bluuebunny/crossref_metadata_2025 huggingface dataset:
Frostbite: incidence and predisposing factors in mountaineers
Authors: Harirchi I , Arvin A , Vash J H , Zafarmand V
Published: November 2005

Background:Frostbite, the most common cold injury, occurs in mountaineers, a major group at risk, more often than in the general population.

Objectives:To describe the incidence of frostbite and the situations associated with it in mountaineering, emphasising factors that can be modified to decrease its frequency and severity.

Methods:In this cross sectional, questionnaire based study, 637 mountaineers were asked if they had suffered any frostbite injuries during the preceding two years and to provide the personal and circumstantial details.

Results:The mean incidence was 366/1000 population per year. Grade 1 injury (83.0%) and hands (26.4%) and feet (24.1%) involvement were most common. There was a significant relation between lack of proper equipment (odds ratio 14.3) or guide (p<0.001) and the injury. Inappropriate clothing, lack or incorrect use of equipment, and lack of knowledge of how to deal with cold and severe weather were claimed to be the main reasons for the injury.

Conclusions:In high altitude and winter expeditions, mountaineers should wear appropriate clothing, have the necessary equipment such as quality boots and mittens, use a competent guide, and have training on how to tackle cold weather. They should also avoid wet clothing, windy terrains, and should never remain in the same position for long periods to reduce the risk of cold injuries.
Classifying sports medicine diagnoses: a comparison of the International classification of diseases 10-Australian modification (ICD-10-AM) and the Orchard sports injury classification system (OSICS-8)
Authors: Rae K , Britt H , Orchard J , Finch C
Published: November 2005

Background:The International classification of diseases 10-Australian modification (ICD-10-AM) and the Orchard sports injury classification system (OSICS-8) are two classifications currently being used in sports injury research.

Objectives:To compare these two systems to determine which was the more reliable and easier to apply in the classification of injury diagnoses of patients who presented to sports physicians in private sports medicine practice.

Methods:Ten sports physicians/sports physician registrars each coded one of 10 different lists of 30 sports medicine diagnoses according to both ICD-10-AM and OSICS-8 in random order. The coders noted the time taken to apply each classification system, and allocated an ease of fit score for individual diagnoses into the systems. The 300 diagnoses were each coded twice more by “expert” coders from each system, and these results compared with those of the 10 volunteers.

Results:Overall, there was a higher level of agreement between the different coders for OSICS-8 than for ICD-10-AM. On average, it was 23.5 minutes quicker to complete the task with OSICS-8 than with ICD-10-AM. Furthermore, there was also higher concordance between the three coders with OSICS-8. Subjective analysis of the codes assigned indicated reasons for disagreement and showed that, in some instances, even the “expert” coders had difficulties in assigning the most appropriate codes.

Conclusions:Based on the results of this study, OSICS-8 appears to be the preferred system for use by inexperienced coders in sports medicine research. The agreement between coders was, however, lower than expected. It is recommended that changes be made to both OSICS-8 and ICD-10-AM to improve their reliability for use in sports medicine research.
Initial effects of anti-pronation tape on the medial longitudinal arch during walking and running
Authors: Vicenzino B , Franettovich M , McPoil T , Russell T , Skardoon G
Published: November 2005

Objectives:To investigate the effect of an augmented LowDye taping technique on the medial longitudinal arch of the foot during dynamic tasks such as walking and jogging, and to elucidate the relation between tape induced changes in static and dynamic foot posture.

Methods:Seventeen subjects (mean (SD) age 27 (5.8) years) who were asymptomatic and exhibited a navicular drop greater than 10 mm were studied. Medial longitudinal arch height standardised to foot length during standing and at mid-stance of walking and jogging was measured from digital video images taken before and after the application of an anti-pronation taping technique. A no tape control condition was also included.

Results:Compared with the no tape control condition, tape produced a significant mean (SD) increase in the medial longitudinal arch height index of 0.031 (0.015), 0.026 (0.014), and 0.016 (0.017) during standing, walking, and jogging respectively (p<0.05). The relative increase in medial longitudinal arch height represents an anti-pronation effect. The tape induced changes in the medial longitudinal arch height measured during standing correlated strongly with those measured during walking and jogging (Pearson’sr =  0.7 and 0.76 respectively).

Conclusions:The augmented LowDye tape was effective in controlling pronation during both static and dynamic activity. Tape induced changes in static foot posture paralleled those during walking and jogging.
Effects of dominant somatotype on aerobic capacity trainability
Authors: Chaouachi M , Chaouachi A , Chamari K , Chtara M , Feki Y , Amri M , Trudeau F
Published: November 2005

Purpose:This study examined the association between dominant somatotype and the effect on aerobic capacity variables of individualised aerobic interval training.

Methods:Forty one white North African subjects (age 21.4±1.3 years; V˙o2max = 52.8±5.7 ml kg−1min−1) performed three exercise tests 1 week apart (i) an incremental test on a cycle ergometer to determine V˙o2maxand V˙o2at the second ventilatory threshold (VT2); (ii) a VAM-EVAL track test to determine maximal aerobic speed (vV˙o2max); and (iii) an exhaustive constant velocity test to determine time limit performed at 100%vV˙o2max(tlim100). Subjects were divided into four somatometric groups: endomorphs-mesomorphs (Endo-meso; n = 9), mesomorphs (Meso; n = 11), mesomorphs-ectomorphs (Meso-ecto; n = 12), and ectomorphs (Ecto; n = 9). Subjects followed a 12 week training program (two sessions/week). Each endurance training session consisted of the maximal number of successive fractions for each subject. Each fraction consisted of one period of exercise at 100% ofvV˙o2maxand one of active recovery at 60% ofvV˙o2max. The duration of each period was equal to half the individual tlim100 duration (153.6±39.7 s). After the training program, all subjects were re-evaluated for comparison with pre-test results.

