bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expectant management of tubal ectopic pregnancy: prediction of successful outcome using decision tree analysis
Authors: Elson J. , Tailor A. , Banerjee S. , Salim R. , Hillaby K. , Jurkovic D. 
Published: May 2004

AbstractObjectiveTo establish whether a decision tree based on a combination of clinical, morphological and biochemical parameters could be constructed to help in the selection of women with tubal ectopic pregnancies for expectant management.MethodsThis was a prospective observational study in a tertiary referral early pregnancy unit in an inner city teaching hospital. The study group consisted of 179 women with ultrasound diagnosis of ectopic pregnancy. Demographic, clinical and ultrasound data were recorded in each case at the initial visit. In addition all women had a blood sample taken for the measurements of serum β‐human chorionic gonadotropin (β‐hCG) and progesterone. Clinically stable women with non‐viable pregnancies and no signs of hematoperitoneum were managed expectantly on an outpatient basis until their serum β‐hCG declined to <20 IU/L. Women who developed pelvic pain during follow‐up and those with non‐declining serum β‐hCG were offered surgery.ResultsA total of 107/179 (59.8%) tubal ectopics were considered suitable for expectant management. Ectopic pregnancy resolved spontaneously in 75/107 (70%) women, which was 41.9% of the total number of tubal ectopics. Maternal age, initial serum β‐hCG and progesterone were all significantly different in pregnancies that resolved spontaneously compared to those requiring surgery (P < 0.05). Initial serum β‐hCG level was the best predictor of the outcome of expectant management. These differences enabled a construction of a four‐level decision tree to estimate the likelihood of successful expectant management.ConclusionsThere are significant differences in demographic, ultrasound and biochemical findings between spontaneously resolving ectopics and those requiring treatment. Decision tree analysis may be used as a guide to estimate the probability of successful expectant management in individual cases. Copyright © 2004 ISUOG. Published by John Wiley & Sons, Ltd.
Intra‐ and interobserver repeatability of femur length measurement in early pregnancy
Authors: Rosati P. , Bartolozzi F. , Guariglia L. 
Published: May 2004

AbstractObjectiveTo assess the intra‐ and interobserver reproducibility of songographic measurement of fetal femur length between 10 and 16 weeks of gestation.MethodsFemur length was measured three times by the same trained observer in each fetus of 136 pregnant women. A second trained observer then repeated the measurements. The coefficient of variation, intraclass correlation coefficient and repeatability coefficient with 95% CIs were calculated for each observer and between the two observers.ResultsThe inter‐ and intraobserver repeatabilities of femur length were good. For interobserver correlation, the coefficient of variation was 4.6% (95% CI, 3.0–6.2), the intraclass correlation coefficient was 0.82 (95% CI, 0.69–0.95) and the repeatability coefficient was 2.1 (95% CI, 1.8–2.7). For intraobserver correlation, the coefficient of variation was 4.2% (95% CI, 3.2–5.6), the intraclass correlation coefficient was 0.91 (95% CI, 0.75–0.97) and the repeatability coefficient was 3.23 (95% CI, 2.33–3.86) for Observer 2. Similar results were obtained for the other observer.ConclusionTransvaginal femur length measurement is technically feasible and easy to perform between 10 and 16 weeks of gestation. The high degree of intra‐ and interobserver repeatability indicates it to be a reproducible method. Copyright © 2004 ISUOG. Published by John Wiley & Sons, Ltd.
Morphometrical relationships between South‐east Asian deer (Cervidae, tribe Cervini): evolutionary and biogeographic implications
Authors: Meijaard E. , Groves C. P. 
Published: May 2004

