雷公藤内酯醇洗脱支架与雷帕霉素洗脱支架对冠状动脉支架内再狭窄作用的对比研究

目的 比较雷公藤内酯醇洗脱支架与西罗莫司（sirolimus,雷帕霉素）洗脱支架预防冠状动脉支架植入术后再狭窄的作用.方法 选用杂种幼猪30只,随机分成裸支架组、雷公藤内酯醇洗脱支架组和西罗莫司洗脱支架组,每组各植入支架10枚.术后28 d,进行冠状动脉造影、组织病理检查以及免疫组化检测血管平滑肌细胞中增殖细胞核抗原（proliferating cell nuclear antigen,PCNA）.结果 雷公藤内酯醇洗脱支架组与西罗莫司洗脱支架组支架内最小内径相似（P＞0.05）,均大于裸支架组（P＜0.01）;雷公藤内酯醇洗脱支架组新生内膜面积与西罗莫司洗脱支架组相似（P＞0.05）,均小于裸支架组（P＜0.01）.雷公藤内酯醇洗脱支架组与西罗莫司洗脱支架组的PCNA阳性细胞数相似（P＞0.05）,均少于裸支架组（P＜0.01）.结论 雷公藤内酯醇洗脱支架能抑制平滑肌细胞增殖,其预防冠状动脉支架内再狭窄的作用与西罗莫司洗脱支架相似.     

完全可降解聚乳酸西罗莫司洗脱支架在小型猪冠状动脉模型中的实验研究

目的评价新型全降解聚乳酸西罗莫司洗脱支架（XinsorbTM）在小型猪冠状动脉抑制新生内膜增殖的有效性和安全性。方法裸金属支架（Bare metal stent,BMS）16枚和Xinsorb支架16枚分别随机置入16头小型猪的前降支（16枚）和右冠状动脉（16枚）。置入30d和90d,复查冠状动脉造影后处死部分动物取出支架段血管,将支架分成等长的两部分,一半用树脂包埋后制作硬组织切片,苏木素和伊红染色（haematoxylin and eosin,HE）分析组织形态,评价新生内膜增殖及管腔狭窄率;另一半用戊二醛固定后用扫描电镜观察支架段血管内皮化情况。结果 Xinsorb支架置入后未出现支架内血栓,并有效防止血管弹性回缩造成的血管狭窄。病理分析提示：置入30d,Xinsorb支架比BMS能显著减少新生内膜面积（0.9±0.2）mm2比（2.2±0.2）mm2（P〈0.05）和管腔狭窄面积（19.3±3.4）%比（38.2±5.3）%（P〈0.05）,置入30d时BMS内皮化完全,但Xinsorb支架表面有部分未完全内皮化,Xinsorb支架内皮化完全所需的时间在30～90d。结论 Xinsorb支架在置入小型猪冠状动脉90d内,可以有效地支撑血管壁防止弹性回缩并抑制新生内膜增殖,在置入早期轻度延迟内皮的修复。     

雷公藤内酯醇洗脱支架对冠状动脉支架内再狭窄的影响

目的研究雷公藤内酯醇洗脱支架预防冠状动脉支架植入术后再狭窄的有效性及安全性。方法杂种幼猪20只,分别植入雷公藤内酯醇洗脱支架和普通裸金属支架各10枚。术后28d比较两组的冠状动脉造影形态、组织病理及血生化结果。结果支架部位血管腔面积裸支架组小于雷公藤内酯醇组(P<0.05)、支架内增生内膜面积及内膜增生程度裸支架组大于雷公藤内酯醇组(P<0.05)。未发现明显毒副作用。结论雷公藤内酯醇洗脱支架能抑制新生内膜的形成,在支架植入后4周能预防再狭窄的形成。     

比较雷公藤内酯醇与西罗莫司洗脱支架预防再狭窄

目的 比较雷公藤内酯醇洗脱支架与西罗莫司(sirolimus,雷帕霉素)洗脱支架预防冠状动脉支架植入术后再狭窄的作用.方法 选用杂种幼猪30只,随机分成裸支架组、雷公藤内酯醇洗脱支架组和西罗莫司洗脱支架组,每组各植入支架10枚.术后28 d,进行冠状动脉造影、组织病理检查以及免疫组化检测血管平滑肌细胞中增殖细胞核抗原(proliferating cell nuclear antigen,PCNA).结果 雷公藤内酯醇洗脱支架组与西罗莫司洗脱支架组支架内最小内径相似(P＞0.05),均大于裸支架组(P＜0.01);雷公藤内酯醇洗脱支架组新生内膜面积与西罗莫司洗脱支架组相似(P＞0.05),均小于裸支架组(P＜0.01).雷公藤内酯醇洗脱支架组与西罗莫司洗脱支架组的PCNA阳性细胞数相似(P＞0.05),均少于裸支架组(P＜0.01).结论 雷公藤内酯醇洗脱支架能抑制平滑肌细胞增殖,其预防冠状动脉支架内再狭窄的作用与西罗莫司洗脱支架相似.     

