肠易激综合征大鼠内脏敏感性异常与结肠及中枢神经系统5-HT和c-fos表达的关系

目的研究便秘型肠易激综合征（C-IBS）大鼠模型对直肠球囊扩张的内脏敏感性改变和肠神经系统及中枢神经系统5-羟色胺（5-HT）、c-fos的分布和异常表达。方法C-IBS大鼠模型组应用冰水灌胃方法建立（A组,n=10）和正常对照大鼠（B组,n=10）。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1.0 mL扩张容量时腹部收缩反射（AWR）的次数。结肠、回盲部肌间神经丛及下丘脑、前扣带回5-HT和c-fos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进行分析。结果直肠内球囊扩张时,A组引起腹部收缩的最小容量阈值略高于B组,无明显统计学差异（P〉0.05）,直肠球囊扩张体积1.0 mL时A组3 min AWR低于B组（10.3±3.3vs18.3±5.5,P〈0.05）。A组结肠、回盲部5-HT、c-fos阳性肌间神经丛的数目及OD值均明显高于B组（P〈0.05）;A组下丘脑及前扣带回5-HT、c-fos阳性神经组织面积及OD值也明显高于B组。结论C-IBS大鼠模型存在对直肠球囊扩张的内脏敏感性异常,肠神经系统及中枢神经系统5-HT、c-fos的异常表达可能参与C-IBS大鼠内脏敏感性异常的调节。     

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。     

内脏高敏感大鼠结肠5-羟色胺转运体蛋白的表达

目的:探讨5-羟色胺转运体蛋白(SERT)在内脏高敏感性中的作用,为功能性胃肠病的发病机制研究提供理论基础.方法:采用乳鼠醋酸灌肠建立大鼠慢性内脏高敏感动物模型,同时设立对照组.待乳鼠成年后应用直肠内球囊扩张评估腹壁撤离反射(AWR)的方法,评估其内脏敏感性;检测髓过氧化物酶(MPO)评价其肠道黏膜炎症程度;用RT-PCR方法评价大鼠结肠SERT的mRNA水平,免疫组织化学方法评价大鼠结肠SERT的表达:用ELISA方法检测血浆和结肠组织5-HT水平.结果:乳鼠醋酸灌肠建立的大鼠慢性内脏高敏感模型组与对照组相比HE染色显示结肠黏膜未见明显急、慢性炎症改变;两组大鼠结肠组织MPO水平没有显著性差异;在不同容量下的AWR评分慢性内脏高敏感模型组显著高于对照组(P<0.01).血浆5-HT水平慢性内脏高敏感模型组明显高于对照组(95.75±15.99vs 72.17±8.01,P<0.01),而两组结肠组织5-HT含量没有明显差异.免疫组织化学研究显示内脏高敏感模型组结肠上皮SERT表达水平显著低于对照组(0.187±0.010 vs 0.191±0.011,P<0.011,而其结肠SERT mRNA水平显著高于对照组(16.02±3.7 vs 10.05±2.12,P<0.01).结论:内脏高敏感大鼠外周5-HT水平的增高主要来源于其灭活的减少而非合成的增加,与SERT的关系密切.结肠SERT可能具有不同的亚型和功能.     

