高血压药对糖尿病肾病血液透析患者代谢的影响

目的比较血管紧张素转换酶抑制剂（ACEI）、钙离子拮抗剂（CCB）和β-受体阻滞剂等抗高血压药对糖尿病肾病及高血压透析患者的血糖和代谢的影响。方法糖尿病肾病血液透析患者分别经福辛普利（Fosinopril）、维拉帕米（Verapamil）和普萘洛尔（Propranol01）治疗5个月后记录透析前后心率和血压改变，检测透析前空腹血糖、糖化血红蛋白（HbA1c）、果糖胺、胰岛素、胆固醇和甘油三脂等。结果Fosinopril、Verapamil对血糖及物质代谢无不良影响，Propranolol可引起血糖、果糖胺、HbA1c和甘油三脂升高及透析过程中低血压和心率减慢。结论Fosinopril、Verapamil和Propranolol均为控制糖尿病肾病透析患者轻、中度高血压的较可靠药物，且Fosinopril和Verapamil对糖尿病患者血糖和物质代谢无不良影响。     

心肺转流时间对氧代谢的影响

目的对心脏瓣膜手术病人麻醉与手术期间的氧代谢进行测定,探讨心肺转流(CPB)时间对其后氧代谢的影响。方法选择36例择期行心脏瓣膜手术病人,根据CPB时间,将病人分为S组(CPB≤150 min)和L组(CPB>150 min)。采用Swan-Ganz导管技术及反向Fick检测方法对麻醉手术期间的氧代谢进行测定。检测时点为麻醉前、CPB前、CPB停止10 min和60 min。结果麻醉前两组的pH、PaCO2、PaO2等血气参数维持在正常范围,但氧供(DO2)减少,氧摄取率(O2ER)增加。CPB前,两组病人DO2显著降低(P<0.05),S组的氧耗(VO2)显著降低(P<0.05)。CPB后10min到60 min期间,DO2、VO2显著增加(P<0.05),L组O2ER显著增加(P<0.05)。CPB后10 min和60 min,两组的pH、PaCO2及PaO2等虽与麻醉前比较有显著改变,但两组的变化是一致的。CPB后10 min两组的心指数(CI)较麻醉前和CPB前有极显著升高(P<0.01)。CPB后L组的VO2有增高趋势(P<0.05),O2ER明显大于S组。结论CPB对其后氧代谢有明显影响,随着CPB时间延长,CPB后氧代谢障碍更显著。     

土壤环境基因组技术及其在新药发现中的应用

土壤是微生物最重要的生境，土壤微生物具有极大的多样性。然而传统培养技术只能得到约1％的微生物纯培养，其余都是未被纯培养微生物。利用土壤环境基因组技术，可以把未被纯培养微生物的基因克隆到载体中并在宿主中进行表达，获得比已培养微生物丰富的代谢产物多样性，这为我们发现新颖结构先导化合物以及新药开辟了新的道路。本文介绍应用环境基因组技术构建土壤DNA文库的思路和方法。     

血色病肝脏铁过度沉着症1例

1.病例资料：患者，男，48岁。以“乏力、多饮、多尿、多食，伴消瘦4个月，加重1周”入院。既往有乙型肝炎和地中海贫血病史30年，无输血史，无血色病家族史，曾行“脾脏切除”治疗。查体：慢性贫血面容，全身皮肤黄染有散在色素沉着，巩膜黄染，双手肝掌，男性乳房发育；肼右肋下3cm，剑突下5cm，质硬；腹部未触及肿块。     

Preclinical Drug Metabolism in the Age of High-Throughput Screening: An Industrial Perspective

With the advent of genomics, combinatorial paradigms and high-throughput screen (HTS)-based pharmacological testing, the number of compounds flowing through the discovery pipeline is likely to escalate. At the same time, with increased knowledge of the human drug-metabolizing enzymes and the availability of in vitro absorption-metabolism (AM) models, Preclinical Drug Metabolism is poised to meet the challenges of HTS. In order to be successful, however, a rational HTS strategy (vs. serendipitous HTS) has to be employed. Such a strategy is based on automation, validation and integration of in vitroAM models and database management (AVID). A generalized strategy for rational (AVID-based) HTS in Preclinical Drug Metabolism is described briefly.     

