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.

This is a case report of an expansion of the right internal iliac artery aneurysm after an exclusion operation. A 72-year-old man, had undergone aneurysmectomy and graft replacement of a right external iliac artery aneurysm and a ruptured left iliac artery aneurysm, and exclusion of a right internal iliac artery aneurysm in 1995. Computed tomography showed an expansion of the right internal iliac artery aneurysm in 2003. We performed graft replacement and bypassing to the right external iliac artery. The patient had a satisfactory postoperative course.

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 patient is a women in her 60s. After medical examinations, she was told that the result of fecal occult blood reaction testing was positive. Moreover, colonoscopy found type 2 cancer in her sigmoid colon. The patient underwent sigmoidectomy. The 3D dissection of lymph node and colorectal side-to-end anastomosis were performed. Pathologically, the case was diagnosed as moderately differentiated adenocarcinoma (stage II). Adjuvant chemotherapy was not given. During follow-up observation, the tumor marker levels were elevated above normal. A work-up revealed a recurrence of the cancer on the abdominal wall. The lesion was surgically removed with a margin of about 2 cm from the tumor secured. Pathological diagnosis of this recurrent case was not inconsistent with the previous diagnosis of sigmoid colon cancer. As the relapse was thought to be due to the implantation of cancer cells in the abdominal wall, we need to follow the surgical procedure with scrupulous care and exercise the utmost precaution to protect incision wound on the abdominal wall.

We evaluated the relation of changes in skin temperature, measured by thermography, to clinical symptoms and findings in patients who underwent coronary artery bypass surgery using the radial artery. All had a negative Allen test before operation. Ten consecutive patients who underwent surgery at least 3 months prior to the study were selected. Left radial artery grafts were harvested in all patients. Skin temperature was measured twice, before and after exercise. Two patients had a cold sensation at the arterial harvest site at rest. Three, including these two, complained of pain along the harvest site after exercise. No differences in temperature were observed before and after exercise in the ulnar aspects of the palm or forearm on either the left or right side. On the other hand, the increase in radial aspect temperature on the left side was smaller than that on the right. Skin temperature was clearly decreased after loaded exercise in 3 patients. We believe that the indications of grafting should be carefully considered because patients can show findings associated with circulatory disturbance at arterial harvest sites.

Long-term administration of anticonvulsants is necessary for patients prone to convulsions in order to prevent seizures. However, continuous administration of anticonvulsants can often provoke liver dysfunction and impair cognitive ability. Some Japanese herbal medicines (Kampo formulae) have long been known to inhibit seizures and to have a protective effect on liver function. To elucidate these effects, Kampo formulae (Saikokeishi-to and Shakuyakukanzo-to) were administered to patients with convulsive seizures and liver dysfunction due to cerebrovascular disorders, traumatic brain injury and brain tumors. Administration of anticonvulsant drugs was decreased simultaneously with administration of these Kampo formulae.
The results indicated inhibition of convulsive seizures and a definite recovery of liver function. Improvements were also observed in cognitive function. Based on these findings, it is suggested that Kampo formulae are useful for patients with seizures and/or liver dysfunction, and that the dosage of anticonvulsant drugs may be decreased when Kampo formulae are also being administered.

In 2013, the fifth Tokyo International Conference on African Development (TICAD V) will be hosted by the Japanese government. TICAD, which has been held every five years, has played a catalytic role in African policy dialogue and a leading role in promoting the human security approach (HSA). We review the development of the HSA in the TICAD dialogue on health agendas and recommend TICAD’s role in the integration of the HSA beyond the 2015 agenda. While health was not the main agenda in TICAD I and II, the importance of primary health care, and the development of regional health systems was noted in TICAD III. In 2008, when Japan hosted both the G8 summit and TICAD IV, the Takemi Working Group developed strong momentum for health in Africa. Their policy dialogues on global health in Sub-Saharan Africa incubated several recommendations highlighting HSA and health system strengthening (HSS). HSA is relevant to HSS because it focuses on individuals and communities. It has two mutually reinforcing strategies, a top-down approach by central or local governments (protection) and a bottom-up approach by individuals and communities (empowerment). The “Yokohama Action Plan,” which promotes HSA was welcomed by the TICAD IV member countries. Universal health coverage (UHC) is a major candidate for the post-2015 agenda recommended by the World Health Organization. We expect UHC to provide a more balanced approach between specific disease focus and system-based solutions. Japan’s global health policy is coherent with HSA because human security can be the basis of UHC-compatible HSS.

We encountered a case of hypercobalaminemia induced by oral intake of an energy drink after total gastrectomy. The patient was referred to our hospital due to findings suspicious for gastric cancer on screening. A 20 mm type 0-IIc lesion was detected in the gastric subcardia on esophagogastroduodenoscopy. Total gastrectomy followed by Roux-en-Y reconstruction was performed. He was discharged without complications. His basal serum vitamin B₁₂ level was initially maintained with monthly intramuscular injections of vitamin B₁₂. After 9 months, his serum vitamin B₁₂ level suddenly increased up to 36-fold higher than the normal range and persisted there for one year without vitamin B₁₂ injections. The patient ultimately reported consuming half a bottle of an energy drink each day during this time period. This case demonstrates the risk of unexpected hypervitaminemia resulting from self-administration of nutritional supplements.

Out of 104 patients with perimembranous or infundibular-isolated ventricular septal defect (VSD), causative factors of Prol and AR, and the operative indication were studied in 17 with prolapse of the aortic cusp (Prol) and 10 with aortic valve regurgitation (AR). The left to right shunt ratio and the size of VSD were smaller in patients with Prol or AR than in those with the normal aortic cusp, suggesting that hemodynamics might take part in the cause of Prol or AR. Twenty-two patients underwent VSD closure only, four valvuloplasty and one aortic valve replacement. Residual AR was occurred in three out of ten patients. After surgery, AR was disappeared in six out of seven patients with the first grade preoperative AR, but AR remained in all two patients with the second grade preoperative AR. Careful preoperative observation and early operation before the appearance of AR are the important factors for avoiding residual regurgitation after aortic valvuloplasty.

A lower abdominal tumor with thrill and bruit was pointed out in a 59-year-old female. Angiography showed a pelvic arteriovenous malformation (AVM) with remarkably dilated vessels resembling an aneurysm. Feeding arteries for this AVM originated from the right internal iliac artery, right lumbar artery and right renal artery, and drainage blood flowed into the inferior vena cava from the dilated vessel via a large vein. At operation the right internal iliac artery and right lumbar artery were ligated and the dilated vessel with AVM, which connected with the right renal artery, was resected. An angiography 16 days after the operation revealed the normal arteries without AVM and the right internaal iliac artery filled through collateral arteries. Recently catheter embolization in frequently the first choice for treatment of AVM. However, in the case of AVM with aneurysmal dilated vessels, surgical resection should be selected.