软胶囊崩解迟缓现象影响因素研究

目的：研究储存条件以及软胶囊处方对明胶胶片稳定性的影响，探讨软胶囊崩解迟缓的原因。方法：制备明胶胶片模拟软胶囊囊壳，采用溶胀动力学法测定明胶胶片平衡溶胀量(Seq)，同时测定软胶囊内容物溶媒PEG400中甲醛含量。以上述结果为指标，考察不同储存条件与胶囊处方对明胶胶片交联程度的影响。结果：空白明胶胶片在40℃条件下Seq与对照组具有极显著性差异，PEG400中甲醛含量增加。含有甘油、山梨醇、二氧化钛等辅料的胶片浸泡在PEG400中后Seq与对照组具有极显著性差异，PEG400中甲醛含量量著增加。加速条件下含有抗氧剂的胶片Seq与PEG400中甲醛含量变化不大。结论：在考察的储存条件中，温度对软胶囊稳定性影响较大。含有一些常用辅料的明胶胶片易受PEG400中外源性醛类杂质的影响，Seq降低。低沮保存、纯化辅料以及添加抗氧剂有助于缓解软胶囊崩解迟缓现象的发生。     

Combined evaluation of first pass radionuclide angiography and equilibrium radionuclide ventriculography in the diagnosis of coronary artery disease

Results of 203 patients who underwent first pass radionuclide angiography (FP) and quantitative equilibrium radionuclide ventriculography (qERNV) were stored in a data base system and evaluated statistically. Eighty eight of these patients also underwent exercise equilibrium radionuclide ventriculography (E-qERNV). In patients with coronary artery disease (CAD) without previous myocardial infarction (MI), evaluation of global and regional ejection fraction (gEF, rEF) at rest revealed a poor sensitivity of 64%, the specificity was about 71% (qERNV). FP at rest revealed similar values of sensitivity (69%) and specificity (83%). Additional assessment of stress induced changes of gEF, significantly (P<0.05) improved sensitivity of qERNV in CAD patients without a history of previous MI to 84% (specificity 86%). In patients with one previous MI, however, similar values of sensitivity were found (RFP: 87%, R-qERNV: 84%, E-qERNV: 93%). In patients with several MI's, sensitivity was above 90% at rest and during exercise (R-FP: 96%, R-qERNV: 93%, E-qERNV: 100%).     

Radionuclide venography vs Tc-99m-RBC equilibrium angiography: A comparative paired study

Combined direct injection venography (DIV) and equilibrium angiography (EA) were performed in 13 patients, by injecting in vitro labeled ^99mTc autologous RBC, via pedal veins, and imaging the first pass and the equilibrium phase. This paired comparative study of DIV with EA shows that DIV has advantages over EA because it provides selective information on the deep venous system from the calves to the inferior vena cava. DIV provides information on the flow dynamics and the high contrast first pass images provide better definition of non filling venous segments as well as visualization of collaterals. When using ^99mTc-MAA, lung perfusion can also be imaged. DIV is recommended as the procedure of choice for the diagnosis of DVT and EA should be employed only when pedal vein injection is not possible.     

Influence of interaction force levels on degree of motor adaptation in a stable dynamic force field

Studies have shown that the point-to-point reaching movements of subjects seated in a dark, rotating room demonstrate errors in movement trajectories and endpoints, consistent with the direction of the Coriolis force perturbations created by room rotation. Adaptation of successive reaches and the presence of postrotation aftereffects have indicated that subjects form internal models of the Coriolis field dynamics in order to make appropriate movement corrections. It has been argued that these findings are inconsistent with predictions of peripheral stabilization assumed in equilibrium-point models of motor control. A possibility that has been raised, however, is that the Coriolis field findings may in fact stem from changes in control commands elicited due to the magnitude and destabilizing nature of the Coriolis perturbations. That is, it has been suggested that a perturbation threshold exists, below which central reactions are not necessary in order to maintain movement stability. We tested the existence of a perturbation threshold in normal-speed reaching movements. Twelve normal human subjects performed non-visually guided reaching movements while grasping a robotic manipulandum. The endpoints and trajectory deviations of their movements were measured before, during, and after a position-dependent force field (similar to a Coriolis field in terms of the time history of applied forces) was applied to their movements. We examined the responses to a range of perturbation field strengths from small to considerable. Our experimental results demonstrated a substantial adaptation response over the entire range of perturbation field magnitudes examined. Neither the amount of adaptation after 5 trials nor after 25 trials was found to change as disturbance magnitudes decreased. These findings indicate that there is an adaptive response even for small perturbations; i.e., threshold behavior was not found. This result contradicts the assertion that peripheral stabilization mechanisms enable the central controller to ignore small details of peripheral or environmental dynamics. Our findings instead point to a central dynamic modeler that is both highly sensitive and continually active. The results of our study also showed that subjects were able to maintain baseline pointing accuracies despite exposure to perturbation forces of sizeable magnitude (more than 7 N).     

