血吸虫对吡喹酮抗药性的研究XⅧ日本血吸虫吡喹酮抗性株与敏感株混合感染子代成虫对吡喹酮的敏感性

目的　测定实验诱导产生的日本血吸虫吡喹酮抗性株与实验室保种传代的日本血吸虫吡喹酮敏感株混合感染后产生的子代成虫对吡喹酮的敏感性。方法　取实验室诱导产生的日本血吸虫吡喹酮抗性株[吡喹酮半数有效剂量（ED50值）为277.4 mg/kg]尾蚴与实验室传代保种的日本血吸虫吡喹酮敏感株（吡喹酮ED50值为99.6 mg/kg）尾蚴,分别按1∶1和2∶1混合后感染小鼠。后在实验室经小鼠⁃钉螺循环8代后,取尾蚴感染小鼠。感染35 d后将小鼠分为对照组及5个给药组。5个给药组分别按37.5、75、150、300 mg/kg和600 mg/kg剂量一次性灌胃给予吡喹酮,对照组给予2.5%聚氧乙烯蓖麻油。给药14 d后解剖鼠并以静脉灌注法收集成虫,计算减虫率及吡喹酮对虫株的ED50值。取经12轮亚治疗剂量吡喹酮诱导筛选的日本血吸虫吡喹酮抗性株,置实验室经小鼠⁃钉螺循环常规传代,取子8代日本血吸虫尾蚴感染实验鼠,测定吡喹酮对此子代成虫的ED50值。结果　日本血吸虫吡喹酮抗性株与敏感株尾蚴按1∶1混合感染小鼠后,吡喹酮对子8代成虫ED50值为135.2 mg/kg;日本血吸虫吡喹酮抗性株与敏感株尾蚴按2∶1混合感染小鼠后,吡喹酮对子8代成虫ED50值为129.2 mg/kg;日本血吸虫吡喹酮抗性株未予吡喹酮压力传代,吡喹酮对子8代后成虫ED50值为208.4 mg/kg。 结论　与实验室诱导的抗性株相比,日本血吸虫吡喹酮抗性株与敏感株尾蚴混合感染同一宿主后所获的子代成虫对吡喹酮抗性有所降低。日本血吸虫吡喹酮抗性株不经药物压力传代,其子代成虫仍可能够维持对吡喹酮的抗性。     

吡喹酮对体外生活期曼氏血吸虫的作用

本文报道吡喹酮对曼氏血吸虫的虫卵孵化、毛蚴和尾蚴的作用。将感染曼氏血吸虫的小鼠粪便内的虫卵用沉淀法进行分离,并放在有光刺激和27℃的条件下孵出毛蚴,然后将毛蚴和从感染的扁卷螺内逸出的尾蚴培育在含有吡喹酮的药液中。实验在室温条件下进行。实验用雌性 CFI/W74株小鼠,在感染后7天或8周解剖动物,计数童虫和成虫数,与对照组相比较来评价药物的疗效。     

吡喹酮体外处理日本血吸虫卵对鼠肺肉芽肿形成的影响

我们曾用吡喹酮早期治疗感染日本血吸虫的小鼠后,可以抑制虫卵肝肉芽肿的形成。为探讨其抑制机理,我们应用鼠肺肉芽肿模型进行了进一步研究。观察体外用吡喹酮处理的日本血吸虫卵,在鼠体内形成肺肉芽肿的动态变化。材料和方法一、吡喹酮处理虫卵昆明远交鼠30只,雌雄不拘,每只小鼠经腹部皮肤人工感染日本血吸虫尾蚴80～100条。56d 后取肝脏,常规分离虫卵。分离纯卵用500μg/ml 浓度吡喹酮药液按1%(w/v)配成悬液,置4℃     

左旋吡喹酮对感染小鼠肝内日本血吸虫虫卵肉芽肿的影响

吡喹酮作为一种有效的抗血吸虫药物,其有效成分主要存在于左旋同分异构体中。此药不仅能杀死血吸虫成虫,还可以抑制宿主组织内的虫卵周围炎症反应。本实验应用小剂量的左旋吡喹酮治疗感染日本血吸虫小鼠,观察其对肝脏病变的影响。一、材料与方法体重20～22g 雄性小鼠120只经腹部皮肤感染40条日本血吸虫尾蚴。感染后30d,将小鼠随机分成3组:(1)左旋吡喹酮治疗组(简称 LPQ 组),以75mg/kg 左旋吡喹酮(LPQ)悬液灌胃给药;(2)消旋吡喹酮治疗组(简称 PZQ 组),以150mg/kg 消旋吡喹酮(PZQ)悬液灌胃给药;(3)对照组,不给药。每组分别在给药后3、7、14、21、     

