#1
Interferon-ß-1b Treatment Modulates TNF and IFN Spontaneous Gene Expression In MS
Gayo A, Mozo L, Suarez A, Tunon A, Lahoz C, Gutierrez C
Neurology. 1999 Jun 10;52(9):1764-70
Hospital Central de Asturias, Dept of Immunology,
Universidad de Oviedo, Spain
PMID# 10371521; UI# 99297931
Abstract
Background
Interferon beta (IFN-ß) lessens the overall frequency of acute attacks in the Relapsing/Remitting form of Multiple Sclerosis (RRMS). IFN-ß may act by decreasing the synthesis of inflammatory Cytokines.
Objectives
To determine whether IFN-ß-1b treatment had an initial and sustained effect on the in vivo synthesis and secretion of Tumor Necrosis Factor alpha (TNF) and IFN.
Methods
A highly sensitive reverse-transcriptase PCR technique was used to measure baseline levels of mRNA in freshly isolated cells from patients before therapy and at 3, 6, and 12 months of treatment.
Also, protein concentration was measured in Serum and in culture supernatants from mitogen-stimulated cells. The authors studied 16 patients, of whom 11 did not have clinical exacerbations, whereas 5 had one clinical relapse each during the study.
Results
Mean values of TNF mRNA levels in the 11 stable patients decreased significantly at 3 and 6 months of treatment in comparison with initial data. After 6 months of therapy, IFN-ß-1b downmodulated TNF transcripts in the 5 patients who experienced relapse.
In this group of patients, TNF levels rose sharply to reach pretreated values at 1 year of IFN-ß-1b treatment. At the beginning of therapy, 6 patients had high concentrations of Serum TNF, which decreased to normal values following IFN-ß-1b therapy.
IFN mRNA expression also diminished after 6 and 12 months of IFN-ß-1b therapy in the group of stable patients, whereas nonrelevant variations were observed in patients who had one relapse.
Initially, patients' peripheral MonoNuclear cells secreted diminished amounts of TNF and IFN on PHA + PMA mitogen stimulation in comparison with normal control subjects.
After 1 year of therapy, IFN-ß-1b restored the normal production of TNF, whereas therapy did not restore IFN secretion to control values.
Conclusion
IFN-ß-1b decreases the spontaneous expression of two proinflammatory Cytokines.
Comment in:
Neurology 1999 Jun 10;52(9):1729-30
#2
Mechanisms Of High-Dose IntraVenous ImmunoGlobulins In DeMyelinating Diseases
Stangel M, Toyka KV, Gold R
Arch Neurol 1999 Jun;56(6):661-3
Cambridge University, MRC Centre for Brain Repair, England
PMID# 10369303; UI# 99295977
Abstract
Administration of high-dose IntraVenous ImmunoGlobulins has become one of the most successful new treatment regimens for DeMyelinating diseases.
In a decade of molecular medicine, it came as a surprise that a natural blood product would prove effective in several disorders, including Guillain-Barre Syndrome, Chronic Inflammatory DeMyelinating Polyneuropathy, Multifocal Motor Neuropathy, and, probably, Multiple Sclerosis.
Many experimental studies, both in vivo and in vitro, have shown that IntraVenous ImmunoGlobulins can interfere with the Immune System at several levels. In addition, IntraVenous ImmunoGlobulins may promote ReMyelination in DeMyelinating Disease associated with Viral infections.
At present, no single mode of action has been identified as the crucial mechanism, which leads us to suggest that multiple effects may act in concert.
#3
Trigeminal Neuralgia Triggered By Auditory Stimuli In Multiple Sclerosis
Hartmann M, Rottach KG, Wohlgemuth WA, Pfadenhauer K
Arch Neurol 1999 Jun;56(6):731-3
Zentralklinikum Augsburg, Dept of Neurology, Germany
PMID# 10369314; UI# 99295988
Abstract
Objectives
To describe a patient with a DeMyelinating BrainStem lesion who developed right-sided Trigeminal Neuralgia triggered by Auditory stimuli and to discuss the PathoPhysiological mechanisms underlying this unusual phenomenon.
Design & Setting
Case report, referral center.
Patient
A 27-year-old man who presented with clinical signs of a BrainStem lesion developed right-sided Trigeminal Neuralgia triggered by Auditory stimuli to the right Ear.
Magnetic Resonance Imaging and ElectroPhysiological studies demonstrated a DeMyelinating lesion in the Pons affecting the right Lateral Lemniscus and the right Trigeminal Pathway.
This phenomenon completely subsided within 4 days. After a relapse, the diagnosis of clinically definite Multiple Sclerosis was made.
Conclusion
Lateral spread of impulse activity within the DeMyelinating Pontine lesion is the likely explanation for the unusual phenomenon of Trigeminal Neuralgia triggered by Auditory stimuli.
