Glycation of lipoproteins and accelerated atherosclerosis in non-insulin-dependent diabetes mellitus

Summary We used a new and remarkably simple method to examine the extent of in vivo lipoprotein glycation in type II diabetic patients with atherosclerosis and diabetic patients with no complications. Serum glycated lipoprotein levels were determined by agarose gel film electrophoresis in 48 non-diabetic control subjects and 39 diabetic patients, of whom 26 had no complications and 13 had atherosclerotic heart disease. Fasting serum glucose, glycohemoglobin and serum fructosamine concentrations (indicators of glycemia) and total cholesterol, triglyceride, low-density lipoprotein-, very low-density lipoprotein-and high-density lipoprotein-cholesterol concentrations and the low-density lipoprotein/high-density lipoprotein ratio (serum lipid profile) were also detewrmined in the control and diabetic subjects. Glycated low-density lipoprotein and very low-density lipoprotein concentrations were significantly increased in diabetic patients compared with controls; but only glycated very low-density lipoprotein was significantly increased in atherosclerotic patients compared with diabetics without complications. The lipid profile parameters were not significantly increased in patients compared with controls. In diabetics, especially those with poorly controlled hyperglycemia and atherosclerosis, glycation of lipoprotein fractions might be more important than serum lipid and lipoprotein abnormalities. The significant correlation between atherosclerosis and glycated very low-density lipoprotein, suggests that very low-density lipoprotein glycation could be responsible for the development of atherosclerosis in diabetes.     

Self-regulated learning instructional support for students enrolled in an accelerated nursing program

BackgroundNursing students in accelerated programs come from diverse cultural and educational backgrounds and must adapt to the academic rigor and rapid pace inherent in accelerated programs. The student must progress to a level of independence and self-regulation to become a lifelong learner. However, there is little evidence of the impact of an accelerated program on students’ self-regulation.AimsTo determine if:

• •Teaching for SRL improved students’ self-regulatory strategy use in an accelerated nursing program.
• •There are differences between international and domestic students’ motivational and learning strategy use.

MethodsA quasi-experimental design using the Motivational Strategies for Learning Questionnaire (MSLQ) was employed to assess motivational behaviours and learning strategies of students before and after participating in instructional activities over the first semester of an accelerated program. Data from two open-ended questions were analysed using content analysis.FindingsSeventy-six students completed pre and post surveys. Student median scores were above average on motivational behaviours and learning strategies with a slight decrease post-intervention. High correlation of motivational behaviours and learning strategies of both groups were quantitatively identified and supported by qualitative data.At post-intervention, international students had statistically significantly lower task value and lower control of learning beliefs than domestic students. All median values for motivational behaviours and learning strategies decreased for both groups at post-intervention, except help-seeking which increased for domestic students.DiscussionThis study demonstrated the complexity and cognitive load of condensed programs can be challenging, particularly for novice learners and international students.ConclusionThis study contributes to the research base for curriculum development and learning outcomes for students in accelerated programs beyond nursing.     

Assay of insulin-like activity by the isolated fat cell method IV. The biological activity of proinsulin

Summary The effect of bovine proinsulin and related factors on the glucose metabolism of isolated, rat, fat cells was studied. The dose-response curve of proinsulin was parallel to that of insulin and the action of the two proteins showed an identical time course. The activity of single chain proinsulin was about 0.5 U/mg (as estimated from its ability to increase the conversion of¹⁴C-glucose to¹⁴CO₂ or to¹⁴C-glycerides by fat cells) and rose to about 17 U/mg after treatment with trypsin. — The activity of insulin was quantitatively recovered in the presence of proinsulin. Split chain proinsulin showed an activity of 5 U/mg, which rose to about 18 U/mg after treatment with trypsin. Connecting peptide did not influence the glucose metabolism in the absence or presence of insulin. — There was no conversion of proinsulin in the isolated cell incubation medium to insulin or a similar molecule with high biological activity. The activity was the same on rat epididymal fat pads as on isolated fat cells, and there was no significant suppression by Kunitz pancreatic trypsin inhibitor in either system. — The following was concluded: the biological activity of proinsulin on rat isolated fat cells and epididymal fat pads is about 2 per cent of that of insulin, and the effect is caused by the proinsulin molecule itself. The reason for the low biological activity is presumably a smaller affinity for insulin receptors.

