bluuebunny/crossref_metadata_2025 huggingface dataset:
Iron in the Ross Sea: 2. Impact of discrete iron addition strategies
Authors: Arrigo Kevin R. , Tagliabue Alessandro
Published: March 2005

Presented are results of a regional‐scale numerical investigation into the effectiveness of Fe fertilization as a means to increase the efficiency of the biological pump in Fe‐limited waters of the Ross Sea, Antarctica. This investigation was conducted using a modified version of the Coupled Ice And Ocean (CIAO) ecosystem model of the Ross Sea sector of the Southern Ocean. Four sets of experiments were performed, investigating the impacts of differences in (1) timing of fertilization, (2) duration of fertilization, (3) amount of Fe added, and (4) size of the fertilized patch. Results show that the stimulation of air‐sea CO2 exchange (FCO2) depends primarily on the timing of fertilization, regardless of the amount of Fe added. When Fe was added at the optimal time of year, FCO2 from the atmosphere into the Ross Sea was increased by 3–22%, depending on fertilization strategy. Increasing patch size produced the largest response, and increasing initial Fe concentration produced the smallest. In all cases, as the intensity of Fe fertilization increased, the fertilization efficiency (increase in CO2 uptake per unit added Fe) dropped. Strategies that maximized the fertilization efficiency resulted in relatively little additional CO2 being drawn out of the atmosphere. To markedly increase oceanic uptake of atmospheric CO2 would require the addition of large amounts of Fe due to the low fertilization efficiencies associated with maximum air‐sea CO2 exchange. Our results also show that differences in the fertilization strategy should be kept in mind when comparing the results of different Fe fertilization experiments.
Mahanine, a carbazole alkaloid from Micromelum minutum, inhibits cell growth and induces apoptosis in U937 cells through a mitochondrial dependent pathway
Authors: Roy Molay Kumar , Thalang Vipaporn Na , Trakoontivakorn Gassinee , Nakahara Kazuhiko
Published: March 2005

Mahanine, a naturally occurring carbazole alkaloid in some Asian vegetables, has been shown to exhibit antimutagenicity, antimicrobial activity, cytotoxicity, and other biological properties.

In the present study, we investigated the effect of mahanine on the activation of the apoptotic pathway in human leukemia U937 cells. Various end points were used to screen for apoptosis: Morphological changes in cells, the relative numbers of viable and apoptotic cells; translocation of membrane bound phosphatidylserine and DNA analysis.

We found that mahanine‐induced apoptosis in U937 cells involved activation of caspases, including caspase‐3, release of cytochrome c into cytosol, loss of mitochondrial membrane permeability, and decreased levels of cellular ATP.

Pretreatment of cells with cyclosporine A, prior to/concomitant with exposure to mahanine, effectively prevented the deleterious effects of the alkaloid on cellular integrity and viability.

As mitochondrial permeability is known to be important in the regulation of cytochrome c release, our observations indicate that mitochondria are the principal target of mahanine. More specifically, we propose that mahanine causes the mitochondrial membranes to lose their permeability, resulting in caspase‐3 activation and apoptosis.

British Journal of Pharmacology (2005) 145, 145–155. doi:10.1038/sj.bjp.0706137
The role of nitric oxide synthase in reduced vasocontractile responsiveness induced by prolonged α1‐adrenergic receptor stimulation in rat thoracic aorta
Authors: Gürdal Hakan , Can Alp , Uğur Mehmet
Published: March 2005

Prolonged exposure (6–12 h) of rat aorta to alpha1‐adrenergic receptor (α1AR) agonist phenylephrine (Phe) leads to a decrease in α1AR‐mediated vasoconstriction. This reduced responsiveness to α1AR stimulation was strongly dependent on the intactness of the endothelium.

We examined the effect of Phe on nitric oxide synthase (NOS) activity by measuring the conversion of [3H]L‐arginine to [3H]L‐citrulline in rat aorta or in endothelial cells isolated from rat aorta. Phe stimulation increased NOS activity in control aortas. This response was antagonized by prazosin. However, Phe increased neither the activity of NOS nor intracellular Ca2+ in the isolated endothelial cells from the control aortas, whereas acetylcholine (Ach) was able to stimulate both responses in these cells. This result suggests that Phe stimulates α1AR on vascular smooth muscle cells and has an indirect influence on endothelial cells to increase NOS activity.

In Phe‐exposed aortic rings, basal NOS activity was found to have increased compared to vehicle‐exposed control rings. Stimulation with Phe or Ach caused a small increase over basal NOS activity in these preparations. Prolonged exposure to Phe also caused an enhancement of Ach‐mediated vasorelaxation in rat aorta.

Immunoblot and reverse transcription–polymerase chain reaction experiments showed that prolonged exposure of rat aorta to Phe resulted in an increased expression of eNOS, but not iNOS. This increase was antagonized by nonselective antagonist prazosin. Immunohistochemical staining experiments also showed that expression of eNOS increased in endothelial cells after Phe exposure of the aortas.

These results, all together, showed that prolonged exposure of rat aorta to α1AR agonist Phe enhanced the expression of eNOS and basal NOS activity, which probably causes a decreased vasocontractile response to Phe or to other agonists such as 5HT (5‐hydroxytryptamine) in rat aorta.

This phenomenon can be considered more as a functional antagonism of vasocontractile response to agonists mediated by endothelium than a specific desensitization of α1AR‐mediated signalling in vascular smooth muscle cells.

