bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing valid indicators of injury incidence for “all injury”
Authors: Cryer C , Langley J D
Published: June 2006

Background/aims:This paper focuses on the methods used to develop indicators for “all injury” incidence for the New Zealand Injury Prevention Strategy (NZIPS), launched in June 2003. Existing and previously proposed New Zealand national non-fatal injury indicators exhibited threats to validity.

Population/setting:The total population of New Zealand.

Methods:The authors proposed fatal and new non-fatal injury indicators for “all injury” based on national mortality and hospitalizations data. All of the candidate indicators were subjected to a systematic assessment of validity, using the International Collaborative Effort on Injury Statistics (ICE) criteria. Based on the results of that validation, the authors identified four proposed NZIPS indicators.

Results:The proposed “all injury” indicators were as follows: age standardized injury mortality rate per 100 000 person-years at risk; number of injury deaths; age standardized serious non-fatal injury rate per 100 000 person-years at risk; and number of cases of serious non-fatal injury. The authors identified no threat-to-validity when assessed against the ICE criteria. The estimated numbers and rates of serious non-fatal injury increased over the period, in contrast to the numbers and rates of fatal injury.

Conclusion:The authors have proposed serious non-fatal injury indicators that they judge suffer substantially less bias than traditional non-fatal injury indicators. This approach to indicator development is consistent with the view that before newly proposed indicators are promulgated, they should be subjected to formal validation. The authors are encouraged that the New Zealand Government has accepted these arguments and proposed indicators, and are starting to act on some of their recommendations, including the development of complementary indicators.
HYDRODYNAMICS OF THE VACUUM
Authors: STEVENSON P. M.
Published: June 2006

Hydrodynamics is the appropriate "effective theory" for describing any fluid medium at sufficiently long length scales. This paper treats the vacuum as such a medium and derives the corresponding hydrodynamic equations. Unlike a normal medium the vacuum has no linear sound-wave regime; disturbances always "propagate" nonlinearly. For an "empty vacuum" the hydrodynamic equations are familiar ones (shallow water-wave equations) and they describe an experimentally observed phenomenon — the spreading of a clump of zero-temperature atoms into empty space. The "Higgs vacuum" case is much stranger; pressure and energy density, and hence time and space, exchange roles. The speed of sound is formally infinite, rather than zero as in the empty vacuum. Higher-derivative corrections to the vacuum hydrodynamic equations are also considered. In the empty-vacuum case the corrections are of quantum origin and the post-hydrodynamic description corresponds to the Gross–Pitaevskii equation. We conjecture the form of the post-hydrodynamic corrections in the Higgs case. In the (1+1)-dimensional case the equations possess remarkable "soliton" solutions and appear to constitute a new exactly integrable system.
STABILITY OF COLOR-FLAVOR LOCKED STRANGELETS
Authors: KIRIYAMA O.
Published: June 2006

The stability of color-flavor locked (CFL) strangelets is studied in the three-flavor Nambu–Jona-Lasinio model. We consider all quark flavors to be massless, for simplicity. By making use of the multiple reflection expansion, we explicitly take into account finite size effects and formulate the thermodynamic potential for CFL strangelets. We find that the CFL gap could be large enough so that the energy per baryon number of CFL strangelets is greatly affected. In addition, if the quark–quark coupling constant is larger than a certain critical value, there is a possibility of finding absolutely stable CFL strangelets.
LEPTON MIXING AND SEESAW MECHANISM
Authors: FALCONE D.
Published: June 2006

In the context of a typical model for fermion mass matrices, possibly based on the horizontal U (2) symmetry, we explore the effect of the type II seesaw mechanism on lepton mixings. We find that the combined contribution of type I and type II terms is able to explain the large but not maximal 1-2 mixing and the near maximal 2-3 mixing, while the 1-3 mixing angle is predicted to be small.
SUPERSYMMETRIC CANONICAL COMMUTATION RELATIONS
Authors: CONSTANTINESCU FLORIN
Published: June 2006

We discuss the unitarily-represented supersymmetric canonical commutation relations which are subsequently used to canonically quantize massive and massless chiral, antichiral and vector fields. The canonical quantization shows some new facets which do not appear in the nonsupersymmetric case. Our tool is the supersymmetric positivity generating the Hilbert–Krein structure of the N = 1 superspace.
How do red blood cells cause hypoxic vasodilation? The SNO-hemoglobin paradigm
Authors: Allen Barry W. , Piantadosi Claude A.
Published: June 2006

One of the most intriguing areas of research in erythrocyte physiology is the interaction of hemoglobin with nitric oxide (NO). These two molecules independently fulfill diverse and complex physiological roles, while together they subtly modulate microvascular perfusion in response to second-by-second changes in local metabolic demand, contributing to hypoxic vasodilation. It is through an appreciation of the temporal and structural constraints of the microcirculation that the principal requirements of the physiological interplay between NO and hemoglobin are revealed, elucidating the role of the erythrocyte in hypoxic vasodilation. Among the candidate molecular mechanisms, only S-nitrosohemoglobin (SNO-hemoglobin) directly fulfills the physiological requirements. Thus, NO is transported by red blood cells to microvascular sites of action in protected form as an S-nitrosothiol on the highly conserved hemoglobin β-93 Cys residue, invariant in birds and mammals. SNO-hemoglobin dispenses NO bioactivity to microvascular cells on the release of oxygen, physiologically coupling hemoglobin deoxygenation to vasodilation. SNO-hemoglobin is the archetype for the role of S-nitrosylation in a newly identified class of biological signals, and disturbances in SNO-hemoglobin activity are associated with the pathogenesis of several important vascular diseases.
Prolactin-releasing peptide, food intake, and hydromineral balance in goldfish
Authors: Kelly Scott P. , Peter Richard E.
Published: June 2006

