Older Adults with Fear of Falling Show Deficits in Motor Imagery of Gait.

OBJECTIVE: Understanding of the underlying mechanisms of Fear of Falling (FoF) could help to expand potential treatments. Given the nature of motor performance, the decline in the planning stage of motor execution may be associated with an expression of FoF. The aim of this study was to assess the planning/prediction accuracy in motor execution in people with FoF using gait-related motor imagery (MI). DESIGN: Cross-sectional case/control study. SETTING: Three health centers in Japan. PARTICIPANTS: Two hundred and eighty-three community-dwelling older adults were recruited and stratified by presence of FoF as FoF group (n=178) or non-FoF group (n=107). MEASUREMENTS: Participants were tested for both imagery and execution tasks of a Timed Up and Go (TUG) test. The participants were first asked to imagine the trial (iTUG) and estimate the time it would take, and then perform the actual trial (aTUG). The difference between iTUG and aTUG (Δ TUG) was calculated. RESULTS: The FoF group was significantly slower in aTUG, but iTUG duration was almost identical between the two groups, resulting in significant overestimation in the FoF group. The adjusted logistic regression analysis showed that increased Δ TUG (i.e., tendency to overestimate) was significantly associated with FoF (OR = 1.05; 95% CI = 1.02-1.10). Low frequency of going outdoors was also associated with FoF (OR 2.95; 95% CI: 1.16-7.44). CONCLUSIONS: Older adults with FoF overestimate their TUG performance, reflecting impairment in motor planning. Overestimation of physical capabilities can be an additional explanation of the high risk of falls in this population.

Plasma concentrations of coffee polyphenols and plasma biomarkers of diabetes risk in healthy Japanese women.

Coffee consumption has been reported to reduce the risk of type 2 diabetes in experimental and epidemiological studies. This anti-diabetic effect of coffee may be attributed to its high content in polyphenols especially caffeic acid and chlorogenic acid. However, the association between plasma coffee polyphenols and diabetic risks has never been investigated in the literature. In this study, fasting plasma samples were collected from 57 generally healthy females aged 38-73 (mean 52, s.d. 8) years recruited in Himeji, Japan. The concentrations of plasma coffee polyphenols were determined by liquid chromatography coupled with mass tandem spectrometer. Diabetes biomarkers in the plasma/serum samples were analysed by a commercial diagnostic laboratory. Statistical associations were assessed using Spearman's correlation coefficients. The results showed that plasma chlorogenic acid exhibited negative associations with fasting blood glucose, glycated hemoglobin and C-reactive protein, whereas plasma total coffee polyphenol and plasma caffeic acid were weakly associated with these biomarkers. Our preliminary data support previous findings that coffee polyphenols have anti-diabetic effects but further replications with large samples of both genders are recommended.

Role of multidrug resistance protein 2 (MRP2) in chemoresistance and clinical outcome in oesophageal squamous cell carcinoma.

BACKGROUND: Although multidrug resistance protein 2 (MRP2) confers chemoresistance in some cancer types, its implication on oesophageal squamous cell carcinoma (ESCC) remains unclear. METHODS: We evaluated MRP2 expression by immunohistochemistry and RT-PCR using 81 resected specimens from ESCC patients who did or did not receive neo-adjuvant chemotherapy (NACT), including 5-fluorouracil, doxorubicin, and cisplatin (CDDP). Correlation between MRP2 expression and response to chemotherapy was also examined in 42 pre-therapeutic biopsy samples and eight ESCC cell lines. RESULTS: MRP2-positive immunostaining was more frequently observed in ESCCs with NACT than in those without NACT (27.3 vs 5.4%). The MRP2-positive patients showed poorer prognosis than MRP2-negative patients (5-year survival rate, 25.6 vs 55.7%). Concordantly, ESCC with NACT showed 2.1-fold higher mRNA expression of MRP2 than those without NACT (P=0.0350). In pre-therapeutic biopsy samples of patients with NACT, non-responders showed 2.9-fold higher mRNA expression of MRP2 than responders (P=0.0035). Among the panel of ESCC cell lines, TE14 showed the highest MRP2 mRNA expression along with the strongest resistance to CDDP. Inhibition of MRP2 expression by small-interfering RNA reduced chemoresistance to CDDP. CONCLUSION: Our data suggested that MRP2 is one of molecules, which regulate the sensitivity to chemotherapy including CDDP in advanced ESCC patients.

