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FCT is also acknowledged for the grant attributed to Joana Silva (SFRH/BD/103255/2014). This work was supported by the Portuguese Foundation for Science and Technology (FCT) through the strategic project UID/04292/2020 grant to MARE—Marine and Environmental Sciences Centre and UIDP/ 04046/2020 and UIDB/04046/2020 granted to BioISI—BioSystems and Integrative Sciences Institute, through POINT4PAC project (Oncologia de Precisao: Terapias e Tecnologias Inovadoras (SAICTPAC/0019/ 2015-LISBOA- 01–0145-FEDER-016405)), through CROSS-ATLANTIC project (PTDC/BIA-OUT/29250/2017), co-financed by COMPETE (POCI-01–0145-FEDER-029250) and through Molecules for Health project (PTDC/ BIA-BQM/28355/2017). This work was also funded by the Integrated Programme of SR&TD Smart Valorization of Endogenous Marine Biological Resources Under a Changing Climate (Centro01–0145-FEDER-000018), co-funded by Centro 2020 Programme, Portugal 2020, European Union, through the European Regional Development Fund. The treatment of Parkinson´s disease (PD) has benefited from significant advances resulting from the increasing research efforts focused on new therapeutics. However, the current treatments for PD are mostly symptomatic, alleviating disease symptoms without reversing or retarding disease progression. Thus, it is critical to find new molecules that can result in more effective treatments. Within this framework, this study aims to evaluate the neuroprotective and anti-inflammatory effects of three compounds (eleganolone, eleganonal and fucosterol) isolated from the brown seaweed Bifurcaria bifurcata. In vitro neuroprotective effects were evaluated on a PD cellular model induced by the neurotoxin 6-hydroxydopamine (6-OHDA) on SH-SY5Y human cells, while lipopolysaccharide (LPS) -stimulated RAW 264.7 macrophages were used to evaluate the anti-inflammatory potential. Additionally, the underlying mechanisms of action were also investigated. Compounds were isolated by preparative chromatographic methods and their structural elucidation attained by NMR spectroscopy. Among the tested compounds, eleganolone (0.1–1 μM; 24 h) reverted the neurotoxicity induced by 6-OHDA in about 20%. The neuroprotective effects were mediated by mitochondrial protection, reduction of oxidative stress, inflammation and apoptosis, and inhibition of NF-kB pathway. The results suggest that eleganolone may provide advantages in the treatment of neurodegenerative conditions and, therefore, should be considered for future preclinical studies. info:eu-repo/semantics/publishedVersion

Copyright © Ordem dos Médicos 2020, Multiple sclerosis typically affects young women of reproductive age. Therefore, all healthcare professionals involved in the follow-up of multiple sclerosis patients must be prepared to discuss pregnancy and breastfeeding issues and provide the best possible counselling. However, there are still many doubts and heterogeneous clinical approaches partly due to the lack of consensus and guidelines. Concerning the handling of disease modifying therapies during pregnancy and postpartum, existing uncertainties have been complicated by the increase in the number of treatments available in recent years. This article aims to present the state-of-the-art and provide guidance based on the best level of available evidence and expert opinion regarding the management of multiple sclerosis patients at different stages: pregnancy planning, pregnancy, partum, and the postpartum period., Este trabalho teve o financiamento de uma bolsa de investigação da Roche Farmacêutica Química LDA: EPAM129844-G.

