2型糖尿病患者一氧化氮及血小板活化异常与肾病的关系

目的探索一氧化氮(NO)及血小板活化异常与糖尿病肾病(DN)的关系.方法 74例2型糖尿病(DM)患者测定了血清NO,其中62例同时测定了血浆α-颗粒膜蛋白(GMP140)的水平,并依据24小时尿白蛋白排出率(UAER)将其分为正常白蛋白尿组(DM1)、微量白蛋白尿组(DM2)、大量白蛋白尿组(DM3),并与37例正常人对照(NC).结果血清NO在DM1较NC明显升高,但DM2、DM3却较NC有显著性的降低;血浆GM140在DM各组均较NC升高,特别是DM2、DM3组较NC明显升高.DM合并高血压者血NO较无高血压者明显降低,而GMP140均较无高血压者为高(P＜0.05).血NO与GMP140呈显著负相关(rs＝-0.52,P＜0.05).结论 NO在2型DM早期升高,引起肾小球高灌注状态,后期下降,导致血小板活化增加.NO水平的异常及血小板活化的增强与DN的发生、发展密切有关.     

对氧磷酯酶1与2型糖尿病肾病的关系

目的　探讨血清对氧磷酯酶 1(PON1)活性与 2型糖尿病 (DM)并发肾病 (DN)的关系。方法　血清PON1活性用酚乙酸酯为底物测定 ,血浆氧化型低密度脂蛋白 (ox LDL)用ELISA法测定 ,尿 2 4小时微量白蛋白用放免法测定。结果　 91例 2型DM患者的PON1活性比 5 4例正常对照显著降低〔(138.2± 31.4 )kU/Lvs (184 .1± 2 9.5 )kU/L ,P <0 .0 0 1〕 ,且 2型DM的Ⅰ组 (UAER <30mg/ 2 4h)、Ⅱ组 (UAER 30～ 30 0mg/ 2 4h)和Ⅲ组 (UAER >30 0mg/ 2 4h)相比 ,PON1活性依次显著下降〔(15 1.8± 2 4 .5 )kU/L ,(12 4 .5± 32 .8)kU/L ,(10 1.1± 36 .6 )kU/L ,P <0 .0 1〕 ,而ox LDL的浓度却依次显著升高〔(6 16 .2± 135 .7) μg/L ,(75 3.9± 132 .5 ) μg/L ,(875 .1± 15 3.2 ) μg/L ,P <0 .0 1〕。PON1活性与ox LDL的浓度呈高度负相关 (r =- 0 .83,P <0 .0 0 1) ,也与UAER呈负相关 (r =- 0 .2 8,P<0 .0 5 ) ,多元回归分析表明PON1活性是 2型DM并发DN的高度危险因素 (P <0 .0 1)。结论　PON1活性在 2型DM显著下降 ,且在并发DN的 2型DM患者下降更显著。PON1活性与ox LDL呈负相关。PON1活性降低是 2型DM并发DN的高度危险因素     

对氧磷脂酶-1和氧化低密度脂蛋白在2型糖尿病肾病中的作用

目的 探讨2型糖尿病（DM0对氧磷脂酶－1（PON－1）和氧化低密度脂蛋白（ox-LDL)与内皮细胞和血小板功能的关系,以及对糖尿病肾病（DN）发生、发展的影响。方法 用酚乙酸酯为底物的速率法测定91例2型DM患者血清PON－1,用ELISA法测定ox-LDL,同时测定血清一氧化氮（NO）、血管性假血友病因子（VWF）及血浆颗粒膜蛋白（GMP140）,并与正常人作对照,以24h尿白蛋白排泄率（UAER）将DM患者分成三组。结果 血清PON－1活性在2型DM三组中与对照组比较显著降低（P＜0．01）,血浆ox-LDL浓度则显著升高（P＜0．01）,二者在DM三组之间的差别有显著性（P＜0．05）。PON－1与尿白蛋白呈显著性负相关（P＜0．01）,ox-LDL则与之呈显著性正相关（P＜0．01）,二者之间呈负相关（P＜0．01）。PON－1与血NO呈正相关,与GMP 140呈显著负相关;ox-LDL与血NO呈负相关,与VWF、GMP140呈正相关,经Logistic回归分析,提示ox-LDL是DN的危险因子。结论 DM的高血糖和脂代谢紊乱造成的PON－1酶活性下降以及脂质过氧化物的堆积,使内皮细胞的完整性及功能受损,同时血小板的活化程度明显增强。它们的共同作用与DN的发生、发展密切相关。     

