bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emerging evidence for a similar role of glutamate receptors in the nervous and immune systems
Authors: Boldyrev Alexander A. , Carpenter David O. , Johnson Peter 
Published: September 2005

AbstractThe role of glutamate receptors in synaptic transmission and excitotoxicity in the nervous system is well established. Recent evidence has emerged that glutamatergic mechanisms also exist in a wide variety of non‐neuronal cells. In the case of thymocytes and lymphocytes, several types of glutamate receptor are expressed which can induce functional changes. This review focuses on the cellular function of NMDA‐activated ionotropic and groups I and III metabotropic glutamate receptors in lymphocytes. Levels of exogenous and endogenous circulatory agonists and antagonists for lymphocyte glutamate receptors, notably homocysteine metabolites, are markedly increased in certain disease states and may be involved in disorders of the immune system. In addition to glutamate and aspartate, these compounds are active at glutamate receptors and increase the excitotoxic effects of glutamate in both neurons and lymphocytes. Increased levels of compounds acting at glutamate receptors may be risk factors for organ damage, for example in both heart and kidney disease. We conclude that glutamate is involved in signaling in immunocompetent cells and that the expression of both ionotropic and metabotropic glutamate receptors may have regulatory functions in immunocompetent cells, as well as in the nervous system. In addition, glutamate may serve as a signaling agent between the immune and nervous systems.
Role of AP‐1 in ethanol‐induced N‐methyl‐d‐aspartate receptor 2B subunit gene up‐regulation in mouse cortical neurons
Authors: Qiang Mei , Ticku Maharaj K. 
Published: September 2005

AbstractActivator protein 1 (AP‐1) has been reported to regulate the gene expression in a wide variety of cellular processes in response to stimuli. In this study, we investigated the DNA‐protein binding activities and promoter activity in the N‐methyl‐d‐aspartate R2B (NR2B) gene AP‐1 site in normal and ethanol‐treated cultured neurons. The identity of the AP‐1 site as the functional binding factor is suggested by the specific binding of nuclear extract derived from cultured cortical neurons to the labeled probes and the specific antibody‐induced supershift. Mutations in the core sequence resulted in a significantly reduced promoter activity and the ability to compete for the binding. Moreover, treatment of the cultured neuron with 75 mm ethanol for 5 days caused a significant increase in the AP‐1 binding activity and promoter activity. The AP‐1 DNA‐binding complex in control and ethanol‐treated nuclear extract was composed of c‐Fos, FosB, c‐Jun, JunD, and phosphorylated CREB (p‐CREB). Western blot analysis showed that p‐CREB and FosB significantly increased, whereas c‐Jun decreased. The DNA affinity precipitation assay indicated that FosB, p‐CREB, and c‐Jun increased in the AP‐1 complex following ethanol treatment. These results suggest that AP‐1 is an active regulator of the NR2B transcription and ethanol‐induced changes may result at multiple levels in the regulation including AP‐1 proteins expression, CREB phosphorylation and perhaps reorganization of dimmers.
How to measure non‐consistency of medical practices with available evidence in therapeutics: a methodological framework
Authors: Boissel Jean‐Pierre , Nony Patrice , Amsallem Emmanuel , Mercier Catherine , Estève Jacques , Cucherat Michel 
Published: September 2005

AbstractSince the early 1980s many studies showed a gap between available evidence and medical practice. They were designed to assess the real impact of randomized clinical trials on the practice of medicine. Their results substantiated a knowledge translation problem. However, they were qualitative findings, i.e. a gap exists or not, although the problem is quantitative (how large is the gap?) and has several components that should be documented according to the objective of the study. In this article, we explored the components and the various contexts in which the measure of the distance between practice and knowledge is considered. All these features should be taken into account for a more accurate and relevant assessment of the distance.
Population pharmacokinetics of ketanserin in pre‐eclamptic patients and its association with antihypertensive response
Authors: Hanff Lidwien M. , Visser Wil , Steegers Erik A.P. , Vulto Arnold G. 
Published: September 2005