The Traditional Japanese Medicine Rikkunshito Promotes Gastric Emptying via the Antagonistic Action of the 5-HT(3) Receptor Pathway in Rats.

The traditional Japanese medicine rikkunshito ameliorates the nitric oxide-associated delay in gastric emptying. Whether rikkunshito affects gastric motility associated with 5-hydroxytryptamine (serotonin: 5-HT) receptors or dopamine receptors is unknown. We examined the effects of rikkunshito on the delay in gastric emptying induced by 5-HT or dopamine using the phenol red method in male Wistar rats. 5-HT (0.01-1.0 mg kg(-1), i.p.) dose dependently delayed gastric emptying, similar to the effect of the 5-HT(3) receptor agonist 1-(3-chlorophenyl) biguanide (0.01-1.0 mg kg(-1), i.p.). Dopamine also dose dependently delayed gastric emptying. The 5-HT(3) receptor antagonist ondansetron (0.04-4.0 mg kg(-1)) and rikkunshito (125-500 mg kg(-1)) significantly suppressed the delay in gastric emptying caused by 5-HT or 1-(3-chlorophenyl) biguanide. Hesperidin (the most active ingredient in rikkunshito) suppressed the 5-HT-induced delayed gastric emptying in a dose-dependent manner, the maximum effect of which was similar to that of ondansetron (0.4 mg kg(-1)). The improvement obtained by rikkunshito or ondansetron in delaying gastric emptying was completely blocked by pretreatment with atropine. Rikkunshito appears to improve delay in gastric emptying via the antagonistic action of the 5-HT(3) receptor pathway.

Hedgehog signal activation in oesophageal cancer patients undergoing neoadjuvant chemoradiotherapy.

The zinc finger protein glioma-associated oncogene homologue 1 (Gli-1) is a critical component of the Hedgehog (Hh) signalling pathway, which is essential for morphogenesis and stem-cell renewal, and is dysregulated in many cancer types. As data were not available on the role of Gli-1 expression in oesophageal cancer progression, we analysed whether it could be used to predict disease progression and prognosis in oesophageal cancer patients undergoing neoadjuvant chemoradiotherapy (CRT). Among 69 patients with histologically confirmed oesophageal squamous cell carcinomas (ESCCs), 25 showed a pathological complete response after preoperative CRT. Overall survival (OS) was significantly associated with lymph-node metastasis, distant metastasis, and CRT, and was further correlated with the absence of both Gli-1 nuclear expression and residual tumour. All patients with Gli-1 nuclear expression (10.1%) had distant or lymph-node metastasis, and six out of seven died within 13 months. Furthermore, patients with Gli-1 nuclear-positive cancers showed significantly poorer prognoses than those without (disease-free survival: mean DFS time 250 vs 1738 months, 2-year DFS 0 vs 54.9%, P=0.009; OS: mean OS time 386 vs 1742 months, 2-year OS 16.7 vs 54.9%, P=0.001). Our study provides the first evidence that Gli-1 nuclear expression is a strong and independent predictor of early relapse and poor prognosis in ESCC after CRT. These findings suggest that Hh signal activation might promote cancer regrowth and progression after CRT.

Heme-regulated eIF2alpha kinase (HRI) is required for translational regulation and survival of erythroid precursors in iron deficiency.

