[Recent progress on the lupine alkaloids in leguminous plants growing mainly in Japan].

The existence of the lupine alkaloids in leguminous plants mainly growing in Japan has been thoroughly ascertained, and 106 kinds of lupine alkaloids, including 51 kinds of novel lupine-type alkaloids, have been isolated and characterized from 28 species belonging to the 9 genera of leguminous plants (Table 1). Among them (e.g. Fig. 1-2), a number of unusual types of alkaloids (e.g. Fig. 2) may be regarded as possible metabolites of the lupine alkaloids that coexist in the same plant, such as (+)-kuraramine-type, (-)-mamanine-type (Fig. 3), (-)-tsukushinamine-type (Fig. 5) and (+)-hupeol-type (Fig. 7) alkaloids, or as products of alternative biosynthetic pathway, such as tashiromine-type and (-)-camoensidine-type alkaloids in the Maackia species. The biosynthetic pathways (Fig. 8) by enzymes (Fig. 9) and some of biological activities (e.g. Table 2) of the lupine alkaloids have also been presented. The leguminous plants that accumulate the common lupine alkaloids may be divided into three main groups: plants which produce the matrine, the cytisine/sparteine, and the lupinine-type alkaloids. In addition, the Maackia species and a few other species produce rare bases. Some of more detailed chemical properties of the lupine alkaloids that have been isolated and studied in our laboratory, including a newly proposed biosynthetic pathway, biotechnological studies, a summary of biological activities, and a discussion of chemotaxonomic aspects of the leguminous plants which accumulate lupine alkaloids, have been reviewed by authors in English papers shown in References 1, 55, 65, and also reviewed by one of the authors (I.M.) in a Japanese papers shown in Ref. 66, in which many aspects of the active research history on (+)-matrine and its relatively alkaloids since 1892 in Japan are described.

The hypoglycemic effect of (7R*,9aS*)-7-phenyl-octahydroquinolizin-2-one in mice.

(-)-Multiflorine (1), which was isolated from leguminous plants, produced a hypoglycemic effect when administered to mice with streptozotocin-induced diabetes. (-)-Multiflorine has an enaminone type conjugation on the A-ring, which is unusual in lupine alkaloids. Proceeding on the assumption that the A-B ring is responsible for the activity, several compounds bearing quinolizidin-2-one were synthesized and their hypoglycemic effects were examined. The hypoglycemic effect of (7R*,9aS*)-7-phenyl-octahydroquinolizin-2-one was approximately 4 times stronger than that of (-)-multiflorine measured by oral glucose tolerance test in normal mice. This result indicates that compounds possessing the quinolizidin-2-one ring system as the basic structure may be possible lead compounds for a new type of diabetes drug.

Lupin alkaloids from Chinese Maackia amurensis.

Two new alkaloids were isolated together with 16 known lupin alkaloids from the leaves and stems of Chinese Maackia amurensis. Their structures were determined by spectroscopic methods to be (-)-6alpha-methoxylupanine and (-)-5alpha-(12-cytisinylmethyl)-6alpha-hydroxylupan ine and identified by comparison with synthetic samples. The structures of lupin alkaloids were also related to the geographical distributions of the Maackia plants.

kappa-Opioid receptor-mediated antinociceptive effects of stereoisomers and derivatives of (+)-matrine in mice.

The antinociceptive effects of seven matrine-type lupin alkaloids were examined using the acetic acid-induced abdominal contraction test (the writhing test) and the tail-flick test in mice. (+)-Allomatrine, the C-6 epimer of (+)-matrine, produced the antinociceptive effect at 1/3 potency of (+)-matrine or pentazocine. It was demonstrated that the antinociceptive effects of (+)-allomatrine were mediated through the activation of kappa-opioid receptors, while the antinociceptive effect of (+)-matrine was mediated by both mu- and kappa-opioid receptors. (-)-Sophoridine, the C-6 epimer of (+)-matrine, (+)-sophoranol, (-)-14 beta-hydroxymatrine and (+)-matrine N-oxide, which possess a hydrophilic group, and (-)-sophocarpine and (-)-sophoramine having a double bond(s) did not show significant antinociceptive activity.

Effects of concomitant usage of milrinone and catecholamine for weaning from cardiopulmonary bypass.

