西咪替丁抗疟作用的研究Ⅱ.西咪替丁对鼠疟的影响

西咪替丁（ＣＭＤ）４ｄ抑制法抗鼠疟作用结果显示：在剂量为５０ｍｇ／ｋｇ·ｄ、１００ｍｇ／ｋｇ·ｄ和２００ｍｇ／ｋｇ·ｄ时，该药对伯氏疟原虫氯喹敏感株、抗性株及约氏疟原虫氯喹敏感株感染小鼠的红内期疟原虫，均有明显的抑制作用，３组平均抑制率分别为６４．９５％、７７．９７％和５８．１６％。ＣＭＤ对伯氏疟原虫氯喹抗性株的抑制作用显著高于伯氏疟原虫氯喹敏感株（Ｐ＜０．０５）和约氏疟原虫氯喹敏感株（Ｐ＜０．０１）。     

伯氏疟原虫氯喹结合蛋白的分离与定量

目的： 分离伯氏疟原虫敏感株（ Ｃ Ｓ） 与抗氯喹株的氯喹（ｃｈｌｏｒｏｑｕｉｎｅ Ｃ Ｑ） 结合蛋白。方法： 给两株感染鼠ｉｇ Ｃ Ｑ４００ ｍｇ／ｋｇ , ３ ｈ 后, 收集伯氏疟原虫用（ Ｕｌｔｒｏｇｅｌ Ｒ） Ａｃ Ａ３４ 凝胶柱分离蛋白, 按 Ｂｅｒｇｑｖｉｓｔ 法抽提与蛋白结合的 Ｃ Ｑ, 然后用 Ｈ Ｐ Ｌ Ｃ （ 外标法） 定量。结果： Ｃ Ｓ 有５８ 个蛋白峰, 均与 Ｃ Ｑ 结合, 其中以 Ｎｏ６４ ～８６部分（ 峰９） 结合的 Ｃ Ｑ 量最多, 占总结合量的１６４ ％ 。抗氯喹伯氏疟原虫（ Ｃ Ｒ） 有４０ 个蛋白峰, 除８ 个峰外,均与 Ｃ Ｑ 结合, 结合量最多的蛋白部分与 Ｃ Ｓ相同, 在 Ｎｏ６０ ～８３ 部分（ 峰６ 及峰７） , 但是它与 Ｃ Ｑ 的结合能力（ Ｃ Ｑｎｍｏｌ／ ｍｇ 蛋白） 显著高于 Ｃ Ｓ。结论： 分离与测定了 Ｃ Ｓ和 Ｃ Ｒ 两株疟原虫各个蛋白峰的分布与定量, 及其与 Ｃ Ｑ 结合的能力。在同一株疟原虫中, 各蛋白与 Ｃ Ｑ 的结合能力存有差异, 在 Ｃ Ｓ与 Ｃ Ｒ 间此差异更大。     

伯氏疟原虫氯喹结合蛋白的分离与定量

目的： 分离伯氏疟原虫敏感株（ Ｃ Ｓ） 与抗氯喹株的氯喹（ｃｈｌｏｒｏｑｕｉｎｅ Ｃ Ｑ） 结合蛋白。方法： 给两株感染鼠ｉｇ Ｃ Ｑ４００ ｍｇ／ｋｇ , ３ ｈ 后, 收集伯氏疟原虫用（ Ｕｌｔｒｏｇｅｌ Ｒ） Ａｃ Ａ３４ 凝胶柱分离蛋白, 按 Ｂｅｒｇｑｖｉｓｔ 法抽提与蛋白结合的 Ｃ Ｑ, 然后用 Ｈ Ｐ Ｌ Ｃ （ 外标法） 定量。结果： Ｃ Ｓ 有５８ 个蛋白峰, 均与 Ｃ Ｑ 结合, 其中以 Ｎｏ６４ ～８６部分（ 峰９） 结合的 Ｃ Ｑ 量最多, 占总结合量的１６４ ％ 。抗氯喹伯氏疟原虫（ Ｃ Ｒ） 有４０ 个蛋白峰, 除８ 个峰外,均与 Ｃ Ｑ 结合, 结合量最多的蛋白部分与 Ｃ Ｓ相同, 在 Ｎｏ６０ ～８３ 部分（ 峰６ 及峰７） , 但是它与 Ｃ Ｑ 的结合能力（ Ｃ Ｑｎｍｏｌ／ ｍｇ 蛋白） 显著高于 Ｃ Ｓ。结论： 分离与测定了 Ｃ Ｓ和 Ｃ Ｒ 两株疟原虫各个蛋白峰的分布与定量, 及其与 Ｃ Ｑ 结合的能力。在同一株疟原虫中, 各蛋白与 Ｃ Ｑ 的结合能力存有差异, 在 Ｃ Ｓ与 Ｃ Ｒ 间此差异更大。     

