替加色罗对内脏感觉过敏大鼠模型的抗伤害性感觉作用

目的　了解结直肠机械刺激对大鼠内脏感觉功能的影响以及替加色罗对大鼠内脏感觉功能的调节作用。方法　 8～ 2 1日龄大鼠每天行结直肠扩张 (CRD组 ,压力 6 0mmHg) ,对照组仅用导管在肛门周围轻微接触。 8～ 1 0周龄时用自制气囊扩张大鼠降结肠和直肠 ,观察动物的腹壁回撤反射(AWR)以测定内脏感觉。选取 8～ 1 0周龄的雄性大鼠分为CRD组、对照组和溶媒对照组 ,观察腹腔注射替加色罗前后的AWR评分。结果　扩张压力与AWR评分显著相关 (P <0 .0 1 ) ;CRD组在 4 0、6 0、80mmHg的压力扩张下 ,AWR评分明显高于对照组 (1 .96± 0 .1 6比 1 .36± 0 .1 6、2 .82± 0 .1 3比 2 .1 7± 0 .1 4、3.2 1± 0 .1 4比 2 .5 9± 0 .1 4 ,P <0 .0 1 ) ;在 4 0、6 0、80mmHg扩张压力下 ,CRD组的AWR评分在用替加色罗后较用药前明显降低 (1 .95± 0 .5 0比 1 .32± 0 .5 5、3.0 5± 0 .4 8比 2 .32± 0 .5 4、3.2 5± 0 .6 3比 2 .77± 0 .5 1 ,P <0 .0 5 ) ;对照组和溶媒对照组的AWR评分在用药前后差异无显著性。结论　新生大鼠给予结直肠机械刺激在成年后可导致慢性内脏感觉过敏 ;替加色罗通过提高对结直肠扩张的疼痛阈值 ,具有抗伤害性感觉作用     

替加色罗对应激大鼠回盲部黏膜5-羟色胺含量的影响

目的研究束缚应激导致的内脏高敏感性大鼠回盲部黏膜5-羟色胺(5-HT)含量的变化及替加色罗对应激大鼠回盲部黏膜5-HT含量的影响。方法雄性Wistar大鼠24只,分为对照组、应激组和替加色罗组,采用免疫组化方法观察3组大鼠回盲部黏膜5-HT的分布并作定量分析,应用免疫电镜观察应激组和替加色罗组大鼠回盲部肠上皮嗜铬细胞的5-HT含量。结果应激组大鼠回盲部组织5-HT阳性细胞的吸光度值显著低于对照组大鼠(0·326±0·035比0·362±0·042,P<0·001),替加色罗组大鼠为0·364±0·033,与应激组大鼠比较显著增高(P<0·001),在电镜下胶体金颗粒主要分布于肠嗜铬细胞的分泌颗粒,替加色罗组胶体金阳性的分泌颗粒明显多于应激组。结论应激大鼠肠黏膜5-HT阳性细胞释放5-HT的增加可能是其内脏高敏感性的发生机制之一,替加色罗改善内脏高敏感性的作用是部分通过调节胃肠道5-HT的含量达到的。     

替加色罗对结肠炎诱导的大鼠腰骶髓Fos、P物质和降钙素基因相关肽表达的影响

背景:临床研究发现,替加色罗可以明显改善肠易激综合征患者的腹部不适和腹痛,但其调节内脏感觉的机制目前尚不清楚。目的:观察替加色罗对结肠炎诱导的大鼠腰骶髓Fos、P物质(SP)和降钙素基因相关肽(CGRP)表达的影响,探讨替加色罗降低内脏敏感性的作用途径。方法:成年雄性Sprague-Dawley大鼠24只,以三硝基苯磺酸灌肠诱导结肠炎并随机分为实验组1:替加色罗灌胃,每天2mg/kg;实验组2:替加色罗灌胃,每天1mg/kg;对照组:生理盐水灌胃,2.0ml/d。连续灌胃7天后,采用免疫组化方法检测大鼠腰骶髓Fos、SP和CGRP的表达。结果:结肠炎可诱导对照组大鼠腰骶髓(L5～S1)背角深层Fos表达以及背角浅层SP和CGRP表达。实验组1大鼠腰骶髓背角Fos阳性神经元数(22.0±7.7)和SP密度(12.5%±1.4%)显著低于对照组(62.2±18.9和35.9%±8.9%,P<0.05),CGRP密度(1.2%±1.1%)与对照组(2.8%±2.4%)相比无显著差异。实验组2大鼠腰骶髓背角Fos、SP和CGRP的表达与对照组相比均无显著差异。结论:替加色罗可以明显减少结肠炎诱导的大鼠腰骶髓背角Fos和SP的表达,其降低内脏敏感性的作用可能与抑制脊髓背角SP的表达有关。     