A potential role for prolactin-releasing peptide (PrRP) in appetite regulation and hydromineral balance in goldfish was examined. PrRP was found to be expressed in discrete regions of the goldfish brain, in particular, the hypothalamus. Intraperitoneal (IP) or intracerebroventricular administration of PrRP had dose-dependent effects to suppress food intake in goldfish. Hypothalamic PrRP mRNA expression significantly increased after feeding, as well as after 7 days of food deprivation. Refeeding fish after 7 days food deprivation did not result in a postprandial increase in PrRP mRNA expression. These data suggest an anorexigenic role for PrRP in the short term around a scheduled meal time, but not over the longer term. IP injection of PrRP significantly increased pituitary prolactin (PRL) mRNA levels, suggesting involvement in the regulation of lactotroph activity. Acclimating goldfish to an ion-poor environment decreased serum osmolality and increased PrRP and PRL mRNA levels, providing evidence for PrRP involvement in hydromineral balance through its actions on lactotrophs. Acclimation to ion-poor water diminished the anorexigenic properties of PrRP in goldfish, indicating that a role for PrRP in goldfish satiation is counterbalanced by alternate systemic needs (i.e., osmoregulatory). This was further supported by an ability to reinstate the anorexigenic actions of PrRP in fish acclimated to ion-poor water by feeding a salt-rich diet. These studies provide evidence that PrRP is involved in regulating appetite and hydromineral balance in fish, and that the degree of involvement in either process varies according to overall systemic needs in response to environmental conditions.
Oxidative phosphorylation and its coupling to mitochondrial creatine and adenylate kinases in human gastric mucosa
Authors: Gruno Marju , Peet Nadezhda , Seppet Evelin , Kadaja Lumme , Paju Kalju , Eimre Margus , Orlova Ehte , Peetsalu Margot , Tein Andres , Soplepmann Jaan , Schlattner Uwe , Peetsalu Ants , Seppet Enn K.
Published: June 2006

Energy metabolism in gastrobiopsy specimens of the antral and corpus mucosa, treated with saponin to permeabilize the cells, was studied in patients with gastric diseases. The results show twice lower oxidative capacity in the antral mucosa than in the corpus mucosa and the relative deficiency of antral mitochondria in complex I. The mucosal cells expressed mitochondrial and cytosolic isoforms of creatine kinase and adenylate kinase (AK). Creatine (20 mM) and AMP (2 mM) markedly stimulated mitochondrial respiration in the presence of submaximal ADP or ATP concentrations, and creatine reduced apparent Kmfor ADP in stimulation of respiration, which indicates the functional coupling of mitochondrial kinases to oxidative phosphorylation. Addition of exogenous cytochrome c increased ADP-dependent respiration, and the large-scale cytochrome c effect (≥20%) was associated with suppressed stimulation of respiration by creatine and AMP in the mucosal preparations. These results point to the impaired mitochondrial outer membrane, probably attributed to the pathogenic effects of Helicobacter pylori. Compared with the corpus mucosa, the antral mucosa exhibited greater sensitivity to such type of injury as the prevalence of the large-scale cytochrome c effect was twice higher among the latter specimens. Active chronic gastritis was associated with decreased respiratory capacity of the corpus mucosa but with its increase in the antral mucosa. In conclusion, human gastric mucosal cells express the mitochondrial and cytosolic isoforms of CK and AK participating in intracellular energy transfer systems. Gastric mucosa disease is associated with the altered functions of these systems and oxidative phosphorylation.
Mammary gland copper transport is stimulated by prolactin through alterations in Ctr1 and Atp7A localization
Authors: Kelleher Shannon L. , Lönnerdal Bo
Published: June 2006

Milk copper (Cu) concentration declines and directly reflects the stage of lactation. Three Cu-specific transporters (Ctr1, Atp7A, Atp7B) have been identified in the mammary gland; however, the integrated role they play in milk Cu secretion is not understood. Whereas the regulation of milk composition by the lactogenic hormone prolactin (PRL) has been documented, the specific contribution of PRL to this process is largely unknown. Using the lactating rat as a model, we determined that the normal decline in milk Cu concentration parallels declining Cu availability to the mammary gland and is associated with decreased Atp7B protein levels. Mammary gland Cu transport was highest during early lactation and was stimulated by suckling and hyperprolactinemia, which was associated with Ctr1 and Atp7A localization at the plasma membrane. Using cultured mammary epithelial cells (HC11), we demonstrated that Ctr1 stains in association with intracellular vesicles that partially colocalize with transferrin receptor (recycling endosome marker). Atp7A was primarily colocalized with mannose 6-phosphate receptor (M6PR; late endosome marker), whereas Atp7B was partially colocalized with protein disulfide isomerase (endoplasmic reticulum marker), TGN38 ( trans-Golgi network marker) and M6PR. Prolactin stimulated Cu transport as a result of increased Ctr1 and Atp7A abundance at the plasma membrane. Although the molecular mechanisms responsible for these posttranslational changes are not understood, transient changes in prolactin signaling play a role in the regulation of mammary gland Cu secretion during lactation.
Adrenergic control of venous capacitance during moderate hypoxia in the rainbow trout (Oncorhynchus mykiss): role of neural and circulating catecholamines
Authors: Sandblom Erik , Axelsson Michael
Published: June 2006