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Untersuchungen der Insulinähnlichen Aktivität an isolierten Fettzellen. IV. Die biologische Aktivität von Proinsulin

Zusammenfassung Die Wirkung von Rinderproinsulin und verwandter Faktoren auf den Glucosestoffwechsel von isolierten Ratten-Fettzellen wurde untersucht. Die Dosis-Wirkungskurve von Proinsulin verlief parallel zu der von Insulin, und die Einwirkung beider Proteine zeigte einen identischen Zeitablauf. Die Aktivität von einkettigem Proinsulin betrug etwa 0.5 E/mg (wie aus seiner Fähigkeit geschlossen wurde, die Umwandlung von¹⁴C-Glucose in¹⁴CO₂ oder¹⁴C-Glyceride in Fettzellen zu steigern), und erhöhte sich nach Trypsinbehandlung a,uf etwa 17 E/mg. — In Gegenwart von Proinsulin ließ sich die Aktivität von Insulin quantitativ wiederfinden. Proinsulin mit gesprengter Kette wies eine Aktivität von 5 E/mg auf, die nach Trypsinandauung auf 18 E/mg anstieg. C-Peptid beeinflußte den Glucosestoffwechsel weder mit noch ohne Insulinzusatz. — In der Inkubationsflüssigkeit von isolierten Zellen ließ sich keine Umwandlung von Proinsulin in Insulin oder ein ähnliches Molokül mit hoher biologischer Aktivität nachweisen. Aktivitätsmessungen am Ratten-Nebenhoden-Fettgewebsanhang erbrachten die gleichen Resultate wie an isolierten Fettzellen, und der Kunitz-Pankreas-Trypsin-Inhibitor führte in keinem der beiden Systeme zu einer signifikanten Hemmung. — Es wurden folgende Schlüsse gezogen: Proinsulin weist an isolierten Ratten-Fettzellen und am epididymalen Fettgewebsanhang der Ratte etwa 2% der biologischen Aktivität von Insulin auf, und der Effekt wird durch das ProinsuIin-Molekül selbst hervorgerufen. Der Grund für die niedrige biologische Aktivität ist vermutlich in einer geringeren Affinität zu den Insulin-Receptoren zu suchen.

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Dosage de l'activité insulinique par la méthode des cellules adipeuses isolées. IV. L'activité biologique de la proinsuline

Résumé L'effet de la proinsuline bovine et de facteurs analogues sur le métabolisme glucidique de cellules adipeuses isolées de rat a été étudié. La courbe dose-réponse de la proinsuline était paralléle à celle de l'insuline et l'action des deux protéines montrait une évolution dans le temps identique. L'activité de la proinsuline à chaîne unique était d'environ 0.5 U/mg (calculée d'aprés sa capacité à augmenter la conversion de glucose-¹⁴C en¹⁴CO₂ ou en glycérides¹⁴C par des cellules adipeuses) et montait à environ 17 U/mg aprés traitement avec de la trypsine. L'activité de l'insuline a été retrouvée quantitativement en présence de pro insuline. Laproinsuline à chaîne rompue montrait une activité de 5 U/mg qui s'élevait à 18 U/mg aprés traitement par la trypsine. Le polypeptide de connexion n'influençait pas le métabolisme glucidique avec ou sans insuline. Dans le milieu d'incubation, il n'y avait pas de conversion de proinsuline en insuline ou en une molécule comparable avec une activité biologique élevée. L'activité était la même avec du tissu adipeux épididymaire de rat qu'avec des cellules adipeuses isolées et il n'y avait pas de suppression significative par l'inhibiteur de trypsine pancréatique de Kunitz dans aucun des deux systémes. Nous sommes arrivés aux conclusions suivantes: L'activité biologique de la proinsuline sur des cellules adipeuses isolées du rat et sur le tissu adipeux épididymaire correspond à environ 2% de celle de l'insuline et l'effet est causé par la molécule de proinsuline elle-même. La raison pour cette activité biologique basse est probablement une affinité réduite pour les récepteurs de l'insuline.

     

起源于左侧希氏-浦肯野系统的特发性加速性室性自主心律

目的 介绍起源于左侧希氏-浦肯野系统的特发性加速性室性自主心律,揭示其临床特征并探讨可能的电生理机制.方法 回顾分析4例特发性加速性室性自主心律患者的心电图形态特征、临床表现、治疗方法及预后.结果 4例患者,男性2例,平均年龄48(40～54)岁,均无器质性心脏病.室性自主心律均呈右束支阻滞型,其QRS时限0.11～0.13 s,符合左侧希氏-浦肯野系统起源,其中3例电轴右偏,1例电轴左偏.自主心律RR间期不规则,平均频率为87(55～110)次/min,与窦性心律交替出现.所有患者临床均表现为发作性心悸.1例患者室性自主心律在短期服用普罗帕酮后消失,另1例短期服用维拉帕米后消失,余2例未予以特殊处理后自然消退.平均随访4.5(2～8)年,临床无心律失常发作,亦无其他心血管事件发生.结论 起源于左侧希氏-浦肯野系统的加速性室性自主心律是左侧希氏-浦肯野系统特发性室性心律失常的一种表现形式,多数为自限性,临床呈良性经过.     

