预防日本血吸虫尾蚴感染新药——紫香驱蚴灵对实验动物毒性的研究

紫香驱蚴灵是预防日本血吸虫尾蚴感染的新型皮肤外用药。经毒性试验研究证实，大鼠口服ＬＤ５０为２６３６（２２０７—３１４８）ｍｇ／ｋｇ，皮肤给药的ＬＤ５０＞５３２５ｍｇ／ｋｇ。家兔皮肤敷药部位未见红斑和水肿，豚鼠皮肤过敏试验，未见过敏反应，表明紫香驱蚴灵属低毒类、无刺激性、弱致敏性物质，局部皮肤外用是较安全的     

乙肝消毒液的皮肤刺激与皮肤过敏试验

本文报告乙肝消毒液对家免皮肤的刺激试验及对豚鼠皮肤的过敏试验。结果表明，家兔皮肤对乙肝消毒液无刺激反应；豚鼠皮肤对乙肝消毒液无过敏反应。     

龙血竭栓对兔直肠破损黏膜刺激性和对豚鼠皮肤致敏性实验

目的:观察龙血竭栓的刺激性与致敏性。方法:以龙血竭栓对新西兰兔直肠破损黏膜单次及多次给药,观察其对兔直肠破损黏膜的刺激性;采用Buehler法对豚鼠皮肤给药,观察龙血竭栓对其致敏性。结果:新西兰兔直肠破损黏膜单次和多次给药,各剂量组动物给药后未见疼痛症状,粪便未见明显异常,肛门区域和肛门括约肌局部组织未见充血、水肿等现象,直肠破损黏膜未发现药物相关的明显组织病理学改变。Buehler实验龙血竭栓组动物过敏反应发生率为0%,实验期间未见任何过敏性反应症状。结论:龙血竭栓对兔直肠破损黏膜无刺激性,对豚鼠无致敏作用。     

中药克菌宁洗剂毒性试验研究

克菌宁治疗妇科疾病有肯定疗效,杀菌力强,不产生耐药性等特点。非临床安全性试验证实,小鼠灌胃最大耐受量187.5克原生药、是临床用药的375倍,对家兔完整和破损皮肤无刺激反应。对豚鼠皮肤无致敏作用。每公斤体重25克原生药可使家兔阴道粘膜组织     

舒肤软膏对皮肤刺激性及致敏作用

目的:观察舒肤软膏对皮肤是否有刺激作用及致敏作用。方法:采用豚鼠,用药物反复致敏接触皮肤,末次致敏后14天进行攻击,0小时、24小时、48小时、72小时观察皮肤有无红斑、水肿现象,并计算致敏率;采用家兔进行皮肤刺激试验,用同体完整皮肤和破损皮肤对照法观察舒肤软膏对皮肤的刺激作用。结果:舒肤软膏组豚鼠皮肤致敏率为0;家兔完整皮肤组、破损皮肤组接触舒肤软膏后不同时间均未见异常反应。结论:舒肤软膏无皮肤致敏反应和皮肤刺激性反应,局部应用较安全。舒肤软膏对皮肤刺激性及致敏作用@李晓冰$泸州医学院药理教研室 @刘剑$泸州医学院药…     

重组鼠疫组分疫苗毒理学研究

目的研究重组鼠疫组分疫苗的毒理学作用以评价其安全性,为进一步临床研究提供实验依据。 方法对重组鼠疫组分疫苗进行急性毒性试验,将疫苗1次给予小鼠后,观察所产生的毒性反应和死亡情况,及小鼠对该药物的最大耐受量。分别进行小鼠和豚鼠的异常毒性试验,观察动物有无异常反应,7d后每只动物体重变化。进行家兔的局部刺激试验,注射给药后对动物和注射部位进行肉眼观察,取注射局部皮肤组织进行病理检查。进行豚鼠的全身过敏试验,将致敏的动物静脉快速注射攻击,观察豚鼠有无过敏症状。 结果2种浓度疫苗经腹腔和皮下2种途径注射小鼠,均未引起小鼠的异常症状和死亡,小鼠对重组鼠疫组分疫苗的最大耐受量大于10000μg／kg。小鼠和豚鼠的异常毒性试验表明,注射后7d每组动物均全部健存、无异常反应,且7d后每只动物体重均有增加,均符合2005年版《中华人民共和国药典》三部要求。局部刺激试验中疫苗对家兔注射局部皮肤未引起明显的组织病理学改变。全身过敏试验未出现任何异常反应。 结论重组鼠疫组分疫苗的急性毒性试验、异常毒性试验、局部刺激试验和全身过敏试验毒理学实验结果显示,重组鼠疫组分疫苗用皮下注射的途径进行免疫是安全的。     

