甲苯达唑、阿苯达唑和吡喹酮对小鼠细粒棘球蚴囊壁丙氨酸转氨酶和天门冬氨酸转氨酶的影响（英）

感染细粒棘球蚴达１０－１２个月的小鼠ｉｇ甲苯达唑（Ｍｅｂ）２５－５０ｍｇ·ｋｇ－１·ｄ－１×７－１４ｄ，其体内瘪囊壁与充盈囊壁的丙氨酸转氨酶（ＡＬＴ）抑制率为６７．８％－７８．９％和１１．３％－４５．４％，ｉｇ阿苯达唑３００ｍｇ·ｋｇ－１·ｄ－１×１４ｄ对充盈囊壁ＡＬＴ的抑制率为４０．７％，而ｉｇ吡喹酮５００ｍｇ·ｋｇ－１·ｄ－１×１４ｄ的则无明显影响。用上述药物治疗时，仅Ｍｅｂ５０ｍｇ·ｋｇ－１·ｄ－１组对天门冬氨酸转氨酶（ＡＳＴ）有抑制作用，抑制率为２６％－４３．９％。     

吡喹酮脂质体、吡喹酮、阿苯达唑、氟苯达唑和甲苯达唑对泡球蚴病的疗效观察

本文对小鼠继发性腹腔泡球蚴病用吡喹酮脂质体、吡喹酮、阿苯达唑、氟苯达唑和甲苯达唑进行实验治疗。５个治疗组对小鼠均能抑制泡球蚴增殖生长，抑制率分别为６８．７％，１４．３％，７０．０％，４８．３％和７７．０％。吡喹酮经脂质体包裹后，较吡喹酮组疗效明显提高（Ｐ＜０．０１）。各治疗组泡球蚴生发层均有不同程度损伤，与实验对照组有显著性差异（Ｐ＜０．０１），以吡喹酮脂质体对泡状棘球蚴损伤程度最重。超微结构显示，各治疗组对小鼠泡球蚴组织均有广泛的变化，以阿苯达唑组变化最重，细胞大部分解体。提示各种化疗药物对泡球蚴组织有广泛的细胞内效应。     

抗包虫药物的实验研究——Ⅲ.甲苯达唑和阿苯达唑体外抗细粒棘球蚴原头节的作用

在20％小牛血清-RPMI 1640中培养的细粒棘球蚴原头节经甲苯达唑或阿苯达唑20μg/ml作用3～5d后,其死亡率分别为42.4～64.2％和40.6％。用囊液培养原头节时,两种药物的效果更差。甲苯达唑或阿苯达唑与低浓度的吡喹酮合并应用时,原头节的死亡率较两药单用的明显增加。小鼠1次口服甲苯达唑或阿苯达唑1g/Kg后4h,其血清具有较强的抗原头节作用。     

吡喹酮、阿苯达唑和甲苯达唑对小鼠细粒棘球蚴生发膜超微结构的影响

小鼠感染的细粒棘球蚴囊经吡喹酮、阿苯达唑和甲苯达唑治疗后,其生发膜的超微结构均示有广泛的变化,主要是皮层基质变性、溶解和空泡变化;皮层细胞核周胞质的溶解、空泡形成,线粒体密集、变性、肿大,间质及肌束的广泛或局灶性溶解,以及囊腔面的溶解和脱落。甲苯达唑和阿苯达唑尚可引起角质层的损害及核染色质减少等。     

吡喹酮、甲苯达唑及阿苯达唑对感染鼠体内外细粒棘球蚴作用的组织学比较

本文比较了吡喹酮、甲苯达唑及阿苯达唑对体内、外细粒棘球蚴组织学的影响。结果表明,三种药物均能引起生发层表面粗糙、间质疏松、空泡变性、生发细胞结构模糊、核伊红深染及细胞崩解等病变,均以甲苯达唑组的为最重,发生率亦较高,而吡喹酮与阿苯达唑组的相似,均较轻,发生率亦较低,停药后,一些生发层的损害逐渐恢复正常,以吡喹酮及阿苯达唑组的较迅速,而甲苯达唑组的则较缓慢。     

