对乙酰氨基酚引起的肝衰竭

<正>急性肝衰竭(ALF)为大多数肝病的严重结局,病因多样,其中对乙酰氨基酚是重要的致病原因。对乙酰氨基酚是大多数非处方感冒药的主要成分,患者容易自行加大用药剂量、或多个同成分药物重叠使用,或长期过量服用。在欧美国家,对乙酰氨基酚是导致急性肝衰竭的首要原因,在我国,对乙酰氨基酚引起的肝衰竭也是仅次于乙型肝炎病毒的重要因素。急性肝衰竭是肝细胞大量死亡,其特点是发病突然,死亡率高,目前缺乏有效的治疗手段,往往依赖于肝移植,但又受到肝源缺     

固有免疫细胞在急性肝衰竭发生和发展中的作用及研究进展

急性肝衰竭(ALF)是一种高病死率的临床危重病,其特征是无基础肝病患者的肝功能进行性恶化,常伴有黄疸、凝血功能障碍和肝性脑病。ALF的发病机制很复杂,尚未完全阐明。嗜肝病毒、药物毒物、自身免疫性疾病、缺血等不同病因均可引起急性肝损伤,可迅速进展为ALF甚至死亡,目前尚无特效治疗药物和方法。因此,深入探究ALF的发病机制并寻找有效的治疗方法显得尤为重要。本文综述了ALF相关的固有免疫机制,以及固有免疫细胞在ALF发生和发展过程中的作用。     

胆固醇与肝再生关系及其在肝衰竭治疗中的意义和潜在价值

肝衰竭为临床上常见的严重肝病症候群,属内科危急重症之一。其病理学是以大面积肝细胞死亡为特征,核心机制是内毒素、免疫反应和炎症级联反应等。肝细胞有效再生以代偿肝功能是促进肝衰竭良好转归的生理基础,并直接影响肝衰竭患者的预后和生存质量。临床实践中已发现血清胆固醇水平低的肝衰竭患者病死率极高,但胆固醇作为肝细胞合成代谢指标,其与肝细胞再生的关系并未引起足够的重视。本文从胆固醇与肝再生关系出发,综述其在肝衰竭临床治疗中的意义和潜在价值,以期从另一角度了解肝衰竭的发病机制,为肝衰竭的诊疗、药物研发提供新思路。     

组合式人工肝治疗的原则与应用

急性肝衰竭(ALF)常伴有多脏器功能不全(multipleorgans dysfuction sydrome,MODS),危重肝衰竭患者MODS发生率接近60%.因此,ALF患者的人工肝治疗除了需要替代复杂的肝脏代谢功能之外,尚需要逆转导致患者死亡的MODS.     

猪急性肝衰竭模型的建立及猪纤维介素的表达

目的 建立一个模拟人类疾病进程的猪急性肝衰竭(ALF)模型,用于ALF治疗药物的临床前安全性评价及疗效评价,检测模型中猪纤维介素(pfg12)的表达情况,为针对fg12的基因治疗提供基础和依据. 方法造模组耳静脉快速注射D-氨基半乳糖盐酸盐,剂量1.2 g/kg;对照组耳静脉快速注射5%的葡萄糖,剂量12 ml/kg.观察两组动物临床表现,肝功能指标和肝组织病理学改变,实时定量PCR检测肝组织中pfg12 mRNA表达,免疫组织化学检测肝组织中pfg12蛋白的表达.采用重复测量数据的方差分析和独立样本t检验进行统计学处理.结果 成功建立了与人在临床表现、肝脏生物化学指标、组织病理学改变相似的猪ALF模型;实时定量PCR检测结果显示造模组猪肝组织中pfg12的mRNA表达水平显著增加,与对照组比较,差异具有统计学意义(t=7.695,P＜0.05).免疫组织化学显示造模组猪肝组织中有明显的pfg12蛋白的表达,主要分布在肝细胞坏死区域的肝细胞、炎症浸润细胞、肝血窦内皮细胞及血管内皮细胞,对照组动物肝组织未见pfg12阳性着色.结论 以D-氨基半乳糖盐酸盐诱导的猪ALF模型可用于评价肝衰竭治疗药物的临床前疗效及安全性;pfg12在猪ALF动物模型的肝组织中异常高表达,提示其参与了ALF时肝细胞坏死的发生和发展过程.     

