bluuebunny/crossref_metadata_2025 huggingface dataset:
z-SCALING AND JET PRODUCTION IN HADRON–HADRON COLLISIONS AT HIGH ENERGIES
Authors: TOKAREV M. V. , DEDOVICH T. G.
Published: August 2004

Inclusive jet production in [Formula: see text] and pp collisions at high energies in the framework of the concept of z-scaling is studied. The available experimental data on the cross-section of jet production obtained by the UA1, UA2, CDF and D0 Collaborations are used for analysis. The scaling function ψ(z) is expressed via inclusive cross-section Ed3σ/dq3 and jet multiplicity density ρ(s,η). The properties of z-scaling, the energy and angular independence of ψ(z) and the power behavior, ψ(z)~z-α, of jet and dijet production were found. Based on the properties of z-scaling, the dependence of the cross-section of jets produced in [Formula: see text] and pp collisions on transverse momentum q⊥ over the central range is predicted. The obtained results can be of interest for future experiments planned at RHIC, LHC, HERA and Tevatron to search for new phenomena in hadron–hadron, hadron–nucleus and nucleus–nucleus collisions.
INTERACTIONS OF A STRING INSPIRED GRAVITON FIELD
Authors: BRANSON THOMAS P. , RODGERS V. G. J. , YASUDA TAKESHI
Published: August 2004

We continue to explore the possibility that the graviton in two dimensions is related to a quadratic differential that appears in the anomalous contribution of the gravitational effective action for chiral fermions. A higher dimensional analog of this field might exist as well. We improve the defining action for this diffeomorphism tensor field and establish a principle for how it interacts with other fields and with point particles in any dimension. All interactions are related to the action of the diffeomorphism group. We discuss possible interpretations of this field.
A CALOGERO–SUTHERLAND MODEL BASED ON THE APERIODIC VIRASORO ALGEBRA
Authors: TWAROCK REIDUN
Published: August 2004

We derive a new model of Calogero–Sutherland type based on the aperiodic Virasoro algebra, which is an aperiodic analog of the Virasoro algebra with generators in a one-to-one correspondence with an aperiodic point set. It is shown that the Hamiltonian obtained in this setting contains an additional term with respect to the corresponding model based on the Virasoro algebra, and may thus be considered as a perturbation of the latter. The solvability of the model follows from the results about the highest weight representations of the aperiodic Virasoro algebra. The additional term in the Hamiltonian is shown to depend on a parameter, which is given in terms of model specific data such as a representation number, and a set of operators which appear as a consequence of the aperiodic setting in the framework of oscillator representations.
NONCOMMUTATIVE GEOMETRY, QUANTIZATION AND TOPOLOGICAL ASPECTS OF A FERMION
Authors: GHOSH P. , BANDYOPADHYAY P.
Published: August 2004

It is pointed out here that noncommutative geometry having the space–time manifold X=M4×Z2 leads to the quantization of a fermion when the discrete space–time is incorporated as an internal variable. The chiral description of fermions in this geometry necessitates the introduction of a disconnected gauge group for the external Abelian field interacting with the matter field in a chiral symmetric way. The symmetry breaking then gives rise to chiral anomaly which is responsible for the topological origin of mass and is linked up with the nonvanishing value of the Berry phase.
TOPOLOGICAL ASPECTS OF CHIRAL ANOMALY, ORIGIN OF MASS AND ELECTROWEAK THEORY
Authors: BANDYOPADHYAY PRATUL
Published: August 2004

It is here shown that the topological property of a fermion which gives rise to the fermion number and is related to chiral anomaly may be taken to lead to weak interaction gauge bosons when currents are written in chiral form. The gauge bosons attain mass topologically through the generation of internal helicities and thus no Higgs scalar is needed to have spontaneous symmetry breaking. Moreover the group structure SU(2)×U(1) is inbuilt here for electroweak unification. The Weinberg angle gets a physical meaning and strangeness changing neutral lepton current interaction is automatically forbidden. This formalism also suggests that at very high temperature, weak interaction will be of long range in nature.
Mechanism of CO Tolerance on Molybdenum-Based Electrocatalysts for PEMFC
Authors: Santiago Elisabete I. , Batista Marcelo S. , Assaf Elisabete M. , Ticianelli Edson A.
Published: August 2004

In this work, the mechanism of CO tolerance for the hydrogen oxidation reaction (HOR) was investigated on Mo-based carbon dispersed electrocatalysts (Mo/C and PtMo/C). Gas-diffusion electrodes with a diffusion layer formed by Mo/C and a catalyst layer composed by Pt/C, PtRu/C, or PtMo/C, showed enhanced electrocatalytic activity for the HOR in the presence of CO. This phenomenon was associated to a lowering of the CO concentration in the gas channel of the electrodes promoted by a water gas shift (WGS) reaction taking place in the Mo/C layer. The occurrence of this reaction was confirmed by gas chromatographic analyses of the CO content, conducted at the outlet of a Mo/C reactor operating at 100°C and fed with different

H

2

O
/

H

2

/
CO
/

CO

2

mixtures. Experiments made in the presence of

CO

2

indicated an additional CO poisoning effect due to the reversing of the WGS reaction, but the Mo-based electrodes still showed a performance superior to that of the standard state-of-the-art PtRu/C. © 2004 The Electrochemical Society. All rights reserved.
Sex modifies exercise and cardiac adaptation in mice
Authors: Konhilas John P. , Maass Alexander H. , Luckey Stephen W. , Stauffer Brian L. , Olson Eric N. , Leinwand Leslie A.
Published: August 2004

