prospective, multi-center, observational study on the use of interferon beta-1a [Rebif] therapy in Egyptian patients with multiple sclerosis

The primary objective of this study is to describe the disease characteristics of the cohort of MS patients undergoing Rebif treatment. This is a multicentre, open label, non comparative, non randomized study conducted in Egypt on the use of interferon beta-1a [Rebif] therapy in Egyptian patients with relapsing multiple sclerosis according to McDonald criteria. Egyptian patients with relapsing multiple sclerosis who are naïve to interferon and are 18 to 65 years old. A total number of 36 patients were enrolled. include the mean number of relapses, time from diagnosis to start of treatment, number of relapses prior to start of treatment, annualized relapse rate, incidence of adverse events associated with Rebif therapy and number and location of lesions in MRI. 7 patients were excluded from Intention-to-Treat Population as they were enrolled regardless of the inclusion/exclusion criteria. Therefore, the Per Protocol Population included 29 patients including 11 males and 18 females and with a mean age of 31.41 years old. The number of reported relapses was 4.3 and 11 at visit 1, visit 2 and end of the study respectively. Despite this increase, only 13 out of 29 patients [44.83% - 95%CI: 28.4% to 62.4%] had relapse attacks during the study [48 weeks]. The annualized relapse rate was 0.79 +/- 0.41 [95% CI] relapse per year. 9 patients out of 36 patients [25% - 95%CI: 13.75 to 41.07%] in the safety population had adverse events during the study. 2 were reported at baseline, 5 at visit 1, 1 at visit two and 1 at visit 3. The adverse events were elevated liver enzymes [2], depression [2], injection site pain [1], allergic skin reaction [2] and flu like symptoms [1]. Compared to previously reported results, this study indicates that Rebif appears to have a favorable efficacy profile as well as a favorable safety profile in delaying MS progression in Egyptian patients

Tratamiento de la esclerosis múltipple: la era del natalizumab / Treatment of Multiple Sclerosis: the era of Natalizumab

La esclerosis múltiple es una enfermedad inflamatoria crónica y autoinmune del sistema nervioso central. Produce un variado abanico de síntomas que suelen llevar a la incapacidad del paciente que la padece. Para su tratamiento se ha empleado una amplia gama de drogas, todas destinadas a contrarrestar la respuesta inflamatoria. Entre ellas se destacan los corticoides, acetato de glatiramer, interferón beta, entre otras. Ninguna de ellas trata la causa primaria de la enfermedad pero pueden aminorar su progresión y retrasar la aparición de nuevos síntomas. Sin embargo, no son capaces de lograr el control de la enfermedad sin que sus efectos adversos o sus pautas y formas de administración se interpongan en la terpéutica. La introducción del natalizumab en el tratmiento de la esclerosis múltiple constituye un avance sin precedentes. Esta droga controla el progreso de la enfermedad como ninguna de sus antecesoras con una muy baja frecuencia de administración y una gran aceptación del tratamiento por parte de los pacientes. Sin embargo, el riesgo de aparición de leucoencefalopatía multifocal progresiva durante el tratamiento con natalizumab hace que su terapéutica requiera un enfoque multidisciplinario de profesionales de la salud

Multple Sclerosis is a chronic, inflammatory and autoimmune disease of the central nervous system. It causes a wide range of symptoms which may lead to the impairment of the patient that suffers from it. Numerous drugs have been used for its treatment to counteract the inflammatory response. Among these drugs are corticosteriods, glatiramer acetate and Interferon beta. Although none of them treat the primary cause of the disease, they may slow down its progression and delay the appearance of new symptoms. In addition, they are not capable of achieving the control of the disease without their adverse effects, guidelines, or ways of administration interposing in the therapeutic treatment. The introduction of natalizumab in the treatment of multiple sclerosis is an unprecedented advance. This drug controls the progression of the disease in a way which none of the former drugs has achieved, with a very low frequency of administration and a high treatment acceptance by the patients. However, the risk of developing progressive multifocal leukoencephalopathy during treatmente with natalizumab makes its therapeutic treatment require a multidisciplinary approach on the part of healthcare professionals

[Effect of the sera of patients with multiple sclerosis on apoptosis and nitric oxide production of endothelial cells]

