In vivo effects of cytokines on psoriatic skin grafted on nude mice: involvement of the tumour necrosis factor (TNF) receptor

Following engraftment of human involved psoriatic skin to nude mice there is a partial normalization of pathology associated with a loss of inflammatory leucocytes. However, the epidermis remains hyperproliferative, which may reflect a primary defect. The roles of TNF-α, IL-1 and IL-6 in epidermal hyperproliferation of grafted psoriatic lesions were investigated. Before and after treatment, grafts were analysed to determine epidermal thickness and labelling index (LI). HLA-DR, intercellular adhesion molecule-1 (ICAM-1), and TNF receptor (TNF-R; p75 and p55) expression were determined by immunoperoxidase staining. Psoriatic epidermis was found consistently to be negative for p55 TNF-R and p75 TNF-R before grafting. Following engraftment, TNF-R-positive cells (i.e. p55 by keratinocytes; p75 by epidermal dendritic cells) were identified throughout the epidermis. Higher numbers of p75 TNF-R epidermal dendritic cells were found in grafts following a course of TNF-α, IL-6 or IL-1 treatment. The p55 form of the TNF-R expressed by keratinocytes was significantly elevated after treatment with TNF-α or IL-6. HLA-DR and ICAM-1 were also expressed in these grafts. TNF-α, anti-IL-1, and anti-IL-6 treatment induced a marked decrease in the epidermal thickness and LI of psoriatic graft tissue, correcting the hyperproliferation associated with psoriatic epidermis. Supraphysiological levels of TNF-α may saturate and consequently down-regulate their own receptors, leading to a paradoxical inhibitory effect.     

Effects of the irreversible α-adrenoceptor antagonists phenoxybenzamine and benextramine on the effectiveness of nifedipine in inhibiting α 1- and α 2-adrenoceptor mediated vasoconstriction in pithed rats

Summary In pithed normotensive rats, i.v. injection of the selective ₁-adrenoceptor agonist cirazolien produced vasoconstriction which was largely resistant to inhibition by nifedipine. On the other hand, the pressor effects of the selective ₁-adrenoceptor agonists St 587 and Sgd 101/75 were much more effectively blocked by nifedipine, although not as effectively as the pressor effects to the selective ₂-adrenoceptor agonist B-HT 920. The sensitivity to inhibition of vasoconstriction in pithed rats to the different agonists increased in the order cirazoline St 587 ₁-, but not to ₂-adrenoceptor activation was dose-dependently enhanced. The potency of nifedipine to inhibit ₁-vasoconstriction by cirazoline, St 587 and Sgd 101/75 was increased maximally to the level of efficacy at which nifedipine antagonized B-HT 920-induced vasoconstriction. The dose of phenoxybenzamine required to maximally increase the potency and efficacy of nifedipine to antagonize vasoconstriction of the ₁-adrenoceptor agonists was inversely related to the level of sensitivity to blockade by nifedipine of the vasoconstriction they produced. In contrast, pretreatment of rats with the irreversible antagonist, benextramine (10 mg/kg, i.v., –100 to –60 min) did not increase the potency or efficacy of nifedipine to antagonize vasoconstriction to cirazoline, St 587, Sgd 101/75 or B-HT 920, despite irreversible blockade of ₁- and ₂-adrenoceptors. These data suggest that phenoxybenzamine, but not benextramine, selectively inhibits the ₁-adrenoceptor mediated vasoconstrictor mechanism that is independent of influx of extracellular calcium. Moreover, the results show that the existence of receptor reserve or the number of ₁-adrenoceptors activated does not determine the relative contribution of calcium influx-independent mechanisms in ₁-adrenoceptor-mediated vasoconstriction.Preliminary data were communicated at the Joint Meeting of the French and German Pharmacological and Toxicological Societies, Freiburg i. Br., September 19–22, 1983 (Timmermans et al. 1983a) and at the Winter Meeting of the British Pharmacological Society, London, January 1984 (De Jonge et al. 1984)     

