- Email: [email protected]
3-31-06 Possible role of tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) in multiple sclerosis (MS)
Multiple Sclerosis 13-31-06
1 Possible role of tumor necrosis factor-a (TNF-a) and transformina arowth factor-0 ITGF-0) in multiple sclerosi&$4S) ’ . ’ ’
Dragana Djordjevic, Ace Jovicic, Milena Kataranoska ‘, Marina Jovanovic’ Slobodan Cirkovic ‘. Department of Neurolog) Department of Medical Research, Military Medical Academ)! Be/grade, tigoslavia, ’ Department Radiology; Military Medical Academy Be/grade, Yugoslavia
13-31-09
, of
lmmunomodulatory and proinflamatory cytokines are major mediators of pathological events in MS. The aim of this study was to evaluate presence and significance of TNF-cz and TGF-,9 in cerebrospinal fluid (CSF) and plasma of MS patients. In 38 MS patients blood and CSF samples were obtained in acute phase, and at the same time clinical, CSF immunohemical anlysis and MRI examinations were performed. Controls were 27 patients with other neurological disease (OND). TNF-(r and TGF$ were measured by ELISA test. Only in 2 (5.2%) CSF and 4 (10.5%) plasma samples of MS patients TNF-cy was detected, in those with severely damaged blood-brain barrier and multiple active demyelinating lesions. In controls, TNFa wasn’t detected in CSF, and in plasma was measurable in 6 (22.2%) patients. TGF-,9 was detected in all but in 8 (17%) CSF samples of MS patients, in controls in 50%. In plasma it was detected in all samples. TGF$ levels were higher in MS patients with favourable clinical, immunohemical CSF and MRI profile. In conclusion, presence of TGF-,¶ in CSF and plasma of MS patients, might underfine its immunomodulatory effect, while absence of increased levels of TNF-(u, apart from method limitations, marks its importance in inflammatory process of severe active disease.
13-31-07
1 Multiple sclerosis - high dose intravenous imunoglobulin G (IVIG) treatment
D. Djordjevic, A. Jovicic, S. Cirkovic’, R. Raicevic, E. Dincic, V. Lekovic-Cedic. Department of Neuro/w Mi/itary Medical Academy; Be/grade, Yugoslavia, ’ Department of Radiologyl Military Medical Academy Belgrade, Yugoslavia Considering its immunomodulatory effect, IVIG therapy may have potential role in multiple sclerosis (MS) treatment. In this open study, during 1.5 year follow-up period 7 (6 female, 1 male) patients with relapsing-remitting MS were treated with IVIG, 0.4 gikg during 5 days, and then as a single dose after 3, 6 and 9 months period. At the same time clinical, immunohemical CSF analysis and MRI evaluation were performed each time. In all patients clinical improvement were evident after IVIG administration, as well as blood-brain barrier healing and increased IgG intrathscal synthesis. No side-effects were registered. Four female patients were stable, without MRI signs of disease activity: in male patient there was constant improvement; in 1 female patient after initial improvement there was deterioration; the last female patient was clinically stable with MRI signs of disease activity. In conclusion IVIG is safe, potentially effective treatment in MS.
I
3-31-08
CPP32 executioner lesions
protein and Fas ligand in MS
P. Dowling, S. Raval, W. Husar, J. Menonna, S. Cook, B. Blumberg. Neurology Service, VA New Jersey Health Care System, East Orange, NJ, USA, Department of Neurosciences, UMD-New Jersey Medical School, Newark, NJ, USA
Summary: lmmunohistcchemical methods were used to search for CPP32 and the Fas receptodfas ligand system in multiple sclerosis (MS) white matter lesions. We found large numbers of Fas-L bearing cells in acute and chronic MS lesions, and very few positive cells in non-inflammatory controls. Four of six brains from non-MS neuropathologic conditions associated with inflammation and white matter disease were, however, also positive for Fas-L. Double staining with cell specific markers revealed that the pattern of ligand positive cells in chronic MS lesions was complex and composed of several different cell types which were primarily resident glial cells with a small overlay of macrophages. Fas./APO 1 (CD95) receptor expression in MS tissue was also evaluated and marked up-regulation of the receptor was found. In addition, marked increase in cytoplasmic CPP32 was present in oligodendroglia from MS lesions but was rarely present in control tissue. TUNEL positive dying cells were found in MS lesions and showed excellent colccalization with both CPP32 and Fas ligand, indicating that the Fas death system may contribute to plaque pathogenesis and that CPP32 maybe a major villain in precipitating the accelerated cell death found in MS white matter.
