bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypoxic pulmonary hypertension is prevented in rats with common bile duct ligation
Authors: Imamura Masatoshi , Luo Bao , Limbird Jennifer , Vitello Andrea , Oka Masahiko , Ivy D. Dunbar , McMurtry Ivan F. , Garat Chrystelle V. , Fallon Michael B. , Carter Ethan P.
Published: November 2004

Biliary cirrhosis in the rat triggers intrapulmonary vasodilatation and gas-exchange abnormalities that characterize the hepatopulmonary syndrome. This vasodilatation correlates with increased levels of pulmonary microcirculatory endothelial NO synthase (eNOS) and hepatic and plasma endothelin-1 (ET-1). Importantly, during cirrhosis, the pulmonary vascular responses to acute hypoxia are blunted. The purpose of this work was to examine the pulmonary vascular responses and adaptations to the combination of liver cirrhosis and chronic hypoxia (CH). In addition to hemodynamic measurements, we investigated whether pulmonary expression changes of eNOS, ET-1 and its receptors (endothelin A and B), or heme oxygenase 1 in experimental cirrhosis affect the development of hypoxic pulmonary hypertension. We induced cirrhosis in male Sprague-Dawley rats using common bile duct ligation (CBDL) and exposed them to CH (inspired Po2≈ 76 Torr) or maintained them in Denver (Den, inspired Po2≈ 122 Torr) for 3 wk. Our data show 1) CBDL-CH rats had a persistent blunted hypoxic pulmonary vasoconstriction similar to CBDL-Den; 2) the development of hypoxic pulmonary hypertension was completely prevented in the CBDL-CH rats, as indicated by normal pulmonary arterial pressure and lack of right ventricular hypertrophy and pulmonary arteriole remodeling; and 3) selective increases in expression of ET-1, pulmonary endothelin B receptor, eNOS, and heme oxygenase 1 are potential mechanisms of protection against hypoxic pulmonary hypertension in the CBDL-CH rats. These data demonstrate that unique and undefined hepatic-pulmonary interactions occur during liver cirrhosis and chronic hypoxia. Understanding these interactions may provide important information for the prevention and treatment of pulmonary hypertension.
AMP kinase expression and activity in human skeletal muscle: effects of immobilization, retraining, and creatine supplementation
Authors: Eijnde Bert O. , Derave Wim , Wojtaszewski Jørgen F. P. , Richter Erik A. , Hespel Peter
Published: November 2004

The effects of leg immobilization and retraining in combination with oral creatine intake on muscle AMP-activated protein kinase (AMPK) protein expression and phosphorylation status were investigated. A double-blind trial was performed in young healthy volunteers ( n = 22). A cast immobilized the right leg for 2 wk, whereafter the knee-extensor muscles of that leg were retrained for 6 wk. Half of the subjects received creatine monohydrate throughout the study (Cr; from 15 g down to 2.5 g daily), and the others ingested placebo (P; maltodextrin). Before and after immobilization and retraining, needle biopsies were taken from the right and left vastus lateralis muscles. In the right leg of P and Cr, immobilization did not affect AMPK α1-, α2-, and β2-subunit expression or AMPK α-subunit phosphorylation status. However, irrespective of the treatment received, retraining increased the degree of α-subunit phosphorylation by ∼25% ( P < 0.05) and increased AMPK α1-subunit expression ( P < 0.05) in both groups. From the start to the end of the study, AMPK subunit protein expression and α-subunit phosphorylation status were unchanged in the contralateral control leg. It is concluded that immobilization-induced muscle inactivity for 2 wk does not alter AMPK α1-, α2-, and β2-subunit expression or α-AMPK phosphorylation status. Furthermore, the present observations indicate that AMPK probably is not implicated in the previously reported beneficial effects of oral creatine supplementation on muscle during immobilization and rehabilitative weight training.
Is carbon monoxide-mediated cyclic guanosine monophosphate production responsible for low blood pressure in neonatal respiratory distress syndrome?
Authors: van Bel Frank , Latour Vincent , Vreman Hendrik J. , Wong Ronald J. , Stevenson David K. , Steendijk Paul , Egberts Johannes , Krediet Tannette G.
Published: November 2004

Infant respiratory distress syndrome (RDS) involves inflammatory processes, causing an increased expression of inducible heme oxygenase with subsequent production of carbon monoxide (CO). We hypothesized that increased production of CO during RDS might be responsible for increased plasma levels of vasodilatory cGMP and, consequently, low blood pressure observed in infants with RDS. Fifty-two infants (no-RDS, n = 21; RDS, n = 31), consecutively admitted to the neonatal intensive care unit (NICU) between January and October 2003 were included. Hemoglobin-bound carbon monoxide (COHb), plasma cGMP, plasma nitric oxide (NOx), and bilirubin were determined at 0–12, 48–72, and at 168 h postnatally, with simultaneous registration of arterial blood pressure. Infants with RDS had higher levels of cGMP and COHb compared with no-RDS infants (RDS vs. no-RDS: cGMP ranging from 76 to 101 vs. 58 to 82 nmol/l; COHb ranging from 1.2 to 1.4 vs. 0.9 to 1.0%). Highest values were reached at 48–72 h [RDS vs. no-RDS mean (SD): cGMP 100 (39) vs. 82 (25) nmol/l ( P < 0.001); COHb 1.38 (0.46) vs. 0.91 (0.26)% ( P < 0.0001)]. Arterial blood pressure was lower and more blood pressure support was needed in RDS infants at that point of time [RDS vs. no-RDS mean (SD): mean arterial blood pressure 33 (6) vs. 42 (5) mmHg ( P < 0.05)]. NOx was not different between groups and did not vary with time. Multiple linear regression analysis showed a significant correlation between cGMP and COHb, suggesting a causal relationship. Mean arterial blood pressure appeared to be primarily correlated to cGMP levels ( P < 0.001). We conclude that a CO-mediated increase in cGMP causes systemic vasodilation with a consequent lower blood pressure and increased need for blood pressure support in preterm infants with RDS.
Cyclooxygenase-2 and an early stage of chronic hypoxia-induced pulmonary hypertension in newborn pigs
Authors: Fike Candice D. , Kaplowitz Mark R. , Zhang Yongmei , Pfister Sandra L.
Published: November 2004

