Progressive ms

BACKGROUND: The peak blood lactate response to an exhaustive exercise test in a number of chronic conditions has been shown to differ from that seen in healthy, untrained individuals. However, this has not been investigated for patients with multiple sclerosis (MS). OBJECTIVE: The main objective was to determine and compare the peak blood lactate response to exercise and the maximal workload between two groups of MS patients with different illness severity. METHODS: Twenty-five patients with a relapsing-remitting disease course (Group RR) and 41 patients with a secondary- or primary chronic progressive disease course (group CP) performed an exhaustive incremental bicycle ergometry...

To examine changes in anti-JC Virus (JCV) index measurements over time in multiple sclerosis (MS) patients to better understand this test, which is used in assessing risk of progressive multifocal leukoencephalopathy (PML) with natalizumab. We aim to describe and compare seroconversion rates, variability of JCV antibody index values, and changes in index values over time between patients on natalizumab therapy and patients naïve to natalizumab. Anti-JCV index values are used to help decide whether to start, continue, or stop treatment...

PURPOSE: The prevalence of epilepsy among patients with multiple sclerosis (MS) has been found higher than in the general population. Although cortical pathology may be involved, the causal link between MS and epileptic seizures is still unclear. We aimed to identify and describe the patients with active epilepsy in a previously described population based MS-cohort. METHODS: Medical records of all patients with MS in Nordland County on January 1, 2010, were scrutinizing for evidence of comorbid seizures and epilepsy...

Sulfonated steroids (s-St) have been usually regarded as inactive metabolites but are progressively considered as precursors for the intra-tissue formation of bioactive steroids. Moreover, independent effects without preceding removal of the sulfate group have been observed. We use the porcine testicular-epididymal compartment as a model to investigate the still largely unknown s-St physiology as the boar exhibits an intriguingly broad s-St spectrum predominantly originating from the testis. The application of LC-MS/MS in steroidomics enables the determination of unconjugated and intact sulfonated steroids with currently highest specificity and good sensitivity, allowing the concurrent measuring of numerous analytes in larger quantities of samples...

BACKGROUND: Multiple sclerosis is a degenerative inflammatory disease of the CNS characterised by immune-mediated destruction of myelin and progressive neuroaxonal loss. Myelin in the CNS is a specialised extension of the oligodendrocyte plasma membrane and clemastine fumarate can stimulate differentiation of oligodendrocyte precursor cells in vitro, in animal models, and in human cells. We aimed to analyse the efficacy and safety of clemastine fumarate as a treatment for patients with multiple sclerosis...

BACKGROUND: Treatment with erythropoietin (Epo) in experimental autoimmune encephalomyelitis (EAE), the rodent model of multiple sclerosis (MS), has consistently been shown to ameliorate disease progression and improve overall outcome. The effect has been attributed to modulation of the immune response and/or preservation of the central nervous system (CNS) tissue integrity. It remains unclear, however, if (a) Epo acts primarily in the CNS or the periphery and if (b) Epo's beneficial effect in EAE is mainly due to maintaining CNS tissue integrity or to modulation of the immune response...

The MALDI-based mass spectrometry, over the last three decades, has become an important analytical tool. It is a gentle ionization technique, usually applicable to detect and characterize analytes with high molecular weights like proteins and other macromolecules. The earlier difficulty of detection of analytes with low molecular weights like small organic molecules and metal ion complexes with this technique arose due to the cluster of peaks in the low molecular weight region generated from the matrix. To detect such molecules and metal ion complexes, a four-prong strategy has been developed...

Horse urine is easily collected and contains molecules readily measurable using mass spectrometry that can be used as biomarkers representative of health, disease or drug tampering. This study aimed at analyzing microliter levels of horse urine to purify, identify and quantify proteins, polar metabolites and non-polar lipids. Urine from a healthy 12 year old quarter horse mare on a diet of grass hay and vitamin/mineral supplements with limited pasture access was collected for serial-omics characterization. The urine was treated with methyl tert-butyl ether (MTBE) and methanol to partition into three distinct layers for protein, non-polar lipid and polar metabolite content from a single liquid-liquid extraction and was repeated two times...

Metabolic syndrome (MS) is a worldwide healthcare issue and a dominant risk factor for the development of incurable diseases affecting the entire body. The hepatic manifestations of MS include nonalcoholic fatty liver disease (NAFLD) and its progressive variant, nonalcoholic steatohepatitis (NASH). NASH is known to progress to liver cirrhosis and hepatocellular carcinoma (HCC). Excellent animal models for determining the mechanism of pathogenesis and establishing therapeutic treatment of NASH/HCC are strongly required worldwide...

OBJECTIVE: The link between cerebral vasoreactivity and cognitive status in multiple sclerosis remains unclear. The aim of the present study was to investigate a potential decrease of cerebral vasoreactivity in multiple sclerosis patients and correlate it with cognitive status. METHODS: Thirty-three patients with multiple sclerosis (nine progressive and 24 remitting forms, median age: 39 years, 12 males) and 22 controls underwent MRI with a hypercapnic challenge to assess cerebral vasoreactivity and a neuropsychological assessment...

