肺动脉高压发病机制的进展带来临床治疗的革命

肺动脉高压发病机制的研究,包括离子通道机制、血管内皮功能舒缩因子失衡机制、炎症机制以及遗传基因学机制等方面取得了重大进展.由此,开发了一系列针对肺动脉高压发病机制的新型药物,如前列环素衍生物、内皮素受体拮抗剂、5型磷酸二酯酶抑制剂、鸟苷酸环化酶激活剂等,使肺动脉高压临床治疗发生了翻天覆地的变化.当然,要想从根本上治愈肺动脉高压,仍然任重而道远.肺动脉高压发病机制的进展带来临床治疗的革命是转化医学的光辉典范之一.     

肺动脉高压治疗过程中抗凝药物应用的研究进展

肺动脉高压是一组以肺血管阻力持续增加为特征的临床综合征,其发病机制复杂,预后差。有研究表明原位血栓形成及凝血功能紊乱在肺动脉高压的发病机制中起着重要作用,是肺动脉高压发生发展的重要机制之一。但目前关于抗凝药物在肺动脉高压中的应用始终无统一的结论,本文就肺动脉高压治疗过程中应用抗凝药物的病理学和生理学基础及目前抗凝药物在肺动脉高压应用情况及最新进展展开综述。     

肺动脉高压发病机制的研究进展

肺动脉高压（Pulmonary Arteria Hypertension,PAH）是以肺血管阻力进行性升高和右心功能进行性衰竭为主要特征的病理过程,是临床众多疾病常见的并发症,也可以原因不明.虽然对肺动脉高压的研究已有100多年,但其发病机制尚未完全明了,可能与缺氧、神经体液、先天性、遗传等因素有关[1].近年来,细胞生物学和分子遗传学的飞速发展促进了对肺动脉高压发病机制的深入研究,进而带动了肺动脉高压诊断学和治疗学研究的进步.本文综述了近几年来国内外有关肺动脉高压研究进展,系统探讨了肺动脉高压发病机制以及治疗进展,为临床治疗提供一定理论依据.     

肺动脉高压治疗的最新进展

肺动脉高压是各种原因引起的肺动脉压力持续升高的临床综合征.若缺乏相应的治疗,将导致肺血管重塑,最终发展为右心衰竭,预后极差.但早期诊断及合理治疗可提高该病患者的生存率并改善患者的生存质量.近年,对肺动脉高压发病机制认识的不断深入推动了肺动脉高压治疗手段的发展,现将肺动脉高压治疗的最新进展综述如下.     

门脉高压性肺动脉高压研究进展

门脉高压性肺动脉高压是一种特殊类型的肺动脉高压,现从发病率、发病机制、临床特点、诊断及治疗等方面阐述门脉高压性肺动脉高压的研究进展。     

肺动脉高压新的临床分类与组织病理学改变

肺动脉高压新的临床分类反映了当前对肺动脉高压发病机制和诊治策略的最新认识.肺动脉高压多样的组织病理改变也反映了致病因素、预后和对各种治疗的反应不同.重新评估肺动脉高压的组织病理学改变,会获取对临床诊治新的启示,有利于弥补非组织形态技术研究的不足.     

032 钾通道开放剂治疗低氧性肺动脉高压

本文论述了与低氧性肺动脉高压关系密切的钾通道种类及特性,强调钾通道活性的抑制和钾通对膜电位改变及胞内钙离子敏感性的降低,可能是低氧性肺动脉高压发病机制的中心环节,阐明了钾通道开放剂的种类、作用部位及作用原理,回顾了近年来国外应用钾通道开放剂治疗低氧性肺动脉高压的研究进展,证实钾通道开放剂可有效地降低肺动脉高压,为治疗低氧性肺动脉高压提供了新的治疗途径.     

肺动脉高压与免疫

肺动脉高压是临床上常见的疾病,其发病机制尚未完全清楚。免疫因素在肺动脉高压的发病机制中起重要作用。自身免疫紊乱、免疫细胞、免疫分子在其发生过程中起着重要作用,免疫抑制疗法为肺动脉高压治疗提供了新的途径。     

肺动脉高压治疗新视野

随着肺动脉高压发病机制研究的突破性进展,针对不同信号通路的关键作用靶点逐渐被认识。至今已有10多种新型肺动脉高压靶向药物陆续上市,目前治疗肺动脉高压的靶向药物主要有作用于内皮素通路的药物,作用于一氧化氮通路的药物和作用于前列环素通路的药物。上述药物主要用于治疗动脉性肺动脉高压和慢性血栓栓塞性肺动脉高压,其在临床中的应用极大地改善了肺动脉高压患者的预后。     

肺动脉高压治疗进展

动脉型肺动脉高压是临床上的治疗难题,近年来,随着对PAH发病机制认识的深入,开发了一系列针对肺动脉高压不同发病机制的特异性药物。肺动脉高压的常规治疗包括氧疗、抗凝、利尿治疗等,钙通道阻滞剂仅应用于急性血管反应试验阳性的患者,且其药物剂量要足够大。特异性血管扩张药物包括前列环素类似物、内皮素受体拮抗剂和磷酸二酯酶抑制剂等,随着特异性血管扩张剂的开发与应用,肺动脉高压患者的预后已明显改观。     

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.