氨氯地平产生的兔股动脉舒张部分由NO介导

目的研究氨氯地平舒张周围血管的作用是否与激活一氧化氮合酶(NOS)有关.方法利用家兔股动脉恒流灌注模型,观察股动脉内灌注有效浓度的氨氯地平后灌注压的变化及NOS抑制剂L-NAME对其作用的影响.结果氨氯地平缓慢平稳降低周围血管阻力,NOS抑制剂L-NAME能部分阻断这种作用.结论氨氯地平产生的周围血管舒张作用部分通过刺激NO生成而实现.     

左旋哨基精氨酸甲基酯对大鼠食管静脉曲张影响的酶组化研究

目的：探讨一氧化氮（NO）在食管静脉曲张发生机制中的作用,初步观察使用一氧化氮合酶（NOS）抑制剂治疗食管静脉曲张的可能性。方法：采用NADPH－d黄递酶组化染色与图像分析方法,观察NOS抑制剂左旋肖基精氨酸甲基酯（L－NAME）灌胃给药对食管静脉曲张大鼠食管壁组织学改变及NOS表达平均光密度值的影响。结果：模型组食管、粘膜下静脉壁及食管浆膜外静脉壁粘膜上皮NOS表达较假手术组增多,给予L－NAME后,食管壁NOS表达显著下调（P＜0．01）,L－NAME组10只大鼠中7只食管浆膜外静脉和粘膜下静脉迂曲扩张情况较模型组减轻。结论;大鼠食管静脉曲张的发病机制中有NO的参与;L－NAME对大鼠食管静脉曲张具有一定保护作用。     

左旋精氨酸抑制大鼠心脏移植术后移植物血管病的研究

目的探讨左旋精氨酸(L—Arg)预防和治疗心脏移植术后移植物血管病的作用。方法建立大鼠异位心脏移植动物模型，观察给与L—Arg、一氧化氮合酶(NOS)抑制药物左旋精氨酸甲酯(L—NAME)后不同时间移植心脏冠状血管的改变。结果L—Arg组大鼠无移植物血管病(CAV)的形成和一氧化氮(NO)能大量合成，L—NAME组大鼠有CAV形成。结论NOS抑制药物L—NAME加重移植后移植物血管病病变，L—Arg可以预防和减轻移植后移植物血管病的病变，NO具有抑制新生内膜形成的作用。     

高浓度Ca2+对大鼠脑线粒体呼吸功能的影响

应用分离的大鼠脑线粒体,给予外源性高浓度Ca^2＋及一氧化氮合酶（NOS）抑制剂-L-硝基-精氨酸甲酯（L—NAME）,检测一氧化氮（NO）含量及线粒体呼吸功能。结果显示高浓度Ca^2＋引起NO含量升高,线粒体呼吸功能降低,L—NAME通过抑制NOS活性使NO合成减少,对线粒体呼吸功能有保护作用。认为,外源性高浓度Ca^2＋可激活线粒体NOS,使NO合成增多,导致线粒体呼吸功能降低。     

吲哚布芬舒张血管的作用及机制研究

目的研究吲哚布芬对离体大鼠胸主动脉张力的影响,并探讨其作用机制。方法采用离体血管张力记录法,观察吲哚布芬对大鼠主动脉血管环的作用及不同工具药的影响。结果吲哚布芬（0.3μmol/L、1μmol/L、3μmol/L、10μmol/L和30μmol/L）对KCl（30mmol/L）预收缩的血管环具有浓度依赖性舒张作用,去内皮组舒张作用弱于内皮完整组,说明此舒张作用具有部分内皮依赖性。在KCl预收缩基础上,非特异性NOS抑制剂L-NAME（100μmol/L）处理大鼠胸主动脉后,吲哚布芬的舒张血管作用部分被抑制;加入钾通道阻滞剂4-氨基吡啶4-AP（1mmol/L）、氯化钡BaCl2（1mmol/L）、格列苯脲Gli（10μmol/L）和四乙胺TEA（10mmol/L）,吲哚布芬舒张血管作用均被抑制。结论吲哚布芬具有浓度依赖的舒张血管作用且具有部分内皮依赖性;而其舒血管作用可被反向钠钙交换体阻滞剂KB-R7943增强。吲哚布芬对大鼠胸主动脉的舒张作用可能与KATP通道、Kv通道、KCa通道和KiR通道有关。     

一氧化氮和前列腺素在门静脉高压性胃病大鼠胃粘膜灌注中的作用

目的 探讨一氧化氮（NO）和前列腺素在门静脉高压性胃病（PHG）大鼠胃粘膜灌注中的作用。方法 部分结扎大鼠门静脉主干2周后,采用中性红清除率法测定大鼠胃粘膜血流量（GMBF）,同时观察门静脉压力（PVP）的变化。结果 PHG组大鼠GMBF和PVP显著高于假手术组（t=3.431、3．312,P＜0．01）。低剂量的NO合成酶抑制剂L－硝基－精氨酸甲酯（L－NAME）呈剂量依赖性降低PHG大鼠GMBF,而对假手术组GMBF无明显影响;高剂量的L－NAME（12mg/kg)能非常显著降低PHG和假手术组大鼠GMBF。前列腺素环氧合酶抑制剂消炎痛能明显降低PHG组大鼠GMBF,而对假手术组GMBF无明显影响;预先给消炎痛处理后在假手术组大鼠中,静脉注射低剂量L－NAME（4mg/kg)前后GMBF无明显变化,高剂量L－NAME（12mg/kg)降低大鼠的GMBF与未用消炎痛处理组比无明显变化;预先给消炎痛处理后在PHG组大鼠中,L－NAME剂量（4mg/kg、12mg/kg)依赖性降低大鼠的GMBF与未用消炎痛处理组比无明显改变。结论 NO、前列腺素在调节PHG大鼠的GMBF起重要作用,但两者无协同作用。     

