IL-10 has a protective role in experimental autoimmune uveoretinitis

The role of IL-10 in the regulation of ocular autoimmune disease was studied in experimental autoimmune uveoretinitis (EAU) elicited in mice by immunization with the retinal antigen interphotoreceptor retinoid binding protein. IL-10-deficient mice were susceptible to EAU, indicating that pathogenesis can occur without presence of IL-10. Treatment of normal mice with IL-10 for 5 days after uveitogenic immunization ameliorated subsequent EAU scores, and down-regulated antigen-specific production of tumor necrosis factor-alpha and IFN- gamma. A concomitant treatment with IL-4 further reduced disease, and resulted in emergence of antigen-specific IL-4 and IL-10 production, as well as in enhancement of the IgG1 antibody isotype. IL-4 by itself was not protective. Only IL-10, but not IL-4, was able to inhibit the function of differentiated uveitogenic T cells in culture. Expression of mRNA for Th1 and Th2 cytokines in the eye during the course of EAU showed that while a Th1 pattern predominated early, IL-10 mRNA expression coincided with down-regulation of the Th1 response and resolution of EAU. Systemic neutralization of IL-10 during the expression phase of EAU resulted in elevated disease scores. Our results suggest that endogenous IL-10 limits expression of EAU and may play a role in the natural resolution of disease. The data further suggest that exogenous IL-10 may be useful in therapeutic control of autoimmune uveitis. While IL-10 by itself is sufficient to suppress Th1 effector development and function, a concomitant administration of IL-4 is required to shift the autoimmune response towards a non-pathogenic Th2 pathway.      

急性分离的大鼠骶髓后连合核神经元由抑制性氨基酸诱导的电流反应(英文)

应用制霉菌素穿孔全细胞电压钳技术．在急性分离的大鼠骶髓后连合核（SDCN）神经元上，研究抑制性氨基酸诱导的反应的电生理学和药理学特性。当钳制电压为-40mV时，γ-氨基丁酸（GABA）、甘氨酸（Gly）和牛磺酸（Tau）均诱导产生内向电流。它们的EC50值分别是GABA5．2×10-5M，Gly4．0×10-5M及Tau1．6×10-4M。其Hill系数分别为GABA1．21，Gly1．27和Tau1．23。所有这些电流均在膜电位为-1．8mV左右时翻转。此外．Tau和Gly反应问还存在很强的交叉脱敏。结果提示，GABAA，Gly和Tau作为递质，通过受体Cl-通道复合体．在调节SDCN社经元伤害性传递中可能有重要作用。     

聚醚型聚氨酯材料表面纤维蛋白原的吸附性研究

本文采用放射性同位素标记的方法研究了嵌段聚醚型聚氨酯在纯纤维蛋白原溶液中和稀释血浆中的表面纤维蛋白原吸附性规律，考察了聚醚型聚氨酯的特性粘数及溶液体系中的ＮａＣｌ浓度对材料表面纤维蛋白原吸附性的影响，结果表明，随着聚合物特性粘数的增大，材料表面的纤维蛋白原吸附量呈降低的趋势；溶液体系中盐浓度的降低导致纤维蛋白原凝固性增强，在纯纤维蛋白原溶液中，材料表面纤维蛋白原的吸附量相应增多，而在稀释血浆中，纤维蛋白原的吸附量相应减少，在达到最低值后又有上升的趋向，表明纤维蛋白原在材料表面的吸附还受血浆中其它大分子的影响。     

脑内源性β-内啡肽对应激诱发促肾上腺皮质激素和催乳素释放的调节

在预先埋植第三脑室导管和预置颈外静脉导管的SD大鼠中,脑室内微量注射β-内啡肽抗血清,并与脑室内注射正常兔血清的大鼠对比。看到注射β-内啡肽抗血清后,ACTH和催乳素因限制性应激的释放,分别被抑制了46.1％和71.2％。说明中枢内源性β-内啡肽可能是ACTH和催乳素在某种应激时相伴释放的重要调节因素之一。     