British Journal of Pharmacology (2005) 145, 203–210. doi:10.1038/sj.bjp.0706177
Characteristics of attenuated endothelium‐dependent relaxation seen in rabbit intrapulmonary vein following chronic nitroglycerine administration
Authors: Kusama Nobuyoshi , Kajikuri Junko , Watanabe Yoshimasa , Suzuki Yoshikatsu , Katsuya Hirotada , Itoh Takeo
Published: March 2005

This study was undertaken to determine whether long‐term in vivo administration of nitroglycerine (NTG) downregulates the endothelium‐dependent relaxation induced by acetylcholine (ACh) in the rabbit intrapulmonary vein and, if so, whether the type 1 angiotensin II receptor (AT1R) blocker valsartan normalizes this downregulated relaxation.

In strips treated with the cyclooxygenase inhibitor diclofenac, ACh induced a relaxation only when the endothelium was intact. A small part of this ACh‐induced relaxation was inhibited by coapplication of two Ca2+‐activated K+‐channel blockers (charybdotoxin (CTX)+apamin) and the greater part of the response was inhibited by the nitric‐oxide‐synthase inhibitor Nω‐nitro‐L‐arginine (L‐NNA).

The endothelium‐dependent relaxation induced by ACh, but not the endothelium‐independent relaxation induced by the nitric oxide donor NOC‐7, was significantly reduced in NTG‐treated rabbits (versus those in NTG‐nontreated control rabbits). The attenuated relaxation was normalized by coapplication of valsartan with the NTG.

In the vascular wall, both the amount of localized angiotensin II and the production of superoxide anion were increased by in vivo NTG treatment. These variables were normalized by coapplication of valsartan with the NTG.

It is suggested that long‐term in vivo administration of NTG downregulates the ACh‐induced endothelium‐dependent relaxation, mainly through an inhibition of endothelial nitric oxide production in the rabbit intrapulmonary vein. A possible role for AT1R is proposed in the mechanism underlying this effect.

British Journal of Pharmacology (2005) 145, 193–202. doi:10.1038/sj.bjp.0706178
Curcumin modulation of Na,K‐ATPase: phosphoenzyme accumulation, decreased K+ occlusion, and inhibition of hydrolytic activity
Authors: Mahmmoud Yasser A
Published: March 2005

Curcumin, the major constitute of tumeric, is an important nutraceutical that has been shown to be useful in the treatment of many diseases. As an inhibitor of the sarcoplasmic reticulum Ca2+‐ATPase, curcumin was shown to correct cystic fibrosis (CF) defects in some model systems, whereas others have reported no or little effects on CF after curcumin treatment, suggesting that curcumin effect is not due to simple inhibition of the Ca2+‐ATPase.

We tested the hypothesis that curcumin may modulate other members of the P2‐type ATPase superfamily by studying the effects of curcumin on the activity and kinetic properties of the Na,K‐ATPase.

Curcumin treatment inhibited Na,K‐ATPase activity in a dose‐dependent manner (K0.5∼14.6 μM). Curcumin decreased the apparent affinity of Na,K‐ATPase for K+ and increased it for Na+ and ATP. Kinetic analyses indicated that curcumin induces a three‐fold reduction in the rate of E1P → E2P transition, thereby increasing the steady‐state phosphoenzyme level. Curcumin treatment significantly abrogated K+ occlusion to the enzyme as evidenced from kinetic and proteolytic cleavage experiments. Curcumin also significantly decreased the vanadate sensitivity of the enzyme.

Thus, curcumin partially blocks the K+ occlusion site, and induces a constitutive shift in the conformational equilibrium of the enzyme, towards the E1 conformation.

The physiological consequences of curcumin treatment previously reported in different epithelial model systems may, at least in part, be related to the direct effects of curcumin on Na,K‐ATPase activity.

British Journal of Pharmacology (2005) 145, 236–245. doi:10.1038/sj.bjp.0706185
Vortex nucleation in the process of phase separation of a supersaturated He3–He4 mixture
Authors: Pashitskiı̆ E. A. , Mal’nev V. N. , Naryshkin R. A.
Published: March 2005

It is shown that subcritical phase-separation nuclei (domains of decomposition) arising spontaneously in a supersaturated He3–He4 mixture can become centers of hydrodynamic vortex generation in the presence of a local nonzero or global vorticity of the liquid. The acceleration of the “rigid-body” vortex rotation of an incompressible fluid within a domain is due to the joint action of convective and Coriolis forces in the presence of a convergent radial flow whose velocity is linked by the continuity equation to the velocity of an ascending vertical flow, which increases with height. Such flows, which arise on account of the chemical and dynamical equilibrium between the domains of decomposition and the surrounding metastable He3–He4 mixture, compensate the escape of the light He3 component from the volume of the domain to the surface of the liquid on account of its buoyancy in the Earth’s gravity. Depending on the conditions of the decomposition of the solution inside the domains, acceleration of the vortices can occur according to an exponential law or by a scenario of nonlinear “explosive” instability. The formation and growth of such hydrodynamic vortices in decomposing He3–He4 mixtures gives rise to quantum vortices in the superfluid component and, as a consequence, leads to acceleration of the process of heterogeneous decomposition (phase separation) in comparison with homogeneous decomposition.
Influence of internal stresses on the superconductivity of nanocrystalline vanadium films
Authors: Kuz’menko V. M. , Chernyaeva T. P.
Published: March 2005

