水飞蓟宾-磷脂酰胆碱复合物对氨基半乳糖胺与BCG＋LPS诱导的小鼠肝损伤的影响

目的：研究水飞蓟宾-磷脂酰胆碱复合物（silybin-phosphatidylcholine compound,SPC）对D-半乳糖胺（D-galactosamine,D-galN）和脂多糖（lipopolysaccharide,LPS）与卡介苗（Bacillus Calmette-Guerin Vaccine,BCG）诱导的小鼠肝损伤实验的影响.方法：将100只小鼠随机分成10组,分别用于SPC对D-galN和LPS＋BCG诱导的小鼠肝损伤影响实验.分别用D-galN和LPS＋BCG复制肝损伤动物模型,测定血清中ALT、AST和肝组织中TG水平并进行肝脏病理组织学检查.用200mg·Kg-1 SPC剂量对2种肝损伤小鼠进行处理,观察SPC对血清酶学及组织学改变的影响.结果：SPC不同程度的使D-galN和LPS＋ BCG诱导升高的ALT、AST和TG明显降低（p〈0.05）,并能减轻两种肝损伤动物模型肝脏组织学结构的改变.结论：SPC对D-galN和LPS＋BCG诱导的肝损伤具有明显的保护作用.     

肝衰竭研究进展

肝功能衰竭（肝衰竭）是临床常见的严重肝病症候群.引起肝衰竭的病因主要包括肝炎病毒、药物及肝毒性物质、病原体感染、妊娠急性脂肪肝、自身免疫性肝病等.乙型肝炎病毒（HBV）感染居肝衰竭病因之首,酒精性、药物性肝衰竭呈上升趋势.导致肝衰竭的诱因复杂多样,包括劳累、感染、药物、病毒变异等,比较突出的是核苷（酸）类似物抗病毒治疗相关因素,包括中断、减量使用核苷（酸）类药物、HBV变异以及抗病毒药物使用不规范等,列为可明确追寻的诱因,也提示应重视抗病毒药物临床应用的规范化[1].     

肝衰竭内科治疗的思路

肝衰竭是由多种因素引起的严重肝脏损害,导致合成、解毒、排泄和生物转化等功能发生严重障碍或失代偿,出现以凝血功能障碍、黄疸、肝性脑病、腹水等为主要表现的一组临床症候群[1].我国肝衰竭的首要病因为肝炎病毒（主要是乙型肝炎病毒）,其次是药物及肝毒性物质（如乙醇、化学制剂等）.在西方国家,药物是引起急性、亚急性肝衰竭的主要因素[2];酒精性肝损害常导致慢性或慢加急性肝衰竭.肝衰竭在儿童中多可见于遗传代谢性疾病.肝衰竭的治疗手段主要包括内科综合治疗、人工肝支持系统辅助治疗及肝移植术治疗等,其中内科综合治疗是基础,但内科综合治疗仍未取得实质性的突破,缺乏特效药物及方法,病死率仍然较高[34].因此,肝衰竭内科治疗过程中,正确的思路非常重要.     

天然蒙脱石对大鼠急性肝衰竭血中内毒素及单核细胞表面Toll样受体4表达的影响

目的研究大鼠急性肝衰竭时血中内毒素（LPS）及单核细胞表面TLR4表达的变化以及天然蒙脱石（思密达）对其表达的影响。方法腹腔注射半乳糖胺建立大鼠急性肝衰竭模型。50只SD雄性大鼠随机分为空白组（A组）、对照组（B组）、模型组（C组）、思密达预防组（D组）和思密达治疗组（E组）。采用双色荧光染色法检测血中LPS;荧光素标记的抗TLR4/抗CD14对大鼠血液单核细胞表面TLR4及CD14分子进行免疫荧光染色,流式细胞仪检测。结果与A组比较,C组、D组和E组LPS及TLR4表达均显著增高（P〈0.01）;与C组比较,D组和E组LPS及TLR4表达显著降低（P〈0.05）;D组与E组相比,D组LPS及TLR4表达较低（P〈0.05）;B组与A组比较LPS及TLR4差异均无统计学意义（P〉0.05）。结论大鼠急性肝衰竭时,血中LPS及TLR4的表达显著上调,用思密达预防和治疗后显著下调,且预防组下调更为显著。     

肝衰竭/重型肝炎的研究进展

本文对肝衰竭／重型肝炎的新进进行综述。在定义上倾向于将急性肝衰竭与慢性肝衰竭及脑病型与非脑病型分开；对新近提出的终末期肝病模型（MELD）预后判断公式进行评价；应用拉米夫定（LAM）治疗伴乙型肝炎病毒（HBV）复制的肝衰竭有效，但肝炎肝硬化患者因不当停药所致肝功能不全患者有所增多；LAM加乙型肝炎病毒免疫球蛋白（HBIg)预防肝移植后HBV感染有效，但其逸逸株有增多趋势；当前国际上将肝性脑病（HE）分为三种类型，A型为急性肝衰竭相关HE（ALFA－HE），B型为不伴有内在肝病的门体分离，C型指在慢性肝病／肝硬化基础上发生的HE。     

