Kanehiko Hisamichi

Ampelopsins F and G, novel bridged plant oligostilbenes from Ampelopsis brevipedunculata var. hancei roots (vitaceae)

Abstract Ampelopsins F and G, two novel oligostilbenes containing structurally unusual dibenzobicyclo[3.2.1]octadiene system have been isolated from the roots of Ampelopsis brevipedunculata var. hancei and their structures established on the basis of spectroscopic evidence.

NOVEL OLIGOSTILBENES FROM VITIS COIGNETIAE

Phytochemical investigation on oligostilbenes in a methanol extract of Vitis coignetiae (Japanese name: yama-budou) resulted in the isolation of a novel slilbene dimer, ɛ-viniferin diol, and two novel slilbene tetramers, vitisin B and its stereoisomer cis-vitisin B. The structures of the oligostilbenes were determined by spectroscopic evidence and chemical reactions.

NMR studies and structural assignment of paederoside

Detailed and extensive nmr analyses of paederoside have been carried out resulting to allow complete assignment of all of the 1 H and 13 C signals. The results provided unambiguous bases to support methyl thiocarbonate structure (3) for paederoside, a novel natural sulfur-containing iridoid glucoside of Paederia scandens

Monitoring Serum Levels of Sorafenib and Its N-Oxide Is Essential for Long-Term Sorafenib Treatment of Patients with Hepatocellular Carcinoma

Sorafenib, an oral multi-kinase inhibitor, is the final therapy prior to palliative care for advanced hepatocellular carcinoma (HCC). However, due to its adverse effects, 20% of patients must discontinue sorafenib within 1 month after first administration. To identify ways to predict the adverse effects and administer the drug for longer periods, we explored the relationship between the duration of sorafenib treatment and the pharmacokinetics of sorafenib and its major metabolite, sorafenib N-oxide. Twenty-five subjects enrolled in the study were divided into two groups: patients with dosage reduced or withdrawn due to adverse effects (n = 8), and patients with dosage maintained for 1 month after initial administration (n = 17). We evaluated early sorafenib accumulation as the area under the curve of sorafenib and sorafenib N-oxide concentrations during days 1-7 (AUC(sorafenib) and AUC(N-oxide), respectively). Inter-group comparison revealed that AUC(N-oxide) and AUC ratio (AUC(N-oxide)/AUC(sorafenib)) were significantly higher in the dosage reduction/withdrawal group (P = 0.031 and P = 0.0022, respectively). Receiver operating characteristic analysis indicated that AUC(N-oxide) and AUC ratio were reliable predictors of adverse effects. When patients were classified by cut-off points (AUC(N-oxide:) 2.0 μg ∙ day/mL, AUC ratio: 0.13), progression-free survival was significantly longer in patients with AUC(N-oxide) ≤ 2.0 μg ∙ day/mL (P = 0.0048, log-rank test). In conclusion, we recommend to simultaneously monitor serum levels of sorafenib and its N-oxide during the early stage after the first administration, which enables us to provide safe and long-term therapy for each HCC patient with sorafenib.

Sa1441 Do Protease Inhibitors Influence Visceral Pain Sensitivity in Patients With Irritable Bowel Syndrome

Background and Aims: Several studies have reported that gastric scintigraphy is a useful and non-invasive modality to assess the gastric motility, especially gastric emptying. Recently, many researchers have suggested that the measuring gastric emptying in addition to gastric accommodation is essential to evaluate gastric motility. Gastric accommodation is considered as postprandial relaxation of the proximal stomach. However, we have little knowledge of gastric scintigraphy to assess gastric accommodation. Accordingly, we aimed to clarify the usefulness of gastric scintigraphy in the assessment of gastric accommodation in comparison with gastric barostat which is a gold standard modality. Patients and Methods: Seventeen healthy volunteers (male/female 10/ 7; mean age 33.8 ± 10.5 years) were enrolled in this study. Test meal consisted of curry with rice; radiolabeled 99mTc (37 MBq) was used for scintigraphy. Volunteers ingested the test meal in the upright position with scintigraphic images recorded over time. Radioactivity in the upper-third andwhole stomachwas calculated to evaluate gastric accommodation. In the barostat procedure, a gastric balloon was inserted nasally and distended after a liquid meal ingestion (250 ml, 375 kcal). The maximal volume of distending balloon was measured to evaluate gastric accommodation. Thereafter, we investigated the correlation between scintigraphic and barostat accommodation. We next validated the reproducibility and intraand inter-observer variation for the scintigraphic test. Finally, we evaluated the diagnostic performance of scintigraphy using sumatriptan which delays gastric emptying and improves gastric accommodation as a positive control. The scintigraphic test was repeated in the same volunteers after one week. Data were evaluated by three investigators. Results: Accommodation measured with scintigraphy and barostat correrlated (r=0.524, p<0.05). For the scintigraphic test, sumatriptan significantly increased (51.5 ± 16.4 %) gastric accommodation compared with the control (38.4 ± 13.8 %) (p<0.01). Moreover, sumatriptan significantly delayed the gastric emptying (50 % half emptying time) at 60, 90, 120 and 150 min after the experimental start, respectively (p<0.05). The data obtained from repeated scintigraphic tests was highly reproducible (r=0.75) with significant differences observed among the investigators (r=0.90). Conclusions: Gastric scintigraphy is a useful modality to assess gastric accommodation and emptying.