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Finely dispersed Y 2 O 3 :Eu, Y 2 Si 2 O 7 :Eu, YF 3 :Ce and YF 3 :Eu luminescent phosphors are synthesized using a hydrothermal method. A process is developed for obtaining Y 2 O 3 :Eu phosphors with a reduced particle size by hydrothermal precipitation with the addition of an inert finely dispersed filler (Aerosil) followed by rapid thermal annealing (RTA). Another process is suggested for the synthesis of finely dispersed Y 2 Si 2 O 7 :Eu phosphor via hydrothermal precipitation followed by microwave annealing. The effect of the synthesis conditions on the properties of YF 3 :Ce and YF 3 :Eu nanosized phosphors is studied and hydrothermal processing conditions were determined so as to provide the adjustment of their luminescence spectra due to the variation of the activator valency (Eu 3+ /Eu 2+ and Ce 3+ /Ce 2+ ). Besides earlier defined luminescence centers comprising Eu 2+ ions in orthorhombic and cubic coordination positions of YF 3 crystal lattice, the studied phosphors involve two additional types of luminescence centers relating to Eu(II), supposedly corresponding to Eu 2+ in the same coordination positions located on the surface of the phosphor particles. Using the obtained data, an energy chart of Eu(II)-based luminescence centers in YF 3 :Eu nanosized phosphors is suggested. The resulting nanoscale particle size and luminescence spectra features of the synthesized phosphors YF 3 :Ce and YF 3 :Eu make them potentially useful for photodynamic therapy of cancer in combination with the photosensitizer Rose Bengal. The composition involving the synthesized Y 2 O 3 :Eu phosphor and photosensitizer Photoditazine was shown to provide an effective destruction of tumor cell cultures. Graphical abstract A hydrothermal procedure is developed for obtaining YF 3 :Eu nanosized phosphors with adjustable luminescence spectra due to the activator valence variation (Eu 3+ /Eu 2+ ). An energy chart for Eu 2+ -based luminescence centers is suggested for the considered phosphors. Highlights Y 2 O 3 :Eu nanosized phosphor is synthesized via hydrothermal precipitation followed by RTA. Finely dispersed Y 2 Si 2 O 7 :Eu is synthesized via hydrothermal precipitation with the addition of Aerosil followed by microwave annealing. An energy chart of Eu(II)-based luminescence centers in YF 3 :Eu nanosized phosphors is defined. Nanosized phosphors promising for the application in photodynamic therapy of cancer coupled with the photosensitizer Rose Bengal are obtained.

Summary A randomized placebo-controlled trial was conducted to examine the effect of daily oral 1 mg minodronate on vertebral fractures in 704 postmenopausal women with established osteoporosis for 24 months. Minodronate treatment reduced vertebral fractures by 59% without serious adverse events. Minodronate is a safe and effective bisphosphonate for osteoporosis treatment. Introduction Minodronate increases bone mineral density (BMD) in postmenopausal osteoporotic patients. However, its efficacy in reducing osteoporotic fractures has not been tested. Methods To examine anti-fracture efficacy and safety of daily oral minodronate in postmenopausal women with established osteoporosis, a randomized, double-blind, placebo-controlled trial was conducted in 704 postmenopausal women (55 to 80 years) with one to five vertebral fractures and low BMD. Subjects were randomly assigned to receive daily oral 1 mg minodronate (n = 359) or placebo (n = 345) for 24 months, with daily supplements of 600 mg calcium and 200 IU vitamin D₃. Results Daily 1 mg minodronate for 24 months reduced the risk of vertebral fractures by 59% (95% CI, 36.6-73.3%). Furthermore, when fractures during the first 6 months were eliminated, the risk of vertebral fractures from 6 to 24 months was reduced by 74% in minodronate-treated group. Minodronate treatment also reduced height loss. Bone turnover markers were suppressed by about 50% after 6 months of minodronate treatment and remained suppressed thereafter. The overall safety profile including gastrointestinal safety was similar between the two groups. Conclusions Daily oral minodronate is safe, well-tolerated, and is effective in reducing vertebral fracture risk in postmenopausal women with established osteoporosis.

Summary Although feeding diets containing the extract powder of Lepidium meyenii (maca), a plant growing in Peru's Central Andes, increases serum testosterone concentration associated with enhanced ability of testosterone production by Leydig cells in male rats, changes in testicular steroidogenesis‐related factors by the maca treatment are not known. This study examined the effects of maca on testicular gene expressions for luteinizing hormone receptor, steroidogenic acute regulatory protein and steroidogenic enzymes. Eight‐week‐old male rats were given the diets with or without (control) the maca extract powder (2%) for 6 weeks, and mRNA levels were determined by reverse transcription quantitative real‐time PCR. The results showed that the testicular mRNA level of HSD3B1 (3β‐hydroxysteroid dehydrogenase; 3β‐HSD) increased by the treatment, whereas the levels of the other factors examined did not change. These results suggest that increased expression of 3β‐HSD gene may be involved in the enhanced steroidogenic ability by the maca treatment in rat testes.

