ABSTRACT
Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease of the central nervous system (CNS). The etiology of MS is not well understood, but it's likely one of the genetic and environmental factors. Approximately 85% of patients have relapsing-remitting MS (RRMS), while 10-15% have primary progressive MS (PPMS). Epstein-Barr virus (EBV) and Human herpesvirus 6 (HHV-6), members of the human Herpesviridae family, are strong candidates for representing the macroenvironmental factors associated with MS) pathogenesis. Antigenic mimicry of EBV involving B-cells has been implicate in MS risk factors and concomitance of EBV and HHV-6 latent infection has been associated to inflammatory MS cascade. To verify the possible role of EBV and HHV-6 as triggering or aggravating factors in RRMS and PPMS, we compare their frequency in blood samples collected from 166 MS patients. The presence of herpes DNA was searched by real-time PCR (qPCR). The frequency of EBV and HHV-6 in MS patients were 1.8% (3/166) and 8.9% (14/166), respectively. Among the positive patients, 100% (3/3) EBV and 85.8% (12/14) HHV-6 are RRMS and 14.4% (2/14) HHV-6 are PPMS. Detection of EBV was 1.2% (2/166) and HHV-6 was 0.6% (1/166) in blood donors. About clinical phenotype of these patients, incomplete multifocal myelitis, and optic neuritis were the main CNS manifestations. These are the first data about concomitant infection of these viruses in MS patients from Brazil. Up to date, our findings confirm a higher prevalence in female with MS and a high frequency of EBV and HHV-6 in RRMS patients.
Subject(s)
Epstein-Barr Virus Infections , Herpesvirus 6, Human , Multiple Sclerosis , Neurodegenerative Diseases , Humans , Female , Herpesvirus 4, Human/genetics , Herpesvirus 6, Human/genetics , DNA, Viral , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/epidemiology , Brazil/epidemiologyABSTRACT
Abstract Organometallic compounds, Bis (2,4,6,8 teramethyl-indacenyl) di Iron (1), Bis (2,4,6,8 teramethyl s-indacenyl) mono iron, mono cobalt (2), and Bis (2,6 diethyl-4,8-dimethyl-s-indacenyl) di cobalt (3) were synthesised by means of salt elimination strategy, using Fe(II) and Co(II) salts. The compounds were characterised through spectroscopic and electrochemical methods. Magnetic measurements were carried out by Physical Property Measurement System (PPMS). Mossbauer spectroscopic data reveals that in all compounds, surprisingly, Iron is in +3 oxidation state. DFT calculations have been carried out to understand the change in the oxidation state of a metal. DFT study confirms the electron transfer nature of ligand to metal. Cyclic voltametric study on these compounds shows a large separation (ΔE>800mV) between two oxidation peaks confirming the strong interaction between the metal centres. Magnetic measurements on these organometallic compounds reveals that they exhibit a ferrimagnetic behaviour at temperatures below 40 K.
Resumen En este trabajo se sintetizaron los compuestos organometálicos Bis (2,4,6,8 terametil-indacenil) férrico (1), Bis (2,4,6,8 terametil s-indacenil) ferroso, cobaltoso (2) y Bis (2,6 dietil-4,8-dimetil-s-indacenil) di cobalto (3) mediante la estrategia de eliminación de sales, utilizando sales de Fe(II) y Co(II).Los compuestos se caracterizan por métodos espectroscópicos y electroquímicos. Las mediciones magnéticas se llevaron a cabo mediante el sistema de medición de propiedades físicas (PPMS). Los datos espectroscópicos Mossbauer revelan que, en todos los compuestos, sorprendentemente, el hierro se encuentra en el estado de oxidación +3. También se realizaron cálculos DFT para comprender el cambio en el estado de oxidación de los metales. El estudio DFT confirmó la naturaleza de transferencia de electrones del ligando al metal. El estudio voltamperométrico cíclico de estos compuestos muestra una gran separación (ΔE>800mV) entre los dos picos de oxidación que confirman la fuerte interacción entre los centros metálicos. Las mediciones magnéticas de estos compuestos organometálicos revelan que presentan un comportamiento ferrimagnético a temperaturas inferiores a 40 K.