Results:Pre- and post-training data were grouped by dominant somatotype. Two way ANOVA revealed significant somatotype-aerobic training interaction effects (p<0.001) for improvements invV˙o2max, V˙o2maxexpressed classically and according to allometric scaling, and V˙o2at VT2. There were significant differences among groups post-training: the Meso-ecto and the Meso groups showed the greatest improvements in aerobic capacity.

Conclusion:The significant somatotype-aerobic training interaction suggests different trainability with intermittent and individualised aerobic training according to somatotype.
Effect of swimming intensity on subsequent cycling and overall triathlon performance
Authors: Peeling P D , Bishop D J , Landers G J
Published: November 2005

Objectives:To investigate the effects of different swimming intensities on subsequent cycling and overall triathlon performance.

Methods:Nine highly trained, male triathletes completed five separate laboratory sessions comprising one graded exercise test, a swim time trial (STT), and three sprint distance triathlons (TRI). The swimming velocities of the three TRI sessions were 80–85% (S80), 90–95% (S90), and 98–102% (S100) of the STT velocity. Subsequent cycling and running were performed at a perceived maximal intensity. Swimming stroke mechanics were measured during the swim. Plasma lactate concentration and ratings of perceived exertion were recorded at the conclusion of the swim and over the course of subsequent cycling and running. Oxygen consumption was recorded during the cycle.

Results:The S80 and S90 cycle times were faster than the S100 cycle time (p<0.05). The overall triathlon time of S80 was faster than that of S100 (p<0.05). The S100 swim was characterised by a greater stroke rate than S80 and S90 (p<0.05) and a greater plasma lactate concentration than S80 (p<0.01).

Conclusion:A swimming intensity below that of a time trial effort significantly improves subsequent cycling and overall triathlon performance.
Increased adrenal androgen secretion with inhibition of 11β-hydroxylase in HIV-infected women
Authors: Koutkia Polyxeni , Berry Jacqueline , Eaton Kristina , Breu Jeff , Grinspoon Steven
Published: November 2005

Adrenal androgen production is reduced in association with disease severity in HIV-infected women. This response may be maladaptive in terms of maintenance of lean body mass, functional status, and immune function. The aim of this study was to assess whether the use of an adrenal enzyme inhibitor of 11β-hydroxylase might increase androgen production in this population. We conducted a randomized, double-blind, placebo-controlled study of metyrapone (500 mg po qid) or placebo for 2 wk in 10 HIV-infected women with AIDS wasting [weight <90% ideal body weight (IBW) or weight loss >10%] and reduced androgen levels. Basal and ACTH-stimulated androgen, mineralocorticoid, and glucocorticoid levels were measured at baseline and after 14 days of treatment. Subjects were similar in age (40.9 ± 0.9 yr), weight (91.7 ± 3.5% IBW) and hormone concentrations at study entry. Total testosterone (84 ± 54 vs. −0.4 ± 2 ng/dl, P = 0.024), free testosterone (6.5 ± 2.8 vs. 0.1 ± 0.1 pg/ml, P = 0.024), DHEA (5.0 ± 3.2 vs. −0.6 ± 0.5 μg/l, P = 0.024), and 11-deoxycortisol (2,145 ± 820 vs. −14 ± 22 ng/dl, P = 0.024) levels increased in response to metyrapone compared with placebo treatment. In response to ACTH, significant increases in the DHEA/cortisol ratio (174 ± 48 vs. 3 ± 3, P = 0.008) were seen in the metyrapone group compared with placebo. Blood pressure and electrolytes did not change, and signs of adrenal insufficiency were not apparent. These data demonstrate that inhibition of 11β-hydroxylase with metyrapone increases adrenal androgen secretion in HIV-infected women. Further studies are needed to assess the physiological effects of this strategy to increase anabolic hormone levels in severe stress, including detailed testing to rule out the potential risk of concomitant adrenal insufficiency.
Spectral characteristics of skin sympathetic nerve activity in heat-stressed humans
Authors: Cui Jian , Sathishkumar Mithra , Wilson Thad E. , Shibasaki Manabu , Davis Scott L. , Crandall Craig G.
Published: November 2005

Skin sympathetic nerve activity (SSNA) exhibits low- and high-frequency spectral components in normothermic subjects. However, spectral characteristics of SSNA in heat-stressed subjects are unknown. Because the main components of the integrated SSNA during heat stress (sudomotor/vasodilator activities) are different from those during normothermia and cooling (vasoconstrictor activity), we hypothesize that spectral characteristics of SSNA in heat-stressed subjects will be different from those in subjects subjected to normothermia or cooling. In 17 healthy subjects, SSNA, electrocardiogram, arterial blood pressure (via Finapres), respiratory activity, and skin blood flow were recorded during normothermia and heat stress. In 7 of the 17 subjects, these variables were also recorded during cooling. Spectral characteristics of integrated SSNA, R-R interval, beat-by-beat mean blood pressure, skin blood flow variability, and respiratory excursions were assessed. Heat stress and cooling significantly increased total SSNA. SSNA spectral power in the low-frequency (0.03–0.15 Hz), high-frequency (0.15–0.45 Hz), and very-high-frequency (0.45–2.5 Hz) regions was significantly elevated by heat stress and cooling. Interestingly, heat stress caused a greater relative increase of SSNA spectral power within the 0.45- to 2.5-Hz region than in the other spectral ranges; cooling did not show this effect. Differences in the SSNA spectral distribution between normothermia/cooling and heat stress may reflect different characteristics of central modulation of vasoconstrictor and sudomotor/vasodilator activities.
Effect of modulating cardiac A1adenosine receptor expression on protection with ischemic preconditioning
Authors: Lankford Amy R. , Yang Jiang-Ning , Rose'Meyer Roselyn , French Brent A. , Matherne G. Paul , Fredholm Bertil B. , Yang Zequan
Published: November 2005

