bluuebunny/crossref_metadata_2025 huggingface dataset:
A MODEL STUDY OF THE EQUATION OF STATE OF QCD
Authors: ZONG HONG-SHI , SUN WEI-MIN
Published: October 2008

In this paper, we give a direct method for calculating the partition function, and hence the equation of state (EOS) of QCD at finite chemical potential and zero temperature. In the EOS derived in this paper, the pressure density is the sum of two terms: the first term [Formula: see text] (the pressure density at μ = 0) is a μ-independent constant; the second term, which is totally determined by G[μ](p) (the dressed quark propagator at finite μ), contains all the nontrivial μ-dependence. By applying a general result in the rainbow-ladder approximation of the Dyson–Schwinger approach obtained in our previous study, Phys. Rev. C71, 015205 (2005), G[μ](p) is calculated from the model quark propagator proposed in Phys. Rev. D20, 2947 (1979). From this the full analytic expression of the EOS of QCD at finite μ and zero T is obtained. A comparison between our EOS and the cold, perturbative EOS of QCD of Fraga, Pisarski and Schaffner-Bielich is made. It is expected that our EOS can provide a possible new approach for the study of neutron stars. In the final part of this paper, our method is generalized to the case of finite temperature and the EOS of QCD at finite μ and T is derived. A comparison is made between the EOS derived in this paper and the EOS obtained in previous literatures by directly generalizing the CJT effective action at μ = 0 and T = 0 to finite μ and finite T.
NILPOTENT SYMMETRY INVARIANCE IN THE SUPERFIELD FORMULATION: THE (NON-)ABELIAN 1-FORM GAUGE THEORIES
Authors: MALIK R. P.
Published: October 2008

We capture the off-shell as well as the on-shell nilpotent Becchi–Rouet–Stora–Tyutin (BRST) and anti-BRST symmetry invariance of the Lagrangian densities of the four (3+1)-dimensional (4D) (non-)Abelian 1-form gauge theories within the framework of the superfield formalism. In particular, we provide the geometrical interpretations for (i) the above nilpotent symmetry invariance, and (ii) the above Lagrangian densities, in the language of the specific quantities defined in the domain of the above superfield formalism. Some of the subtle points, connected with the 4D (non-)Abelian 1-form gauge theories, are clarified within the framework of the above superfield formalism where the 4D ordinary gauge theories are considered on the (4, 2)-dimensional supermanifold parametrized by the four space–time coordinates xμ (with μ = 0, 1, 2, 3) and a pair of Grassmannian variables θ and [Formula: see text]. One of the key results of our present investigation is a great deal of simplification in the geometrical understanding of the nilpotent (anti-)BRST symmetry invariance.
LHC DISCOVERIES UNFOLDED
Authors: LYKKEN JOSEPH , SPIROPULU MARIA
Published: October 2008

With the LHC (Large Hadron Collider) data arriving soon, carrying discoveries, we discuss a strategy for synthesizing a set of early measurements illuminating the dark matter of the universe.
THOUGHTS ON A LONG VOYAGE
Authors: SUSSKIND LEONARD
Published: October 2008

Some thoughts of a former particle physicist.
A NEW INTEGRABLE LATTICE HIERARCHY AND ITS TWO DISCRETE INTEGRABLE COUPLINGS
Authors: LI LING , DONG HUANHE
Published: October 2008

Starting from a discrete isospectral problem, a hierarchy of nonlinear Liouville integrable lattice soliton equations are derived. Through enlarging associated spectral problems, two kinds of discrete integrable couplings are constructed for the resulting lattice hierarchy.
BINDING ENERGIES OF A NEGATIVE TRION IN A QUANTUM DOT
Authors: XIE WENFANG
Published: October 2008

The binding energies of a negative trion confined in a quantum dot are calculated using the exact diagonalization method. Both the spin singlet and triplet states are considered. Our results show that the binding energies are sensitive to the strength of the confinement potential as well as the electron–hole mass ratio.
ADAPTIVE SYNCHRONIZATION FOR UNKNOWN STOCHASTIC CHAOTIC NEURAL NETWORKS WITH MIXED TIME-DELAYS BY OUTPUT COUPLING
Authors: TANG YANG , FANG JIAN-AN , LU SUOJUN , MIAO QINGYING
Published: October 2008

This paper is concerned with the synchronization problem for a class of stochastic neural networks with unknown parameters and mixed time-delays via output coupling. The mixed time-delays comprise the time-varying delay and distributed delay, and the neural networks are subjected to stochastic disturbances described in terms of a Brownian motion. Firstly, we use Lyapunov functions to establish general theoretical conditions for designing the output coupling matrix. Secondly, by using the adaptive feedback technique, a simple, analytical and rigorous approach is proposed to synchronize the stochastic neural networks with unknown parameters and mixed time-delays. Finally, numerical simulation results are given to show the effectiveness of the proposed method.
QUANTUM DEVICES BASED ON MODERN BAND STRUCTURE ENGINEERING AND EPITAXIAL TECHNOLOGY
Authors: RAZEGHI MANIJEH
Published: October 2008

Modern band structure engineering is based both on the important discoveries of the past century and modern epitaxial technology. The general goal is to control the behavior of charge carriers on an atomic scale, which affects how they interact with each other and their environment. Starting from the basic semiconductor heterostructure, band structure engineering has evolved into a powerful discipline, employing lower dimensionality to demonstrate new material properties. Several modern technologies under development are used as examples of how this discipline is enabling new types of devices and new functionality in areas with immediate application.
Adaptation to Marginal Habitats
Authors: Kawecki Tadeusz J.
Published: October 2008