胰岛素对牛胸主动脉内皮细胞血管内皮生长因子受体表达的影响及其与一氧化氮合酶活性的关系

目的　评价胰岛素对培养的牛胸主动脉内皮细胞血管内皮生长因子 (VEGF)受体flt 1、flk 1 KDR表达的影响及其与一氧化氮合酶 (NOS)的关系。方法　取新生的小牛胸主动脉 ,作血管内皮细胞原代及传代培养 ,取 4 6代培养细胞用于实验 ;应用不同浓度 ( 30mU L、30 0mU L、30 0 0mU L)的胰岛素和NOS抑制剂 (L NAME)干预培养过程 ,4 8h后取培养细胞 ,应用免疫组化法测定flt 1、flk 1 KDR和NOS3的表达水平。结果　不同浓度胰岛素孵育组后内皮细胞flt 1、flk 1 KDR的表达水平差异无显著性 ,L NAME孵育后各组内皮细胞flt 1、flk 1 KDR的表达水平较单纯胰岛素孵育组差异无显著性。结论　胰岛素对内皮细胞flt 1、flk 1 KDR的表达无直接影响 ;内皮细胞NOS3的活性不是内皮细胞VEGF受体flt 1、flk 1 KDR表达的主要影响因素     

氨氯地平拮抗ox-LDL损伤大鼠骨髓源性内皮祖细胞血管样结构形成及机制

目的探索氨氯地平拮抗氧化型低密度脂蛋白(ox-LDL)损伤大鼠骨髓源性内皮祖细胞(EPC)血管样结构形成及其作用机制。方法实验分为对照组、ox-LDL组(50 mg/L ox-LDL)和氨氯地平组(50 mg/L ox-LDL+0.5μmol/L氨氯地平)。差异贴壁法培养分离EPC,ac-LDL摄取和结合UEA-1鉴定EPC,Transwell测定细胞迁移,Matrigel法测血管生成,Western blot和RT-PCR分别检测内皮型一氧化氮合酶(e NOS)的蛋白水平和mRNA表达情况,DCFH-DA法检测活性氧(ROS)水平,Griess法测定一氧化氮(NO)含量。结果 EPC经50 mg/L的ox-LDL处理后,细胞的迁移能力下降近3倍,血管样结构形成能力明显下降,用0.5μmol/L氨氯地平干预可部分恢复EPC的迁移能力,并显著恢复EPC的血管样结构形成能力(P0.05)。机制研究发现,ox-LDL下调EPC e NOS mRNA和蛋白表达水平,显著减少NO的含量(P0.01),氨氯地平显著拮抗ox-LDL的上述作用;EPC经50 mg/L的ox-LDL处理后,细胞内ROS含量显著增加(P0.01),氨氯地平显著减少胞内ROS的水平(P0.05)。结论氨氯地平对ox-LDL损伤EPC血管样结构的形成有显著拮抗作用,其作用与上调e NOS表达和降低细胞内ROS水平有关。     

NO在心血管病中的临床意义

1980年FttChgott等”’在血管内皮细胞中发现的血管内皮舒张因子（EDRF）具有舒张血管、降低血压、抑制血管平滑肌细胞增殖和血小板粘附等重要的生理作用，现已证实就是NO。近年来，人们对NO在心血管系统中的分布、生理功能及心血管病中的关系进行了深入广泛的研究。IN0生理作用NO是由L一精氨酸（L－Arg）和分子氧在NO合成酶（NOS）催化下生成的，NOS则是NO生成的关键酶，NO的半衰期仅约6S，迅速转化为较稳定的代谢产物亚硝酸／硝酸根离子（N07／NOI）。能合成和释放NO的细胞包括内皮细胞、白细胞、单核／巨噬细胞、肝细胞、…     

一氧化氮参与了缺血预处理后5''-核苷酸酶的延迟升高

目的：观察在缺血预处理期间抑制一氧化氮合酶对24h后5‘-核苷酸酶活性的影响和对缺血预处理第二保护窗的影响。方法：阻断免冠脉5min，再灌注10min，重复4次，造成缺血预处理。在缺血预处理期间静脉注射一氧化氮合酶抑制剂N^G-硝基－L－精氨酸甲酯（L－NAME），缺血预处理后24,提取心肌标本测量5‘-核苷酸酶性，或阻断冠脉30min再灌注120min，测量心肌梗死面积。结果：缺血预处理24h后，心肌细胞膜和胞浆5‘-核苷酸酶活性均较假手术对照组明显升高。静脉注射L－NAME阻断了缺血预处理所致的细胞膜和胞浆5‘-核苷酸酶活性的升高。缺血预处理组心梗面积明显小于对照组，而L－NAME阻断了这种保护作用。结论：一氧化氮参与了缺血预处理所致的5‘-核苷酸酶活性的延迟升高。延迟升高的5‘-核苷酸酶活性可能参与了缺血预处理的第二保护窗。     

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.