AbstractTwo hundred and fourteen skulls of Asian deer species (Cervini) were measured and the resulting craniometric data analysed using multivariate statistics. Our results suggest that elements of skull shape as determined by morphometrics can be used as phylogenetic characters and depict phylogenetic relationships among Cervini deer species that is not far removed from the picture given by molecular studies and other characters. Morphometrics‐based phylogeny was used in combination with other phylogenies and palaeoenvironmental reconstructions to investigate factors that may have influenced evolutionary changes. Our data indicate the need for a revision of the genus and subgenus level taxonomy of the Cervini.
Enamel hypoplasia provides insights into early systemic stress in wild and captive giraffes (Giraffa camelopardalis)
Authors: Franz‐Odendaal Tamara A. 
Published: May 2004

AbstractEnamel hypoplasia, a developmental tooth defect, provides a permanent record of systemic stress during early life. The incidence and distribution of linear enamel hypoplasia has been used by anthropologists and palaeontologists to assess the health status of past populations but has not been applied by wildlife biologists studying extant animals. This study investigates enamel hypoplasia in 23 Giraffa camelopardalis skulls from wild and captive animals of various ages and sex to determine whether any systemic stress events are unique to life in captivity. Results indicate that wild giraffes are relatively stress‐free as they do not have linear defects. Based on the distribution of linear defects in other giraffes, three key stress periods during the first 6 years of giraffe life were identified. The first stress event occurs during weaning, the second at about 3 years of age and the third, which is the least common, at 4–5 years of age. All three stress events were observed in both male and female giraffes. This study highlights the usefulness of assessing enamel hypoplasia in both wild and captive animals as well as the need for further research on tooth developmental timings in many wild ungulates. Some left–right asymmetry was observed in the development of linear and non‐linear defects, which has implications for the aetiology of these defects.
Bv8, the amphibian homologue of the mammalian prokineticins, modulates ingestive behaviour in rats
Authors: Negri Lucia , Lattanzi Roberta , Giannini Elisa , Felice Milena De , Colucci Antonella , Melchiorri Pietro 
Published: May 2004

The small protein Bv8, secreted by the skin of the frog Bombina variegata, belongs to a novel family of secreted proteins whose mammalian orthologues have been identified and named prokineticins (PK‐1 and PK‐2).
Bv8 (from 2.5 to 60 pmol) injected into the lateral ventricles of rat brain suppressed diurnal, nocturnal, deprivation‐induced and neuropeptide Y‐stimulated feeding and stimulated diurnal drinking. Nocturnal drinking was increased only in fasted rats.
PK‐2 mRNA is expressed in discrete areas of the rat brain, including the suprachiasmatic nucleus (SCN), medial preoptic area (MPA) and nucleus of the solitary tract (NTS). In the SCN neurons, PK‐2 mRNA is highest during the light phase of the circadian cycle and undetectable during the dark phase.
The G‐protein‐coupled receptor prokineticin receptor 2 (PKR‐2), which binds Bv8 and PK‐2 with high affinity, is mainly expressed in the piriform cortex, paraventricular thalamic nucleus, parataenial nucleus (PT), SCN, hypothalamic paraventricular (PVH) and dorsomedial (DMH) nuclei, arcuate nucleus (ARC) and subfornical organ (SFO) of the rat brain.
Bv8 microinjected into the ARC, at doses from 0.02 to 2.0 pmol during night‐time or from 0.2 to 5 pmol in 24‐h‐fasted rats, selectively suppressed feeding without affecting drinking. When injected into the SFO, Bv8 (from 0.2 to 2 pmol) stimulated drinking but did not affect feeding. Bv8 injections into other brain areas left rat ingestive behaviours unchanged.
We hypothesize that PK‐2‐rich projections from SCN neurons to PKR‐expressing ARC neurons could transmit the circadian rhythm of feeding, whereas inputs from the PK‐2‐expressing NTS neurons to the PKR‐2‐expressing SFO neurons could transmit visceral information on the water–electrolyte balance and osmotic regulation.

