Thursday, October 11, 2012

Azathioprine


Azathioprine is an immunosuppressant used widely in the treatment of various autoimmune diseases. He was extracted from the analysis of the results of randomized trials 7 (five and two double-blind, single blind) with patients who suffer from MS 793 by oral azathioprine (1-3 mg/kg/m2) reduces the frequency of relapses and little impact very EDSS. These results have been criticized on the grounds that used a sufficient dose of azathioprine in some studies. Side effects of azathioprine toxicity, gastrointestinal tract, and blood and liver. Another risk potential long-term cancer, but in the controlled trial, case-control, short-term (less than 5 years) are not associated with significantly increased risk. Treatment requires close monitoring and ongoing patient, including blood counts and liver function tests.

Treatment with IVIG


Has large multicenter study in Europe and Canada for IVIG (1.0 g / kg / month) in secondary progressive MS. Results on the clinical and magnetic resonance imaging (MRI) is negative.
Treatment with IVIG rarely cause serious side effects. Including aseptic meningitis, kidney failure, and vascular injury and viral infections, eczema and anaphylaxis. Another potential problem associated with its use is high contrast composition of supplements on the market, confirmed by many studies.

Can exercise and in addition to the immunosuppressive effects (due to the fact that the suppression of the production of proinflammatory cytokines, or they contain antibodies to fight different styles self) promotion of IVIG leaning back, and according to some studies. However, small studies are performed at the Mayo Clinic does not support the hypothesis that IVIG can reverse neurological deficits and visual long.

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Protocol Optimization


In addition, reduces treatment nearly half the pace of setbacks has no obvious effect on the severity of the outbreak. However, it is possible that not blind protocol optimization, which may be biased study results. Unfortunately, MRI are not included in the protocol, and the book did not produce any data on changes EDSS "confirmed" the three months and six months.

In another clinical study, we investigate the effect of high doses of IVIG (2.0 g / kg / month for 6 months) to assess disease activity as measured by magnetic resonance imaging (MRI), but there was a high dropout rate due to side effects.

In double-blind study, 40 patients Israeli with RRMS random IVIG because of loading dose (0.4 mg / kg / day for 5 days), followed by enhanced access to a unique (0.4 mg / kg) or placebo, administered every two months for two years. Treatment was reduced almost 40 percent. Percent in annual relapse rate, in addition to its impact on the EDSS. However, it did not differ significantly between the two groups in total lesion load on magnetic resonance imaging (MRI) of the brain.

Intravenous Immunoglobulin


Immunoglobulins (IgG) for intravenous administration (IVIG) have different effects on the immune system.

During the first small studies that did not show multicenter study wide effectiveness convincing Australian found that the monthly management of low-dose IVIG effective and well tolerated. A group of patients 148 RRMS (EDSS 1-6) randomly into two groups, one treated with IVIG monthly dose of 0.15 to 0.20 kg / g split and the other received a placebo for two years. Was ultimately the main effects of treatment on clinical disability (as measured by the change in EDSS), and the proportion of patients who have debilitating disability, remained stable or deteriorating (difference of one point at least on EDSS). The analysis is based on the plan showed that IVIG therapy have a significant positive impact, albeit modest, in EDSS.

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Demyelinating Disease


The study showed Enyoropathologyekal MS lesions clearly that the process of demyelination occurs in the presence of inflammatory cells and cytokines. Traditionally, demyelination and inflammation MS tie (MS often known as inflammatory demyelinating disease). Research has confirmed recently. Was a significant correlation between the deficit and the clinical onset of permanent nerve cells themselves (especially on the axon)

These insights into the functioning of the immune system led to the development of therapeutic strategies, conducted consisting, for example, prevents management of anti-inflammatory cytokines in patients with MS or treatments that pro-inflammatory cytokines. However, limited ability to predict the effect of such an intervention by the complexity of the network formed by the immune system, with many interrelated factors and mechanisms that vary depending on the stage of the disease. Even more difficult than outside entity heterogeneous MS patients, and that we will see a variety of phenomena such as the masses of the destruction of the cells, and the process of demyelination with or without the participation of the principal cells work as oligodendrogliopathie 'primary.

Given our limited understanding of the pathogenesis of MS, generally or in a particular person, can not be achieved any specific therapeutic progress to be achieved at the expense of clinical trials. These tests are to be carried out on large numbers for a long time, because the path is highly variable and unpredictable disease, and the difficulty in accurately measure neurological disability.

Cytokines


Recent data show that cytokines can be divided into two categories. First. Of inflammatory cytokines, including tumor necrosis factor alpha (TNF alpha) and interferon gamma, which may direct tissue damage in MS second layer, and cytokines anti-inflammatory, including 4 - interleukin (IL-4), interleukin -10 (IL -10), and transforming growth factor beta (TGF-beta), to suppress or prevent the disease.

There are many B cells in MS plaques and close to the latter, but they are relatively rare in the cerebrospinal fluid (CSF). These are the cells to ensure local production of immune. Antibodies are immune, but in September, it's not nature made against this antigen antibodies. In an attempt to search, and students have to discover antigen antibody inconclusive so far.

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