Activation of A1adenosine receptors (A1ARs) may be a crucial step in protection against myocardial ischemia-reperfusion (I/R) injury; however, the use of pharmacological A1AR antagonists to inhibit myocardial protection has yielded inconclusive results. In the current study, we have used mice with genetically modified A1AR expression to define the role of A1AR in intrinsic protection and ischemic preconditioning (IPC) against I/R injury. Normal wild-type (WT) mice, knockout mice with deleted (A1KO−/−) or single-copy (A1KO+/−) A1AR, and transgenic mice (A1TG) with increased cardiac A1AR expression underwent 45 min of left anterior descending coronary artery occlusion, followed by 60 min of reperfusion. Subsets of each group were preconditioned with short durations of ischemia (3 cycles of 5 min of occlusion and 5 min of reperfusion) before index ischemia. Infarct size (IF) in WT, A1KO+/−, and A1KO−/−mice was (in % of risk region) 58 ± 3, 60 ± 4, and 61 ± 2, respectively, and was less in A1TG mice (39 ± 4, P < 0.05). A strong correlation was observed between A1AR expression level and response to IPC. IF was significantly reduced by IPC in WT mice (35 ± 3, P < 0.05 vs. WT), A1KO+/−+ IPC (48 ± 4, P < 0.05 vs. A1KO+/−), and A1TG + IPC mice (24 ± 2, P < 0.05 vs. A1TG). However, IPC did not decrease IF in A1KO−/−+ IPC mice (63 ± 2). In addition, A1KO−/−hearts subjected to global I/R injury demonstrated diminished recovery of developed pressure and diastolic function compared with WT controls. These findings demonstrate that A1ARs are critical for protection from myocardial I/R injury and that cardioprotection with IPC is relative to the level of A1AR gene expression.
Isolation and characterization of coronary endothelial and smooth muscle cells from A1adenosine receptor-knockout mice
Authors: Teng Bunyen , Ansari Habib R. , Oldenburg Peter J. , Schnermann J. , Mustafa S. Jamal
Published: November 2005

Mice have been used widely in in vivo and in vitro cardiovascular research. The availability of knockout mice provides further clues to the physiological significance of specific receptor subtypes. Adenosine A1receptor (A1AR)-knockout (A1KO) mice and their wild-type (A1WT) controls were employed in this investigation. The heart and aortic arch were carefully removed and retroinfused with enzyme solution (1 mg/ml collagenase type I, 0.5 mg/ml soybean trypsin inhibitor, 3% BSA, and 2% antibiotics) through the aortic arch. The efflux was collected at 30-, 60-, and 90-min intervals. The cells were centrifuged, and the pellets were mixed with medium [medium 199-F-12 medium with 10% FBS and 2% antibiotics (for endothelial cells) and advanced DMEM with 10% FBS, 10% mouse serum, 2% GlutaMax, and 2% antibiotics (for smooth muscle cells)] and plated. Endothelial cells were characterized by a cobblestone appearance and positive staining with acetylated LDL labeled with 1,1′-dioctadecyl-3,3,3′,3-tetramethylindocarbocyanine perchlorate. Smooth muscle cells were characterized by positive staining of smooth muscle α-actin and smooth muscle myosin heavy chain. Homogeneity of the smooth muscle cells was ∼91%. Western blot analysis showed expression of smoothelin in the cells from passages 3, 7, and 11 in A1WT and A1KO mice. Furthermore, the A1AR was characterized by Western blot analysis using an A1AR-specific antibody. To our knowledge, this is the first isolation and successful characterization of smooth muscle cells from the mouse coronary system.
Stem cell mobilization by hyperbaric oxygen
Authors: Thom Stephen R. , Bhopale Veena M. , Velazquez Omaida C. , Goldstein Lee J. , Thom Lynne H. , Buerk Donald G.
Published: November 2005

We hypothesized that exposure to hyperbaric oxygen (HBO2) would mobilize stem/progenitor cells from the bone marrow by a nitric oxide (·NO) -dependent mechanism. The population of CD34+cells in the peripheral circulation of humans doubled in response to a single exposure to 2.0 atmospheres absolute (ATA) O2for 2 h. Over a course of 20 treatments, circulating CD34+cells increased eightfold, although the overall circulating white cell count was not significantly increased. The number of colony-forming cells (CFCs) increased from 16 ± 2 to 26 ± 3 CFCs/100,000 monocytes plated. Elevations in CFCs were entirely due to the CD34+subpopulation, but increased cell growth only occurred in samples obtained immediately posttreatment. A high proportion of progeny cells express receptors for vascular endothelial growth factor-2 and for stromal-derived growth factor. In mice, HBO2increased circulating stem cell factor by 50%, increased the number of circulating cells expressing stem cell antigen-1 and CD34 by 3.4-fold, and doubled the number of CFCs. Bone marrow ·NO concentration increased by 1,008 ± 255 nM in association with HBO2. Stem cell mobilization did not occur in knockout mice lacking genes for endothelial ·NO synthase. Moreover, pretreatment of wild-type mice with a ·NO synthase inhibitor prevented the HBO2-induced elevation in stem cell factor and circulating stem cells. We conclude that HBO2mobilizes stem/progenitor cells by stimulating ·NO synthesis.
Nonuniformity of axial and circumferential remodeling of large coronary veins in response to ligation
Authors: Choy Jenny Susana , Dang Quang , Molloi Sabee , Kassab Ghassan S.
Published: November 2005

