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Introduction: Compliance mismatch between the aortic wall and Dacron Grafts is a clinical problem concerning aortic haemodynamics and morphological degeneration. The aortic stiffness introduced by grafts can lead to an increased left ventricular (LV) afterload. This study quantifies the impact of compliance mismatch by virtually testing different Type-B aortic dissection (TBAD) surgical grafting strategies in patient-specific, compliant computational fluid dynamics (CFD) simulations. Materials and Methods: A post-operative case of TBAD was segmented from computed tomography angiography data. Three virtual surgeries were generated using different grafts; two additional cases with compliant grafts were assessed. Compliant CFD simulations were performed using a patient-specific inlet flow rate and three-element Windkessel outlet boundary conditions informed by 2D-Flow MRI data. The wall compliance was calibrated using Cine-MRI images. Pressure, wall shear stress (WSS) indices and energy loss (EL) were computed. Results: Increased aortic stiffness and longer grafts increased aortic pressure and EL. Implementing a compliant graft matching the aortic compliance of the patient reduced the pulse pressure by 11% and EL by 4%. The endothelial cell activation potential (ECAP) differed the most within the aneurysm, where the maximum percentage difference between the reference case and the mid (MDA) and complete (CDA) descending aorta replacements increased by 16% and 20%, respectively. Conclusion: This study suggests that by minimising graft length and matching its compliance to the native aorta whilst aligning with surgical requirements, the risk of LV hypertrophy may be reduced. This provides evidence that compliance-matching grafts may enhance patient outcomes. [ABSTRACT FROM AUTHOR]

A novel photonic crystal fiber (PCF) design is proposed and analyzed with highly negative dispersion for THz applications. The reported PCF has TOPAS background material due to its low material loss in THz regime. Further, dual porous cores are constructed and selectively infiltrated with liquid crystal (LC) material to control the dispersion characteristics of the reported PCF. The basic operation of the suggested dual core LCPCF (DC-LCPCF) depends on the optical coupling between the supported modes of the two porous core regions in the THz regime to achieve high negative dispersion for the two fundamental polarizations: transverse electric (TE) and transverse magnetic (TM). The coupling can be switched between the TE and TM modes by applying an external electric field on the LC material via two metallic electrodes. The full vectorial finite element method (FVFEM) is utilized to study the dispersion characteristics of the DC-LCPCF structure. The obtained results reveal that the TE and TM modes have large negative chromatic dispersions of − 44.57 ps/THz/cm and − 30.59 ps/THz/cm at frequencies of 0.386 THz and 0.4027 THz, respectively. So, it will be a solution for further innovation of fiber devices in the THz regime. [ABSTRACT FROM AUTHOR]

Purpose: The main aim of the current trial was to explore our hypothesis that cooling head wraps lower the core temperature more effectively than ice packs on the head during forced-air warming after pediatric cardiac surgeries. Methods: This study was a single-center Randomized Controlled Trial. Participants were children with a weight ≤ 10 kg and hyperthermia during forced-air warming after cardiac surgeries. When the core temperature reached 37.5 °C, ice packs on the head (group C) or a cooling head wrap (group H) were used as cooling devices to decrease the core temperature. The primary outcome was the core temperature. The secondary outcomes were the foot surface temperature and heart rate. We measured all outcomes every 30 min for 240 min after the patient developed hyperthermia. We conducted two-way ANOVA as a pre-planned analysis and also the Bonferroni test as a post hoc analysis. Results: Twenty patients were randomly assigned to groups C and H. The series of core temperatures in group H were significantly lower than those in group C (p < 0.0001), and post hoc analysis showed that there was no significant difference in core temperatures at T0 between the two groups and statistically significant differences in all core temperatures at T30-240 between the two groups. There was no difference between the two groups' surface temperatures and heart rates. Conclusions: Compared to ice packs on the head, head cooling wraps more effectively suppress core temperature elevation during forced-air warming after pediatric cardiac surgery. [ABSTRACT FROM AUTHOR]

The phase equilibria of the Ce-Co-Zr ternary system at 873 and 1073 K were determined for the first time by using equilibrated alloys in combination with scanning electron microscopy with energy dispersive spectroscopy and x-ray diffraction. No stable ternary intermetallic compounds were detected in the Ce-Co-Zr ternary system. Due to the partial substitution of Ce by Zr, the metastable binary intermetallic compound CeCo7 with a solubility of 3.3 at.% Zr is stabilized at 873 K. The experimental results demonstrate that the maximum solubilities of Zr in the intermetallic compounds Ce2Co17, CeCo5, Ce5Co19, Ce2Co7, CeCo3, and CeCo2 at 873 K are 4.3, 2.6, 2.4, 9.0, 17.9, 3.5 at.%, respectively, while the maximum solubilities of Ce in the intermetallic compounds Co23Zr6, Co2Zr, and CoZr2 are 6.7, 1.7, and 2.3 at.%. Meanwhile, the maximum solubilities of Zr in Ce2Co17, CeCo5, Ce5Co19, Ce2Co7, CeCo3 and CeCo2 at 1073 K were measured to be 4.0, 7.5, 1.9, 6.8, 17.1, and 9.1 at.%, respectively, while the maximum solubilities of Ce in the intermetallic compounds Co23Zr6 and Co2Zr were determined to be 7.0 and 4.5 at.%, respectively. Finally, the isothermal sections of the Ce-Co-Zr ternary system at 873 and 1073 K were established in this work. [ABSTRACT FROM AUTHOR]

A facile and sensitive approach is introduced to precisely determine trace amounts of prostate specific antigen (PSA) by gold nanostructures deposited on fluorine-doped tin oxide (FTO) electrodes. The gold electrode fabrication is carried out by integration of two techniques of vacuum-deposition and electrochemical growth. The electrode was successfully used as a label-free immunosensor for PSA determination in human serum samples. The dependency of the biosensor performance on various fabrication parameters have been investigated and the optimized fabrication rout has been specified. This label-free immunosensor presents a noticeable performance with a large range of linearity from 0.05 to 30 ng/mL, a low detection limit of 5.7 pg/mL, and a long-term stability of 4 weeks. The obtained results for PSA determination in real samples show a good agreement with ELISA results with less than 10% deviation. [ABSTRACT FROM AUTHOR]

