MS. It (ms + it)

Distribution by Scientific Domains

Selected Abstracts

Functional analysis of DM64, an antimyotoxic protein with immunoglobulin-like structure from Didelphis marsupialis serum

FEBS JOURNAL, Issue 24 2002
Surza L. G. Rocha
Bothrops snake venoms are known to induce local tissue damage such as hemorrhage and myonecrosis. The opossum Didelphis marsupialis is resistant to these snake venoms and has natural venom inhibitors in its plasma. The aim of this work was to clone and study the chemical, physicochemical and biological properties of DM64, an antimyotoxic protein from opossum serum. DM64 is an acidic protein showing 15% glycosylation and with a molecular mass of 63 659 Da when analysed by MALDI-TOF MS. It was cloned and the amino acid sequence was found to be homologous to DM43, a metalloproteinase inhibitor from D. marsupialis serum, and to human ,1B-glycoprotein, indicating the presence of five immunoglobulin-like domains. DM64 neutralized both the in vivo myotoxicity and the in vitro cytotoxicity of myotoxins I (mt-I/Asp49) and II (mt-II/Lys49) from Bothrops asper venom. The inhibitor formed noncovalent complexes with both toxins, but did not inhibit the PLA2 activity of mt-I. Accordingly, DM64 did not neutralize the anticoagulant effect of mt-I nor its intracerebroventricular lethality, effects that depend on its enzymatic activity, and which demonstrate the dissociation between the catalytic and toxic activities of this Asp49 myotoxic PLA2. Furthermore, despite its similarity with metalloproteinase inhibitors, DM64 presented no antihemorrhagic activity against Bothrops jararaca or Bothrops asper crude venoms, and did not inhibit the fibrinogenolytic activity of jararhagin or bothrolysin. This is the first report of a myotoxin inhibitor with an immunoglobulin-like structure isolated and characterized from animal blood. [source]

Simvastatin affects cell motility and actin cytoskeleton distribution of microglia

GLIA, Issue 2 2006
Hedwich F. Kuipers
Abstract Statin treatment is proposed to be a new potential therapy for multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system. The effects of statin treatment on brain cells, however, are hardly understood. We therefore evaluated the effects of simvastatin treatment on the migratory capacity of brain microglial cells, key elements in the pathogenesis of MS. It is shown that exposure of human and murine microglial cells to simvastatin reduced cell surface expression of the chemokine receptors CCR5 and CXCR3. In addition, simvastatin treatment specifically abolished chemokine-induced microglial cell motility, altered actin cytoskeleton distribution, and led to changes in intracellular vesicles. These data clearly show that simvastatin inhibits several immunological properties of microglia, which may provide a rationale for statin treatment in MS. 2005 Wiley-Liss, Inc. [source]

Nutrition and diet in the clinical management of multiple sclerosis

A. Payne
For many years, medical interest in the relationship between nutrition and multiple sclerosis (MS) has focused largely on aetiology and the influence of dietary fat on the rate and severity of disease. While the cause of MS remains unknown and the influence of dietary fat is unclear, recent studies on antioxidant intake and oxidative stress in MS are strengthening the rationale in support of a healthy eating regime following diagnosis. Dietary intake in MS and the influence of advanced disease on nutritional status are less well researched and documented. Both obesity and malnutrition may occur with detrimental consequences to functional abilities. Cognitive difficulties, dysphagia and the side-effects of drug treatment may further contribute to deterioration in nutritional status. This paper aims to provide a practical overview of dietary management in MS. It reviews the available evidence relating nutrition to MS and discusses dietary management, with particular emphasis on the identification and alleviation of factors affecting nutritional status. [source]

A Magnetization Transfer MRI Study of Deep Gray Matter Involvement in Multiple Sclerosis

Jitendra Sharma MD
ABSTRACT Background/Purpose: Gray matter involvement in multiple sclerosis (MS) is of growing interest with respect to disease pathogenesis. Magnetization transfer imaging (MTI), an advanced MRI technique, is sensitive to disease in normal appearing white matter (NAWM) in patients with MS. Design/Methods: We tested if MTI detected subcortical (deep) gray matter abnormalities in patients with MS (n= 60) vs. age-matched normal controls (NL, n= 20). Magnetization transfer ratio (MTR) maps were produced from axial proton density, conventional spin-echo, 5 mm gapless slices covering the whole brain. Region-of-interest,derived MTR histograms for the caudate, putamen, globus pallidus, thalamus, and NAWM were obtained. Whole brain MTR was also measured. Results: Mean whole brain MTR and the peak position of the NAWM MTR histogram were lower in patients with MS than NL (P < .001) and mean whole brain MTR was lower in secondary progressive (SP, n= 10) than relapsing-remitting (RR, n= 50, P < .001) patients. However, none of the subcortical gray matter nuclei showed MTR differences in MS vs. NL, RR vs. SP, or SP vs. NL. Conclusions: The MTI technique used in this cohort was relatively insensitive to disease in the deep gray matter nuclei despite showing sensitivity for whole brain disease in MS. It remains to be determined if other MRI techniques are more sensitive than MTI for detecting pathology in these areas. [source]

