bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural and Drug
Diffusion Models of Conventional and Auxetic Drug-Eluting
Stents
Authors: Dolla William Jacob
S. , Fricke Brian
A. , Becker Bryan R.
Published: March 2007

Most balloon angioplasty procedures include the insertion of tiny cylindrical wire mesh structures, called cardiovascular stents, into the artery to prevent the elastic recoil that follows arterial dilatation. The scaffolding characteristics of the stent provide strength to the artery wall. However, vascular injury during stent deployment and∕or recognition of the stent as a foreign material triggers neointimal hyperplasia, causing re-closure, or restenosis, of the artery. A recent advancement to counteract restenosis is to employ drug-eluting stents to locally deliver immunosuppressant and antiproliferative drugs. In this project, Fick’s law of diffusion was used to model drug diffusion from the stent matrix into the adjacent arterial tissue. An analytical procedure was also developed to estimate the circumferential and the flexural stiffnesses of stents. Furthermore, a unique auxetic (negative Poisson’s ratio) stent structure was proposed that exhibits high circumferential strength in its expanded configuration and low flexural rigidity in its crimped configuration. Results generated with the analytical diffusion model, developed in this project, compare favorably with previously published clinical and experimental data. The circumferential and flexural stiffnesses estimated using the analytical procedure developed in this project compare favorably with the results from rigorous finite element analyses and previously published experimental data.
Nanoporous Alumina Membranes for Enhancing Hemodialysis
Authors: Huang Zhongping , Zhang Weiming , Yu Jianping , Gao Dayong
Published: March 2007

The nonuniformity of pore size and pore distribution of the current hemodialysis membrane results in low efficiency of uremic solute removal as well as the loss of albumin. By using nanotechnology, an anodic alumina membrane (ceramic membrane) with self-organized nanopore structure was produced. The objective of this study was to fabricate nanoporous alumina membranes and investigate the correlation between various anodization conditions and the pore characteristics in order to find its potential application in artificial kidney/hemodialysis. An aluminum thin film was oxidized in two electrolytes consisting of 3% and 5% sulfuric acid and 2.7% oxalic acid. The applied voltages were 12.5, 15, 17.5, and 20V for sulfuric acid and 20, 30, 40, and 50V for oxalic acid. Pore size and porosity were determined by analyzing Scanning Electron Microscopy (SEM) images and hydraulic conductivity was measured. Results show that pore size increased linearly with voltage. Acid concentration affected pore formation but not pore size and pore distribution. Hydraulic conductivity of the ceramic membrane was higher than that of the polymer dialysis membrane. The optimal formation conditions for self-organized nanopore structure of the ceramic membrane were 12.5-17.5V in 3–5% sulfuric acid at 0°C. Under these conditions, ceramic membranes with pores size of ∼10nm diameter can be produced. In conclusion, we used anodic alumina technology to reliably produce in quantity ceramic membranes with a pore diameter of 10-50nm. Because of more uniform pore size, high porosity, high hydraulic conductivity, and resistance to high temperature, the ceramic membrane has the potential application as a hemodialysis membrane.
LIGHT PSEUDO-GOLDSTONE BOSONS WITHOUT EXPLICIT SYMMETRY BREAKING
Authors: BOUZAS ANTONIO O.
Published: March 2007

A mechanism is discussed to obtain light scalar fields from a spontaneously broken continuous symmetry without explicitly breaking it. If there is a continuous manifold of classical vacua in orbit space, its tangent directions describe classically massless fields that may acquire mass from perturbations of the potential that do not break the symmetry. We consider the simplest possible example, involving a scalar field in the adjoint representation of SU (N). We study the scalar mass spectrum and its renormalization group running at one-loop level including scalar and pseudoscalar Yukawa couplings to a massive Dirac fermion.
MATRIX MODELS AND QCD WITH CHEMICAL POTENTIAL
Authors: AKEMANN G.
Published: March 2007

The random matrix model approach to quantum chromodynamics (QCD) with nonvanishing chemical potential is reviewed. The general concept using global symmetries is introduced, as well as its relation to field theory, the so-called epsilon regime of chiral perturbation theory (∊χPT). Two types of matrix model results are distinguished: phenomenological applications leading to phase diagrams, and an exact limit of the QCD Dirac operator spectrum matching with ∊χPT. All known analytic results for the spectrum of complex and symplectic matrix models with chemical potential are summarised for the symmetry classes of ordinary and adjoint QCD, respectively. These include correlation functions of Dirac operator eigenvalues in the complex plane for real chemical potential, and in the real plane for imaginary isospin chemical potential. Comparisons of these predictions to recent lattice simulations are also discussed.
CRYSTAL HABIT OF MINERALS — A CRYSTAL CHEMICAL APPROACH
Authors: HAUCK J. , MIKA K.
Published: March 2007

Homogeneous particles A like carbon atoms in diamond, CO3ions in CaCO3, or sulfur molecules in sulfur with different A–A interactions are ordered in such a way that the bulk structure can be characterized by the self-coordination numbers Ti, i = 1-3, of nearest, second, and third neighbors. There are about 500 sets with increased Tivalues and about 500 sets with reduced Tivalues, which can be obtained from characteristic lattice complexes. The different sets with increased Tivalues are characterized by S, L, or R for sphere, layer, or rod packing. Two or more particles A, B, C, etc., can belong to the same set like Na and Cl atoms in NaCl or different sets like Ca and F atoms in CaF2. The Dirichlet domains of A and B ( CaF2) or A + B ( NaCl ) are approaches to the morphological lattices (cubes or rhombododecahedra). Planes with a high density of A positions and thus low h k l values like the {111} planes of octahedra are derived from Bravais' theory. The morphological lattices of layer or rod packings are layers or rods because of the increased densities of A in layers or rods.
AN APPLICATION OF NONEXTENSIVE PARAMETER: THE NONEXTENSIVE GAS AND REAL GAS
Authors: ZHENG YAHUI , DU JIULIN
Published: March 2007

