白细胞介素-10在川崎病炎性细胞因子介导的血管损伤中的作用初探

目的　探讨白细胞介素 10 (IL 10 )在炎性细胞因子介导的川崎病血管内皮损伤中的作用及机制。方法　建立人脐静脉内皮细胞培养模型 ,ELISA双抗体夹心法检测川崎病患儿外周血单个核细胞 (PBMC)活化后培养上清IL 6、IL 1β、肿瘤坏死因子 α(TNF α)、IL 10的分泌量 ;AnnexinV/PI双染色法 ,流式细胞仪检测川崎病患儿PBMC培养上清所诱导的内皮细胞凋亡率 ;凝胶电泳迁移率转换实验 (EMSA)检测所活化PBMC核因子NF κB活性。结果　川崎病组患者PBMC体外刺激活化后IL 6、IL 1β、TNF α等炎性细胞因子及IL 10的分泌量均明显高于正常对照组 (P <0 0 1) ,其培养上清所诱导内皮细胞凋亡率 (38 4± 7 8) %较正常组 (2 8± 0 8) %明显升高。抗IL 6、TNF αMcAb、IL 1ra加入川崎病患儿PBMC培养上清 ,可不同程度抑制川崎病患儿PBMC培养上清所诱导内皮细胞的凋亡 ,而抗IL 10McAb加入川崎病患儿PBMC培养上清所诱导内皮细胞的凋亡细胞反而增多 ,凋亡细胞的百分率高达 (5 8 6± 14 6 ) %。川崎病患儿PBMC刺激活化后核因子NF κB活性显著增高。于PBMC培养上清加入IL 10 ,可见伴随着IL 6、IL 1β、TNF α等炎性细胞因子在PBMC中的表达降低 ,NF κB活性也降低 ,同时内皮细胞凋亡明显减少。结论　IL 10抑制川崎病患儿免疫     

不稳定型心绞痛炎性因子与冠状动脉病变的对比研究

目的 :探讨不稳定型心绞痛 (UA)患者血清炎症因子水平、冠状动脉病变形态学特征及二者的相互关系。方法 :用免疫浊度法及放射免疫法测定 30例UA患者 (UA组 )、35例稳定型心绞痛 (SA)患者 (SA组 )、37例非冠心病患者 (对照组 )血清C 反应蛋白 (CRP)、白细胞介素 1β(IL 1β)、肿瘤坏死因子 α(TNF α)水平。对UA及SA患者冠状动脉造影所示斑块形态进行分析 ,按积分法评定冠状动脉病变狭窄程度。结果 :①UA组患者血清CRP、IL 1β、TNF α水平均明显高于SA组 (P <0 .0 5～ 0 .0 1)及对照组 (P <0 .0 1) ,后两组间差异无显著性意义 (P >0 .0 5 ) ;②UA组患者Ⅱ型斑块的发生率明显高于SA组 (6 6 .6 7%∶2 0 % ,P <0 .0 1) ;③SA组患者冠状动脉狭窄程度较UA组重 ,两组比较差异有显著性意义 (P <0 .0 5 ) ;④Ⅱ型斑块患者的血清CRP、IL 1β、TNF α水平均明显高于其他斑块类型 (P <0 .0 5～ 0 .0 1) ,而不同冠状动脉病变支数及狭窄程度间血清CRP、IL 1β、TNF α水平差异均无显著性意义 (P >0 .0 5 )。结论 :UA患者体内存在炎性细胞活化及炎症反应 ;斑块破裂及血栓形成可能与炎症反应有关 ;炎症在UA的发病中发挥了重要作用。     

晚期糖基化终产物修饰的β_2-微球蛋白刺激人关节滑膜细胞分泌促炎症细胞因子

目的　旨在探讨晚期糖基化终产物 (AGEs)修饰的 β2 微球蛋白 (AGE β2 m)对人关节滑膜细胞的病理生物学作用。方法　分离、培养正常人关节B型滑膜细胞 ,与AGE β2 m共同孵育 ,用ELISA法检测培养上清液中肿瘤坏死因子 α(TNF α)和白细胞介素 1β (IL 1β)水平。 结果　AGE β2 m诱导滑膜细胞分泌TNF α和IL 1β ,诱导作用具有时间和剂量依赖规律。抗AGE受体抗体预处理滑膜细胞能明显抑制AGE β2 m引起的TNF α和IL 1β分泌。结论　AGE β2 m通过AGE受体介导的作用 ,刺激人类关节B型滑膜细胞产生TNF α和IL 1β ,这种生物学效应可能参与了透析相关性淀粉样变 (DRA)时关节局部的炎症反应和组织损伤。     

