Objective: Acanthopanax senticosus Harms extract (ASE) is an ingredient of functional foods, such as health supplements, in Japan. We investigated the effects of ASE on CYP2C9 activity.
Methods and Results: CYP2C9-catalyzed diclofenac 4′-hydroxylase activities in human intestinal and liver microsomes (abbreviated as HIM and HLM, respectively) were significantly decreased by the addition of ASE in a concentration-dependent manner. Kinetic studies of diclofenac 4′-hydroxylase in HLM revealed that ASE addition significantly decreased V_max but had no effect on K_m. These results suggest that diclofenac 4′-hydroxylase activity is suppressed by ASE addition in a non-competitive manner. Then, we investigated the time courses of diclofenac 4′-hydroxylase activity in rat liver microsomes after ASE oral administration (50 to 400 mg/kg). Diclofenac 4′-hydroxylase activities were significantly lowered by the administration of 200 and 400 mg/kg ASE at 0.5 to 4 hr compared with control (0 hr). Furthermore, we investigated the effects of ASE oral administration on the pharmacokinetics of tolbutamide (substrate for CYP2C9) in rats. The area under the concentration-time curve of tolbutamide after ASE oral administration (400 mg/kg) was enhanced by approximately 1.6 times compared with that without ASE oral administration.
Conclusion: These findings indicated that ASE inhibits human intestinal and hepatic CYP2C9 activities.

Objective: By using human liver microsomes (HLM), we analyzed the effects of 14 known components of A.senticosus Harms on the activities of CYP2C9 and CYP3A4.
Methods and Results: Sesamin and quercetin inhibited both enzyme activities, whereas quercitrin strongly inhibited CYP3A4 activity. The 50% inhibitory concentrations (IC₅₀s) of sesamin and quercetin on CYP2C9 activity were approximately 124- and 59-fold higher and the IC₅₀s of sesamin, quercetin, and quercitrin on CYP3A4 activity were approximately 427-, 135-, and 22-fold higher than that of A. senticosus Harms extract (ASE), respectively. All these components inhibited both CYP3A4 and CYP2C9 in a non-competitive manner. However, these components are present in small amounts in ASE.
Conclusion: Therefore, the food-drug interactions caused by A. senticosus Harms are presumed to be due to the additive or synergistic interaction of these components or the other existing components, including their metabolites.

The inhibitory effects of the freeze-dried powder of the aqueous extract of black tea leaf (JAT) on α-glucosidase activity were investigated. We initially examined the effects of JAT addition on yeast α-glucosidase activity. JAT significantly and dose-dependently inhibited α-glucosidase activity and more strongly inhibited the activity than acarbose, the positive control. Then, we examined the effects of oral administration of JAT on sucrose tolerance in type 2 diabetes mellitus model db/db mice. Both JAT and acarbose administered groups showed a dose-dependent decrease in plasma glucose levels after the sucrose loading compared with the control group. Notable was that the plasma glucose levels of the 500 mg/kg JAT administered group exhibited a significant decrease 30 min or longer after the sucrose loading. On the other hand, no significant difference in plasma insulin levels was seen between the JAT administered group and the control group. We also measured small intestinal sucrase activity in db/db mouse at 30 min after JAT oral administration. Compared to control mice, small intestinal sucrase activity was significantly decreased in the 500 mg/kg JAT administered mice. These findings indicate that JAT may be a useful natural material for the prevention and therapy of type 2 diabetes mellitus.

Isho-ho was used to successfully treat three cases of muscular weakness. The first case was a 59-year-old woman. In May of 1993, she began to suffer from a feeling of general lethargy. The condition was diagnosed as multiple myositis, and prednisolone was administered. However, since she still experienced loss of strength in the lower limbs, she was introduced to the authors' department for treatment in August of 1994. Administration of Isho-ho improved the loss of strength in the lower limbs and increased her grip strength.
The second case was a 42-year-old woman who complained of unusual sensations in the tips of her fingers and toes starting in mid-September, 1994. In November of the same year, she began to experience a loss of strength in the limbs. In February of 1995, the condition was diagnosed as chronic inflammatory demyelinatory multiple neuropathy by the same department, and large doses of steroids were administered. Although this treatment delayed the loss of strength in the lower back and legs, actual improvement in the condition did not occur until Isho-ho was given.
The third case involved a 63-year-old man who began to experience a loss of strength in the lower limbs in 1984. In 1988, the loss of strength became pronounced. In June of the same year, he sought treatment at the authors' department, and the condition was diagnosed as bulbar myelinic muscular atrophy. In October of 1993, he was unable to get out of bed unassisted, and was admitted to the authors' department. He was given Isho-ho, and reported a decrease in the feeling of a loss of strength in the lower limbs, and a disappearance of greater pectoral muscle spasms. These results suggest that Isho-ho is not only effective for loss of strength in the lower limbs, but may also be efficacious for loss of strength, numbness and muscle spasms in the upper limbs.

We report an operative case of papillary muscle rupture after myocardial infarction with sustained ventricular tachycardia. A 56-year-old man referred to our emergency room in shock. Emergency CAG showed total occlusion of the left circumflex artery, in which we placed a metallic stent. Even after re-canalization of the coronary artery was achieved, circulation was unstable. IABP and PCPS were used to maintain the systemic circulation. Trans-esophageal echocardiography showed papillary muscle rupture and massive mitral regurgitation. Under total cardiopulmonary bypass and cardiac arrest, we performed mitral valve replacement with a 27mm SJM mechanical valve. PCPS was continued after surgical treatment because of pulmonary congestion. Since the patient's circulation and respiratory function improved, PCPS and IABP were removed on postoperative days 3 and 5. However, after removal of IABP, ventricular tachycardia appeared and IABP, PCPS were re-inserted. After adequate medication with Amiodarone and Carbedirol, ventricular tachycardia was controlled. PCPS and IABP were then removed uneventfully on postoperative days 14 and 19.

