bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of englitazone on KATP and calcium‐activated non‐selective cation channels in CRI‐G1 insulin‐secreting cells
Authors: Rowe I. C. M. , Lee K. , Khan R. N. , Ashford M. L. J. 
Published: July 2006

The effects of englitazone sodium, an antidiabetic agent, on ion channel activity in the CRI‐G1 insulin secreting cell line was examined by use of the patch clamp technique.
Application of englitazone to the outside of CRI‐G1 cells in the whole‐cell recording configuration produced concentration‐dependent inhibition of KATP currents with an IC50 value of 8 μM. The inhibition of the K+ current was not affected by the removal of Mg2+ ions from or the addition of trypsin to the solution bathing the intracellular surface of the cell membrane.
Englitazone also inhibited KATP channel activity in recordings from inside out excised membrane patches. The concentration‐dependence of inhibition was identical to that observed in whole‐cell recordings and was voltage‐independent. Single channel recordings confirmed that neither the absence or presence of Mg2+ ions nor the addition of trypsin at the intracellular surface of the membrane influenced the inhibition of KATP channels by englitazone.
Englitazone also inhibited Ca2+‐activated non‐selective cation (NSCa) channels in inside‐out patches in a concentration‐dependent and voltage‐independent manner with an IC50 value of 10 μM. In comparison, the non‐sulphonylurea KATP channel blocker ciclazindol produced a slight voltage‐dependent inhibition of the NSCa channel at a concentration of 20 μM.
In whole‐cell recordings englitazone, at a relatively high concentration (50 μM) in comparison with that required to block KATP and NSCa channels, inhibited voltage‐activated Ca2+ currents by 33% but did not inhibit voltage‐activated K+ and Na+ currents.
It is concluded that englitazone is a novel blocker of NSCa and KATP channels. The inhibition of KATP channels occurs following procedures that dissociate sulphonylurea receptor coupling to the channel. The equipotent and voltage‐independent inhibition of NSCa and KATP channels by englitazone may indicate a common mechanism of block.
Characterization of nociceptin hyperalgesia and allodynia in conscious mice
Authors: Hara Naoki , Minami Toshiaki , Okuda‐Ashitaka Emiko , Sugimoto Tetsuo , Sakai Masato , Onaka Masahiko , Mori Hidemaro , Imanishi Toshihiro , Shingu Koh , Ito Seiji 
Published: July 2006

Intrathecal (i.t.) administration of nociceptin and high doses of morphine induced allodynia in response to innocuous tactile stimuli, and i.t. nociceptin evoked hyperalgesia in response to noxious thermal stimuli in conscious mice. Here we have characterized the nociceptin‐induced allodynia and compared it with the morphine‐induced allodynia and the nociceptin‐evoked hyperalgesia.
Nociceptin‐induced allodynia was evoked by the first stimulus 5 min after i.t. injection, reached a maximum at 10 min, and continued for a 50 min experimental period. Dose‐dependency of the allodynia showed a bell‐shaped pattern from 50 pg to 5 ng kg−1, and the maximum effect was observed at 2.5 ng kg−1.
Morphine‐induced allodynia reached the maximum effect at 15 min and declined progressively until cessation by 40–50 min. The dose‐response curve showed a bell‐shaped pattern, similar to that induced by nociceptin, with a maximum effect at 0.5 mg kg−1, five orders of magnitude higher than that of nociceptin.
The allodynia evoked by nociceptin and morphine were dose‐dependently blocked by glycine, D(−)‐2‐amino‐5‐phosphonovaleric acid (D‐AP5, an N‐methyl‐D‐aspartate (NMDA) receptor antagonist), γ‐D‐glutamylaminomethyl sulphonic acid (GAMS, a non‐NMDA receptor antagonist) and methylene blue (a soluble guanylate cyclase inhibitor), but were not affected by muscimol (a γ‐aminobutyric acidA (GABAA) receptor agonist) and baclofen (a GABAB receptor agonist).
Morphine did not inhibit forskolin‐stimulated cyclicAMP formation in cultured cells expressing the nociceptin receptor.
Nociceptin‐induced hyperalgesia was evoked 10–15 min after i.t. injection. Nociceptin produced a monophasic hyperalgesic action over a wide range of doses from 5 fg to 50 ng kg−1. The nociceptin‐induced hyperalgesia was blocked by glycine only among the agents examined.
None of the pain responses evoked by nociceptin and morphine were blocked by naloxone.
These results demonstrate that, whereas the mechanisms of the nociceptin‐induced allodynia and hyperalgesia are evidently distinct, they involve a common neurochemical event beginning with the disinhibition of the inhibitory glycinergic response. Morphine may induce allodynia through a pathway common to nociceptin, but the nociceptin receptor does not mediate the action of high doses of morphine.
The neuropeptide Y (NPY) Y1 receptor antagonist BIBP 3226: effects on vascular responses to exogenous and endogenous NPY in the pig in vivo
Authors: Malmström Rickard E. , Balmér Karin C. , Lundberg Jan M. 
Published: July 2006