Although the physiological role of tissue-specific translational control of gene expression in mammals has long been suspected on the basis of biochemical studies, direct evidence has been lacking. Here, we report on the targeted disruption of the gene encoding the heme-regulated eIF2alpha kinase (HRI) in mice. We establish that HRI, which is expressed predominantly in erythroid cells, regulates the synthesis of both alpha- and beta-globins in red blood cell (RBC) precursors by inhibiting the general translation initiation factor eIF2. This inhibition occurs when the intracellular concentration of heme declines, thereby preventing the synthesis of globin peptides in excess of heme. In iron-deficient HRI(-/-) mice, globins devoid of heme aggregated within the RBC and its precursors, resulting in a hyperchromic, normocytic anemia with decreased RBC counts, compensatory erythroid hyperplasia and accelerated apoptosis in bone marrow and spleen. Thus, HRI is a physiological regulator of gene expression and cell survival in the erythroid lineage.

Cancer chemopreventive activity of carotenoids in the fruits of red paprika Capsicum annuum L.

Capsanthin and related carotenoids isolated from the fruits of red paprika Capsicum annuum L. showed potent in vitro anti-tumor-promoting activity with inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Among them, capsanthin diester and capsorbin diester showed strong inhibitory effects. Furthermore, capsanthin , capsanthin 3'-ester and capsanthin 3,3'-diester , major carotenoids in paprika, exhibited potent anti-tumor-promoting activity in an in vivo mouse skin two-stage carcinogenesis assay using 7, 12-dimethylbenz[a]anthracene as an initiator and TPA as a promoter.

Cholesterol-lowering effects of maitake (Grifola frondosa) fiber, shiitake (Lentinus edodes) fiber, and enokitake (Flammulina velutipes) fiber in rats.

The effects of mushroom fibers on serum cholesterol and hepatic low-density lipoprotein (LDL) receptor mRNA in rats were investigated. Rats were fed a cholesterol-free diet with 50 g/kg cellulose powder (CP), 50 g/kg maitake (Grifola frondosa) fiber (MAF), 50 g/kg shiitake (Lentinus edodes) fiber (SF), or 50 g/kg enokitake (Flammulina velutipes) fiber (EF) for 4 weeks. There were no significant differences in the body weight, food intake, liver weight, cecum weight, and cecum pH among the groups. Cecal acetic acid, butyric acid, and total short-chain fatty acid (SCFA) concentrations in the SF and EF groups were significantly higher than those in the other groups. The serum total cholesterol concentration in the CP group was significantly higher than that in the MAF and EF groups. The very LDL (VLDL) + intermediate-density lipoprotein (IDL) + LDL-cholesterol concentration in the CP group was significantly higher than that in the MAF, SF, and EF groups, whereas the high-density lipoprotein (HDL)-cholesterol concentration in the EF group was significantly lower than that in the other groups at the end of the 4-week feeding period. The hepatic LDL receptor mRNA level in the EF group was significantly higher than that in the CP group. The fecal cholesterol excretion in the MAF, SF, and EF groups was significantly higher than that in the CP group. The results of this study demonstrate that MAF and EF lowered the serum total cholesterol level by enhancement of fecal cholesterol excretion, and in particular, by enhancement of hepatic LDL receptor mRNA in EF group.

Structure of three new carotenoids with a 3-methoxy-5-keto-5,6-seco-4,6-cyclo-beta end group from the seeds of Pittosporum tobira.

Three new carotenoids with a 3-methoxy-5-keto-5,6-seco-4,6-cyclo-beta end group (1-3) have been isolated from the seeds of Pittosporum tobira. Their structures were elucidated by detailed analyses of nuclear magnetic resonance and UV data.

Capsanthone 3,6-epoxide, a new carotenoid from the fruits of the red paprika Capsicum annuum L.

The structure of a new carotenoid, isolated from the fruits of the red tomato-shaped paprika Capsicum annuum L., was elucidated to be (3S,5R,6S,5'R)-3,6-epoxy-5,6-dihydro-5-hydroxy-beta,kappa-carotene-3',6'-dione by spectroscopic analyses, including fast atom bombardment collision-induced dissociation-mass spectrometry/mass spectrometry (FAB CID-MS/MS) and was designated capsanthone 3,6-epoxide. Capsanthone 3,6-epoxide is assumed to be an oxidative metabolite of capsanthin 3,6-epoxide in paprika.

