一种结肠炎相关的结肠癌模型的复制

目的:建立一个成功率高、简单、易行、价廉、短期成功的结肠炎相关的结肠癌模型.方法:5周龄ICR♂小鼠320只,随机分为实验组(1-7)和阴性(8)对照组.实验1-3组分别ip10,15,20 mg/kg的1,2-二甲肼(DMH)1 wk后,再给予小鼠饮用含20 g/L的右旋葡聚糖苷钠(DSS)饮用水1 wk.实验4-6组的小鼠仅通过ip给予10,15,20 mg/kg的DMH.实验7组小鼠则只饮用含20 g/L DSS的饮用水,第8组小鼠不给予任何处理.每周记录小鼠体质量及进食量,在4,9,13 wk分别处死部分小鼠以观察小鼠的结肠炎癌变情况,并于20 wk处死剩余小鼠.结果:ip DMH(10,15,20 mg/kg)1 wk后,再饮用含20 g/L DSS的饮用水1 wk 4 wk可见40%小鼠便血.1 wk后,便血消失.至9 wk时,约有30%的小鼠再次出现便血体征.13 wk时,约10%的小鼠出现脱肛现象.20 wk时,40%左右的小鼠出现脱肛现象.在20 wk 100% ♂ ICR小鼠出现结肠腺癌,称取脾脏、胸腺以及结肠质量,结果发现,脾脏、结肠质量显著增加,胸腺质量明显减少,与对照组小鼠相比有显著性差异(脾脏质量:0.64±0.03,0.75±0.03,0.78±0.01 g vs 0.16±0.05 g,P＜0.01;结肠质量:0.93±0.06,0.96±0.02,0.01±0.06 g vs 0.31±0.06 g,P＜0.01;胸腺质量:0.027±0.001 gvs 0.045±0.004 g,P＜0.05;0.026±0.002 g vs0.045±0.004 g,P＜0.05;0.016±0.003 g vs0.045±0.004 g,P＜0.01).结论:致癌剂DMH和致炎剂DSS可诱导ICR小鼠结肠腺癌的形成,较好的模拟了结肠炎癌变过程,方法价廉、简便、易行.     

地龙提取液对结肠炎相关性结肠癌Wnt/β-catenin信号通路的影响

[目的]探讨地龙提取液对结肠炎相关性结肠癌疗效及其作用机制。[方法]小鼠随机分为空白组、模型组、地龙提取液(低、中、高剂量组)和美沙拉嗪组,并采用AOM/DSS法复制结肠炎相关性结肠癌癌前病变动物模型。治疗结束后分别测量各组小鼠胸腺、脾脏及结肠的质量,并光镜下观察结肠组织病理学改变,免疫印迹法检测结肠组织中Wnt/β-catenin信号通路中相关蛋白的表达。[结果]地龙提取液能够显著增加小鼠胸腺的质量和结肠长度(P0.05),减少脾脏和结肠质量(P0.05),降低AOM/DSS诱导小鼠的成瘤率(P0.05),改善CAC小鼠结肠组织的病理学形态;此外,地龙提取液能够显著减少CAC小鼠结肠组织中Wnt3a、phospho-GSK-3β、β-catenin、c-Myc、cyclin-D1蛋白表达(P0.05),增加APC、Axin1、GSK-3β、phospho-β-catenin、Bcl-2蛋白的表达(P0.05)。[结论]地龙提取液能够预防结肠炎后结肠癌的发生与发展,其作用机制是通过抑制Wnt/β-catenin信号通路的活化实现的。     