细粒棘球蚴囊经甲苯达唑、阿苯达唑或阿苯达唑亚砜作用后其生发层的形态学变化和药物含量

小鼠的继发性细粒棘球蚴囊在含甲苯达唑阿苯达唑或阿苯达唑亚枫1及10μg/ml的培养液中培养l～7d时,囊壁所含各药物的量相近,但生发层的受损以甲苯达唑组较重,次为阿苯达唑亚砜和阿苯达唑组。感染小鼠ig上述3种苯并咪唑类化合物的等效剂量1～14d后24h,囊壁的药物含量甚低,但生发层的损害仍以甲苯达唑组的较重,并认为阿苯达唑亚矾是阿苯达唑的有效代谢物。     

甲苯达唑、阿苯达唑及其代谢物实验治疗小鼠继发性细粒棘球蚴病的研究

在疗程为10～14d时,甲苯达唑对小鼠继发性细粒棘球蚴病的最低有效剂量为25mg/kg/d,阿苯达唑的为100mg/kg/d。在所用的疗程下,甲苯达唑的剂量较阿笨达唑100～300mg/kg/d低3～11倍时,它们的疗效相仿,但甲苯达唑100mg/kg/d的疗效则优于剂量大l～2倍的阿苯达唑。甲苯达唑与阿苯达唑合并治疗未能明显提高疗效,但此2种药物并用吡喹酮治疗则疗效明显提高。实验证明阿苯达 唑亚砜的疗效优于阿苯达唑,而阿苯达唑用则无效。     

阿苯达唑脂质体对小鼠细粒棘球蚴囊超微结构的影响

目的:探讨阿苯达唑脂质体(liposom alalbendazole,L-ABZ)及其联合西咪替丁(cim etidine,CTD)治疗小鼠细粒棘球蚴病的病理形态变化。方法:将阿苯达唑脂质体及西咪替丁(1.5% 乳液阿苯达唑200 m g/kg,西咪替丁100 m g/kg),经口灌喂感染小鼠3个月后,用光镜和电镜观察小鼠肝、腹细粒棘球蚴囊结构的病理改变。结果:以阿苯达唑脂质体联合西咪替丁治疗组细粒棘球蚴囊组织变性坏死改变最为显著,与对照组有显著性差异(P< 0.01)。结论:脂质体包封阿苯达唑,可提高阿苯达唑的抗细粒棘球蚴作用,西咪替丁具有明显的协同作用     

吡喹酮、甲苯达唑及阿苯达唑对细粒棘球蚴作用的组织化学比较

本文比较了吡喹酮、甲苯达唑及阿苯达唑对NIH鼠体内细粒棘球蚴组织化学的影响。结果表明,三种药物治疗3～14天,均能迅速引起生发层内糖原、AKP、ACP及ATP酶的减少、减弱或消失,以甲苯达唑组的为最明显,阿苯达唑及吡喹酮的较轻,但对生发层内DNA、RNA、蚤白质结合的酪氨酸、色氨酸、组氨酸以及碱性蛋白质的影响仅见于7及14天。亦以甲苯达唑组的较为显著。停药后,上述变化的恢复时间,吡喹酮及阿苯达唑的分别为14～30及30天,而甲苯达唑组的则需90天。     

阿苯达唑亚砜和吡喹酮长疗程对细粒棘球蚴生发层超微结构的影响

感染继发性细粒棘球蚴的小鼠口服阿苯达唑亚砜150mg/kg·d×28d 时,细粒棘球蚴囊的生发层超微结构的变化主要是皮层受损、皮层细胞核周胞质广泛溶解和空泡形成、线粒体肿大和变性等,与阿苯达唑相仿。感染小鼠口服吡喹酮500mg/kg·d,连给3个月时,生发层超微结构的变化与给药15～30d 的相仿。动物剖检时仅少数囊塌陷和干瘪。这些囊的超微结构于停药6个月后仍示有严重损害。     

甲苯达唑、阿苯达唑和吡喹酮实验治疗小鼠继发性细粒棘球蚴病的观察

小鼠于感染继发性细粒棘球蚴后用甲苯达唑口服治疗,剂量为12.5～100mg/kg/d×10时囊肿抑制率为49.2～77.5％,用阿苯达唑100～300mg/kg/d×10～14治疗的为61.3～72.1％,而用吡喹酮400mg/kg/d,或800mg/kg/d,2次均服,疗程为10d时则无效,但若给服500mg/kg/d×14,囊肿抑制率为63.4％。药物有效各组的每鼠平均囊数,除个别组外,均较相应对照组的为少。此外,甲苯达唑与吡喹酮合并服用,有一定的增效作用。     

