bluuebunny/crossref_metadata_2025 huggingface dataset:
A TECHNIQUE FOR PLANE-SYMMETRIC SOUND FIELD ANALYSIS IN THE FAST MULTIPOLE BOUNDARY ELEMENT METHOD
Authors: YASUDA Y. , SAKUMA T.
Published: May 2005

The fast multipole boundary element method (FMBEM) is an advanced BEM, with which both the operation count and the memory requirements are O(Na log b N) for large-scale problems, where N is the degree of freedom (DOF), a ≥ 1 and b ≥ 0. In this paper, an efficient technique for analyses of plane-symmetric sound fields in the acoustic FMBEM is proposed. Half-space sound fields where an infinite rigid plane exists are typical cases of these fields. When one plane of symmetry is assumed, the number of elements and cells required for the FMBEM with this technique are half of those for the FMBEM used in a naive manner. In consequence, this technique reduces both the computational complexity and the memory requirements for the FMBEM almost by half. The technique is validated with respect to accuracy and efficiency through numerical study.
DYNAMIC RESPONSE OF A THREE-DIMENSIONAL FLUID CHANNEL BOUNDED BY AN ELASTIC FLOOR IN THE PRESENCE OF A SUBMERGED INCLUSION VIA BEM
Authors: TADEU ANTÓNIO , GODINHO LUÍS , ANTÓNIO JULIETA
Published: May 2005

Numerical methods for computing the three-dimensional pressure field in a flat fluid channel bounded either by a rigid boundary, an elastic semi-infinite medium or by a layer of sediment, subjected to incoherent line sources are presented. After verification Greens functions are incorporated in a Boundary Element Method (BEM) code that simulates the pressure variation inside the fluid channel in the vicinity of a rigid or elastic inclusion, avoiding the discretization of the fluid and solid channel interfaces. After the verification of the solution, the models developed are then used to simulate the pressure variation within the fluid channel in the presence of infinitely long rigid and elastic inclusions of differing sizes, when the channel is struck by a spatially-sinusoidal harmonic pressure line load. The results are then compared with those obtained when the channel floor is assumed to be rigid. Time domain results are given by means of inverse Fourier transforms, to help understand how the mechanical properties of the channel floor may affect the variation of the pressure field within the channel.
GENOME TREES AND THE NATURE OF GENOME EVOLUTION
Authors: Snel Berend , Huynen Martijn A. , Dutilh Bas E.
Published: May 2005

Genome trees are a means to capture the overwhelming amount of phylogenetic information that is present in genomes. Different formalisms have been introduced to reconstruct genome trees on the basis of various aspects of the genome. On the basis of these aspects, we separate genome trees into five classes: (a) alignment-free trees based on statistic properties of the genome, (b) gene content trees based on the presence and absence of genes, (c) trees based on chromosomal gene order, (d) trees based on average sequence similarity, and (e) phylogenomics-based genome trees. Despite their recent development, genome tree methods have already had some impact on the phylogenetic classification of bacterial species. However, their main impact so far has been on our understanding of the nature of genome evolution and the role of horizontal gene transfer therein. An ideal genome tree method should be capable of using all gene families, including those containing paralogs, in a phylogenomics framework capitalizing on existing methods in conventional phylogenetic reconstruction. We expect such sophisticated methods to help us resolve the branching order between the main bacterial phyla.
Anabolic growth hormone action improves submaximal measures of physical performance in patients with HIV-associated wasting
Authors: Esposito John G. , Thomas Scott G. , Kingdon Lori , Ezzat Shereen
Published: May 2005

Growth hormone (GH) treatment reverses the muscle loss allegedly responsible for diminished aerobic capacity and increased fatigue in patients with HIV-associated wasting. This study examined whether submaximal measures of physical performance can be used as objective measures of the functional impact of GH treatment-induced anabolism. We randomized 27 HIV-positive men [mean (SD) age, 43.9 (7.2) yr; body mass, 71.9 (10.4) kg; BMI, 23.1 (2.8) kg/m2] with unintentional weight loss despite antiretroviral therapy to receive GH (6 mg) or placebo in a double-blinded, placebo-controlled, cross-over trial with a 3-mo washout. Lean body mass (LBM), maximum oxygen uptake (V̇o2 peak), ventilatory threshold (VeT), 6-min walk test (6MWT) distance and work, profile of mood states (POMS) fatigue and vigor scores, and Nottingham health profile (NHP) energy and physical mobility scores were measured. LBM significantly increased after 3 mo of GH treatment vs. placebo (means ± SE, 3.7 ± 0.6 vs. 0.3 ± 0.4 kg; P < 0.001). VeT significantly improved (17.6 ± 3.7 vs. −5.9 ± 2.5%; P < 0.001), but V̇o2 peak did not change significantly. 6MWT distance improved (24.9 ± 9.7 vs. 19.9 ± 11.6 m; P > 0.05) and 6MWT work increased significantly more after 3 mo of GH treatment (33.3 ± 8.8 vs. 16.5 ± 7.5 kJ; P < 0.05). POMS scores of fatigue and vigor and the NHP score of energy improved, yet the changes were not statistically significant. GH treatment improved VeT linearly to the increase in LBM ( r =0.43, P = 0.037) and 6MWT work ( r = 0.51, P = 0.008), and the increase in 6MWT work correlated with increase in LBM ( r = 0.45, P = 0.024). Improvement in 6MWT work above the median (27.3 kJ) showed a decrease in fatigue ( r = −0.62, P = 0.024). We concluded that GH treatment-induced LBM gains in HIV-associated wasting were functionally relevant, as determined by effort-independent submaximal measures of cardiopulmonary exercise testing.
Carbon monoxide protects against the development of experimental necrotizing enterocolitis
Authors: Zuckerbraun Brian S. , Otterbein Leo E. , Boyle Patricia , Jaffe Ronald , Upperman Jeffrey , Zamora Ruben , Ford Henri R.
Published: May 2005

