bluuebunny/crossref_metadata_2025 huggingface dataset:
Fas-independent mitochondrial damage triggers cardiomyocyte death after ischemia-reperfusion
Authors: Gomez L. , Chavanis N. , Argaud L. , Chalabreysse L. , Gateau-Roesch O. , Ninet J. , Ovize M.
Published: July 2005

The Fas/Fas ligand and mitochondria pathways have been involved in cell death in several cell types. We combined the genetic inactivation of the Fas receptor ( lpr mice), on the one hand, to the pharmacological inhibition of the mitochondrial permeability transition pore (mPTP), on the other hand, to investigate which of these pathways is predominantly activated during prolonged ischemia-reperfusion. Anesthetized C57BL/6JICO (control) and C57BL/6- lpr mice were pretreated with either saline or cyclosporin A (CsA; 40 mg/kg, 3 times a day), an inhibitor of the mPTP, and underwent 25 min of ischemia and 24 h of reperfusion. After 24 h of reperfusion, hearts were harvested: infarct size was assessed by 2,3,5-triphenyltetrazolium chloride staining, myocardial apoptosis by caspase 3 activity, and mitochondrial permeability transition by Ca2+-induced mPTP opening using a potentiometric approach. Infarct size was comparable in untreated control and lpr mice, ranging from 77 ± 5% to 83 ± 3% of the area at risk. CsA significantly reduced infarct size in control and lpr hearts. Control and lpr hearts exhibited comparable increase in caspase 3 activity that averaged 57 ± 18 and 49 ± 5 pmol·min−1·mg−1, respectively. CsA treatment significantly reduced caspase 3 activity in control and lpr hearts. The Ca2+overload required to open the mPTP was decreased to a similar extent in lpr and controls. CsA significantly attenuated Ca2+-induced mPTP opening in both groups. Our results suggest that the Fas pathway likely plays a minor role, whereas mitochondria are preferentially involved in mice cardiomyocyte death after a lethal ischemia-reperfusion injury.
Late preconditioning induced by NO donors, adenosine A1 receptor agonists, and δ1-opioid receptor agonists is mediated by iNOS
Authors: Guo Yiru , Stein Adam B. , Wu Wen-Jian , Zhu Xiaoping , Tan Wei , Li Qianhong , Bolli Roberto
Published: July 2005

Although ischemia-induced late preconditioning (PC) is known to be mediated by inducible nitric oxide (NO) synthase (iNOS), the role of this enzyme in pharmacologically induced late PC remains unclear. We tested whether targeted disruption of the iNOS gene abrogates late PC elicited by three structurally different NO donors [diethylenetriamine/NO (DETA/NO), nitroglycerin (NTG), and S-nitroso- N-acetyl-penicillamine (SNAP)], an adenosine A1 receptor agonist [2-chloro- N6-cyclopentyladenosine (CCPA)], and a δ1-opioid receptor agonist (TAN-670). The mice were subjected to a 30-min coronary occlusion followed by 24 h of reperfusion. In iNOS knockout ( iNOS−/−) mice, infarct size was similar to wild-type (WT) controls, indicating that iNOS does not modulate infarct size in the absence of PC. Pretreatment of WT mice with DETA/NO, NTG, SNAP, TAN-670, or CCPA 24 h before coronary occlusion markedly reduced infarct size. In iNOS−/− mice, however, the late PC effect elicited by DETA/NO, NTG, SNAP, TAN-670, and CCPA was completely abrogated. Furthermore, in WT mice pretreated with TAN-670 or CCPA, the selective iNOS inhibitor 1400W also abolished the delayed PC properties of these drugs; 1400W had no effect in WT mice. These data demonstrate that iNOS plays an obligatory role in NO donor-induced, adenosine A1 receptor agonist-induced, and δ1-opioid receptor agonist-induced late PC, underscoring the critical role of this enzyme as a common mediator of cardiac adaptations to stress.
Isoflurane induces second window of preconditioning through upregulation of inducible nitric oxide synthase in rat heart
Authors: Wakeno-Takahashi Mayu , Otani Hajime , Nakao Shinichi , Imamura Hiroji , Shingu Koh
Published: July 2005

The second window of preconditioning (SWOP) induced by inhalation of volatile anesthetics has been documented in the rat heart and is triggered by nitric oxide synthase (NOS), but involvement of NOS in the mediator phase of isoflurane-induced SWOP has not been demonstrated. We tested the hypothesis that isoflurane-induced SWOP is mediated through upregulation of inducible NOS (iNOS). Rats inhaled 0.75 minimum alveolar concentration (MAC) isoflurane, 1.5 MAC isoflurane, or O2 for 2 h. After 24, 48, 72, and 96 h, the isolated heart was perfused with buffer and subjected to 30 min of ischemia followed by 2 h of reperfusion. Inhalation of 0.75 and 1.5 MAC isoflurane significantly limited infarct size after ischemia-reperfusion 24–72 h after isoflurane inhalation. The maximum effect was obtained 48 h after inhalation of 1.5 MAC isoflurane. Postischemic left ventricular function was improved only 48 h after inhalation of 1.5 MAC isoflurane. iNOS expression and activity in the heart were increased 24–72 h after inhalation of 1.5 MAC isoflurane; this increase was less pronounced after inhalation of 0.75 MAC isoflurane. A selective iNOS inhibitor, 1400W (10 μM), abolished iNOS activation and cardioprotection induced 48 h after inhalation of 1.5 MAC isoflurane. These results suggest that isoflurane inhalation induces SWOP after 24–72 h through overexpression and activation of iNOS in the rat heart.
Overexpression of eNOS in brain stem reduces enhanced sympathetic drive in mice with myocardial infarction
Authors: Sakai Koji , Hirooka Yoshitaka , Shigematsu Hideaki , Kishi Takuya , Ito Koji , Shimokawa Hiroaki , Takeshita Akira , Sunagawa Kenji
Published: July 2005

