibodies as a biomarker for relapsing-remitting multiple sclerosis.

There is an unmet need to develop specific biomarkers for multiple sclerosis (MS) to aid in the diagnosis, improve the management of patients and the monitoring of the effectiveness of treatment. We have screened serum from patients with relapsing-remitting MS (RRMS, n = 107) against a library of glycans on a glycan chip, and have found significantly higher levels of IgM anti-Glc(alpha1,4)Glc(alpha) antibodies (anti-Galpha4Galpha antibodies) than in patients suffering from other neurological diseases (OND, n = 50, p < 0.0001), and other autoimmune diseases (OAD, n = 27, p = 0.02). No significant differences were found relative to patients having primary progressive MS (n = 16). No significant differences were detected between the levels of IgM anti-Galpha4Galpha antibodies in sera from patients with RRMS in relapsing versus remitting state, and in patients treated with immunotherapy versus untreated patients. To test whether the highly significant difference in the levels of IgM anti-Galpha4Galpha between RRMS and OND group is due to general increase in IgM levels, we have measured total serum IgM in a subgroup of 62 MS and 48 OND patients. Although the total IgM was significantly lower in the OND than the RRMS group (p = 0.0007), analysis of covariance (ANCOVA) reveled no statistically significant relationship to the covariate (total IgM). Furthermore, following normalizing the values to total IgM the difference in the levels of IgM anti-Galpha4Galpha between the MS and OND groups was found highly significant (p < < 0.0001). The present findings support further assessment of serum anti-Galpha4Galpha antibodies as a potential biomarker for MS, which may confirm disease diagnosis and aid in its management.

Adult↗