血小板激活因子拮抗剂SRI63-441对缺血再灌注损伤大鼠心肌的保护作用

目的 研究血小板激活因子拮抗剂SRI63-441对大鼠缺血再灌注损伤心肌的保护作用。方法 将实验大鼠分成3组,对照组未行缺血及药物治疗,再灌注组及SRI63—441治疗组结扎大鼠左冠状动脉前降支(LAD)缺血30分钟后,行再灌注10小时,其中治疗组结扎前1分钟给予SRI63—441(1mg/kg),观察大鼠再灌注心律失常,再灌注区心肌组织中丙二醛浓度、超氧化物歧化酶活性的变化。结果 SRI63—441能明显降低再灌注时室性心律失常的严重程度,使缺血30分钟再灌注10小时大鼠的心肌梗塞面积从21.6±3.1％降至12.7±2.5％,心肌组织中脂质过氧化最终产物丙二醛(MDA)含量下降,超氧化物歧化酶(SOD)活性升高。结论SRI63—441用于大鼠心肌缺血再灌注可减少心肌损伤,提示PAF为心肌再灌注损伤的重要介质,而PAF拮抗剂有可能用于心肌缺血再灌注损伤的治疗。     

四种苦豆子生物碱对巨噬细胞上清液中环氧化酶活性的影响

目的:研究苦参碱(matrine MT)、氧化苦参碱(oxymatrine OMT)、槐果碱(sophocarpine SC)、槐定碱(sophoridine SRI)4种苦豆子类生物碱对环氧化酶活性的影响.方法:用LPS刺激小鼠腹腔巨噬细胞产生PGE2,放免法测定4种生物碱对给予外源性花生四烯酸AA后其产物PGE2的含量来反映生物碱对环氧化酶-2(COX2)的影响;用A23187刺激小鼠腹腔巨噬细胞产生6-Keto-PGF1a,放免法测定4种生物碱对给予外源性花生四烯酸AA后其产物6-Keto-PGF1a含量反映生物碱对环氧化酶-1(COX1)的影响.结果:4种生物碱对COX1均有一定的抑制作用,且具有剂量-效应关系.除MT外,其余3种生物碱对COX2均有明显的抑制作用,且具有良好的剂量-效应关系.结论:除MT为COX1选择性抑制剂外,其余三种苦豆子生物碱均具有COX2选择性抑制作用.     

Is third trimester serotonin reuptake inhibitor use associated with postpartum hemorrhage?

As serotonin reuptake inhibitor (SRI) use may decrease platelet function, previous research has shown a relationship between SRI use and an increased risk for bruising and bleeding. The literature regarding the association between SRI use during pregnancy and increased bleeding at delivery, referred to as postpartum hemorrhage (PPH), is mixed. In secondary analyses from two prospective observational studies of pregnant women with mood disorders, 263 women were exposed to an SRI (n = 51) or not (n = 212) in the third trimester. To be precise, we used the terminology estimated blood loss (EBL) >600 cc rather than the term PPH because the current definition of PPH differs. The occurrence of EBL >600 cc was determined using the Peripartum Events Scale (PES) completed from obstetrical records by a blinded medically trained member of the study team. EBL >600 cc occurred in 8.7% of women in this cohort. There was no statistically significant difference in the rates of EBL >600 cc in the 24 h after delivery in women taking SRIs during the third trimester (9.8%) compared to non-exposed women (8.5%). Utilizing generalizing estimating equations, the odds of EBL >600 cc in each group were not significantly different (OR 1.17, CI-0.41-3.32, p = 0.77). When the SRI group was limited to women with exposure at the time of delivery, the difference in the odds of EBL >600 cc was unchanged (OR 1.16, CI = 0.37–3.64, p = 0.79). In population, both third trimester and use at delivery of SRIs during pregnancy was not associated with an increased risk of excessive blood loss.     

