bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anxiety disorders in anorexia nervosa and bulimia nervosa: co-morbidity and chronology of appearance
Authors: Godart N.T. , Flament M.F. , Lecrubier Y. , Jeammet P. 
Published: January 2003

SummaryThe objectives of the study were to assess lifetime prevalence of specific anxiety disorders, and their age of onset relative to that of eating disorders (ED), in a French sample of patients with anorexia nervosa (AN) or bulimia nervosa (BN). We assessed frequencies of seven anxiety disorders and childhood histories of separation anxiety disorder among 63 subjects with a current DSM-IV diagnosis of an ED, using the Composite International Diagnostic Interview (CIDI). Eighty-three percent of subjects with AN and 71% of those with BN had at least one lifetime diagnosis of an anxiety disorder. By far, the most frequent was social phobia (55% of the anorexics and 59% of the bulimics). When present, the co-morbid anxiety disorder had predated the onset of the ED in 75% of subjects with AN, and 88% of subjects with BN. Our results are consistent with those of studies conducted in other countries, and show that an anxiety disorder frequently exists before an ED. This has to be taken in consideration for successful treatment of patients with AN or BN.
Trends in the prevalence of social phobia in the United States: a synthetic cohort analysis of changes over four decades
Authors: Heimberg R.G. , Stein M.B. , Hiripi E. , Kessler R.C. 
Published: January 2003

SummaryPrevious analysis of data from the U.S. National Comorbidity Survey (NCS) suggested that the lifetime prevalence of social phobia in the community has increased significantly in recent cohorts. Furthermore, a latent class analysis of NCS data revealed two primary classes of persons with social phobia: those with exclusive speaking fears and those with one or more other social-evaluative fears. Social phobia in the other social fear group is more persistent, more impairing, and more highly co-morbid with other DSM-III-R disorders. The current report presents data on whether the cohort effect is a general aspect of social phobia or is specific to one of the NCS social phobia subtypes, and whether the cohort effect varies as a function of socio-demographic characteristics. Data were drawn from the NCS. Social phobia was assessed with a revised version of the Composite International Diagnostic Interview. Retrospective age of onset reports were used to estimate Kaplan-Meier survival curves for first onset of social phobia in each cohort represented in the survey. Comparison of these curves allowed us to make synthetic estimates based on retrospective reports of intercohort trends in lifetime prevalence. The lifetime prevalence of social phobia appears to have increased in recent cohorts. However, this increase does not exist among social phobics with exclusive fears of speaking. The increase is most pronounced among white, educated, and married persons, and it is not explained by increased co-morbidity with other mental disorders. The fact that the cohort effect is more pronounced for social phobia with one or more non-speaking fears is important in that this is generally a more severe form of the disorder with an earlier age of onset than social phobia with pure speaking fears. The fact that the cohort effect is most pronounced among people with social and economic advantage (i.e., white, married, well-educated) is intriguing and raises questions about the etiologic process that warrant further study in future research.
Epidemiology of social phobia: a clinical approach
Authors: Faravelli C. , Zucchi T. , Viviani B. , Salmoria R. , Perone A. , Paionni A. , Scarpato A. , Vigliaturo D. , Rosi S. , D’adamo D. , Bartolozzi D. , Cecchi C. , Abrardi L. 
Published: January 2003

SummaryThe recent epidemiologic studies report extremely varied rates for social phobia (SP). One of the reasons for this may be the difficulty in diagnosing SP, the boundaries of which are uncertain. A community survey was carried out using doctors with experience in clinical psychiatry as interviewers, and a clinical diagnostic instrument. Two thousand three hundred and fifty-five people (out of the 2,500 randomly selected from the population) living in Sesto Fiorentino, a suburb of Florence, Italy, were interviewed by their own general practitioner, using the MINI plus six additional questions. Six hundred and ten of the 623 subjects that were found positive for any form of psychopathology at the screening interview, and 57 negative subjects, were re-interviewed by residents in psychiatry using the Florence Psychiatric Interview (FPI). The FPI is a validated composite instrument that has the format of a structured clinical research record. It was found that 6.58% of subjects showed social anxiety not attributable to other psychiatric or medical conditions during their life. Social or occupational impairments meeting DSM-IV diagnostic requirements for SP was detected in 76 subjects (lifetime prevalence = 3.27%). Correction for age raises the lifetime expected prevalence to 4%. Sex ratio was approximately (F:M) 2:1. The most common fear was speaking in public (89.4%), followed by entering a room occupied by others (63.1%) and meeting with strangers (47.3%). Eighty-six point nine percent of subjects with SP complained of more than one fear. The mean age of onset (when the subjects first fully met DSM-IV criteria for SP) was 28.8 years, but the first symptoms of SP usually occurred much earlier, with a mean age of onset at 15.5 years. Ninety-two percent of cases with SP also showed at least one other co-morbid psychiatric disorder during their life. Lifetime prevalence of avoidant personality disorder (APD) was 3.6%. Forty-two point nine percent of cases with SP also had APD, whereas 37.9% of cases with APD developed SP.
A European perspective on social anxiety disorder
Authors: Lecrubier Y. , Wittchen H.U. , Faravelli C. , Bobes J. , Patel A. , Knapp M. 
Published: January 2003