复方中药注射液对小白鼠艾氏腹水癌细胞膜表面的(Na~+-K~+)-ATP酶和微绒毛影响的电镜观察

本实验应用电镜细胞化学和扫描电镜技术,观察到小白鼠艾氏腹水癌细胞在复方中药注射液的连续作用下,膜表面(Na~+-K~+)-ATP酶活性减弱,微绒毛减退等变化,同时观察到该复方中药注射液对癌细胞增殖的抑制作用,抑瘤率可达87%,癌细胞增殖和(Na~+-K~+)-ATP酶活性及微绒毛的多少有平行关系。讨论了该复方中药抑制癌细胞增殖与膜表面(Na~+-K~+)-ATP酶活性和微绒毛变化的关系。     

内皮型、诱导型一氧化氮合酶在乳腺癌中的表达

目的 :研究内皮型一氧化氮合酶 (eNOS)、诱导型一氧化氮合酶 (iNOS)在乳癌中表达及与淋巴结转移的关系。方法 :采用免疫组化S P法检测 60例乳癌中eNOS和iNOS的表达。结果 :eNOS和iNOS阳性在乳癌中表达率分别为 75 0 %和71 7%。在淋巴结转移组和无淋巴结转移组中eNOS阳性表达率分别为 66 7%和 83 3 % ,两组间差异无统计学意义 (χ2 =2 2 2 ,P >0 0 5) ,而iNOS在淋巴结转移和无转移组中阳性表达率分别为 53 3 %和 90 0 % ,两组间差异有统计学意义 (χ2 =9 93 ,P <0 0 1 )。结论 :内皮型、诱导型一氧化氮合酶在乳腺癌中高表达 ;iNOS的表达与乳腺癌的淋巴转移相关     

一氧化氮合酶与缺氧复氧所致神经细胞凋亡及银杏叶提取物的保护作用

目的　探讨一氧化氮 (NO)在缺氧复氧诱导神经细胞凋亡中的作用及中药银杏叶提取物的保护机制。方法　实验使用胎龄 16～ 17日Wistar大鼠的大脑皮层神经细胞进行原代分离培养 ;采用Wright Giemsa染色 ,光镜、透射电子显微镜观察 ;原位末端标记法确立缺氧复氧神经细胞凋亡病理模型 ;应用NADPH d组织化学方法检测神经细胞一氧化氮合酶 (NOS)的表达并用计算机图像分析系统进行定量检测。　结果　缺氧复氧可以使大鼠大脑皮层神经细胞发生凋亡 ,随缺氧时间的延长 ,凋亡细胞数渐多 ,至缺氧 8h复氧 18h达高峰 ;在缺氧 2h(H2 R0 组 )和缺氧 8h复氧 18h(R8R1 8)组中神经细胞NOS表达均显著增高 ,与正常对照组比有显著性差异 (P <0 0 1;P <0 0 5 )。EGB能显著抑制此双时相NOS活性的增强 ,并明显降低神经细胞凋亡率。　结论　缺氧复氧损伤可诱导培养的大鼠大脑皮层神经细胞发生凋亡。NOS表达增强从而使NO产生增加可能是缺氧复氧诱导神经细胞凋亡的机制之一。银杏叶提取物 (EGB)经下调NOS表达活性 ,抑制NO的产生保护培养的大鼠大脑皮层神经细胞免于凋亡。     

Formation of 6-nitro-norepinephrine from nitric oxide and norepinephrine in the spinal cord and its role in spinal analgesia