Nanocrystalline vanadium films 7–20 nm thick are obtained by crystallization of amorphous condensates of this metal by heating to a temperature T<60 K. Immediately after completion of the crystallization the critical temperature of the superconducting transition Tc of these films is 3.1–4.3 K. When the films are heated to room temperature in an ultrahigh vacuum the values of Tc decrease by ≈0.4 K. It is shown that this decrease is due, in particular, to relief of the tensile stresses that arise in the films during crystallization.
Enhancement of the Josephson current by magnetic field in superconducting tunnel structures with a paramagnetic spacer
Authors: Krivoruchko V. N. , Koshina E. A.
Published: March 2005

The dc Josephson critical current of a (S/M)IS tunnel structure in a parallel magnetic field is investigated (here S is a superconductor, S/M is a proximity-coupled S and paramagnetic metal M bilayer, and I is an insulating barrier). We consider the case when, due to Hund’s rule, in the metal M the effective molecular interaction aligns the spins of the conduction electrons antiparallel to the localized spins of magnetic ions. It is predicted that for the tunnel structures under consideration there are conditions such that the destructive action of the internal and the applied magnetic fields on Cooper pairs is weakened, and increase of the applied magnetic field causes field-induced enhancement of the critical tunnel current. The experimental realization of this interesting effect of the interplay between superconductivity and magnetism is also discussed.
Influence of phase transitions on the excitonic absorption spectrum of K2CdI4
Authors: Yunakova O. N. , Miloslavsky V. K. , Kovalenko E. N.
Published: March 2005

The absorption spectrum of thin films of K2CdI4 in the energy interval 3.6–5.1 eV is investigated on heating and cooling in the temperature range 90–430 K. The temperature dependence of the spectral position Em(T) and half-width Γ(T) of the long-wavelength exciton band in K2CdI4 reveals the presence of second-order phase transitions at 400 and 220 K and a first-order transition at 320 K. The sequence of phase transitions in K2CdI4 is like those in the similar compounds Rb2CdI4 and Cs2CdI4.
The Influence of Restricted Viewing Conditions on Egocentric Distance Perception: Implications for Real and Virtual Indoor Environments
Authors: Creem-Regehr Sarah H , Willemsen Peter , Gooch Amy A , Thompson William B
Published: March 2005

We carried out three experiments to examine the influence of field of view and binocular viewing restrictions on absolute distance perception in real-world indoor environments. Few of the classical visual cues provide direct information for accurate absolute distance judgments to points in the environment beyond about 2 m from the viewer. Nevertheless, in previous work it has been found that visually directed walking tasks reveal accurate distance estimations in full-cue real-world environments to distances up to 20 m. In contrast, the same tasks in virtual environments produced with head-mounted displays (HMDs) show large compression of distance. Field of view and binocular viewing are common limitations in research with HMDs, and have been rarely studied under full pictorial-cue conditions in the context of distance perception in the real-world. Experiment 1 showed that the view of one's body and feet on the floor was not necessary for accurate distance perception. In experiment 2 we manipulated the horizontal and the vertical field of view along with head rotation and found that a restricted field of view did not affect the accuracy of distance estimations when head movement was allowed. Experiment 3 showed that performance with monocular viewing was equal to that with binocular viewing. These results have implications for the information needed to scale egocentric distance in the real-world and reduce the support for the hypothesis that a limited field of view or imperfections in binocular image presentation are the cause of the underestimation seen with HMDs.
Configural Processing and Perceptions of Head Tilt
Authors: Collishaw Stephan M , Hole Graham J , Schwaninger Adrian
Published: March 2005

Configural processing is important for face recognition, but its role in other types of face processing is unclear. In the present study, participants made judgments of head tilt for faces in which the vertical position of the internal facial region was varied. We found a highly reliable relationship between inner-face position and perceived head tilt. We also found that changes in inner-face position affected the perceived dimensions of an individual unchanged facial feature: compared to control faces, nearly two-thirds of faces in which the features had been moved down were judged to have a longer nose. This finding suggests an early integration of configural and featural processing to create a stable holistic percept of the face. The demonstration of holistic processing at a basic perceptual level (as opposed to during face recognition) is important as it constrains possible models of the relationships between featural and configural processing.
T cells that cannot respond to TGF-β escape control by CD4+CD25+ regulatory T cells
Authors: Fahlén Linda , Read Simon , Gorelik Leonid , Hurst Stephen D. , Coffman Robert L. , Flavell Richard A. , Powrie Fiona
Published: March 2005

CD4+CD25+ regulatory T (T reg) cells play a pivotal role in control of the immune response. Transforming growth factor-β (TGF-β) has been shown to be required for T reg cell activity; however, precisely how it is involved in the mechanism of suppression is poorly understood. Using the T cell transfer model of colitis, we show here that CD4+CD45RBhigh T cells that express a dominant negative TGF-β receptor type II (dnTβRII) and therefore cannot respond to TGF-β, escape control by T reg cells in vivo. CD4+CD25+ T reg cells from the thymus of dnTβRII mice retain the ability to inhibit colitis, suggesting that T cell responsiveness to TGF-β is not required for the development or peripheral function of thymic-derived T reg cells. In contrast, T reg cell activity among the peripheral dnTβRII CD4+CD25+ population is masked by the presence of colitogenic effector cells that cannot be suppressed. Finally, we show that CD4+CD25+ T reg cells develop normally in the absence of TGF-β1 and retain the ability to suppress colitis in vivo. Importantly, the function of TGF-β1−/− T reg cells was abrogated by anti–TGF-β monoclonal antibody, indicating that functional TGF-β can be provided by a non–T reg cell source.
Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1
Authors: Arita Makoto , Bianchini Francesca , Aliberti Julio , Sher Alan , Chiang Nan , Hong Song , Yang Rong , Petasis Nicos A. , Serhan Charles N.
Published: March 2005