SummaryEpidemiologic surveys conducted across Europe indicate that the lifetime prevalence of social anxiety disorder in the general population is close to 7%. The disorder in adulthood rarely presents in its ‘pure’ form and 70–80% of patients have at least one other psychiatric disorder, most commonly depression. Social anxiety disorder is a risk factor for the development of depression and alcohol/substance use or dependence, especially in cases with an early onset (< 15 years). Individuals with social anxiety disorder have significant functional impairment, notably in the areas of initiation and maintenance of social/romantic relationships and educational and work achievement. The economic consequences of social anxiety disorder are considerable, with a high level of diminished work productivity, unemployment and an increased utilisation of medical services amongst sufferers. Effective treatment of social anxiety disorder would improve its course and its health and economic consequences.
Up‐regulation of kinin B1 receptor in the lung of streptozotocin‐diabetic rat: autoradiographic and functional evidence
Authors: Vianna Rose Mari J , Ongali Brice , Regoli Domenico , Calixto João Batista , Couture Réjean 
Published: January 2003

The function and autoradiographic binding expression of kinin B1 receptors were evaluated in the lungs of Streptozotocin (STZ)‐diabetic rats.
The intrapleural injection (i.pl.) of des‐Arg9‐bradykinin (des‐Arg9‐BK) (50 and 100 nmol per site), a selective B1 receptor agonist, increased time‐dependently the mononuclear and neutrophil cells influx in the pleural cavity of rats treated with STZ (65 mg kg−1, i.p., 4 days earlier). This effect was significantly less in control rats.
The influx of mononuclear and polymorphonuclear neutrophil cells induced by des‐Arg9‐BK was significantly inhibited by two B1 receptor antagonists (des‐Arg10‐Hoe140 or R‐715, 100 nmol per site, 5 min earlier), but not by two B2 receptor antagonists (Hoe140, 10 nmol or NPC 18884, 100 nmol per site, 5 min earlier). However, Hoe140 prevented the higher basal leukocyte influx seen in STZ‐diabetic rats.
Leukocyte infiltration induced by des‐Arg9‐BK in STZ‐diabetic rats was significantly reduced after treatment with insulin (2 U per day, s.c. over 4 days) or with an anti‐PMN antibody (0.1 ml of a 1 : 20 dilution, i.pl. 5 min earlier).
Specific B1 receptor binding sites were seen in lung sections from both control and STZ‐diabetic rats, yet the density of labelling was much greater in diabetic rats and particularly after intrapleural injection of des‐Arg9‐BK. Treatment with insulin or with the anti‐PMN antibody markedly reduced B1 receptor binding sites occurring after the injection of des‐Arg9‐BK in STZ‐diabetic rats.
Data suggest that the B1 receptor is up‐regulated in the lungs of STZ‐diabetic rats, and its activation increases leukocyte infiltration into the pleural cavity. The overexpression of B1 receptors seems to depend on neutrophils influx and appears to be associated with hyperglycaemia.

British Journal of Pharmacology (2003) 138, 13–22. doi:10.1038/sj.bjp.0704999
5‐hydroxyindole causes convulsions and increases transmitter release in the CA1 region of the rat hippocampus
Authors: Mannaioni Guido , Carpenedo Raffaella , Moroni Flavio 
Published: January 2003

5‐hydroxyindole (5‐OHi) is a proposed tryptophan metabolite able to cause convulsions when systemically injected into rodents. We studied its effects using microdialysis in vivo and electrophysiological approaches in vitro.
Local administration of 5‐OHi into the CA1 region of the rat hippocampus, via a microdialysis probe, significantly increased glutamate concentrations in the dialysates.
In rat hippocampal slices, using extracellular recordings in the CA1 region, 5‐OHi (30–300 μM) increased the amplitude of population spikes and fEPSPs.
In the same preparation, using intracellular recordings in CA1 pyramidal neurons, 5‐OHi reduced the latency of firing induced by direct depolarization and increased both evoked excitatory and slow inhibitory postsynaptic potential amplitudes, without affecting the resting membrane potential, the after‐hyperpolarization or the neuronal input resistance. It also altered GABAA‐mediated neurotransmission by increasing the frequency and the amplitude of pharmacologically isolated spontaneous inhibitory postsynaptic currents (sIPSC).
In separate experiments, performed by measuring AMPA or NMDA‐induced depolarization in cortical wedges, 5‐OHi did not modify glutamate receptor agonist responses.
Our results show that 5‐OHi causes convulsions, modifies the properties and the function of the hippocampal circuitry, and facilitates the output of both excitatory and inhibitory transmitters.