西咪替丁抗疟作用的研究：Ⅱ.西咪替丁对鼠疟的影响

西咪替丁４ｄ抑制法抗鼠疟作用结果显示：在剂量为５０ｍｇ／ｋｇ．ｄ，１００ｍｇ／ｋｇ．ｄ和２００ｍｇ／ｋｇ．ｄ时，该药对伯氏疟原虫氯喹敏感株，抗性株及约氏疟原虫氯喹敏感株感染小鼠的红内期疟原虫，均有明显的抑制作用，３组平均抑制率分别为６４．９５％，７７．９７％和５８．１６％。ＣＭＤ对伯氏疟原虫氯喹抗性株的抑制作用显著高于伯氏疟原虫氯喹敏感析和约氏疟原虫氯喹敏感株。     

云南省恶性疟原虫对氯喹抗性的纵向监测

应用ＷＨＯ推荐的体外微量测定法于停用氯喹前的１９８１年及停药后的１９８４、１９８８—１９９０和１９９２年在云南省南部的勐腊县测得恶性疟原虫对氯喹的抗性率分别为９７．４％、１００％、９６．１％及９３．７％；ＩＤ５０依次为１７０、１３２、１２５及１１０ｎｍｏｌ／Ｌ，ＩＤ９５为１０００、７４０、７０７及５７６ｎｍｏｌ／Ｌ；平均抑制量分别为５５．４、４６．７、４５．８及３５．４ｐｍｏ１／井。与１９８１年测得结果相比，抗性率无明显变化；ＩＤ５０分别下降２２．３％（Ｐ＜０．０５）、２６．４％（Ｐ＜０．０５）及３５．３％（Ｐ＜０．０１），ＩＤ９５依次下降２６．０％（Ｐ＜０．０５）、２９．３％（Ｐ＜０．０５）及４２．４％（Ｐ＜０．０１）。平均抑制量分别下降１５．７％（Ｐ＞０．０５）、１７．３％（Ｐ＜０．０５）及３６．１％（Ｐ＜０．０１）。提示云南南部恶性疟原虫对氯喹的抗性并不稳定，而是随药物压力的下降而降低。     

海南省乐东县恶性疟原虫对氯喹抗性的变化

目的：监测海南省停用氯喹后抗氯喹恶性疟原虫对氯喹抗性的消长。方法：选择恶性疟原虫对氯喹有高度抗性且恶性疟发病率较高的海南省乐东县为观察点,采用ＷＨＯ标准体外微量法和体内四周法,间隔一定时间检测一次。结果：停用氯喹１８年,体外法,抗性率由１９８１年的９７．９％下降至１９９７年的２６．７％（Ｐ＜０．００１）,完全抑制裂殖体形成的平均药浓度由１０．４６±７．１４ｐｍｏｌ／μｌ血降至１．６３±１．４７ｐｍｏｌ／μｌ血（Ｐ＜０．００１）;体内法,抗性率由１９８１年的８４．２％降为１９９７年的１８．４％（Ｐ＜０．００１）,ＲⅢ占抗性病例的比例由５３．１％降为１４．３％。结论：海南省停用氯喹后恶性疟原虫对氯喹逐渐恢复了敏感性     