胰岛素治疗对高脂喂养的糖尿病大鼠胰岛B细胞分泌变化的影响

目的观察胰岛素治疗对长期高脂喂养的糖尿病(DM)大鼠B细胞分泌功能的影响。方法2003-08~2004-11对华中科技大学同济医学院附属协和医院内分泌实验室的DM大鼠随机分为糖尿病正常饮食组(DN,n=10)、糖尿病高脂饮食组(DH,n=10)、糖尿病高脂饮食胰岛素治疗组(DHI,n=10)及正常Wistar大鼠正常饮食对照组(NC,n=10)。于胰岛素治疗后行口服葡萄糖耐量试验(OGTT)和胰岛素释放试验(IRT),并根据血糖和血胰岛素值计算糖负荷后胰岛素增值与血糖增值的比值(ΔI30/ΔG30)和修正的B细胞胰岛素分泌指数(MBCI)。留取空腹血浆测定游离脂肪酸(FFA)和甘油三酯(TG)。留取尾部胰腺组织测定胰腺内TG和FFA。结果与DN组和NC组相比,DH组血和胰腺内TG及FFA计量明显增多(分别为对DN组,P<0·01、P<0·01;对NC组,P<0·01、P<0·01;对DN组,P<0·01、P<0·05;对NC组,P<0·01、P<0·01),此外,ΔI30/ΔG30和MBCI显著降低(分别为对DN组,P<0·01、P<0·05,对NC组,P<0·01、P<0·01)。胰岛素治疗后,与DH组相比,胰腺内TG和FFA计量明显下降(分别为P<0·01、P<0·01),同时ΔI30/ΔG30、MCBI均得到明显改善(P<0·01、P<0·05)结论长期高脂饮食喂养可导致T2DM大鼠胰腺内FFA和TG沉积,并进一步损伤胰岛B细胞胰岛素的分泌;胰岛素治疗对高脂饮食所致的上述影响有一定的改善作用。     

糖尿病大鼠一氧化氮与骨代谢变化的研究

目的　研究糖尿病 (DM )大鼠血清一氧化氮 (NO)与早期骨代谢改变的关系。方法2 0只SD大鼠分为 2组 ,一组以链脲佐菌素诱导建立糖尿病 (STZ DM )大鼠模型 ,另一为正常对照组 ,测定 2组大鼠的空腹血糖 (FBG)、HbA1c、血清胰岛素、全身、股骨和腰椎骨密度 (BMD)、骨代谢相关指标〔血清钙、骨钙素、降钙素、甲状旁腺素 (PTH)、维生素D3 及尿吡啶酚 /肌酐比〕和血清NO水平。结果　STZ DM大鼠与正常对照组相比 ,血清NO水平显著升高〔(5 1.3± 11.9vs 38.1± 12 .0 )μmol/L ,P <0 .0 1〕 ;全身、股骨和腰椎的BMD显著降低〔(0 .15± 0 .0 7vs 0 .2 1± 0 .0 2 ) g/cm2 ,P<0 .0 1;(0 .16± 0 .0 2vs 0 .19± 0 .0 3) g/cm2 ,P <0 .0 5 ;(0 .12± 0 .0 4vs 0 .18± 0 .0 6 ) g/cm2 ,P <0 .0 5〕 ;血清钙浓度显著升高〔(135 .9± 11.3vs 117.2± 6 .5 )mg/L ,P <0 .0 0 1〕 ,骨钙素水平显著升高〔(0 .0 7± 0 .0 4vs 0 .0 5± 0 .0 1) μg/L ,P <0 .0 5〕 ,维生素D3 水平显著降低〔(7.6± 1.9vs 11.6± 4 .1)μg/L ,P <0 .0 5〕 ,尿吡啶酚 /肌酐显著降低〔(4.8± 0 .8vs 75 .8± 6 0 .7)nmol/mmolCr,P <0 .0 1〕 ;而降钙素和PTH水平改变无统计学意义。相关性分析显示 ,血清NO与尿吡啶酚排泄呈负相关 (r= - 0 .74 ,     