金荞麦提取物对IBS大鼠脊髓镇痛的干预机制

目的:观察金荞麦(Fagopyrumcymosum,Fag)提取物对肠易激综合征(irritablebowelsyndrome,IBS)样结肠刺激(colonirritation,CI)模型内脏高敏感性的改善作用以及对动物脊髓背角内5-HT及其受体的影响.方法:采用结肠刺激新生期乳大鼠来制作IBS样CI模型.CI大鼠成年后给予口服Fag2wk,并用腹壁撤退反射(AWR)评分来评价给药后CI大鼠内脏高敏感性的变化,取大鼠脊髓用免疫组织化学法观察5-HT免疫染色,用蛋白印迹法检测5-HT1A受体(5-HT1AR)、5-HT3A受体(5-HT3AR)表达.结果:和对照组比,CI组大鼠AWR评分明显增高(20mmHg:0.625±0.518vs1.333±0.778;30mmHg:0.750±0.463vs1.667±0.888;40mmHg:1.125±0.641vs2.000±0.739;50mmHg:1.500±0.926vs2.583±0.793;60mmHg:2.125±0.991vs3.083±0.669;均P<0.05);且脊髓内5-HT染色度增加(11.250±4.833vs21.125±7.827,P<0.01),5-HT3A受体表达升高(179.038±29.786,P<0.01),5-HT1A受体则表达降低(64.523±16.873,P<0.01);高剂量Fag可降低CI大鼠AWR评分(20mmHg:0.250±0.002;30mmHg:0.875±0.044;40mmHg:1.250±0.036;50mmHg:1.875±0.050;60mmHg:2.625±0.037;均P<0.05),并下调脊髓内5-HT(13.375±5.579,P<0.05)和5-HT3AR的表达(114.200±20.983,P<0.05),上调5-HT1AR的表达(93.008±13.523,P<0.05);低剂量Fag则对CI大鼠的影响不明显.结论:Fag对IBS样CI大鼠有镇痛作用,并通过调节其脊髓内5-HT及其受体来改善痛觉过敏.     

5-羟色胺4受体在调节应激大鼠内脏敏感性中的作用

目的研究束缚应激大鼠内脏敏感性及血浆5-羟色胺(5-HT)水平的改变,探讨5-HT4受体激动剂和拮抗剂对束缚应激大鼠内脏高敏感性的影响及对血浆5-HT水平的调节作用.方法雄性Wistar大鼠32只,分为对照组、应激组、5-HT4受体激动剂(1 mg/kg替加色罗,腹腔注射)组和5-HT4受体拮抗剂(3 mg/kg GRI13808,腹腔注射)组.以直肠内球囊扩张(0.4～1.2 ml)时腹壁收缩情况代表其内脏敏感性,分别观察各组大鼠腹壁收缩情况;荧光法测定各组大鼠血浆5-HT水平.结果束缚应激2 h后,应激组大鼠在各个容量直肠扩张时的腹壁收缩次数均较对照组显著增多(0.4 ml10.00±3.74比6.57±1.40;0.8 ml16.75±2.92比11.86±3.44;1.2 ml19.50±4.24比14.86±3.19;P<0.05);应激组大鼠血浆5-HT水平的增幅较对照组显著增高(154.60±19.43比97.75±17.95,P<0.001).在0.4～1.2 ml不同容量的直肠扩张时,5-HT4受体激动剂组的腹壁收缩次数依次为5.86±2.34、10.57±3.26、12.14±2.91;5-HT4受体拮抗剂组依次为3.80±1.48、11.40±3.29、12.40±2.07,均较应激组显著减少(P<0.05,P<0.01).两者均明显降低了应激组大鼠血浆5-HT水平的增加(113.74±13.18比154.60±19.43,P<0.01;47.00±17.17比154.60±19.43,P<0.001).结论应激引起的内脏高敏感性与外周5-HT水平相关;5-HT4受体激动剂及拮抗剂可部分通过影响外周5-HT的释放而改善内脏高敏感性.     