Central venous blood pressure (Pven) increases in response to hypoxia in rainbow trout ( Oncorhynchus mykiss), but details on the control mechanisms of the venous vasculature during hypoxia have not been studied in fish. Basic cardiovascular variables including Pven, dorsal aortic blood pressure, cardiac output, and heart rate were monitored in vivo during normoxia and moderate hypoxia (PWO2= ∼9 kPa), where PWO2is water oxygen partial pressure. Venous capacitance curves for normoxia and hypoxia were constructed at 80–100, 90–110, and 100–120% of total blood volume by transiently (8 s) occluding the ventral aorta and measure Pvenduring circulatory arrest to estimate the mean circulatory filling pressure (MCFP). This allowed for estimates of hypoxia-induced changes in unstressed blood volume (USBV) and venous compliance. MCFP increased due to a decreased USBV at all blood volumes during hypoxia. These venous responses were blocked by α-adrenoceptor blockade with prazosin (1 mg/kg body mass). MCFP still increased during hypoxia after pretreatment with the adrenergic nerve-blocking agent bretylium (10 mg/kg body mass), but the decrease in USBV only persisted at 80–100% blood volume, whereas vascular capacitance decreased significantly at 90–110% blood volume. In all treatments, hypoxia typically reduced heart rate while cardiac output was maintained through a compensatory increase in stroke volume. Despite the markedly reduced response in venous capacitance after adrenergic blockade, Pvenalways increased in response to hypoxia. This study reveals that venous capacitance in rainbow trout is actively modulated in response to hypoxia by an α-adrenergic mechanism with both humoral and neural components.
Zebrafish and giant danio as models for muscle growth: determinate vs. indeterminate growth as determined by morphometric analysis
Authors: Biga P. R. , Goetz F. W.
Published: June 2006

The zebrafish has become an important genetic model, but their small size makes them impractical for traditional physiological studies. In contrast, the closely related giant danio is larger and can be utilized for physiological studies that can also make use of the extensive zebrafish genomic resources. In addition, the giant danio and zebrafish appear to exhibit different growth types, indicating the potential for developing a comparative muscle growth model system. Therefore, the present study was conducted to compare and characterize the muscle growth pattern of zebrafish and giant danio. Morphometric analyses demonstrated that giant danio exhibit an increased growth rate compared with zebrafish, starting as early as 2 wk posthatch. Total myotome area, mean fiber area, and total fiber number all exhibited positive correlations with larvae length in giant danio but not in zebrafish. Morphometric analysis of giant danio and zebrafish larvae demonstrated faster, more efficient growth in giant danio larvae. Similar to larger teleosts, adult giant danio exhibited increased growth rates in response to growth hormone, suggesting that giant danio exhibit indeterminate growth. In contrast, adult zebrafish do not exhibit mosaic hyperplasia, nor do they respond to growth hormone, suggesting they exhibit determinate growth like mammals. These results demonstrate that giant danio and zebrafish can be utilized as a direct comparative model system for muscle growth studies, with zebrafish serving as a model organism for determinate growth and giant danio for indeterminate growth.
Evidence for a role of neuroepithelial bodies as complex airway sensors: comparison with smooth muscle-associated airway receptors
Authors: Adriaensen Dirk , Brouns Inge , Pintelon Isabel , De Proost Ian , Timmermans Jean-Pierre
Published: June 2006

The epithelium of intrapulmonary airways in many species harbors diffusely spread innervated groups of neuroendocrine cells, called neuroepithelial bodies (NEBs). Data on the location, morphology, and chemical coding of NEBs in mammalian lungs are abundant, but none of the proposed functions has so far been fully established. Besides C-fiber afferents, slowly adapting stretch receptors, and rapidly adapting stretch receptors, recent reviews have added NEBs to the list of presumed sensory receptors in intrapulmonary airways. Physiologically, the innervation of NEBs, however, remains enigmatic. This short overview summarizes our present understanding of the chemical coding and exact location of the receptor end organs of myelinated vagal airway afferents in intrapulmonary airways. The profuse populations that selectively contact complex pulmonary NEB receptors are compared with the much smaller group of smooth muscle-associated airway receptors. The main objective of our contribution was to stimulate the idea that the different populations of myelinated vagal afferents that selectively innervate intraepithelial pulmonary NEBs may represent subpopulations of the extensive group of known electrophysiologically characterized myelinated vagal airway receptors. Future efforts should be directed toward finding out which airway receptor groups are selectively coupled to the complex NEB receptors.
Oral arginine attenuates the growth hormone response to resistance exercise
Authors: Collier S. R. , Collins E. , Kanaley J. A.
Published: June 2006

