bluuebunny/crossref_metadata_2025 huggingface dataset:
The PRECEDE-PROCEED model: application to planning a child pedestrian injury prevention program.
Authors: Howat P. , Jones S. , Hall M. , Cross D. , Stevenson M.
Published: October 2008

OBJECTIVES: The objectives were first, to modify the PRECEDE-PROCEED model and to use it is as a basis for planning a three year intervention trial that aims to reduce injury to child pedestrians. A second objective was to assess the suitability of this process for planning such a relatively complex program. SETTING: The project was carried out in 47 primary schools in three local government areas, in the Perth metropolitan area. METHODS: The program was developed, based on extensive needs assessment incorporating formative evaluations. Epidemiological, psychosocial, environmental, educational, and demographic information was gathered, organised, and prioritised. The PRECEDE-PROCEED model was used to identify the relevant behavioural and environmental risk factors associated with child pedestrian injuries in the target areas. Modifiable causes of those behavioural and environmental factors were delineated. A description of how the model facilitated the development of program objectives and subobjectives which were linked to strategy objectives, and strategies is provided. RESULTS: The process used to plan the child pedestrian injury prevention program ensured that a critical assessment was undertaken of all the relevant epidemiological, behavioural, and environmental information. The gathering, organising, and prioritising of the information was facilitated by the process. CONCLUSIONS: The use of a model such as PRECEDE-PROCEED can enhance the development of a child injury prevention program. In particular, the process can facilitate the identification of appropriate objectives which in turn facilitates the development of suitable interventions and evaluation methods.
A review of risk factors for child pedestrian injuries: are they modifiable?
Authors: Wazana A. , Krueger P. , Raina P. , Chambers L.
Published: October 2008

PURPOSE: To identify modifiable risk factors for child pedestrian injuries. DATA SOURCES: (1) MEDLINE search from 1985 to 1995; search term used was traffic accidents; (2) review of reference lists from retrieved articles and books; (3) review of reference lists from three systematic reviews on childhood injuries and (4) consultation with 'key informants'. STUDY SELECTION: All studies that examined the risk factors for child pedestrian injuries were targeted for retrieval. Seventy potentially relevant articles were identified using article titles, and, when available, abstracts. Of the 70 retrieved articles, 44 were later assessed as being relevant. QUALITY ASSESSMENT: Articles were classified on the basis of study design as being either descriptive (hypothesis generating) (26) or analytical (hypothesis testing) (18) studies. Consensus was used for difficult to classify articles. DATA EXTRACTION: Variables judged to be risk factors for child pedestrian injuries were extracted by one author. DATA SYNTHESIS: A qualitative summary of the information extracted from relevant articles is presented in tabular form. RESULTS: Risk factors for child pedestrian injuries were classified as: (1) child, (2) social and cultural, (3) physical environment, and (4) driver. Risk factors within each classification are summarized and discussed.
Swimming pool immersion accidents: an analysis from the Brisbane Drowning Study
Authors: Pearn John H , Nixon James
Published: October 2008

An analysis of a consecutive series of 66 swimming pool immersion accidents is presented; 74% of these occurred in in-ground swimming pools. The estimated accident rate per pool is fives times greater for in-ground pools compared with above-ground pools, where pools are inadequately fenced. Backyard swimming pools account for 74% of pool accidents. Motel and caravan park pools account for 9% of childhood immersion accidents, but the survival rate (17%) is very low. Fifty per cent of pool accidents occur in the family's own backyard pool, and 13.6% in a neighbour's pool; in the latter the survival rate is still low at only 33%. In only one of the 66 cases was there an adequate safety fence; in 76% of cases there was no fence or barrier whatsoever. Tables of swimming pool accidents by age, season, site, and outcome are presented.
THEORETICAL STUDY OF THE ELECTRON TRANSPORT THROUGH THE CYSTEINE AMINO ACID NANOMOLECULAR WIRE
Authors: GANJI M. D. , AGHAIE H. , GHOLAMI M. R.
Published: October 2008

In this paper, we study the electrical transport and Negative Differential Resistance (NDR) in a single molecular conductor consisting of a cysteine sandwiched between two Au (111) electrodes via the Density Functional Theory-based Nonequilibrium Green's Function (DFT-NEGF) method. We show that (surprisingly, despite their apparent simplicity, these Au /cysteine/ Au nanowires are shown to be a convenient NDR device) the smallest two-terminal molecular wire can exhibit NDR behavior to date. Experiments with a conventional or novel self-assembled monolayer (SAM) are proposed to test these predictions.

The projected density of states (PDOSs) and transmission coefficients T(E) under various external voltage biases are analyzed, and it suggests that the variation of the coupling between the molecule and the electrodes with external bias leads to NDR.
THREE-DIMENSIONAL PHONON TRANSPORT SIMULATION FOR NANO/MICROSTRUCTURED MATERIALS
Authors: SAKURAI A. , MARUYAMA S. , KOMIYA A. , MIYAZAKI K.
Published: October 2008

The Discrete Ordinates Radiation Element Method (DOREM), which is radiative transfer code, is applied for solving phonon transport of nano/microscale materials. The DOREM allows phonon simulation with multi-dimensional complex geometries. The objective of this study is to apply the DOREM to the nano/microstructured materials. It is confirmed that significant changes of the heat transport phenomena with different characteristic length scales and geometries are observed. This study also discusses further variations for understanding of heat transport mechanisms.
Quantum Gate Entangler and Entangling Capacity of a General Multipartite Quantum System
Authors: Heydari Hoshang
Published: October 2008

We construct quantum gate entangler for general multipartite states based on the construction of complex projective varieties. We also discuss in detail the construction of quantum gate entangler for higher dimensional bipartite and multipartite quantum systems. Moreover, we construct and discuss entangling capacity of general multipartite quantum systems.
On the Kondo Problem and Thermodynamics of Dilute Magnetic Alloys
Authors: Maćkowiak J.
Published: October 2008

An argument is given showing that Coulomb attraction between conduction electrons and impurity ions in a dilute magnetic alloy (DMA) can be disregarded, provided the system's inverse temperature β is replaced by an effective inverse temperature t < β. This replacement allows one to remove the singularity in Kondo's expression for DMA impurity resistivity and to extend his theory to 0 K. The extended Kondo formula agrees with experimental data on resistivity of CuFe in the range of low temperatures and in the neighbourhood of the resistivity minimum.