British Journal of Pharmacology (2004) 142, 181–191. doi:10.1038/sj.bjp.0705686
Salicylidene salicylhydrazide, a selective inhibitor ofβ1‐containing GABAAreceptors
Authors: Thompson S A , Wheat L , Brown N A , Wingrove P B , Pillai G V , Whiting P J , Adkins C , Woodward C H , Smith A J , Simpson P B , Collins I , Wafford K A 
Published: May 2004

A high‐throughput assay utilizing the voltage/ion probe reader (VIPR) technology identified salicylidene salicylhydrazide (SCS) as being a potent selective inhibitor ofα2β1γ1θGABAAreceptors with a maximum inhibition of 56±5% and an IC50of 32 (23, 45) nM.Evaluation of this compound using patch‐clamp electrophysiological techniques demonstrated that the compound behaved in a manner selective for receptors containing theβ1 subunit (e.g. maximum inhibition of 68.1±2.7% and IC50value of 5.3 (4.4, 6.5) nMonα2β1γ1 receptors). The presence of aβ1 subunit was paramount for the inhibition with changes betweenα1 andα2,γ1 andγ2, and the presence of aθsubunit having little effect.On all subtypes, SCS produced incomplete inhibition with the greatest level of inhibition atα1β1γ1θreceptors (74.3±1.4%). SCS displayed no use or voltage dependence, suggesting that it does not bind within the channel region. Concentration – response curves to GABA in the presence of SCS revealed a reduction in the maximum response with no change in the EC50or Hill coefficient. In addition, SCS inhibited pentobarbitone‐induced currents.Threonine 255, located within transmembrane domain (TM) 1, and isoleucine 308, located extracellularly just prior to TM3, were required for inhibition by SCS.SCS did not compete with the known allosteric modulators, picrotoxin, pregnenolone sulphate, dehydroepiandrosterone 3‐sulphate, bicuculline, loreclezole or mefenamic acid. Neither was the inhibition by SCS influenced by the benzodiazepine site antagonist flumazenil.In conclusion, SCS is unique in selectively inhibiting GABAAreceptors containing theβ1 subunitviaan allosteric mechanism. The importance of threonine 255 and isoleucine 308 within theβ1 subunit and the lack of interaction with a range of GABAAreceptor modulators suggests that SCS is interacting at a previously unidentified site.British Journal of Pharmacology(2004)142, 97–106. doi:10.1038/sj.bjp.0705689
The complexities of the cardiovascular actions of cannabinoids
Authors: Randall Michael D , Kendall David A , O'Sullivan Saoirse 
Published: May 2004

The cardiovascular actions of cannbinoids are complex. In general they cause vasorelaxation in isolated blood vessels, while in anaesthetised animals they cause multiphasic responses which involve an early bradycardia and long‐lasting hypotension. However, in conscious animals, the picture is one of bradycardia followed by pressor responses. Clearly, the responses to cannabinoids are dependent on the experimental conditions and synthetic cannabinoids and endocannabinoids exhibit different pharmacologies. In terms of mechanisms involved in the vascular responses to cannabinoids, the following have been implicated: the involvement of ‘classical’ cannabinoid receptors, the involvement of a novel endothelial cannabinoid receptor, the release of nitric oxide, the release of endothelium‐derived hyperpolarising factor (EDHF), the activation of vanilloid receptors, metabolism of endocannabinoids to vasoactive molecules, and both peripheral inhibition and central excitation of the sympathetic nervous system.British Journal of Pharmacology (2004) 142, 20–26. doi:10.1038/sj.bjp.0705725
Vascular relaxation response to hydrogen peroxide is impaired in hypertension
Authors: Gao Yu‐Jing , Zhang Yongde , Hirota Simon , Janssen Luke J , Lee Robert M K W 
Published: May 2004