选择性环氧合酶-2抑制剂PC407对TNBS诱导的大鼠溃疡性结肠炎的治疗作用

目的:观察新型选择性环氧合酶-2抑制剂PC407对2,4,6-三硝基苯磺酸(2,4,6-trinitrobenzenesulfonic acid,TNBS)诱导的大鼠溃疡性结肠炎的疗效并探讨其机制.方法:应用TNBS/乙醇灌肠复制大鼠溃疡性结肠炎模型,实验设正常对照组、模型对照组、塞来昔布阳性对照组(18 mg/kg)和PC407治疗组(9,18 mg/kg),ig给药,每天1次,共6 d,观察稀便出现情况.实验第7天,麻醉大鼠,分离大鼠结肠、脾脏、胸腺,观察各组实验动物体质量变化及结肠组织病理学改变,选用稀便率、结肠指数、溃疡比、胸腺指数和脾脏指数作为衡量治疗效果的指标,采用免疫组织化学方法检测结肠黏膜环氧合酶-2(COX-2)和肿瘤坏死因子a(tumor necrosis factor-alpha,TNF-a)的变化.结果:与模型组相比,18 mg/kg PC407治疗可明显阻止结肠炎大鼠的体质量下降(258.9 gvs 223.6 g,P＜0.05),降低稀便发生率(30% vs80%.P＜0.01),改善大鼠结肠组织损伤及病理学改变,包括降低结肠指数(5.03±1.26 mg/gvs 7.60±2.07 mg/g.P＜0.01)及溃疡比(24.69%±2.83% vs 36.13%±9.64%,P＜0.01);同时,PC407治疗可对抗结肠炎症引起的胸腺萎缩(1.964-0.48 mg/g vs 1.08±0.32 mg/g,P＜0.01)和脾脏肿大(2.85±0.33 mg/g vs 3.87±0.96mg/g,P＜0.01),显著降低结肠炎大鼠结肠黏膜COX-2和TNF-a的阳性表达率(30.6%±7.0%vs 67.4%±1.2%,19.5%±3.0% vs 52%±4.7%,P＜0.01).9 mg/kg PC407也可以改善以上指数,只是作用没有18 mg/kg明显.结论:PC407对TNBS/醇诱导的大鼠溃疡性结肠炎治疗作用良好,其机制可能通过下调COx-2及TNF-a的表达,从而缓解结肠炎症.     

金丝桃苷对葡聚糖硫酸钠诱导小鼠结肠炎Nrf2/ARE信号通路的作用

目的探讨金丝桃苷(Hyperoside,Hyp)对葡聚糖硫酸钠(DSS)诱导的结肠炎小鼠肠黏膜Nrf2/ARE信号通路的影响。方法用DSS诱导结肠炎小鼠模型,实验设对照组、模型组、DSS+Hyp低剂量组(DSS+Hyp 80 mg/kg)、DSS+Hyp高剂量组(DSS+Hyp 120 mg/kg),每组6只;质量浓度为30 g/L的DSS自由饮水7 d制成结肠炎小鼠模型同时于造模前7 d开始予Hyp灌胃治疗,连续14 d。观察小鼠结肠炎疾病活动指数(DAI)和结肠组织病理变化,Western blotting法检测小鼠结肠组织细胞核核转录因子(Nuclearfactor-erythroid 2-rdated factor-2,Nrf-2)表达水平,RT-PCR检测小鼠结肠组织Nrf-2、超氧化物歧化酶(SOD)表达水平。结果与模型组比较,对照组、Hyp+DSS诱导组的结肠炎小鼠DAI降低(P0.01)。Hyp能够明显改善结肠病理损伤。与模型组比较,Hyp明显提高Nrf2的表达(P0.05)。对照组、Hyp+DSS诱导组小鼠结肠SOD mRNA的相对表达量与模型组比较显著升高(P0.05)。结论 Hyp对DSS诱导的结肠炎小鼠模型有保护作用,其作用机制可能与Nrf2/ARE信号通路有关。     

虎杖苷对葡聚糖硫酸钠诱导小鼠溃疡性结肠炎的作用及其对Hedgehog通路影响

目的探讨虎杖苷对葡聚糖硫酸钠(dextran sodium sulfate,DSS)诱导的溃疡性结肠炎(ulcerative colitis,UC)的作用及其对结肠组织中Hedgehog信号通路的影响。方法实验设置空白组、模型组、药物干预组(虎杖苷15 mg/kg、30 mg/kg、45 mg/kg) 5组,每组6只;小鼠自由饮用质量浓度为30 g/L的DSS共7 d组建UC模型,空白组正常饮水的同时予质量浓度为9 g/L的生理盐水,腹腔注射7 d;模型组造模同时予质量浓度为9 g/L的生理盐水,腹腔注射7 d;药物干预组造模同时分别予虎杖苷15 mg/kg、30 mg/kg、45 mg/kg,腹腔注射7 d。观察小鼠结肠炎相关的疾病活动指数(disease activity index,DAI)和结肠组织病理评分,RT-PCR检测小鼠结肠组织中的炎症因子IL-6、IL-17、TNF-α、IL-1β、IL-23,同时检测小鼠结肠组织中Hedgehog信号通路的转录因子Gli1 mRNA和蛋白质的表达水平。结果与模型组相比,空白组和药物干预组中DAI降低(P 0. 05);虎杖苷药物干预后结肠病理损伤明显改善;与模型组相比,药物干预组(中、高剂量)中的炎症因子IL-6、IL-17、TNF-α、IL-1β、IL-23 mRNA水平明显降低(P 0. 05),同时药物干预组中Gli1的蛋白水平明显升高,差异均有统计学意义(P 0. 05)。结论虎杖苷对DSS诱导的小鼠急性结肠炎模型具有明显的抗炎作用,其抗炎机制可能与上调Hedgehog信号通路有关。     