Necrotizing enterocolitis (NEC) is a disease of neonates that is increasing in incidence and often results in significant morbidity and mortality. Carbon monoxide (CO), a byproduct of the catabolism of heme, is known to have anti-inflammatory and antiapoptotic properties. In this study, we aimed to demonstrate that inhaled CO protects against the development of intestinal inflammation in a model of experimental NEC as well as decreases enterocyte cell death in vitro. Additionally, we also aimed to demonstrate that CO decreases enterocyte production of inducible nitric oxide synthase (iNOS) and nitric oxide (NO). Neonatal rats were exposed to intermittent hypoxia exposure and formula feeding to induce experimental NEC. Animals randomized to CO treatment were put in an environment containing 0.025% CO for 1 h/day on days 1–3 of life. All animals were killed on day 4 of life. In vitro experiments were performed with IEC-6 cells, a rat enterocyte cell line. Cells were examined for viability, iNOS production, and elaboration of NO. We found that CO diminished levels of serum inflammatory cytokines and nitrites, protected against intestinal inflammation, and decreased ileal iNOS production and protein nitration in a model of experimental NEC. In vitro, CO decreased cytokine- or hypoxia/endotoxin-induced iNOS and NO production. CO also abrogated TNF-α- and actinomycin D-induced apoptosis or hypoxia/endotoxin-induced cell death. In conclusion, 1 h of daily low-dose inhaled CO protected against the development of intestinal inflammation in a model of experimental NEC. iNOS and NO production were decreased by CO both in vivo and in vitro. CO may prove to be a useful clinical adjunct in the treatment of NEC.
Inhibition of surfactant activity byPneumocystis cariniiorganisms and components in vitro
Authors: Wang Zhengdong , Foye Adam , Chang Yusuo , Chess Patricia R. , Wright Terry W. , Bhagwat Samir , Gigliotti Francis , Notter Robert H.
Published: May 2005

This study examines the direct inhibitory effects of Pneumocystis carinii ( Pc) organisms and chemical components on the surface activity and composition of whole calf lung surfactant (WLS) and calf lung surfactant extract (CLSE) in vitro. Incubation of WLS suspensions with intact Pc organisms (107per milligram of surfactant phospholipid) did not significantly alter total phospholipid levels or surfactant protein A content. Incubation with intact Pc organisms also did not impair dynamic surface tension lowering in suspensions of WLS or centrifuged large surfactant aggregates on a bubble surfactometer (37°C, 20 cycles/min, 0.5 and 2.5 mg phospholipid/ml). However, exposure of WLS or CLSE to disrupted (sonicated) Pc organisms led to severe detriments in activity, with minimum surface tensions of 17–19 mN/m vs. <1 mN/m for surfactants alone. Extracted hydrophobic chemical components from Pc (98.8% lipids, 0.1 mM) reduced the surface activity of WLS and CLSE similarly to sonicated Pc organisms, whereas extracted hydrophilic chemical components from Pc (primarily proteins) had only minor effects on surface tension lowering. These results indicate that in addition to surfactant dysfunction induced by inflammatory lung injury and edema-derived inhibitors in Pc pneumonia, disrupted Pc organisms in the alveolar lumen also have the potential to directly inhibit endogenous and exogenous lung surfactants in affected patients.
Response of the ubiquitin-proteasome pathway to changes in muscle activity
Authors: Reid Michael B.
Published: May 2005

The ubiquitin-proteasome pathway plays a critical role in the adaptation of skeletal muscle to persistent decreases or increases in muscle activity. This article outlines the basics of pathway function and reviews what we know about pathway responses to altered muscle use. The ubiquitin-proteasome pathway regulates proteolysis in mammalian cells by attaching ubiquitin polymers to damaged proteins; this targets the protein for degradation via the 26S proteasome. The pathway is constitutively active in muscle and continually regulates protein turnover. Conditions of decreased muscle use, e.g., unloading, denervation, or immobilization, stimulate general pathway activity. This activity increase is caused by upregulation of regulatory components in the pathway and leads to accelerated proteolysis, resulting in net loss of muscle protein. Pathway activity is also increased in response to exercise, a two-phase response. An immediate increase in selective ubiquitin conjugation by constitutive pathway components contributes to exercise-stimulated signal transduction. Over hours-to-days, exercise also stimulates a delayed increase in general ubiquitin conjugating activity by inducing expression of key components in the pathway. This increase mediates a late-phase rise in protein degradation that is required for muscle adaptation to exercise. Thus the ubiquitin-proteasome pathway functions as an essential mediator of muscle remodeling, both in atrophic states and exercise training.
Adrenomedullin: angiogenesis and gene therapy
Authors: Nagaya Noritoshi , Mori Hidezo , Murakami Shinsuke , Kangawa Kenji , Kitamura Soichiro
Published: May 2005

Adrenomedullin (AM) is a potent, long-lasting vasodilator peptide that was originally isolated from human pheochromocytoma. AM signaling is of particular significance in endothelial cell biology since the peptide protects cells from apoptosis, promotes angiogenesis, and affects vascular tone and permeability. The angiogenic effect of AM is mediated by activation of Akt, mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2, and focal adhesion kinase in endothelial cells. Both AM and its receptor, calcitonin receptor-like receptor, are upregulated through a hypoxia-inducible factor-1-dependent pathway under hypoxic conditions. Thus AM signaling plays an important role in the regulation of angiogenesis in hypoxic conditions. Recently, we have developed a nonviral vector, gelatin. Positively charged gelatin holds negatively charged plasmid DNA in its lattice structure. DNA-gelatin complexes can delay gene degradation, leading to efficient gene transfer. Administration of AM DNA-gelatin complexes induces potent angiogenic effects in a rabbit model of hindlimb ischemia. Thus gelatin-mediated AM gene transfer may be a new therapeutic strategy for the treatment of tissue ischemia. Endothelial progenitor cells (EPCs) play an important role in endothelial regeneration. Interestingly, EPCs phagocytose ionically linked DNA-gelatin complexes in coculture, which allows nonviral gene transfer into EPCs. AM gene transfer into EPCs inhibits cell apoptosis and induces proliferation and migration, suggesting that AM gene transfer strengthens the therapeutic potential of EPCs. Intravenous administration of AM gene-modified EPCs regenerate pulmonary endothelium, resulting in improvement of pulmonary hypertension. These results suggest that in vivo and in vitro transfer of AM gene using gelatin may be applicable for intractable cardiovascular disease.
Freezing tolerance of the European water frogs: the good, the bad, and the ugly
Authors: Voituron Yann , Joly Pierre , Eugène Michel , Barré Hervé
Published: May 2005