The essential fatty acid eicosapentaenoic acid (EPA) present in fish oils displays beneficial effects in a range of human disorders associated with inflammation including cardiovascular disease. Resolvin E1 (RvE1), a new bioactive oxygenated product of EPA, was identified in human plasma and prepared by total organic synthesis. Results of bioaction and physical matching studies indicate that the complete structure of RvE1 is 5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-EPA. At nanomolar levels, RvE1 dramatically reduced dermal inflammation, peritonitis, dendritic cell (DC) migration, and interleukin (IL) 12 production. We screened receptors and identified one, denoted earlier as ChemR23, that mediates RvE1 signal to attenuate nuclear factor–κB. Specific binding of RvE1 to this receptor was confirmed using synthetic [3H]-labeled RvE1. Treatment of DCs with small interference RNA specific for ChemR23 sharply reduced RvE1 regulation of IL-12. These results demonstrate novel counterregulatory responses in inflammation initiated via RvE1 receptor activation that provide the first evidence for EPA-derived potent endogenous agonists of antiinflammation.
A national strategy for smoking cessation treatment in England
Authors: McNeill Ann , Raw Martin , Whybrow Janet , Bailey Patsy
Published: March 2005

In 1998 the UK government published a White Paper on tobacco which set out the development of smoking cessation treatment services across England. This paper presents a detailed analysis of the events leading up to the inclusion of smoking cessation treatment services within the White Paper, and the background to the evaluation of those services, the results of which are the subject of the remaining papers in this supplement.
How effective are the English smoking treatment services in reaching disadvantaged smokers?
Authors: Chesterman John , Judge Ken , Bauld Linda , Ferguson Janet
Published: March 2005

Aims  To determine the effectiveness of smoking cessation services in enabling smokers living in disadvantaged areas to access treatment services, and to assess the extent of variations between areas.

Design  Observational study of administrative information linked with survey data.

Setting  A representative sample of 19 of the 95 English health areas in 2001.

Measurements  All England smoking data by deprivation category obtained from the Health Survey of England were used to estimate neighbourhood smoking prevalence rates. Area of residence data from smokers setting a quit date were used to calculate the proportion of smokers in receipt of treatment services in different economic deprivation categories.

Findings  In general, treatment services were seeing smokers from the most disadvantaged areas where smoking prevalence rates were highest; 32.3% of all smokers in receipt of treatment services lived in the most disadvantaged quintile of areas compared with 9.6% resident in the most advantaged quintile. An indicator of ‘positive discrimination’ was calculated for each health authority area to quantify the extent to which the proportion of disadvantaged smokers being treated was greater than the proportion in the local population. This figure ranged from just under 0% to 18%.

Conclusions  National Health Service (NHS) smoking cessation services have been successful in reaching smokers from disadvantaged communities. If improved access to support for smokers living in the poorest communities can be extended, sustained and translated into long‐term quitting then smoking cessation services have the potential to make a useful contribution to addressing inequalities in health.
The cost‐effectiveness of the English smoking treatment services: evidence from practice
Authors: Godfrey Christine , Parrott Steve , Coleman Tim , Pound Elspeth
Published: March 2005

Aims To investigate the cost‐effectiveness of English specialist smoking cessation services.

Design Combination of observational cost and outcome data from English smoking cessation services to calculate cost‐effectiveness ratios. Multivariate analysis of factors influencing variation in services’ cost‐effectiveness.

Setting Fifty‐eight of the 92 specialist smoking cessation services in England in 2000/01.

Methods Services’ costs were estimated using survey data which described services’ configurations, staffing, interventions delivered and development. Information on services’ throughput and outcomes (as biochemically validated 4‐week smoking cessation rates) were obtained from routine sources. With reference to relevant literature and assumptions about relapse and background cessation rates, 4‐week cessation rates were converted first to 1‐year rates. One‐year cessation rates were adjusted to reflect the likely permanent smoking cessation rate attributable to service intervention and finally attributable life‐years gained were calculated. A wide variety of sensitivity analyses was performed to test the robustness of the average cost‐effectiveness ratio, calculated by combining the cost and life‐year gained estimates, for all services. With additional data on deprivation levels in services’ areas, ordinary least‐squares regression techniques were used to investigate variations in individual services’ costs per client and cost‐effectiveness ratios.

Findings Using an up‐to‐date estimate for health gain accrued by stopping smoking, the average cost per life gained was £684 (95% CI 557–811), falling to £438 when savings in future health‐care costs were counted. With the worst case assumptions, the estimate of cost‐effectiveness rose to £2693 per life‐year saved (£2293 including future health‐care costs) and fell to £227 (£102) under the most favourable assumptions. Findings are comparable to previous published studies. The regression results suggest that different factors influence cost per client and the net cost per life‐year saved, indicating that decision makers should be careful in setting performance targets for these services.

