胶原与血管成形术后再狭窄的关系

目的探讨细胞外基质的主要成分--胶原在血管成形术后再狭窄形成中的作用.方法在兔的两次损伤再狭窄模型上,应用Masson染色方法,观察胶原在血管成形术后不同时间点的含量变化与位置.结果胶原含量在血管成形术后第2d起开始减少,第4d最少,1周以后逐渐增加,12周观察结束时最多;早期2周内动脉壁胶原变化主要发生在中膜与内膜,而4周以后主要发生在外膜.结论血管成形术后1周内胶原的减少在平滑肌细胞迁移与增殖中起重要作用,之后胶原的增多是增厚内膜的主要成分,后期在外膜存在的增加及排列的不规则可能参与动脉重构.     

Roscovitine抑制大鼠颈总动脉球囊损伤后内膜增生的研究

目的:观察roscovitine对球囊损伤后大鼠颈总动脉血管平滑肌细胞及内膜增生的抑制作用,以期提供新型的支架涂层药物。方法:建立大鼠颈总动脉球囊损伤模型模拟经皮冠状动脉腔内介入术(PCI)术后再狭窄,干预组损伤局部给予roscovitine(200μmol/L)孵育10分钟。14天后取材,免疫荧光染色观察roscovitine对局部血管平滑肌细胞增殖的作用;HE染色观察roscovitine对内膜增生的作用。结果:本研究建立了大鼠颈总动脉球囊损伤模型,球囊损伤后14天,局部血管平滑肌细胞增殖活跃、内膜增生明显。Roscovitine干预后,血管平滑肌细胞增殖率明显降低,内膜增生被显著抑制,管腔狭窄率和内膜中膜面积比值显著降低。结论:Roscovitine显著抑制大鼠颈总动脉球囊损伤后局部血管平滑肌细胞增殖,进而有效抑制内膜增生,降低再狭窄发生率。     

益气活血解毒方对血管损伤后外膜早期炎症和血管重构的影响

目的观察球囊损伤血管内膜后外膜早期炎症和血管重构的变化及益气活血解毒方对其的影响。方法实验采用球囊导管拉伤大鼠左侧颈总动脉内膜模型,造模动物随机分为模型组、阿托伐他汀组、血府逐瘀组和益气活血解毒组,另以假手术组作对照。灌胃给药7 d后取材,行HE染色,观察血管壁各层面积和厚度的变化,免疫组织化学染色,观察血管壁各层单核细胞趋化因子-1(MCP-1)及巨噬细胞特异性标志物CD68表达的变化。结果与假手术组比较,模型组血管内膜面积明显增大(P0.01),外膜变厚(P0.05),管腔变化不明显,CD68的含量显著升高(P0.05)。与模型组相比,益气活血解毒方明显减少血管内膜的面积(P0.05),降低CD68的含量(P0.01)。与血府逐瘀组相比,益气活血解毒组外膜厚度明显降低(P0.05)。结论球囊损伤大鼠颈总动脉早期,血管以正性重构为主,外膜增厚和炎症反应明显;益气活血解毒方能有效改善血管重构,可能与其能降低巨噬细胞浸润,抑制外膜炎症反应有关。     