Reduced nitric oxide (NO) in the brain might contribute to enhanced sympathetic drive in heart failure (HF). The aim of this study was to determine whether increased NO production induced by local overexpression of endothelial NO synthase (eNOS) in the nucleus tractus solitarius (NTS) of the brain stem reduces the enhanced sympathetic drive in mice with HF. Myocardial infarction (MI) was induced in mice by ligating the left coronary artery. MI mice exhibited left ventricular dilatation and a reduced left ventricular ejection fraction. Urinary norepinephrine excretion in MI mice was greater than that in sham-operated mice, indicating that sympathetic drive was enhanced in this model. Thus this model has features that are typical of HF. Western blot analysis and immunohistochemical staining for neuronal NOS (nNOS) indicated that nNOS protein expression was significantly reduced in the brain stem of MI mice. MI mice had a significantly smaller increase in blood pressure evoked by intracisternal injection of NG-monomethyl-l-arginine than sham-operated mice. Adenoviral vectors encoding either eNOS (AdeNOS) or β-galactosidase (Adβgal) were transfected into the NTS to examine the effect of increased NO production in the NTS on the enhanced sympathetic drive in HF. After the gene transfer, urinary norepinephrine excretion was reduced in AdeNOS-transfected MI mice but not in Adβgal-transfected MI mice. These results indicate that nNOS expression in the brain stem, especially in the NTS, is reduced in the MI mouse model of HF, and increased NO production induced by overexpression of eNOS in the NTS attenuates the enhanced sympathetic drive in this model.
Ontogeny of phosphoinositide 3-kinase signaling in developing heart: effect of acute β-adrenergic stimulation
Authors: Tseng Yi-Tang , Yano Naohiro , Rojan Adam , Stabila Joan P. , McGonnigal Bethany G. , Ianus Vlad , Wadhawan Rajan , Padbury James F.
Published: July 2005

Signaling pathways underlying transition of cardiomyocyte growth from hyperplasia in fetal/newborn to hypertrophy in postnatal/adult hearts are not well understood. We have shown that β-adrenergic receptor (β-AR)-mediated regulation of neonatal cardiomyocyte proliferation involves p70 ribosomal protein S6 kinase (p70S6K). Here we examined the ontogeny of phosphoinositide 3-kinase (PI3K)/p70S6K signaling pathway in rat hearts and investigated the influence of β-AR on this pathway during development. Cardiac PI3K and p70S6K1 activities were high in the embryonic day 20 fetus, decreased gradually postnatally, and were low in the adult. In contrast, p70S6K2 was barely detectable. Phosphorylation of p70S6K1, Akt, and phosphoinositide-dependent protein kinase 1 were markedly increased in late gestation and early postnatal life but not in adult hearts. Phosphatase and tensin homolog on chromosome 10 (PTEN), a negative regulator of PI3K, was highly expressed in adult hearts but only at low levels and mostly in the phosphorylated (inactivated) form in the fetus. β-AR stimulation resulted in increased cardiac p70S6K1 activity only in animals ≥2 wk old, whereas Akt level was increased in all developmental stages tested. These increases were accompanied by increased Bcl-2 associated death promoter (Ser136) phosphorylation without changes in PTEN level. Thus there is globally high input of cardiac PI3K signaling during the fetal-neonatal transition period. Inactivation of PTEN may in part contribute to the high activity of PI3K signaling, which coincides with the period of high cardiomyocyte proliferation. β-AR stimulation activates cardiac p70S6K1 and Akt in postnatal animals and may activate cardiac survival signals. These data provide further evidence for the importance of β-AR and PI3K signaling in the regulation of cardiac growth during development.
Testosterone augments endotoxin-mediated cerebrovascular inflammation in male rats
Authors: Razmara Ali , Krause Diana N. , Duckles Sue P.
Published: July 2005

Activation of inflammatory mechanisms contributes to cerebrovascular pathophysiology. Male gender is associated with increased stroke risk, yet little is known about the effects of testosterone in the cerebral circulation. Therefore, we explored the impact of testosterone treatment on cerebrovascular inflammation with both in vivo and in vitro models of inflammation. We hypothesized that testosterone would augment the expression of two vascular markers of cellular inflammation, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Using four groups of male rats [intact, orchiectomized (ORX), and ORX treated with either testosterone (ORXT) or the testosterone metabolite 17β-estradiol (ORXE)], we determined effects of the sex hormones on cerebrovascular inflammation after intraperitoneal LPS injection. Western blot analysis showed that induction of inflammatory markers was increased in cerebral blood vessels from ORXT rats compared with intact or ORX rats. In contrast, in cerebral blood vessels from ORXE rats, there was a significant decrease in endotoxin-induced COX-2 and iNOS protein levels. Confocal microscopy of cerebral blood vessels from ORXT rats showed increased COX-2 and iNOS immunoreactivity in both endothelial and smooth muscle cells after LPS treatment. In vitro incubation with LPS also induced COX-2 in pial vessels isolated from the four animal treatment groups, with the greatest induction observed in ORXT vessels compared with the ORX and ORXE groups. Production of PGE2, a principal COX-2-derived prostaglandin end product, was also greatest in cerebral vessels isolated from ORXT rats. In conclusion, testosterone increases cerebrovascular inflammation; this effect may contribute to stroke differences between men and women.
Increased expression of iNOS is associated with endothelial dysfunction and impaired pressor responsiveness in streptozotocin-induced diabetes
Authors: Nagareddy Prabhakara Reddy , Xia Zhengyuan , McNeill John H. , MacLeod Kathleen M.
Published: July 2005