The ability to adapt to marginal habitats, in which survival and reproduction are initially poor, plays a crucial role in the evolution of ecological niches and species ranges. Adaptation to marginal habitats may be limited by genetic, developmental, and functional constraints, but also by consequences of demographic characteristics of marginal populations. Marginal populations are often sparse, fragmented, prone to local extinctions, or are demographic sinks subject to high immigration from high-quality core habitats. This makes them demographically and genetically dependent on core habitats and prone to gene flow counteracting local selection. Theoretical and empirical research in the past decade has advanced our understanding of conditions that favor adaptation to marginal habitats despite those limitations. This review is an attempt at synthesis of those developments and of the emerging conceptual framework.
Sorting Out Astrocyte Physiology from Pharmacology
Authors: Fiacco Todd A. , Agulhon Cendra , McCarthy Ken D.
Published: October 2008

A number of exciting findings have been made in astrocytes during the past 15 years that have led many researchers to redefine how the brain works. Astrocytes are now widely regarded as cells that propagate Ca2+ over long distances in response to stimulation, and, similar to neurons, release transmitters (called gliotransmitters) in a Ca2+-dependent manner to modulate a host of important brain functions. Although these discoveries have been very exciting, it is essential to place them in the proper context of the approaches used to obtain them to determine their relevance to brain physiology. This review revisits the key observations made in astrocytes that greatly impact how they are thought to regulate brain function, including the existence of widespread propagating intercellular Ca2+ waves, data suggesting that astrocytes signal to neurons through Ca2+-dependent release of glutamate, and evidence for the presence of vesicular machinery for the regulated exocytosis of gliotransmitters.
Autonomic Neurotransmission: 60 Years Since Sir Henry Dale
Authors: Burnstock Geoffrey
Published: October 2008

In the early twentieth century, Sir Henry Dale and others described brilliant studies of autonomic neurotransmission utilizing acetylcholine and noradrenaline. However, within the past 60 years, new discoveries have changed our understanding of the organization of the autonomic nervous system, including the structure and function of the nonsynaptic autonomic neuroeffector junction, the multiplicity of neurotransmitters, cotransmission, neuromodulation, dual control of vascular tone by perivascular nerves and endothelial cells, the molecular biology of receptors, and trophic signaling. Further, it is now recognized that an outstanding feature of autonomic neurotransmission is the inherent plasticity afforded by its structural and neurochemical organization and the interaction between expression of neural mediators and environmental factors. In this way, autonomic neurotransmission is matched to ongoing changes in demands and can sometimes be compensatory in pathophysiological situations.
Pharmacology of Nicotine: Addiction, Smoking-Induced Disease, and Therapeutics
Authors: Benowitz Neal L.
Published: October 2008

Nicotine sustains tobacco addiction, a major cause of disability and premature death. Nicotine binds to nicotinic cholinergic receptors, facilitating neurotransmitter release and thereby mediating the complex actions of nicotine in tobacco users. Dopamine, glutamate, and gamma aminobutyric acid release are particularly important in the development of nicotine dependence, and corticotropin-releasing factor appears to contribute to nicotine withdrawal. Nicotine dependence is highly heritable. Genetic studies indicate roles for nicotinic receptor subtypes, as well as genes involved in neuroplasticity and learning, in development of dependence. Nicotine is primarily metabolized by CYP 2A6, and variability in rate of metabolism contributes to vulnerability to tobacco dependence, response to smoking cessation treatment, and lung cancer risk. Tobacco addiction is much more common in persons with mental illness and substance abuse disorders, representing a high proportion of current smokers. Pharmacotherapeutic approaches to tobacco addiction include nicotine replacement, bupropion, and varenicline, the latter a selective nicotine receptor partial agonist.
Probiotics enhance pancreatic glutathione biosynthesis and reduce oxidative stress in experimental acute pancreatitis
Authors: Lutgendorff Femke , Trulsson Lena M. , van Minnen L. Paul , Rijkers Ger T. , Timmerman Harro M. , Franzén Lennart E. , Gooszen Hein G. , Akkermans Louis M. A. , Söderholm Johan D. , Sandström Per A.
Published: October 2008

Factors determining severity of acute pancreatitis (AP) are poorly understood. Oxidative stress causes acinar cell injury and contributes to the severity, whereas prophylactic probiotics ameliorate experimental pancreatitis. Our objective was to study how probiotics affect oxidative stress, inflammation, and acinar cell injury during the early phase of AP. Fifty-three male Sprague-Dawley rats were randomly allocated into groups: 1) control, 2) sham procedure, 3) AP with no treatment, 4) AP with probiotics, and 5) AP with placebo. AP was induced under general anesthesia by intraductal glycodeoxycholate infusion (15 mM) and intravenous cerulein (5 μg·kg−1·h−1, for 6 h). Daily probiotics or placebo were administered intragastrically, starting 5 days prior to AP. After cerulein infusion, pancreas samples were collected for analysis including lipid peroxidation, glutathione, glutamate-cysteine-ligase activity, histological grading of pancreatic injury, and NF-κB activation. The severity of pancreatic injury correlated to oxidative damage ( r = 0.9) and was ameliorated by probiotics (1.5 vs. placebo 5.5; P = 0.014). AP-induced NF-κB activation was reduced by probiotics (0.20 vs. placebo 0.53 OD450nm/mg nuclear protein; P < 0.001). Probiotics attenuated AP-induced lipid peroxidation (0.25 vs. placebo 0.51 pmol malondialdehyde/mg protein; P < 0.001). Not only was AP-induced glutathione depletion prevented (8.81 vs. placebo 4.1 μmol/mg protein, P < 0.001), probiotic pretreatment even increased glutathione compared with sham rats (8.81 vs. sham 6.18 μmol/mg protein, P < 0.001). Biosynthesis of glutathione (glutamate-cysteine-ligase activity) was enhanced in probiotic-pretreated animals. Probiotics enhanced the biosynthesis of glutathione, which may have reduced activation of inflammation and acinar cell injury and ameliorated experimental AP, via a reduction in oxidative stress.
Endothelin-3 stimulates survival of goblet cells in organotypic cultures of fetal human colonic epithelium
Authors: Kalabis Jiri , Li Gang , Fukunaga-Kalabis Mizuho , Rustgi Anil K. , Herlyn Meenhard
Published: October 2008

