全结肠黑变病的临床特征分析

[目的]探讨全结肠黑变病（MC）的临床特征。[方法]对近3年来诊断的90例全MC患者相关资料进行分析。[结果]90例中,便秘58例,45例长期或间断服用蒽醌类泻药,腹泻8例,并发结肠癌3例,结肠息肉28例,溃疡性结肠炎3例。[结论]全MC的发病与服用蒽醌类泻药及便秘有关,便秘及服泻药时间越长、服药量越大,其MC程度越重。全MC还可能与炎症性肠病及腹泻本身有关。该病是一种良性疾病,与结肠肿瘤的发生有一定关系,停用刺激性泻药,纠正习惯性便秘可以逆转病变。     

86例结肠黑变病回顾分析

目的探讨结肠黑变病（MC）的发病特征、临床与内镜特点、发病原因及其与大肠腺瘤、大肠癌及溃疡性结肠炎的关系。方法选择2007年1月～2010年12月本院内镜室结肠镜检记录、相关病理记录及定期随访资料,进行数据分析。结果 2007年～2010年MC检出率呈逐年上升趋势;老年患者检出率高于中青年（P〈0.01）,男性患者多集中在老年（P〈0.01）,女性患者检出率无年龄差异,老年患者检出率无性别差异,中青年患者女性检出率高于男性（P〈0.01）;便秘为MC最常见症状,其次是腹痛;病变可累及各肠段;长期便秘及服用蒽醌类泻剂易患MC;MC与结肠腺瘤病发病密切相关（P=0.012）,与结肠癌和溃疡性结肠炎无明显相关性。停用蒽醌类泻药结肠黑变能治愈或明显减轻。结论 MC的检出率呈逐年增加的趋势;老年人及中青年女性易患本病;临床表现缺乏特异性;容易合并结肠腺瘤;便秘及服用蒽醌类泻剂与MC密切相关;MC预后良好。     

结肠黑变病临床特点和内镜诊断分析(附145例报告)

[目的]探讨结肠黑变病(MC)的临床和内镜特点.[方法]对2004年1月～2009年12月经结肠镜检出的145例MC患者的临床资料、内镜下表现及并发息肉、肿瘤的检查结果进行回顾性分析.[结果]6 841例肠镜检查患者中检出MC145例,检出率2.11%;不同性别的检出率差异无统计学意义(P>0.05);>60岁的患者检出率明显高于<60岁患者(P<0.05);多数有便秘和(或)服用泻药病史;MC病变程度与服用泻药时间呈明显正相关(P<0.05).MC较易合并直径<0.5 cm的山田Ⅰ型结肠息肉.[结论]老年人易患MC;MC的发生与便秘和长期服用泻药有关;MC与结肠息肉、肿瘤发生有一定相关性,定期的肠镜随访是非常必要的.     

78例结肠黑变病临床分析

目的 分析结肠黑变病(MC)的病因及与其结肠肿瘤的关系.方法 对78例结肠黑变病患者的临床资料进行回顾性分析.结果 便秘患者56例(23.1%),其中长期服用泻药患者38例(48.7%),无明确服泻药史患者18例(23.1%);合并有腺瘤样息肉16例;合并结肠癌1例.结论 便秘及服用泻药是导致MC发生的重要因素;泻剂中多为蒽醌类.结肠黑变病与结肠肿瘤的关系值得进一步研究.     

中药经结肠治疗机治疗慢性腹泻85例

[目的]观察中药经结肠治疗机治疗慢性腹泻的疗效.[方法]选取170例慢性腹泻患者,分为对照组及治疗组各85例,分别采用活菌制剂、经结肠灌注透析治疗机清洗肠腔后保留灌入中药等治疗.治疗15 d后判断疗效.[结果]对照组显效49例,有效23例,无效13例,总有效率为84.71%;治疗组显效57例,有效25例,无效3例,总有效率为96.47%.两组总有效率比较差异有统计学意义(P＜0.01).[结论]经结肠治疗机灌洗及给药,效果比较理想,可作为慢性腹泻治疗的一个有效手段.     