How an individual's sex and genetic background modify cardiac adaptation to increased workload is a topic of great interest. We systematically evaluated morphological and physiological cardiac adaptation in response to voluntary and forced exercise. We found that sex/gender is a dominant factor in exercise performance (in two exercise paradigms and two mouse strains) and that females of one of these strains have greater capacity to increase their cardiac mass in response to similar amounts of exercise. To explore the biochemical mechanisms for these differences, we examined signaling pathways previously implicated in cardiac hypertrophy. Ca2+/calmodulin-dependent protein kinase (CaMK) activity was significantly greater in males compared with females and increased after voluntary cage-wheel exposure in both sexes, but the proportional increase in CaMK activity was twofold higher in females compared with males. Phosphorylation of glycogen synthase kinase-3β (GSK-3β) was evident after 7 days of cage-wheel exposure in both sexes and remained elevated in females only by 21 days of exercise. Despite moderate increases in myocyte enhancer factor-2 (a downstream effector of CaMK) transcriptional activity and phosphorylation of Akt with exercise, there were no sex differences. Mitogen-activated protein kinase signaling components (p38 mitogen-activated protein kinase and extracellular regulated kinase 1/2) were not different between male and female mice and were not affected by exercise. We conclude that females have increased exercise capacity and increased hypertrophic response to exercise. We have also identified sex-specific differences in hypertrophic signaling within the cardiac myocyte that may contribute to sexual dimorphism in exercise and cardiac adaptation to exercise.
Endothelial cell PECAM-1 confers protection against endotoxic shock
Authors: Maas Matthias , Stapleton Michelle , Bergom Carmen , Mattson David L. , Newman Debra K. , Newman Peter J.
Published: August 2004

Platelet endothelial cell adhesion molecule-1 (PECAM-1; CD31) is a 130-kDa member of the Ig superfamily that is expressed on platelets and leukocytes and is highly enriched at endothelial cell-cell junctions. Previous studies showed that this vascular cell adhesion and signaling receptor functions to regulate platelet activation and thrombosis, to suppress apoptotic cell death, to mediate transendothelial migration of leukocytes, and to maintain the integrity of the vasculature. Because systemic exposure to the bacterial endotoxin LPS triggers an acute inflammatory response that involves many of these same processes, we compared the pathophysiological responses of wild-type versus PECAM-1-deficient mice to LPS challenge. We found that PECAM-1-deficient mice were significantly more sensitive to systemic LPS administration than their wild-type counterparts and that the lack of PECAM-1 expression at endothelial cell-cell junctions could account for the majority of the increased LPS-induced mortality observed. The diverse functional roles played by PECAM-1 in thrombosis, inflammation, apoptosis, and the immune response may make this molecule an attractive target for the development of novel therapeutics to manage and treat endotoxic shock.
Fractalkine/CX3CL1 production by human airway smooth muscle cells: induction by IFN-γ and TNF-α and regulation by TGF-β and corticosteroids
Authors: Sukkar Maria B. , Issa Razao , Xie Shaoping , Oltmanns Ute , Newton Robert , Chung Kian Fan
Published: August 2004

Chemokine synthesis by airway smooth muscle cells (ASMC) may be an important process underlying inflammatory cell recruitment in airway inflammatory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Fractalkine (FKN) is a recently described CX3C chemokine that has dual functions, serving as both a cell adhesion molecule and a chemoattractant for monocytes and T cells, expressing its unique receptor, CX3CR1. We investigated FKN expression by human ASMC in response to the proinflammatory cytokines IL-1β, TNF-α, and IFN-γ, the T helper 2-type cytokines IL-4, IL-10, and IL-13, and the fibrogenic cytokine transforming growth factor (TGF)-β. Neither of these cytokines alone had any significant effect on ASMC FKN production. Combined stimulation with IFN-γ and TNF-α induced FKN mRNA and protein expression in a time- and concentration-dependent manner. TGF-β had a significant inhibitory effect on cytokine-induced FKN mRNA and protein expression. Dexamethasone (10−8–10−6M) significantly upregulated cytokine-induced FKN mRNA and protein expression. Finally, we used selective inhibitors of the mitogen-activated protein kinases c-Jun NH2-terminal kinase (JNK) (SP-610025), p38 (SB-203580), and extracellular signal-regulated kinase (PD-98095) to investigate their role in FKN production. SP-610025 (25 μM) and SB-203580 (20 μM), but not PD-98095, significantly attenuated cytokine-induced FKN protein synthesis. IFN-γ- and TNF-α-induced JNK phosphorylation remained unaltered in the presence of TGF-β but was inhibited by dexamethasone, indicating that JNK is not involved in TGF-β- or dexamethasone-mediated regulation of FKN production. In summary, FKN production by human ASMC in vitro is regulated by inflammatory and anti-inflammatory factors.
Vascular changes after intra-amniotic endotoxin in preterm lamb lungs
Authors: Kallapur Suhas G. , Bachurski Cindy J. , Cras Timothy D. Le , Joshi Shubhada N. , Ikegami Machiko , Jobe Alan H.
Published: August 2004