Cells within the normal human colonic epithelium undergo a dynamic cycle of growth, differentiation, and death. The organotypic culture system of human fetal colonic epithelial cells seeded on top of collagen gels with embedded colonic fibroblasts allowed prolonged culture of the colonic epithelial cells (Kalabis J, Patterson MJ, Enders GM, Marian B, Iozzo RV, Rogler G, Gimotty PA, Herlyn M. FASEB J 17: 1115–1117, 2003). Herein, we have evaluated the role of endothelin-3 (ET3) and both cognate endothelin receptors (ETRA, ETRB) for human colonic epithelial cell growth and survival. ET3 was produced continuously by the fibroblasts as a result of adenovirus-mediated gene transfer. The presence and function of the endothelin receptors (ETRs) in epithelial cells was evaluated by [3H]thymidine incorporation using primary epithelial cells in monoculture and by immunohistochemistry on human fetal and adult paraffin-embedded tissues. In organotypic culture, ET3 increased the number of goblet cells but not of enteroendocrine cells. The increase in goblet cells was caused by prolonged cell survival and differentiation. The inhibition of both ETRA and ETRB significantly decreased the number of goblet cells and proliferation in epithelial cells, whereas the number of enteroendocrine cells remained unchanged. ET3 induced activation of IκB and MAPK in the epithelial cells, suggesting that these signaling pathways mediate its proproliferation and prosurvival activities. Our results demonstrate that ET3 is involved in regulating human colonic epithelial cell proliferation and survival, particularly for goblet cells, and may be an important component of colonic homeostasis.
Calcium/calmodulin-dependent phosphorylation of tumor protein D52 on serine residue 136 may be mediated by CAMK2δ6
Authors: Chew Catherine S. , Chen Xunsheng , Zhang Hanfang , Berg Eric A. , Zhang Han
Published: October 2008

Tumor protein D52 is expressed at relatively high levels in cells within the gastrointestinal tract that undergo classical exocytosis and is overexpressed in several cancers. Current evidence supports a role for D52 in the regulation of vesicular trafficking. D52 function(s) are regulated by calcium-dependent phosphorylation; however, the intracellular mechanisms that mediate this process are not well characterized. The goal of this study was to identify the calcium-dependent phosphorylation site(s) in D52 and to characterize the protein kinase(s) that mediate this phosphorylation. Using mass spectrometry and site-directed mutagenesis, we identified a single amino acid residue, S136, that undergoes increased phosphorylation upon elevation of intracellular Ca2+concentration. A phosphospecific antibody (pS136) was produced and used to characterize D52 kinase activity in gastric mucosal, colonic T84, and HEK293 cells. By using D52 as a substrate, a protein kinase with a molecular weight ( Mr) of ∼50 kDa was identified with “in gel” assays. This kinase comigrated with rat brain calcium/calmodulin-dependent protein kinase (CAMK2)α cross-reacted with pan-specific CAMK2 antibodies as well as with anti-active CAMK2 (pT286/287) antibody when activated. Carbachol-stimulated phosphorylation of S136was inhibited by the CAMK2 inhibitor KN93 (IC5038 μM) and by the calmodulin antagonist W7 (IC503.3 nM). A previously uncharacterized CAMK2 isoform, CAMK2δ6, which has the same domain structure and Mras CAM2α, was identified in gastric mucosa by RT-PCR. The cloned, expressed protein comigrated with D52 kinase and colocalized with D52 protein in T84 and HEK293 cells. These findings support a role for CAMK2δ6 in the mediation of D52 phosphorylation.
Estrogen prevents intestinal inflammation after trauma-hemorrhage via downregulation of angiotensin II and angiotensin II subtype I receptor
Authors: Chen Jianguo , Yang Shaolong , Hu Shunhua , Choudhry Mashkoor A. , Bland Kirby I. , Chaudry Irshad H.
Published: October 2008