冠心病患者血中白介素-1β、肿瘤坏死因子α和血脂含量变化及意义

目的 :探讨白介素 1β(IL 1β)、肿瘤坏死因子α(TNF α)与血脂的关系及其在冠心病 (CHD)发病机制中的作用。方法 :对 6 4例患者行冠状动脉造影 ,其中CHD组 33例 ,非CHD组 31例。测定两组血清中总胆固醇(TC)、甘油三酯 (TG)、高密度脂蛋白胆固醇 (HDL C) ,IL 1β和TNF α。 结果 :CHD组血TC、TG、IL 1β、TNF α显著高于非CHD组 (P <0 .0 1) ,而HDL C显著低于非CHD(P <0 .0 1) ;CHD组TNF α与TC呈显著正相关 (r =0 .86 2 ,P <0 .0 1) ,非CHD组TNF α与TC不相关。结论 :IL 1β、TNF α与血脂异常之间存在一定联系 ,三者可能均参与了CHD发生、发展过程     

充血性心力衰竭患者某些细胞因子的变化及胺碘酮对其影响的研究

检测充血性心力衰竭 (CHF)患者血清肿瘤坏死因子 α(TNF α)、白细胞介素 1β(IL 1β)和IL 6的变化 ,以及胺碘酮对培养的正常人及CHF患者单核细胞 (PBMC)分泌上述细胞因子的影响 ,以明确上述细胞因子在CHF发生过程中的作用 ,以及胺碘酮作用于CHF的免疫学机制。取 2 0例正常人和 2 0例Ⅲ～Ⅳ级的CHF患者静脉血 :①测其血清TNF α、IL 1β和IL 6含量 ;②离心取PBMC ,分别加入胺碘酮和脂多糖 (LPS)等 ,使胺碘酮的终浓度为 0 ,0 .1,1和10 μmol/ml进行培养 ,经 2 4h孵化后 ,取培养液上清 ,用酶联免疫吸附法 (ELISA)测培养上清中TNF α、IL 1β和IL 6。结果 :CHF患者血清TNF α、IL 1β和IL 6明显高于对照组 (P均 <0 .0 0 1) ,并随心衰程度的加重而增加 (P <0 .0 0 1)。TNF α与IL 1β和IL 6呈正相关 (r=0 .96 84,0 .9786 ;P均 <0 .0 0 1)。胺碘酮对两组PBMC分泌TNF α、IL 1β和IL 6均具有抑制作用 ,并呈剂量依赖性。结论 :①细胞因子TNF α、IL 1β和IL 6参与CHF的发生 ;②胺碘酮可能通过抑制细胞因子的产生 ,对心力衰竭患者产生改善心功能作用。     

细胞因子对白血病抑制因子和IL-6在骨髓基质细胞表达的调节

目的 :研究白细胞介素 1(IL 1)、TNF α、白细胞介素 4 (IL 4 )对骨髓基质细胞白血病抑制因子 (LIF)和白细胞介素 6 (IL 6 )表达的调节。方法 :用酶联免疫吸附试验 (ELISA)测定各细胞因子作用下的LIF与IL 6水平 ,用逆转录 聚合酶链反应 (PT PCR)测定各细胞因子作用下的LIF与IL 6转逆子水平。结果 :在IL 1、TNF α作用下LIF与IL 6水平明显升高 (P <0 .0 5 ) ,IL 4作用下IL 6水平明显升高 (P <0 .0 5 ) ,而LIF水平却明显降低 (P <0 .0 5 )。结论 :IL 1、TNF α有上调骨髓基质细胞LIF与IL 6表达 ,IL 4能上调骨髓基质细胞IL 6表达 ,却下调LIF的表达。     

肿瘤坏死因子α、白细胞介素1β对牛肺动脉内皮细胞凋亡的影响及意义

目的　研究肿瘤坏死因子α(TNF α)、白细胞介素 1β(IL 1β)对牛肺动脉内皮细胞 (BPEC)损伤的机制及在急性肺损伤 (ALI)发病过程中的作用。方法　建立BPEC的体外培养 ,采用流式细胞仪膜联蛋白V 异硫氰酸荧光素 (Annexin VFITC)、碘化吡啶 (PI)染色检测TNF α、IL 1β对BPEC凋亡的影响以及抗TNF α单克隆抗体、AC DEVD CHO (caspase 3的竞争性抑制剂 )的保护效应。结果　 (1)TNF α作用 2 4h ,随着其浓度的增加 (浓度为 50 0、10 0 0、2 0 0 0U/ml) ,BPEC凋亡率逐渐增加 [分别为(8 2 1± 0 70 ) %、(9 63± 0 71) %、(17 43± 1 99) % ] ,与对照组 [(3 0 9± 0 0 8) % ]比较差异有显著性(P均 <0 0 5) ;(2 )TNF α (2 0 0 0U/ml)培养时间延长 (分别为 6、12、2 4、3 6h) ,BPEC凋亡率逐渐增加 [分别为 (6 72± 0 3 8) %、(7 72± 1 66) %、(12 95± 0 3 2 ) %、(17 70± 1 79) % ,P均 <0 0 5] ;(3 )加入抗TNF α单抗、AC DEVD CHO的TNF α组的BPEC凋亡率 [(7 78± 0 2 1) %、(7 3 2± 0 11) % ]显著高于单纯TNF α(2 0 0 0U/ml)组 [(10 59± 0 49) % ,P均 <0 0 1] ,而加入IL 1β的TNF α组的凋亡率 [(10 73±0 60 ) % ]与单纯TNF α组比较差异无显著性 (P >0 0 5)。结论　ALI过程中是TNF     