A new series of cobalt/zinc-grafted mesoporous silica nanoparticles (CZ-MSN) catalysts were synthesized and characterized using FTIR, SEM, TEM, XRD and nitrogen adsorption-desorption. The molar ratio of Si/Zn was 10 and the amounts of cobalt atom were 1, 3, 5 and 7 wt% (denoted as CZM-X). The nitrogen adsorption/desorption results showed that the surface area increased from 322 in CZM-7 to 408 m2g−1 in CZM-1. The catalytic activity was investigated for the oxidation reaction by cyclohexanone oxime synthesis from cyclohexanimine using ozone gas flow under UV light at room temperature for 20 min. The results showed that the oxidation of cyclohexanimine to cyclohexanone oxime was 98% over CZM-1 and its selectivity was 97%. The catalytic activity decreased with increasing the cobalt atoms as the order of CZM-1 > CZM-3 > CZM-5 > CZM-7 > Zn-MSN > MSN. The significant advantages of using CZM-1 including high conversion and selectivity, low reaction temperature, and short reaction time. This study introduces a new pathway for oxime synthesis with excellent performance. [ABSTRACT FROM AUTHOR]

Silica sol-gel matrices and its organically modified analogues that contain aqueous electrolytes, ionic liquids, or other ionic conductors constitute stand-alone solid-state electrochemical cells when hosting electrodes or serve as modifying films on working electrodes in conventional cells. These materials facilitate a wide variety of analytical applications and are employed in various designs of power sources. In this review, analytical applications are the focus. Solid-state cells that serve as gas sensors, including in chromatographic detectors of gas-phase analytes, are described. Sol-gel films that modify working electrodes to perform functions such as hosting electrochemical catalysts and acting as size-exclusion moieties that protect the electrode from passivation by adsorption of macromolecules are discussed with emphasis on pore size, structure, and orientation. Silica sol-gel chemistry has been studied extensively; thus, factors that control its general properties as frameworks for solid-state cells and for thin films on the working electrode are well characterized. Here, recent advances such as the use of dendrimers and of nanoscale beads in conjunction with electrochemically assisted deposition of silica to template pore size and distribution are emphasized. Related topics include replacing aqueous solutions as the internal electrolyte with room-temperature ionic liquids, using the sol-gel as an anchor for functional groups and modifying electrodes with silica-based composites. [ABSTRACT FROM AUTHOR]

A new approach has been developed to improve sensing performances of electrochemically grown Au nanostructures (AuNSs) based on the pre-seeding of the electrode. The pre-seeding modification is simply carried out by vacuum thermal deposition of 5 nm thin film of Au on the substrate followed by thermal annealing at 500 °C. The electrochemical growth of AuNSs on the pre-seeded substrates leads to impressive electrochemical responses of the electrode owing to the seeding modification. The dependence of the morphology and the electrochemical properties of the AuNSs on various deposition potentials and times have been investigated. For the positive potentials, the pre-seeding leads to the growth of porous and hole-possess networks of AuNSs on the surface. For the negative potentials, AuNSs with carved stone ball shapes are produced. The superior electrode was achieved from AuNSs developed at 0.1 V for 900 s with pre-seeding modification. The sensing properties of the superior electrode toward glucose detection show a high sensitivity of 184.9 µA mM−1 cm−2, with a remarkable detection limit of 0.32 µM and a wide range of linearity. The excellent selectivity and reproducibility of the sensors propose the current approach as a large-scale production route for non-enzymatic glucose detection. [ABSTRACT FROM AUTHOR]

Purpose: White adipose tissue (WAT) browning plays a crucial role in energy metabolism. However, it remains unclear whether WAT browning is involved in the adipose reduction following sleeve gastrectomy (SG). Adiponectin is upregulated after Roux-en-Y gastric bypass surgery. The role of adiponectin in SG was further investigated in the current study. Materials and Methods: Diabetic Sprague Dawley rats were randomly divided into control, sham + libitum, sham + food restriction, and sleeve groups. Browning markers, including uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor (PPAR) γ, and PPARγ coactivator-1 alpha (PGC-1α), were examined 4 weeks after the operation. Results: UCP1, PPARγ, and PGC-1α expression were significantly higher in the sleeve group compared to the other study groups. The adipose tissue of the sleeve group exhibited tissue weight loss and additional morphological browning features. In addition, adiponectin expression in the sleeve group was significantly increased. Adiponectin upregulated the expression of the browning genes and sirtuin 1 (SIRT1) in 3T3-L1 adipocytes. SIRT1 could increase the WAT browning levels, revealing that adiponectin induced the browning process via the upregulation of SIRT1. Furthermore, SIRT1 represented a positive regulatory feedback loop for adiponectin. SIRT1 activated adenosine monophosphate-activated protein kinase (AMPK), which can mediate WAT browning. Inhibition of the AMPK signaling pathway by dorsomorphin decreased UCP1, PPARγ, and PGC-1α expression. However, additional studies are needed to understand the relationship between adiponectin and glucose homeostasis. Conclusions: Sleeve gastrectomy increased adiponectin levels, which in turn upregulated SIRT1. Thus, SIRT1 may function as an endocrine signal to mediate WAT browning. [ABSTRACT FROM AUTHOR]

In this study, the distribution patterns of P2X1 to P2X7 receptors in the anterior pituitary cells of rat were studied with single-, double-, and triple-labeling immunofluorescence, combined method of immunofluorescence and in situ hybridization, and Western blot. The results showed that the expression level of the P2X4 receptor protein was highest, followed by P2X5, P2X3, P2X2, P2X6, and P2X7 receptor proteins, but no P2X1 receptor protein was detected. Strong P2X4 receptor-immunoreactivity was detected in almost all the anterior pituitary cells. Different combinations of P2X receptors were detected in each individual cell type of the rat anterior pituitary. Gonadotrophs express P2X4, P2X5, and P2X6 receptors. Corticotrophs express P2X3 and P2X4 receptors. Folliculo-stellate cells express P2X2 and P2X4 receptors, and somatotrophs, lactotrophs, and thyrotrophs express only P2X4 receptors. The macrophages with Iba-1-ir expressed P2X7 receptors. The possible functions of these P2X receptors in each individual cell type of the rat anterior pituitary are discussed. [ABSTRACT FROM AUTHOR]