The effect of nicergoline on the lower urinary tract muscle

Summary Two series of experiments were performed to determine whether nicregoline possesses an alpha-adrenergic blocking action on the lower urinary tract musculature in dogs and humans. One series consisted of in vivo studies of urethral pressure profile recordings in 19 female dogs, and their responses to adrenergic stimulation with noradrenaline or methoxamine, alone and following administration of nicergoline. The other series consisted of in vitro isometric studies of 61 strips of human prostate, and the establishement of dose response curves to nor-adrenaline alone and in the presence of various concentrations of nicergoline. In both sets of experiments clear evidence of an alpha-adrenergic blocking effect was obtained. From the in vitro experiments, the Kb of nicergoline was calculated as 9x10^-9 M.     

霍乱弧菌LPS诱导小鼠腹腔巨噬细胞产生TNF的研究

本研究采用霍乱弧菌古典生物型５６９Ｂ菌株及ＥＩ-Ｔｏｒ生物型菌株，以Ｗｅｓｔｐｈａｌ的热酚-水法及高速离心等方法提取ＬＰＳ，血凝法测其效价，并比较不同菌株的ＬＰＳ刺激小鼠腹腔巨噬细胞产生ＴＮＦ的情况。实验表明５６９Ｂ菌株ＬＰＳ血凝效价较高，诱导小鼠腹腔巨噬细胞产生ＴＮＦ的能力较强。     

Electrical coupling, without dye coupling, between mammalian astrocytes and oligodendrocytes in cell culture

Evidence of electrical and dye coupling between oligodendrocytes and astrocytes was sought in cultures of mouse spinal cord. Cell identity was verified using cell specific antigenic markers. In most experiments current was injected into oligodendrocytes while recording voltage in nearby astrocytes. Nine of 17 oligodendrocyte-astrocyte cell pairs showed weak electrical coupling; the average estimated coupling ratio was 0.03 +/- 0.06 (cf. 0.11 for oligodendrocyte-oligodendrocyte and 0.44 for astrocyte-astrocyte pairs; Kettenmann and Ransom: Glia, 1: 64-73, 1988). Application of 0.5 mM BaCl2 or 44.6 mM CsCl depolarized astrocytes and oligodendrocytes and was estimated to increase the coupling ratio between these cells 3-5-fold; these effects were rapid in onset and completely reversible. In 5 of 7 cases, oligodendrocyte-astrocyte pairs that appeared uncoupled in normal solution exhibited coupling during Ba++ or Cs+ exposure. The actions of these cations are believed to be mediated by blockade of glial K+ channels. Depolarization, per se, as induced by increasing [K+]o, did not increase coupling ratio. The fluorescent dye lucifer yellow (LY) was injected into 10 oligodendrocytes, 8 of which were electrically coupled to nearby astrocytes, and never passed into astrocytes in detectable quantities. Likewise, astrocytes injected with LY stained other astrocytes, but never oligodendrocytes. These findings document the presence of weak electrical coupling between astrocytes and oligodendrocytes, in the absence of dye coupling. Weak coupling of this sort could subserve metabolic interactions between these cells mediated by the passage of small but important molecules such as cyclic AMP, but would not allow strong electrical interactions. If such coupling among glial cells is widespread, it would constitute a "metabolic syncytium" that could serve to coordinate glial behavior.     

Hemodynamic differences between carvedilol and labetalol in the cutaneous circulation

The effects of labetalol and carvedilol on local cutaneous microvascular perfusion and calculated local cutaneous microvascular resistance were investigated in anesthetized rats at submaximal doses that produced equivalent reductions in blood pressure and heart rate. Labetalol decreased cutaneous perfusion (– 25% ± 3%) without significantly affecting cutaneous vascular resistance ( – 6% ± 3%). In marked contrast, carvedilol dramatically increased cutaneous perfusion ( + 64% ± 9%) and significantly reduced cutaneous vascular resistance ( – 57% ± 3%). These results suggest that carvedilol and labetalol possess differences in the mechanisms by which they produce vasodilation in vivo.     