食管扩张刺激后兔食管内脏感觉改变及其中枢机制的实验研究

目的 探讨食管扩张刺激后兔食管内脏感觉改变及P物质(SP)、降钙素基因相关肽(CGRP)、5-羟色胺(5-HT)、Fos蛋白在中枢神经系统的作用.方法 新西兰白兔20只分为三组:食管扩张组(A组,n=8)和对照组(B组,n=6),分别给予0.9cm食管球囊扩张及假手术刺激,每次持续30 s,每日2次,共14 d,以及空白对照组(C组,n=6).采用动物行为学评分评价食管内脏感觉改变,免疫组化法观察幼兔食管下段黏膜、脊髓和脑组织中神经递质CGRP、SP、5-HT及Fos蛋白的表达.结果 动物食管机械扩张后,在行为学评分为1、2、3分时,A组球囊直径较B、C组明显减小(P＜0.05);A组食管、脊髓和延髓孤束核(NTS)的SP表达明显高于B、C组(P＜0.05),而B、C组间差异无统计学意义(P＞0.05);A组食管黏膜、脊髓、NTS、中脑导水管周围灰质(PAG)、丘脑的CGRP、Fos阳性细胞数较B、C组明显增多(P＜0.05);在食管和脊髓,A组5-HT的表达较B、C组显著升高(食管:27.67±3.27比11.00±1.79和11.17±1.33;脊髓24.00±5.22比11.33±2.94和11.83±2.48,P＜0.01),而在PAG,B组(17.67±2.07)和C组(16.83±2.32)5-HT的表达较A组(13.17±2.04)增多(P＜0.05).在脊髓,CGRP与Fos、SP与Fos、CGRP与SP有明显的相关性(相关系数分别为0.813、0.779、0.772,P值分别为0.025、0.034、0.036).结论 持续的食管扩张可引起食管内脏敏感性增高,食管的机械扩张刺激通过脊髓、NTS、PAG、丘脑传导,且SP、CGRP、5-HT等在食管内脏感觉发生中发挥着重要作用.     

逍遥散对腹腔注射卵清清蛋白致肠易激综合征大鼠内脏敏感性的作用

[目的]研究腹腔注射鸡卵清清蛋白(Alb)致肠易激综合征(IBS)大鼠内脏敏感性的变化及逍遥散的调节作用。[方法]采用腹腔注射鸡卵清Alb法建立IBS大鼠模型。实验动物随机分为正常组,模型组,阳性对照(匹维溴胺)组,逍遥散高、中、低剂量组,观察各组大鼠引起腹部收缩反射的最小容量阈值及不同扩张容量下腹壁肌电活动的变化,研究逍遥散的干预作用。[结果]腹腔注射鸡卵清Alb致IBS大鼠内脏敏感性明显增高(P<0.01)。而逍遥散能降低结、直肠扩张引起IBS大鼠腹部收缩反射的最小容量阈值,降低IBS大鼠不同扩张容量下的腹壁肌电活动(P<0.05,<0.01),且有一定的量-效关系。[结论]腹腔注射鸡卵清Alb致IBS大鼠内脏敏感性增高,逍遥散可降低IBS大鼠的内脏高敏感性。     

迷走传入神经功能异常在内脏高敏感形成中的作用

目的:初步探讨迷走传入神经在醋酸诱导的结肠敏感鼠模型内脏高敏感形成中的作用.方法:采用乳大鼠于出生第10天给予0.5%醋酸灌肠,建立慢性内脏高敏感动物模型,观察直肠内球囊扩张(colorectal distension,CRD)下腹壁撤离反射(withdrawal reflex,AWR)及腹外斜肌放电活动(electromyography,EMG)的变化,评估内脏敏感性.采用电生理学方法记录大鼠颈部迷走传入神经自发放电,观察在CRD下模型组与对照组大鼠迷走神经放电活动.免疫组织化学法观察大鼠孤束核及结肠中c-fos分布及表达情况.结果:与对照组相比,模型组AWR评分及EMG幅值显著增高(P<0.05),HE染色及MPO水平显示两组大鼠结肠均无明显炎症表现,结果提示内脏高敏感模型鼠建立;给予直肠内球囊扩张后模型组迷走神经放电活动明显高于对照组(P<0.05);与对照组相比,模型组大鼠孤束核及结肠肌间神经丛中c-fos表达明显增加(孤束核15.00%±1.85%vs47.30%±2.79%,近端结肠1.00%±0.12%%vs1.90%±0.17%,中端结肠1.10%±0.17%vs1.90%±0.18%,远端结肠1.10%±0.12%vs2.10%±0.17%,均P<0.01).结论:乳鼠醋酸灌肠诱导形成的内脏高敏模型大鼠迷走神经活化存在异常.     

