吡酮酸类抗菌药物的研究Ⅷ.1-对氟苯基-6-氟-1,4-二氢-4-氧-7-(1-哌嗪)噌啉-3-羧酸及其类似物的合成和构效关系

为探讨构效关系,合成了1-对氟苯基-6-氟-1,4-二氢-4-氧-7-(1-哌嗪)噌啉-3-羧酸及其喹啉、萘啶、吡啶[2,3-C]哒嗪环系类似物16个。测定了对大肠杆菌的MIC。用Hückel分子轨道理论(HMO)方法计算了四个母体环上电子密度。结果表明:环中氮的位置对药效团——3位羧基和4位羰基氧原子上电子密度的影响较大而影响其抗菌活性。喹啉、萘啶两环系的3位羧基和4位羰基氧原子上的电子密度较高,其体外抗菌活性较高;而噌啉及吡啶[2,3-C]哒嗪两环系的电子密度较低,其体外抗菌活性较低甚至消失。     

Effect of timing of oocyte denudation and micro-injection on survival, fertilization and embryo quality after intracytoplasmic sperm injection

In human in-vitro fertilization (IVF), the oocytes are surrounded by cumulus and corona cells at the time of insemination so that their maturity cannot easily be evaluated. The best IVF results are obtained if the oocytes are inseminated 2-6 h after retrieval. In the intracytoplasmic sperm injection (ICSI) procedure, the oocytes are denuded by enzymatic and mechanical treatment in order to be able to perform the injection. As a consequence, the nuclear maturity of the oocytes can be evaluated and only those that have extruded the first polar body are injected. However, metaphase-II oocytes that have not yet reached cytoplasmic maturity cannot be recognized. The purpose of this study was to investigate the effect of different timing of cumulus- corona cell removal and injection on the outcome of ICSI. For this we allowed the oocytes to complete in-vitro cytoplasmic maturation in two different culture conditions: (i) surrounded by their cumulus and corona cells or (ii) totally denuded. We performed three different studies on sibling oocytes obtained after a standardized buserelin/human menopausal gonadotrophin (HMG) protocol. We investigated the effect of early (1-2 h after retrieval) and late (5-6 h after retrieval) oocyte denudation and injection on the survival and fertilization of the injected oocytes and on embryo cleavage after fertilization. We found no statistically significant differences between early and late injection, indicating that after a standardized buserelin/HMG protocol the metaphase-II oocytes do not need time for further cytoplasmic maturation. Furthermore, a different timing of cumulus-corona cell removal has no effect on the outcome of ICSI, suggesting that the surrounding cells are not necessary for survival, fertilization and cleavage after ICSI.      

Percoll gradient centrifugation can be omitted in sperm preparation for intracytoplasmic sperm injection

Prior to intracytoplasmic sperm injection (ICSI), seminal fluid is currently washed out from the ejaculated semen and further sperm selection is carried out by a discontinuous Percoll gradient. Possible deleterious effects from the sperm-separating substance Percoll on sperm function or embryo cleavage after in-vitro fertilization (IVF) have, to our knowledge, not yet been reported and the use of Percoll has been widely accepted in IVF. In this study, we examined whether the omission of the Percoll step in the sperm preparation has any influence on the outcome of the ICSI procedure. Two methods of sperm preparation for ICSI were compared in a controlled study on sibling oocytes: washing the semen sample once, followed by a Percoll gradient centrifugation versus washing the sperm sample twice without a Percoll gradient centrifugation. The mean fertilization rates were similar for the two sperm preparation methods: 78.2 +/- 21.4 and 75.0 +/- 24.1% respectively of the intact oocytes displaying two pronuclei. Cleavage rates did not differ statistically between the two groups. Whereas in both groups similar percentages of excellent, good and poor quality embryos were obtained, the percentage of fair quality embryos was significantly higher in the group without Percoll (16.3 +/- 20.1 versus 9.1 +/- 15.7%). However, no statistical differences were observed in either the percentage of transferable embryos or in the percentage of embryos actually transferred or frozen in the two groups. In conclusion, spermatozoa from ejaculates that are washed out from the seminal fluid without any further selection can be used for ICSI without any adverse effect on fertilization and embryo cleavage.      