This study investigated the combined effect of resistance exercise and arginine ingestion on spontaneous growth hormone (GH) release. Eight healthy male subjects were studied randomly on four separate occasions [placebo, arginine (Arg), placebo + exercise (Ex), arginine + exercise (Arg+Ex)]. Subjects had blood sampled every 10 min for 3.5 h. After baseline sampling (30 min), subjects ingested a 7-g dose of arginine or placebo (blinded, randomly assigned). On the exercise days, the subject performed 3 sets of 9 exercises, 10 repetitions at 80% one repetition maximum. Resting GH concentrations were similar on each study day. Integrated GH area under the curve was significantly higher on the Ex day (508.7 ± 169.6 min·ng/ml; P < 0.05) than on any of the other study days. Arg+Ex (260.5 ± 76.8 min·ng/ml) resulted in a greater response than the placebo day but not significantly greater than the Arg day. The GH half-life and half duration were not influenced by the stimulus administered. The GH secretory burst mass was larger, but not significantly, on the Arg, Ex, and Arg+Ex day than the placebo day. Endogenous GH production rate (Ex > Arg+Ex > Arg > placebo) was greater on the Ex and Arg+Ex day than on the placebo day ( P < 0.05) but there were no differences between the Ex and Arg+Ex day. Oral arginine alone (7 g) stimulated GH release, but a greater GH response was seen with exercise alone. The combined effect of arginine before exercise attenuates the GH response. Autonegative feedback possibly causes a refractory period such that when the two stimuli are presented there will be suppression of the somatotrope.
15° Head-down tilt attenuates the postexercise reduction in cutaneous vascular conductance and sweating and decreases esophageal temperature recovery time
Authors: McInnis Natalie H. , Journeay W. Shane , Jay Ollie , Leclair Emily , Kenny Glen P.
Published: June 2006

The following study examined the effect of 15° head-down tilt (HDT) on postexercise heat loss and hemodynamic responses. We tested the hypothesis that recovery from dynamic exercise in the HDT position would attenuate the reduction in the heat loss responses of cutaneous vascular conductance (CVC) and sweating relative to upright seated (URS) recovery in association with an augmented hemodynamic response and an increased rate of core temperature decay. Seven male subjects performed the following three experimental protocols: 1) 60 min in the URS posture followed by 60 min in the 15° HDT position; 2) 15 min of cycle ergometry at 75% of their predetermined V̇o2 peak followed by 60 min of recovery in the URS posture; or 3) 15 min of cycle ergometry at 75% of their predetermined V̇o2 peak followed by 60 min of recovery in the 15° HDT position. Mean skin temperature, esophageal temperature (Tes), skin blood flow, sweat rate, cardiac output (CO), stroke volume (SV), heart rate (HR), total peripheral resistance, and mean arterial pressure (MAP) were recorded at baseline, end exercise, 2, 5, 8, 12, 15, and 20 min, and every 5 min until end of recovery (60 min). Without preceding exercise, HDT decreased HR and increased SV ( P ≤ 0.05). During recovery after exercise, a significantly greater MAP, SV, CVC, and sweat rate and a significantly lower HR were found with HDT compared with URS posture ( P ≤ 0.05). Subsequently, a significantly lower Tes was observed with HDT after 15 min of recovery onward ( P ≤ 0.05). At the end of 60 min of recovery, Tes remained significantly elevated above baseline with URS ( P ≤ 0.05); however, Tes returned to baseline with HDT. In conclusion, extended recovery from dynamic exercise in the 15° HDT position attenuates the reduction in CVC and sweating, thereby significantly increasing the rate of Tes decay compared with recovery in the URS posture.
Changes in finger-aorta pressure transfer function during and after exercise
Authors: Stok Wim J. , Westerhof Berend E. , Karemaker John M.
Published: June 2006

Noninvasive finger blood pressure has become a surrogate for central blood pressure under widely varying circumstances. We tested the validity of finger-aorta transfer functions (TF) to reconstruct aortic pressure in seven cardiac patients before, during, and after incremental bicycle exercise. The autoregressive exogenous model method was used for calculating finger-aorta TFs. Finger pressure was measured noninvasively using Finapres and aortic pressure using a catheter-tip manometer. When applying the individual TFs found during rest for reconstruction of aortic pressure during all workloads, systolic pressure was increasingly underestimated, with large variation between subjects: +4.0 to −18.1 mmHg. In most subjects, diastolic pressure was overestimated: −3.9 to +5.5 mmHg. Pulse pressure estimation varied between +4.5 and −21.9 mmHg. In all cases, wave distortion was present. Postexercise, error in reconstructed aortic systolic pressure slowly declined, and diastolic pressure was overestimated. During rest, the TF gain had a minimum between 3.65 and 4.85 Hz (Fmin). During exercise, Fmin shifted to frequencies between 4.95 and 7.15 Hz at the maximum workload, with no change in gain. Postexercise, gain in most subjects shifted to values closer to unity, whereas Fmin did not return to resting values. Within each subject, aorta-Finapres travel time was linearly related to mean pressure. During exercise, Fmin was linearly related to both delay and heart rate. We conclude that, during increasing exercise, rest TFs give an increasingly unreliable reconstruction of aortic pressure, especially at higher heart rates.
Reflections on the Disciplinary Gulf between the Natural and Social Sciences
Authors: Wright Susan
Published: June 2006

The general purpose of this essay is to explore key features of the disciplinary gulf between the natural and social sciences, and, in particular, differences in fundamental assumptions concerning the nature and purpose of knowledge. The essay contrasts the claims of the natural sciences to objectivity and universality with those of the social sciences, especially the qualitative social sciences, to the historical and cultural contingency of knowledge. It examines the ways in which the use of two ‘key words’ – ‘expertise’ and ‘responsibility’ – serves to maintain the disciplinary gulf by reinforcing assumptions concerning the neutrality and technical nature of scientific knowledge and how those concepts marginalize social and ethical dimensions to create a politically influential hierarchy of knowledge claims.
Britain’s Genetically Modified Crop Controversies: The Agriculture and Environment Biotechnology Commission and the Negotiation of ‘Uncertainty’
Authors: Grove-White Robin
Published: June 2006

