bluuebunny/crossref_metadata_2025_split huggingface dataset:
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
A national strategy for smoking cessation treatment in England
Authors: McNeill Ann , Raw Martin , Whybrow Janet , Bailey Patsy 
Published: March 2005

ABSTRACTIn 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

ABSTRACTAims  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

ABSTRACTAims 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

AimThe 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.MethodPaclitaxel 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.ResultsAfter 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.ConclusionA 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

AimsThe 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.MethodsTwenty‐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.ResultsAIx 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.ConclusionsGTN 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

AimThe 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.MethodsThe 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.ResultsThree 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.ConclusionsWe 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

AbstractClimate 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

AbstractVertical 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

AbstractSurveys 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

AbstractThe 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

AbstractSignificant 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.