Kallikrein-related peptidases (KLKs) are a family of serine peptidases that are deregulated in numerous pathological conditions, with a multitude of KLK-mediated functional roles implicated in the progression of cancer. Advances in multidimensional mass spectrometry (MS)-based proteomics have facilitated the quantitative measurement of deregulated KLK expression in cancer, identifying certain KLKs, as well as their substrates, as potential cancer biomarkers. Areas covered: In this review, we discuss how these approaches have been utilized for KLK biomarker discovery and unbiased substrate determination in complex protein pools that mimic the in vivo extracellular microenvironment...

Ion mobility spectrometry is an analytical technique known for more than 100 years, which entails separating ions in the gas phase based on their size, shape and charge. While ion mobility spectrometry alone can be useful for some applications (mostly security analysis for detecting certain classes of narcotics and explosives), it becomes even more powerful in combination with mass spectrometry and high-performance liquid chromatography. Indeed, the limited resolving power of ion mobility spectrometry alone can be tackled when combining this analytical strategy with mass spectrometry or liquid chromatography with mass spectrometry...

OBJECTIVE: Previous work measures spinal cord thinning in chronic progressive myelopathies, including HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and multiple sclerosis (MS). Quantitative measurements of spinal cord atrophy are important in fully characterizing these and other spinal cord diseases. We aimed to investigate patterns of spinal cord atrophy and correlations with clinical markers. METHODS: Spinal cord cross sectional area was measured in individuals (24 healthy controls (HC), 17 asymptomatic carriers of HTLV-1 (AC), 47 HAM/TSP, 74 RRMS, 17 SPMS, and 40 PPMS) from C1 to T10...

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With the increase in incidence of type 1 diabetes (T1DM), particularly in Westernised societies, there is an urgent need to understand the early molecular and metabolic alterations that accompany the autoimmune disease. This is not least because in murine models early intervention can prevent the development of overt disease. In this study we have applied a liquid chromatography (LC-) and gas chromatography (GC-) mass spectrometry (MS) metabolomics and lipidomics analysis of blood plasma and pancreas tissue extracts to follow the progression of disease in three models related to autoimmune diabetes: the non-obese diabetic (NOD) mouse, which is susceptible to the development of autoimmune diabetes, and the NOD-E (transgenic NOD mice that express the I-E heterodimer of the major histocompatibility complex II) and NOD- severe combined immunodeficiency (SCID) mouse strains, two models protected from the development of diabetes...

Application of various proteomics methodologies have been implemented for the global and targeted proteome analysis of many different types of biological samples such as tissue, urine, plasma, serum, blood, and cell lines. Among the aforementioned biological samples, tissue has an exceptional role into clinical research and practice. Disease initiation and progression is usually located at the tissue level of different organs, making the analysis of this material very important for the understanding of the disease pathophysiology...

Alzheimer's disease (AD) is characterized by extracellular deposition of amyloid-β (Aβ) plaques. These protein deposits impair synaptic plasticity thereby producing a progressive decline in cognitive function. Current therapies are merely palliative and only slow cognitive decline. Poly-N-methylated Aβ-Peptide C-Terminal Fragments (MEPTIDES) were recently shown to reduce Aβ toxicity in vitro and in Drosophila melanogaster, however whether these novel compounds are effective in inhibiting Aβ-induced toxicity in the mammalian brain remains unclear...

Blood markers other than islet autoantibodies are greatly needed to indicate the pancreatic beta cell destruction process as early as possible, and more accurately reflect the progression of Type 1 Diabetes Mellitus (T1D). To this end, a longitudinal proteomic profiling of human plasma using TMT-10plex-based LC-MS/MS analysis was performed to track temporal proteomic changes of T1D patients (n=11) across 9 serial time points, spanning the period of T1D natural progression, in comparison with those of the matching healthy controls (n=10)...

The use of magnetic nanostructures as theranostic agents is a multiplex task as physiochemical and biochemical properties including excellent magneto-responsive properties, low toxicity, colloidal stability and facile surface engineering capability are all required. Nonetheless, much progress has been made in recent years synthesis of "all-in-one" MNPs remain unambiguously challenging. Towards this direction, in this study is presented a facile incorporation of a soft magnetic phase (MnFe2O4 NPs) with a hard phase (CoFe2O4 NPs) in the presence of the biocompatible polymer sodium dodecyl sulfate (SDS), into spherical and compact bi-magnetic nanoclusters (NCs) with modulated magnetic properties that critically enhance hyperthermic efficiency and MRI contrast effect...

OBJECTIVES: to investigate the relationship between osteocalcin and non alcoholic fatty liver disease (NAFLD) in obese children. METHOD: 60 obese children with NAFLD were taken as patient group and 60 non - NAFLD children with matches age, sex and BMI were taken as control group. Anthropometric measurements, abdominal ultrasonography for diagnosis and grading of NAFLD, and laboratory investigations in the form of liver function tests, lipid profile, fasting serum glucose and insulin, and serum osteocalcin levels were done for all children...