Chorioamnionitis is associated with preterm delivery and bronchopulmonary dysplasia (BPD), characterized by impaired alveolar and pulmonary vascular development and vascular dysfunction. To study the vascular effects in a model of chorioamnionitis, preterm lambs were exposed to 20 mg of intra-amniotic endotoxin or saline for 1, 2, 4, or 7 days and delivered at 122 days gestational age (term = 150 days). This intra-amniotic endotoxin dose was previously shown to induce lung maturation. The effect of intra-amniotic endotoxin on expression of endothelial proteins was evaluated. Muscularization of the media and collagen deposition in adventitia of small pulmonary arteries was used to assess vascular remodeling. Compared with controls, bronchoalveolar lavage fluid protein content was increased 2 days after intra-amniotic endotoxin exposure. Vascular endothelial growth factor (VEGF) 165 isoform mRNA decreased 2–4 days after intra-amniotic endotoxin. VEGF, VEGF receptor-2, endothelial nitric oxide synthase (eNOS), platelet endothelial cell adhesion molecule-1, and Tie-2 protein expression in the lung coordinately decreased 1–7 days after intra-amniotic endotoxin. Intra-amniotic endotoxin appeared to selectively decrease eNOS expression in small pulmonary vessels compared with large vessels. Medial smooth muscle hypertrophy and increased adventitial fibrosis were observed 4 and 7 days after intra-amniotic endotoxin. These results demonstrate that, in the preterm lamb lung, antenatal inflammation inhibits endothelial cell protein expression followed by vascular remodeling changes in small pulmonary arteries. Exposure to antenatal inflammation may cause vascular remodeling and contribute to the development of BPD.
Early response to bleomycin is characterized by different cytokine and cytokine receptor profiles in lungs
Authors: Cavarra Eleonora , Carraro Fabio , Fineschi Silvia , Naldini Antonella , Bartalesi Barbara , Pucci Annalisa , Lungarella Giuseppe
Published: August 2004

The sensitivity to the fibrosis-inducing effect of bleomycin varies considerably from species to species, the reasons for which are unknown. The variability of the response in different strains of mice is well documented. Recent evidence indicates that the upregulated expression of cytokines and cytokine receptors may be involved. We evaluated the expression pattern of some cytokines and their receptors in C57Bl/6J bleomycin-sensitive and Balb/C bleomycin-resistant mice. Animals from both strains received, under ether anesthesia, either saline (50 μl) or bleomycin (0.1 U/50 μl) intratracheally. At various times after the treatment, the lungs were analyzed for cytokines and cytokine receptors by histochemistry and their mRNA by RNase protection assay. A significantly increased expression of TNF-α and IL-1β was observed in both strains. However, an upregulated lung expression for TNF-α and IL-1 receptors was observed in C57Bl/6J-sensitive animals only. This profile is evident from 63 h onward. In addition to TNF-α, bleomycin administration also resulted in the upregulated expression of TGF-β in the lungs of both strains at 8 h and in an enhanced expression of TGF-β receptors I and II in C57Bl/6J mice only. The upregulation of TGF-β receptor expression was preceded in this strain by an increased expression of IL-4, IL-13, and IL-13 receptor-α (at 8 h after bleomycin) and followed by an upregulation of gp130 and IL-6. The difference we observed in the cytokine receptor profile may offer an additional explanation for the different fibrogenic response of the two mouse strains to bleomycin.
Inhibition by cytoplasmic nucleotides of a new cation channel in freshly isolated human and rat type II pneumocytes
Authors: Mair Norbert , Frick Manfred , Bertocchi Cristina , Haller Thomas , Amberger Albert , Weiss Helmut , Margreiter Raimund , Streif Werner , Dietl Paul
Published: August 2004

Here we report a 26- to 29-pS cation channel abundantly expressed in freshly isolated and primary cultured type II cells from rat or healthy human lungs. The channel was never spontaneously active in cell-attached patches but could be activated by cell permeabilization with β-escin. Excised patch-clamp experiments revealed activation by Ca2+ concentrations at the cytoplasmic side in the micromolar range. High concentrations of amiloride (>10 μM) at the extracellular side did not inhibit. The channel was equally permeable for K+ and Na+ but was essentially impermeable for Cl−, Ca2+, and Mg2+. It was blocked by adenosine nucleotides (cytoplasmic side) with the following order of potency: AMP ≈ ADP (EC50 ≤ 10 μM) > ATP ≫ adenosine ≫ cyclic AMP. The blocking effect of ATP was reproduced by its nonhydrolyzable analogs AMPPNP or ATP-γ-S. GTP did not inhibit. Cd2+ blocked the channel with an EC50 ≈ 55.5 nM. We conclude that type II cells express a Ca2+-dependent, nucleotide-inhibited, nonselective, and Ca2+-impermeable cation channel (NSCCa/AMP) with tonically suppressed activity. RT-PCR confirmed expression of TRPM4b, a channel with functional characteristics almost identical with NSCCa/AMP. Potential physiological roles are discussed.
Hypoxic pulmonary vasoconstriction and pulmonary artery tissue cytokine expression are mediated by protein kinase C
Authors: Tsai Ben M. , Wang Meijing , Pitcher Jeffrey M. , Meldrum Kirstan K. , Meldrum Daniel R.
Published: August 2004

