bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uptake of Lipiodol™–cytotoxic conjugates by hepatoblastoma cells
Authors: Towu E , Al-Mufti R , Spitz L , Marron K , Winslet M 
Published: March 2003

Abstract

Background
Improvements in the management of children with hepatoblastoma have followed advances made in cytotoxic agents and treatment regimens. The aim of this study was to quantify the effect of Lipiodol™, an iodinated poppy-seed oil, on the uptake of anthracyclic cytotoxic conjugates by hepatoblastoma cells in culture.

Methods
Monolayer cultures of (1) a hepatoblastoma cell line generated from freshly explanted tumour tissue, (2) an immortal hepatoblastoma cell line (C3a) and (3) a human hepatocyte cell line were exposed to doxorubicin 10 µg/ml with or without 2 per cent Lipiodol™ for 1–72 h. The fluorescence intensity in the treated cells, which correlates with intracellular doxorubicin concentration, was measured by confocal laser scanning microscopy. Cytotoxicity was assessed by trypan blue exclusion and electron microscopy.

Results
Doxorubicin accumulated in the nucleus and cytoplasm of all the cell lines. With Lipiodol™, the mean fluorescence intensity of intracellular doxorubicin was increased for up to 48 h in both hepatoblastoma lines, but not in the hepatocyte cell line. Lipiodol™ increased the uptake and intracellular concentration of doxorubicin in the hepatoblastoma cells in culture. Lipiodol™ also enhanced the cytotoxicity of doxorubicin on the cultured hepatoblastoma cells.

Conclusion
Lipiodol™ significantly enhanced the uptake of doxorubicin by hepatoblastoma cells in culture. Lipiodol™–doxorubicin targeted treatment of hepatoblastoma may improve the intracellular uptake and hence cytotoxicity of doxorubicin in vivo, enabling a reduction in the total dose administered and side-effects.
Foraging mode of a Madagascan iguanian lizard,Oplurus cuvieri cuvieri
Authors: Mori A. , Randriamahazo H. J. A. R. 
Published: March 2003

AbstractThe foraging mode of lizards has been extensively studied in members of most major families. One neglected taxon is Opluridae, a distinct Iguanian group endemic to Madagascar. We studied the foraging mode ofOplurus cuvieri cuvieriin a dry forest in north‐western Madagascar. Quantitative data on the number of movements per minute and percentage of time spent in moving indicated thatO. c. cuvieriis a typical ambusher, although the lizard occasionally fed on plant materials by active foraging. Possible seasonal changes in foraging activity were suggested. The results support the previous view that insectivorous iguanian lizards are ambush foragers.
Contrasting patterns of leaf water potential and gas exchange responses to drought in seedlings of tropical rainforest species
Authors: Bonal D. , Guehl J.‐M. 
Published: March 2003

Summary

The leaf gas exchange and water potential (Ψw) responses to a soil drying cycle and to increasing atmospheric water vapour pressure deficit were compared in seedlings of three tropical rainforest canopy species in a growth chamber.
Eperua
falcata Aub. presented an anisohydric behaviour in relation to soil drought. The decrease in predawn Ψw at the beginning of the drying cycle was accompanied by a more pronounced decrease in midday Ψw. Stomatal closure occurred from a volumetric soil water content (Θ) of 0·1 m3 m−3, which corresponded to approximately one third of the available soil water.
Diplotropis
purpurea (Rich.) Amsh. displayed an isohydric behaviour. Midday Ψw did not decrease – and the difference between predawn and midday Ψw did not increase – over a large range of Θ (to less than 0·1 m3 m−3). Stomatal conductance (gs) was more sensitive to soil drought than in Eperua.
A unique behaviour was found in Virola michelii: Heckel. Midday Ψw remained remarkably stable, and close to predawn Ψw, over the drying cycle as long as leaves did not dry, and gs was extremely sensitive to soil drought. These results led us to postulate the existence of a homeostatic regulation of Ψw in Virola.
The three species differed in their stomatal sensitivity to atmospheric drought. Eperua was the least and Diplotropis the most sensitive. Virola, even though extremely sensitive to soil drought, displayed an intermediate sensitivity of gs to atmospheric drought.
These findings suggest that the survival of Eperua, Diplotropis and Virola in the tropical rainforest of French Guiana may depend partly on local hydrological conditions.
Outcome of indirect competition between two aphid species mediated by responses in their common host plant
Authors: Petersen M. K. , Sandström J. P. 
Published: March 2003