Amisulpiride augmentation in treatment resistant obsessive-compulsive disorder: an open trial

Despite the effectiveness of clomipramine and selective serotonin reuptake inhibitors (SSRIs) in the treatment of obsessive-compulsive disorder (OCD), 40% to 60% of patients who receive an adequate treatment with these agents have significant persisting symptoms. Newer atypical antipsychotic drugs showed efficacy as augmenting agents in patients with OCD resistant to serotonin reuptake inhibitors (SRIs). The objective of this study was to evaluate the efficacy and safety of amisulpiride augmentation in treatment resistant OCD. A total of 20 patients diagnosed with OCD according to DSM-IV criteria and having a history of resistance to treatment with SRIs were included in the study. Amisulpiride 200 mg/day was added to ongoing SRI treatment and titrated up to 600 mg/day in flexible doses. The mean amisulpiride dose was 325 +/- 106 mg/day. The patients were assessed with the Yale-Brown obsessive-compulsive scale (Y-BOCS) at baseline and at week 12 of amisulpiride treatment. Side effects were monitored by the UKU side effect rating scale. The reduction in Y-BOCS scores between the baseline (26.7 +/- 6.3) and the end of the treatment (12.5 +/- 2.8) was statistically significant (p=0.0001). The most commonly observed side effects included weight gain (14 patients, 70%), mild sedation (13 patients, 65%) and asthenia (7 patients, 35%). This study has several limitations and, hence, the results are preliminary and require confirmation in a randomized controlled trial. In conclusion, this study suggests that amisulpiride may be a promising option as an augmentation strategy in treatment resistant OCD.     

Diagnostic algorithm: how to make use of new 2D, 3D and 4D ultrasound technologies in breast imaging

The aim of this publication is to present a time saving diagnostic algorithm consisting of two-dimensional (2D), three-dimensional (3D) and four-dimensional (4D) ultrasound (US) technologies. This algorithm of eight steps combines different imaging modalities and render modes which allow a step by step analysis of 2D, 3D and 4D diagnostic criteria. Advanced breast US systems with broadband high frequency linear transducers, full digital data management and high resolution are the actual basis for two-dimensional breast US studies in order to detect early breast cancer (step 1). The continuous developments of 2D US technologies including contrast resolution imaging (CRI) and speckle reduction imaging (SRI) have a direct influence on the high quality of three-dimensional and four-dimensional presentation of anatomical breast structures and pathological details. The diagnostic options provided by static 3D volume datasets according to US BI-RADS analogue assessment, concerning lesion shape, orientation, margin, echogenic rim sign, lesion echogenicity, acoustic transmission, associated calcifications, 3D criteria of the coronal plane, surrounding tissue composition (step 2) and lesion vascularity (step 6) are discussed. Static 3D datasets offer the combination of long axes distance measurements and volume calculations, which are the basis for an accurate follow-up in BI-RADS II and BI-RADS III lesions (step 3). Real time 4D volume contrast imaging (VCI) is able to demonstrate tissue elasticity (step 5). Glass body rendering is a static 3D tool which presents greyscale and colour information to study the vascularity and the vascular architecture of a lesion (step 6). Tomographic ultrasound imaging (TUI) is used for a slice by slice documentation in different investigation planes (A-,B- or C-plane) (steps 4 and 7). The final step 8 uses the panoramic view technique (XTD-View) to document the localisation within the breast and to make the position of a lesion simply reproducible.     

血小板激活因子拮抗剂SRI63-441对缺血再灌注损伤大鼠心肌的保护作用

目的 :研究血小板激活因子拮抗剂SRI6 3 - 44 1对大鼠缺血再灌注损伤心肌的保护作用。方法 :将实验大鼠分成 3组 ,对照组未行缺血及药物治疗 ,再灌注组及SRI6 3- 44 1治疗组结扎大鼠左冠状动脉前降支 (LAD)缺血 30min后 ,行再灌注 10h ,其中治疗组结扎前 1min给予SRI6 3 - 44 1(1mg/kg) ,观察大鼠再灌注心律失常 ,再灌注区心肌组织中丙二醛浓度、超氧化物歧化酶活性的变化。结果 :SRI6 3- 44 1能明显降低再灌注时室性心律失常的严重程度 ,使缺血 30min再灌注 10h大鼠的心肌梗塞面积从 (2 1 6± 3 1) %降至 (12 7± 2 5 ) % ,心肌组织中脂质过氧化最终产物丙二醛 (MDA)含量下降 ,超氧化物歧化酶 (SOD)活性升高。结论 :SRI6 3 - 44 1用于大鼠心肌缺血再灌注可减少心肌损伤 ,揭示PAF为心肌再灌注损伤的重要介质 ,而PAF拮抗剂有可能用于心肌缺血再灌注损伤的治疗。     

