隐孢子虫病的流行与诊断研究进展

隐孢子虫病是一种在世界范围内流行的人兽共患寄生虫病,各种受感染的家畜是其主要传染源,大多数地表水中能检出隐孢子虫卵囊。该病常造成小范围的暴发,是免疫功能低下或免疫功能缺陷患者致死的主要原因之一。目前隐孢子虫的检测技术有了较快的发展,能快速、简便、高效地对临床隐孢子虫病作出诊断,有助于对免疫功能缺陷的隐孢子虫病患者及早治疗。该文对隐孢子虫病的流行与诊断进行了综述。     

我国隐孢子虫病流行现状与防控进展

隐孢子虫(Cryptosporidium spp.)可通过人和动物进行传播进而引发人体隐孢子虫病,是导致全球腹泻最重要的六种病原体之一,对儿童和免疫功能低下人群威胁极大,并可引起突发公共卫生事件。隐孢子虫病目前尚无有效治疗和预防的药物和疫苗,防控难度极大,在世界范围内受到越来越多的关注和重视。为此,本文概述了自1987年我国报道第1例隐孢子虫病病例以来人体隐孢子虫感染情况,并对水源和食物污染、家养动物感染、季节性流行情况等传播风险因素进行了梳理,总结了我国隐孢子虫病的防控进展、面临的挑战以及防治策略等现实问题。现有的调查和研究结果显示,我国的人源性隐孢子虫分布广泛,HIV/AIDS患者、恶性肿瘤患者和吸毒人员等群体均是需要重点关注的易感人群,主要致病虫种包括人隐孢子虫(C.hominis)和微小隐孢子虫(C.parvum)。考虑到隐孢子虫病的风险因素和防控现状,我国应当在监测网络、防控措施、防治技术、水源净化和健康教育等方面实施综合防控策略,从“寄生虫-人类-保虫宿主-环境”等各个防治环节践行“One Health”理念,从而实现隐孢子虫病的有效监测和控制。     

隐孢子虫动物模型的建立

本文通过饮水给予免疫抑制药和用人源隐孢子虫卵囊感染ＮＩＨ小鼠，建立了隐孢子虫感染小鼠模型。实验结果显示：免疫功能抑制组比正常组易感，两者感染度有显著性差异（Ｐ＜０．０５）。通过动物实验进一步证明免疫功能正常宿主感染隐孢子虫为自限性感染，免疫功能低下或缺陷者感染隐孢子虫可引起严重腹泻甚至死亡。     

隐孢子虫感染模型及体外培养研究进展

隐孢子虫是一种重要的人兽共患寄生原虫,能引起婴幼儿和免疫低下人群及动物以胃肠道腹泻为主的严重消化道疾病。隐孢子虫动物感染模型和体外培养体系的建立,为隐孢子虫的生长发育过程、免疫学、疫苗研究、药物筛选和疗效考核以及卵囊灭活技术提供了良好的基础。本文就近年来隐孢子虫的动物感染模型和体外培养体系的发展及其应用情况作一综述。     

隐孢子虫卵囊3种分离纯化方法的比较

隐孢子虫（cryptos poridium parvum,C,P）是一种引起人类和动物腹泻的重要病原体，日益受到国内外学者的重视。我国于1987年在南京首次发现该病例，此后许多地区陆续有病例报道。隐孢子虫引起的腹泻是艾滋病病人致死的主要原因。隐孢子虫主要寄生于宿主的胃肠道，卵囊随粪便排出体外，易感者经粪口途径感染隐孢子虫后发病。检查粪便中的隐孢子虫卵囊是诊断隐孢子虫病的主要依据，从粪便标本中分离纯化卵囊，是对隐孢子虫进行深入研究的前提。本研究选择3种原虫分离纯化方法，用于隐孢子虫卵囊的分离纯化，并进行了初步比较。     