Using an asymptotic solution of the thermodynamics of a dilute s-d system at inverse temperature t, the impurity thermodynamic functions are derived and shown to provide good agreement with experimental data on CuFe , CuCr and ( LaCe ) Al 2 alloys in the low-temperature range. The magnitude of these functions agrees with experiment and does not require rescaling as in previous s-d theories. Nonlinear dependence of CuFe heat capacity on impurity concentration has been accounted for the first time.
Enhanced recovery of mechanical function in the canine heart by seeding an extracellular matrix patch with mesenchymal stem cells committed to a cardiac lineage
Authors: Potapova Irina A. , Doronin Sergey V. , Kelly Damon J. , Rosen Amy B. , Schuldt Adam J. T. , Lu Zhongju , Kochupura Paul V. , Robinson Richard B. , Rosen Michael R. , Brink Peter R. , Gaudette Glenn R. , Cohen Ira S.
Published: October 2008

The need to regenerate tissue is paramount, especially for the heart that lacks the ability to regenerate after injury. The urinary bladder extracellular matrix (ECM), when used to repair a right ventricular defect, successfully regenerated some mechanical function. The objective of the current study was to determine whether the regenerative effect of ECM could be improved by seeding the patch with human mesenchymal stem cells (hMSCs) enhanced to differentiate down a cardiac linage. hMSCs were used to form three-dimensional spheroids. The expression of cardiac proteins was determined in cells exposed to the spheroid formation and compared with nonmanipulated hMSCs. To determine whether functional calcium channels were present, the cells were patch clamped. To evaluate the ability of these cells to regenerate mechanical function, the spheroids were seeded on ECM and then implanted into the canine heart to repair a full-thickness right ventricular defect. As a result, many of the cells spreading from the spheroids expressed cardiac-specific proteins, including sarcomeric α-actinin, cardiotin, and atrial natriuretic peptide, as well as the cell cycle markers cyclin D1 and proliferating cell nuclear antigen. A calcium current similar in amplitude to that of ventricular myocytes was present in 16% of the cells. The cardiogenic cell-seeded scaffolds increased the regional mechanical function in the canine heart compared with the unmanipulated hMSC-seeded scaffolds. In addition, the cells prelabeled with fluorescent markers demonstrated myocyte-specific actinin staining with sarcomere spacing similar to that of normal myocytes. In conclusion, the spheroid-derived cells express cardiac-specific proteins and demonstrate a calcium current similar to adult ventricular myocytes. When these cells are implanted into the canine heart, some of these cells appear striated and mechanical function is improved compared with the unmanipulated hMSCs. Further investigation will be required to determine whether the increased mechanical function is due to a differentiation of the cardiogenic cells to myocytes or to other effects.
Permeability change of arterial endothelium is an age-dependent function of lesion size in apolipoprotein E-null mice
Authors: Lee Kwangdeok , Saidel Gerald M. , Penn Marc S.
Published: October 2008

The remodeling process of the arterial wall in atherosclerosis involves intimal thickening, which can be related to the barrier functions of the endothelial cell layer (ECL) and internal elastic lamina (IEL) using horseradish peroxidase (HRP) as a tracer. To evaluate the ECL and IEL permeabilities ( PECL and PIEL, respectively) and intimal transport parameters, e.g., apparent HRP velocity ( VI) and diffusivity, we compared simulations with a mathematical model to experimental data. In this study, we injected HRP into the vein of apolipoprotein E-null mice and measured HRP concentration profiles in lesioned areas of aortas. Lesion size was characterized by lower, middle, and upper ranges of the intimal/medial thickness (δI/δM): 0 < δI/δM ≤ 0.5, 0.5 < δI/δM ≤ 1.0, and δI/δM > 1.0. The PECL (in micrometers per minute) of 5-mo-old mice in the middle range (0.98 ± 0.14) was significantly greater than that in the lower range (0.21 ± 0.03) but not significantly different from mice in the upper range (0.99 ± 0.55). The PECL of 12-mo-old mice increased significantly with the relative intimal thickness: 0.27 ± 0.04 in the lower range, 1.12 ± 0.15 in the middle range, and 1.74 ± 0.24 in the upper range. In both age groups, VI (in micrometers per minute) increased significantly from lower to upper ranges of intimal thickness. However, PIEL did not change significantly with relative intimal thickness and age. In the upper range of intimal thickness, PECL and VI were significantly greater in 12-mo-old mice than in 5-mo-old mice. These data indicate an interaction between lesion growth and aging that leads to progressive loss in the integrity of the endothelial barrier function. Furthermore, the IEL is not a significant barrier between the intima and tunica media in the atherosclerotic process.
Nerve stimulation induced overflow of neuropeptide Y and modulation by angiotensin II in spontaneously hypertensive rats
Authors: Byku Mirnela , Macarthur Heather , Westfall Thomas C.
Published: October 2008