中缅边境西段缅甸恶性疟原虫对氯喹,青蒿琥酯及咯萘啶的敏…

应用Ｒｉｅｃｋｍａｎｎ体外微量法测得中缅边境西段缅甸境内感染的恶性疟原虫对氯喹及我国抗疟新药青蒿琥酯及咯萘啶的抗性率分别为１００％、１４．３％及１９．０％，半数抑制量依次为２４９．４、４．２及１２．１ｎｍｏｌ／Ｌ。３例抗青蒿琥酯恶性疟原虫对氯喹和咯萘啶的ＩＤ５０分别为３３５、６ｎｍｏｌ／Ｌ和４３．１ｎｍｏｌ／Ｌ；４例抗咯萘啶恶性疟原虫对氯喹和青蒿琥酯的ＩＤ５０分别为２６０．１ｎｍｏｌ／Ｌ和５．０ｎ     

磷酸咯萘啶与复方磺胺多辛、伯喹伍用治疗抗氯喹地区恶性疟疗效的进一步观察

磷酸咯萘啶８００ｍｇ（基质）与复方磺胺多辛２片，伯喹４５ｍｇ（基质）伍用，在抗氯喹恶性疟流行区治疗恶性疟４２例，平均退热时间３９．０±１７．３ｈ，平均原虫无性体转阴时间４１．５±１３．６ｈ。服药后４８ｈ疟原虫无性体下降率为９７．６—１００％，２８天内复燃率为１０．３％（３／２９）；治后５天内配子体清除率达８７．５％。与５年前的疗效相似。显示该方案并不随恶性疟原虫对咯萘啶的敏感性下降而下降，当地临床观察证实恶性疟原虫对复方磺胺多辛、乙胺嘧啶的抗性率达４１．７％。     

靶向伯氨喹抗约氏疟原虫红外期作用的初步研究

用半乳糖基新糖白蛋白（Ｇ－ＮＧＡ）包裹伯氨喹（ＰＱ）制成的靶向伯氨喹（ＴＰＱ）静脉注射（ｉｖ）感染约氏疟原虫子孢子２ｈ的Ｗｉｓｔａｒ大鼠，４２ｈ时，２０ｍｇ／ｋｇ和１０ｍｇ／ｋｇＴＰＱ组子孢子发育率（ＳＰＶ）分别为１．２％和２．８％，仅分别为对照组的６％左右和１５％，约有９０％红外期（ＥＥＦ）呈现退变或发育受到明显抑制；２０ｍｇ／ｋｇＰＱ组ＳＰＶ为５．０％，为对照组的２６％，半数以上ＥＥＦ均呈退变或发育受到抑制。昆明株小鼠ｉｖ约氏疟原虫子孢子后２ｈ分别注射药物，ＴＰＱ１０ｍｇ／ｋｇ组和ＰＱ２０ｍｇ／ｋｇ组原虫血症前期较对照组明显后延，尤其是ＴＰＱ１０ｍｇ／ｋｇ组中２只鼠均未出现原虫血症。结果提示ＴＰＱ抗ＥＥＦ药效明显优于ＰＱ。     

伯氏疟原虫氯喹敏感株和抗性株在疟色素形成和致病性上的差异

目的：研究伯氏疟原虫氯喹敏感株（Ｎ）和抗性株（ＲＣ）在疟色素形成和致病性上的差异。方法：用伯氏疟原虫氯喹敏感株和抗性株分别感染ＩＲＣ小鼠。实验分为５组：正常对照组（ＮＣ）,氯喹治疗对照组（ＣＣ）,Ｎ株感染组（Ｎ）,ＲＣ株感染组（ＲＣ）和ＲＣ株感染加氯喹治疗组（ＲＣＣ）,比较各组间末梢血中疟原虫的形态、原虫血症、肝脏组织学及超微结构的改变。结果：Ｎ组肝细胞损害较严重,细胞内线粒体肿胀融合,溶酶体增多,肝血窦内疟原虫少见。ＲＣ组炎症反应较突出,主要为单核细胞浸润以及枯否细胞活跃,大滋养体和裂殖体在肝血窦滞留;肝细胞损害较轻,表现为线粒体增生、肿胀及空泡化。Ｎ株疟原虫富含内食物泡,其内有疟色素颗粒,被寄生红细胞结构较完整;而ＲＣ株疟原虫外食物泡较多,位于疟原虫外围的红细胞胞质内,被寄生的红细胞呈蜂窝样改变,食物泡内无疟色素。结论：ＲＣ株疟原虫可能改变了原敏感株（Ｎ株）对血红蛋白的摄取和消化方式,从而阻碍了疟色素形成;Ｎ株和ＲＣ株疟原虫可能因诱导宿主免疫反应的明显差异,导致ＲＣ株较Ｎ株致病力为弱     