Survival and some physiological responses to freezing were investigated in three European water frogs ( Rana lessonae, Rana ridibunda, and their hybridogen Rana esculenta). The three species exhibited different survival times during freezing (from 10 h for R. lessonae to 20 h for R. ridibunda). The time courses of percent water frozen were similar; however, because of the huge differences in body mass among species (from 10 g for Rana lessonae to nearly 100 g for Rana ridibunda), the ice mass accumulation rate varied markedly (from 0.75 ± 0.12 to 1.43 ± 0.11 g ice/h, respectively) and was lowest in the terrestrial hibernator Rana lessonae. The hybrid Rana esculenta exhibited an intermediate response between the two parental species; furthermore, within-species correlation existed between body mass and ice mass accumulation rates, suggesting the occurrence of subpopulations in this species (0.84 ± 0.08 g ice/h for small R. esculenta and 1.78 ± 0.09 g ice/h for large ones). Biochemical analyses showed accumulation of blood glucose and lactate, liver glucose (originating from glycogen), and liver alanine in Rana lessonae and Rana esculenta but not in Rana ridibunda in response to freezing. The variation of freeze tolerance between these three closely related species could bring understanding to the physiological processes involved in the evolution of freeze tolerance in vertebrates.
Micropuncture gene delivery and intravital two-photon visualization of protein expression in rat kidney
Authors: Tanner George A. , Sandoval Ruben M. , Molitoris Bruce A. , Bamburg James R. , Ashworth Sharon L.
Published: May 2005

Understanding molecular mechanisms of pathophysiology and disease processes requires the development of new methods for studying proteins in animal tissues and organs. Here, we describe a method for adenoviral-mediated gene transfer into tubule or endothelial cells of the rat kidney. The left kidney of an anesthetized rat was exposed and the lumens of superficial proximal tubules or vascular welling points were microinfused, usually for 20 min. The microinfusion solution contained adenovirus with a cDNA construct of either 1) Xenopus laevis actin depolymerizing factor/cofilin [XAC; wt-green fluorescent protein (GFP)], 2) actin-GFP, or 3) GFP. Sudan black-stained castor oil, injected into nearby tubules, allowed us to localize the microinfused structures for subsequent visualization. Two days later, the rat was anesthetized and the kidneys were fixed for tissue imaging or the left kidney was observed in vivo using two-photon microscopy. Expression of GFP and GFP-chimeric proteins was clearly seen in epithelial cells of the injected proximal tubules and the expressed proteins were localized similarly to their endogenously expressed counterparts. Only a minority of the cells in the virally exposed regions, however, expressed these proteins. Endothelial cells also expressed XAC-GFP after injection of the virus cDNA construct into vascular welling points. An advantage of the proximal tubule and vascular micropuncture approaches is that only minute amounts of virus are required to achieve protein expression in vivo. This micropuncture approach to gene transfer of the virus cDNA construct and intravital two-photon microscopy should be applicable to study of the behavior of any fluorescently tagged protein in the kidney and shows promise in studying renal physiology and pathophysiology.
Red blood cell lactate transport in sickle disease and sickle cell trait
Authors: Pattillo Robin E. , Gladden L. Bruce
Published: May 2005

This study determined and compared rates and mechanisms of lactate transport in red blood cells (RBCs) of persons with 1) sickle cell disease (HbSS), 2) sickle cell trait (HbAS), and 3) a control group (HbAA). Blood samples were drawn from 30 African-American volunteers (10 HbSS, 10 HbAS, 10 HbAA). Lactate influx into RBCs was measured by using [14C]lactate at six (2, 5, 10, 15, 25, and 40 mM) unlabeled lactate concentrations. The monocarboxylate transporter pathway was blocked by p-chloromercuriphenylsulfonic acid to determine its percent contribution to total lactate influx. Generally, total lactate influx into RBCs from the HbSS group was significantly greater than influx into RBCs from HbAS or HbAA, with no difference between HbAS and HbAA. Faster influx into HbSS RBCs was attributed to increased monocarboxylate transporter activity [increased apparent Vmax( V′max)]. V′max(4.7 ± 0.6 μmol·ml−1·min−1) for HbSS RBCs was significantly greater than V′maxof HbAS RBCs (2.9 ± 1.5 μmol·ml−1·min−1) and HbAA RBCs (2.0 ± 0.5 μmol·ml−1·min−1). Km(42.8 ± 8 mM) for HbSS RBCs was significantly greater than Km(27 ± 12 mM) for HbAA RBCs. We suspect that elevated erythropoietin levels in response to chronic anemia and/or pharmacological treatment (erythropoietin injections, hydroxyurea ingestion) is the underlying mechanism for increased lactate transport capacity in HbSS RBCs.
Management of Prolonged Urinary Leakage at the Urethro-Vesical Anastomosis
Authors: Kylmälä Timo , Kaipia Antti , Matikainen Mika
Published: May 2005