By application of the nonextensive statistics to the ideal gas model, we establish a nonextensive gas model. If we regard the nonextensive gas as a real gas, we can use the nonextensive parameter q ∈ ℝ in Tsallis statistics to describe Joule coefficient, Joule–Thomson coefficient, second virial coefficient and etc. We also derive an expression, with a multiplier T1-q, of the heat capacity of the nonextensive gas. We can prove that in the quasi-equilibrium system there is 1 - q > 0, 2 so the heat capacity still vanishes if temperature tends to zero, just as that in Boltzmann-Gibbs statistics.
MONTE CARLO SIMULATIONS OF STEADY-STATE TRANSPORT IN WURTZITE PHASE GaN SUBMICROMETER n+nn+ DIODE
Authors: ARABSHAHI H.
Published: March 2007

Monte Carlo simulation of electron transport in a GaN diode of n+nn+ structure with a 0.4 or 0.6 μm long active layer is described. The anode voltage ranges from 10 to 50 V. The distributions of electron energies and electron velocities, and the profiles of the electron density, electric field, potential and average electron velocity are computed. Based on these data, the near ballistic nature of the electron transport in the 0.4 μm-long diode and the importance of the back-scattering of electrons from the anode n+-layer are discussed. Also, the effects of the lattice temperature and doping on the length of the active layer are discussed.
ELECTRON-SPIN FILTERING IN HYBRID FERROMAGNETIC/SEMICONDUCTOR NANOSYSTEM
Authors: LU MAO-WANG
Published: March 2007

The spin-dependent transport of electrons in realistic ferromagnetic/semiconductor hybrid nanosystems was investigated theoretically. This kind of nanosystem can be experimentally realized by depositing a magnetized ferromagnetic strip with arbitrary magnetization direction on the surface of a semiconductor heterostructure. It is revealed that a large spin-polarized current can be achieved in such a device. It is also shown that the spin polarity of the electron transport can be switched by adjusting the structural parameters and location of the ferromagntic strip in the system. These interesting properties may provide an alternative scheme to spin-polarized electrons into semiconductors, and such a nanosystem may be used as a spin filter.
ER-DOPED LEAD–BISMUTHATE GLASSES: MAGNETIC AND STRUCTURAL PROPERTIES
Authors: CULEA E. , POP LIDIA , MUNTEAN RAVECA , BOSCA MARIA , BRATU I. , BOGDAN M.
Published: March 2007

The effect of erbium-doping on the structural and magnetic properties of the x Er 2 O 3-(1-x)[3 Bi 2 O 3· PbO ] lead-bismuthate glasses was investigated. The glasses were investigated by infra-red spectroscopy (IR) and magnetic susceptibility measurements. The temperature dependence of the reciprocal susceptibility indicates that the erbium ions are isolated in samples with lower erbium ion content (x≤0.05) but for a higher content, a negative superexchange interaction between the magnetic erbium ions occurs. A structural model for the glasses is suggested on the basis of the IR spectral data.
FACTORS NURTURING ACADEMIC ENTREPRENEURSHIP IN TAIWAN
Authors: YANG PHIL Y. , CHANG YUAN-CHIEH , CHEN MING-HUEI
Published: March 2007

Although academic research institutions have become a major player in protecting, transferring, and commercializing their knowledge base, little research has examined in enterprising research results from the angle of academic entrepreneurs. This paper examined the factors fostering academic entrepreneurship from institutional, organizational, and individual aspects, especially in Taiwan. Based on the Patent Database of the National Science Council, Taiwan, 474 academic entrepreneurs who owned patents were identified. Via a postal survey, 229 questionnaires were collected with an overall. response rate of 48%. Through factor analysis, five key success factors fostering academic entrepreneurship were identified. The key success factors to foster academic entrepreneurship in Taiwan include entrepreneurial network, organizational infrastructures, entrepreneurial legitimacy, entrepreneurial pro-activeness, and entrepreneurial rewards. Thus, the paper concluded that nurturing academic entrepreneurship in Taiwan is evidently shaped by not only micro factors such as entrepreneurial networks and characteristics but also macro factors such as entrepreneurial infrastructures and rewards from universities and increasing legitimacy of academic entrepreneurship.
MEANING IN LIFE AS AN OPPORTUNITY FOR ENTERPRISE
Authors: VAN GELDEREN MARCO
Published: March 2007

This paper's starting point is the idea that a market for meaning in life exists that consists of several submarkets. Suppose someone wants to enter this market with a business or organization that tries to alleviate meaninglessness. How can the person shape the proposition that he or she wants to offer? We propose that Baumeister's (1992) theory of needs for meaning can serve as a useful tool. Baumeister states that meaning is generated when the needs for a goal, fulfillment, context, control, and self-worth are simultaneously met. Taking the market for alternative spiritual courses as a case example, we show that this theory is adequate for describing the variety of alternative spiritual courses in terms of a limited number of meaning models. Would-be providers on the market for meaning in life can create propositions by following, reordering, or creating meaning models. Examples of such propositions are given for a number of submarkets.
Hypoglycemic detection at the portal vein is mediated by capsaicin-sensitive primary sensory neurons
Authors: Fujita Satoshi , Bohland MaryAnn , Sanchez-Watts Graciela , Watts Alan G. , Donovan Casey M.
Published: March 2007