抗咯萘啶的伯氏疟原虫感染红细胞多胺量的测定

目的：了解疟原虫的多胺代谢与咯萘啶（ＰＮＤ）抗药性的关系。方法：感染伯氏疟原虫ＡＮＫＡ株（ＰＳ）和由该株培育的中抗ＰＮＤ品系（ＰＲＡ）及高抗ＰＮＤ品系（ＰＲＢ）的昆明株小鼠于腹腔接种（ｉｐ）后ｄ７取血，经薄层层析后用荧光分光光度法测定正常ＲＢＣ、ＰＳ、ＰＲＡ和ＰＲＢ感染ＲＢＣ的丁二胺（ＰＴＣ）、精脒（ＳＰＤ）和精胺（ＳＰＭ）量。另有感染ＰＳ和ＰＲＢ的小鼠于ｉｐ后ｄ６分别１次灌胃（ｉｇ）ＰＮＤ５ｍｇ／ｋｇ和１０ｍｇ／ｋｇ，ｄ７取血，按上述方法测定给药后感染ＲＢＣ的多胺量，并与不给药组比较。结果：ＰＳ感染ＲＢＣ的多胺量均明显高于未感染疟原虫的正常ＲＢＣ，而感染ＰＲＡ和ＰＲＢ的ＲＢＣ多胺量又显著高于ＰＳ感染ＲＢＣ，且多胺量的增高与抗性程度有关。经ＰＮＤ治疗后ＰＳ感染ＲＢＣ的ＳＰＤ和ＳＰＭ较未治疗组显著下降，而ＰＲＢ感染ＲＢＣ则未见明显变化。结论：伯氏疟原虫对ＰＮＤ的抗药性与其多胺代谢有关。     

伯氏疟原虫氯喹抗性逆转的实验观察

目的 寻找伯氏疟原虫氯喹抗性逆转剂.方法 将健康昆明小鼠72只(雌、雄各半)每只腹腔注射0.2 ml伯氏疟原虫ANKA株氯喹敏感系(chloroquine sensitive,CS)或由其选育的高抗氯喹系(chloroquine resistance,CR),按下述随机分组后灌胃给药治疗,观察各组疗效.(1)小鼠感染CS疟原虫30 min后随机均分为4组,每组6只,给D-6182{(Z,Z)-N,N,N-三甲基-2,3-双[(1-氧代-9-十八碳烯酸)-氧代]-1-丙胺基盐酸盐|、C-2832[胆畄醇-3-N-(二甲胺基乙基)氨甲酸酯]、Ket(酮替酚)、0.1%西黄蓍胶(对照组),连续灌药5 d.于D1至D7每天每鼠取尾血涂片作常规镜检,确定各实验组的原虫血症.(2)小鼠感染CR疟原虫后第3天随机均分为8组,每组6只,给D-6182、C-2832、Ket组、氯喹组、0.1%西黄蓍胶对照组及给予D-6182、C-2832、Ket后2 h再加灌服小剂量12 mg/(kg·d)氯喹(5%ED90),连续5 d.每鼠于D4至D7每天取尾血涂片作常规镜检,确定各实验组的原虫血症,并计算各组的原虫减虫率.结果 (1)感染伯氏疟原虫CS株的小鼠,分别灌服80 mg/(kg·d)D-6182、120 mg/(kg·d)C-2832或10 mg/(kg·d)Ket连续5 d,各给药组与对照组小鼠的原虫感染率自D1至D4逐日上升,至D4达峰值,D5时对照组小鼠原虫感染率继续上升,而各给药组维持在D4的峰值水平.(2)感染伯氏疟原虫CR株的小鼠给适宜剂量的C-2832、D-6182或Ket后2 h加灌服小剂量氯喹12 mg/(kg·d)(5%ED90),此后连续5 d(D3-D7),于D4原虫减虫率可达到97.77%、99.28%或96.73%,而在D7可达到99.81%、98.87%或100.00%.结论 C-2832和D-6182两种化合物对伯氏疟原虫CR株感染小鼠的氯喹抗性具有逆转作用,其逆转能力与Ket相当.     