猪急性肝衰竭模型的建立及猪纤维介素的表达

目的 建立一个模拟人类疾病进程的猪急性肝衰竭(ALF)模型,用于ALF治疗药物的临床前安全性评价及疗效评价,检测模型中猪纤维介素(pfg12)的表达情况,为针对fg12的基因治疗提供基础和依据. 方法造模组耳静脉快速注射D-氨基半乳糖盐酸盐,剂量1.2 g/kg;对照组耳静脉快速注射5%的葡萄糖,剂量12 ml/kg.观察两组动物临床表现,肝功能指标和肝组织病理学改变,实时定量PCR检测肝组织中pfg12 mRNA表达,免疫组织化学检测肝组织中pfg12蛋白的表达.采用重复测量数据的方差分析和独立样本t检验进行统计学处理.结果 成功建立了与人在临床表现、肝脏生物化学指标、组织病理学改变相似的猪ALF模型;实时定量PCR检测结果显示造模组猪肝组织中pfg12的mRNA表达水平显著增加,与对照组比较,差异具有统计学意义(t=7.695,P＜0.05).免疫组织化学显示造模组猪肝组织中有明显的pfg12蛋白的表达,主要分布在肝细胞坏死区域的肝细胞、炎症浸润细胞、肝血窦内皮细胞及血管内皮细胞,对照组动物肝组织未见pfg12阳性着色.结论 以D-氨基半乳糖盐酸盐诱导的猪ALF模型可用于评价肝衰竭治疗药物的临床前疗效及安全性;pfg12在猪ALF动物模型的肝组织中异常高表达,提示其参与了ALF时肝细胞坏死的发生和发展过程.     

急性肝衰竭的治疗进展

急性肝衰竭(acute liver failure,ALF)是指原来无肝脏疾病(主要指肝硬化)的患者,由于肝细胞大量坏死或功能丧失发生急性严重肝功能不全,导致以肝性脑病(hepatic encephalopathy,HE)和凝血功能障碍为主要特征的临床综合征。此综合征病情严重、临床症状复杂、病死率高。患者的生存率与病因、脑病程度及多器官衰竭密切有关,主要的死因是感染和进行性脑水肿。随着肝移植的开展,短期生存率超过境5%。尽管如此,急性肝衰竭的治疗仍面临一些挑战。1重症监护与一般治疗对于确诊的ALF的患者,尽早转入重症监护病房(ICU)中密切观察生命体征,严格消…     

MAPK信号通路与急性肝衰竭发病机制的研究进展

<正>急性肝衰竭(ALF)的发生是多种因素共同作用引起的结果,具体的分子生物学致病机制也较为复杂,其中肝细胞的变性和坏死是通过多种信号通路来实现的。丝裂酶原活化蛋白激酶(MAPK)是目前研究较多的一条,它与细胞的炎性损伤有关,尤其与肝细胞炎症和坏死的发生密切相关。急性肝衰竭具有起病急、病情发展迅速、死亡率高等特点,其发病因素多种多样,除了HBV/HCV感染外,酒精、药物、肝     

免疫反应与炎症损伤在肝衰竭发病机制中的作用

肝衰竭是临床上常见的严重肝病症候群,该病救治难度大,病死率高,属于内科危急重症之一。肝细胞大量死亡、肝细胞死亡程度超过肝再生的能力被认为是肝衰竭发生发展的核心事件,直接损伤和免疫介导的炎症损伤是这一过程的两个主要因素。越来越多的证据表明,宿主免疫反应与炎症级联反应在肝衰竭发病机制中极为重要。综述了免疫调节(先天性和适应性)与炎症损伤(炎症诱导物、感受细胞、炎症介质)在肝衰竭过程中的作用机制,以及免疫反应/免疫细胞与炎症反应/炎症因子的交互作用,以期有助于了解肝衰竭的发病机制,为肝衰竭的诊疗、药物研发提供新思路。     

肝衰竭的临床病理基础

肝衰竭是由严重的合成和代谢紊乱导致的一组肝细胞功能障碍性疾病,病死率高。组织病理学对肝衰竭的诊断、分型及预后判断临床意义重大。广泛的肝细胞死亡与肝细胞再生贯穿肝衰竭的临床病理过程,肝细胞的死亡方式以坏死为主,且与细胞凋亡、焦亡及自噬等细胞死亡方式并存。各型肝衰竭有其相对的病理学特征,急性肝衰竭强调的是一次性打击导致的一致性大块性或亚大块性坏死,亚急性肝衰竭系多次打击引起的新旧病变交杂的亚大块或杂以大块性肝坏死,慢加急性肝衰竭是在慢性肝病背景基础上发生的一次或多次打击导致的广泛肝细胞坏死,慢性肝衰竭组织学上呈小结节或大小结节混合性肝硬化,纤维间隔以Ⅰ型胶原为主的致密宽隔,Laennec分期多为F4c,肝实质细胞数量及功能显著下降,并呈现明显的肝内血管结构异常及血循环紊乱,肝脏易见炎症活动病变。肝细胞死亡引发大量炎细胞在肝脏内募集和Kupffer细胞过激活,刺激免疫介导的肝脏病理损伤,及炎症激活后引发的全身炎症反应综合征,是肝衰竭致多器官衰竭的主要病理生理机制。     

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.