Objectives: The aim of this study was to evaluate postmarketing dimethyl fumarate (DMF) safety and effectiveness in a real-world population with relapsing-remitting multiple sclerosis (RRMS). Methods: This was a retrospective, single-center study with RRMS patients treated with DMF. Demographic, clinical, and imagiological characteristics were analyzed, including annualized relapse rate (ARR), Expanded Disability Status Scale, "No Evidence of Disease Activity 3," previous treatment, adverse events, treatment duration, and reason for discontinuation. We investigated which baseline variables were associated with clinical and radiological outcomes. Results: We included 176 patients (70.4% females) with a median on-treatment follow-up time of 25.5 months. In total, 139 patients received prior disease-modifying therapies, and 37 were treatment-naive. Annualized relapse rate decreased by 77.1% in the total population (P < 0.001) and also decreased in the naive, tolerability switch, and efficacy switch groups by 95.8%, 56.7%, and 76.6% (P < 0.001). No Evidence of Disease Activity 3 status after 12 months of DMF treatment was maintained in 69.2% patients. Thirty patients (17%) discontinued treatment because of adverse drug reactions, and 21 (11.9%) because of lack of effectiveness. The occurrence of first relapse during follow-up was associated with higher ARR in the year before DMF start (hazard ratio, 4.833; P < 0.001) and prior exposure to multiple sclerosis treatments (tolerability and efficacy switchers). Conclusions: In this real-world audit, DMF appeared to be effective and safe for RRMS. Additionally, the study suggested that naive patients strongly benefit from DMF, and DMF also improves ARR in patients who switched from injectable therapies due to tolerability and efficacy issues. info:eu-repo/semantics/publishedVersion

A esclerose múltipla afeta tipicamente mulheres jovens em idade reprodutiva. Desta forma, todo os profissionais de saúde envolvidos no seguimento destes doentes deverão estar preparados para abordar as questões relacionadas com a gravidez e amamentação e fornecer o melhor aconselhamento possível. No entanto, existem ainda muitas dúvidas e abordagens clínicas heterogéneas em parte devido à ausência de consensos e normas orientadoras. No que concerne ao manuseamento das terapêuticas modificadoras de doença durante os períodos de gravidez e pós-parto, as incertezas têm sido agravadas devido ao aumento do número de fármacos disponíveis nos últimos anos. Este artigo visa apresentar a informação mais atual e fornecer orientações baseadas no melhor nível de evidência disponível e na opinião de peritos relativamente ao seguimento das doentes com esclerose múltipla em diferentes etapas: planificação da gravidez, gravidez, parto e período pós-parto., Multiple sclerosis typically affects young women of reproductive age. Therefore, all healthcare providers involved in the follow-up of multiple sclerosis patients must be prepared to discuss pregnancy and breastfeeding issues, and provide the best possible counselling. However, there are still many doubts and heterogeneous clinical approaches partly due to the lack of consensus and guidelines. Concerning the handling of disease modifying therapies during pregnancy and the postpartum period, uncertainties have been complicated by the increase in recent years of the number of available treatments. This article aims to present the state-of-the-art and provide guidance based on the best level of available evidence and expert opinion regarding the management of multiple sclerosis patients at different stages: pregnancy planning, pregnancy, partum, and the postpartum period.

Introduction: Sex hormones may modulate the clinical course of multiple sclerosis (MS) [1]. Sex steroids interact with cholesterol metabolism and the serum lipid profile has been associated with progression of disability in MS patients [2]. We hypothesized that the putative associations between lipoprotein metabolism and severity of MS could be modulated by sex steroids exposure. The aim of this study was to investigate whether oral contraceptives (OC) use changes the lipoprotein profile associated with disability in patients with MS. Materials and methods: Clinical data was collected from 133 women with the diagnosis of relapsing-remitting MS prior to the start of disease-modifying therapies. Patients who were using OC after disease onset (DO) (OC+, n = 57) were compared to those who never used OC or discontinued its intake before DO (OC−, n = 76). In both cohorts of subjects, the associations between the apolipoprotein E (ApoE) polymorphism and plasma lipid levels and the Expanded Disability Status Score (EDSS) and the Multiple Sclerosis Severity Score (MSSS) were evaluated using a hierarchic multiple regression analysis after adjustment for confounders. Approval for the study by the local Ethical Committee was obtained and all participants signed a written informed consent. Results: In patients carrying the E3/E3 phenotype of ApoE (73.7%), EDSS and MSSS were lower in OC + in comparison with OC- subgroup of patients (p