Summary

This study evaluates the potential for indirect competition between two phloem‐feeding aphids as mediated by a shared host, pecan Carya illinoensis. In a greenhouse experiment, one of two aphid species, Monellia caryella and Melanocallis caryaefoliae, were introduced to pecan seedlings, removed for a period, and then introduced for a second time. Aphid performance and food quality, i.e. phloem amino acid concentration and composition, were measured in leaves after the first and second exposure to aphids. After the second exposure, leaves had been fed upon previously by either conspecifics or heterospecifics, and both direct and delayed effects were evaluated on adjacent leaves.
The performance of M. caryaefoliae was reduced by previous aphid feeding of both conspecifics and heterospecifics. The performance of M. caryella was unaffected by prior aphid feeding.
Feeding by M. caryaefoliae induced changes in amino acid content of the phloem. This alteration occurred within infested leaves and did not cause any changes in the phloem of adjacent leaves.
Feeding by M. caryella did not induce changes in phloem amino acid content, but seemed to inhibit M. caryaefoliae’s ability to alter the phloem. The inhibition caused by M. caryella was local and might be the cause of the indirect competition observed.
Effects of a toxicant on population growth rates: sublethal and delayed responses in blowfly populations
Authors: MOE S. J. , STENSETH N. C. , SMITH R. H. 
Published: March 2003

Summary

Previous studies have shown that cadmium exposure of blowfly populations (Lucilia sericata[Meigen 1826]) results in reduced population growth rate, but also in higher individual mass, because of reduced competition for food. In this study, the discrepancy between the positive effect on individual growth and the negative effect on population growth is investigated, by measuring direct and delayed effects of cadmium in the adult stage.
Blowfly populations were exposed to cadmium through the diet in four treatment combinations: larval stage, adult stage, both stages or neither stage. The effects on accumulation of cadmium, survival, development time, mass and reproductive rate were measured.
Cadmium was accumulated from both stages.
Individuals exposed to cadmium in the larval stage had higher mean pupal and adult mass (because of reduced densities), but also reduced adult longevity and fecundity.
Adult longevity and fecundity were also reduced by cadmium exposure in the adult stage.
In stage‐structured populations, the link between individual‐level and population‐level responses to a toxicant may be complicated by stage‐specific sensitivities to the toxicant, by delayed responses in the adult stage to sublethal effects in the juvenile stage, and by density‐dependent compensatory responses to toxicant‐induced mortality.
Measuring natural abundance of 13C in respired CO2: variability and implications for non‐invasive dietary analysis
Authors: PERKINS S. E. , SPEAKMAN J. R. 
Published: March 2003

Summary

Three experiments were performed, using laboratory mice (Mus musculus) as a model species, to evaluate the potential of using measurements of carbon isotope ratios in expired CO2 for tracing diets.
Breath 13C signatures of mice fed a constant diet (−21·4‰ ± 0·35) reflected their diet, but were depleted by on average −5·7‰. Body mass, sex and age were independent and significant factors correlated with the variability of 13C enrichment in respired CO2.
Breath 13C signatures from starved mice (7 h) were lower than unstarved mice by 2·0‰. Subsequently when starved mice were fed a small meal of a new diet, breath 13C signatures approached those of the new diets within 15 min, returning to preingestion levels after 105 min.
After a permanent diet switch 13C values of breath were not asymptotic within 6 days, possibly because of use of fat reserves during the daytime carrying an isotopic memory of the previous diet. Hence, individual breath 13C signatures may vary according to nutritive state and previous dietary history.
Interindividual variability was measured at 3·3‰. The implications are that large samples of individuals will be required to distinguish between diets of different populations where the isotopic difference between their diets was small – for example, that expected between herbivorous and carnivorous diets. However, breath would be suitable for distinguishing between dietary intakes of individuals for food types that are isotopically more distinct – such as between C3 and C4 plants.
Variation in nitrogen‐use traits within and between five Carex species growing in the lowland mires of northern Japan
Authors: Nakamura T. , Uemura S. , Yabe K. 
Published: March 2003