The antagonistic effects of the neuropeptide Y (NPY) Y1 receptor antagonist BIBP 3226 on equally prominent vascular responses evoked by sympathetic nerve stimulation and exogenous NPY were compared during different intravenous (i.v.) infusions of the antagonist (0.19–190 nmol kg−1 min−1, for 30 min).
High frequency sympathetic nerve stimulation in reserpine‐treated pigs in vivo evoked non‐adrenergic vasoconstrictor responses in kidney and hind limb, in the latter followed by a long‐lasting phase of decreased blood flow. The vascular response in the kidney and the long‐lasting phase in hind limb resembled the effects of exogenous NPY administered i.v. (kidney) and intraarterially (i.a.) (in the hind limb, which only responded to higher NPY doses).
Plasma levels of BIBP 3226 reached a plateau within 20 min and the inhibitory effects on vascular responses were studied during the last ten minutes of infusion. The elimination of BIBP 3226 from plasma was found to fit a two‐compartment model with an α‐phase of 2.0±0.2 min and a β‐phase of 20.1±0.9 min.
Significant inhibition of presumably Y1 receptor‐mediated vascular responses evoked by both endogenous and exogenous NPY in kidney and hind limb was seen even during low‐dose infusion of BIBP 3226 (1.9 nmol kg−1 min−1), when plasma levels of the antagonist reached 59±8 nM. The maximum inhibitory effects of BIBP 3226 were seen during the highest‐dose infusion (190 nmol kg−1 min−1), when the long‐lasting vasoconstrictor responses in hind limb to sympathetic nerve stimulation and exogenous NPY administration (i.a.) were abolished. Simultaneously, the vascular responses in kidney to exogenous NPY were inhibited by 89% and to sympathetic nerve stimulation by 60%.
It is concluded that BIBP 3226 has a short half‐life in plasma and should preferably be given by i.v. infusions to maintain blockade and avoid non‐specific effects. Furthermore, BIBP 3226 dose‐dependently and with similar potency antagonizes vascular responses to exogenous and endogenous NPY both in the kidney and hind limb of the reserpine‐treated pig in vivo. Thus, inhibition of vascular responses to exogenous NPY may be a good indicator of the dose of this antagonist needed to inhibit sympathetic Y1 receptor‐transmission.
The effect of the neuropeptide substance P on desensitization of ATP receptors of PC12 cells
Authors: Khiroug L. , Giniatullin R. , Talantova M. , Nistri A. 
Published: July 2006

Patch clamp recording (whole cell configuration) was employed to investigate the modulatory action of substance P on inward currents elicited by adenosine 5′‐triphosphate (ATP, focally applied via a pressure pipette) from phaechromocytoma (PC12) cells usually held at −70 mV.
Bath‐applied substance P (0.2–20 μM) had no effect on baseline membrane current but reversibly reduced ATP peak currents in a concentration‐dependent fashion. The depressant effect was not associated with a change in the ATP current reversal potential.
Equiamplitude peak responses induced by 50 μM or 5 mM ATP were differentially affected by substance P which preferentially reduced currents evoked by 5 mM ATP. In the presence of substance P a conditioning pulse of ATP evoked a stronger depression to subsequent test pulses of the same agonist.
Combined patch clamping and confocal laser imaging of intracellular Ca2+ ([Ca2+]i) of single PC12 cells showed that substance P (applied by a pressure pipette) per se had no effect on [Ca2+]i or current baseline, although it reduced the inward current and associated [Ca2+]i rise elicited by ATP.
These results are interpreted as due to facilitation by substance P of desensitization of ATP‐gated P2X2 receptors of PC12 cells. It is proposed that the novel modulation by this peptide of ATP responses may serve as a model for further studies aimed at elucidating the action of substance P on purinergic neurotransmission.
Effects of trout bradykinin on the motility of the trout stomach and intestine: evidence for a receptor distinct from mammalian B1 and B2 subtypes
Authors: Jensen Jorgen , Michael Conlon J. 
Published: July 2006

