bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of ERK1/2 signalling pathways induced by adenosine receptor subtypes in newborn rat cardiomyocytes
Authors: Germack Renée , Dickenson John M 
Published: January 2004

Adenosine A1, A2A, and A3 receptors (ARs) and extracellular signal‐regulated kinase 1/2 (ERK1/2) play a major role in myocardium protection from ischaemic injury. In this study, we have characterized the adenosine receptor subtypes involved in ERK1/2 activation in newborn rat cardiomyocytes.
Adenosine (nonselective agonist), CPA (A1), CGS 21680 (A2A) or Cl‐IB‐MECA (A3), all increased ERK1/2 phosphorylation in a time‐ and dose‐dependent manner. The combined maximal response of the selective agonists was similar to adenosine alone. Theophylline (nonselective antagonist) inhibited completely adenosine‐mediated ERK1/2 activation, whereas a partial inhibition was obtained with DPCPX (A1), ZM 241385 (A2A), and MRS 1220 (A3).
PD 98059 (MEK1; ERK kinase inhibitor) abolished all agonist‐mediated ERK1/2 phosphorylation. Pertussis toxin (PTX, Gi/o blocker) inhibited completely CPA‐ and partially adenosine‐ and Cl‐IB‐MECA‐induced ERK1/2 activation. Genistein (tyrosine kinase inhibitor) and Ro 318220 (protein kinase C, PKC inhibitor) partially reduced adenosine, CPA and Cl‐IB‐MECA responses, without any effect on CGS 21680‐induced ERK1/2 phosphorylation. H89 (protein kinase A, PKA inhibitor) abolished completely CGS 21680 and partially adenosine and Cl‐IB‐MECA responses, without any effect on CPA response.
Cl‐IB‐MECA‐mediated increases in cAMP accumulation suggest that A3AR‐induced ERK1/2 phosphorylation involves adenylyl cyclase activation via phospholipase C (PLC) and PKC stimulation.
In summary, we have shown that ERK1/2 activation by adenosine in cardiomyocytes results from an additive stimulation of A1, A2A, and A3ARs, which involves Gi/o proteins, PKC, and tyrosine kinase for A1 and A3ARs, and Gs and PKA for A2AARs. Moreover, the A3AR response also involves a cAMP/PKA pathway via PKC activation.

British Journal of Pharmacology (2004) 141, 329–339. doi:10.1038/sj.bjp.0705614
Topiramate hyperpolarizes and modulates the slow poststimulus AHP of rat olfactory cortical neurones in vitro
Authors: Russo Emilio , Constanti Andrew 
Published: January 2004

The effects of the novel antiepileptic drug topiramate (TPM) were investigated in rat olfactory cortex neurones in vitro using a current/voltage clamp technique.
In 80% of recorded cells, bath application of TPM (20 μM) reversibly hyperpolarized and inhibited neuronal repetitive firing by inducing a slow outward membrane current, accompanied by a conductance increase. The response was reproducible after washout, and was most likely carried largely by K+ ions, although other ionic conductances may also have contributed.
In 90% of cells, TPM (20 μM) also enhanced and prolonged the slow (Ca2+‐dependent) poststimulus afterhyperpolarization (sAHP) and underlying slow outward tail current (sIAHP). This effect was due to a selective enhancement/prolongation of an underlying L‐type Ca2+ current that was blocked by nifedipine (20 μM); the TPM response was unlikely to involve an interaction at PKA‐dependent phosphorylation sites.
The carbonic anhydrase (CA) inhibitor acetazolamide (ACTZ, 20 μM) and the poorly membrane permeant inhibitor benzolamide (BZ, 50 μM) both mimicked the membrane effects of TPM, in generating a slow hyperpolarization (slow outward current under voltage clamp) and sAHP enhancement. ACTZ and BZ occluded the effects of TPM in generating the outward current response, but were additive in producing the sAHP modulatory effect, suggesting different underlying response mechanisms.
In bicarbonate/CO2‐free, HEPES‐buffered medium, all the membrane effects of TPM and ACTZ were reproducible, therefore not dependent on CA inhibition.
We propose that both novel effects of TPM and ACTZ exerted on cortical neurones may contribute towards their clinical effectiveness as anticonvulsants.