Isolation of a series of apocarotenoids from the fruits of the red paprika Capsicum annuum L.

Eleven apocarotenoids (1-11) including five new compounds, 4, 6, 9, 10 and 11, were isolated from the fruits of the red paprika Capsicum annuum L. The structures of new apocarotenoids were determined to be apo-14'-zeaxanthinal (4), apo-13-zeaxanthinone (6), apo-12'-capsorubinal (9), apo-8'-capsorubinal (10), and 9,9'-diapo-10,9'-retro-carotene-9,9'-dione (11) by spectroscopic analysis. The other six known apocarotenoids were identified to be apo-8'-zeaxanthinal (1), apo-10'-zeaxanthinal (2), apo-12'-zeaxanthinal (3), apo-15-zeaxanthinal (5), apo-11-zeaxanthinal (7), and apo-9-zeaxanthinone (8) which have not been previously found in paprika. These apocarotenoids were assumed to be oxidative cleavage products of C(40) carotenoid such as capsanthin in paprika.

Steroidal saponins from Hemerocallis fulva var. kwanso.

Two steroidal saponins, hemeroside A and B, were isolated from the aerial part of Hemerocallis fulva var. kwanso for the first time. The structures of these compounds were established as 24S-hydroxy-neotokorogenin 1-O-alpha-L-arabinopyranosyl 24-O-beta-D-glucopyranoside (1) and isorhodeasapogenin 3-O-beta-D-glucopyranosyl-(1-->3)-[beta-D-xylopyranosyl-(1-->2)]-beta-D-glucopyranosyl-(1-->4)-beta-D-galactopyranoside (2) through NMR experiments.

Evaluation of hepatocellular carcinoma after treatment with transcatheter arterial chemoembolization: comparison of Lipiodol-CT, power Doppler sonography, and dynamic MRI.

BACKGROUND: The purpose of this study was to compare the ability of Lipiodol-computed tomography (CT), power Doppler (PD) sonography, and dynamic magnetic resonance imaging (MRI) in evaluating the therapeutic effect of transcatheter arterial chemoembolization (TACE) on hepatocellular carcinoma (HCC). METHODS: TACE was performed by injecting an emulsion consisting of Lipiodol and a chemotherapeutic drug, followed by gelatin sponge particles, into 54 patients with 84 HCC lesions. Five to 7 days later, Lipiodol-CT, PD sonography, and dynamic MRI were performed. Findings from the three modalities were correlated with relapse within 1 year after TACE. RESULTS: All lesions with blood flow on PD sonography or intratumoral enhancement on dynamic MRI relapsed regardless of the findings with Lipiodol-CT. None of the negatively enhanced lesions on dynamic MRI relapsed regardless of the Lipiodol-CT findings. However, the readers could not evaluate the contrast uptake in 14 lesions that were already hyperintense on the precontrast images. These cases were considered unsuitable for qualitative assessment and reduced the applicability of MRI to 83% of the examined lesions (70 of 84). Although PD sonography perfectly predicted relapse in superficial (0-5 cm from abdominal surface) lesions of the right hepatic lobe, blood flow in deep (>5 cm) or left lobe lesions was undetectable regardless of the occurrence of relapse. As a result, Lipiodol-CT displayed 76.0% sensitivity, 67.6% specificity, and 72.6% accuracy. The sensitivity, specificity, and accuracy of PD sonography were 34.0%, 100%, and 60.7%, respectively. In the 70 lesions in which evaluation was possible, dynamic MRI achieved 100% sensitivity, 100% specificity, and 100% accuracy. CONCLUSION: Of the three modalities, dynamic MRI was the best for evaluating the efficacy of TACE in the treatment of HCC. We also found that superficial lesions of the right lobe are good candidates for PD sonography. However, high signals on precontrast MR images, motion artifacts, and ultrasonic attenuation remain key limitations.