The potential application of Fucus spiralis, Bifurcaria bifurcata, Codium tomentosum and Codium vermilara extracts as post-harvest treatments in minimally processed (MP) Fuji apple was investigated. 0.5% solutions of each extract were applied to MP Fuji apple and its effect on product quality was assessed over 20 days of storage at 4 ± 2 °C in terms of moisture content, soluble solids concentration (SSC), firmness, browning index (BI) and POD and PPO activities. Application of Codium tomentosum extract resulted in a significant reduction in BI in comparison to all other tested treatments. POD and PPO activities were also significantly lower in MP apple treated with Codium tomentosum extract. These results identify Codium tomentosum extract functionality of reducing enzymatic browning, suggesting the potential application of this extract as a natural additive in MP fruit. Industrial relevance This study shows the advantages of using a novel post-harvest treatment based in edible seaweed extracts to preserve fresh-cut fruits, in particular Fuji apple. The results show clearly that this type of dipping treatment decreases browning index and inhibits enzymatic activities when compared with citric acid and control treatment (water). Codium tomentosum extract solution showed the highest efficacy, suggesting the potential application of this extract as a natural additive to be a substitute of chemicals used in food industry and its use has been restricted. This process is efficient, versatile and of simple implementation at the industrial level once the only change in the industrial process consists in the type of post-harvest solution treatment. Associated to the easy adaptation in the industrial process, the exponential development in aquaculture sector allows the obtention of this raw material in a sustained way. Extract functionality was attributed to its demarked inhibitory action on enzymatic activities of polyphenol oxidase and peroxidase, two major enzymes involved in enzymatic browning processes.

Background: The mechanisms underlying the influence of sex hormones in multiple sclerosis (MS) are uncertain. Sex steroids interact with cholesterol metabolism and the serum lipid profile has been associated with the severity of the disease. We hypothesized that the putative associations between lipoprotein metabolism and MS could be modulated by sex steroids exposure. The aim of this study was to investigate whether oral contraceptives (OC) use changes the lipoprotein profile associated with disability in patients with multiple sclerosis. Methods: Clinical data was collected from 133 relapsing-remitting multiple sclerosis (RRMS) women with a mean of 6.5 years of disease duration and prior to the start of disease-modifying therapies. Patients who were using OC after disease onset (DO) (OC+, n = 57) were compared to those who never used OC or discontinued its intake before DO (OC-, n = 76). In both cohorts of subjects, the associations between the apolipoprotein E (ApoE) polymorphism, and plasma lipid levels, and the annualized relapse rate (RR), the Expanded Disability Status Score (EDSS), and the Multiple Sclerosis Severity Score (MSSS) were evaluated using a hierarchic multiple regression analysis after adjustment for confounders. Results: Low density lipoprotein (LDL) levels were associated with higher EDSS (p = 0.010) and MSSS (p = 0.024) in the whole studied cohort. In E3/E3 phenotype carriers (73.7%), EDSS and MSSS were lower in OC+ in comparison with OC- subgroup of patients (p < 0.01). LDL and total cholesterol were associated with EDSS (p = 0.005 and p = 0.043, respectively), and LDL and the triglyceride/high density lipoprotein ratio with MSSS (p = 0.011 and p = 0.048, respectively) in OC+ patients. In OC- subgroup of patients, ApoE levels were associated with EDSS (p = 0.012) and MSSS (p = 0.031). No significant interactions between the lipid variables or OC use and RR were observed. Conclusions: Serum lipid profile is associated with protective effects of OC use on disability of RRMS patients. Lipoprotein metabolism may be involved in the modulatory effects of sex steroids on the severity of the disease. Merck Bayer Health Care Teva PPAR/2006 LIPESBETA/2005 LILERICOP/2004 FCT-Foundation of Science and Technology, I.P. (Portugal) UID/BIM/04583/2019 info:eu-repo/semantics/publishedVersion