Multiple sclerosis [MS] is one of the chronic autoimmune diseases of the central nervous system with unknown etiology. The present study aimed to investigate the apoptosis and nitric oxide [NO] production of endothelial cells treated with serum of patients with MS and response to interferon beta [IFN- beta] therapy. Human umbilical vein endothelial cells were treated with sera from patients with active MS [in relapse], MS in remission, or sera from healthy volunteers [each n = 10]. Nitric oxide [NO] levels were determined in culture supernatants by Greiss method and endothelial cell apoptosis was assessed by annexin V-propidium iodide staining. Effects of IFN-beta-1b on endothelial cell apoptosis and NO production were tested at increasing doses [10, 100, and 1000 U/ml]. Compared with healthy people, only apoptosis of endothelial cells treated with serum of patients with relapsing phase increased, P<0.01; while there was no significant difference between apoptosis of endothelial cells treated with serum of patients in remission phase and healthy controls. Apoptosis of endothelial cells treated with sera of patients in relapse was decreased by IFN-beta-1b at 10 U/ml, P<0.05. The same dose also led to a significant increase in nitric oxide production. The results suggest that endothelial cells injury and apoptosis may play a role in MS etiology and represents a potential therapeutic mechanism of action for IFN-beta-1b in MS therapy

Avances en esclerosis múltiple: tratamiento / Advances in multiple sclerosis: treatment

En los últimos 10 años el estudio de la Esclerosis Múltiple (EM) ha presentado numerosos avances clínicos y terapéuticos, que han permitido un manejo más racional de la enfermedad, con significativo beneficio para los pacientes. De ser una enfermedad crónica sin tratamientos específicos, actualmente existen al menos seis fármacos con demostrada actividad sobre la enfermedad, y herramientas útiles para establecer pronósticos y controlar la evolución. En el presente trabajo (dividido en dos partes) se analizaran algunos aspectos de los avances observados en EM, especialmente aquellos que han incidido directa o indirectamente en un beneficio para los pacientes, y que apuntan a un tratamiento precoz de la enfermedad.

New data gathered for the past 5-10 years suggest that it is possible to define the rísk of clinically definite MS, as well as long term disability. This is specially significant in patients presenting with a Clinically Isolated Syndrome (OS), based on clinical presentation and MRI imaging. Longitudinal studies of patients with OS have permitted the realization of clinical trials of early treatment with Interferon Beta (1 a, 1 b) and Glatiramer acetate on these patients. These trials have shown significant benefit with all these treatments, and it is expected a better prognosis for patients with Multiple Sclerosis at early stages.

impact of IFN beta 1a and IFN beta-1b on the clinical and MRI responses in patients with relapsing-remitting multiple sclerosis

Multiple Sclerosis [MS] is a common demyelinating and inflammatory disease of the CNS with a presumed autoimmune etiology. IFN beta-1a and IFN beta-1b have a proven treatment effect on RRMS presumably through its regulatory properties on T-cell activation and cytokines production. Here we studied the clinical and MRI effects of these drugs in four groups of clinically and laboratory [Cerebrospinal fluid evaluation revealed elevation of immunoglobulin [IgG] synthesis rate and oligoclonal bands] definite RRMS patients for 18 months. In IFN beta-1a group [n = 25], the patients used IFN beta-la 30 micro g [6MU] intramuscular once a week, the other three groups of IFN beta-1a [n = 25] 22 micro g [6MU], IFN beta-la 44 micro g [n = 25] and IFN beta-1b 8MU [0.25 mg] [n = 25] were injected subcutaneously 3-time a week. In comparison with the pre-treatment values, reduction in the relapse rate was statistically significant in IFN beta-la 44 micro g, IFN beta-la 30 micro g and IFN beta-lb 8MU groups more than IFN beta-la 22 micro g [P < 0.001, 0.008, 0.001 and > 0.5 respectively], and the mean EDSS significantly reduced in the IFN beta-lb [P < 0.001], IFN beta-la intramuscular [P < 0.02] and 44 micro g IFN beta-la [P < 0.001], in contrast to 22 micro g IFN beta-la treated patients [P > 0.5]. Moreover, IFN beta-lb [P < 0.001] and 44ug IFN beta-la [P < 0.003] groups showed highly statistical significant reduction in MRI disease activity load [p < 0.05] in comparison with 22micro g IFN beta-1a [p < 0.5] and IFN beta-la intramuscular groups [p < 0.07]. The study confirmed also the effect of beta-IFNs on the short term physical disability scale [p < 0.01] while they have no significant effect on long term disability scale [p > 0.64]. Additionally, beta-IFNs groups showed no statistically significant severe drugs adverse effects [p > 0.8] while revealed significant effects of recovered side effects [p < 0.01]. The common adverse effects of lFN beta that were significantly found [p < 0.01], are flu-like symptoms, fatigue, chills and fever, injection site pain and local redness, headache, irregular menses and mild depression specially with IFN beta-la intramuscular. No difference in the clinical suspicions of binding antibodies development to beta-IFNs was found. On the whole, all groups showed significant reduction of relapse frequency and MRI load with different values [p < 0.01]. In summary, this study does make available meaningful and helpful clinical and radiological data to the clinician regarding the relative efficacy of each therapy in RRMS. First, the results of our study suggest that IFN beta-lb 8MU and IFN beta-1a 44 micro g may be more optimal choices than IFN beta-la 30 micro g Intramuscular and IFN beta-la 22 micro g at the currently available dose in treatment of RRMS patients. Secondly, the results do not differ from remarks made after 18 months of treatment in larger and more rigorously controlled studies. Thirdly, therapy does construct a difference and early treatment should be encouraged