Studies in streptozotocin (STZ)-induced diabetic rats have demonstrated cardiovascular abnormalities such as depressed mean arterial blood pressure (MABP) and heart rate (HR), endothelial dysfunction, and attenuated pressor responses to vasoactive agents. We investigated whether these abnormalities are due to diabetes-associated activation of inducible nitric oxide synthase (iNOS). In addition, the effect of the duration of diabetes on these abnormalities was also evaluated. Diabetes was induced by administration of 60 mg/kg STZ via the tail vein. One, 3, 9, or 12 wk after STZ injection, MABP, HR, and endothelial function were measured in conscious unrestrained rats. Pressor response curves to bolus doses of methoxamine (MTX) and angiotensin II (ANG II) were constructed in the presence of N-[3(aminomethyl)benzyl]-acetamidine, dihydrochloride (1400W), a specific inhibitor of iNOS. Depressed MABP and HR and impairment of endothelial function were observed as early as 3 wk after induction of diabetes. Acute inhibition of iNOS with 1400W (3 mg/kg iv) restored the attenuated pressor responses to both MTX and ANG II without affecting the basal MABP and HR. Immunohistochemical and Western analysis blot studies in cardiovascular tissues revealed decreased expression of endothelial nitric oxide synthase (eNOS) concomitant with increased expression of iNOS and nitrotyrosine with the progression of diabetes. Our findings suggest that induction of iNOS in cardiovascular tissues is dependent on the duration of diabetes and contributes significantly to the depressed pressor responses to vasoactive agents and potentially to endothelial dysfunction.
Determination of layer-specific mechanical properties of human coronary arteries with nonatherosclerotic intimal thickening and related constitutive modeling
Authors: Holzapfel Gerhard A. , Sommer Gerhard , Gasser Christian T. , Regitnig Peter
Published: July 2005

At autopsy, 13 nonstenotic human left anterior descending coronary arteries [71.5 ± 7.3 (mean ± SD) yr old] were harvested, and related anamnesis was documented. Preconditioned prepared strips ( n = 78) of segments from the midregion of the left anterior descending coronary artery from the individual layers in axial and circumferential directions were subjected to cyclic quasi-static uniaxial tension tests, and ultimate tensile stresses and stretches were documented. The ratio of outer diameter to total wall thickness was 0.189 ± 0.014; ratios of adventitia, media, and intima thickness to total wall thickness were 0.4 ± 0.03, 0.36 ± 0.03, and 0.27 ± 0.02, respectively; axial in situ stretch of 1.044 ± 0.06 decreased with age. Stress-stretch responses for the individual tissues showed pronounced mechanical heterogeneity. The intima is the stiffest layer over the whole deformation domain, whereas the media in the longitudinal direction is the softest. All specimens exhibited small hysteresis and anisotropic and strong nonlinear behavior in both loading directions. The media and intima showed similar ultimate tensile stresses, which are on average three times smaller than ultimate tensile stresses in the adventitia (1,430 ± 604 kPa circumferential and 1,300 ± 692 kPa longitudinal). The ultimate tensile stretches are similar for all tissue layers. A recently proposed constitutive model was extended and used to represent the deformation behavior for each tissue type over the entire loading range. The study showed the need to model nonstenotic human coronary arteries with nonatherosclerotic intimal thickening as a composite structure composed of three solid mechanically relevant layers with different mechanical properties. The intima showed significant thickness, load-bearing capacity, and mechanical strength compared with the media and adventitia.
Regulation of oxygen delivery during induced polycythemia in exercising dogs
Authors: Lindenfeld JoAnn , Weil John V. , Travis Victoria L. , Horwitz Lawrence D.
Published: July 2005

Previous studies have concluded that polycythemia decreases oxygen delivery primarily because of a large fall in cardiac output associated with a rise in systemic vascular resistance that has been attributed to increased blood viscosity. However, because other studies have shown that polycythemia may not reduce oxygen delivery, an alternative hypothesis is that cardiac output falls in response to a rising oxygen content, thereby maintaining oxygen delivery constant. To determine whether oxygen content participates in the regulation of cardiac output during polycythemia, we studied eight chronically instrumented dogs trained to exercise on a treadmill. The dogs underwent exchange transfusion with packed red blood cells containing methemoglobin, which caused an increase in hematocrit from 35 ± 1 to 50 ± 1% and in viscosity, with little change in oxygen content. The expected fall in exercise cardiac output failed to occur after exchange transfusion with red blood cells containing methemoglobin (7.5 ± 4 vs. 6.8 ± 0.5 l/min; P = not significant), and there was no rise in systemic vascular resistance. Methylene blue was then administered intravenously to facilitate conversion of methemoglobin to oxyhemoglobin, which increased oxygen content (12.8 ± 0.9 vs. 18.4 ± 0.9 vol%; P < 0.01) with no change in hematocrit or viscosity. Resting cardiac output did not change significantly, but there was a significant decrease in exercise output (6.8 ± 0.5 vs. 5.8 ± 0.4 l/min; P < 0.05). Thus we conclude that the fall in cardiac output seen in acute polycythemia results in part from the regulation of oxygen delivery and is not due solely to increased blood viscosity.
Myocardial perfusion reserve in adults with cyanotic congenital heart disease
Authors: Brunken Richard C. , Perloff Joseph K. , Czernin Johannes , Campisi Roxana , Purcell Susan , Miner Pamela D. , Child John S. , Schelbert Heinrich R.
Published: July 2005