The pressure-induced remodeling of coronary veins is important in coronary venous retroperfusion. Our hypothesis is that the response of the large coronary veins to pressure overload will depend on the degree of myocardial support. Eleven normal Yorkshire swine from either sex, weighing 31–39 kg, were studied. Five pigs underwent ligation of the left anterior descending (LAD) vein, and six served as sham-operated controls. The ligation of the coronary vein caused an increase in pressure intermediate to arterial and venous values. After 2 wk of ligation, the animals were euthanized and the coronary vessels were perfusion-fixed with glutaraldehyde. The LAD vein was sectioned, and detailed morphometric measurements were made along its length from the point of ligation near the base down to the apex of the heart. The structural remodeling of the vein was circumferentially nonuniform because the vein is partially embedded in the myocardium; it was also axially nonuniform because it is tethered to the myocardium to different degrees along its axial length. The wall area was significantly larger in the experimental group, whereas luminal area in the proximal LAD vein was significantly smaller in the same group compared with sham-operated controls. The wall thickness-to-radius ratio was also significantly larger in the experimental group in proportion to the increase in pressure. The major conclusion of this study is that the response of the vein depends on the local wall stress, which is, in part, determined by the surrounding tissue. Furthermore, the geometric remodeling of the coronary vein restores the circumferential stress to the homeostatic value.
Myocardial fibrosis, impaired coronary hemodynamics, and biventricular dysfunction in salt-loaded SHR
Authors: Varagic Jasmina , Frohlich Edward D. , Díez Javier , Susic Dinko , Ahn Jwari , González Arantxa , López Begoña
Published: November 2005

Arterial pressure in most experimental and clinical hypertensions is exacerbated by salt. The effects of salt excess on right and left ventricular (RV and LV, respectively) functions and their respective coronary vasodilatory responses have been less explored. We therefore examined the effects of 8 wk of NaCl excess (8% in food) on arterial pressure, RV and LV functions (maximal rate of increase and decrease of ventricular pressure; dP/d tmax and dP/d tmin), coronary hemodynamics (microspheres), and collagen content (hydroxyproline assay and collagen volume fraction) in young adult normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR), aged 16 wk by the end of the study. Prolonged salt excess in WKY and SHR elevated pressure only modestly, but it markedly increased LV mass, especially in SHR. Moreover, salt excess significantly impaired RV and LV diastolic function in SHR but only LV diastolic function in WKY rats. However, salt loading affected neither RV nor LV contractile function in both strains. Interstitial and perivascular collagen deposition was increased, whereas coronary vasodilatory responses to dipyridamole diminished in both ventricles in the salt-loaded SHR but not in WKY rats. Therefore, accumulation of ventricular collagen as well as altered myocardial perfusion importantly contributed to the development of salt-related RV and LV dysfunctions in this model of naturally occurring hypertension. The unique effects of salt loading on both ventricles in SHR, but not WKY rats, strongly suggest that nonhemodynamic mechanisms in hypertensive disease participate pathophysiologically with salt-loading hypertension. These findings point to the conclusion that the concept of “salt sensitivity” in hypertension is far more complex than simply its effects on arterial pressure or the LV.
Mitogen-activated protein kinase activation and regulation in the pressure-loaded fetal ovine heart
Authors: Olson Aaron K. , Protheroe Kristin N. , Segar Jeffrey L. , Scholz Thomas D.
Published: November 2005

The mitogen-activated protein (MAP) kinase signaling pathways help to mediate the hypertrophic response of the pressure-loaded adult heart, although their importance in fetal myocardium is less known. The goal of this study was to determine the role the MAP kinase signaling pathways play in regulating the response of the fetal heart to a pressure load. Aortic (Ao) and pulmonary artery (PA) bands were placed in 132-day fetal sheep for 7 days. Protein levels of the total and active (phosphorylated) terminal MAP kinases extracellular signal-regulated kinase (ERK/P-ERK), c-Jun NH2-terminal kinase (JNK/P-JNK), and p38/P-p38 and the MAP kinase phosphatases MKP-1, MKP-2, and MKP-3 were made in the right and left ventricular (RV and LV) free walls. In both Ao- and PA-banded animals, total heart weight normalized to body weight was significantly increased, largely due to an increase in RV free wall mass in the Ao-banded animals and an increase in septal mass in the PA-banded fetuses. Total protein levels of the three terminal kinases and of P-ERK and P-JNK remained stable in both groups of banded animals. However, P-p38 was significantly increased in RV and LV of Ao- and PA-banded fetuses. Whereas MKP-1 and MKP-2 protein levels were unchanged following Ao- and PA-banding, MKP-3 protein levels were significantly increased in the RV of the PA-banded animals. These findings indicate that the MAP kinase signaling pathways are active in the fetal heart and help to modulate the response of prenatal myocardium to a pressure load.
Extracellular lactate as a dynamic vasoactive signal in the rat retinal microvasculature
Authors: Yamanishi Shigeki , Katsumura Kozo , Kobayashi Takatoshi , Puro Donald G.
Published: November 2005