Although angiotensin II (Ang II) plays a key role in development of organ ischemia-reperfusion injury, it remains unclear whether it is involved in development of intestinal injury following trauma-hemorrhage (T-H). Studies have shown that 17β-estradiol (E2) administration following T-H improves small intestinal blood flow; however, it is unclear whether Ang II plays a role in this E2-mediated salutary effect. Male Sprague-Dawley rats underwent laparotomy and hemorrhagic shock (removal of 60% total blood volume, fluid resuscitation after 90 min). At onset of resuscitation, rats were treated with vehicle, E2, or E2 and estrogen receptor antagonist ICI 182,780 (ICI). A separate group of rats was treated with Ang II subtype I receptor (AT1R) antagonist losartan. At 24 h after T-H, plasma Ang II, IL-6, TNF-α, intercellular adhesion molecule (ICAM)-1, cytokine-induced neutrophil chemoattractant (CINC)-1 and CINC-3 levels, myeloperoxidase (MPO) activity, and AT1R expression were determined. T-H significantly increased plasma and intestinal Ang II, IL-6, TNF-α levels, intestinal ICAM-1, CINC-1, CINC-3 levels, MPO activity, and AT1R protein compared with shams. E2 treatment following T-H attenuated increased intestinal MPO activity, Ang II level, and AT1R protein expression. ICI administration abolished the salutary effects of E2. In contrast, losartan administration attenuated increased MPO activity without affecting Ang II and AT1R levels. Thus Ang II plays a role in producing small intestine inflammation following T-H, and the salutary effects of E2 on intestinal inflammation are mediated in part by Ang II and AT1R downregulation.
Mitochondrial apoptotic signaling is elevated in cardiac but not skeletal muscle in the obese Zucker rat and is reduced with aerobic exercise
Authors: Peterson Jonathan M. , Bryner Randall W. , Sindler Amy , Frisbee Jefferson C. , Alway Stephen E.
Published: October 2008

Mitochondrial apoptosis and apoptotic signaling modulations by aerobic training were studied in cardiac and skeletal muscles of obese Zucker rats (OZR), a rodent model of metabolic syndrome. Comparisons were made between left ventricle, soleus, and gastrocnemius muscles from OZR ( n = 16) and aged-matched lean Zucker rats (LZR; n = 16) that were untrained ( n = 8) or aerobically trained on a treadmill for 9 wk ( n = 8). Cardiac Bcl-2 protein expression levels were ∼50% lower in the OZR compared with the LZR, with no difference in either of the skeletal muscles. Bax protein expression levels were similar in skeletal muscles of the OZR compared with the LZR. Furthermore, mitochondrial apoptotic signaling was not different in skeletal muscles of OZR and LZR groups. However, there was an approximate sevenfold increase in the Bax protein accumulation in the myocardial mitochondrial-rich protein fraction of the OZR compared with the LZR. Additionally, there was an increase in cytosolic cytochrome c released from the mitochondria, caspase-9 and caspase-3 activity, with a corresponding elevation in DNA fragmentation in the cardiac muscles of the OZR compared with the LZR. Exercise training reduced cardiac Bax protein levels, the mitochondrial localization of Bax, cytosolic cytochrome c, caspase activity, and DNA fragmentation in cardiac muscles of the OZR after exercise, with no change in the skeletal muscles. These data show that mitochondrial apoptosis is elevated in the cardiac but not skeletal muscles of the OZR, but aerobic exercise training was effective in reducing cardiac mitochondrial apoptotic signaling.
Partitioning of nasal and pulmonary resistance changes during noninvasive plethysmography in mice
Authors: Agrawal Anurag , Singh Shashi Kant , Singh Vijay Pal , Murphy Edward , Parikh Indu
Published: October 2008

Double-chamber plethysmography is a well established noninvasive method of assessing airflow obstruction in small lab animals. It allows measurement of the specific airway resistance (sRaw), which unlike enhanced pause (Penh), is a meaningful airway mechanics parameter. Since sRaw is measured in spontaneously breathing mice, a limitation of the method is the inability to exclude nasal resistance changes. We recently showed that mice are not truly obligate nasal breathers and that after nasal occlusion, nasally breathing mice can transition to an oral mode of breathing. We now show that it is experimentally possible to algebraically separate the average nasal and pulmonary (including laryngeal) components of total airway resistance change by a series of measurements made across groups of mice breathing nasally or orally, assuming that oral resistance remains constant. Using this approach, we show that nasal resistance change comprises one-half or more of the total resistance change during methacholine challenge. Inhibition of mucin secretion from airway goblet cells attenuates pulmonary but not nasal airway hyperresponsiveness (AHR), and nasal AHR in a murine model of rhinitis may be related to edema.
Effects of exercise training and hypercholesterolemia on adenosine activation of voltage-dependent K+channels in coronary arterioles
Authors: Heaps Cristine L. , Jeffery Elise C. , Laine Glen A. , Price Elmer M. , Bowles Douglas K.
Published: October 2008