功能性便秘与结肠黑变病关系的探讨

目的 研究功能性便秘与结肠黑变病(melanosis coli．MC)之间的关系。方法 根据罗马Ⅱ标准选择功能性便秘病人109例，按MC的诊断标准明确其中14例为MC，同时了解便秘程度和服泻药情况，对所有MC患均行病理学检查。结果 MC患女性多于男性，发病年龄偏高，本组结肠镜检出率为0．62％，占功能性便秘的22．02％，功能性便秘发生MC均为重度便秘病人，有长期服蒽类泻药史，以全结肠和升结肠部位多见。病理表现为黏膜内含有大量含色素颗粒的单核吞噬细胞沉积，上皮细胞正常。结论 功能性便秘是引起MC的主要原因，尤以服蒽类泻剂为甚，因泻剂可诱导结肠黏膜上皮细胞凋亡，且凋亡上皮细胞数量与MC的程度呈正相关，因此，可能会增加患结直肠癌发病的危险性。     

老年人大肠黑变病的临床和内镜特点分析

目的探讨老年人大肠黑变病(Melanosis coli,MC)的病因及其临床和内镜特点。方法总结我院自2000年-2010年间电子结肠镜检查4 821例中发现60岁以上58例老年MC的临床资料,并进行回顾性分析。结果老年MC病变多累及1个或多个肠段,全结肠发病率较高,58例中25例伴有大肠息肉,其中大肠腺瘤23例,5例伴有结肠癌,便秘49例,服用泻药53例。结论老年MC的病因主要与便秘和长期服用蒽醌类泻药有关,其伴发大肠息肉和结肠癌几率增加。     

复方苦参结肠溶胶囊治疗溃疡性结肠炎24例

[目的]观察复方苦参结肠溶胶囊治疗溃疡性结肠炎(湿热内蕴证)患者的临床疗效及安全性.[方法]采用随机、双盲双模拟、对照的方法共入组溃疡性结肠炎(湿热内蕴证)患者43例,其中试验组24例,对照组19例,试验组给予以复方苦参结肠溶胶囊及美沙拉嗪肠溶片模拟剂,对照组予以美沙拉嗪肠溶片及复方苦参结肠溶胶囊模拟剂,8周后对患者的中医症候积分、肠镜下表现、肠黏膜病理组织学炎症程度及Sutherland疾病活动指数积分等指标进行评价,并观察不良反应发生情况.[结果]2组患者经治疗后均能明显改善中医症候、肠镜下表现、肠黏膜病理组织学炎症程度及降低Sutherland疾病活动指数积分;2组均未发生严重不良反应.[结论]复方苦参结肠溶胶囊治疗轻、中度溃疡性结肠炎(湿热内蕴证)具有较好的治疗效果,同时具有较好的安全性,可以作为该病治疗的一种选择.     

通因通用法治疗溃疡性结肠炎的临床及实验研究

[目的]观察调肠通络饮(TTD)对溃疡性结肠炎(UC)患者的疗效及对实验性UC大鼠血小板功能的影响.[方法]103例UC患者随机分为两组,分别予TTD、柳氮磺胺砒啶(SASP)治疗后,观察临床综合疗效与结肠黏膜病变疗效;以2,4,6三硝基苯磺酸(TNBS)诱导实验性大鼠结肠炎,分别予TTD、SASP治疗后腹主动脉采血,测血小板黏附率、血小板聚集性,血浆与结肠组织中血栓烷B2(TXB2)、6-酮-前列腺素F1α(125 I-6-Keto-PGF1α),并取结肠组织,作病理观察.[结果]TTD组综合疗效明显优于SASP组;TTD能显著改善UC大鼠结肠病理状态,降低血浆及结肠组织中TXB2,升高血浆6-Keto-PGF1α.[结论]TTD为治疗UC的有效方药,能改善UC大鼠病损状况,有抑制血小板功能亢进的作用.     