Lentil is one of the most important food legume species, however its genetic and genomic resources remained largely uncharacterized and unexploited. In the past few years, a number of genetic maps have been constructed and marker resources have been developed in lentil. These resources could be exploited for understanding the extent and distribution of genetic variation in genus Lens and also for developing saturated and consensus genetic maps suitable for quantitative trait loci (QTL) mapping and marker-assisted selection. The present study aims to enrich polymerase chain reaction-based linkage map of F10 recombinant inbred lines (RILs) population of 94 individuals derived from cross WA8649090 × Precoz and identification of QTLs linked to early plant vigour traits. Of the 268 polymorphic markers (93 simple sequence repeats (SSR), three inter-simple sequence repeats (ISSRs) and 172 random amplified polymorphic DNA (RAPDs)), 265 (90 SSRs, three ISSRs and 172 RAPDs) were mapped on seven linkage groups, varying in length between 25.6 and 210.3 cM, coverage of 809.4 cM with an average marker spacing of 3.05 cM. The study also reported assigning of 24 new cross-genera SSRs of Trifolium pratense on the present linkage map. The RILs along with the parents were screened for shoot length, root length, seedling length, dry weight, number of leaves and number of branches based on two replications under polyhouse conditions. A QTL-hotspot consisting of six QTLs for shoot length (cm), root length (cm) and seedling length (cm) was observed between a map distances of 56.61 and 86.81 cM on LG1. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate whether layer-specific regional peak-systolic longitudinal strain (LS) measurement on transthoracic echocardiogram (TTE) with exercise stress can be useful for the detection of functionally significant coronary artery disease as confirmed by invasive fractional flow reserve (FFR) in stable patients. This is a prospective analysis of 88 coronary arteries in 30 stable patients undergoing invasive FFR measurement and ergometer exercise stress TTE. Regional LS in the mid, endocardial and epicardial layers was calculated at rest, peak stress and early and late recovery phases after the exercise stress test. The endocardial-to-epicardial LS ratio was calculated as an indicator of endocardial-layer dependency of the left ventricular myocardium. Ischemic FFR defined as FFR ≤ 0.80 was observed in 33 of 88 coronary arteries. The mid-, endocardial- and epicardial-layer LS at early recovery (− 15.4 ± 5.2 vs. − 13.0 ± 4.4%, P = 0.040; − 15.7 ± 5.1 vs. − 13.2 ± 4.5%, P = 0.029; − 14.6 ± 5.1 vs. − 12.4 ± 4.0%, P = 0.038, respectively) and the percent change in the endocardial-to-epicardial LS ratio from baseline to peak stress, early recovery, and late recovery phases (1.5 ± 11.2% vs. 6.6 ± 10.5%, P = 0.009; 2.8 ± 8.9% vs. 7.1 ± 12.6%, P = 0.002; 5.2 ± 8.8% vs. 8.5 ± 13.7%, P = 0.026; respectively) were significantly more impaired in the ischemic territories (FFR ≤ 0.80) compared with the non-ischemic territories (FFR > 0.80). According to the receiver operating characteristic curve analysis, a combination of endocardial LS and percent change in the endocardial-to-epicardial LS ratio at early recovery phase plus visual evaluation of LV wall motion had incremental diagnostic value for the detection of the ischemic territory compared with visual evaluation alone (area under the curve = 0.752 and 0.618, P = 0.006). The results of this study suggested that assessing layer-specific LS and the endocardial-to-epicardial LS ratio after exercise stress on speckle-tracking TTE may have potential for objective and quantitative evaluation in the assessment of myocardial ischemia. Further studies in a larger population are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Introduction and purpose: Estimation of the contractility of the left ventricle during exercise is an important part of the rehabilitation protocol. It is known that cardiac contractility increases with an increase in heart rate. This phenomenon is called the force-frequency relation (FFR). Using wave intensity, we aimed to evaluate FFR noninvasively during graded exercise.Methods: We enrolled 83 healthy subjects. Using ultrasonic diagnostic equipment, we measured wave intensity (WD), which was defined in terms of blood velocity and arterial diameter, in the carotid artery and heart rate (HR) before and during bicycle ergometer exercise. FFRs were constructed by plotting the maximum value of WD (WD1) against HR. We analyzed the variation among FFR responses of individual subjects.Results: WD1 increased linearly with an increase in HR during exercise. The average slope of the FFR was 1.0 ± 0.5 m/s3 bpm. The slope of FFR decreased with an increase in body mass index (BMI). The slopes of FFRs were steeper in men than women, although there were no differences in BMI between men and women.Conclusions: The FFR was obtained noninvasively by carotid arterial wave intensity (WD1) and graded exercise. The slope of the FFR decreased with an increase in BMI, and was steeper in men than women. [ABSTRACT FROM AUTHOR]

Vector flow mapping (VFM) is a novel echocardiographic technology that shows blood flow vectors and vortexes, enabled the hydrokinetic evaluation of hemodynamics within the left ventricle. VFM provides several unique parameters: circulation, vorticity, vortex area, and energy loss. The present study aims to reveal a relationship between VFM parameters and cardiac function. Five healthy Beagle dogs were anesthetized and administered with dobutamine (0, 2, 4, 8, 12 µg/kg/min). Pressure-volume diagrams were acquired to assess cardiac function using pressure-volume conductance catheter. Systolic maximum circulation, vorticity, vortex area, and energy loss were measured using VFM. The systolic maximum circulation, systolic vorticity, systolic vortex area, and systolic energy loss were increased by dobutamine administration. There was a strongly significant correlation between the systolic maximum circulation and ejection fraction (r = 0.76), maximal positive left ventricular (LV) pressure derivatives (dP/dt max) (r = 0.80), and end-systolic LV elastance (r = 0.73). Systolic vorticity and systolic vortex area were strongly correlated with ejection fraction (r = 0.76, 0.68) and dP/dt max (r = 0.76, 0.69), and end-systolic LV elastance (r = 0.62, 0.74), respectively. Systolic energy loss was strongly correlated with dP/dt max (r = 0.78), systolic maximum circulation (r = 0.81), and systolic vorticity (r = 0.82). The present study revealed that systolic VFM parameters are associated with the LV contractility. Furthermore, systolic energy loss was susceptible to the systolic vortex parameters such as systolic vorticity and systolic maximum circulation. Systolic VFM parameters are new hydrokinetic indices reflecting LV contractility. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to determine the capacity of Si to mitigate Al toxicity in upland rice plants ( Oryza sativa L.) by evaluating plant growth and the Si and Al uptake kinetics. Methods: Plants were grown for 40 days, after which the Si and Al uptake kinetics (Cmin, Km and Imax) were analyzed. Then, the shoots and roots were separated, and the dry matter, root morphology and Si and Al concentration and accumulation in the plant were evaluated. Results: Aluminum decreased plant growth and the Si uptake capacity by decreasing the root growth and Si transport system efficiency in the upland rice roots (> Km and > Cmin). Silicon mitigated Al toxicity in the upland rice plants by decreasing Al transport to the plant shoots, although it did not reduce the Al uptake rate (Imax). Si treatment increased the growth of upland rice plant shoots grown in the presence of Al without influencing the root growth. The alleviation of Al toxicity by Si is more evident in the susceptible upland rice cultivar Maravilha. Conclusions: Silicon mitigated Al toxicity in the upland rice plants by decreasing Al transport to the plant shoots but did not reduce the Al uptake rate by roots. [ABSTRACT FROM AUTHOR]