OBJECTIVES The aim of this study was to evaluate postmarketing fingolimod safety and effectiveness in a real-world clinical population. METHODS This was a retrospective, single-center study with active multiple sclerosis patients treated with fingolimod with at least 12 months of follow-up. Demographic and clinical and imaging characteristics, including annualized relapse rate (ARR), Expanded Disability Status Score, previous treatment, adverse events, treatment duration, and reason for discontinuation, were analyzed. RESULTS Sixty-three patients were included; 61.9% were females. Mean age and mean disease duration were 30.9 ± 9.3 years and 11.4 ± 6.9 years, respectively. Fifty-one patients received prior first-line disease-modifying therapies, 11 patients were previously treated with natalizumab, and 1 was treatment naive. The ARR decreased by 75.3% for the total population at the end of the first year of treatment (P < 0.0001). The proportion of relapse-free patients improved significantly. All patients previously treated with natalizumab switched because of safety concerns, although the ARR kept low after treatment initiation. Only 3 patients (4.8%) discontinued treatment because of adverse drug reactions, and 2 (3.2%) because of lack of effectiveness. CONCLUSIONS In this real-world audit, fingolimod appeared to be effective after first-line treatment failure in reducing disease activity and progression of disability throughout the observational period and may be an effective option after natalizumab. Fingolimod was well tolerated with low rates of discontinuation and adverse events.

Introdução: A esclerose múltipla caracteriza-se pela presença de lesões inflamatórias a nível do encéfalo e medula espinhal. A ressonância magnética é atualmente um exame indispensável no diagnóstico, na avaliação da atividade da doença e na resposta ao tratamento. Embora na nossa prática as vantagens da ressonância magnética estejam bem estabelecidas, continuam a existir dificuldades técnicas (uso de sequências e protocolos não padronizados) e clínicas (frequência de exames não adequada) que podem dificultar o diagnóstico e o seguimento dos doentes. Neste contexto, o Grupo de Estudos de Esclerose Múltipla e a Sociedade Portuguesa de Neurorradiologia, após discussão conjunta, designaram um comité de peritos para a criação de recomendações adaptadas à realidade nacional sobre a utilização da ressonância magnética na esclerose múltipla. O objetivo deste documento é publicar as primeiras recomendações de consenso portuguesas sobre a utilização da ressonância magnética na esclerose múltiplana prática clínica.Material e Métodos: O Grupo de Estudos de Esclerose Múltipla e a Sociedade Portuguesa de Neurorradiologia, após discussão do tema em reuniões de âmbito nacional e de uma reunião do grupo de trabalho que teve lugar na Figueira da Foz em maio de 2017, designaram um comité de peritos que elaboraram por método de consenso vários protocolos padronizados sobre o uso da ressonância magnética no diagnóstico e seguimento da esclerose múltipla. O documento teve como base a melhor evidência científica e a opinião dos peritos. Posteriormente, o documento foi enviado para escrutínio à maioria dos responsáveis de consulta de esclerose múltipla e dos departamentos de neurorradiologia; os comentários e sugestões foram considerados. Os protocolos técnicos referentes à aquisição de imagem e a informação que deverá constar no relatório destes exames serão publicados numa publicação separada.Resultados: Neste artigo são propostas várias orientações práticas para promover estratégias padronizadas para serem aplicadas na prática clínica dos profissionais de saúde portugueses no que se refere ao uso da ressonância magnética na esclerose múltipla.Conclusão: Os autores esperam que estas primeiras orientações portuguesas, sobre a utilização da ressonância magnética na esclerose múltipla na prática clínica, baseadas nas melhores evidências e práticas clínicas disponíveis, sirvam para otimizar a gestão da esclerose múltipla e melhorar o tratamento destes doentes em Portugal.

Background: Cancer represents a serious threat for human health with high social and economic impacts worldwide. Therefore, the development of new anticancer drugs is of most importance. The aim of the present study was to evaluate the antitumor potential of twelve algae from Portugal coast on an in vitro model of human hepatocellular carcinoma (HepG-2 cells).Results: Both extracts of Asparagopsis armata (1000 µg/ml; 24 h) presented high cytotoxicity with 11.22 ± 2.98 and 1.51 ± 0.38 % of HepG-2 live cells, respectively. Sphaerococcus coronopifolius methanolic and dichloromethane extracts (1000 µg/ml) also generated high reduction on HepG-2 viability (14.04 ± 2.62 and 12.84 ± 3.82 % of HepG-2 live cells, respectively). The most potent anti-proliferative activity was induced by dichloromethane extract (1000 µg/ml; 24 h) of Sphaerococcus coronopifolius, Asparagopsis armata and Plocamium cartilagineum with 99.61 ± 0.27, 98.56 ± 0.81 and 85.13 ± 1.04 % of cell’s proliferation reduction, respectively. Sphaerococcus coronopifolius dichloromethane extract exhibited the highest potency both on cytotoxicity and anti-proliferation assays with an IC50 of 14.1 and 32.3 μg/ml, respectively.Conclusions: Sphaerococcus coronopifolius is a promising source of new molecules with possible application on cancer therapeutics.