Our objective was to determine whether cyclooxygenase (COX)-2-dependent metabolites contribute to the altered pulmonary vascular responses that manifest in piglets with chronic hypoxia-induced pulmonary hypertension. Piglets were raised in either room air (control) or hypoxia for 3 days. The effect of the COX-2 selective inhibitor NS-398 on responses to arachidonic acid or acetylcholine (ACh) was measured in endothelium-intact and denuded pulmonary arteries (100- to 400-μm diameter). Pulmonary arterial production of the stable metabolites of thromboxane and prostacyclin was assessed in the presence and absence of NS-398. Dilation to arachidonic acid was greater for intact control than for intact hypoxic arteries, was unchanged by NS-398 in intact arteries of either group, and was augmented by NS-398 in denuded hypoxic arteries. ACh responses, which were dilation in intact control arteries but constriction in intact and denuded hypoxic arteries, were diminished by NS-398 treatment of all arteries. NS-398 reduced prostacyclin production by control pulmonary arteries and reduced thromboxane production by hypoxic pulmonary arteries. COX-2-dependent contracting factors, such as thromboxane, contribute to aberrant pulmonary arterial responses in piglets exposed to 3 days of hypoxia.
Reduction of caveolin-3 expression does not inhibit stretch-induced phosphorylation of ERK2 in skeletal muscle myotubes
Authors: Bellott Anne Claire , Patel Kalpit C. , Burkholder Thomas J.
Published: November 2004

Mechanotransduction is critical to the maintenance and growth of skeletal muscle, but the mechanism by which cellular deformations are converted to biochemical signals remains unclear. Among the earliest and most ubiquitous responses to mechanical stimulation is the phosphorylation and activation of mitogen-activated protein kinases, in particular ERK2. Caveolin-3 (CAV-3) binds ERK2 and its upstream activators in inactive states on the caveolae of resting muscle. Caveolae are deformed by stretch, and it was hypothesized that this deformation might disrupt the CAV-3-dependent inhibition of ERK2 to affect stretch-induced activation. Stretch-induced phosphorylation of ERK2 in myotubes was both amplitude and velocity dependent, consistent with a viscoelastic mechanism, such as deformation of caveolae. Chemical disruption of caveolae by cholesterol depletion increased ERK2 activation by up to 176%. Small interfering RNA oligomers were then used to knock down expression of CAV-3 in cultured myotubes before mechanical stimulation, with the expectation that reducing CAV-3 expression would eliminate the stretch-induced activation of ERK2. Knockdown reduced CAV-3 protein content by 55% but did not significantly alter the stretch-induced increase in ERK2 phosphorylation, suggesting that CAV-3 is not an essential element of the mechanotransduction pathway, although the limited extent of knockdown limits the strength of this conclusion.
Preexercise metabolic alkalosis induced via bicarbonate ingestion accelerates V̇o2kinetics at the onset of a high-power-output exercise in humans
Authors: Zoladz Jerzy A. , Szkutnik Zbigniew , Duda Krzysztof , Majerczak Joanna , Korzeniewski Bernard
Published: November 2004

The present study investigated the effect of preexercise metabolic alkalosis on the primary component of oxygen uptake (V̇o2) kinetics, characterized by τ1. Seven healthy physically active nonsmoking men, aged 22.4 ± 1.8 (mean ± SD) yr, maximum V̇o2(V̇o2 max) 50.4 ± 4 ml·min−1·kg−1, performed two bouts of cycling, corresponding to 40 and 87% of V̇o2 max, lasting 6 min each, separated by a 20-min pause, once as a control study and a few days later at ∼90 min after ingestion of 3 mmol/kg body wt of NaHCO3. Blood samples for measurements of bicarbonate concentration and hydrogen ion concentration were taken from antecubital vein via catheter. Pulmonary V̇o2was measured continuously breath by breath. The values of τ1were calculated by using six various approaches published in the literature. Preexercise level of bicarbonate concentration after ingestion of NaHCO3was significantly elevated ( P < 0.01) compared with the control study (28.96 ± 2.11 vs. 24.84 ± 1.18 mmol/l; P < 0.01), and [H+] was significantly ( P < 0.01) reduced (42.79 ± 3.38 nmol/l vs. 46.44 ± 3.51 nmol/l). This shift ( P < 0.01) was also present during both bouts of exercise. During cycling at 40% of V̇o2 max, no significant effect of the preexercise alkalosis on the magnitude of τ1was found. However, during cycling at 87% of V̇o2 max, the τ1calculated by all six approaches was significantly ( P < 0.05) reduced, compared with the control study. The τ1calculated as in Borrani et al. (Borrani F, Candau R, Millet GY, Perrey S, Fuchsloscher J, and Rouillon JD. J Appl Physiol 90: 2212–2220, 2001) was reduced on average by 7.9 ± 2.6 s, which was significantly different from zero with both the Student's t-test ( P = 0.011) and the Wilcoxon's signed-ranks test ( P = 0.014).
Synchrotron X-Ray Microtomographic Investigation of Mineral Concentrations at Micrometre Scale in Sound and Carious Enamel
Authors: Dowker S.E.P. , Elliott J.C. , Davis G.R. , Wilson R.M. , Cloetens P.
Published: November 2004