Coronary arterioles from hypercholesterolemic swine display attenuated adenosine-mediated vasodilatation that is attributable to the elimination of voltage-dependent K+(Kv) channel stimulation. For the present study, we tested the hypotheses that exercise training would correct impaired adenosine-induced dilatation in coronary arterioles from hypercholesterolemic pigs through restoration of adenosine activation of Kv channels and that vasodilatation to the receptor-independent adenylyl cyclase activator, forskolin, would also be attenuated in arterioles from hypercholesterolemic pigs. Pigs were randomly assigned to a control (NC) or high-fat, high-cholesterol (HC) diet for 20 wk. Four weeks after the diet was initiated, pigs from both groups were assigned to exercise training (Ex; 5 days/wk for 16 wk) or sedentary (Sed) protocols, resulting in four groups of pigs: NC-Sed, NC-Ex, HC-Sed, and HC-Ex. Arterioles (∼150 μm) from both HC-Sed and HC-Ex pigs displayed impaired adenosine-mediated dilatation that was attributable to the elimination of 4-aminopyridine (4-AP; 1 mM)-sensitive Kv channel activation compared with NC counterparts. Arteriolar smooth muscle whole cell Kv currents were significantly reduced in HC-Sed compared with NC-Sed, although HC-Ex and NC-Ex did not differ. Forskolin-mediated dilatation was attenuated by 4-AP (1 mM) and in a concentration-dependent manner by tetraethylammonium (TEA; 0.1–1 mM) in NC-Sed but not HC-Sed. Further, TEA-sensitive Kv currents were diminished in cells of HC-Sed compared with NC-Sed pigs. Quantitative RT-PCR revealed similar expression levels of Kv3.1 and 3.3 in arterioles of NC-Sed and HC-Sed swine with undetectable expression of Kv1.1, 3.2, and 3.4. Taken together, these results suggest that hypercholesterolemia-mediated attenuation of adenosine-induced vasodilatation in coronary arterioles is not corrected by exercise training and is likely attributable to an impairment in the pathway coupling adenylyl cyclase with a highly TEA-sensitive Kv channel isoform(s).
Effect of resistance exercise on muscle steroidogenesis
Authors: Vingren Jakob L. , Kraemer William J. , Hatfield Disa L. , Anderson Jeffrey M. , Volek Jeff S. , Ratamess Nicholas A. , Thomas Gwendolyn A. , Ho Jen-Yu , Fragala Maren S. , Maresh Carl M.
Published: October 2008

Circulating testosterone is elevated acutely following resistance exercise (RE) and is an important anabolic hormone for muscle adaptations to resistance training. The purpose of this study was to examine the acute effect of heavy RE on intracrine muscle testosterone production in young resistance-trained men and women. Fifteen young, highly resistance-trained men ( n = 8; 21 ± 1 yr, 175.3 ± 6.7 cm, 90.8 ± 11.6 kg) and women ( n = 7; 24 ± 5 yr, 164.6 ± 6.7 cm, 76.4 ± 15.6 kg) completed 6 sets of 10 repetitions of Smith machine squats with 80% of their 1-repetition maximum. Before RE and 10 and 70 min after RE, muscle biopsies were obtained from the vastus lateralis. Before RE, after 3 and 6 sets of squats, and 5, 15, 30, and 70 min into recovery from RE, blood samples were obtained using venipuncture from an antecubital vein. Muscle samples were analyzed for testosterone, 17β-hydroxysteroid dehydrogenase (HSD) type 3, and 3β-HSD type 1 and 2 content. Blood samples were analyzed for glucose and lactate concentrations. No changes were found for muscle testosterone, 3β-HSD type 1 and 2, and 17β-HSD type 3 concentrations. However, a change in protein migration in the Bis-Tris gel was observed for 17β-HSD type 3 postexercise; this change in migration indicated an ∼2.8 kDa increase in molecular mass. These findings indicate that species differences in muscle testosterone production may exist between rats and humans. In humans, muscle testosterone concentrations do not appear to be affected by RE. This study expands on the current knowledge obtained from animal studies by examining resting and postexercise concentrations of muscle testosterone and steroidogenic enzymes in humans.
Septic Acute Kidney Injury: New Concepts
Authors: Bellomo Rinaldo , Wan Li , Langenberg Christoph , May Clive
Published: October 2008

Acute kidney injury (AKI) is a serious condition that affects many ICU patients. The most common causes of AKI in ICU are severe sepsis and septic shock. The mortality of AKI in septic critically ill patients remains high despite of our increasing ability to support vital organs. This is partly due to our poor understanding of the pathogenesis of sepsis-induced renal dysfunction. However, new concepts are emerging to explain the pathogenesis of septic AKI, which challenge previously held dogma. Throughout the past half century, septic AKI has essentially been considered secondary to kidney ischemia. However, recent models of experimental sepsis have challenged this notion by demonstrating that, in experimental states, which simulate the hemodynamic picture most typically seen in man (e.g. hyperdynamic sepsis) renal blood flow, actually increases as renal vascular resistance decreases. These experimental observations provide proof of concept that septic AKI can occur in the setting of renal hyperemia and that ischemia is not necessary for loss of glomerular filtration rate (GFR) to occur. They also suggest that similar hemodynamic event may occur in man. In addition, preliminary studies in septic sheep show that, when ATP is measured using an implanted phosphorus coil and magnetic resonance technology, renal bioenergetics are preserved in the setting of advanced septic shock. While these findings need to be confirmed, they challenge established paradigms and offer a new conceptual framework of reference for further investigation and intervention in man.
The Bioartificial Kidney and Bioengineered Membranes in Acute Kidney Injury
Authors: Ding Feng , Humes H. David
Published: October 2008

The treatment of severe acute kidney injury (AKI) with dialysis or hemofiltration remains suboptimal with high levels of morbidity and mortality. Current renal replacement therapies substitute for the small solute clearance function of the kidney but do not replace the lost reclamation, metabolic and endocrine functions of this organ. Cell therapy and tissue engineering offer hope of fuller replacement of kidney function in renal failure patients. A renal tubule assist device (RAD) that includes a conventional hemodialysis filter and a bioreactor containing living renal proximal tubule cells has been successfully engineered. Differentiated activity of these cells and survival advantages have been demonstrated in large-animal models of sepsis and AKI. Data from phase I/II and phase II clinical studies have shown that the addition of renal tubule cell therapy to conventional continuous renal replacement therapy (CRRT) treatment resulted in a significant clinical impact on survival, and that RAD treatment demonstrated an acceptable safety profile. Another substantive advance for the treatment of AKI will be the development of nanofabrication technology to further improve the clearance function of the kidney to replicate glomerular permselectivity while retaining high rates of hydraulic permeability. New developments in this translational research area will improve the unmet medical needs of patients with renal failure.
Distant-Organ Changes after Acute Kidney Injury
Authors: Feltes Carolyn M. , Van Eyk Jennifer , Rabb Hamid
Published: October 2008