We tested the hypothesis that extracellular lactate regulates the function of pericyte-containing retinal microvessels. Although abluminally positioned pericytes appear to adjust capillary perfusion by contracting and relaxing, knowledge of the molecular signals that regulate the contractility of these mural cells is limited. Here, we focused on lactate because this metabolic product is in the retinal extracellular space under both physiological and pathophysiological conditions. In microvessels freshly isolated from the adult rat retina, we used perforated-patch pipettes to monitor ionic currents, fura-2 to measure calcium levels, and time-lapse photography to visualize changes in mural cell contractility and lumen diameter. During lactate exposure, pericyte calcium rose; these cells contracted, and lumens constricted. This contractile response appears to involve a cascade of events resulting in the inhibition of Na+/Ca2+exchangers (NCXs), the decreased of which function causes pericyte calcium to increase and contraction to be triggered. On the basis of our observation that gap junction uncouplers minimized the lactate-induced rise in pericyte calcium, we propose that the NCXs inhibited by lactate are predominately located in the endothelium. Indicative of the importance of endothelial/pericyte gap junctions, uncouplers of these junctions switched the pericyte response to lactate from contraction to relaxation. In addition, we observed that hypoxia, which closes microvascular gap junctions, also switched lactate’s effect from vasocontraction to vasorelaxation. Thus the response of pericyte-containing retinal microvessels to extracellular lactate is metabolically modulated. The ability of lactate to serve as a vasoconstrictor when energy supplies are ample and a vasodilator under hypoxic conditions may be an efficient mechanism to link capillary function with local metabolic need.
Iroquoisgenes influence proximo-distal morphogenesis during rat lung development
Authors: van Tuyl Minke , Liu Jason , Groenman Freek , Ridsdale Ross , Han Robin N. N. , Venkatesh Vikram , Tibboel Dick , Post Martin
Published: November 2005

Lung development is a highly regulated process directed by mesenchymal-epithelial interactions, which coordinate the temporal and spatial expression of multiple regulatory factors required for proper lung formation. The Iroquois homeobox ( Irx) genes have been implicated in the patterning and specification of several Drosophila and vertebrate organs, including the heart. Herein, we investigated whether the Irx genes play a role in lung morphogenesis. We found that Irx1– 3 and Irx5 expression was confined to the branching lung epithelium, whereas Irx4 was not expressed in the developing lung. Antisense knockdown of all pulmonary Irx genes together dramatically decreased distal branching morphogenesis and increased distention of the proximal tubules in vitro, which was accompanied by a reduction in surfactant protein C-positive epithelial cells and an increase in β-tubulin IV and Clara cell secretory protein positive epithelial structures. Transmission electron microscopy confirmed the proximal phenotype of the epithelial structures. Furthermore, antisense Irx knockdown resulted in loss of lung mesenchyme and abnormal smooth muscle cell formation. Expression of fibroblast growth factors (FGF) 1, 7, and 10, FGF receptor 2, bone morphogenetic protein 4, and Sonic hedgehog (Shh) were not altered in lung explants treated with antisense Irx oligonucleotides. All four Irx genes were expressed in Shh- and Gli2-deficient murine lungs. Collectively, these results suggest that Irx genes are involved in the regulation of proximo-distal morphogenesis of the developing lung but are likely not linked to the FGF, BMP, or Shh signaling pathways.
Nitric oxide induces phosphodiesterase 4B expression in rat pulmonary artery smooth muscle cells
Authors: Busch Cornelius J. , Liu Heling , Graveline Amanda R. , Bloch Kenneth D.
Published: November 2005

Phosphodiesterases (PDE) metabolize cyclic nucleotides limiting the effects of vasodilators such as prostacyclin and nitric oxide (NO). In this study, DNA microarray techniques were used to assess the impact of NO on expression of PDE genes in rat pulmonary arterial smooth muscle cells (rPASMC). Incubation of rPASMC with S-nitroso-l-glutathione (GSNO) increased expression of a PDE isoform that specifically metabolizes cAMP (PDE4B) in a dose- and time-dependent manner. GSNO increased PDE4B protein levels, and rolipram-inhibitable PDE activity was 2.3 ± 1.0-fold greater in GSNO-treated rPASMC than in untreated cells. The soluble guanylate cyclase (sGC) inhibitor, 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one, and the cAMP-dependent protein kinase inhibitor, H89, prevented induction of PDE4B gene expression by GSNO, but the protein kinase G (PKG) inhibitors, Rp-8-pCPT-cGMPs and KT-5823, did not. Incubation of rPASMC with IL-1β and tumor necrosis factor-α induced PDE4B gene expression, an effect that was inhibited by l- N6-(1-iminoethyl)lysine, an antagonist of NO synthase 2 (NOS2). The GSNO-induced increase in PDE4B mRNA levels was blocked by actinomycin D but augmented by cycloheximide. Infection of rPASMC with an adenovirus specifying a dominant negative cAMP response element binding protein (CREB) mutant inhibited the GSNO-induced increase of PDE4B gene expression. These results suggest that exposure of rPASMC to NO induces expression of PDE4B via a mechanism that requires cGMP synthesis by sGC but not PKG. The GSNO-induced increase of PDE4B gene expression is CREB dependent. These findings demonstrate that NO increases expression of a cAMP-specific PDE and provide evidence for a novel “cross talk” mechanism between cGMP and cAMP signaling pathways.
Control of intracellular trafficking of ICAM-1-targeted nanocarriers by endothelial Na+/H+exchanger proteins
Authors: Muro Silvia , Mateescu Madalina , Gajewski Christine , Robinson Mary , Muzykantov Vladimir R. , Koval Michael
Published: November 2005