Determination of free fractions of tricyclic antidepressants

Summary The plasma protein binding of amitriptyline, imipramine, clomipramine, and their primary demethylated metabolites were studied by means of a method combining dialysis and gas chromatography. Equilibrium in dialysis of serum containing amitriptyline and its metabolite nortriptyline was attained in about 0.5 h with the drug dissolved in the serum compartment, and in about 2 h with the drug passing from the buffer to the serum compartment.The calculation of free fractions was influenced by variations with dialysis time in the volumes of serum and buffer. Increase of pH in serum increased the protein binding of the weakly basic drugs studied, and made the Donnan distribution effects more pronounced. At pH 7.4, the Donnan effect was negligible.Binding parameters for the 6 tricyclic antidepressant substances studied were estimated for the binding to ₁-acid glycoprotein and for total binding in serum. For ₁-acid glycoprotein, the k-values ranged from 1·10⁵ to 8·10⁵ M^–1, and for pooled serum from 0.4·10⁵ to 8·10⁵ M^–1. The determined number of binding sites on the ₁-acid glycoprotein was, on average 0.87 for the 6 substances. In serum, the binding capacity was 2–14 times the concentration of ₁-acid glycoprotein.     

Radioisotope assessment of heart damage in hypertransfused thalassaemic patients

Twenty-five thalassaemic patients treated with repeated blood transfusion (BT) and intensive iron removal therapy were studied by echocardiography and rest/stress equilibrium gated radionuclide angiocardiography (EGNA). Stress left ventricular ejection fraction (LVEF) showed an important negative correlation with number of BTs (r = –0.75). Abnormal values of stress LVEF were measured after 200 BTs: these data demonstrate the effectiveness of stress LVEF in the follow-up of patients who have undergone repeated BTs and the clinical importance of intensive chelation therapy. Peak filling rate did not show diagnostic value in the early detection of iron cardiotoxicity. However, its inverse correlation with BT (r = –60) indicates that iron overload depresses the diastolic parameters.     

阿莫西林对格列美脲血浆蛋白结合率的影响

目的 研究阿莫西林对格列美脲蛋白结合率的影响。方法 采用平衡透析法结合高效液相色谱法，比较未加和加入阿莫西林后格列美脲的血浆蛋白结合率。结果 4种浓度下，单用格列美脲时的血浆蛋白结合率分别为94.2％、92.8％、91．4％、91．0％；与阿莫西林合用时，格列美脲的血浆蛋白结合率依次变为90．9％、89．0％、89．6％、90．0％。结论 与阿莫西林合用后，格列美脲的血浆蛋白结合率下降。     

Effects of nitric oxide donors on the afferent resting activity in the cephalopod statocyst

The effects of bath applications of the nitric oxide (NO) donors sodium nitroprusside (SNP), diethylamine sodium (DEA), 3-morpholinosydnonimine (SIN-1), and S-nitroso-N-acetyl-penicillamine (SNAP) on the resting activity (RA) of afferent crista fibers were studied in isolated statocysts of the cuttlefish Sepia officinalis. The NO donors had three different effects: inhibition, excitation, and excitation followed by an inhibition. The SNAP analog N-acetyl-DL-penicillamine (xSNAP; with no NO moiety) had no effect. When the preparation was pre-treated with the NO synthase inhibitor N(G)-nitric-L-arginine methyl ester HCl (L-NAME), the NO donors were still effective. When the preparation was pre-treated with the guanylate cyclase inhibitors methylene blue (M-BLU) or cystamine (CYS), NO donors had only excitatory effects, whereas their effects were inhibitory only when pre-treatment was with the adenylate cyclase inhibitors nicotinic acid (NIC-A), 2',3'-dideoxyadenosine (DDA), or MDL-12330A. When pre-treatment was with a guanylate and an adenylate cyclase inhibitor combined, NO donors had no effect; in that situation, the RA of the afferent fibers remained and the preparation still responded to bath applications of GABA. Selective experiments with statocysts from the squid Sepioteuthis lessoniana and the octopod Octopus vulgaris gave comparable results. These data indicate that in cephalopod statocysts an inhibitory NO-cGMP and an excitatory NO-cAMP signal transduction pathway exist, that these two pathways are the key pathways for the action of NO, and that they have only modulatory effects on, and are not essential for the generation of, the RA.     

我国医疗服务业供需结构问题分析

文章描述了我国的医疗服务业供需状况及服务利用情况 ,从纵向和横向两个方面讨论了供需结构不匹配的问题 :我国医疗卫生资源在各分科、各类型医疗服务主体之间的配置并不均衡。文章还给出了用于衡量不均衡度的指标DED(DisequilibriumDegree,DED) ,并计算得到纵横两向资源配置的不均衡度分别为 32 .92和 7.4 6 8。最后文章提出了如何进行调整的对策思路 ,以求加强卫生资源的合理配置 ,达到在同样的投入下满足更多的医疗服务需求的目的。     

Aqueous solubility: Simple predictive methods (in silico,in vitro and bio-relevant approaches)

Aqueous solubility is a key physicochemical attribute required for the characterisation of an active pharmaceutical ingredient (API) during drug discovery and beyond. Furthermore, aqueous solubility is highly important for formulation selection and subsequent development processes. This review provides a summary of simple predictive methods used to assess aqueous solubility as well as an assessment of the more complex in silico methodologies and a review of the recent solubility challenge. In addition, a summary of experimental methods to determine solubility is included, with a discussion of some potential pitfalls.