Conclusions In 2000/01, English smoking cessation services provided cost‐effective services operating well below the benchmark of £20 000 per quality‐adjusted life‐year saved (QALY) that is used by the National Institute for Clinical Excellence in the United Kingdom.
Population pharmacokinetics of orally administered paclitaxel formulated in Cremophor EL
Authors: De Jonge Milly E. , Huitema Alwin DR. , Schellens Jan HM. , Rodenhuis Sjoerd , Beijnen Jos H.
Published: March 2005

Aim

The vehicle Cremophor EL (CrEL) has been shown to impair the absorption of paclitaxel by micellar entrapment of the drug in the gastrointestinal tract. The goal of this study was to develop a semimechanistic population pharmacokinetic model to study the influence of CrEL on the oral absorption of paclitaxel.

Method

Paclitaxel plasma‐concentration time profiles were available from 55 patients (M:F, 17 : 38; total 67 courses; 797 samples), receiving paclitaxel orally once or twice daily (dose range 60–360 mg m−2) together with 12–15 mg kg−1 cyclosporin A. A population pharmacokinetic model was developed using the nonlinear mixed effect modelling program NONMEM.

Results

After absorption, paclitaxel pharmacokinetics were best described using a two‐compartment model with linear distribution from the central compartment into a peripheral compartment and first‐order elimination. Paclitaxel in the gastrointestinal tract was modelled as free fraction or bound to CrEL, with only the free fraction available for absorption into the central compartment. The equilibrium between free and bound paclitaxel was influenced by the concentration of CrEL present in the gastrointestinal tract. The concentration of CrEL in the gastrointestinal tract decreased with time with a first order rate constant of 1.73 h−1. The bioavailability of paclitaxel was independent of the dose and of CrEL. Estimated apparent paclitaxel clearance and volume of distribution were 127 l h−1 and 409 l, respectively. Large interpatient variability was observed. Covariate analysis did not reveal significant relationships with any of the pharmacokinetic parameters.

Conclusion

A pharmacokinetic model was developed that described the pharmacokinetics of orally administered paclitaxel. CrEL strongly influenced paclitaxel absorption from the gastrointestinal tract resulting in time‐dependent but no significant dose‐dependent absorption over the examined dose range studied.
Comparative effects of glyceryl trinitrate and amyl nitrite on pulse wave reflection and augmentation index
Authors: Greig Lynn D. , Leslie Stephen J. , Gibb Fraser W. , Tan Sherilyn , Newby David E. , Webb David J.
Published: March 2005

Aims

The influence of vasodilators on augmentation index (AIx) offers a simple, rapid and noninvasive method of evaluating vascular function. Glyceryl trinitrate (GTN) is widely used as an endothelium‐independent vasodilator, although other nitrates that are shorter acting may have advantages in clinical studies. The aim of this study was to compare the effects of two short‐acting nitrates, GTN and amyl nitrite, which have differing pharmacodynamic profiles.

Methods

Twenty‐one healthy volunteers (15 male; mean age 35 years, range 21–56 years) attended on three occasions and received sublingual GTN (0.5 mg for 3 min), inhaled amyl nitrite (0.2 ml inhaled for 30 s), or no treatment in a randomized cross‐over design. Haemodynamic responses of AIx, blood pressure and thoracic bioimpedance (heart rate, cardiac index) were assessed by measurement at baseline, every 60 s for the first 5 min, and then every 5 min for a further 55 min.

Results

AIx was reduced by amyl nitrite (peak effect −9 ± 2% at 1 min, P < 0.002) and GTN (peak effect −12 ± 3% at 4 min, P < 0.05). Compared with amyl nitrite, the onset and offset of action of GTN was slower. Amyl nitrite initially increased heart rate by 27 ± 4% (P < 0.001) and cardiac index by 13 ± 3% (P < 0.001) whereas GTN had no significant effect (P > 0.05). Neither agent affected blood pressure.

Conclusions

GTN causes a slower and more sustained reduction in AIx than amyl nitrite. Although amyl nitrite causes a more rapid fall and recovery in AIx, it induces a reflex tachycardia that may limit interpretation of the initial (1 min) but not later (2 min) changes in AIx. The prolonged offset of GTN suggests that a sufficient washout period must be included when making repeated measures or when assessing the subsequent effects of other agents.
Mechanistic pharmacokinetic modelling of ephedrine, norephedrine and caffeine in healthy subjects
Authors: Csajka C. , Haller C. A. , Benowitz N. L. , Verotta D.
Published: March 2005

Aim

The combination of ephedrine and caffeine has been used in herbal products for weight loss and athletic performance‐enhancement, but the pharmacokinetic profiles of these compounds have not been well characterized. This study aimed to develop a mechanistic model describing ephedrine, norephedrine, and caffeine pharmacokinetics and their interactions in healthy subjects.

Methods

The pharmacokinetic model was developed based on the simultaneous modelling using plasma samples gathered from two clinical trials. The treatments consisted of single‐doses of pharmaceutical caffeine and ephedrine, given alone or together, and an herbal formulation containing both caffeine and ephedrine. We used a mixed‐effect statistical model and the program NONMEM to take account of intersubject variability.