The sympathetic nervous system and renin-angiotensin system are both thought to contribute to the development and maintenance of hypertension in experimental models such as the spontaneously hypertensive rat (SHR). We demonstrated that periarterial nerve stimulation (NS) increased the perfusion pressure (PP) and neuropeptide Y (NPY) overflow from perfused mesenteric arterial beds of SHRs at 4–6, 10–12, and 18–20 wk of age, which correspond to prehypertensive, developing hypertensive, and maintained hypertensive stages, respectively, in the SHR. NS also increased PP and NPY overflow from mesenteric beds of Wistar-Kyoto (WKY) normotensive rats. NS-induced increases in PP and NPY were greater in vessels obtained from SHRs of all three ages compared with WKY rats. ANG II produced a greater increase in PP in preparations taken from SHRs than WKY rats. ANG II also resulted in a greater increase in basal NPY overflow from 10- to 12-wk-old and 18- to 20-wk-old SHRs than age-matched WKY rats. ANG II enhanced the NS-induced overflow of NPY from SHR preparations more than WKY controls at all ages studied. The enhancement of NS-induced NPY overflow by ANG II was blocked by the AT1receptor antagonist EMD-66684 and the angiotensin type 2 receptor antagonist PD-123319. In contrast, ANG II greatly enhanced norepinephrine overflow in the presence of PD-123319. Both captopril and EMD-66684 decreased neurotransmitter overflow from SHR mesenteric beds; therefore, we conclude that an endogenous renin-angiotensin system is active in this preparation. It is concluded that the ANG II-induced enhancement of sympathetic nerve stimulation may contribute to the development and maintenance of hypertension in the SHR.
Soluble epoxide hydrolase inhibition and gene deletion are protective against myocardial ischemia-reperfusion injury in vivo
Authors: Motoki Atsuko , Merkel Matthias J. , Packwood William H. , Cao Zhiping , Liu Lijuan , Iliff Jeffrey , Alkayed Nabil J. , Van Winkle Donna M.
Published: October 2008

Soluble epoxide hydrolase (sEH) metabolizes epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids. EETs are formed from arachidonic acid during myocardial ischemia and play a protective role against ischemic cell death. Deletion of sEH has been shown to be protective against myocardial ischemia in the isolated heart preparation. We tested the hypothesis that sEH inactivation by targeted gene deletion or pharmacological inhibition reduces infarct size (I) after regional myocardial ischemia-reperfusion injury in vivo. Male C57BL\6J wild-type or sEH knockout mice were subjected to 40 min of left coronary artery (LCA) occlusion and 2 h of reperfusion. Wild-type mice were injected intraperitoneally with 12-(3-adamantan-1-yl-ureido)-dodecanoic acid butyl ester (AUDA-BE), a sEH inhibitor, 30 min before LCA occlusion or during ischemia 10 min before reperfusion. 14,15-EET, the main substrate for sEH, was administered intravenously 15 min before LCA occlusion or during ischemia 5 min before reperfusion. The EET antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (EEZE) was given intravenously 15 min before reperfusion. Area at risk (AAR) and I were assessed using fluorescent microspheres and triphenyltetrazolium chloride, and I was expressed as I/AAR. I was significantly reduced in animals treated with AUDA-BE or 14,15-EET, independent of the time of administration. The cardioprotective effect of AUDA-BE was abolished by the EET antagonist 14,15-EEZE. Immunohistochemistry revealed abundant sEH protein expression in left ventricular tissue. Strategies to increase 14,15-EET, including sEH inactivation, may represent a novel therapeutic approach for cardioprotection against myocardial ischemia-reperfusion injury.
No impact of protein phosphatases on connexin 43 phosphorylation in ischemic preconditioning
Authors: Totzeck Andreas , Boengler Kerstin , van de Sand Anita , Konietzka Ina , Gres Petra , Garcia-Dorado David , Heusch Gerd , Schulz Rainer
Published: October 2008

Cardiac connexin 43 (Cx43) is involved in infarct propagation, and the uncoupling of Cx43-formed channels reduces infarct size. Cx43-formed channels open upon Cx43 dephosphorylation, and ischemic preconditioning (IP) prevents the ischemia-induced Cx43 dephosphorylation. In addition to the sarcolemma, Cx43 is also present in the cardiomyocyte mitochondria. We now examined the interaction of Cx43 with protein phosphatases PP1α, PP2Aα, and PP2Bα and the role of such interaction for Cx43 phosphorylation in preconditioned myocardium. Infarct size (in %area at risk) in left ventricular anterior myocardium of Göttinger minipigs subjected to 90 min of low-flow ischemia and 120 min of reperfusion was 23.1 ± 2.7 [ n = 7, nonpreconditioned (NIP) group] and was reduced by IP to 10.0 ± 3.2 ( n = 6, P < 0.05). Mitochondrial and gap junctional Cx43 dephosphorylation increased after 85 min of ischemia in NIP myocardium, whereas Cx43 phosphorylation was preserved with IP. PP2Aα and PP1α, but not PP2Bα, were detected by Western blot analysis in the left ventricular myocardium. Cx43 coprecipitated with PP2Aα but not with PP1α. Although the total PP2Aα immunoreactivity (confocal laser scan) was increased to 154 ± 24% and 194 ± 13% of baseline ( P < 0.05) after 85 min of ischemia in NIP and IP myocardium, respectively, the PP2A activities were similar between the groups. The amount of PP2Aα coimmunoprecipitated with Cx43 remained unchanged. Only PP2Aα coprecipitates with Cx43 in pig myocardium. This interaction is not affected by IP, suggesting that PP2Aα is not involved in the prevention of the ischemia-induced Cx43 dephosphorylation by IP.
Maximal stimulation-induced in situ myosin light chain kinase activity is upregulated in fetal compared with adult ovine carotid arteries
Authors: Injeti Elisha R. , Sandoval Renan J. , Williams James M. , Smolensky Alexander V. , Ford Lincoln E. , Pearce William J.
Published: October 2008

