bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of propagule size and maternal nest‐site selection on survival and behaviour of neonate turtles
Authors: KOLBE J. J. , JANZEN F. J. 
Published: March 2003

Summary Maternal effects are widely recognized as important ecological and evolutionary forces, with fitness consequences for both offspring and parents. However, little is known about the impact of maternal effects on the survival and behaviour of offspring in the field. Two potentially important maternal effects that influence the phenotypes and survival of neonates are (i) propagule size effects (i.e. egg size, hatchling size and clutch effects) and (ii) nest‐site selection, which influences incubation conditions and the suitability of habitat for neonates after hatching. We experimentally removed the effects of variable incubation conditions to focus on how propagule size effects and nest‐site microhabitat characteristics influence hatchling survival and behaviour in the Common Snapping Turtle,Chelydra serpentina. Using eight simultaneous experimental releases of neonates under ecologically relevant field conditions, we detected no influence of propagule size effects on hatchling turtle survival or behaviour. Egg mass, hatchling mass, hatchling carapace length and clutch did not predict the probability of survival, nor did they influence hatchling behaviour. However, nest‐site microhabitat characteristics were important for both survival and behaviour. The probability of hatchling survival increased with decreasing amounts of ground vegetation and slope at the release point. Hatchlings took longer to reach the fence when released in areas with more ground vegetation and dispersed farther when released from greater distances and at lower slopes. Therefore, variation in maternal behaviour, such as nest‐site selection, is an important effect because it results in differential survival and behaviour of offspring in this population, whereas variation in maternal size effects alone does not.
Limits to food intake by the Prairie Vole: effects of time for digestion
Authors: Zynel C. A. , Wunder B. A. 
Published: March 2003

Summary

Prairie Voles (Microtus ochrogaster Wagner) are among the smallest vegetation‐feeding mammalian herbivores, and thus show a high ratio of energetic expenditure to energy content of ingested food that may lead to digestive bottlenecks. By varying the periodicity of 3 h of food availability, it was found that energy assimilation in Prairie Voles is not limited by the time required to consume food, but by the time required to digest and absorb food.
Three hours is all the time that is necessary for a Prairie Vole to consume the food needed for 1 day. Although voles offered food in one 3‐h block per 24 h increased dry matter digestibility, they could not consume enough food to maintain body mass. However, when offered 3 h of food availability but divided into six 30‐min periods evenly spaced throughout 24 h Prairie Voles reached a level of food intake similar to that of control voles fed ad libitum and stabilized body mass similar to controls.
It is suggested that a vole’s stomach capacity limits intake for each feeding bout, regardless of how empty the following chambers are after any period of food restriction and the rate of stomach emptying may dictate the feeding bout periodicity. The amount of stomach contents (1·1–1·4 g) found in voles held under similar conditions to those in our experiments closely resembles the amount of food consumed (0·78–1·4 g) during each of the six 30‐min periods of feeding.
The bottleneck limits intake of food and keeps feeding bouts spaced. The time required for digestion may be the cause for a vole’s observed 2–4 h ultradian activity rhythm. Evidence is given that spacing between activity periods may be adjusted to the metabolic demands of the species.
Juvenile Atlantic Salmon (Salmo salar) with relatively high standard metabolic rates have small metabolic scopes
Authors: Cutts C. J. , Metcalfe N. B. , Taylor A. C. 
Published: March 2003

Summary

There is an established relationship between metabolism and behavioural dominance in several fish species, such that individuals with higher standard metabolic rates tend to be more dominant. It has also been suggested that metabolic scope increases with standard metabolic rate.
Energetically expensive behaviours attributable to dominance, such as aggression, can be carried out to a greater extent within larger metabolic scopes. This study therefore tests the hypothesis that juvenile salmon with higher standard metabolic rates (which tend to be dominant) have larger metabolic scopes.
It was found that salmon with high standard metabolic rates (corrected for body mass) in fact had smaller metabolic scopes than conspecifics with relatively low standard metabolic rates. Possible reasons for their potential dominance while having small metabolic scopes and high relative standard metabolic rates are discussed.
Multigenerational familial medullary thyroid cancer (FMTC): evidence for FMTC phenocopies and association with papillary thyroid cancer
Authors: Fugazzola L. , Cerutti N. , Mannavola D. , Ghilardi G. , Alberti L. , Romoli R. , Beck‐Peccoz P. 
Published: March 2003