Lipids are one of the key macromolecules of life and play crucial and transversal biological roles in all live organisms: they are the major component of cellular membranes; are important fuel molecules; one of the main means of energy storage; are present in important signal transduction pathways; are precursors for hormonal synthesis, transport and also contribute towards the absorption of fat-soluble vitamins, etc. Apart from the nutritional, physiological and regulatory function, lipids are directly or indirectly (as vehicle) linked to fl avors and aromatic substances. There is a general agreement that lipids are critical for food, food processing and in cooking (Lichtenstein et al. 1998; Berg et al. 2007; Schmid 2010).

Background and purpose: The influence of apolipoprotein E (ApoE) polymorphism on clinical severity of multiple sclerosis (MS) is still controversial. Cigarette smoking has been suggested to influence the progression of disability in these patients. In this study, we aimed to investigate whether an interaction of smoking with the ApoE polymorphism influences the progression of disability in MS patients. Methods: Smoking history from 205 female patients with MS was obtained. Clinical data collected include age at onset, disease duration, annual relapse rate, the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score (MSSS). ApoE polymorphism was examined in all patients and stratified according to smoking status and associations with the clinical data investigated. Results: There were no significant associations between cigarette smoking and any of the clinical characteristics in the whole group of patients. In women carrying the ApoE E4 isoform, smokers had a lower EDSS (P = 0.033) and MSSS (P = 0.023) in comparison with non-smokers. Conclusion: Our data suggest that in women with MS carrying the ApoE E4 isoform, cigarette smoking may have a protective influence on disease progression and accumulation of disability. These findings need to be confirmed by future large longitudinal studies.

A healthy 58-year-old male presented with dysarthria, bilateral horizontal nystagmus, right dysmetria, and marked gait ataxia, which had started 6 days before, after falling from a tree. MRI (Figure) revealed lesions in the right cerebellum extending to the peduncle and pons. Thorough laboratory investigations revealed a positive HIV-1 serology with a serum CD4 count of 47 and a positive PCR for JC virus in otherwise normal CSF, establishing the diagnosis of progressive multifocal leukoencephalopathy (PML). PML presentation with lesions confined to the posterior fossa alone is unusual1,2 and descriptions as the first manifestation of HIV are very rare3.

The original glucose-based formulation of Betaferon®/Betaseron® (interferon beta-1b) requires refrigerated storage. A refrigeration-free formulation of interferon beta-1b, based on mannitol, is stable at room temperature for up to 2 years, and offers a greater degree of flexibility for patients with multiple sclerosis (MS). We compared the safety and tolerability of the two formulations in a 24-week, randomized, double-blind, parallel group, Phase IV clinical study conducted in 303 patients with MS. Patients received the glucose formulation (IFNβ-1b-G) for 8 weeks, and were then randomized to receive either IFNβ-1b-G or the refrigeration-free formulation (IFNβ-1b-M) for a further 8 weeks. On completion of the double-blind phase, all patients received IFNβ-1b-M for an 8-week follow-up period. The primary outcome measure was the proportion of injection sites that developed reactions per patient during the double-blind period. In addition, a range of secondary outcomes relating to these reactions was also assessed. The difference in the proportion of injection-site reactions between the two groups was not statistically significant (59% IFNβ-1b-G versus 60% IFNβ-1b-M). There were no statistically significant differences observed between the two treatment groups in any of the secondary tolerability endpoints. The results from this study demonstrate that the tolerability and safety profiles of both formulations are extremely good, and that the refrigeration-free formulation of interferon beta-1b is comparable with that of the original glucose formulation.