Acute kidney injury (AKI) contributes significantly to morbidity and mortality in both adults and children. While clinical data suggest that AKI contributes to and exacerbates multiorgan failure, the physiologic and molecular mechanisms responsible for these interactions were previously unknown. New data linking AKI with distant-organ dysfunction includes evidence that inflammatory cascades are abnormal after organ injury. Leukocyte trafficking, cytokine expression, cell adhesion-molecule expression and membrane ion and water-channel expression in distant organs are deranged after kidney injury. The responses to oxidative stress after AKI are also altered, suggesting complex mechanisms of crosstalk between the injured kidney and distant organs. Novel methodologies, including genomics and proteomics, are now being employed to unravel interorgan communication to accelerate clinically meaningful discovery for this serious disease.
Emerging Therapies for Extracorporeal Support
Authors: Bouchard Josée , Khosla Nitin , Mehta Ravindra L.
Published: October 2008

Dialytic therapies have undergone major technological developments in the last decade and emerging techniques are promoted not only for acute kidney injury, but also for sepsis, acute decompensated heart failure, and acute and acute-on-chronic liver failure. New devices specifically target the pathophysiological mechanisms involved in these conditions. In septic shock and sepsis, high-volume hemofiltration, coupled plasma filtration adsorption, cascade hemofiltration and high permeability hemofiltration enhance removal of pro-inflammatory mediators, while in liver failure, Molecular Adsorbents recycling System (MARS®) and Prometheus® favor the elimination of albumin-bound toxins such as bilirubin. In acute decompensated heart failure, simplified ultrafiltration machines are used to reach negative fluid balance in a minimalist setting. In the context of limited resources and growing expansion in the availability of technologies, a critical assessment is required and the use of these devices needs to be put in perspective. This article reviews the mechanisms, advantages and limitations of these techniques along with the current evidence available regarding their influence on major clinical outcomes.
Weaning Preterm Infants from Mechanical Ventilation
Authors: Bancalari Eduardo , Claure Nelson
Published: October 2008

Mechanical ventilatory support is required by a large number of neonates in respiratory failure. However, its use in preterm infants is frequently associated with acute complications and long-term respiratory sequelae. Therefore, it is recommended to avoid or limit the exposure to ventilatory support. This is a review of existing practices and novel strategies to achieve weaning of ventilatory support in this population.
Non-Erosive Reflux Disease – Defining the Entity and Delineating the Management
Authors: Modlin Irvin M. , Hunt Richard H. , Malfertheiner Peter , Moayyedi Paul , Quigley Eamon M. , Tytgat Guido N.J. , Tack Jan , Holtmann Gerald , Moss Steven F.
Published: October 2008

In the developed world, most patients with gastroesophageal reflux disease (GERD) do not exhibit erosions when examined by standard white light endoscopy. Despite the high prevalence of such non-erosive reflux disease (NERD), relatively little is known of its underlying pathophysiology, hence there is no clear guide to clinical management. To establish areas of agreement or uncertainty in NERD, an international meeting was held in Vevey, Switzerland, in late 2007. The goal was to document current thinking in the areas of clinical presentation, assessment of clinical outcome, pathobiological mechanisms, and define optimal clinical strategies to diagnose and manage NERD. After extensive debates, the modified Delphi technique was utilized to reach a consensus on 85 specific statements. In addition, it was proposed that NERD be defined as ‘a subcategory of GERD characterised by troublesome reflux-related symptoms in the absence of esophageal mucosal erosions/breaks at conventional endoscopy and without recent acid suppressive therapy’. Evidence in support of this diagnosis may include responsiveness to acid suppression therapy, abnormal reflux monitoring or the identification of specific novel endoscopic findings. Defining the current state of knowledge in NERD should help improve the elucidation and management of this condition in the future.
Epidemiology of Non-Erosive Reflux Disease
Authors: El-Serag Hashem B.
Published: October 2008

Non-erosive reflux disease (NERD) is a relatively new entity, the definition of which has been evolving and involves the use of symptoms, endoscopy, and objective evidence of reflux or reflux-related damage. The closest entity to NERD that is examined by available epidemiologic studies is defined by the presence of gastroesophageal reflux disease (GERD) symptoms in the absence of esophageal erosions or Barrett’s esophagus. In this review, I identified two population-based studies, one non-community study, and several endoscopy-based studies that provided information on several aspects of NERD. Most of GERD is NERD (50–85%), and therefore one can estimate 11–12% of the general population and considerably higher proportions of patients presenting to endoscopy (37–87%) may have NERD. Risk factors for NERD including absence of hiatus hernia, low BMI, and presence of Helicobacter pylori indicate that it is a ‘milder’ part of the GERD spectrum. Other associations of NERD include younger age, female sex, and psychological comorbidities that resemble those of functional gut disorders. The temporal trends in NERD are unclear, and are probably increasing because GERD symptom prevalence has increased.
Structural Abnormalities of Endoscopy-Negative Reflux Disease – Real or Perceived?
Authors: Vieth Michael
Published: October 2008