中西医结合治疗急性胰腺炎22例

[目的]研究中西医结合治疗急性胰腺炎(AP)的临床与机制.[方法]采用生长抑素、中药通里攻下等综合措施治疗AP 22例,其中重症急性胰腺炎(SAP)5例.[结果]AP病程缩短,无一例发生并发症;SAP无一例死亡.[结论]中西医结合治疗AP疗效显著.     

血管紧张素Ⅱ受体1及周期素激酶抑制剂p27在血管紧张素Ⅱ诱导系膜细胞肥大中的作用

目的：在周期素激酶抑制剂p27和血管紧张素Ⅱ受体1（AT1）水平,研究血管紧张素Ⅱ(AngⅡ）诱导系膜细胞（MC）肥大的分子机制。方法：用蛋白印迹（western杂交）方法测定MC中p27蛋白水平,用[^3H]胸腺嘧啶核苷[^3H]TdR)及[^3H]leu掺入方法测定MC的肥大情况,观察p27反义寡苷酸（ODN）转染对MC肥大程度的影响。用ELISA方法测定MC中细胞外基质（ECM）蛋白（Ⅳ型原及纤维连接蛋白）结果：AngⅡ使无血清培养MC中p27增多,[^3H]leu掺入增加,[^3H]TdR掺入减少,MC中ECM水平增高,p27反义ODN转染使AngⅡ的上述作用减弱;氯沙坦可降低AngⅡ刺激的MC中的p27水平,减少[^3H]leu掺入,增加[^3H]TdR掺入,降低MC中的ECM水平,且上述作用呈剂量依赖性。结论：AngⅡ通过AT1受体可提高p27水平,诱导MC细胞肥大,而氯沙坦可减轻AngⅡ诱导的MC细胞肥大程度。     

高糖培养的系膜细胞肥大与周期素激酶抑制剂p27的关系

目的：研究周期素激酶抑制剂p27在高糖培养系膜细胞（MC）肥大中的作用。方法：蛋白印迹（western杂交）方法测定MC裂解液P27蛋白水平,[^3H]TdR）及[^3H]leu)掺入方法测定MC细胞的肥大情况,观察P27反义寡核苷酸（ODN）转染对高糖培养MC肥大的影响。结果：高糖（450mg/dl)无血清培养的MC同正常糖（100mg/dl)无血清培养的MC相比,P27水平增高,[^3H]leu掺入增加,[^3H]TdR掺入减少;p27反义ODN转染后高糖无血清培养MC[^3H]leu掺入减少,[^3H]TdR掺入增加,用甘露醇提高正常培养液渗透压并不增加MC中p27水平,结论：高糖培养的MC中P27水平明显增高,增高的P27在高糖培养MC细胞肥大中起重要作用。     

Tumor-initiating activity in mouse skin and carcinogenicity in rat mammary gland of fluorinated derivatives of benzo[a]pyrene and 3-methylcholanthrene

