全反式维甲酸对大鼠腹主动脉球囊损伤后新生内膜形成和内皮再生的影响

为研究全反式维甲酸对球囊损伤的大鼠腹主动脉内皮再生和新生内膜形成的影响 ,制作球囊损伤的大鼠腹主动脉剥脱模型 ,将 12只血管损伤的Wistar大鼠随机分为两组 ,对照组 (n =6 )腹腔内注射脂肪乳剂 (1mL/d) ,全反式维甲酸组 (n =6 )腹腔内注射溶解于脂肪乳剂的全反式维甲酸 [4 μg/ (g·d) ],球囊损伤 14天后 ,采用原位灌注固定取材 ,染色 ,进行组织学观察和形态学分析。结果显示 ,全反式维甲酸组球囊损伤血管段的内皮再生面积大于对照组 ,而新生内膜形成面积小于对照组。结果提示 ,全反式维甲酸具有促进损伤血管内皮再生和抑制新生内膜形成的作用     

雷帕霉素对大鼠球囊损伤后血管平滑肌细胞迁移及内膜增殖的抑制作用

本文通过建立大鼠腹主动脉球囊损伤模型 ,应用新型免疫抑制剂雷帕霉素进行干预 ,观察雷帕霉素对损伤后大鼠在体血管平滑肌细胞 (VSMC)迁移及内膜增殖的抑制作用。1 材料与方法 :成年健康雄性SD大鼠 (清洁级 ) 4 8只 ,体重 (2 5 0± 5 0 )g,随机分为 3组 :(1)球囊损伤组 (n =16 ) ,单纯行腹主动脉球囊损伤术 ;(2 )羧甲基纤维素钠组 (n =16 ) ,球囊损伤术前术后肌肉注射羧甲基纤维素钠作为对照 ;(3)雷帕霉素组 (n =16 ) ,行腹主动脉球囊损伤术 ,术前 3d开始肌肉注射雷帕霉素 (溶于羧甲基纤维素钠溶液中 ) 0 5mg·kg- 1 ·d- 1 ,术后连续 1…     

罗格列酮对大鼠腹主动脉球囊损伤后再狭窄的影响

目的 探讨罗格列酮对球囊损伤后血管再狭窄的作用及机制.方法 采用大鼠腹主动脉球囊损伤模型,随机分为假手术组、球囊损伤模型组、罗格列酮干预组,ELISA法测定术后1、3、7、14 d血清MMP-9及ICAM-1水平,取14 d时腹主动脉病理测定内膜增生面积.结果 罗格列酮干预组与损伤组相比内膜增生面积减少.模型组术后血清ICAM-1、MMP-9水平明显增高,分别于术后3 d、7 d时达高峰,罗格列酮干预组血清ICAM-1、MMP-9较模型组降低（P＜0.05）.结论 罗格列酮可抑制球囊损伤后再狭窄的形成,其防治再狭窄的机制可能与降低血清ICAM-1和MMP-9的水平有关.     

粒细胞集落刺激因子对大鼠颈总动脉损伤后新生内膜增生的影响

目的探讨粒细胞集落刺激因子（G-CSF）对动脉粥样硬化（AS）大鼠颈总动脉球囊损伤后再狭窄的影响。方法Wistar大鼠48只,随机分为3组:普通饮食组（普食组,n=6）,高脂饮食组（高脂组,n=42）。高脂组又分为:G-CSF组（n=21）和生理盐水组（NS组,n=21）。高脂饮食后1个月用HE染色及透射电镜证明AS形成情况。G-CSF组和NS组分别于高脂饮食后1个月给予G-CSF或生理盐水干预6d,然后行左颈总动脉球囊损伤术,术后14、21、90d分别用扫描电镜、HE染色及图像分析观察血管内皮形成及内膜的增生情况。结果高脂组大鼠高脂饮食后1个月可见AS的早期改变,行球囊损伤后可见大鼠颈总动脉内膜逐渐增厚,但是G-CSF组明显小于NS组,G-CSF组损伤血管内皮较快恢复连续性,G-CSF组内膜与中膜面积比值（Ai/Am）远小于NS组（P<0.01）。结论G-CSF可以加速AS大鼠损伤血管的再内皮化、抑制血管损伤后再狭窄的发生。     