从肠肌间神经丛抑制性神经递质的改变探讨IBS不同亚型的发病机制

目的:检测腹泻型IBS(D-IBS)和便秘型IBS(C-IBS)动物模型肠肌间神经丛的抑制性神经递质一氧化氮(NO)的差异,来探讨肠肌间神经丛神经递质的改变对IBS亚型的影响．方法:采用乙酸灌肠加束缚应激的方法造成D-IBS动物模型,同时设立灌肠对照和空白对照．采用冰水每日灌胃共14 d的方法造成C-IBS动物模型,同时设立灌胃对照和空白对照．检测各组大鼠粪便性状、内脏敏感性及肠肌间神经丛抑制性神经递质No的含量．结果:在高容量球囊扩张时,D-IBS组大鼠的腹肌收缩次数比C-IBS组及灌肠、空白对照组均明显增多(1．2 mL:7．22±2．01 vs 2．77±0．78,2．89±1．17,3．59±1．08; 1．6 mL:8．11±1．94 vs 2．89±1．67,2．44±1．42, 2．89±1．22,P<0．05)．在低容量球囊扩张时,C-IBS组大鼠的腹肌收缩次数比对照组及D-IBS组明显减少(0．4 mL:0．44±0．22 vs 2．44±0．67;0．8 mL:1．56±0．74 vs 6．31±1．74,P<0．05)．C-IBS组和灌胃对照组的粪粒数、粪便湿重及粪便含水量均小于空白对照组(2．00±0．66, 2.33±0．50 vs 3．67±1．00;0．80±0．32,1．69±0．49 vs 2．14±0．27;39．24±3．11,40．67±2．84 vs 48．38±2．79, P<0．05);D-IBS组粪便湿重和粪便含水量均高于灌肠和空白对照组(2.31±0．72 vs 1．52±0．58,1．57±0．56, P<0．05;65．31±3．31 vs 53．41±2．73,55．78±3．99． P<0．05)．C-IBS组首次排黑便时间比灌胃和空白对照组明显延长(277．89±25．08 vs 205．44±15．74, 189．22±18．45,P<0．05)．结肠组织学分析显示各组大鼠均无明显结肠炎性表现．C-IBS组NO阳性的神经元细胞数显著多于D-IBS组和对照组(303．50±14．43 vs 200．89±16．67,185．78±16．66,P<0．01),而D-IBS组和对照组NO阳性的神经元细胞数无显著差异(P>0．05)．结论:抑制性神经递质NO的数量的增加与IBS不同亚型、内脏敏感性及动力异常相关,提示NO的改变与 IBS不同亚型发病机制有一定关系．     

大鼠肠道高敏性模型的建立及其内脏敏感性评估

目的　内脏高敏感性是肠易激综合征 (IBS)的重要病理生理特征之一 ,该文旨在建立内脏高敏性动物模型 ,并用两种方法验证该模型的有效性。方法　取出生后 8～ 2 1d的大鼠 ,每天给予直肠内醋酸刺激 ,分别在出生后 6、8及 10周 ,对这些成年后的大鼠进行直肠扩张 ,评估其腹部收缩反射(AWR)阈值 ;并在出生 12周后测定大鼠腹壁肌电活动 ,验证敏感性有无异常改变。结果　与新生期生理盐水刺激组 (NS组 )和成年醋酸刺激组 (AA组 )相比 ,直肠扩张时 ,新生期醋酸刺激组大鼠 (NA组 )腹部抬高和背部拱起的容量阈值显著降低 (P值均 <0 .0 1) ;0 .5、0 .8、1.2ml扩张容量下腹壁肌电活动明显增强 (P分别 <0 .0 1,<0 .0 5和 0 .0 5 )。结论　新生期肠道内的慢性刺激 ,可以在成年后引起慢性内脏敏感性增高 ,而肠黏膜未见异常病理改变 ,符合IBS的基本特征。     

Glucose and insulin concentration in amniotic fluid and in maternal blood in early and in late pregnancy

Glucose concentration in the amniotic fluid decreases towards the end of gestation, whereas the insulin concentration increases. The ratio between fetal (amniotic fluid) glucose to maternal glucose is reduced by about 50% at the end of pregnancy, whereas the ratio of C peptide is increased four times. The higher glucose concentration in amniotic fluid in early pregnancy could be explained by a lower fetal metabolic rate in the early stage of development and a low insulin activity of the fetus.     