In phenylephrine (1 μM)‐precontracted rat superior mesenteric arteries (MA), hydrogen peroxide (H2O2, 0.3 and 1 mM) caused a biphasic response: a transient contraction followed by a relaxation. In the presence of thromboxane A2/prostaglandin H2 (TP) receptor antagonist (SQ 29548), the contractile component of the biphasic response was abolished. The relaxation response to H2O2 was smaller in spontaneously hypertensive rats (SHR) when compared with normotensive Wistar–Kyoto rats (WKY).
The mechanisms for the attenuated relaxation to H2O2 in the SHR were studied. KCl (40 mM) prevented the relaxation response. Calcium‐dependent K+ channel (KCa) blockers (tetraethylammonium chloride, TEA; iberiotoxin, and charybdotoxin) showed a greater inhibition of H2O2 relaxation in SHR than in WKY, whereas voltage‐dependent K+‐channel (Kv) blocker 4‐aminopyridine was more effective in inhibiting the relaxation in WKY than in SHR.
H2O2 (1 mM) greatly enhanced the frequency and intensity of the spontaneous transient outward K+ currents in SHR MA, and the effects of H2O2 were inhibited by iberiotoxin, while in WKY MA the K+ currents induced by H2O2 were mainly of the Kv type. The consequence of the activation of different types of K+ channel was that the net increase in mean outward K+ current density in response to H2O2 was smaller in SHR than in WKY, which may account for the attenuated relaxation response to H2O2 in the SHR.
The contractile responses of MA to TEA, iberiotoxin, and charybdotoxin were greater in SHR than in WKY.
In summary, an attenuated relaxation response to H2O2 was found in SHR MA when compared to WKY. In contrast to the activation of Kv channels in WKY, H2O2 markedly enhanced KCa activity in SHR, resulting in an attenuation of the increase in mean outward K+ current density in response to H2O2. These results suggest that alteration in K+ channel activation by reactive oxygen species may play a role in the development of hypertension in SHR.

British Journal of Pharmacology (2004) 142, 143–149. doi:10.1038/sj.bjp.0705727
Effect of acute and chronic lamotrigine on basal and stimulated extracellular 5‐hydroxytryptamine and dopamine in the hippocampus of the freely moving rat
Authors: Ahmad Shagufta , Fowler Leslie J , Whitton Peter S 
Published: May 2004

We have studied the effects of acute and chronic treatment with the anticonvulsant lamotrigine (LTG) on basal and stimulated extracellular 5‐hydroxytryptamine (5‐HT), dopamine (DA) and their metabolites in the hippocampus of freely moving rats using in vivo microdialysis.
Acute LTG (10 and 20 mg kg−1) decreased extracellular 5‐HT, but had no effect on its metabolite 5‐hydroxyindoleacetic acid (5‐HIAA). Dialysate DA was also decreased by LTG as were its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). When transmitter release was stimulated by either 50 μM veratridine or 100 mM K+, marked increases in the release of both transmitters occurred, but LTG was entirely without effect on this.
In chronic experiments, rats were dialysed after 2, 4, 7, 14 and 21 days of LTG treatment (5 mg kg−1, twice daily). During this period a progressively different response to the drug was seen. After 2 days, basal extracellular 5‐HT was significantly greater in treated rats than control rats. This effect persisted up to 14 days, but by 21 days 5‐HT levels had returned to control values. 5‐HIAA levels were unaltered and there was no effect of LTG on veratridine or K+ stimulated 5‐HT release.
Similarly, DA concentrations significantly increased after 2–7 days of LTG treatment, but returned and remained at basal values thereafter. During the treatment period LTG had no effect on extracellular DOPAC, but HVA followed a similar pattern to its parent transmitter. As with 5‐HT, at no time point did LTG have any effect on stimulated DA release.
These neurochemical findings observed in these experiments are considered in relation to the use of LTG in bipolar disorder.