The sensitivity of the Cl−/HCO3−exchanger to dopamine D1- and D2-like receptor stimulation in immortalized renal proximal tubular epithelial cells from the spontaneous hypertensive rat (SHR) and Wistar-Kyoto rat (WKY) was examined. The activity of the Cl−/HCO3−exchanger (in pH U/s) in SHR cells (0.00191) was greater than in WKY cells (0.00126). The activity of Cl−/HCO3−exchanger was exclusively observed at the apical cell side and probably occurs through the SLC26A6 anion transporter that is expressed in both WKY and SHR cells. Stimulation of D1-like receptors with SKF-38393 markedly attenuated the HCO3−-dependent intracellular pH recovery in WKY cells but not in SHR cells. Stimulation of D2-like receptors with quinerolane did not alter Cl−/HCO3−exchanger activity in both WKY and SHR cells. The selective D1-like receptor antagonist SKF-83566 prevented the effect of SKF-38393. Both WKY and SHR cells responded to dibutyryl-cAMP (DBcAMP) with inhibition of the Cl−/HCO3−exchanger, and downregulation of PKA (overnight exposure to DBcAMP) abolished the inhibitory effect of both DBcAMP and SKF-38393 in WKY cells. Both SHR and WKY cells responded to forskolin with increases in the formation of cAMP. However, only WKY responded to SKF-38393 with increases in the formation of cAMP that was prevented by SKF-83566. It is concluded that WKY cells respond to D1-like dopamine receptor stimulation with inhibition of the apical Cl−/HCO3−(SLC26A6) exchanger and SHR cells have a defective D1-like dopamine response.

Background Neuromyelitis Optica (NMO) is an inflammatory demyelinating disease of the CNS. There have been few epidemiologic studies on NMO, none in Portugal. Objective To analyze the clinical, biological and MRI characteristics from a cohort of Portuguese patients who fulfilled the Wingerchuk 2006 NMO/NMOSD criteria. To identify and characterize those who had concomitant autoimmune disease or circulating autoantibodies. Methods We performed an observational, retrospective, multicenter study in 5 Hospital Centers in Portugal. Results Sixty-seven patients fulfilled the inclusion criteria. They were mainly Caucasian, 55 female. Median age at onset was 32.0 years and mean follow-up 7.4 ± 6.0 years. Twenty-one patients were definite NMO and optic neuritis (ON) the most frequent initial presentation. Forty-six were classified as NMO spectrum disorders. The main subtypes were recurrent ON and single longitudinally extensive transverse myelitis. Twenty-four patients had positive AQP4-IgG. Twenty-three had other circulating autoantibodies. Fifteen out of 67 patients had concomitant autoimmune disease. There was a significant correlation between the presence of autoimmune disease and the positivity for AQP4-IgG. Five patients died, all definite NMO. Conclusion This is the first study about this rare disease in Portugal. Demographic features were similar to other studies. The existence of concomitant autoimmune disease was significantly associated with seropositivity for AQP4-IgG.

Introduction. Camptocormia is an extreme flexion of the toracolum­bar spine that exacerbates by walking and is relieved in the supine position. It is described with increasing frequency in association with Parkinson disease (PD). Its pathogenesis remains unclear. One of the hypotheses proposed defends that when associated with PD probably it is a focal action dystonia of the paraspinal muscles. Dystonia may be accompanied of a “geste antagoniste”. It is a kind of trick that en­ables the patient to alleviate dystonic posture. We present two cases in which the patients use sensory tricks to alleviate their posture during gait. Case Reports. Patient 1: A 74-year–old woman, with a 2-year of PD. Clinical examination disclosed parkinsonian signs and camp­tocormia. She was able to partially overcome it by pushing her hands against her thighs. Patient 2: A 80-year-old woman, with a 1-year probable PD. Neurological examination revealed postural instability, freezing gait and camptocormia that partially remits when she pushes a bar at the level of her waist. Conclusions. The particularity of these cases is that patients are able to improve camptocormia during gait by specific tricks. This clinical improvement supports the hypothesis that camptocormia in PD is a focal dystonia of the paraspinal muscles.

