Ocular autoimmunity: the price of privilege?

Summary:  The eye is the prototypic immune-privileged organ. Its antigens were once believed to be expressed exclusively in the eye, which resides behind an efficient blood–organ barrier, and were believed to be unknown to the immune system. Self-tolerance to ocular components was therefore believed to be based not on immune tolerance but on immune ignorance. It is now known that the relationship between the immune system and the eye is much more complex. On the one hand, immune privilege is now known to involve not only sequestration but also active mechanisms that (i) inhibit innate and adaptive immune processes within the eye and (ii) shape the response that develops systemically to antigens released from the eye. On the other hand, retinal antigens are found in the thymus and have been shown to shape the eye-specific T-cell repertoire. However, thymic elimination of self-reactive T cells is incomplete, and such 'escapee' T cells are tolerized in the periphery as they recirculate through the body by encounter with self-antigen in healthy tissues. Due to the relative inaccessibility of the healthy eye to the immune system, peripheral tolerance mechanisms may not operate efficiently for ocular antigens, leaving a weak link in the homeostasis of tolerance. The case shall be made that although immune privilege protects vision by keeping the immune system at bay, a potential for developing destructive anti-retinal autoimmunity may be the price for the day-to-day protection afforded by immune privilege against inflammatory insults.     

Photodynamic therapy; a comparison with other immunomodulatory treatments of adjuvant-enhanced arthritis in MRL-lpr mice.

Although numerous experimental immunomodulatory regimens have been reported to be effective in the treatment of rheumatoid arthritis, they also produce undesirable side effects. An alternative specific modality of localized treatment is photodynamic therapy (PDT). In this study we treated 13-week-old MRL-lpr mice whose spontaneous arthritis was enhanced by intradermal injection of Freund's complete adjuvant (FCA). One group received transcutaneous photodynamic therapy at days 0, 10, and 20, following the FCA injection. The other groups were injected with 1 mg/kg per day indomethacin, 40 mg/kg per day cyclosporin A (CsA), or treated with 3 Gy sublethal whole body irradiation (WBI). The development of swelling was monitored for 1 month, at which time proteinuria, lymphadenopathy and the histopathology of the joints and kidneys were assessed. The results demonstrated that PDT and the conventional treatments significantly ameliorated swelling of the hindlimbs from 70% in the untreated FCA-injected animals to below the 19% level characteristic of the unmanipulated control. Histological examination showed a reduction in pannus formation, and cartilage and bone destruction, the characteristics of adjuvant-enhanced arthritis. PDT did not affect the survival rate, lymphoproliferation, or proteinuria of the treated animals. However, indomethacin increased proteinuria, and was less effective in preventing cartilage and bone destruction. Furthermore, lower doses of CsA and WBI exacerbated arthritis activity. These results indicate that photodynamic therapy can inhibit the development of adjuvant-enhanced arthritis in MRL-lpr mice with similar effectiveness to the conventional treatments, but without their negative side effects.     

Alterations in alanine metabolism in diabetic dogs during short-term treatment with an artificial B cell

Summary The flux rates of plasma glucose and alanine were studied isotopically (6-³H-glucose and U-¹⁴C-alanine simultaneously) in resting chronically diabetic dogs during short-term treatment with an artificial B cell where the insulin was infused into a peripheral vein. Despite perfect blood glucose control and normal glucose flux rates, the concentration and rates of appearance and disappearance of alanine were significantly elevated in the diabetic animals before, during and after an exogenous glucose load. The incorporation of the carbon moiety of alanine into circulating glucose was also increased, but diminished to a near-normal extent when exogenous glucose was given. The plasma clearance rates for alanine in the diabetic dogs were normal throughout the study. It is concluded that normal blood glucose control in diabetes does not necessarily mean normalization of the entire metabolic network. On the basis of peripheral hyperinsulinaemia alanine formation from glucose and branched chain amino acids is elevated in muscle. This may explain increased flux of alanine despite normal blood glucose control.     