Postnatal decreases in vascular reactivity involve decreases in the thick filament component of myofilament calcium sensitivity, which is measured as the relationship between cytosolic calcium concentration and myosin light chain (MLC20) phosphorylation. The present study tests the hypothesis that downregulation of thick filament reactivity is due to downregulation of myosin light chain kinase (MLCK) activity in adult compared with fetal arteries. Total MLCK activity, calculated as %MLC20phosphorylated per second in intact arteries during optimal inhibition of myosin light chain phosphatase activity, was significantly less in adult (6.56 ± 0.29%) than in fetal preparations (7.39 ± 0.53%). In situ MLC20concentrations (μM) in adult (198 ± 28) and fetal arteries (236 ± 44) did not differ significantly. In situ MLCK concentrations (μM), however, were significantly greater in adult (8.21 ± 0.59) than in fetal arteries (1.83 ± 0.13). In situ MLCK activities (ng MLC20phosphorylated·s−1·ng MLCK−1) were significantly less in adult (0.26 ± 0.01) than in fetal arteries (1.52 ± 0.11). In contrast, MLCK activities in adult (15.8 ± 1.5) and fetal artery homogenates (17.3 ± 1.3) were not significantly different. When in situ fractional activation was calculated, adult values (1.72 ± 0.17%) were significantly less than fetal values (9.08 ± 0.83%). Together, these results indicate that decreased thick filament reactivity in adult compared with fetal ovine carotid arteries is due at least in part to greater MLCK activity in fetal arteries, which in turn cannot be explained by differences in MLCK, MLC20, or calmodulin concentrations. Instead, this difference appears to involve age-related differences in fractional activation of the MLCK enzyme.
PER3polymorphism and cardiac autonomic control: effects of sleep debt and circadian phase
Authors: Viola Antoine U. , James Lynette M. , Archer Simon N. , Dijk Derk-Jan
Published: October 2008

A variable number tandem repeat polymorphism in the coding region of the circadian clock PERIOD3 ( PER3) gene has been shown to affect sleep. Because circadian rhythms and sleep are known to modulate sympathovagal balance, we investigated whether homozygosity for this PER3 polymorphism is associated with changes in autonomic nervous system (ANS) activity during sleep and wakefulness at baseline and after sleep deprivation. Twenty-two healthy participants were selected according to their PER3 genotype. ANS activity, evaluated by heart rate (HR) and HR variability (HRV) indexes, was quantified during baseline sleep, a 40-h period of wakefulness, and recovery sleep. Sleep deprivation induced an increase in slow-wave sleep (SWS), a decrease in the global variability, and an unbalance of the ANS with a loss of parasympathetic predominance and an increase in sympathetic activity. Individuals homozygous for the longer allele ( PER35/5) had more SWS, an elevated sympathetic predominance, and a reduction of parasympathetic activity compared with PER34/4, in particular during baseline sleep. The effects of genotype were strongest during non-rapid eye movement (NREM) sleep and absent or much smaller during REM sleep. The NREM-REM cycle-dependent modulation of the low frequency-to-(low frequency + high frequency) ratio was diminished in PER35/5individuals. Circadian phase modulated HR and HRV, but no interaction with genotype was observed. In conclusion, the PER3 polymorphism affects the sympathovagal balance in cardiac control in NREM sleep similar to the effect of sleep deprivation.
Pharmacogenomics of anesthetic drugs in transgenic LQT1 and LQT2 rabbits reveal genotype-specific differential effects on cardiac repolarization
Authors: Odening Katja E. , Hyder Omar , Chaves Leonard , Schofield Lorraine , Brunner Michael , Kirk Malcolm , Zehender Manfred , Peng Xuwen , Koren Gideon
Published: October 2008

Anesthetic agents prolong cardiac repolarization by blocking ion currents. However, the clinical relevance of this blockade in subjects with reduced repolarization reserve is unknown. We have generated transgenic long QT syndromes type 1 (LQT1) and type 2 (LQT2) rabbits that lack slow delayed rectifier K+currents ( IKs) or rapidly activating K+currents ( IKr) and used them as a model system to detect the channel-blocking properties of anesthetic agents. Therefore, LQT1, LQT2, and littermate control (LMC) rabbits were administered isoflurane, thiopental, midazolam, propofol, or ketamine, and surface ECGs were analyzed. Genotype-specific heart rate correction formulas were used to determine the expected QT interval at a given heart rate. The QT index (QTi) was calculated as percentage of the observed QT/expected QT. Isoflurane, a drug that blocks IKs,prolonged the QTi only in LQT2 and LMC but not in LQT1 rabbits.Midazolam, which blocks inward rectifier K+current ( IK1), prolonged the QTi in both LQT1 and LQT2 but not in LMC. Thiopental, which blocks both IKsand IK1, increased the QTi in LQT2 and LMC more than in LQT1. By contrast, ketamine, which does not block IKr, IKs, or IK1, did not alter the QTi in any group. Finally, anesthesia with isoflurane or propofol resulted in lethal polymorphic ventricular tachycardia (pVT) in three out of nine LQT2 rabbits. Transgenic LQT1 and LQT2 rabbits could serve as an in vivo model in which to examine the pharmacogenomics of drug-induced QT prolongation of anesthetic agents and their proarrhythmic potential. Transgenic LQT2 rabbits developed pVT under isoflurane and propofol, underlining the proarrhythmic risk of IKsblockers in subjects with reduced IKr.
Deficient BH4production via de novo and salvage pathways regulates NO responses to cytokines in adult cardiac myocytes
Authors: Ionova Irina A. , Vásquez-Vivar Jeannette , Whitsett Jennifer , Herrnreiter Anja , Medhora Meetha , Cooley Brian C. , Pieper Galen M.
Published: October 2008

