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Ōkawa, Japan

Zhang H.,Shenyang University | Zhang H.,Saga University | Ozaki I.,Saga University | Hamajima H.,Saga University | And 6 more authors.
Oncology Reports | Year: 2011

Although 5-fluorouracil (5-FU) is one of the most commonly used chemotherapeutic agents in various cancer including hepatocellular carcinoma (HCC), chemoresistance has precluded single use of 5-FU in clinical settings. Since menatetrenone, an analogue of vitamin K2 (VK2), inhibits growth of cancer cells including HCC cells in vitro and in vivo, we examined VK2 modulation of HCC cell response to 5-FU. VK2 pretreatment dose-dependently enhanced growth-inhibition by 5-FU through a G1 cell cycle arrest. VK2 inhibited 5-FU-induced NF-κB activation and cyclin D1 expression. Therefore, combination of VK2 and 5-FU might represent a new therapeutic strategy for patients with HCC. Source


Miyauchi K.,Juntendo University | Yamazaki T.,University of Tokyo | Watada H.,Juntendo University | Tanaka Y.,St. Marianna University School of Medicine | And 10 more authors.
Circulation Journal | Year: 2012

Background: Angiotensin II receptor blocker (ARB) as a first-line drug for hypertension in diabetes often fails to control blood pressure adequately. The objective of the study was to evaluate the effect of amlodipine combined therapy on home blood pressure (HBP) useful for management of hypertension. Methods and Results: A total of 263 type 2 diabetes with hypertension refractory to standard dose of ARB were randomized to increased ARB regimen (n=132) or amlodipine combination regimen (n=131). The primary endpoint was change in morning HBP at 1 year. The combination regimen significantly lowered morning HBP than the increased ARB regimen (158.2/82.5 mmHg in the combination regimen, 157.3/84.4 mmHg in the increased ARB regimen, at baseline; 142.7/76.3 vs. 155.0/83.1 mmHg, respectively, P<0.001 for both, at 8 weeks; 139.6/74.6 vs. 149.1/78.1 mmHg, respectively, P<0.001 for systolic and P=0.010 for diastolic, at 1year). The combination regimen showed significantly higher rates of achieving target morning HBP at 8 weeks (11.3% vs. 2.7%, P=0.015). In the combination regimen, estimated glomerular filtration rate declined slower, and carotid intima-media thickness decreased in contrast to the increased ARB regimen. Conclusions: In type 2 diabetes patients with hypertension refractory to standard dose of ARB, the amlodipine combination regimen provides superior antihypertensive effect on HBP to the increased ARB regimen, and beneficial effects on reducing risks of cardiovascular events. Source


Mori T.,Takagi Hospital
Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica | Year: 2011

I report a case of schizophrenia in which depressive and negative symptoms relapsed on switching from oral risperidone to risperidone long-acting injection (RLAI). The patient, with a 31-year history of schizophrenia, did not fully understand his disease. Therefore, adherence to medication had been extremely poor. The discontinuation of medication led to the recurrence of the disease. After hospital treatment, he was discharged to a group home. From then, the disease had been kept in remission by risperidone at 4 mg/day, and RLAI was introduced for the purpose of further social reintegration and QOL improvement. After starting RLAI at 25 mg, however, a stiff expression and irritability appeared. Therefore, RLAI was increased up to 50 mg, but depressive and negative symptoms relapsed. Subsequently, RLAI was discontinued and oral risperidone was re-administered, and the above mental symptoms improved in a relatively rapid manner. The difference in the ratio of plasma and brain concentrations between each active moiety, risperidone and 9-OH risperidone (paliperidone), resulting from the difference in administration routes, was suggested to be involved as the main factor. In this case, it is likely that positive symptoms did not relapse because plasma concentrations of the active moiety itself were well maintained by introducing RLAI. However, depressive and negative symptoms relapsed possibly as a result of reduced affinity for the alpha2A receptor with relatively decreased plasma concentrations of 9-OH risperidone when compared to oral administration. Another possibility is that negative symptoms were secondary induced by excess administration of antipsychotics, but there has been no such report on RLAI so far. For the reason noted above, careful follow-up is considered necessary when switching from oral risperidone to RLAI because mental symptoms might get worse. Source


Motoshima S.,Takagi Hospital
Fukuoka igaku zasshi = Hukuoka acta medica | Year: 2012

Patients with moyamoya disease (MMD) exhibit narrowed internal carotid arteries (ICAs) because the distal ends of the bilateral ICAs have become progressively stenosed, starting mainly in childhood. Accordingly, the petrous carotid canals in MMD patients are suspected to be more hypoplastic than those in control subjects. In this study, the diagnostic value of conventional computed tomography for MMD patients was retrospectively evaluated by comparing the caliber of the bilateral carotid canals in MMD patients with that in control subjects. Thirty-five patients with MMD (15 males, 20 females; age range/average age: 6-71 / 26.1 years old) and age- and sex-matched control subjects underwent conventional head computed tomography. The maximal petrous carotid canal diameters of the two groups were measured and compared. The maximal petrous carotid canal diameter was significantly smaller in the moyamoya patients (mean +/- standard deviation [mm] = 4.70 +/- 0.61) than in the control subjects (5.62 +/- 0.61, p < 0.01). Conventional head computed tomography revealed narrowed petrous carotid canals in the MMD patients. This basic information could be utilized to screen patients who will require further examination, especially among those with underlying MMD. Source


Sakaida I.,Yamaguchi University | Yanase M.,National Center for Global Health and Medicine | Kobayashi Y.,Hamamatsu University School of Medicine | Yasutake T.,Takagi Hospital | And 2 more authors.
Journal of International Medical Research | Year: 2012

OBJECTIVES: This study investigated the pharmacokinetic and pharmaco - dynamic profile of tolvaptan, and verified its efficacy and safety in patients with liver cirrhosis-associated ascites, with insufficient response to conventional diuretic treatment. METHODS: This multicentre, doubleblind, parallel-group study allocated patients with cirrhosis to receive either 3.75 or 7.5 mg/day tolvaptan orally, once daily, for 7 days. Pharmacokinetic, pharmacodynamic and efficacy variables were measured. RESULTS: Tolvaptan was shown to have high plasma concentrations, and prolongedduration of maximum concentration and half life, in these patients with impaired hepatic function. Tolvaptan resulted in dose-dependent decreases in body weight and ascites volume, and increases in urine output. There were no effects on urinary or serum electrolytes. Tolvaptan was well tolerated, with a good safety profile. CONCLUSIONS: Tolvaptan at 3.75 mg/day exerts some effects due to the pharmacokinetic profile in patients with liver cirrhosis. Tolvaptan at 7.5 mg/day is a clinically useful option for treating patients who do not respond well to conventional diuretics. © SAGE Publications Ltd 2012. Source

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