AbstractKetanserin is an antihypertensive drug that is increasingly being used parenterally in the treatment of pre‐eclampsia. Because of lack of efficacy in a substantial part of our pre‐eclamptic patients, we determined the plasma concentrations of ketanserin in 51 pre‐eclamptic patients. Population pharmacokinetic parameters were assessed using the iterative two‐stage Bayesian population procedure. The influence of individual pharmacokinetic parameters on antihypertensive response, expressed as the attainment of a diastolic blood pressure ≤90 mmHg using ketanserin treatment, was analysed. Almost all plasma concentrations of ketanserin were in or above the therapeutic range. The individual pharmacokinetics of ketanserin in pre‐eclamptic patients showed an accurate fit using a three‐compartment model. The pharmacokinetic parameters in our pre‐eclamptic population were a metabolic clearance (Clm) of 37.9 ± 10.86 L/h and volume of distribution (V1) of 0.544 ± 0.188 L/kg, which is comparable with data from healthy volunteers. Despite a considerable inter‐individual variation, no correlation was found between differences in pharmacokinetic parameters and antihypertensive response. We conclude that therapeutic plasma levels can be obtained in pre‐eclamptic patients with a fixed dosage schedule of ketanserin and differences in antihypertensive responses within a pre‐eclamptic population cannot be attributed to pharmacokinetic differences.
Modulation of spontaneous alternation performance of mice treated with thioperamide and tacrine in a cross maze task
Authors: Vohora Divya , Pal Shanthi N. , Pillai K.K. 
Published: September 2005

AbstractA combination of sub‐effective doses of thioperamide (7.5 mg/kg, i.p.) and tacrine (0.5 mg/kg, i.p.) enhanced performance in a spatial memory task in mice. This was shown by a significant increase in their spontaneous alternation scores in a cross maze test.
Effect ofN‐benzoyl‐d‐phenylalanine on lipid profile in liver of neonatal streptozotocin diabetic rats
Authors: Pari Leelavinothan , Ashokkumar Natarajan 
Published: September 2005

AbstractThe effect ofN‐benzoyl‐d‐phenylalanine (NBDP) and metformin combination treatment on liver lipids and lipid peroxidation markers was studied in neonatal streptozotocin (nSTZ) diabetic rats. Oral administration of NBDP (50, 100 and 200 mg/kg body weight) and metformin (500 mg/kg body weight) for 6 weeks significantly reduced the elevated blood glucose, liver cholesterol, triglycerides, free fatty acids and phospholipids. The combination treatment also caused a significant decrease in hepatic hydroxymethyl glutaryl‐coenzyme A reductase, Thiobarbituric Acid Reactive Substances (TBARS) and significant increase in reduced glutathione levels. The results show that NBDP and metformin improve the hepatic lipid profile and antioxidant status in nSTZ diabetic rats. Combination treatment was more effective than either drug alone.
Characterization of human cytochrome P450 isoenzymes involved in the metabolism of vinorelbine
Authors: Beulz‐Riché Dominique , Grudé Pascale , Puozzo Christian , Sautel François , Filaquier Christian , Riché Christian , Ratanasavanh Damrong 
Published: September 2005

AbstractVinorelbine (VRL) (IV Navelbine®) is a semi‐synthetic vinca alkaloid, used in therapeutics for the treatment of non‐small‐cell lung cancer and advanced breast cancer. The aim of this study was to characterize the cytochrome P450 (CYP) isoenzymes involved in VRL metabolism. VRL was incubated at 1.28 × 10−5 m for 90 min with human hepatic microsomes prepared from 14 donors (one woman and 13 men aged from 27 to 76 years old) and characterized for CYP1A2, CYP2D6, CYP2E1 and CYP3A4 activities. A four‐combined‐approach study was performed, including correlation between CYP activities and VRL metabolism among the 14 batches of microsomes, inhibition of VRL biotransformation by isoform‐selective substrates and by specific inhibitory antibodies, and incubation with supersomes®. Analysis of unchanged VRL and its metabolites was performed using an HPLC method coupled with both radioactive and UV detections. No correlation between CYP1A2 or CYP2E1 and VRL metabolism was observed in the 14 batches of microsomes used. A correlation was shown between VRL metabolism and CYP3A4 activity as determined with the dextromethorphan N‐demethylase and nifedipine oxidase activities (r2 = 0.80 and 0.59, respectively). These results were strengthened by a correlation between the metabolism extent of VRL and CYP3A4 protein content determined by immunoblotting (r2 = 0.75). Furthermore, VRL biotransformation was inhibited by troleandomycine, the CYP3A4‐specific inhibitor substrate (80% of inhibition) and by anti‐CYP3A antibodies (36% of inhibition). On the contrary, a low correlation with CYP2D6 activity as determined by dextrometorphan O‐demethylation (r2 = 0.31) was established. CYP2D6 supersomes® did not metabolize the drug whereas 63.4% of VRL were metabolized by microsomes overexpressing CYP3A4 isoform. These data indicated that CYP3A4 is the main enzyme involved in the hepatic metabolism of VRL in human, whereas CYP2D6 is not involved.
Public Service Broadcasting*
Authors: Armstrong Mark 
Published: September 2005

