狼疮肾炎患者尿单核细胞趋化蛋白-1检测的临床意义

目的探讨狼疮肾炎患者尿单核细胞趋化蛋白-1(MCP-1)水平变化在狼疮肾炎中的临床意义。方法采用酶联免疫吸附试验(ELISA)方法对23例狼疮肾炎,13例原发性肾炎和12名健康对照者的尿MCP-1水平进行检测,比较分析其与肾脏损害及其与肾脏组织病理活动性指数(AI)的相关关系。结果狼疮肾炎患者尿MCP-1水平为(1130±403)pg/mg肌酐,显著高于对照者(141±109)pg/mg肌酐(P<0.01)和原发性肾炎患者(452±174)pg/mg肌酐(P<0.01)。狼疮肾炎患者尿MCP-1水平与24h尿蛋白(r=0.558,P<0.05)、血肌酐(r=0.869,P<0.01)、尿N-乙酰-D-氨基葡萄糖酶(NAG)(r=0.617,P<0.05)及肾脏组织病理AI(r=0.751,P<0.01)呈显著正相关。结论狼疮肾炎患者尿MCP-1水平可作为了解肾脏活动性病变的一个分子指标。     

狼疮肾炎尿液转化生长因子-β1巨噬细胞炎症蛋白-1α和中性粒细胞明胶酶相关脂质运载蛋白检测的临床意义

目的 拟判断尿液中转化生长因子(TGF)-β1,巨噬细胞炎症蛋白(MIP)-lα和中性粒细胞明胶酶相关脂质运载蛋白(NGAL)与狼疮肾炎病理的相关性.方法 酶联免疫吸附试验(ELISA)法检测入选对象尿液中TGF-β1,MIP-lαt和NGAL的水平.分析3种尿液标记物与病理分型、Austin评分和组织学半定量评分的相关性.统计采用t检验、方差分析和X2检验;相关性分析采用Pearson相关分析.结果 ①狼疮肾炎患者组与非肾损害SLE和健康对照组相比,尿液中TGF-β1[(351±219),(92±60),(74±29) pg/ml],MIP-1α [(18.0±15.5),(8.5±2.3),(7.1±1.9) pg/ml]和NGAL[(1.104±0.519),(0.181±0.030),(0.146±0.024) ng/ml]水平差异有统计学意义(F值分别为15.88,6.49,35.95;P均＜0.01),而与非狼疮肾炎肾小球疾病组患者差异无统计学意义.②在狼疮肾炎不同病理分型中3种尿液标记物差异有统计学意义(P＜0.01),但这种改变在同一病理类型中狼疮肾炎组和其他肾小球疾病组之间差异无统计学意义.③狼疮肾炎患者尿液中3种标记物与组织病理半定量评分相关性分析结果显示,尿液中TGF-β1与系膜基质增生指数(MsMI)、肾小球慢性病变指数(GCI)、肾间质萎缩和肾间质纤维化指数(TCI)、小动脉慢性病变指数(VCI)密切相关;MIP-1α与内皮细胞增生指数(endol)、活动性新月体及节段性袢坏死(dGAI)、VCI有相关性;而NGAL与endol,dGAI,MsHI有明显相关性.而3种标记物与狼疮肾炎患者肾活检活动性和慢性指数的相关性分析结果显示,TGF-β1与慢性指数明显相关(r=0.89,P＜0.01),而MIP-1α和NGAL与活动性指数明显相关(r=0.71,P＜0.01;r=0.60,P＜0.01).结论 狼疮肾炎患者尿液中TGF-β1与肾脏的病变的慢性化相关.而MIP-1α和NGAL与肾脏活动病理相关.     

