喷雾干燥对干扰素α-2b稳定性的影响

 目的研究不同方法来提高蛋白质在喷雾干燥过程中的稳定性。方法以干扰素α-2b为模型药,分别考察喷雾干燥条件、pH值及缓冲体系、赋形剂及添加剂对干扰素α-2b活性的影响。结果在雾化气体流速约575 L·h^-1、进口温度110℃的喷雾干燥条件下,利用大豆卵磷脂、十二烷基硫酸钠、羟丙基甲基纤维素、羟丙基β-环糊精、L-赖氨酸为添加剂,干扰素α-2b的活性损失较小。结论干扰素α-2b在喷雾干燥过程中的稳定性可以通过工艺及处方因素得到提高。     

干扰素β治疗复发-缓解型多发性硬化

干扰素 β已经成功用于治疗复发 缓解型多发性硬化。其免疫调节作用表现为减少复发 缓解型多发性硬化病人临床症状和在MRI水平观察到的复发率和病灶负荷 ,以及延缓功能障碍的进展。还可以延缓相关的继发性进展型多发性硬化病人功能障碍的进展 ,以及延缓临床孤立综合征发展成临床确诊的多发性硬化。虽然干扰素治疗过程中可出现一些轻微的不良反应 ,但大多数情况下无需减量或停药。中和抗体的出现可能影响疗效 ,但尚无证据表明抗体出现后就可能会完全失效。基于该疗法的安全性和可靠性 ,可以说干扰素 β是目前多发性硬化治疗中最有希望的药物之一     

重组人干扰素α-2b两步柱色谱分离纯化工艺研究

通过改进柱色谱条件,两步柱色谱分离纯化重组人干扰素α-2b,简化了工艺,缩短了生产流程,纯化倍率达到5.6倍,纯度98%.蛋白比活性1.43×108IU/mg蛋白,活性回收率58%.     

Good results for early treatment of clinically isolated syndrome prior to multiple sclerosis with interferon beta-1b and glatiramer group

The first sign of developing multiple sclerosis is a clinically isolated syndrome that resembles a multiple sclerosis relapse. Objective/methods: The objective was to review the clinical trials of two medicines in clinically isolated syndromes (interferon β and glatiramer acetate) to determine whether they prevent progression to definite multiple sclerosis. In the BENEFIT trial, after 2 years, 45% of subjects in the placebo group developed clinically definite multiple sclerosis; the rate was lower in the interferon β-1b group. All subjects were then offered interferon β-1b, and the original interferon β-1b group became the early-treatment group and the placebo group became the delayed-treatment group. After 5 years, the number of subjects with clinical definite multiple sclerosis remained lower in the early-treatment than in the late-treatment group. In the PreCISe trial, after 2 years, the time for 25% of the subjects to convert to definite multiple sclerosis was prolonged in the glatiramer group. Interferon β-1b and glatiramer acetate slow the progression of clinically isolated syndromes to definite multiple sclerosis. However, it is not known whether this early treatment slows the progression to the physical disabilities experienced in multiple sclerosis.     

Noninterferon-based adjuvant therapy for high-risk melanoma

High-dose interferon is the only treatment approved by the FDA for adjuvant therapy of melanoma. However, its efficacy in this setting is questionable and its administration is associated with considerable toxicity. Many new agents are being tested clinically that hold the promise of greater efficacy and less toxicity but none of these have yet shown efficacy in controlled trials. These include biologics such as vaccines, cytokines, monoclonal antibodies, gene transfer, cellular therapies and angiogenesis inhibitors as well as chemotherapy combinations.     

Defining a new molecular basis of systemic lupus erythematosus through transcriptional profiling

Data generated using high-throughput DNA microarrays are changing the way we think about systemic lupus erythematosus (SLE). The identification of an interferon gene-expression signature in the majority of patients with SLE, especially those with severe SLE, has stimulated substantial interest in targeting the interferon pathway for the treatment SLE and has catalyzed new inquiries into the utility of interferon signaling as a diagnostic and prognostic biomarker for SLE. As these genomic datasets enlarge and mature, new signatures are being identified that implicate other pathways dysregulated in SLE, including oxidative phosphorylation, immunoglobulin production and granulocyte maturation. Highly anticipated longitudinal studies will be important in defining how this information will ultimately change the way SLE is managed in the clinical setting.     

Relationship between cryoglobulinemia-associated nephritis and HCV infection

The pathogenetic mechanisms in hepatitis C virus (HCV)-related cryoglobulinemia are sustained by the chronic lymphocyte stimulation of HCV infection, and include the synthesis of IgM rheumatoid factor and tissue deposition of immunocomplexes, characterized by abnormal kinetics and an underlying lymphoproliferative disorder. Based on postulated pathogenetic mechanisms, therapeutic strategies include antiviral, immunosuppressive and immunomodulatory treatments. Combined interferon and ribavirin has shown a better response rate than interferon alone. Pegylated interferons are currently recommended in association with ribavirin. Advances in tolerance might be achieved by tailoring doses and treatment duration according to genotype and individual factors. Conventional immunosuppressive therapy has been widely used in patients with progressive renal involvement or relapsing disease. Rituximab is a promising alternative treatment option for severe cryoglobulinemic vasculitis and nephritis. Although the optimal treatment strategy in HCV-related cryoglobulinemia has not been determined yet, an algorithm based on the clinical severity of disease could be proposed, in which rituximab might be a first-line option in severe cases.     

Assessment of intracellular cytokines and regulatory cells in patients with autoimmune diseases and primary immunodeficiencies — Novel tool for diagnostics and patient follow-up

Serum and intracytoplasmic cytokines are mandatory in host defense against microbes, but also play a pivotal role in the pathogenesis of autoimmune diseases by initiating and perpetuating various cellular and humoral autoimmune processes.