3－硝基－1，2，4－三唑类乏氧细胞放射增敏剂的构效关系

为了寻找毒性低、增敏作用强的乏氧细胞放射增敏剂，设计并合成了一系列５－溴－，５－甲基－，和５－未取代的３－硝基－１，２，４－三唑－１－乙酰胺类化合物，用ＨｅＬａＳ３细胞进行了体外试验。结果表明５－溴取代衍生物的增敏作用强于相应的５－甲基－或５－未取代的硝基三唑衍生物，但是它们的毒性亦增大。修饰１位乙酰胺侧链也可以改变化合物的增敏作用和亲脂性。在所测定的化合物中ＴＡ－１０１［２－（３－硝基－１－三唑基）乙酰胺］由于有高的增敏作用和低亲脂性，可能是一个有希望的放射增敏剂。     

灯盏花素对豚鼠单一心室肌细胞ICa的抑制作用

目的：观察灯盏花素对豚鼠单一心室肌细胞钙离子电流（ＩＣａ）的影响。方法：应用全细胞膜片钳制技术。结果：灯盏花素能明显抑制心室肌细胞的Ｃａ＾２＋通道,使ＩＣａ减小。此作用有明显的电压依赖性。在峰电流电压下作用最明显,而对其反转电位无明显影响。在指令电位０ｍＶ时,０．５ｍｇ％灯盏花素使ＩＣａ减小５．４％,１ｍｇ％灯盏花素使ＩＣａ减小２２．９％（Ｐ〈０．０１）,２ｍｇ％灯盏花素使ＩＣａ减小４５．０％（Ｐ     

Determination of malondialdehyde-induced DNA damage in human tissues using an immunoslot blot assay

Malondialdehyde (MDA) is a product of lipid peroxidation and prostaglandin biosynthesis. It is mutagenic and carcinogenic and the major adduct formed by reaction with DNA, a highly fluorescent pyrimidopurinone (M1-dG), has been detected in healthy human liver and leukocyte DNA. Analytical methods used so far for the detection of M1- dG have not been applied to a large number of individuals or variety of samples. Often, only a few microg of DNA from human tissues are available for analysis and a very sensitive assay is needed in order to detect background levels of M1-dG in very small amounts of DNA. In this paper, the development of an immunoslot blot (ISB) assay for the measurement of MI-dG in 1 microg of DNA is described. The limit of detection of the assay is 2.5 adducts per 10(8) bases. A series of human samples were analysed and levels of 5.6-9.5 (n = 8) and 3.1-64.3 (n = 42) of M1-dG per 10(8) normal bases were detected in white blood cell and gastric biopsy DNA, respectively. Results on four human samples were compared with those obtained using an HPLC/32P-post- labelling (HPLC/PPL) method previously developed and indicated a high correlation between M1-dG levels measured by the two assays. The advantages of ISB over other assays including HPLC/PPL, such as the possibility of analysing 1 microg DNA/sample and the fact that it is less time-consuming and laborious, means that it can be more easily used for routine analysis of a large number of samples in biomonitoring studies.      

Detection of human sperm acrosome reaction: comparison between methods using double staining, Pisum sativum agglutinin, concanavalin A and transmission electron microscopy

The acrosome reaction is an important marker for human sperm function. Since different laboratory techniques may be used for the detection of this exocytotic process, the purpose of the present study was to compare three common markers [Pisum sativum agglutinin (PSA), concanavalin A (ConA), double staining] and transmission electron microscopy for identification of acrosomal changes. Preliminary findings had demonstrated that similar results were achieved with Trypan Blue and Hoechst 33258 staining. Therefore, supravital stainings were omitted. In various experiments, human spermatozoa were treated with two concentrations (10 and 3.3 microM) of calcium ionophore A23187 for 15, 30 and 60 min after capacitation for 3 and 6 h at 37 degrees C. The percentages of spermatozoa with acrosomal loss detected by fluorescein isothiocyanate (FITC)-ConA were consistently lower than those obtained by double staining or FITC-PSA, which showed comparable results. Following 6 h of capacitation and incubation with 10 microM ionophore for 1 h at 37 degrees C, 25.9 +/- 15.7% of all spermatozoa showed almost complete loss of the acrosomal content. Binding of FITC- ConA to the acrosomal region was observed in 27.0 +/- 13.2% of spermatozoa obtained from the same sample. FITC-ConA and double staining or FITC-PSA detect different stages of the acrosome reaction and may be helpful for a differentiated evaluation of this sperm function.      

Outcome of criminal investigation into allegations of sexual abuse

The aim was to study the outcome of criminal investigation into allegations of sexual abuse made by 160 children assessed over a two year period in a specialist paediatric unit in the North of England. In all, 141 of the 160 children (88%) were female, and 99 (62%) were aged under 12 years. There were 145 males and nine females named by children in allegations of sexual abuse. Fathers formed the largest single group of alleged male perpetrators (56/176). None of the nine alleged female abusers was prosecuted. Of the 145 males, 57 reached trial; 49 were convicted, an 86% conviction rate of those sent to trial and a rate of proven sexual offence (including cautions) of 44% (54/124) among men originally interviewed by the police. Twenty five per cent of children (17/68) who could have testified did so, most giving evidence against someone who was known to them. Pragmatic selection of cases for prosecution resulted in an outcome highly vindicating of the decision to prosecute. The possible effects of this process are discussed.     