AbstractThis essay discusses the merits of public intervention in the provision of television broadcasting services. I argue that intervention was justified in the past, when there were just a few channels and when advertising was the sole source of commercial funds. However, the advent of subscription television overcomes many of the market failures that once existed. Moreover, asymmetric treatment of broadcasters acts to distort the incentives of commercial broadcasters. Finally, viewers have an increasing ability to avoid unappealing, but perhaps socially desirable, content, which further weakens the case for public intervention in the market.
The New Deal for Young People Five Years On*
Authors: De Giorgi Giacomo 
Published: September 2005

AbstractThe New Deal for Young People is the major welfare‐to‐work programme in the UK. It is a mandatory multistage policy targeted at 18‐ to 24‐year‐old unemployed people. This paper investigates the long‐term effectiveness of the programme in terms of enhancing the (re‐)employment probability of participating men. It exploits the eligibility rule to identify a suitable counterfactual relying upon a simple regression discontinuity design. The combination of job‐search assistance, training, wage subsidies and job experience enhances employability by about 4.6 per cent and this effect lasts over different cohorts.
Conceptualizing and Categorizing Race and Ethnicity in Health Services Research
Authors: Ford Marvella E. , Kelly P. Adam 
Published: September 2005

Objectives. Veterans Affairs (VA) patient populations are becoming increasingly diverse in race and ethnicity. The purpose of this paper is to (1) document the importance of using consistent standards of conceptualizing and categorizing race and ethnicity in health services research, (2) provide an overview of different methods currently used to assess race and ethnicity in health services research, and (3) suggest assessment methods that could be incorporated into health services research to ensure accurate assessment of disease prevalence and incidence, as well as accounts of appropriate health services use, in patients with different racial and ethnic backgrounds.Design. A critical review of published literature was used.Principal Findings. Race is a complex, multidimensional construct. For some individuals, institutionalized racism and internalized racism are intertwined in the effects of race on health outcomes and health services use. Ethnicity is most commonly used as a social–political construct and includes shared origin, shared language, and shared cultural traditions. Acculturation appears to affect the strength of the relationships among ethnicity, health outcomes, and health services use.Conclusions. Improved and consistent methods of data collection need to be developed for use by VA researchers across the country. VA research sites with patients representing specific population groups could use a core set of demographic items in addition to expanded modules designed to assess the ethnic diversity within these population groups. Improved and consistent methods of data collection could result in the collection of higher‐quality data, which could lead to the identification of race‐ and ethnic‐specific health services needs. These investigations could in turn lead to the development of interventions designed to reduce or eliminate these disparities.
Does Wait‐List Size at Registration Influence Time to Surgery? Analysis of a Population‐Based Cardiac Surgery Registry
Authors: Sobolev Boris , Levy Adrian , Hayden Robert , Kuramoto Lisa 
Published: September 2005

Objective. To determine whether the probability of undergoing coronary bypass surgery within a certain time was related to the number of patients on the wait list at registration for the operation in a publicly funded health system.Methods. A prospective cohort study comparing waiting times among patients registered on wait lists at the hospitals delivering adult cardiac surgery. For each calendar week, the list size, the number of new registrations, and the number of direct admissions immediately after angiography characterized the demand for surgery.Results. The length of delay in undergoing treatment was associated with list size at registration, with shorter times for shorter lists (log‐rank test 1,198.3, p<.0001). When the list size at registration required clearance time over 1 week patients had 42 percent lower odds of undergoing surgery compared with lists with clearance time less than 1 week (odds ratio [OR] 0.58 percent, 95 percent, confidence interval [CI] 0.53–0.63), after adjustment for age, sex, comorbidity, period, and hospital. The weekly number of new registrations exceeding weekly service capacity had an independent effect toward longer service delays when the list size at registration required clearance time less than 1 week (OR 0.56 percent, 95 percent CI 0.45–0.71), but not for longer lists. Every time the operation was performed for a patient requiring surgery without registration on wait lists, the odds of surgery for listed patients were reduced by 6 percent (OR 0.94, CI 0.93–0.95).Conclusion. For wait‐listed patients, time to surgery depends on the list size at registration, the number of new registrations, as well as on the weekly number of patients who move immediately from angiography to coronary bypass surgery without being registered on a wait list. Hospital managers may use these findings to improve resource planning and to reduce uncertainty when providing advice on expected treatment delays.
Helicobacter pylori“Rescue” Therapy After Failure of Two Eradication Treatments
Authors: Gisbert Javier P. , Pajares José María 
Published: September 2005

