咪唑立宾在肾移植术后的应用

目的 探讨咪唑立宾（MZR）在肾移植术后的临床应用效果。方法 选取2003年8月至2004年4月间肾移植术后采用环孢素A（CsA）或他克莫司（FK506）＋MZR＋激素三联免疫抑制方案的患者112例，定期检查患者用药后的血常规、肝肾功能、尿酸、血糖、血脂等生化指标；对乙型肝炎病毒、丙型肝炎病毒、艾滋病病毒、巨细胞病毒、EB病毒、腺病毒及带状疱疹病毒进行抗原学或者抗体监测；疑有排斥反应时，行移植肾穿刺病理检查。统计病毒感染发生情况，评价该治疗方案的安全性。结果 肾移植术后随访12～20个月，患者的人／肾存活率均为96％；急性排斥发生率为11．6％，经冲击治疗后全部逆转；患者主要不良反应是高尿酸血症，但可以控制而不需要停药；巨细胞病毒感染率为11．6％，未发生巨细胞病毒病；有1例感染腺病毒。结论 MZR是一种安全有效的免疫抑制剂，病毒感染的发生率相对较低。由于肾移植术后应用MZR患者主要不良反应是高尿酸血症，因此要注意对患者的尿酸进行控制。     

Investigation of the anti-complement agents, FUT-175 and K76COOH, in discordant xenotransplantation

Abstract: We examined whether hyperacute rejection (HAR) of a discordant xenograft in a nonhuman primate model could be inhibited by the anticomplement agents, FUT-175 (FUT) and K76COOH (K76). The inhibitory effect of FUT and K76 on baboon sera was studied in vitro by i) complement-mediated hemolysis of sheep erythrocytes (by measuring serum CH50) and ii) cytotoxicity to cultured pig kidney (PK15) cells. The in vivo administration of FUT (at 0.2–25 mg/kg/h i.v. continuously) and K76 (50 mg/kg i.v. bolus) allowed evaluation of the serum levels of these drugs. Both FUT and K76 inhibited serum CH50 in a concentration-dependent manner. An enhanced effect was obtained by combining K76 with FUT therapy. High concentrations of FUT (>10^-4 M) and K76 (>10³ μxg/ml) were necessary to suppress serum CH50 to <5% of the normal level. However, PK15 cytotoxicity remained at >50% in the presence of i) 10^-4 M of FUT, ii) 10³ μg/ml of K76, and iii) 10^-6 M of FUT + 10³ μg/ml of K76. Pig heart transplantation (HTX) was performed in two baboons receiving FUT (1 mg/kg/h i.v. continuously) and K76 (at 200 mg/kg ×1 or 400 mg/kg + 200 mg/kg × 2 i.v, respectively). Cytotoxicity of the serum to PK15 cells at the time of HTX showed 39% and 1% cell death, respectively, in these two baboons, and the CH50 level was 1% (of control level) and 0%, respectively. Graft survival was 4.5 hours and 10 hours (with death of the baboon), respectively (compared with a mean of 29 minutes in control experiments). Both excised grafts showed typical features of hyperacute rejection. Immunopathological studies revealed deposition of C1q, C3d, C6, properdin, and Factor B, demonstrating that complement activation was not fully inhibited by FUT and K76. We conclude that i) FUT and K76 are indeed potent complement inhibitors, ii) the dosages of FUT and K76 necessary to suppress complement-mediated injury cannot be extrapolated from previously reported data obtained from serum CH50 levels, and iii) higher (possibly toxic) dosages will be required to inhibit complement activation completely. It seems unlikely that HAR will be prevented by these drugs alone, although they may be beneficial when combined with other forms of therapy.     

Structure-activity relationship of macrocyclic and linear gadolinium chelates: Investigation of transmetallation effect on the zinc-dependent metallopeptidase angiotensin-converting enzyme

Transmetallation between commercially available solutions of gadolinium (Gd) chelates and the zinc (Zn)-dependent angiotensin-converting enzyme (ACE) was investigated. In vitro, the strongest inhibitions were observed for the linear Gd complexes, Gd diethylene-triamine pentaacetic acid (DTPA) bis-methylamide (BMA) (IC₅₀ = .016 ± .006 mmol/1) and Gd-DTPA (IC₅₀ = .350 ± .034 mmol/1). The two macrocycles Gd tetraazacyclododecane tetraacetic acid (DOTA) and Gd-HP-DO3A were similar and 400 times less active than Gd-DTPA-BMA. These effects were mainly due to the presence of free ligand for DTPA and calcium (Ca) chelate in the case of DTPA-BMA because the addition of Zn²⁺ in the same quantities suppresses their inhibitory effects. In vivo, these two solutions of linear Gd chelates significantly inhibited ACE activity (Gd-DTPA: 67 ± 9% versus baseline; and Gd-DTPA-BMA: 73 ± 2% versus baseline at the clinical dose of .1 mmol/kg), whereas no significant effect was observed for the two macrocyclic chelates Gd-DOTA and Gd-HP-DO3A. Formulating the Gd chelate solution with either an excess of free ligand or Ca chelate (to decrease Gd³⁺ release) in the case of linear Gd chelate may have deleterious biologic consequences.     