Squamous cell carcinoma of the esophagus infiltrating the respiratory tract is less sensitive to preoperative concurrent radiation and chemotherapy.

BACKGROUND: The prognosis of upper thoracic esophageal cancer is poor when compared with middle and lower thoracic esophageal cancer because the tumor easily infiltrates the respiratory tract and surgical en-bloc resection is difficult. Recently, preoperative chemoradiation therapy has been shown to lead to down-staging of the disease and improve prognosis. But the benefit of this therapy for tumors infiltrating the respiratory tract remains unknown. STUDY DESIGN: Fifty-six patients with thoracic esophageal cancer infiltrating neighboring organs, but with no hematogeneous metastasis, were given preoperative concurrent chemotherapy (5-fluorouracil and cisplatin) and radiation (40 Gy) therapy. When a clinical response was observed, making a curative resection potentially possible, patients were scheduled for esophagectomy with extended lymphadenectomy. Patient prognosis with respect to the organs infiltrated by the tumors was estimated by calculating survival curves using the Kaplan-Meier method and comparing the curves by the log-rank test. RESULTS: The prognosis was significantly poorer for patients with tumors infiltrating the respiratory tract (T) or aorta plus respiratory tract (A + T) than for patients with tumors infiltrating the aorta alone (A) or other organs (Oth) (p < 0.05 for Oth versus T; p < 0.05 for Oth versus A + T; p < 0.0001 for A versus T; p < 0.0001 for A versus A + T by log-rank test). Patients positive for respiratory tract invasion (T, T + A), compared with those negative for respiratory tract invasion (A, Oth), showed a poorer clinical response to chemoradiation (3.0%, 45.5%, 39.4%, and 9.1% versus 4.3%, 82.6%, 4.3%, and 8.7% in complete response (CR), partial response (PR), nonresponse (NC) and progressive disease (PD), respectively, p = 0.0156) and surgical resectability (36.4% vs. 87.0%, p = 0.0003). Histologic effectiveness (8.3%, 50.0%, and 41.7% versus 25.0%, 70.0%, and 5.0% in grade 3, grade 2, and grade 1, respectively, for patients with respiratory tract invasion versus those without it, p = 0.0189) and histologic stages (8.3%, 8.3%, 8.3%, 8.3%, 25.0%, and 41.7% versus 20.0%, 0%, 15.0%, 25.0%, 40.0%, and 0% in pathologic CR, stage I, stage IIA, stage IIB, stage III, and stage IV, respectively, for patients with respiratory tract invasion versus those without it, p = 0.0496) were significantly better in patients negative for respiratory tract invasion; the percentages of patients with lymph node metastasis did not differ significantly between the two groups. Comparison of the recurrence patterns showed that local failure was most common in patients with respiratory tract invasion, and distant failure was the leading cause of recurrence in patients without it. CONCLUSIONS: Because the prognosis of patients with thoracic esophageal cancer infiltrating the respiratory tract is extremely poor, partially because of the low local effectiveness of preoperative concurrent chemotherapy and radiation therapy, caution is needed when deciding on salvage surgery.

Unrecognized hepatic steatosis and non-alcoholic steatohepatitis in adjuvant tamoxifen for breast cancer patients.

Adjuvant tamoxifen has become the treatment of choice against estrogen receptor-positive breast cancer. Adverse effects are rarely observed and since symptoms of hepatic steatosis, non-alcoholic steatohepatitis and cirrhosis are usually negligible, such effects are not well characterized despite large cohort studies of adjuvant tamoxifen. This issue remains to be systematically studied. The present study consisted of 136 breast cancer patients treated with or without tamoxifen. Patients had laboratory tests once each month and underwent abdominal computed tomography (CT) annually for 5 years. The extent of hepatic steatosis was assessed by CT as the liver/spleen ratio. While receiving adjuvant tamoxifen, 40 of 105 patients developed hepatic steatosis (liver/spleen ratio <0.9) without obvious changes in body mass index. Twenty-one had a liver spleen ratio of <0.5, whereas none of the 31 patients treated without tamoxifen had a ratio <0.9 or <0.5 (p<0.0001 and p<0.0001, respectively). Hepatic steatosis was recognized in 35 of the 40 patients within the first 2 years of receiving adjuvant tamoxifen and 21 of the 40 had increased transaminase levels. Liver biopsy revealed NASH in 6 of 7 patients among the 21 with a liver/spleen ratio of <0.5. A subset of individuals given adjuvant tamoxifen developed progressive hepatic steatosis without significant changes in the body mass index. We suggest a liver/spleen ratio of <0.5 as a criterion upon which liver biopsy should be recommended since NASH frequently occurred in such patients.

