Artepillin C was extracted from Brazilian propolis. Artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) has a molecular weight of 300.40 and possesses antibacterial activity. When artepillin C was applied to human and murine malignant tumor cells in vitro and in vivo, artepillin C exhibited a cytotoxic effect and the growth of tumor cells was clearly inhibited. The artepillin C was found to cause significant damage to solid tumor and leukemic cells by the MTT assay, DNA synthesis assay, and morphological observation in vitro. When xenografts of human tumor cells were transplanted into nude mice, the cytotoxic effects of artepillin C were most noticeable in carcinoma and malignant melanoma. Apoptosis, abortive mitosis, and massive necrosis combined were identified by histological observation after intratumor injection of 500 microg of artepillin C three times a week. In addition to suppression of tumor growth, there was an increase in the ratio of CD4/CD8 T cells, and in the total number of helper T cells. These findings indicate that artepillin C activates the immune system, and possesses direct antitumor activity.

In order to evaluate the functional characteristics of the intramyocardial capacitance vessels during prolonged diastole, we analyzed the response of coronary vein flow after stepwise changes of coronary artery pressure in anesthetized open-chest dogs by using our newly developed laser Doppler velocimeter with an optical fiber. The peripheral portion of the great cardiac vein was isolated and the optical fiber tip was inserted into the vessel. The left anterior descending coronary artery was cannulated and connected to a reservoir to regulate coronary perfusion pressure. Intracoronary adenosine administration was carried out to avoid any change in coronary vasomotor tone. After 15 seconds of occlusion of the perfusion route, the heart was arrested by pacing-off. Two seconds later, coronary perfusion pressure was increased stepwise to a preset target pressure. This procedure was repeated by changing target pressure at 4 (or 5) different pressure levels (31-105 mm Hg). The great cardiac vein flow became zero due to the cardiac arrest and remained at zero for a moment (dead time) after the initiation of reperfusion. Then the flow reappeared and increased with first order time delay. The presence of dead time indicates the existence of unstressed volume, and the first order time delay represents the product of resistance and capacitance. The unstressed volume with a minimal vasomotor tone for perfusion pressure of 60-90 mm Hg was 5.2 +/- 2.2 ml per 100 g left ventricle, which is comparable to coronary blood flow for several beats. The capacitance at perfusion pressure of 60-90 mm Hg was 0.08 +/- 0.04 ml/mm Hg per 100 g left ventricle, while that at low perfusion pressure (30-50 mm Hg) was 0.14 +/- 0.09 ml/mm Hg per 100 g left ventricle. These results indicate that the intramyocardial capacitance vessels have two functional components, and that the phasic nature of coronary vein flow is solely the result of the myocardial squeezing of the blood in the capacitance vessels.

In the present study, characteristics of the phasic flow pattern in the great cardiac vein and the mechanism of such pattern formation were investigated using a laser Doppler velocimeter with an optic fiber probe. The laser Doppler velocimeter allowed measurements of venous blood velocity under more physiological conditions than were possible with previous methods. Moreover, venous blood flow measurement in the great cardiac vein mirrors the effects of myocardial contraction on the venous flow more directly than does measurement in the coronary sinus. Thus, our method is considered very useful. Results obtained from the present study are as follows: 1) Measurement of the phasic flow in the great cardiac vein was made in 11 anesthetized dogs using our laser Doppler method. The blood velocity curve obtained in the great cardiac vein was always characterized by a prominent systolic flow wave (SFW). The mean value for the maximum velocities under control conditions in 11 cases was 40 +/- 13 cm/s. The blood velocity increased with the onset of left ventricular ejection and decreased gradually after the peak formation at mid- or late systole.--2) Besides the above SFW, one or two small wave components were frequently observed during the atrial contraction period and/or during the isovolumic contraction phase. On the waveform during the atrial contraction period, two cases showed forward flow, while one case showed reverse flow. The small reverse flow waves during the isovolumic contraction phase were found in seven cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Lumin is a potent cell-activating agent and a photosensitizer characterized by absorption peaks at 670 nm and 770 nm. It has already been demonstrated that macrophase activity is enhanced greatly by lumin administration with laser light irradiation and that this method is useful in cancer immunotherapy. In this study, a new needle type therapeutic system was developed for the immunotherapy of cancer growing in deep human organs. A human lung cancer grafted onto nude mice was strongly cicatrized by collagen fibres about four weeks after the first treatment. The collagen fibres seemed to seal-off the tumor and prevent its growth with intense cicatrization. In addition, a high T/B cell ratio of lymphocytes was observed in the peripheral blood of the treated mice, although the thymus is congenitally absent from nude mice. These results demonstrated that the system is a reliable method for cancer treatment in deep organs without side effects and/or major surgical intervention.

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