In vivo effects of immunostimulating lipopeptides on mouse liver microsomal cytochromes P-450 and on paracetamol-induced toxicity

Summary Immunomodulating lipopeptides lauroyl-L-Ala--D-Glu-LL-A2pmNH2-Gly (RP 44.102) and lauroyl-L-Ala--D-Glu-LL-A2pmNH2 (RP 56.142) were found to protect mice against the hepatotoxicity of paracetamol, which is due to cytochrome P-450 dependent formation of toxic metabolites and radicals. In fact they decreased the amount of hepatic microsomal cytochrome P-450, and the level of CCl₄-induced lipid peroxidation. In contrast lauroyl-L-Ala--D-Glu-DD-A2pmNH2 (RP 53.204), which only differs by the configuration of the two chiral carbons of A2pm (diaminopimelic acid) and is not an immunomodulating agent, failed to protect against poisoning by paracetamol and had no effect on the level of hepatic cytochrome P-450 or the microsomal CCl₄-induced lipid peroxidation. This provides a clear connection between the immunostimulating properties of a compound and its effects on xenobiotic biotransformations.     

Bromelain: biochemistry, pharmacology and medical use

Bromelain is a crude extract from the pineapple that contains, among other components, various closely related proteinases, demonstrating, in vitro and in vivo, antiedematous, antiinflammatory, antithrombotic and fibrinolytic activities. The active factors involved are biochemically characterized only in part. Due to its efficacy after oral administration, its safety and lack of undesired side effects, bromelain has earned growing acceptance and compliance among patients as a phytotherapeutical drug. A wide range of therapeutic benefits has been claimed for bromelain, such as reversible inhibition of platelet aggregation, angina pectoris, bronchitis, sinusitis, surgical traumas, thrombophlebitis, pyelonephritis and enhanced absorption of drugs, particularly of antibiotics. Biochemical experiments indicate that these pharmacological properties depend on the proteolytic activity only partly, suggesting the presence of nonprotein factors in bromelain. Recent results from preclinical and pharmacological studies recommend bromelain as an orally given drug for complementary tumor therapy: bromelain acts as an immunomodulator by raising the impaired immunocytotoxicity of monocytes against tumor cells from patients and by inducing the production of distinct cytokines such as tumor necrosis factor-α, interleukin (Il)-1β, Il-6, and Il-8. In a recent clinical study with mammary tumor patients, these findings could be partially confirmed. Especially promising are reports on animal experiments claiming an antimetastatic efficacy and inhibition of metastasis-associated platelet aggregation as well as inhibition of growth and invasiveness of tumor cells. Apparently, the antiinvasive activity does not depend on the proteolytic activity. This is also true for bromelain effects on the modulation of immune functions, its potential to eliminate burn debris and to accelerate wound healing. Whether bromelain will gain wide acceptance as a drug that inhibits platelet aggregation, is antimetastatic and facilitates skin debridement, among other indications, will be determined by further clinical trials. The claim that bromelain cannot be effective after oral administration is definitely refuted at this time. Received 25 August 2000; received after revision 29 March 2001; accepted 30 March 2001     

海洋细菌1202菌株产胞外多糖的适宜条件

应用响应面法(ResponseSurfaceMethod,RSM)对海洋细菌1202菌株胞外多糖发酵培养基进行优化.结果表明,适宜的发酵培养基组成为:蔗糖4%,酵母膏0.05%,玉米浆1.5%,CaCO30.15%,KH2PO40.08%,MgSO4·7H2O0.05%,FeSO4·7H2O0.01%,NaCl0.1%,pH7.5.在装液量为50mL(500mL三角瓶),接种量5%时,于28℃摇瓶培养7d,胞外多糖的产量可达到8.3mg/mL,转化率为20.75%.     

The potential role of endogenous bacteriophages in controlling invading pathogens

Bacteriophages (phages) are omnipresent in our environment, and recent studies highlight their potential impact on the microbial world. Phages can also be present in mammalian organisms, including man (intestines, oral cavity, urine, sputum and serum). Data are available which suggest that those endogenous phages could play an important role in eliminating bacteria and regulating the body ecosystem. Furthermore, our most recent findings suggest that phages can exert immunosuppressive action in the gut, helping control local inflammatory and autoimmune reactions, and demonstrate anticancer activity. We hypothesize that phages could act in concert with the immune system in immunosurveillance against bacteria, viruses and cancer.article dedicated to Professor Ludwik Hirszfeld to commemorate the 50^th anniversary of his deathReceived 8 September 2004; received after revision 18 October 2004; accepted 21 October 2004     

Casein,a prohormone with an immunomodulating role for the newborn?

Summary Maternal colostrum and milk, the earliest food of the newborn, should not only be considered as supplying nutrients, but also as agents providing protection against aggressions from the new environment. Indeed by enzymatic digestion of the main milk proteins, the caseins, biologically active peptides are released; they may be implicated in the stimulation of the newborn's immune system. From this point of view a strategic active zone has been characterized in -casein. A possible role of casein as a prohormone for the newborn is suggested.     

复方健胃消食浸膏粉免疫调节作用的实验研究

 目的 探讨复方健胃消食浸膏粉对小鼠的免疫调节作用,开发传统中药复方制剂新的保健价值。方法 给予6-8周龄,18-22g,雌性BALB/C 小鼠复方健胃消食浸膏粉,设一个对照组和剂量分别为0.2g/kg.bw、0.6g/kg.bw和1.8g/kg.bw的三个干预组,干预30天后,进行细胞免疫、体液免疫和NK细胞功能检验,测定脾脏T淋巴细胞增殖能力、迟发变态反应(DTH)的程度、抗体生成数、半数溶血值（HC50）和NK细胞的活性。结果 与对照组相比,复方健胃消食浸膏粉能明显增加小鼠T淋巴细胞的增殖能力和DTH的程度,提高小鼠抗体生成数和NK细胞的活性。结论 复方健胃消食浸膏粉具有增强小鼠细胞免疫、体液免疫和NK细胞活性的功能。