白细胞介素-6与低氧性肺动脉高压关系的探究

肺动脉高压（PAH）是一种常见的临床症状,凡是能引起血管阻力增大、血流量增多的因素都可成为其诱因。低氧性肺动脉高压（HPH）则是以低氧性肺动脉收缩和低氧性肺血管重构引起的肺动脉压持续升高为特征的病症。急、慢性低氧均可引起白细胞介素-6（IL-6）的分泌,导致炎症细胞浸润,继而通过对动脉内膜的改建引起PAH。     

内皮素受体拮抗剂在心血管疾病临床应用的进展

内皮素（endothelin，ET）是血管内皮细胞分泌的迄今所知作用最强和持续最久的收缩血管的多肽。自1988年ET-1被首次发现以来，已经发现呼吸循环系统存在3种ET（ET-1、ET-2和ET-3）和2种受体（ETA-R和ETB-R）。ET-1的活性远大于能引起多种心血管疾病的血管紧张素Ⅱ、抗利尿激素和去甲肾上腺素。因此，内皮素受体拮抗剂（endothelin-receptor antagonist，ETRA）在临床的应用受到极大关注。现就ETRA在心血管疾病临床应用的进展综述如下。     

内皮素受体拮抗剂预防低氧性肺动脉高压的实验研究

内皮细胞合成的内皮素(ＥＴ)具有极强的促肺血管平滑肌细胞收缩和增生的作用。慢性低氧可引起血浆及肺组织匀浆中ＥＴ1水平升高,ＥＴ通过与ＥＴ1选择性受体(ＥＴＡ)或非选择性受体(ＥＴＢ)结合,参与慢性低氧性肺动脉高压的发病过程。为进一步探讨ＥＴ在低氧性肺动脉高压发病中的作用,本研究采用ＥＴＡ受体拮抗剂ＢＱ123进行预防处理,观察其对低氧性肺动脉高压的预防效应。一、材料和方法1动物模型的复制:雄性Ｗｉｓｔａｒ大鼠30只,体重200～220ｇ。分为低氧组、ＢＱ123组和对照组,每组10只。低氧组:将大鼠置于自制常压低氧舱内,向舱内充入氮…     

内皮素-1在肺动脉高压发病中作用的研究进展

肺动脉高压(Pulmonary arterial hypertension,PAH)的发病率呈逐年上升趋势,若无及时干预,病情严重者最终会进展为心功能不全,然而,新型肺血管扩张剂的应用增加了肺动脉高压患者的中位生存期。在寻求了解这种疾病发病机制及探索肺血管疾病精准治疗的进程中,由内皮细胞释放的血管活性物质的表达已被证实与PAH密切相关,其中内皮素-1(ET-1)对于肺动脉高压的作用尤为显著。本文就ET-1在肺动脉高压中的机理及其新型肺血管扩张剂的应用作一综述。     

老年肺心病患者内皮素的检测

近年来研究证明在呼吸系统有广泛内皮素(ET)和ET受体分布,对肺功能和肺循环有重要调节作用。慢阻肺(COPD)时低氧性肺动脉高压形成的一个病理特征是肺动脉平滑肌细胞异常增生及肺血管的改建。这在肺动脉高压发生以及不可逆转性肺动脉高压形成中居重要地位。已有研究报道,肺心病患者血浆ET增高,ET参与了肺动脉高压的形成。老年肺心病患者中ET是否有改变?其意义何在?为此我们进行了这方面的工作。     

肺动脉高压治疗新方法——内皮素受体A治疗性疫苗

肺动脉高压(PAH)是一种慢性致死性疾病,现有针对PAH的药物虽有一定的治疗效果,但其预后仍不尽人意,需要探索新的治疗方法。治疗性疫苗是治疗PAH的新方法。内皮素(ET)系统,尤其是ET-1和内皮素受体A(ETAR)的异常激活与PAH的发病机制密切相关,ETAR是PAH治疗性疫苗的理想靶点。我们最近成功研发出一种以ETAR为靶点的PAH治疗性疫苗ETRQβ-002。该疫苗能显著降低两种PAH动物模型的肺动脉压,改善甚至逆转肺小动脉重构和右心室肥厚,且没有发现明显的靶器官免疫损害和肝肾功能异常,说明ETRQβ-002是一种能有效并且安全地治疗PAH的治疗性疫苗。     

内皮素研究新进展

内皮素几乎产生和作用于机体的所有组织。其生成分三步骤:内皮素原前体(203个氨基酸残基)→大内皮素(39个氨基酸残基)→内皮素(21个氨基酸残基)。内皮素受体分ET_A和ET_B两种类型。ET_A选择性地与ET—1结合;ET_B无选择地与ET—1、ET—2、ET—3结合。目前应用最广的内皮素受体拮抗剂是选择性抑制ET—1受体的BQ—123。肺动脉高压时,肺血管产生的内皮素增加。     

抑郁影响肺血管重构病理生理学机制

 肺动脉高压(PAH)属肺高血压疾病第一大类,是一类以进行性肺动脉压力和肺血管阻力升高为特点,导致肺血管重构,最终引起右心衰竭而死亡的少见病,治疗主要目的是缓解症状及延长生存期^[1]。尽管靶向药物如内皮素(ET)受体拮抗剂、五磷酸二酯酶抑制剂、前列腺素类似物可改善运动耐力,但治疗费用昂贵,患者体能丧失可能导致失业,加剧了经济负担。因此,疾病进展、生活质量下降、活动能力丧失、社会孤立及失业易成为PAH患者的精神负担而导致抑郁。     

U50488H对低氧性肺动脉高压大鼠体内一氧化氮、内皮素及血管紧张素Ⅱ水平的影响

目的研究κ阿片受体激动剂（U50488H）对低氧性肺动脉高压（HPH）大鼠体内一氧化氮（NO）、内皮素（ET）及血管紧张素Ⅱ（Ang Ⅱ）等血管活性物质水平的影响,初步探讨其防治HPH的作用机制。方法将实验动物随机分为正常对照组、低氧2周组、低氧2周+生理盐水组及低氧2周+U50488H组,采用低压低氧法建立大鼠HPH动物模型。2周后收集大鼠动脉血和肺组织,检测不同标本中血管活性物质NO、ET和Ang Ⅱ水平。结果慢性低氧2周后,大鼠血清及肺组织中NO水平显著降低,而血浆及肺组织中的ET和Ang Ⅱ水平则显著升高（P<0.01）。U50488H可明显升高HPH大鼠血清及肺组织NO水平,同时显著降低HPH大鼠血浆及肺组织中的ET和Ang Ⅱ水平（P<0.01）。结论U50488H可调节HPH大鼠体内的血管活性物质水平,其有可能通过刺激血液及肺组织NO的分泌,抑制ET和Ang Ⅱ的产生来实现对HPH的防治作用。     

艾森曼格综合征的治疗现状

艾森曼格综合征（Eisenmenger＇s syndrome，ES）是由各种心脏与大血管先天性异常交通导致肺动脉压增高至主动脉水平。伴肺血管阻力显著增高[〉10 Wood单位，1 Wood单位=8 kPa／（L·s）]，出现反向或双向分流的一组病理现象。近年随着治疗技术的进展，尤其内皮素（endothelins，ET）受体拮抗剂、磷酸二酯酶（phosphodiesterase，PDE）抑制剂和类前列环素（prostacyclin，PGI2）类等靶向治疗药物的推广，给包括ES在内的肺动脉高压（pulmonary arterial hypertension，PAH）患者带来了新的曙光。     

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.     

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.     

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.