#4
Urinary Myelin Basic Protein-Like Material In Multiple Sclerosis During Interferon-ß-1b Treatment
Whitaker JN, Layton BA, Bartolucci AA, Mitchell GW, Bashir K, Goodwin J, Kachelhofer RD
Arch Neurol 1999 Jun;56(6):687-91
Univ of Alabama at Birmingham, School of Medicine, Center for NeuroImmunology, Dept of Neurology, Birmingham Veterans Medical Center, 35233-7340, USA
jnwhit@uab.edu
PMID# 10369307; UI# 99295981
Abstract
Objectives
To determine levels of Urinary myelin basic protein-like material (MBPLM) in patients with Multiple Sclerosis (MS) openly treated with Interferon-ß-1b and to correlate these with clinical changes.
Background
Levels of Urinary MBPLM correlate with the presence of the progressive phase of MS and with the disease burden detected on T2-weighted, Cranial Magnetic Resonance Imaging. Measurement of Urinary MBPLM level may be a feasible test for monitoring or predicting response to therapeutic measures.
Design & Methods
In a prospective study at one site, 166 patients with MS (131 with Relapsing/Remitting [RR] and 35 with Secondary/Progressive [SP] disease) were treated for a minimum of 1 year and up to 3 years with Interferon-ß-1b and underwent assessment for neurologic disability (Expanded Disability Status Scale and Scripps Neurological Rating Scale) and change in disease subtype.
Urine samples were obtained at 1219 of 1378 clinic visits, and Urinary MBPLM level was determined and related to creatinine level to adjust for renal function.
Results
Statistical analysis using the general linear models procedure confirmed previous findings that the level of Urinary MBPLM related to Urinary creatinine level (MBPLM/creatinine) was higher (P<.001) in patients with SP than RR MS.
Of the 131 patients with RR MS, SP disease developed in 13 during the observation period. Compared with those in the RR group, the RR to SP group had a higher level (P<.001) of Urinary MBPLM and did not differ from the SP group.
Conclusions
The level of Urinary MBPLM is higher in SP MS than RR MS but not in RR MS that converts to SP MS. Level of Urinary MBPLM may permit the examination of treatment tested to prevent RR disease from becoming Progressive.
#5
Risk of Epilepsy In Multiple Sclerosis
A population-based study in Iceland
Olafsson E, Benedikz J, Hauser WA
Epilepsia 1999 Jun;40(6):745-7
National Univ Hospital (Landspitalinn), Dept of Neurology, Reykjavik, Iceland
PMID# 10368072; UI# 99294538
Abstract
Purpose
Several clinical series reported an association between Multiple Sclerosis (MS) and Epilepsy. We conducted a total population study in Iceland to determine the risk for developing Epilepsy in patients with MS compared with that expected in the general population.
Methods
Medical records of the 188 incidence cases of Clinically Definite MS first diagnosed in Iceland during the 25-year study period (1965-1989) were reviewed.
The cases were followed up through 1994 or until death to identify those developing seizures or Epilepsy. The expected number of cases with Epilepsy in the MS-incidence cohort were calculated based on the age-specific incidence for Epilepsy in Iceland and the age-specific person years of follow-up in the MS cohort.
Results
During the 2,771 person years of observation after diagnosis of Clinically Definite MS, three MS patients developed Epilepsy. One additional case developed Epilepsy after onset of MS symptoms but before diagnosis of MS.
The cumulative incidence of Epilepsy by 10 years after diagnosis of MS was 1.9%. Given the age-specific person years of follow-up after diagnosis of MS, only one case of Epilepsy would have been expected; standardized incidence ratio (SIR), 3.0 (95% confidence interval (CI), 0.6-8.8).
Conclusions
MS is a risk factor for developing Epilepsy. Patients with MS have a threefold increase in risk for developing Epilepsy when compared with that expected in the general population. The reason for this increased risk is unclear and needs further investigation.
#6
Upregulation Of InterCellular Adhesion Molecule-1 Expression On Human Endothelial Cells By Tumor Necrosis Factor- In An In Vitro Model Of The Blood-Brain Barrier
Dobbie MS, Hurst RD, Klein NJ, Surtees RA
Brain Res 1999 Jun 5;830(2):330-336
Univ, College London, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK
PMID# 10366690
Abstract
Adhesion molecules on the Endothelial surface of the Blood-Brain Barrier (BBB) play an important role in the PathoGenesis of many EncCphalopathies, including Multiple Sclerosis (MS) and Cerebral Malaria (CM).
The expression of four surface molecules of relevance to MS and CM on the immortalized human umbilical vein Endothelial Cell line, ECV304, was investigated using ImmunoFluorescence Flow Cytometry.
We found that ECV304 cells express InterCellular Adhesion Molecule-1 (ICAM-1) and low levels of CD36, but not Vascular Cell Adhesion Molecule-1 (VCAM-1) or E-Selectin.
This expression pattern was unaltered on ECV304 cells which were co-cultured with C6 Glioma cells; conditions under which the Endothelial Cells display enhanced Barrier formation.
Tumor Necrosis Factor-alpha (TNF-), which is elevated in MS and CM, decreased the integrity of the Barrier in co-cultured Endothelial Cells and upregulated the expression of ICAM-1 nine-fold. The significance of elevated ICAM-1 expression in relation to the binding of parasitised Erythrocytes at the BBB in CM is discussed.
Copyright 1999 Elsevier Science B.V.
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