血管内皮细胞增生是胃癌相关性病变

目的观察胃癌间质组织中血管内皮细胞(EC)早期病变,探讨血管EC增生性改变在肿瘤发生、发展过程中作用.方法利用手术切除胃癌组织和化学诱发大鼠胃癌,观察血管结构特征并用抗人和抗鼠免疫组化进行标记.结果肿瘤间带血管EC明显增生,约占血管总数的60%,这些增生的血管EC,有的形成腺样结构,有的异形和癌变.结论胃癌间质血管EC的病理性改变,是肿瘤发生、发展的重要因素,抗人Ⅷ因子和抗鼠VEGF阳性也说明血管EC增生是肿瘤相关性病变.     

褪黑素抑制四氧嘧啶糖尿病大鼠垂体-肾上腺轴功能

观察褪黑素对以四氧嘧啶诱发大鼠糖尿病时垂体-肾上腺轴的影响。结果提示褪黑素对糖尿病模型大鼠的垂体-肾上腺轴有抑制作用，对急性代谢紊乱有保护作用。     

A randomized trial of nicotinamide and vitamin E in children with recent onset type 1 diabetes (IMDIAB IX)

OBJECTIVE: Various adjuvant therapies have been introduced along with intensive insulin therapy in patients with recent onset type 1 diabetes. Nicotinamide (NA), administered at diagnosis of the disease, can have beneficial effects on the clinical remission rate, improve metabolic control and preserve or slightly increase beta-cell function, probably by reducing toxicity due to free oxygen radicals. Vitamin E, a known antioxidant, inhibits lipid peroxidation; this can lead to protection of islet beta cells from the combined effects of interleukin 1, tumor necrosis factor and gamma interferon. The aim of the present study was to investigate whether the addition of vitamin E to NA could improve metabolic control and the residual beta-cell function, as measured by C-peptide secretion, in children and adolescents with recent onset type 1 diabetes; patients were followed-up for 2 years after diagnosis. PATIENTS AND STUDY DESIGN: Recent onset type 1 diabetes patients (n=64, mean age 8.8 years) were recruited by participating centres of the IMDIAB group. Thirty-two patients were randomized to NA (25 mg/kg body weight) plus vitamin E (15 mg/kg body weight); 32 patients acted as controls and received NA only at the same dose as above. Intensive insulin therapy was applied to both treatment groups. RESULTS: There were three drop outs during the 2-year follow-up period. Overall, patients assigned to the NA+vitamin E group or the NA group did not significantly differ in terms of glycated hemoglobin (HbA1c) levels, insulin requirement or baseline C-peptide secretion. Patients diagnosed at an age of less than 9 years showed significantly reduced C-peptide levels compared with those aged over 9 years at diagnosis and at the 2-year follow-up but there were no differences between the NA and NA+vitamin E treated groups. However at 6 months, patients over 9 years of age treated with NA+vitamin E showed significantly higher C-peptide compared with the NA group (P<0.003). In both age groups and in the different treatment groups, C-peptide levels found at diagnosis were preserved 2 years later. CONCLUSIONS: The use of NA alone, or in combination with vitamin E, along with intensive insulin therapy is able to preserve baseline C-peptide secretion for up to 2 years after diagnosis. This finding is of particular interest for pre-pubertal children with type 1 diabetes and has never been reported before.     