Trout bradykinin ([Arg0,Trp5,Leu8]‐bradykinin; trout BK), recently isolated from kallikrein‐treated trout plasma, produced sustained and concentration‐dependent contractions of isolated longitudinal muscle from rainbow trout stomach (pD2=7.01±0.03) and proximal small intestine (pD2=7.37±0.07). The maximum responses were 85±2% (stomach) and 101±35% (intestine) of the corresponding responses to 10−5 M acetylcholine. Strips of circular smooth muscle from trout stomach and intestine did not contract in response to trout BK.
The potency of trout BK on gastric smooth muscle motility was significantly (5 fold; P<0.01) reduced in the presence of the cyclo‐oxygenase inhibitor, indomethacin (10−5 M) and by 4 fold (P<0.05) in the presence of the lipoxygenase inhibitor, MK‐886 (10−6 M), but there was no effect on the maximum response. Potency was also significantly reduced in the presence of 10−6 M methysergide (3 fold; P<0.02) and 10−6 M tetrodotoxin (2 fold, P<0.05) but atropine was without effect.
[Tyr0,Trp5,Leu8]‐BK was a full agonist but was approximately 50 fold less potent (pD2=5.35±0.08) than trout BK, [Arg0,Trp5,Leu8]des‐Arg9‐BK was a partial agonist (pD2=6.80±0.03; 56±7% of the maximum response to trout BK) but [Trp5,Leu8]‐BK, [Trp5,Leu8]‐des‐Arg9‐BK and mammalian BK produced no, or only very weak, contractions of the trout stomach.
The mammalian B1 receptor antagonist, [Leu8]des‐Arg9‐BK was without effect on the response of the trout stomach to trout BK. The potent mammalian B2 receptor antagonist Hoe 140 was a partial agonist (pD2=7.44±0.12; 57±15% of the maximum response to trout BK).
We conclude that the effects of trout BK on the motility of rainbow trout gastric smooth muscle are mediated through interaction with a receptor that has appreciably different ligand‐binding properties than the mammalian B1 and B2 receptor subtypes. An involvement of arachidonic acid metabolites and 5‐hydroxytryptaminergic nerves in the mechanism of action of the peptide is suggested.
A review of the cranial characteristics of the Wild Boar (Susscrofa Linnaeus 1758), with systematic conclusions
Authors: GENOV PETER VASSILEV 
Published: July 2006

AbstractThe Wild Boar Sus scrofa L. is widely distributed in Europe, Asia and North‐West Africa. It has also been introduced into the USA and Argentina. Authors have described 22 subspecies on the basis of cranium shape and size. Differences in taxonomic characters have been evaluated using one‐way ANOVA and multiple comparisons have been performed with the Bonferroni Test. Cranium shape does not allow reliable statistical distinction, and is not valid as a diagnostic tool. Cranium profile‐which only differs for the male specimens, with populations differing at a value of 26.9%, or at the subspecies level 24.4%–cannot be used as a diagnostic tool. The length, width and their proportions of the third upper molar tooth show the following differences between subspecies: 39.1%, 41.0% and 8.3% for males and 36.1%, 41.7% and 16.7% for females, respectively. Only the first two criteria are useful as diagnostic tools. The percentage distance between the palatum durum and the basipterygoideus suture, the length of the third lower molar tooth and proportion between the height of lacrimal bone at the orbit and its lower suture length differ as follows: at the subspecies level 46.7%, 38.5% and 56.4% for the male specimens and 36.1%, 45.8% and 55.6% for the female ones. All of these characters can be used as diagnostic criteria. Taking these taxonomic characters and the four shapes of the lacrimal bone together with the rear margin of palatum durum as a basis, only four subspecies of Wild Boar are recognizable: Sus scrofa scrofa, inhabiting North‐West Africa, Europe and West Asia; Sus scrofa ussuricus, which inhabits North Asia and Japan; Sus scrofa cristatus, which inhabits the Asia Minor peninsula, India and the Far‐East; and Sus scrofa vittatus, which inhabits Indonesia.
Dose–response in direct comparisons of different doses of aspirin, ibuprofen and paracetamol (acetaminophen) in analgesic studies
Authors: McQuay Henry J. , Moore R. Andrew 
Published: July 2006