In patients with cyanotic congenital heart disease (CCHD), a right-to-left shunt results in systemic hypoxemia. Systemic hypoxemia incites a compensatory erythrocytosis, which increases whole blood viscosity. We considered that these changes might adversely influence myocardial perfusion in CCHD patients. Basal and hyperemic (intravenous dipyridamole) perfusion measurements were obtained with [13N]ammonia positron emission tomographic imaging in left (LV) and right (RV) ventricular and septal myocardium in 14 adults with CCHD [age: 34.1 yr (SD 6.5)]; hematocrit: 62.2% (SD 4.8)] and 10 healthy controls [age: 34.1 yr (SD 6.5)]. In patients, basal perfusion measurements were higher in LV [0.77 (SD 0.24) vs. 0.55 ml·min−1·g−1 (SD 0.09), P < 0.02], septum [0.71 (SD 0.16) vs. 0.49 ml·min−1·g−1 (SD 0.09), P < 0.001], and RV [0.77 (SD 0.30) vs. 0.38 ml·min−1·g−1 (SD 0.09), P < 0.001]. However, basal measurements normalized for the rate-pressure product were similar to those of controls. Calculated oxygen delivery relative to rate-pressure product was higher in the patients [2.2 (SD 0.8) vs. 1.6 (SD 0.4) × 10−5 ml O2·min−1·g tissue−1·(beats·mmHg)−1 in the LV, P < 0.05, and 2.0 (SD 0.7) vs. 1.4 (SD 0.3) × 10−5 ml O2·min−1·g tissue−1·(beats·mmHg)−1 in the septum, P < 0.01]. Hyperemic perfusion measurements in CCHD patients did not differ from controls [LV, 1.67 (SD 0.60) vs. 1.95 ml·min−1·g−1 (SD 0.46); septum, 1.44 (SD 0.56) vs. 1.98 ml·min−1·g−1 (SD 0.69); RV, 1.56 (SD 0.56) vs. 1.65 ml·min−1·g−1 (SD 0.64), P = not significant], and coronary vascular resistances were comparable [LV, 55 (SD 25) vs. 48 mmHg·ml−1·g·min (SD 16); septum, 67 (SD 35) vs. 50 mmHg·ml−1·g·min (SD 21); RV, 59 (SD 26) vs. 61 mmHg·ml−1·g·min (SD 27), P = not significant]. These findings suggest that adult CCHD patients have remodeling of the coronary circulation to compensate for the rheologic changes attending chronic hypoxemia.
Endotoxin-induced acute lung injury requires interaction with the liver
Authors: Siore Amsel M. , Parker Richard E. , Stecenko Arlene A. , Cuppels Chris , McKean Martha , Christman Brian W. , Cruz-Gervis Roberto , Brigham Kenneth L.
Published: July 2005

Clinical and laboratory data indicate that the liver plays an important role in the incidence, pathogenesis, and outcome of acute lung injury/acute respiratory distress syndrome. To distinguish direct effects of endotoxin on the lungs from liver-dependent effects during the early phase of the response to endotoxemia, we used an in situ perfused piglet preparation in which only the ventilated lung or both the lung and liver could be included in a blood perfused circuit. We monitored pulmonary vascular resistance, oxygenation, neutrophil count, lung edema as reflected by wet-dry weights of lung tissue, perfusate concentrations of TNF-α, IL-6, and 8-isoprostane (a marker of oxidative stress), and activation of the transcription factor (NF-κB) in lung tissue before and for 2 h after endotoxin. When only the lung was perfused, endotoxin caused pulmonary hypertension and neutropenia; but oxygenation was maintained; TNF-α, IL-6, and 8-isoprostane levels were minimally elevated; and there was no lung edema. When both the liver and lung were perfused, endotoxin caused marked hypoxemia, large increases in perfusate TNF-α, IL-6, and 8-isoprostane concentrations, and severe lung edema. NF-κB activation in the lung was greatest when the liver was in the perfusion circuit. We conclude that the direct effects of endotoxemia on the lungs include vasoconstriction and leukocyte sequestration, but not lung injury. Intense activation of the inflammatory response and oxidative injury that results in pulmonary edema and hypoxemia (acute lung injury) requires interaction of the lungs with the liver.
Role of Rho-kinase in reexpansion pulmonary edema in rabbits
Authors: Sawafuji Makoto , Ishizaka Akitoshi , Kohno Mitsutomo , Koh Hidefumi , Tasaka Sadatomo , Ishii Yoshiki , Kobayashi Koichi
Published: July 2005

Reexpansion of a collapsed lung increases the microvascular permeability and causes reexpansion pulmonary edema. Neutrophils and their products have been implicated in the development of this phenomenon. The small GTP-binding proteins Rho and its target Rho-kinase (ROCK) regulate endothelial permeability, although their roles in reexpansion pulmonary edema remain unclear. We studied the contribution of ROCK to pulmonary endothelial and epithelial permeability in a rabbit model of this disorder. Endothelial and epithelial permeability was assessed by measuring the tissue-to-plasma (T/P) and bronchoalveolar lavage (BAL) fluid-to-plasma (B/P) ratios with 125I-labeled albumin. After intratracheal instillation of 125I-albumin, epithelial permeability was also assessed from the plasma leak (PL) index, the ratio of 125I-albumin in plasma/total amount of instilled 125I-albumin. T/P, B/P, and PL index were significantly increased in the reexpanded lung. These increases were attenuated by pretreatment with Y-27632, a specific ROCK inhibitor. However, neutrophil influx, neutrophil elastase activity, and malondialdehyde concentrations in BAL fluid collected from the reexpanded lung were not changed by Y-27632. In endothelial monolayers, Y-27632 significantly attenuated the H2O2-induced increase in permeability and mitigated the morphological changes in the actin microfilament cytoskeleton of endothelial cells. These in vivo and in vitro observations suggest that the Rho/ROCK pathway contributes to the increase in alveolar barrier permeability associated with reexpansion pulmonary edema.
Sendai virus-induced alterations in lung structure/function correlate with viral loads and reveal a wide resistance/susceptibility spectrum among mouse strains
Authors: Faisca Pedro , Anh Dao Bui Tran , Desmecht Daniel J.-M.
Published: July 2005