British Journal of Pharmacology (2004) 141, 285–301. doi:10.1038/sj.bjp.0705617
Identification of interstitial cells of Cajal in corporal tissues of the guinea‐pig penis
Authors: Hashitani Hikaru , Suzuki Hikaru 
Published: January 2004

This study shows for the first time the presence of interstitial cells of Cajal (ICC) and their possible role in the initiation of spontaneous excitation in the corporal tissue of the guinea‐pig penis. ICC, which were identified by their c‐kit immunoreactivity, were abundantly distributed in the corporal smooth muscle meshwork. Spontaneous increases in the intracellular calcium concentration ([Ca2+]i; calcium transients) were visualized in preparations loaded with the fluorescent dye fura‐2. Ca transients originated from the boundary of muscle bundles and then spread throughout the meshwork (Ca waves). Ca waves were strongly suppressed by either CPA (10 μM), ryanodine (50 μM) or 2‐APB (10 μM), and their synchronicity was disrupted by 18β‐GA (30 μM). These results suggest that ICC in the corporal tissue may have a role as pacemakers to drive the bulk of smooth muscles, and that intracellular Ca2+ stores and gap junctions are critical for the generation of spontaneous excitation.British Journal of Pharmacology (2004) 141, 199–204. doi:10.1038/sj.bjp.0705622
Genetic predisposition to acute gastrointestinal bleeding after NSAIDs use
Authors: Martínez Carmen , Blanco Gerardo , Ladero José M , García‐Martín Elena , Taxonera Carlos , Gamito Francisco G , Diaz‐Rubio Manuel , Agúndez José A G 
Published: January 2004

Impaired drug metabolism is a major cause of adverse drug reactions, and it is often caused by mutations at genes coding for drug‐metabolising enzymes. Two amino‐acid polymorphisms of cytochrome P4502C9 (CYP2C9), an enzyme involved in the metabolism of several nonsteroidal anti‐inflammatory drugs (NSAIDs), were studied in 94 individuals with acute bleeding after NSAIDs use and 124 individuals receiving NSAIDs with no adverse effects. The frequency of CYP2C9 variant alleles was increased in overall bleeding patients, with a significant trend to higher risk with increasing number of variant alleles (P=0.02). The odds ratio for bleeding patients receiving CYP2C9 substrates (n=33) was 2.5 for heterozygous and 3.7 for homozygous carriers of mutations (P<0.015), suggesting that the inherited impairment of CYP2C9 activity increases the risk for severe adverse drug reactions after NSAIDs use.British Journal of Pharmacology (2004) 141, 205–208. doi:10.1038/sj.bjp.0705623
Ouabain exerts biphasic effects on connexin functionality and expression in vascular smooth muscle cells
Authors: Martin Patricia E M , Hill Nathan S , Kristensen Bo , Errington Rachael J , Griffith Tudor M 
Published: January 2004

Correction to: British Journal of Pharmacology (2003) 140, 1261–1271. doi:10.1038/sj.bjp.0705556

We have compared the effects of ouabain on the maintenance of gap junctional communication in rat aortic A7r5 smooth muscle cells, monkey COS‐1 fibroblasts and human HeLa epithelial cells.
Ouabain (1 mM) interrupted dye coupling between confluent A7r5 cells within ∼1 h, and high concentrations of ouabain were similarly required to reduce coupling between COS‐1 cells selected to express the rat α1 Na+/K+‐ATPase subunit, which is ouabain resistant. By contrast, low concentrations of ouabain (1–10 μM) attenuated dye transfer in wild‐type COS‐1 and HeLa cells, whose endogenous α1 subunits possess relatively high affinity for the glycoside (Ki∼0.3 vs ∼100 μM) Ouabain‐induced reductions in dye transfer therefore correlated with the ability of the glycoside to bind to the Na+/K+‐ATPase isoenzymes expressed in these different cell lines.
No consistent relationship between inhibition of intercellular dye transfer and secondary changes in [Ca2+]i or pHi could be identified following incubation with ouabain.
In separate experiments, the effects of ouabain on real‐time trafficking of connexin (Cx) protein were monitored by time‐lapse microscopy of A7r5 cells transfected to express a fluorescent Cx43‐green fluorescent protein (GFP) and the ability of the glycoside to modulate endogenous expression of Cx40 and Cx43 evaluated in A7r5 cells by immunochemical and Western blot analysis.
Ouabain (1 mM) depressed vesicular trafficking of Cx43‐GFP after ∼1 h, and caused a time‐dependent loss of endogenous Cx40 and Cx43 protein that was first evident at 2 h and almost complete after 4 h. These effects of ouabain on Cx expression were reversed ∼90 min following washout of the glycoside.
We conclude that ouabain exerts biphasic effects on intercellular communication that involve an initial decrease in gap junctional permeability followed by a global reduction in the expression of Cx protein. Further studies are necessary to establish to what extent these actions of ouabain reflect inversion of the normal [Na+]i/[K+]i ratio and/or conversion of the Na+/K+‐ATPase into a general signal transducer that regulates downstream protein synthesis.