AimsEstablishing the dose–response relationship for clinically useful doses of aspirin, ibuprofen and paracetamol has been difficult. Indirect comparison from meta‐analysis is compromised by too little information at some doses.MethodsA systematic review of randomized, double‐blind trials in acute pain comparing different doses of aspirin, ibuprofen and paracetamol was therefore undertaken.ResultsFifty trials were found. Numerical superiority of higher over lower dose was found by the original authors in 37/50 trials (74%) and statistical superiority in 11/50 (22%). Twenty‐eight trials had design, quality and data reporting characteristics to allow pooling of common doses; in 3/28 (11%) of the individual trials our calculations showed statistical superiority of higher over lower dose. Pooled comparison of 1000/1200 mg aspirin over 500/600 mg was statistically superior, with a number‐needed‐to‐treat (NNT) for higher over lower dose of 16 (8 to > 100). Pooled comparison of 400 mg ibuprofen over 200 mg was statistically superior, with an NNT for higher over lower dose of 10 (6–23). Pooled comparison of 1000 mg paracetamol over 500 mg was statistically superior, with an NNT for higher over lower dose of 9 (6–20).ConclusionsUse of trials making direct comparison of two different doses of target drugs revealed the underlying dose–response curve for clinical analgesia.
Effects of gender, age, diabetes mellitus and renal and hepatic impairment on tadalafil pharmacokinetics
Authors: Forgue S. Thomas , Phillips Diane L. , Bedding Alun W. , Payne Christopher D. , Jewell Hayley , Patterson Beverley E. , Wrishko Rebecca E. , Mitchell Malcolm I. 
Published: July 2006

AimsTo evaluate the effects of gender, age, diabetes mellitus, renal and hepatic impairment on tadalafil pharmacokinetics and tolerability.MethodsSix single‐dose (5, 10 or 20 mg orally) clinical pharmacology studies were conducted in the UK, Belgium, Poland and Germany in healthy male and female subjects, elderly subjects and subjects with diabetes mellitus, renal impairment, end‐stage renal failure (ESRF) or hepatic impairment. The gender study also incorporated administration of 10 mg tadalafil daily for 10 days.ResultsSystemic exposure in the elderly was 25% greater than in young subjects (mean AUC ratio 1.25; 90% confidence interval 0.972, 1.61). The AUC was 19% lower in subjects with diabetes mellitus than in healthy age/gender‐matched controls. Pharmacokinetics in female subjects were essentially similar to those in males. Exposure in subjects with mild or moderate renal insufficiency was approximately twice that in healthy subjects. The mean AUC for the major metabolite (total methylcatechol glucuronide) in the presence of ESRF was three times the mean for healthy subjects. Haemodialysis contributed negligibly to elimination of tadalafil or the metabolite. Hepatic impairment had negligible effects on exposure. The most common adverse events in these six studies were headache, back pain and myalgia. A 10‐mg dose was not well tolerated by subjects with moderate renal dysfunction in this study.ConclusionsNo clinically significant effect of gender, age, diabetes mellitus or hepatic impairment on tadalafil pharmacokinetics was observed. Renal insufficiency resulted in increased systemic exposure. Tadalafil was not associated with any serious clinically significant adverse events or study discontinuations due to adverse events.
Why do we still use stepwise modelling in ecology and behaviour?
Authors: WHITTINGHAM MARK J. , STEPHENS PHILIP A. , BRADBURY RICHARD B. , FRECKLETON ROBERT P. 
Published: July 2006

Summary

The biases and shortcomings of stepwise multiple regression are well established within the statistical literature. However, an examination of papers published in 2004 by three leading ecological and behavioural journals suggested that the use of this technique remains widespread: of 65 papers in which a multiple regression approach was used, 57% of studies used a stepwise procedure.
The principal drawbacks of stepwise multiple regression include bias in parameter estimation, inconsistencies among model selection algorithms, an inherent (but often overlooked) problem of multiple hypothesis testing, and an inappropriate focus or reliance on a single best model. We discuss each of these issues with examples.
We use a worked example of data on yellowhammer distribution collected over 4 years to highlight the pitfalls of stepwise regression. We show that stepwise regression allows models containing significant predictors to be obtained from each year's data. In spite of the significance of the selected models, they vary substantially between years and suggest patterns that are at odds with those determined by analysing the full, 4‐year data set.
An information theoretic (IT) analysis of the yellowhammer data set illustrates why the varying outcomes of stepwise analyses arise. In particular, the IT approach identifies large numbers of competing models that could describe the data equally well, showing that no one model should be relied upon for inference.
Inhibition of rot translation by RNAIII, a key feature of agr function
Authors: Geisinger Edward , Adhikari Rajan P. , Jin Ruzhong , Ross Hope F. , Novick Richard P. 
Published: July 2006