Summary Comparative studies of tumor-initiating activity in mouse skin and carcinogenicity in rat mammary gland were conducted with benzo[a]pyrene (BP) and 3-methylcholanthrene (MC) derivatives. SENCAR mice were initiated with BP, 6-fluorobenzo[a]pyrene (6-FBP), 6-methylBP, 7-FBP, 8-FBP, 9-FBP, 10-FBP, or 10-azaBP and promoted with tetradecanoyl phorbol acetate. The same compounds plus BP 7,8-dihydrodiol were tested by intramammillary injection in female Sprague-Dawley rats. Tumor-initiating activity in mice and/or carcinogenicity in rats were observed for BP, 6-methylBP, 6-, 7-, 8-, and 10-FBP, whereas 9-FBP was inactive in both experiments and 10-azaBP was only marginally active in the mammary gland. BP 7,8-dihydrodiol was carcinogenic in rat mammary gland, although it was less potent than BP. MC, 8-FMC, 10-FMC, and 3-methylcholanthrylene were also tested in Sprague-Dawley rats by intramammillary injection. All compounds were carcinogenic, with MC displaying the most potent activity. The less potent carcinogenic activity of BP 7,8-dihydrodiol in the mammary gland, compared with BP, and the moderate-to-weak tumor-initiating and/or carcinogenic activity of 7-, 8-, and 10-FBP suggest that the bay-region diol-epoxide pathway does not play a significant role in the activation of BP in these two target tissues. Similarly, the carcinogenic activity of 8-FMC and 10-FMC, in which the bay-region diol-epoxide pathway is blocked, suggests that this mechanism of activation is not important in the carcinogenicity of MC in rat mammary gland.Abbreviations used 10-azaBP 10-azabenzo[a]pyrene - BP benzo[a]pyrene - BP 7,8-dihydrodiol 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene - 6-FBP 6-fluorobenzo[a]pyrene - 7-FBP 7-fluorobenzo[a]pyrene - 8-FBP 8-fluorobenzo[a]pyrene - 9-FBP 9-fluorobenzo[a]pyrene - 10-FBP 10-fluorobenzo[a]pyrene - 8-FMC 8-fluoro-3-methylcholanthrene - 10-FMC 10-fluoro-3-methylcholanthrene - 6-methylBP 6-methylbenzo[a]pyrene - MC 3-methylcholanthrene - MCL 3-methylcholanthrylene - PAH polycyclic aromatic hydrocarbons - TBA tumor-bearing animals Supported by Public Health Service grants CA32376 and CA36727 and a seed research grant from the University of Nebraska Medical Center     

二金汤对功能性消化不良大鼠胃窦肥大细胞和血清一氧化氮的影响

[目的]观察二金汤方对功能性消化不良(FD)大鼠胃窦部肥大细胞数量和血清一氧化氮(NO)的影响,探讨其可能的作用机制.[方法]采用不规则进食加稀酸喂养制作大鼠FD模型,并随机分成二金汤大、小剂量、多潘立酮、0.85%氯化钠液(正常)及模型组,共5组,连续给药28 d后,以硝酸还原酶法测定血清NO;中性红染色法对胃窦黏膜肥大细胞进行计数.[结果]与正常组相比,模型组大鼠血清NO和胃窦黏膜肥大细胞计数增多(P＜0.05).二金汤大剂量组血清NO和胃窦部肥大细胞数较模型组显著降低(P＜0.05),与正常组相仿.[结论]二金汤方具有降低血清NO和胃窦部肥大细胞数作用,可能是其治疗FD的机制.     

Both early and delayed treatment with melanocortin 4 receptor-stimulating melanocortins produces neuroprotection in cerebral ischemia

Ischemic stroke is one of the main causes of death and disability. We investigated whether melanocortin peptides, which have protective effects in severe hypoxic conditions, also produce neuroprotection in a gerbil model of ischemic stroke. A 10-min period of global cerebral ischemia, induced by occluding both common carotid arteries, caused impairment in spatial learning and memory that was associated with activation of inflammatory and apoptotic pathways, including severe DNA damage and delayed neuronal death, in the hippocampus. Treatment with nanomolar doses of the melanocortin analog [Nle4, D-Phe7] alpha-MSH [which activates the melanocortin receptor subtypes (MC) mainly expressed in central nervous system, namely MC3 and MC4] modulated the inflammatory and apoptotic cascades and reduced hippocampus injuries even when delayed up to 9 h after ischemia, with consequent dose-dependent improvement in subsequent functional recovery. The selective MC3 receptor agonist gamma2-MSH had no protective effects. Pharmacological blockade of MC4 receptors prevented the neuroprotective effects of [Nle4, D-Phe7] alpha-MSH and worsened some ischemia outcomes. Together, our findings suggest that MC4 receptor-stimulating melanocortins might provide potential to develop a class of drugs with a broad treatment window for a novel approach to neuroprotection in ischemic stroke.     