Serum ferritin levels have been found to be increased in patients with active progressive multiple sclerosis (MS). However, its levels are reported to be unchanged in stable and in active relapsing-remitting (RR) form of the disease. No research to date has assessed the influence of interferon β (IFN-β) on ferritin concentrations. In this study, serum ferritin levels were measured in 43 individuals with RR-MS and 38 age- and sex-matched control volunteers. There were no significant differences between controls and patients under stable and untreated conditions. In patients at 12 months after the beginning of IFN-β therapy, ferritin levels were higher in women and in men, in comparison with baseline (71.4 ± 58.6 vs 43.4 ± 29.9 ng/mL, P = 0.0006 and 216.0 ± 124.3 vs 127.8 ± 74.9 ng/mL, P = 0.0022, respectively). These results suggest that larger prospective studies are required to evaluate the role of serum ferritin in MS and its potential usefulness in monitoring responses to immunomodulatory therapies.

Experimental and clinical data suggest a role of sex steroids in the pathogenesis of multiple sclerosis (MS). Scant information is available about the potential effect of oral contraceptive (OC) use on the prognosis of the disease. We aimed to evaluate this. The study population consisted of 132 women with relapsing-remitting MS before receiving disease modifying treatment and a mean disease duration 6.2 (SD 5.1) years. Three groups of patients were distinguished according to their OC behavior: [1] never-users, patients who never used OC [2] past-users, patients who stopped OC use before disease onset, and [3] after-users, those who used these drugs after disease onset. Multiple linear and logistic regression models were used to analyze the association between oral contraceptive use and annualized relapse rates, disability accumulation and severity of the disease. After-user patients had lower Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS) values than never users (p

Interferon-beta (IFN-beta) therapy for multiple sclerosis (MS) is associated with a potential for induction of neutralizing antibodies (NAbs). Because immune reactivity depends on changes in lipoprotein metabolism, we investigated whether plasma lipoprotein profiles could be associated with the development of NAbs. Thirty-one female MS patients treated with subcutaneously administered IFN-beta were included. Demographic and clinical characteristics were compared between NAbs response groups using t tests for continuous and logistic regression analysis and Fisher’s exact tests for categorical data, respectively. Multivariate logistic regression was used to evaluate the effect of potential confounders. Patients who developed NAbs had lower apoE levels before treatment, 67 (47–74) mg/L median (interquartile range), and at the moment of NAb analysis, 53 (50–84) mg/L, in comparison to those who remained NAb-negative, 83 (68–107) mg/L, P = 0.03, and 76 (66–87) mg/L, P = 0.04, respectively. When adjusting for age and smoking for a one-standard deviation decrease in apoE levels, a 5.6-fold increase in the odds of becoming NAb-positive was detected: odds ratios (OR) 0.18 (95% CI 0.04–0.77), P = 0.04. When adjusting for apoE, smoking habit became associated with NAb induction: OR 5.6 (95% CI 1.3–87), P = 0.03. These results suggest that apoE-containing lipoprotein metabolism and, possibly, tobacco smoking may be associated with risk of NAb production in female MS patients treated with IFN-beta.

To assess whether interferon β1a (IFNβ1a) therapy affects plasma lipoprotein metabolism, twelve patients with relapsing-remitting multiple sclerosis (MS) were studied during a two-year follow-up period. High density lipoprotein (Hdl2) cholesterol and the Hdl2/Hdl3 ratio were increased at year 2 and lipoprotein (a) was transitorily increased at year 1, in comparison to baseline levels. Apolipoprotein A-I was lower and apolipoprotein E higher at year 1, only in a subgroup of patients who experienced relapses and/or progressed during therapy. These findings suggest that IFNβ1a treatment is associated with changes in the lipoprotein metabolism. Alterations in this metabolism could be related to the immunomodulatory actions of the drug and the disease activity in multiple sclerosis patients.