bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterisation of opioid receptors involved in modulating circular and longitudinal muscle contraction in the rat ileum
Authors: Gray Andrew C , White Paul J , Coupar Ian M 
Published: January 2005

The aim of the present investigation was to characterise the opioid receptor subtypes present in the rat ileum using a method that detects drug action on the enteric nerves innervating the circular and longitudinal muscles.
Neurogenic contractions were reversibly inhibited by morphine (circular muscle pEC50, 6.43±0.17, Emax 81.7±5.0%; longitudinal muscle pEC50, 6.65±0.27, Emax 59.7±7.8%), the μ‐opioid receptor‐selective agonist, DAMGO ([D‐Ala2,N‐Me‐Phe4,Gly5‐ol]enkephalin acetate) (circular pEC50, 7.85±0.04, Emax 97.8±3.6%; longitudinal pEC50, 7.35±0.09, Emax 56.0±6.1%), the δ‐selective agonist DADLE ([D‐Ala2,D‐Leu5]enkephalin acetate) (circular pEC50, 7.41±0.17, Emax, 93.3±8.4%; longitudinal pEC50, 6.31±0.07, Emax 66.5±5.2%) and the κ‐selective agonist U 50488H (trans‐(±)‐3,4‐dichloro‐N‐methyl‐N‐[2‐(1‐pyrrolidinyl)cyclohexyl]benzeneacetamide methanesulphonate) (circular pEC50, 5.91±0.41, Emax, 83.5±26.8%; longitudinal pEC50, 5.60±0.08, Emax 74.3±7.2%). Agonist potencies were generally within expected ranges for activity at the subtype for which they are selective, except for U 50488H, which was less potent than expected.
The μ and δ receptor‐selective antagonists, CTAP (H‐D‐Phe‐Cys‐Tyr‐D‐Trp‐Arg‐Thr‐Pen‐Thr‐NH2) and naltrindole, caused progressive, parallel rightward shifts in the DAMGO and DADLE curves, respectively. Analysis indicated conformity to theoretical simple competitive antagonist behaviour. U 50488H effects were insensitive to the κ‐selective antagonist, n‐BNI. A high concentration (1 μM) of naltrexone caused apparent potentiation of U 50488H effects.
CTAP pKB estimates were consistent with previously reported values for μ receptor antagonism (circular 7.84±0.17, longitudinal 7.64±0.35). However, the naltrindole pKB estimates indicated lower antagonist potency than expected (circular 8.22±0.23, longitudinal 8.53±0.35).
It is concluded that μ and possibly atypical δ receptors (but not κ receptors) mediate inhibition of contraction in this model. Nonopioid actions of U 50488H are probably responsible for the inhibitory effects seen with this compound.

British Journal of Pharmacology (2005) 144, 687–694. doi:10.1038/sj.bjp.0706107
Relationship between brain serotonin transporter binding, plasma concentration and behavioural effect of selective serotonin reuptake inhibitors
Authors: Hirano Kazufumi , Kimura Ryohei , Sugimoto Yumi , Yamada Jun , Uchida Shinya , Kato Yasuhiro , Hashimoto Hisakuni , Yamada Shizuo 
Published: January 2005

The present study was undertaken to characterise the relationship between in vivo brain serotonin transporter (SERT) binding, plasma concentration and pharmacological effect of selective serotonin reuptake inhibitors (SSRIs) in mice. Oral administration of fluvoxamine, fluoxetine, paroxetine and sertraline at pharmacologically relevant doses exerted dose‐ and time‐dependent binding activity of brain SERT as revealed by significant increases in KD for specific [3H]paroxetine binding, and the in vivo SERT‐binding potency was in the order of paroxetine≫fluoxetine, sertraline>fluvoxamine.
The time courses of brain SERT binding by SSRIs in mice were mostly in parallel to those of their plasma concentrations. Also, norfluoxetine (active metabolite) has been suggested to contribute largely to the long‐lasting binding activity of brain SERT after the fluoxetine administration.
Oral administration of each SSRI suppressed significantly the marble‐burying behaviour with no change in locomotor activity in mice, and the extent and time course of suppression agreed well with those of brain SERT binding. Thus, the pharmacological potencies of SSRIs in the attenuation of marble‐burying behaviour correlated significantly with their brain SERT binding activities.
In conclusion, the present study has provided the first in vivo evidences to support that fluvoxamine, fluoxetine, paroxetine and sertraline orally administered bind to the pharmacologically relevant brain SERT in mice and that their SERT‐binding characteristics is closely associated with the pharmacokinetics and inhibition of marble‐burying behaviour.