To elucidate the type of spinal afferent involved in hypoglycemic detection at the portal vein, we considered the potential role of capsaicin-sensitive primary sensory neurons. Specifically, we examined the effect of capsaicin-induced ablation of portal vein afferents on the sympathoadrenal response to hypoglycemia. Under anesthesia, the portal vein was isolated in rats and either capsaicin (CAP) or the vehicle (CON) solution applied topically. During the same surgery, the carotid artery (sampling) and jugular vein (infusion) were cannulated. One week later, all animals underwent a hyperinsulinemic hypoglycemic clamp, with glucose (variable) and insulin (25 mU·kg−1·min−1) infused via the jugular vein. Systemic hypoglycemia (2.76 ± 0.05 mM) was induced by minute 75 and sustained until minute 105. By design, no significant differences were observed in arterial glucose or insulin concentrations between groups. When hypoglycemia was induced in CON, the plasma epinephrine concentration increased from 0.67 ± 0.05 nM at basal to 36.15 ± 2.32 nM by minute 105. Compared with CON, CAP animals demonstrated an 80% suppression in epinephrine levels by minute 105, 7.11 ± 0.55 nM ( P < 0.001). A similar response to hypoglycemia was observed for norepinephrine, with CAP values suppressed by 48% compared with CON. Immunohistochemical analysis of the portal vein revealed an 85% decrease in the number of calcitonin gene-related peptide-reactive nerve fibers following capsaicin-induced ablation. That the suppression in the sympathoadrenal response was comparable to our previous findings for total denervation of the portal vein indicates that hypoglycemic detection at the portal vein is mediated by capsaicin-sensitive primary sensory neurons.
Transgenic MSH overexpression attenuates the metabolic effects of a high-fat diet
Authors: Lee Michelle , Kim Andrea , Chua Streamson C. , Obici Silvana , Wardlaw Sharon L.
Published: March 2007

To determine whether long-term melanocortinergic activation can attenuate the metabolic effects of a high fat diet, mice overexpressing an NH2-terminal POMC transgene that includes α- and γ3-MSH were studied on either a 10% low-fat diet (LFD) or 45% high-fat diet (HFD). Weight gain was modestly reduced in transgenic (Tg-MSH) male and female mice vs. wild type (WT) on HFD ( P < 0.05) but not LFD. Substantial reductions in body fat percentage were found in both male and female Tg-MSH mice on LFD ( P < 0.05) and were more pronounced on HFD ( P < 0.001). These changes occurred in the absence of significant feeding differences in most groups, consistent with effects of Tg-MSH on energy expenditure and partitioning. This is supported by indirect calorimetry studies demonstrating higher resting oxygen consumption and lower RQ in Tg-MSH mice on the HFD. Tg-MSH mice had lower fasting insulin levels and improved glucose tolerance on both diets. Histological and biochemical analyses revealed that hepatic fat accumulation was markedly reduced in Tg-MSH mice on the HFD. Tg-MSH also attenuated the increase in corticosterone induced by the HFD. Higher levels of Agrp mRNA, which might counteract effects of the transgene, were measured in Tg-MSH mice on LFD ( P = 0.02) but not HFD. These data show that long-term melanocortin activation reduces body weight, adiposity, and hepatic fat accumulation and improves glucose metabolism, particularly in the setting of diet-induced obesity. Our results suggest that long-term melanocortinergic activation could serve as a potential strategy for the treatment of obesity and its deleterious metabolic consequences.
Effect of hypoxia on the release of vascular endothelial growth factor and testosterone in mouse TM3 Leydig cells
Authors: Hwang Guey-Shyang , Wang Shyi-Wu , Tseng Wen-Min , Yu Ching-Han , Wang Paulus S.
Published: March 2007

Hypoxia has been shown to stimulate the expression of vascular endothelial growth factor (VEGF), which is a major mediator for angiogenesis and vasculogenesis. During hypoxia, VEGF promotes angiogenesis in the testis. However, the effect of VEGF on the steroidogenesis of testosterone and the cell proliferation in Leydig cells is unclear. To assess the effects and the action mechanisms of hypoxia, a mouse TM3 Leydig cell line was employed in the present study. The Leydig cells were incubated in an incubator chamber (95% N2-5% CO2) for 1–24 h. The cultured media were collected and assayed by testosterone RIA and VEGF enzyme immunoassay. 3-(4,50-Dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide assay was used to detect the proliferation of Leydig cells. The present results showed that the proliferation of Leydig cells was enhanced significantly by hypoxia. The basal VEGF release was increased, and the response of VEGF production to human chorionic gonadotropin (hCG) was also enhanced in hypoxic condition. During hypoxia, administration of hCG or VEGF stimulated proliferation of Leydig cells, but the stimulatory effect was abolished by the administration of anti-VEGF antibody. Higher doses of VEGF stimulated testosterone release in a dose-dependent manner. Administration of anti-VEGF antibody abolished the stimulatory effect of VEGF on testosterone release. These data suggest that hypoxia stimulates cell proliferation and testosterone release in Leydig cells via an increase of VEGF production.
Mild renal ischemia-reperfusion reduces charge and size selectivity of the glomerular barrier
Authors: Andersson Maria , Nilsson Ulf , Hjalmarsson Clara , Haraldsson Börje , Nyström Jenny Sörensson
Published: March 2007