多沙唑嗪对血管狭窄和血清一氧化氮的影响

目的探讨多沙唑嗪对兔腹主动脉球囊损伤后血管狭窄的影响,及其与血清一氧化氮、血管内膜中膜平滑肌细胞增生的关系。方法23只新西兰兔随机分为正常对照组、球囊损伤组、多沙唑嗪组。正常对照组不予任何方式处理。另两组行腹主动脉球囊损伤术,同时多沙唑嗪组应用多沙唑嗪控释片4mg/d,观察各组血清一氧化氮以及血管损伤处血管狭窄、血管内膜中膜增殖细胞核抗原(PCNA)的变化。结果应用多沙唑嗪4周后多沙唑嗪组血清一氧化氮含量增高,血管损伤处血管内膜、外膜增生减轻,新生内膜面积减少,管腔面积增加,内弹力层和外弹力层包围面积增加,血管内膜中膜PCNA阳性平均灰度降低。结论多沙唑嗪可以抑制球囊损伤后兔腹主动脉血管的狭窄,抑制血管内膜中膜平滑肌细胞增殖,增加血清一氧化氮含量。     

全反式维甲酸对球囊剥脱大鼠胸主动脉内皮后平滑肌细胞增殖和P21表达的影响

目的：探讨全反式维甲酸（ATRA）对球囊损伤大鼠胸主动脉后管腔狭窄、血管平滑肌细胞（VSMC）增殖及细胞周期依赖性激酶抑制蛋白P21表达规律的影响。方法：54只SD大鼠随机分为三组。对照组不进行球囊损伤，术后28天处死；手术组和ATRA治疗组行球囊剥脱胸主动脉内皮术，分别于术后2d、7d、14d、28d处死。取胸主动脉应用HE染色、免疫组化和计算机图像分析法进行形态学、PCNA和P21表达水平检测。结果：①正常动脉壁不表达PCNA及P21。②手术组中膜VSMC术后2d PCNA表达达高峰，后迅速下降；而新生内膜在术后7d现并高表达PCNA，14d、28d内膜迅速增厚，其中PCNA表达逐渐下降。P21在术后14d新生内膜中可见少量表达，28d表达增多。③ATRA治疗组术后7d新生内膜中已有P21表达，14d、28d大量表达，而PCNA的表达明显低于手术组，显著抑制VSMC的迁移和增殖、内膜增生和管腔狭窄（P〈0．01）。④P21表达与PCNA表达呈负相关（P〈0．001）。结论：ATRA可通过诱导P21蛋白表达，抑制VSMC迁移和增殖，从而抑制球囊剥脱大鼠胸主动脉内皮后新生内膜过度增生和管腔狭窄。     

Fas配体基因导入对大鼠颈动脉损伤后新生内膜的影响

目的 :探讨腺病毒载体介导 Fas配体 （Fas L）基因导入对大鼠颈动脉损伤后新生内膜的影响。方法 :利用重组腺病毒载体将 Fas L 导入大鼠颈动脉球囊损伤的内膜 ,14d后观察其对新生内膜形成的影响。结果 :通过腺病毒载体介导导入 Fas L 基因的被球囊损伤的大鼠颈动脉 ,与 Ad- β gal基因的对照组相比较 ,14d后损伤血管新生内膜 /中膜面积比降低了 73%（P<0 .0 1）。结论 :Fas L 可抑制新生内膜的增生。     