系统性红斑狼疮患者血清卵泡抑素样蛋白1表达水平及其临床意义

目的 检测系统性红斑狼疮(SLE)患者血清中卵泡抑素样蛋白1(FSTL1)的水平及FSTL1在狼疮肾炎肾脏组织中的表达,探讨其在SLE疾病中的临床意义.方法 酶联免疫吸附试验(ELISA)法检测54例SLE患者及27名健康对照组血清FSTL1水平.免疫组织化学染色检测狼疮肾炎患者肾脏组织及健康者肾脏组织中FSTL1的表达情况.采用Mann-WhitneyU/检验、t检验、X2检验及Pearson检验进行统计分析.结果 SLE组FSTL1血清水平(26±21) μg/L显著高于健康对照组(12±14) μg/L(P＜0.01);SLE高血压组明显高于非高血压组(P＜0.01);SLE病程≥5年组与病程＜5年组之间差异有统计学意义(P＜0.01);血清FSTL1表达水平与SLE疾病活动指数(SLEDAI)评分(r=0.319,P=0.022)、年龄(r=0.700,P＜0.01)、病程(r=0.513,P＜0.01)、补体C4 (r=0.443,P=0.004)、总胆固醇(r=0.460,P=0.001)呈正相关;与血小板计数(r=-0.422,P=0.001)、抗双链DNA(dsDNA)抗体水平(r=--0.276,P=0.046)呈负相关.FSTL1主要表达在肾小管上皮细胞胞质内.结论 FSTL1在SLE患者血清中明显升高,且与疾病活动性有关.提示FSTL1在SLE发病机制中起一定作用.     

系统性红斑狼疮患者血浆单核细胞化学吸引蛋白-1检测及其临床意义

目的 分析血浆单核细胞化学吸引蛋白-1(MCP-1)水平与系统性红斑狼疮(SLE)脏器受累及病情严重性的关系,探讨检测血浆MCP-1水平的临床意义.方法 采用酶联免疫吸附试验(ELISA)法检测95例SLE患者血浆MCP-1水平,并与21名健康体检者对照.结果 血浆MCP-1水平在SLE患者为(849±289)pg/ml,显著高于健康对照组的(426±266)pg/ml(P<0.01);在SLE患者,血浆MCP-1水平在有狼疮肾炎(LN)者明显高于无LN患者(P<0.01),并发狼疮脑病的患者也明显高于无中枢神经系统损害的患者(P相似文献   

狼疮肾炎肾组织核转录因子-κB单核细胞趋化因子-1与CD68的表达及相关分析

目的 对狼疮肾炎(LN)肾组织进行核转录因子-κB(NF-κB)、单核细胞趋化因子(MCP-1)及巨噬细胞特异性抗体(CD68)检测,探讨其与LN肾脏病理及临床指标的关系.方法 应用免疫组织化学二步法检测49例LN肾组织NF-κB、MCP-1及CD68,原位杂交法检测49例LN肾组织NF-κB,并与肾脏病理及临床指标进行分析.结果 ①LN肾组织中NF-κB、MCP-1及CD68表达均比对照组显著升高(P＜0.01);其中Ⅳ型LN肾组织中NF-κB、MCP-1及CD68的表达比非Ⅳ型LN及对照组明显增加(P＜0.01,P＜0.05).原位杂交与免疫组织化学法检测NF-κB差异无统计学意义(P＞0.05).②LN肾组织中,NF-κB的表达与肾组织活动性指数、尿蛋白定量(24 h)及血清肌酐均高于对照组,且三者之间差异有统计学意义(P＜0.01,P＜0.01,P＜0.05);MCP-1与CD68的表达在肾小球和肾小管中仅与肾组织活动性指数(r=0.447,0.532,P＜0.05)、尿蛋白定量(24 h)(r=0.357,0.368,P＜0.05)呈正相关,而与血肌酐之间差异无统计学意义(P＞0.05).结论 NF-κB通过活化MCP-1进一步诱导巨噬细胞可能是LN肾脏损害的原因之一,NF-κB信号途径有望成为抑制巨噬细胞在肾脏局部浸润和增生的一个新的治疗靶点.     