Despite recent discoveries of molecules in podocytes, the mechanisms behind most conditions of proteinuria are still poorly understood. To understand more about this delicate barrier, we studied the functional and morphological effects of mild (15 min) renal ischemia-reperfusion injury (IRI). Renal function was studied in rats in vivo, followed by a more detailed analysis of the glomerular barrier in cooled (8°C) isolated perfused kidneys (cIPK). Renal blood flow was quickly restored, whereas the glomerular filtration rate remained halved 30 min after IRI. Tubular cell activity was intact as judged from the unaffected Cr-EDTA U/P concentration ratio. In vivo, the fractional clearance (θ) for albumin increased 16 times. In rats subjected to cIPK starting 30 min after in vivo IRI, θalbuminwas 15 times and θFicoll_36Å1.8 times higher than in control cIPKs. According to the heterogeneous charged fiber model, IRI reduced the fiber charge density to 38% of control ( P < 0.01, n = 7). Morphometric analysis with electron microscopy did not reveal any changes in the podocytes or the glomerular basement membrane (GBM) after IRI, suggesting more subtle changes of the GBM and/or the endothelial glycocalyx. We conclude that mild renal IRI induces formation of reactive oxygen species, massive proteinuria, and loss of charged fibers with no apparent change in morphology. These novel findings stress the importance of other components of the barrier, such as proteoglycans produced by the glomerular cells, and provide a tentative explanation for the mechanisms behind proteinuria in glomerulonephritis, for example.
Role of Rho-GTPases in complement-mediated glomerular epithelial cell injury
Authors: Zhang Hui , Cybulsky Andrey V. , Aoudjit Lamine , Zhu Jianxin , Li Hongping , Lamarche-Vane Nathalie , Takano Tomoko
Published: March 2007

Visceral glomerular epithelial cells (GEC) are essential for maintenance of normal glomerular permselectivity. The actin cytoskeleton is a key determinant of GEC morphology and function. In the rat passive Heymann nephritis (PHN) model of membranous nephropathy, complement C5b-9 induces nonlytic GEC injury associated with morphological changes of GEC and proteinuria. The current study addresses the role of Rho family of small GTPases in complement-mediated GEC injury. When cultured rat GEC were stimulated with complement C5b-9 for 18 h, RhoA activity increased, whereas Rac1/Cdc42 activities decreased, compared with control cells. Similar changes in Rho-GTPase activities were observed in glomeruli from rats with PHN. The amount of active p190RhoGAP, a negative upstream regulator of RhoA, was decreased in complement-stimulated GEC, potentially contributing to increased RhoA activity. To address the functional effects of Rho-GTPases, GEC were transfected with constitutively active (CA) or dominant negative (DN) Rho-GTPase mutants. GEC transfected with CA-RhoA showed a smaller and round contour and prominent cortical F-actin. In contrast, GEC transfected with CA-Rac1 demonstrated morphological changes that resembled process formation. In addition, expression of CA-RhoA attenuated complement-mediated cytotoxicity, whereas cytotoxicity was augmented by DN-RhoA. Thus exposure of GEC to complement alters the balance of RhoA, Rac1, and Cdc42 activities. The activity of Rac1 may contribute to process formation, while activation of RhoA (e.g., in the setting of complement attack), with or without blunting of Rac1 activity, may have an opposite effect, i.e., contribute to foot process effacement. Activation of RhoA increases the resistance of GEC to complement-mediated injury.
M1 Muscarinic Receptor Modulation of Kir2 Channels Enhances Temporal Summation of Excitatory Synaptic Potentials in Prefrontal Cortex Pyramidal Neurons
Authors: Carr David B. , Surmeier D. James
Published: March 2007

The cholinergic innervation of the prefrontal cortex (PFC) plays a pivotal role in regulating executive functions. Muscarinic receptors activated by acetylcholine depolarize pyramidal neurons in the rodent PFC homologue, but the mechanisms mediating this modulation are controversial. To address this question, we studied the responses of layer V rat pre- and infralimbic cortex pyramidal neurons to muscarinic receptor stimulation. Consistent with previous findings, M1 receptor stimulation produced a strong depolarization, leading to tonic firing. Voltage-clamp analysis revealed that M1 activation reduced constitutively active inwardly rectifying (Kir2) K+ channel currents. Blocking protein kinase C activation or depleting intracellular Ca2+ stores did not affect the modulation. However, reversal of the modulation was prevented by the phosphoinositide kinase inhibitor, wortmanin, suggesting the modulation was mediated by depletions of membrane phosphatidylinositol-4,5-bisphosphate (PIP2). Reduction of Kir2 channel currents by M1 receptor stimulation significantly increased the temporal summation of excitatory synaptic potentials (EPSPs) evoked by repetitive stimulation of layer I. This action was complimented by M2/4 receptor mediated presynaptic inhibition of the same terminals. As a consequence of this dual modulation, the responses to a single, isolated afferent volley was reduced, but the response to a high-frequency afferent burst was potentiated.
Modulation of Inhibitory Activity by Nitric Oxide in the Thalamus
Authors: Yang Sunggu , Cox Charles L.
Published: March 2007