About two thirds of individuals affected by gastroesophageal reflux disease suffer from endoscopy-negative esophageal reflux disease. Often, these individuals do not receive adequate medication. In contrast, erosive reflux disease is much better defined and even subclassified as mucosal breaks of the esophageal epithelium. It is known from large trials that gastroesophageal reflux disease is probably not a categorical disease without further progression. On the other hand, the first structural changes of the esophageal epithelium indicating the beginning of reflux disease are unknown. Furthermore, it is not known when reflux esophagitis is structurally healed (besides symptom relief). Histological markers are based on observations made without clinical correlation. It has gradually become clear that there are no specific reflux-induced esophageal lesions. All described histological criteria can be also observed in other esophageal conditions. Structural abnormalities are believed to be found more often close to the lesser gastric curvature or the right esophageal wall. Furthermore, it could be shown with a standardized biopsy protocol that a good correlation with clinical findings is possible. Conventional histological criteria include thickness of basal cell layer, length of papillae and inflammatory infiltrates. New criteria include dilation of intercellular spaces and changes of protein distribution within intercellular spaces. All changes are reversible with PPI therapy. In conclusion, structural abnormalities are not specific for gastroesophageal reflux disease or NERD but are reversible with PPI, which underlines their relevance.
Is There a Unifying Role for Visceral Hypersensitivity and Irritable Bowel Syndrome in Non-Erosive Reflux Disease?
Authors: Tack Jan
Published: October 2008

Non-erosive reflux disease (NERD) is a common condition, characterized by symptoms that are attributable to reflux of gastric content into the esophagus in the absence of erosive lesions in the distal esophagus. The underlying pathophysiology is considered to be multifactorial. This review summarizes the current understanding of the role of visceral hypersensitivity in the pathogenesis of NERD symptoms and the mechanisms implicated in the pathogenesis of esophageal hypersensitivity.
Economic Reflections on Proton Pump Inhibitor Therapy for Non-Erosive Reflux Disease
Authors: Moayyedi Paul
Published: October 2008

Proton pump inhibitor (PPI) therapy for gastroesophageal reflux disease is a good example of the evolution of economic analysis. Initial studies were simple models constructed on spreadsheets and described the most cost-effective therapy in terms of cost per cure of esophagitis. This tells a third-party payer what is the most efficient approach to healing esophagitis (technical efficiency) but does not give any indication of whether treating esophagitis is good value for money in the first place or whether health care dollars would be better spent in treating other diseases (allocative efficiency). As economic analyses became more sophisticated, more complex models were constructed. Outcomes were expressed in terms of cost per quality-adjusted life year gained or the question was framed in terms of the probability a strategy would be cost effective depending on willingness to pay for a month free from symptoms. These approaches answer the question of whether treating gastroesophageal reflux disease is good value for money. Models have traditionally evaluated treatment of esophagitis, but this does not address the most efficient therapy of non-erosive reflux disease. This article describes a simplified model (for illustrative purposes only) and suggests that PPI therapy is a cost-effective approach for the treatment of esophagitis whether generic or proprietary PPI costs are applied. PPI therapy is also likely to be a cost-effective strategy for non-erosive reflux disease at generic but not at proprietary prices.
When Child Development Meets Economic Game Theory: An Interdisciplinary Approach to Investigating Social Development
Authors: Gummerum Michaela , Hanoch Yaniv , Keller Monika
Published: October 2008

Game theory has been one of the most prominent theories in the social sciences, influencing diverse academic disciplines such as anthropology, biology, economics, and political science. In recent years, economists have employed game theory to investigate behaviors relating to fairness, reciprocity, and trust. Surprisingly, this research has not found much resonance in psychological research on social development, even though the two disciplines share a common interest in explaining similar social behaviors and phenomena. We argue that combining economic game theory with developmental psychology can prove to be valuable for both disciplines: developmental psychology can contribute its knowledge about the ontogenesis of social abilities and competencies to economic research, thus providing economists with new theories and understanding. Game theory, on the other hand, can offer developmental psychologists new methodologies and tools for investigating social development.
Prevalence of Waterpipe Smoking among Rural Pregnant Women in Southern Iran
Authors: Mirahmadizadeh Alireza , Nakhaee Nouzar
Published: October 2008

Objective: To estimate the prevalence of waterpipe smoking among rural pregnant women in Southern Iran and to identify the impact of maternal waterpipe smoking on baby’s birth weight. Subjects and Methods: A population-based survey was conducted in rural areas of Southern Iran in 2004 using existing health records and interviewing all mothers during the 10 days after delivery. Maternal exclusion criteria included cigarette smoking during pregnancy, a history or occurrence of epilepsy, diabetes and hypertension (gestational and/or essential) during pregnancy, factors that have been proved to have detrimental effects on birth weight. Results: Of the 2,808 mothers interviewed, 224 (8%) were waterpipe smokers of which 90 (3.2%) and 134 (4.8%) were occasional (smoking less than once per day) and daily (at least once per day) smokers, respectively. Six hundred and seventy-four (24%) were passively exposed to waterpipe smoke during pregnancy and 322 (11.5%) were exposed to second-hand cigarette smoke. Mothers who started smoking during the first trimester had lower birth weight babies (3,215 ± 612 g) compared to those who started smoking during the second or third trimesters (3,447 ± 550 g, p = 0.04). Conclusion: Waterpipe smoking during pregnancy is prevalent in Southern Iran and appears to be a risk factor for low birth weight babies.
Technetium-99m-Labelled Sulesomab (LeukoScan) in the Evaluation of Soft Tissue Infections
Authors: Quigley Anne-Marie , Gnanasegaran Gopinath , Buscombe John R. , Hilson Andrew J.W.
Published: October 2008

