静脉预注H1,H2受体阻滞药对减轻鱼精蛋白副作用的研究

将３０例ＡＳＤ、ＶＳＤ患者随机分为对照与预防用药两组，对比观察Ｈ１、Ｈ２受体阻滞药苯海拉明、西米替丁对减轻鱼精蛋白副作用的效果和应用鱼精蛋白后补体Ｃ３、Ｃ４、ＣＨ５０浓度变化。结果发现预防用药组血液动力学变化明显小于对照组，两组之间差异显著（Ｐ＜０．０１）。应用鱼精蛋白后Ｃ３、Ｃ４、ＣＨ５０均下降，与用药前相比差异显著（Ｐ＜０．０１）。提示鱼精蛋白中和肝素可引起补体激活、组胺释放，Ｈ１、Ｈ２受体阻滞药能够减轻鱼精蛋白引起的血压下降。     

Inhibition of inflammatory angiogenesis in rats by loco-regional administration of hydrocortisone and protamine

We have studied the antiangiogenetic effects of hydrocortisone and protamine given intra-arterially. The cornea of male, Sprague-Dawley rats were cauterized with silver nitrate. The following treatments were given :30 g hydrocortisone topical (t.p.), b.i.d., 50 mg/kg/day intraperitoneally (i.p.) or intra-arterially (i.a.), 10 mg/ kg/day protamine i.p. or i.a. Saline was administered to the control groups. In separate experiments we also evaluated the anti-inflammatory effects of hydrocortisone, i.p., on the cauterized corneas.Five days after cauterization, the animals were killed, exsanguinated and India ink was injected to show the network of neovessels. The percentage area of the cornea covered by neovessels was measured morphometrically and evaluated statistically. Hydrocortisone t.p. (–84%), i.a. (–60%) and protamine i.a. (–44%) significantly inhibited angiogenesis in the cauterized cornea. Either drugs, i.p., had any antiangiogenetic effects, but hydrocortisone significantly reduced cell infiltration of the corneas. The results suggest that locoregional administration of antiangiogenetic drugs might be clinically useful.     

Immunocytochemical studies of protamine-induced blood-brain barrier opening to endogenous albumin

The cellular mechanisms of blood-brain barrier (BBB) opening to endogenous albumin in the mouse brain after intracarotid infusion of solutions of protamine free base (PB) or protamine sulfate (PS) were studied using quantitative immunocytochemistry. Ultrathin sections of brain samples embedded at low temperature in Lowicryl. K4M were exposed to anti-mouse albumin antiserum followed by protein A-gold. Using morphometry, the density of immunosignals (gold particles per m²) was recorded over four compartments: vascular lumen, endothelial profiles, subendothelial space (including the basement membrane), and brain parenchyma (neuropil). In addition, the adsorption of endogenous albumin evidenced by the number of gold particles per m of the endothelial luminal plasmalemma was quantitatively evaluated. In the applied experimental conditions, PB was found to be strongly cytotoxic as indicated by the appearance of rapid degenerative changes and the disruption of the endothelial lining with concomitant clumping of the blood plasma. The action of PS was milder, offering a better opportunity for detailed ultrastructural and morphometric examination of brain samples during consecutive steps of PS action (2, 5, 10 and 30 min). As early as 10 min after infusion of PS solution, the adsorption of blood plasma albumin to the endothelial luminal surface was increased 2.5 times. Simultaneously, the immunolabelling of the endothelial profiles and subendothelial space was significantly increased. These results suggest that BBB disruption occurs through enhanced adsorption of albumin or albumin-protamine complexes to the luminal plasmalemma, followed by transendothelial vesicular transport, rather than through modification of interendothelial junctional complexes. This process appears to be focally disseminated throughout the cerebral vascular network and declines at 30 min following infusion of PS solution.     