The dorsal lateral geniculate nucleus (dLGN) is essential for the transfer of visual information from the retina to visual cortex, and inhibitory mechanisms can play a critical in regulating such information transfer. Nitric oxide (NO) is an atypical neuromodulator that is released in gaseous form and can alter neural activity without direct synaptic connections. Nitric oxide synthase (NOS), an essential enzyme for NO production, is localized in thalamic inhibitory neurons and cholinergic brain stem neurons that innervate the thalamus, although NO-mediated effects on thalamic inhibitory activity remain unknown. We investigated NO effects on inhibitory activity in dLGN using an in vitro slice preparation. The NO donor, SNAP, selectively potentiated the frequency, but not amplitude, of spontaneous inhibitory postsynaptic currents (sIPSCs) in thalamocortical relay neurons. This increase also persisted in tetrodotoxin (TTX), consistent with an increase in GABA release from presynaptic terminals. The SNAP-mediated actions were attenuated not only by the NO scavenger carboxy-PTIO but also by the guanylyl cyclase inhibitor ODQ. The endogenous NO precursor l-arginine produced actions similar to those of SNAP on sIPSC activity and these l-arginine–mediated actions were attenuated by the NOS inhibitor L-NMMA acetate. The SNAP-mediated increase in sIPSC activity was observed in both dLGN and ventrobasal thalamic nucleus (VB) neurons. Considering the lack of interneurons in rodent VB, the NO-mediated actions likely involve an increase in the output of axon terminals of thalamic reticular nucleus neurons. Our results indicate that NO upregulates thalamic inhibitory activity and thus these actions likely influence sensory information transfer through thalamocortical circuits.
MyD88-dependent changes in the pulmonary transcriptome after infection withChlamydia pneumoniae
Authors: Rodríguez Nuria , Mages Jörg , Dietrich Harald , Wantia Nina , Wagner Hermann , Lang Roland , Miethke Thomas
Published: March 2007

Chlamydia pneumoniae, an intracellular bacterium, causes pneumonia in humans and mice. Toll-like receptors and the key adaptor molecule myeloid differentiation factor-88 (MyD88) play a critical role in inducing immunity against this microorganism and are crucial for survival. To explore the influence of MyD88 on induction of immune responses in vivo on a genome-wide level, wildtype (WT) or MyD88−/−mice were infected with C. pneumoniae on anesthesia, and the pulmonary transcriptome was analyzed 3 days later by microarrays. We found that the infection caused pulmonary cellular infiltration in WT but not MyD88−/−mice. Furthermore, it induced the transcription of 360 genes and repressed 18 genes in WT mice. Of these, 221 genes were not or weakly induced in lungs of MyD88−/−mice. This cluster contains primarily genes encoding for chemokines and cytokines like MIP-1α, MIP-2, MIP-1γ, MCP-1, TNF, and KC and other immune effector molecules like immunoresponsive gene-1 and TLR2. Arginase was highly induced after C. pneumoniae infection and was MyD88 dependent. Genes induced by interferons were abundant in a cluster of 102 genes that were only partially MyD88 dependent. Also, lcn2 (lipocalin-2) and timp1 were represented within this cluster. Interestingly, a set of 37 genes including sprr1a was induced more strongly in MyD88−/−mice, and most of them are involved in the regulation of cellular replication. In summary, ex vivo analysis of the pulmonary transcriptome on infection with C. pneumoniae demonstrated a major impact of MyD88 on inflammatory responses but not on interferon-type responses and identified MyD88-independent genes involved in cellular replication.
Genome-level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcome
Authors: Wong Hector R. , Shanley Thomas P. , Sakthivel Bhuvaneswari , Cvijanovich Natalie , Lin Richard , Allen Geoffrey L. , Thomas Neal J. , Doctor Allan , Kalyanaraman Meena , Tofil Nancy M. , Penfil Scott , Monaco Marie , Tagavilla Mary Ann , Odoms Kelli , Dunsmore Katherine , Barnes Michael , Aronow Bruce J.
Published: March 2007

Human septic shock involves multiple genome-level perturbations. We have conducted microarray analyses in children with septic shock within 24 h of intensive care unit admission, using whole blood-derived RNA. Based on sequential statistical and expression filters, there were 2,482 differentially regulated gene probes (1,081 upregulated and 1,401 downregulated) between patients with septic shock ( n = 42) and controls ( n = 15). Both gene lists encompassed several biologically relevant gene ontologies and canonical pathways. Notably, many of the genes downregulated in the patients with septic shock, relative to the controls, participate in gene ontologies related to metal or zinc homeostasis. Comparison of septic shock survivors ( n = 33) and nonsurvivors ( n = 9) demonstrated differential regulation of 63 gene probes. Among the 63 gene probes differentially regulated between septic shock survivors and nonsurvivors, two isoforms of metallothionein (MT) demonstrated increased expression in the nonsurvivors. Consistent with the ability of MT to sequester zinc in the intracellular compartment, nonsurvivors had lower serum zinc levels compared with survivors. In a corroborating study of murine sepsis, MT-null mice demonstrated a survival advantage compared with wild-type mice. These data represent the largest reported cohort of pediatric patients with septic shock that has undergone genome-level expression profiling based on microarray. The data are biologically plausible and demonstrate that genome-level alterations of zinc homeostasis may be prevalent in clinical pediatric septic shock.
Expression of Sex-Determining Genes in the Scalp of Men with Androgenetic Alopecia
Authors: Chen WenChieh , Yang Chao-Chun , Tsai Ren-Yeu , Liao Chen-Yu , Yen Yu-Ta , Hung Chiu-Ling , Chen Ko-Fan , Tsai Shaw-Jenq , Zouboulis Christos C.
Published: March 2007