替加色罗治疗内脏高敏感大鼠前后感觉阈值的变化

目的　观察 5 HT4受体部分激动剂替加色罗对内脏高敏感大鼠在直结肠扩张时感觉阈值的变化。方法　 2 4只内脏高敏感大鼠随机分为三组 ,分别给予替加色罗 4mg/kg、2mg/kg及生理盐水灌胃 ,每日 1次 ,共 8周 ,治疗前及治疗后 2、4、8及停药后 2周进行直结肠球囊扩张 ,并记录大鼠的初始、疼痛、最大耐受感觉时压力阈值。结果　治疗前各组的初始、疼痛、最大耐受感觉时压力阈值无明显差异 ,治疗后 4周治疗组 1、治疗组 2及对照组的初始感觉压力阈值分别为 10± 3 .5、9.0± 2 .2、5 .0± 4.9mmHg ,疼痛感觉压力阈值分别是 2 4.0± 5 .9、2 0 .0± 4.5、9.0± 5 .3mmHg ,最大耐受压力阈值分别是 3 6.4± 5 .7、3 8.0± 8.2、2 5 .2± 5 .9mmHg ,两治疗组与对照组比较 ,各压力阈值明显升高 ,有显著性差异 ,P <0 .0 5 ,而且这种作用可以持续存在直至停止治疗后 2周。两治疗组间无显著性差异。结论　替加色罗可以有效提高IBS内脏高敏感大鼠对直结肠扩张的感觉阈值 ,可改善IBS的腹痛或腹部不适症状。     

替加色罗对大鼠结直肠扩张所致自主神经张力变化的影响

背景:结直肠扩张可影响自主神经系统的活动,而心率变异性(HRV)可反映自主神经系统的功能状态。目的:探讨结直肠扩张对自主神经功能的影响,以及替加色罗对自主神经功能的调节作用。方法:18只成年雄性大鼠随机分为药物组(腹腔注射替加色罗)和溶媒对照组,清醒状态下记录心电信号,通过HRV频域分析比较两组大鼠结直肠扩张前后交感神经张力[P1/(P1 P2)]和迷走神经张力[P2/(P1 P2)]的变化。结果:在溶媒对照组,与基础状态相比,结直肠扩张能显著提高P1/(P1 P2)(0.326±0.141对0.403±0.142,P<0.05),降低P2/(P1 P2)(0.674±0.141对0.597±0.142,P<0.05);腹腔注射替加色罗后,扩张期的P1/(P1 P2)和P2/(P1 P2)与基础状态相比无显著变化(0.293±0.130对0.275±0.103, P>0.05;0.706±0.130对0.724±0.103,P>0.05)。结论:结直肠扩张可显著提高交感神经张力,降低迷走神经张力。替加色罗对结直肠扩张所致的自主神经张力变化有抑制作用。     