Summary Although feeding diets containing the extract powder of Lepidium meyenii (maca), a plant growing in Peru's Central Andes, increases serum testosterone concentration associated with enhanced ability of testosterone production by Leydig cells in male rats, changes in testicular steroidogenesis-related factors by the maca treatment are not known. This study examined the effects of maca on testicular gene expressions for luteinizing hormone receptor, steroidogenic acute regulatory protein and steroidogenic enzymes. Eight-week-old male rats were given the diets with or without (control) the maca extract powder (2%) for 6 weeks, and mRNA levels were determined by reverse transcription quantitative real-time PCR. The results showed that the testicular mRNA level of HSD3B1 (3[beta]-hydroxysteroid dehydrogenase; 3[beta]-HSD) increased by the treatment, whereas the levels of the other factors examined did not change. These results suggest that increased expression of 3[beta]-HSD gene may be involved in the enhanced steroidogenic ability by the maca treatment in rat testes.

Summary Although Lepidium meyenii (maca), a plant growing in Peru's central Andes, has been traditionally used for enhancing fertility and reproductive performance in domestic animals and human beings, effects of maca on reproductive organs are still unclear. This study examined whether feeding the hydroalcoholic extract powder of maca for 6 weeks affects weight of the reproductive organs, serum concentrations of testosterone and luteinising hormone (LH), number and cytoplasmic area of immunohistochemically stained Leydig cells, and steroidogenesis of cultured Leydig cells in 8‐week‐old male rats. Feeding the extract powder increased weight of seminal vesicles, serum testosterone level and cytoplasmic area of Leydig cells when compared with controls. Weight of prostate gland, serum LH concentration and number of Leydig cells were not affected by the maca treatment. The testosterone production by Leydig cells significantly increased when cultured with 22R‐hydroxycholesterol or pregnenolone and tended to increase when cultured with hCG by feeding the extract powder. The results show that feeding the hydroalcoholic extract powder of maca for 6 weeks increases serum testosterone concentration associated with seminal vesicle stimulation in male rats, and this increase in testosterone level may be related to the enhanced ability of testosterone production by Leydig cells especially in the metabolic process following cholesterol.

Homeostasis model assessment as a clinical index of insulin resistance in type 2 diabetic patients treated with sulfonylureas. M Emoto , Y Nishizawa , K Maekawa , Y Hiura , H Kanda , T Kawagishi , T Shoji , Y Okuno and H Morii Second Department of Internal Medicine, Osaka City University Medical School, Japan. Abstract OBJECTIVE: To investigate whether the insulin resistance index (IR) assessed by homeostasis model assessment (HOMA) is associated with the insulin resistance index assessed by euglycemic-hyperinsulinemic clamp (clamp IR) in type 2 diabetic patients who received sulfonylureas (SUs), as well as in those treated by diet alone. RESEARCH DESIGN AND METHODS: Retrospectively, the association between HOMA IR and clamp IR was analyzed in 80 type 2 diabetic subjects (53 subjects treated with SUs and 27 subjects treated with diet alone). The 80 subjects, selected because they had not received insulin therapy, were among 111 diabetic participants in a clamp study for evaluation of insulin resistance from May 1993 to December 1997 in Osaka City University Hospital. RESULTS: The HOMA IR showed a hyperbolic relationship with clamp IR. The log-transformed HOMA IR (all subjects, r = -0.725, P < 0.0001; SU group, r = -0.727, P < 0.0001; diet group, r = -0.747, P < 0.0001) correlated more strongly with clamp IR than did HOMA IR per se (all subjects, r = -0.594, P < 0.0001; SU group, r = -0.640, P < 0.0001; diet group, r = -0.632, P = 0.0004). The univariate regression line between log-transformed HOMA IR and clamp IR in the SU group did not differ from that in the diet group (slope, -6.866 vs. -5.120, P > 0.05; intercept, 6.566 vs. 5.478, P > 0.05). Stepwise multiple regression analyses demonstrated that the log-transformed HOMA IR was the strongest independent contributor to clamp IR (R2 = 0.640, P < 0.0001). CONCLUSIONS: The HOMA IR strongly correlated with the clamp IR in type 2 diabetic patients treated with SUs as well as in those treated with diet alone.