Adult rat cardiac myocytes typically display a phenotypic response to cytokines manifested by low or no increases in nitric oxide (NO) production via inducible NO synthase (iNOS) that distinguishes them from other cell types. To better characterize this response, we examined the expression of tetrahydrobiopterin (BH4)-synthesizing and arginine-utilizing genes in cytokine-stimulated adult cardiac myocytes. Intracellular BH4and 7,8-dihydrobiopterin (BH2) and NO production were quantified. Cytokines induced GTP cyclohydrolase and its feedback regulatory protein but with deficient levels of BH4synthesis. Despite the induction of iNOS protein, cytokine-stimulated adult cardiac myocytes produced little or no increase in NO versus unstimulated cells. Western blot analysis under nonreducing conditions revealed the presence of iNOS monomers. Supplementation with sepiapterin (a precursor of BH4) increased BH4as well as BH2, but this did not enhance NO levels or eliminate iNOS monomers. Similar findings were confirmed in vivo after treatment of rat cardiac allograft recipients with sepiapterin. It was found that expression of dihydrofolate reductase, required for full activity of the salvage pathway, was not detected in adult cardiac myocytes. Thus, adult cardiac myocytes have a limited capacity to synthesize BH4after cytokine stimulation. The mechanisms involve posttranslational factors impairing de novo and salvage pathways. These conditions are unable to support active iNOS protein dimers necessary for NO production. These findings raise significant new questions about the prevailing understanding of how cytokines, via iNOS, cause cardiac dysfunction and injury in vivo during cardiac inflammatory disease states since cardiac myocytes are not a major source of high NO production.
Isovolemic exchange transfusion with increasing concentrations of low oxygen affinity hemoglobin solution limits oxygen delivery due to vasoconstriction
Authors: Cabrales Pedro , Tsai Amy G. , Intaglietta Marcos
Published: October 2008

O2-carrying fluids based on hemoglobin (Hb) are in various stages of clinical trials to determine their suitability as O2-carrying plasma expanders. Polymerized Hb solutions are characterized by their vasoactivity, low O2affinity, oncotic effect, prolonged shelf life, and stability. Physiological responses to facilitated O2transport after exchange transfusion with polymerized bovine Hb (PBH) were studied in the hamster window chamber model during acute moderate anemia to determine how PBH affects microvascular perfusion and tissue oxygenation. The anemic state [29% hematocrit (Hct)] was induced by hemodilution with a plasma expander (70 kDa dextran). After hemodilution, animals were randomly assigned to different exchange transfusion groups. Study groups were based on the concentration of PBH used, namely: PBH at 13 g Hb/dl [PBH13], PBH diluted to 8 (PBH8) or 4 (PBH4) g Hb/dl in albumin solution at matching colloidal osmotic pressure (COP), and no PBH (only albumin solution) at matching COP (PBH0). Measurement of systemic parameters, microvascular hemodynamics, capillary perfusion, and intravascular and tissue O2levels was performed at 18% Hct. Restitution of O2-carrying capacity with PBH13 increased arterial pressure and triggered vasoconstriction, low perfusion, and high peripheral resistance. PBH4 and PBH0 exhibited lower arterial pressures compared with PBH13. Exchange transfused animals with PBH8 and PBH4 better maintained perfusion and functional capillary density than PBH13. Blood gas parameters and acid-base balance were recovered proportional to microvascular perfusion. Arterial O2tensions were improved with PBH4 and PBH8 by preventing O2precapillary release and increasing O2reserve. Further studies to establish PBH optimal dosage, efficacy, safety, and its effect on outcome are indicated before Hb-based O2-carrying blood substitutes are implemented in routine practice.
Myosin phosphorylation triggers actin polymerization in vascular smooth muscle
Authors: Chen Xuesong , Pavlish Kristin , Benoit Joseph N.
Published: October 2008

A variety of contractile stimuli increases actin polymerization, which is essential for smooth muscle contraction. However, the mechanism(s) of actin polymerization associated with smooth muscle contraction is not fully understood. We tested the hypothesis that phosphorylated myosin triggers actin polymerization. The present study was conducted in isolated intact or β-escin-permeabilized rat small mesenteric arteries. Reductions in the 20-kDa myosin regulatory light chain (MLC20) phosphorylation were achieved by inhibiting MLC kinase with ML-7. Increases in MLC20phosphorylation were achieved by inhibiting myosin light chain phosphatase with microcystin. Isometric force, the degree of actin polymerization as indicated by the F-actin-to-G-actin ratio, and MLC20phosphorylation were determined. Reductions in MLC20phosphorylation were associated with a decreased force development and actin polymerization. Increased MLC20phosphorylation was associated with an increased force generation and actin polymerization. We also found that a heptapeptide that mimics the actin-binding motif of myosin II enhanced microcystin-induced force generation and actin polymerization without affecting MLC20phosphorylation in β-escin-permeabilized vessels. Collectively, our data demonstrate that MLC20phosphorylation is capable of triggering actin polymerization. We further suggest that the binding of myosin to actin triggers actin polymerization and enhances the force development in arterial smooth muscle.
Modulation of glucocorticoid receptor expression, inflammation, and cell apoptosis in septic guinea pig lungs using methylprednisolone
Authors: Kamiyama Koki , Matsuda Naoyuki , Yamamoto Seiji , Takano Ken-ichi , Takano Yasuo , Yamazaki Hiromi , Kageyama Shun-ichiro , Yokoo Hiroki , Nagata Takuya , Hatakeyama Noboru , Tsukada Kazuhiro , Hattori Yuichi
Published: October 2008