To estimate the effectiveness of concomitant usage of milrinone and catecholamine for weaning from cardiopulmonary bypass (CPB), a clinical study was made, in elective coronary artery bypass grafting (CABG) cases. 24 consecutive patients underwent elective CABG in our institute. In all cases, moderate hypothermia and cardioplegic(St. Thomas solution) cardiac arrest were performed. In 12 cases, continuous intravenous 0.25 microgram/kg/min of milrinone, 3 micrograms/kg/min of dobutamine (DOB) and dopamine (DOA) as the initial doses, were used concomitantly as inotropic agents (Group-I). The same initial doses of catecholamine (DOB and DOA) as the Group-I were administered in another 12 patients (Group-II). When the pump flow of CPB decreased to a half, these drugs were administered in both groups. Hemodynamic data were measured before CPB, just after operation, 3, 6, 12, 24, 48, and 72 hours after operation. There were no significant differences in aortic and pulmonary artery pressure between both groups. However, cardiac index (CI) of the Group-I demonstrated significantly (p < 0.01) higher values than that of Group-II until 24 hours after surgery. Systemic vascular resistance index (SVRI) of the Group-I demonstrated significantly (p < 0.01) lower value than that of Group-II from 3 to 12 hours after operation. There were no significant differences in oxygen delivery (DO2) and oxygen consumption (VO2) between both groups. These results suggested that concomitant usage of milrinone and low dose catecholamine increased CI and decreased SVRI, and made weaning from CPB very easy, demonstrating excellent hemodynamics. This high potential phosphodiesterase inhibitor may be suitable for not only weaning from CPB but also post-cardiotomy cardiogenic shock.

Post-operative effects of olprinone after coronary artery bypass grafting.

The aim of this study was to test the effects of olprinone after coronary artery bypass grafting (CABG). In order to prevent hypotension caused by olprinone, low doses of catecolamines were used concomitantly. Total 22 elective CABG cases were evaluated. In all cases, moderate hypothermia and cardioplegic cardiac arrest were performed. In 10 cases, continuous intravenous 0.1 microg/kg/min of olprinone, 3 microg/kg/min of dobutamine (DOB) and dopamine (DOA) as the initial doses, were used concomitantly (Group I). As a control, the same initial doses of catecolamine (DOB and DOA) of Group I were administered in another 12 patients (Group II). When the pump flow of cardiopulmonary bypass (CPB) was decreased to half, these drugs were administered in both groups. Hemodynamics were recorded before CPB, just after the operation and 3, 6, 12, 24, 48, and 72 hours after the operation. Three hours after the operation, both mean aortic pressure (AoP) and pulmonary artery pressures (PAP) of Group I demonstrated significantly lower values than those of Group II. Cardiac index (CI) of Group I showed significantly higher values than that of Group II until 6 hours after surgery. The systemic vascular resistance index (SVRI) of Group I indicated a significantly lower value than that of Group II until 24 hours after the operation. Pulmonary capillary wedge pressure (PCWP) of Group I demonstrated a significantly lower value than that of Group II. There were no significant differences in urine output, oxygen delivery (DO2) and oxygen consumption (VO2) between both groups. Olprinone increased CI and decreased SVRI, and it showed easy weaning from CPB, demonstrating excellent hemodynamics after CABG. These results suggested that this new phosphodiesterase inhibitor may be effective for not only weaning from CPB but also post-cardiotomy cardiogenic shock.

Antinociceptive effects of (+)-matrine in mice.

The antinociceptive potency of matridin-15-one ((+)-matrine) was examined using the acetic acid-induced abdominal contraction test and the tail-flick test in mice. (+)-Matrine, at doses of 1 to 10 mg/kg, s.c., produced a marked and dose-dependent inhibition of the number of acetic acid-induced abdominal contractions in mice. The antinociceptive effect of (+)-matrine in the acetic acid-induced abdominal contraction test in mice was identical to that of pentazocine. Indeed, there was no significant difference in the ED50 (mg/kg with 95% confidence limits) values for the inhibition of acetic acid-induced abdominal contractions between (+)-matrine (4.7 (4.1-5.3)) and pentazocine (3.3 (2.2-5.0)). Furthermore, in the tail-flick assay, (+)-matrine at doses of 10 and 30 mg/kg, s.c., again produced a dose-dependent antinociceptive effect. When nor-binaltorphimine (20 mg/kg, s.c.), a selective kappa-opioid receptor antagonist, was administered 3 h before treatment with (+)-matrine, the antinociceptive effect of (+)-matrine was markedly antagonized. Furthermore, the antinociceptive effect of (+)-matrine was partially antagonized by pretreatment with beta-funaltrexamine, a selective mu-opioid receptor antagonist. Naltrindole, a selective delta-opioid receptor antagonist, had no effect on the antinociceptive effect of (+)-matrine. In conclusion, (+)-matrine produced an antinociceptive effect mainly through the activation of kappa-opioid receptors and partially through mu-opioid receptors.