Summarybackground Occurrence in a familial setting is well established for medullary thyroid carcinoma (MTC) and has been more recently reported for papillary thyroid cancer (PTC). Germline mutations or rearrangements of the RET proto‐oncogene are the genetic background of the majority of hereditary MTCs and of about 25–40% of PTCs.patients A large multigenerational familial medullary thyroid cancer (FMTC) family, comprised of four generations and a total of 60 subjects, has been fully evaluated. Studies on germline RET mutations and polymorphisms, on somatic RET activation and on haplotyping with RET‐linked markers, were performed.results RET mutational analysis revealed a rare missense point mutation in exon 15 of RET (A891S), associated with FMTC. Haplotype analysis showed a co‐segregation between the allelic variant 5 of D10S578 marker (which is tightly linked to the RET locus) and the RET mutation. Two patients, from different branches of the family, did not harbour the point mutation A891S despite histological confirmation of MTC. In these cases, haplotype analysis excluded the involvement of the RET gene itself in the pathogenesis of the MTC. In three patients, the coexistence, in different foci, of medullary and papillary thyroid cancer was documented. The genetic studies did not show ret/PTC rearrangements. The microsatellite analysis excluded co‐segregation of RET locus with the MTC/PTC phenotype.conclusions We report a full clinical and molecular analysis of a large FMTC kindred with an uncommon RET mutation. In two family members, phenotype and genotype were not concordant, representing the first evidence of FMTC phenocopies. Furthermore, the association of familial forms of medullary and papillary thyroid cancers has been found in 30% of patients undergoing thyroidectomy for MTC. In these situations, genetic analyses excluded the possible germline involvement of RET. Though FMTC phenocopies are likely to represent an exceptional finding, such a possibility should be taken into account in the genetic counselling for MEN 2 syndromes.
Study of diurnal fluctuations of plasma methoxyamines in healthy volunteers
Authors: Hoizey Guillaume , Lukas‐Croisier Céline , Frances Carole , Grulet Hervé , Delemer Brigitte , Millart Hervé , Devillier Philippe , Caron Jean 
Published: March 2003

Summaryobjective We studied the diurnal fluctuations of plasma concentrations of methoxyamines (metanephrine and normetanephrine) and of their parent amines (epinephrine and norepinephrine) in normotensive subjects.design Serial blood sampling at 09·00 h, 11·00 h, 12·00 h, 14·00 h, 16·00 h, 18·00 h and 20·00 h in 28 healthy volunteers at rest. Determination of plasma concentrations of free catecholamines and total methoxyamines (free and sulpho‐conjugates) was carried out by high‐performance liquid chromatography with electrochemical detection.results Mean (± SD) plasma concentrations of total metanephrine (MN) and normetanephrine (NMN) were 4·31 ± 1·73 nmol/l (range: 0·96–9·3 nmol/l) and 8·13 ± 2·54 nmol/l (range: 3·14–17·0 nmol/l), respectively. The NMN/MN ratio ranged between 0·8 and 7·8 (mean ± SD 2·1 ± 1·0). Mean plasma concentrations of free epinephrine and norepinephrine were 0·21 ± 0·12 nmol/l (range: 0·06–1·39 nmol/l) and 1·61 ± 0·62 nmol/l (range: 0·47–4·01 nmol/l), respectively. Despite marked intraindividual fluctuations, mean methoxyamine and catecholamine levels remained constant over the entire duration of the experiment.conclusions The absence of fluctuations of plasma levels of total methoxyamines suggests that their measurement could be carried out at any time within the diurnal time frame. Further investigations, however, remain necessary to validate these findings in patients with hypertension and/or pheochromocytoma, and to explain the ever important intraindividual variation in plasma concentrations of methoxyamines and of their parent compounds.
A 6‐month large‐scale study into the safety of tamsulosin
Authors: Michel M. C. , Bressel H.‐U. , Goepel M. , Rübben H. 
Published: March 2003

