Expression of intercellular adhesion molecule 1 (ICAM-1) is reduced in permanent focal cerebral ischemic mouse brain using an adenoviral vector to induce overexpression of interleukin-1 receptor antagonist

Our previous studies have demonstrated that overexpression of recombinant human interleukin-1 receptor antagonist protein (IL-1ra) via gene transfer can reduce ischemic brain injury. However, the mechanism of action of IL-1ra in ischemia is unclear. Since interleukin-1 can up-regulate intercellular adhesion molecules in endothelium, the present study was designed to determine whether overexpression of the IL-1ra can reduce the expression of intercellular adhesion molecule-1 (ICAM-1) after ischemic injury. Normal saline or adenovirus vector (1x109 particles) encoding the human IL-1ra gene (Ad.RSVIL-1ra) or the Escherichia coli LacZ gene (Ad.RSVlacZ) was injected into the right lateral cerebral ventricle of adult CD-1 mice. After five days, permanent middle cerebral artery occlusion (MCAO) was achieved for 24 h using an intraluminal suture. Cerebral blood flow was monitored by transcranial laser Doppler flowmetry to verify the occlusion. ICAM-1 protein was quantified using Western blot analysis and localized using immunohistochemistry. After MCAO, surface blood flow in the ischemic hemisphere was decreased to 9-11% of the baseline. There were fewer ICAM-1 positive vessels in the ischemic cortex of the Ad.RSVIL-1ra transfected mice than in the Ad.RSVlacZ transfected and saline treated mice (138+/-19 vs. 249+/-25, 284+/-22, p<0.05). Western blot analysis shows that ICAM-1 protein decreased 50-60% in the Ad. RSVIL-1ra group compared to the other two groups. There were no significant differences in the numbers of positive vessels in the ischemic basal ganglia and contralateral hemisphere among the three groups. Our studies suggest that IL-1ra overexpression can down-regulate the expression of ICAM-1 in the ipsilateral cortex in ischemic mice. Interleukin-1 may play an important role in the activation of inflammatory reaction during focal cerebral ischemia by promoting leukocyte adhesion on the endothelium cells.     

Update on sequential isologous rat organ transplantation: pancreaticoduodenal and kidney transplantations

This periodic report includes intermittent results of consecutive pancreaticoduodenal (Pd) and kidney (Kt) transplants in inbred rats and results on double kidney transplants that did not follow sequential transplant protocol. Eight 24-month-old Lewis pancreas, kidney, and aorta served histological controls showing normal histological architecture with no atherosclerosis developed in the aorta. Thirty-four month old pancreas and thirty-two month old kidneys, which resided in young hosts for at least three occasions, appeared as youthful Pd and Kt grafts. They show normal histological appearance for more than the expected life span of a Lewis rat. The fact that not only pancreases but also kidneys outlived their host leads to the study of other different organs' viability as aged valuable grafts. Nevertheless, the threats by the development of atherosclerosis in graft-associated aortas resulted in slow progression of the follow-ups.     

Immunization with a LEAPS heteroconjugate containing a CTL epitope and a peptide from beta-2-microglobulin elicits a protective and DTH response to herpes simplex virus type 1

A ligand epitope antigen presentation system (LEAPS) heteroconjugate vaccine containing a CTL epitope (H1) from the HSV-1 immediate early protein ICP27 (322-332) and a peptide sequence (J) from beta-2-microglobulin (35-50) elicited protection from intraperitoneal viral challenge and promoted DTH responses. The H1 peptide and other H1 containing heteroconjugates did not elicit protection or DTH responses. Antibody to the H1 peptide could not be detected by ELISA following vaccination with peptide, heteroconjugate or natural infection. The LEAPS heteroconjugate appears to prime a Thl-like response which is subsequently boosted by infection. These studies show that attachment of the J peptide can make a CTL epitope into a vaccine which is immunogenic and promotes a protective Th1 type of response.     

电针对去势大鼠外周血淋巴细胞雌激素受体影响的研究

目的　从生殖内分泌 -免疫网络角度探讨电针治疗围绝经期综合征的作用机制。方法　以去势大鼠为实验对象 ,取双侧三阴交、太溪、后三里穴 ,采用放射免疫法和流式细胞分析技术 ,观察电针治疗对去势大鼠血清雌激素 (E2 )、促黄体生成素 (LH)、促卵泡生成素(FSH)及外周血淋巴细胞内雌激素受体 (ER)水平的影响。结果　电针可使去势大鼠血清E2 明显升高 ,LH及FSH明显下降 ,外周血淋巴细胞内ER明显升高 ,与造模组比较有显著性差异。结论　电针可明显改善去势大鼠的生殖内分泌功能 ,并能调节免疫细胞的雌激素受体表达。     