Ivabradine inhibits hyperpolarization-activated cyclic nucleotide-gated channels in the sinus node, thereby reducing heart rate, and heart rate reduction improves regional myocardial blood flow and contractile function in ischemic myocardium. Accordingly, ivabradine reduces anginal symptoms in patients with stable coronary artery disease but does not improve their clinical outcome. Heart rate reduction with ivabradine in patients with symptomatic heart failure reduces symptoms, attenuates remodeling, and improves clinical outcome. In pigs and mice, ivabradine reduces infarct size from myocardial ischemia/reperfusion, even when heart rate reduction is abrogated by atrial pacing. Improved viability is also observed in isolated ventricular cardiomyocytes subjected to simulated ischemia/reperfusion. These beneficial effects are attributed to reduced reactive oxygen species formation from the mitochondria. There is also evidence for a heart rate-independent benefit from ivabradine in the vasculature of mice and humans, and in left ventricular contractile function of pigs. Finally, in mice, ivabradine also has anti-aging potential. [ABSTRACT FROM AUTHOR]

We previously reported that glucocorticoid receptor β (GRβ) regulates injury-mediated astrocyte activation and contributes to glioma pathogenesis via modulation of β-catenin/T-cell factor/lymphoid enhancer factor (TCF/LEF) transcriptional activity. The aim of this study was to characterize the mechanism behind cross-talk between GRβ and β-catenin/TCF in the progression of glioma. Here, we reported that GRβ knockdown reduced U118 and Shg44 glioma cell proliferation in vitro and in vivo. Mechanistically, we found that GRβ knockdown decreased TCF/LEF transcriptional activity without affecting β-catenin/TCF complex. Both GRα and GRβ directly interact with TCF-4, while only GRβ is required for sustaining TCF/LEF activity under hormone-free condition. GRβ bound to the N-terminus domain of TCF-4 its influence on Wnt signaling required both ligand- and DNA-binding domains (LBD and DBD, respectively). GRβ and TCF-4 interaction is enough to maintain the TCF/LEF activity at a high level in the absence of β-catenin stabilization. Taken together, these results suggest a novel cross-talk between GRβ and TCF-4 which regulates Wnt signaling and the proliferation in gliomas. [ABSTRACT FROM AUTHOR]

In traditional OLAP systems, roll-up and drill-down operations over data cubes exploit fixed hierarchies defined on discrete attributes, which play the roles of dimensions, and operate along them. New emerging application scenarios, such as sensor networks, have stimulated research on OLAP systems, where even continuous attributes are considered as dimensions of analysis, and hierarchies are defined over continuous domains. The goal is to avoid the prior definition of an ad-hoc discretization hierarchy along each OLAP dimension. Following this research trend, in this paper we propose a novel method, founded on a density-based hierarchical clustering algorithm, to support roll-up and drill-down operations over OLAP data cubes with continuous dimensions. The method hierarchically clusters dimension instances by also taking fact-table measures into account. Thus, we enhance the clustering effect with respect to the possible analysis. Experiments on two well-known multidimensional datasets clearly show the advantages of the proposed solution. [ABSTRACT FROM AUTHOR]

Main conclusion: Rapid uniform germination and accumulation of biomass during initial phase of seedling establishment is an essential phenotypic trait considered as early seedling vigour for direct seeded situation in rice irrespective of environment. Enhanced role of carbohydrate, amylase, growth hormones, antioxidant enzymes and ascorbic acid brings changes in vigour and phenotype of seedling. Abstract: Early establishment and demanding life form dominate the surroundings. Crop plant that has better growth overdrives the weed plant and suppresses its growth. Seedling early vigour is the characteristic of seed quality and describes the rapid, uniform germination and the establishment of strong seedlings in any environmental condition. The phenotype of modern rice varieties has been changed into adaptable for transplanted rice with thirst toward water and selection pressure for semi-dwarf architecture resulting in reduced early vigour. Decreasing freshwater availability and rising labour cost drives the search for a suitable alternative management system to enhance grain yield productivity for the burgeoning world population. In view of these issues, much attention has been focused on dry direct-seeded rice, because it demands low input. A rice cultivar with a strong seedling vigour trait is desirable in case of direct seeding. However, seedling vigour has not been selected in crop improvement programmes in conventional breeding due to its complex nature and quantitative inheritance. Molecular markers have been proven effective in increasing selection efficiency, particularly for quantitative traits that are simply inherited. Marker-assisted selection approach has facilitated efficient and precise transfer of genes/QTL(s) into many crop species and suggests a speedy and efficient technique over conventional breeding and selection methods. In this review, we present the findings and investigations in the field of seedling vigour in rice that includes the nature of inheritance of physio-morphological and biochemical traits and QTLs to assist plant breeders who work for direct-seeded rice. [ABSTRACT FROM AUTHOR]

Background and purpose: Estimation of the contractility of the left ventricle during exercise is important in drawing up a protocol of cardiac rehabilitation. It has been demonstrated that color Doppler- and echo tracking-derived carotid arterial wave intensity is a sensitive index of global left ventricular (LV) contractility. We assessed the feasibility of measuring carotid arterial wave intensity and determining force−frequency (contractility−heart rate) relations (FFRs) during exercise totally noninvasively. Methods: We measured carotid arterial wave intensity with a combined color Doppler and echo tracking system in 25 healthy young male volunteers (age 20.8 ± 1.2 years) at rest and during exercise. FFRs were constructed by plotting the maximum value of wave intensity (WD) against heart rate (HR). Results: We first confirmed that HR increased linearly with an increase in work load in each subject ( r = 0.95 ± 0.04). WD increased linearly with an increase in HR. The goodness-of-fit of the regression line of WD on HR in each subject was very high ( r = 0.48−0.94, p < 0.0001, respectively). The slope of the WD-HR relation ranged 0.30−2.20 [m/s (beat/min)]. Conclusions: Global LV FFRs can be generated in healthy young volunteers with an entirely noninvasive combination of exercise and wave intensity. These data should show the potential usefulness of the FFR in the context of cardiac rehabilitation. [ABSTRACT FROM AUTHOR]

Here, we present a simple method for controlling the density of Au nanoparticles (Au NPs) on a modified silicon substrate, by destabilizing the colloidal Au NPs with 3-mercaptopropyltrimethoxylsilane (3-MPTMS) for microelectromechanical-system-based applications to reduce tribological issues. A silicon surface was pretreated with a 3-MPTMS solution, immediately after which thiolated Au NPs were added to it, resulting in their uniform deposition on the silicon substrate. Without any material property change of the colloidal Au NPs, we observed the formation of large clusters Au NPs on the modified silicon surface. Analysis by scanning electron microscopy with energy dispersive X-ray spectroscopy indicated that the addition of 3-MPTMS resulted in an alternation of the chemical characteristics of the solution. Atomic force microscopy imaging supported the notion that silicon surface modification is the most important factor on tribological properties of materials along with ligand-modified Au NPs. The density of Au NPs on a silicon surface was significantly dependent on several factors, including the concentration of colloidal Au NPs, deposition time, and concentration of 3-MPTMS solution, while temperature range which was used throughout experiment was determined to have no significant effect. A relatively high density of Au NPs forms on the silicon surface as the concentrations of Au NPs and 3-MPTMS are increased. In addition, the maximum deposition of Au NPs on silicon wafer was observed at 3 h, while the effects of temperature variation were minimal. [ABSTRACT FROM AUTHOR]