ABSTRACTNowadays, apart from having to know well first‐line eradication regimens, we must also be prepared to face Helicobacter pylori treatment failures. Therefore, in designing a treatment strategy we should not focus on the results of primary therapy alone, but also on the final – overall – eradication rate. After failure of a combination of proton pump inhibitor (PPI), amoxicillin, and clarithromycin, the use of empirical quadruple therapy (PPI–bismuth–tetracycline–metronidazole), has been generally used as the optimal second‐line therapy. Even after two consecutive failures, several studies have demonstrated that H. pylori eradication can finally be achieved in almost all patients if several “rescue” therapies are consecutively given. It seems that performing culture even after a second eradication failure may not be necessary, as it is possible to construct an overall strategy to maximize H. pylori eradication, based on the different possibilities of empirical treatment (when antibiotic susceptibilities are unknown). Thus, if one does not want to perform culture before the administration of the third treatment after failure of the first two, different empirical treatments exist, including regimens based on: 1, amoxicillin (amoxicillin–PPI at high doses); 2, amoxicillin plus tetracycline (PPI–bismuth–tetracycline–amoxicillin, or ranitidine–bismuth–citrate–tetracyline–amoxicillin); 3, rifabutin (rifabutin–amoxicillin–PPI); 4, levofloxacin (levofloxacin–amoxicillin–PPI); and 5, furazolidone (furazolidone–bismuth–tetracycline–PPI).
Helicobacter pylori Infection is Associated with Reduced Circulating Ghrelin Levels Independent of Body Mass Index
Authors: Shiotani Akiko , Miyanishi Teruo , Uedo Noriya , Iishi Hiroyasu 
Published: September 2005

ABSTRACTBackground.  Ghrelin stimulates growth hormone and has orexigenic and adipogenic effects. Plasma ghrelin levels are reduced in obesity and possibly in Helicobacter pylori infection.Aim.  To investigate whether there was a relation between H. pylori infection, body mass index (BMI) and serum ghrelin or leptin levels.Methods.  University students undergoing an annual health check‐up were invited to participate. H. pylori status was based on the presence of specific IgG H. pylori antibodies in urine. Fasting serum ghrelin, leptin levels, and pepsinogen I and II levels were measured by enzyme immunoassay (EIA).Results.  Eight hundred and one students volunteered. There was no significant difference in the height and BMI between those with and without H. pylori infection. The population of ghrelin study consisted of 132 (66 H. pylori‐positive and 66 H. pylori‐negative) students matched for age, sex, and BMI. The ghrelin level in the H. pylori‐positive group was significantly lower (median 55 pmol/l) compared to the H. pylori‐negative group (103 pmol/l) (p < .00001). Leptin, triglyceride, total cholesterol, and HDL‐cholesterol were not different between the two groups, whereas LDL‐cholesterol levels were significantly higher (106 versus 100 mg/dl) (p = .03) in the H. pylori‐positive group. Leptin levels correlated with the BMI (r = 0.53) (p < .00001). Among H. pylori‐positive subjects, ghrelin correlated only with pepsinogen I levels (r = 0.26, p = .04).Conclusions.  H. pylori infection was associated with a reduction in circulating ghrelin levels independent of sex and BMI.
Long‐Term Follow‐up after Eradication of Helicobacter pylori with Omeprazole, Clarithromycin, and Tinidazole (OCT Regimen) in a Japanese Population
Authors: Ando Takafumi , Minami Masaaki , Mizuno Tomokazu , Watanabe Osamu , Ishiguro Kazuhiro , Ina Kenji , Kusugami Kazuo , Nobata Kazuo , Nishiwaki Tsuyoshi , Tsuzuki Tomoyuki , Shimada Masaaki , El‐Omar Emad , Goto Hidemi 
Published: September 2005