替加色罗对糖尿病大鼠胃排空功能及Ghrelin、P物质表达的影响

目的:研究替加色罗对糖尿病大鼠胃排空功能及胃组织Ghrelin、P物质表达的影响,探讨替加色罗对糖尿病胃轻瘫的治疗作用及其可能的机制.方法:50只清洁级♂Wistar大鼠随机分为正常对照组(NC组,n=10)、糖尿病组(DM组,n=10)、低剂量替加色罗治疗组(TEG-L组,n=10)、中剂量替加色罗治疗组(TEG-M组,n=10)和高剂量替加色罗治疗组(TEG-H组,n=10).ip链脲佐菌素(STZ)制备糖尿病大鼠模型,8 wk后分别以0.1,0.5和1 mg/kg的剂量给予TEG-L,M和H组大鼠ip替加色罗连续3 d,采用酚红灌胃法检测胃排空,免疫组化技术检测各组大鼠胃黏膜Ghrelin与胃窦组织SP的表达.结果:TEG各组大鼠Ghrelin(34.721±6.759,33.547±6.255,35.141±5.987)与SP的积分光密度(13.548±1.078,13.952±1.246,11.845±1.567)均低于NC组(Ghrelin:43.514±5.323,P<0.05,P<0.01,P<0.01;SP:16.383±2.275,均P<0.01)而高于DM组(Ghrelin:26.626±4.596,均P<0.05;SP:9.257±1.636,均P<0.01);Ghrelin积分光密度在TEG各组之间无显著性差异,而TEG-L,M组SP积分光密度均高于TEG-H组(均P<0.05).结论:替加色罗可通过促进胃组织Ghrelin与SP的表达释放来改善糖尿病大鼠延迟的胃排空.     

阻断Nav1.8表达对大鼠内脏高敏感性影响的研究

目的通过阻断Nav1．8钠通道的表达研究其对内脏高敏感性的影响。方法以新生大鼠直肠内气囊扩张法制成动物模型，连续3d，每天2次鞘内注射Nav1．8钠通道反义寡核苷酸以阻断Nav1．8的表达，并以行为学腹部收缩反射（AWR）评分和脊髓c-Fos的表达为指标观察大鼠内脏高敏感的改变情况。结果鞘内注射Nav1．8钠通道反义寡核苷酸使大鼠Nav1．8 mRNA的表达下降。行为学检测发现造模组大鼠AWR评分下降，脊髓c-Fos样免疫反应（c-FLI）阳性细胞总数减少，主要是1区和3区的细胞数减少，而注射错配寡核苷酸组无明显改变。对照组则不论注射错配寡核苷酸或反义寡核苷酸AWR评分和脊髓c—FLI阳性细胞数均无明显改变。结论鞘内注射反义寡核苷酸阻断Nav1．8的表达，可以降低造模大鼠内脏高敏感状态。     

焦虑大鼠内脏敏感性增高以及行直结肠扩张后血清皮质酮的变化及意义

目的内脏高敏感性是肠易激综合征( 1BS)症状最重要的病理生理机制之一,焦虑可能与内脏高敏的发生密切相关。本研究旨在探讨焦虑对大鼠直结肠敏感性的作用以及血清皮质酮与内脏高敏的关系。方法Wistar大鼠随机分为对照组和焦虑组两组,通过对大鼠行空瓶刺激2周建立以焦虑为主要表现的慢性情绪应激模型。造模期间,观察大鼠的攻击、探究和修饰三种行为,对其进行情绪性行为学分析。造模结束后,以腹部回缩反射(AWR)评分为指标观察大鼠对直结肠气囊扩张(CRD)的反应性,评估内脏敏感性。然后将两组各随机分为扩张组和非扩张组,对扩张组行CRD ,并取血清,对血清皮质酮定量测定。结果空瓶刺激期间,同对照组相比,焦虑组探究、攻击行为明显增多,修饰行为减少(P <0 0 1)。焦虑组在2 0mmHg、40mmHg、60mmHg和80mmHg的扩张压力下的AWR评分均显著高于对照组(P <0 0 1)。焦虑组与对照组相比血清皮质酮水平明显升高(P <0 0 1) ,但各组扩张后皮质酮水平较扩张前仅有轻微升高,无显著差异(P >0 0 5 )。结论焦虑对IBS内脏高敏起一定作用,其发挥作用的机制可能并非单一通过下丘脑_垂体_肾上腺皮质系统(HPA轴)来实现,推测还可能与脑内单胺类神经递质NE浓度的改变有关。     