Pulmonary arteries exhibit a marked vasoconstriction when exposed to hypoxic conditions. Although this may be an adaptive response to match lung ventilation with perfusion, the potential consequences of sustained pulmonary vasoconstriction include pulmonary hypertension and right heart failure. Concomitant production of proinflammatory mediators during hypoxia may exacerbate acute increases in pulmonary vascular resistance. We hypothesized that acute hypoxia causes pulmonary arterial contraction and increases the pulmonary artery tissue expression of proinflammatory cytokines via a protein kinase C (PKC)-mediated mechanism. To study this, isometric force displacement was measured in isolated rat pulmonary artery rings during hypoxia in the presence and absence of the PKC inhibitors calphostin C or chelerythrine. In separate experiments, pulmonary artery rings were treated with the PKC activator thymeleatoxin for 60 min. After hypoxia, with or without PKC inhibition, or PKC activation alone, pulmonary artery rings were subjected to mRNA analysis for TNF-α and IL-1β via RT-PCR. Our results showed that, in isolated pulmonary arteries, hypoxia caused a biphasic contraction and increased expression of TNF-α and IL-1β mRNA. Both effects were inhibited by PKC inhibition. PKC activation resulted in pulmonary artery contraction and increased the pulmonary artery expression of TNF-α and IL-1β mRNA. These findings suggest that hypoxia induces the expression of inflammatory cytokines and causes vasoconstriction via a PKC-dependent mechanism. We conclude that PKC may have a central role in modulating hypoxic pulmonary vasoconstriction, and further elucidation of its involvement may lead to therapeutic application.
Acute and chronic increases in osmolality increase excitatory amino acid drive of the rostral ventrolateral medulla in rats
Authors: Brooks Virginia L. , Freeman Korrina L. , O’Donaughy Theresa L.
Published: August 2004

Water deprivation is associated with increased excitatory amino acid (EAA) drive of the rostral ventrolateral medulla (RVLM), but the mechanism is unknown. This study tested the hypotheses that the increased EAA activity is mediated by decreased blood volume and/or increased osmolality. This was first tested in urethane-anesthetized rats by determining whether bilateral microinjection of kynurenate (KYN, 2.7 nmol) into the RVLM decreases arterial pressure less in water-deprived rats after normalization of blood volume by intravenous infusion of isotonic saline or after normalization of plasma osmolality by intravenous infusion of 5% dextrose in water (5DW). Water-deprived rats exhibited decreased plasma volume and elevated plasma osmolality, hematocrit, and plasma sodium, chloride, and protein levels (all P < 0.05). KYN microinjection decreased arterial pressure by 24 ± 2 mmHg ( P < 0.05; n = 17). The depressor response was not altered following isotonic saline infusion but, while still present ( P < 0.05), was reduced ( P < 0.05) to −13 ± 2 mmHg soon after 5DW infusion. These data suggest that the high osmolality, but not low blood volume, contributes to the KYN depressor response. To further investigate the action of increased osmolality on EAA input to RVLM, water-replete rats were also studied after hypertonic saline infusion. Whereas KYN microinjection did not decrease pressure immediately following the infusion, a depressor response gradually developed over the next 3 h. Lumbar sympathetic nerve activity also gradually increased to up to 167 ± 19% of control ( P < 0.05) 3 h after hypertonic saline infusion. In conclusion, acute and chronic increases in osmolality appear to increase EAA drive of the RVLM.
l-Arginine uptake affects nitric oxide production and blood flow in the renal medulla
Authors: Kakoki Masao , Kim Hyung-Suk , Arendshorst William J. , Mattson David L.
Published: August 2004

Experiments were performed to determine whether l-arginine transport regulates nitric oxide (NO) production and hemodynamics in the renal medulla. The effects of renal medullary interstitial infusion of cationic amino acids, which compete with l-arginine for cellular uptake, on NO levels and blood flow in the medulla were examined in anesthetized rats. NO concentration in the renal inner medulla, measured with a microdialysis-oxyhemoglobin trapping technique, was significantly decreased by 26–44% and renal medullary blood flow, measured by laser Doppler flowmetry, was significantly reduced by 20–24% during the acute renal medullary interstitial infusion of l-ornithine, l-lysine, and l-homoarginine (1 μmol·kg−1·min−1each; n = 6–8/group). In contrast, intramedullary infusion of l-arginine increased NO concentration and medullary blood flow. Flow cytometry experiments with 4-amino-5-methylamino-2′,7′-difluorescein diacetate, a fluorophore reactive to intracellular NO, demonstrated that l-ornithine, l-lysine, and l-homoarginine decreased NO by 54–57% of control, whereas l-arginine increased NO by 21% in freshly isolated inner medullary cells (1 mmol/l each, n > 1,000 cells/experiment). The mRNA for the cationic amino acid transporter-1 was predominantly expressed in the inner medulla, and cationic amino acid transporter-1 protein was localized by immunohistochemistry to the collecting ducts and vasa recta in the inner medulla. These results suggest that l-arginine transport by cationic amino acid transport mechanisms is important in the production of NO and maintenance of blood flow in the renal medulla.
Role of endothelin in mediating postmenopausal hypertension in a rat model
Authors: Yanes Licy L. , Romero Damian G. , Cucchiarelli Valeria E. , Fortepiani Lourdes A. , Gomez-Sanchez Celso E. , Santacruz Francisco , Reckelhoff Jane F.
Published: August 2004

Cardiovascular disease is the leading cause of death in women after menopause. Hypertension, a major cardiovascular risk factor, becomes more prevalent after menopause. The mechanisms responsible for the increase in blood pressure (BP) in postmenopausal women are unknown. We have recently characterized the aged, postestrous-cycling (PMR) spontaneously hypertensive rats (SHR) as a model of postmenopausal hypertension. The purpose of the present study was to determine whether endothelin plays a role in the increased BP in PMR. Premenopausal female SHR, aged 4–5 mo (YF), and PMR, aged 16 mo, were studied. Expression of preproendothelin-1 mRNA was not different in either renal cortex or medulla between PMR and YF ( n = 7–8/group). In contrast, ET-1 peptide expression was significantly higher in renal cortex of PMR than in renal cortex of YF, but there was no difference in medullary ET-1. Expression of endothelin ETA receptor (ETAR) mRNA was lower in renal cortex and medulla of PMR than of YF. Additional groups of rats ( n = 6–7/group) were treated for 3 wk with the ETAR antagonist ABT-627 (5 mg·kg−1·day−1). BP was significantly higher in PMR than in YF. ETAR antagonist reduced BP in PMR by 20% to the level found in control YF. ETAR antagonist had no effect on BP in YF. These data support the hypothesis that the increase in BP in PMR is mediated in part by endothelin and the ETAR.
Regional hemodynamics during postexercise hypotension. II. Cutaneous circulation
Authors: Wilkins Brad W. , Minson Christopher T. , Halliwill John R.
Published: August 2004