Correlation between the intima-media thickness of the carotid artery and aortic pulse-wave velocity in patients with type 2 diabetes. Vessel wall properties in type 2 diabetes. H Taniwaki , T Kawagishi , M Emoto , T Shoji , H Kanda , K Maekawa , Y Nishizawa and H Morii Second Department of Internal Medicine, Osaka City University Medical School, Japan. Abstract OBJECTIVE: The aim of this study was to assess the relationship between atherotic (structural) and sclerotic (functional) changes in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Aortic distensibility and carotid intimal-media thickness (IMT) were evaluated using carotid-femoral aortic pulse-wave velocity (a-PWV) and high-resolution B-mode ultrasonography in 271 patients with type 2 diabetes and 285 age-matched control subjects. RESULTS: a-PWV and carotid IMT were significantly higher in the patients than in the control subjects in all age-groups (P < 0.0001, respectively). The carotid IMT and a-PWV were significantly correlated with age in both the patients with type 2 diabetes and control subjects. There was a significant positive relationship between the carotid IMT and a-PWV in both the patients (r = 0.482, P < 0.0001) and control subjects (r = 0.424, P < 0.0001). The slope of the regression line for the carotid IMT to the a-PWV was significantly steeper in the diabetic patients than in the control subjects (P < 0.05). Multiple regression analysis in all subjects showed that age, diabetic state, and cigarette smoking were independently common risk factors for the increase in carotid IMT and a-PWV. In the diabetic patients, the independent risk factors associated with the carotid IMT were age, hyperlipidemia, and duration of diabetes (R2 = 0.232, P < 0.0001), while those associated with a-PWV were age and duration of diabetes (R2 = 0.334, P < 0.0001). CONCLUSIONS: The results indicated that diabetic patients showed more advanced changes in atherosis than that in sclerosis as compared with age- and sex-matched control subjects. Such atherotic changes in diabetic patients may be associated with hyperlipidemia.

The safety and efficacy of raloxifene, a selective estrogen receptor modulator (SERM), has been studied extensively in large, global clinical trials. However, the effect of raloxifene on bone mineral density (BMD) and on biochemical markers of bone turnover in Japanese postmenopausal women with osteoporosis has not been rigorously evaluated. This study was designed to assess the safety and efficacy of raloxifene in Japanese postmenopausal women with osteoporosis following 1 year of therapy. Participants in this multicenter trial were randomly assigned to receive placebo, raloxifene 60 mg/day (RLX60), or raloxifene 120 mg/day (RLX120). Lumbar spine BMD was measured at baseline, 24, 40, and 52 weeks, and biochemical markers of bone turnover were assessed at baseline, 12, 24, and 52 weeks. Serum lipids were assessed at baseline, 12, 24, 40, and 52 weeks, and breast examinations and transvaginal ultrasound of the endometrium were performed at enrollment and 52 weeks. Compared with baseline, women taking RLX60 had significant increases in lumbar spine (L2-L4) BMD at 24 weeks (+3.3%, p<0.001) through 52 weeks (+3.5%, p<0.001) of therapy, and similar results were observed in the RLX120 group. Markers of bone turnover and total cholesterol and LDL-C were significantly reduced, and no significant treatment-group difference was observed for patients reporting at least one adverse event following randomization. In addition, there were no reported venous thromboembolic events (VTE) in any treatment group. The results of this study demonstrate that raloxifene is associated with early increases in lumbar spine BMD, has favorable effects on biochemical markers of bone turnover and lipid profile, and is well tolerated in postmenopausal Japanese women.

To test the effect of amino-terminal peptide 1-34 of human parathyroid hormone (hPTH (1-34)) as a possible bone anabolic agent in the treatment of osteoporosis, weekly subcutaneous injection of 50 units (L group), 100 units (M group) or 200 units (H group) of hPTH (1-34) was started in 220 patients with osteoporosis at 71 institutions randomly divided into three groups in a double-masked system. Lumbar spine bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) increased by 0.6%, 3.6% and 8.1% after 48 weeks in groups L, M and H respectively, responses in groups M and H being significantly higher than in L (p<0.05, Mann-Whitney U-test). Since the coefficient of variation for lumbar spine measurement stayed at 1-2.5%, increases of 3.6% and 8.1% appeared significant. Metacarpal BMD and cortical thickness measured by radiogrammetry did not change significantly. Serum calcium decreased in each group and serum phosphorus decreased in groups M and H. Urinary calcium/creatinine decreased at the 12th week in group H and at the 24th and 48th weeks in groups M and L. Serum 25(OH) vitamin D and 1,25(OH)(2) vitamin D decreased in each group at the 48th week (p<0.05). Serum bone-type alkaline phosphatase was increased at the fourth week in groups H and M and decreased at the 48th week in group H. Urinary hydroxyproline, pyridinoline and deoxypyridinoline declined significantly in each group. Backache improved in 30-40% of each group. No serious adverse effects were found during the test period. Intermittent weekly injection of hPTH (1-34) increased lumbar BMD in osteoporosis, suggesting usefulness in the treatment of osteoporosis.

We describe a novel multi-GeV photon detector which operates under an intense flux of neutrons. It is composed of lead–aerogel sandwich counter modules. Its salient features are high photon detection efficiency and blindness to neutrons. Monte Carlo (MC) simulations show that the efficiency for photons with energy larger than 1 GeV is expected to be higher than 99.5% and that for 2 GeV/$c$ neutrons is less than 1%. Performance of photon detection with an underlying large flux of neutrons was measured by a partial detector with 12 modules. We confirm the efficiency for photons with energy $>1$ GeV is consistent with the MC expectation within an uncertainty of 8.2%.