依沙吖啶引产失败后用卡前列甲酯栓的疗效

目的：观察３５例中期妊娠用依沙吖啶１次羊膜腔注射引产失败后，再用卡前列甲酯栓的效果。方法：卡前列甲酯栓１ｍｇ，放置于阴道后穹窿，若３ｈ后无宫缩，再放１次。结果：３５例孕妇引产成功率１００％。引产后２４ｈ内阴道流血量２００±２０ｍＬ。出现腹泻，恶心等不良反应各１例。结论：卡前列７甲酯栓用于对依沙吖啶中期引产失败后效果满意。     

Effects of Myocardial Water Exchange on T1 Enhancement during Bolus Administration of MR Contrast Agents

Interpretation of first-pass myocardial perfusion studies employing bolus administration of T₁ magnetic resonance (MR) contrast agents requires an understanding of the relationship between contrast concentration and image pixel intensity. The potential effects of myocardial water exchange rates among the intravascular, interstitial, and cellular compartments on this relationship are controversial. We directly studied these issues in isolated, nonbeating canine interventricular septa. Myocardial T₁ was measured three times/s during bolus transit of intravascular (albumin-Gd-DTPA and poly-lysine-Gd-DTPA) and extracellular (gadoteridol) contrast agents. For polylsine-Gd-DTPA, the peak changes in myocardial 1/T₁ (ΔR1) scaled nonlinearly with perfusate contrast concentration whereas a linear relationship would be expected for fast water exchange among the vascular, interstitial, and cellular compartments. For all agents, the peak ΔR1 were much smaller than the values expected on the basis of fast myocardial water exchange. The data demonstrate that in isolated myocardial tissue, myocardial T₁ enhancement during bolus administration of contrast can be strongly affected by myocardial water exchange for both intravascular and extracellular MR contrast agents.     

五种螯合剂对大鼠体内微量元素影响的观察

观察了５种常用螯合剂对大鼠体内微量元素排出量、组织分布的变化。结果表明，５种螯合剂可不同程度地增加机体必需微量元素Ｚｎ、Ｃｕ、Ｍｇ和Ｃａ经尿液排出量。ＥＤＴＡ和ＤＴＰＡ的影响尤为明显。ＥＤＴＡ和ＤＴＰＡ可使Ｚｎ经尿液的排出量增加１６－５２倍，ＤＴＰＡ使肝脏Ｚｎ含量减少１５．９％（Ｐ〈０．０５），肝脏Ｃｕ含量下降６０％（Ｐ〈０．０５）。ＥＤＴＡ和ＤＴＰＡ注射后，肾中Ｚｎ含量明显增高，相当对照大鼠３．     

吡那地尔对高血压心脏结构和功能重构的影响

在等降压剂量下吡那地尔和赖诺普利可使４月龄自发性高血压大鼠的血压下降６．０￣８．０ｋＰａ，并接近同种属正常血压大刀瓣血压水平。     

Autonomic control of acid phosphatase exocrine secretion by the rat prostate

Summary In vivo prostatic secretion was collected from retired breeder Sprague Dawley rats using a method for isolated perfusion of the rat prostatic urethra. Enzymatic acid phosphatase determination was performed on the collected effluent. Control acid phosphatase secretion was 24.2±2.7 nm over 30 minutes. Intravenous phenylephrine 5 mg/kg stimulated a 10 fold increase in acid phosphatase secretion. The secretion seen with phenylephrine was dose dependent and could be blocked with prazosin, but not yohimbine, atropine, or propranolol. Intravenous -adrenergic agonist isoproterenol caused no increase in the secretion of rat prostatic acid phosphatese. Intravenous administration of the cholinergic agonist pilocarpine also resulted in a dose dependent rise in acid phosphatase secretion. The stimulation seen could be blocked by atropine but not phentolamine or propranolol. The stimulation of acid phosphatase secretion seen with ₁ adrenergic or cholinergic agonists was not additive. Intravenous vasoactive intestinal peptide did not stimulate acid phosphatase secretion nor did it augment the secretion induced by ₁ adrenergic or cholinergic agonists. Release of acid phosphatase into rat prostatic exocrine secretion is under both ₁ adrenergic and cholinergic control.Supported by the US Veterans Administration     

Clinical applications of colour Doppler energy imaging in the female reproductive tract and pregnancy

This review describes the usefulness of colour Doppler energy (CDE) (or power Doppler) imaging to measure vascularization in the female reproductive tract. CDE imaging is characterized by an increased sensitivity to flow, and thus may be useful in low-flow states and when optimal Doppler angles cannot be obtained. In addition, longer segments of vessels and more individual vessels can be visualized with CDE imaging. The role of CDE imaging in the evaluation of stromal vasculature in normal and in polycystic ovaries is described, and the relationship between follicular vascularity and outcome following in-vitro fertilization are discussed, together with the findings obtained from the evaluation of thecal arteriole of corpus luteum in early pregnancy. The fundamental role of CDE imaging in differentiation among ovarian masses is also reviewed. We summarize the role of CDE imaging in pregnancy, and describe two new applications of three-dimensional power Doppler sonography and the use of ultrasound contrast media. In conclusion, CDE imaging can replace conventional colour Doppler when the information on the direction of flow is not useful. Moreover, the technique appears superior to others for describing microvascular architecture and determining the presence or absence of flow.