Vascular tolerance to nitroglycerin in ascorbate deficiency

AIMS: Nitroglycerin (GTN) acts through release of a nitric oxide (NO)-related activator of soluble guanylate cyclase in vascular smooth muscle. Besides enzymatic GTN bioactivation catalysed by aldehyde dehydrogenase, non-enzymatic reaction of GTN with ascorbate also results in the formation of a bioactive product. Using an established guinea pig model of ascorbate deficiency, we investigated whether endogenous ascorbate contributes to GTN-induced vasodilation. METHODS AND RESULTS: Guinea pigs were fed either standard or ascorbate-free diet for 2 or 4 weeks prior to measuring the GTN response of aortic rings and isolated hearts. The effects of ascorbate on GTN metabolism were studied with purified mitochondrial aldehyde dehydrogenase (ALDH2) and isolated mitochondria. Ascorbate deprivation led to severe scorbutic symptoms and loss of body weight, but had no (2 weeks) or only slight (4 weeks) effects on aortic relaxations to a direct NO donor. The EC(50) of GTN was increased from 0.058 +/- 0.018 to 0.46 +/- 0.066 and 5.5 +/- 0.9 microM after 2 and 4 weeks of ascorbate-free diet, respectively. Similarly, coronary vasodilation to GTN was severely impaired in ascorbate deficiency. The potency of GTN was reduced to a similar extent by ALDH inhibitors in control and ascorbate-deficient blood vessels. Up to 10 mM ascorbate had no effect on GTN metabolism catalysed by purified ALDH2 or liver mitochondria isolated from ascorbate-deficient guinea pigs. CONCLUSION: Our results indicate that prolonged ascorbate deficiency causes tolerance to GTN without affecting NO/cyclic GMP-mediated vasorelaxation.     

脱钙骨联合干细胞移植修复兔股骨缺损

目的:观察骨髓间充质干细胞与脱钙骨复合修复兔股骨的长段骨-骨膜缺损,以及修复负重骨缺损的可行性。方法:实验于2002-09/2003-10在哈尔滨医科大学中心实验室完成。①将24只新西兰大白兔从自体骨髓中分离出骨髓间充质干细胞,将第2代骨髓基质干细胞5×108L-1中加入小牛脱钙骨,轻轻混匀后用注射器抽吸走离心管内6～8mL空气,人为造成管内负压,培养4h,使细胞进入小牛脱钙骨孔隙内,制成骨髓基质干细胞复合物。②制备成兔双侧股骨中段10mm骨-骨膜缺损模型,常规钢板螺钉固定;取其中20只兔右侧股骨缺损处植入复合物作为实验组,左侧股骨缺损处植入小牛脱钙骨作为对照组,空白组不植入任何材料。③在8,12,16和24周各时间点(实验组和对照组各取5只)分别行标本的大体观察和骨密度测试,比较其修复骨缺损的能力。结果:①各组骨缺损修复标本大体观察:实验组8周骨缺损处有部分修复,12,16周骨缺损完全修复,对照组在8周时有少量新骨形成,12,16周植入物部分被新骨代替,骨缺损区塑形差;空白组骨缺损未修复。②实验组、对照组骨标本的骨密度值:8,12和16周时实验组的骨密度值均大于对照组(0.936±0.056比0.618±0.034,1.238±0.024比1.052±0.037,1.605±0.062比1.227±0.047,P<0.05);24周时实验组骨密度与对照组比较,差异无统计学意义(1.635±0.033,1.563±0.112,P>0.05)。结论:骨髓间充质干细胞构建的组织工程骨早期修复骨缺损能力较强,且较单纯小牛脱钙骨成骨量大、迅速,能够对负重骨缺损进行有效的修复。     

哮喘动物模型免疫炎症反应发生验证的要点

目的:了解哮喘免疫炎症反应发生和验证要点,为确保实验的成功打下基础。方法:就哮喘模型制备的动物选择,模型制备的时间,模型制备的方法以及如何评定动物哮喘模型成功作经验性的总结及对国内外对哮喘模型比较经典的认同的方法加以阐述。结果:①选用豚鼠制备哮喘模型,可以很好的观察哮喘发作症状,接受致敏物质后反应程度与其他动物相比较强,能产生I型变态反应。②哮喘模型的制备时间应避开冬天,春夏时节最为合适,制备的哮喘模型炎症反应明显。③1%卵蛋白雾化吸入激发哮喘比较科学。④通过哮喘症状,动物肺功能仪测定肺功能,苏木精伊红病理染色,酶联免疫吸附测定血清IgE水平4种方法做哮喘免疫炎症反应的定性分析。结论:根据不同的研究目的选用相应的动物、恰当的致敏时间,制定稳妥的方法和良好检验手段是确保实验成功的关键。     

