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Aims: The aim of this study was to determine differences in the acute and chronic impact of adaptive servo-ventilation (ASV) on left chamber geometry and function in patients with chronic heart failure (CHF)., Methods and Results: An acute ASV study was performed to measure echocardiographic parameters before and 30 min after the initiation of ASV therapy in 30 CHF patients (mean age: 69 years, 23 male). The chronic effects of ASV therapy were also evaluated in 26 of these 30 patients over a mean follow-up period of 24 weeks. Patients were divided into two groups according to the status of ASV therapy [ASV group (n= 15) and withdrawal group (n= 11)]. In the acute study, heart rate and blood pressure were significantly decreased 30 min after the ASV therapy compared with baseline. Stroke volume and cardiac output were significantly increased in conjunction with a reduction in systemic vascular resistance. Multivariate regression analysis revealed baseline E/e' to be an independent predictor for absolute increase in cardiac output. In the chronic study, a significant reduction of left ventricular (LV)/left atrial (LA) volumes and the severity of mitral regurgitation (MR), and improved LV diastolic function parameters were noted in the ASV group. These beneficial effects were not observed in the withdrawal group., Conclusion: The acute beneficial impact of ASV is mainly associated with the reduction of afterload resulting in an increase in stroke volume and cardiac output. In contrast, chronic ASV therapy produces LV and LA reverse remodelling resulting in an improvement in LV function and the severity of MR in patients with CHF.

Melatonin exists in numerous living organisms including vertebrates, insects, fungi, bacteria, and plants. Extensive studies have been conducted on the physiological roles of melatonin in various plant species. In plants, melatonin seems to act in antioxidant protection, as a growth promoter, and in photoperiodism. However, the mechanisms by which melatonin carries out these roles remain unclear. We manipulated the endogenous melatonin content in tomato plants by modifying the metabolic enzyme indoleamine 2,3-dioxygenase (IDO). The OsIDO gene was isolated from rice (Oryza sativa) and characterized using 3-D homology modeling and reverse genetic approaches. The amino acid sequence of OsIDO showed high homology to the Ustilago maydis IDO. The 3-D model structure of OsIDO is composed of a small and a large domain. Transgenic tomato plants constitutively expressing the OsIDO gene exhibited a decrease in their melatonin content. Moreover, the number of lateral leaflets decreased in transgenic plants. Protein extracts taken from these plants showed activity degradation, demonstrating the function of OsIDO. These results suggest the involvement of IDO in plant melatonin metabolism and a possible role in plant leaf development., (© 2010 The Authors. Journal of Pineal Research © 2010 John Wiley & Sons A/S.)

Melatonin is found in a wide variety of plant species. Several investigators have studied the physiological roles of melatonin in plants. However, its role is not well understood because of the limited information on its biosynthetic pathway. To clarify melatonin biosynthesis in plants, we isolated a cDNA-coded arylalkylamine N-acetyltransferase (AANAT), a possible limiting enzyme for melatonin biosynthesis, from Chlamydomonas reinhardtii (designated as CrAANAT). The predicted amino acid sequence of CrAANAT shares 39.0% homology to AANAT from Ostreococcus tauri and lacks cAMP-dependent protein kinase phosphorylation sites in the N- and C-terminal regions that are conserved in vertebrates. The enzyme activity of CrAANAT was confirmed by in vitro assay using Escherichia coli. Transgenic plants constitutively expressing the CrAANAT were produced using Micro-Tom, a model cultivar of tomato (Solanum lycopersicum L.). The transgenic Micro-Tom exhibited higher melatonin content compared with wild type, suggesting that melatonin was synthesized from serotonin via N-acetylserotonin in plants. Moreover, the melatonin-rich transgenic Micro-Tom can be used to elucidate the role of melatonin in plant development.