British Journal of Pharmacology (2005) 144, 695–702. doi:10.1038/sj.bjp.0706108
Role of descending noradrenergic system and spinal α2‐adrenergic receptors in the effects of gabapentin on thermal and mechanical nociception after partial nerve injury in the mouse
Authors: Tanabe Mitsuo , Takasu Keiko , Kasuya Noriyo , Shimizu Shinobu , Honda Motoko , Ono Hideki 
Published: January 2005

To gain further insight into the mechanisms underlying the antihyperalgesic and antiallodynic actions of gabapentin, a chronic pain model was prepared by partially ligating the sciatic nerve in mice. The mice then received systemic or local injections of gabapentin combined with either central noradrenaline (NA) depletion by 6‐hydroxydopamine (6‐OHDA) or α‐adrenergic receptor blockade.
Intraperitoneally (i.p.) administered gabapentin produced antihyperalgesic and antiallodynic effects that were manifested by elevation of the withdrawal threshold to a thermal (plantar test) or mechanical (von Frey test) stimulus, respectively.
Similar effects were obtained in both the plantar and von Frey tests when gabapentin was injected intracerebroventricularly (i.c.v.) or intrathecally (i.t.), suggesting that it acts at both supraspinal and spinal loci. This novel supraspinal analgesic action of gabapentin was only obtained in ligated neuropathic mice, and gabapentin (i.p. and i.c.v.) did not affect acute thermal and mechanical nociception.
In mice in which central NA levels were depleted by 6‐OHDA, the antihyperalgesic and antiallodynic effects of i.p. and i.c.v. gabapentin were strongly suppressed.
The antihyperalgesic and antiallodynic effects of systemic gabapentin were reduced by both systemic and i.t. administration of yohimbine, an α2‐adrenergic receptor antagonist. By contrast, prazosin (i.p. or i.t.), an α1‐adrenergic receptor antagonist, did not alter the effects of gabapentin.
It was concluded that the antihyperalgesic and antiallodynic effects of gabapentin are mediated substantially by the descending noradrenergic system, resulting in the activation of spinal α2‐adrenergic receptors.

British Journal of Pharmacology (2005) 144, 703–714. doi:10.1038/sj.bjp.0706109
Effects of diltiazem and nifedipine on transient outward and ultra‐rapid delayed rectifier potassium currents in human atrial myocytes
Authors: Gao Zhan , Sun Haiying , Chiu Shui‐Wah , Lau Chu‐Pak , Li Gui‐Rong 
Published: January 2005

It is unknown whether the widely used L‐type Ca2+ channel antagonists diltiazem and nifedipine would block the repolarization K+ currents, transient outward current (Ito1) and ultra‐rapid delayed rectifier K+ current (IKur), in human atrium. The present study was to determine the effects of diltiazem and nifedipine on Ito1 and IKur in human atrial myocytes with whole‐cell patch‐clamp technique.
It was found that diltiazem substantially inhibited Ito1 in a concentration‐dependent manner, with an IC50 of 29.2±2.4 μM, and nifedipine showed a similar effect (IC50=26.8±2.1 μM). The two drugs had no effect on voltage‐dependent kinetics of the current; however, they accelerated Ito1 inactivation significantly, suggesting an open channel block.
In addition, diltiazem and nifedipine suppressed IKur in a concentration‐dependent manner (at +50 mV, IC50=11.2±0.9 and 8.2±0.8 μM, respectively). These results indicate that the Ca2+ channel blockers diltiazem and nifedipine substantially inhibit Ito1 and IKur in human atrial myocytes.

British Journal of Pharmacology (2005) 144, 595–604. doi:10.1038/sj.bjp.0706113
Capsaicin exhibits neuroprotective effects in a model of transient global cerebral ischemia in Mongolian gerbils
Authors: Pegorini Simona , Braida Daniela , Verzoni Chiara , Guerini‐Rocco Chiara , Consalez Gian Giacomo , Croci Laura , Sala Mariaelvina 
Published: January 2005