British Journal of Pharmacology (2004) 142, 136–142. doi:10.1038/sj.bjp.0705737
Bradykinin‐induced relaxation of coronary microarteries: S‐nitrosothiols as EDHF?
Authors: Batenburg Wendy W , Popp Rüdiger , Fleming Ingrid , Vries René de , Garrelds Ingrid M , Saxena Pramod R , Danser A H Jan 
Published: May 2004

To investigate whether S‐nitrosothiols, in addition to NO, mediate bradykinin‐induced vasorelaxation, porcine coronary microarteries (PCMAs) were mounted in myographs.
Following preconstriction, concentration–response curves (CRCs) were constructed to bradykinin, the NO donors S‐nitroso‐N‐penicillamine (SNAP) and diethylamine NONOate (DEA‐NONOate) and the S‐nitrosothiols L‐S‐nitrosocysteine (L‐SNC) and D‐SNC. All agonists relaxed PCMAs. L‐SNC was ∼5‐fold more potent than D‐SNC.
The guanylyl cyclase inhibitor ODQ and the NO scavenger hydroxocobalamin induced a larger shift of the bradykinin CRC than the NO synthase inhibitor L‐NAME, although all three inhibitors equally suppressed bradykinin‐induced cGMP responses.
Complete blockade of bradykinin‐induced relaxation was obtained with L‐NAME in the presence of the large‐ and intermediate‐conductance Ca2+‐activated K+‐channel (BKCa, IKCa) blocker charybdotoxin and the small‐conductance Ca2+‐activated K+‐channel (SKCa) channel blocker apamin, but not in the presence of L‐NAME, apamin and the BKCa channel blocker iberiotoxin.
Inhibitors of cytochrome P450 epoxygenase, cyclooxygenase, voltage‐dependent K+ channels and ATP‐sensitive K+ channels did not affect bradykinin‐induced relaxation.
SNAP‐, DEA‐NONOate‐ and D‐SNC‐induced relaxations were mediated entirely by the NO‐guanylyl cyclase pathway. L‐SNC‐induced relaxations were partially blocked by charybdotoxin+apamin, but not by iberiotoxin+apamin, and this blockade was abolished following endothelium removal. ODQ, but not hydroxocobalamin, prevented L‐SNC‐induced increases in cGMP, and both drugs shifted the L‐SNC CRC 5–10‐fold to the right.
L‐SNC hyperpolarized intact and endothelium‐denuded coronary arteries.
Our results support the concept that bradykinin‐induced relaxation is mediated via de novo synthesized NO and a non‐NO, endothelium‐derived hyperpolarizing factor (EDHF). S‐nitrosothiols, via stereoselective activation of endothelial IKCa and SKCa channels, and through direct effects on smooth muscle cells, may function as an EDHF in porcine coronary microarteries.

British Journal of Pharmacology (2004) 142, 125–135. doi:10.1038/sj.bjp.0705747
Thromboxane receptor stimulation associated with loss of SKCa activity and reduced EDHF responses in the rat isolated mesenteric artery
Authors: Crane G J , Garland C J 
Published: May 2004

The possibility that thromboxane (TXA2) receptor stimulation causes differential block of the SKCa and IKCa channels which underlie EDHF‐mediated vascular smooth muscle hyperpolarization and relaxation was investigated in the rat isolated mesenteric artery.
Acetylcholine (30 nM–3 μM ACh) or cyclopiazonic acid (10 μM CPA, SERCA inhibitor) were used to stimulate EDHF‐evoked smooth muscle hyperpolarization. In each case, this led to maximal hyperpolarization of around 20 mV, which was sensitive to block with 50 nM apamin and abolished by repeated stimulation of mesenteric arteries with the thromboxane mimetic, U46619 (30 nM–0.1 μM), but not the α1‐adrenoceptor agonist phenylephrine (PE).
The ability of U46619 to abolish EDHF‐evoked smooth muscle hyperpolarization was prevented by prior exposure of mesenteric arteries to the TXA2 receptor antagonist 1 μM SQ29548.
Similar‐sized smooth muscle hyperpolarization evoked with the SKCa activator 100 μM riluzole was also abolished by prior stimulation with U46619, while direct muscle hyperpolarization in response to either levcromakalim (1 μM, KATP activator) or NS1619 (40 μM, BKCa activator) was unaffected.
During smooth muscle contraction and depolarization to either PE or U46619, ACh evoked concentration‐dependent hyperpolarization (to −67 mV) and complete relaxation. These responses were well maintained during repeated stimulation with PE, but with U46619 there was a progressive decline, so that during a third exposure to U46619 maximum hyperpolarization only reached –52 mV and relaxation was reduced by 20%. This relaxation could now be blocked with charybdotoxin alone. The latter responses could be mimicked with 300 μM 1‐EBIO (IKCa activator), an action not modified by exposure to U46619.
An early consequence of TXA2 receptor stimulation is a reduction in the arterial hyperpolarization and relaxation attributed to EDHF. This effect appears to reflect a loss of SKCa activity.