British Journal of Pharmacology (2003) 138, 245–253. doi:10.1038/sj.bjp.0705007
Unproductive cleavage and the inactivation of protease‐activated receptor‐1 by trypsin in vascular endothelial cells
Authors: Nakayama Tetsuzo , Hirano Katsuya , Shintani Yoshinobu , Nishimura Junji , Nakatsuka Akio , Kuga Hirotaka , Takahashi Shosuke , Kanaide Hideo 
Published: January 2003

Using fura‐2 fluorometry of [Ca2+]i in response to thrombin, trypsin and protease‐activated receptor activating peptides (PAR‐APs), we determined whether trypsin cleaves protease‐activated receptor 1 (PAR1) and activates it in the endothelial cells of the porcine aortic valves and human umbilical vein.
Once stimulated with thrombin, the subsequent application of trypsin induced a [Ca2+]i elevation similar to that obtained without the preceding stimulation with thrombin in the valvular endothelial cells. However, the preceding stimulation with trypsin abolished the subsequent response to thrombin, but not to bradykinin or substance P.
The response to PAR1‐AP (SFLLRNP) was significantly (P<0.05) reduced by the preceding stimulation with thrombin and PAR1‐AP in the valvular endothelial cells, while, importantly, it remained unaffected by the preceding stimulation with either trypsin or PAR2‐AP (SLIGRL). The response to PAR2‐AP was reduced by the preceding stimulation with trypsin and PAP2‐AP. PAR1‐AP attenuated the subsequent responses not only to thrombin and PAR1‐AP but also to trypsin and PAR2‐AP, while PAR2‐AP specifically attenuated the subsequent responses to trypsin and PAR2‐AP.
In human umbilical vein endothelial cells, a higher affinity PAR1‐AP (haPAR1‐AP) (Ala‐pF‐Arg‐Cha‐HArg‐Tyr‐NH2) specifically attenuated the responses to thrombin but not trypsin. On the other hand, the response to haPAR1‐AP was significantly (P<0.05) attenuated by the preceding stimulation with thrombin but not trypsin.
In conclusion, trypsin cleaved PAR1 but did not activate it in the endothelial cells. Moreover, the trypsin‐cleaved PAR1 was no longer responsive to thrombin.

British Journal of Pharmacology (2003) 138, 121–130. doi:10.1038/sj.bjp.0705008
Butyrylcholinesterase and acetylcholinesterase activity and quantal transmitter release at normal and acetylcholinesterase knockout mouse neuromuscular junctions
Authors: Minic Jasmina , Chatonnet Arnaud , Krejci Eric , Molgó Jordi 
Published: January 2003

The present study was performed to evaluate the presence and the physiological consequences of butyrylcholinesterase (BChE) inhibition on isolated phrenic‐hemidiaphragm preparations from normal mice expressing acetylcholinesterase (AChE) and BChE, and from AChE‐knockout mice (AChE−/−) expressing only BChE.
Histochemical and enzymatic assays revealed abundance of AChE and BChE in normal mature neuromuscular junctions (NMJs).
In normal NMJs, in which release was reduced by low Ca2+/high Mg2+ medium BChE inhibition with tetraisopropylpyrophosphoramide (iso‐OMPA) or bambuterol decreased (∼50%) evoked quantal release, while inhibition of AChE with fasciculin‐1, galanthamine (10, 20 μM) or neostigmine (0.1–1 μM) increased (50–80%) evoked quantal release. Inhibition of both AChE and BChE with galanthamine (80 μM), neostigmine (3–10 μM), O‐ethylS‐2‐(diisopropylamino)ethyl‐methylphosphono‐thioate (MTP) or phospholine decreased evoked transmitter release (20–50%).
In AChE−/− NMJs, iso‐OMPA pre‐treatment decreased evoked release.
Muscarinic toxin‐3 decreased evoked release in both AChE−/− and normal NMJs treated with low concentrations of neostigmine, galanthamine or fasciculin‐1, but had no effect in normal NMJs pretreated with iso‐OMPA, bambuterol, MTP and phospholine.
In normal and AChE−/− NMJs pretreatment with iso‐OMPA failed to affect the time course of miniature endplate potentials and full‐sized endplate potentials.
Overall, our results suggest that inhibition or absence of AChE increases evoked quantal release by involving muscarinic receptors (mAChRs), while BChE inhibition decreases release through direct or indirect mechanisms not involving mAChRs. BChE apparently is not implicated in limiting the duration of acetylcholine action on postsynaptic receptors, but is involved in a presynaptic modulatory step of the release process.