新型生物全降解药物洗脱支架置入小型猪冠状动脉后冠状动脉造影及连续血管内超声评价

目的评价聚左旋乳酸/无定形磷酸钙（PLLA/ACP）新型生物全降解药物支架置入猪冠状动脉6个月内支架弹性回缩及有效性。方法将16枚新型生物支架随机置入小型猪冠状动脉内,行冠状动脉造影检查（术后即刻、随访终点）和血管内超声（IVUS）检查（术后即刻、1个月、6个月）,并且,在术后1个月和6个月分别处死12、4只动物,取支架置入部位血管固定行苏木素-伊红（HE）染色,观察内膜增生情况和支架贴壁情况。结果各小型猪随访终点造影复查可见支架置入段血管血流通畅,无狭窄及血栓形成等现象。IVUS检查提示,平均支架面积和平均支架直径在置入术后1个月和术后6个月时分别与术后即刻比较,差异均无统计学意义[平均支架面积：（6.08±1.30）mm2、（6.00±0.60）mm2比（5.97±0.53）mm2,P〉0.05;平均支架直径：（2.76±0.30）mm、（2.76±0.14）mm比（2.75±0.12）mm,P〉0.05],提示支架未发生显著弹性回缩;病理形态学分析提示,支架置入段血管轻度狭窄,未见支架贴壁不良。结论新型生物全降解支架置入小型猪冠状动脉6个月后,未发现显著支架弹性回缩,具有足够的支撑性能;内膜增生程度较轻,能够保证管腔通畅。     

双抗支架联合内皮祖细胞移植防治支架内晚期再狭窄

目的：探讨双抗-[CD34、血管内皮生长因子受体（VEGFR）-2]支架联合局部移植内皮祖细胞（EPCs）防治血管支架内晚期再狭窄的效果.方法：以反复浸泡吹干法制备双抗支架.兔动脉粥样硬化模型建立后动脉内置入药物涂层支架（药物涂层支架组,8只）或双抗支架＋ EPCs移植（双抗支架组,8只）.随访2月.观察管腔最狭窄百分比、支架内血管新生内膜增生.结果：与药物涂层支架组比较,双抗支架组支架内管腔面积狭窄百分比[（28.3±4.2）％比（8.8±1.45）％]、血管新生内膜面积[（1.44±0.34）m2比（0.46±0.21） m2]、最大内膜厚度[（172±5.0）μmm比（105±4.9）μmm]明显减少（P均＜0.05）.结论：双抗支架＋EPCs移植可显著降低支架内晚期再狭窄.     

可降解聚乳酸涂层西罗莫司洗脱支架在小型猪冠状动脉模型中的实验研究

目的评价新型L605钴铬合金平台可降解聚乳酸共聚物载体西罗莫司药物洗脱支架（bioabsorbable polymeric sirolimus-eluting stent,BPSES）在小型猪冠状动脉抑制新生内膜增殖的有效性和安全性。方法金属裸支架（bare mental stent,BMS）18枚、单纯可降解聚乳酸共聚物涂层支架（bioabsorbable polymer-only stent,BPOS）18枚以及BPSES 18枚被分别随机置入18头小型猪的前降支（18枚）、回旋支（18枚）以及右冠状动脉（18枚）。置入28天和90天,复查冠状动脉造影评价管腔丢失。置入7天、28天以及90天处死部分动物行塑料包埋硬组织切片染色组织形态学分析。结果置入28天及90天,BPSES与BMS相比,显著降低管腔丢失（28天0.54±0.45 mm比1.11±0.45mm,P=0.048;90天0.42±0.34 mm比0.96±0.41 mm,P=0.024）。在损伤积分相似的情况下,置入28天时BPSES较BMS新生内膜面积明显减少（0.90±0.40 mm2比1.88±0.71 mm2,P=0.015）,而在90天时亦叮见此趋势,7天、28天和90天BPSES和BPOS炎症反应及内皮化程度与BMS相似。结论BPSES在置入小型猪冠状动脉28天后,可以安全有效地抑制新生内膜增殖,90天时亦可见此趋势。     