[Primary pulmonary cryptococcosis treated by thoracoscopic resection].

A 37-year-old man was admitted to the hospital because of an abnormal shadow in the right lower field on a chest roentgenogram. The lesion was calcified and was therefore suspected to be benign. Thoracoscopic resention was performed. The pathological diagnosis was cryptococcosis of the lung. The lesion was completely resected, so no antifungal drug was given. The patient was doing well as of 12 months after the operation.

[Flavone constituents in the seeds of Sophora vicii folia Hance].

Four flavone compounds have been separated from the mature seeds of Sophora vicii folia. By means of physico-chemical and spectroscopic analysis, their structures have been identified as 5,7,3'-trihydroxy-4'-methoxyflavone (I); 7,3'-dihydroxy-1'-methoxyflavone (II); 7,4'-dihydroxyflavone (III) and 7,3',4'-trihydroxyflavone (IV). All of them are found in S. viciifolia for the first time, and I and II are found Sophora genus for the first time.

[A case of thoracoscopic pulmonary lobectomy for lung cancer].

A case of thoracoscopic right lower pulmonary lobectomy is reported. A 79-year-old man was admitted to our hospital after the accidental finding of a right pulmonary growth. A computed tomography (CT) scan of the thorax confirmed the presence of a neoplasm, 2.5 cm in diameter, at the posterior-basal segment of the right lower lobe. Considering the general condition of the patient and the characteristics of the lesion, we decided to perform a assess the possibility of a thoracoscopic lobectomy instead of the traditional posterolateral approach. The pulmonary artery was dissected with the new endoscopic cherry dissector, and ligated with the polyester suture material and Endo Clip then dived with Endo scissors. The lower pulmonary vein was dissected with this endoscopic cherry dissector and divided with Endo GIA 30 clamping the new thoracoscopic De Bakey type vascular clamp. The specimen was extracted through the minimal thoracotomy (15 cm). The postoperative course was uneventful with minimal postoperative pain, and the patient was discharged after complete surgical recovery with excellent functional and cosmetic results.

[A case of mitral stenosis with a new open pivot bileaflet valve].

The ATS Medical Open Pivot Bileaflet Valve was developed by Villafana who also developed St. Jude Medical valve and put to the first clinical use by Sadeghi on May 4, 1992. Since then, its clinical uses have been made in cases more than 1,000 in the world, centering on Europe, and its usefulness has been reported elsewhere from the aspected of its durability, anti-thrombogenic property, hemolysis, less noise and surgical operability. ATS valve was developed with 9 characteristics as (1) open pivot; (2) removed Struts; (3) wide area orifice; (4) improved stillness; (5) improved durability; (6) small loss of energy; (7) rotating orifice; (8) x-ray impermeability of orifice; (9) and easily sutured orifice. A report is made here on our experience of a clinical case of mitral stenosis by ATS valve (the first case in Japan) on September 28, 1993.

Relationship between mammary tumourigenesis and uterine adenomyosis in four strains of mice.

The development and the progression of uterine adenomyosis were compared with those of mammary tumours in four strains of mice with different mammary tumour potentials. Cumulative mammary tumour incidences were the highest and the lowest in SHN and C3H/He, respectively, and intermediate in SLN and GR/A. However, the growth rate of palpable mammary tumours was higher in SHN and SLN than in GR/A and C3H/He, between which no difference was observed. SHN was also higher than SLN in this parameter. While almost all mice bearing mammary tumours developed adenomyosis in all strains, there was an apparent strain-difference in the progression of this lesion which paralleled well that of mammary tumours. All results indicate the intimate relationship between the development and the progression of both lesions in mice.