吡喹酮对曼氏血吸虫虫卵的作用及其控制脑型血吸虫病的可行性

吡喹酮对血吸虫成虫有很强的杀伤力,但对虫卵的作用尚未取得一致的意见。脑型血吸虫病,主要与虫卵毒素的分泌及虫卵肉芽肿的形成有关。为此,作者研究了吡喹酮不同疗程对曼氏血吸虫虫卵的影响,并探讨了吡喹酮用于脑型血吸虫病的可行性。实验用小鼠,每鼠感染曼氏血吸虫波多黎各株尾蚴200条,7周后,选择每克粪便虫卵在100个以上的阳性鼠作为观察对象。将感染度相似的动物分配在同一实验组内。实验一:共4组,每组10个鼠。1.吡喹酮60mg/kg     

吡喹酮是否具有免疫调节作用

血吸虫病是一种免疫性疾病，主要的致病机理是血吸虫卵在肝脏和肠组织的沉积，虫卵释放出可溶性抗原，引起一系列免疫反应，形成虫卵肉芽肿（Ⅳ型超敏反应），不断破坏肝脏和肠组织结构等。吡喹酮具有显著的杀血吸虫作用，但实验显示，吡喹酮不杀日本血吸虫成熟期卵及发育期卵，对虫卵的发育无明显影响。肖树华等以小鼠做实验，于感染血吸虫尾蚴后32d一次口服毗喹酮300mg／kg，于不同时间剖杀小鼠，取肝组织压片，作卵谱检查，并与未治疗感染鼠对照。结果，治后1～3d，肝组织的卵谱与对照组相似，给药后7～14d，Ⅰ期（初产卵与空泡发育期）、Ⅱ期（发育期）虫卵相继消失，而Ⅲ期（成熟期）、Ⅳ期（变性或死亡期）虫卵则增多；治后21～27d，除Ⅲ期虫卵增多外，其余各期虫卵均少。卵谱观察的结果表明，吡喹酮对日本血吸虫卵的发育无明显影响。     

血吸虫对吡喹酮抗药性的研究ⅩⅦ 日本血吸虫吡喹酮抗性株在小鼠体内的生物学特性

目的实验观察日本血吸虫吡喹酮抗性株在终宿主小鼠体内的生物学特性,探索日本血吸虫吡喹酮抗性株对终宿主的致病力及传播强度。方法分别采用日本血吸虫江苏吡喹酮敏感株和抗性株、湖南吡喹酮敏感株和抗性株尾蚴定量感染小鼠,建立小鼠-钉螺-小鼠生活史循环,观察比较各虫株的虫卵开放前期、产卵量及虫卵分布、对终宿主的易感性、虫体生长发育等生物学特性。结果日本血吸虫江苏吡喹酮敏感株和抗性株虫卵开放前期分别为36.1 d和36.8d(t=0.907,P=0.372),粪便中虫卵数分别为14.6只/100 mg和21.2只/100 mg(t=2.946,P=0.007),回收成虫数分别为20.5条/鼠和25.1条/鼠(t=2.128,P=0.042),组织中虫卵数分别为31 303只/对成虫和38 594只/对成虫(t=2.185,P=0.040)、肝脏虫卵数分别为14 810只/对成虫和19 715只/对成虫(t=2.934,P=0.007),肠组织中虫卵数分别为16 493只/对成虫和18 879只/对成虫(t=1.044,P=0.309);江苏敏感株和抗性株雌雄合抱虫体长度(t=0.328,P=0.744)、雌虫体长(t=0.386,P=0.701)及雄虫体长(t=0.332,P=0.741)差异均无统计学意义。日本血吸虫湖南吡喹酮敏感株和抗性株虫卵开放前期分别为35.5 d和35.6 d(t=0.169,P=0.867),粪便中虫卵数分别为13.3只/100 mg和18.9只/100 mg(t=3.622,P=0.001),回收成虫数分别为17.6条/鼠和25.1条/鼠(t=3.153,P=0.004),组织中虫卵数分别为30 932只/对成虫和53 903只/对成虫(t=3.865,P=0.001),肝脏虫卵数分别为12 307只/对成虫和26 363只/对成虫(t=4.388,P0.01),肠组织中虫卵数分别为18 625个/对成虫和27 541个/对成虫(t=2.679,P=0.012);湖南敏感株和抗性株雌雄合抱虫体长度(t=0.853,P=0.397)、雌虫体长(t=0.573,P=0.569)及雄虫体长(t=0.742,P=0.461)差异均无统计学意义。结论日本血吸虫吡喹酮抗性株产卵量和肝组织虫卵沉积量均明显高于敏感株,提示其对终宿主的致病性更强;抗性株感染鼠粪便中排出虫卵数明显多于敏感株,提示抗性株的传播能量高于敏感株。     