The genetically modified crop controversies in Britain between 1997 and 2004 involved tensions surrounding the role of science in policy. The author of the paper was a member of the Agriculture and Environment Biotechnology Commission, a novel government advisory body created in 2000, which played a central role in negotiating new policy frameworks. The commission was also a key influence in the creation and execution of the three-pronged official ‘GM dialogue’ in 2002 and 2003. New understandings of ‘uncertainty’, both scientific and social, emerged as a result. The outcomes have relevance for the future political handling of other technological fields, including human genetics.
Public Engagement as a Means of Restoring Public Trust in Science – Hitting the Notes, but Missing the Music?
Authors: Wynne Brian
Published: June 2006

This paper analyses the recent widespread moves to ‘restore’ public trust in science by developing an avowedly two-way, public dialogue with science initiatives. Noting how previously discredited and supposedly abandoned public deficit explanations of ‘mistrust’ have actually been continually reinvented, it argues that this is a symptom of a continuing failure of scientific and policy institutions to place their own science-policy institutional culture into the frame of dialogue, as possible contributory cause of the public mistrust problem.
Transversal Wavelength-Independent Microradiography, a Method for Monitoring Caries Lesions over Time, Validated with Transversal Microradiography
Authors: Thomas R.Z. , Ruben J.L. , de Vries J. , ten Bosch J.J. , Huysmans M.C.D.N.J.M.
Published: June 2006

This paper describes a microradiographic method for measuring mineral concentration in a transversal geometry with thick (≤3.2 mm) sections: transversal wavelength-independent microradiography (T-WIM). It was tested on bovine enamel and dentin samples in vitro, and the results were validated with those of transversal microradiography (TMR). 48 enamel and 48 dentin samples (3.2 × 3.2 × 1.5 mm) were embedded in acrylic resin, randomly divided into six groups of 8 dentin or 8 enamel samples, and demineralized for 0 (sound control), 1, 2, 3, 4, or 5 weeks. For T-WIM, samples were imaged on film with polychromatic 40-kV Cu X-rays with an Al (0.25 mm)/Ni (0.02 mm) filter together with an aluminium/zinc step wedge. TMR slices (about 80 µm for enamel and about 130 µm for dentine) were subsequently cut from the centre of the samples and subjected to TMR. Microradiographs from both methods were digitized and image analysis software was used to calculate lesion depth and mineral loss. The relations between T-WIM and TMR results for mineral loss (ΔZ) and lesion depth were nearly linear (r ≧ 0.96) for both enamel and dentin. The slopes of the regression lines were between 0.99 and 1.02 except for ΔZ in dentine, which was 0.89. It was concluded that T-WIM is a suitable method for TMR on thick samples.
Mosquito Bite Therapy: Evidenced-Based
Authors: Modjtahedi Bobeck S. , Modjtahedi Sara P. , Mansury Ahmad M. , Maibach Howard I.
Published: June 2006

Mosquito bites in humans are characterized by an immediate wheal-and-flare type I hypersensitivity response, followed by a delayed type IV papular reaction approximately 24 h later. An intense pruritic reaction may accompany all phases of the bite. Prophylactically administered oral second-generation antihistamines inhibit the immediate histamine induced wheal-and-flare in skin, and some studies show that they are also useful in alleviating delayed bite symptoms. Topical antihistamines have not been documented to be useful in treatment; however, topical ammonium solution and other common allergic reaction remedies are promising as after-bite treatments. This review assesses the current evidence analyzing the efficacy of prophylactic, oral, second-generation antihistamines as well as topical therapies for mosquito bites.
Relationship of ENOS and RAS Gene Polymorphisms to Initial Peritoneal Transport Status in Peritoneal Dialysis Patients
Authors: Akcay Ali , Micozkadioglu Hasan , Atac Fatma Belgin , Agca Erhan , Ozdemir Fatma Nurhan
Published: June 2006

Background: Peritoneal membrane permeability is of major importance for adequate dialysis and fluid balance in peritoneal dialysis (PD) therapy. The peritoneal capillary endothelium plays a key role in peritoneal transport. Nitric oxide derived from endothelial cells is related to the maintenance of vascular permeability. We investigated the relationship between the endothelial nitric oxide synthase (ENOS) gene polymorphism, the renin-angiotensin system (RAS) gene polymorphisms, and initial peritoneal transport type in PD patients. Methods: This study included 74 incident continuous ambulatory PD patients. The ENOS gene polymorphism was identified at the 4a/b variable number of tandem repeats in intron 4. Genetic polymorphisms of the renin-angiotensin system were performed for the angiotensin-converting enzyme I/D, angiotensinogen M235T, and angiotensin II type 1 receptor A1166C and type 2 receptor C3123A by polymerase chain reaction. Patients were divided into two groups according to the initial peritoneal equilibration test results performed within 3 months of PD therapy: group 1 consisted of high/high average transporters (n = 41), and group 2 consisted of low/low average transporters (n = 33). Results: Demographic, clinical, and laboratory data were similar between the two groups (p > 0.05). Group 1 had a significantly higher prevalence of the ENOS b/b genotype than group 2 (78% vs. 48.5%, p < 0.008). In contrast, group 2 had a significantly greater prevalence of the ENOS a/a+a/b genotype than group 1 (51.5% vs. 22%, p < 0.008). Genetic polymorphisms of the renin-angiotensin system were not associated with initial peritoneal transport type (p > 0.05). Conclusions: Modulation of the nitric oxide activity via the ENOS a/b polymorphism may have a considerable effect on the basal peritoneal permeability.
Residual Renal Function and Volume Control in Peritoneal Dialysis Patients
Authors: Cheng Li-Tao , Chen Wei , Tang Wen , Wang Tao
Published: June 2006