British Journal of Pharmacology (2004) 141, 374–384. doi:10.1038/sj.bjp.0705671
Dietary behaviour of German adults differing in levels of sport activity
Authors: Beitz Roma , Mensink Gert BM , Henschel Yvonne , Fischer Beate , Erbersdobler Helmut F 
Published: January 2004

AbstractObjective:To analyse the dietary behaviour of persons engaging in different levels of sport activity.Design:A cross-sectional survey analysis.Setting:A population-based sample of German adults.Subjects:A total of 1756 men and 2254 women participating in the German National Health Interview and Examination Survey and the integrated German Nutrition Survey 1998.Results:Among both genders, the median micronutrient intakes of active persons were more preferable than those of sedentary persons when German current reference values were used as a criterion. The median nutrient densities were also higher in the diet of active persons, especially those of vitamin E, calcium, magnesium, and among women also those of folate and vitamin C. On average, active persons consumed higher amounts of fruit/vegetable juice, drinking water, milk products (including cheese) and fruits. Active men additionally consumed higher amounts of vegetables and vegetable fat. The contribution of dietary supplements to the total nutrient intake was 3%, on average, for active men and women. Compared with sedentary persons, this contribution was significantly higher for vitamins, and among men also for calcium and magnesium.Conclusion:There was no indication of an impaired micronutrient intake of active and moderately active persons compared with sedentary persons.
Reliability and validity of a food-frequency questionnaire for Chinese postmenopausal women
Authors: Xu Liangzhi , Dibley Michael J , D'Este Catherine 
Published: January 2004

AbstractObjectives:(1) To determine the reliability and validity of a food-frequency questionnaire (FFQ) for use in epidemiological research in postmenopausal women; and (2) to compare the volume estimation (VE) and weight estimation (WE) method of administration of this questionnaire.Design:An initial list of foods was derived and modified after pre-testing in 22 subjects. Test-retest reliability was assessed in 21 subjects who had repeat administrations of the questionnaire 14 days apart (FFQ1, FFQ2). The validity of the FFQ was assessed by comparing nutrient intakes with those from a 4-day food record.Setting:Chengdu, People's Republic of China.Subjects:Twenty-two postmenopausal women (50–70 years) were recruited from The Second University Hospital, West China University of Medical Sciences, Chengdu and participated in the pre-test. Another 21 women (50–70 years) were randomly selected from the general population of all five districts of Chengdu and participated in the reliability and validity sub-studies.Results:Energy, protein, carbohydrate, magnesium and sodium intakes in this sample were less than the Recommended Dietary Allowances (RDAs) for 45–70-year-old women in China. Intake of non-cooking fat was higher than the Chinese RDA. Pearson correlation coefficients and intra-class correlation coefficients (ICCs) for reliability of the VE FFQ ranged from 0.51 to 0.85 and from 0.51 to 0.81, respectively; for the WE FFQ, they ranged from 0.22 to 0.86 and from 0.21 to 0.81. Correlation coefficients and ICCs for validity of the WE FFQ ranged from 0.36 to 0.69 and from 0.34 to 0.57, respectively; corresponding values for the VE FFQ were −0.30 to 0.65 and −0.14 to 0.65.Conclusions:Both the VE and WE FFQs were reliable and valid except for sodium intake. The VE FFQ provided more valid estimates of nutrient intakes than did the WE FFQ.
Dietary selenium intake by men and women in high and low selenium areas of Punjab
Authors: Hira Charanjeet K , Partal Kulprakash , Dhillon KS 
Published: January 2004