Immunopurification of human plasma kininogens

Human plasma kininogens were purified by immunoadsorption on Sepharose columns using two different approaches, either removing protein impurities with the respective immunospecific polymers or applying an anti-kininogen-specific immunoadsorbent column. An anti-kininogen serum developed and investigated in this laboratory in earlier studies was used. This antiserum recognizes the native conformational determinants in the kininogen heavy chain, the common denominator in plasma kininogens, and reacts with three heterogeneous molecular forms of high mol. wt kininogen (mol. wts 103,000, 92,000 and 90,000) as well as with low mol. wt kininogen. Heterogeneity of kininogens was shown by SDS gel electrophoresis and immunoelectrophoresis. With the antibody-specific polymers the yield was 80-100% compared to 75% or lower when several consecutive immunoadsorption steps were applied to remove impurities. Both methods serve the purpose of preparing immunologically pure kininogens suitable for immunization.     

The effect of label affinity on the sensitivity and specificity of a hapten radioimmunoassay: a comparison of three [125I]diphenylhydantoin radioligands with the 14C-labelled drug.

The effect on the sensitivity and specificity of a radioimmunoassay for diphenylhydantoin (DPH)has been investigated using three 125I-labelled tyrosine ester derivatives of DPH having different bridge lengths between the tyrosine moiety and the DPH moiety and 14C-labelled DPH. The results demonstrate that for a hapten which does not completely fill the antibody-binding sites, greatest sensitivity is achieved when the bridge of the iodine label is most dissimilar to that present in the original immunogen, when the hapten and label affinities are nearly equivalent. Greatest specificity is achieved with the label which most resembles the original immunogen. These results illustrate the difficulty of designing satisfactory labels for assays of both high specificity and sensitivity since minimal changes in label structure may produce greatly amplified changes in the subsequent affinity of the label for the antiserum.     

Pharmacokinetic and pharmacodynamic profiles of the novel serotonin and norepinephrine reuptake inhibitor desvenlafaxine succinate in ovariectomized Sprague-Dawley rats

Desvenlafaxine succinate (DVS) is a novel serotonin (5-HT) and norepinephrine (NE) reuptake inhibitor (SNRI) that is currently in clinical development for the treatment of major depressive disorder and vasomotor symptoms associated with menopause. Previous studies have documented the pharmacokinetic and pharmacodynamic profiles of DVS in male rats. Similar studies, however, have not been performed in ovariectomized (OVX) rats, a model that mimics the loss of ovarian hormones that occurs at menopause. The goal of the present study, therefore, was to characterize the pharmacokinetic and pharmacodynamic properties of DVS in OVX rats. Desvenlafaxine levels peaked in plasma, brain (total brain minus hypothalamus) and hypothalamus at concentrations of 7.0, 10.8 and 9.5 microM (assuming 1 g = 1 ml), respectively, 30 min post-dosing DVS (30 mg/kg, oral). The apparent terminal half-lives of desvenlafaxine in plasma, brain and hypothalamus were 3.0, 2.1 and 2.5 h, respectively. Based on AUC(0-last), brain to plasma and hypothalamus to plasma ratios were 1.7 and 1.3, respectively. Microdialysis experiments in the medial preoptic area of the hypothalamus showed that DVS (30 mg/kg, s.c.), in the presence of WAY-100635 (5-HT(1A) antagonist), increased 5-HT levels 225% at 1 h post-dosing. Norepinephrine levels increased 44% at 3 h post-dosing while dopamine levels were unchanged. Thus, in OVX rats, DVS has good pharmacokinetic properties, rapid brain penetration, excellent brain penetrability and selectively increases 5-HT and NE levels in the hypothalamus. This work supports the notion that DVS could have utility for treating disorders in menopausal women in which changes in 5-HT and/or NE have been implicated.