Targeting nanocarriers (NC) loaded by antioxidant enzymes (e.g., catalase) to endothelial cell adhesion molecules (CAM) alleviates oxidative stress in the pulmonary vasculature. However, antioxidant protection is transient, since CAM-targeted catalase is internalized, delivered to lysosomes, and degraded. To design means to modulate the metabolism and longevity of endothelial cell (EC)-targeted drugs, we identified and manipulated cellular elements controlling the uptake and intracellular trafficking of NC targeted to ICAM-1 (anti-ICAM/NC). BAPTA, thapsigargin, amiloride, and EIPA inhibited anti-ICAM/NC uptake by EC and actin rearrangements induced by anti-ICAM/NC (required for uptake), suggesting that member(s) of Na+/H+exchanger family proteins (NHE) regulate these processes. Consistent with this hypothesis, an siRNA specific for the plasmalemma NHE1, but not the endosome-associated NHE6, inhibited actin remodeling induced by anti-ICAM/NC and internalization. Anti-ICAM/NC binding to EC stimulated formation of a transient ICAM-1/NHE1 complex. One hour after uptake, ICAM-1 dissociated from NHE1, and anti-ICAM/NC were transported to NHE6-positive vesicles en route to lysosomes. Inhibition of PKC (an activator of intracellular NHE) accelerated nanocarrier lysosomal trafficking. In contrast, monensin, which enhances the endosomal sodium influx and proton efflux maintained by NHE6, inhibited delivery of anti-ICAM/NC to lysosomes by switching their trafficking to a plasma membrane recycling pathway. This markedly prolonged the protective effect of catalase-coated anti-ICAM/NC. Therefore, 1) NHE1 and NHE6 regulate distinct phases of anti-ICAM/NC uptake and trafficking; 2) pharmacological agents affecting these regulatory elements alter the itinerary of anti-ICAM/NC intracellular trafficking; and 3) these agents modulate duration of the therapeutic effects of targeted drugs.
Differential effects of water and saline intake on water deprivation-induced c-Fos staining in the rat
Authors: Gottlieb Helmut B. , Ji Lisa L. , Jones Heath , Penny Maurice L. , Fleming Tiffany , Cunningham J. Thomas
Published: November 2005

We studied c-Fos staining in adult male rats after 48 h of water deprivation and after 46 h of water deprivation with 2 h of access to water or physiological saline. Controls were allowed ad libitum access to water and physiological saline. For immunocytochemistry, anesthetized rats were perfused with a commercially available antibody for c-Fos. Dehydration significantly increased plasma vasopressin (AVP), osmolality, plasma renin activity (PRA), hematocrit, and sodium concentration and decreased urinary volume. Fos staining was significantly increased in the median preoptic nucleus, organum vasculosum of the lamina terminalis, supraoptic nucleus (SON), and magnocellular and parvocellular paraventricular nucleus (PVN), as well as the area postrema, nucleus of the solitary tract (NTS), and rostral ventrolateral medulla (RVL). Rehydration with water significantly decreased AVP levels and Fos staining in the SON, PVN, and RVL and significantly increased Fos expression in the perinuclear zone of the SON, NTS, and parabrachial nucleus. Rehydration with water was associated with decreased urinary sodium concentration and hypotonicity, and hematocrit and PRA were comparable to levels seen after dehydration. After rehydration with saline, plasma osmolality, hematocrit, and PRA were not different from control, but plasma AVP and urinary sodium concentration were increased. In the SON, Fos staining was significantly increased, with a great percentage of the Fos cells also stained for oxytocin compared with water deprivation. Changes in Fos staining were also observed in the NTS, RVL, parabrachial nucleus, and PVN. Rehydration with water or saline produces differential effects on plasma AVP, Fos staining, and sodium concentration.
μ Opioid Receptor Activation Inhibits GABAergic Inputs to Basolateral Amygdala Neurons Through Kv1.1/1.2 Channels
Authors: Finnegan Thomas F. , Chen Shao-Rui , Pan Hui-Lin
Published: November 2005

The basolateral amygdala (BLA) is the major amygdaloid nucleus distributed with μ opioid receptors. The afferent input from the BLA to the central nucleus of the amygdala (CeA) is considered important for opioid analgesia. However, little is known about the effect of μ opioids on synaptic transmission in the BLA. In this study, we examined the effect of μ opioid receptor stimulation on the inhibitory and excitatory synaptic inputs to CeA-projecting BLA neurons. BLA neurons were retrogradely labeled with a fluorescent tracer injected into the CeA of rats. Whole cell voltage-clamp recordings were performed on labeled BLA neurons in brain slices. The specific μ opioid receptor agonist, (d-Ala2, N-Me-Phe4,Gly5-ol)-enkephalin (DAMGO, 1 μM), significantly reduced the frequency of miniature inhibitory postsynaptic currents (mIPSCs) in 77% of cells tested. DAMGO also significantly decreased the peak amplitude of evoked IPSCs in 75% of cells examined. However, DAMGO did not significantly alter the frequency of mEPSCs or the peak amplitude of evoked EPSCs in 90% and 75% of labeled cells, respectively. Bath application of the Kv channel blockers, 4-AP (Kv1.1, 1.2, 1.3, 1.5, 1.6, 3.1, 3.2), α-dendrotoxin (Kv1.1, 1.2, 1.6), dendrotoxin-K (Kv1.1), or tityustoxin-Kα (Kv1.2) each blocked the inhibitory effect of DAMGO on mIPSCs. Double immunofluorescence labeling showed that some of the immunoreactivities of Kv1.1 and Kv1.2 were colocalized with synaptophysin in the BLA. This study provides new information that activation of presynaptic μ opioid receptors primarily attenuates GABAergic synaptic inputs to CeA-projecting neurons in the BLA through a signaling mechanism involving Kv1.1 and Kv1.2 channels.
Fractal Noises and Motions in Time Series of Presympathetic and Sympathetic Neural Activities
Authors: Gebber Gerard L. , Orer Hakan S. , Barman Susan M.
Published: November 2005