The present study tested the hypothesis that epicardial fat may be associated with augmented central aortic pressure and impaired left ventricular (LV) function. We studied 134 consecutive patients undergoing left-sided cardiac catheterization for coronary artery disease (CAD) and examined the relation of epicardial fat volume measured by multi-detector computed tomography to ascending aortic pressure and LV ejection fraction determined by cardiac catheterization as well as indices of LV diastolic function assessed by Doppler echocardiography [early diastolic mitral annular velocity (e′) and a ratio of early diastolic mitral inflow to annular velocities (E/e′)]. Epicardial fat volume indexed to body surface area correlated positively with age (r = 0.24, P < 0.01), body mass index (r = 0.38, P < 0.001), systolic aortic pressure (r = 0.21, P < 0.05), aortic pulse pressure (r = 0.23, P < 0.01), LV ejection fraction (r = 0.22, P < 0.05) and E/e′ (r = 0.24, P < 0.05) and did negatively with e′ (r = −0.31, P < 0.05). In multivariate linear regression including potential confounders, increased epicardial fat volume index correlated with aortic systolic and pulse pressure and LV diastolic function indices, but not LV ejection fraction. In conclusion, we found that epicardial fat was associated with augmented central aortic pressure and LV diastolic dysfunction in patients with known or suspected CAD. [ABSTRACT FROM AUTHOR]

Purpose: High fructose consumption provokes metabolic perturbations that result in chronic low-grade inflammation and insulin resistance. Glucocorticoids, potent anti-inflammatory hormones, have important role in pathogenesis of diet-induced metabolic disturbances. The aim of this study was to examine the link between glucocorticoid metabolism and inflammation in the liver of fructose-fed rats. Methods: Fructose-fed male Wistar rats consumed 60 % fructose solution for 9 weeks. Glucocorticoid prereceptor metabolism and signaling were analyzed by measuring the level of 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and hexose-6-phosphate dehydrogenase expression, as well as via determination of intracellular corticosterone concentration, glucocorticoid receptor subcellular distribution and expression of its target gene, phosphoenolpyruvate carboxykinase. Nuclear factor kappa B (NFκB), tumor necrosis factor alpha (TNFα) and the level of inhibitory phosphorylation of insulin receptor substrate-1 (IRS-1) on Ser were analyzed as markers of hepatic inflammation. The protein and/or mRNA levels of all examined molecules were assessed by Western blot and/or qPCR. Results: Fructose-rich diet led to an enhancement of 11βHSD1 protein level in the liver, without affecting intracellular level of corticosterone and downstream glucocorticoid signaling. On the other hand, proinflammatory state was achieved through NFκB activation and increased TNFα expression, while elevated level of inhibitory phosphorylation of IRS-1 was observed as an early hallmark of insulin resistance. Conclusion: High-fructose diet does not influence hepatic glucocorticoid signaling downstream of the receptor, permitting development of NFκB-driven inflammation. The alteration in 11βHSD1 expression is most likely the consequence of enhanced inflammation, finally leading to disruption of insulin signaling in the rat liver. [ABSTRACT FROM AUTHOR]

Purpose: High fructose consumption provokes metabolic perturbations that result in chronic low-grade inflammation and insulin resistance. Glucocorticoids, potent anti-inflammatory hormones, have important role in pathogenesis of diet-induced metabolic disturbances. The aim of this study was to examine the link between glucocorticoid metabolism and inflammation in the liver of fructose-fed rats. Methods: Fructose-fed male Wistar rats consumed 60 % fructose solution for 9 weeks. Glucocorticoid prereceptor metabolism and signaling were analyzed by measuring the level of 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and hexose-6-phosphate dehydrogenase expression, as well as via determination of intracellular corticosterone concentration, glucocorticoid receptor subcellular distribution and expression of its target gene, phosphoenolpyruvate carboxykinase. Nuclear factor kappa B (NFκB), tumor necrosis factor alpha (TNFα) and the level of inhibitory phosphorylation of insulin receptor substrate-1 (IRS-1) on Ser were analyzed as markers of hepatic inflammation. The protein and/or mRNA levels of all examined molecules were assessed by Western blot and/or qPCR. Results: Fructose-rich diet led to an enhancement of 11βHSD1 protein level in the liver, without affecting intracellular level of corticosterone and downstream glucocorticoid signaling. On the other hand, proinflammatory state was achieved through NFκB activation and increased TNFα expression, while elevated level of inhibitory phosphorylation of IRS-1 was observed as an early hallmark of insulin resistance. Conclusion: High-fructose diet does not influence hepatic glucocorticoid signaling downstream of the receptor, permitting development of NFκB-driven inflammation. The alteration in 11βHSD1 expression is most likely the consequence of enhanced inflammation, finally leading to disruption of insulin signaling in the rat liver. [ABSTRACT FROM AUTHOR]

Platelets get easily activated when in contact with a surface. Therefore in the design of microfluidic blood analysis devices surface activation effects have to be taken into account. So far, platelet-surface interactions have been quantified by morphology changes, membrane marker expression or secretion marker release. In this paper we present a simple and effective method that allows quantification of platelet-surface interactions in real-time. A calcium indicator was used to visualize intracellular calcium variations during platelet adhesion. We designated cells that showed a significant increase in cytosolic calcium as responding cells. The fraction of responding cells upon binding was analyzed for different types of surfaces. Thereafter, the immobilized platelets were chemically stimulated and the fraction of responding cells was analyzed. Furthermore, the time between the binding or chemical stimulation and the increased cytosolic calcium level (i.e. the response delay time) was measured. We used surface coatings relevant for platelet-function testing including Poly-L-lysine (PLL), anti-GPIb and collagen as well as control coatings such as Bovine Serum Albumin (BSA) and mouse immunoglobulin (IgG). We found that a lower percentage of responding cells upon binding, results in a higher percentage of responding cells upon chemical stimulation after binding. The measured delay time between platelet binding under sedimentation and calcium response was the lowest on a PLL-coated surface, followed by an anti-GPIb and collagen-coated surface and IgG-coated surface. The presented method provides real-time information of platelet-surface interactions on a single cell as well as on a cell ensemble level. For future in-vitro diagnostic tests, this real-time single-cell function analysis can reveal heterogeneities in the biological processes of a cell population. [ABSTRACT FROM AUTHOR]