AbstractObjective:To determine the selenium intake of adults residing in high and low selenium areas of rural Punjab.Design:All food samples consumed by the subjects were collected and analysed for selenium content. Based on food intake data and selenium content of foods, the selenium intake of the subjects was calculated. Hair, fingernails and urine samples from a sub-sample of subjects were collected and analysed for selenium.Setting:Three villages from the selenium-endemic area of Nawan Shahr District and two villages from the non-endemic area of Ludhiana District, Punjab, India, were covered.Subjects:Forty families from each of the two areas, with one adult male and one adult female in the age range of 20–40 years, were surveyed. Thus a total of 80 men and 80 women constituted the study sample.Results:In the selenium-endemic area, the average selenium intake of both men and women was more than nine times that in the non-endemic area and exceeded the maximum tolerable limit in more than 60% of men. Mean selenium content of the hair, nails and urine of both men and women was tens of times higher than in the non-endemic area.Conclusions:High selenium intake in the endemic area resulted in high selenium content in the hair, nails and urine of men and women. In addition, clinical symptoms of selenium toxicity were also observed in some of the subjects. Selenium intake in the non-endemic area was marginally below the suggested value. Based on the study results, steps need to be taken to educate the public in the endemic area to avoid selenium toxicity.
Consistency of use of plant stanol ester margarine in Finland
Authors: Simojoki Meri , Luoto Riitta , Uutela Antti , Boice John D , McLaughlin Joseph K , Puska Pekka 
Published: January 2004

AbstractObjective:The aims of this study were to investigate the consistency of use of plant stanol ester margarine and to characterise consistent and inconsistent users.Design:A cohort of plant stanol ester margarine users was established based on 14 national surveys conducted by the National Public Health Institute in Finland between 1996 and 1999. A follow-up study questionnaire was developed and sent to 1294 users in 2000.Setting:Subjects who reported using plant stanol ester margarine in both the original survey and the follow-up study were classified as consistent users, and the rest as inconsistent users.Subjects:The study population consisted of 1094 subjects aged 18–87 years, 590 men and 504 women.Results:There were 357 (33%) consistent and 737 (67%) inconsistent users of plant stanol ester margarine in the study population. Consistent users were more likely to be men and to have a higher household income than inconsistent users. Both consistent and inconsistent users were predominantly middle-aged persons with a healthy lifestyle and diet as well as a history of cardiovascular disease. Healthfulness was the main factor affecting bread spread choice among 94% of the consistent users and 59% of the inconsistent users.Conclusions:The use of plant stanol ester margarine is more often inconsistent than consistent. There is nevertheless a relatively large subgroup of long-term users of plant stanol ester margarine. It is important to examine the health effects especially among these regular users.
Consumption of foods by young children with diagnosed campylobacter infection – a pilot case–control study
Authors: Cameron Scott , Ried Karin , Worsley Anthony , Topping David 
Published: January 2004

AbstractObjective:To determine whether parentally reported habitual intake of specific foods differed between children with diagnosedCampylobacter jejuniinfection and children of a comparison group without diagnosed infection.Design, setting and subjects:Information was collected from the parents or primary caregivers of South Australian children aged 1–5 years with diagnosedC. jejuni(cases,n=172) and an age- and gender-matched group of uninfected children (controls,n=173). Frequency of consumption of 106 food and drink items was determined for the preceding two months by food-frequency questionnaire. Four children in the control group had recorded diarrhoeal episodes during the assessment period and were excluded, so 169 responses were evaluated for this group. Information was gathered on possible confounders including socio-economic status. Response frequencies were classified into three levels of consumption (rarely, weekly or daily) and statistical comparison was made by frequency of consumption of foods versus the ‘rarely’ classification for cases and controls, respectively.Results:Frequency of consumption of most foods, including starchy foods and fruits and vegetables, did not differ between cases and controls. However, reported consumption of eight food items (block and processed cheese (slices and spread), salami/fritz (a form of processed sausage), chicken nuggets, pasteurised milk, fish (canned or fresh) and hot French fries) was significantly higher by controls.Conclusions:The hypothesis that reported consumption of starchy foods was lower by cases than by controls was not supported by the data. However, consumption of some processed and unprocessed foods was higher by controls. Some of these foods have established bactericidal actionsin vitrothat may indicate a possible mechanism for this apparent protection.
Nutrition and lifestyle in relation to bowel movement frequency: a cross-sectional study of 20 630 men and women in EPIC–Oxford
Authors: Sanjoaquin Miguel A , Appleby Paul N , Spencer Elizabeth A , Key Timothy J 
Published: January 2004