两种不同测定方法监测人血浆中依替米星浓度的比较

目的:比较HPLC法和微生物法测定人血浆中依替米星浓度的差异。方法:选取入院时确诊为复杂尿路感染而肾功能正常患者6名,给予硫酸依替米星注射液200mg,qd,加入9.0mg/mL(0.9%)氯化钠注射液250mL中静脉滴注,连续用药7d,于第2天给药后及第5天给药前取对侧静脉采血2mL,分别采用HPLC法和微生物法测定血浆中药物的浓度。结果:HPLC法平均回收率为96.38%,日内、日间RSD分别为5.04%和6.21%;微生物法平均回收率为101.78%,日内、日间RSD分别为4.95%和6.03%。结论:两种方法回收率和精密度基本一致,受试者血浆中依替米星浓度测得值差异无统计学意义(P>0.05)。     

A computer graphical user interface for survival mixture modelling of recurrent infections

Recurrent infections data are commonly encountered in medical research, where the recurrent events are characterised by an acute phase followed by a stable phase after the index episode. Two-component survival mixture models, in both proportional hazards and accelerated failure time settings, are presented as a flexible method of analysing such data. To account for the inherent dependency of the recurrent observations, random effects are incorporated within the conditional hazard function, in the manner of generalised linear mixed models. Assuming a Weibull or log-logistic baseline hazard in both mixture components of the survival mixture model, an EM algorithm is developed for the residual maximum quasi-likelihood estimation of fixed effect and variance component parameters. The methodology is implemented as a graphical user interface coded using Microsoft visual C++. Application to model recurrent urinary tract infections for elderly women is illustrated, where significant individual variations are evident at both acute and stable phases. The survival mixture methodology developed enable practitioners to identify pertinent risk factors affecting the recurrent times and to draw valid conclusions inferred from these correlated and heterogeneous survival data.     

Comparison and evaluation of a novel bioassay and high‐performance liquid chromatography for the clinical measurement of serum voriconazole concentrations

The aim of this study was to develop and validate a novel bioassay for determining serum voriconazole (VRC) concentrations and to compare its routine clinical performance with that of high‐performance liquid chromatography (HPLC). The biological activity of VRC was measured by a plate diffusion assay using a VRC‐hypersusceptible Candida kefyr strain. The bioassay’s utility was tested by measuring steady‐state VRC concentrations in 100 serum probes from VRC‐treated patients. The HPLC system used solvent extraction with hexane : dichloromethane followed by reversed‐phase HPLC with ultraviolet detection. The intra‐day and inter‐day accuracy of the bioassay was <5%, while that of HPLC was <1%. The precision (mean coefficient of variation, 3.5%) was equal for both the methods. The limit of quantification was lower for HPLC (0.2 mg l^?1) than for the bioassay (0.5 mg l^?1). The result of linear regression analysis was HPLC = 1.0178 (bioassay) + 0.328; R² = 0.88; n = 100. Results of the serum panel ranged from 0.5 to more than 8.0 mg l^?1 for the bioassay and from 0.26 to 10.1 mg l^?1 for HPLC. Especially in laboratories without access to HPLC, the bioassay may be a clinically useful tool for therapeutic drug monitoring.     

基于神经氨酸酶活性检测的板蓝根品质的生物评价

采用流感病毒神经氨酸酶 (NA) 体外活性荧光检测法测定板蓝根的NA抑制生物活性, 并建立板蓝根抗病毒生物效价检测方法。研究表明板蓝根具有抑制NA的活性, IC₅₀ = (0.90 ± 0.20) mg·mL^-1 (相当于生药), 其量效曲线形状与阳性对照药磷酸奥司他韦相似, 提示二者对NA的抑制可能具有相同的作用方式。采用“质反应平行线”法设计和优化的板蓝根抗病毒生物效价检测方法, 重复性较好 (RSD = 5.78%), 实际样品检测结果均能通过可靠检验 (偏离直线P > 0.05、偏离平行P > 0.05)。研究结果表明, 所建立的生物效价检测方法可以作为板蓝根品质生物评价的方法之一。     

The transgenic mouse assay as an alternative test method for regulatory carcinogenicity studies—Implications for REACH

REACH, an EU regulation that requires the submission of safety data in support of the protection of human and environmental health, mandates that registration should be achieved with the minimum amount of animal testing possible. Under REACH, a two-year carcinogenicity assay may be required for certain chemicals produced at >1000 metric tonnes per year. In addition, some chemicals that are found to be genotoxic will also require testing. Alternative methods have been explored in an attempt to improve the predictivity of this bioassay as well as to reduce the number of animals used for such testing. This research has focused on the use of transgenic/knockout mouse models. Study results from selected models indicate that they are useful in hazard identification, even if they are not entirely suitable for risk assessment on their own. Carcinogenic hazard assessment can be greatly enhanced and animal use reduced if the traditional two-year rat bioassay is combined with a well conducted transgenic mouse assay. Importantly, the use of transgenic animals to supplement a traditional two-year carcinogenicity study may help reduce the number of false negatives, one of the unstated goals of REACH via the precautionary principle.