Ultracytochemical studies of the blood-meningeal barrier (BMB) in rat spinal cord

Summary Alkaline phosphatase(AP),5-nucleotidase(5N) and nucleoside diphosphatase (NDPase) activities were studied by cytochemical methods applied to light and electron microscopy in the microvasculature of spinal cord leptomeningeal strips of normal and protamine sulfate (PS) treated rats. The increased permeability to intravenously injected horseradish peroxidase was observed in some segments of microvessels of PS treated rats. Enhanced formation of plasmalemmal pits and deep invaginations, formation of numerous pinocytic vesicles and the appearance of channel-like structures in the cytoplasm of endothelial cells were the most striking ultrastructural evidence of increased permeability of the affected microvessels. All of these structures also showed activity of AP, and to lesser extent, of NDPase; 5N activity was mainly associated with the delimiting membranes of pinocytic vesicles. Our data present evidence that a shift of enzymatic activity from luminal to abluminal surface of affected endothelial cells results from membrane flow accompanying increased transport activity via formation of pinocytic vesicles and channel-like structures.Supported in part by a grant from NINCDS No. 17271-01Visiting scientist from the Neurological Institute of the University of Vienna, Vienna, Austria     

硫酸鱼精蛋白注射液细菌内毒素检查法标准研究

目的:建立硫酸鱼精蛋白注射液细菌内毒素的检查方法.方法:按<中国药典>2000年版二部附录ⅪE、ⅪX F进行实验和结果判断.结果:用三个不同生产厂家,不同标示灵敏度鲎试剂进行研究,硫酸鱼精蛋白注射液最大不干扰浓度为0.042mg/ml,并对两个生产厂家的6批样品进行检查,均无干扰作用,其细菌内毒素量均小于6EU/mg.结论:本品可以用细菌内毒素检查法(凝胶法)代替热原检查法控制细菌内毒素的含量,硫酸鱼精蛋白注射液的细菌内毒素理论限值为6EU/mg.     

门冬胰岛素治疗妊娠糖尿病的临床研究

目的：探讨门冬胰岛素治疗妊娠糖尿病（GDM）的临床效果。方法将复旦大学附属中山医院分院2010年4月—2013年8月确诊的GDM初诊患者136例随机分为对照组和治疗组,每组68例。对照组餐前30 min皮下注射精蛋白生物合成人胰岛素注射液;治疗组每日3餐进食前皮下注射门冬胰岛素30注射液。对两组患者进行随访,比较其血糖控制情况、炎性因子及母婴结局。结果治疗后两组患者空腹血糖（FPG）、餐后2 h血糖（2 h PG）、糖化血红蛋白（HbA1C）和尿C肽均明显好转,与治疗前差异具有统计学意义（P＜0.01）。治疗后,治疗组FPG、2 h PG、HbA1C低于对照组,餐后0.5、2 h尿C肽高于对照组,两组比较差异有统计学意义（P＜0.05、0.01）。治疗组血糖达标时间、每日胰岛素用量、低血糖发生率均低于对照组,两组比较差异具有统计学意义（P＜0.05）。治疗后,两组患者C-反应蛋白（CRP）、白细胞介素6（IL-6）、和正五聚蛋白（PTX-3）均较治疗前显著降低,同组治疗前后差异具有统计学意义（P＜0.01）;治疗后,治疗组这些指标低于对照组,两组比较差异有统计学意义（P＜0.01）。两组患者母婴结局差异均无统计学意义,未出现严重不良反应。结论门冬胰岛素治疗妊娠糖尿病具有较好的临床疗效,可减少药物用量,缩短血糖达标时间,对GDM炎性症状改善良好,值得临床推广应用。     

心脏直视手术中鱼精蛋白过敏性休克的救治

回顾体外循环后鱼精蛋白拮抗肝素期间发生过敏性休克、心搏骤停2例，均属严重肺血管收缩型毒性反应。结合文献复习，作者认为：严重的鱼精蛋白过敏反应发病急骤，临床表现严重。立即二次转机辅助循环，应用副肾素、抗组织胺类药物和大剂量激素，及时补足血容量是主要抢救措施。而鱼精蛋白毒性反应发生与否与有无鱼类食物过敏史、注射途径、是否二次使用鱼精蛋白、鱼精蛋白皮试是否阴性均无相关性。缓慢注射（＞3min）可防止快速给药反应型毒性反应的发生，但无助于防止严重肺血管收缩型毒性反应的发生。     