After an acute bout of exercise, there is an unexplained elevation in systemic vascular conductance that is not completely offset by an increase in cardiac output, resulting in a postexercise hypotension. The contributions of the splanchnic and renal circulations are examined in a companion paper (Pricher MP, Holowatz LA, Williams JT, Lockwood JM, and Halliwill JR. J Appl Physiol 97: 2065–2070, 2004). The purpose of this study was to determine the contribution of the cutaneous circulation in postexercise hypotension under thermoneutral conditions (∼23°C). Arterial blood pressure was measured via an automated sphygmomanometer, internal temperature was measured via an ingestible pill, and skin temperature was measured with eight thermocouples. Red blood cell flux (laser-Doppler flowmetry) was monitored at four skin sites (chest, forearm, thigh, and leg), and cutaneous vascular conductance (CVC) was calculated (red blood cell flux/mean arterial pressure) and scaled as percent maximal CVC (local heating to 43°C). Ten subjects [6 men and 4 women; age 23 ± 1 yr; peak O2 uptake (V̇o2 peak) 45.8 ± 2.0 ml·kg−1·min−1] volunteered for this study. After supine rest (30 min), subjects exercised on a bicycle ergometer for 1 h at 60% of their V̇o2 peak and were then positioned supine for 90 min. Exercise elicited a postexercise hypotension reaching a nadir at 46.0 ± 4.5 min postexercise (77 ± 1 vs. 82 ± 2 mmHg preexercise; P < 0.05). Internal temperature increased (38.0 ± 0.1 vs. 36.7 ± 0.1°C preexercise; P < 0.05), remaining elevated at 90 min postexercise (36.9 ± 0.1°C vs. preexercise; P < 0.05). CVC at all four skin sites was elevated by the exercise bout ( P < 0.05), returning to preexercise values within 50 min postexercise ( P > 0.05). Therefore, although transient changes in CVC occur postexercise, they do not appear to play an obligatory role in mediating postexercise hypotension under thermoneutral conditions.
Diffusing capacity reexamined: relative roles of diffusion and chemical reaction in red cell uptake of O2, CO, CO2, and NO
Authors: Chakraborty Saikat , Balakotaiah Vemuri , Bidani Akhil
Published: August 2004

This paper presents an analytical expression for the diffusing capacity (Θt) of the red blood cell (RBC) for any reactive gas in terms of size and shape of the RBC, thickness of the unstirred plasma layer surrounding the RBC, diffusivities and solubilities of the gas in RBC and boundary layer, hematocrit, and the slope of the dissociation curve. The expression for Θthas been derived by spatial averaging of the fundamental convection-diffusion-reaction equation for O2in the RBC and has been generalized to all cell shapes and for other reactive gases such as CO, NO, and CO2. The effects of size and shape of the RBC, thickness of the unstirred plasma layer, hemoglobin concentration, and hematocrit on Θthave been analyzed, and the analytically obtained expression for Θthas been validated by comparison with different sets of existing experimental data for O2and CO2. Our results indicate that the discoidal shape of the human RBC with average dimensions of 1.6-μm thickness and 8-μm diameter is close to optimal design for O2uptake and that the true reaction velocity in the RBC is suppressed significantly by the mass transfer resistance in the surrounding unstirred layer. In vitro measurements using rapid-mixing technique, which measures Θtin the presence of artificially created large boundary layers, substantially underpredicts the in vivo diffusing capacity of the RBC in the diffusion-controlled regime. Depending on the conditions in the RBC, uptake of less reactive gases (such as CO) undergoes transition from reaction-limited to diffusion-limited regime. For a constant set of morphological parameters, the theoretical expression for Θtpredicts that Θt,NO> Θt,CO2> Θt,O2> Θt,CO.
Effects of nitrogen and helium on CNS oxygen toxicity in the rat
Authors: Arieli R. , Ertracht O. , Oster I. , Vitenstein A. , Adir Y.
Published: August 2004

The contribution of inert gases to the risk of central nervous system (CNS) oxygen toxicity is a matter of controversy. Therefore, diving regulations apply strict rules regarding permissible oxygen pressures (Po2). We studied the effects of nitrogen and helium (0, 15, 25, 40, 50, and 60%) and different levels of Po2 (507, 557, 608, and 658 kPa) on the latency to the first electrical discharge (FED) in the EEG in rats, with repeated measurements in each animal. Latency as a function of the nitrogen pressure was not homogeneous for each rat. The prolongation of latency observed in some rats at certain nitrogen pressures, mostly in the range 100 to 500 kPa, was superimposed on the general trend for a reduction in latency as nitrogen pressure increased. This pattern was an individual trait. In contrast with nitrogen, no prolongation of latency to CNS oxygen toxicity was observed with helium, where an increase in helium pressure caused a reduction in latency. This bimodal response and the variation in the response between rats, together with a possible effect of ambient temperature on metabolic rate, may explain the conflicting findings reported in the literature. The difference between the two inert gases may be related to the difference in the narcotic effect of nitrogen. Proof through further research of a correlation between individual sensitivity to nitrogen narcosis and protection by N2 against CNS oxygen toxicity in rat may lead to a personal O2 limit in mixed-gas diving based on the diver sensitivity to N2 narcosis.
CT-based geometry analysis and finite element models of the human and ovine bronchial tree
Authors: Tawhai Merryn H. , Hunter Peter , Tschirren Juerg , Reinhardt Joseph , McLennan Geoffrey , Hoffman Eric A.
Published: August 2004