Detection of carcinogen-induced stimulation of cytochrome P-448-associated enzymes by 14CO2 breath analysis studies using dimethylaminoazobenzene.

Rats pretreated with three agents known to stimulate cytochrome P-448-associated enzymes, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3-methylcholanthrene (3MC), and Aroclor 1254 were studied with a 14CO2 breath analysis technique after administration of [14C-dimethyl]aminoazobenzene (DMAB). The half-life of breath 14CO2 after [14C]DMAB administration was significantly decreased in the TCDD-, 3MC-, and Aroclor 1254-treated rats compared with controls. In vitro studies indicated that DMAB N-demethylase was increased by these three agents. Phenobarbital, an inducer of cytochrome P-450-associated enzymes, had no effect on 14CO2 half-life or on DMAB N-demethylase. Studies with [14C]aminopyrine, a cytochrome P-450 substrate, showed that TCDD and 3MC had no effect on 14CO2 half-life or aminopyrine N-demethylase; Aroclor 1254 and phenobarbital decreased 14CO2 half-life and stimulated aminopyrine N-demethylase. The data suggest that a [14C]DMAB breath analysis technique may be useful for in vivo studies of inducers of cytochrome P-448.     

健脾理气化痰法针刺对高脂饲养胰岛素抵抗大鼠骨骼肌葡萄糖转运体4蛋白表达的影响

[目的]探讨健脾理气化痰法针刺对高脂饲养胰岛素抵抗大鼠骨骼肌葡萄糖转运体4（GLuT4）蛋白表达及胰岛素敏感性的影响。[方法]40只Wistar大鼠分别用高脂饲料、普通饲料喂养。经高胰岛素-正常葡萄糖钳夹术确定高脂饲养制备IR模型成功后,将模型大鼠随机分为模型组和电针组（取足三里、中脘、丰隆、关元穴）,普通饲料喂养组为正常组。治疗6周后,行腹腔糖耐量、腹腔胰岛素耐量实验测量各组大鼠血糖水平;治疗8周后,采用免疫组化法检测各组大鼠股四头肌GLUT4蛋白的表达。[结果]与模型组比较,电针组胰岛素降低血糖的效果显著增强（P〈o．01）;与模型组比较,电针组股四头肌GLUT4蛋白的表达水平增加（P〈o．05）。[结论]健脾理气化痰法针刺具有提高胰岛素敏感性的作用,并能显著提高股四头肌GLUT4蛋白的表达水平。     

The effects of various cell growth factors and cyclosporin A, an immunosuppressive agent, on cloned osteoblastic cell line, MC3T3-E1 cells

Cloned MC3T3-E1 cells which have retained several osteoblast-like characteristics were derived from newborn mouse calvaria. In order to elucidate the function of osteoblasts, the effects of 1,25(OH)2D3, interleukin (IL)-1 beta, IL-3, interferon(INF)-gamma and epidermal growth factor(EGF) on the activity of alkaline phosphatase(Al-P'ase), DNA synthesis and the production of prostaglandin E2(PGE2) in MC3T3-E1 cells were studied. The influence of cyclosporin A(CSA), a potent immunosuppressive agent, was also studied. The following results were obtained: 1. 1,25(OH)2D3 increased the incorporation of [45Ca]Cl2 into matrix and accelerated the calcification of MC3T3-E1 cells. 2. Al-P'ase activity and the incorporation of [3H]-thymidine into MC3T3-E1 cells were increased by 1,25(OH)2D3 but decreased by IL-1 beta, INF-gamma, IL-3 and EGF. 3. IL-1 beta increased and INF-gamma decreased PG-E2 production by MC3T3-E1 cells. 4. CSA decreased either Al-P'ase activity or incorporation of [3H]-thymidine, and increased PG-E2 production in MC3T3-E1 cells. CSA which was simultaneously incubated with these various cell growth factors, showed a similar effect to that of CSA alone. These results suggest that cytokines produced from immune cells, could affect osteoblasts besides that of calcium regulating hormones like parathyroid hormone and 1,25(OH)2D3, implying a probability for the participation of immunocompetent cells in the regulation of bone metabolism.     