There is widespread involvement of purinergic signalling in endocrine biology. Pituitary cells express P1, P2X and P2Y receptor subtypes to mediate hormone release. Adenosine 5′-triphosphate (ATP) regulates insulin release in the pancreas and is involved in the secretion of thyroid hormones. ATP plays a major role in the synthesis, storage and release of catecholamines from the adrenal gland. In the ovary purinoceptors mediate gonadotrophin-induced progesterone secretion, while in the testes, both Sertoli and Leydig cells express purinoceptors that mediate secretion of oestradiol and testosterone, respectively. ATP released as a cotransmitter with noradrenaline is involved in activities of the pineal gland and in the neuroendocrine control of the thymus. In the hypothalamus, ATP and adenosine stimulate or modulate the release of luteinising hormone-releasing hormone, as well as arginine-vasopressin and oxytocin. Functionally active P2X and P2Y receptors have been identified on human placental syncytiotrophoblast cells and on neuroendocrine cells in the lung, skin, prostate and intestine. Adipocytes have been recognised recently to have endocrine function involving purinoceptors. [ABSTRACT FROM AUTHOR]

We examined the contribution of arterial wave reflection to early abnormalities in left ventricular relaxation, whether this association was modified by gender or hypertension and the role of reflected wave timing and amplitude. We studied a cohort of normotensive and untreated essential hypertensive Taiwanese participants (675 men, 601 women, mean age 52 years). Doppler flow and applanation tonometry were performed to assess carotid-femoral pulse wave velocity (PWV) and augmentation index (AI). Diastolic parameters including the ratio between the peak velocity of early and late diastolic mitral inflow (E/A), E-deceleration time and left atrial (LA) diameter were measured by echocardiography. In multivariate models predicting E/A, women were more likely to have lower E/A than men (β=−0.08, P<0.001). AI was significantly associated with lower E/A in both men (β=−0.09, P=0.005) and women (β=−0.12, P<0.001) independent of PWV. Inclusion of AI in the overall model reduced the gender difference in E/A by 61% and rendered it nonsignificant. There was a significant interaction between AI and hypertension (P=0.02). The inverse association between AI and E/A was significant only in normotensive men and women, and only for the amplitude but not timing of the reflected wave. In conclusion, the contribution of wave reflection to left ventricular diastolic dysfunction was independent of arterial stiffness, more pronounced in normotensive individuals and explained a significant portion of the gender difference in diastolic function. [ABSTRACT FROM AUTHOR]

Background: Aluminium (Al) toxicity and drought stress are two major constraints for crop production in the world, particularly in the tropics. The variation in rainfall distribution and longer dry spells in much of the tropics during the main growing period of crops are becoming increasingly important yield-limiting factors with the global climate change. As a result, crop genotypes that are tolerant of both drought and Al toxicity need to be developed. Scope: The present review mainly focuses on the interaction of Al and drought on root development, crop growth and yield on acid soils. It summarizes evidence from our own studies and other published/related work, and provides novel insights into the breeding for the adaptation to these combined abiotic stresses. The primary symptom of Al phytotoxicity is the inhibition of root growth. The impeded root system will restrict the roots for exploring the acid subsoil to absorb water and nutrients which is particularly important under condition of low soil moisture in the surface soil under drought. Whereas drought primarily affects shoot growth, effects of phytotoxic Al on shoot growth are mostly secondary effects that are induced by Al affecting root growth and function, while under drought stress root growth may even be promoted. Much progress has recently been made in the understanding of the physiology and molecular biology of the interaction between Al toxicity and drought stress in common bean ( Phaseolus vulgaris L.) in hydroponics and in an Al-toxic soil. Conclusions: Crops growing on acid soils yield less than their potential because of the poorly developed root system that limits nutrient and water uptake. Breeding for drought resistance must be combined with Al resistance, to assure that drought resistance is expressed adequately in crops grown on soils with acid Al-toxic subsoils. [ABSTRACT FROM AUTHOR]

Submergence-induced suppression of seedling vigor is a serious constraint particularly in the direct seeding rice cultivation system. To identify quantitative trait loci (QTLs) associated with seedling vigor in rice under submergence, a mapping population of 98 Backcross Inbred Lines derived from a cross of Nipponbare/Kasalath//Nipponbare was used. Phenotypic evaluation of seedling vigor under submergence was based on shoot length (SHL), root length (RTL) and shoot fresh weight (SFW) using a test tube bioassay method. Thirty-two putative QTLs were detected among which 7 were for SHL, 11 for RTL and 14 for SFW. Phenotypic evaluation was also made of the parental lines and a set of 54 chromosome segment substitution lines in which Nipponbare segments were substituted for by their homologous Kasalath segments covering the entire rice genome. Two QTLs with more than 10 % contribution to the total phenotypic variance were verified for SHL, and at least one for RTL and six for SFW on chromosomes 1, 3, 4, 6 and 7 at the 1 % significance level. Among these, all but two showed reductions in one, two or all three traits. Our present and previous results suggest that the Nipponbare genome has a potential to improve seedling vigor under submergence and that japonica germplasms can be used to breed for this important trait in indica rice. [ABSTRACT FROM AUTHOR]

The ability to search, process, extract, evaluate and integrate information for learning purposes has clearly become the basic skills of the twenty first century. Although this process is often taken as a cognitive process, research has shown a strong connection between emotion and cognition. Recent research has suggested that positive emotions can influence the way cognitive material is organized and processed. This study examined the relationship between students' emotional states prior to task engagement to their problem-solving patterns. Results revealed that students with positive emotions, compared to the negative and mixed emotion groups, were characterized as regulatory problem-solvers who were more engaged in self-regulatory activities. Students with negative emotions were characterized by less variety of search activities as well as little or no regulatory activities. [ABSTRACT FROM AUTHOR]

Thermal-driven attachment of gold nanoparticles (AuNPs), of which size was less than 50 nm, onto the surfaces of indium tin oxide (ITO) is reported as a new phenomenon. This was permitted by preparing AuNPs via the reduction of hydrogen tetrachloroaurate (HAuCl) with ascorbic acid (AA). While the AuNPs prepared via the AA reduction sparsely attached on the surface of ITO even at room temperature, a heat-up treatment at ca. 75 °C caused denser attachment of AuNPs on ITO surfaces. The attached density and the homogeneity after the thermal treatment were better than those of AuNP/ITO prepared using 3-aminopropyl-trimethoxysilane linker molecules. The denser attachment was observed similarly both by the immersion of ITO samples after the preparations of AuNPs by AA and by the in situ preparation of AuNPs with AA together with ITO samples. Thus, it is considered that the thermal-driven attachment of AuNPs would occur after the formation of AuNPs in the aqueous solutions, not via the growth of AuNPs on ITO surfaces. The preparation of AuNPs with AA would be a key for the thermal-driven attachment because the same attachments were not observed for AuNPs prepared with citrate ions or commercially available tannic acid-capped AuNPs. [ABSTRACT FROM AUTHOR]