尿L-FABP、KIM-1、NGAL和血清cystatin C在糖尿病肾病中的变化及意义

目的 探讨尿液肝型脂肪酸结合蛋白(L-FABP)、肾损伤分子-1(KIM-1)、中性粒细胞明胶酶相关载脂蛋白(NGAL)和血清半胱氨酸蛋白酶抑制剂(cystatin)C水平在糖尿病肾病患者中的改变以及临床意义.方法 纳入2011年10月至2012年10月泸州医学院附属医院内分泌科确诊为2型糖尿病(T2DM)的住院患者118例,根据尿微量白蛋白/肌酐比值(UACR)分为正常白蛋白尿组(n=45)、微量白蛋白尿组(n=42)以及大量白蛋白尿组(n=31).同时选择同期健康体检者41名作为正常对照组.采用ELISA法检测尿L-FABP、KIM-1和NGAL,免疫比浊法检测血清cystatin C.所有尿液检测指标经尿肌酐校正,比较各组间各标志物的变化情况及与UACR、估计的肾小球滤过率(eGFR)的相关性.结果 与正常对照组相比,糖尿病各组尿L-FABP和血清cystatin C水平明显升高,(x2=77.959,104.003,P均＜0.05);尿KIM-1水平亦明显升高(x2=29.711,P＜0.05).微量白蛋白尿组与大量白蛋白尿组尿NGAL水平较正常对照组和正常白蛋白尿组明显升高(x2=23.833,P＜0.05),但在正常白蛋白尿组与正常对照组间未见明显变化.尿L-FABP、KIM-1、NGAL及血清cystatin C与UACR呈正相关(r=0.719,0.427,0.327,0.726,P均＜0.01);仅L-FABP、血清cystatin C与eGFR呈负相关(r=-0.301、-0.791,P＜ 0.01).结论 尿L-FABP、KIM-1、NGAL和血清cystatin C在糖尿病肾病早期显著升高,其中尿L-FABP和血清cystatin C可能是反映糖尿病肾损伤较好的生物学指标.     

类风湿关节炎患者血清中肿瘤坏死因子凋亡样微弱诱导剂和凋亡调节蛋白生存素水平的检测和意义

目的 检测类风湿关节炎(RA)患者血清中肿瘤坏死因子样凋亡微弱诱导剂(TWEAK)和凋亡调节蛋白生存素(survivin)的水平,以探讨其在RA中的意义.方法 采用酶联免疫吸附试验(ELISA)方法测定61例RA患者和35名健康对照组血清中TWEAK和survivin水平,同时测定RA患者关节功能、X线分期、关节压痛数和肿胀数、红细胞沉降率、类风湿因子、C反应蛋白等各项临床指标,进行相关性分析.结果 RA患者血清中TWEAK水平[(479±381)pg/ml]与健康对照组TWEAK水平[(421±87)pg/ml]差异无统计学意义.RA患者血清中survivin水平[(159±82)pg/ml]比对照组[(119±24)pg/ml]增高(P＜0.05),且血清gurvivin水平与RA患者关节X线分期呈正相关(r=0.29,P＜0.05).结论 血清TWEAK水平与RA的关系还需要更深入的研究.Survivin与关节侵蚀性相关,可能成为新的判断病情及治疗的新指标.     

