Antimicrobial diterpenoids from Eupatorium glutinosum (Asteraceae).

The antimicrobial properties of the hexane extract from the leaves and twigs of the Eupatorium glutinosum was tested against two Gram-negative and two Gram-positive bacteria. Bioassay guided fractionation leads characteristically to isolation and structure elucidation of two active compounds: 15-hydroxy-7-labden-17-oic acid and its acetate. These results validate the vernacular medicinal uses of the plant in folkloric medicine. Dammara-20, 24-dien-3-acetate, stigmasterol and epi-friedelanone have been also isolated in addition to the palmitate of nepehinol for the first time as naturally occurring.

Optical mapping of ventricular defibrillation in isolated swine right ventricles: demonstration of a postshock isoelectric window after near-threshold defibrillation shocks.

BACKGROUND: Investigators who studied ventricular defibrillation by use of optical mapping techniques failed to observe an initial defibrillation event (isoelectric window or quiescent period) shown by electrode mapping studies. This discrepancy has important implications for the mechanisms of defibrillation. The purpose of the present study was to demonstrate an optical equivalent of an isoelectric window after a near-threshold defibrillation shock. Methods and Results-- We studied 10 isolated, perfused swine right ventricles. Upper limit of vulnerability was determined by shocks on T waves. A 50% probability of successful defibrillation (DFT50) was determined with an up-down algorithm. Immediately after unsuccessful defibrillation shock, new wavefronts were generated. When the shock strength was low, immediate reinitiation of reentry and ventricular fibrillation might occur without a postshock isoelectric window. However, if the shock strength was within 50 V of DFT50 (near-threshold), a synchronized activation occurred, followed by organized repolarization that ended 64+/-18 ms after shock. After a period of quiescence (18+/-24 ms), activation recurred 83+/-33 ms after shock and reinitiated ventricular fibrillation. Similar patterns of activation, including a quiescent period, were observed after shock was applied on the T wave of the paced beat that induced ventricular fibrillation. Upper limit of vulnerability correlated well with DFT50. CONCLUSIONS: In isolated swine right ventricles, an optical equivalent of an isoelectric window exists after near-threshold defibrillation shocks. These findings support the idea that a near-threshold defibrillation shock terminates all activation wavefronts but fails to halt ventricular fibrillation because the same shock reinitiates ventricular fibrillation after an isoelectric window.

Effects of diacetyl monoxime and cytochalasin D on ventricular fibrillation in swine right ventricles.

Whether or not the excitation-contraction (E-C) uncoupler diacetyl monoxime (DAM) and cytochalacin D (Cyto D) alter the ventricular fibrillation (VF) activation patterns is unclear. We recorded single cell action potentials and performed optical mapping in isolated perfused swine right ventricles (RV) at different concentrations of DAM and Cyto D. Increasing the concentration of DAM results in progressively shortened action potential duration (APD) measured to 90% repolarization, reduced the slope of the APD restitition curve, decreased Kolmogorov-Sinai entropy, and reduced the number of VF wave fronts. In all RVs, 15-20 mmol/l DAM converted VF to ventricular tachycardia (VT). The VF could be reinduced after the DAM was washed out. In comparison, Cyto D (10-40 micromol/l) has no effects on APD restitution curve or the dynamics of VF. The effects of DAM on VF are associated with a reduced number of wave fronts and dynamic complexities in VF. These results are compatible with the restitution hypothesis of VF and suggest that DAM may be unsuitable as an E-C uncoupler for optical mapping studies of VF in the swine RVs.

Dynamics of intramural and transmural reentry during ventricular fibrillation in isolated swine ventricles.

The intramural dynamics of ventricular fibrillation (VF) remain poorly understood. Recent investigations have suggested that stable intramural reentry may underlie the mechanisms of VF. We performed optical mapping studies of VF in isolated swine right ventricles (RVs) and left ventricles (LVs). Nine RV walls were cut obliquely in their distal edge exposing the transmural surface. Six LV wedge preparations were also studied. Results showed that intramural reentry was present. In RV, 28 of 44 VF episodes showed reentry; 15% of the activation pathways were reentrant. Except for 4 episodes, reentry was transmural, involving subendocardial structures as the papillary muscle (PM) or trabeculae. In LV, reentry was observed in 27 of 27 VF episodes; 23% of the activations were part of reentrant pathways (P<0.05 compared with RV). All LV reentrant pathways were truly intramural (confined to the wall) and were frequently located at the PM insertion. In both ventricles, reentry was spatially and temporally unstable. Histological studies showed abrupt changes in fiber orientation at sites of reentry and wave splitting. Connexin 40 immunostaining demonstrated intramyocardial Purkinje fibers at sites of reentry in the PM root and around endocardial trabeculae. Our results confirm that reentry is frequent-but unstable-in the myocardial wall during VF. In RV, reentry is mostly transmural and requires participation of subendocardial structures. The LV has a greater incidence of reentry and is intramural. Anisotropic anatomic structures played key roles in the generation of wave splitting and in the maintenance of reentry.