Urinary leakage at the urethrovesical anastomosis is a rare but troublesome complication after radical prostatectomy. Usually, the anastomosis is almost watertight when tested during the operation and small leakages typically seal off in a few days. We describe 3 cases with postoperative urinary leakage where we have utilized a simple procedure of replacing the standard Foley catheter with another catheter with extra side fenestrations close to the anastomosis. Side fenestrations provide efficient drainage at the anastomosis area leading to a rapid resolution of the leakage. The method described represents an effective and low-risk solution to a potentially harmful complication.
Efficacy of Unilateral Nerve Sparing in Radical Perineal Prostatectomy
Authors: Brehmer Bernhard , Kirschner-Hermanns Ruth , Donner Andreas , Reineke Thorsten , Knüchel-Clarke Ruth , Jakse Gerhard
Published: May 2005

Aim: We determine the efficacy of unilateral nerve-sparing radical perineal prostatectomy in preserving the sexual function. Patients and Methods: Ninety-two patients with histologically confirmed unilateral prostate cancer were scheduled for contralateral nerve preservation. The perioperative morbidity was assessed using the patients’ chart reviews. Postoperative health-related quality of life, urinary continence, and potency were evaluated prospectively with questionnaires provided before surgery and then after 6, 12, and 24 months. Results: Unilateral nerve preservation was performed in 88 of the 92 patients. Due to extensive scarring or prostatic size, the procedure was terminated as regular radical prostatectomy in 4 other patients. The perioperative complication rate was low and of minor significance, except in 1 patient who experienced a significant myoglobulinuria due to a prolonged procedure. Blood transfusions were necessary in 5 (5.4%) patients. Ureteral reimplantation was performed in 1 patient because of ureteral stricture. Positive surgical margins were present in 12 (18%) of 67 pT2 patients and in 8 (35%) of 23 pT3 patients. A proportion of 48% (15/31) of the patients followed for more than 24 months and who had a good erectile function prior to surgery reported unassisted sexual intercourse. However, only 4 of these patients were completely satisfied with all aspects of sexual performance, as asked in a short version of the International Index of Erectile Function questionnaire. Conclusions: Unilateral nerve-sparing radical perineal prostatectomy is technically feasible and yields excellent results in terms of potency preservation for prostates <60 ml. However, the quality of erections is decreased, even in patients with erections sufficient for intercourse. Hence, appropriate sexual counseling in conjunction with medical therapy should be offered to all patients.
Prulifloxacin versus Ciprofloxacin in the Treatment of Adults with Complicated Urinary Tract Infections
Authors: Carmignani G. , de Rose A.F. , Olivieri L. , Salvatori E. , Rosignoli M.T. , Dionisio P.
Published: May 2005

Introduction: The present study was performed to evaluate the efficacy and safety of a 10-day regimen of prulifloxacin 600 mg once daily as compared to ciprofloxacin 500 mg twice daily in the treatment of patients with complicated urinary tract infections (UTIs). Materials and Methods: 257 patients (mean age ± SD 62.3 ± 16.5) were enrolled and orally treated with prulifloxacin (127 patients) or ciprofloxacin (130 patients). The study was designed as a randomized, double-blind, double-dummy, controlled clinical trial. The primary efficacy parameter was the eradication of infecting strains (<103 cfu/ml). The clinical outcome and tolerability were also assessed. Results: At baseline, the most common infecting strains were Escherichia coli (62.8%), Proteus mirabilis (7.1%) and Klebsiella pneumoniae (4.1%). At the early follow-up, the rate of patients showing successful treatment was 90.8% in the prulifloxacin group, and 77.8% in the ciprofloxacin group (p = 0.008). A positive clinical outcome was observed in 94.8 and 93.3% of prulifloxacin- and ciprofloxacin-treated patients. Both drugs were well tolerated. Two patients dropped out for treatment-related adverse events. Conclusions: The high urinary concentrations of prulifloxacin, combined with a broad-spectrum antimicrobial activity, allow its use in the empiric therapy of UTIs.
Possibilities and Limitations of Fibrin Glue Usage in Nephron-Sparing Surgery: Experimental Study
Authors: Stojkovic Ivica , Savic Vojin , Djokic Milan , Balint Bela , Ljubenovic Slobodan , Ignjatovic Ivan
Published: May 2005

Introduction: The possibilities and limitations of fibrin glue (FG) usage in nephron-sparing surgery were studied. Materials and Methods: A prospective experimental study was carried out in 50 pigs: 30 with polar resection, and 20 with mediorenal wedge resection of the kidney. Hemostatic sutures, FG, and FG with a muscle ‘cup’ in animals with polar resection of the kidney were compared. FG and sutures in animals with the wedge resection of the kidney were studied as well. Bleeding, hot ischemia time, complication rate, and additional scarring were also analyzed. Results: Suture hemostasis is safe but with significant adverse effects in both polar and wedge resection of kidney. FG was not efficient as a sole hemostatic agent for polar resection. It was as efficient as hemostatic suture for wedge resection of the kidney. FG with a muscle ‘cup’ on a pole of the kidney achieved good results in animals with polar resection of the kidney. Histological analysis confirmed better results with FG because of both the less intense and smaller area of additional scarring. Conclusion: FG is a reliable and efficient hemostatic agent for nephron-sparing surgery whenever both sided gluing is possible.
A Possible Antienuretic Effect of Reboxetine in Children and Adolescents with Attention Deficit/Hyperactivity Disorder: Case Series
Authors: Toren Paz , Ratner Sharon , Laor Nathaniel , Lerer-Amisar Dana , Weizman Abraham
Published: May 2005