肝脏可溶性复合物不同剂量、不同途径移植对肿瘤细胞增殖抑制的体内外实验

目的:肝脏可溶性复合物具有保护肝脏、刺激肝组织再生等生物学活性,观察天然物质肝脏可溶性复合物对肿瘤细胞生长增殖的抑制作用.方法:实验于2006-05/2007-02在四川大学华西医院生物治疗国家重点实验室实验肿瘤研究室完成.①分离人胚胎、成年及新生小鼠肝脏组织,生理盐水清洗、剪碎、筛网过滤,用生理盐水制备混悬液,3 000 r/min离心,收集上清,制备肝脏可溶性复合物.②体外实验:用上述不同来源的肝脏可溶性复合物体外处理肿瘤细胞,四甲基偶氮唑盐比色法测定其对乳腺癌细胞EMT6增殖的影响.③体内实验:观察成年鼠肝脏可溶物质对乳腺癌细胞EMT6体内生长的抑制作用及其对荷瘤鼠生存状况的影响,包括不同给药剂量及不同给药途径两个实验,给药途径包括在接种肿瘤细胞部位的对侧腋下、同侧腋下、腹腔注射及灌胃等.结果:①体外实验显示不同来源的肝脏可溶性复合物能明显抑制肿瘤细胞EMT6增殖率,肿瘤增殖抑制率均显著高于血清白蛋白处理组(P＜0.05),并呈剂量依赖性.②成年鼠肝脏可溶物质8mg/L组抑瘤率高于2,4 mg/L组(P＜0.05),未观察到明显毒副效应.③比较不同给药途径,成年鼠肝脏可溶物质同侧注射组的抑瘤率较其他3组的抑瘤率高(P＜0.05),各成年鼠肝脏可溶物质给予组的体质量增长率比相应生理盐水对照组高(P＜0.05).④与相应生理盐水对照组比较,在同侧腋下注射成年鼠肝脏可溶物质的小鼠生存期明显延长(P＜0.05).结论:肝脏可溶性复合物具有抑制肿瘤细胞生长的作用,并且呈一定的剂量依赖性.不同的给药途径中,在接种肿瘤细胞部位的同侧腋下给药抑瘤效果最好.     

盐酸戊乙奎宁在水溶液中的降解机理

Penequine hydrochloride (Ⅰ) is a new potent anticholinergic drug, the degradation mechanism of Ⅰ in aqueous solutions is reported in this paper. Ⅰ is an ethereal compound, stable in neutral and alkaline solutions, but it decomposes in strong acidic solutions. Its main degradation products have been separated and identified by means of TLC, MS, GC/MS and GC/FTIR. With reference to the general degradation rule of ethereal compound and the structure of the degradation products, we deduced that the ether linkage of Ⅰ splits in acidic solutions by the catalysis of hydrogen ion, producing 3- quinuclidinol (DP1) and 1-phenyl- 1-cyclopentyl glycol. The latter turns into 1-phenyl-l-cyclopentyl acetaldehyde through dehydration and rearrangement. In addition, small amounts of other degradation compounds, e. g. benzaldehyde, acetophenone, phenylcyclopentyl ketone, etc. have also been found, but the mechanism remains to be further studied.     

Seizures and metabolic disease

Seizures represent an important clinical manifestation of inborn errors of metabolism. The presence of myoclonic seizures and very early onset are clues to a metabolic disorder. Specific correlations between age of seizure onset and electroencephalogram patterns with inborn errors of metabolism are discussed. The explosion of information in neurogenetics and metabolism mandates increasing awareness of appropriate metabolic diagnostic and therapeutic strategies in the setting of certain epilepsies. Specific laboratory, imaging, and treatment considerations are included to present updated material in a field that continues to expand rapidly.     

