Reversible Adsorption of Soluble Hexameric Insulin onto the Surface of Insulin Crystals Cocrystallized with Protamine: An Electrostatic Interaction

Mixing pharmaceutical preparations of soluble neutral regular insulin solution (NRI) and neutral protamine Hagedorn (NPH) crystalline insulin suspension leads to a reduction in the measurable amount of soluble insulin in the formulation supernatant. However in spite of the loss in soluble insulin, the time-actions of these components have been shown, in clinical trials, to be unaffected. The interaction between these different physical forms of insulin has been studied using reversed-phase HPLC, isothermal titrating calorimetry, and Doppler electrophoretic light scattering analysis. Sorbent surface and solution perturbation studies revealed that the NRI adsorbs to the surface of the NPH crystal with an equilibrium constant ranging from 10⁴ M^–1 to 10⁷ M^–!, depending on the protamine concentration, pH, ionic strength, and temperature. This adsorption behavior suggests that the binding is mediated by electrostatic interactions arising between the positively-charged NPH crystal and the negatively-charged NRI hexamer. Doppler electrophoretic light scattering results, used to probe the pH-dependent surface charge of NPH and soluble insulin hexamer, support the conclusion that electrostatic interactions mediate the adsorption process. Adsorption studies under physiological conditions indicate that the elevated temperature and ionic strength, in a subcutaneous depot, are sufficient to lead to the dissociation of the NRI/NPH complex that exists in these NPH mixture formulations.     

Effect of regular training on the anthropometric parameters and urine steroids in childhood

The changes in the anthropometric data and urine steroid metabolites caused by regular training in children in two age groups (11 and 14 years old) were investigated. The skinfolds of older girls participating in regular athletic, swimming or soccer training were thinner compared with age-matched control groups (P < 0.01) and their body mass and constitution were lower (P < 0.05). In the other groups no significant differences were observable in the anthropometric parameters. The trained children in all groups had significantly higher exercise times on the cycle ergometer (P < 0.01, in young boysP < 0.05). The strength of their hands was lower in three trained groups: in younger boys (P < 0.05), in younger girls (P < 0.01) and in older girls (right handP < 0.01, left handP < 0.05). The urinary excretion of androsterone (P < 0.02), 11-ketopregnanetriol (P < 0.01) and pregnenetriol (P < 0.02) was decreased in the older trained girls; pregnenetriol was increased in younger boys (P < 0.05). Urinary excretion of cortisol metabolites was increased in trained boys [in younger boys: tetrahydrocorticosterone (P < 0.05) and 20-hydroxycortisol (P < 0.05); in older boys allotetrahydrocortisol (P < 0.02), cortisol (P < 0.05) and 20-hydroxycortisol (P < 0.05)]. There were no significant differences in the younger girls. In the trained older girls urinary excretion of cortisol metabolites was decreased: tetrahydrocortisone (P < 0.02), allotetrahydrocorticosterone (P < 0.01), tetrahydrocortisol (P < 0.05), -cortolone (P < 0.01), cortisol (P < 0.02), 6-hydroxycortisol (P < 0.01) and 20-hydroxycortisol (P < 0.05). A multivariate analysis of the data from the trained groups and sedentary, age-matched control groups showed that regular training has a significant effect on steroid excretion.     