Background: Fluid overload is not uncommon in patients on continuous ambulatory peritoneal dialysis (CAPD). Previous studies suggested that residual renal function (RRF) played an important role in maintaining fluid balance. However, good fluid status should be a balance between fluid intake and removal. Therefore, in the present study, we investigated the effect of RRF on patients’ fluid status after focusing on the balance between fluid intake and removal in CAPD patients. Methods: In this cross-sectional study, 195 stable CAPD patients in a single center were included. Patients were divided into three groups according to their urine output: anuric group with urine ≤100 ml/day, oliguric group with urine ≤400 ml/day and UO >400 ml group with urine >400 ml/day. Fluid status was evaluated by bioimpedance analysis and mean arterial pressure (MAP). The sodium removal and plasma sodium concentration were also measured. All the patients were educated to try to achieve good volume control by focusing on salt and fluid intake and their removals. Results: There were 51, 31 and 113 patients in anuric, oliguric and UO >400 ml group, respectively. Anuric patients were older and had been on CAPD longer than that of the oliguric and UO >400 ml patients (p < 0.05). The urine output in the three groups were 9.28 ± 22.68, 236.13 ± 75.43 and 1,013.34 ± 541.54 ml/day, respectively (p < 0.001). Bioimpedance analysis showed that the differences of extracellular water, intracellular water and total body water were not statistically significant among the three groups. However, there was significant difference in MAP among the three groups (MAP in anuric, oliguric and UO >400 ml groups were 93.27 ± 13.35, 96.63 ± 9.94 and 102.36 ± 13.70 mm Hg, p < 0.01), and UO >400 ml group had higher MAP than anuric and oliguric groups (p < 0.05). The total sodium removal (renal + peritoneal) in anuric, oliguric and UO >400 ml groups were 96.44 ± 60.18, 98.95 ± 73.82 and 134.64 ± 72.44 mmol/day, respectively (p < 0.01). The UO >400 ml group also had higher plasma sodium concentration than anuric and oliguric groups (plasma sodium in the three groups were 137.49 ± 3.43, 137.82 ± 2.63 and 139.15 ± 3.30 mmol/l, respectively; p < 0.01). Conclusions: This study showed that extracellular water among anuric, oliguric and UO >400 ml groups was not significantly different, which suggested that RRF may be not so important as expected in maintaining good volume status. The higher blood pressure in patients with higher RRF and higher sodium and fluid removal in the present study suggested restricting salt and fluid intake might be more important for better blood pressure control in CAPD patients.
Influence of TH1/TH2 Switched Immune Response on Renal Ischemia-Reperfusion Injury
Authors: Marques Vilmar Paiva , Gonçalves Giselle Martins , Feitoza Carla Quarin , Cenedeze Marcos Antonio , Fernandes Bertocchi Ana Paula , Damião Marcio Jose , Pinheiro Helady Sanders , Antunes Teixeira Vicente Paula , dos Reis Marlene Antônia , Pacheco-Silva Alvaro , Saraiva Câmara Niels Olsen
Published: June 2006

Background/Aims: Recent evidence shows a critical role of the CD4+ T cell with the Th1/Th2 paradigm as a possible effector mechanism in ischemia and reperfusion injury. We hypothesize that a polarized Th1 activation response may negatively influence the renal IRI through its relationship with chemokine production (MCP-1) and with a protective tissue response (HO-1). Methods: We subjected mice to renal ischemia for 45 min using IL-4 and IL-12 knockout C57BL/6. We then measured serum urea levels, performed histomorphometric analysis for tubular necrosis and regeneration, and evaluated the mRNA expression of HO-1, t-bet, Gata-3 and MCP-1 by real-time PCR at 24, 48 and 120 h after surgery. Results/Conclusions: The IL-4 knockout mice had a statistically significant rise in serum urea levels post IRI compared with control animals. The IL-12-deficient mice were not affected. The IL-4-deficient mice had a statistically significant increase in tubular injury and impairment in cell regeneration. The IRI in IL-4-deficient mice was accompanied by higher levels of HO-1, t-bet and later up-regulation of MCP-1. These findings suggest that the deleterious effects of the Th1 cell involve increased production of chemokines such as MCP-1.
The Kind of Vascular Access Influences the Baseline Inflammatory Status and Epoetin Response in Chronic Hemodialysis Patients
Authors: Movilli Ezio , Brunori Giuliano , Camerini Corrado , Vizzardi Valerio , Gaggia Paola , Cassamali Silvia , Scolari Francesco , Parrinello Giovanni , Cancarini Giovanni C.
Published: June 2006