自体骨髓单个核细胞移植治疗下肢缺血性疾病中细胞因子的作用

目的:评估自体骨髓单个核细胞移植治疗下肢动脉缺血性疾病中几种细胞因子的作用。方法:实验于2006-09/12在河北医科大学唐山临床学院中心实验室完成。实验材料:日本大耳白兔40只,清洁级,5月龄,体质量2.5～3.0kg,由华北煤炭医学院动物中心提供(合格证为SCXK-2005-0002),采用完全随机设计方法将日本大耳白兔分为4组:对照组、缺血组、磷酸盐缓冲液组、骨髓单个核细胞治疗组,10只/组。实验方法:对照组不作任何干预措施,其他3组建立日本大耳白兔右下肢缺血模型。取右下肢缺血模型制备2周后的兔,分离获取骨髓单个核细胞。缺血组制备右下肢缺血模型后不作其他干预措施。磷酸盐缓冲液组模型制备2周后,用1mL注射器将0.01mol/L磷酸盐缓冲液分15点注射于右下肢股骨中点股内收肌群内。骨髓单个核细胞治疗组模型制备2周后,用1mL注射器将1×109L-1骨髓单个核细胞悬液分15点注射于右下肢股内收肌群内。实验评估:造模后3d切取内收肌组织标本,测量其组织匀浆中血管内皮生长因子、碱性成纤维细胞生长因子、白细胞介素1β的含量;4周后行数字减影血管造影术,术后取右下肢内收肌标本,采用CD34免疫组织化学法检测毛细血管密度,观察下肢血管再生情况。结果:40只日本大耳白兔均进入结果分析。①移植后4周腹主动脉造影检测:骨髓单个核细胞治疗组结扎股动脉处的远端毛细血管生成较明显,血管成网状。缺血组及磷酸盐缓冲液组结扎处远端毛细血管生成不明显。②CD34免疫组织化学方法检测毛细血管密度:对照组平均为16个/×400高倍镜,缺血组和磷酸盐缓冲液组平均为5个/×400高倍镜,治疗组毛平均为20.5个/×400高倍镜。骨髓单个核细胞治疗组肌肉标本毛细血管密度明显高于缺血组和磷酸盐缓冲液组(P<0.05)。③造模后3d检测细胞因子含量:缺血组、磷酸盐缓冲液组、骨髓单个核细胞治疗组的碱性成纤维细胞生长因子含量明显高于对照组[(1.83±0.90),(3.22±2.10),(3.20±1.56),(3.75±1.07)ng/g,P<0.05]。骨髓单个核细胞治疗组白细胞介素1β含量明显高于对照组、缺血组、磷酸盐缓冲液组[(10.87±6.42),(10.74±6.32),(11.80±4.50),(16.73±4.21)ng/g,P<0.05],各组血管内皮生长因子水平差异不明显(P>0.05)。结论:自体骨髓单个核细胞移植治疗缺血性疾病过程中,白细胞介素1β对毛细血管的生成起主要作用。     

Effect of submucosal injection of dexamethasone on postoperative discomfort after third molar surgery: a prospective study.

PURPOSE: The purpose of this study was to evaluate the effect of submucosal administration of dexamethasone sodium phosphate on discomfort after mandibular third molar surgery. PATIENTS AND METHODS: Sixty-one consecutive patients requiring surgical removal of a single mandibular impacted third molar under local anesthesia were randomly placed into 3 groups. After the onset of local anesthesia, the experimental groups received dexamethasone at 2 different doses (4 or 8 mg) as submucosal injection, and the control group received no drug. Standardized surgical and analgesic protocols were followed. Maximum interincisal distance and facial contours were measured at baseline and at postsurgery days 2 and 7. Pain was objectively measured by counting the number of analgesic tablets required. The patients' perception of the severity of symptoms was assessed with a follow-up questionnaire (PoSSe scale). RESULTS: On the second postoperative day, facial edema showed a statistically significant reduction in both dexamethasone 4-mg and dexamethasone 8-mg groups compared with the control group, but no statistically significant differences were observed between the 2 dosage regimens of dexamethasone. By contrast, there was no statistically significant difference between all groups when postoperative swelling was evaluated at day 7 (P > .50). The treatment group had a limited and nonsignificant effect on pain and trismus when compared with the control group at the 2 times of evaluation. CONCLUSIONS: Parenteral use of dexamethasone 4 mg, given as an intraoral injection at the time of surgery, is effective in the prevention of postoperative edema. Increasing the dose to 8 mg provides no further benefit.