Aims  Tamsulosin is an α1‐adrenoceptor antagonist for the treatment of symptomatic benign prostatic hyperplasia with a tolerability similar to that of placebo in short‐term, placebo‐controlled studies with limited patient numbers. The present study was designed to test the safety of tamsulosin treatment in a large cohort of men during a prolonged period of time, particularly with regard to comedications.Methods  A multicentre, open‐label phase IIIb study with 1784 patients receiving 0.4 mg o.d. tamsulosin for 6 months was performed according to good clinical practice guidelines. The analysis was performed on an intention‐to‐treat basis and powered to detect adverse events (AE) occurring in 0.15% of patients with 95% confidence.Results  During a total drug exposure time of 811 patient years, 386 AE were recorded in 253 patients (14.2%; 95% confidence intervals [CI] 12.0–15.2%). Twenty‐nine patients suffered 44 serious AE including five fatal events (CI 0.12–0.73%) due to myocardial infarction (n = 3) and to pneumonia and a car accident (one each), but all deaths were judged to be unlikely to be related to study medication. The frequency of AE in patients without any comedication (n = 1095) was 13.0% (CI 11.3–14.9%). In a logistic regression analysis β‐adrenoceptor blockers, converting enzyme inhibitors, antidiabetics and diuretics did not significantly affect the odds ratio for having AE. However, concomitant α‐adrenoceptor antagonists (a protocol violation) and treatment with verapamil (which also has α‐adrenoceptor antagonist activity) significantly enhanced the odds ratio for having AE to 3.87 (CI 1.52–9.85) and 3.17 (CI 1.52–6.58), respectively. Minor increases in the odds ratio, which did not reach statistical significance, were also observed for Ca2+ antagonists other than verapamil and for nitrates.Conclusions  We conclude that tamsulosin has a good safety profile relative to AE rates in the placebo arms of previous studies on tamsulosin even in the presence of most potentially complicating comedications. No major unexpected severe AE were recorded during our 6 months study.
Comparison of the effects of nadolol and bisoprolol on the isoprenaline‐evoked dilatation of the dorsal hand vein in man
Authors: Abdelmawla A. H. , Langley R. W. , Szabadi E. , Bradshaw C. M. 
Published: March 2003

Aims  We attempted to explore the possible differential involvement of β‐adrenoceptor subtypes in the dilator response of the human dorsal hand vein to isoprenaline by examining the ability of bisoprolol, a selective β1‐adrenoceptor antagonist, and nadolol, a nonselective β1/β2‐adrenoceptor antagonist, to antagonize the response.Methods  Twelve healthy male volunteers participated in four weekly sessions. In the preliminary session a dose‐response curve to the vasoconstrictor effect of phenylephrine was constructed and the dose producing 50–75% maximal response was determined for each individual. In each of the remaining three (treatment) sessions, nadolol (40 mg), bisoprolol (5 mg) or placebo was ingested, and isoprenaline hydrochloride (3.33–1000 ng min−1) was infused locally into the dorsal hand vein along with a constant dose of phenylephrine hydrochloride (to preconstrict the vein) 2 h after the ingestion of the drugs. Changes in vein diameter were monitored with the dorsal hand vein compliance technique. Subjects were allocated to treatment session according to a double‐blind balanced cross‐over design. Systolic and diastolic blood pressure, and heart rate were also measured.Results  Isoprenaline produced dose‐dependent venodilatation which was antagonized by nadolol but remained unaffected by bisoprolol (anova with repeated measures: P < 0.025; Dunnett's test: placebo vs nadolol, P < 0.01; placebo vs bisoprolol, P = NS). Mean log ED50 (ng min−1) was significantly increased in the presence of nadolol and remained unchanged in the presence of bisoprolol (anova, P < 0.025; Dunnett's test: placebo vs nadolol, P < 0.005; placebo vs bisoprolol, P = NS; differences between mean log ED50[95% CI]: placebo vs bisoprolol −0.11 [‐0.38, 0.16], placebo vs nadolol 0.32[0.09, 0.72], bisoprolol vs nadolol −0.43 [‐0.71, −0.15]). Mean Emax did not differ in the three treatment conditions.
Conclusions

The failure of bisoprolol to attenuate isoprenaline‐evoked venodilatation in the human dorsal hand vein argues against the involvement of a β1‐adrenoceptor‐mediated component in the isoprenaline‐evoked venodilatory responses. The possibility cannot be excluded that the consequences of β1‐adrenoceptor blockade by bisoprolol might have been obscured by a possible venodilator effect of bisoprolol.
In vitro metabolism and drug interaction potential of a new highly potent anti‐cytomegalovirus molecule, CMV423 (2‐chloro 3‐pyridine 3‐yl 5,6,7,8‐tetrahydroindolizine 1‐carboxamide)
Authors: Bournique Bruno , Lambert Nicole , Boukaiba Rachid , Martinet Michel 
Published: March 2003