中缅边境西段缅甸恶性疟原虫对氯喹、青蒿琥酯及咯萘啶的敏感性体外测定

应用Rieckmann体外微量法测得中缅边境西段缅甸境内感染的恶性疟原虫对氯喹及我国抗疟新药青蒿琥酯及咯萘啶的抗性率分别为100％、14.3％及19.0％,半数抑制量(ID_(50)依次为249.5、4.2及12.1nmol/L。3例抗青蒿琥酯恶性疟原虫对氯喹和咯萘啶的ID_(50)分别为335.6nmol/L和43.1nmol/L;4例抗咯萘啶恶性疟原虫对氯喹和青蒿琥酯的ID_(50)分别为260.1nmol/L和5.0nmol/L。结果显示抗青蒿琥酯恶性疟原虫对咯萘啶及氯喹有明显的交叉抗性;抗咯萘啶恶性疟原虫对青蒿琥酯无交叉抗性。当地恶性疟原虫对氯喹的抗性程度明显高于云南南部恶性疟原虫,但对其它2种药物的敏感性则无明显差别,提示当地恶性疟原虫对青蒿琥酯及咯萘啶无交叉抗性。     

衰老大鼠急性肺损伤诱导肝功能受损的研究

目的　观察脂多糖 (LPS)致衰老大鼠的急性肺损伤 (ALI)是否可进一步诱发肝功能受损及银杏叶提取物 (GBE)对其是否有保护作用。方法　雄性Wistar大鼠 3 0只复制成衰老模型。再随机分成对照组 (静脉注射生理盐水 ) ;LPS组 (静脉注射LPS)及GBE +LPS组 (注LPS前 7天开始每天GBE灌胃 1次 )。注LPS后 2、6h收集血液并取肺、肝。制备肺、肝组织匀浆待测。结果　衰老大鼠在注射LPS后 2、6h时形成ALI。对照组注射LPS表明 ,2h血中总胆红素含量及谷丙转氨酶 (GPT)活性为(10 9± 0 6)mg/L、(2 6± 3 )U ,LPS 6h组为 (3 0 1± 2 1)mg/L、(88± 12 )U ,两组比较差异有显著性 (P均<0 0 0 1) ;对照组注射LPS表明 ,2h血和肺组织中每毫克蛋白中丙二醛 (MDA)含量分别为 (15 9±1 8) μmol/L、(18 8± 2 1)nmol,LPS 2h组为 (2 2 1± 1 9) μmol/L、(2 8 8± 3 1)nmol,两组比较差异有显著性 (P均 <0 0 0 1) ;而每毫克蛋白血和肺组织中超氧化物歧化酶 (SOD)活性对照组分别为 (2 5 5±2 6)mU/L、(3 6 1± 2 4)U ,LPS 2h组分别为 (2 0 6± 1 9)mU/L、(3 2 0± 2 7)U ,两组比较差异有显著性(P <0 0 1和 0 0 5 )。对照组注射LPS表明 ,2h时肺组织中每毫克蛋白中谷胱甘肽过氧化物酶 (GSH PX)及Na+ K+ ATP酶活性     

Assessment of cortisol and ACTH responses to the desmopressin test in patients with Cushing's syndrome and simple obesity