Synchrotron X-ray microtomography (XMT) was used to measure the linear attenuation coefficient (LAC) for 1.9-µm sidelength voxels within approximal brown spot lesions and sound human enamel. XMT demonstrated three-dimensional features, notably sheets with ∼30 µm periodicity having low LAC, identified as regions of demineralization corresponding to Retzius lines. Quantitative three-dimensional measurements of mineral concentration, derived from LAC with assumption of a single model composition, were consistent with previous measurements of sound and carious enamel from microradiographic projections. The uncertainty in measurements of mineral concentration and mineral fraction volume was investigated by modelling enamel with a range of composition and component densities. This analysis showed that, although mineral concentration can be determined from LAC with an error of <0.2 g cm–3, the variation in pore fraction volume within caries lesions cannot be reliably determined from X-ray attenuation measurements alone.
Typing of Mutans Streptococci by Arbitrarily Primed PCR in Patients Undergoing Orthodontic Treatment
Authors: Liu Jiarong , Bian Zhuan , Fan Mingwen , He Hong , Nie Min , Fan Bing , Peng Bin , Chen Zhi
Published: November 2004

The aim of this study was to clarify the genotypic stability of mutans streptococci (MS) longitudinally during orthodontic treatment. Plaque samples were obtained from the supragingival smooth surface of the upper right teeth at four stages: prior to and after 1, 3 and 6 months of orthodontic treatment. Levels of total viable count, total streptococci and MS in dental plaque of 17 patients were recorded. Streptococci isolated from dental plaque samples were identified as MS on the basis of their morphological and biochemical properties. DNA was prepared from 713 strains of MS and the strains were then identified with polymerase chain reaction (PCR) again. Arbitrarily primed PCR (AP-PCR) fingerprinting was applied in determining the genotypes of MS. The results indicated that levels of total viable count, total streptococci and MS increased significantly after the fixed appliances were bonded. A maximum of 3 different genotypes were found in an individual. All the genotypes were found again after the application of the fixed appliances in 17 patients. A new AP-PCR typing pattern was found after the application of fixed appliances for 1 month in patient 1. That strain was not detected either prior to or after 3, or 6 months of treatment. The result indicated that the MS clones were very stable during orthodontic treatment.
The Photo-Activated Antibacterial Action of Toluidine Blue O in a Collagen Matrix and in Carious Dentine
Authors: Williams J.A. , Pearson G.J. , Colles M.J. , Wilson M.
Published: November 2004

The main aim of this study was to determine the susceptibility to photo-activated disinfection (PAD) of Streptococcus mutans when the organism was present in a collagen matrix – an environment similar to that which would exist within a carious tooth. In addition, the susceptibility to PAD of bacteria present in carious human teeth was also determined. Light was delivered to the collagen and teeth using a system comprising a 0.8-mm diameter isotropic tip emitting light at 633 ± 2 nm. A single concentration of TBO (10 µg/ml) was used with both collagen and dentine. Two contact times, 30 and 180 s, were evaluated in intact collagen and additionally, for 180 s only, in collagen partially disrupted by shredding. The effect of energy doses from 1.8 to 14.4 J on the kills attained was assessed by determining the number of surviving viable bacteria. In carious dentine, two contact times, 30 and 60 s and one energy dose, 4.8 J, were used. Antibacterial effects were less than those obtained using planktonic suspensions with a maximum mean log reduction of 1.4 in shredded collagen and dentine. Increasing contact time increased the antibacterial effectiveness in both substrates although this was not always of statistical significance. Shredding the collagen resulted in significantly increased bacterial kills compared to those obtained in intact collagen for the 30-second contact time. The collagen matrix appeared to be a suitable model for carious dentine with advantages of availability and reproducibility. The results of this study have shown that PAD can achieve appreciable kills of oral bacteria, including S. mutans, when the organisms are embedded in a collagen gel or are present in carious teeth.
The Relative Anticaries Effectiveness of Three Fluoride-Containing Dentifrices in Puerto Rico
Authors: Stookey G.K. , Mau M.S. , Isaacs R.L. , Gonzalez-Gierbolini C. , Bartizek R.D. , Biesbrock A.R.
Published: November 2004

