指数程序升温药物稳定性试验

介绍了一种新的程序升温(指数程序升温)药物稳定性预测加速试验方法及计算方法。在这一新的程序升温方法中,温度每升高10℃,升温速率将增大2～4倍:dT/dt=a^(T-T₀)/10·(dT/dt)₀,使药物在高温和低温范围内的降解程度尽可能一致,提高了试验准确度。采用单因素优选法和数值积分法处理试验数据,避免了任何近似处理,使计算结果准确可靠。与线性升温、倒数升温和对数升温加速试验进行了对比,结果表明,指数程序升温法的准确性优于其它3种升温法。     

Relationship of Psychosocial Risk Factors, Certain Personality Traits and Myocardial Infarction in Indians: A Case�Ccontrol Study

Objective:

To investigate the relationship of psychosocial factors (lack of social support, stress and subjective well-being) and personality traits with myocardial infarction (MI).

Materials and Methods:

A case–control study involving 100 cases and 100 matched controls was conducted in Lok Nayak Hospital, New Delhi.

Results:

Stress over 1 year was significantly higher in cases (P < 0.001). However, difference was not significant when scores of social support (P = 0.2), Presumptive Stressful Life Event (PSLE) over lifetime (P = 0.058) and subjective well-being (P = 0.987) were compared. MI was significantly associated with hyperactive (P < 0.001), dominant (P = 0.03), egoistic (P < 0.001) and introvert (P < 0.001) personalities.

Conclusion:

Certain personality traits and recent stress may be important risk factors of MI, especially in Indians. The finding may have implications on the preventive strategies planned for MI patients.     

漫反射光谱法研究维生素C与片剂辅料的相互作用

漫反射是一束光射到一定厚度的不透明不光滑固体表面上,光被部分吸收和部分散射后,向各个方向的反射。反射光的分数称为反射率。测定反射率时一般与某种白色粉末(例如硫酸钡)相比较,测得的反射率为相对反射率。以相对反射率对波长作图所得的曲线称为漫反射光     

Cyclic neutropenia (CN): a clue to the control of granulopoiesis

A simple quantitative feedback model of granulopoiesis is presented and discussed within the framework of existing data on granulopoiesis in both normals and patients with cyclic neutropenia (CN). The model assumes that the controlled compartment is the bone marrow pool of mature neutrophils (PMNs), which sends a negative feedback signal to the mitotic pool of early granulocyte precursors (i.e., CFU-C, myeloblasts, etc.) thus controlling the granulocyte production rate. Three parameters are found to play important roles in determining the response of the system to perturbations. These are: TM, the granulocyte maturation time; a, a parameter reflecting the strength of the negative feedback exerted by mature PMNs on the granulocyte production rate; and b, a parameter describing the leakiness of the bone marrow for PMN egress. It is shown that depending on the relative magnitudes of a and b, the system will either respond to perturbations with a damped oscillation (a less than b: the normal state) or with a sustained oscillation (a greater than b: the CN state). In both cases, the oscillation period is found to approximately equal 2TM. Deductions of the values of a, b, and TM from experimental data are consistent with the predictions of the model and show an increased value of a in CN relative to the normal state. This suggests an overly active feedback mechanism as the pathophysiologic basis of CN. In addition, the model can explain how various therapeutic agent correct CN and also provides insight into why other hematologic cell lines and CSA oscillate in CN.     

Serum interleukin 2 receptor levels in childhood acute lymphoblastic leukemia

The clinical significance of interleukin 2 receptor (IL2R) concentrations in serum was determined for 344 children with newly diagnosed acute lymphoblastic leukemia (ALL). Serum levels of IL2R in patients (267 to 80,000 U/mL, median 2,007 U/mL) were significantly higher than normal control values (170 to 738 U/mL, median 347 U/mL) (P less than .0001). Measurements in cases of T cell ALL were lower than in the non-T, non-B cases (P = .02). Among the 264 patients with non-T, non-B ALL, but not in those with T cell disease, higher serum IL2R levels (greater than 2,000 U/mL) were associated with a poorer treatment outcome (P = .04). In a multivariate analysis, serum IL2R level contributed independent prognostic information beyond that conveyed by leukocyte count, race, and age (P = .04). One explanation for these results is that soluble IL2R competes with normal lymphocyte- integrated IL2R for the ligand and thus could suppress host antitumor immunity.     

程序变温法确定药物降解反应级数

通过电子计算机模拟程序升温加速试验,从理论上阐明了常规的程序升温法不能确定药物降解反应级数的原因是因为同一组数据可由不同的反应级数和活化能的组合所拟合;解决这一问题的关键是在一个变温程序中包含升温和降温部分;据此提出了一种新的程序变温方法(程序升降温法)。利用这种方法,可以真正做到只通过一次程序变温加速试验,就获得包括反应级数在内的药物降解的动力学参数,且确定反应级数的能力与恒温法相近似。     

4-芳杂环单/双氨甲基酚衍生物的合成和量化计算

本文在前报的基础上,设计和合成了4-芳杂环取代的氨甲基酚衍生物28个。初步药理试验表明,多数显示不同程度的抗炎活性。用CNDO/2法计算所得数据提示,该类化合物分子中的氨甲基氮和酚羟基氧与受体正电荷中心的结合,可能对抗炎活性起着重要作用。