尿急性肾损伤标志物与抗中性粒细胞胞浆抗体相关性肾炎预后相关性研究

目的分析尿中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)及肾脏损伤分子-1(kidney injury molecule-1,KIM-1)与抗中性粒细胞胞浆抗体(anti-neutrophil cytoplasmic antibody,ANCA)相关性肾炎(ANCA associated glomerulonephritis,AAGN)严重程度及预后的关系。方法回顾2009年4月至2013年11月间南京军区南京总医院肾脏科住院的69例AAGN患者,其中抗过氧化物酶抗体阳性61例,抗蛋白酶3抗体阳性8例,肾活检进行病理分型及肾小管间质炎症细胞浸润和肾间质纤维化及肾小管萎缩半定量积分。尿NGAL及KIM-1采用ELISA方法检测,Spearman检验分析尿NGAL及KIM-1与肾脏损害指标(血肌酐、尿蛋白及血白蛋白)的关系,采用Mann-Whitney检验比较组间差异,分析尿NGAL及KIM-1与肾小管病变评分及肾脏预后的关系。结果69例AAV肾脏病理类型:局灶型14例,新月体型26例,混合型29例。基线肌酐:276.69(47.74~1193.40)μmol/L,24 h尿蛋白定量1.61(0.11~9.78)g。3种病理类型之间尿NGAL及KIM-1差异无统计学意义。尿NGAL与尿蛋白及Scr呈正相关(r值分别为0.3242、0.3257,P分别为0.0095、0.0081),与血清白蛋白呈负相关(r=-0.3964,P=0.0009)。尿KIM-1与血清白蛋白呈负相关(r=-0.2539,P=0.0413),但与血肌酐及尿蛋白无相关性。尿KIM-1与肾间质浸润细胞程度相关,差异有统计学意义(P=0.0413)。尿NGAL与肾间质浸润细胞程度无相关性。45例随访24(14~58)个月,13例进入终末期肾脏疾病者基线尿NGAL高于未进入终末期肾脏疾病者[(117.6(3.06~518.4)μg/L对28.86(2.17~461.5)μg/L,P=0.0372)],多因素COX回归分析示尿NGAL为不良肾脏预后的独立危险因素(HR 1.012,95%CI 1.001~1.022,P=0.033)。结论尿NGAL水平反映AAGN的严重程度,为不良肾脏预后的独立危险因素,而KIM-1与间质浸润细胞程度相关。     

尿中性粒细胞明胶酶相关脂质运载蛋白在神经急症患者肾损伤早期诊断中的价值

目的:探讨尿中性粒细胞明胶酶相关脂质运载蛋白(NGAL)在神经急症患者肾损伤早期诊断中的价值。方法:选取神经急症患者295例,按照是否发生肾损伤,将其分为急性肾损伤组(48例)和非肾损伤组(247例)。比较2组患者的一般资料,分析尿NGAL水平与肾损伤之间关系,肾损伤的危险因素。结果:肾损伤组患者血清胱抑素-C(Cy C)、高敏C反应蛋白(hs-CRP)、血钙、血磷、血尿素氮(BUN)、血肌酐、β2微球蛋白及尿NGAL水平明显高于非肾损伤组(P 0. 05)。Pearson相关性分析显示,尿NGAL水平与肾损伤呈正相关(r=0. 334,P=0. 001);多因素回归分析显示,血肌酐、尿NGAL及血CyC为肾损伤独立危险因素;尿NGAL水平诊断肾损伤的效能高于血肌酐和CyC。结论:神经急症患者尿NGAL水平升高可以作为早期诊断肾损伤的生物学指标。     

尿巨噬细胞趋化蛋白-1和巨噬细胞集落刺激因子对狼疮肾炎复发的诊断作用

目的探讨在成功的泼尼松和环磷酰胺诱导治疗后,引起弥漫增生型(Ⅳ型)狼疮肾炎复发的预测指标。方法收集弥漫增生型狼疮肾炎病例,将泼尼松和环磷酰胺诱导治疗成功的病例纳入研究对象。记录临床和实验室资料,于治疗开始后6个月时检测患者尿巨噬细胞趋化蛋白(MCP)-1和巨噬细胞集落刺激因子(M-CSF)。追踪治疗后的复发情况。结果共收集到64例诱导治疗成功的病例,经平均(27±3)个月随访,18例(28%)患者发生至少一次肾性复发,其复发的平均时间为(14±4)个月。复发组患者尿MCP-1和M-CSF水平明显高于缓解维持组。尿MCP-1和M-CSF升高,及血C3降低和抗dsDNA抗体阳性均是Ⅳ型狼疮肾炎复发的独立预测因子。有7例患者出现血肌酐倍增(CRX2),肾性复发是CRX2的惟一预测因子。结论尿MCP-1和M-CSF持续升高是Ⅳ型狼疮肾炎复发的独立预测因子。该研究提示监测诱导缓解患者肾组织炎症指标可有利于指导狼疮肾炎的治疗。     

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.     

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.     

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.     

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.