雷帕霉素药物洗脱支架对糖尿病小型猪冠状动脉支架置入后内膜增生的影响

目的:评估雷帕霉素药物洗脱支架(SES)对糖尿病小型猪冠状动脉支架置入后内膜增生的作用.方法:建立链脲菌素诱导的糖尿病小型猪模型(糖尿病组,n=12),随机选取2支冠状动脉置入SES,共计置入24枚支架,术后饲养6个月,与非糖尿病置入SES支架的小型猪模型(对照组,n=12)比较冠状动脉造影、血管内超声及组织切片检查结果.结果:两组动物支架置入冠状动脉分布,术前参照血管直径[糖尿病组:(2.78±0.35)mm,对照组:(2.81±0.29)mm]及术后即刻最小管腔内径[糖尿病组:(2.90±0.42)mm,对照组:(2.89±0.33)mm]均相似(P均>0.05).术后6个月糖尿病组支架内狭窄程度[(35.6±9.2)%和(7.9±3.1)%,P<0.001]、支架内晚期管腔丢失[(0.32±0.09)mm和(0.09±0.04)mm,P<0.001]、新生内膜厚度[血管内超声:(0.35±0.12)mm和(0.11±0.08)mm,P<0.05]及新生内膜面积[血管内超声:(1.29±0.51)mm~2和(0.26±0.11)mm~2,P<0.001;组织切片:(1.24±0.76)mm~2和(0.19±0.08)mm~2,P<0.05]均显著高于对照组.结论:糖尿病小型猪冠状动脉置入SES后内膜增生程度显著高于无糖尿病模型.     

聚-消旋乳酸-乙醇酸涂层支架置入小型猪冠状动脉后损伤处愈合过程的观察

目的 :了解聚—消旋乳酸—乙醇酸 (PLGA)涂层支架置入冠状动脉后损伤处的愈合过程。方法 :用摩尔比 60∶40的消旋乳酸与乙醇酸共混聚合浸涂Dragon支架制成PLGA涂层支架作为涂层组 ,Dragon支架作为对照组 ,支架置入小型猪冠状动脉 ,7日期与 1个月期各 8只猪 ,每只置入两枚支架。支架置入前、后、终点时行冠状动脉造影 ,处死动物后分离取出支架置入段冠状动脉 ,固定并制备标本行扫描电子显微镜 (SEM )观察与组织学检查。结果 :7日期 1只于支架置入右冠状动脉后 3h、左冠状动脉前降支后 1 5h时死亡 ,组织学示损伤后 1 5h已经有血细胞附着 ,3h见到纤维素附着。所有支架置入成功。SEM示 7日期两组均完全内皮化 ,制备标本时撕裂处见内皮下为纤维素。组织学示 7日期对照组 2支、涂层组 1支支架血管段形成血栓 ;7日期内膜组织成份主要为附着的纤维素 ,偶见到平滑肌细胞、纤维母细胞 ,表面为一层内皮细胞 ,两组间无差异 ;1个月期内膜组分主要为纤维素样肌性组织及细胞外基质 ,内膜增生的程度两组间无差异。各组 1个月期内膜均较 7日期的明显增厚。结论 :冠状动脉损伤 +支架置入后的愈合过程为 ,血小板附着于损伤处→纤维素附着→内皮细胞与中层平滑肌细胞移行、增生 ,内膜增生。纤维素附着可能是内皮化的基础。猪     

粉防已碱对AngⅡ诱导血管平滑肌细胞增殖及NF-κB通路的影响

采用血管紧张素Ⅱ（AngⅡ）诱导培养Wistar大鼠胸主动脉血管平滑肌细胞（VSMC）,MTT比色法测定粉防已碱（Tet）对血管平滑肌细胞抑制增殖率;考马斯亮蓝法测定蛋白含量;免疫印记法测定NF-κB（p65）及其抑制物（I-κBα）表达;凝胶电泳迁移率分析测定核转录因子-κB（NF-κB）体外活性。发现Tet能显著抑制血管平滑肌细胞增殖;抑制VSMC胞核NF-κB表达,同时抑制胞浆I-κBα磷酸化;同时显著抑制NF-κB体外活性。提示Tet明显抑制AngⅡ诱导的VSMC增殖,机制与调控NF-κB通路有关。     

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.