细胞间黏附分子-1在实验性自身免疫性脑脊髓炎大鼠中表达的动态变化及作用

目的探讨细胞间黏附分子-1(ICAM-1)在实验性自身免疫性脑脊髓炎(EAE)大鼠中表达的动态变化及其作用。方法分别取免疫后第4、6、8、10、12、14、16、18、20天EAE大鼠脑和脊髓制成石蜡切片,行HE染色和ICAM-1半定量免疫组化分析。结果免疫后第8天ICAM-1表达即出现明显上调,早于临床症状的发生;随免疫后时间的延长,ICAM-1表达呈逐渐增高后缓慢下降的变化趋势,并且与EAE大鼠病情评分呈显著正相关(r=0.57,P=0.003)。结论ICAM-1的表达上调可能在EAE发病中具重要作用。     

生物衍生骨-WO-1药物缓释系统结构特征和体外药物释放的研究

目的制备生物衍生骨-WO-1药物缓释系统,对其理化性质和WO-1的体外释放情况进行评价。方法采用PluronicF-127负载WO-1制作生物衍生骨-WO-1药物缓释系统。扫描电镜观察生物衍生骨及生物衍生骨-WO-1药物缓释系统形貌特征,测量其孔径和孔隙率;应用X线衍射分析仪和X线能量散射分析仪对其成分进行分析;应用高效液相色谱分析仪评价WO-1在双蒸水中1~7d的药物释放情况。结果生物衍生骨具有天然的网状孔隙结构,孔隙间互相连通;生物衍生骨-WO-1药物缓释系统也具有互相连通的网状孔隙结构,孔径和孔隙率分别为522.43±16.75μm和55%,低于生物衍生骨的孔径623.67±12.31μm和孔隙率75%。生物衍生骨-WO-1药物缓释系统主要成分为羟基磷灰石,钙/磷比为1.54;生物衍生骨钙/磷比为1.77。药物释放实验生物衍生骨-WO-1药物缓释系统1d表现为爆发释放,溶液浓度为4.6μg/ml,此后可连续释放6d,浓度维持在0.2~0.8μg/ml。结论生物衍生骨-WO-1药物缓释系统可望成为一种更佳的骨组织工程支架材料,有待于进一步进行体内研究。     

A presenilin 1 mutation (L420R) in a family with early onset Alzheimer disease,seizures and cotton wool plaques,but not spastic paraparesis

Over 100 mutations in the presenilin‐1 gene (PSEN1) have been shown to result in familial early onset Alzheimer disease (EOAD), but only a relatively few give rise to plaques with an appearance like cotton wool (CWP) and/or spastic paraparesis (SP). A family with EOAD, seizures and CWP was investigated by neuropathological study and DNA sequencing of the PSEN1 gene. Aβ was identified in leptomeningeal vessels and in cerebral plaques. A single point mutation, p.L420R (g.1508T > G) that gives rise to a missense mutation in the eighth transmembrane (TM8) domain of PS1 was identified in two affected members of the family. p.L420R (g.1508T > G) is the mutation responsible for EOAD, seizures and CWP without SP in this family.     

血管内皮生长因子及炎性因子在油酸性犬急性呼吸窘迫综合征中的变化

目的探讨油酸性急性呼吸窘迫综合征（ARDS）beagle犬血浆及肺泡灌洗液血管内皮生长因子（VEGF）、可溶性细胞间黏附分子-1（ICAM-1）、白细胞介素-8（IL-8）、肿瘤坏死因子-α（TNF—α）水平的改变。方法12只英国纯种beagle犬，静脉注射油酸0．15mL／kg，在注射油酸前、后1h，出现ARDS的典型表现时，抽血测VEGF、sICAM-1、IL-8、TNF—α，并对此时相作肺泡灌洗液VEGF、sICAM—1、IL-8、TNF-α的测定。结果beagle犬静脉注射油酸后1h血浆TNF—α升高（P〈0．05），血浆反肺泡灌洗液IL8、sICAM-1和VEGF在1h较油酸前没有明显变化（P〉0．05），beagle犬油酸型ARDS模型建立后血浆及肺泡灌洗液VECF、sICAM-1、IL-8、TNF—α均显著高于建模前（P〈0．05）。结论VEGF、sICAM-1、IL-8、TNF～α在beagle犬油酸型ARDS发生发展过程中可能均起重要作用，其水平的高低可能与ARDS严重程度及预后有关。     

针对MAGE-1基因RNAi在恶性胶质瘤SHG-44细胞中的作用研究

目的构建抑制黑色素瘤抗原-1(MAGE-1)的siRNA表达载体,鉴定其在人恶性胶质瘤细胞系SHG-44细胞中对MAGE-1基因表达的干涉作用。方法化学合成2对编码短发夹RNA序列的靶向MAGE-1基因寡核苷酸链,克隆到经BglⅡ、HindⅢ双酶切的pSUPER载体上,重组构建RNA干涉(RNAi)质粒载体。利用逆转录多聚酶链反应(RT-PCR)、流式细胞术和荧光显微镜,检测经稳定转染后SHG-44细胞中MAGE-1的表达,以了解siRNA的干扰效果。结果重组构建的pSUPER-MAGE-1载体经双酶切电泳及插入基因片段序列分析,表明寡核苷酸链成功插入到预计位点,并且序列与预期完全一致。稳定转染后G418筛选出的SHG-44多克隆细胞MAGE-1的表达经RT-PCR、流式细胞术和荧光显微镜检测,2对siRNA均有较明显的干涉作用。结论成功构建了针对MAGE-1基因的siRNA表达载体,抑制SHG-44细胞中的MAGE-1分子的表达。     