温敏型阴道酸缓冲原位凝胶的制备与质量评价

制备了一种具有温度敏感特性的凝胶体系,室温下为液体,体温时变为半固体凝胶。这种液体—凝胶转变的响应速率迅速,使其易于铺展、附着在阴道壁和子宫颈上,与阴道壁及子宫颈充分接触,同时便于在阴道内滞留。酸缓冲体系的建立,可保持阴道的pH值在3.5~4.5之间,由此恢复和维持正常的阴道酸性环境。家兔阴道给药无明显的全身及局部的毒性反应,家兔阴道也无刺激性反应。本品对多数细菌具有抑制作用,对皮肤无致敏作用,同时还有一定的杀精子作用。     

注射用Rtnf的全身过敏性和血管局部刺激性作用研究

目的:观察Rtnf是否具有血管刺激作用、全身过敏反应,评价其注射用药的安全性。方法:通过家兔耳缘静脉刺激实验、豚鼠全身主动过敏实验(ASA)观察注射用药Rtnf的安全性。结果:注射用Rtnf对家兔血管内皮无损伤和刺激作用,病理切片观察,耳廓皮肤的表皮和真皮各结构完好,未见变性、坏死、缺失,表皮下乳头层及网织层无炎细胞渗出、无出血,血管内无血栓形成,附件结构正常;豚鼠未出现过敏现象。结论:在本次实验条件下,注射用Rtnf溶血性试验符合注射用药安全性要求;无血管刺激作用;对豚鼠不致敏。     

痛立舒口服液动物毒理学研究

目的：研究痛立舒口服液小白鼠急性毒性和大白鼠60天长期毒性试验。方法：采用小白鼠最大耐受量测定法和长期毒性试验进行研究。结果：痛立舒口服液对小鼠灌胃给药的LD50＞189g(生药)kg。大鼠长期毒性试验对动物一般行为活动、体重增长、外周血象、肝肾功能及病理组织学检查等与对照组比较未见明显差异(P＞0.05)。     

国产虫草素(cordycepin)抗小鼠迟发型超敏反应的实验研究

目的：研究国产虫草素抗小鼠迟发型超敏反应的作用及其免疫机理。方法：用2，4-二硝基氯苯（2，4-DNCB）对昆明种小鼠皮肤致敏和诱发，制成迟发型超敏反应模型。以国产虫草素溶液作为实验组，分为两个剂量组（实验组1：12mg／kg；实验组2：16mg／kg），以生理盐水作为阴性对照组，所有溶液均为间隔24小时（最后一次间隔为4小时）重复腹腔注射给药。计算激发后各组小鼠左右耳耳廓肿胀厚度差、耳廓增重值及肿胀度，进行统计分析。并经过HE染色观察虫草素对小鼠致炎耳炎症病理变化及脾脏病理变化的影响。结果：两种给药剂量的国产虫草素溶液对模型鼠红斑，水肿。渗出的接触性皮炎损害有明显抑制作用，可减轻由于充血、水肿等炎症反应导致的局部皮损增厚及重量的增加。与生理盐水对照组相比。两实验组虫草素溶液的抗炎作用均有显著性差异（厚度差：P〈0．0001；肿胀度：P〈0．05）；两实验组间的抗炎作用也有显著性差异（厚度差及肿胀度均为P〈0．05），且与给药剂量相关。三组小鼠脾指数未见明显差异（P〉0．05），脾脏组织病理变化未见明显差异。结论：虫草素以24小时间隔（最后一次给药间隔为4小时）经腹腔注射后，可能通过其免疫调节作用对迟发型超敏反应引起的小鼠接触性皮炎发挥明显的抑制效应，该效应与给药剂量相关，同时对脾脏组织未见明显毒性作用。     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

What will studies of Fulani individuals naturally exposed to malaria teach us about protective immunity to malaria?

There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.     

The universal muscular chamber. A basic unit of the genitourinary, cardiovascular, gastro-intestinal, skeletal, cutaneous, respiratory and other systems, endocameral hypertension; and spasm, the key to their idiopathic diseases and arthropathies

Starting with the integument, we see many organs are contractile sacs or multiples thereof, which tubes or bags constitute the major part of the entire body. Recognition of this basic unit and its characteristics sheds new light, individually and collectively, on many disorders previously considered unrelated. Muscular tears and perforations develop in the walls of these chambers, being no way peculiar to those organs, wherein, hydrochloric acid occurs. So, it is not necessary to explain the absence of excessive acid from patients who exhibit holes in the gastric, uterine, aortic, duodenal, rectal, pulmonary, retina, and other walls. Muscle, not acid is the great common factor relating idiopathic disorders in the gastrointestinal tract to each other and to similar diseases in other systems. When the units are linked together, the lesions tend to appear as arthropathies, i.e. at the joints. Rephrasing common-place observations, frees us from conventional, conceptual cul-de-sacs. An observation is only as good as its interpretation, so all possibilities must be considered, otherwise, we will remain blinded by our misconceptions.