Aims
To identify the enzymes involved in the metabolism of CMV423, a new anticytomegalovirus molecule, to evaluate its in vitro clearance and to investigate its potential involvement in drug/drug interactions that might occur in the clinic.
Methods
The enzymes involved in and the kinetics of CMV423 biotransformation were determined using pools of human liver subcellular fractions and heterologously expressed human cytochromes P450 (CYP) and FMO. The effect of CMV423 on CYP probe activities as well as on indinavir and AZT metabolism was determined, and 26 drugs were tested for their potential to inhibit or activate CMV423 metabolism.
Results
CMV423 was oxidized by CYP and not by FMO or cytosolic enzymes. The Km values for 8‐hydroxylation to rac‐RPR 127025, an active metabolite, and subsequent ketone formation by human liver microsomes were 44 ± 13 µm and 47 ± 11 µm, respectively, with corresponding Vmax/Km ratios of 14 and 4 µl min−1 nmol−1 P450. Inhibition with selective CYP inhibitors indicated that CYP1A2 was the main isoform involved, with some participation from CYP3A. Expressed human CYP1A1, 1A2, 2C9, 3A4 and 2C8 catalysed rac‐RPR 127025 formation with Km values of < 10 µm, 50 ± 21 µm, 55 ± 19 µm, circa 282 ± 61 µm and circa 1450 µm, respectively. CYP1B1, 2A6, 2B6, 2C19, 2D6, 2E1 or 3A5 did not catalyse the reaction to any detectable extent. CYP1A1 and 3A4 also catalysed ketone formation from rac‐RPR 127025. In human liver microsomes, CMV423 at 1 and 10 µm inhibited CYP1A2 activity up to 31% and 63%, respectively, CYP3A4 activity up to 40% (10 µm) and CYP2C9 activity by 35% (1 and 10 µm). No effect was observed on CYP2A6, 2D6 and 2E1 activities. CMV423 had no effect on indinavir and AZT metabolism. Amongst 26 drugs tested, none inhibited CMV423 metabolism in vitro at therapeutic concentrations.
Conclusions
CMV423 is mainly metabolized by CYP1A2 and 3A4. Its metabolism should not be saturable at the targeted therapeutic concentrations range (Cmax < 1 µm). CMV423 will probably affect CYP1A2 and 1A1 activities in vivo to some extent, but no other drug–drug interactions are expected.
The effects of an oral contraceptive containing ethinyloestradiol and norgestrel on CYP3A activity
Authors: Belle Donna J. , Callaghan John T. , Gorski J. Christopher , Maya Juan F. , Mousa Omiema , Wrighton Steven A. , Hall Stephen D. 
Published: March 2003

Aims  To examine the effects of an oral contraceptive containing ethinyloestradiol and norgestrel on intestinal and hepatic CYP3A activity using midazolam as a probe substrate.Methods  In a nonblinded sequential study, nine healthy women received simultaneous doses of intravenous midazolam (0.05 mg kg−1) and oral 15N3‐midazolam (3 mg) on days 0, 4, 6, 8, and 14. On study day 5, Ovral™ (50 µg ethinyloestradiol/500 µg norgestrel) was administered for 10 days. Serum and urine samples were assayed for midazolam, 15N3‐midazolam and metabolites by liquid chromatography‐mass spectrometry. A Digit Symbol Substitution Test (DSST) was used to assess changes in the pharmacodynamic activity of midazolam.Results  Moderate (% CV 26–46) interindividual variability in the pharmacokinetics of midazolam were observed. Compared with baseline, AUC(0,∞)iv ratios (95% CIs) after 2, 4, and 10 days treatment with OC were 89% (79, 101), 96% (85, 109), and 88% (77, 99), respectively. The AUC(0,∞)oral ratios (95% CIs) were 101% (82, 125), 105% (85, 130), and 114% (92, 141), respectively, after 2, 4, and 10 days OC treatment compared with baseline. Concomitant administration of the oral contraceptive, Ovral™ for 2, 4 or 10 days did not significantly alter the area under the curve, clearance, or half‐life of midazolam after either oral or intravenous administration. No alterations in pharmacodynamic effects of midazolam were observed between treatment days. Mean DSST scores strongly correlated with mean total midazolam blood concentrations (r = −0.936).Conclusions  Administration of Ovral™ for 10 days had no impact on intestinal or hepatic CYP3A activity as determined by midazolam metabolism.
Quaternary alluvial fan sedimentation in the Dehradun Valley Piggyback Basin, NW Himalaya: tectonic and palaeoclimatic implications
Authors: Kumar Singh A. , Parkash B. , Mohindra R. , Thomas J. V. , Singhvi A. K. 
Published: March 2003