The Paramyxoviridae family includes some of the most important and ubiquitous disease-causing viruses of infants and children, most of which cause significant infections of the respiratory tract. Evidence is accumulating in humans that genetic factors are involved in the severity of clinical presentation. As a first step toward the identification of the genes involved, this study was undertaken to establish whether laboratory mouse strains differ in susceptibility to Sendai virus, the murine counterpart of human type-1 parainfluenza virus which, historically, has been used extensively in studies that have defined the basic biological properties of paramyxoviruses in general. With this purpose in mind, double-chamber plethysmography data were collected daily for 7 days after inoculation of Sendai virus in six inbred strains of mice. In parallel, histological examinations and lung viral titration were carried out from day 5 to day 7 after inoculation. Pulmonary structure/function values closely reflected the success of viral replication in the lungs and revealed a pattern of continuous variation with resistant, intermediate, and susceptible strains. The results unambiguously suggest that BALB/c (resistant) and 129Sv (susceptible) strains should be used in crossing experiments aimed at identifying the genes involved in resistance to Paramyxoviridae by the positional cloning approach.
Pathways for clearance of surfactant protein A from the lung
Authors: Jain Deepika , Dodia Chandra , Fisher Aron B. , Bates Sandra R.
Published: July 2005

Uptake and degradation of125I-surfactant protein A (SP-A) over a 1-h period was studied in alveolar cells in culture and in isolated perfused lungs to elucidate the mechanism for clearance of the protein from the alveolar space. Specific inhibitors of clathrin- and actin-dependent endocytosis were utilized. In type II cells, uptake of SP-A, compared with controls, was decreased by 60% on incubation with clathrin inhibitors (amantadine and phenylarsine oxide) or with the actin inhibitor cytochalasin D. All agents reduced SP-A metabolism by alveolar macrophages. Untreated rat isolated perfused lungs internalized 36% of instilled SP-A, and 56% of the incorporated SP-A was degraded. Inhibitors of clathrin and actin significantly reduced SP-A uptake by ∼54%, whereas cytochalasin D inhibited SP-A degradation. Coincubation of agents did not produce an additive effect on uptake of SP-A by cultured pneumocytes or isolated perfused lungs, indicating that all agents affected the same pathway. Thus SP-A clears the lung via a clathrin-mediated pathway that requires the polymerization of actin.
Mechanisms behind Pb-induced disruption of Na+and Cl−balance in rainbow trout (Oncorhynchus mykiss)
Authors: Rogers Joseph T. , Patel Monika , Gilmour Kathleen M. , Wood Chris M.
Published: July 2005

The mechanism of Pb-induced disruption of Na+and Cl−balance was investigated in the freshwater rainbow trout ( Oncorhynchus mykiss). Na+and Cl−influx rates were reduced immediately in the presence of 2.40 ± 0.24 and 1.25 ± 0.14 μM Pb, with a small increase in efflux rates occurring after 24-h exposure. Waterborne Pb caused a significant decrease in the maximal rate of Na+influx without a change in transporter affinity, suggesting a noncompetitive disruption of Na+uptake by Pb. Phenamil and bafilomycin markedly reduced Na+influx rate but did not affect Pb accumulation at the gill. Time-course analysis in rainbow trout exposed to 0, 0.48, 2.4, and 4.8 μM Pb revealed time- and concentration-dependent branchial Pb accumulation. Na+-K+-ATPase activity was significantly reduced, with 4.8 μM exposure resulting in immediate enzyme inhibition and 0.48 and 2.4 μM exposures inhibiting activity by 24 h. Reduced activity was weakly correlated with gill Pb accumulation after 3- and 8-h exposures; this relationship strengthened by 24 h. Reduced Na+uptake was correlated with gill Pb burden after exposures of 3, 8, and 24 h. Immediate inhibition of branchial carbonic anhydrase activity occurred after 3-h exposure to 0.82 ± 0.05 or 4.30 ± 0.05 μM Pb and continued for up to 24 h. We conclude that Pb-induced disruption of Na+and Cl−homeostasis is in part a result of rapid inhibition of carbonic anhydrase activity and of binding of Pb with Na+-K+-ATPase, causing noncompetitive inhibition of Na+and Cl−influx.
An efficient g‐centroid location algorithm for cographs
Authors: Prakash V.
Published: July 2005

In 1998, Pandu Rangan et al. Proved that
locating the g‐centroid for an arbitrary graph is
𝒩𝒫‐hard by reducing the problem of finding the maximum
clique size of a graph to the g‐centroid location problem. They
have also given an efficient polynomial time algorithm for
locating the g‐centroid for maximal outerplanar graphs,
Ptolemaic graphs, and split graphs. In this paper, we present an
O(nm) time algorithm for locating the g‐centroid for
cographs, where n is the number of vertices and m is the
number of edges of the graph.
Solitary‐wave propagation and interactions for a sixth‐order generalized Boussinesq equation
Authors: Feng Bao-Feng , Kawahara Takuji , Mitsui Taketomo , Chan Youn-Sha
Published: July 2005