玉蟾抗衰茶保健抗衰作用的实验观察

玉蟾抗衰茶以川绿茶为基质,加入中药配方,精工制作而成,使茶叶的保健治疗作用增强,并具有益气补血,健脾固肾功用。动物实验证实:饮用该茶安全,有增强体力、抗疲劳与抗缺氧能力,能延长动物(家蚕)生命周期。经临床验证本品有降低人体血脂、增强精力、清爽神智等功能,为中老年理想的保健饮料。     

Chemical and statistical considerations in the determination of partition coefficients of weakly ionizable drugs and poisons

Equations have been developed that relate the concentration (or a parameter directly proportional to concentration, such as optical absorbance) of a weakly ionizable solute in a water-immiscible phase, in equilibrium with an aqueous phase, to the pH of the aqueous phase, the partition coefficient of the unionized solute and the phase volume ratio. These relationships have been used in the design of experimental methods for determining partition coefficients, which require measurement of solute concentration in only one phase. Data obtained in this way permit ready recognition of deviations from assumptions made in the development of the model; these assumptions include insolubility of the ionized solute in the water-immiscible phase and lack of interaction between buffer components and solute. Conditions for optimal liquid—liquid extraction of weakly ionizable solutes are more easily recognized. With these techniques, the negative logarithm of the acid dissociation constant (pK′_a) and the logarithm of the octanol—water partition coefficient (log P) have been measured for warfarin (pK′_a = 5.15 ± 0.04; log P = 2.82 ± 0.06), strychnine (pK′_a = 8.29 ± 0.02; log P = 2.23 ± 0.04), phenol (pK′_a = 9.88 ± 0.02; log P = 1.75 ± 0.05), procaine (pK′_a = 8.11 ± 0.04; log P = 1.10 ± 0.08), and ephedrine (pK′_a = 9.92 ± 0.01; log P = 1.65 ± 0.04) at 21°C.     

生存研究样本量设计表及其使用方法

目的 :本文就两样本生存研究所需样本量用广义渐近正态法设计出 15 30个方案 ,制成设计表供临床使用。方法 :利用C语言编制程序 ,按通用格式打印设计表。结果 :常用方案查表可得。这些与两样本生存率检验相匹配 ,具有还原性 ,摆脱了比例危险的假设 ,在常见临床条件下观测功效符合预定功效。结论 :这些设计表适用于两样本癌症临床研究的设计 ,尤其便于临床医师或有关研究人员使用     

人卵巢癌SCID小鼠移植瘤模型、细胞系建立及其生物学特性研究

目的建立人卵巢癌SCID小鼠移植瘤模型和相应体外细胞系.方法将病理证实的人卵巢浆液性乳头状腺癌手术切除标本移植于SCID小鼠皮下,成瘤后行鼠间传代,取移植瘤细胞体外分离培养、传代和建系,并应用细胞、分子生物学手段对移植瘤和建系细胞进行一系列生物学特性检测.结果历时14个月传至5代,皮下移植瘤存活率为90%,持续6个月,体外建系(OVA-319)细胞生长稳定.镜下观察组织形态学和超微结构符合原肿瘤组织基本特征;染色体分布在12～46条之间,多为异倍体,显示人类肿瘤异常染色体;流式细胞术和RT-PCR技术分析原代、体内移植瘤和OVA-319细胞结果一致,表现为瘤细胞生长活跃、细胞周期分布相仿,MAGE-2基因在mRNA水平异常表达.结论人卵巢癌SCID小鼠移植瘤模型和OVA-319细胞系为人类肿瘤的研究提供了良好的实验材料.     

乙肝清胶囊对实验性肝损伤的保护作用

目的：通过本实验观察乙肝清胶囊的保肝降酶作用。方法：实验采用四氯化碳（CCl4）和D－氨基半乳糖（D－Gal）,造成动物急性实验性肝损伤,测定小鼠和大鼠血清GPT和LDH,并进行组织形态学观察。结果：乙肝清胶囊灌胃给药对CCl4和D－Gal急性肝损伤所引起的小鼠和大鼠GPT和LDH升高,均具有明显的抑制作用,且对小鼠和大鼠肝组织病理损伤具有一定保护作用,其1－2g/kg与联苯双酯15mg/kg作用效果接近。结论：乙肝清胶囊对化学物质的所引起的小鼠和大鼠急性肝损伤,具有保肝降酶作用。     

通络胶囊治疗偏头痛的临床与实验研究

认为正气不足、病理体质为偏头痛的发病基础 ,以气血失调为主 ,寒热虚实错杂是本病的基本病机。据此确立扶正固本、祛风活络、化瘀止痛的治疗原则 ,拟通络胶囊治疗偏头痛 30例 ,与太极通天液治疗 30例对照 ,结果表明 ,治疗组愈显率 83.33% ,总有效率 93.33% ,与对照组相比有显著性差别 (P<0 .0 1) ,在改善兼症方面亦优于对照组 (P<0 .0 5或 P<0 .0 1) ,并能改善患者颅内血管功能状态。动物实验表明 ,通络胶囊能提高实验动物痛阈 ,同时提高大鼠下丘脑 5 - HT及 β-内啡呔水平 ,并能改善大鼠软脑膜微循环。