天然蒙脱石对急性肝衰竭大鼠的肠道干预实验

目的建立大鼠急性肝衰竭模型,并给予天然蒙脱石进行肠道干预研究。方法随机将40只大鼠分为正常对照组、模型组、思密达预防组和思密达治疗组,采用腹腔注射半乳糖胺法建立大鼠急性肝衰竭模型,观察大鼠肝功能、内毒素（LPS）及肝脏和回肠组织的病理学变化。结果与正常对照组比,模型组、思密达预防组和治疗组大鼠血ALT、AST、TBiL和LPS升高,Alb下降（P〈0．05）;与模型组比,思密达预防组和治疗组大鼠血ATJT、AST、TBiL和LPS下降,Alb升高（P〈0．05）;思密达预防组比治疗组大鼠血ALT、AST、TBiL和LPS更低（P〈0．01）;模型组大鼠肝脏形态学发生严重的病变,而预防组和治疗组病变较轻。结论应用天然蒙脱石进行肠道干预急性肝衰竭大鼠可明显减轻肝脏病理学改变,改善肝功能,降低LPS水平。     

生脉散对急性肝衰竭大鼠内毒素诱导细胞因子的影响

[目的]探讨生脉散对急性肝衰竭大鼠内毒素（LPS）诱导细胞因子水平的影响。[方法]采用胁氨基半乳糖腹腔注射法制作急性肝衰竭大鼠模型。予生脉散灌胃2h及8h后,检测血清LPS与细胞因子水平。[结果]D-氨基半乳糖能明显增加大鼠血清白细胞介素6（IL-6）、细胞间黏附分子1（ICAM-1）和IL-1β水平（P〈0．01）,随着D-氨基半乳糖作用时间延长的趋势明显减弱,但对血清LPS、肿瘤坏死因子α（TNF-α）水平无明显影响（P〉0．05）;生脉散能显著降低D氨基半乳糖肝衰竭大鼠血清IL-6、ICAM-1和IL-1β水平（P〈0．01,〈O．05）。LPS攻击2h和8h后,能明显诱导D-氨基半乳糖大鼠血清LPS、TNF-α、IL-6、ICAM-1和IL-1β水平增加（P〈0．01）;除在8h对TNF-α无影响外,生脉散能明显减轻LPS攻击D-氨基半乳糖大鼠后对血清LPS、TNF-α、IL-6、ICAM-1和IL-1β水平的影响（P〈0．01,〈O．05）。[结论]SD大鼠在急性肝衰竭状态下,存在严重LPS血症,并引起细胞因子水平变化的炎症级联反应,生脉散可通过调节细胞及炎症因子水平起到治疗作用。     

肾上腺皮质激素在肝衰竭治疗中应用的新认识

迄今为止,急性、亚急性和慢加急性肝衰竭的临床救治仍十分棘手,内科多采用综合支持治疗,使用肾上腺皮质激素（GCs）是治疗肝衰竭的潜在方法之一.对于免疫抑制治疗停止后,出现乙型肝炎病毒（HBV）再激活的患者,及早重新给予长期大剂量的GCs,可防止出现重型肝炎或肝衰竭.但以后的临床实践结果未能予以肯定.上世纪80年代以前应用GCs较多,但各家疗效不一,90年代则有否定的趋势,近年来随着核苷（酸）类似物（NUCs）抗病毒治疗的增多,GCs应用也有所增多[1].目前临床上仍存争议,主要包括以下两个方面：一是对适应证选择、剂量及疗程的掌握;二是对GCs不良反应及并发症的防治.     

HGF及其受体c-met在肝衰竭与部分肝切除模型中表达差异性研究

目的研究HGF及其受体c-met在肝衰竭和部分肝切除两种动物模型肝组织的表达差异。方法分别采用D-GalN/LPS腹腔注射和70%肝脏外科切除术建立肝衰竭和部分肝切除模型,同时以健康大鼠作为对照组。采用ELISA法检测血清HGF水平,采用Real-time PCR和Western-blot法分别检测肝组织c-met基因和蛋白的表达水平。结果与对照组比,部分肝切除模型大鼠血清HGF及其受体c-met表达水平均有明显升高（P〈0.01）,而在肝衰竭模型大鼠血清HGF水平虽有升高,但c-met蛋白表达水平却明显降低（P〈0.01）。结论肝细胞c-met表达水平的降低是D-GalN/LPS诱导肝衰竭大鼠肝细胞再生障碍的主要原因。     

重型肝炎诊断应与国际接轨

西方国家由肝炎病毒感染所致的严重肝炎较少见,而药物和毒品引起的肝衰竭较常见,故主要从肝衰竭角度进行研究,绝少有“重型肝炎”的表述。自从1970年Trey提出暴发性肝衰竭（fulminanthenaticfailure,FHF）概念以来,相继有许多学者建议对肝衰竭的分型进行修改补充。或主张修改FHF的发病时间限定,或另外提出亚暴发性肝衰竭（subfulminanthePaticfailure,SFHF）、迟发性肝衰竭（lateonsethePaticfailure,LOHF）、越急性肝衰竭（hyperacutehepaticfailure,HAHF）、急性肝衰竭（acutehepatiCfailuer,AHF）、亚急性肝衰竭（ub…     

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.     

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.     

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.     

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.