We used Allan factor analysis to classify time series of the discharges of single presympathetic neurons in the cat medullary lateral tegmental field (LTF) and rostral ventrolateral medulla (RVLM) and of the postganglionic vertebral sympathetic nerve. These time series fell into two classes of fractal-based point processes characterized by statistically self-similar behavior reflecting long-range correlations among data points. Classification of a time series as either a fractional Gaussian noise (fGn)–or fractional Brownian motion (fBm)–based point process depended on the scaling exponent, α, of the power law in the Allan factor curve. fGn is defined as 0 < α < 1 and fBm as 1 < α < 3. The process responsible for the fractal spike trains of 11 of 12 classifiable LTF neurons with sympathetic nerve-related activity was fGn. In contrast, the process responsible for the fractal spike trains of eight of nine classifiable RVLM presympathetic neurons was fBm. The time series of simultaneously recorded vertebral sympathetic nerve discharge and the arterial pulse also were fBm-based signals. Because a fBm signal is the cumulative sum of the elements comprising the corresponding fGn signal, these results show smoothing of fractal time series in a feedforward direction from medullary presympathetic neurons to postganglionic sympathetic neurons. This may involve integration by RVLM neurons of their LTF inputs or independent fractal processes acting at different levels of the network controlling sympathetic nerve discharge. Whether feedforward smoothing of fractal signals is a feature in other neural systems is open to investigation.
Space-time in the Study of Time: An Exercise in Critical Interdisciplinarity
Authors:   Fraser
Published: November 2005

Space-time is a four-dimensional abstract space, an analytical tool used in carrying out the program of relativity theory. That program requires that the laws of physics be stated in mathematical forms that remain unaffected - that are not changed - by the motion of the coordinate system in which they are applied. The nature of time, as understood in the context of space-time, differs from the common idea of time in that it makes no provisions for a "now" - for a present - and for the passing of time. Ideas about a present instant and about the passage of time have to be imported into physics from domains of knowledge outside physics. With the help of evolutionary epistemology based on evolutionary ontology, this paper locates the time of relativity's space-time in the integrated, interdisciplinary study of time.
Time, Perpetuity and Eternity in Late Antique Platonism
Authors: Siniossoglou Niketas
Published: November 2005

This paper focuses on the late antique conception of time, eternity and perpetual duration and examines the relation between these concepts and Plato's cosmology. By exploring the controversy between pagan philosophers (Proclus, Ammonius, Simplicius, Olympiodorus) and Christian writers (Aeneas of Gaza, Zacharias of Mytilene, Philoponus) in respect to the interpretation of Plato's Timaeus, I argue that the Neoplatonic doctrine of the perpetuity (αιδóτηζ) of the world derives from a) the intellectual paradigm presupposed by the conceptual framework of late antiquity and b) the commentators' principal concern for a coherent conception of Platonic cosmology essentially free from internal contradictions.
Time and the Privileged Observer
Authors:   Hancock
Published: November 2005

This paper addresses the persistent problem concerning the integration of physical (external) with psychological (internal) expressions of time. While the history of cosmological science demonstrates the fallacy of the conception of the physically privileged observational point in the Universe, I argue that it is just such a privileged position which characterizes the unitary nature of individual human consciousness. A rational, but flawed implication of this latter observation is that there is a unique spatiotemporal point within the brain at which reality is experienced. This flaw can be exposed through reference to the sensory simultaneity problem. Evidence indicates that since no such unique neural location exists, the brain finesses the issue of absolute timing at a sensory level by simply avoiding the problem of time-tagging such events altogether. While this finesse solves the simultaneity conundrum at a sensory level, I argue that the need for personal temporal continuity and the ability to outpace exogenous time by the projection of possible futures are solved elsewhere in the brain. A brief account of these latter properties is also presented.
"Une hérésie en matière judiciaire"? The Role of the Judge ad hoc in the International Court
Authors: Scobbie Iain
Published: November 2005

In international law, the unfolding of the principle of the equality of the litigants — the sovereign equality of the litigant States — has resulted in their ability to nominate a judge to participate in the decision of the dispute by the International Court of Justice on terms of complete formal equality with the regular, or titular, judges. The institution of the judge ad hoc, appointed by the parties after a dispute has been submitted to the International Court, is alien to domestic systems of adjudication, but essential differences between municipal and international litigation must be given their due. The article questions, however, whether there is any solid basis for the continuation of the system of judges ad hoc.
Prosecutor v. Dragan Nikolić (Decision of the Interlocutory Appeal Concerning Legality of Arrest), Case No. IT-94-2-AR73
Authors: Sloan James
Published: November 2005