OBJECTIVE: The desmopressin test has recently been introduced in clinical practice as an adjunctive tool in the differential diagnosis of ACTH-dependent Cushing's syndrome (CS). It has been reported that the majority of patients with pituitary-dependent CS (Cushing's disease, CD) respond to desmopressin, while no such response is usually observed in other forms of this syndrome. In the present study, the responsiveness of the HPA axis to desmopressin was studied in a group of obese subjects. In addition, the ability of desmopressin administration to differentiate between patients with obesity and the various forms of Cushing's syndrome was investigated. DESIGN AND SUBJECTS: Cortisol and ACTH responses to the administration of desmopressin (10 microg bolus i.v.) were examined in 20 consecutive patients with obesity (14 women and six men; BMI range: 34.5-66.7 kg/m2). Obese subjects had no clinical stigmata of CS. In all obese patients, either an overnight (dex 1 mg at 2300 h) (n = 8) or a formal low-dose (dex 0.5 mg 6-hourly for 2 days) (n = 12) dexamethasone suppression test was performed for the exclusion of Cushing's syndrome. Three of eight subjects showed failure of cortisol suppression (i.e. F > 28 nmol/l) to the overnight dexamethasone suppression test, but they had undetectable cortisol levels (< 28 nmol/l) on further testing with the formal 2-day test. All but two of the remaining subjects had undetectable cortisol levels (< 28 nmol/l) following the formal 2-day, low-dose, dexamethasone suppression test. For comparison, desmopressin responses were also tested in 33 patients with CS of varied aetiologies (25 patients with pituitary-dependent CS, three patients with occult ectopic ACTH secretion and five patients with primary adrenal CS). A positive response was considered to be an increment greater than 20% and 50% from baseline levels of cortisol and ACTH, respectively. RESULTS: Mean cortisol (F) and ACTH levels did not differ from the baseline at any time point following desmopressin administration in the obese group (basal F: 417 +/- 41, peak F: 389 +/- 32 nmol/l, P > 0.05; basal ACTH: 33.5 +/- 4.3, peak ACTH: 50.6 +/- 16.6 ng/l, P > 0.05), or in patients with occult ectopic or primary adrenal CS. In contrast, in the group of patients with CD, there was a significant rise in the mean ACTH and F levels from baseline (basal F: 725 +/- 50, peak F: 1010 +/- 64 nmol/l, P < 0.01; basal ACTH: 88.6 +/- 11.8, peak ACTH: 351 +/- 64 ng/l, P < 0.01). Cortisol responses greater than 20% from baseline were observed in 21/25 (84%) patients with CD, but in only 3/20 (15%) of the obese patients. With regard to ACTH, increments greater than 50% over baseline were observed in 23/25 (92%) of patients with CD, and in only 3/20 (15%) of the obese patients. As previously reported, none of the patients with occult ectopic ACTH secretion or primary adrenal CS had a positive response. CONCLUSIONS: The prevalence of subjects who met the criteria adopted to define positive cortisol and ACTH responses to the desmopressin test was significantly higher in the group of patients with Cushing's disease than in the group of patients with obesity. It is therefore suggested that this test may be occasionally useful in the differentiation between simple obesity and the pituitary-dependent form (but not other forms) of Cushing's syndrome.     

Oleic acid-induced lung injury in rats and effects of caffeic acid phenethyl ester