Results

Three hundred and seventy‐nine ephedrine, 352 norephedrine, 417 caffeine plasma concentrations and 40 ephedrine urine concentrations were obtained from 24 subjects. A one‐compartment model with first‐order absorption described the caffeine data. Caffeine clearance was 0.083 l min−1 (CV 38%) and decreased to 0.038 l min−1 in presence of oral contraceptive therapy, its volume of distribution was 38.6 l (CV 20%) and its absorption rate constant was 0.064 l min−1 (CV 50%). A four‐compartment model described the pharmocokinetics of ephedrine and norephedrine. Ephedrine was eliminated mostly renally, with a clearance of 0.34 l min−1 (CV 11%), and a volume of distribution of 181 l (CV 19%). Nonlinearity in the conversion of ephedrine to norephedrine was observed. Different models showed that the simultaneous administration of caffeine, or the amount of caffeine in the absorption compartment, was associated with a slower rate of absorption of ephedrine. A 32% greater relative bioavailability of herbal compared with pharmaceutical ephedrine administration was observed.

Conclusions

We describe a mechanistic model for ephedrine, norephedrine and caffeine pharmacokinetics and their interactions. The relative bioavailability of ephedrine differed between the herbal supplement compared with the pharmaceutical formulation. Concomitant ingestion of caffeine slowed the absorption rate of ephedrine, which is mainly related to the amount of the former in the absorption compartment. A saturable process appears to be involved in the metabolism of ephedrine to norephedrine.
The importance of episodic weather events to the ecosystem of the Bering Sea shelf
Authors: BOND NICHOLAS A. , OVERLAND JAMES E.
Published: March 2005

Climate variability on decadal time scales is generally recognized to influence high‐latitude marine populations. Our recent work in studying air–sea interactions in the Bering Sea suggests that interannual to decadal climate variability is important through its modulation of the frequencies and magnitudes of weather events on intraseasonal time scales. We hypothesize that it is these weather events that directly impact the marine ecosystem of the Bering Sea shelf. The linkages between the event‐scale weather and the ecosystem are illustrated with three examples: walleye pollock (Theragra chalcogramma), Tanner crabs (Chionoecetes bairdi), and coccolithophorid phytoplankton (Emiliania huxleyi). We hypothesize that the strong recruitment of walleye pollock that occurred in 1978, 1982, and 1996 can be attributed in part due to the seasonably strong storms that occurred in the early summer of those years. These storms caused greater than normal mixing of nutrients into the euphotic zone which presumably led to sustained primary productivity after the spring bloom and, possibly, enhanced prey concentrations for pollock larvae and their competitors. Recruitment of Tanner crab was particularly strong for the 1981 and 1984 year‐classes. These years had periods of prominent east wind anomalies along the Alaska Peninsula during the previous winter. Such winds promote flow through Unimak Pass, and hence an enhanced flux of nutrient‐rich water onto the shelf. This mechanism may have ultimately resulted in favorable feeding conditions for Tanner crab larvae. Finally, an unprecedented coccolithophorid bloom occurred over the Bering Sea shelf in the summer of 1997. This summer featured lighter winds and greater insolation than usual after a spring that included a very strong May storm. This combination brought about a warm, nutrient‐poor upper mixed layer by mid‐summer. This provided a competitive advantage for coccolithophorid phytoplankton in 1997 and to a lesser extent in 1998. Unusually high concentrations of coccolithophores persisted for the following two years although physical environmental conditions did not remain favorable. While slow variations in the overall aspects of the physical environment may be important for setting the stage, we propose that the significant multi‐year adjustments in the marine ecosystem of the Bering Sea shelf are more directly caused by major air–sea interaction events on intraseasonal time scales.
Mechanism of body cavity temperature regulation of chum salmon (Oncorhynchus keta) during homing migration in the North Pacific Ocean
Authors: AZUMAYA TOMONORI , ISHIDA YUKIMASA
Published: March 2005

Vertical movement patterns of five chum salmon (Oncorhynchus keta) during homing migration were examined using archival tags. The standard deviation of the depth and ambient and body cavity temperatures during daytime were larger than those during night‐time. Vertical movements through the thermocline with a periodicity of less than 1 h were observed during daytime in addition to the diel vertical movement patterns in the open ocean. During these periods of frequent short‐term vertical movements, the difference between the body cavity temperature and ambient temperature was large while the variance of the body cavity temperature was less than that of the ambient temperature. From the results of a random simulation, the variation of the body cavity temperature was shown to decrease due to these periodic high frequency movements in comparison with random vertical movements. The whole‐body heat‐transfer coefficient k (s−1), which was estimated by a heat budget model, was 1.48 × 10−3. The k of chum salmon was larger than that of bigeye tuna (Thunnus obesus) by about one order of magnitude for the cooling of the body. The k of chum salmon did not change like tuna, which are physiologically adapted to conserve body cavity temperature. This indicates that the regulation of body cavity temperature by chum salmon is dependent on the vertical movements only. The maintenance of the body cavity temperature is concluded to be advantageous for their maturation and growth from the relationship between energy input and output during their homing migration.
Larval lobster (Homarus americanus) distribution and drift in the vicinity of the Gulf of Maine offshore banks and their probable origins
Authors: HARDING G. C. , DRINKWATER K. F. , HANNAH C. G. , PRINGLE J. D. , PRENA J. , LODER J. W. , PEARRE S. , VASS W. P.
Published: March 2005