In a 5 June 2003 decision, the appeals chamber of the ICTY considered for the first time the question of whether it possessed jurisdiction to proceed with a case, despite the fact that the accused was before it by virtue of an illegal capture. The appeals chamber's decision to overlook breaches of international law in order to ensure Dragan Nikolić's conviction was arrived at without a thorough review of the relevant facts or law, resulting in a precedent that is seriously flawed.
Investor-State Treaty-Based Arbitration in 2004
Authors: Sampliner Gary , Teitelbaum Ruth
Published: November 2005

The year 2004 was an active year for both the filing and rendering of decisions in investor-State treaty-based arbitrations. New decisions addressed a wide variety of issues relating to the jurisdiction and admissibility of claims under international investment treaties, as well as the coverage and meaning of their substantive provisions. This article analyzes the decisions issued in 2004 by investor-State tribunals and in annulment proceedings. It also describes developments occurring during the year concerning transparency and accountability in investor-State arbitration.
Consequences of the Prestige Sinking for European and International Law
Authors: Frank Veronica
Published: November 2005

The Prestige sinking in 2002 triggered a call for a re-evaluation of the existing regime governing merchant shipping. The European Union (EU) played a crucial role in the resulting regulatory reform. This article examines the public international law issues raised by the accident and the main initiatives taken at the European and international level, especially within the International Maritime Organization (IMO). It discusses, inter alia, the suggestion to amend the United Nations Convention on the Law of the Sea, new developments in the field of Particularly Sensitive Sea Areas, phasing out of single hull tankers, EU membership of IMO, flag State control and enforcement and "places of refuge". It is concluded that, despite the positive post-Prestige outcomes, some gaps still remain. For the time being, however, there is no need for new rules but rather for taking full advantage of, clarifying and effectively enforcing the existing ones.
Protecting Sensitive Marine Environments: The Role and Application of Ships' Routeing Measures
Authors: Roberts Julian
Published: November 2005

The application of ships' routeing measures as a means to regulate shipping for the specific purpose of protecting sensitive marine areas is becoming increasingly widespread and acceptable within the international community. While the potential for coastal states to regulate navigation for such purposes would seem to be in conflict with the traditional tenants of freedom of navigation, current practice at both the state and international level addresses this concern.This paper discusses the application of ships' routeing measures for the protection of the marine environment from the activities of international shipping, as illustrated by current state practice. Consideration is given to the evolution of IMO measures to address environmental concerns and in particular the application of mandatory routeing measures.
Death Certificates in Germany, England, The Netherlands, Belgium and the USA
Authors: Das
Published: November 2005

Every country has its own legal system regarding post mortem examinations and death certificates. The authorities want to know the cause and the manner of death of their citizens and especially whether someone is responsible for the death of someone else.In this article a comparison is made between the legal regulations in the Netherlands, Belgium, Germany, England and the USA. Specific attention is given to the following aspects: which official performs the post mortem exam, what is the role of the attending physician by issuing the death certificate and how is the privacy of the deceased protected.
Health, Disability & Parental Interests: Adopting a Contextual Approach in the Reproductive Torts
Authors: Priaulx Nicolette
Published: November 2005

Illustrating the limitations of the notion that caring for a disabled child is harmful and sufficiently distinctive from the (judicially viewed harmless) experience of caring for non-disabled children, this article takes issue with the differential outcomes of the reproductive torts where success pivots upon the presence or absence of disability. Since caring for any child must be seen as bringing about a significant caring responsibility, if there is a difference in the burden that results, this will be a matter of extent, not kind. Also taking a critical view of the House of Lords recent determination of Rees v Darlington Memorial Hospital, this article notes that nor can a "common approach" to all claims of wrongful conception and birth offer an equitable alternative. Ignoring context and treating all reproductive outcomes equally for the purposes of compensation is certain to result in manifest unfairness. The thrust of the argument is that it is essential that the law embrace a more contemporary and contextual approach, based on the value of reproductive autonomy.
The Importance of National Laws in the Implementation of European Legislation of Biomedical Research
Authors: Gytis Andrulionis , Sprumont Dominique
Published: November 2005

The industrialization and internationalization of biomedical research is not without consequences on the regulation of research or, at least, on the interpretation of that regulation. As more research is done at the international level, the pharmaceutical industry and the research community are calling for a harmonized regulation to limit the administrative burden of controlling clinical trials and to fasten the R&D process. The purpose of this paper is to analyse briefly the role of the national laws in that process. Part I will outline the structure and the nature of the international regulation of research in a European perspective. Using the examples of research ethics committees (RECs), informed consent and the question of liability and liability insurance, Part II will analyze the importance of the national laws in the implementation of this international regulation.
From System Into Networking: The Social Shape of Ecumenism in the 21st Century
Authors: Witte Henk
Published: November 2005

On the threshold of post-modernism, the shape of ecumenism is in a process of change. It passes from a system to a form of networking. This article reflects on this process against the background of the question of the French sociologist of religion Jean-Paul Willaime whether ecumenism is out-of-date. According to Willaime, ecumenism has become a disordered pluralism. He only draws attention to the nihilistic and pluralistic character of post-modernism, but does not look at its aesthetic-mystic dimension. The history of western ontology shows three consecutive ways of experiencing reality: substance, system, and structure (Heinrich Rombach). Ecumenism has been developed as a system, in which unity predominates, but post-modern culture, with its priority to pluralism, challenges it to shape itself as networking and to think about unity in more sacramental and in more juridical terms.