左旋吡喹酮、右旋吡喹酮和消旋吡喹酮的体外与体内抗不同发育期日本血吸虫的作用

目的：测定消旋吡喹酮（Ｐｒａ）、左旋吡喹酮（Ｌ－Ｐｒａ）和右旋吡喹酮（Ｄ－Ｐｒａ）对不同发育期日本血吸虫的作用。方法：用含２０％小牛血清的ＰＲＭＩ１６４０培养不同发育期的血吸虫，测定上述三种药物的体外抗血吸虫作用。体内试验系于小鼠感染血吸虫尾蚴后不同时间灌服（ｉｇ）Ｐｒａ、Ｌ－Ｐｒａ或Ｄ－Ｐｒａ，根据残留平均虫数评估药效。结果：依据药物引起虫的皮层损害程度，虫龄为２８ｄ（ｄ２８）和３５ｄ（ｄ３５）的成虫对Ｌ－Ｐｒａ最敏感，而１４ｄ（ｄ１４）童虫则最不敏感。在药物浓度为０．１－１μｇ／ｍｌ时，Ｌ－Ｐｒａ的抗血吸虫作用较Ｐｒａ的为强，即使Ｌ－Ｐｒａ的浓度减至Ｐｒａ最低有效药浓度的１／２亦有效。在体外，上述浓度的Ｄ－Ｐｒａ对不同发育期血吸虫无明显作用。感染小鼠ｉｇ单剂量的Ｌ－Ｐｒａ，Ｐｒａ或Ｄ－Ｐｒａ３００ｍｇ／ｋｇ或５００ｍｇ／ｋｇ，仅前２种药物对３ｈ（ｄｏ）、２１ｄ（ｄ２１）童虫和ｄ２８及ｄ３５成虫有较明显的疗效，而对３ｄ（ｄ３）、７ｄ（ｄ７）和ｄ１４童虫的疗效甚差或无效。与Ｌ－Ｐｒａ和Ｐｒａ相比，Ｄ－Ｐｒａ仅对ｄ３５成虫有较差的疗效。感染ｄ３５血吸虫成虫的小鼠用Ｌ－Ｐｒａ１５０ｍｇ／ｋｇｉｇ治疗，其疗效与用Pra 300mg/kg 治疗的相仿。D-Pra 的总剂量增至L -Pra 的2—6 倍时亦仅示很差的疗效。结论: 在消旋Pra 中,L-Pra 是抗血吸虫的活性成分。     

阿苯达唑脂质体生发层单抗复合物治疗小鼠细粒棘球蚴病效果观察

目的　评价阿苯达唑免疫脂质体 (IL - Alb)治疗小鼠细粒棘球蚴病的效果。　方法　每只小鼠感染约 10 0 0个细粒棘球绦虫原头蚴 ,80天后随机分为 5组 ,4个治疗组分别给予阿苯达唑 (Alb)、阿苯达唑脂质体 (L-Alb)、阿苯达唑亚砜脂质体 (L - Albso)及 IL - Alb,按原药 10 0 m g/ (kg.d)× 5 d ip,连续 3个疗程 ,另 1组为对照组。治疗效果按囊重抑制率、常规病理切片、超微结构及高效液相色谱法测定囊药含量 4个指标综合评价。　结果　L - Alb治疗组 ,囊重抑制率为 80 .3% ,囊药含量为 2 .18μg/ g,优于 Alb组囊重抑制率为 6 1.2 % ,囊药含量为 0 .76μg/ g;而 IL- Alb组的囊重抑制率为 91.45 % ,囊药含量为 5 .15 μg/ g。组织病理损伤以 IL- Alb组较重。　结论　免疫脂质体作为 Alb载体 ,可增加药物的靶特异性 ,提高 Alb治疗细粒棘球蚴的疗效。     

阿苯达唑和甲苯达唑对蛔虫和钩虫作用的超微结构观察

在体外美洲钩虫成虫接触药物后活动性明显下降，体表皱缩，随着作用时间延长，蠕动缓慢，咽收缩无力并且不规律，体态膨胀不均匀，48小时内虫体趋于不动。药物对体内蛔虫和体外钩虫作用的超微结构显示：微绒毛变性且部分消失；肠细胞分泌颗粒积聚并融合，出现自噬空泡，糖原减少，线粒体变性。蛔虫卵细胞间出现溶酶体，子宫细胞内质网疏松，分泌颗粒融合，糖原缺乏；精细胞充满致密小体，线粒体广泛变性。未见钩虫生殖细胞超微结构明显变化。     