Reboxetine is a selective norepinephrine reuptake inhibitor. Objectives: To evaluate the antienuretic effect of reboxetine in children with attention deficit and mood disorders. Methods: Six children aged 12–15 years with primary nocturnal enuresis and with attention deficit/hyperactivity disorder with or without other comorbid disorders were treated with reboxetine (4–8 mg/day). Monitoring of enuretic frequency was recorded at baseline and once a week for 6 weeks. Results: A statistically significant decrease in bedwetting was noted along the assessment points (p < 0.001), with the maximal change noted in the first week of treatment (p = 0.004). Reboxetine was well tolerated with minimal and transient side effects. Conclusions: reboxetine may possess an antienuretic effect in some children with the attention deficit/hyperactivity disorder.
Effect of Fentanyl on Lidocaine-Induced Convulsions in Mice
Authors: Cherng Chen-Hwan , Wong Chih-Shung
Published: May 2005

This study was undertaken to examine the effect of fentanyl on lidocaine-induced convulsions in mice. Seventy-five male mice were used and divided into five groups, 15 in each. Convulsions were obtained by lidocaine injection subcutaneously (150 mg/kg), in a dose volume of 0.1 ml/10 g body weight over the upper back. The five groups were: (a) control group: pretreated with normal saline; (b) F50 group: pretreated with fentanyl 50 µg/kg; (c) F100 group: pretreated with fentanyl 100 µg/kg; (d) F200 group: pretreated with fentanyl 200 µg/kg, and (e) F100+N group: pretreated with fentanyl 100 µg/kg plus naloxone 1 mg/kg. The pretreatments were given intraperitoneally (i.p.) 5 min prior to lidocaine injection. After lidocaine injection, the latency to the onset of generalized convulsions was observed for 12 min and recorded. The severity of convulsions was assessed and scored as 1 = mild, 2 = moderate, and 3 = severe. The recovery or death of the mice were also recorded. Student’s t, Mann-Whitney U, and Fisher’s exact tests were used to analyze the data. Compared with the control group (431.7 ± 37.3 s), the latencies of onset of convulsions in the fentanyl groups were dose-dependently decreased (F50: 331.0 ± 37.1 s; F100: 240.3 ± 28.6 s, p < 0.001; F200: 188.7 ± 19.4 s, p < 0.001), and the decreased latency was reversed by naloxone (F100+N: 412.9 ± 34.1 s). Compared with the control group (1.13 ± 0.19), the severities of convulsions in the fentanyl groups were also increased in a dose-dependent manner (F50: 1.47 ± 0.19; F100: 1.93 ± 0.21, p < 0.05; F200: 2.46 ± 0.17, p < 0.001). Similarly, the increased severity was reversed by naloxone (F100+N: 1.33 ± 0.16). There was no death in the control and naloxone-treated groups. The incidences of death were 2/15 in F50 group, 5/15 in F100 group, and 7/15 in the F200 group (p < 0.05). The results of this study demonstrated that fentanyl potentiates the lidocaine-induced convulsions in a dose-dependent manner in mice, and this effect may be mediated by an opioid mechanism.
Can Teachers’ Behavior Ratings Be Used to Screen Early Adolescent Boys for Psychiatric Diagnoses?
Authors: Carbonneau René , Tremblay Richard E. , Vitaro Frank , Saucier Jean-François
Published: May 2005

The present study examined if a short, 22-item teacher rating questionnaire could be used to screen young adolescent boys for psychiatric diagnoses. Subjects were 239 12-year-old boys from a community sample of low socioeconomic status families. Child and parent versions of the Diagnostic Interview Schedule for Children were used to provide DSM-III-R diagnoses. Results show a low to moderate screening value for the Short Social Behavior Questionnaire (S-SBQ) scales, with best results for externalizing disorders. The method used to establish the diagnoses had an impact on the screening efficacy of the S-SBQ, higher prevalence rates resulting in a lower proportion of false-positives for the same cutoff point. Additional research is needed to assess the screening efficacy of the S-SBQ across ages and gender, but results suggest that teacher ratings with the S-SBQ could be used to screen boys with externalizing disorders at the end of elementary school.
Markers of Endothelial Cell Activation/Injury: CD146 and Thrombomodulin Are Related to Adiponectin in Kidney Allograft Recipients
Authors: Małyszko Jolanta , Małyszko Jacek S. , Brzosko Szymon , Wołczynski Sławomir , Myśliwiec Michal
Published: May 2005

Background: Adiponectin may be used for assessing the risk of coronary artery disease (CAD) and may be related to the development of acute coronary syndrome. Decreased adiponectin has been associated with some risk factors for cardiovascular diseases such as male sex, obesity and diabetes mellitus. Adiponectin has antiatherogenic properties and attenuates endothelial inflammatory responses. CD146, a novel cell adhesion molecule, is localized at the endothelial junction. In kidney allograft recipients, endothelial dysfunction and atherosclerosis are almost universal. The aim of this cross-sectional study was to evaluate possible relations between adiponectin, CD146, and other markers of endothelial cell injury in 82 stable kidney transplant recipients (mean age 45 years, mean time after transplantation 47 months) with and without CAD. Methods: Adiponectin and markers of endothelial injury: CD146, von Willebrand factor, thrombomodulin, ICAM, CD40L, P-selectin and other hemostatic markers were assessed using commercially available kits. Results: Patients with CAD had evidence of more pronounced endothelial dysfunction, procoagulant state and lower adiponectin than patients without CAD. Adiponectin correlated significantly, in univariate analysis, with CD146 (r = 0.29, p = 0.009), thrombomodulin (r = 0.37, p = 0.001), protein Z (r = –0.25, p = 0.03), BMI (r = –0.26, p = 0.047), serum creatinine (r = 0.26, p = 0.02) and urea (r = 0.38, p = 0.001). CD146 correlated significantly with von Willebrand factor (r = 0.33, p = 0.002), thrombomodulin (r = 0.25, p = 0.025), age (r = 0.34, p = 0.001), platelets (r = –0.33, p = 0.002), serum urea (r = 0.24, p = 0.039), cholesterol (r = 0.24, p = 0.046), ICAM (r = 0.23, p = 0.036), protein C activity (r = –0.26, p = 0.019) and tended to correlate with serum creatinine and time after transplantation. In multivariate linear regression, independent predictors of adiponectin were CD146, thrombomodulin and urea, and of CD146 was mainly age of patients. Conclusions: Endothelial dysfunction and procoagulant state are more pronounced in kidney transplant recipients with CAD, particularly in those with lower GFR. In kidney transplant recipients, markers of endothelial cell injury are significantly increased relative to healthy volunteers. Elevation of adiponectin may be a defense mechanism against endothelial damage, reflected by elevated CD146 and thrombomodulin.
PECAM-1 Mediates NO-Dependent Dilation of Arterioles to High Temporal Gradients of Shear Stress
Authors: Bagi Zsolt , Frangos John A. , Yeh Jiunn-Chern , White Charles R. , Kaley Gabor , Koller Akos
Published: May 2005

