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The MS pathophysiology may be among factors for the lower CV risk factors in MS patients. Future studies should examine whether the chronic use of many pharmacological agents influence CV risk factors in MS patients.

The significant reduction of sRAGE in MS patients relative to healthy controls supports the potential role for RAGE axis in MS clinical pathology. Lower levels of sRAGE may be associated with enhanced inflammatory responses. Based on these observations, further investigations into the role of sRAGE in MS clinical pathology is warranted.

BackgroundThis study compared the level of advanced glycation end products (AGEs), N-(Carboxymethyl)lysine (CML) and N-(Carboxyethyl)lysine (CEL), in patients with multiple sclerosis (MS) and healthy controls (HCs), correlating these markers with clinical indicators of MS disease severity.MethodsCML and CEL plasma levels were analyzed in 99 MS patients and 43 HCs by tandem mass spectrometry (LC/MS/MS). Patients were stratified based on drug modifying therapies (DMTs) including interferon beta, glatiramer acetate and natalizumab.ResultsThe level of plasma CEL, but not CML, was significantly higher in DMT-naïve MS patients when compared to HCs (P < 0.001). Among MS patients, 91% had higher than mean plasma CEL observed in HCs. DMTs reduced CML and CEL plasma levels by approximately 13% and 40% respectively. CML and CEL plasma levels correlated with the rate of MS clinical relapse.ConclusionOur results suggest that AGEs in general and CEL in particular could be useful biomarkers in MS clinical practice. Longitudinal studies are warranted to determine any causal relationship between changes in plasma level of AGEs and MS disease pathology. These studies will pave the way for use of AGE inhibitors and AGE-breaking agents as new therapeutic modalities in MS.

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SUMMARYObjectives: This retrospective study aimed to determine (1) the association between the use of three major disease modifying therapies (DMTs) (Interferon-beta [IFN-b], Glatiramer acetate [GA], Natalizumab [NTZ]) and cardiovascular (CV) risk factors in multiple sclerosis (MS) patients, and (2) the association between the use of CV drugs (antihypertensive, hypolipidemic, and antiplatelets) and other drugs acting on the CV system (antispastics/anticonvulsants/anxyolitics, antidepressants/stimulants), and MS disease severity. Methods: The charts of 188 patients with MS, who were taking one of the three DMTs, and 110 patients, who were na€ ıve to these drugs, were retrospectively reviewed. The obtained data included height and weight, fasting lipid profiles, plasma glucose, systolic and diastolic BP, smoking habit, list of medications, and indicators of MS disease severity. Results: The use of DMTs was associated with higher diastolic BP readings, as well as higher plasma glucose and HDL-C plasma levels. In addition, there was an association between CV risk factors and the type of DMTs. When compared to DMT-na€ ıve patients with MS, the use of IFN-b and GA was associated with higher CV risk factors, whereas the use of NTZ was associated with lower CV risk factors. In DMT-na€ ıve patients, the use of CV and related drugs was associated with higher Extended Disability Status Scale (EDSS) and higher MS Severity Scale (MSSS). Conclusion: There is an association between higher CV risk factors and the use of DMTs. Furthermore, CV and related drugs have the potential for modulating MS disease severity.

This pilot study examined the status of the master iron regulatory peptide, hepcidin, and peripheral related iron parameters in Alzheimer’s disease (AD) and mild cognitive impairment patients, and evaluated the relationship between iron dyshomeostasis and amyloid-beta (Aβ), cognitive assessment tests, neuroimaging and clinical data. Frozen serum samples from the Oregon Tissue Bank were used to measure serum levels of hepcidin, ferritin, Aβ40, Aβ42 using enzyme-linked immunosorbent assay. Serum transferrin levels were determined indirectly as total iron binding capacity, serum iron was measured and the percent saturation of transferrin calculated. The study variables were correlated with the patients’ existing cognitive assessment tests, neuroimaging, and clinical data. Hepcidin, and iron-related proteins tended to be higher in AD patients than controls, reaching statistical significance for ferritin, whereas Aβ40, Aβ42 serum levels tended to be lower. Patients with pure AD had three times higher serum hepcidin levels than controls; gender differences in hepcidin and iron-related proteins were observed. Patient stratification based on clinical dementia rating-sum of boxes revealed significantly higher levels of iron and iron-related proteins in AD patients in the upper 50% as compared to controls, suggesting that iron dyshomeostasis worsens as cognitive impairment increases. Unlike Aβ peptides, iron and iron-related proteins showed significant association with cognitive assessment tests, neuroimaging, and clinical data. Hepcidin and iron-related proteins comprise a group of serum biomarkers that relate to AD diagnosis and AD disease progression. Future studies should determine whether strategies targeted to diminishing hepcidin synthesis/secretion and improving iron homeostasis could have a beneficial impact on AD progression.

The study is aimed to determine the role of luteolin (3',4',5,7-tetrahydroxyflavone), alone and in combination with human interferon-beta (IFN-β), in modulating the immune response(s) of peripheral blood mononuclear cells (PBMCs) isolated from multiple sclerosis (MS) patients. PBMC proliferation in the presence or absence of these drugs was determined and the production of proinflammatory cytokines (IL-1β, TNF-α), and the ratio of cell migration mediator MMP-9, and its inhibitor, TIMP-1 was assessed in the culture supernatants. Luteolin reduced, in a dose-dependent manner, the proliferation of PBMCs, and modulated the levels of IL-1β and TNF-α released by PBMCs in the culture supernatants. Luteolin reduced the MMP-9/TIMP-1 ratio via lowering MMP-9 production. In the majority of cases, luteolin, when combined with IFN-β, had additive effects in modulating cell proliferation, IL-1β, TNF-α, MMP-9 and TIMP-1.