Summary

Theory suggests that there should be a trade‐off between nitrogen productivity (A) and mean residence time of nitrogen in plant tissues (MRT), and that this trade‐off depends on the N availability of the habitats. To test this, we studied A, MRT and nitrogen‐use efficiency (NUE, reciprocal of N concentration in the dead shoot) in wetland Carex species sampled from seven lowland mires in Japan.
The NUE and MRT of unproductive species that usually grow in acidic and N‐poor habitats exceeded those of productive species that are abundant in weakly acidic and N‐rich habitats. Except for the most productive species, C. lyngbyei, interspecific differences in A were small, irrespective of productivity.
Intraspecific variation in A was relatively large in contrast to those in NUE and MRT. Within each species, no parameter correlated with the concentration of total dissolved nitrogen (TDN) in the soil water.
Although NUE and MRT of the plants growing in the weakly acidic habitats correlated negatively with TDN, they were constantly high in the acidic habitats regardless of the TDN concentration. Responses of A did not correlate with TDN concentration of soil water in either acidic or weakly acidic habitats.
A trade‐off between A and MRT in the five Carex species was not detected in relation to habitat N richness. We suggest that soil water acidity dominates the ecological performance of the Carex species, and that the trade‐off between A and MRT does not necessarily apply to wetland vegetation.
Classical and nonclassical 21‐hydroxylase deficiency: a molecular study of Argentine patients
Authors: Dain Liliana B. , Buzzalino Noemí D. , Oneto Adriana , Belli Susana , Stivel Mirta , Pasqualini Titania , Minutolo Carolina , Charreau Eduardo H. , Alba Liliana G. 
Published: March 2003

SummaryobjectiveTo characterize the molecular basis of the 21‐hydroxylase deficiency in a group of Argentine patients presenting the classical and nonclassical forms of the disease.DESIGNTo analyse the frequency of point mutations in the CYP21 gene by DNA amplification and mutation detection.patientsForty‐one patients from 36 nonrelated families: 25 nonclassical (NC), 11 salt‐wasting (SW) and five simple virilising (SV). A total of 27 parents and 13 nonaffected siblings were also analysed.MEASUREMENTS Basal steroid hormones and 17‐hydroxyprogesterone levels following adrenal stimulation with adrenocorticotrophic hormone were measured, together with an analysis of 10 point mutations in the CYP21 gene.results A total of 83% and 74·4% classical and nonclassical chromosomes, respectively, were characterized. The intron 2 mutation was the most prevalent among classical alleles. In addition, a high frequency for R356W was observed in both groups (13·3 and 6·9%, respectively), while V281L was the most frequent mutation among the nonclassical patients with a frequency of 39·5%. No alleles containing P30L were observed, and one de novo mutation (R356W) was found. A total of 68·3% patients were fully genotyped, and all but one showed no genotype/phenotype discrepancy. Though the cut‐off value for post‐ACTH 17‐hydroxyprogesterone stimulation was 30·25 nmol/l (10·00 µg/l), the lowest value observed in the fully genotyped nonclassical group was 42·35 nmol/l (14·00 µg/l).conclusions The high number of unidentified alleles in the nonclassical group suggests that less frequent mutations, or the presence of new ones, might be the cause of the disease in the Argentine population. Alternatively, the cut‐off value in the ACTH‐stimulated 17‐hydroxyprogesterone test might overestimate the diagnosis of the nonclassical form by including some patients with heterozygous status.
Incidence of adverse drug reactions in paediatric in/out‐patients: a systematic review and meta‐analysis of prospective studies
Authors: Impicciatore Piero , Choonara Imti , Clarkson Amanda , Provasi Davide , Pandolfini Chiara , Bonati Maurizio 
Published: March 2003

Aims  To explore the usefulness of data derived from observational studies on adverse drug reactions (ADRs) in defining and preventing the risk of pharmacological interventions in children in different health care settings.Methods  A systematic review of studies on ADRs in hospitalized children, in outpatient children, and on ADRs causing paediatric hospital admissions was performed. Studies were identified through a search of the MEDLINE and EMBASE databases. The inclusion criteria required that the population was not selected for particular conditions or drug exposure and prospective monitoring was used for identifying ADRs. Data were analysed by a random‐effects model.Results  Seventeen prospective studies were included. In hospitalized children, the overall incidence of ADRs was 9.53% (95% confidence interval [CI], 6.81,12.26); severe reactions accounted for 12.29% (95%CI, 8.43,16.17) of the total. The overall rate of paediatric hospital admissions due to ADRs was 2.09% (95%CI, 1.02,3.77); 39.3% (95%CI, 30.7,47.9) of the ADRs causing hospital admissions were life threatening reactions. For outpatient children the overall incidence of ADRs was 1.46% (95%CI, 0.7,3.03).Conclusions  The results show that ADRs in children are a significant public health issue. The completeness and accuracy of prescription reporting as well as clinical information from studies was a rarity, making it difficult for health practitioners to implement evidence based preventive strategies. Further, methodologically sound drug surveillance studies are necessary for an effective promotion of a safer use of drugs in children.
Pharmacokinetic–pharmacodynamic model for perindoprilat regional haemodynamic effects in healthy volunteers and in congestive heart failure patients
Authors: Bellissant Eric , Giudicelli Jean‐François 
Published: March 2003