SummaryRNAIII is a 514 nt regulatory RNA that is the effector molecule of the staphylococcal agr quorum‐sensing system, regulating a large set of virulence and other accessory genes at the level of transcription. RNAIII was discovered nearly 20 years ago and we long ago hypothesized that it would function by regulating the synthesis or activity of one or more intermediary transcription factors. We have finally confirmed this hypothesis, showing that Staphylococcus aureus RNAIII regulates the synthesis of a major pleiotropic transcription factor, Rot, by blocking its translation. RNAIII has a complex secondary structure with several stable hairpins that have highly C‐rich end loops, unusual in an AT‐rich organism. We noted that these loops are complementary to two G‐rich stem loops of the rot mRNA translation initiation region (TIR). Pairing of the complementary RNAs would be predicted to occlude the rot Shine–Dalgarno (SD) site and to block rot translation. Through a combination of transcriptional and translational fusions and Northern and Western blot hybridization analyses, we show that RNAIII does, indeed, block rot translation. Through alterations in the C‐rich loops of RNAIII and the G‐rich loops of rot, we show that the sequences of these loops are critical for inhibition of rot translation and suggest that this inhibition is affected by pairing between the complementary stem loops, followed by the cleavage of rot mRNA. We propose that the RNAIII–rot mRNA interaction plays a key role in agr regulation of staphylococcal virulence.
Regulation by blue light and heat shock of gene transcription in the fungus Phycomyces: proteins required for photoinduction and mechanism for adaptation to light
Authors: Rodríguez‐Romero Julio , Corrochano Luis M. 
Published: July 2006

SummaryThe gene hspA for the heat‐shock protein HSP100 is induced by blue light and heat shock in the zygomycete fungus Phycomyces blakesleeanus. We have investigated the molecular details of the regulation of hspA gene transcription. We have cloned 1.9 kb of hspA upstream DNA sequence and identified many DNA segments possibly involved in heat‐shock and blue‐light regulation. We have identified several gene products required for hspA photoactivation and found that they are also required for mycelial photoresponses, a suggestion for a common signal transduction pathway. In addition, we have found that beta‐carotene, or a chemical derivative, is required for hspA gene photoactivation. The activation of hspA after blue light‐exposure or a heat shock is transient, suggesting the adaptation to the stimulus. The adaptation of hspA photoactivation seems to be the result of a novel mechanism causing a light‐dependent loss of gene transcription. We propose that a reduction in the amount of MADA, a putative flavin‐binding zinc‐finger protein, in light‐exposed mycelia may cause a reduced hspA photoactivation, providing a simple explanation for adaptation to light.
The biosynthetic pathway for aurofusarin in Fusarium graminearum reveals a close link between the naphthoquinones and naphthopyrones
Authors: Frandsen Rasmus J. N. , Nielsen Nikoline J. , Maolanon Nicolai , Sørensen Jens C. , Olsson Stefan , Nielsen John , Giese Henriette 
Published: July 2006

SummaryFungal polyketide biosynthesis typically involves multiple enzymatic steps and the encoding genes are often found in gene clusters. A gene cluster containing PKS12, the polyketide synthase gene responsible for the synthesis of the pigment aurofusarin, was analysed by gene replacement using Agrobacterium tumefaciens‐mediated transformation to determine the biosynthesis pathway of aurofusarin. Replacement of aurR1 with hygB shows that it encodes a positively acting transcription factor that is required for the full expression of PKS12, aurJ, aurF, gip1 and FG02329.1, which belong to the gene cluster. AurR1 and PKS12 deletion mutants are unable to produce aurofusarin and rubrofusarin. Bio‐ and chemoinformatics combined with chemical analysis of replacement mutants (ΔaurJ, ΔaurF, Δgip1, ΔaurO and ΔPKS12) indicate a five‐step enzyme catalysed pathway for the biosynthesis of aurofusarin, with rubrofusarin as an intermediate. This links the biosynthesis of naphthopyrones and naphthoquinones together. Replacement of the putative transcription factor aurR2 results in an increased level of rubrofusarin relative to aurofusarin. Gip1, a putative laccase, is proposed to be responsible for the dimerization of two oxidized rubrofusarin molecules resulting in the formation of aurofusarin.