猪静脉桥血管重建中平滑肌细胞和成纤维细胞表型转化

目的动态观察静脉桥再狭窄动物模型中血管平滑肌细胞和外膜成纤维细胞表型转化和增殖活性的变化,评价血管平滑肌细胞和外膜成纤维细胞表型转化及增殖迁移对血管重塑的影响。方法建立猪静脉桥再狭窄模型,采用血管病理形态学和免疫组织化学方法,观察术后7、14和30d血管重塑及血管壁中增殖细胞核抗原、平滑肌α肌动蛋白和骨桥蛋白表达变化。结果①术后7d新生内膜形成并逐渐增厚,于术后30d达最大;内弹力板围绕面积于术后7d逐渐减小,术后30d管腔面积最小(P<0.05);重塑指数和外弹力板围绕面积术后7d稍有增大,其后不断减小,术后14～30d明显减小(P<0.05)。②增殖细胞核抗原染色发现,血管外膜成纤维细胞和血管平滑肌细胞增殖指数术后7d显著增加,术后14d增殖细胞核抗原阳性表达达高峰,术后30d回到基线水准。③平滑肌α肌动蛋白染色发现,术后7d中膜阳性面积减少,外膜和内膜中出现阳性表达;术后14d中膜血管平滑肌细胞阳性表达显著减少,外膜成纤维细胞和内膜中阳性表达显著增加;术后30d中膜血管平滑肌细胞阳性表达恢复,外膜阳性表达较术后14d和7d明显减少,内膜阳性表达较术后14d变化不明显。④骨桥蛋白染色发现,术后7d中膜血管平滑肌细胞阳性表达明显;术后14d中膜血管平滑肌细胞阳性表达较术后7d减少,而内膜中血管平滑肌细胞阳性表达显著增加且达高峰;术后30d中膜血管平滑肌细胞有少部分阳性表达,内膜中血管平滑肌细胞阳性表达较术后14d减少;外膜在术后各时间点均呈阴性表达。结论血管平滑肌细胞和成纤维细胞的表型转化和增殖活性改变对血管重塑起重要作用,参与并促进了血管桥再狭窄的发生过程。     

冠状动脉损伤修复中Ⅲ型胶原的表达及其与血管平滑肌细胞增生的关系

目的探讨血管损伤修复中Ⅲ型胶原的表达规律及其与血管平滑肌细胞(VSMC)增生的关系.方法26只犬冠状动脉内置入过大钽丝支架建立再狭窄模型,分别于术后7d、14d和28d处死动物,用透射电镜及免疫组化染色技术观察新生内膜中Ⅲ型胶原表达和VSMC特征,并用图象处理技术对Ⅲ型胶原的染色密度作定量分析.结果支架置入后7d以VSMC移行增生为主,14d时VSMC增生达高峰并有较多胶原表达,28d时VSMC由合成型逐渐转变为收缩型并表达大量胶原,Ⅲ型胶原在不同时间阶段的表达量具有显著差异(P<0.05).结论Ⅲ型胶原可能在再狭窄形成的后期内膜增生中起重要作用.     

卡托普利对动脉腔内成形术局部平滑肌细胞超微结构影响的实验研究

本实验在建立兔右髂动脉粥样硬化狭窄模型的基础上,观察卡托普利对成形术局部血管内膜平滑肌细胞(SMCs)超微结构的影响.结果表明,扩张术后1～2周血管内膜SMCs.由收缩型转变为合成型;卡托普利可使SMCs胞浆中与合成及增生功能有关的细胞器(粗面内质网和线粒体)明显减少,单位体积SMCs胞浆内细胞器作密度显著降低.提示卡托普利可有效抑制SMCs增殖程度,对防止再狭窄发生有重要意义.     

放射性支架对血管局部表达PDGF的影响

目的 :评价化学镀法制备的 32 P放射性支架对再狭窄的预防作用 ,并探讨其作用机制。方法 :以化学镀法制备 32 P放射支架 ,与非放射支架配对后 ,随机植入兔双侧髂动脉 ,术后 3 0 d病理组织学观察内膜面积及腔内径的变化 ;半定量 RT PCR检测支架植入后局部动脉壁 PDGF表达的变化。结果 :12只支架全部成功植入 ,术后 3 0 d造影未见动脉瘤及局部血栓形成 ;病理组织学观察发现 :两种支架植入均使血管内膜增生 ;放射支架侧血管管腔面积显著大于对照侧 （3 .41± 0 .19m m2 vs2 .97± 0 .40 m m2 ,P<0 .0 5 ） ,而其新生内膜面积显著小于对照侧 （0 .49± 0 .2 1mm2 vs 0 .5 8± 0 .17mm2 ,P<0 .0 1） ;放射性支架植入使局部动脉壁表达 PDGF显著减少 （P<0 .0 1）。结论 :化学镀法制备的放射性 32 P支架安全有效 ,较低的放射活度即可有效防止支架内狭窄 ;放射性支架减少动脉壁局部 PDGF的表达 ,继而减弱了对平滑肌细胞迁移增生的刺激作用 ,使再狭窄减轻     