ABSTRACTBackground.  The long‐term benefit of Helicobacter pylori eradication treatment that includes metronidazole on peptic ulcer disease in Japan is unclear. We investigated the rate of H. pylori re‐infection and ulcer relapse after H. pylori eradication.Materials and methods.  A total of 266 patients with endoscopically confirmed peptic ulcer disease and H. pylori infection were treated with triple therapy of omeprazole 40 mg (20 mg b.i.d.), clarithromycin 800 mg (400 mg b.i.d.), and tinidazole 1000 mg (500 mg b.i.d.) for 7 days. Endoscopy with gastric biopsy was performed before and 1 month, 6 months, 1.5 years, and 3.5 years after therapy. H. pylori status was determined by H. pylori culture, rapid urease test, and histopathology. 13C‐urea breath test was done at 6 months after eradication therapy. Treatment was deemed successful when all tests were negative at 6 months after therapy by endoscopic biopsy.Results.  Successful H. pylori eradication was achieved in 262/266 (98.5%) patients with peptic ulcer. Total relapse of peptic ulcer occurred in 8/262 (3%) patients after eradication, with 3/262 (1.1%) occurring within 1.5 years after treatment and 5/262 (1.9%) within 3.5 years. All relapsed patients were found to be H. pylori‐positive at the time of relapse. Of the 262 patients who experienced eradication, 20 (7.6%) were subsequently re‐infected, six (2.3%) within 1.5 years and 14 (5.3%) within 3.5 years.Conclusion.  Triple therapy with omeprazole, clarithromycin, and tinidazole (OCT) is useful for H. pylori eradication in Japan, but there is an appreciable re‐infection rate in this population.
Immunity Markers in Patients with Helicobacter pylori Infection: Effect of Eradication
Authors: Dore Maria Pina , Fastame Laura , Tocco Andreina , Negrini Riccardo , Delitala Giuseppe , Realdi Giuseppe 
Published: September 2005

ABSTRACTBackground.  Helicobacter pylori is a microorganism able to stimulate a robust inflammatory and systemic immune response.Aim.  The aim of our study was to evaluate autoimmune markers in dyspeptic patients positive for H. pylori infection compared to a control group of non‐H. pylori‐infected subjects. The kinetics of cryoglobulins and autoantibodies was evaluated after treatment of the infection.Patients and methods.  Dyspeptic patients with active H. pylori infection and age‐ and sex‐matched healthy H. pylori‐ negative controls were studied. Markers of immunity were compared, in H. pylori‐infected patients before, 6 months and 1 year after the end of therapy. Results were also compared between those with and without successful eradication therapy.Results.  Eighty‐six individual were entered (43 H. pylori‐infected). H. pylori‐infected patients had higher levels of IgG and/or IgA and/or IgM (22/43 versus 2/43). Circulating immune complexes and cryoglobulins were detected in patients more often than controls (p < .05 for both). Autoantibodies were observed in 13 patients (30% versus 5% in controls) and antithyroid antibodies in 12 (p < .04 versus controls). Lower levels of C3 and/or C4 complement fractions were observed in infected patients with respect to controls (7/43 versus 1/43; p = .014). After 1 year of follow‐up, the markers of autoimmunity dramatically improved in patients eradicated for H. pylori infection compared to those in whom therapy failed. No patient developed a clinical autoimmune disorder.Conclusions.  Additional studies are necessary to ascertain the clinical significance of the modifications of autoimmune markers in patients with H. pylori infection.
Contribution of dppA to Urease Activity in Helicobacter pylori 26695
Authors: Davis Gregg S. , Mobley Harry L.T. 
Published: September 2005

ABSTRACTBackground.  The gastric pathogen Helicobacter pylori produces urease in amounts up to 10% of its cell protein. This enzyme, which catalyzes the hydrolysis of urea to ammonia and carbon dioxide, protects the bacterium from gastric acid. Urease, a nickel metalloenzyme, requires active uptake of nickel ions from the environment to maintain its activity. NixA is a nickel transport protein that resides in the cytoplasmic membrane. Mutation of nixA significantly reduces but does not abolish urease activity, strongly suggesting the presence of a second transporter. We postulated that the dipeptide permease (dpp) genes that are homologous to the nik operon of Escherichia coli could be a second nickel transporter. The predicted Dpp polypeptides DppA, DppC, and DppD of H. pylori share approximately 40%, 53%, and 56% amino acid sequence identity with their respective E. coli homologs.Methods.  A mutation in dppA, constructed by insertional inactivation with a chloramphenicol resistance cassette, was introduced by allelic exchange into H. pylori strain 26695.Results.  When compared to the parental strain, urease activity was not decreased in a dppA mutant.Conclusions.  DppA does not contribute to the synthesis of catalytically active urease in H. pylori 26695 and is likely not a nickel importer in H. pylori