ABSTRACT The Dehradun Valley, a synclinal intermontane valley piggyback basin within the Siwalik Group rocks in the NW Himalaya, is separated from the Lesser Himalayan formations in the north by a major intraplate thrust, the Main Boundary Thrust (MBT) and from the Indogangetic Plains in the south by the Himalayan Frontal Fault (HFF). Major parts of the Dehradun Valley are covered by three fans, from west to east the Donga, Dehradun and Bhogpur fans, deposited by streams following the topography produced by activity of the MBT and probable footwall imbricate thrusts, starting at about 50 ka.The Donga and Dehradun fans were fed by small streams and characterized mainly by sediment gravity‐flow deposits (debris flow and mudflow deposits) in the proximal zone, and mostly mudflow deposits and minor braided stream deposits in the middle zone during the period 50–10 ka. Palaeosols were weakly developed in the proximal zone and moderately to strongly developed in the middle zone. The degree of development of palaeosol was mainly a function of rate of sedimentation and to some extent entrenchment of streams into the fan surface. Since 10 ka, deposition has been typically by braided streams. The Bhogpur fan has been marked by deposition from relatively larger braided streams since 50 ka.The fan sequences in the Dehradun Valley are synorogenic and their deposition started due to activity of the southern footwall imbricate of the MBT, i.e. Bhauwala Thrust on the Donga and Dehradun fans. In these fans, major fan sequences show retrogradation (50–10 ka) related to a decrease in the activity of the MBT and related imbricates and activity of more hinterlandward imbricates with time. After 10 ka a thin prograding sequence was deposited due to uplift of the fans, which resulted from the activity on a thrust in the distal parts of the fans. It suggests an out‐of‐sequence activity of faults in the MBT imbricate system. Cross‐faults divide the Siwalik formations in the footwall of the MBT into three blocks, which were marked by decreasing subsidence or possibly uplift from east to west. Thrusting on the HFF was not piggyback type but synchronous with activity of the MBT and its imbricates. The development of the Mohand fault‐bend anticline above the HFF changed the nature of the basin from foreland to piggyback type, shed minor colluvial deposits prior to 10 ka, and folded the southernmost fan deposits in the western, narrow parts of the valley.A major change in climate from a cold, dry climate with strong seasonal variations prevailing since 50 ka to warm and humid climate at about 10 ka resulted in a change in depositional processes from sediment gravity‐flows to braided streams.
Modulation of glycine responses by dihydropyridines and verapamil in rat spinal neurons
Authors: Chesnoy‐Marchais Dominique , Cathala Laurence 
Published: March 2003

AbstractAlthough glycine receptors (GlyRs) are responsible for the main spinal inhibitory responses in adult vertebrates, in the embryo they have been reported to mediate depolarizing responses, which can sometimes activate dihydropyridine‐sensitive l‐type calcium channels. However, these channels are not the only targets of dihydropyridines (DHPs), and we questioned whether GlyRs might be directly modulated by DHPs. By whole‐cell recording of cultured spinal neurons, we investigated modulation of glycine responses by the calcium channel antagonists, nifedipine, nitrendipine, nicardipine and (R)‐Bay K 8644, and by the calcium channel, agonist (S)‐Bay K 8644. At concentrations between 1 and 10 µm, all these DHPs could block glycine responses, even in the absence of extracellular Ca2+. The block was stronger at higher glycine concentrations, and increased with time during each glycine application. Nicardipine blocked GABAA responses from the same neurons in a similar manner. In addition to their blocking effects, nitrendipine and nicardipine potentiated the peak responses to low glycine concentrations. Both effects of extracellular nitrendipine on glycine responses persisted when the drug was present in the intracellular solution. Thus, these modulations are related neither to calcium channel modulation nor to possible intracellular effects of DHPs. Another type of calcium antagonist, verapamil (10–50 µm), also blocked glycine responses. Our results suggest that some of the effects of calcium antagonists, including the neuroprotective and anticonvulsant effects of DHPs, might result partly from their interactions with ligand‐gated chloride channels.