The objective of this research was to evaluate the anticaries effectiveness of a low-dose (500 ppm F, low-NaF) sodium fluoride dentifrice, a high-dose (2,800 ppm F, high-NaF) sodium fluoride dentifrice and an experimental 0.454% stabilized stannous fluoride (1,100 ppm F) with sodium hexametaphosphate (SnF2-HMP) dentifrice, each relative to a standard 1,100 ppm F sodium fluoride positive control dentifrice. Subjects (n = 955, with ∼239 per group) with a mean age of 10.6 (∼9–12 years) were randomly assigned to one of four dentifrice treatments. Two calibrated examiners independently measured visual-tactile caries as DMFS that was supplemented with a radiographic examination at baseline, 12 months and 24 months for each subject. Generally similar results were independently observed by both examiners at the conclusion of the 2-year study period. Considering all subjects that attended at least 60% of the supervised brushing sessions, statistically significantly less caries was observed in the high-NaF group compared to the control group. Similarly, statistically significantly less caries was observed in the SnF2-HMP group as compared to the control group. Differences in caries increments between the low-NaF and control groups were not statistically significant. One of the examiners observed these same statistically significant differences after 1 year. In conclusion, the results of this clinical trial indicated that while no difference in caries increments was observed between the low-NaF and control groups, both the high-NaF and the SnF2-HMP groups experienced significantly fewer lesions than the control group.
Acid Resistance of Enamel Subsurface Lesions Remineralized by a Sugar-Free Chewing Gum Containing Casein Phosphopeptide-Amorphous Calcium Phosphate
Authors: Iijima Y. , Cai F. , Shen P. , Walker G. , Reynolds C. , Reynolds E.C.
Published: November 2004

The aim of this clinical study was to investigate the acid resistance of enamel lesions remineralized in situ by a sugar-free chewing gum containing casein phosphopeptide-amorphous calcium phosphate nanocomplexes (CPP-ACP: Recaldent™). The study utilized a double-blind, randomized, crossover design with two treatments: (i) sugar-free gum containing 18.8 mg of CPP-ACP, and (ii) sugar-free gum not containing CPP-ACP as control. Subjects wore removable palatal appliances with insets of human enamel containing demineralized subsurface lesions and chewed the gum for 20 min 4 times per day for 14 days. After each treatment the enamel slabs were removed and half of each lesion challenged with acid in vitro for 8 or 16 h. The level of remineralization was determined using microradiography. The gum containing CPP-ACP produced approximately twice the level of remineralization as the control sugar-free gum. The 8- and 16-hour acid challenge of the lesions remineralized with the control gum resulted in 65.4 and 88.0% reductions, respectively, of deposited mineral, while for the CPP-ACP-remineralized lesions the corresponding reductions were 30.5 and 41.8%. The acid challenge after in situ remineralization for both control and CPP-ACP-treated lesions resulted in demineralization underneath the remineralized zone, indicating that the remineralized mineral was more resistant to subsequent acid challenge. The results show that sugar-free gum containing CPP-ACP is superior to an equivalent gum not containing CPP-ACP in remineralization of enamel subsurface lesions in situ with mineral that is more resistant to subsequent acid challenge.
A Study in vitro of the Abrasive Effect of the Tongue on Enamel and Dentine Softened by Acid Erosion
Authors: Gregg T. , Mace S. , West N.X. , Addy M.
Published: November 2004

The palatal aspect of upper anterior teeth appears to be one site of predilection for erosion. This raises the question of whether abrasion of softened enamel and dentine by the tongue has a role in this process. The aim of this study in vitro was to determine whether enamel and dentine specimens licked by the tongue after exposure to acid lost more tissue than when exposed to acid alone. Flat enamel and dentine specimens were prepared from human third molars and taped to expose a window of tissue. Three groups of specimens were exposed to citric acid for 10 min followed by 60 s tongue licking, ultrasonication or immersion in water. Two further groups of enamel specimens were placed in a low erosive drink for 10 min with or without licking. At the end of 5, 10 and 15 treatment cycles tissue loss was measured by profilometry. Enamel loss was significantly greater with licking and ultrasonication compared to water immersion. Dentine loss was greater with licking and ultrasonication compared to water immersion, but differences only reached significance for ultrasonication. The low erosive drink produced one third of the citric acid erosion and licking had no effect. The results suggest that the tongue could exert an abrasive effect on dental tissues softened by erosion, thereby increasing the overall loss of tooth substance.
CC-Chemokine RANTES Is Increased in Serum and Urine in the Early Post-Transplantation Period of Human Renal Allograft Recipients
Authors: Baer Patrick C. , Koziolek Michael , Fierlbeck Wolfgang , Geiger Helmut
Published: November 2004

Background: The chemokine RANTES is a potent chemoattractant for T cells and monocytes that has been shown to enhance inflammation. The aim of our study was to investigate whether RANTES is upregulated within the early post-transplantation period that may influence short-time allograft function rate. Methods: Serum and urine samples from transplanted renal allograft recipients (n = 17) were obtained from specimens taken for diagnostic reasons. Four patients developed biopsy-proven rejection episodes within the first month. Time course of RANTES was studied within the first 12 days after renal transplantation using ELISA technique. Data were tested for significances between patients with rejection and without rejection, compared to healthy volunteers as controls, and correlated with clinical data. Results: In the control group RANTES concentration was 37.2 ± 2.7 ng/ml (serum) and 8.1 ± 1.3 pg/ml (urine), respectively. In transplanted recipients serum RANTES was significantly upregulated up to 132 ± 28 ng/ml on day 1 after transplantation and remained elevated within the first 12 days (n = 17). Time course of urine RANTES demonstrated elevated concentrations with 754 ± 115 pg/ml on day 1 followed by an continuous decrease to 22.3 ± 7 pg/ml on day 12 (n = 17). No significant differences could be detected between patients with rejection and without rejection episodes. Conclusions: In contrast to data of other urinary marker molecules (like IL-6), there are no significant differences between the rejection and non-rejection group. RANTES is therefore not suitable for early detection of rejection. Nevertheless, serum and urine RANTES concentrations were highly elevated in freshly transplanted renal allograft recipients reflecting an activated immune system.
Nonpeptide Corticotropin-Releasing Hormone Receptor Type 1 Antagonists and Their Applications in Psychosomatic Disorders
Authors: Contoreggi Carlo , Rice Kenner C. , Chrousos George
Published: November 2004