Protective effect of exogenous transferrin against hyperoxia: A study on premature rabbits

We hypothesized that an increase in plasma iron binding capacity would decrease the generation of oxygen radicals and of lipid peroxides. To test this hypothesis, we studied whether supplementation of transferrin (TF) in premature rabbits would modify the degree of hyperoxic lung injury. Animals, delivered prematurely at 29 days of gestation (term 31 days), were randomized and given either 0.5 g/kg of albumin (Alb) (n = 116) or 0.5 g/kg of iron-free TF (n = 132) intravenously within 2 hours after birth. Another group was randomized to receive saline (n = 15), or either 0.35 g/kg (n = 12) or 0.70 g/kg of iron-free TF (n = 8). After exposure to a 100% oxygen environment for 2 or 4 days, the animals were killed, and plasma and bronchoalveolar lavage (BAL) fluid was recovered. Infusion of TF caused a dose-dependent increase in the concentration of TF and an increase in the unsaturated iron-binding capacity. Administration of TF at birth increased the gradient of TF between serum and alveolar epithelial lining fluid on day 4, suggesting decreased alveolar-capillary permeability. BAL fluid and plasma from TF-supplemented animals contained less lipid peroxidation products and more inhibitor of lipid peroxidation than BAL fluid or plasma from Alb-treated animals. In TF-treated animals, the recovery of protein in BAL fluid (TF group, 1.26 ± 0.07 mg; Alb group, 1.78 ± 0.10 mg; P = 0.02) and the water content of the extravascular lung tissue (TF group, 78.5 ± 1.4%; Alb group, 83.2 ± 1.3%; P = 0.05) were lower than in Alb-treated animals. We propose that supplementation of iron-free TF decreases iron-catalyzed redox reactions and may decrease hyperoxic lung injury in the premature. Pediatr. Pulmonol. 1997; 24:429–437. © 1997 Wiley-Liss, Inc.     

Tegumental changes in adult Schistosoma mansoni harboured in mice treated with praziquantel enantiomers

Praziquantel administered to the host causes damage to the tegument of Schistosoma mansoni. In this study, the effects of racemic praziquantel (Pra) and its enantiomers, levo-praziquantel (L-Pra) and dextro-praziquantel (D-Pra) were compared using scanning electron microscopy (SEM). Mice infected with S. mansoni for 49 days were treated with a single dose of Pra (300 mg/kg), L-Pra (150 mg/kg) or D-Pra (150 or 600 mg/kg). Groups of three mice were killed after 4 and 24 h, and schistosomes collected by perfusion and examined by SEM. Treatment with Pra or L-Pra, for 4 or 24 h, caused tegumental damage to S. mansoni including severe swelling, vacuolization, fusion of the tegumental ridges and loss or shortening of the spines on the tubercles, collapse and peeling. After treatment with D-Pra at 150 mg/kg, no apparent damage was observed. When the dosage was increased to 600 mg/kg, after 4 h lesions on the tegument similar to those induced by Pra or L-Pra were seen, but less severe. After 24 h, there was evidence of recovery. The study thus clearly showed that L-Pra was more active than D-Pra in causing tegumental damage. D-Pra showed a qualitatively similar activity at a higher concentration. It is possible that this effect was due at least to some extent to the small amount of L-Pra (<2%) which was present in the preparation of D-Pra used.     