Capsaicin, the irritant principle of hot peppers, is a vanilloid agonist known to activate the transient receptor potential channel vanilloid subfamily member 1 (VR1), recently reported to be involved in neurodegeneration. The present study investigated the role of VR1 in a model of global cerebral ischemia in gerbils.
Over the dose range tested, capsaicin (0.01, 0.025, 0.05, 0.2 and 0.6 mg kg−1), given 5 min after recirculation, dose‐dependently antagonized the ischemia‐induced electroencephalographic total spectral power decrease and restored relative frequency band distribution evaluated 7 days after ischemia.
Capsaicin, at all tested doses, fully prevented ischemia‐induced hyperlocomotion evaluated 1 day after ischemia.
Capsaicin dose‐dependently antagonized ischemia‐induced memory impairment evaluated in a passive avoidance task, 3 days after ischemia.
Capsaicin showed a dose‐dependent hypothermic effect evaluated for 2 h after recirculation.
At 7 days after ischemia, a progressive survival of pyramidal cells in the CA1 subfield in capsaicin‐treated gerbils, with a maximum of 80%, at a dose of 0.2 mg kg−1, was obtained.
The selective VR1 antagonist, capsazepine (0.01 mg kg−1), reversed capsaicin‐induced protective effects, in a competitive manner.
These results suggest that the neuroprotective effect of capsaicin may be attributable, at least in part, to VR1 desensitization and provide a valuable target for development of interventional pharmacological strategies.

British Journal of Pharmacology (2005) 144, 727–735. doi:10.1038/sj.bjp.0706115
Biomarkers in nutritional epidemiology
Authors: Bingham Sheila A 
Published: January 2005

AbstractObjective:To illustrate biomarkers of diet that can be used to validate estimates of dietary intake in the study of gene–environment interactions in complex diseases.Design:Prospective cohort studies, studies of biomarkers where diet is carefully controlled.Setting:Free–living individuals, volunteers in metabolic suites.Subjects:Male and female human volunteers.Results:Recent studies using biomarkers have demonstrated substantial differences in the extent of measurement error from those derived by comparison with other methods of dietary assessment. The interaction between nutritional and genetic factors has so far largely gone uninvestigated, but can be studied in epidemiological trials that include collections of biological material. Large sample sizes are required to study interactions, and these are made larger in the presence of measurement errors.Conclusions:Diet is of key importance in affecting the risk of most chronic diseases in man. Nutritional epidemiology provides the only direct approach to the quantification of risks. The introduction of biomarkers to calibrate the measurement error in dietary reports, and as additional measures of exposure, is a significant development in the effort to improve estimates of the magnitude of the contribution of diet in affecting individual disease risk within populations. The extent of measurement error has important implications for correction for regression dilution and for sample size. The collection of biological samples to improve and validate estimates of exposure, enhance the pursuit of scientific hypotheses, and enable gene–nutrient interactions to be studied, should become the routine in nutritional epidemiology.
Measurement of household food security in the USA and other industrialised countries
Authors: Radimer Kathy L , Radimer Kathy L 
Published: January 2005

Abstract Objective: To describe the history and current status of household food security measurement.Conclusions:In the 1980s evidence of rising levels of hunger was a concern for many, but disputed by some, Americans. Acknowledgement and quantification of hunger was hindered by the lack of an accepted definition and measure of hunger. Qualitative research at Cornell provided a conceptual framework, description, definition and survey items for hunger. The Community Childhood Hunger Identification Project developed an instrument used in numerous communities. Based upon these initiatives, widely accepted definitions of hunger and food insecurity, and the US Household Food Security Module for its measurement, now exist. The module classifies households as food-secure, or food-insecure without hunger or with moderate or severe hunger, and contains household-, adult- and child-referent items. Its inclusion in the Current Population Survey (CPS) since 1995 has yielded annual estimates of food insecurity. A six-item short form of the module, for surveys with severe time constraints, classifies households only as food-secure or food-insecure without or with hunger and contains no child-specific items. Surveys using the 18-item or short-form module can compare results with published national data from the CPS. Information about the module is available at http://www.ers.usda.gov/briefing/foodsecurity and http://www.fns.usda/fsec. Current research on food security measurement includes measurement of individual food insecurity and hunger, module performance regarding hunger duration and frequency, performance of the module in population subgroups, and the effect of translations on module meaning and performance. National surveys in Canada, New Zealand and Australia also have measured food security.
Transcutaneous penetration of toluene in rat skin a microdialysis study
Authors: Klede Monika , Schmitz Harald , Göen Thomas , Fartasch Manigé , Drexler Hans , Schmelz Martin 
Published: January 2005