糖尿病患者血清中IL-4、TNF-a的检测及分析

目的 探讨白介素４（ＩＬ－４）、肿瘤坏死因子（ＴＮＦ－ａ）水平与糖尿病关系。方法 采用ＥＬＩＳＡ法测定５４例糖尿病患者及４０例健康人血清ＩＬ－４、ＴＮＦ－ａ含量。结果 糖尿病患者ＩＬ－４平均含量明显低于健康人（Ｐ〈０．０５）,且与血糖一负相关（ｒ＝－０．３４７,Ｐ〈０．０５）。ＴＮＦ－ａ含量略高于对照组,但无统计学意义。结论 糖尿病患者内存在细胞免疫功功能紊乱,自身免疫功能调节失衡影响糖尿病的发生     

侧柏叶乙酸乙酯提取物对豚鼠离体气管平滑肌的作用

用离体豚鼠气管条,探讨侧柏叶乙酸乙酯提取物对气管平滑肌作用。结果表明,侧柏叶乙酸乙酯提取物能抑制乙酰胆碱,氯化钾所致气管平滑肌收缩,而且能使乙酰胆碱收缩气管平没肌的量效曲线右移,并抑制最大效应,其作用为剂量依赖性心肌肥厚提示侧柏叶乙酸乙酯提取物松驰气管平滑肌作用机制可能与影响Ｃａ＾２＋的跨膜转运有关。     

戈米辛J和异型南五味子丁素对大鼠胸主动脉的作用

目的研究由南五味子属药用植物分离的戈米辛Ｊ（ｇｏｍｉｓｉｎＪ,ＧＪ）和异型南五味子丁素（ｈｅｔｅｒｏｃｌｉｔｉｎＤ,ＨＤ）对血管平滑肌的作用。方法采用离体大鼠胸主动脉标本,观察他们对高钾去极化收缩和对ＣａＣｌ２、ＮＡ量效曲线的影响。结果ＧＪ和ＨＤ能抑制ＫＣｌ所致的收缩,其ＩＣ５０（９５％可信限）分别为３．８（２．４～５．９）和７．５（１．４～３９）μｍｏｌ／Ｌ;ＧＪ和ＨＤ能使ＣａＣｌ２量效曲线右移,最大效应降低,其ｐＤ′２值分别为５．１３±０．０７和４．７７±０．１８;ＧＪ和ＨＤ也可使ＮＡ量效曲线右移和最大效应降低,其ｐＤ′２值分别为３．７２±０．２３和３．３１±０．２７。结论ＧＪ和ＨＤ能抑制ＫＣｌ、ＣａＣｌ２和ＮＡ产生的血管收缩,而且对ＣａＣｌ２的致缩作用强于对ＮＡ的收缩作用,提示他们具有钙拮抗活性。     

类风湿性关节炎患者血清IL-6、TNF水平变化及其意义探讨

采用细胞生物学方法测定类风湿性关节炎（ Ｒ Ａ）１４ 例血清 Ｉ Ｌ－ ６ 、 Ｔ Ｎ Ｆ 水平,均显著高于正常对照组（ Ｐ＜ ０ ．００１） 。相关分析显示 Ｉ Ｌ－ ６ 与 Ｔ Ｎ Ｆ 水平变化呈正相关（ Ｐ＜ ０ ．０１） , Ｉ Ｌ－ ６ 、 Ｔ Ｎ Ｆ 与血沉亦呈正相关（ Ｐ＜０ ．０５） 。认为, Ｉ Ｌ－ ６ 、 Ｔ Ｎ Ｆ 参与 Ｒ Ａ 的发病,两者在致病中有协同相同;其水平变化与 Ｒ Ａ 的活动性及血沉相关。