A phase I clinical and pharmacokinetic study of the angiogenesis inhibitor, tecogalan sodium

BACKGROUND: Tecogalan sodium is an angiogenesis inhibitor isolated from a sulfated polysaccharide produced by the bacterium Arthrobacter. The antiangiogenic effect of tecogalan sodium is thought to be mediated by the inhibition of binding of basic fibroblast growth factor to cellular receptors. PATIENTS AND METHODS: A phase I study was conducted in thirty-three patients with refractory malignancies, including AIDS-associated Kaposi's sarcoma. Patients received a single i.v. infusion every three weeks with the infusion duration ranging from one to twenty-four hours. Seven different dosage levels were studied (125, 185, 240, 300, 390, 445, and 500 mg/m2). RESULTS: The primary dose-limiting toxicity was prolongation of the activated partial thromboplastin time with peak times being between 1.0-4.0 times the upper limit of normal. This toxicity was ameliorated at a given dose level by prolonging the infusion time. Other common toxicities included fever (40%) and rigors (31%) which were well controlled with acetominophen and meperidine. The serum half-life of tecogalan sodium was between 1-1.5 hours and < 25% of unchanged drug was excreted in the urine. CONCLUSIONS: The recommended phase II dose of tecogalan sodium on this schedule is 390 mg/m2 over 24 hours. Other schedules including continuous administration should be investigated to maximize the efficacy of this novel angiogenesis inhibitor.     

Adaptive non-linear speed control of induction motors

In this paper we present two adaptive non-linear speed control algorithms for induction motors. They employ input-output linearization techniques for the motor model in the stator fixed reference frame. The first control algorithm directly tracks speed and rotor flux. The second is designed using torque and rotor flux tracking and is extended for speed control. A key point is that this algorithm ensures exact current limitation in the known parameter case. The adaptation based on Lyapunov design can cope with rotor and stator resistance variations. Significant simulations using sampled controllers are presented emphasizing adaptation and current limitation effects.     

双曝光全息术用于兔子输卵管特性研究

用单模氩离子激光器拍摄了离休兔子输卵管的双曝光全息相干图。实验结果给出了正常输卵管与非正常输卵管在相干条纹形状上的差异以及相干条纹与溶液、压力及压力传递方向的关系。通过建立数学模型,对输卵管的形变作了定性分析。     

Integration of endothelial cells in multicellular spheroids prevents apoptosis and induces differentiation

Single endothelial cells (EC) seeded in suspension culture rapidly undergo apoptosis. Addition of survival factors, such as VEGF and FGF-2, does not prevent apoptosis of suspended EC. However, when cells are allowed to establish cell-cell contacts, they become responsive to the activities of survival factors. These observations have led to the development of a three-dimensional spheroid model of EC differentiation. EC spheroids remodel over time to establish a differentiated surface layer of EC and a center of unorganized EC that subsequently undergo apoptosis. Surface EC become quiescent, establish firm cell-cell contacts, and can be induced to express differentiation antigens (e.g., induction of CD34 expression by VEGF). In contrast, the unorganized center spheroid cells undergo apoptosis if they are not rescued by survival factors. The responsiveness to the survival factor activities of VEGF and FGF-2 was not dependent on cell shape changes since it was retained after cytochalasin D treatment. Taken together, these findings characterize survival factor requirements of unorganized EC and indicate that polarized surface EC differentiate to become independent of exogenous survival factors. Furthermore, they demonstrate that spheroid cell culture systems are useful not just for the study of tumor cells and embryonic stem cells but also for the analysis of differentiated functions of nontransformed cells.     

Neue n-heterocyclische triglycidylverbindungen

A short survey on heterocyclic glycidyl compounds is given and synthesis of 1,3-bis-(hydantoin-3-yl)-propan-2-ol-derivatives from hydantoins and epichlorhydrin is described. These syntheses and possible intermediates are discussed. Preparation of triglycidylcompounds from these substances is given and properties after curing are mentioned.     

Untersuchungen über die basisch katalysierte reaktion von melamin mit formaldehyd

Reaction products of melamine and formaldehyde can be modified by treatment with N -diethyl-trimethylsilyl-amine to yield materials, which are soluble in organic solvents and can easily be fractionated by gel permeation chromatography. Moreover, gel permeation chromatography is used for the quantitative investigation of the course of the sodium-hydroxyde catalysed methylolation of melamine. For this purpose the differential refractometer is calibrated to the corresponding peak area in the chromatograms. In the quantitative determination of the methylolation reaction of melamine in alkaline aqueous solution a difference between the injected and the amount calculated from calibration data was observed. This difference is caused by the presence of polyoxymethylene glycols in the methylolmelamines. Polyoxymethylene glycols are also found in technical melamine-formaldehyde resins.