Overproduction of corticotropin-releasing hormone (CRH) and stress system abnormalities are seen in psychiatric diseases such as depression, anxiety, eating disorders, and addiction. Investigations of CRH type 1 receptor (CRHR1) nonpeptide antagonists suggest therapeutic potential for treatment of these and other neuropsychiatric diseases. However, overproduction of CRH in the brain and on its periphery and disruption of the hypothalamic-pituitary-adrenal axis are also found in ‘somatic’ disorders. Some rare forms of Cushing’s disease and related pituitary/adrenal disorders are obvious applications for CRHR1 antagonists. In addition, however, these antagonists may also be effective in treating more common somatic diseases. Patients with obesity and metabolic syndrome who often have subtle, but chronic hypothalamic-pituitary-adrenal hyperactivity, which may reflect central dysregulation of CRH and consequently glucocorticoid hypersecretion, could possibly be treated by administration of CRHR1 antagonists. Hormonal, autonomic, and immune aberrations are also present in chronic inflammatory, autoimmune, and allergic diseases, with considerable evidence linking CRH with the observed abnormalities. Furthermore, autonomic dysregulation is a prominent feature of common gastrointestinal disorders, such as irritable bowel syndrome and peptic ulcer disease. Patients with irritable bowel syndrome and other gastrointestinal disorders frequently develop altered pain perception and affective symptoms. CRH acts peripherally to modulate bowel activity both directly through the autonomic system and centrally by processing viscerosensory and visceromotor neural signals. This review presents clinical and preclinical evidence for the role of CRH in the pathophysiology of these disorders and for potential diagnostic and therapeutic applications of CRHR1 antagonists. Recognition of a dysfunctional stress system in these and other diseases will alter the understanding and treatment of ‘psychosomatic’ disorders.
Plasminogen Activator Expression Correlates with Genetic Differences in Vascular Remodeling
Authors: Korshunov Vyacheslav A. , Solomatina Marina A. , Plekhanova Olga S. , Parfyonova Yelena V. , Tkachuk Vsevolod A. , Berk Bradford C.
Published: November 2004

Intima-media thickening (IMT) of the carotid artery, a form of vascular remodeling, correlates well with coronary artery disease risk in humans. Vascular remodeling in response to blood flow is a complex process that critically involves altered cell matrix interactions. To gain insight into these events, we performed partial carotid ligation (left carotid (LCA) = low flow and right carotid (RCA) = high flow) in 2 inbred mouse strains: C57Bl/6J (C57) and FVB/NJ (FVB). To evaluate the role of the 2 major matrix-degrading systems, plasminogen activators (PAs) and matrix metalloproteinases (MMPs), we compared the expression of u-PA, t-PA, MMP-2 and MMP-9 in ligated carotids of C57 and FVB mice. The extent of remodeling was greater in response to low LCA than high RCA flow. Despite a similar decrease in LCA flow in both strains, maximal IMT volume was greater in FVB (82 ± 7 × 10–6 µm3) than in C57 (38 ± 4 × 10–6 µm3) after ligation. Among PAs and MMPs, increased expression of t-PA and u-PA correlated with increased IMT (p < 0.0005 and p < 0.001, respectively). MMP-2, MMP-9 and tissue inhibitors of metalloproteinase-2 expression also increased, but did not differ between strains. In summary, flow-induced IMT of the carotid is genetically determined and correlates with t-PA and u-PA expression in 2 inbred mouse strains.
TGF-β1, -β2 and -β3 Cooperate to Facilitate Tubulogenesis in the Explanted Quail Heart
Authors: Holifield Jennifer S. , Arlen Angela M. , Runyan Raymond B. , Tomanek Robert J.
Published: November 2004

Background: Transforming growth factor-β (TGF-β) isoforms have been implicated as both pro- and anti-angiogenic modulators. In this study we addressed the roles of TGF-β isoforms on coronary tubulogenesis. Methods: Embryonic (E6) quail ventricular specimens were explanted onto collagen gels allowing endothelial cells to migrate and form vascular tubes. Growth factors and/or neutralizing growth factor antibodies were added to the cultures. Endothelial cells were identified using a quail endothelial cell marker, QH1. Image analysis was used to quantify aggregate tube length. Results: Addition of any isoform (TGF-β1, TGF-β2 or TGF-β3) virtually prevented tubulogenesis (>95% inhibition), while stimulation of tubulogenesis occurred by adding neutralizing antibodies to TGF-β3, but not to TGF-β1 or -β2. When all three isoforms were added, tubulogenesis was enhanced, indicating the key role of TGF-β3. Documentation of the inhibitory effect of TGF-β isoforms on tubulogenesis is further supported by our experiments in which the marked enhancement of tube formation by bFGF and VEGF was negated when exogenous TGF-β1, -β2, or -β3 were added to the cultures. Conclusions: (1) TGF-β1, -β2 and -β3 each inhibits angiogenesis; (2) cooperation between the three TGF-β isoforms and other angiogenic factors is essential for the regulation of normal tubulogenesis and (3) the stimulatory effect of VEGF or bFGF on tubulogenesis is negated by exogenous TGB-βs.
Effects of the Dietary Flavonoid Chrysin in Isolated Rat Mesenteric Vascular Bed
Authors: Villar Inmaculada Concepción , Galisteo Milagros , Vera Rocío , O’Valle Francisco , García-Saura María Francisca , Zarzuelo Antonio , Duarte Juan
Published: November 2004