Osteoporosis in celiac disease and in endocrine and reproductive disorders

As the increase in lifespan brings to light diseases that were previously not clinically detectable, osteoporosis has become an issue of worldwide significance. The disease is marked by a loss of bone mass; the bones become less dense, fragile and more prone to fracturing. Because it is regulated by endocrine and environmental factors, osteoporosis presents a multifactorial etiopathogenesis, with the genetic component accounting for 70% of an individual variation in bone mass density （BMD）, the principal determinant, with age, of fracture risk. Pathological conditions such as celiac disease （CD） exacerbate the process of bone loss, so that the occurrence of osteoporosis in celiac subjects is of particular note： indeed, the screening of osteoporosis patients for this disease is advisable, since it may be the only sign of undiagnosed CD. An increase in interleukin IL-1β, of the IL-1 system, in the relatives of celiac patients confirms the genetic predisposition to osteoporosis and its presence is evidence of an association between the two conditions. The direct effect on the bones of CD is secondary to poor absorption of calcium and vitamin D. In women osteoporosis is indirectly associated with early menopause and amenorrhea, and it may follow prolonged breast-feeding and frequent pregnancies, while in men it is associated with hypogonadism and GH deficit. These endocrine and non-endocrine factors exert their effects on bones by modulating the RANK/RANK-L/OPG system. An appropriate lifestyle from adolescence onwards, together with early diagnosis of and treatment for CD and primaryand secondary endocrine pathologies are important for the prevention of damage to the bones.     

Anti-malarial efficacy of pyronaridine and artesunate in combination in vitro and in vivo

Pyronaridine is a Mannich base anti-malarial with demonstrated efficacy against drug resistant Plasmodium falciparum, P. vivax, P. ovale and P. malariae. However, resistance to pyronaridine can develop quickly when it is used alone but can be considerably delayed when it is administered with artesunate in rodent malaria models. The aim of this study was to evaluate the efficacy of pyronaridine in combination with artesunate against P. falciparum in vitro and in rodent malaria models in vivo to support its clinical application. Pyronaridine showed consistently high levels of in vitro activity against a panel of six P. falciparum drug-sensitive and resistant strains (Geometric Mean IC50=2.24 nM, 95% CI=1.20-3.27). In vitro interactions between pyronaridine and artesunate showed a slight antagonistic trend, but in vivo compared to pyronaridine and artesunate administered alone, the 3:1 ratio of the combination, reduced the ED90 of artesunate by approximately 15.6-fold in a pyronaridine-resistant P. berghei line and by approximately 200-fold in an artesunate-resistant line of P. berghei. Complete cure rates were achieved with doses of the combination above or equal to 8 mg/kg per day against P. chabaudi AS. These results indicate that the combination had an enhanced effect over monotherapy and lower daily doses of artesunate could be used to obtain a curative effect. The data suggest that the combination of pyronaridine and artesunate should have potential in areas of multi-drug resistant malaria.     

Differentiation pathways in carcinogenesis and in chemo- and radioresistance

Cancer stem cells (CSCs) share many features with embryonic stem cells (ESCs) such as the ability for self-renewal and differentiation. Signaling pathways that are involved in these processes are also involved in chemo- and radioresistance (e.g. Wnt, Notch and Hedgehog pathways). This review is focused on the influence of three important differentiation pathways on carcinogenesis and on chemo- and radioresistance in ESCs and CSCs.     

Telemedicine and Advances in Urban and Rural Healthcare Delivery in Africa

Telecardiology holds great promise for Africa, from tele-echocardiography and tele-ECG s, to home monitoring and text messaging for medication adherence monitoring. The burden of disease is great and there is an extreme shortage of health professionals. Telemedicine can provide access to scarce specialist care, improve the quality of care in rural areas and reduce the need for rural patients to travel to seek medical attention. International cross border service can alleviate the shortage of doctors. But telecardiology, and telemedicine uptake in general, has been poor in Africa. Legal and ethical issues around local and cross border telemedicine have not been resolved. The literature was reviewed and obstacles to telemedicine in Africa and current telemedicine activities in Africa, are described. There are few sustained telemedicine services in Africa with the exception of tele-education. There is an expectation that mobile phones will facilitate a range of telemedicine activities in Africa. Africa needs telemedicine.