Wide adoption of direct-seeded rice practices has been hindered by poorly leveled fields, heavy rainfall and poor drainage, which cause accumulation of water in the fields shortly after sowing, leading to poor crop establishment. This is due to the inability of most rice varieties to germinate and reach the water surface under complete submergence. Hence, tolerance of anaerobic conditions during germination is an essential trait for direct-seeded rice cultivation in both rainfed and irrigated ecosystems. A QTL study was conducted to unravel the genetic basis of tolerance of anaerobic conditions during germination using a population derived from a cross between IR42, a susceptible variety, and Ma-Zhan Red, a tolerant landrace from China. Phenotypic data was collected based on the survival rates of the seedlings at 21 days after sowing of dry seeds under 10 cm of water. QTL analysis of the mapping population consisting of 175 F families genotyped with 118 SSR markers identified six significant QTLs on chromosomes 2, 5, 6, and 7, and in all cases the tolerant alleles were contributed by Ma-Zhan Red. The largest QTL on chromosome 7, having a LOD score of 14.5 and an R of 31.7 %, was confirmed using a BCF population. The QTLs detected in this study provide promising targets for further genetic characterization and for use in marker-assisted selection to rapidly develop varieties with improved tolerance to anaerobic condition during germination. Ultimately, this trait can be combined with other abiotic stress tolerance QTLs to provide resilient varieties for direct-seeded systems. [ABSTRACT FROM AUTHOR]

Background: Endotoxemia is a major cause of mortality in large animals and there are several therapeutic regimens for the treatment of endotoxemia. Recent studies have suggested the anti-inflammatory effects of insulin in endotoxemic human and laboratory animal models but to the best of our knowledge there is no report on the possible therapeutic effect of insulin in large animal endotoxemia. Objective: This experiment was conducted to evaluate the anti-inflammatory effects of insulin regular compared with flunixin meglumine on the treatment of endotoxemia in sheep. Methods: Lipopolysaccharide from Escherichia coli was administered intravenously to ewes. Anti-inflammatory effects of flunixin meglumine (at 2.2 mg/kg) and insulin regular (at 1.5 and 3 IU/kg) were evaluated by determination of serum concentrations of acute phase proteins, inflammatory cytokines and oxidative stress biomarkers. Results: Insulin regular at 3 IU/kg controlled the acute phase response following endotoxemia induction. The anti-inflammatory potency of insulin regular at 3 IU/kg was significantly higher than at 1.5 IU/kg and of flunixin meglumine at 2.2 mg/kg ( P < 0.05). Conclusion: Insulin regular induces its anti-inflammatory effects in a dose-dependent manner. Intravenous use of insulin regular can be a potential new therapeutic regimen for endotoxemia in large animal medicine. [ABSTRACT FROM AUTHOR]

Seedling vigor is among the major determinants of stable stand establishment in direct-seeded rice ( Oryza sativa L.) in temperate regions. Quantitative trait loci (QTL) for seedling vigor were identified using 250 recombinant inbred lines (RILs) derived from a cross between two japonica rice cultivars Kakehashi and Dunghan Shali. Seedling heights measured at 14 days after sowing were 20.3 and 29.4 cm for Kakehashi and Dunghan Shali, respectively. For the RILs, the height ranged from 14.1 to 31.7 cm. Four putative QTLs associated with seedling height were detected. qPHS3- 2, the major QTL that was located on the long arm of chromosome 3, accounted for 26.2 % of the phenotypic variance. Using progeny of the near isogenic lines (NILs) produced by the backcross introduction of a chromosome segment carrying this major QTL into an elite cultivar Iwatekko, we fine-mapped qPHS3- 2 to a 81-kb interval between two markers, ID_CAPS_01 and RM16227. Within this mapped region, we identified the gene OsGA20ox1, which is related to gibberellin (GA) biosynthesis. The relative expression levels of GA20ox1 in seedlings of Dunghan Shali and NILs were higher than that of Iwatekko. Concomitantly, the amount of endogenous active GA was higher in Dunghan Shali and the NILs compared to the level detected in Iwatekko. These results indicate that OsGA20ox1 is a strong candidate gene for major QTL controlling seedling vigor in rice. [ABSTRACT FROM AUTHOR]

Glucocorticoid-induced hypertension is a common clinical problem that is poorly understood, thus rendering treatment strategies sub-optimal. This form of hypertension has been commonly thought to be mediated by excess sodium and water reabsorption by the renal mineralocorticoid receptor. However, experimental and clinical data in both humans and animal models suggest important roles for the glucocorticoid receptor as well, in both the pathogenesis and maintenance of this hypertension. The glucocorticoid receptor is widely expressed in a number of organ systems relevant to blood pressure regulation, including the kidney, the brain and the vasculature. In vitro studies in isolated kidney tissues as well as in vascular smooth muscle and vascular endothelial cells have attempted to elucidate the molecular physiology of glucocorticoid-induced hypertension, but have generally been limited by the inability to study signaling pathways in an intact organism. More recently, the power of mouse genetics has been employed to examine the tissue-specific contributions of vascular and extra-vascular tissues to this form of hypertension. Here we review recent developments in our understanding of the pathogenesis of glucocorticoid-induced hypertension. [ABSTRACT FROM AUTHOR]

Root border cells (RBCs), which are generated during plant growth and surround the root cap, and iron plaque (IP), ubiquitously formed on the root surfaces of rice, are known to alleviate aluminum (Al) toxicity. To verify the interactive effects of IP and RBCs on ameliorating Al toxicity, two rice cultivars differing in Al resistance were used to compare Al tolerance between cultivars. Additionally, root elongation, Al uptake and RBCs viability were measured as indicators of the effects of Al. The amounts of DCB-extractable Fe and Al on the root surfaces were much higher in the presence of IP than the absence. IP presence significantly decreased Al-induced inhibition of root elongation and Al contents in roots and root tips. The removal of RBCs from the root tips caused a more severe inhibition of root elongation and a higher Al accumulation in rice roots and root tips. Furthermore, root growth inhibition and Al contents in roots and root tips were significantly lower in roots with a combination of IP and RBCs than in roots with IP or RBCs only. The formation of IP on the root surface maintained higher RBCs viability and depressed mucilage exudation in an Al-tolerant rice cultivar. The results suggest that both IP and RBCs ameliorate Al toxicity, and IP has a greater capacity for Al resistance. The combination of IP and RBCs exhibited a synergistic effect associated with Al resistance. [ABSTRACT FROM AUTHOR]