We study the solitary waves and their interaction for a six‐order generalized Boussinesq equation (SGBE) both numerically and analytically. A shooting method with appropriate initial conditions,
based on the phase plane analysis around the equilibrium point, is used to construct the solitary‐wave solutions for this nonintegrable equation. A symmetric three‐level implicit finite difference scheme with a free parameter θ is proposed to study the propagation and interactions of solitary waves. Numerical simulations show the propagation of a single solitary wave of SGBE, and two solitary waves pass by each other without changing their shapes in the head‐on collisions.
Remarques sur la frontière de martin biharmonique et la représentation intégrale des fonctions biharmoniques
Authors: El Kadiri Mohamed , Haddad Sabah
Published: July 2005

Soit (Ω, ℋ) un espace biharmonique
fort au sens de Smyrnelis dont les espaces harmoniques associés
sont des espaces de Brelot qui vérifient l′axiome de
proportionnalité. On montre que s′il existe un couple ℋ‐harmonique >0 sur Ω, alors lénsemble des points
minimaux de la frontière de Martin biharmonique de Ω qui
ne sont pas les pôles de couples biharmoniques minimaux est
négiligeable dans un sens que l′on précisera. Dans
le cas classique d′un domaine lipschitzien borné de
ℝn, nous montrons que cet ensemble est vide.

Let (Ω, ℋ) be a strong biharmonic space of Smyrnelis such that the harmonic spaces associeted are Brelot spaces satisfying the axiom of proportionnality. We prove that if there exists a biharmonic pair greater than 0 on Ω, then the set of minimal points of the biharmonic Martin boundary of Ω, that are not the poles of minimal biharmonic pairs, is negligible in some meaning that we will precise. For the classical case of a bounded Lipschitz domain of ℝn, we prove that this set is empty.
Atrial Myocardial Deformation Properties Predict Maintenance of Sinus Rhythm After External Cardioversion of Recent-Onset Lone Atrial Fibrillation
Authors: Di Salvo Giovanni , Caso Pio , Lo Piccolo Rosalia , Fusco Angela , Martiniello Alfonso R. , Russo Maria G. , D’Onofrio Antonio , Severino Sergio , Calabró Paolo , Pacileo Giuseppe , Mininni Nicola , Calabró Raffaele
Published: July 2005

Background—

Accurate echocardiographic parameters to predict maintenance of sinus rhythm in patients with atrial fibrillation (AF) are poorly defined. This study was conducted to assess the atrial myocardial properties during AF through myocardial velocity, strain rate, and strain and to compare their prognostic value in maintaining sinus rhythm in patients with lone AF with standard transthoracic (TTE) and transesophageal echocardiography (TEE).

Methods and Results—

Sixty-five consecutive patients with lone AF for ≤3 months underwent TTE, TEE, and myocardial velocity and strain and strain rate imaging examinations before successful external cardioversion. Maintenance of sinus rhythm was assessed during a 9-month follow-up. Atrial myocardial velocity, strain, and strain rate values in AF patients were compared with those of age- and sex-matched referents. Moreover, clinical and echocardiographic parameters of patients with maintenance of sinus rhythm (MSR patients) over the 9-month follow-up period (n=25) were compared with those from patients with AF recurrence (AFR patients; n=40). Atrial myocardial properties assessed by myocardial velocity, strain rate, and strain were significantly reduced (
P
<0.0001) in patients (velocity, 3.2±1.4 cm/s; strain, 23.3±19%; strain rate, 2±0.9 seconds
−1
) compared with referents (velocity, 5.7±1.3 cm/s; strain, 92±26%; strain rate, 4.2±1.8 seconds
−1
). The individual predictors of sinus rhythm maintenance were atrial appendage flow velocity (MSR patients, 39±12 cm/s; AFR patients, 32±15 cm/s;
P
<0.01) assessed by TEE and atrial strain (MSR patients, 33±27%; AFR patients, 17±9%;
P
=0.0007) and strain rate (MSR patients, 2.7±1 seconds
−1
; AFR patients, 1.6±0.6 seconds
−1
;
P
<0.0001) peak systolic values. Atrial strain (
P
<0.0001; coefficient, 0.015; SE, 0.003) and strain rate (
P
<0.0001; coefficient, 0.372; SE, 0.075) parameters alone were confirmed as independent predictors of sinus rhythm maintenance by multivariable analysis.

Conclusions—

Patients with higher atrial strain and strain rate appear to have a greater likelihood of staying in sinus rhythm. If the current data are verified in future studies, then additional pharmacological therapy and maintenance of anticoagulants for a longer period may need to be considered in those with lower atrial strain and strain rate measurements.
Coronary Calcification Improves Cardiovascular Risk Prediction in the Elderly
Authors: Vliegenthart Rozemarijn , Oudkerk Matthijs , Hofman Albert , Oei Hok-Hay S. , van Dijck Wim , van Rooij Frank J.A. , Witteman Jacqueline C.M.
Published: July 2005

Background—

Coronary calcification detected by electron beam tomography may improve cardiovascular risk prediction. The technique is particularly promising in the elderly because the predictive power of cardiovascular risk factors weakens with age. We investigated the prognostic value of coronary calcification for cardiovascular events and mortality in a general, asymptomatic population of elderly subjects.

Methods and Results—

From 1997 to 2000, electron beam tomography scanning to assess coronary calcification was performed in subjects of the population-based Rotterdam Study. Risk factors were measured by standardized procedures. Coronary calcium scores were available for 1795 asymptomatic participants (mean age, 71 years; range, 62 to 85 years). During a mean follow-up of 3.3 years, 88 cardiovascular events, including 50 coronary events, occurred. The risk of coronary heart disease increased with increasing calcium score. The multivariate-adjusted relative risk of coronary events was 3.1 (95% CI, 1.2 to 7.9) for calcium scores of 101 to 400, 4.6 (95% CI, 1.8 to 11.8) for calcium scores of 401 to 1000, and 8.3 (95% CI, 3.3 to 21.1) for calcium scores >1000 compared with calcium scores of 0 to 100. The predictive value in subjects >70 years of age was similar. Risk prediction based on the cardiovascular risk factors improved when coronary calcification was added.