Background: The regulation of the cutaneous steroidogenesis in patients with androgenetic alopecia remains largely unclear. Objective: The purpose of this study was to quantify the expression of the sex-determining genes in different scalp areas. Methods: Paired scalp specimens from frontal and occipital scalp areas of 10 patients were examined by real-time RT-PCR for mRNA expression and of 40 patients (mean age 34.9 years, range 22–58) by Western blotting for protein analysis. Results: The SOX-9 mRNA was most abundant in the skin, while SF-1 mRNA was sparsely detected. The protein levels of DAX-1, SRY and WT-1 were significantly higher in the bald scalp (p = 0.003, 0.004 and 0.03, respectively). Only the SRY expression showed a positive correlation with the baldness severity in Norwood-Hamilton classification (p = 0.024). There was no association between patient’s age and the protein levels. Immunostaining of SOX-9 was detected in the outer root sheath keratinocytes of hair follicles but not in the dermal papillae. Conclusion: Further study on a larger population, including normal subjects and female patients, is needed to confirm the pathogenic role of sex-determining genes in androgenetic alopecia.
Angioedema in Renal Transplant Recipients on Sirolimus
Authors: Mahé Emmanuel , Morelon Emmanuel , Lechaton Sophie , Kreis Henri , de Prost Yves , Bodemer Christine
Published: March 2007

Background:Most drug-associated angioedemas are induced by angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, or nonsteroidal anti-inflammatory drugs. Recently, the responsibility of immunosuppressive agents given to transplant recipients in the development of angioedema has been discussed. Objective: To describe, in detail, angioedema episodes in renal transplant recipients (RTRs) on sirolimus. Methods: A cross-sectional study in a university hospital. Eighty consecutive RTRs on sirolimus were studied. Results: Angioedema without urticaria occurred a mean of 5 times in 12/80 (15%) RTRs taking sirolimus. It was predominantly located on the face (83%), with mucous membrane involvement in 7 (58%) patients, and was life threatening in 1. Another putative cofactor for angioedema without urticaria was identified in 9 (75%) patients: drugs (n = 8), food allergy or physical activity (n = 3). Tacrolimus intake was significantly associated with sirolimus-associated angioedema. Conclusion: Our results suggested a causal relationship between sirolimus and angioedema in RTRs.
Concurrence of Systemic Lupus Erythematosus and Pemphigus: Coincidence or Correlation?
Authors: Malik Mohsin , Ahmed A. Razzaque
Published: March 2007

Background: Pemphigus and systemic lupus erythematosus (SLE) have previously been reported to coexist in the same patient. However, the relationship between the 2 diseases has not been elucidated. Objective: This review was conducted to examine the relationship between pemphigus and SLE when they occur together in the same patient. Methods: We conducted a retrospective review of the literature to identify previously reported cases of pemphigus and SLE coexisting in the same patient. The temporal relationship, clinical course, response to therapy and effects of 1 disease on the other were examined. Results: Eight patients with a dual diagnosis of pemphigus and SLE have been previously reported. Most were female and non-Caucasian, with a mean age of 41 years. In the 8 patients reviewed here clinical outcomes, organ system involvement and demographic profiles are more typical of SLE. Seven of these 8 patients had pemphigus vulgaris, and 1 had pemphigus erythematosus. The limited follow-up did not permit studying issues of disease interaction. An additional 17 patients with pemphigus have been reported who have features suggestive of SLE. Organ system involvement in these patients was less typical of SLE. Conclusion: It appears that a true dual diagnosis of pemphigus and SLE is less common than suggested by the literature. Comparing patients with only pemphigus or only SLE to those with both may provide insights into genetic predisposition and pathogenesis, and provide an opportunity to study the effects of drugs that influence their course.
Temperament and Character Profile in Patients with Essential Hyperhidrosis
Authors: Karaca Semsettin , Emul Murat , Kulac Mustafa , Yuksel Seref , Ozbulut Omer , Guler Ozkan , Gecici Omer
Published: March 2007

Background/Aims: The main debates on hyperhidrosis are whether there are some personality features such as anxiety or stress, or whether the psychological symptoms are due to negative social feedback from early life. We aimed to investigate the temperament and character dimensions with a psychobiological inventory. Methods: We recruited patients with hyperhidrosis (n = 26) and chronic renal failure (n = 44) as well as healthy subjects (n = 22) from dermatology and nephrology clinics and the general population in Afyonkarahisar. All subjects were required to perform a temperament and character inventory. Results: The total novelty seeking score in hyperhidrosis was significantly lower than in controls. There was no significance in total harm avoidance scores between hyperhidrosis patients and controls. The total reward dependence and persistence scores were significantly higher in hyperhidrosis patients. The fear of uncertainty in the harm avoidance scale was found to be significantly greater in hyperhidrosis patients. Regarding character dimensions, the total score in each of the subscales self-directedness, cooperativeness and self-transcendence was found to be higher in hyperhidrosis patients. Conclusion: The higher scores of all subscales of character dimensions in hyperhidrosis patients suggest that hyperhidrosis is not related with social phobia or personality disorder.
Cardiac Troponin T: A Useful Early Marker for Cardiac and Respiratory Dysfunction in Neonates
Authors: Awada H. , Al-Tannir M. , Ziade M.F. , Alameh J. , El Rajab M.
Published: March 2007