The use of glucocorticoids for treatment of sepsis has waxed and waned during the past several decades, and recent randomized controlled trials have evoked a reassessment of this therapy. Most glucocorticoid actions are mediated by its specific intracellular receptors (GRs). Thus we initially evaluated whether sepsis and high-dose corticosteroid therapy can regulate guinea pig pulmonary expression of GRs: active receptor, GRα, and dominant negative receptor, GRβ. Sepsis induction by LPS injection (300 μg/kg ip) decreased mRNA and protein levels of GRα and increased protein expression of GRβ in lungs. High-dose methylprednisolone (40 mg/kg ip), administered simultaneously with LPS, markedly potentiated the decrease in GRα expression but slightly affected the increase in GRβ expression. Consequently, this led to a significant reduction in GRα nuclear translocation. Nevertheless, methylprednisolone treatment strongly eliminated LPS induction of NF-κB activity, as determined by NF-κB nuclear translocation and by gel mobility shift assays. Furthermore, the LPS-induced increase in inflammatory cells in bronchoalveolar lavage fluid was blunted by administration of the corticosteroid. On the other hand, immunofluorescent staining for cleaved caspase-3 showed a marked increase in this proapoptotic marker in lung sections, and terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling (TUNEL) represented an enhanced appearance of cell apoptosis in lungs and spleen when methylprednisolone was given together with LPS. Cell apoptosis is now considered to play a role in the pathogenesis of septic syndrome. We thus suggest that the action of glucocorticoids at high doses to accelerate sepsis-induced cell apoptosis may overwhelm their therapeutic advantages in septic shock.
Thrombin-mediated increases in cytosolic [Ca2+] involve different mechanisms in human pulmonary artery smooth muscle and endothelial cells
Authors: Sacks Richard S. , Firth Amy L. , Remillard Carmelle V. , Agange Negin , Yau Jocelyn , Ko Eun A. , Yuan Jason X.-J.
Published: October 2008

Thrombin is a procoagulant inflammatory agonist that can disrupt the endothelium-lumen barrier in the lung by causing contraction of endothelial cells and promote pulmonary cell proliferation. Both contraction and proliferation require increases in cytosolic Ca2+concentration ([Ca2+]cyt). In this study, we compared the effect of thrombin on Ca2+signaling in human pulmonary artery smooth muscle (PASMC) and endothelial (PAEC) cells. Thrombin increased the [Ca2+]cytin both cell types; however, the transient response was significantly higher and recovered quicker in the PASMC, suggesting different mechanisms may contribute to thrombin-mediated increases in [Ca2+]cytin these cell types. Depletion of intracellular stores with cyclopiazonic acid (CPA) in the absence of extracellular Ca2+induced calcium transients representative of those observed in response to thrombin in both cell types. Interestingly, CPA pretreatment significantly attenuated thrombin-induced Ca2+release in PASMC; this attenuation was not apparent in PAEC, indicating that a PAEC-specific mechanism was targeted by thrombin. Treatment with a combination of CPA, caffeine, and ryanodine also failed to abolish the thrombin-induced Ca2+transient in PAEC. Notably, thrombin-induced receptor-mediated calcium influx was still observed in PASMC after CPA pretreatment in the presence of extracellular Ca2+. Ca2+oscillations were triggered by thrombin in PASMC resulting from a balance of extracellular Ca2+influx and Ca2+reuptake by the sarcoplasmic reticulum. The data show that thrombin induces increases in intracellular calcium in PASMC and PAEC with a distinct CPA-, caffeine-, and ryanodine-insensitive release existing only in PAEC. Furthermore, a dynamic balance between Ca2+influx, intracellular Ca2+release, and reuptake underlie the Ca2+transients evoked by thrombin in some PASMC. Understanding of such mechanisms will provide an important insight into thrombin-mediated vascular injury during hypertension.
The fibrinolytic system and the regulation of lung epithelial cell proteolysis, signaling, and cellular viability
Authors: Shetty Sreerama , Padijnayayveetil Joseph , Tucker Torry , Stankowska Dorota , Idell Steven
Published: October 2008

The urokinase-type plasminogen activator (uPA), its receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1) are key components of the fibrinolytic system and are expressed by lung epithelial cells. uPA, uPAR, and PAI-1 have been strongly implicated in the pathogenesis of acute lung injury (ALI) and pulmonary fibrosis. Recently, it has become clear that regulation of uPA, uPAR, and PAI-1 occurs at the posttranscriptional level of mRNA stability in lung epithelial cells. uPA further mediates its own expression in these cells as well as that of uPAR and PAI-1 through induction of changes in mRNA stability. In addition, uPA-mediated signaling controls the expression of the tumor suppressor protein p53 in lung epithelial cells at the posttranslational level. p53 has recently been shown to be a trans-acting uPA, uPAR, and PAI-1 mRNA-binding protein that regulates the stability of these mRNAs. It is now clear that signaling initiated by uPA mediates dose-dependent regulation of lung epithelial cell apoptosis and likewise involves changes in p53, uPA, uPAR, and PAI-1 expression. These findings demonstrate that the uPA-uPAR-PAI-1 system of lung epithelial cells mediates a broad repertoire of responses that encompass but extend well beyond traditional fibrinolysis, involve newly recognized interactions with p53 that influence the viability of the lung epithelium, and are thereby implicated in the pathogenesis of ALI and its repair.
Sodium-, potassium-, chloride-, and bicarbonate-related effects on blood pressure and electrolyte homeostasis in deoxycorticosterone acetate-treated rats
Authors: Ziomber Agata , Machnik Agnes , Dahlmann Anke , Dietsch Peter , Beck Franz-Xaver , Wagner Hubertus , Hilgers Karl F. , Luft Friedrich C. , Eckardt Kai-Uwe , Titze Jens
Published: October 2008

