A quasi-randomized controlled trial of Ninjin'yoeito for the treatment of postpartum anemia and the prevention of postpartum depression.

AIM: To study the effect of Ninjin'yoeito (NYT) on postpartum anemia and on the development of postpartum depression (PPD). METHODS: In this prospective, single-center, open-label, quasi-randomized controlled trial, patients with anemia 1-2 days postdelivery were randomized to receive either NYT or an oral iron preparation for 4 weeks. The primary endpoint was the hemoglobin (Hb) level. Secondary endpoints were fatigue (assessed by the numerical rating scale [NRS]) and prevalence of postpartum depressive symptoms, as defined by an Edinburgh postnatal depression scale (EPDS) score ≥9. Hb levels and fatigue were measured before, and 4 weeks after, treatment and the EPDS was measured 4 weeks posttreatment. RESULTS: Of 1066 participants (NYT group: 532, iron group: 534) 1061 (NYT group: 529, iron group: 532) underwent full analysis. The Hb level increased significantly in both groups (p < 0.001), and there were no significant differences between the groups in terms of the change in Hb levels (NYT: 2.4 ± 0.8 g/dL vs. iron: 2.5 ± 0.7 g/dL, p = 0.098). Fatigue decreased significantly in the NYT group (p < 0.001) but did not change in the iron group, and the difference was significant (p < 0.001). There was a significant difference between the two groups in terms of the prevalence of postpartum depressive symptoms (NYT: 5.7% vs. iron: 9.4%, odds ratio [OR] = 0.58, 95% confidence interval [CI] = 0.36-0.93). CONCLUSION: The results suggest that NYT improves postpartum anemia and fatigue, and may be able to prevent the development of PPD.

Oxygen-sensitive quantum dots for possible nanoscale oxygen imaging in cultured cells.

Quantum dots (QDs) are the semiconductor crystal with a nanometer particle size that emit fluorescence of a size-dependent wavelength. In this study, we examined whether L-cysteine-capped CdTe quantum dots (QD580, diameter ~4 nm) might be used as an optical probe for intracellular oxygen (O2) in cultured cells. QD580 was successfully introduced in cultured COS-7 cells by incubating cells with 10 nM QD580 for 5-60 min at 37°C. Cells were exposed to 20 % O2 (0.5 h), then 0.5 % O2 or 20 % O2 (1 h), and finally 20 % O2 (0.5 h) gases. We found significant increases in the fluorescence intensity at 0.5 % O2. However, when compared with QD580 in buffer solution, QD580 fluorescence in cells was considerably weak and vulnerable to repeated excitation light exposures. The present study demonstrated the potential of L-cysteine-capped CdTe QDs as a nanoscale probe for intracellular O2 in cultured cells. Further improvement of the QD is necessary for quantitative assessment of O2 in the cell.

Chemoselective hydrogenation of nitroarenes with carbon nanofiber-supported platinum and palladium nanoparticles.

Platinum and palladium nanoparticles supported on three types of carbon nanofibers (CNFs) are synthesized and used as catalysts in the hydrogenation of nitroarenes. Nanosized platinum particles dispersed on platelet-type CNF efficiently catalyze the reduction of functionalized nitroarenes to the corresponding substituted anilines in high turnover numbers with other functional groups remaining intact.

Phytosterols dissolved in diacylglycerol oil reinforce the cholesterol-lowering effect of low-dose pravastatin treatment.

BACKGROUND AND AIMS: Dietary therapy using phytosterols can reinforce statin treatment; however the value of a low-dose combination of those agents remains to be investigated. Plant sterols (PS), dissolved in diacylglycerol (DAG) oil, (PS/DAG) can be effective at a relatively low dose. The objective of the present study was to examine the effect of PS/DAG oil on blood cholesterol concentrations in hypercholesterolemic outpatients on low-dose pravastatin (10 mg/day). METHODS AND RESULTS: The patients (n=61) were randomly assigned to one of three groups, who consumed TAG (control), DAG or PS/DAG oil. The average intake of PS from the PS/DAG oil during the test period was significantly higher than that for TAG and DAG oils (502 vs. 49 and 38 mg/day, P<0.05). Significant cholesterol-lowering effects from the baseline were observed in the case of the PS/DAG oil treatment alone. Changes in low-density lipoprotein (LDL) cholesterol were inversely correlated with baseline serum campesterol concentrations (r=-0.560, P<0.05), but not baseline LDL cholesterol concentrations. In addition, serum apolipoprotein B concentrations were reduced to a greater extent in subjects with high versus low levels of baseline campesterol (-13.2 mg/dL vs. -3.1 mg/dL, P<0.05). Furthermore, there was a mild, but significant reduction in serum lipoprotein (a) concentration from the baseline (-5.9 mg/dL), which was correlated with the reduction in serum apolipoprotein B concentration (r=0.596, P<0.05). CONCLUSION: A low-dose combination of PS/DAG oil and pravastatin may be a useful strategy for further ameliorating blood cholesterol and lipoprotein (a) concentrations for hypercholesterolemic patients with a low response to pravastatin.