In the present study, the effects of the bioflavonoid chrysin (5,7-dihydroxyflavone) were analyzed on the perfusion pressure of isolated mesenteric vascular bed. The vasorelaxant effects of chrysin were more potent on intact endothelium than on denuded vessels. This endothelium-dependent response induced by chrysin was inhibited in the presence of NG-nitro-L-arginine methyl ester (L-NAME), KCl, tetraethylammonium (TEA), BaCl2, TEA plus L-NAME, and ouabain plus BaCl2, while incubations with indomethacin and glibenclamide did not modify the response induced by this bioflavonoid. Neither gap junction inhibition with carbenoxolone nor epoxyeicosatrieconic acid synthesis inhibition with sulfaphenazole (selective CYP 2C/3A inhibitor) or 7-ethoxyresorufin (selective CYP 1A inhibitor) inhibited the chrysin-induced relaxation. Moreover, chrysin increased L-NAME-sensitive cGMP accumulation in intact vascular mesenteric preparation. In conclusion, chrysin shows vasodilator effects on resistance vessels, which depend partially on the functional endothelium and appear to be related to the NO/cGMP pathway and, possibly to the release of endothelium-derived hyperpolarizing factor.
Prevalence of Polycystic Ovary Syndrome in Girls Aged 14–18 Years in Isfahan, Iran
Authors: Hashemipour Mahin , Faghihimani Sussan , Zolfaghary Behzad , Hovsepian Silva , Ahmadi Fahimeh , Haghighi Sassan
Published: November 2004

Objective: To determine the prevalence of clinical polycystic ovary syndrome (PCOS) in 14- to 18-year-old high school girls in Isfahan, Iran. Methods: In this cross-sectional study, 1,000 high school girls (14–18 years old) were selected by multi-stage random sampling from different high schools in Isfahan. Following physical examination, a single physician recorded the presence of hirsutism, severe acne, androgenic alopecia, menstrual dysfunction and obesity using a validated questionnaire. Clinical PCOS was diagnosed if menstrual dysfunction and clinical hyperandrogenism were detected. Results: Clinical PCOS was present in 30 (3%), hirsutism in 60 (6%), menstrual dysfunction in 74 (7.4%) and severe acne in 47 (4.7%) of the population studied. Conclusion: The prevalence of clinical PCOS in our study population was similar to those of other studies; however, the prevalence could have been higher with hormonal assessment.
Good Outcomes after Resection of Large Hepatocellular Carcinoma in the Non-Cirrhotic Liver
Authors: Verhoef C. , de Man R.A. , Zondervan P.E. , Eijkemans M.J.C. , Tilanus H.W. , IJzermans J.N.M.
Published: November 2004

Background: The results of partial liver resection of hepatocellular carcinoma (HCC) in non-cirrhotic livers are not well known. Therefore a retrospective study was conducted. Methods: The medical records of 180 patients with HCC were reviewed. In 40 patients (22%), HCC occurred in a non-cirrhotic liver. A detailed analysis of these patients was performed. The diagnosis HCC was based on imaging and/or percutaneous ultrasound-guided biopsy. A biopsy of the remaining liver and peroperative findings documented the absence of cirrhosis. Results: Twenty-two patients underwent partial liver resection. There was no surgical mortality. The median tumour diameter in the operated patients was 10 cm. Survival rates for operated patients at 1 and 5 years were 96 and 68%, respectively. Significant factors reducing survival were portal vein thrombosis, positive lymph nodes, microscopic vascular invasion and tumour recurrence. Tumour size at the initial moment of diagnosis was not of predictive value. After surgery with curative intent disease-free interval at 1 and 5 years were 86 and 56%, respectively. Conclusion: In selected patients without cirrhosis, HCC can be treated successfully by surgical resection, independent of the tumour diameter, with a 5-year survival rate of 68%.
Survey among Surgeons on Surgical Treatment Strategies for Secondary Peritonitis
Authors: Lamme B. , Boermeester M.A. , de Vos R. , van Ruler O. , van Till J.W.O. , Obertop H.
Published: November 2004

Background: There is controversy about performing either a planned relaparotomy (PR) or relaparotomy on demand (ROD) in patients with secondary peritonitis. Subjective factors influencing surgeons in decision making for either surgical treatment strategy have never been studied. Methods: All 858 surgeons of the Association of Surgeons of The Netherlands were sent a survey with 16 case vignettes simulating peritonitis patients and evaluating the preference for PR or ROD. Results: Sixty-two percent of surgeons responded to the survey. Of the returned surveys, 407 were eligible for evaluation. The responding surgeons had a slight overall preference for the ROD strategy, as shown by the mean overall preference score of 5.2 (range 3.54–6.52, with a maximal score of 7). Gastrointestinal surgeons and surgeons working in regional and smaller hospitals were significantly more in favour of a ROD strategy than their counterparts. Factors significantly influencing the preference towards PR were ischaemia as aetiology and performing a primary anastomosis; as for ROD, it was small bowel as focus, local extent of contamination and the question whether abdominal closure was possible. However, there was a considerable variability in treatment decisions by surgeons. Conclusion: The majority of responding surgeons would make a choice for a particular treatment strategy based on peritonitis and surgical treatment characteristics. There was a slight overall preference towards the ROD strategy despite the considerable variability per case vignette.
Characterization of Microcrack Development in BMI-Carbon Fiber Composite under Stress and Thermal Cycling
Authors: Ju Jaehyung , Morgan Roger J.
Published: November 2004

