Pharmacological studies of lumisantonin derivatives, with special reference to anti-inflammatory effect and to histamine-release inhibitory action

A number of derivatives and related compounds of lumisantonin were submitted to evaluatien for the action of histamine-release inhibition and antiinflammatory effect, as they structurally resemble guaiazulene in which these actions had been proved. Nineteen compounds of these suppressed 50 per cent or more of the increase in urinary excretion of histamine due to ovomucoid injection. Five of them markedly inhibited all the edemas in the rat hind paws induced by local inoculation of dextran, hyaluronidase, histamine, and 5-hydroxytryptamine. Among these compounds, #32(methyl pyrophotosantoninate) showed a superior effect of inhibition than guaiazulene on all of these edemas, although the effects of two drugs were comparable in the case of oral administration. The members showing the edema inhibition likewise evidently protected passive cutaneous anaphylaxis in guinea pigs by the intraperitoneal administration; the effect of #32 was more marked than guaiazulene. This effect could be observed when applied to the skin with an ointment containing the compouhd in a concentration of more than 0.03 per cent 24 hours before. In vitro histamine releases from the minced lung tissue of sensitized guinea pig elicited by antigen and sinomenine were both inhibited by these compounds. These findings indicate that the main sites of the histamine-release inhibition and of the anti-inflammatory effect of these compounds are in the local tissue. Compound #32 failed to show any analgesic effect in mice, but possessed a considerable antipyretic action in rats. Some of the compounds in the tests depressed guinea-pig ileal strip while guaiazulene increased peristalsis, but any of these actions was not recognized with #32 even in a high concentration. Most of the members effective in inhibiting edemas as well as histamine release proved to be less toxic than guaiazulene. #32 was well tolerated in the doses of 6g/kg orally and of 4g/kg intraperitoneally by mice. The growth curves for three weeks of rats practically did not deviate from that of the controls by daily administration of 1g/kg of #32 by stomach tube and there were no gross and microscopical abnormalities in the main organs and blood.</p

Stress analysis in a layered aortic arch model under pulsatile blood flow

BACKGROUND: Many cardiovascular diseases, such as aortic dissection, frequently occur on the aortic arch and fluid-structure interactions play an important role in the cardiovascular system. Mechanical stress is crucial in the functioning of the cardiovascular system; therefore, stress analysis is a useful tool for understanding vascular pathophysiology. The present study is concerned with the stress distribution in a layered aortic arch model with interaction between pulsatile flow and the wall of the blood vessel. METHODS: A three-dimensional (3D) layered aortic arch model was constructed based on the aortic wall structure and arch shape. The complex mechanical interaction between pulsatile blood flow and wall dynamics in the aortic arch model was simulated by means of computational loose coupling fluid-structure interaction analyses. RESULTS: The results showed the variations of mechanical stress along the outer wall of the arch during the cardiac cycle. Variations of circumferential stress are very similar to variations of pressure. Composite stress in the aortic wall plane is high at the ascending portion of the arch and along the top of the arch, and is higher in the media than in the intima and adventitia across the wall thickness. CONCLUSION: Our analysis indicates that circumferential stress in the aortic wall is directly associated with blood pressure, supporting the clinical importance of blood pressure control. High stress in the aortic wall could be a risk factor in aortic dissections. Our numerical layered aortic model may prove useful for biomechanical analyses and for studying the pathogeneses of aortic dissection

AC current loss of a meander-shaped QMG current limiting device

The AC current loss of a meander-shaped QMG current limiting device was measured. Although the frequency was changed in the range of 35–200 Hz, an obvious frequency dependence of the AC current loss was not observed. Hence, the pinning loss is dominant in the observed AC current loss. The specimen seemed to be homogeneous and not to be damaged during a manufacturing process, since the voltages in the measured sections were nearly the same and the energy loss density coincided with the result on the bridge specimen. The experimental result of the AC loss agreed well with Norris\u27s formula for an elliptic cross-section. However, the theoretical prediction by Irie–Yamafuji\u27s model does not agree well with experimental result