Economic Issues in the Treatment of BPH

The long-term cost of effective management for benign prostatic hyperplasia (BPH) remains an important issue in pharmacoeconomics because about 25% of men aged 50 yr and older experience voiding problems due to BPH. With the ageing population and the increase in the percentage of patients with BPH for whom any type of treatment can be considered, a substantial increase in total costs to society can be expected. The up-front costs of interventional approaches to BPH are being replaced by a pattern of long-term medical and preventive therapy. The age-adjusted rate of transurethral resection of the prostate (TURP) reached a high point in 1987 and TURP rates, but not costs, have been in decline ever since. Mean 1-yr treatment costs (medical therapy and TURP) have been estimated in a pan-European study to be 858 Euros per patient, 75% of which were medication costs. Using a 2-yr time frame for treatment, Medicare costs for finasteride, terazosin, and TURP have been estimated as $3874, $2161, and $1820, respectively. The available models of the total long-term cost for all therapies for BPH remain compromised by a lack of inclusion of indirect costs, the lack of true long-term data and, critically, the lack of human cost information (patient preference). Only medical therapy provides a preventive as well as symptomatic potential and, if all of the issues were fully incorporated, it is likely that medical therapy would be increasingly recognised as economically preferable.     

脑出血后IGF-1在脑组织中的表达及其对细胞凋亡的影响

目的研究胰岛素样生长因子-1（IGF-1）在实验性大鼠脑出血后脑组织中的表达厦其对细胞凋亡的影响。方法应用立体定向技术，将自体未抗凝血注入大鼠基底节区以制备脑出血模型；将动物分为正常对照组、实验组厦干预组，分别在不同时间断头取脑以制作标本，连续切片分别作IGF-1阳性细胞免疫组化染色及TUNEL染色。结果脑出血后2h血肿周围脑组织表达IGF-1，24h达表达高峰，7d时恢复正常；TUNEL染色阳性细胞于脑出血后8h开始出现，3d时达高峰，7d时仍有表达；给予外源性IGF-1后，凋亡细胞显著减少，与同时点实验组相比，差别有显著性。结论脑出血后IGF-1可抑制细胞凋亡的发生，从而减轻脑出血后继发性脑损伤。     

Cause-specific and total mortality in the Canterbury (New Zealand) insulin-treated Diabetic Registry population: a 15-year follow-up study.

AIMS: To establish all-cause and cause-specific death rates, and risk factors for mortality in insulin-treated diabetic individuals living in the province of Canterbury, New Zealand. METHODS: Insulin-treated diabetic subjects (n = 995) on the Canterbury Diabetes Registry were followed up over 15 years and vital status determined. Death rates were standardized and hazard regression was used to model the effects of demographic covariates on relative survival time. RESULTS: There were 419 deaths in 11 226.3 person-years of follow-up with a standardized mortality ratio (SMR) of 2.0 (95% confidence interval (CI) 1.8-2.2). Relative mortality was greatest for the group aged 0-29 years (SMR 3.0 (95% CI 2.4-3.7)). After controlling for diabetes duration and gender, a 10-year increment in age of onset was associated with a 33% decrease in relative hazard (95% CI 29-36%), indicating that excess mortality due to diabetes declines with rising age of onset. After controlling for age of onset and gender, each 10-year increment in duration of diabetes is associated with a 26% decrease in relative hazard (95% CI 24-29%), indicating that with longer survival the mortality hazard approaches the general population hazard. Relative mortalities were increased for cardiovascular, renal and respiratory disease, but not malignancy. Relative mortality from acute metabolic complications was increased in the subgroup with age of onset of diabetes < 30 years and requiring insulin within 1 year of diagnosis. CONCLUSIONS: Mortality rates are high for insulin-treated diabetic individuals relative to the general population.     

PINK1 mutations in sporadic early-onset Parkinson's disease.

Pathogenic PINK1 mutations have been described in PARK6-linked Parkinson's disease (PD) patients of Asian origin. However, data on the frequency of PINK1 mutations in sporadic early-onset Parkinson's disease (EOPD) Asian patients are lacking. The objectives of this study were to report the frequency of PINK1 mutations of sporadic EOPD in an Asian cohort comprising of ethnic Chinese, Malays, and Indians, and to highlight a PINK1-positive patient who presented with restless legs symptoms. Eighty consecutive sporadic EOPD patients from the movement disorder clinics of two major tertiary institutions in the country were included. We performed sequence analysis of all the coding and exon-intron junctions of the PINK1 using specific primer sets. In addition, we genotyped polymorphisms detected from the analysis in a group of sporadic PD patients and controls. Three different mutations (two homozygous nonsense and one heterozygous missense) in the putative kinase domain were found in three patients, giving a 3.7% frequency of PINK1 mutations in our EOPD cohort. All the mutations were absent in 200 healthy controls. One patient with a novel homozygous nonsense PINK1 mutation presented unusually with restless legs symptoms. Separately, analysis of the frequency of four PINK1 polymorphisms in a group of sporadic PD and controls did not reveal any significant differences. We highlight a 3.7% frequency of PINK1 mutations in an Asian cohort (ethnic Chinese, Malay, and Indian) of EOPD. The phenotypic spectrum associated with PINK1-positive patients may be wider than previously reported. Polymorphisms of PINK1 do not appear to modulate risk of PD in our population.