芎芍胶囊对实验性兔动脉粥样硬化血管壁胶原的影响

目的观察芎芍胶囊对实验性兔动脉粥样硬化血管重构过程中血管壁胶原的影响,探讨芎芍胶囊干预动脉粥样硬化的机制。方法采用球囊剥脱兔腹主动脉内皮结合高脂饮食方法建立实验性动脉粥样硬化模型,80只兔随机分为正常对照组、单纯内皮损伤组、模型3天组、模型2周组、模型6周组、模型6周普罗布考组、模型6周芎芍胶囊小剂量组、模型6周芎芍胶囊大剂量组。采用弹力纤维染色和苦味酸天狼猩红染色方法,利用计算机图像分析仪测定血管病理形态学指标、胶原含量和光密度值。结果高脂模型组内皮损伤后3天,动脉内膜无增厚,管腔无狭窄,2周时管腔出现代偿性扩张,6周时管腔却明显缩小,增殖指数明显升高。各药物组在抑制内膜增殖方面以芎芍大剂量组及普罗布考组作用尤为明显。模型2周时内膜胶原堆积不明显,中外膜Ⅰ型胶原较正常组明显增加,Ⅲ型胶原明显减少,Ⅰ型胶原的增加占主导地位,因而胶原总量增加,并达到高峰。6周时,中外膜Ⅰ型胶原增加的幅度小于Ⅲ型胶原减少的幅度,胶原总量增加不显著,而内膜胶原逐渐堆积达到高峰。各用药组内膜胶原减少,中外膜胶原总量减少,芎芍大剂量组内膜胶原含量较模型6周组明显减少,中外膜胶原总量在各组中亦最少。结论动脉粥样硬化过程中管腔的丢失是内膜增生和病理性血管重构共同作用的结果,胶原在病理性血管重构过程中起到了关键作用。大剂量芎芍胶囊可通过调节动脉粥样硬化过程中血管壁胶原的含量改善病理性血管重构和抑制内膜增生,起到预防管腔狭窄的作用。     

猪冠状动脉介入损伤后血管壁平滑肌细胞增生与血浆组织因子水平的关系

目的 探讨猪冠状动脉介入损伤后损伤局部血管壁平滑肌细胞增生程度与血浆组织因子水平的关系.方法 制作猪冠状动脉介入损伤模型,测量介入手术前后血浆组织因子浓度以及损伤局部血管壁平滑肌细胞迁移、增牛情况,探讨二者之间的联系.结果 30例血管标本均存在不同程度的平滑肌细胞增生,其中60%的标本达到再狭窄标准.再狭窄组术后血浆组织冈子水平显著高于非再狭窄组(术后30 min 688.36±91.57 ng/L比514.87±68.73 ng/L,术后24 h 706.09±89.59ng/L比539.22±70.51 ng/L,P均＜0.05);血管损伤后血管段新牛内膜而积与术后各时点外周血组织因子浓度正相关(r30min=0.834,r24h=0.810,P均＜0.05).结论 冠状动脉介入术后血浆组织因子水平显著升高,并且其升高程度与介入局部平滑肌细胞增生程度正相关,可能作为预测介入术后再狭窄的一项检测指标.     

局部应用前列腺素E1对兔颈动脉损伤后内膜增生的影响

目的观察局部应用医用胶携载前列腺素E1,对兔颈总动脉损伤后内膜增生的影响。方法将40只兔随机分成假手术组、对照组、前列腺素E1组、医用胶组,每组各10只,球囊导管法损伤右侧颈总动脉内膜,术后2周切取损伤血管,通过形态学观察和免疫组织化学检查,了解内膜增生和平滑肌细胞增殖情况。结果前列腺素E1组血管内膜面积、管腔狭窄率、增殖的平滑肌细胞数等指标均较对照组显著减少(P<0.01),而医用胶组无明显效果(P>0.05)。结论医用胶携载前列腺素E1局部用于血管外膜可有效抑制血管损伤后内膜的增生,对防治动脉手术后管腔再狭窄有潜在的应用价值。     

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.