Conclusions—

Coronary calcification is a strong and independent predictor of coronary heart disease, also in the elderly. Coronary calcification improves prediction of coronary events based on cardiovascular risk factors. Risk stratification by assessment of coronary calcification may have an important role in the primary prevention of coronary heart disease events in the elderly.
Aggressive Versus Moderate Lipid-Lowering Therapy in Hypercholesterolemic Postmenopausal Women
Authors: Raggi Paolo , Davidson Michael , Callister Tracy Q. , Welty Francine K. , Bachmann Gloria A. , Hecht Harvey , Rumberger John A.
Published: July 2005

Background—

Women have been underrepresented in statin trials, and few data exist on the effectiveness and safety of statins in this gender. We used sequential electron-beam tomography (EBT) scanning to quantify changes in coronary artery calcium (CAC) as a measure of atherosclerosis burden in patients treated with statins.

Methods and Results—

In a double-blind, multicenter trial, we randomized 615 hyperlipidemic, postmenopausal women to intensive (atorvastatin 80 mg/d) and moderate (pravastatin 40 mg/d) lipid-lowering therapy. Patients also submitted to 2 EBT scans at a 12-month interval (mean interval 344±55 days) to measure percent change in total and single-artery calcium volume score (CVS) from baseline. Of the 615 randomized women, 475 completed the study. Mean±SD percent LDL reductions were 46.6%±19.9% and 24.5%±18.5 in the intensive and moderate treatment arms, respectively (
P
<0.0001), and National Cholesterol Education Program Adult Treatment Panel III LDL goal was reached in 85.3% and 58.8% of women, respectively (
P
<0.0001). The total CVS% change was similar in the 2 treatment groups (median 15.1% and 14.3%, respectively;
P
=NS), and single-artery CVS% changes and absolute changes were also similar (
P
=NS). In both arms, there was a trend toward a greater CVS progression in patients with prior cardiovascular disease, diabetes mellitus, and hypertension, whereas hormone replacement therapy had no effect on progression.

Conclusions—

In postmenopausal women, intensive statin therapy for 1 year caused a greater LDL reduction than moderate therapy but did not result in less progression of coronary calcification. The limitations of this study (too short a follow-up period and the absence of a placebo group) precluded determination of whether progression of CVS was slowed in both arms or neither arm compared with the natural history of the disease.
Statin Therapy May Be Associated With Lower Mortality in Patients With Diastolic Heart Failure
Authors: Fukuta Hidekatsu , Sane David C. , Brucks Steffen , Little William C.
Published: July 2005

Background—

No therapy has been shown to improve survival in heart failure (HF) with a normal ejection fraction (EF). There are plausible reasons to hypothesize that statins may be of benefit in HF with a normal EF.

Methods and Results—

We evaluated 137 patients with HF and an EF ≥0.50. The effect of treatment received at study entry on survival was determined. During a follow-up of 21±12 months, 20 deaths were observed. Treatment with an ACE inhibitor or receptor blocker, β-blocker, or calcium blocker had no significant effect on survival. In contrast, treatment with a statin was associated with a substantial improvement in survival (relative risk of death [95% CI] 0.22 [0.07 to 0.64];
P
=0.006). Patients receiving statins had higher baseline LDL cholesterol than those not receiving statins (153±45 versus 98±33 mg/dL,
P
<0.01). After statin therapy, LDL cholesterol levels fell to a similar level (101±32 mg/dL) as in patients not receiving statins (98±33 mg/dL). After adjustment for differences in baseline clinical variables between groups (hypertension, diabetes, coronary artery disease, and serum creatinine), statin therapy was associated with lower mortality (adjusted relative risk of death [95% CI] 0.20 [0.06 to 0.62];
P
=0.005). Similarly, after propensity matching, statin therapy was associated with improved survival (log-rank 6.12;
P
=0.013) and a trend toward improved survival without cardiovascular hospitalization (log-rank 3.02;
P
=0.082).

Conclusions—

Statin therapy may be associated with improved survival in patients with HF and a normal EF.
Directional Wavelet Analysis of Inhomogeneity in the Surface Wave Field from Aerial Laser Scanning Data
Authors: Gorman Richard M. , Hicks D. Murray
Published: July 2005

Modern measurement techniques such as aerial laser scanning allow for rapid determination of the spatial variation of sea surface elevation. Wave fields obtained from such data show spatial inhomogeneity associated with the presence of wave groups. A method based on two-dimensional directional wavelet analysis is described by which such inhomogeneity can be characterized in the spatial and wavenumber domains. The directional wavelet method has been applied to aerial laser scanning measurements of nearshore wave conditions off the east coast of New Zealand’s South Island. A high level of spatial variability was observed, with evidence of ensembles of wave-group envelopes of quasi-Gaussian form. These envelopes occur, with variations in spatial location, across a range of wavelet scales and directions.
Adjusting Internal Model Errors through Ocean State Estimation
Authors: Stammer Detlef
Published: July 2005