珍珠七十丸对SHRsp脑卒中及高血压防治作用的研究

目的 :研究珍珠七十丸对卒中型自发性高血压大鼠 (SHRsp)血压、体重、脑卒中及生存率的影响。 方法 :8周龄SHRsp按血压水平随机分为 3组 ,即对照组、珍珠七十丸预防组与治疗组 ,每组 10只 ,其中预防组于分组后灌胃给予珍珠七十丸每天 150mg·kg^-1,治疗组于 10周龄开始灌胃给予相同剂量。实验期间每天观察动物饮食、行为活动及存活情况 ,每周称体重 ,每2周测定血压 ,记录SHRsp脑卒中首次发作时间。结果 :珍珠七十丸对遗传性高血压有良好的防治作用 ,治疗组及预防组血压均较同期对照组血压低 (P<0.05或P<0.01)。珍珠七十丸可改善SHRsp动物一般行为活动 ,预防组动物体重持续增加 (P<0.05或P<0.01) ;治疗组动物体重在 14周龄时亦明显大于同期对照组 (P<0 .05)。对照组有 60%动物发生脑卒中 ,其中 20%死亡 ,而预防组及治疗组仅各有 20%动物发生脑卒中 ,且没有动物死亡。结论 :珍珠七十丸具有明显的降压作用 ,对高血压引起的脑卒中也有一定的保护作用。     

中药炮制机理初探

开展中药炮制机理研究，揭示其炮制内涵变化实质，是确定中药饮片最佳炮制工艺，制定饮片质量标准，提高临床治疗疗效，发展炮制学科理论水平的关键。     

1-氨基茚的合成

目的：合成1-氨基茚。方法：以苯丙酰氯为初始原料，经3步反应合成1-氨基茚。由TLC确定每步反应终点。结果：目标化合物结构经MS确证，纯度经GSMS测定达97．8％。结论：该法合成了1-氨基茚，收率达39．2％。     

Metabolism and pharmacokinetics of a dipeptidyl peptidase IV inhibitor in rats, dogs, and monkeys with selective carbamoyl glucuronidation of the primary amine in dogs.

The pharmacokinetics and metabolism of the l-threo isoleucine thiazolidide dipeptidyl peptidase IV inhibitor, di-[2S,3S]-2-amino-3-methyl-pentanoic-1,3-thiazolidine fumarate (ILT-threo) and its allo stereoisomer (ILT-allo) were evaluated in rats, dogs, and monkeys. Both compounds were well absorbed (>80%) in all species, and most of the dose (>60%) was recovered in urine. Metabolites identified in all species included a sulfoxide (M1), a sulfone (M2), and a carbamoyl glucuronide (M3). For both compounds, parent drug had moderate systemic clearance in rats and dogs ( approximately 20-35 ml/min/kg in both species) and lower clearance in monkeys ( approximately 6-9 ml/min/kg). In rats, M1 was present in systemic circulation in concentrations similar to that of parent drug, whereas in dogs and monkeys, exposures to M1 were higher than for parent drug. In dogs, exposures to the sulfoxide metabolite were approximately 2 to 3 times higher after administration of ILT-allo than after administration of ILT-threo. Carbamoyl glucuronidation was an important biotransformation pathway in dogs. Circulating levels of M3 were significant in the dog, and present only in trace levels in rats and monkeys. M3 could be produced in in vitro systems in a NaHCO3 buffer under a CO2-saturated atmosphere and in the presence of UDP-glucuronic acid and alamethicin.     

Treatment of 30 cases of rheumatoid arthritis by needle-warming therapy

取双侧肾俞、足三里和曲池,进行温针,并配合内服中药治疗类风湿性关节炎患者30例,以西药常规治疗30例为对照.治疗3个月后,两组有效率分别为86.7%和60.0%,疗效差异有统计意义(P＜0.05).     

Expression of hepatoma-derived growth factor is a strong prognostic predictor for patients with early-stage non-small-cell lung cancer.

PURPOSE: Hepatoma-derived growth factor (HDGF), which is unrelated to hepatocyte growth factor, can stimulate DNA synthesis and cell proliferation on entering the nucleus. We hypothesize that HDGF plays an important role in biologic behavior of early-stage non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Ninety-eight patients with pathologic stage I NSCLC who underwent curative surgery were studied. Immunohistochemistry was used to determine the expression level of HDGF in the tumor specimens. The intensity of the protein staining and percentage of stained tumor cells were used to determine a labeling index. Statistical analyses, all two-sided, were performed to determine the prognostic effect of HDGF expression levels on clinical parameters and outcomes. RESULTS: The mean +/- standard deviation HDGF labeling index in the 98 tumors was 185 +/- 41. Patients whose tumors had higher HDGF indexes (>/= 185) had a significantly poorer probability of overall survival at 5 years after surgery than did those with lower HDGF indexes (0.26 v 0.82; P <.0001). Similarly, the 5-year disease-specific and disease-free survival probabilities were lower in those with higher HDGF indexes (0.42 v 0.92, and 0.34 v 0.71; P <.0001 and P =.0008; respectively). Multivariate analysis indicated that HDGF level was an independent predictor of overall, disease-specific, and disease-free survivals. CONCLUSION: Overexpression of HDGF is common in early-stage NSCLC. The expression level in tumor cells is strongly correlated with poor overall, disease-specific, and disease-free survivals, suggesting HDGF may be a powerful prognostic marker for patients with early-stage NSCLC.