Wallerian Degeneration: A Major Component of Early Axonal Pathology in Multiple Sclerosis

Tomasz Dziedzic
Abstract Axonal loss is a major component of the pathology of multiple sclerosis (MS) and the morphological basis of permanent clinical disability. It occurs in demyelinating plaques but also in the so-called normal-appearing white matter (NAWM). However, the contribution of Wallerian degeneration to axonal pathology is not known. Here, we analyzed the extent of Wallerian degeneration and axonal pathology in periplaque white matter (PPWM) and lesions in early multiple sclerosis biopsy tissue from 63 MS patients. Wallerian degeneration was visualized using an antibody against the neuropeptide Y receptor Y1 (NPY-Y1R). The number of SMI-32-positive axons with non-phosphorylated neurofilaments was significantly higher in both PPWM and plaques compared to control white matter. APP-positive, acutely damaged axons were found in significantly higher numbers in plaques compared to PPWM. Strikingly, the number of NPY-Y1R-positive axons undergoing Wallerian degeneration was significantly higher in PPWM and plaques than in control WM. NPY-Y1R-positive axons in PPWM were strongly correlated to those in the lesions. Our results show that Wallerian degeneration is a major component of axonal pathology in the periplaque white matter in early MS. It may contribute to radiological changes observed in early MS and most likely plays a major role in the development of disability. [source]

Obliterating intracranial vasculopathy mimicking multiple sclerosis

M. Boentert
Background,,, The first ever diagnosis of multiple sclerosis (MS) requires consideration of both diagnostic criteria and differential diagnosis. Clinicians are particularly challenged by rare conditions which may mimic MS symptoms and relapses. Case report,,, We report the case of a young female patient who presented with relapsing left hemispheric symptoms that were highly suspicious of MS but were caused by an idiopathic occlusive angiopathy of the circle of Willis. Conclusion,,, Occlusive disease of the great cerebral arteries in young patients is a rare but important differential diagnosis of MS. It has to be considered in patients presenting with the first symptoms suspicious of MS as substantial treatment consequences will arise. [source]

Cooperative interaction of n -butylammonium ion with 1,3-alternate tetrapropoxycalix [4]arene: NMR and theoretical study

Jaroslav K
Abstract The interaction of 1,3-alternate tetrapropoxycalix[4]arene (1) with n -butylammonium ion (2) in CD2Cl2 was examined using 1H, 13C and 14N NMR spectroscopy and DFT (density functional theory) calculations. NMR shows that 1 forms with 2 an equimolecular hydrogen-bonded complex with the equilibrium constant 5.91 103 l/mol at 296 K. The structure of the complex can be shown to be asymmetric at 203 K, with 2 interacting by hydrogen bonds with the two ethereal oxygen atoms of one half of 1 and with the , system of the other half, but is rapidly averaged to an apparent C4h symmetry by chemical exchange at higher temperatures. Using two related but independent techniques based on transverse and rotating-frame proton relaxation, it is shown that only an intermolecular exchange of 2 between the bound and free states takes place, in contrast to previously studied interaction of 1 with H3O+. Its correlation time is 0.169 ms. It is shown by DFT calculations that such swift exchange is not possible without a cooperative interaction of both 2 and 1 with several molecules of water present. Similarities and contrasts between the exchange processes of 2 and H3O+ bound to 1 are discussed, in particular with respect to the apparent quantum tunneling of the latter inside the molecule of the complex. Copyright 2008 John Wiley & Sons, Ltd. [source]

After-effects of near-threshold stimulation in single human motor axons

Hugh Bostock
Subthreshold electrical stimuli can generate a long-lasting increase in axonal excitability, superficially resembling the phase of superexcitability that follows a conditioning nerve impulse. This phenomenon of ,subthreshold superexcitability' has been investigated in single motor axons in six healthy human subjects, by tracking the excitability changes produced by conditioning stimuli of different amplitudes and waveforms. Near-threshold 1 ms stimuli caused a mean decrease in threshold at 5 ms of 22.1 6.0% (mean s.d.) if excitation occurred, or 6.9 2.6% if excitation did not occur. The subthreshold superexcitability was maximal at an interval of about 5 ms, and fell to zero at 30 ms. It appeared to be made up of two components: a passive component linearly related to conditioning stimulus amplitude, and a non-linear active component. The active component appeared when conditioning stimuli exceeded 60% of threshold, and accounted for a maximal threshold decrease of 2.6 1.3%. The passive component was directly proportional to stimulus charge, when conditioning stimulus duration was varied between 0.2 and 2 ms, and could be eliminated by using triphasic stimuli with zero net charge. This change in stimulus waveform had little effect on the active component of subthreshold superexcitability or on the ,suprathreshold superexcitability' that followed excitation. It is concluded that subthreshold superexcitability in human motor axons is mainly due to the passive electrotonic effects of the stimulating current, but this is supplemented by an active component (about 12% of suprathreshold superexcitability), due to a local response of voltage-dependent sodium channels. [source]