Background: Cardiac troponin T (cTnT) has been proposed as specific biochemical marker for myocardial infarction in adults. Cardiac function in neonates could be influenced by the severity of respiratory distress and its ventilatory management. Objectives: To establish a normal range of cTnT in healthy neonates, compare troponin concentrations among healthy neonates and those in respiratory distress (sick) and detect whether any correlation occurs between severity of respiratory distress and troponin concentrations. Methods: Concentrations of cTnT were compared between sick and healthy infants, accountingfor confounding variables in a prospective investigation manner. Age at sampling, need for ventilation, durationof respiratory support, and inotropic use in addition to neonatal and maternal characteristics were assessed. Results: Samples were collected from164 neonates (116 healthy and 48 sick).The medians [interquartile ranges] of cTnT in healthy and sick infants were 0.044 [0.027–0.073]µg/l and 0.121 [0.065–0.238] µg/l, respectively, with p < 0.0001. The 99th percentile for healthy neonates was 0.244 µg/l. Comparing both groups, there were significantdifferences concerning gestation, birth weight, Apgar at 5 min and admission to neonatal intensive care unit. Troponin concentrations in subgroups of sick infants including hypotensive, ventilated and dead infants were higher than other infants of the same subgroup. CTnT was positively correlated to the duration of respiratory support in ventilated neonates. Conclusion: CTnT may prove to be a useful early marker for cardiac and respiratory dysfunction in newborns.
Improved Survival with Single-Agent Paclitaxel Consolidation/Maintenance Therapy in Advanced Ovarian Carcinoma
Authors: Micha John P. , Goldstein Bram H. , Graham Cheri , Rettenmaier Mark A. , Brown III John V. , Hu Jim C. , Markman Maurie
Published: March 2007

Objectives: Consolidation/maintenance therapy in the standard management of ovarian cancer remains controversial, primarily due to the unknown impact of this strategy on overall survival. Methods: We examined the survival of a previously reported patient population consecutively treated with either 3 cycles (group A; n = 13 patients) or 12 cycles (group B; n = 13) of single-agent paclitaxel consolidation following 6 cycles of primary induction chemotherapy comprising 6 cycles of carboplatin (AUC = 5), paclitaxel (175 mg/m2) and gemcitabine (800 mg/m2). Results: There were no differences in the 2 patient populations regarding known relevant prognostic factors (age, stage, tumor grade). The median progression-free survival was 11 months for group A and 24 months for group B (p = 0.0062). The median overall survival in group A was 38 months and was not reached in group B (p = 0.0019). Current follow-up for these 2 patient groups exceeds 43 months. Conclusion: We recognize the important limitations of this study, particularly its sample size and nonrandomized nature. However, these data provide support for the conclusion that paclitaxel ‘maintenance/consolidation’ therapy may favorably impact overall and progression-free survival in advanced ovarian cancer patients who achieve an excellent response to primary platinum-based chemotherapy.
Effects of Glucose-Free Dialysis Solutions on Human Peritoneal Mesothelial Cells
Authors: Chang Jer-Ming , Lin Shih-Pi , Lai Yung-Hsiung , Chen Hung-Chun
Published: March 2007

Background: Glucose-free dialysis solutions may be more biocompatible owing to the physiological pH and the lack of glucose degradation products, and the effects can be reflected by the changes in some markers of peritoneal mesothelial cells (PMC). Method: Peritoneal effluents were collected in 17 CAPD patients after one daily exchange of glucose-containing dialysate to Nutrineal (1.1% amino acid-based PDF), and human PMC were cultured from peritoneal effluent and treated with various peritoneal dialysis (PD) solutions. Results: The level of cancer antigen 125 (CA125) in peritoneal effluent increased significantly after using Nutrineal® for 3 months (p = 0.045), whereas that of procollagen I peptide (PICP) remained unaltered. Production of CA125 by human PMC showed a time-responsive increase after stimulation with Nutrineal and Extraneal (icodextran-based PDF). An increased expression of CA125 was observed in cultured human PMC treated with various PD solutions, and the increase induced by Nutrineal was lower than that induced by 4.25% Dianeal® and Extraneal®. A lower increase was also observed for lactate dehydrogenase (LDH). The levels of heat shock protein 70 (HSP70), however, were not altered. Conclusion: Nutrineal is more biocompatible to the peritoneal membrane than the conventional PD solutions tested herein, reflected by both the in vivo and in vitro response of CA125.
Macroporous Beads for Lipase Immobilization
Authors: Bhushan Indu , Parshad Rajinder , Qazi G.N. , Ingavle Ganesh , Jamalpure Trupti M. , Rajan C.R. , Ponrathnam S. , Gupta V.K.
Published: March 2007

Lipase isolated from Arthrobacter sp. (RRLJ-1, MTCC No. 5125, named ABL), is effective in resolving a wide range of racemic drug intermediates. In this study, ABL was immobilized on a series of synthetic macroporous epoxy copolymers beads with varying pore sizes, surface area and hydrophobicity. Poly(glycidyl methacrylate-co-ethylene dimethacrylate) beads, with 75% crosslink density and 10% of epoxy groups modified with dibutyl amine [GMA-EGDM-75 (10% DBA)] had a pore volume of 0.77 mL/g and a surface area of 86.05 m 2/g; these beads were optimally suitable for ABL immobilization. The covalent binding of the lipase was optimized by varying the ionic strength, buffers, pH, temperature and time. The optimal binding was achieved in 100 mM phosphate buffer at 4°C, pH 7.0 in three hours. Under these conditions the polymer retained 34 units and 12 mg of ABL per gram. Immobilized ABL displayed enhanced thermal, organic solvent and pH stability compared to the free enzyme. The immobilized enzyme was used repeatedly (fifteen cycles) to resolve the fluoxitine intermediate (racemic ethyl-3-hydroxy-3-phenyl propanoate) without any loss in stereospecificity. The resolution time of fluoxitine intermediate was reduced to almost half (from 84 to 48 hours) by using the immobilized enzyme.
Novel Scaffold Containing Transforming Growth Factor-β1 DNA for Cartilage Tissue Engineering
Authors: Tong Jian-Cheng , Yao Shang-Long
Published: March 2007