Choroid plexus carcinomas in children: MRI features and patient outcomes

Choroid plexus carcinomas (CPC) are rare malignant intracranial neoplasms usually occurring in young children. The objectives of this study were to characterize the preoperative MRI features of CPC, determine the frequency of disseminated disease in the CNS at diagnosis, and assess patient outcomes. The preoperative cranial MR images of 11 patients with CPC were retrospectively reviewed for lesion location, lesion size, un-enhanced and enhanced MRI signal characteristics, and presence of disseminated intracranial tumor. Postoperative cranial and spinal MRI images were reviewed for residual, recurrent, and/or disseminated tumor. The study group included six male and five female patients ranging in age from 5 months to 5.3 years (median=1.8 years). CPC were located in the lateral (n=8), fourth (n=1), and third (n=1) ventricles, and foramen of Luschka (n=1). Mean tumor size was 5.2cm×4.9cm×5.0 cm. On short-TR images, CPC had heterogeneous, predominantly intermediate signal with foci of high signal in 45% of lesions from areas of hemorrhage. On long-TR/long-TE images, solid portions of CPC typically had heterogeneous, intermediate-to-slightly-high signal. Small zones of low signal on long-TR/long-TE images were seen in 55% of the lesions secondary to areas of hemorrhage and/or calcifications. Tubular flow voids representing blood vessels were seen in 55% of the lesions. Zones of high signal comparable to CSF were seen in 64% of CPC secondary to cystic/necrotic zones. All CPC showed prominent contrast enhancement. Irregular enhancing margins suggesting subependymal invasion were seen in 73% of the lesions. Findings consistent with edema in the brain adjacent to the enhancing lesions were seen in 73% of CPC. CPC caused hydrocephalus in 82% of patients at diagnosis. Two patients died from hemorrhagic complications from surgical biopsies. Disseminated tumor in the leptomeninges was present in 45% of patients at diagnosis and was associated with a poor prognosis. The 1-year and 5-year survival probabilities were 55% and 45%, respectively. In conclusion, MRI features commonly associated with CPC include large intraventricular lesions with irregular enhancing margins; heterogeneous signal on long TR/long TE images and short-TR images; edema in adjacent brain; hydrocephalus; and presence of disseminated tumor. MRI evidence of disseminated tumor at diagnosis is associated with a poor prognosis.     

Dose reduction fluoroscopy in pediatrics

BACKGROUND: It is essential that we find ways to reduce radiation exposure to children and maintain image quality. OBJECTIVES: We compared radiation dose, image quality, and spatial resolution when continuous and pulse fluoroscopy with a full and half dose are applied to a phantom. The film-screen technique was compared to fluoroscopy with the digitized spot technique (fluoro grab image) in procedures such as voiding cystourethrogram (VCUG). MATERIALS AND METHODS: Using a 15.1-cm Plexiglas phantom, we obtained dosimetry in milligrays (mGy), spatial resolution in number of line pairs per millimeter (lp/mm), and threshold contrast resolution in number of visible holes. To measure total radiation dose, we calculated the average elapsed fluoroscopy time for VCUG to be approximately 3 min and estimated the average number of exposures as 10. Dosimetry was obtained for full dose and half dose continuous, for 15 pulses per second (pps), 7.5 pps, and 3.75 pps. These were also calculated with normal, magnification 1, and magnification 2 factors. RESULTS: Results of the two most relevant parameters are shown: continuous full-dose fluoroscopy, 3 min, 10 photo spots, total dose of 28.7 mGy with 2 lp/mm of resolution and a threshold contrast of 2.2%, versus 3.75 pps half-dose fluoroscopy, 3 min, grab images, total dose of 3.7 mGy with 1.9 lp/mm of resolution and a threshold contrast of 2.3%. CONCLUSION: With minimal loss of resolution there is significant dose reduction (87%) when using 3.75 pps with digitized imaging.