Caffeic acid phenethyl ester (CAPE) is a phenolic antioxidant and is an active anti-inflammatory component of honeybee propolis. The authors evaluated the effects of CAPE on oxidative stress and lung damage in an oleic acid (OA)-induced lung-injury model. Rats were divided into 5 groups as sham, OA, CAPE, pre-OA-CAPE, and post-OA-CAPE. Acute lung injury was induced by intravenous administration of 100 mg/kg of OA. Pre-OA-CAPE group received CAPE (10 micromol/kg. intravenously) 15 minutes before OA infusion and post-OA-CAPE group received CAPE 2 hours after OA administration. Malondialdehyde (MDA) level of plasma, bronchoalveolar lavage fluid (BALF), and lung tissue; myeloperoxidase activity of BALF and lung tissue; Na(+)-K(+) ATPase activity of lung tissue; and total protein content of BALF were measured. Light microscopic analyses of lung specimens were performed. The increased MDA levels in lung homogenates (47.98+/-13.75 nmol/mL), BALF (31.12+/-3.07 nmol/mL), and plasma (61.84+/-15.34 nmol/mL) decreased significantly to 24.33+/-3.09 nmol/mL (P = 0.000), 23.19+/-4.97 nmol/mL (P = 0.002), and 27.36+/-5.37 nmol/mL (P = 0.000), respectively, following CAPE administration in pre-OA-CAPE group. Another important finding was the restoration of the enzymatic activity of Na(+)-K(+) ATPase from a value of 203.89+/-32.18 nmol Pi/mg Protein/h in OA group, to a value of 302.17+/-51.90 nmol Pi/mg Protein/h (P = 0.012) in pre-OA-CAPE group with CAPE treatment. CAPE has been shown to have a clear attenuating effect on oxidative damage in experimental animal studies. However, further investigations are necessary to suggest CAPE as a treatment agent in critically ill patients with lung injury.     

Activity of GH/IGF-I axis in patients with dilated cardiomyopathy

OBJECTIVE: There is evidence showing that GH and IGF-I have specific receptors in the heart and that these hormones are able to promote cardiac remodelling and inotropism. It has been reported that patients with dilated cardiomyopathy (DCM) benefit from treatment with rhGH showing a striking increase in cardiac contractility. However, until now, the activity of GH/IGF-I axis in DCM has never been clearly assessed. PATIENTS: To clarify this point, we enrolled 39 patients with idiopathic or post-ischaemic DCM (36 M/3 F; age (mean +/- S.D.) 55.3 +/- 9.0 years; BMI: 25.3 +/- 3.2 kg/m2; New York Heart Association class (NYHA) I/2, II/19, III/15, IV/3) and 42 age-matched controls (CS, 38 M/4 F; age 56.0 +/- 7.8 years; BMI: 24.9 +/- 1.5 kg/m2). DCM patients were characterized by a left-ventricular diastolic diameter of 73.8 +/- 8.3 mm, a shortening fraction of 15.9 +/- 6.4% and a left ventricular ejection fraction of 25.1 +/- 8.7%. In all subjects clinical and biochemical indices of renal and hepatic function as well as nutritional parameters were in the normal range. MEASUREMENTS: In both groups we studied: a) IGF-I levels in basal conditions and after administration of low rhGH doses for 4 days (5.0 or 10.0 mu/kg/day x 4 days); b) the acute GH-response to GHRH (1.0 mu/kg i.v.) or hexarelin (HEX, 2.0 mu/kg i.v.), a peptidyl GH secretagogue (GHRP); c) mean GH concentration (mGHc) over 10 h sampling (every 20 min) from 2200 h to 0800 h. RESULTS: Basal IGF-I levels in DCM were lower (P = 0.000039) than in CS (135.2 +/- 46.8 vs. 193.7 +/- 63.7 mu/l), whereas, basal IGFBP-3 and GHBP2 levels in DCM and CS were similar (2.5 +/- 1.3 vs. 2.6 +/- 0.5 mg/l and 25.3 +/- 3.6 vs. 28.3 +/- 5.0%; P = 0.95 and P = 0.085, respectively). After 4 days of 5.0 mu/kg/day rhGH administration, IGF-I levels in DCM (215.4 +/- 82.0 mu/l; P = 0.0023 vs. baseline) remained lower (P = 0.027) than those in CS (280.0 +/- 80.7 mu/l; P = 0.000080 vs. baseline). After 10.0 mu/kg/day for 4 days, IGF-I levels in DCM (297.2 +/- 109.2 mu/l; P = 0.0033 vs. baseline) were similar (P = 0.76) to those in CS (310.9 +/- 81.7 mu/l; P = 0.000060 vs. baseline). The GH response to GHRH in DCM was lower (P = 0.0022) than that in CS (hAUC0-120: 192.0 +/- 177.3 vs. 345.3 +/- 191.1 mu/l/h) whereas that to HEX in DCM and CS was similar (611.0 +/- 437.5 vs. 535.4 +/- 302.8 mu/l/h; P = 0.95). Within the DCM group, basal and rhGH-stimulated IGF-levels as wel as the GH response to GHRH or HEX were not different among NYHA classes and did not show any correlation with ECHO parameters. The mGHc in DCM (1.0 +/- 0.5 mu/l) was similar (P = 0.57) to that in CS (0.9 = 0.7 mu/l). CONCLUSIONS: Our present data demonstrate that in dilated cardiomyopathy patients with severe left ventricular dysfunction basal IGF-I levels are reduced whereas the IGF-I response to low rhGH doses is preserved. These findings suggest a normal peripheral GH sensitivity in dilated cardiomyopathy. On the other hand, though nocturnal mean GH concentration in dilated cardiomyopathy patients is similar to that in normal subjects, the somatotroph responsiveness to GHRH, but not that to hexarelin, is reduced. Thus, subtle alterations in the activity of GH/IGF-I axis are present in dilated cardiomyopathy.     