甘油果糖对人RBC、大鼠RBC的作用及输液安全性的研究

目的:探讨甘油果糖注射液(Glycerol and Fructose Injection)对人红细胞(Red blood cell,RBC),大鼠RBC的作用及对大鼠输液安全性的研究,以指导临床应用。方法:以40例健康成人RBC、32只sD大鼠RBC为研究对象,进行体外溶血试验;以72只SD大鼠为研究对象,进行输液安全性研究,研究组为甘油果糖注射液,对照组为生理盐水注射液,应用改良酸化甘油溶解实验测定甘油果糖注射液对人RBC和大鼠RBC的溶解程度,应用邻-甲联苯胺氧化显色法测定甘油果糖注射液对上清液游离血红蛋白(Hemoglbin,HB)含量的影响。同时测定研究组和对照组大鼠血浆游离HB、蛋白非结合胆红素(间接胆红素)、尿素氮(Blood urea nitrogen,BUN)、肌酐的含量,以对甘油果糖注射液安全性进行研究。结果:体外试验为甘油果糖注射液对人RBC和大鼠RBC的溶解程度与生理盐水相似,对上清液游离HB含量无明显影响。对大鼠给予甘油果糖注射液和生理盐水,最快输液速度6ml/min和最大输液量30ml/kg/d,24小时后测定大鼠血浆游离HB、蛋白非结合胆红素、BUN、肌酐的含量,两组结果相似。结论:甘油果糖注射液在体外对人RBC和大鼠RBC无明显溶解作用。在大鼠体内也没有发现有溶血作用,对肾脏功能影响与生理盐水相似。     

Evidence from proton magnetic resonance spectroscopy for a metabolic cascade of neuronal damage in shaken baby syndrome

OBJECTIVE: The purpose of this study was to use proton magnetic resonance spectroscopy (MRS) as a metabolic assay to describe biochemical changes during the evolution of neuronal injury in infants after shaken baby syndrome (SBS), that explain the disparity between apparent physical injury and the neurological deficit after SBS. METHODOLOGY: Three infants [6 months (A), 5 weeks (B), 7 months (C)] with SBS were examined repeatedly using localized quantitative proton MRS. Examinations were performed on days 7 and 13 (A), on days 1, 3, 5, and 12 (B), and on days 7 and 19 (C) posttrauma. Long-term follow-up examinations were performed 5 months posttrauma (A) and 4.6 months posttrauma (B). Data were compared to control data from 52 neurologically normal infants presented in a previous study. RESULTS: Spectra from parietal white matter obtained at approximately the same time after injury (5 to 7 days) showed markedly different patterns of abnormality. Infant A shows near normal levels of the neuronal marker N-acetyl aspartate, creatine, and phosphocreatine, although infant C shows absent N-acetyl aspartate, almost absent creatine and phosphocreatine, and a great excess of lactate/lipid and lipid. Analysis of the time course in infant B appears to connect these variations as markers of the severity of head injury suffered in the abuse, indicating a progression of biochemical abnormality. The principal cerebral metabolites detected by MRS that remain normal up to 24 hours fall precipitately to approximately 40% of normal within 5 to 12 days, with lactate/lipid and lipid levels more than doubling concentration between days 5 and 12. CONCLUSIONS: A strong impression is gained of MRS as a prognostic marker because infant A recovered although infants B and C remained in a state consistent with compromised neurological capacity. Loss of integrity of the proton MR spectrum appears to signal irreversible neurological damage and occurs at a time when clinical and neurological status gives no indication of long-term outcome. These results suggest the value of sequential MRS in the management of SBS.     

Solitary epidermolytic acanthoma: a clinical and histopathological study

Background Epidermolytic acanthoma (EA) is an uncommon cutaneous entity that typically presents as a solitary lesion, or, less commonly, as multiple or disseminated discrete lesions. It usually appears at or after middle‐age, and has been reported in various locations including the face, trunk, extremities and genitalia. Histopathologically, EA shows epidermolytic hyperkeratosis (EHK) involving either the entire thickness of the epidermis or just the granular and upper spinous layers. Objective and methods To describe the clinical and microscopic features of EA, we retrospectively reviewed all cases diagnosed as EA at the Skin Pathology Laboratory at Boston University between 1999 and 2009. Results Solitary EA is more common in men (65%) and usually presents as a hyperkeratotic papule on the trunk (45%) or extremities (25%). Histopathologically, all cases of solitary EA showed the classical features of hyperkeratosis, acanthosis and EHK. Three architectural patterns were observed on scanning magnification: papillomatous (55%), cup‐shaped (40%) and acanthotic (15%). Additional common features encountered included focal parakeratosis (85%), and a sparse to mild superficial perivascular lymphocytic infiltrate (90%). Conclusion This large case series of solitary EA reviews the clinical features of this entity and describes several new histological variants.     

Whiplash headache is transitory worsening of a pre-existing primary headache

Acute and chronic whiplash headache are new diagnostic entities in the ICHD-2 (5.3, 5.4). In a prospective cohort study, 210 rear-end collision victims were identified consecutively from police records and asked about head and neck pain in questionnaires after 2 weeks, 3 months and 1 year. The results were compared with those of matched controls who were also followed for 1 year. Of 210 accident victims, 75 developed headache within 7 days. Of these, 37 had also neck pain and complied with the criteria for acute whiplash headache. These 37 had the same headache diagnoses, headache features, accompanying symptoms and long-term prognosis as the 38 without initial neck pain who therefore did not comply with the acute whiplash headache diagnosis. Previous headache was a major risk factor for headache both in the acute and chronic stage. Compared with the non-traumatized controls, headache in the whiplash group had the same prevalence, the same diagnoses and characteristic features, and the same prognosis. Both acute and chronic whiplash headache lack specificity compared with the headache in a control group, and have the same long-term prognosis, indicating that such headaches are primary headaches, probably elicited by the stress of the situation.