5-氨基水杨酸在结肠炎癌变模型小鼠中的初步研究

目的 应用5-氨基水杨酸(5-ASA) 干预偶氮氧甲烷(AOM)联合葡聚糖硫酸钠(DSS)诱导小鼠结肠炎癌变的模型,观察结肠过氧化物酶体增殖物激活受体γ(PPAR-γ)、β-catenin的表达水平.方法 36只BALB/c小鼠均分为对照组、模型组和干预组.模型组和干预组均于实验前1d予AOM 10 mg/kg腹腔注射,继以自由饮用4％DSS 1周,再普通饮水2周,饮用DSS及普通饮水共重复3个循环.干预组于实验前3d予5-ASA 150 mg/kg饲喂至实验结束.对照组于实验前1d予0.9％ NaCl溶液腹腔注射,普通饮水9周.监测小鼠疾病症状,评价实验1周末及9周末结肠组织学病理变化,检测9周末结肠PPAR-γ、β-catenin蛋白及结肠PPAR-γ mRNA表达水平.统计学处理采用t检验.结果 干预组饮用DSS 1周后结肠炎疾病活动指数(DAD为1.81+0.59,9周末平均肿瘤数为4.11±1.05,均较模型组(DAI为2.47±0.53,肿瘤数为9.71±2.29)明显降低(t=2.88和6.55,P均＜0.01).干预组结肠PPAR-γ蛋白(2.11±1.36)及mRNA(1.45±0.10)平均表达水平均较模型组(分别为0.43±0.53,0.57±0.08)明显增加(t=3.07和18.99,P均＜0.01).各组间β-catenin表达差异无统计学意义(P＞0.05).结论 5-ASA有效减轻AOM和DSS诱导的小鼠结肠炎癌变模型的炎性反应及肿瘤负荷,同时促进PPAR-γ在结肠中的表达,而对结肠中β-catenin的表达无明显影响.     

小鼠实验性结肠炎中骨桥蛋白的变化

目的 观察骨桥蛋白(osteopontin,OPN)在右旋葡聚糖硫酸钠(dextran sodium sulfate,DSS)诱导的小鼠结肠炎中的变化,探讨OPN在炎症性肠病(inflammatory bowel disease,IBD)发病中的作用.方法 32只雄性BALB/C小鼠随机分为对照组(予蒸馏水饮用23 d)、模型组(5%DSS饮用9 d后2.5%DSS维持2周)、柳氮磺胺吡啶(SASP)治疗组(在模型组基础上从第10天起予SASP 600 mg/kg灌胃2周)和英夫利昔治疗组(在模型组基础上在第10天予尾静脉注射英夫利昔100 mg/kg 1次).酶联免疫法检测小鼠血浆OPN浓度,逆转录聚合酶链反应和Western印迹法检测小鼠结肠组织中OPN的mRNA水平和蛋白质水平表达,免疫组化法检测OPN在结肠组织中的定位表达.结果 各组小鼠的血浆OPN浓度分别为(5.26±1.93)、(10.21±2.37)、(4.58±1.83)和(4.82±1.83)ng/ml;结肠组织中OPN mRNA表达量分别为(0.36±0.16)、(0.71±0.17)、(0.32±0.07)和(0.42±0.22);结肠组织中OPN的蛋白表达量分别为(0.44±0.10)、(0.85±0.04)、(0.61±0.11)和(0.58±0.17);结肠黏膜固有层OPN阳性细胞数分别为(46.6±10.9)、(155.5±43.8)、(73.1±6.8)和(70.6±8.3).与对照组相比,模型组血浆和结肠组织中OPN的表达明显增高(P均<0.05),SASP治疗组和英夫利昔治疗组OPN的表达均较SASP治疗组下降(P均<0.05),SASP治疗组和英夫利昔治疗组OPN的表达差异无统计学意义.结论 OPN在DSS诱导的小鼠结肠炎中表达增加,经药物治疗后表达降低.OPN促进了DSS诱导的小鼠结肠炎的发生.     

