Monomethylfumarate affects polarization of monocyte-derived dendritic cells resulting in down-regulated Th1 lymphocyte responses

Psoriasis vulgaris, a type-1 cytokine-mediated chronic skin disease, can be treated successfully with fumaric acid esters (FAE). Beneficial effects of this medication coincided with decreased production of IFN-gamma. Since dendritic cells (DC) regulate the differentiation of T helper (Th) cells, this study focussed on effects of monomethylfumarate (MMF, bioactive metabolite of FAE) on polarization of monocyte-derived DC. MMF-incubated, lipo-polysaccharide-stimulated DC (MMF-DC) produced dramatically (p<0.05) reduced levels of IL-12p70 and IL-10 (8+/-4% and 20+/-4%, respectively) compared to control DC. MMF-DC were mature. MMF affected polarization of DC irrespective of polarization factor(s) and ligands for the various Toll-like receptors used. Coculture of MMF-DC with naive and primed allogenous Th cells resulted in lymphocytes producing less IFN-gamma, i.e. 59% and 54% of that by the respective Th cells cocultured with control DC. IL-4 production by primed, but not naive Th cells cocultured with MMF-DC was decreased as compared to cocultures with control DC. IL-10 production by naive and primed Th cells cocultured with MMF-DC and control DC did not differ. In addition, MMF inhibited LPS-induced NF-kappaB activation in DC. Together, beneficial effects of FAE in psoriasis involve modulation of DC polarization by MMF such that these cells down-regulate IFN-gamma production by Th cells.     

First-line therapy in relapsing remitting multiple sclerosis

Today, first-line treatments for multiple sclerosis include injectable immunomodulators – some of which have been on the market for nearly 25 years – as well as teriflunomide and dimethyl fumarate, which are more recent, but have opened the way for oral treatments. These drugs are considered similar in effectiveness, and their safety and side-effect profiles are generally reassuring. These treatments have been associated with a reduction in radiological and clinical disease activity, and a positive effect on patient quality of life, especially when introduced early in the disease process. This article will discuss data on first-line treatments currently available in France, their effectiveness and safety, and their place in pediatric patients and in woman who plan to become pregnant.     

河北省磁县农村农户储粮化学防霉效果观察

目的探讨富马酸二甲酯(dimethylfumarate，DMF)、磷化铝(aluminiumphosphide，AP)和除霉净在农户储粮防霉实践中的实际应用价值。方法采用河北省磁县农户储存小麦容器中现场施药和实验室霉菌分离培养计数的方法，观察分析DMF、AP和除霉净对储粮霉菌生长的抑制作用。结果磁县农户储存小麦霉菌污染比较普遍，1996～1999年霉菌污染率为67.5%到100%，3种化学防霉药物对磁县农户储存小麦均有防霉效果，DMF、AP、DMF/AP和除霉净防霉有效率分别为91.2%、85.2%、100%和100%，霉菌生长抑制率分别为(61.9±21.6)%、(64.0±21.6)%、(72.5±18.0)%和(63.1±24.3)%。结论MF、AP和除霉净对河北省磁县储粮均有防霉效果，但AP有一定毒性不宜推广使用。     

Psoriasis treatment: Unconventional and non-standard modalities in the era of biologics

Psoriasis is a potentially debilitating inflammatory dermatosis affecting 0.2%-4.8% of the population worldwide causing a significant occupational, personal or psychosocial morbidity to these patients for life. The basic aim of psoriasis therapy is to control the disease to maximum possible extent and improve the patient’s quality of life. Management of triggers for flare-ups, lifestyle modifications, and dietary supplements are often recommended. Intermittent or rotational therapy with frequent alterations in treatment options is usually needed to reduce toxicity of anti-psoriatic drugs in the absence of safer alternatives. Currently, several biological agents categorized as either T-cell targeted (e.g., Alefacept, Efalizumab) or cytokine modulating (e.g., Adalimumab, Infliximab, Etanercept) are available for treating severe psoriasis. However, their high cost is often precluding for most patients. The usefulness of systemic (methotrexate, cyclosporine, acitretin or several other therapeutic agents) or topical (tar, anthralin, corticosteroids or calcipotriol ointments, phototherapy with or without psoralens) therapies has been well established for the management of psoriasis. The literature is also replete with benefits of less used non-standard and unconventional treatment modalities (hydroxycarbamide, azathioprine, leflunomide, mycophenolate mofetil, isotretinoin, fumarates, topical calcineurin inhibitors, peroxisome proliferator-activated receptors agonists, statins, sulfasalazine, pentoxifylline, colchicine, grenz ray therapy, excimer laser, climatotherapy and balneophototherapy, peritoneal dialysis, tonsillectomy, ichthyotherapy, etc.). These can be used alternatively to treat psoriasis patients who have mild/minimal lesions, are intolerant to conventional drugs, have developed side effects or achieved recommended cumulative dose, where comorbidities pose unusual therapeutic challenges, or may be as intermittent, rotational or combination treatment alternatives.     

延胡索酸二甲酯对大鼠醌还原酶和谷胱甘肽—S—转移酶的诱导作用

目的　探讨延胡索酸二甲酯（ＤＭＦ） 对大鼠主要脏器醌还原酶和谷胱甘肽Ｓ转移酶的诱导作用和意义。方法　雄性Ｗｉｓｔａｒ 大鼠饮食中补充０ ．２ ％ ＤＭＦ,于６ 、２４ 、７２ 小时、１ 和２ 周后取血并处死动物,用酶动力学法测定大鼠腺胃、肝、肺、肾和心脏中的醌还原酶（ＱＲ） 和谷胱甘肽Ｓ转移酶（ＧＳＴｓ） 活性,并按此法测定血清ＱＲ、ＧＰＴ和乳酸脱氢酶含量。结果　服用ＤＭＦ２４ 、７２ 小时、１ 和２ 周后可观察到腺胃、肝、肺、肾脏中ＱＲ 和ＧＳＴｓ 活性显著增高（ Ｐ＜ ０ ．０００ １ 或Ｐ＜ ０ ．０１） ,同时血清ＱＲ 活性也显著增高（ Ｐ＜ ０ ．０１ ,或Ｐ＜ ０ ．０００ １） 。ＤＭＦ对血清ＧＰＴ 和乳酸脱氢酶的活性则无影响。结论　ＤＭＦ对大鼠腺胃、肝、肺、肾和血清中的ＱＲ 和ＧＳＴｓ 活性具有诱导作用,ＤＭＦ有望成为人类抗氧化损伤的保护剂和解毒剂。