Melatonin exists in a considerable variety of plant species. However, the physiological roles of melatonin in plants are not well understood. In this study, the distribution and accumulation of melatonin during leaf and fruit development were analyzed in Micro-Tom, a model cultivar of tomato (Solanum lycopersicum L.). Melatonin was extracted using an acetone-methanol method and measured by enzyme-linked immunosorbent assay. Melatonin was detected in leaves, stems, roots, flowers, fruits, seedlings and seeds in the range of 1.5-66.6 ng/g fresh weight, with seeds containing the highest concentration of melatonin. In fruits and leaves, melatonin concentrations varied depending on the developmental stage, suggesting that melatonin controls some of the processes involved in plant maturation.

Background and Purpose: Many drugs associated with acquired long QT syndrome (LQTS) directly block human ether-a-go-go-related gene (hERG) K(+) channels. Recently, disrupted trafficking of the hERG channel protein was proposed as a new mechanism underlying LQTS, but whether this defect coexists with the hERG current block remains unclear. This study investigated how ketoconazole, a direct hERG current inhibitor, affects the trafficking of hERG channel protein., Experimental Approach: Wild-type hERG and SCN5A/hNa(v) 1.5 Na(+) channels or the Y652A and F656C mutated forms of the hERG were stably expressed in HEK293 cells. The K(+) and Na(+) currents were recorded in these cells by using the whole-cell patch-clamp technique (23 degrees C). Protein trafficking of the hERG was evaluated by Western blot analysis and flow cytometry., Key Results: Ketoconazole directly blocked the hERG channel current and reduced the amount of hERG channel protein trafficked to the cell surface in a concentration-dependent manner. Current density of the hERG channels but not of the hNa(v) 1.5 channels was reduced after 48 h of incubation with ketoconazole, with preservation of the acute direct effect on hERG current. Mutations in drug-binding sites (F656C or Y652A) of the hERG channel significantly attenuated the hERG current blockade by ketoconazole, but did not affect the disruption of trafficking., Conclusions and Implications: Our findings indicate that ketoconazole might cause acquired LQTS via a direct inhibition of current through the hERG channel and by disrupting hERG protein trafficking within therapeutic concentrations. These findings should be considered when evaluating new drugs.

A pulse sequence that enables simultaneous acquisition of T2-weighted and fluid-attenuated images is presented. This sequence is referred to as FASCINATE (Fluid-Attenuated Scan Combined with Interleaved Non-ATtEnuation). In this new technique, the inversion pulse of conventional fast fluid-attenuated inversion recovery (FLAIR) is replaced with a fast spin echo (FSE) acquisition that has an additional 180(y)-90(x) pulse train for driven inversion. By using appropriate scan parameters, the first part of the sequence provides T2-weighted images and the second part provides fluid-attenuated images, thus allowing simultaneous acquisition in a single scan time comparable to that of fast FLAIR. FASCINATE was compared with conventional scanning techniques using a normal volunteer and a patient. A signal simulation was also conducted. In the human study, both T2-weighted and fluid-attenuated images from FASCINATE showed the same image quality as conventional images, suggesting the potential for this technique to replace the combination of fast FLAIR and T2-weighted FSE for scan time reduction., (Copyright 2003 Wiley-Liss, Inc.)

As a means of improving the biological properties of materials for use as bone substitutes, functionally graded carbonate apatite containing Mg, FGMgCO3Ap, was synthesized at 60 degrees C and pH 7.4 using a gradient magnesium supply system. X-ray diffraction analysis of FGMgCO3Ap showed a poorly crystallized apatitic pattern, similar to that of human bone. ESCA analysis clearly showed the negative gradient distribution in Mg1s intensity (atomic concentration) of magnesium from the crystal surface toward the inner core. When the FGMgCO3Ap crystals were mixed with collagen, the resulting FGMgCO3Ap-collagen composite, irradiated with UV light for 4 h, retained their features in the saline solution. After washing away the nonadhesive cells, a cell adhesion assay showed that the optical density of the FGMgCO3Ap-collagen composite was higher than that of the CO3Ap-collagen composite. SEM observation showed that the osteoblast-like cells adhered well to the surface of the FGMgCO3Ap-collagen composite. Staining with hematoxylin-eosin and alizarin red confirmed the existence of a great many more cells and a thicker extracellular matrix layer on the FGMgCO3Ap-collagen composite than on the CO3Ap-collagen composite. This result demonstrated the acceleration effect of magnesium ions on osteoblast adhesion on the FGMgCO3Ap-collagen composite., (Copyright 2002 Wiley Periodicals, Inc.)