A 72-year-old woman was admitted with a sensation of compression and shortness of breath. A mass was detected in the right atrium (RA) by transthoracic echocardiography. Preoperative chest computed tomography showed an RA tumor measuring 30×24 mm in the lateral wall. We performed resection under the cardiopulmonary bypass. Histopathological examination confirmed that this tumor was a lipoma.

Most patients with taste disorders are usually treated with zinc, but there still remain many untreatable patients, including non-responders and those of advanced age. In this study, we report on three patients with hypogeusia who showed improvement after the administration of Kampo medicine. A 49-year-old female diagnosed with hypogeusia and hyposensation of the oral cavity responded to Oren-gedoku-to. A 43-year-old male diagnosed as having schizophrenia and hypogeusia and a 76-year-old female with idiopathic hypogeusia responded to Saiko-ka-ryukotsu-borei-to. Kampo medicines are considered to normalize zinc-related neuro-transmissions originating in the vallate taste buds. Furthermore, the curative effect of Oren-gedoku-to on inflammation-injured oral cavity membranes, and the psychotropic effect of Saiko-ka-ryukotsu-borei-to on improving hypogeusia, were shown in our patients. It should be noted that the recent increase in aged patients complaining of taste disorders might be related to aging-associated depression. Saiko-ka-ryukotsu-borei-to or related Kampo formulations are considered to have wide applications for depressed or aged patients with hypogeusia.

Recent studies showed that high biocompatibility and reduction of uremic toxin contributed to the improvement of freatment outcome in hemodialysis patients.Therefore, a high-flux membrane dialyzer, especially polysulfone (PS) membrane, was generally used in dialysis. However, it was suggested that the higher efficiency of reduction in uremic toxins might cause an increase in the albumin leakage through the dialyzer membrane during dialysis, resulting in a decrease in serum albumin concentration. In this study, we used two different dialyzer membranes with high biocompatibility, namely, ethylenevinylalcohol (EVAL) membrane and improved PS membrane with a very lower leakage of serum albumin. After using these two types of mambrane of six straight months, we examined the effect of each dialyzer membrane characteristic on the serum total protein and albumin concentration. The reduction rates of each uremic solute and serum total protein concentration were significantly higher. The serum albumin concentration and its rate of change with the passing of time tended to increase in the case of the PS membrane. But in the case of EVAL membrane, these values tended to decrease. These results suggested that the differences in the changes in the serum total protein and albumin concentration might result from the differences in the efficiency of the reduction of uremic toxins. Therefore, it is necessary to consider the usage of the dialyzer membrane with a higher reduction of uremic solutes and a lower leakage of serum albumin to add to the higher biocompatibility specially in hemodialysis patients with hypoproteinemia.
Membranes ; Concentration ; Reduction (chemical) ; Serum Albumin ; Hemodialysis

Emergency coronary artery bypass grafting (CABG) in patients with acute coronary syndrome (ACS) is still associated with high mortality and morbidity, and early outcome is poor compared with outcome in patients with stable angina. The purpose of this study was to examine the clinical results of on-pump beating heart CABG vs. off-pump coronary artery bypass (OPCAB) for ACS patients. From a total of 432 CABG patients, we retrospectively analyzed 72 (16.7%) patients who underwent emergency CABG between 2004 and 2008. Emergency CABG cases were divided into 2 operative groups : an on-pump beating-heart CABG group (on, n=31) and an OPCAB group (off, n=41). A preoperative history of acute myocardial infarction (AMI), detection of troponin T, preoperative creatine phosphokinase (CPK) value, low ejection fraction, presence of mitral regurgitation (MR) (>II) and cardiomegaly were markedly higher in the on group. There were no statistically significant differences in intraoperative factors. In-hospital mortality was 3.2% (1 patient) in the on group and 7.3% (3 patients) in the off group. Furthermore, statistically significant differences were found between the 2 groups in incidence of all-cause morbidity (on=71.0% : off=41.5%, p=0.01), respiratory failure (on=58.1% : off=29.3%, p=0.01), ICU stay (on=6.5±4.6 days : off=4.1±3.2 days, p=0.01), and necessary inotropic support (on=51.6% : off=17.1%, p=0.02). Multivariate regression analysis of preoperative and intraoperative factors was performed to identify independent factors for in-hospital mortality and morbidity. On multivariate analysis of preoperative factors, only the pre-CPK value reached statistical significance as an independent factor for in-hospital mortality and morbidity.

This is a case report of a rare combination of a single coronary artery and a coronary artery fistula. An 8-year-old girl was asymptomatic with a grade II continuous murmur in the third left intercostal space. Selective coronary angio-graphy revealed that a single coronary artery arising from the left aortic sinus was dilated and ended as a fistula to the outflow tract of the right ventricle. At operation, the fistula could not be exposed on the surface of the heart. On cardiopulmonary bypass, the aorta was clamped, and the fistula was closed by direct suture in the right ventricle. The postoperative course was uneventful with no complications.