Background: The best way to reduce endoscopic retrograde cholangiopancreatography (ERCP) complications is not to perform it if it is unnecessary. Both intraoperative and postoperative ERCP rely on use of intraoperative cholangiography as a final diagnostic test for choledocholithiasis (CLD) whenever clinical data are unable to rule out CLD. Intraoperative ERCP could become a therapeutic option when a previous preoperative ERCP fails. We present our experience with intraoperative ERCP. Patients and methods: This is a descriptive and prospective study of a cohort of 82 patients with moderate risk of CLD. They were operated on by laparoscopic cholecystectomy with intraoperative cholangiography (IOC). We performed intraoperative ERCP using the rendezvous technique. Results: Thirty-six out of 82 patients had an abnormal IOC study. Mean age was 58.7 years (standard deviation, SD 16.6, 25-83 years), and 60.6% were females. Ultrasound study showed that 51.4% of patients had a dilated bile duct. Magnetic resonance cholangiography (MRC) was performed on three patients (8.3%). The success rate of intraoperative ERCP was 88.2%. Three out of the 36 patients (8.8%) had ERCP complications [2 mild papillary bleeding (5.8%), 1 acute pancreatitis (2.9%)]. The rate of conversion to open surgery was 5% with a surgical complications rate of 4% [one injured duct and two surgical bleeding which required re-operation (2.5%)]. There were no mortalities. Four patients (11.1%) needed post-surgical ERCP, with a residual CLD rate of 5.6% (two patients) in the postoperative period. Mean surgical time was 181 min (SD 60, 75-345 min). Mean hospital stay was 6.2 days (SD 4.7, 2-24 days). Conclusions: Intraoperative ERCP is an option to prevent performing ERCP unnecessarily on patients with moderate risk of CLD not confirmed using appropriate radiological studies. It can resolve the biliary disease in a single step with a similar success rate to standard ERCP, but with low morbidity, especially of acute pancreatitis. The residual CLD rate is also very low. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor-1 (IGF-1) plays the role in cellular lipid synthesis and cell proliferation. However, the role of IGF-1 on the growth of colon cancer cell line HCT-8 is not clear. In this study, HCT-8 cells were exposed to IGF-1 at 0, 10, 50, or 100 ng/ml in serum-free medium. Fatty acid/lipid synthesis in HCT-8 cells was examined by 2-14C-acetate incorporation. HCT-8 cell growth and proliferation were determined by MTT assay and Trypan blue exclusive viable cell counting. We found that in serum starvation conditions, IGF-1 at 10-100 ng/ml induced dose-dependent down regulation of both the ACCα expression and the phosphorylation in HCT-8 cells, maintaining a balance in ACCα activity and lipid synthesis. IGF-1 reduced p-ATM, p-AMPK, and then p-ACCα protein levels in HCT-8 cells. IGF-1 increased p-Akt levels, but decreased p-ERK1/2 levels, leading to the decrease in ACCα protein and mRNA levels. Similarly, ERK1/2 inhibitor PD98059 reduced ACCα expression. IGF-1 influences neither HCT-8 cell growth nor their p53 protein levels and PARP cleavage. In a word, IGF-1 reduced ACCα phosphorylation via an ATM/AMPK signaling pathway and suppressed ACCα expression through an ERK1/2 transduction, playing a dual role in regulating ACCα activity and lipogenesis. This may render a cell with survival advantages under a serum starvation crisis, representing a novel mitogenic role of IGF-1. [ABSTRACT FROM AUTHOR]

AMP-activated protein kinase (AMPK) is activated under conditions that deplete cellular ATP and elevate AMP levels such as glucose deprivation and hypoxia. The AMPK system is primarily thought of as a regulator of metabolism and cell proliferation. Little is known about the regulation and the effects of AMPK in somatotroph cells. We present results from 'in vitro' studies showing that AMPK activity has a role in regulating somatotroph function in normal rat pituitary and is a promising target for the development of new pharmacological treatments affecting cell proliferation and viability of pituitary adenomatous cells. In parallel, we show 'in vivo' data obtained in the rat suggesting that AMPK is an intracellular transducer that may play a role in mediating the effects of the pharmacological treatment with dexamethasone on somatotrophs. In rat pituitary cell cultures, the AMP analog AICAR induced a rapid and clear-cut activation of AMPK. AICAR decreased GH release and total cellular GH content. An appropriate level of AMPK activation was essential for GH3 adenomatous cells. Remarkably, over-activation by AICAR induced apoptosis of GH3 whereas the AMPK inhibitor compound C was more effective at reducing cell proliferation. The role of endocrine or paracrine factors in regulating AMPK phosphorylation and activity in GH3 cells has been also studied. As to 'in vivo' studies, western blot analysis revealed a significant decrease of phosphorylated AMPK alpha-subunit in pituitary homogenates of DEX-treated rats versus controls, suggesting reduced AMPK activity. In conclusion, our studies showed that AMPK has a role in regulating somatotroph function in normal rat pituitary and proliferation of pituitary adenomatous cells. [ABSTRACT FROM AUTHOR]

This study was performed to investigate the effect of monthly oral administration of 500 μg of calcidiol (25-hydroxyvitamin D(3)) for 4 months on both serum vitamin D levels and sequential changes of parameters of calcium metabolism; 18 normal women aged 24-72 years were investigated. There was a significant increase of serum 25(OH)D after the first administration; thereafter all values persisted significantly higher compared to the basal value (P < 0.001). Mean 1,25(OH)(2)D serum levels peaked at day 3 and then tended to stabilize following day 30. During the first month, all mean values observed following the initial administration were significantly higher than basal values. The first calcidiol dose produced a significant reduction of serum PTH levels (P < 0.001), which then remained constant over time. Concerning serum calcium and phosphorus, we were not able to demonstrate any significant change during the entire observation period. Considering the single values for both serum ionized and total calcium, the values of Ca(2+) exceeded upper limits of normal on only two occasions. Regarding biochemical markers of bone remodeling, mean changes of serum bone isoenzyme of alkaline phosphatase activity showed a significant trend to decrease, starting at day 30. No significant changes of serum CTX values were noted. Overall, 24-h urinary excretion of calcium did not change, seven values exceeding the threshold of 4 mg/kg body weight. Monthly administration of 500 μg of 25-hydroxyvitamin D(3) may be considered an alternative for vitamin D repletion, without any detrimental effect. [ABSTRACT FROM AUTHOR]