Abstract:  Percutaneous absorption of lipophilic substances has major implications for therapeutical use or toxicological effects. We, therefore, using dermal microdialysis, measured local toluene concentrations and assessed the effects of duration of exposure, skin barrier disruption and the use of skin‐care products.Three microdialysis membranes (3000 kDa) were inserted intradermally at a length of 2 cm in the abdominal skin of 82 anaesthetized male Wistar rats. They were perfused with albumin solution (5%) at 10 µl/min. A skin area of 1.5 × 0.6 cm above the membranes was exposed to toluene (100%, 200 µl) for 15 or 240 min. Dialysate was sampled at 20‐min intervals. Using GC‐FPD (gas charomotography flame photometric detector), it was analysed for toluene. In addition, the effects of tape stripping and pretreatment with topical products were assessed. In each of the 12 permutations of exposure time, pretreatments and tape stripping, five to eight animals were investigated.Maximum toluene concentrations were reached at 60 min after exposure (3.07 ± 0.40 µg/ml, 15 min; 5.38 ± 0.92 µg/ml, 240 min). In 15‐min exposure experiments, dermal toluene concentrations decreased slowly to reach baseline values after 240 min. After 240‐min exposure, a plateau of approximately 6 µg/ml was reached after 60 min. Neither tape stripping nor the pretreatment with barrier cream induced a significant change on dermal toluene concentrations.The slow kinetics of toluene penetration results in a steep concentration gradient in the skin with very‐high local toluene concentrations and a delayed wash out, which might be relevant not only toxicologically, but also therapeutically.
What is the pathogenesis of acne?
Authors: Zouboulis C. C. , Eady A. , Philpott M. , Goldsmith L. A. , Orfanos C. , Cunliffe W. C. , Rosenfield R. 
Published: January 2005

Abstract:  For a long time, the mantra of acne pathogenesis debates has been that acne vulgaris lesions develop when (supposedly largely androgen‐mediated) increased sebum production, ductal hypercornification, and propionibacteria come together with local inflammatory process in the unlucky affected individual. And yet, the exact sequence, precise interdependence, and choreography of pathogenic events in acne, especially the ‘match that lights the fire’ have remained surprisingly unclear, despite the venerable tradition of acne research over the past century.However, exciting recent progress in this – conceptually long somewhat stagnant, yet clinically, psychologically, and socioeconomically highly relevant – everyday battlefield of skin pathology encourages one to critically revisit conventional concepts of acne pathogenesis. Also, this provides a good opportunity for defining more sharply key open questions and intriguing acne characteritics whose underlying biological basis has far too long remained uninvestigated, and to emphasize promising new acne research avenues off‐the‐beaten‐track – in the hope of promoting the corresponding development of innovative strategies for acne management.
Involvement of the EN‐2 gene in normal and abnormal development of the human arcuate nucleus
Authors: Lavezzi Anna Maria , Ottaviani Giulia , Mauri Maria , Terni Lorella , Matturri Luigi 
Published: January 2005

SummaryIn this study, we wanted to evaluate whether the engrailed EN‐2 gene, a homeobox gene with an essential role in the development of the rhombic lip derivatives in different species, is (1) expressed also in man in the differentiation process of the medullary arcuate nucleus (ArcN) and (2) involved in sudden unexplained perinatal and infant death, frequently related to developmental defects of the ArcN. We evaluated by means of the monoclonal antibody 4D9, exclusively recognizing engrailed‐2 protein, the expression of the EN‐2 gene in the ArcN on histological sections of the brainstems of 30 subjects aged from 17 gestational weeks to 10 postnatal months, who had died of known (17 cases) and unknown causes (13 cases). We observed in the greater number of the cases that the expression of the EN‐2 gene is very high in the ArcN neurons from the 17th to the 22nd gestational week, then decreases up to the first days after birth and later disappears. Moreover, in eight of the 13 sudden deaths (61%), a hypoplasia of the ArcN was present. In almost all of these cases, EN‐2 expression was negative. In conclusion, we support the role of the EN‐2 gene in the normal neuronal development and in the anatomic organization of the human ArcN as well as the possible existence of EN‐2 mutations related to hypoplasia of this nucleus.
Hepatocyte progenitors in man and in rodents – multiple pathways, multiple candidates
Authors: Laurson Joanna , Selden Clare , Hodgson Humphrey J. F. 
Published: January 2005