Resumo Compostos organometálicos, Bis (2,4,6,8 terametil-indacenil) di ferro (1), Bis (2,4,6,8 terametil s-indacenil) mono ferro, mono cobalto (2) e Bis (2,6 dietil-4,8-dimetil-s-indacenil) di cobalto (3) foram sintetizados por estratégia de eliminação de sal, utilizando sais de Fe(II) e Co(II). Os compostossão caracterizados por métodos espectroscópicos e eletroquímicos. As medições magnéticas foram realizadas pelo Sistema de Medição de Propriedades Físicas (PPMS). Os dados espectroscópicos Mossbauerrevelam que em todos os compostos, surpreendentemente, o ferro está em +3 estado de oxidação.Os cálculos do DFT foram realizados para entender a mudança no estado de oxidação de um metal. O estudo DFT confirma a natureza da transferência de elétrons do ligante para o metal. O estudovoltamétrico cíclico dessescompostosmostrauma grande separação (ΔE>800mV) entre dois picos de oxidação confirmando a forteinteração entre os centros metálicos. As medições magnéticas nestescompostos organometálicos revelam que eles apresentam um comportamento ferrimagnético a uma temperatura abaixo de 40 K.
ABSTRACT
BACKGROUND: Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS). B cells have an essential role in the disease pathogenesis and therefore selective B-cell depletion are commonly used to treat the disease. Rituximab (RTX), a chimeric anti-CD20 monoclonal antibody had demonstrated reduced inflammatory activity and radiological activity in MS patients. Due to economic constrains and treatment access limitations, RTX is often used as a treatment alternative in these patients. Here, we described our center experience in RTX -treated MS patients. METHODS: A single-center observational retrospective study was conducted in a Mexican cohort MS during 2010 to 2020. All patients had a confirmed MS diagnosis.All patients received fixed scheme involving induction with 1 g on day one and day 15, followed by 500 mg-1 g every six months for maintenance. Annual Relapse Rate (ARR), Progression index (PI), Expanded Disability Status Scale (EDSS) and MRI activity of the disease were evaluated. Comparison between naïve and non-naïve patients was also conducted. RESULTS: A total of 85 patients were included. The mean age at diagnosis was 33.13 (±8.90) years with 73 (85.9%) being RRMS. 39 (34.1%) were treatment-naïve. While treated with RTX, 62(72.9%) patients reached a free-of-relapse status, with statistically significant decrease in the mean ARR from 0.82 to 0.36 [0.14 (95%CI: 0.09-0.20), p = 0.0001 and EDSS [0.25 CI 0-0.5 (p = 0.034)] and a decrease in their T1 Gd-enhancing MRI lesions (1.64 vs. 0.12 CI 0.70-2.30, p = 0.004. 29 (29.4%) patients achieved NEDA-3. Among all patients, only 2 (2.4%) experienced infusion-related mild adverse events. No serious adverse events were reported. CONCLUSION: We found significant clinical and radiological improvement in naïve and non-naïve MS patients treated with RTX.
Subject(s)
Antineoplastic Agents , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Antineoplastic Agents/therapeutic use , Humans , Immunologic Factors/adverse effects , Multiple Sclerosis/chemically induced , Multiple Sclerosis/diagnostic imaging , Multiple Sclerosis/drug therapy , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Retrospective Studies , Rituximab/adverse effectsABSTRACT
BACKGROUND: Although solid information on the natural history of primary progressive multiple sclerosis (PPMS) is available, evidence regarding impact of disease activity on PPMS progression remains controversial. OBJECTIVE: To describe the clinical characteristics, presence or absence of MRI activity, and natural history of a PPMS cohort from two referral centers in Argentina and assess whether clinical and/or radiological disease activity correlated with disability worsening. METHODS: Retrospective study conducted at two MS clinics in Buenos Aires, Argentina, through comparative analysis of patients with and without evidence of disease activity. RESULTS: Clinical and/or radiologic activity was presented in 56 (31%) of 178 patients. When stratified by age at onset, we found that for every 10 years of increase in age at onset, risk of reaching EDSS scores of 4 and 6 increased by 26% and 31%, respectively (EDSS 4: HR 1.26, CI 95%: 1.06-1.50; EDSS 6: HR 1.31, CI 95%: 1.06-1.62). Patients who presented clinical exacerbations reached EDSS scores of 6, 7 and 8 faster than those without associated exacerbations (p = 0.009, p = 0.016 and p = 0.001, respectively). Likewise, patients who presented gadolinium-enhancing lesions during the course of disease reached EDSS scores of 7 earlier (p = 0.002). CONCLUSION: Older age at onset and presence of clinical and/or radiological disease activity correlated with accelerated disability progression in this cohort of PPMS patients.