A new retro-carotenoid from the petals of the Californian yellow poppy Eschscholtzia californica.

A new retro-carotenoid (1) isolated from the petals of the Californian yellow poppy, Eschscholtzia californica, was determined to be (all-E)-(3S,5R,3'S)-4',5-retro-beta,beta-carotene-3,5,3'-triol by spectroscopic analysis.

Lymphangioma of the colon: a case report and review of the Japanese literature.

Intraabdominal lymphangiomas are rare, although these lesions can occur in the mesentery, omentum, retroperitoneum, or gastrointestinal tract wall. Here we report a case of lymphangioma of the transverse colon and review the other cases reported in the Japanese literature. Our patient presented with lower abdominal pain and barium enema revealed a filling defect in the transverse colon. Colonoscopy disclosed a submucosal tumor, which changed shape with alteration the patient's position and showed the cushion sign. This lesion was covered with normal-looking mucosa. A correct diagnosis was made from these findings. Knowledge of these endoscopic features may help physicians to provide appropriate diagnosis and treatment of colonic lymphangioma.

Gastroprotection by Liu-Jun-Zi-Tang (TJ-43): possible mediation of nitric oxide but not prostaglandins or sulfhydryls.

Liu-Jun-Zi-Tang (TJ-43), a herbal medicine exerting gastroprotective action, was examined for its mechanism of action in rats. TJ-43 significantly inhibited gastric mucosal damage caused by absolute ethanol at doses over 500 mg/kg in a dose-dependent way. Pretreatment with indomethacin or with N-ethylmaleimide did not affect the gastroprotective effect of TJ-43. However, pretreatment with NG-nitro-L-arginine partially but significantly reversed the protective effect of this drug. These findings suggest that the gastroprotective effect of TJ-43 occurs partly through nitric oxide but not through prostaglandins or sulfhydryls.

An antitumor promoter from Moringa oleifera Lam.

In the course of studies on the isolation of bioactive compounds from Philippine plants, the seeds of Moringa oleifera Lam. were examined and from the ethanol extract were isolated the new O-ethyl-4-(alpha-L-rhamnosyloxy)benzyl carbamate (1) together with seven known compounds, 4(alpha-L-rhamnosyloxy)-benzyl isothiocyanate (2), niazimicin (3), niazirin (4), beta-sitosterol (5), glycerol-1-(9-octadecanoate) (6), 3-O-(6'-O-oleoyl-beta-D-glucopyranosyl)-beta-sitosterol (7), and beta-sitosterol-3-O-beta-D-glucopyranoside (8). Four of the isolates (2, 3, 7, and 8), which were obtained in relatively good yields, were tested for their potential antitumor promoting activity using an in vitro assay which tested their inhibitory effects on Epstein-Barr virus-early antigen (EBV-EA) activation in Raji cells induced by the tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA). All the tested compounds showed inhibitory activity against EBV-EA activation, with compounds 2, 3 and 8 having shown very significant activities. Based on the in vitro results, niazimicin (3) was further subjected to in vivo test and found to have potent antitumor promoting activity in the two-stage carcinogenesis in mouse skin using 7,12-dimethylbenz(a)anthracene (DMBA) as initiator and TPA as tumor promoter. From these results, niazimicin (3) is proposed to be a potent chemo-preventive agent in chemical carcinogenesis.