S185 1 Anti-Oxidant therapy wlth tirllazad mesylate reduces autoimmune CNS demyellnation in experimental allergic encephalomyelkis (EAE)
J.-P. Ertilinna, N. Setila, M. RayIt& E. Soppi, A.A. Salmi, M. Panelius, R. Salonen. Departments of Viro/ogy and Pathology; University of Turku, Turks, Finland, Turku Immunology Centre, University of Turku, Turku, Fin/and Therapy with anti-oxidant, tirilazad mesylate (TM, Freedox) was applied for treatment of different murine models of EAE. SJL and BALB/c mice were induced to develop EAE and injected intravenously with different doses of TM or NaCl for 21 days after EAE induction. Histological and immunological samples were collected from groups of TM-treated and NaCI-injected control mice during preclinical, clinical and recovered phase of EAE. TM-treatment was more effective in the treatment of BALB/c son EAE than in SJL EAE. Clinical signs of EAE were reduced by 60% in BALB/c son EAE mice treated with TM-doses from 1.0 to 10.0 m&g/day. In SJL EAE mice the effect was modest but 20% reduction in mortality to EAE was observed. Histologically, BALB/c son EAE mice with anti-oxidant-therapy with TM had reduced CNS inflammation, blood-brain barrier (BBB) damage and demyelination as compared to NaCl injected control mice. Immunologically, TM-treatment did not cause immunosuppression despite its 21-aminosteroid structure and antigen-specific reactivity of regional lymph node and spleen-derived lymphocytes was not reduced. The number of macrophages infiltrating the CNS was reduced in TM-treated BALB/c son EAE mice suggesting the possibility that TM-treatment may affect toxic demyelination induced by macrophage-lineage of cells which are present in lesser number in the CNS lesions of SJL EAE mice We conclude, that anti-oxidant therapy with TM results in enhanced protection against autoimmune-mediated CNS demyelination in BALB/c son EAE mice by restricting autoimmune-mediated inflammation and demyelination within the CNS of BALB/c son EAE mice.
13-31-l 0 1 Multiple sclerosis. Institutional prevalence method
unit cost by
Gustav0 Esquivel Romero, NoB Barroso Rodriguez, Noemi Santos, Jo& A. Forment Hemandez, Jose R. Herrera PBrez. Hospital Especialidades Cenrro MBdico National La Raza, Mexico Multiple sclerosis (ME) is a chronic demyelinizating disease, affects to economic persons, actually is defined as a autoimmune disease, diagnosis is made by clinical picture and magnetic resonance with gadolinium (MRI). At present we do not have knowledge of cost studies in Mexico. Object: Evaluate cost of attentions, hospitalization, prescriptions and nonworking days in our hospital caused by ME during 1995. Methods: We studied hospital statistics; the data we analyzed by prevalence methods expressed by proportions. Design: Prevalence, retroactive, non azarized, open study. Results: There were 144,818 attentions, 1,700 form ME; cost attention for ME was $4,080,000 USD (1.17% total amount), first visit (41%), subsequent visit (59%). The number of prescriptions were 107,951; 1,633 to ME (1.15%). Total of non working days were 71,951, 4.19% from the total hospital expenditure ($877,400 USD) td ME. Hospitalization were 0.6% from tot& 6,004 MRI were taken by de hospital, 4.19% corresponding to EM ($274,176 USD). Conclusi&s: The attention to ME-patients cost (0.61%) from hospital derogation. Non-working days were the principal cause of ME expenditure. Comments: If we pretend to give a better Quality patient attention, physician must know the cost of the attention given. An economic social disaster will occur if incidence and/or prevalence of these disease increase in a short time.
