Opportunities for recombinant antigen and antibody expression in transgenic plants--technology assessment

Plants are now gaining widespread acceptance as a general platform for the large-scale production of recombinant proteins. The principle has been demonstrated by the success of a diverse repertoire of proteins, with therapeutic molecules showing the most potential for added value. Over the past 10 years, several efficient plant-based expression systems have emerged. However, a number of issues remain to be addressed before plant bioreactors can be accepted and adopted widely in preference to the established microbial and mammalian platforms. Overcoming bottlenecks imposed by low yields, poor and inconsistent product quality and difficulties with downstream processing are the most important goals for researchers working in this field. The achievement of these goals is conditional on the development of extraction and processing steps that comply with GMP standards, including extensive quality assurance and control procedures. Such rigorous and validated standards should be combined with measures applied earlier in production to ensure product sustainability and quality, such as the use of master seed banking procedures. Moreover, there are several further challenges concerning topics of environmental impact, biosafety and risk assessment, which reflect the release of transgenic plants, as well the safety of the plant-derived products themselves. We are facing a growing demand for protein diagnostics and therapeutics, but lack the capacity to meet those demands using established facilities. A shift to plant bioreactors may, therefore, become necessary within the next few years, making it more imperative that the technical and regulatory limitations are addressed and solved. The production of pharmaceutical proteins in plants will only realize its huge potential if the products are provided at consistent high quality levels, allowing the delivery of clinical grade proteins that will gain regulatory approval and which can be used routinely in clinical trials.     

Determinants of response to a parent questionnaire about development and behaviour in 3 year olds: European multicentre study of congenital toxoplasmosis

Background  

We aimed to determine how response to a parent-completed postal questionnaire measuring development, behaviour, impairment, and parental concerns and anxiety, varies in different European centres.     

Echocardiographic assessment of the right ventricular stress-velocity relationship under normal and chronic overload conditions

The effects of chronic volume or pressure overload on the velocity of right ventricular ejection have not been previously well defined. We hypothesized that, as formerly shown for the left ventricle, there would be a direct relationship between the velocity of ejection and an estimate of systolic wall stress. METHODS: Echocardiograms of asymptomatic patients, not on cardiac medications, with either an isolated secundum atrial septal defect > or = 5 mm in diameter or isolated pulmonic stenosis with a peak instantaneous pressure gradient > or = 20 mmHg, were reviewed. Forty-one patients with an atrial septal defect and 34 with pulmonary stenosis met criteria, and were compared to age-matched normal controls. Total subjects were 127 with ages ranging from 1 day to 54 years. Right ventricular monoplane ejection fraction, ejection time corrected for heart rate (ETc), mean normalized systolic ejection rate (MNSERc) and meridianal peak-systolic wall stress (WSps) were measured. RESULTS: Compared to controls, ejection fractions were not significantly different, but WSps averaged 81% and 110% higher, ETc 8% and 9% longer, and MNSERc 5% and 9% slower in the atrial septal defect and pulmonary stenosis groups, respectively. Among all subjects WSps had a significant linear correlation with ETc (r = 0.61, P < 0.01), MNSERc (r =-0.46, P < 0.01), and ejection fraction (r =-0.19, P < 0.05). CONCLUSIONS: Increases in WSps cause an incremental slowing of MNSERc in the right ventricle, with a relationship that is linear over a wide range of normal and abnormal loading conditions.     

Pharmacokinetic interactions of topiramate

Topiramate is a new antiepileptic drug (AED) that has been approved worldwide (in more than 80 countries) for the treatment of various kinds of epilepsy. It is currently being evaluated for its effect in various neurological and psychiatric disorders. The pharmacokinetics of topiramate are characterised by linear pharmacokinetics over the dose range 100-800 mg, low oral clearance (22-36 mL/min), which, in monotherapy, is predominantly through renal excretion (renal clearance 10-20 mL/min), and a long half-life (19-25 hours), which is reduced when coadministered with inducing AEDs such as phenytoin, phenobarbital and carbamazepine. The absolute bioavailability, or oral availability, of topiramate is 81-95% and is not affected by food. Although topiramate is not extensively metabolised when administered in monotherapy (fraction metabolised approximately 20%), its metabolism is induced during polytherapy with carbamazepine and phenytoin, and, consequently, its fraction metabolised increases. During concomitant treatment with topiramate and carbamazepine or phenytoin, the (oral) clearance of topiramate increases 2-fold and its half-life becomes shorter by approximately 50%, which may require topiramate dosage adjustment when phenytoin or carbamazepine therapy is added or discontinued. From a pharmacokinetic standpoint, topiramate is a unique example of a drug that, because of its major renal elimination component, is not subject to drug interaction due to enzyme inhibition, but nevertheless is susceptible to clinically relevant drug interactions due to induction of its metabolism. Unlike old AEDs such as phenytoin and carbamazepine, topiramate is a mild inducer and, currently, the only interaction observed as a result of induction by topiramate is that with ethinylestradiol. Topiramate only increases the oral clearance of ethinylestradiol in an oral contraceptive at high dosages (>200 mg/day). Because of this dose-dependency, possible interactions between topiramate and oral contraceptives should be assessed according to the topiramate dosage utilised. This paper provides a critical review of the pharmacokinetic interactions of topiramate with old and new AEDs, an oral contraceptive, and the CNS-active drugs lithium, haloperidol, amitriptyline, risperidone, sumatriptan, propranolol and dihydroergotamine. At a daily dosage of 200 mg, topiramate exhibited no or little (with lithium, propranolol and the amitriptyline metabolite nortriptyline) pharmacokinetic interactions with these drugs. The results of many of these drug interaction studies with topiramate have not been published before, and are presented and discussed for the first time in this article.     