Effect of lipid-lowering therapy with atorvastatin on atherosclerotic aortic plaques detected by noninvasive magnetic resonance imaging.

OBJECTIVES: We sought to elucidate the effects of 20-mg versus 5-mg atorvastatin on thoracic and abdominal aortic plaques. BACKGROUND: Regression of thoracic aortic plaques by simvastatin was demonstrated using magnetic resonance imaging (MRI). However, the effects of different doses of statin have not been assessed. METHODS: Using MRI, we investigated the effects of 20-mg versus 5-mg atorvastatin on thoracic and abdominal aortic plaques in 40 hypercholesterolemic patients who were randomized to receive either dose. Treatment effects were evaluated as changes in vessel wall thickness (VWT) and vessel wall area (VWA) of atherosclerotic lesions from baseline to 12 months of treatment. RESULTS: The 20-mg dose induced a greater low-density lipoprotein (LDL) cholesterol reduction than did the 5-mg dose (-47% vs. -34%, p < 0.001). Although 20 mg and 5 mg reduced C-reactive protein (CRP) levels (-47% and -28%), the degree of CRP reduction did not differ between the two doses. The 20-mg dose reduced VWT and VWA of thoracic aortic plaques (-12% and -18%, p < 0.001), whereas 5 mg did not (+1% and +4%). Regarding abdominal aortic plaques, even 20 mg could not reduce VWT or VWA (-1% and +3%), but instead progression was observed with 5-mg treatment (+5% and +12%, p < 0.01). Notably, the degree of plaque regression in thoracic aorta correlated with LDL cholesterol (r = 0.64) and CRP (r = 0.49) reductions. Although changes in abdominal aortic plaques only weakly correlated with LDL cholesterol reduction (r = 0.34), they correlated with age (r = 0.41). CONCLUSIONS: One-year 20-mg atorvastatin treatment induced regression of thoracic aortic plaques with marked LDL cholesterol reduction, whereas it resulted in only retardation of plaque progression in abdominal aorta. Thoracic and abdominal aortic plaques may have different susceptibilities to lipid lowering.

[Clinical analysis of cases with multidrug-resistant tuberculosis--inpatients at National Hospitals in Kyushu between 1998 and 2003].

PURPOSE: Clinical analysis of inpatients with multidrug-resistant tuberculosis in Kyushu. OBJECT AND METHOD: Clinical analysis of fifty-six patients with multidrug-resistant tuberculosis, who were admitted between 1998 and 2003, at 12 national hospitals in Kyushu was performed retrospectively. RESULTS: The average age was 62.1 +/- 18.6 years, with an age range of 21 to 95 years. There were 44 males and 12 females. Seven of the 14 patients, who were under 49 years old, had not received treatment previously. Twenty nine patients had underlying diseases, which included 10 (17.9%) diabetes mellitus, 5 (8.9%) hepatic disease, and 4 (7.1%) renal insufficiency. Clinical classification of the cases were 54 pulmonary and 2 extrapulmonary tuberculosis. There were 41 (75.9%) bilateral lesions of the lung. In 8 cases, strains were resistant to only 2 drugs (isoniazid, rifampicin). In 27 cases, strains were resistant to at least 5 drugs. The prognosis was as follows: In 27 patients who were resistant to at least 5 drugs, six patients (22.2%) converted to negative on culture and 10 patients (37.0%) died. In 29 patients who were resistant to less than 5 drugs, seventeen patients (58.6%) converted to negative on culture and 6 patients (20.7%) died. Surgical operation was performed in only 7 cases. The sputum smear and culture of 2 surgical patients, who had poor control of diabetes mellitus, became positive thereafter. The other 5 surgical patients were in remission with negative cultures. CONSIDERATION: Half of the patients who were under 49 years old had not received treatment previously. More than half of the patients had underlying diseases. Patients, who were resistant to at least 5 drugs showed a lower bacteriological negative conversion-rate and higher death rate than patients who were resistant to less than 5 drugs.