2型糖尿病肾病患者血清细胞粘附分子变化与氧化应激的关系

目的　探讨 2型糖尿病肾病患者 (DN)血清细胞粘附分子变化及其与氧化应激的关系。　方法　检测DN患者血清可溶性细胞间粘附分子 1(sICAM 1)、可溶性血管细胞粘附分子 1(sVCAM 1)、血清丙二醛 (MDA)含量和超氧化物歧化酶 (SOD)活性。　结果　早期DN及DN患者血清sVCAM 1水平〔分别为 (1 75± 0 48)、(1 91± 0 2 7)mg/L〕明显高于对照组〔(1 6 7± 0 72 )mg/L ,P <0 0 5和0 0 1〕 ,DN组明显高于单纯糖尿病 (DM)组〔(1 5 8± 0 39)mg/L ,P <0 0 5〕 ;DM组、早期DN组和DN组患者血清sICAM 1〔分别为 (75 6 0 0± 12 5 47)、(80 2 2 1± 12 4 81)、(897 6 0± 10 5 80 ) μg/L〕明显高于对照组〔(5 82 6 4± 10 2 73) μg/L ,P <0 0 0 1〕 ,其中DN组明显高于单纯DM组和早期DN组 (分别P <0 0 1和<0 0 5 ) ;单纯DM组、早期DN组和DN组患者血清SOD活性〔分别为 (86 5 9± 13 85 )、(85 6 9±11 32 )、(71 73± 16 35 )NU/L〕显著性低于对照组〔(92 73± 11 2 5 )NU/ml,P <0 0 1〕 ,MDA含量〔分别为(3 99± 1 36 )、(4 2 6± 1 95 )、(6 5 0± 2 98)nmol/ml〕显著性高于对照组〔(3 72± 0 5 7)nmol/ml,P <0 0 1〕。DM患者血清sVCAM 1与sICAM 1、收缩压、尿素氮 (BUN)和肌酐 (Cr)呈正相     

2型糖尿病肾病患者血清脂联素水平的变化

目的:观察2型糖尿病肾病(DN)患者血清脂联素(adiponectin, ADPN)水平变化及其临床意义. 方法:正常对照组(NC)10例;2型糖尿病患者53例,根据尿白蛋白排泄率(UAER)及血清肌酐(SCr)水平分成糖尿病组(DM,UAER<30 mg/g,SCr<132.6 μmol/L)、糖尿病肾病组(DN1,≥30 mg/g,SCr<132.6 μmol/L)和晚期糖尿病肾病组(DN2,UAER≥300 mg/g,SCr>132.6 μmol/L);应用酶联免疫吸附法(ELISA)测定各组血清中的ADPN、可溶性血管细胞粘附分子1(sVCAM-1)水平. 结果:DN2组的血清ADPN水平高于NC组、DM组和DN1组(P<0.05);DN1组的ADPN高于NC组和DM组,但无统计学差异;DM组的ADPN水平低于NC组,但无统计学差异.sVCAM-1在NC组、DM组、DN1组和DN2组依次逐渐增高.相关分析显示ADPN与尿酸(UA)、SCr、肾小球滤过率(eGFR)呈显著相关关系(P<0.05),多元逐步回归分析显示SCr是ADPN的独立相关因素(决定系数为r2＝0.265,β＝3.130,P<0.01).无论在研究对象总体还是糖尿病患者中,ADPN与sVCAM-1均呈正相关性(相关系数分别为0.331,P<0.01;0.316,P<0.05) 结论:2型糖尿病肾病患者血清ADPN水平升高可能与肾功能减退有关,血清ADPN升高可能参与了糖尿病肾病患者的内皮功能损害机制.     