Objective: To perform a retrospective review of all patients receiving technetium-99m (99mTc)-labelled sulesomab over a 4-year period to determine if soft tissue infections can be accurately identified. Methods and Materials: We reviewed the results of 124 99mTc-sulesomab studies performed over a 4-year period. Of these, 34 were performed for undiagnosed fever in which soft tissue infection was suspected to be the main cause. The patients’ clinical notes, microbiology reports and other imaging findings were reviewed to determine the clinical outcome following the scan. The scans were regarded as being true-positives if (i) uptake correlated with the site from which fluid or tissue was obtained and which grew bacteria, and/or (ii) the site of abnormality was reported as having an infection on other imaging or (iii) there was a clinical correlation with the referring clinician’s evaluation of the patient. Planar imaging was performed using standard protocols, together with single-photon emission computed tomography (if required) at 1 and 4 h after injection of 20–30 mCi (740–1,110 MBq) 99mTc-sulesomab. Results: Three patients were unevaluable. In the remaining 31 patients, 21 99mTc-sulesomab studies were regarded as true-positives and 6 patients had true-negative scans. One patient had a false-positive scan (abnormal uptake with negative microbiology) and 3 had false-negative scans (infection confirmed but a negative scan). Conclusion: In suspected soft tissue infection, 99mTc-sulesomab imaging has a sensitivity of 88% with a specificity of 86% and overall accuracy of 87%. 99mTc-sulesomab provides an accurate method of imaging for suspected soft tissue infection, which is also fast and convenient, as cell labelling is not required.
The Role of CYP2C9 Gene Polymorphisms on Anticoagulant Therapy after Heart Valve Replacement
Authors: Yıldırım Hatice , Tamer Lülüfer , Sucu Nehir , Atik Uğur
Published: October 2008

Objective: The aim of the present study was to investigate the role of CYP2C9 gene polymorphisms after heart valve replacement in a group of patients on warfarin therapy. Materials and Methods: The study population consisted of 74 patients with heart valve replacement. Peripheral blood was collected into evacuated tubes containing EDTA, and DNA was extracted from circulating leukocytes by using a high pure PCR template preparation kit. CYP2C9*2, CYP2C9*3 alleles were detected by using real-time PCR. Results: The patients with CYP2C9*1/*3 and CYP2C9*2/*3 genotypes were taking 28.21 and 24.47 mg, respectively, as mean weekly warfarin dose, whereas patients with CYP2C9*1/*1 genotype were taking 33.90 mg. Conclusion: The data show that patients with CYP2C9*1/*3 and CYP2C9*2/*3 genotypes needed a lower maintenance dose of warfarin than patients with CYP2C9*1/*1 wild-type genotype.
Endobronchial Metastasis from Testicular Seminoma
Authors: Özsu Savaş , Erol M. Muharrem , Öztuna Funda , Ersöz Şafak , Kavgacı Halil , Aksoy Hamit Z.
Published: October 2008

Objective: To present a case of endobronchial metastasis from a seminoma mimicking a primary pulmonary mass on X-ray radiograph. Clinical Presentation and Intervention: A 27-year-old man presented with a 1-month history of hemoptysis. Thorax computerized tomography of the patient obtained at the level of the main right bronchi demonstrated a mass with a size of 7 × 6 cm and a peripheral lobulated nodule. Bronchoscopic examination showed narrowing and multiple nodules in the right upper and right intermediary lobar bronchi. Histopathological examination of bronchial biopsies and brushing confirmed endobronchial metastasis of the testicular seminoma. Conclusion: This case shows the prognostic significance of distinguishing endobronchial metastasis from primary lung carcinoma.
Oxaliplatin/5-Fluorouracil/Leucovorin (FOLFOX4) Regimen as an Adjuvant Chemotherapy in the Treatment of Advanced Jejunal Adenocarcinoma: A Report of 2 Cases
Authors: Chen Chao-Wen , Wang Wen-Ming , Su Yu-Chung , Wu Jeng-Yih , Hsieh Jan-Sing , Wang Jaw-Yuan
Published: October 2008

Objective: To present our clinical experience of 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX4) regimen administered as an adjuvant chemotherapy to 2 patients with advanced jejunal adenocarcinoma. Case Presentation and Intervention: A 55-year-old woman presented with recurrent upper abdominal pain, nausea and vomiting. A small bowel series as well as the abdominal computed tomography scan revealed an irregular narrowing lesion at the proximal jejunum. The patient then underwent an exploratory laparotomy and the jejunal adenocarcinoma with localized peritoneal metastasis was found (R0 resection, T3N1M1, stage IV). Chemotherapy with FOLFOX4 regimen of 12 cycles was initiated after the curative resection. No adverse event was observed during the period of chemotherapy. She has been well without evidence of recurrence for over 20 months postoperatively. The second case was a 77-year-old female presenting with mechanical ileus. Surgical exploration revealed a proximal jejunal adenocarcinoma with regional lymph node involvement (R0 resection, T3N1M0, stage III). She also received the FOLFOX4 chemotherapy of 12 cycles with an uneventful course. No obvious toxicity developed except for temporary grade I peripheral neuropathy and skin eruption. This patient has survived well and has been free of this disease for over 12 months since the operation. Conclusion: This report showed that adjuvant chemotherapy with FOLFOX4 regimen seems effective and well tolerated in these 2 patients with advanced jejunal adenocarcinoma. Further investigation of a large number of patients with long-term follow-up is needed to confirm these findings.