The susceptibility of lipoprotein(a) to copper oxidation is correlated with the susceptibility of autologous low density lipoprotein to oxidation.

OBJECTIVES: Lipoprotein(a) [Lp(a)] can be oxidized by copper in vitro in a way comparable to low-density lipoprotein (LDL). We sought to determine whether the susceptibility of Lp(a) to oxidation is correlated with the susceptibility of autologous heterogeneous LDL, with apolipoprotein(a) [apo(a)] molecular size, or with both factors. DESIGN AND METHODS: We examined shifts in electrophoretic mobility of Lp(a) and LDL caused by copper oxidation in plasma samples from 81 healthy men. The effect of copper oxidation on different-sized apo(a) was also evaluated. RESULTS: There was a close correlation between the relative electrophoretic mobilities of oxidized Lp(a) and oxidized LDL in subjects, especially with small-sized apo(a) (n = 25, r = 0.72, p < 0.0001). Oxidative processes in Lp(a) resulted in the degradation of large-, but not small-sized apo(a). CONCLUSIONS: The susceptibility of Lp(a) to oxidation is correlated with that of autologous LDL. Large-sized apo(a) may be involved in the Lp(a) oxidation.

Plasma vascular endothelial growth factor level is elevated in patients with multivessel coronary artery disease.

BACKGROUND: Vascular endothelial growth factor (VEGF) has been implicated in both angiogenesis and ischemia. However, the relationship between plasma VEGF level and coronary artery disease remains unknown. HYPOTHESIS: Plasma VEGF level may be associated with severe coronary artery disease and other cardiovascular risk factors. METHODS: We examined plasma VEGF concentration and coronary risk factors in 73 patients who underwent coronary angiography and 70 apparently healthy control subjects. According to the number of the three major coronary vessels with significant (> or = 75%) stenosis, we divided the patients into two groups: the mild stenosis group (0- and single-vessel disease, n = 36) and the severe stenosis group (double- and triple-vessel disease, n = 37). RESULTS: The log VEGF value of the severe stenosis group was significantly higher than that of the mild stenosis (p < 0.05) and control groups (p < 0.05). Furthermore, there was a significant positive trend in the log VEGF value according to the number of vessels with significant stenosis (p = 0.016). However, there was no significant difference in log VEGF value between the mild stenosis and control groups. Soluble vascular cellular adhesion molecule, soluble intracellular adhesion molecule, and other coronary risk factors were found to be associated with the presence of vessel stenosis. CONCLUSION: Unlike established coronary risk factors, the plasma VEGF level may be associated with only severe coronary ischemia such as multiple coronary vessel disease.

Efficacy and effects on lipid metabolism of combination treatment with losartan + hydrochlorothiazide versus losartan + amlodipine: a 48-week prospective, multicenter, randomized, open-label trial.