The objective of this research was to determine the effect of thermal cycling on the development of microcracks in bismaleimide (BMI)-carbon fiber composites (5250-4 RTM/IM7 4-harness satin weave fabric). By clamping composite specimens on the radial sides of half cylinders having two different radii (78.74 and 37.96 mm), two different strain conditions with respect to the neutral axis (0.406 to 0.406% and -0.843 to 0.843%) were applied to the composites. Three different thermal cycling experiments: (1) -196 to 250°C, (2) 23°C to (i) 150°C, (ii) 200°C, (iii) 250°C, and (3) -196 to 23°C were performed as a function of stress, number of thermal cycles, heating or cooling rate, and humidity conditions. An in situ monitoring microscope was used to observe the microcrack development during the experiment. The results suggest that there is a higher probability of microcracking with increasing number of thermocycles, higher prestrain, and humidity. The principle findings are that the full cycles from 196 up to 250°C cause the most significant microcrack development. Observations indicate that the high-temperature portion of the cycle under load causes fiber–matrix interface failure. Subsequent exposure to higher stresses in the cryogenic temperature region results in composite matrix microcracking due to the additional stresses associated with the fiber–matrix thermal expansion mismatch.
The Potential and Use of Electronic Conferencing: a study of women’s involvement in a global context
Authors: Fisher Julie
Published: November 2004

Paper presented at the Sixth Water Information Summit: Breaking The Barriers Let Water Information Flow! Waterweb Consortium and IRC International Water And Sanitation Centre September 9-12 Delft, The Netherlands 2003. Provides an analysis of subscription and participation rates by gender and region for six e-conferences which focussed on water supply and sanitation issues. Raises questions about why differential rates of access and participation exist for men and women, and identifies some of the disincentives that exist against women’s participation. Suggested learning points for those engaged in e-conference management are listed as initial guidance on the design and implementation of future women-friendly e-conferences.
Building Partnerships: a strategy for bridging the water resources information and knowledge divide in the Caribbean
Authors: Gopaul Herold
Published: November 2004

Paper presented at the Sixth Water Information Summit: Breaking The Barriers; Let Water Information Flow! organized by Waterweb Consortium and IRC International Water and Sanitation Centre, 9-12 September 2003, Delft, The Netherlands. The inadequacy of information and data on water resources and on water demand and supply is a clear indication of weaknesses in data gathering and information generation in the Caribbean. In many countries there is a lack of recognition of the value of in-depth, sustained information. The problem seems to be caused by the disparate agencies responsible for data collection and the fragmented approach to the management of the sector, inadequate human and institutional capacity, inadequate training, poor organization and inadequate financial resources. Presents a number of initiatives currently underway in the Caribbean with regards to partnership building in the water sector. These include the Sustainable Development Network in Jamaica, Integrating Watershed and Coastal Areas Management in the Caribbean SIDS, Caribbean Dialogue on Water and Climate and Inter-American Water Resources Network.
Breaking into a World of Perfection
Authors: Bijsterveld Karin , Schulp Marten
Published: November 2004

Professional music journals frequently publish descriptions of newly registered patents concerning classical musical instruments. Only a few of the many proposals for innovation actually enter production. The large number of ideas for improving musical instruments such as the violin, the flute and the bassoon contrasts strikingly with the stability of the often age-old design of these instruments. Notably, the instruments of the symphony orchestra have basically retained their features since the mid-19th century. Compared with many other artefacts of Western culture, such stability in design and outlook is remarkable. Why is this? And what strategies do today’s innovation-seeking instrument makers use to break into this world of perfection? How, in other words, do they innovate and sell in a tradition-bound field? Moreover, how could insights in such strategies be valid for fields of technology-development in which tradition and craft have a similar significance? To address these questions, we examined music journals and, based on interviews and promotional literature, we explored the views and opinions of 12 instrument makers and promoters of unusually constructed flutes, bassoons, saxophones, violas, guitars and oboe-reeds. To account for their work, we will focus on the role of attachment to technology, on the go-betweens whose creative marginality enables them to connect technological and musical cultures and on the relevance of recasting tradition so as to innovate and sustain tradition at the very same time.
Succinoylated Poly[N-(2- Hydroxyethyl)-L-Glutamine] Derivatives for Drug Delivery
Authors: de Winne Katleen , Roseeuw Eveline , Pagnaer John , Schacht Etienne
Published: November 2004

A series of succinoylated poly[N-(2-)- L-glutamine] (PHEG) derivatives was synthesized by reacting PHEG with succinic anhydride in the presence of N,N-dimethylaminopyridine as a catalyst. The size of the derivatives were measured by dynamic light scattering in buffers (pH 5.5 and 7.4, respectively) the lysosomal and physiological pH. The degradability of the succinoylated polymers toward cathepsin B was followed by gel permeation chromatography. It was demonstrated that an increase of modification results in decreased biodegradability. Conjugation of mitomycin C (MMC) with a succinoylated PHEG derivative through a collagenase-sensitive Pro-Leu-Gly-Pro- Leu spacer resulted in a water-soluble MMC conjugate. This conjugate was shown to be hydrolytically stable in buffers of lysosomal and physiological pH and able to release MMC in the presence of the bacterial collagenase clostridium histolyticum.
Penalty and Crime with Lumpy Choices
Authors: Franckx Laurent
Published: November 2004