SummaryIn severe injury, liver‐cell progenitors may play a role in recovery, proliferating, and subsequently differentiating into mature liver cells. Identifying these progenitors has major therapeutic potential for ex vivo pharmaceutical testing, bioartificial liver support, tissue engineering and gene therapy protocols. Potential liver‐cell progenitors have been identified from bone marrow, peripheral blood, cord blood, foetal liver, adult liver and embryonic stem cells. Differences and similarities are found among cells isolated from rodents and humans. This review will discuss identifying markers and differentiation potential in in vitro and in vivo models of these putative progenitors in both humans and rodents.
Apoptosis in chronic viral hepatitis parallels histological activity: An immunohistochemical investigation using anti‐activated caspase‐3 and M30 Cytodeath antibody
Authors: McPartland Jo L. , Guzail Muna Ali , Kendall Charles H. , Pringle James Howard 
Published: January 2005

SummaryApoptosis is implicated as a major pathogenic mechanism in chronic hepatitis B and C. Previous studies of the relationship between apoptotic rates and histological necroinflammatory activity have produced conflicting results. Hepatocyte apoptosis was assessed in liver tissue from 32 cases of chronic viral hepatitis, seven cases of hepatocellular carcinoma (HCC) and six cases of steatohepatitis as non‐viral disease controls and eight cases of control liver. Apoptotic rates were measured using H&E morphological assessment and immunohistochemical staining with antibodies to activated caspase‐3 and M30. Histological necroinflammatory activity of viral hepatitis cases was scored using the Knodell scoring system, and the cases were divided according to their score into group 1 (mean 2.43 ± 0.48) and group 2 (mean 7.80 ± 0.49). Apoptotic indices were significantly higher in group 2 than group 1 using H&E (11.53 ± 2.70 vs. 0 ± 0, P = 0.015) and activated caspase‐3 (22.01 ± 5.27 vs. 1.79 ± 1.79, P = 0.03) methods but were not significantly higher with M30 (3.80 ± 1.74 vs. 0 ± 0, P = 0.207). Apoptotic scores using an antibody to activated caspase‐3 are significantly higher in cases of chronic viral hepatitis with greater histological necroinflammatory scores, supporting a central role for apoptosis in disease pathogenesis. This method offers an alternative to routine histological assessment for measuring disease activity.
Histopathology of spleen allograft rejection in miniature swine
Authors: Dor Frank J. M. F. , Gollackner Bernd , Kuwaki Kenji , Ko Dicken S. C. , Cooper David K. C. , Houser Stuart L. 
Published: January 2005

SummarySpleen transplantation (SpTx) has established donor‐specific tolerance in rodents, but not in large animals or humans. We report the histopathology of rejection in an established model of SpTx in major histocompatibility complex (MHC)‐defined miniature swine. Of the 17 SpTx, rejection was observed in two grafts transplanted into untreated, MHC‐matched, minor antigen‐disparate recipients (group 1, n = 4), but not in the two that received a 12‐day course of cyclosporin A (CyA). Rejection also occurred in five grafts transplanted into fully MHC‐disparate recipients (group 2, n = 12), one of which was untreated and four of which received some form of immunosuppressive therapy. One recipient of an MHC class‐I‐mismatched spleen treated with 12 days of CyA did not show rejection. Following biopsy and/or necropsy, fixed allograft tissue sections were treated with multiple stains, immunohistochemical markers and TUNEL assay. Common features of rejection occurred in grafts from both groups, but with varying time courses. Necrosis developed as early as day 8 in group 2 and day 27 in group 1, ranging from focal fibrinoid necrosis of arteriolar walls and sinusoids to diffuse liquefactive necrosis, usually associated with haemorrhage. Other features of rejection included white pulp expansion by atypical cells and decreased staining of basement membranes and reticular fibres. A doubling of the baseline TUNEL index preceded histologically identifiable rejection. This study establishes histologic guidelines for diagnosing and, perhaps, in future studies, predicting acute rejection of splenic allografts transplanted across known histocompatibility barriers in a large‐animal model.
A dyadic assessment of forgiveness in intimate relationships
Authors: Friesen Myron D. , Fletcher Garth J. O. , Overall Nickola C. 
Published: January 2005

AbstractThis study investigated forgiveness by examining couples’ recollections and perceptions of specific incidents of transgressions in their relationships. The results replicated previous research but also produced some novel findings. Results showed that more positive attributions and relationship quality independently predicted higher internal forgiveness, whereas expressed forgiveness was related only to relationship quality. Overall, the sample was negatively biased in their perceptions of their partner's forgiveness, but those participants who tended toward a positive bias were happier with their relationships as were their partners. Results are discussed in terms of prior research and theories of forgiveness and related social judgments in intimate relationships.