BACKGROUND: Both combination therapies of an angiotensin II receptor blocker (ARB) with the thiazide diuretic hydrochlorothiazide (HCTZ) and an ARB with a calcium channel blocker (CCB) are recommended to achieve blood pressure (BP) goals in antihypertensive treatment. However, although HCTZ is known to have unfavorable effects on lipid metabolism, the effects of HCTZ in the ARB + HCTZ combination on lipid metabolism have not been fully elucidated. OBJECTIVE: The aim of this study was to compare the effects on lipid metabolism of combination treatment with the ARB losartan + HCTZ and losartan + the CCB amlodipine and to assess the efficacy in BP lowering of these 2 combination therapies. The metabolism of glucose, uric acid (UA), and high-sensitivity C-reactive protein (hs-CRP), an inflammation marker of atherosclerosis, were also assessed in association with lipid metabolism. METHODS: This 48-week, prospective, randomized, open-label trial was conducted at 2 clinics and 2 hospitals in Tokorozawa City (Saitama, Japan) and Shinjuku-ku Ward (Tokyo, Japan). Eligible patients had a systolic BP (SBP) >140 mm Hg and/or diastolic BP (DBP) >90 mm Hg despite a >1-month history of monotherapy with an ARB. Patients were randomly assigned to receive losartan 50 mg/d + HCTZ 12.5 mg/d (LOS + HCTZ) or losartan 50 mg/d + amlodipine 5 mg/d (LOS + CCB) for 48 weeks. Follow-up visits were scheduled at 4, 8, 12, 24, and 48 weeks. Biochemical measurements were centrally measured at a single institute. Tolerability and treatment compliance were assessed by physicians every 4 weeks. RESULTS: A total of 112 patients were enrolled; 26 were excluded from the final analysis, leaving 42 and 44 patients in the LOS + HCTZ and LOS + CCB groups, respectively, included in the final analysis. At 48 weeks, SBP and DBP were significantly decreased in the 2 treatment groups (both, P < 0.0001). The decrease in SBP was significantly greater in the LOS + HCTZ group than in the LOS + CCB group (P < 0.001). The difference in the decrease in DBP between the 2 groups was nonsignificant. There were no significant differences in the changes from baseline (Δ) in any of the lipid parameters between the 2 groups. The decreases at 8 and 12 weeks in LDL-C, TC, and apolipoprotein (apo) B were significantly greater in the LOS + CCB group compared with those in the LOS + HCTZ group. The between-group differences in ΔTG, ΔHDL-C, ΔapoA-1, and ΔapoE throughout the study were nonsignificant. Changes in fasting plasma glucose (FPG), hemoglobin A1c, and hs-CRP were not significantly different between the 2 groups. The between-group difference in ΔUA in men was not significant, but a significant difference was found in women (LOS + HCTZ, 0.74 mg/dL; LOS + CCB, 0.28 mg/dL [P = 0.0017]). No clinically significant adverse events were reported with either treatment throughout the study. CONCLUSIONS: The findings from the present study suggest that LOS + HCTZ was more efficacious in decreasing SBP than was LOS + CCB in the management of hypertension refractory to ARB monotherapy. Unfavorable effects on lipid metabolism were not observed with either combination therapy.

Ruthenium nanoparticles on nano-level-controlled carbon supports as highly effective catalysts for arene hydrogenation.

The reaction of three types of carbon nanofibers (CNFs; platelet: CNF-P, tubular: CNF-T, herringbone: CNF-H) with [Ru3(CO)12] in toluene heated at reflux provided the corresponding CNF-supported ruthenium nanoparticles, Ru/CNFs (Ru content = 1.1-3.8 wt %). TEM studies of these Ru/CNFs revealed that size-controlled Ru nanoparticles (2-4 nm) exist on the CNFs, and that their location was dependent on the surface nanostructures of the CNFs: on the edge of the graphite layers (CNF-P), in the tubes and on the surface (CNF-T), and between the layers and on the edge (CNF-H). Among these Ru/CNFs, Ru/CNF-P showed excellent catalytic activity towards hydrogenation of toluene with high reproducibility; the reaction proceeded without leaching of the Ru species, and the catalyst was reusable. The total turnover number of the five recycling experiments for toluene hydrogenation reached over 180,000 (mol toluene) (mol Ru)(-1). Ru/CNF-P was also effective for the hydrogenation of functionalized benzene derivatives and pyridine. Hydrogenolysis of benzylic C-O and C-N bonds has not yet been observed. Use of poly(ethylene glycol)s (PEGs) as a solvent made possible the biphasic catalytic hydrogenation of toluene. After the reaction, the methylcyclohexane formed was separated by decantation without contamination of the ruthenium species and PEG. The insoluble PEG phase containing all of the Ru/CNF was recoverable and reusable as the catalyst without loss of activity.

Computational analysis suggests that alternative first exons are involved in tissue-specific transcription in rice (Oryza sativa).

MOTIVATION: Transcription start site selection and alternative splicing greatly contribute to diversifying gene expression. Recent studies have revealed the existence of alternative first exons, but most have involved mammalian genes, and as yet the regulation of usage of alternative first exons has not been clarified, especially in plants. RESULTS: We systematically identified putative alternative first exon transcripts in rice, verified the candidates using RT-PCR, and searched for the promoter elements that might regulate the alternative first exons. As a result, we detected a number of unreported alternative first exons, some of which are regulated in a tissue-specific manner. SUPPLEMENTARY INFORMATION: http://www.bioinfo.sfc.keio.ac.jp/research/intron.