Objective—

In response to changes in wall shear stress (WSS) the vascular endothelium releases several factors, among others nitric oxide. On the basis of studies of endothelial cells in culture, suggesting that platelet endothelial cell adhesion molecule-1 (PECAM-1) is specifically involved in sensing and coupling high temporal gradients of fluid shear stress with activation of eNOS, we hypothesized that dilations of isolated skeletal muscle arterioles from PECAM-1 knockout mice (PECAM-KO) will be reduced to rapid increases in WSS elicited by increases in perfusate flow.

Methods and Results—

Small and large step increases in flow resulted in substantial dilations in arterioles of WT mice (45±4%), but they were markedly reduced in arterioles of PECAM-KO mice (22±5%). The initial slope of dilations, when WSS increased rapidly, was greater in vessels of WT than those of PECAM-KO mice (slopes: 0.378 and 0.094, respectively), whereas the second phase of dilations, when flow/shear stress was steady, was similar in the 2 groups (slopes: 0.085 and 0.094, respectively). Inhibition of eNOS significantly reduced the initial phase of dilations in arterioles from WT, but not from those of PECAM-KO mice. The calcium ionophore A23187 elicited similar NO-mediated dilation in both WT and PECAM-KO mice.

Conclusions—

In isolated arterioles of PECAM-KO mice activation of eNOS and consequent dilation by agonists is maintained, but the dilation to high temporal gradients of wall shear stress elicited by increases in perfusate flow is reduced. Thus, we propose that PECAM-1 plays an important role in the ability of the endothelium to sense and couple high temporal gradients of wall shear stress to NO-mediated arteriolar dilation during sudden changes in blood flow in vivo.
Dysregulated Osteoprotegerin/RANK Ligand/RANK Axis in Clinical and Experimental Heart Failure
Authors: Ueland Thor , Yndestad Arne , Øie Erik , Florholmen Geir , Halvorsen Bente , Frøland Stig S. , Simonsen Svein , Christensen Geir , Gullestad Lars , Aukrust Pål
Published: May 2005

Background—

Persistent inflammation appears to play a role in the development of heart failure (HF). Osteoprotegerin (OPG), the receptor activator of nuclear factor-κB (RANK), and RANK ligand (RANKL) are newly discovered members of the tumor necrosis factor superfamily that are critical regulators in bone metabolism but appear also to be involved in immune responses. We hypothesized that the OPG/RANK/RANKL axis could be involved in the pathogenesis of heart failure (HF), and this hypothesis was investigated in both experimental and clinical studies.

Methods and Results—

Our main and novel findings were as follows: (1) In a rat model of postinfarction HF, we found persistently increased gene expression of OPG, RANK, and RANKL in the ischemic part of the left ventricle (LV) and, for OPG, in the nonischemic part that involved both noncardiomyocyte and in particular cardiomyocyte tissue. (2) Enhanced myocardial protein levels of OPG, RANK, and RANKL, in particular, were also seen in human HF, and using immunohistochemistry, we localized these mediators to cardiomyocytes within the LV in both experimental and clinical HF. (3) In human HF, we also found increased systemic expression of RANKL (T cells and serum) and OPG (serum), with increasing levels according to functional, hemodynamic, and neurohormonal disease severity. (4) RANKL increased total matrix metalloproteinase activity in human fibroblasts, which indicates a matrix-degrading net effect and suggests a potential mechanism by which enhanced RANKL expression in HF may contribute to LV dysfunction.

Conclusions—

These findings suggest a potential role for known mediators of bone homeostasis in the pathogenesis of HF and possibly represents new targets for therapeutic intervention in this disorder.
Increased Prevalence of Coronary Artery Aneurysms Among Cocaine Users
Authors: Satran Aaron , Bart Bradley A. , Henry Christopher R. , Murad M. Bilal , Talukdar Sumaiya , Satran Daniel , Henry Timothy D.
Published: May 2005

Background—

Cocaine abuse has been implicated in multiple cardiovascular complications. Coronary artery aneurysms (CAAs) and ectasia occur in 0.2% to 5.3% of patients referred for angiography and are associated with atherosclerosis, Kawasaki’s disease, and several rare disorders. After observing CAAs in multiple young cocaine users, we investigated the prevalence of CAAs among cocaine users undergoing coronary angiography.

Methods and Results—

Clinical and angiographic characteristics of 112 consecutive patients with a history of cocaine use and coronary angiography were compared with a control group of similar age and risk factors from an existing angiographic database over the same time period. Coronary angiograms were independently read by 3 reviewers blinded to cocaine use. Cocaine users were young (mean age, 44 years), predominantly male (80%), and cigarette smokers (95%). Control patients had higher rates of diabetes (33%) and more severe coronary artery disease (
P
=0.01). Previous myocardial infarction was common in both groups (45% of cocaine users, 38% of control patients). Despite the frequent history of myocardial infarction among cocaine users, 48% had nonobstructive coronary artery disease. Among cocaine users, 34 of 112 (30.4%) had CAAs compared with 6 of 79 (7.6%) in the control group (
P
<0.001). Cocaine use was a strong predictor of CAA by univariate and multivariate analyses.