[Comparison of therapeutic effects of SMANCS (+TAE) and Non-SMANCS/LpTAE].

Therapeutic effects of SMANCS and LpTAE were evaluated for hepatocellular carcinoma (HCC). Since June 1995, SMANCS has been used in 59 patients for their first treatment. LpTAE had been performed for HCC before introduction of SMANCS in our hospital, and 71 patients treated after 1992 were chosen for comparison with the therapeutic effect of SMANCS. Among the patients treated with SMANCS, complete and partial responses (CR and PR) were obtained in 24 cases (41%) and 17 cases (33%), respectively. SMANCS accompanied by TAE was more effective than SMANCS alone. The effects did not depend on the level of the hepatic arterial branch at which SMANCS was administered. In patients treated with LpTAE, CR and PR were obtained in 12 cases (17%) and 18 cases (25%), respectively. SMANCS was significantly more effective than LpTAE. Because of our short experience with SMANCS, we could only show a two year survival rate. The one- and two-year survival rates for SMANCS were 71% and 57%, respectively. They were not significantly different from those for LpTAE, at 80% and 60%. Despite good results of treatment for HCC, a better prognosis could not be expected by SMANCS in this study. These results may be explained as follows. The evaluating the cause of death within two years after first treatment, hepatic failure was more common in patients treated with SMANCS. After treatment by SMANCS, 11 patients (55%) died from hepatic failure. On the other hand, 4 patients (15%) died from hepatic failure after LpTAE. Although there is no significant difference of Child Pugh score, this may indicate that SMANCS has been used for patients with lesser hepatic reserve and this leads to early deaths in patients treated with SMANCS. However, because of the short experience in this study, further observation is necessary for precise evaluation of clinical efficacy of SMANCS.

Ameliorating effects of SDZ ENA 713 on age-associated decreases in learning performance and brain choline acetyltransferase activity in rats.

In the present study, we have investigated the effects of SDZ ENA 713 on spatial learning deficits in aged rats. Using the same animals, the effect of SDZ ENA 713 on choline acetyltransferase was simultaneously studied to obtain a basis for the behavioral study. In the aged rats, the spatial learning and choline acetyltransferase activity in the frontal cortex were significantly deteriorated compared with young adult rats. SDZ ENA 713 (0.2 mg/kg) significantly shortened the time to reach a hidden platform without affecting swim rates in the water maze task. SDZ ENA 713 (0.1 and 0.2 mg/kg) inhibited aging-induced decreases in choline acetyltransferase activity in the frontal cortex. These results suggest that SDZ ENA 713 ameliorates aging-induced learning deficits and cholinergic dysfunction in rats.

[Clinical evaluation of Cernilton on benign prostatic hypertrophy--a multiple center double-blind study with Paraprost].

A multiple center double blind study was performed to study the effectiveness of Cernilton (CN) on benign prostatic hypertrophy in comparison to Paraprost (PP). Among a total of 192 patients, overall effect was studied on 159 patients, overall safety rate on 178 patients and rate of effectiveness on 159 patients. There were no differences between the two groups in the selected patients, criteria for exclusion and drop out cases or background data of the patients. Impression of patients and overall effect by committee and physician judgment were slightly higher in the CN group compared to the PP group, but there was no significant difference between the two groups. For the improvement in subjective symptoms, the rate of moderate improvement or more after 4 weeks by committee judgement was higher in the CN group compared to the PP group. The rate of improvement in protracted miction, which is an effective marker of urinary disturbance, was also higher in the CN group compared to the PP group. An analysis of objective symptoms showed a significant improvement in residual urinary volume, average flow rate, maximum flow rate and prostatic weight in the CN group. A significant improvement in the phased change of residual urinary volume was also seen in the CN group. No side effects or abnormalities in clinical test levels were noted in the CN group. By committee judgement, the rate of more than moderate effectiveness was 49.1% in the CN group compared to 41.2% in the PP group, but there was no significant difference between the two groups. By physician's judgment, the rate of more than moderate effectiveness was 49.4% in the CN group compared to 46.3% in the PP group, but there was also no significant difference between the two groups. These results suggested that Cernilton was an effective drug for benign prostatic hypertrophy.

[Adjuvant chemotherapy after surgery in advanced gastric cancer].

Two hundred and fifty-four patients with advanced gastric cancer underwent radical surgery and ftorafur (FT) or 5-fluorouracil (5-FU) was orally administered as the adjuvant chemotherapy (ACT). Recurrence after ACT were analyzed by the quantification method II. As a result, it was found that: 1) ACT over 2 years could lower the recurrence rate, and careful follow-up is still necessary up to 4 years, and 2) after the remission induction therapy with mitomycin C and/or 5-FU and cytarabine, 12 mg/kg/day of FT for the first year and 8 mg for the second year are advisable.