The interpretation of experimental results from functional medical imaging is complicated by intersubject and interspecies differences in airway geometry. The application of computational models in understanding the significance of these differences requires methods for generation of subject-specific geometric models of the bronchial airway tree. In the current study, curvilinear airway centerline and diameter models have been fitted to human and ovine bronchial trees using detailed data segmented from multidetector row X-ray-computed tomography scans. The trees have been extended to model the entire conducting airway system by using a volume-filling algorithm to generate airway centerline locations within detailed volume descriptions of the lungs or lobes. Analysis of the geometry of the scan-based and model-based airways has verified their consistency with measures from previous anatomic studies and has provided new anatomic data for the ovine bronchial tree. With the use of an identical parameter set, the volume-filling algorithm has produced airway trees with branching asymmetry appropriate for the human and ovine lung, demonstrating the dependence of the method on the shape of the lung or lobe volume. The modeling approach that has been developed can be applied to any level of detail of the airway tree and into any volume shape for the lung; hence it can be used directly for different individuals or animals and for any number of scan-based airways. The resulting models are subject-specific computational meshes with anatomically consistent geometry, suitable for application in simulation studies.
Venous excess: a new approach to cardiovascular control and its teaching
Authors: Reddi B. A. J. , Carpenter R. H. S.
Published: August 2004

The circulatory control system is driven partly by factors relating to the arterial side and partly by factors relating to the venous side. Students are generally provided with a conceptually clear account of the arterial side, based on sound homeostatic mechanisms of negative feedback from a well-defined error signal, arterial pressure. However, on the venous side, teaching is often based on the notion of venous return, a concept that, as normally presented, is imprecise and intangible, a frequent cause of confusion that may lead to errors of clinical practice. Although one can trace these misconceptions back to some of Guyton's publications, Guyton himself was well aware of the complexities of venous resistance and capacitance but has not always been well served by subsequent misinterpretation. The fundamental problem with venous return that makes it inappropriate for controlling the circulation is that it lacks the essential requirement of being an error signal. We propose instead a new variable, venous excess, which represents the accumulation of any mismatch between the rate of blood entering the great veins and the rate of leaving, the cardiac output. As well as being directly observable without intervention (in a patient's jugular vein), it meets all of the requirements of an error signal: via the Starling mechanism it stimulates cardiac output, regulates venous compliance, and in the longer term is an important determinant of fluid intake and excretion, and these effects act to reduce the original perturbation. Based on this concept, we suggest a simple and secure basis for teaching the control of the circulation that avoids undue reliance on entities that are difficult to specify or measure and emphasizes the role of feedback and the similarities between the arterial and venous mechanisms.
Model of local temperature changes in brain upon functional activation
Authors: Collins Christopher M. , Smith Michael B. , Turner Robert
Published: August 2004

Experimental results for changes in brain temperature during functional activation show large variations. It is, therefore, desirable to develop a careful numerical model for such changes. Here, a three-dimensional model of temperature in the human head using the bioheat equation, which includes effects of metabolism, perfusion, and thermal conduction, is employed to examine potential temperature changes due to functional activation in brain. It is found that, depending on location in brain and corresponding baseline temperature relative to blood temperature, temperature may increase or decrease on activation and concomitant increases in perfusion and rate of metabolism. Changes in perfusion are generally seen to have a greater effect on temperature than are changes in metabolism, and hence active brain is predicted to approach blood temperature from its initial temperature. All calculated changes in temperature for reasonable physiological parameters have magnitudes <0.12°C and are well within the range reported in recent experimental studies involving human subjects.
Involvement of p42/44 MAPK and RhoA protein in augmentation of ACh-induced bronchial smooth muscle contraction by TNF-α in rats
Authors: Sakai Hiroyasu , Otogoto Shinobu , Chiba Yoshihiko , Abe Kazuho , Misawa Miwa
Published: August 2004

Bronchial asthma is characterized by chronic inflammation of airway tissues and nonspecific airway hyperresponsiveness (AHR), but the underlying mechanisms of AHR have yet to be elucidated. Recently, tumor necrosis factor-α (TNF-α) has been identified as a proinflammatory cytokine that might be important in the hyperresponsiveness of airway tissue. We have investigated the effects of SB-203580 (a p38 MAPK inhibitor), U-0126 (an inhibitor of p42/44 MAPK activation), and cycloheximide (an inhibitor of protein synthesis) on TNF-α-augmented ACh-induced bronchial smooth muscle contraction. We have also investigated the phosphorylation of p42/44 MAPK and upregulation of RhoA protein by TNF-α. Treatment of rat bronchial smooth muscles with TNF-α (300 and 1,000 ng/ml for 24 h) resulted in a significant upward shift in the concentration-response curve to ACh, but not to high K+, compared with control tissues. The effect of TNF-α was completely blocked by pretreatment with U-0126 or cycloheximide, but not with SB-203580. Immunoblotting demonstrated that p42/44 MAPK was phosphorylated and RhoA protein was increased in bronchial tissue by TNF-α. Furthermore, the TNF-α-induced upregulation of RhoA protein was abolished by U-0126 pretreatment. In conclusion, we suggest that TNF-α might be one of the important mediators involved in the pathogenesis of augmented bronchial smooth muscle contractility in AHR. For the first time, we have demonstrated that augmentation of ACh-induced contractile response evoked by TNF-α was mediated by synthesis of protein, such as RhoA, through activation of p42/44, but not p38 MAPK, in rat bronchial smooth muscle.
Effect of prolonged exercise and carbohydrate ingestion on type 1 and type 2 T lymphocyte distribution and intracellular cytokine production in humans
Authors: Lancaster G. I. , Khan Q. , Drysdale P. T. , Wallace F. , Jeukendrup A. E. , Drayson M. T. , Gleeson M.
Published: August 2004