Changes in enzyme activity in normal and histologically inflamed oesophageal epithelium.

Oesophageal biopsies were obtained from 74 patinets undergoing upper gastrointestinal fibreoptic endoscopy. Thirteen patients with histological evidence of inflammation had a raised alkaline phosphatase activity (2.7 +/- 1.6 nmol/mg protein/min) compared with 49 normal controls (1.2 +/- 0.68 nmol/mg protein/min: P less than 0.001). The acid phosphatase level was lower (8.4+/- 4.0 vs. 5.8 +/- 2.2 nmol/mg protein/min: P less than 0.05) and the glucuronidase activity raised (0.44 +/- 0.17 vs 0.81 +/- 0.32 nmol/mg protein/min: P less than 0.001) and their ratio declined (24.0 +/- 1.9 nmol/mg protein/min: P less than 0.001) in patients with oesophagitis. This may be due to differential secretion of membrane coating granules, a form of lysosome found isophagitis--was assessed by point counting. The volume density rose from 10.9 +/- 4.25% in normal biopsies to 46.4+/-12.5% (P less than 0.001) in oesophagitis. These results show a consistent pattern that possibly indicates an intermediate stage between the clinically, histologically, and biochemically normal oesophagus and one that is inflamed on endoscopy.     

COMPARISON OF THE ACTH AND CORTISOL RESPONSES TO PROVOCATIVE TESTING WITH GLUCAGON AND INSULIN HYPOGLYCAEMIA IN NORMAL SUBJECTS

The glucagon stimulation test (GST) is often used to assess pituitary ACTH reserve, particularly when other tests are contra-indicated. In a preliminary investigation, in patients with pituitary disease, we failed to demonstrate the ACTH dependence of the cortisol response. We have therefore compared the ACTH, cortisol and glucose responses to glucagon (1 mg s.c.), insulin (0.2 U/kg i.v., ITT) and placebo in six healthy male volunteers, sampling every 10 min for 6 h. During the GST, mean +/- SD serum cortisol rose from 256 +/- 80 nmol/l to a peak of 481 +/- 164 nmol/l (range 289-717 nmol/l, P less than 0.01) in comparison with 280 +/- 81 nmol/l to 602 +/- 110 nmol/l (range 493-742 nmol/l) during the ITT (P less than 0.002). The mean peak cortisol levels achieved in the two tests did not differ significantly. In the GST, plasma ACTH rose from a mean basal value of 10.9 +/- 16.6 ng/l to a mean peak level of 123 +/- 76 ng/l (P less than 0.02) (ACTH ng/l x 0.225 = pmol/l). The corresponding values in the ITT were 7.1 +/- 16.2 ng/l and 263 +/- 91 ng/l (P less than 0.001). The mean peak ACTH level was significantly greater during the ITT (P less than 0.05). Thus the cortisol response was ACTH dependent in both the GST and the ITT in normal subjects. Furthermore, the ACTH response was of sufficient duration to be detected by the usual procedure of sampling every 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)