Effect of UVB 311 nm irradiation on normal human skin

Ultraviolet radiation B (UVB) on the skin induces erythema, inflammation and modifications of the immune system. These changes have been reported after excessive short-term or long-term exposure to broad spectrum UVB. In this study, we examined the effects of local repetitive UVB irradiation of 311 nm wavelength on the skin of seven young volunteers. Skin biopsies were taken before and after UVB irradiation, and we immunohistochemically analyzed the expression of CD1a and HLA-DR antigens of Langerhans cells (LC), the possible infiltration of dermis/epidermis by CD11b macrophages, the modifications or the induction of intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1) involved in the binding of leukocytes to the endothelial surface and the development of perivascular infiltrates of LFA-1⁺ mononuclear cells. We also determined the expression of substance P receptors (SPR) using biotinylated substance P (SPB). Exposure of UVB 311 nm induced a drastic reduction of CD1a⁺ cells and a moderate increase of HLA-DR⁺ dendritic cells in the epidermis without infiltration by CD11b macrophages. An increase of the binding of SPB to upper layer epidermal cells was noted in five of seven biopsies. In the dermis, vessel-associated ICAM-1 expression increased and an induction of E-selectin occurred on nearly 20 to 40% of endothelial cells, but VCAM-1 expression remained undetectable. The percentage of LFA-1⁺ cells did not change significantly after irradiation. These observations may be compatible with a selective role of UVB 311 nm on the skin immune response.     

Effects of capsaicin in temporomandibular joint arthritis in rats

Temporomandibular joint (TMJ) arthritis was induced in female Lewis rats by unilateral injection of a suspension of heat-killed Mycobacterium butyricum in paraffin oil into the TMJ. Control rats received paraffin oil by the same route. Arthritic and control rats were pretreated either with capsaicin or denervation of the mandibular branch of the trigeminal nerve. Tissues were collected for neuropeptide extraction and analysed by radioimmunoassay and reverse-phase high-performance liquid chromatography. In all groups, the levels of substance P- (SP), calcitonin gene-related peptide- (CGRP) and neuropeptide Y- (NPY) like immunoreactivity (LI) were higher in the trigeminal ganglia than in the TMJs. In control rats, capsaicin significantly lowered the levels of SP-LI in the trigeminal ganglia and TMJ, but not CGRP-LI and NPY-LI. In the arthritic rats, capsaicin pretreatment significantly lowered the SP-LI and CGRP-LI in the trigeminal ganglia and TMJ, but not the NPY-LI. In the trigeminal ganglia the unilateral denervation significantly lowered SP-LI in control rats, and in arthritic rats SP-LI and CGRP-LI. On the denervated side of the arthritic TMJ, NPY-LI, SP-LI and CGRP- LI were significantly lowered as compared to the arthritic control rats and to the contralateral side. In this rat model, pretreatment with capsaicin and surgical denervation decreased the neuropeptide content in the trigeminal ganglia and the TMJ. The results clearly demonstrate a close interaction between increased neuropeptide release from sensory and sympathetic neurones after induction of arthritis in the rat.     

地塞米松促胎儿肺成熟的三种用药方式对母体糖代谢的影响

【目的】探讨地塞米松的用药方式对孕妇糖代谢的影响。【方法】对 1999年 9月至 2 0 0 1年 1月在本院住院的15 0名不同用药方式使用地塞米松促胎儿肺成熟的孕妇进行研究 ,在用药前及用药后 18～ 2 4h抽取肘前静脉血查空腹血糖、血浆C肽 ,糖负荷后 2h血糖、血浆C肽。【结果】使用地塞米松后 ,空腹血糖值、糖负荷后 2h血糖值、空腹C肽及糖负荷后 2hC肽值较用药前高 ;用药方式对母体空腹血糖值和空腹C肽值的影响差异无统计学意义 (P >0 0 5 ) ,对母体糖负荷后 2h血糖值和糖负荷后 2hC肽值的影响差异有统计学意义 (P <0 0 5 ) ;不同糖代谢状态的受试者使用地塞米松后 ,空腹C肽值、糖负荷后 2hC肽值的改变差异有统计学意义 (P <0 0 5 )。【结论】孕妇使用地塞米松促胎儿肺成熟对母体的糖代谢均有一定程度的影响 ,用药过程中和用药后需严密监测母体血糖和胎儿宫内状况     

放射性碘标记的抗肺癌单克隆抗体在载瘤裸鼠体内的代谢

放射性碘标记的抗人肺癌单克隆抗体2E3和6DI注入载人肺癌移植瘤裸鼠体内,静脉血放射性-时间曲线符合二室开放模型;血放射性清除半减期为3.4d,表观分布容积636ml/kg;标记抗体在体内的脱碘率为18.6％,脱落的放射性碘绝大部分从尿排出。腹腔给药吸收快,半吸收期2.08h,生物利用度89％。~(125)I标记的单克隆抗体注射后1～3d,放射性主要分布在肿瘤、血、肝、脾中,其次为肺、肾、胃、小肠;此后,血和正常组织的放射性下降,肿瘤中的放射性较高。~(131)I标记的单克隆抗体能使移植瘤清晰显像。