升主动脉注射鱼精蛋白对体外循环后C3a和C5a的影响

目的观察和评价通过升主动脉及上腔静脉注射鱼精蛋白不同注射途径对体外循环后婴儿血浆C3a、C5a的影响。方法年龄≤12个月行体外循环心内直视手术的患儿60例,应用随机数字表法随机分为实验组30例（经升主动脉注射鱼精蛋白组）和对照组30例（经腔静脉注射鱼精蛋白组）。于注射鱼精蛋白前（T1）、注射鱼精蛋白后1h（T2）取右心房肝素抗凝血1ml,用ELISA法测定血浆C3a、C5a浓度。结果实验组患儿注射鱼精蛋白前后血浆C3a浓度[（18．762±3．792）μg/L与（19．554±3．453）μg/L,t=-0．846,P=0．20]、C5a浓度[（0．843±0．159）μg/L与（0．825±0．119）μg／L,t=0．496,P=0．31],差异均无统计学意义（P均〈0．05）;对照组患儿注射鱼精蛋白前后血浆C3a浓度[（18．780±3．864）μg／L与（22．961±3．501）μg/L,t=-4．392,P〈0．01]、C5a浓度[（0．839±0．157）μg／L与（0．979±0．116）μg／L,t=-3．928,P〈0．01]均显著增高。注射鱼精蛋白后1h对照组患儿血浆C3a浓度较实验组显著增高[（22．961±3．501）μg／L与（19．554±3．453）μg/L,t=-3．795,P〈0．01]、C5a浓度亦较实验组显著增高[（0．979±0．116）μg/L与（0．825±0．119）μg／L,t=-5．075,P〈0．01]。结论升主动脉途径注射鱼精蛋白可显著减少体外循环后婴儿血浆C3a、C5a浓度。     

Evaluation of sperm selection procedure based on hyaluronic acid binding ability on ICSI outcome

PURPOSE: To compare the efficiency of routine sperm selection method with HA-selection procedure for fertilization rate, embryo development, implantation and pregnancy rates as well as evaluating the relationship between HA-binding ability with sperm protamine deficiency and DNA fragmentation. METHODS: Semen samples were obtained from the 50 couples undergoing ICSI. The percentage of fertilization rate, cleavage and quality of embryos compared between two procedures (routine sperm selection and HA-binding selection). The semen samples were assessed for DNA fragmentation and protamine deficiency by sperm chromatin dispersion (SCD) test and Chromomycin A3 (CMA3) staining, respectively. RESULTS: A significant inverse correlation was observed between percentage of HA binding with protamine deficiency, DNA fragmentation and abnormal sperm morphology (P < 0.05). Furthermore, in current study, oocytes inseminated by HA sperm selection procedure had significantly higher fertilization rate (P < 0.05). While the pregnancy and implantation rates were insignificantly increased. CONCLUSION: The results suggest that normal sperm have higher chance to bind HA and therefore, HA sperm selection procedure may select sperm with normal protamine content and low DNA fragmentation, but to confirm the effect of HA sperm selection on the ICSI outcome requires further studies.     

An economic assessment of analogue basal–bolus insulin versus human basal–bolus insulin in subjects with type 1 diabetes in the UK

ABSTRACT

Background: A recent study demonstrated that treatment of type 1 diabetes with an analogue basal–bolus insulin regimen was associated with improved glycaemic control (HbA_1c –0.22% points, p < 0.001), reduced risk of hypo­glycaemic events (–21%, p = 0.036) and reduction in body mass index (–0.30?kg/m², p < 0.001) compared to a human basal–bolus regimen after 18 weeks.

Methods: A published and validated computer simulation model was used to project long-term economic and clinical outcomes in a simulated cohort of type 1 diabetes patients treated with either insulin detemir plus insulin aspart (analogue) or Neutral Protamine Hagedorn plus human soluble insulin (human), in a UK setting. Probabilities of complications and HbA_1c-dependent adjustments were derived from major clinical and epidemiological studies. Complication and treatment costs were projected over patient lifetimes from a National Health Service perspective. Costs and clinical benefits were discounted at 3.5% annually.

Results: Quality-adjusted life expectancy (QALE) was 0.66 quality-adjusted life years (QALY) higher in the analogue insulin versus the human insulin group (mean ± SD) (7.65 ± 0.09 versus 6.99 ± 0.08). Direct lifetime costs were £1654 greater with analogue versus human insulin treatment (£40?876 ± 1119 versus £39?222 ± 1141), producing an incremental cost effectiveness ratio (ICER) of £2500 per QALY gained. Sensitivity analyses showed the results were robust under a range of plausible scenarios.

Conclusions: Treatment with analogue insulin was associated with a decreased incidence of long-term complications and improved QALE, but slightly higher treatment costs compared to human insulin therapy. Analogue insulin treatment had an ICER within the range generally considered to represent good value for money in the UK.