Aims  We compared the relationships between the plasma concentrations (C) of perindoprilat, active metabolite of the angiotensin I‐converting enzyme inhibitor (ACEI) perindopril, and the effects (E) induced on plasma converting enzyme activity (PCEA) and brachial vascular resistance (BVR) in healthy volunteers (HV) and in congestive heart failure (CHF) patients after single oral doses of perindopril.
Methods
Six HV received three doses of perindopril (4, 8, 16 mg) in a placebo‐controlled, randomized, double‐blind, crossover study whereas 10 CHF patients received one dose (4 mg) in an open study. Each variable was determined before and 6–12 times after drug intake. E (% variations from baseline) were individually related to C (ng ml−1) by the Hill model E=Emax.Cγ/(CE50γ + Cγ). When data showed a hysteresis loop, an effect compartment was used.
Results
(means±s.d.) In HV, relationships between C and E were direct whereas in CHF patients, they showed hysteresis loops with optimal ke0 values of 0.13 ± 0.16 and 0.13 ± 0.07 h−1 for PCEA and BVR, respectively. For PCEA, with Emax set to −100%, CE50 = 1.87 ± 0.60 and 1.36 ± 1.33 ng ml−1 (P = 0.34) and γ = 0.90 ± 0.13 and 1.11 ± 0.47 (P = 0.23) in HV and CHF patients, respectively. For BVR, Emax=−41 ± 14% and −60 ± 7% (P = 0.02), CE50 = 4.95 ± 2.62 and 1.38 ± 0.85 ng ml−1 (P = 0.02), and γ = 2.25 ± 1.54 and 3.06 ± 1.37 (P = 0.32) in HV and CHF patients, respectively.
Conclusions
Whereas concentration‐effect relationships were similar in HV and CHF patients for PCEA blockade, they strongly differed for regional haemodynamics. This result probably expresses the different involvements, in HV and CHF patients, of angiotensinergic and nonangiotensinergic mechanisms in the haemodynamic effects of ACEIs.
Endothelin‐A receptor antagonist inhibits angiotensin II and noradrenaline in man
Authors: Wenzel R. R. , Rüthemann J. , Bruck H. , Schäfers R. F. , Michel M. C. , Philipp Th. 
Published: March 2003

Aims  Endothelin‐1 (ET‐1) is a potent vasoconstrictor produced by the vascular endothelium. The interactions of ET with the mediators of the sympathetic nervous system and the renin‐angiotensin‐system in humans are unclear.Methods  We studied the effects of the ETA‐selective antagonist BQ‐123 and the ETB‐selective antagonist BQ‐788 (both 10−10−10−8m) on ET‐1 (10−16−10−10m), angiotensin II (AT, 10−16−10−10m) and noradrenaline (NA, 10−16−10−10m) induced vasoconstriction in the human skin microcirculation in vivo in 25 healthy male volunteers using laser Doppler flowmetry and double injection technique.Results  BQ‐123 caused a dose‐dependent vasodilatation (maximum effect: + 949 ± 84 AUC‐PU, P < 0.001), whereas BQ‐788 induced mild vasoconstriction (maximum effect: −388 ± 96 AUC‐PU, P < 0.01). In the presence of BQ‐123, but not BQ‐788, ET‐1, AT and NA caused markedly less vasoconstriction at any tested agonist dose; the effect was most pronounced on ET‐1 (maximum effect at 10−14m: + 814 ± 93 AUC‐PU vs ET alone, P < 0.001), followed by noradrenaline (maximim effect at 10−16m: + 580 ± 107 AUC‐PU vs NA alone, P < 0.01) and angiotensin II (maximim effect at 10−14m: + 493 ± 111 AUC‐PU vs AT alone, P < 0.001).Conclusions  ETA‐selective antagonism inhibits vasoconstriction to AT and NA in vivo in healthy subjects. This beneficial effect may be useful for the treatment of patients with cardiovascular disease including hypertension especially in combination therapy with sympatholytic agents and inhibitors of the renin‐angiotensin system.
Effects of anticancer drugs on the metabolism of the anticancer drug 5,6‐dimethylxanthenone‐4‐acetic (DMXAA) by human liver microsomes
Authors: Zhou Shufeng , Chin Rebecca , Kestell Philip , Tingle Malcolm D. , Paxton James W. 
Published: March 2003