Surveys for lobster larvae in offshore waters of the north‐eastern Gulf of Maine in 1983, 1987 and 1989 confirm that local hatching occurs mainly at depths <100 m over the banks, including Georges and Browns Banks. Detailed studies in the vicinity of Georges Bank in late July of both 1987 and 1989 indicate that the first and second moult stages were located primarily over the bank whereas stages III and IV lobster were collected both over and off the bank. At times stage IV lobster were more abundant off the bank than over it. The condition of stage III and IV lobster, as measured by a lipid index, was better off than over Georges Bank in 1988 and 1989 indicating a possible physiological advantage to being off the bank. In addition, the higher surface temperatures off Georges Bank would shorten larval development time to settlement. To determine the probable hatch sites of stage IV lobster collected off of Browns Bank in 1983 and off of Georges in 1987 and 1989, a 3‐D circulation model of the Gulf of Maine was used to simulate larval lobster drift backwards in time. In all cases, areas off Cape Cod, MA, and off Penobscot Bay, ME were suggested as the source of the larvae, although most of the larval trajectories never reached these near‐shore waters that are well‐known, larval hatching areas. The model‐projected larval release times match most closely the observed inshore hatch off Massachusetts but model uncertainties mean that coastal Maine cannot be ruled out as a source. Georges Bank is also a potential source because the present model does not take into account short‐term wind events, off‐bank eddy transport or the possibility of directed off‐bank larval swimming. Examination of weather records prior to and during our 1988 and 1989 sampling periods indicates that winds were not of sufficient intensity and duration to induce larval transport off Georges Bank. The shedding of eddies from the northern flank of Georges Bank into the Gulf of Maine are a relatively common phenomenon during summer but not enough is known about them to evaluate their contribution to possible cross‐bank transport of lobster larvae. Directed larval swimming is another possible source for the stage IV lobster found near Georges Bank. Plankton distributions across the northern frontal zone of Georges Bank in 1988 were used as proxies for the scarce larval lobsters. The more surface distribution of the microplankton, in particular, supports the possibility that wind and eddy events may be important in the transport of stage III and IV lobsters off of Georges Bank. Further studies are needed to evaluate these possible additional sources of advanced stage lobster larvae found off of the offshore banks.
Effects of temperature, salinity, desiccation and chemical treatments on egg embryonation and hatching success of Benedenia seriolae (Monogenea: Capsalidae), a parasite of farmed Seriola spp.
Authors: Ernst I , Whittington I D , Corneillie S , Talbot C
Published: March 2005

The effects of temperature and salinity on the embryonation period and hatching success of eggs of Benedenia seriolae were investigated. Temperature strongly influenced embryonation period; eggs first hatched 5 days after laying at 28 °C and 16 days after laying at 14 °C. The relationship between temperature and embryonation period is described by quadratic regression equations for time to first and last hatching. Hatching success was >70% for B. seriolae eggs incubated at temperatures from 14 to 28 °C. However, no B. seriolae eggs embryonated and hatched at 30 °C and <2% of eggs hatched when incubated at 24 °C after transfer to 30 °C for 48 h. Embryonation period was similar for eggs incubated in sea water at 25, 30 and 35‰ salinity, but increased for eggs incubated at higher or lower salinities. When incubated at salinities ranging from 25 to 45‰, more than 70% of B. seriolae eggs embryonated and hatched. Hatching success was lower at 20 and 50‰ salinity and few or no eggs hatched at 10 and 15‰. Hatching of B. seriolae eggs can be prevented by desiccation for 3 min, by immersion in water at 50 °C for 30 s or by treatment with 25% ethanol for 3 min.
Aeromonas sobria, a causative agent of disease in farmed perch, Perca fluviatilis L.
Authors: Wahli T , Burr S E , Pugovkin D , Mueller O , Frey J
Published: March 2005

Significant numbers of perch, Perca fluviatilis, raised on a pilot fish farm in Switzerland presented focal skin lesions on the lateral sides and fin rot. Mortality rates reached levels of up to 1% of the total fish on the farm per day. Virtually pure cultures of Aeromonas sobria were isolated from the liver, kidney, spleen and skin lesions of affected fish. Aeromonas sobria isolated from the farmed perch had a haemolytic effect on sheep and trout erythrocytes, autoaggregated, was cytotoxic for cultured fish cells and possessed genes involved in type III protein secretion. Experimental infection of naïve perch with a single colony isolate of A. sobria from an affected farm fish resulted in the development of clinical signs identical to those seen on the farm. The results indicate that A. sobria can act as a primary pathogen of perch.
Ultrastructure of Goussia cruciata (Apicomplexa: Coccidia) infecting the liver of horse mackerel, Trachurus trachurus (L.), from Ibero‐Atlantic waters
Authors: Gestal C , Azevedo C
Published: March 2005