British Journal of Pharmacology (2003) 138, 177–187. doi:10.1038/sj.bjp.0705010
Pertussis toxin sensitive and insensitive effects of adenosine and carbachol in murine atria overexpressing A1‐adenosine receptors
Authors: Neumann Joachim , Boknik Peter , Matherne G Paul , Lankford Amy , Schmitz Wilhelm 
Published: January 2003

It was investigated how A1‐adenosine receptor overexpression alters the effects of carbachol on force of contraction and beating rate in isolated murine atria. Moreover, the influence of pertussis toxin on the inotropic and chronotropic effects of adenosine and carbachol in A1‐adenosine receptor overexpressing atria was studied.
Adenosine and carbachol alone exerted negative inotropic and chronotropic effects in electrically driven left atrium or spontaneously beating right atrium of wild‐type mice.
These effects were abolished or reversed by pre‐treatment of animals with pertussis toxin which can interfere with signal transduction through G‐proteins.
Adenosine and carbachol exerted positive inotropic but negative chronotropic effects in atrium overexpressing A1‐adenosine receptors from transgenic mice.
The positive inotropic effects of adenosine and carbachol were qualitatively unaltered whereas the negative chronotropic effects were abolished or reversed in atrium overexpressing A1‐adenosine receptors after pre‐treatment by pertussis toxin.
Qualitatively similar effects for adenosine and carbachol were noted in the presence of isoprenaline, β‐adrenoceptor agonist.
It is concluded that overexpression of A1‐adenosine receptors also affects the signal transduction of other heptahelical, G‐protein coupled receptors like the M‐cholinoceptor in the heart. The chronotropic but not the inotropic effects of adenosine and carbachol in transgenic atrium were mediated via pertussis toxin sensitive G‐proteins.

British Journal of Pharmacology (2003) 138, 209–217. doi:10.1038/sj.bjp.0705012
Restoration of chronic‐ Δ9‐THC‐induced decline in sexuality in male rats by a novel benzoflavone moiety from Passiflora incarnata Linn
Authors: Dhawan Kamaldeep , Sharma Anupam 
Published: January 2003

The present study comprised treatment of healthy male rats with Δ9‐tetrahydrocannabinol (THC, 10 mg kg−1, p.o.), and combinations of THC with benzoflavone moiety (BZF, 10 and 20 mg kg−1, p.o.) isolated from Passiflora incarnata Linneaus, over a period of 30 days.
Upon 30‐days chronic administrations, the THC‐treated male rats had a significant loss of libido (mounting behaviour with non‐oestrous female rats), decrease in sperm count, and number of impregnated pro‐estrous female rats.
Co‐administration of BZF (10 and 20 mg kg−1 p.o.) afforded significant protection against the chronic‐THC‐induced decrease in libido, mating performance and fertility during 30‐day experimental regimen. The 20 mg kg−1 dose of BZF exhibited better results.
Upon discontinuation of THC, treatment with BZF (10 and 20 mg kg−1 p.o.) also facilitated the early restoration chronic‐THC‐induced decline in libido, sperm count and sexual fertility within 7 days.

British Journal of Pharmacology (2003) 138, 117–120. doi:10.1038/sj.bjp.0705015
ADP stimulation of inositol phosphates in hepatocytes: role of conversion to ATP and stimulation of P2Y2 receptors
Authors: Dixon C Jane , Hall John F , Boarder Michael R 
Published: January 2003