银杏叶提取物对大鼠结肠炎的治疗效果及机理研究

目的观察银杏叶提取物对葡聚糖硫酸钠(DSS)诱导的大鼠结肠炎的影响,探讨银杏叶提取物对结肠炎的治疗作用和可能机制。方法将大鼠随机分为3组:正常对照组、DSS模型组和治疗组(DSS 银杏叶提取物)。建立大鼠急性DSS结肠炎模型。治疗组在饮DSS水的同时给予银杏叶提取物灌肠至实验结束。每天观察各组大鼠疾病活动指数(DAI),并在实验结束后ELISA法检测各组大鼠血清及炎症肠段细胞因子TNFα、IL-6表达,TUNEL法检测结肠细胞的凋亡,RT-PCR法检测炎症肠段fas、fasL、bcl和bax的表达。结果自实验第4天开始,治疗组DAI明显低于DSS组。实验结束后,治疗组血清和炎症肠段中TNFα浓度分别为91.53±47.59pg/ml和182.06±115.86pg/ml,较DSS组明显降低(565.32±200.01pg/ml,735.11±205.45mg/ml,P<0.01)。治疗组血清和炎症肠段中IL-6的浓度分别为452.34±159.65pg/ml、559.38±100.77pg/ml,也较DSS组显著降低(939.29±163.93pg/ml、943.41±145.80mg/ml,P<0.01)。治疗组结肠细胞凋亡指数明显低于DSS组(P<0.05),其fas、fasL表达分别为0.049±0.072、0.031±0.085,与DSS组比较显著性降低(0.62±0.73、0.43±0.51,P<0.05);而bcl和bax表达在两组间比较无显著性差异(0.015±0.020vs0.013±0.014,0.23±0.31vs4.02±0.43,P>0.05)。结论银杏叶提取物灌肠能抑制大鼠结肠炎的炎性细胞因子的分泌,通过fas/fasL途径抑制结肠细胞的凋亡,减轻肠道炎症反应,减少肠黏膜的损伤。     

双歧杆菌对小鼠急性实验性结肠炎作用的研究

目的 研究双歧杆菌在葡聚糖硫酸钠(DSS)诱导的急性溃疡性结肠炎小鼠模型中的作用.方法 将80只BALB/C小鼠均分为8组,每组10只.除正常对照组、单纯0501菌株组、单纯c122菌株组外,其他5组动物均给予5%DSS造模7 d.在造模开始前2 d,阴性对照组用0.9%氯化钠液灌肠、阳性对照组用柳氮磺胺吡啶(SASP)20 mg/ml灌肠、DSS+0501菌株组用1×109 CFU/ml 0501菌液灌肠、DSS+c122菌株组用1×109 CFU/ml c122液菌灌肠.9 d后处死动物取结肠标本,行H-E染色,观察镜下结肠病理变化,并用免疫组化染色、RT-PCR技术分析结肠黏膜中白细胞介素(IL)-10 mRNA及蛋白表达.结果 DSS造模过程中给予双歧杆菌灌肠小鼠(0501菌株组和c122菌株组)的结肠炎性反应程度较模型组加重,结肠黏膜IL-10表达减少.而单纯给予双歧杆菌灌肠小鼠(单纯0501菌株组和单纯c122菌株组)未见结肠炎表现.结论 双歧杆菌的某些菌株在结肠黏膜屏障功能受损情况下,可加重溃疡性结肠炎小鼠的结肠黏膜损伤.     

壳聚糖对葡聚糖硫酸钠诱导急性结肠炎小鼠的疗效研究

[目的]本研究旨在探讨壳聚糖对葡聚糖硫酸钠(Dextran sulfate sodium,DSS)诱导急性结肠炎小鼠的疗效和可能机制。[方法]选取Balb/c小鼠40只,随机分为正常对照组、DSS组、美沙拉嗪组及壳聚糖组,除正常组自由饮食外,其余组连续饮用3%DSS溶液7d诱发急性结肠炎,建立溃疡性结肠炎模型,同时分别给予相应药物灌胃治疗,治疗期间每天观察小鼠的体重、粪便性状和血便情况,造模结束后检测结肠组织中性细胞髓过氧化物酶活力(myeloperoxidase,MPO)。[结果]DSS成功诱发急性结肠炎,小鼠有明显腹泻,粘液脓血便,体重减轻等。壳聚糖能有效改善DSS诱导的溃疡性结肠炎症状,降低结肠MPO活性(6.108±1.893U/g:3.502±0.529U/g,P0.01);增加结肠长度,且HE染色的炎症程度和疾病活动指数均有明显改善。[结论]壳聚糖能有效治疗DSS诱发的急性结肠炎,主要通过诱导特异性免疫应答,降低炎症反应,增强机体免疫反应。未来有望成为治疗溃疡性结肠炎的潜在药物。     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

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.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

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.