The present study was undertaken to examine the role of the exercise-induced stress hormone response on the regulation of type 1 and type 2 T lymphocyte intracellular cytokine production. Subjects performed 2.5 h of cycling exercise at 65% maximal O2uptake while ingesting a 6.4% carbohydrate (CHO) solution, 12.8% CHO solution, or a placebo. Peripheral whole blood samples were stimulated and stained for T lymphocyte surface antigens (CD4 and CD8). Cells were then permeabilized, stained for intracellular cytokines, and analyzed using flow cytometry. Exercise resulted in a decrease ( P < 0.05) in the number and percentage of IFN-γ positive CD4+and CD8+T lymphocytes. These stimulated cells produced less IFN-γ immediately postexercise ( P < 0.05) and 2-h postexercise ( P < 0.05) compared with preexercise. However, CHO ingestion, which attenuated the exercise-induced stress hormone response compared with placebo ( P < 0.05), prevented both the decrease in the number and percentage of IFN-γ-positive CD4+and CD8+T lymphocytes and the suppression of IFN-γ production from stimulated CD4+and CD8+T lymphocytes. There was no effect of exercise on the number of, or cytokine production from, IL-4-positive CD4+or CD8+T lymphocytes. These data provide support for the role of exercise-induced elevations in stress hormones in the regulation of type 1 T lymphocyte cytokine production and distribution.
Vascular smooth muscle cell glycocalyx influences shear stress-mediated contractile response
Authors: Ainslie Kristy M. , Garanich Jeffrey S. , Dull Randal O. , Tarbell John M.
Published: August 2004

This study addressed the influence of the rate of shear stress application on aortic smooth muscle cell (SMC) contraction and the role of specific glycosaminoglycans in this mechanotransduction. Rat aortic SMCs were exposed to either a step increase in shear stress (0 to 25 dyn/cm2) or a ramp increase in shear stress (0 to 25 dyn/cm2over 5 min) in a parallel plate flow chamber, and cell contraction was characterized by cell area reduction. SMCs contracted at levels similar to those reported previously and equally in response to both a step and ramp increase in shear stress. When the cells were pretreated with heparinase III or chondroitinase ABC to remove the glycosaminoglycans heparan sulfate and chondroitin sulfate, respectively, from the glycocalyx, the contraction response to increases in shear stress was significantly inhibited. These studies indicate that specific components of the SMC glycocalyx play an important role in the mechanotransduction of shear stress into a contractile response and that the rate of application of shear stress does not affect the SMC contraction.
PI3K-Akt Pathway Suppresses Coagulation and Inflammation in Endotoxemic Mice
Authors: Schabbauer Gernot , Tencati Michael , Pedersen Brian , Pawlinski Rafal , Mackman Nigel
Published: August 2004

Objective—

In endotoxemia, lipopolysaccharide (LPS) induces a systemic inflammatory response and intravascular coagulation. Monocytes orchestrate the innate immune response to LPS by expressing a variety of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), and the procoagulant molecule, tissue factor (TF). In this study, we analyzed the role of the phosphoinositide 3-kinase (PI3K)-Akt pathway in the activation of coagulation and the innate immune response in a mouse model of endotoxemia.

Methods and Results—

Wortmannin and LY294002 were used to inhibit the PI3K-Akt pathway. We found that wortmannin inhibited LPS-induced Akt phosphorylation in blood cells. Inhibition of the PI3K-Akt pathway significantly increased TF mRNA expression in blood cells, TF antigen, and thrombin–antithrombin III levels in the plasma, and fibrin deposition in the liver of endotoxemic mice. Inhibition of the PI3K-Akt pathway also strongly enhanced LPS-induced cytokine expression and the levels of soluble E-selectin in the plasma, suggesting enhanced activation of both monocytes and endothelial cells. Wortmannin treatment also increased the number of macrophages in the liver and kidney of endotoxemic mice. Finally, wortmannin and LY294002 dramatically reduced the survival time of endotoxemic mice.

Conclusions—

These data suggest that the PI3K-Akt pathway suppresses LPS-induced inflammation and coagulation in endotoxemic mice.
In Vivo Transcriptional Response of Cardiac Endothelium to Lipopolysaccharide
Authors: Maresh J. Gregory , Xu Huaxia , Jiang Nan , Shohet Ralph V.
Published: August 2004

Objective—Vascular endothelial cells must integrate stimuli from multiple sources, including plasma, leukocytes, and neighboring components of the vessel. These stimuli are difficult to recapitulate in vitro. We have developed a method to examine the in vivo regulation of gene expression in endothelial cells and have applied it to a model of sepsis.