Intracellular Leishmania amazonensis killing induced by the guanine nucleoside 8-bromoguanosine

Neste trabalho, nos investigamos o efeito da 8-Bromoguanosina, um composto imunoestimulador, na citotoxicidade de macrofagos infectados com Leishmania amazonensis em um sistema in vitro. Os resultados mostraram que macrofagos tratados com 8-Bromoguanosina pre- ou pos-infeccao foram capazes de reduzir a carga parasitaria, monitorada pelo numero de amastigotas por macrofago e a percentagem de celulas infectadas (i.e. indice fagocitico). Sendo a 8-Bromoguanosina inocua para promastigotas, concluimos que o composto induz ativacao celular. Os macrofagos produziriam interferon alfa e beta e teriam seus mecanismos leishmanicidas estimulados. Esses resultados sugerem que compostos como a 8-Bromoguanosina (ribonucleosideos de guanina) podem auxiliar no tratamento contra patogenos intracelulares

Interferon in viral liver diseases: pharmalogical aspects

Descreveram-se os principais tipos de Interferon (IFN) fundamentais. Os IFN alfa, beta e gama foram comparados quanto a origem de açäo. Os principais tópicos analisados foram: receptores, vias metabolicas, proteinas induzidas pelo IFN, efeitos imunes, anticorpos anti-interferon e outros efeitos. Efeitos colaterais e farmacocinetica do IFN foram também analisados

Tratamiento de la esclerosis múltiple con interferones / Treatment of multiple sclerosis with interferons

Despite the important achievements in clinical and experimental aspects of demylinating diseases and multiple sclerosis (MS), its pathogenesis still remains unknown. The most commonly held view is that it is an autoimmune disease, related in some way to a viral infection, that occurs in genetically susceptible hosts. Based on this, many current treatments for MS are designed to modulate the immune response and the interferons are an example. Only beta interferon has a dose dependent efficacy in phase III clinical trials, as treatment for remitting-relapsing forms. It produces a reduction in exacerbation rates and in the burden of the disease, measured by Magnetic Resonance imaging. The clinical use of beta interferon, considering the cost and large tretament period, must be cautious, reserving it only for confirmed remitting-relapsing modalities of MS. There is no clear cut evidence that beta interferon is useful for chronic-progressive MS

Effects of human alpha, beta and gamma interferons on varicella zoster virus in vitro.

The antiviral effects of interferon (IFN) on varicella zoster virus (VZV) and herpes simplex virus (HSV) in vitro were examined. The values for the 50% inhibitory dose (ID50) of IFN-alpha, beta and gamma determined by plaque reduction assay, were 0.813, 0.650 and 13.750 IU/ml, respectively, against VZV and 18.00, 10.38 and 115.0 IU/ml, respectively, against HSV. Thus IFN-alpha and beta were more effective than IFN-gamma against both VZV and HSV and VZV was more sensitive than HSV to the IFNs. Five mutants of VZV which were resistant to acyclovir (ACV), phosphonoacetic acid (PAA) or bromodeoxyuridine (BUDR) were also sensitive to IFN beta, their average ID50 being 1.31 IU/ml. Analysis of virus-specific proteins by the immunofluorescent technique with various antisera showed that IFN had a significant effect before early protein synthesis.