Accumulation of inositol (poly)phosphates (InsPx) has been studied in rat hepatocytes labelled with [3H]inositol. Stimulation with ADP resulted in a significant increase in total [3H]InsPx, whereas 2‐MeSADP had only a small effect and ADPβS was ineffective. UTP and ITP also stimulated substantial increases in [3H]InsPx.
The dose–response curve to ADP was largely unaltered by the presence of the P2Y1 antagonist, adenosine‐3′‐phosphate‐5′‐phosphate (A3P5P). Similarly, inclusion of MRS 2179, a more selective P2Y1 antagonist, had no effect on the dose–response curve to ADP.
The inclusion of hexokinase in the assay reduced, but did not abolish, the response to ADP.
HPLC analysis revealed that ADP in the medium was rapidly converted to AMP and ATP. The inclusion of hexokinase removed ATP, but exacerbated the decline in ADP concentration, leading to increased levels of AMP. 2‐MeSADP was stable in the medium and ATP was largely unaffected.
The addition of the adenylate kinase inhibitor, diadenosine pentaphosphate (Ap5A) significantly reduced the ADP response. HPLC analysis conducted in parallel demonstrated that this treatment inhibited conversion of ADP to ATP and AMP.
Inclusion of the P1 antagonist CGS 15943 had no effect on the dose–response curve to ADP.
These observations indicate that hepatocytes respond to ADP with an increase in inositol (poly)phosphates following conversion to ATP. P2Y1 activation in hepatocytes does not appear to be coupled to inositol 1,4,5‐trisphosphate (Ins(1,4,5)P3) production.

British Journal of Pharmacology (2003) 138, 272–278. doi:10.1038/sj.bjp.0705016
Interaction between cysteines introduced into each transmembrane domain of the rat P2X2 receptor
Authors: Spelta Valeria , Jiang Lin‐Hua , Bailey R Jayne , Surprenant Annmarie , North R Alan 
Published: January 2003

ATP‐gated ion channels (P2X receptors) contain two hydrophobic segments that are presumed to span the plasma membrane (TM1 and TM2). Pairs of cysteines were introduced by mutagenesis into the rat P2X2 receptor, one in TM1 one in TM2, at positions where single substitutions have previously been shown to confer sensitivity to methanethiosulfonates. The receptors were expressed in HEK293 cells; interactions between the cysteines were sought by measuring the effects on ionic currents of dithiothreitol and methanethiosulfonates.
Nine pairs gave normally functioning channels: F44C/I328C, F44C/N333C, F44C/L338C, Q37C/I328C, Q37C/N333C, Q37C/T336C, Q37C/L338C, G30C/I328C, G30C/N333C. None formed functionally detectable disulfide bonds.
Currents at the F44C/L338C receptor had time course and ATP‐sensitivity similar to those for the F44C mutation alone. Methyl‐methanethiosulfonate bound to L338C but did not inhibit ionic current. Methyl‐methanethiosulfonate inhibited currents at F44C, but not at F44C/L338C.
Ethylammonium‐methylthiosulfonate inhibited currents at both F44C and L338C, but not at F44C/L338C. It reversed the rapid current deactivation at F44C/L338C.
The results suggest that a methanethiosulfonate binding to L338C prevents binding to F44C; this might indicate proximity of these two residues.

British Journal of Pharmacology (2003) 138, 131–136. doi:10.1038/sj.bjp.0705018
Adrenergic mechanisms in canine nasal venous systems
Authors: Wang Min , Lung Mary A 
Published: January 2003

We investigated the adrenergic mechanisms of the two venous systems that drain the nasal mucosa, thereby their exact role in eliciting nasal decongestion. The action of endogenously released noradrenaline and exogenous adrenergic agonists on different segments of the nasal venous systems, i.e. collecting (LCV, SCV) and outflow (SPV) veins of posterior venous system, collecting (ACV) and outflow (DNV) veins of anterior venous system and venous sinusoids of the septal mucosa (SM), were studied. In vitro isometric tension of the vascular segments was measured.
Transmural nerve stimulation (TNS) produced constriction in ACV, DNV and SM, primary constriction followed by secondary dilatation in LCV and SCV and dilatation in SPV. Tetrodotoxin (10−6 M) abolished all responses. Phentolamine (10−6 M), prazosin (10−6 M) and rauwolscine (10−7 M) inhibited the constriction in all venous vessels. Propranolol (10−6 M), atenolol (10−6 M) and ICI 118,551 (10−6 M) inhibited the relaxation in SPV but not in LCV and SCV. Phenylephrine and clonidine constricted whereas dobutamine and terbutaline relaxed all venous vessels dose‐dependently.
These results indicate α1‐, α2‐, β1‐ and β2‐adrenoceptors are present in both venous systems. TNS causes constriction of anterior venous system, venous sinusoids and posterior collecting veins primarily via postjunctional α2‐adrenoceptors but relaxation of posterior outflow vein equally via postjunctional β1‐ and β2‐adrenoceptors. The combined action of the two adrenergic mechanisms can reduce nasal airway resistance in vivo by decreasing vascular capacitance and enhancing venous drainage via the posterior venous system.

British Journal of Pharmacology (2003) 138, 145–155. doi:10.1038/sj.bjp.0705020