Aims  To investigate the effects of various anticancer drugs on the major metabolic pathways (glucuronidation and 6‐methylhydroxylation) of DMXAA in human liver microsomes.Methods  The effects of various anticancer drugs at 100 and 500 µm on the formation of DMXAA acyl glucuronide (DMXAA‐G) and 6‐hydroxymethyl‐5‐methylxanthenone‐4‐acetic acid (6‐OH‐MXAA) in human liver microsomes were determined by high performance liquid chromatography (h.p.l.c.). For those anticancer drugs showing significant inhibition of DMXAA metabolism, the inhibition constants (Ki) were determined. The resulting in vitro data were extrapolated to predict in vivo changes in DMXAA pharmacokinetics.
Results
Vinblastine, vincristine and amsacrine at 500 µm significantly (P < 0.05) inhibited DMXAA glucuronidation (Ki = 319, 350 and 230 µm, respectively), but not 6‐methylhydroxylation in human liver microsomes. Daunorubicin and N‐[2‐(dimethylamino)‐ethyl]acridine‐4‐carboxamide (DACA) at 100 and 500 µm showed significant (P < 0.05) inhibition of DMXAA 6‐methylhydroxylation (Ki = 131 and 0.59 µm, respectively), but not glucuronidation. Other drugs such as 5‐fluoroucacil, paclitaxel, tirapazamine and methotrexate exhibited little or negligible inhibition of the metabolism of DMXAA. Pre‐incubation of microsomes with the anticancer drugs (100 and 500 µm) did not enhance their inhibitory effects on DMXAA metabolism. Prediction of DMXAA–drug interactions in vivo based on these in vitro data indicated that all the anticancer drugs investigated except DACA appear unlikely to alter the pharmacokinetics of DMXAA, whereas DACA may increase the plasma AUC of DMXAA by 6%.
Conclusions
These results indicate that alteration of the pharmacokinetics of DMXAA appears unlikely when used in combination with other common anticancer drugs. However, this does not rule out the possibility of pharmacokinetic interactions with other drugs used concurrently with this combination of anticancer drugs.
Repeated local administration of noradrenaline or saline inhibits thermal hyperalgesia in pain‐sensitized human skin
Authors: Drummond Peter D. , Lipnicki Darren M. 
Published: March 2003

Aims  Noradrenaline increases thermal hyperalgesia in skin sensitized to heat by the topical application of capsaicin. The aim of this study was to determine whether desensitization to the hyperalgesic effects of noradrenaline would develop after repeated local administrations of noradrenaline in the skin of the forearm.Methods  Noradrenaline and saline were administered to the forearm by iontophoresis (200 µA, 2 min, over a surface area of 3.1 cm2) two times per day for 4–10 days in 19 healthy subjects. The adequacy of the desensitization procedure was evaluated by measuring noradrenaline‐induced vasoconstriction with laser Doppler fluxmetry. Thresholds and pain ratings to heat were then investigated at treated and control sites before and after the topical application of capsaicin, and after the iontophoresis of noradrenaline.Results  At previously untreated sites blood flow was 49 ± 14% (± 95% confidence intervals) lower than flow at reference sites after the iontophoresis of noradrenaline. Vascular signs of adrenergic desensitization developed after 4–5 days of repeated local administration of noradrenaline in the majority of subjects. In those whose vessels constricted after the acute administration of noradrenaline, the adrenergic response averaged 23 ± 15% at the desensitized site compared with 61 ± 9% at previously untreated sites (P < 0.001). However, similar signs developed after repeated iontophoreses of saline (adrenergic response 7 ± 16% compared with 58 ± 15% at previously untreated sites, P < 0.001). Both the noradrenaline and saline treatments inhibited thermal hyperalgesia after the topical application of capsaicin. Heat‐pain thresholds averaged 43.2 ± 2.5 °C and 43.0 ± 2.3 °C at the noradrenaline and saline pretreated sites compared with 41.4 ± 2.7 °C at the control site (P < 0.05 and P < 0.06, respectively). On a 0–10 scale, heat‐pain ratings to a 7 s, 45 °C stimulus averaged 3.8 ± 1.6 and 3.5 ± 1.7 at the noradrenaline and saline pretreated sites compared with 5.3 ± 1.6 at the control site (P < 0.05). After the iontophoresis of noradrenaline heat‐pain ratings increased 1.6 ± 1.4 at the site pretreated with saline (P < 0.05) compared with only 0.4 ± 1.0 at the site pretreated with noradrenaline (not significant), consistent with local adrenergic desensitization.Conclusions  We conclude that repeated iontophoreses of noradrenaline or saline inhibit vasoconstriction to noradrenaline, and also inhibit increases in thermal hyperalgesia evoked by capsaicin. The release of endogenous stores of noradrenaline by iontophoretic currents might contribute to these effects.