大鼠肠易激综合征肠黏膜下神经丛可塑性的研究

目的探讨大鼠肠黏膜下神经丛内肠神经元及兴奋性神经递质在肠易激综合征(IBS)不同亚型发病中的意义及替加色罗干预的结果。方法成年雄性SD大鼠45只,均分为IBS伴腹泻组(IBS-D)、IBS伴便秘组(IBS-C)、替加色罗干预的IBS-D组、替加色罗干预的IBS-C组和空白对照组共5组。分别采用乙酸灌肠和冰水灌胃方法制成IBS-D和IBS-C大鼠模型,替加色罗干预的两组每日加用替加色罗2 mg/kg体质量灌胃7 d。用蛋白基因产物9.5(PGP9.5)的免疫组化方法及兴奋性神经递质乙酰胆碱的组化染色法检测各组大鼠肠黏膜下神经丛内肠神经元及兴奋性神经递质的变化。结果①肠黏膜下神经丛内肠神经元数目IBS-D模型组(13.19±0.93)和IBS-C组(13.17±1.93)显著低于对照组(18.36±1.71)(P值均<0.01);替加色罗干预的IBS-D组(15.48±1.56)高于IBS-D组,替加色罗干预的IBS-C组(14.82±1.61)高于IBS-C组(P值均<0.05)。②肠黏膜下神经丛内胆碱酯酶阳性的神经元数目IBS-C组(7.56±0.39)显著低于对照组(10.43±1.39)及IBS-D组(10.03±1.13)(P值均<0.01),IBS-D组与对照组差异无统计学意义(P>0.05)。替加色罗干预的IBS-C组(9.51±1.47)显著高于IBS-C组(P<0.01),与对照组差异无统计学意义(P>0.05)。结论肠黏膜下神经丛内肠神经元数量的减少可能是实验大鼠IBS-D模型和IBS-C模型发病的共同机制;IBS-C模型组大鼠胆碱酯酶阳性的神经元数目显著减少与其症状相关。     

替加色罗对便秘型肠易激综合征大鼠模型肠道功能和中枢c-fos表达的影响

目的研究替加色罗对便秘型肠易激综合征（C-IBS）大鼠模型排便、肠道敏感性和中枢神经c-fos表达的影响。方法应用冰水灌胃方法建立C-IBS大鼠模型20只，随机分为替加色罗药物组（A组）和对照组（B组）。A组给予室温20％替加色罗溶液（2mL／只，1次／日）灌胃7d；B组给予等量室温生理盐水灌胃7d。观察灌胃期间两组大鼠灌胃后3h内和3～24h间的大便粒数及含水量变化，停止灌胃后继续观察7d内大便粒数及含水量变化。第14d实验结束后所有大鼠给予直肠内球囊扩张，检测球囊扩张引起腹部收缩反射的最小容量阈值及球囊不同容量扩张时腹部收缩反射的次数，以评价替加色罗对肠道敏感性的影响。脊髓、下丘脑及前扣带回c-los表达应用免疫组织化学染色及计算机图像分析系统半定量分析。结果两组大鼠灌胃后3h内大便粒数及含水量无明显差异（P〉0．05）；A组灌胃后3～24h间的大便粒数及含水量均较B组明显增加（P〈0.05）。直肠内球囊扩张时，A组引起腹部收缩的最小容量阈值略低于B组，无明显统计学差异（P〉0．05）。直肠球囊扩张体积1．0mL时A组腹部收缩反射次数高于B组（P〈0．05）；体积1.5mL、2．0mL高容量扩张时两组无明显差异（P〉0．05）。A组腰骶段脊髓背角、下丘脑和前扣带回的C-fos阳性神经元细胞的面积及OD值均明显低于B组（P〈0．05）。结论替加色罗能改善便秘型肠易激综合征大鼠模型的便秘和肠道敏感性，并减少脊髓、下丘脑及前扣带回c-fos的表达。     

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.     

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.     

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.     

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.