British Journal of Pharmacology (2004) 142, 43–50. doi:10.1038/sj.bjp.0705756
Effects of Trolox on the activity and gene expression of cytochrome P450 in hepatic ischemia/reperfusion
Authors: Eum Hyun‐Ae , Lee Sun‐Mee 
Published: May 2004

The aim of this study was to investigate the effect of Trolox on hepatic microsomal cytochrome P450 (CYP) activity and gene expression during ischemia and reperfusion (I/R).
Rats were subjected to 60 min of hepatic ischemia, and 5 h (acute phase) and 24 h (subacute phase) of reperfusion. Rats were treated intravenously with Trolox (2.5 mg kg−1) or vehicle, 5 min before reperfusion.
The serum alanine aminotransferase level and lipid peroxidation were increased as a result of I/R. These increases were attenuated by Trolox. Reduced glutathione concentration decreased in I/R group, and this decrease was inhibited by Trolox.
Both total hepatic CYP content and NADPH‐cytochrome P450 reductase activity decreased after I/R, which were restored by Trolox.
CYP1A1 activity and its protein level decreased 24 h after reperfusion; decreases which were prevented by Trolox. Both the activity and mRNA expression of CYP1A2 decreased 24 h after reperfusion. The decrease in CYP1A2 mRNA was prevented by Trolox. CYP2B1 activity and mRNA expression decreased 5 h after reperfusion. The decrease in CYP2B1 activity was prevented by Trolox. In contrast, the CYP2E1 activity and its protein level increased 5 h after reperfusion and this increase was prevented by Trolox.
The expression of TNF‐α and iNOS mRNAs increased after I/R. Trolox inhibited increase in iNOS mRNA expression.
Trolox ameliorates hepatic drug‐metabolizing dysfunction, as indicated by abnormalities in CYP isoforms during I/R, and this protection is likely due to the scavenging of reactive oxygen species.

British Journal of Pharmacology (2004) 142, 35–42. doi:10.1038/sj.bjp.0705758
Enhanced inhibition of the EDHF phenomenon by a phenyl methoxyalaninyl phosphoramidate derivative of dideoxyadenosine
Authors: Griffith Tudor M , Chaytor Andrew T , Edwards David H , Daverio Felice , McGuigan Christopher 
Published: May 2004

In rabbit arteries endogenous production of cAMP facilitates electrotonic signalling via gap junctions, thus explaining the ability of P‐site inhibitors of adenylyl cyclase to attenuate EDHF‐type responses. In the present study, we show that a lipophilic phosphoramidate pronucleotide derivative of dideoxyadenosine, 2′,3′‐ddA‐PMAPh, exhibits enhanced activity as an inhibitor of EDHF‐type smooth muscle hyperpolarizations induced by acetylcholine (ACh) compared to the parent nucleoside 2′,3′‐ddA, and that the effects of both compounds can be reversed by the cAMP phosphodiesterase inhibitor IBMX. Neither 2′,3′‐ddA nor 2′,3′‐ddA‐PMAPh depress ACh‐evoked endothelial hyperpolarization directly. Modifications in the lipophilicity of dideoxyadenosine and its direct intracellular delivery as a mononucleotide may thus enhance the ability to inhibit adenylyl cyclase and depress electrotonic signalling via myoendothelial gap junctions.British Journal of Pharmacology (2004) 142, 27–30. doi:10.1038/sj.bjp.0705782