青蒿素对血管平滑肌细胞增殖的影响

目的 :观察青蒿素 (artemisinin ,Art)对体外培养大鼠主动脉平滑肌细胞 (VSMC)的增殖、DNA合成及细胞周期的影响 ,探讨作用机制。方法 :体外培养大鼠主动脉VSMC ,分为不同浓度的Art组及对照组。观察细胞生长曲线 ;四甲基偶氮唑盐微量酶反应 (MTT)法检测细胞活性 ;3H 胸腺嘧啶脱氧核苷(3H- TdR)掺入法观察其对DNA合成的影响 ;通过HE染色、DNA梯带检测和流式细胞术观察细胞的凋亡并测定细胞周期。结果 :与对照组相比 ,各浓度Art组VSMC计数不同程度减少 ,3H- TdR掺入率降低 ,细胞增殖受抑制 ,VSMC凋亡增加 ,并呈浓度依赖性 ;Art诱导细胞凋亡 ;使细胞周期阻滞于G0 / G1 期。结论 :Art对体外培养VSMC的增殖有抑制作用 ,可能通过抑制细胞DNA合成 ,诱导细胞凋亡及干扰细胞周期等途径发挥作用     

充血性心力衰竭炎性细胞因子的改变

目的 :探讨充血性心力衰竭 (CHF)时肿瘤坏死因子 α(TNF α)、白细胞介素 6 (IL 6 )、白细胞介素 1β(IL 1β)和一氧化氮 (NO)的变化 ,及其与CHF关系。 方法 :CHF患者 4 5例和年龄匹配的对照者 17例 ,根据NY HA分级将CHF患者分成Ⅱ、Ⅲ、Ⅳ级 3组 ;根据体重分成恶病质组及非恶病质组。用酶联免疫法测定IL 6 ,用放射免疫法测定IL 1β、TNF α ,用比色法测定NO。 结果 :CHF组血清IL 6、IL 1β、TNF α和NO较对照组明显升高 ,IL 6、NO在心功能Ⅱ、Ⅲ、Ⅳ级时均显著升高 ,TNF α在Ⅲ、Ⅳ级时显著升高 ,而IL 1β在Ⅳ级时才显著升高。不同病因的CHF之间差异无统计学意义 ,恶病质组及非恶病质组之间差异也无统计学意义。血清TNF α与IL 6呈正相关 (r =0 .5 82 9,P <0 .0 1)。结论 :血清IL 6、IL 1β、TNF α、NO水平与CHF的严重程度密切相关 ,可作为判断CHF严重程度的指标 ;IL 6、IL 1β、TNF α在CHF的发生发展中可能起重要作用     

核因子-κB反义寡核苷酸对系膜细胞炎症因子基因表达的影响

目的 :探讨NF κB反义寡核苷酸 (oligodeoxynucleotide ,ODN)对人肾小球系膜细胞炎症因子表达的影响 ,为利用NF κB反义ODN治疗肾小球炎性病变奠定基础。　 方法 :人工合成p65反义、正义及错配ODN并行全程硫代磷酸化修饰。应用核酸酶保护法观察阳离子脂质体介导的不同浓度的反义ODN(0 0 0 1、0 0 1、0 1、1、1 0μmol/L)对系膜细胞TNF α、IL 1α、IL 1 β、MCP 1、IL 8、TGF β1mRNA表达的影响 ,以正义ODN(1 0 μmol/L)及错配ODN(1 0 μmol/L)作为对照组。　 结果 :正常培养状态下 ,系膜细胞可组成型表达TNF α、IL 1 β、IL 8和TGF β1mRNA ,而不表达IL 1α和MCP 1mRNA。细菌脂多糖 (lipopolysaccharide,LPS)刺激后上述 6种炎症因子表达显著上调。p65反义ODN可呈剂量依赖性地抑制LPS诱导的系膜细胞炎性细胞因子TNF α ,IL α,IL 1 β,MCP 1和IL 8的基因表达 ,而对TGF β1无显著抑制作用 ;p65正义及错配ODN均不能抑制炎性细胞因子的表达。　 结论 :p65反义ODN可明显抑制LPS诱导的肾小球系膜细胞炎性细胞因子的表达 ,提示NF κB在肾小球疾病进展中起关键性调控作用 ,其反义ODN有可能应用于肾脏病变的实验性治疗之中     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.