AbstractObjective:To investigate the relationships between nutritional and lifestyle factors and bowel movement frequency.Design:Cross-sectional analysis using data from a prospective study. Mean numbers of bowel movements were calculated in relation to a range of factors. In addition, individuals were categorised according to frequency of bowel movements: fewer than 7 per week (‘less than daily’) versus 7 or more per week (‘daily’), and odds ratios were calculated from logistic regression models. Results for each factor were adjusted for the other factors under consideration.Setting:The European Prospective Investigation into Cancer and Nutrition, Oxford cohort (EPIC–Oxford), UK.Participants:In total, 20,630 men and women aged 22–97 years at recruitment. Thirty per cent of the subjects were vegetarians or vegans.Results:Women had fewer bowel movements on average than men, and were less likely to have daily bowel movements. Mean bowel movement frequency was higher in vegetarians (10.5 in men, 9.1 in women) and especially in vegans (11.6 in men, 10.5 in women) compared with participants who ate meat (9.5 in men, 8.2 in women). There were also significant positive associations between bowel movement frequency and body mass index (BMI), intakes of dietary fibre and non-alcoholic fluids, for both men and women. Vigorous exercise was positively associated with bowel movement frequency in women although results for men were less clear. Alcohol intake was positively associated with bowel movement frequency in men but not in women.Conclusion:Being vegetarian and especially vegan is strongly associated with a higher frequency of bowel movements. Moreover, having a high intake of dietary fibre and fluids and a high BMI are associated with an increase in frequency of bowel movements.
The Chimpanzees’ Tea Party: A New Metaphor for Project Managers
Authors: Drummond Helga , Hodgson Julia 
Published: January 2004

This paper addresses the problem of information technology systems failure. It is argued that conventional approaches to project management assume that success depends upon imposing control. This paper invokes a novel metaphor, namely the chimpanzees’ tea party, for highlighting the limits of this assumption and showing how control-based approaches to project management can be counterproductive. Paradoxically, situations may arise where projects can be more effectively controlled by not attempting to impose control. Mind is the forerunner of everything. Mind is sovereign. All things are generated by mind. (Dhamnapadi, verse 1)
Anaerobes in ejaculates of subfertile men
Authors: Eggert-Kruse Waltraud , Rohr Gerhard , Ströck Wolfram , Pohl Susanne , Schwalbach Beate , Runnebaum Benno 
Published: January 2004

Abstract
The clinical significance of micro-organisms in semen samples of asymptomatic subfertile patients is a matter of constant debate. Usually little attention is paid to anaerobic bacteria as they are sensitive to transportation and culturing, and differentiation is difficult, costly and time-consuming. In the present study, special screening was carried out for anaerobes in ejaculates in addition to the routine microbial cultures of genital secretions of both partners. In addition to standard semen analysis and evaluation of sperm ability to penetrate cervical mucus (CM) in vivo (postcoital testing) and in vitro using a standardized test system, semen samples from 126 randomly chosen males of couples with a median duration of infertility of 4 years were examined for colonization with anaerobic bacteria. All couples were without clinical signs or symptoms of genital tract infection. The special care taken for anaerobic growth in semen samples gave a high rate of positive cultures and showed that nearly all ejaculates (99%) were colonized with anaerobic micro-organisms, and potentially pathogenic species were found in 71% of men. This rate was more than four times higher than that obtained with routine cultures and standard transportation (16%). Anaerobic bacterial growth of ≥106 colony forming units (CFU)/ml was seen in 42% (total range 103-108 CFU/ml). In addition, aerobic growth was found in 96%(≥106 CFU/ml in 21%), potentially pathogenic species in 61% of semen specimens. There were no marked differences in the prevalence of anaerobic micro-organisms in patients with reduced or normal sperm count, motility or morphology. Nor was there any significant difference in anaerobic colonization between samples with impaired or good ability to penetrate CM of female partners (in vivo or in vitro), or the CM of fertile donors in the in-vitro sperm-cervical mucus penetration test (SCMPT) in this asymptomatic group of patients. There was no clear association between microbial colonization and subsequent fertility in vivo within an observation period of 6 months. The results of this study suggest that anaerobic bacteria are often not detected when routine methods for microbial evaluation are used. This should be considered during assisted reproduction and in patients with symptoms of genital tract infection and should lead to further studies in infertile patients where subclinical infection or inflammation is indicated by specific markers in semen samples.