3-31-l 1 A deletion in the repetitive (TGGA)n sequence 5’ to the human YBP gene is associated to multiple sclerosis In ltallan HLA DR2+ patients F.R. Guerini, M. Mediati, D. Caputo, P. Ferrante I. Laboratory of Bio/ogx and Mu/tip/e Sclerosis Unit, Don C. Gnocchi Foundation, IRCCS (Research Hospital), &a/K ’ /nstiWe of Medical Microbiolcgy, University of Milan, #a/y Recently it has been shown that a region of DNA 5’ flanking the first exon of the myelin basic protein (MBP) gene is a site of polymorphism due to the presence of an highly repetitive sequence (TGGA) n. To verify the MBP gene polymorphism in Multiple sclerosis (MS), we perfoned PCR and gel electrophoresis analysis of the region from 1116 nt to 1540 nt. in a group of 99 Italian MS patients and 100 healthy controls. Three different band patterns were observed and the short fragment of 354 bp was found more frequently (p = 0.04) in MS patients (41%) than in controls (31%). The nucleotide sequencing of these two fragment showed that the short form of the polymorphic allele has a deletion of 70 bp and two point mutations. By cross comparison between the HLA profile and MBP polymorphism we have observed that the association of HLA DRP-DQl and MBP 354 bp allele
1 Possible role of tumor necrosis factor-a (TNF-a) and transformina arowth factor-0 ITGF-0) in multiple sclerosi&$4S) ’ . ’ ’
Dragana Djordjevic, Ace Jovicic, Milena Kataranoska ‘, Marina Jovanovic’ Slobodan Cirkovic ‘. Department of Neurolog) Department of Medical Research, Military Medical Academ)! Be/grade, tigoslavia, ’ Department Radiology; Military Medical Academy Be/grade, Yugoslavia
13-31-09
, of
lmmunomodulatory and proinflamatory cytokines are major mediators of pathological events in MS. The aim of this study was to evaluate presence and significance of TNF-cz and TGF-,9 in cerebrospinal fluid (CSF) and plasma of MS patients. In 38 MS patients blood and CSF samples were obtained in acute phase, and at the same time clinical, CSF immunohemical anlysis and MRI examinations were performed. Controls were 27 patients with other neurological disease (OND). TNF-(r and TGF$ were measured by ELISA test. Only in 2 (5.2%) CSF and 4 (10.5%) plasma samples of MS patients TNF-cy was detected, in those with severely damaged blood-brain barrier and multiple active demyelinating lesions. In controls, TNFa wasn’t detected in CSF, and in plasma was measurable in 6 (22.2%) patients. TGF-,9 was detected in all but in 8 (17%) CSF samples of MS patients, in controls in 50%. In plasma it was detected in all samples. TGF$ levels were higher in MS patients with favourable clinical, immunohemical CSF and MRI profile. In conclusion, presence of TGF-,¶ in CSF and plasma of MS patients, might underfine its immunomodulatory effect, while absence of increased levels of TNF-(u, apart from method limitations, marks its importance in inflammatory process of severe active disease.
13-31-07
1 Multiple sclerosis - high dose intravenous imunoglobulin G (IVIG) treatment
D. Djordjevic, A. Jovicic, S. Cirkovic’, R. Raicevic, E. Dincic, V. Lekovic-Cedic. Department of Neuro/w Mi/itary Medical Academy; Be/grade, Yugoslavia, ’ Department of Radiologyl Military Medical Academy Belgrade, Yugoslavia Considering its immunomodulatory effect, IVIG therapy may have potential role in multiple sclerosis (MS) treatment. In this open study, during 1.5 year follow-up period 7 (6 female, 1 male) patients with relapsing-remitting MS were treated with IVIG, 0.4 gikg during 5 days, and then as a single dose after 3, 6 and 9 months period. At the same time clinical, immunohemical CSF analysis and MRI evaluation were performed each time. In all patients clinical improvement were evident after IVIG administration, as well as blood-brain barrier healing and increased IgG intrathscal synthesis. No side-effects were registered. Four female patients were stable, without MRI signs of disease activity: in male patient there was constant improvement; in 1 female patient after initial improvement there was deterioration; the last female patient was clinically stable with MRI signs of disease activity. In conclusion IVIG is safe, potentially effective treatment in MS.
I
3-31-08
CPP32 executioner lesions
protein and Fas ligand in MS
P. Dowling, S. Raval, W. Husar, J. Menonna, S. Cook, B. Blumberg. Neurology Service, VA New Jersey Health Care System, East Orange, NJ, USA, Department of Neurosciences, UMD-New Jersey Medical School, Newark, NJ, USA
Summary: lmmunohistcchemical methods were used to search for CPP32 and the Fas receptodfas ligand system in multiple sclerosis (MS) white matter lesions. We found large numbers of Fas-L bearing cells in acute and chronic MS lesions, and very few positive cells in non-inflammatory controls. Four of six brains from non-MS neuropathologic conditions associated with inflammation and white matter disease were, however, also positive for Fas-L. Double staining with cell specific markers revealed that the pattern of ligand positive cells in chronic MS lesions was complex and composed of several different cell types which were primarily resident glial cells with a small overlay of macrophages. Fas./APO 1 (CD95) receptor expression in MS tissue was also evaluated and marked up-regulation of the receptor was found. In addition, marked increase in cytoplasmic CPP32 was present in oligodendroglia from MS lesions but was rarely present in control tissue. TUNEL positive dying cells were found in MS lesions and showed excellent colccalization with both CPP32 and Fas ligand, indicating that the Fas death system may contribute to plaque pathogenesis and that CPP32 maybe a major villain in precipitating the accelerated cell death found in MS white matter.