Oceanic state estimation is a powerful tool to estimate internal model parameters simultaneously with the model’s initial conditions and surface forcing field that jointly would bring a model into consistency with time-varying large-scale ocean observations. Here an attempt to estimate geographically varying fields of horizontal and vertical viscosity and diffusivity within a 9-yr-long estimation procedure is presented. The estimated coefficients are highly efficient in preserving watermass characteristics and frontal structures by reducing the model temperature and salinity drift, especially around the Southern Ocean. The estimated mean circulation results in stronger transports of western boundary currents and of the Antarctic Circumpolar Current. Moreover, an increase of about 10% in the strength of the meridional overturning circulation and in the poleward heat transport can be found. Estimated changes in the horizontal mixing coefficients seem to agree with the notion that diapycnal mixing is superfically high with Laplacian mixing formulations, especially close to frontal structures in the ocean. In comparison with adjustments in tracer diffusivities (vertically and horizontally), adjustments of viscosity coefficients are fairly minor outside lateral boundary regions, suggesting that state estimation attempts might be most successful in providing enhanced insight into tracer mixing.
Interplay of Wind Forcing and Buoyant Discharge off Montauk Point: Seasonal Changes to Velocity Structure and a Coastal Front
Authors: Codiga Daniel L.
Published: July 2005

Seasonal-mean currents in fall, winter, and spring on the bathymetrically complex continental shelf 15–65 m deep off Montauk Point, outside Block Island Sound, are analyzed using moored profiling current-meter records from a 2.5-yr period. A sharp boundary, or coastal front, occurs where strong, shallow, generally southwestward flow that weakens nearly linearly with increasing depth meets deeper flow nearly opposite in direction (fall/winter) or markedly weaker (spring). Velocities veer clockwise (counterclockwise) with increasing depth inshore (offshore) of the front. Evidence is presented that thermal wind balance holds without major frictional modification: it accounts for the veering, and the seasonal-mean horizontal density gradients it implies are generally toward the southeast quadrant in agreement with limited hydrographic measurements. Substantial seasonal changes in flow and frontal attributes occur because of the interplay of annual cycles in wind forcing and buoyant discharge. In fall and winter, upwelling-favorable wind causes nearshore setdown of sea surface height and an inshore-directed barotropic pressure gradient: shallow down-coast (alongshore to the south and west) currents weaken, and deep currents are up-coast. In spring, buoyant discharge peaks and winds weaken: shallow down-coast flow strengthens and deep flow weakens. The front extends to the seafloor, with attachment depth shallowest in winter, deepest in spring, and intermediate in fall; its width is smaller in fall than in winter. Buoyant discharge theory based on bottom boundary layer density advection dynamics captures these seasonal shifts. Cross-shelf circulation includes offshore (onshore) shallow (deep) motion; deep onshore motion appears enhanced near a canyon and persistent through all three seasons, suggesting wind-driven upwelling is not solely responsible.
Leading Coherent Professional Development: A Comparison of Three Districts
Authors: Firestone William A. , Mangin Melinda M. , Martinez M. Cecilia , Polovsky Terrie
Published: July 2005

A comparison of three urban school systems suggests that district offices can influence teaching through professional development. District leaders can structure their programs to provide coherent and content-focused professional development. The district orientation (vision, emphasis on professional development, use of human resources) set by the dominant coalition of leaders—including but not limited to the superintendent—in each district influenced the coherence and content focus of the professional development programs. District differences in their organizational capacity affected coordination and planning of professional development. The district with the most coherent focus on helping teachers develop deeper knowledge about select subject areas had the greatest teacher-reported influence on teaching practice.
Do Principals With Stronger Academic Backgrounds Hire Better Teachers? Policy Implications for Improving High-Poverty Schools
Authors: Baker Bruce D. , Cooper Bruce S.
Published: July 2005

Principals play an important role in determining the quality of their schools by the selection of teachers. A preponderance of evidence from the economic and education policy literature indicates that teachers with stronger academic backgrounds produce better student outcomes. This article hypothesizes that school principals with certain attributes are likely to favor teachers with similar attributes to their own. This study uses the Schools and Staffing Surveys from 1993 to 1994 to test whether school administrators who attended more selective universities are more or less likely to hire teachers who attended more selective undergraduate institutions. Findings suggest that principals’undergraduate background matters when it comes to their recruitment, selection, and perhaps retention of teachers with strong academic undergraduate backgrounds, especially in high-poverty schools. Principals in high-poverty schools who attended highly or the most selective undergraduate institutions were 3.3 times more likely to hire teachers who attended similar institutions.
Adults Advising Youth: Leading While Getting Out of the Way
Authors: Mitra Dana L.
Published: July 2005

Drawing on 3 years of qualitative data, this article broadens the concept of distributed leadership to include “student voice” in school decision making. Specifically, the article focuses on how adults can foster youth participation and leadership in school reform efforts. In this research, adults needed to work in partnership with youth conscientiously and continuously to develop patterns of interaction that aligned with the values of equitable relations. When adults did not strike a balance between support and letting go, the youth and adults often fell back into traditional teacher-student roles. The article identifies ways in which adults helped youth to move from the periphery to the core of group interactions, especially through a collective focus on developing shared norms, language, and skills.
Another Antigone
Authors: Saxonhouse Arlene W.
Published: July 2005

The Phoenician Women, Euripides’ peculiar retelling and refashioning of the Theban myth, offers a portrait of Antigone before she becomes the actor we mostly know today from Sophocles’ play. In this under-studied Greek tragedy, Euripides portrays the political and epistemological dissolution that allows for Antigone’s appearance in public. Whereas Sophocles’ Antigone appears on stage ready to confront Creon with her appeal to the universal unwritten laws of the gods and later dissolves into the female lamenting a lost womanhood, Euripides’ Antigone experiences the opposite journey, thereby offering insights into the conditions that allow for her exposure in the political arena. A speech by Eteocles at the center of the play questions the existence of absolutes, calls injustice beautiful, and opens the door for Antigone’s entrance into the public sphere. With this speech Eteocles challenges us to consider the conditions of political openness in the modern age.