Methods and Results—We used fluorescent-activated cell sorting to isolate highly purified endothelial cells from the hearts of transgenic mice that express green fluorescent protein driven by the endothelial-specific promoter Tie2. We treated these mice with intraperitoneal lipopolysaccharide and identified those genes within cardiac endothelium that were >3-fold dysregulated 4 and 24 hours later by microarray analysis. These findings were confirmed by real-time polymerase chain reaction and compared with in vitro regulation in a murine endothelial cell line.

Conclusions—The in vivo regulation was distinct and, in general, more robust than that seen in vitro. We identified endothelial-expressed genes not previously recognized to be regulated in response to lipopolysaccharide. This approach provides insight into the cardiac-specific responses of the endothelium that contribute to the specific responses of the heart to sepsis, and can be generalized to the exploration of endothelial responses in any organ.
Endothelial Progenitor Cells
Authors: Urbich Carmen , Dimmeler Stefanie
Published: August 2004

Infusion of different hematopoietic stem cell populations and ex vivo expanded endothelial progenitor cells augments neovascularization of tissue after ischemia and contributes to reendothelialization after endothelial injury, thereby, providing a novel therapeutic option. However, controversy exists with respect to the identification and the origin of endothelial progenitor cells. Overall, there is consensus that endothelial progenitor cells can derive from the bone marrow and that CD133/VEGFR2 cells represent a population with endothelial progenitor capacity. However, increasing evidence suggests that there are additional bone marrow-derived cell populations (eg, myeloid cells, “side population” cells, and mesenchymal cells) and non-bone marrow-derived cells, which also can give rise to endothelial cells. The characterization of the different progenitor cell populations and their functional properties are discussed. Mobilization and endothelial progenitor cell-mediated neovascularization is critically regulated. Stimulatory (eg, statins and exercise) or inhibitory factors (risk factors for coronary artery disease) modulate progenitor cell levels and, thereby, affect the vascular repair capacity. Moreover, recruitment and incorporation of endothelial progenitor cells requires a coordinated sequence of multistep adhesive and signaling events including adhesion and migration (eg, by integrins), chemoattraction (eg, by SDF-1/CXCR4), and finally the differentiation to endothelial cells. This review summarizes the mechanisms regulating endothelial progenitor cell-mediated neovascularization and reendothelialization.
Histamine H
2
-Receptor Antagonist Ranitidine Protects Against Neural Death Induced by Oxygen-Glucose Deprivation
Authors: Malagelada Cristina , Xifró Xavier , Badiola Nahuai , Sabrià Josefa , Rodríguez-Álvarez José
Published: August 2004

Background and Purpose—

Administration of histamine receptor antagonists has been reported to produce contradictory results, either reducing or increasing neural damage induced by ischemia. In this study, we investigated the neuroprotective effects of histamine H
2
-receptor antagonists in an “in vitro” model of ischemia.

Methods—

Cultured rat brain cortical neurons were exposed to oxygen-glucose deprivation (OGD) in the presence or absence of different histaminergic drugs. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide reduction assay. Necrosis and apoptosis were quantified by staining cells with propidium iodide and Hoechst 33258. Caspase 3 activation was determined by immunocytochemistry and Western blot.

Results—

Pretreatment with H
2
antagonists effectively reduced neuronal cell death induced by OGD. Ranitidine decreased the number of necrotic and apoptotic cells. Caspase 3 activation and alteration of the neuronal cytoskeleton were also prevented by ranitidine pretreatment. The neuroprotective effect of ranitidine was still evident when added 6 hours after OGD.

Conclusions—

H
2
-receptor antagonists protected against OGD-induced neuronal death. Ranitidine attenuated cell death even when administered after OGD. These data suggest that this drug, which is currently used for the treatment of gastric ulcers, may be useful in promoting recovery after ischemia.
Magnesium Sulfate Increases the Rate of Hypothermia Via Surface Cooling and Improves Comfort
Authors: Zweifler Richard M. , Voorhees Marc E. , Mahmood M. Asim , Parnell Mel
Published: August 2004

Background and Purpose—

Therapeutic hypothermia shows promise as a treatment for acute stroke. Surface cooling techniques are being developed but, although noninvasive, they typically achieve slower cooling rates than endovascular methods. We assessed the hypothesis that the addition of intravenous MgSO
4
to an antishivering pharmacological regimen increases the cooling rate when using a surface cooling technique.

Methods—

Twenty-two healthy volunteers were studied. Hypothermia was induced using a surface technique with a target tympanic temperature (Ttym) of 34.5°C (target range 34 to 35°C). Subjects received 1 of the following pharmacological regimens: (1) meperidine monotherapy (n=5); (2) meperidine plus buspirone, 30 to 60 mg PO administered at the time of initiation of cooling (n=4); (3) meperidine and ondansetron, 8 to 16 mg IV administered as an 8 mg bolus at the time of initiation of cooling with an optional second dose after 4 hours as needed for nausea (n=5); or (4) meperidine, ondansetron, and MgSO
4
, 4 to 6 g IV bolus followed by 1 to 3 g per hour infusion (n=8). Thermal comfort was evaluated with a 100-mm-long visual analog scale.

Results—

More subjects who received MgSO
4
were vasodilated during hypothermia induction (7 of 8 [88%] versus 4 of 14 [29%];
P
=0.024). MgSO
4
(coefficient −17.265;
P
=0.039), weight (1.838, 0.001), and the initial 2-hour meperidine dose (0.726, 0.003) were found to significantly impact the time to achieve Ttym of 35°C. Subjects who received MgSO
4
had significantly higher mean comfort scores than those who did not (48±15 versus 38±12;
P
<0.001).

Conclusions—

Administration of intravenous MgSO
4
increases the cooling rate and comfort when using a surface cooling technique.