This paper clarifies an issue in the Hirshleifer and Rasmusen-Tsebelis controversy on the effects of penalties on crime: what is the effect of penalties if the transgression of law has a discrete nature and if the law enforcer cannot act as Stackelberg leader? We differentiate between technical (compliance costs) and institutional (penalties) parameters in the potential transgressor’s payoff’s functions. Depending on the penalty structure, we obtain equilibria either in pure or in mixed strategies. We confirm that the role played by penalties in mixed strategy equilibria is fundamentally different from the role they play in pure strategies. We also identify sufficient conditions for the implementability and uniqueness of given equilibria when there are restrictions on the penalties and/or on the incentive schemes for the law enforcers. Finally, we give a rationalization for the use of mixed strategies as a solution concept in law enforcement games.
Equilibrium in the Spatial ‘Valence’ Model of Politics
Authors: Schofield Norman
Published: November 2004

It has been a standard result of the stochastic, or probabilistic, spatial model of voting that vote maximizing candidates, or parties, will converge to the electoral mean (the origin). This conclusion has appeared to be contradicted by empirical studies.

Here, a more general stochastic model, incorporating ‘exogeneous’ valence, is constructed. Contrary to the standard result, it is shown in Theorem 1 of this paper that a potentially severe domain constraint (determined by the electoral and stochastic variance, valence as well as the dimension of the space) is necessary for the existence of equilibrium at the electoral mean. A more stringent condition, independent of the dimension of the space, is shown to be sufficient. An empirical study of Israel for 1992 shows that the necessary condition failed. This suggests that, in proportional electoral systems, a pure strategy equilibrium will almost always fail to exist at the electoral mean. Instead, in both the formal and empirical models, each party positions itself along a major electoral axis in a way which is determined by the valence terms.

A second empirical analysis for Britain for the elections of 1992 and 1997 shows that, in fact, the necessary and sufficient condition for the validity of the ‘mean voter theorem’ was satisfied, under the assumption of unidimensionality of the policy space. Indeed the low valence party, the Liberal Democrat Party, did appear to locate at the electoral center. However, the high valence parties, Labour and the Conservatives, did not. This suggests that, in polities based on plurality rule, valence is a function of activist support rather than a purely exogenous factor. Theorem 2 shows, as in Britain, that exogeneous and activist valence produce opposite effects.
Party Competition and Coalition Formation
Authors: Giannetti Daniela , Sened Itai
Published: November 2004

Formal theory has often been criticized for shying away from empirical testing, which brought some to wonder about its empirical relevance altogether. Theorists, on their side, often responded by accusing much of the empirical work in political science as being devoid of any theoretical guidance. This paper argues that part of the problem is due to the problematic fit between traditional quantitative research and abstract theoretical models. Here, we illustrate how one could bridge the gap by connecting the ever puzzling realities of Italian parliamentary politics with a theoretical model of multiparty parliamentary systems. The empirics of Italian politics raise more questions than answers and the theoretical model we apply seems awfully complex and frustratingly abstract. With the use of relatively simple visual tools, we believe that we help make some sense of the complex realities of Italian politics and, in the process, demonstrate the empirical relevance of the theoretical model we chose to apply.
Networks of Caring
Authors: Hardiman Eric R.
Published: November 2004

This article examines consumer-run agency participation by adults with psychiatric disabilities. Using qualitative data from 10 intensive interviews, the purpose was to explore personal meanings attached to agency membership, and understand the lived experiences of participants. A grounded hermeneutic approach was utilized to analyse results. Findings reveal that individuals balance agency utilization and external peer network development. Organizational factors previously found related to social network enhancement (e.g. empowerment and emphasis on supportive services) were confirmed here. The emergent narratives captured in this study suggest that these agencies function as low-demand, accepting, safe, and sheltering environments while offering opportunities for human connection, shared agency ownership and community. Finally, access to otherwise unavailable peer-focused ‘networks of caring’ was of utmost importance to participants. Implications for the organization and delivery of services are addressed. Social workers and other mental health professionals seeking to maximize community integration and develop natural supports for clients should explore consumer-run agencies.
Keynote Address: Medical Informatics and Emergency Medicine
Authors: Feied Craig F. , Smith Mark S. , Handler Jonathan A.
Published: November 2004

A personal look at some of the developments in practical clinical informatics over the past two decades, with discussion of several successful projects, including the National Center for Emergency Medicine Informatics, the Azyxxi system, Federal Project ER One, the Institutes for Innovation in Medicine, the Medical MediaLab, Project Sentinel, and others. Lessons learned, and hints and suggestions for future developers and informaticists.
Influence of leaf, humidity and applied lubrication on friction in the wheel-rail contact: Pin-on-disc experiments
Authors: Olofsson U , Sundvall K
Published: November 2004

A novel test method has been used to study how applied and natural lubrication (leaf and humidity) influences the coefficient of friction in the wheel-rail contact. A pin-on-disc tribometer placed in a climate chamber was used as the test equipment. The pin-on-disc contact simulates the wheel-rail contact caused by commuter train traffic on straight track. The results show that the coefficient of friction decreases when the relative humidity increases and decreases even more when a leaf is used as a lubricant. By using an elm leaf as the lubricant, the coefficient of friction is reduced by a factor of four compared with the unlubricated case. However, the coefficient of friction decreases even more when a rail lubricant is used.