A novel and selective beta-melanocyte-stimulating hormone-derived peptide agonist for melanocortin 4 receptor potently decreased food intake and body weight gain in diet-induced obese rats

alphaMSH has generally been accepted as the endogenous ligand for melanocortin 4 receptor (MC4R), which plays a major role in energy homeostasis. Targeting MC4R to develop antiobesity agents, many investigators have performed a structure-activity relationship (SAR) studies based on alphaMSH structure. In this report, we performed a SAR study using human betaMSH (5 - 22) (DEGPYRMEHFRWGSPPKD, peptide 1) as a lead sequence to develop potent and selective agonists for MC4R and MC3R. The SAR study was begun with a truncation of N terminus of betaMSH (5 - 22) together with acetylation of the N terminus and amidation of the C terminus of the peptide. Introduction of a cyclic disulfide constrain and replacement of L-Phe with D-Phe afforded a super potent agonist (peptide 5). Furthermore truncation at the C terminus generated a small and potent MC4R and MC3R agonist (Ac-YRcyclo[CEHdFRWC]amide, peptide 6), which exhibited no MC5R and greatly reduced MC1R activity. Molecular modeling of Ac-YRcyclo[CEHdFRWC]amide (peptide 6) revealed that Arg2 in the peptide formed a salt bridge with Glu4. Subcutaneous or intracerebroventricular administration of peptide 6 in rats showed potent in vivo efficacy as evidenced by its effects in reducing energy balance, increasing fat use, and decreasing weight gain in both acute and chronic rat metabolic studies. Furthermore, the antiobesity effect by peptide 6 was manifested only in wild-type but not MC4R-deficient mice, indicating that antiobesity effects of the peptide were attributed largely through MC4R but not MC3R agonist activity of the peptide.     

17β-雌二醇和1,25-二羟维生素D3对成骨细胞MC3T3-E1增殖和分化的影响

目的 探讨雌激素和维生素D对成骨细胞MC3T3-E1增殖和分化的协同调节作用及其机制.方法 小鼠成骨细胞系MC3T3-E1细胞用无酚红α-MEM完全培养基培养;用MTT法检测细胞增殖率;用实时荧光定量PCR法检测干预前后MC3T3-E1细胞中细胞周期相关基因[细胞周期素E( cyclin E)、增殖细胞核抗原(PCNA)和细胞周期素依赖性激酶抑制物(Cdkn2b)]和成骨细胞分化标志物[Ⅰ型胶原( COL Ⅰ)、碱性磷酸酶(ALP)和骨桥蛋白(OPN)]基因的表达.ALP活性染色用BCIP/NBT显色法.结果 单用雌激素17β-雌二醇(E2)可促进MC3T3-E1细胞的增殖,尤其在生理浓度时作用最强,单用维生素D活性产物1,25-二羟维生素D3[1,25-(OH) 2D3]对MC3T3-E1细胞的增殖无影响,1,25 - (OH)2 D3不影响E2对MC3T3-E1细胞的促增殖作用.E2上调MC3T3-E1细胞中cyclin E和PCNA的表达,同时下调Cdkn2b基因的表达,1,25-(OH)2D3单独应用不能影响上述基因表达的变化,也不影响E2对上述基因的调节作用.E2可促进MC3T3-E1细胞中分化标志物(COLⅠ、ALP和OPN)基因的表达,加用1,25-(OH)2D3后可增强此作用.结论 雌激素和维生素D作为两种重要的调节骨代谢的激素,在促进成骨细胞增殖方面可能无协同作用,而在促进其分化方面可能有协同作用.