吡喹酮治疗血吸虫病肝纤维化的实验研究

目的观察吡喹酮对血吸虫病肝纤维化的治疗作用。方法将小鼠随机分为正常对照组、模型组、吡喹酮组。模型组、吡喹酮组小鼠经腹部皮肤感染日本血吸虫尾蚴诱导肝纤维化模型,吡喹酮组于感染8周后灌胃吡喹酮治疗2次。16周末测小鼠血清中ALT、AST;观察小鼠肝脏形态,HE染色观察肝纤维化病理组织变化,测定虫卵肉芽肿面积;免疫组化测定肝脏Ⅰ和Ⅲ型胶原表达。结果吡喹酮治疗可降低血吸虫病肝纤维化小鼠肝脏指数及血清ALT、AST,改善肝组织形态结构,降低肝脏Ⅰ和Ⅲ型胶原表达及虫卵肉芽肿面积。结论吡喹酮对血吸虫病肝纤维化有明显治疗作用。     

血吸虫对吡喹酮抗药性的研究Ⅵ吡喹酮对曼氏血吸虫吡喹酮抗性株和敏感株虫卵肉芽肿形成的影响

目的 体内比较吡喹酮对曼氏血吸虫吡喹酮抗性株与敏感株肝脏虫卵肉芽肿形成的影响。方法 用抗性株与敏感株尾蚴感染小鼠，在感染第58、59、60天每日以200mg／kg微粒化吡喹酮悬液灌胃治疗小鼠，治后35d剖杀小鼠取肝脏做石蜡切片，进行HE染色，显微镜下作病理学观察；以图像分析仪定量测定虫卵肉芽肿的面积。结果 敏感株未治疗组虫卵肉芽肿由大量炎性浸润细胞及少量间质成纤维细胞组成；治疗组则由少量炎性浸润细胞和大量间质成纤维细胞组成；未治疗组肉芽肿的面积明显大于治疗组，两者间差异具有非常显著性。但抗性株治疗组和未治疗组虫卵肉芽肿均由大量炎性浸润细胞和少量间质成纤维细胞组成，两组虫卵肉芽肿的面积间差异无显著性。结论鼠体内吡喹酮的治疗对曼氏血吸虫吡喹酮敏感株和抗性株肝脏虫卵肉芽肿的形成影响作用具有显著差异；在肝组织中，敏感株虫卵对吡喹酮的敏感性高于抗性株。     