Na+ loading without Cl− fails to increase blood pressure in the DOCA model. We compared the changes in the total body (TB) effective Na+, K+, Cl−, and water (TBW) content as well as in intracellular (ICV) or extracellular (ECV) volume in rats receiving DOCA-NaCl, DOCA-NaHCO3, or DOCA-KHCO3. We divided 42 male rats into 5 groups. Group 1 was untreated, group 2 received 1% NaCl, and groups 3, 4, and 5 were treated with DOCA and received 1% NaCl, 1.44% NaHCO3, or 1.7% KHCO3 to drink. We measured mean arterial blood pressure (MAP) directly after 3 wk. Tissue electrolyte and water content was measured by chemical analysis. Compared with control rats, DOCA-NaCl increased MAP while DOCA-NaHCO3 and DOCA-KHCO3 did not. DOCA-NaCl increased TBNa+ 26% but only moderately increased TBW. DOCA-NaHCO3 led to similar TBNa+ excess, while TBW and ICV, but not ECV, were increased more than in DOCA-NaCl rats. DOCA-KHCO3 did not affect TBNa+ or volume. At a given TB(Na++K+) and TBW, MAP in DOCA-NaCl rats was higher than in control, DOCA-NaHCO3, and DOCA-KHCO3 rats, indicating that hypertension in DOCA-NaCl rats was not dependent on TB(Na++K+) and water mass balance. Skin volume retention was hypertonic compared with serum and paralleled hypertension in DOCA-NaCl rats. These rats had higher TB(Na++K+)-to-TBW ratio in accumulated fluid than DOCA-NaHCO3 rats. DOCA-NaCl rats also had increased intracellular Cl− concentrations in skeletal muscle. We conclude that excessive cellular electrolyte redistribution and/or intracellular Na+ or Cl− accumulation may play an important role in the pathogenesis of salt-sensitive hypertension.
Dynamics of Evoked Local Field Potentials in the Hippocampus of Epileptic Rats With Spontaneous Seizures
Authors: Queiroz Claudio M. , Gorter Jan A. , Lopes da Silva Fernando H. , Wadman Wytse J.
Published: October 2008

A change in neuronal network excitability within the hippocampus is one of the hallmarks of temporal lobe epilepsy (TLE). In the dentate gyrus (DG), however, neuronal loss and mossy fiber sprouting are associated with enhanced inhibition rather than progressive hyperexcitability. The aim of this study was to investigate how alterations in excitability take place in association with spontaneous seizures expressed in the DG before, during, and after a seizure. For this purpose, we used freely moving rats that had developed spontaneous seizures after a kainate-induced status epilepticus (SE). Continuous EEG was recorded in the DG during several days along with local field potentials (LFPs) that were evoked every 15–30 s by applying paired-pulse stimuli to the angular bundle. Input-output relations showed increased paired pulse depression in epileptic compared with control rats, suggesting a rather strong inhibition in the DG during the interictal state. A characteristic pattern of changes in intrinsic excitability was observed during the ictal period: an increase in the population spike (PS) amplitude, mostly during the early phase of a seizure and often followed by a decrease of the main evoked potential amplitude. The paired-pulse extracellular postsynaptic potential (fEPSP) ratio increased during the seizure and did slowly recover to preictal levels after the seizure ended. Although clear changes in excitability occurred during and after seizure activity, changes of LFP parameters were more subtle before seizure onset; a significant reduction of LFP and PS amplitudes was observed that started 1–2 min in advance in ∼33% of the cases; in ∼18%, an increase of LFP/PS amplitude was observed; in the other cases, no significant change was observed. Taken together, these results provide evidence that, in this experimental model, DG physiology is more likely to follow the already ongoing seizure activity rather than to contribute to its generation.
An Implicit Iterative Scheme for an Infinite Countable Family of Asymptotically Nonexpansive Mappings in Banach Spaces
Authors: Wang Shenghua , Yu Lanxiang , Guo Baohua
Published: October 2008

Let "Equation missing" be a nonempty closed convex subset of a reflexive Banach space "Equation missing" with a weakly continuous dual mapping, and let "Equation missing" be an infinite countable family of asymptotically nonexpansive mappings with the sequence "Equation missing" satisfying "Equation missing" for each "Equation missing", "Equation missing", and "Equation missing" for each "Equation missing". In this paper, we introduce a new implicit iterative scheme generated by "Equation missing" and prove that the scheme converges strongly to a common fixed point of "Equation missing", which solves some certain variational inequality.
Decreasing Cervical Cancer Mortality in Mexico: Effect of Papanicolaou Coverage, Birthrate, and the Importance of Diagnostic Validity of Cytology
Authors: Lazcano-Ponce Eduardo , Palacio-Mejia Lina Sofía , Allen-Leigh Betania , Yunes-Diaz Elsa , Alonso Patricia , Schiavon Raffaela , Hernandez-Avila Mauricio
Published: October 2008

Background: The reduction in cervical cancer mortality in developed countries has been attributed to well-organized, population-based prevention and control programs that incorporate screening with the Papanicolaou (Pap) smear. In Mexico, there has been a decrease in cervical cancer mortality, but it is unclear what factors have prompted this reduction.