The aim of this study was to investigate the biodegradation of carbonate apatite (CO(3)Ap)/collagen composite membrane as a new guided tissue regeneration membrane in vivo and to estimate its controlled release of CO(3)Ap in vitro. To control the biodegradation of the guided tissue regeneration membrane and to promote hard tissue regeneration in the periodontal region, we added CO(3)Ap into the collagen membrane. To investigate the biodegradation of CO(3)Ap/collagen composite membranes, the prepared membranes (CO(3)Ap:0, 10 wt %) were cut into 5 x 5 x 0.1 mm and subcutaneously implanted into the backside of male rats under general anesthesia. The explanted membranes were investigated histologically. To estimate their controlled release of CO(3)Ap in vitro, the membranes (CO(3)Ap 0-10 wt %, 5 x 5 x 0.1 mm) were immersed into collagenase solution and compulsorily dissolved for 48 h. Histological results suggested that the membrane had a good biocompatibility and the biodegradable period was shortened with the presence of CO(3)Ap. In the solubility experiments of the membrane, eluted Ca concentrations gradually increased with total dependence on the dissolution of the collagen membrane. Our study demonstrated that the biodegradation time can be controlled by CO(3)Ap contents in the membrane and CO(3)Ap could be released from the membrane with the biodegradation period., (Copyright 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 651-656, 2002)

Thermal analysis was used to measure the characteristics of dental resins cured with the use of a new light-activation unit equipped with high illuminant blue light-emitting diodes (LEDs). The characteristics were compared with those of resins cured with the use of two conventional halogen lamp units. The prepared base monomer consisted of a mixture of Bis-GMA and TEGDMA (60:40 by weight), with 0.5 wt% CQ/DMPT or CQ/DMAEMA. The two experimental visible-light-cured resins were polymerized for 40 s. Differential scanning calorimetry (DSC) was used to examine the thermal characteristics of the cured resins. The activation energy for the decomposition of the dental resin was calculated from the peaks of the endothermic curves obtained when the specimens were heated at three different rates (5, 10, and 15 C/min) during DSC. The activation energies calculated for the LED-cured specimens were more than 220 kJ/mol; specimens cured with the use of the halogen units had activation energies of less than 192 kJ/mol. The Knoop hardness number (KHN) of the same specimens was measured, and was higher with the blue LED units than with halogen lamp units. Therefore, dental resins cured using blue LEDs have a higher degree of polymerization and more stable three-dimensional structures than those cured with halogen lamps., (Copyright 2002 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 63: 209--213, 2002; DOI 10.1002/jbm.10126)

In order to study adhesion/decalcification mechanisms of acid interactions with human hard tissues such as bones and teeth, the chemical interaction of five carboxylic acids (acetic, citric, lactic, maleic, and oxalic) and two inorganic acids (hydrochloric and nitric) with enamel and two synthetic hydroxyapatite (HAp) powders with, respectively, a high and a low crystallinity were analyzed using X-ray photoelectron spectroscopy (XPS), atomic absorption spectrophotometry (AAS), and spectrophotometry (S). X-ray diffraction revealed that the crystallinity of the highly crystallized HAp was considerably higher than that of enamel while the crystallinity of the poorly crystallized HAp was similar to that of dentin and bone. XPS of acid-treated enamel demonstrated for all carboxylic acids ionic bonding to calcium of HAp. AAS and S showed for both HAps that all carboxylic and inorganic acids except oxalic acid extracted Ca significantly more than P, leading to a Ca/P ratio close to that of synthetic HAp (2.16 w/w). Oxalic acid extracted hardly any Ca, but substantially more P, leading to a significantly smaller Ca/P ratio than that of HAp. AAS showed that the calcium salt of oxalic acid hardly could be dissolved, whereas the calcium salts of all the other acids were very soluble in their respective acid solution. These results confirm the adhesion/decalcification concept (AD-concept) previously advanced. Depending on the dissolution rate of the respective calcium salts, acids either adhere to or decalcify apatitic substrates. It is concluded that the AD-concept that originally dictated the interaction of carboxylic acids with human hard tissues can be extended to inorganic acids, such as hydrochloric and nitric acid. Furthermore, HAp crystallinity was found not to affect the adhesion/decalcification behavior of acids when interacting with apatitic substrates, so that the AD-concept can be applied to all human hard tissues with varying HAp crystallinity., (Copyright 2001 John Wiley & Sons, Inc.)