阿苯达唑脂质体及槐耳浸膏对小鼠肝细粒棘球蚴感染率影响的实验观察

目的 探讨阿苯达唑脂质体(L-ABZ)及槐耳浸膏(HEF)对小鼠肝细粒棘球蚴病术后感染的抑制作用，了解增强宿主免疫功能对本病术后复发的影响。 方法 雌性昆明小鼠，腹腔注射人肝细粒棘球蚴囊液，3周后取外周血IgG抗体阳性鼠，分为药物治疗组(A、B、C组)和模型对照组(D组), 每组40只。A 组灌胃L-ABZ(75 mg/kg)、B组灌胃HEF(15 000 mg/kg)、C 组两药联用(阿75 mg/kg+槐15 000 mg/kg)。隔天1次，共 3 次。麻醉各组小鼠，打开腹腔，肝脏注射经PBS浸泡20 min的原头节(0.3 ml/只，约含原头节6 000个，下同)，模拟开放式外膜内外囊完整摘除术术中外溢原头节再感染。缝合关闭腹腔，72 h后药物治疗组同法继续治疗1个月，D组灌服蒸馏水0.3 ml/只。E组(8只正常小鼠) 为空白对照。各组小鼠均于3个月后解剖。评价药物疗效（包括肝棘球蚴复发率、组织学观察、测定脾脏指数(SI)及IgG、IgE水平、流式细胞仪检测外周血CD4⁺、CD8⁺ T淋巴细胞百分率）。另取上述外周血IgG抗体阳性鼠分为F、G、H和I 4组，每组约30只, 分别同上述A、B、C和D组同法灌胃治疗, 于肝脏分别注射经20% NaCl、75%乙醇、L-ABZ及PBS浸泡20 min的原头节, 观察其感染率。 结果 C组肝棘球蚴复发率为5.7%，低于A组(17.1%)和B组(24.2%)；棘球蚴色泽发白呈结节状，生发层和角质层破坏严重。脾脏指数(A组为3.84±0.86、B组为3.95±1.01、C组为3.27±0.52)和IgE水平(A组为0.06±0.08、B组为0.07±0.08、C组为0.03±0.03)均明显低于D组(分别为5.46±0.52及0.20±0.02)(P＜0.05)，其中C组降低最为明显。CD8⁺水平，A组为16.61±3.89、B组为18.18±3.90、C组为15.38±2.63，均明显低于D组的32.90±4.71(P＜0.05)。CD4⁺/CD8，A组为3.21±0.70、B组为3.05±0.66、C组为3.53±0.57，均明显高于D组的1.57±0.26(P＜0.05)。C组CD8+降低、CD4⁺/CD8⁺升高最为明显。F、G和H组肝棘球蚴感染率分别为0、0及23.1%，与I 组（31.2%）相比较，差异有统计学意义（P＜0.01）。 结论 HEF可明显增强小鼠免疫功能，与L-ABZ联用可抑制棘球蚴生长，降低术后复发率。L-ABZ在术中对于原头节的杀灭作用不及20％ NaCl和75％乙醇。     

Chronic administration of pentagastrin. Effects on pancreatic protein and nucleic acid contents and protein synthesis in rats.

Groups of rats were injected with either saline or pentagastrin (0.5, 1 or 2 mg/kg/day) for 14 days. Pancreatic weight, DNA, RNA and protein contents as well as the ability of the pancreatic polyribosomes to synthesize protein in a cell-free system were investigated. In all three pentagastrin-treated groups the weight of the pancreas was found to be significantly higher (33-73%) than in the control. DNA, RNA and protein contents were significantly increased by 47, 98 and 85%, respectively, in the group that received the highest dose of the hormone. With respect to ribosomal protein synthesis, while the pentagastrin dose of 1 and 2 mg/kg/day resulted in 25 and 72% augmentation, respectively, the dose of 0.5 mg/kg had no influence on protein synthesis. It is concluded that chronic administration of pentagastrin (2 mg/kg/day for 14 days) causes hyperplasia and hypertrophy of the pancreas.     

普伐他汀治疗非缺血性心力衰竭的初步观察

目的 观察小剂量普伐他汀对非缺血性心力衰竭（心衰）患者心脏功能的影响及应用的安全性。方法 连续人选2005年1月至2006年7月医院就诊的非缺血性病因的心衰患者61例,随机分为普伐他汀（20mg／d）组（n=30）与对照组（n=31）,治疗期6个月。观察治疗前后患者心脏功能、肱动脉血管内皮功能、炎症因子与生化指标的变化。结果 标准心衰治疗的基础上加用普伐他汀20mg／d,与对照组相比,3个月时患者加压反应性充血前后血管内径变化百分率增加;6个月时NYHA分级改善,血浆脑利钠肽水平下降,左心室内径缩小,左室射血分数增加,血浆肿瘤坏死因子-俚有所下降（均为P〈0．01）;对照组患者NYHA分级改善（P〈0．05）,左室射血分数有改善的趋势（P=0．052）。普伐他汀组患者的总胆固醇降低（P〈0．05）,高密度脂蛋白胆固醇无明显变化,无肝、肾功能异常,肌酸激酶无明显增高,1例患者因为过敏反应（皮疹）终止治疗。结论 非缺血性心衰患者在标准心衰治疗的基础上加用普伐他汀20mg／d治疗6个月安全、有效,可以显著改善左室重构与心功能状态,并改善内皮功能,降低炎症因子水平。