日本血吸虫低感染度动物粪便排卵观察北大核心CSCD

目的观察低数量日本血吸虫尾蚴感染实验动物后在其体内存活和粪便排卵状况,为了解低水平流行态势下血吸虫低感染度动物传播能力奠定基础。方法取新鲜逸出的尾蚴2、4、6、8条,分别感染小鼠和家兔,饲养至感染后42d收集小鼠和家兔粪便,连续收集3d,利用浓集法镜检计数每克小鼠粪便虫卵数量(EPG),尼龙袋集卵孵化法观察家兔粪便毛蚴孵化率,以判定粪便中血吸虫卵排出情况。解剖全部实验小鼠与家兔,灌注法收集成虫,计算小鼠和家兔的感染率、体内合抱成虫检获率及虫负荷水平;同时观察小鼠和家兔肝脏表面虫卵结节,并收集家兔血清进行血吸虫抗体检测。结果小鼠感染尾蚴数量为2条时,其感染率、体内合抱成虫检获率、肝脏虫卵结节率和粪便排卵率分别为66.67%、58.33%、58.33%和58.33%,随感染尾蚴数量的增加四者趋于100%,但差异均无统计学意义(χ^(2)值分别为2.455,3.135,3.135和3.135,均P>0.05);小鼠体内平均虫荷和粪便平均EPG随感染尾蚴数量增加而增加(r值分别为0.588和0.533,均P<0.01)。家兔尾蚴感染数量为2条时,其感染率、体内合抱成虫检获率、肝脏虫卵结节率、血检阳性率和粪便孵化阳性率均为40%,除粪便孵化阳性率外(χ^(2)=0.003,P>0.05),其他指标均随感染尾蚴数量的增加趋于100%,差异均有统计学意义(χ^(2)值分别为4.473,4.473,4.473和6.758,P<0.05或P<0.01);随着感染尾蚴数量的增加,家兔体内虫荷增加(r=0.421,P<0.01)。结论感染一对日本血吸虫的小鼠和家兔即可检测到粪便排卵,提示小型适宜哺乳动物宿主传病能力强,应加强监测与控制,消除潜在的传染源隐患。     

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.     

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.     

N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis： Randomized,placebo-controlled pilot study

AIM： To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine （NAC） co-administration with mesalamine in ulcerative colitis （UC） patients.
METHODS： Thirty seven patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine （2.4 g/d） plus N-acetyl-L-cysteine （0.8 g/d） （group A） or mesalamine plus placebo （group B）. Patients were monitored using the Modified Truelove-Witts Severity Index （MTWSI）. The primary endpoint was clinical remission （MTWSI ≤ 2） at 4 wk. Secondary endpoints were clinical response （defined as a reduction from baseline in the MTWSI of ≥ 2 points） and drug safety. The serum TNF-α, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment. RESULTS： Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyl-L-cysteine （group A） and mesalamine plus placebo （group B） respectively （OR = 1.71; 95% CI： 0.46 to 6.36; P = 0.19; NNT = 7.7）. Analysis of variance （ANOVA） of data indicated a significant reduction of MTWSI in group A （P = 0.046） with respect to basal condition without significant changes in the group B （P = 0.735） during treatment. Clinical responses were 66% （group A） vs 44% （group B） after 4 wk of treatment （OR = 2.5; 95% CI： 0.64 to 9.65; P = 0.11; NNT = 4.5）. Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups.
CONCLUSION： In group A （oral NAC combined with mesalamine） contrarily to group B （mesalamine alone）, the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects.     

Delorme's transrectal excision for internal rectal prolapse

Surgical therapy of functional outlet obstruction in patients with internal rectal intussusception may include abdominal, perineal, or transrectal procedures. Because abdominal procedures often result in significant physiologic impact but unrelieved constipation, the authors have elected Delorme's transrectal excision for management of these patients. Since a short-term placebo effect attends many therapies, this report describes results of transrectal excision only after a threeyear postoperative period. Delorme's transrectal excision of internal intussusception accomplished sustained symptomatic relief in over 70 percent of otherwise refractory constipated patients. The association of internal intussusception with other abnormalities underscores the importance of defining both anatomic and functional components when selecting patients whose constipation may require surgical therapy. Critical technical elements, surgical pitfalls, and potential complications of the procedure are discussed.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Toronto, Canada, June 11 to 16, 1989.     

The oral glucose tolerance test: A comparison of the time points on the basis of limit values,normal dispersion,and reproducibility

Summary Time points in the glucose tolerance test (GTT) are compared on the basis of limit values, dispersion within a reference population, and reproducibility. We suggest using the distance between a limit value and the median reference value as a measure of the magnitude of abnormality. The distance between 140 mg/100 ml and the median fasting plasma glucose value is chosen as a standard distance and limits for other points in the GTT are calculated to equal this standard distance of abnormality. We suggest that the probability of correctly interpreting an inividual result is directly related to the reproducibility of the test and inversely related to the percentage of the total range of values which is dispersed among the normal population. The ratio of reproducibility to percentage normal dispersion is proposed as an index of the probability of correctly interpreting an individual result. According to this index, the probability of correct interpretation varies in order: fasting plasma glucose concentration>3-h>2-h>0.5-h>1-h plasma glucose concentration.