Recently, polymerization-initiator-induced radicals have been identified as a biohazard as well as residual monomers. The present investigation was conducted to clarify the leaching behavior of the polymerization initiator and to measure the relationship between the leached amount of polymerization initiator and the degree of conversion of visible light (VL)-cured resin. Moreover, determining a suitable ratio of polymerization initiator to the base monomer according to the above relationship was carried out. The base monomer (UDMA/TEGDMA) was activated with varying concentrations of polymerization initiator (CQ/DMPT, CQ/DMAEMA) from 0.3-0.9 wt%, respectively, which were exposed to light for 40 s. Gas chromatograph mass spectrometry (GCMS) was carried out to evaluate the leached amount of polymerization initiator. The degree of conversion (DC) of the cured sample was estimated using attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. As the result, it was recognized that the leachability of the polymerization initiator (CQ, DMPT, and DMAEMA) depended on the degree of conversion of the VL-cured resin. Therefore, the optimal concentration of polymerization initiator can be determined from the relation between the degree of conversion and the leached amount of polymerization initiator, which is about 0.6 wt% for CQ/DMPT (1:1 in weight) and 0.5 wt% for CQ/DMAEMA (1:1 in weight) relative to the UDMA/TEGDMA (1:1 in weight) monomer., (Copyright 2000 John Wiley & Sons, Inc.)

In terms of mechanical properties and durability, the surface of glass fillers should be decontaminated in order to optimize the silanization process for the production of resin composites. The objective of this study was to evaluate the decontamination efficiency of 18 cleaning methods on glass fillers as pretreatment of silane coupling. X-ray photoelectron spectroscopy revealed that SiO(2) boiled with a 5% sodium peroxodisulfate aqueous solution for 15 min, followed by ultrasonic rinsing with acetone for 30 min was most effective among all the decontamination methods investigated. In addition, nano-indentation measurements on SiO(2) treated by the above-mentioned method revealed that the surface was not significantly weakened as compared to untreated SiO(2). The results of this study should lead to an improved filler-matrix coupling and thus contribute to the development of better wear and fatigue-resistant composites. Therefore, sodium peroxodisulfate is proposed as a presilanization filler decontamination step in the production process of resin composites., (Copyright 2000 John Wiley & Sons, Inc.)

1. The vascular effect of insulin in the mesenteric resistance blood vessel and the role of calcitonin generelated peptide (CGRP)-receptor in insulin-induced vascular responsiveness were investigated in rats. 2. The mesenteric vascular beds isolated from Wistar rats were perfused with Krebs solution, and perfusion pressure was measured with a pressure transducer. In preparations contracted by perfusion with Krebs solution containing methoxamine in the presence of guanethidine, the perfusion of insulin (from 0.1 to 3000 nM) caused a concentration-dependent decrease in perfusion pressure due to vasodilatation. The pD2 value and maximum relaxation (%) were 6.94+/-0.22 and 43.9+/-5.2, respectively. 3. This vasodilator response to insulin was unaffected by 100 nM propranolol (beta-adrenoceptor antagonist) plus 100 nM atropine (muscarinic cholinoceptor antagonist), 100 microM L-NG-nitroarginine (nitric oxide synthase inhibitor), 1 microM ouabain (Na+-K+ ATPase inhibitor), or 1 microM glibenclamide (ATP sensitive K+-channel inhibitor). 4. In preparations without endothelium, perfusion of insulin produced a marked vasodilatation. The pD2 value and maximum relaxation (%) were 7.62+/-0.21 and 81.0+/-4.6, respectively, significantly greater than in preparations with intact endothelium. 5. The vasodilator responses to insulin in the preparations without endothelium were significantly inhibited by CGRP[8 37], a CGRP receptor antagonist, whereas pretreatment with capsaisin, a toxin for CGRP-containing nerves, did not affect insulin-induced vasodilatation. 6. These results suggest that insulin induces non-adrenergic, non-cholinergic and endothelium-independent vasodilatation, which is partially mediated by CGRP receptors.