Conclusions—

This is the first description of an association between cocaine use and CAA. The prevalence of CAA among cocaine users was higher than expected (30.4%), given such a young cohort. Cocaine use may predispose to the formation of CAA, which may in turn be a contributing factor to myocardial infarction.
Reduced Inotropic Reserve and Increased Susceptibility to Cardiac Ischemia/Reperfusion Injury in Phosphocreatine-Deficient Guanidinoacetate-
N
-Methyltransferase–Knockout Mice
Authors: ten Hove Michiel , Lygate Craig A. , Fischer Alexandra , Schneider Jürgen E. , Sang A. Elisabeth , Hulbert Karen , Sebag-Montefiore Liam , Watkins Hugh , Clarke Kieran , Isbrandt Dirk , Wallis Julie , Neubauer Stefan
Published: May 2005

Background—

The role of the creatine kinase (CK)/phosphocreatine (PCr) energy buffer and transport system in heart remains unclear. Guanidinoacetate-
N
-methyltransferase–knockout (GAMT
−/−
) mice represent a new model of profoundly altered cardiac energetics, showing undetectable levels of PCr and creatine and accumulation of the precursor (phospho-)guanidinoacetate (P-GA). To characterize the role of a substantially impaired CK/PCr system in heart, we studied the cardiac phenotype of wild-type (WT) and GAMT
−/−
mice.

Methods and Results—

GAMT
−/−
mice did not show cardiac hypertrophy (myocyte cross-sectional areas, hypertrophy markers atrial natriuretic factor and β-myosin heavy chain). Systolic and diastolic function, measured invasively (left ventricular conductance catheter) and noninvasively (MRI), were similar for WT and GAMT
−/−
mice. However, during inotropic stimulation with dobutamine, preload-recruitable stroke work failed to reach maximal levels of performance in GAMT
−/−
hearts (101±8 mm Hg in WT versus 59±7 mm Hg in GAMT
−/−
;
P
<0.05).
31
P-MR spectroscopy experiments showed that during inotropic stimulation, isolated WT hearts utilized PCr, whereas isolated GAMT
−/−
hearts utilized P-GA. During ischemia/reperfusion, GAMT
−/−
hearts showed markedly impaired recovery of systolic (24% versus 53% rate pressure product recovery;
P
<0.05) and diastolic function (eg, left ventricular end-diastolic pressure 23±9 in WT and 51±5 mm Hg in GAMT
−/−
during reperfusion;
P
<0.05) and incomplete resynthesis of P-GA.

Conclusions—

GAMT
−/−
mice do not develop hypertrophy and show normal cardiac function at low workload, suggesting that a fully functional CK/PCr system is not essential under resting conditions. However, when acutely stressed by inotropic stimulation or ischemia/reperfusion, GAMT
−/−
mice exhibit a markedly abnormal phenotype, demonstrating that an intact, high-capacity CK/PCr system is required for situations of increased cardiac work or acute stress.
Regeneration of Infarcted Myocardium by Intramyocardial Implantation of Ex Vivo Transforming Growth Factor-β–Preprogrammed Bone Marrow Stem Cells
Authors: Li Tao-Sheng , Hayashi Masanori , Ito Hiroshi , Furutani Akira , Murata Tomoaki , Matsuzaki Masunori , Hamano Kimikazu
Published: May 2005

Background—

Recent studies have shown that bone marrow–derived stem cells differentiate into the phenotype of cardiomyocytes in vivo and in vitro. We tried to regenerate infarcted myocardium by implanting ex vivo transforming growth factor (TGF)-β–preprogrammed CD117 (c-kit)–positive (CD117
+
) stem cells intramyocardially.

Methods and Results—

CD117
+
cells were isolated from the bone marrow mononuclear cells of GFP-transgenic or normal C57/BL6 mice. The myogenic differentiation of CD117
+
cells was achieved by cultivation with TGF-β. Using an acute myocardial infarction model, we also tried to regenerate infarcted myocardium by implanting untreated (newly isolated) or preprogrammed (24 hours of cultivation with 5 ng/mL TGF-β
1
) CD117
+
cells intramyocardially. TGF-β increased the cellular expression of myosin, troponins, connexin-43, GATA-4, and NKx-2.5, which suggested that it induced the myogenic differentiation of CD117
+
cells. Compared with the effects of PBS injection only, the microvessel density in the infarcted myocardium was increased significantly 3 months after the implantation of either TGF-β–preprogrammed or untreated CD117
+
cells. Moreover, many of the TGF-β–preprogrammed CD117
+
cells were stained positively for myosin, whereas few of the untreated CD117
+
cells were. Histological analysis revealed newly regenerated myocardium in the left ventricular anterior wall after the implantation of TGF-β–preprogrammed cells but not untreated cells. Furthermore, the left ventricular percent fraction shortening was significantly higher after the implantation of TGF-β–preprogrammed cells than after the implantation of untreated CD117
+
cells.