Background: Arteriovenous grafts (AVG) and tunneled permanent catheters (TPC) are increasingly being used in hemodialysis (HD) patients. However, their role in baseline inflammatory status has not been fully evaluated. Aim of the study was to evaluate the influence of the current kind of vascular access on the baseline inflammatory status, marked by serum C-reactive protein (CRP), and the response to epoetin therapy in a group of iron-replete HD patients, under steady clinical conditions, without evidence of acute infections and/or inflammatory diseases. Methods: We studied 79 patients who had been on bicarbonate HD for 8–410 months and were receiving epoetin therapy. They all had adequate iron stores and stable hemoglobin (Hb) levels. Exclusion criteria were fever, signs of infection, white blood cell count (WBC) >10 × 1,000/µl, for at least 4 weeks before study. 48 patients (group A) had arteriovenous fistula (AVF), 18 patients (group B) AVG, 13 patients (group C) TPC. CRP, Hb, transferrin saturation, serum ferritin, WBC, serum albumin, protein catabolic rate, Kt/V, and epoetin dose (U/kg body weight/week) were measured. CRP values were log-transformed to normalize the distribution. Results: Log-transformed CRP values among the 3 groups were significantly different: group A 1.81 ± 0.48; group B 2.12 ± 0.50, and group C 3.00 ± 0.25 (group A vs. B p < 0.003; group B vs. C p < 0.001; group A vs. C p < 0.0001). CRP and the epoetin dose were directly correlated (r = 0.519; p < 0.0001). The epoetin doses among the 3 groups were significantly different. Multiple regression analysis confirmed AVG and TPC as factors independently influencing CRP levels. Conclusions: AVG and TPC have a higher degree of chronic inflammation than AVF. The epoetin requirement is increased in TPC and AVG compared with AVF.
Disease Management Improves End-Stage Renal Disease Outcomes
Authors: Sands Jeffrey J.
Published: June 2006

Background/Aims: Renal disease management organizations have reported achieving significant decreases in mortality and hospitalization in conjunction with cost savings, improved patient satisfaction and quality of life. Disease management organizations strive to fill existing gaps in care delivery through the standardized use of risk assessment, predictive modeling, evidence-based guidelines, and process and outcomes measurement. Patient self-management education and the provision of individual nurse care managers are also key program components. Methods: As we more fully measure clinical outcomes and total healthcare costs, including payments from all insurance and government entities, pharmacy costs and out of pocket expenditures, the full implications of disease management can be better defined. Results: The results of this analysis will have a profound influence on United States healthcare policy. Conclusion: At present current data suggest that the promise of disease management, improved care at reduced cost, can and is being realized in end-stage renal disease.
Automatic Microelectrode Recording Analysis and Visualization of the Globus Pallidus Interna and Stereotactic Trajectory
Authors: Falkenberg Jon Haakon , McNames James , Burchiel Kim J.
Published: June 2006

Locating deep brain neuronal structures is required to accurately place deep brain stimulation (DBS) electrodes during stereotactic surgery in patients with Parkinson’s disease and other movement disorders. This study investigates the efficacy of automatic microelectrode visualization and analysis methods to help neurosurgeons locate target structures more objectively, consistently, and easily during surgery. Ten patients (4 males and 6 females) who underwent bilateral implantation of DBS electrodes in the globus pallidus interna (Gpi), from 2001 to 2003, at the Oregon Health and Science University and the Portland Veterans Administration Medical Center were included. We compared the efficacy of the microelectrode recording signal energy, power spectral density (PSD), marginal probability density (mPDF), autocorrelation function (ACF), and partial ACF. mPDF and PSD estimates most accurately indicated the borders of the GPi target structure.
Morphological Regeneration and Hepatic Functional Mass after Right Hemihepatectomy
Authors: Kobayashi Takashi , Imamura Hiroshi , Aoki Taku , Sugawara Yasuhiko , Kokudo Norihiro , Makuuchi Masatoshi
Published: June 2006

Background/Aims: Liver has a remarkable ability to regenerate after major resection. However, little is known about the process of morphological regeneration and hepatic functional recovery in human. Methods: Sixteen donors who underwent right hemihepatectomy were enrolled in this prospective clinical study. The preoperative liver volume and remnant liver volume on postoperative days 5, 12 and 28 were calculated from serial transverse computed tomography images. Liver function was evaluated by measuring the intrinsic clearance of antipyrine before and on postoperative days 5 and 12 days, as well as the biochemical and coagulation assay. Results: A smaller residual liver tended to regenerate faster in 28 days. Operative factors, including intraoperative blood loss, inflow occlusion time, liver transection time and duration of operation were not significantly correlated with postoperative liver regeneration. The intrinsic clearances of antipyrine on postoperative days 5 and 12 days were significantly reduced compared to the respective values before the operation (p < 0.001 and p < 0.05, respectively). On the contrary, the intrinsic clearance values per unit liver volume significantly increased on postoperative 12 days (p < 0.05). Conclusion: The microsomal function of individual hepatocytes may be upregulated after right liver resection perhaps in order to compensate for the reduced functional mass of the liver.
Parthenolide Modulates the NF-κB–Mediated Inflammatory Responses in Experimental Atherosclerosis
Authors: López-Franco Oscar , Hernández-Vargas Purificación , Ortiz-Muñoz Guadalupe , Sanjuán Guillermo , Suzuki Yusuke , Ortega Luis , Blanco Julia , Egido Jesús , Gómez-Guerrero Carmen
Published: June 2006

Objective—Activation of transcription factor NF-κB is an important step in the development of vascular damage, because it controls inducible genes, including many inflammatory mediators. The pharmacological modulation of this process is the main objective in the design of new therapies for atherosclerosis. In this work we analyzed the effects of the natural compound parthenolide (PTN), an NF-κB inhibitor.

Methods and Results—In vascular smooth muscle cells (VSMCs) and monocytes stimulated with lipopolysaccharide (LPS), nontoxic doses of PTN reduced IκBα degradation, NF-κB activation, and MCP-1 expression, without inhibiting AP-1 and MAPK. In apoE mice, treatment with low (2 mg/kg, 20 weeks), medium (4 mg/kg, 10 weeks), and high (10 mg/kg, 10 weeks) dose of PTN reduced the size of aortic lesion, decreased macrophage, and increased VSMC content in the lesions. Treated mice showed reduced serum levels of MCP-1 and attenuated NF-κB activity, but not AP-1, in the lesions. Moreover, PTN affects neither apoptotic cell death nor oxidative stress in cultured cells and mice.