Spinally released norepinephrine is thought to produce analgesia in part by stimulating alpha(2)-adrenergic receptors, which in turn leads to nitric oxide synthesis. Also, nitric oxide is known to react with norepinephrine in vivo in the brain to form 6-nitro-norepinephrine, which inhibits neuronal norepinephrine reuptake. In the present study, we tested the hypothesis that formation of 6-nitro-norepinephrine occurs in the spinal cord and that intrathecal administration of 6-nitro-norepinephrine produces analgesia by stimulating norepinephrine release. 6-Nitro-norepinephrine was present in rat spinal cord tissue and microdialysates of the dorsal horn and intrathecal space. Intrathecal norepinephrine injection increased 6-nitro-norepinephrine. 6-Nitro-norepinephrine also stimulated norepinephrine release in dorsal spinal cord in vitro. Intrathecal injection of 6-nitro-norepinephrine produced antinociception and interacted additively with norepinephrine for antinociception. Spinal noradrenergic nerve destruction increased antinociception from intrathecally injected norepinephrine, but decreased antinociception from 6-nitro-norepinephrine.These results suggest a functional interaction between spinal nitric oxide and norepinephrine in analgesia, mediated in part by formation of 6-nitro-norepinephrine. Stimulation of auto-inhibitory alpha(2)-adrenergic receptors at noradrenergic synapses decreases norepinephrine release. Paradoxically, alpha(2)-adrenergic agonist injection increases and alpha(2)-adrenergic antagonist injection decreases norepinephrine release in the spinal cord. 6-Nitro-norepinephrine may be an important regulator of spinal norepinephrine release and could explain the positive feedback on norepinephrine release after activation of spinal alpha(2)-adrenergic receptors.     

Reduced Left Ventricular Compliance and Mechanical Efficiency after Prolonged Inhibition of NO Synthesis in Conscious Dogs

Acute inhibition of NO synthesis decreases left ventricular (LV) work and external efficiency, but it is unknown whether compensatory mechanisms can limit the alterations in LV mechanoenergetics after prolonged NO deficiency. Eight chronically instrumented male mongrel dogs received 35 mg kg⁻¹ day⁻¹ of N ^ω-nitro-L-arginine methyl ester orally for 10 days to inhibit NO synthesis. At spontaneous beating frequency, heart rate, coronary blood flow, peak LV pressure, end-diastolic LV pressure and the maximum derivative of LV pressure (d P /d t _max) were not significantly different vs. baseline, whereas LV end-diastolic diameter (32.5 ± 1.0 vs. 37.6 ± 1.4 mm) and LV stroke work (515 ± 38 vs. 650 ± 44 mmHg mm), were reduced (all P < 0.05). The slope of the LV end-systolic pressure-diameter relationship was increased at 10 days vs. baseline (13.9 ± 1.0 vs. 9.6 ± 0.9 mmHg mm⁻¹, P < 0.05), while the end-diastolic LV diameter was smaller at matched LV end-diastolic pressures. At fixed heart rate (130 beats min⁻¹), cardiac oxygen consumption was increased (12.2 ± 1.5 vs. 9.9 ± 1.0 ml min⁻¹), and the ratio between stroke work and oxygen consumption was decreased by 33 ±7 % (all P < 0.05) after NO inhibition. We conclude that sustained inhibition of NO synthesis in dogs causes a decrease in LV work despite an increased contractility, which is most probably due to reduced diastolic compliance and a decrease in external efficiency. Thus, prolonged NO deficiency is not compensated for on the level of LV mechanoenergetics in vivo .     

Biochemical characterization of atherosclerotic plaque constituents using FTIR spectroscopy and histology

The behavior of vulnerable atherosclerotic plaques is believed to be closely related to plaque composition. There is a need for an effective in vivo technique for examining plaque constituent properties. In this study, Fourier transform infrared spectroscopy using attenuated total reflectance (FTIR-ATR) was used to assess and analyze the biochemical properties of human atherosclerotic plaques. FTIR spectra clearly revealed prominent spectral features corresponding to plaque constituents of interest: the 2930 cm(-1) and 2850 cm(-1) peaks (indicating the presence of lipids), the 1730 cm(-1) peak (lipid esters), the 1550 cm(-1) and 1650 cm(-1) peaks (fibrous tissues), and the 1100-1000 cm(-1) broad phosphate peak (calcification). Spectral data examined on a qualitative basis correlated well with both gross tissue anatomy and histologic features. Gross spatial mappings of tissue sections of both lipidic and calcified plaques were performed. Spectra from various regions of the plaques demonstrated the evolution of lipid peaks, fibrous tissue peaks, and the phosphate calcification band within the plaques. Histologic analysis corroborated the spectral findings in this study.