The current progression in tissue engineering and local gene delivery systems has enhanced applications for cartilage tissue engineering. In this study, porous chitosan/collagen scaffolds were prepared through a freeze-drying process and loaded with plasmid encoding human transforming growth factor-β1 (TGFβ1). Human bone marrow stem cells were seeded in this scaffold, and gene transfection was traced by enhanced green fluorescent protein (EGFP). The expression of type II collagen and aggrecan was detected with reverse transcription-polymerase chain reaction, and cell proliferation was measured every day for six days using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay. The pore diameter of the gene-combined scaffolds was lower than that of the pure chitosan/collagen scaffold. The scaffold containing TGFβ1 plasmid exhibited the highest proliferation rate, and the expression of type II collagen and aggrecan was upregulated in the pEGFP-TGFβ1 scaffold. The potential for chitosan/collagen scaffold combined with pEGFP-TGFβ1 as a substrate candidate in cartilage tissue engineering has been investigated.
Changing images of the State: overloaded, hollowed-out, congested
Authors: Skelcher Chris
Published: March 2007

Three conceptualisations of the UK's state are identified: the overloaded state of the 1960s/1970s; the hollowed-out state of the 1980s/early 1990s; the congested state of the late 1990s. In this latter period the creation of collaborative institutions has become a core strategy in all areas of UK public policy. This rich web of linkages arose in response to the problems inherent in the fragmentation arising from hollowing-out. The resulting partnerships bring together public, private, voluntary and community sector actors. They operate between and around the core institutions of democratic government. These tertiary (partnership) structures have complex accountability relationships with primary (elected) and secondary (appointed) public bodies, as well as with other actors. The example of Northshire shows how inter-linked strategic and specific partnership boards create an alternative, collaborative governance structure for a locality which is largely outside democratic processes. This development has fundamental implications for our appreciation of the institutional framework of UK government, as well as for the debate about and practice of democratic renewal.
Mapping the Development of Primary Care Groups: A Case Study
Authors: Owen Barry , Wall Ann , Cawood Maurice
Published: March 2007

The changes currently being introduced to the ways in which health care is delivered in England, under the general heading of the new NHS, have the potential to be more than just evolutionary and to transform the NHS from one which has been dominated by the secondary sector into one driven by the primary sector. But they do not start from a tabula rasa, retaining the commissioning-providing split which was a feature of the internal market, but giving the commissioning responsibility to newly-constituted Primary Care Groups to which all general practices now belong. There had already been some experimentation along these lines before the Labour Government took office, with a number of Total Purchasing Pilots in different parts of the country, one of which was Wakefield Health Authority. This paper examines what is happening in Wakefield, and begins to assess developments there against a template, proposed by the authors, suggesting the essential features of a primary care led NHS.
Collaboration with the ‘Third Sector’ - Issues of Accountability: Mapping Israeli Versions of this Problematic
Authors: Schwartz Robert , Sharkansky Ira
Published: March 2007

This article explores the possibility, expressed in the literature, that Third Sector Organisations present a solution to what has been called the crisis of accountability. The paper addresses conceptual issues of holding collaborative government to account. Using Israel's Third Sector as a case in point, we illustrate several problems in holding Third Sector Organisations to account. Some of these problems have been well established in the literature on the contract state. Others are unique or particularly salient to Third Sector Organisations. Amongst these is the image of Third Sector Organisations as "do gooders" staffed largely by volunteers and workers highly committed to worthy causes. Are problems of Third Sector accountability equally salient to collaborative as opposed to contracting and grants arrangements? We find examples of accountability problems in all modes of Government - Third Sector undertakings. Our findings suggest that collaborative ventures may stand a better chance at instituting effective controls, depending on the nature and quality of institutional arrangements. More formalised and comprehensive collaborative agreements might reduce the incidence of accountability problems. Comparison with other settings - the United States and the Third World - indicates that our illustration of the problematic of third sector accountability is broadly applicable.
Getting Public Private Partnerships Going in Transport
Authors: Glaister Stephen , Scanlon Rosemary , Travers Tony
Published: March 2007

This paper is a contribution to the debate about appropriate financing mechanisms for public investment in Britain. The paper examines the government's plans for the London Underground Public-Private Partnerships (PPP), against the experience offunding the Channel Tunnel Rail Link (CTRL), and examines alternative funding mechanisms, including bond financing. The keyfindings are that whilst the PFI is a usefulfinancial toolfor certain types of projects and to fill certain types of financing gaps, an alternative option of funding Underground investments by way of a bond issue is preferable, with project management and construction work being undertaken by the private sector. Should the Government go ahead with the PPP in its present form, it is essential that the commitment to undertake a Public Sector Comparator be seen to be a genuine test for good value for money against the best realistic alternative, namely one using the cheaper financing offered by a bond issue. The comparison should be undertaken by an independent agency such as the National Audit Office, and be in the public domain. But the PPP is not the only way forward. The arrangements for the PPP cut across the Government's own desire to return local democracy to London. There is still an opportunity to deliver a cheaper, more democratic, alternative.