血清脂蛋白（a）检测对早期糖尿病肾病诊断价值的探讨

目的探讨血清脂蛋白(a)[Lipoprotein(a),LP(a)]测定对临床早期糖尿病肾病(Diabetic nephropathy,DN)的意义。方法根据24 h尿白蛋白排泄率(UAER)将118例糖尿病患者分为糖尿病无肾病组(A组,41例,UAER<30 mg/24 h)、临床早期DN组(B组,39例,30 mg/24 h≤UAER<300 mg/24 h)及临床DN组(C组,38例,UAER≥300 mg/24 h)。从同期门诊健康体检者中随机选择40例为对照组(D组)。分别测定各组UAER及血清Lp(a)。各组均数的比较用方差分析,各组分别比较UAER和Lp(a)间的直线相关性。结果糖尿病各组与对照组比较血清Lp(a)升高(A组与D组比P<0.05,B、C组与D组比P<0.01),且随DN之肾脏病变进展(UAER增加)而递增(B组与A组比P<0.01,C组与B组比P<0.05)。A组与B组血清Lp(a)水平与UAER呈直线正相关(A组r=0.356,P<0.05;B组r=0.438,P<0.01)。结论血清Lp(a)水平与DN肾损害程度相关,可以作为诊断早期DN的辅助方法之一。     

嗜酸细胞趋化因子在哮喘、慢性支气管炎患者诱导痰中的表达及其与气道炎症的关系

目的　探讨嗜酸细胞趋化因子 (eotaxin)在嗜酸细胞性气道炎症和气流阻塞发生中的作用。方法　收集单纯型慢性支气管炎 (A组 )、慢性喘息性支气管炎 (B组 )、支气管哮喘 (C组 )急性发作期患者各 11例和健康对照者 (D组 ) 7名。用夹心法酶联免疫吸附测定 (ELISA)诱导痰上清液中eotaxin浓度。结果　B组 [(2 3 4± 5 8) % ]、C组 [(2 0 7± 3 1) % ]诱导痰嗜酸细胞占白细胞百分比(EOS/Leu % )分别与A组 [(11 6± 2 6 ) % ]、D组 [(1 2± 0 3) % ]比较 ,差异有显著性 (P均 <0 0 0 1) ;B组eotaxin浓度 [(0 2 90± 0 170 )g/L]与A组 [(0 12 0± 0 0 2 0 )g/L]比较 ,差异有显著性 (P =0 0 0 7) ;B组与D组 [(0 0 30± 0 0 5 0 )g/L]比较 ,差异也有显著性 (P <0 0 0 1) ,C组 [(0 2 40± 0 140 )g/L]与A组比较 ,差异有显著性 (P =0 0 18) ;C组与D组比较差异也有显著性 (P =0 0 0 1) ,但B组EOS/Leu %和eotaxin浓度与C组比较差异均无显著性 (P =0 196、0 490 )。B、C组EOS/Leu %与一秒钟用力呼气容积占预计值百分比 (FEV1占预计值 % )呈负相关 (r分别 =- 0 92 1、- 0 6 6 3,P <0 0 0 1或 0 0 2 6 ) ;C组eotaxin浓度与FEV1占预计值 %呈负相关 (r =- 0 6 43,P =0 0 33)。B、C组eotaxin浓度与E     

糖尿病肾病与血浆内皮素1及C反应蛋白的相关性研究

目的探讨糖尿病肾病（DN）与血浆内皮素1（ET-1）、C反应蛋白（C-RP）的关系。方法测定86例T2DM患者（DM组）和30例健康对照者（NC组）血压、血糖、血脂、SCr、ET-1、C-RP和尿白蛋白排泄率（UAER）。结果血浆ET-1和C-RP在DM组较NC组显著升高（P〈0．05,P〈0．01）,且DM组血浆ET-1和C-RP水平随着SCr、UAER的增加而升高（P〈0．05,P〈0．01）。结论血浆ET-1和C-RP可能参与DN的发生、发展。     

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.