Serum Arsenic and Lipid Peroxidation Levels in Patients with Multiple Sclerosis

Oxidative stress plays a crucial role in the pathogenesis of multiple sclerosis (MS). Previous studies have shown that oxidative stress is one of the main underlying mechanisms of arsenic-induced cellular damage. The aim of this study was to assess the serum levels of arsenic and its relationship with lipid peroxidation in MS patients from Tabriz, as the third polluted city of Iran. The study population included 38 MS female patients and 38 age-matched healthy controls. Serum malondialdehyde (MDA) and arsenic levels were measured using thiobarbituric acid reactive substances (TBARS) assay and electrothermal atomic absorption spectrometry, respectively. The results showed that the arsenic (P?<?0.01) and MDA (P?=?0.03) levels were significantly higher in patients with MS than those in control. Moreover, serum levels of arsenic and MDA were positively correlated in MS patients. The elevated levels of serum arsenic might explain the increased oxidative stress in MS patients. We suggest that high arsenic levels in serum may lead to MS development, and therefore, exposure to this metal should be limited.     

Linoleate and Fatty-acid Patterns of Serum Lipids in Multiple Sclerosis and Other Diseases

The linoleic acid content of serum lipids was measured in 47 patients with multiple sclerosis, 29 patients with other neurological diseases, 35 patients with acute non-neurological illnesses, and 49 healthy control subjects. Reduced linoleic acid content of serum lipids was not specific to multiple sclerosis and occurred in all ill patients with acute non-neurological illness. The fatty-acid pattern of serum lipids in illness resembles that of essential fatty-acid deficiency. It seems that this pattern of reduced linoleic acid content with increased oleic, palmitic, and palmitoleic acid content may be a general phenomenon in ill patients.     

Cannabinoids and Multiple Sclerosis

This review discusses clinical and preclinical evidence that supports the use of cannabinoid receptor agonists for the management of multiple sclerosis. In addition, it considers preclinical findings that suggest that as well as ameliorating signs and symptoms of multiple sclerosis, cannabinoid CB₁ and/or CB₂ receptor activation may suppress some of the pathological changes that give rise to these signs and symptoms. Evidence that the endocannabinoid system plays a protective role in multiple sclerosis is also discussed as are potential pharmacological strategies for enhancing such protection in the clinic.     

Serum Biomarker gMS-Classifier2: Predicting Conversion to Clinically Definite Multiple Sclerosis

Background

Anti-glycan antibodies can be found in autoimmune diseases. IgM against glycan P63 was identified in clinically isolated syndromes (CIS) and included in gMS-Classifier2, an algorithm designed with the aim of identifying patients at risk of a second demyelinating attack.

Objective

To determine the value of gMS-Classifier2 as an early and independent predictor of conversion to clinically definite multiple sclerosis (CDMS).

Methods

Data were prospectively acquired from a CIS cohort. gMS-Classifier2 was determined in patients first seen between 1995 and 2007 with ≥ two 200 µL serum aliquots (N = 249). The primary endpoint was time to conversion to CDMS at two years, the factor tested was gMS-Classifier2 status (positive/negative) or units; other exploratory time points were 5 years and total time of follow-up.

Results

Seventy-five patients (30.1%) were gMS-Classifier2 positive. Conversion to CDMS occurred in 31/75 (41.3%) of positive and 45/174 (25.9%) of negative patients (p = 0.017) at two years. Median time to CDMS was 37.8 months (95% CI 10.4–65.3) for positive and 83.9 months (95% CI 57.5–110.5) for negative patients. gMS-Classifier2 status predicted conversion to CDMS within two years of follow-up (HR = 1.8, 95% CI 1.1–2.8; p = 0.014). gMS-Classifier2 units were also independent predictors when tested with either Barkhof criteria and OCB (HR = 1.2, CI 1.0–1.5, p = 0.020) or with T2 lesions and OCB (HR = 1.3, CI 1.1–1.5, p = 0.008). Similar results were obtained at 5 years of follow-up. Discrimination measures showed a significant change in the area under the curve (ΔAUC) when adding gMS-Classifier2 to a model with either Barkhof criteria (ΔAUC 0.0415, p = 0.012) or number of T2 lesions (ΔAUC 0.0467, p = 0.009), but not when OCB were added to these models.

Conclusions

gMS-Classifier2 is an independent predictor of early conversion to CDMS and could be of clinical relevance, particularly in cases in which OCB are not available.     

Herpes Zoster and Multiple Sclerosis

No significant difference was found between 50 consecutive patients with multiple sclerosis and matched controls in respect of previous infection with rubella or measles and chicken-pox, or of previous vaccination and immunizing injections. Significantly more patients had a past history of herpes zoster compared with the controls.     

Congenital Abnormalities and Multiple Sclerosis

Background  

There is a strong maternal parent-of-origin effect in determining susceptibility to multiple sclerosis (MS). One hypothesis is that an abnormal intrauterine milieu leading to impaired fetal development could plausibly also result in increased susceptibility to MS. A possible marker for this intrauterine insult is the presence of a non-fatal congenital anomaly.     

LINE-1 Hypermethylation in Serum Cell-Free DNA of Relapsing Remitting Multiple Sclerosis Patients

Concentrations of cell-free DNA (cfDNA) circulating in blood and its epigenetic variation, such as DNA methylation, may provide useful diagnostic or prognostic information. Long interspersed nuclear element-1 (LINE-1) constitutes approximately 20% of the human genome and its 5’UTR region is CpG rich. Due to its wide distribution, the methylation level of the 5’UTR of LINE-1 can serve as a surrogate marker of global genomic DNA methylation. The aim of the current study was to investigate whether the methylation status of LINE-1 elements in serum cell-free DNA differs between relapsing remitting multiple sclerosis (RRMS) patients and healthy control subjects (CTR). Serum DNA samples of 6 patients and 6 controls were subjected to bisulfite sequencing. The results showed that the methylation level varies among distinct CpG sites in the 5’UTR of LINE-1 repeats and revealed differences in the methylation state of specific sites in this element between patients and controls. The latter differences were largely due to CpG sites in the L1PA2 subfamily, which were more frequently methylated in the RRMS patients than in the CTR group, whereas such differences were not observed in the L1HS subfamily. These data were verified by quantitative PCR using material from 18 patients and 18 control subjects. The results confirmed that the methylation level of a subset of the CpG sites within the LINE-1 promoter is elevated in DNA from RRMS patients in comparison with CTR. The present data suggest that the methylation status of CpG sites of LINE repeats could be a basis for development of diagnostic or prognostic tests.