The ultrastructure of developmental stages of Goussia cruciata and the pathology they cause in the liver of Trachurus trachurus (Teleostei: Carangidae) caught off the Galician (North‐West Spain) and Portuguese North Atlantic coasts are described. Each oocyst contained four ellipsoidal sporocysts, with two sporozoites. The sporocyst wall consisted of a thick and dense inner layer with transverse striations and a multi‐lamellated outer layer formed by parallel dense internal bands alternating with lighter areas. The lamellae formed filamentous extensions of the wall. The sporocyst wall striation period was smaller than that observed in G. clupearum, which has a similar habitat. The dehiscence suture, characteristic of the genus, was present in the sporocysts of G. cruciata. The sporocysts were arranged in a symmetrical and characteristic cross shape. A large number of sporocysts with sporozoites were observed in direct contact with host liver cells. No macroscopic lesions were observed. In heavily infected fish, aggregations of oocysts were often enveloped in a ‘yellow body’ composed of amylopectin granules derived from the parasite and necrotic or aggregated host cells. Degenerating parasites were frequently observed in liver tissue. Host inflammatory cells were accumulated near some oocysts. The ultrastructure of the parasite, together with its strict host specificity, confirmed G. cruciata as a separate and valid species.
Influence of feeding ratio and size on susceptibility to microsporidial gill disease caused by Loma salmonae in rainbow trout, Oncorhynchus mykiss (Walbaum)
Authors: Becker J A , Speare D J , Dohoo I R
Published: March 2005

Two trials were designed to quantify the effect of feeding ratio and fish size on the cohabitation transmission of Loma salmonae, the causative agent of microsporidial gill disease (MGD) in salmonids, Oncorhynchus spp. To evaluate the effect of feeding ratio on disease onset, groups of 45 rainbow trout, O. mykiss (Walbaum) (RBT), were fed daily at 1% (low), 2% (medium) or 4% (high) of the fish biomass in the tank. There were three tanks at each feeding level: two tanks were exposed to the pathogen and one was a control. For the second objective, 300 RBT were separated into seven tanks so that the weight classifications were small (17–23 g), medium (32–38 g) and large (57–63 g). Each size class was done in duplicate with one control tank containing medium‐sized fish. Separately for each trial, on day 0 post‐exposure (PE) five highly infectious RBT were added to each tank (not including the control tanks) to begin the cohabitation exposure period. Beginning on day 21 PE and continuing biweekly until days 70 and 77 PE for the feeding and fish size trials, respectively, each fish was evaluated for visible branchial xenomas to determine disease onset time. Using survival analysis, the survival curves for the low, medium and high feedings were not significantly different from each other. However, there were significant differences amongst the small, medium and large weight classes in the size trial. The median numbers of days to the development of branchial xenomas was 31, 38 and 42 for small, medium and large size fish, respectively. On any given day, a medium or large sized fish had a hazard ratio for developing branchial xenomas of 0.66 and 0.63, respectively, compared with a small fish. In addition to host species and host strain differences, fish size is now considered a host risk factor for the development of MGD.
Experimental infection of turbot, Scophthalmus maximus (L.), by Aeromonas salmonicida subsp. achromogenes and evaluation of cross protection induced by a furunculosis vaccine
Authors: Björnsdóttir B , Gudmundsdóttir S , Bambir S H , Gudmundsdóttir B K
Published: March 2005

Turbot was shown to be sensitive to injection challenges by Aeromonas salmonicida subsp. achromogenes (Asa). A systemic disease was induced and the bacterium was isolated from various internal organs. Histopathological changes involved haemorrhages, necrosis and degeneration in skin and muscle, haemorrhages and necrosis in kidney, degeneration in the heart muscle, and fusion of the secondary gill lamellae. A polyvalent commercial salmon vaccine, containing A. salmonicida subsp. salmonicida as one of five antigens, did not confer protection in turbot against an experimental Asa infection 13 weeks post‐vaccination. Vaccination induced a significant antibody response against Asa cells but not against extracellular products of the bacterium. The results of the study indicate that Asa may be a potential threat to turbot farming and that the development of new turbot vaccines is needed.
Propagule dispersal and the scales of marine community process
Authors: Kinlan Brian P. , Gaines Steven D. , Lester Sarah E.
Published: March 2005

Benthic marine organisms are characterized by a bipartite life history in which populations of sedentary adults are connected by oceanic transport of planktonic propagules. In contrast with the terrestrial case, where ‘long distance dispersal’ (LDD) has traditionally been viewed as a process involving rare events, this creates the possibility for large numbers of offspring to travel far relative to the spatial scale of adult populations. As a result, the concept of LDD must be examined carefully when applied in a marine context. Any measure of LDD requires reference to an explicit ‘local’ scale, often defined in terms of adult population demography, habitat patchiness, or the average dispersal distance. Terms such as ‘open’ and ‘closed’ are relative, and should be used with caution, especially when compared across different taxa and systems. We use recently synthesized data on marine propagule dispersal potential and the spread of marine invasive species to draw inferences about average and maximum effective dispersal distances for marine taxa. Foremost, our results indicate that dispersal occurs at a wide range of scales in marine communities. The nonrandom distribution of these scales among community members has implications for marine community dynamics, and for the implementation of marine conservation efforts. Second, in agreement with theoretical results, our data illustrate that average and extreme dispersal scales do not necessarily covary. This further confounds simple classifications of ‘short’ and ‘long’ dispersers, because different ecological processes (e.g. range expansion vs. population replenishment) depend on different aspects of the dispersal pattern (e.g. extremes vs. average). Our findings argue for a more rigorous quantitative view of scale in the study of marine dispersal processes, where relative terms such as ‘short’ and ‘long’, ‘open’ and ‘closed’, ‘retained’ and ‘exported’ are defined only in conjunction with explicit definitions of the scale and process of interest. This shift in perspective represents an important step towards unifying theoretical and empirical studies of dispersal processes in marine and terrestrial systems.