S185 1 Anti-Oxidant therapy wlth tirllazad mesylate reduces autoimmune CNS demyellnation in experimental allergic encephalomyelkis (EAE)
J.-P. Ertilinna, N. Setila, M. RayIt& E. Soppi, A.A. Salmi, M. Panelius, R. Salonen. Departments of Viro/ogy and Pathology; University of Turku, Turks, Finland, Turku Immunology Centre, University of Turku, Turku, Fin/and Therapy with anti-oxidant, tirilazad mesylate (TM, Freedox) was applied for treatment of different murine models of EAE. SJL and BALB/c mice were induced to develop EAE and injected intravenously with different doses of TM or NaCl for 21 days after EAE induction. Histological and immunological samples were collected from groups of TM-treated and NaCI-injected control mice during preclinical, clinical and recovered phase of EAE. TM-treatment was more effective in the treatment of BALB/c son EAE than in SJL EAE. Clinical signs of EAE were reduced by 60% in BALB/c son EAE mice treated with TM-doses from 1.0 to 10.0 m&g/day. In SJL EAE mice the effect was modest but 20% reduction in mortality to EAE was observed. Histologically, BALB/c son EAE mice with anti-oxidant-therapy with TM had reduced CNS inflammation, blood-brain barrier (BBB) damage and demyelination as compared to NaCl injected control mice. Immunologically, TM-treatment did not cause immunosuppression despite its 21-aminosteroid structure and antigen-specific reactivity of regional lymph node and spleen-derived lymphocytes was not reduced. The number of macrophages infiltrating the CNS was reduced in TM-treated BALB/c son EAE mice suggesting the possibility that TM-treatment may affect toxic demyelination induced by macrophage-lineage of cells which are present in lesser number in the CNS lesions of SJL EAE mice We conclude, that anti-oxidant therapy with TM results in enhanced protection against autoimmune-mediated CNS demyelination in BALB/c son EAE mice by restricting autoimmune-mediated inflammation and demyelination within the CNS of BALB/c son EAE mice.
13-31-l 0 1 Multiple sclerosis. Institutional prevalence method
unit cost by
Gustav0 Esquivel Romero, NoB Barroso Rodriguez, Noemi Santos, Jo& A. Forment Hemandez, Jose R. Herrera PBrez. Hospital Especialidades Cenrro MBdico National La Raza, Mexico Multiple sclerosis (ME) is a chronic demyelinizating disease, affects to economic persons, actually is defined as a autoimmune disease, diagnosis is made by clinical picture and magnetic resonance with gadolinium (MRI). At present we do not have knowledge of cost studies in Mexico. Object: Evaluate cost of attentions, hospitalization, prescriptions and nonworking days in our hospital caused by ME during 1995. Methods: We studied hospital statistics; the data we analyzed by prevalence methods expressed by proportions. Design: Prevalence, retroactive, non azarized, open study. Results: There were 144,818 attentions, 1,700 form ME; cost attention for ME was $4,080,000 USD (1.17% total amount), first visit (41%), subsequent visit (59%). The number of prescriptions were 107,951; 1,633 to ME (1.15%). Total of non working days were 71,951, 4.19% from the total hospital expenditure ($877,400 USD) td ME. Hospitalization were 0.6% from tot& 6,004 MRI were taken by de hospital, 4.19% corresponding to EM ($274,176 USD). Conclusi&s: The attention to ME-patients cost (0.61%) from hospital derogation. Non-working days were the principal cause of ME expenditure. Comments: If we pretend to give a better Quality patient attention, physician must know the cost of the attention given. An economic social disaster will occur if incidence and/or prevalence of these disease increase in a short time.
3-31-l 1 A deletion in the repetitive (TGGA)n sequence 5’ to the human YBP gene is associated to multiple sclerosis In ltallan HLA DR2+ patients F.R. Guerini, M. Mediati, D. Caputo, P. Ferrante I. Laboratory of Bio/ogx and Mu/tip/e Sclerosis Unit, Don C. Gnocchi Foundation, IRCCS (Research Hospital), &a/K ’ /nstiWe of Medical Microbiolcgy, University of Milan, #a/y Recently it has been shown that a region of DNA 5’ flanking the first exon of the myelin basic protein (MBP) gene is a site of polymorphism due to the presence of an highly repetitive sequence (TGGA) n. To verify the MBP gene polymorphism in Multiple sclerosis (MS), we perfoned PCR and gel electrophoresis analysis of the region from 1116 nt to 1540 nt. in a group of 99 Italian MS patients and 100 healthy controls. Three different band patterns were observed and the short fragment of 354 bp was found more frequently (p = 0.04) in MS patients (41%) than in controls (31%). The nucleotide sequencing of these two fragment showed that the short form of the polymorphic allele has a deletion of 70 bp and two point mutations. By cross comparison between the HLA profile and MBP polymorphism we have observed that the association of HLA DRP-DQl and MBP 354 bp allele