Conclusions—

TGF-β conducted the myogenic differentiation of CD117
+
stem cells by upregulating GATA-4 and NKx-2.5 expression. Therefore, the intramyocardial implantation of TGF-β–preprogrammed CD117
+
cells effectively assisted the myocardial regeneration and induced therapeutic angiogenesis, contributing to functional cardiac regeneration.
Human-Antigen R (HuR) Expression in Hypertension
Authors: Klöss Stephan , Rodenbach Daniela , Bordel Reingart , Mülsch Alexander
Published: May 2005

In aged spontaneously hypertensive rats (SHR), vasorelaxant responses to NO are attenuated compared with normotensive control rats (Wistar-Kyoto [WKY]) because of a decreased expression of the important NO receptor soluble guanylyl cyclase (sGC). Because the expression of sGC subunits α
1
and β
1
is controlled at the post-transcriptional level by the mRNA-binding protein human-antigen R (HuR), we now assessed whether or not altered expression of HuR could account for downregulation of sGCα
1
and sGCβ
1
in genetic hypertension. The expression of HuR (and sGCα
1
and sGCβ
1
) in aortas from aged SHR was significantly decreased at the mRNA and protein level compared with age-matched WKY rats, whereas expression of HuR was not different in prehypertensive young (2 months of age) SHR and age-matched WKY rats. The mRNA-binding activity of HuR in native aortic protein extracts from aged SHR was markedly reduced compared with normotensive WKY rats, as detected by RNA electrophoretic mobility shift analysis, using biotin-labeled adenine and uracil (AU)–rich element (ARE)–containing RNA probes from the 3′-untranslated region of sGCα
1
and sGCβ
1
. In contrast, ARE-binding activity was not different between prehypertensive young SHR and young WKY rats. In vitro RNA degradation assays using the same AU-rich sGC mRNA probes revealed an accelerated sGCα
1
and sGCβ
1
mRNA decay in the presence of native protein extract from hypertensive SHR, which was less rapid with aortic protein from normotensive WKY rats. These findings suggest that in this animal model of genetic hypertension, the reduced expression of sGC subunits is mediated by downregulation of the sGC mRNA–stabilizing protein HuR.
Cyclooxygenase-1–Deficient Mice Have High Sleep-to-Wake Blood Pressure Ratios and Renal Vasoconstriction
Authors: Kawada Noritaka , Solis Glenn , Ivey Nathan , Connors Stephanie , Dennehy Kathryn , Modlinger Paul , Hamel Rebecca , Kawada Julie T. , Imai Enyu , Langenbach Robert , Welch William J. , Wilcox Christopher S.
Published: May 2005

We used cyclooxygenase-1 (COX-1)–deficient mice to test the hypothesis that COX-1 regulates blood pressure (BP) and renal hemodynamics. The awake time (AT) mean arterial pressures (MAPs) measured by telemetry were not different between COX-1+/+and COX-1−/−(131±2 versus 126±3 mm Hg; NS). However, COX-1−/−had higher sleep time (ST) MAP (93±1 versus 97±2 mm Hg;P<0.05) and sleep-to-awake BP ratio (+8.6%;P<0.05). Under anesthesia with moderate sodium loading, COX-1−/−had higher MAP (109±5 versus 124±4 mm Hg;P<0.05), renal vascular resistance (23.5±1.6 versus 30.7±1.7 mm Hg · mL−1· min−1· g−1;P<0.05) and filtration fraction (33.7±2.1 versus 40.2±2.0%;P<0.05). COX-1−/−had a 89% reduction (P<0.0001) in the excretion of TxB2, a 76% reduction (P<0.01) in PGE2, a 40% reduction (P<0.0002) in 6-ketoPGF1α(6keto), a 27% reduction (P<0.02) in 11-βPGF2α(11β), a 35% reduction (P<0.01) in nitrate plus nitrite (NOx), and a 52% increase in metanephrine (P<0.02). The excretion of normetanephrine, a marker for sympathetic nervous activity, was reduced during ST in COX-1+/+(6.9±0.9 versus 3.2±0.6 g · g−1creatinine · 10−3;P<0.01). This was blunted in COX-1−/−(5.1±0.9 versus 4.9±0.7 g · g−1creatinine · 10−3; NS). Urine collection during ST showed lower excretion of 6keto, 11β, NOx, aldosterone, sodium, and potassium than during AT in both COX-1+/+and COX-1−/−, and there were positive correlations among these parameters (6keto versus NOx;P<0.005; 11β versus NOx;P<0.005; and NOx versus sodium;P<0.005). In conclusion, COX-1 mediates a suppressed sympathetic nervous activity and enhanced NO, which may contribute to renal vasodilatation and a reduced MAP while asleep or under anesthesia. COX-1 contributes to the normal nocturnal BP dipping phenomenon.
Vascular and Metabolic Effects of Combined Therapy With Ramipril and Simvastatin in Patients With Type 2 Diabetes
Authors: Koh Kwang Kon , Quon Michael J. , Han Seung Hwan , Ahn Jeong Yeal , Jin Dong Kyu , Kim Hyung Sik , Kim Dae Sung , Shin Eak Kyun
Published: May 2005

Mechanisms underlying biological effects of statin and angiotensin-converting enzyme inhibitor therapies differ. Therefore, we compared vascular and metabolic responses to these therapies either alone or in combination in patients with type 2 diabetes. This was a randomized, double-blind, placebo-controlled crossover trial with 3 treatment arms (each 2 months) and 2 washout periods (each 2 months). Fifty patients with type 2 diabetes were given simvastatin 20 mg and placebo, simvastatin 20 mg and ramipril 10 mg, or ramipril 10 mg and placebo daily during each 2-month treatment period. Ramipril alone or combined therapy significantly reduced blood pressure when compared with simvastatin alone. When compared with ramipril alone, simvastatin alone or combined therapy significantly improved the lipoprotein profile. All 3 treatment arms significantly improved flow-mediated dilator response to hyperemia and reduced plasma levels of malondialdehyde relative to baseline measurements. However, these parameters were changed to a greater extent with combined therapy when compared with simvastatin or ramipril alone (
P
<0.001 by ANOVA). When compared with simvastatin or ramipril alone, combined therapy significantly reduced high-sensitivity C-reactive protein levels (
P
=0.004 by ANOVA). Interestingly, combined therapy or ramipril alone significantly increased plasma adiponectin levels and insulin sensitivity relative to baseline measurements. These changes were significantly greater than in the group treated with simvastatin alone (
P
<0.015 by ANOVA). Ramipril combined with simvastatin had beneficial vascular and metabolic effects when compared with monotherapy in patients with type 2 diabetes.