Background: Recently, transcatheter arterial embolization (TAE) has been used to treat hepatocellular carcinoma (HCC), yet much is still unknown regarding its optimal use., Methods: Eighty-four patients with HCC after TAE underwent surgical resection. Fifty of the tumors were less than 3 cm (small HCC [S-HCC]), and 34 were 3 cm or larger (large HCC [L-HCC]). Necrosis rate, distribution of residual HCC, histopathology of the main tumor, and proliferating activity of residual HCC by means of proliferative cell nuclear antigen (PCNA) were examined. Twenty-two randomly selected patients with HCC treated with standard chemotherapy were used as non-TAE control subjects., Results: A necrosis rate of greater than 95% was seen in 35 cases of S-HCC and in 15 of L-HCC. All five nonencapsulated tumors were L-HCC and had a much lower necrosis rate. No tumors in the control group showed a necrosis rate of greater than 95%. Encapsulated tumors were categorized according to their tumor interiors, capsules, and extracapsular zones. Complete necrosis of the tumor interior was 80.0% and 35.3% in S-HCC and L-HCC, respectively. Viable residual tumors were found mainly in the extracapsular zone in S-HCC, whereas in L-HCC they were located primarily in the tumor interior. Most capsules were affected by tumor necrosis and the subsequent healing process, resulting in a thick secondary capsule. Tumor interior necrosis was uniform and coagulative in S-HCC, in contrast to L-HCC, in which necrotic regions comprised several necrosis units of differing texture and were divided by fibrous septa. In contrast, the control group revealed spotty, sparse necrosis. Non-TAE tumor capsules were thin and pathologically characteristic of those naturally occurring in tumors, as opposed to the thick fibrous capsules, which are inducible by TAE therapy. In the TAE group, the PCNA positivity rates were 37.5%, 52.5%, and 100% in Grades 1, 2, and 3/4 combined, respectively. At the tumor-nontumor boundary of the extracapsular region, PCNA-positive cells were detected in 55.0% of the cases., Conclusions: The thickened tumor capsule serves as a good postoperative indicator of TAE response. Small tumors seem to be affected in the tumor interior, whereas extracapsular invasion undermines the TAE effect. PCNA was helpful in detecting the tumor-nontumor boundary and useful as a parameter of viability of HCC after TAE.

According to the extent of hepatic involvement of the tumor and that of portal vein invasion at the time of initial diagnosis, patients with hepatocellular carcinoma (HCC) were grouped into three or four groups. Correlations among the extent of hepatic involvement, extent of portal vein invasion, and prevalence of hepatitis B surface antigen (HBsAg) and age distribution were examined. The extent of hepatic involvement of the tumor and that of portal vein invasion were significantly greater in patients with positive HBsAg compared with findings in the negative patients (P less than 0.001). For cases of both positive and negative HBsAg, patients with a more extensive HCC were significantly younger. Results of the multivariate logistic regression analysis showed that hepatitis B antigenemia and younger age were statistically significant and independent positive predictors of extensive HCC. These results strongly suggest that hepatitis B surface antigenemia and age play an important role in the growth mode and the kinetics of HCC in Japanese patients.