Evolution of renal replacement therapy in East Germany from 1989 to 1992

Diminished availability of facilities for renal replacementtherapy is known to cause spuriously low acceptance and treatmentrates. In this context the evolution of renal replacement therapyin the former German Democratic Republic is a useful model tostudy and to quantify some of the relevant factors. We performed a survey in all dialysis units for adults in EastGermany (excluding East Berlin) by questionnaire, achievinga response rate of 97%. From December 1989 to December 1992the number of dialysis centres increased from 53 to 96 (+81%),reaching 6.7 centres p.m.p. Of these facilities, 45% were hospitalunits, 29% private units, and 26% dialysis units run by non-profithealth care organizations. The number of dialysis stations forregular dialysis treatment increased from 602 to 1276 (+112%),i.e. 89 stations p.m.p. In parallel, the number of chronic dialysispatients increased from 2127 to 3848 (+81%), i.e. 267 patientsp.m.p. A more detailed survey was carried out in Thüringen andpart of Sachsen, in a region covering 5 million inhabitants.The acceptance rate for chronic dialysis treatment has increasedfrom 49 to 107 patients p.m.p. (+115%). The average age of newpatients increased from 49 to 59 years, the proportion of patientsaged 65 years increased from 16 to 42% and the proportion ofdiabetics from 13 to 35%. Introduction of alternative treatmentmodalities became possible, with 2.3% of the patients receivinghaemofiltrations and 3% CAPD. The proportion of HBs-antigen-positivepatients decreased from 14.2% to 5%. At the end of 1989 in the former GDR (excluding East Berlin),773 patients and, at the end of 1992, 1153 patients were alivewith functioning renal transplants (+49%). The annual rate oftransplantations was 254 in 1989, and 283 in 1992 (+11%), i.e.18 transplantations p.m.p. (including East Berlin). At the end of 1989 2900 patients (193 p.m.p.), and at the endof 1992 5001 patients (347 p.m.p.), werealive on renal replacementtherapy (dialysis or functioning renal transplant) in East Germany,excluding East Berlin; this represents a 72% increase. The figures in East Germany are now almost equivalent to thosein West Germany regarding the number of admissions (incidence),whereas the number of patients on renal replacement therapyis still lower (prevalence).     

口腔扁平苔藓患者种植修复联合治疗5年随访结果1例报告及文献复习

探讨1例伴口腔扁平苔藓（OLP）患者行种植修复的联合治疗方法,阐述多学科联合治疗对患者口腔功能恢复的重要意义。     

普通高校学报目标定位及发展思路探讨

针对我国高校学报发展面临的一些问题,从办刊目标定位和发展思路两个方面进行了初步的分析和探讨。高校学报必须明确办刊的目标定位,从树立创新意识和加强质量控制两个方面实现学报的优势发展。     

论国家主体医疗卫生事业中医患关系的法律属性

国家主体医疗卫生事业中医患关系的法律属性问题是卫生法制建设的一个基本课题。本文认为,国家主体医疗卫生事业,是实际负责向全民提供医疗保障的部门。医患关系不具备民法调整的平等主体间的横向经济关系的三大特征,不是民事法律关系,而是行政法律关系。     

胰岛素和亚硒酸钠最佳配比组方研究

目的 确定普通胰岛素与亚硒酸钠降血糖作用的最佳组方配比.方法 采用小剂量链脲佐菌素腹腔注射联合高糖高脂饲养的大鼠模型,以血糖降低百分率为考察指标,根据权重配方法设不同配比组方6组,分析结果得出最佳理论配比,并进一步做确证性试验考察二者的相互关系.结果 胰岛素与亚硒酸钠对血糖的控制为协同作用,二者比例为1 U:5μg时可显著降低血糖.结论 胰岛素和亚硒酸钠的最佳配比为1 U:5μg.     

国外药物靶标开发的规律与特点分析

随着人类基因组计划的完成、基因功能的发现,以及各种高通量筛选方法的实现,药物靶标已经成为现代创新药物研发的一个重要环节。尽管如此,药物靶标的创新速率仍然维持在非常低的水平上,每年成功上市药物的分子靶标仅有3—5个是新靶标。分析国外药物靶标的开发特点和内在规律,可以为我国生物制药公司和研发机构选择合适的药物靶标提供一些有用的信息。     

血液透析中预防超滤所致低血压的临床体会

目的:分析比较在总超滤量不变的前提下,常规血液透析(HD)与调整后采用分段超滤透析,同时配合可调钠使用的低血压发生情况。方法:33例患者分为老年组与非老年组,按HD分时段发生低血压统计分析。将调整不同时段超滤率和透析液钠离子浓度HD与每组常规HD进行对比。结果:两组低血压多发生在3、4 h时段,老年组低血压发生率高于非老年组,调整不同时段超滤率和钠离子浓度后,两组低血压发生明显减少。结论:单位时间内超滤过多过快是导致低血压发生的主要原因。在确定合理超滤总量后,调整不同时段超滤率采用先快后慢配合可调钠先高后低的使用原则,可明显减少低血压发生率。