肝干细胞移植治疗肝脏疾病的研究进展

肝干细胞移植治疗急、慢性肝衰竭为治疗肝衰竭开辟了一个新途径。采用肝干细胞移植治疗肝衰竭,移植的肝干细胞可直接参与修复肝组织或帮助肝脏渡过危险期,为后期肝移植赢得时间。近年来,肝干细胞移植研究取得较大的进展,为这一技术从实验室向临床过渡奠定了基础。笔者就肝干细胞移植治疗肝脏疾病的研究进展进行简要综述。     

人工肝和干细胞在肝衰竭治疗中的进展

目前肝衰竭的治疗手段主要包括内科综合治疗、人工肝支持系统治疗、肝移植和干细胞移植等,近些年人工肝支持系统和干细胞移植在肝衰竭治疗方面取得了较大的进展。介绍了临床上常用的非生物型人工肝治疗方法和生物型人工肝的细胞来源、细胞培养方式、生物反应器及临床应用等。探讨了干细胞治疗肝衰竭的机制和临床应用。针对人工肝和干细胞治疗肝衰竭临床疗效欠佳的问题,提出了两者联合治疗肝衰竭的可行性。     

性激素对干细胞及干细胞治疗肝纤维化的影响

干细胞治疗肝纤维化已取得实质性进展,但是治疗中干细胞自我更新能力下降影响了疗效,因而提高干细胞自我更新能力尤为紧迫和重要,目前研究认为性激素对干细胞的自我更新能力有影响。以性激素作为切入点,综述了雌激素、雄激素对不同干细胞自我更新能力的影响及不同性别来源的干细胞功能上存在的差异,探讨了性激素对干细胞治疗肝纤维化的影响。认为性激素对将来干细胞治疗肝纤维化时提高干细胞自我更新能力,以及选择合适的细胞有重要的理论和临床价值。     

肝纤维化的干细胞治疗进展

近年来国内外研究表明,在个体发育的不同阶段及不同成体组织中均存在着干细胞.肝脏内不仅存在肝源性干细胞,还存在其他组织来源的干细胞(如骨髓干细胞,胰腺干细胞等),这些干细胞最终可以分化为成熟的肝样细胞.因此,干细胞的替代疗法为终末期肝病患者的肝纤维化治疗提供了新的思路.本文就近年来干细胞治疗肝纤维化方面的相关研究进展作一综述.     

肝干细胞移植的基础研究进展

肝干细胞具有强大的增殖能力，并具有多向分化潜能。肝干细胞移植为各种急性肝衰竭和慢性终末期肝病的治疗提供了一种新思路。本文简要地介绍了近年来关于肝干细胞移植的细胞来源、肝干细胞归巢的分子机制及肝干细胞移植的理论基础等方面的最新研究进展。     

骨髓干细胞移植与肝纤维化

近年来,骨髓干细胞移植被认为是治疗各种肝脏疾病最具潜力的措施之一,其在肝纤维化中的应用研究也日益增多.但肝纤维化本身的慢性病程及病理特征使骨髓干细胞移植的应用具有一定的特殊性.此文针对应用于肝纤维化的骨髓干细胞的移植优势、移植部位、输注途径、种植分化、治疗效果及作用机制作一阐述,为从事骨髓干细胞移植治疗肝纤维化的研究者提供借鉴和指导.     

骨髓造血干细胞与肝再生的相关性研究

感染、中毒等引起的急慢性肝损伤治疗是临床医学领域的世界性难题,干细胞的研究为肝再生提供了全新的思路.肝再生的细胞学机制涉及肝细胞、肝干细胞和骨髓干细胞等. 新近发现骨髓造血干细胞具有向肝细胞转化的潜能,可以在体内外被诱导分化为肝样细胞,移植到肝损伤动物体内可以修复肝组织损伤,这为肝再生研究开辟了新的途径.对骨髓造血干细胞参与肝细胞再生的深入研究,有可能找到肝损伤治疗的有效措施.     

肝干细胞治疗存在的问题及对策

传统的肝细胞移植(HT)治疗开展临床应用已有十余年,在治疗急慢性肝功能衰竭、肝细胞先天性功能缺陷所致的代谢性疾病和血友病等方面取得一定疗效。由于HT治疗主要采用异基因成熟肝细胞,受制于供体来源缺乏、保存困难、细胞体内外增殖能力差、免疫排斥等多种因素,HT治疗尚难以在临床广泛开展。近年来,肝干细胞的研究取得重大进展,以肝干细胞作为移植细胞来源,可望从多个层面解决上述难题。但目前肝干细胞离临床应用仍有较大距离,在实施肝干细胞临床治疗前,迫切需要解决以下几个问题。     

间充质干细胞治疗肝脏疾病的研究进展

间充质干细胞(MSCs)可应用于治疗急性肝衰竭、终末期肝病和遗传代谢性肝病,旁分泌机制是其治疗肝病的重要机制。MSCs还可以通过调节免疫功能减轻炎症反应、抗肝细胞凋亡、抗肝纤维化、促进内源性肝干细胞分化和刺激内源性肝细胞增殖、促进血管增生等修复肝组织。进一步阐明MSCs的治疗机制,合理设计随机双盲对照临床试验,明确干细胞移植可能的副作用,是其广泛应用于临床的前提。     

肝脏再生过程中干细胞分化调控机制的研究进展

肝干细胞属于专能干细胞,为肝内胆管系统源性具有多分化潜的细胞群。肝干细胞既可以向肝细胞分化,又可以向胆管细胞分化,是肝脏组织再生的"种子细胞"。自体肝干细胞移植不会发生免疫排斥,故肝脏干细胞移植理论上可以成为终末期肝病细胞治疗的理想来源,有效解决肝脏供体严重缺乏的临床现状。本文就肝干细胞的生物学特性及其在肝脏损伤再生中的作用及调控机制综述如下。     

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.