隐孢子虫病的流行病学研究进展

隐孢子虫是本世纪初由 Tyzzer 首次描述的,但在以后的几十年中未引起人们的注意。七十年代,隐孢子虫引起几起哺乳类动物的肠炎爆发,从而被重新认识。1976年美国首次报道人隐孢子虫病,嗣后,在免疫缺陷患者中发生本病感染。1982年报道几例免疫功能正常的患者。继芬兰、澳大利亚和英国等先后报道本病患者之后,隐孢子虫被公认是引起人类胃肠炎的主要病因之一。目前,隐孢子虫病呈全球性流行,已报道的地区包括五大洲近30个国家。大规模的选择性人群调查表明,发达国家阳性率在0. 6～20%;发展中国家为4～20%。免疫缺陷患者、低年龄组儿童等重点人群中发病率较高。本病具有一定的季节性,以粪-口传播途径为主,有时在人群中暴发流行。本病发生与接触动物与否、生活习惯等有一定的关系。诊断以粪检为主。目前,本病缺乏特效治疗药物。积极阐明发病机制,加紧发展体外培养和诊断技术,掌握流行病学特征和规律,寻找特效药,是当务之急。     

隐隐子虫动物模型的建立

本文通过饮水给予免疫抑制药和用人源隐孢子虫卵囊感染ＮＩＨ小鼠，建立了隐孢子虫感染小鼠模型。实验结果显示：免疫功能抑制组比正常组易感，两者感染度有显著性差异。通过动物实验进一步证明免疫功能正常宿主感染隐孢子虫为自限性感染，免疫功能低下或缺陷者感染隐孢子虫可引起严重腹泻甚至死亡.     

成都及周边地区5种动物隐孢子虫感染的调查

目的：调查成都及周边地区的猪、羊、鸡、兔等畜禽及猕猴隐孢子虫感染情况。方法：用改良抗酸染色法检查。结果：共采集249份新鲜粪便标本，检查的每种动物中均发现有隐孢子虫感染，而且感染率较高，分别为89．7％、65．3％、41．2％、88．2％及55．0％。通过显微镜下观察初步发现不同粪源的隐孢子虫在形态学上的差异，可为进一步研究不同种株的差异，以及其系统发育关系打下基础。结论：成都及周边地区5种动物均存在隐孢子虫感染。     

几种新现人体隐孢子虫种和基因型流行现状

隐孢子虫是一种寄生于宿主胃肠道上皮细胞内的原虫。人感染后,免疫功能正常者,常引起自限性腹泻;但在高危人群(如儿童、老人和免疫缺陷者等)中可发生严重腹泻和肠外感染,尤其是艾滋病患者。目前,隐孢子虫的分子流行病学研究已鉴定了30个有效种和40多种基因型,其中21个隐孢子虫种和基因型在人体发现。人体隐孢子虫病多数由人隐孢子虫(C.hominis)和微小隐孢子虫(C.parvum)引起。火鸡隐孢子虫(C.meleagridis)、泛在隐孢子虫(C.ubiquitum)、猫隐孢子虫(C.felis)和犬隐孢子虫(C.canis)引起的隐孢子虫病例也逐渐增多。除此之外,随着人体隐孢子虫病分子流行病学数据的增加,在人体内鉴定到一些新的隐孢子虫和基因型。特对上述新现的人体隐孢子虫种和基因型的流行现状进行综述。     

安徽省江北地区规模化猪场隐孢子虫感染现状调查

目的 了解安徽省江北地区猪隐孢子虫感染情况。方法 2014年10-12月从安徽省江北多地规模化猪场共采集500份新鲜猪粪样,采用基于隐孢子虫小亚单位核糖体核糖核酸基因（SSUrDNA）的巢式PCR方法进行检测,并对获得的阳性样本SSUrDNA基因进行序列分析以确定隐孢子虫虫种。结果 安徽省江北地区猪隐孢子虫感染率为4.8%（24/500）,其中阳性样本主要分布在潜山（40.0%）和滁州（6.3%）,其他地区猪场未见隐孢子虫感染。SSUrDNA基因序列分析显示,所有隐孢子虫阳性样本均为种母猪隐孢子虫（Cryptosporidium scrofarum）。> 60日龄猪种母猪隐孢子虫感染率（9.1%）高于< 30日龄（1.2%）和30 ~ 60日龄（1.0%）猪（P 均 < 0.01）。结论 安徽省江北地区规模化猪场存在隐孢子虫感染,且发现的种母猪隐孢子虫可能是人和其他动物隐孢子虫感染的来源,存在人兽共患潜在危害,应引起重视。     

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.