球囊损伤兔腹主动脉壁PTEN的表达变化

目的探讨PTEN在经皮冠状动脉介入治疗（PCI）术后冠状动脉再狭窄形成过程中的作用。方法建立兔腹主动脉球囊损伤模型,采用HE染色方法观察血管新生内膜增生情况,采用免疫组化和Western blot法检测血管壁PTEN蛋白的表达。结果与假手术组相比,球囊损伤后腹主动脉新生内膜面积逐渐增加,壁内PTEN表达减少（P〈0.01）,但新生内膜层的PTEN表达水平高于中膜层（P〈0.01）。结论PTEN的表达变化可能参与了血管损伤后的修复反应,与PCI术后冠状动脉再狭窄的发生、发展有关。     

全反式维甲酸对球囊损伤大鼠胸主动脉内皮后MMP-2和MMP-9表达的影响

目的探讨全反式维甲酸(ATRA)对大鼠胸主动脉球囊损伤后MMP2和MMP9表达的影响,探讨ATRA治疗血管再狭窄的可能机制与作用。方法54只雄性SD大鼠随机分为对照组、模型组和ATRA治疗组。所有大鼠从术前4d至术后处死接受植物油或ATRA混悬液灌胃,球囊剥脱模型组与治疗组大鼠胸主动脉内皮,分别在术后2d、7d、14d及28d取胸主动脉,通过组织学检查、免疫组化结合图象分析技术测定血管壁形态学变化,MMP2和MMP9的蛋白表达水平及ATRA灌胃对其影响。结果1MMP2术后2d开始上升,7d最高,14d后开始下降。2MMP9术后2d在中膜大量表达,7d后表达极少。3术后7d新生内膜开始增生,14d大量新生内膜形成,28d以后内膜继续增厚。4使用ATRA后,血管新生内膜明显减少,MMP2及MMP9蛋白表达也有不同程度下降。结论ATRA能下调血管成形术后MMP2与MMP9的表达,可能在调节细胞外基质的降解、成形术后血管重塑中起作用。     

G-CSF促进Thy1.1+干细胞对球囊损伤后动脉的修复

目的: 探讨粒细胞集落刺激因子（G-CSF）动员自体干细胞及大鼠Thy1.1干细胞局部移植对大鼠颈总动脉球囊损伤后内膜增生的影响,评价干细胞移植对血管再狭窄的作用;探讨G-CSF与Thy1.1干细胞移植是否具有协同作用？G-CSF是否可以促进Thy1.1干细胞对动脉球囊损伤后的修复作用？方法: 将120只雌性大鼠随机分为4组(每组30只),即G-CSF组:于大鼠颈总动脉球囊损伤前7 d,开始皮下注射G-CSF 30 μg/(kg·d),连续注射7 d后进行球囊损伤;干细胞移植组:于颈总动脉球囊损伤后即刻,将约5×106 Thy1.1干细胞(来自4~6周SD大鼠)注入至损伤血管局部;联合移植组:按上述G-CSF组和干细胞移植物的要求,分别注射(入)G-CSF和Thy1.1干细胞;对照组:于颈总动脉球囊损伤后,局部注入等量的生理盐水。各组于术后即刻、3 d、7 d、14 d、28 d,取损伤血管段,HE染色后光镜下检查其病理变化,观察细胞的增殖。用原位杂交方法检查移植细胞的定植、分化情况;并通过RT-PCR方法分析内皮型一氧化氮合酶（eNOS）mRNA的表达。结果: G-CSF组及干细胞移植组内膜增生程度均低于对照组（P<0.05,P<0.01）,eNOS mRNA表达明显高于对照组（P<0.05,P<0.01）。联合移植组内膜增生的程度低于其他组（P<0.05,P<0.01）,eNOS mRNA的表达明显高于其他组（P<0.05,P<0.01）。结论: G-CSF动员自体干细胞及Thy1.1干细胞局部移植可促进大鼠颈总动脉球囊损伤后再内皮化的进程,抑制内膜增生过程,对球囊损伤具有修复作用,可预防血管成形术后的再狭窄。G-CSF与Thy1.1干细胞移植具有协同作用,G-CSF可促进Thy1.1干细胞对动脉球囊损伤后的修复作用。     

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.     

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.     

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.     

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.