Methods: Using data from national indicators, we determined the correlation between cervical cancer mortality rates and Pap coverage, birthrate, and gross national product, using a linear regression model. We determined relative risk of dying of cervical cancer according to place of residence (rural/urban, region) using a Poisson model. We also estimated Pap smear coverage using national survey data and evaluated the validity and reproducibility of Pap smear diagnosis.

Results: An increase in Pap coverage (β = −0.069) and a decrease in birthrate (β = 0.054) correlate with decreasing cervical cancer mortality in Mexico. Self-reported Pap smear rates in the last 12 months vary from 27.4% to 48.1%. Women who live in the central (relative risk, 1.04) and especially the southern (relative risk, 1.47) parts of Mexico have a greater relative risk of dying of cervical cancer than those who live in the north. There is a high incidence of false negatives in cervical cytology laboratories in Mexico; the percentage of false negatives varies from 3.33% to 53.13%.

Conclusions: The decrease in cervical cancer mortality observed in Mexico is proportional to increasing Pap coverage and decreasing birthrate. Accreditation of cervical cytology laboratories is needed to improve diagnostic precision. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2808–17)
Diurnal, Weekly, and Long-Time Variation in Serum Concentrations of YKL-40 in Healthy Subjects
Authors: Johansen Julia S. , Lottenburger Tine , Nielsen Hans Jørgen , Jensen Jens Erik B. , Svendsen Mads N. , Kollerup Gine , Christensen Ib J.
Published: October 2008

Serum YKL-40 is a potential biomarker of prognosis in cancer patients, but assessment of serum YKL-40 requires knowledge of its normal variation. In this study, we evaluated diurnal, weekly, and long-term variation in serum YKL-40 in healthy subjects using a commercial ELISA. The intra-assay coefficient of variation was ≤5.0% and interassay ≤10.2%. Systematic changes in diurnal measurements of serum YKL-40 could not be shown. Physical exercise for 20 min had no effect on serum YKL-40. The within-subject coefficient of variation, including variation over time and interassay, was 28.8% and 30.2% over a period of 2 and 3 years, and the intraclass correlation coefficients were 72.4% and 72.2%, indicating reasonable reliability of serum YKL-40 measurements. The 95% confidence limits for the difference between two measurements (same subject), including interassay variation, were a 52% reduction and a 109% increase in serum YKL-40. These studies show that relatively small variation is found in serum YKL-40 in healthy subjects. However, a single measurement of serum YKL-40 from an individual may not have a prognostic value, and serum YKL-40 alone cannot be a good biomarker for cancer because serum YKL-40 can be elevated in patients with other diseases characterized by inflammation and tissue remodeling. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2603–8)
The Performance of Human Papillomavirus High-Risk DNA Testing in the Screening and Diagnostic Settings
Authors: Cárdenas-Turanzas Marylou , Nogueras-Gonzalez Graciela M. , Scheurer Michael E. , Adler-Storthz Karen , Benedet J.L. , Beck J. Robert , Follen Michele , Cantor Scott B.
Published: October 2008

Objective: We sought to evaluate the performance of the human papillomavirus high-risk DNA test in patients 30 years and older.

Materials and Methods: Screening (n = 835) and diagnosis (n = 518) groups were defined based on prior Papanicolaou smear results as part of a clinical trial for cervical cancer detection. We compared the Hybrid Capture II (HCII) test result with the worst histologic report. We used cervical intraepithelial neoplasia (CIN) 2/3 or worse as the reference of disease. We calculated sensitivities, specificities, positive and negative likelihood ratios (LR+ and LR−), receiver operating characteristic (ROC) curves, and areas under the ROC curves for the HCII test. We also considered alternative strategies, including Papanicolaou smear, a combination of Papanicolaou smear and the HCII test, a sequence of Papanicolaou smear followed by the HCII test, and a sequence of the HCII test followed by Papanicolaou smear.

Results: For the screening group, the sensitivity was 0.69 and the specificity was 0.93; the area under the ROC curve was 0.81. The LR+ and LR− were 10.24 and 0.34, respectively. For the diagnosis group, the sensitivity was 0.88 and the specificity was 0.78; the area under the ROC curve was 0.83. The LR+ and LR− were 4.06 and 0.14, respectively. Sequential testing showed little or no improvement over the combination testing.

Conclusions: The HCII test in the screening group had a greater LR+ for the detection of CIN 2/3 or worse. HCII testing may be an additional screening tool for cervical cancer in women 30 years and older. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2865–71)
Colorectal Cancer Is an Ambulatory Care Sensitive Condition
Authors: Sarfaty Mona , Yuen Elaine
Published: October 2008

Ambulatory Care Sensitive Conditions (ACSC) are conditions where the provision of ambulatory care may affect the probability of hospitalization or the severity of the disease at the time of hospitalization. Population-based measurement of ACSCs can focus attention on aspects of ambulatory care that merit strengthening to improve access, quality, or patient compliance to achieve better outcomes and reduce costs. If colorectal cancer was added to the list of ACSCs, it would highlight the continuum of care that starts in the ambulatory setting and includes risk assessment as well as access to colonoscopy, which is the only means of adenoma removal after a positive screen. Each link in the continuum of care can increase or reduce the rates of colorectal cancer incidence and mortality at the local and national levels. Employing colorectal cancer as an ACSC at the hospital level or state level can provoke policy makers and managers to examine these links for gaps and weaknesses that merit attention and may be addressed. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2531–5)