Conclusion—NF-κB inhibition by PTN retards atherosclerotic lesions in apoE mice, by reducing lesion size and changing plaque composition. This natural compound could represent a novel therapeutic approach to inflammation during vascular damage.
Key Role of Kv1 Channels in Vasoregulation
Authors: Chen Tim T. , Luykenaar Kevin D. , Walsh Emma J. , Walsh Michael P. , Cole William C.
Published: June 2006

Small arteries play an essential role in the regulation of blood pressure and organ-specific blood flow by contracting in response to increased intraluminal pressure, ie, the myogenic response. The molecular basis of the myogenic response remains to be defined. To achieve incremental changes in arterial diameter, as well as blood pressure or organ-specific blood flow, the depolarizing influence of intravascular pressure on vascular smooth muscle membrane potential that elicits myogenic contraction must be precisely controlled by an opposing hyperpolarizing influence. Here we use a dominant-negative molecular strategy and pressure myography to determine the role of voltage-dependent Kv1 potassium channels in vasoregulation, specifically, whether they act as a negative-feedback control mechanism of the myogenic response. Functional Kv1 channel expression was altered by transfection of endothelium-denuded rat middle cerebral arteries with cDNAs encoding c-myc epitope-tagged, dominant-negative mutant or wild-type rabbit Kv1.5 subunits. Expression of mutant Kv1.5 dramatically enhanced, whereas wild-type subunit expression markedly suppressed, the myogenic response over a wide range of intraluminal pressures. These effects on arterial diameter were associated with enhanced and reduced myogenic depolarization by mutant and wild-type Kv1.5 subunit expression, respectively. Expression of myc-tagged mutant and wild-type Kv1.5 subunit message and protein in transfected but not control arteries was confirmed, and isolated myocytes of transfected but not control arteries exhibited anti-c-myc immunofluorescence. No changes in message encoding other known, non-Kv1 elements of the myogenic response were apparent. These findings provide the first molecular evidence that Kv1-containing delayed rectifier K
+
(K
DR
) channels are of fundamental importance for control of arterial diameter and, thereby, peripheral vascular resistance, blood pressure, and organ-specific blood flow.
Motor Imagery
Authors: Sharma Nikhil , Pomeroy Valerie M. , Baron Jean-Claude
Published: June 2006

Background and Purpose—

Understanding brain plasticity after stroke is important in developing rehabilitation strategies. Active movement therapies show considerable promise but depend on motor performance, excluding many otherwise eligible patients. Motor imagery is widely used in sport to improve performance, which raises the possibility of applying it both as a rehabilitation method and to access the motor network independently of recovery. Specifically, whether the primary motor cortex (M1), considered a prime target of poststroke rehabilitation, is involved in motor imagery is unresolved.

Summary of Review—

We review methodological considerations when applying motor imagery to healthy subjects and in patients with stroke, which may disrupt the motor imagery network. We then review firstly the motor imagery training literature focusing on upper-limb recovery, and secondly the functional imaging literature in healthy subjects and in patients with stroke.

Conclusions—

The review highlights the difficulty in addressing cognitive screening and compliance in motor imagery studies, particularly with regards to patients with stroke. Despite this, the literature suggests the encouraging effect of motor imagery training on motor recovery after stroke. Based on the available literature in healthy volunteers, robust activation of the nonprimary motor structures, but only weak and inconsistent activation of M1, occurs during motor imagery. In patients with stroke, the cortical activation patterns are essentially unexplored as is the underlying mechanism of motor imagery training. Provided appropriate methodology is implemented, motor imagery may provide a valuable tool to access the motor network and improve outcome after stroke.
In Vivo X-Ray Angiography in the Mouse Brain Using Synchrotron Radiation
Authors: Kidoguchi Keiji , Tamaki Masahiro , Mizobe Takashi , Koyama Junji , Kondoh Takeshi , Kohmura Eiji , Sakurai Takashi , Yokono Koichi , Umetani Keiji
Published: June 2006

Background and Purpose—

We, for the first time, performed in vivo x-ray angiography in the mouse brain using SPring-8, a third-generation synchrotron radiation facility.

Methods—

A thin PE-50 tube was placed in the unilateral external carotid artery in adult male C57BL/6J mice. While maintaining the blood flow in the internal carotid artery, 33 μL of contrast agent was injected and then selective angiography of the hemisphere was performed.

Results—

The average diameters of cerebral artery were as follows: 142.5±7.90 μm in middle cerebral artery, 138.3±9.35 μm in anterior cerebral artery, 120.5±5.53 μm in posterior cerebral artery, and 162.6±10.87 μm in internal carotid artery (n=5). To demonstrate the changes in diameter, we induced hypercapnia and detected the dilatation of the vessels between 121% and 124% of the original diameters (n=5). We also repeated angiography in the mice before and after intracarotid injection of vasodilatation drugs papaverine hydrochloride, ATP disodium, and fasudil hydrochloride hydrate and demonstrated the chronological changes in the diameters in each artery at 1, 5, 15, and 30 minutes after injection (n=1 for each drug).

Conclusions—

Using only a minimum volume of the contrast agent, synchrotron radiation enables us to study x-ray angiography in the mouse brain. The morphology of the vessels can be clearly observed under physiological conditions. The diameters and their changes can also be successfully studied in vivo.