唐古特大黄提取物不同成分泻下作用的比较研究

目的：研究唐古特大黄提取物不同成分的泻下作用。方法：采用炭末推进方法、酚红排空方法进行肠推进实验,观察大黄提取物各成分(15 g·kg^-1)对小鼠小肠推进和肠水分吸收、大鼠大肠运动的影响。结果：唐古特大黄提取物不同成分与对照组相比,对小鼠小肠推进和肠水分吸收、大肠推进作用均有显著性差异(P<0.01)；与大黄水煎液、醇提液相比,泻下活性存在一些差异。结论：唐古特大黄提取物不同成分均有显著的泻下作用,但与大黄水煎液和醇提液相比有一些差异。     

Coralline hydroxyapatite bone graft substitutes: preliminary report of radiographic evaluation

A new bone graft substitute made by conversion of the calcium carbonate exoskeleton of reef-building sea coral into hydroxyapatite has recently become clinically available. The normal radiographic appearance of two forms of this material is described. In the immediate postoperative period, the exoskeletal architecture of these implants is readily appreciated. With graft incorporation over the ensuing months, their intrinsic structure is gradually lost in association with poor marginal definition. Evolving radiographic findings reflect the biocompatible nature of these implants, which provides the potential for ingrowth of native bone with preservation of the coralline scaffold, resulting in enhanced biomechanical properties.     

急性缺血性卒中影像学检查的建议——美国心脏协会的科学声明（中）

2．3核磁共振血管成像（MRA） 2．3．1背景和方法：在头部MRI检查中常结合MRA,用于急性卒中患者病情评估以指导治疗决策的制定^[19]。日前,有几种不同的MRA技术用于脑血管成像,包括二维时间飞跃（timeof-flight,TOF）序列、三维TOF序列、     

Myocardial infarct size quantification by MR imaging early after coronary artery occlusion in dogs

The feasibility of using magnetic resonance (MR) imaging to estimate myocardial infarct size was explored in an in vitro model using only the inherent differences in contrast between infarcted and noninfarcted myocardium. Eight dogs underwent coronary occlusion; their hearts were removed 6 hours later. Estimates of T2 for normal and infarcted myocardium were derived from MR images. Infarct size was quantified anatomically using triphenyltetrazolium-chloride (TTC) staining and compared with MR estimates. The T2 values derived from the images clearly discriminated between infarcted (126 +/- 22 msec) and normal myocardium (88 +/- 10 msec, P less than .05), providing images with good contrast between normal and infarcted myocardium. Comparable differences in T2 values were also noted from spectrometric determinations. Estimates of infarct size by MR imaging compared well with TTC estimates (r = 0.98) over a wide range of infarct sizes from 3% to 29% of the left ventricular mass. These results suggest the potential for in vivo quantification of infarct size based on the inherent contrast difference between infarcted and normal myocardium.     

急性失代偿性心力衰竭患者血清肌钙蛋白T水平检测的价值

目的：研究肌钙蛋白T的水平变化在急性失代偿性心力衰竭患者预后的价值。方法：选取急诊重症监护室收治的68例急性失代偿性心力衰竭患者,按照cTnT的水平分为cTnT阳性组（27例）和cTnT阴性组（41例）。观察两组患者室性期前收缩发生率、APACHEⅡ评分、在ICU入住时间、住院时间、住院病死率、随访出院后6个月内再入院率及6个月死亡率。结果：两组治疗期间利尿剂、扩血管药物使用、多巴胺和（或）多巴酚丁胺的使用和两组患者6个月随访期间死亡率比较差异无统计学意义（P〉0.05）。入院时APACHEⅡ评分、在ICU入住时间、住院时间、住院病死率及出院后6个月内再入院率比较均显示差异有统计学意义（P〈0.05）。结论：肌钙蛋白T水平是与治疗无关的危险因素之一。伴有肌钙蛋白T升高的急性失代偿性心力衰竭患者有较高的室性期前收缩发生率、较长的住院时间、短期预后差,监测cTnT水平对急性失代偿性心力衰竭患者的病情评估和短期预后有重要作用。     

Massive hemoptysis: control by embolization of the thyrocervical trunk

A case of recurrent hemoptysis following bronchial artery embolization is presented. The bleeding was successfully controlled by embolization of the thyrocervical trunk.