bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal Windows of Statin Use for Immediate Infarct Limitation
Authors: Sanada Shoji , Asanuma Hiroshi , Minamino Tetsuo , Node Koichi , Takashima Seiji , Okuda Hiroko , Shinozaki Yoshiro , Ogai Akiko , Fujita Masashi , Hirata Akio , Kim Jiyoong , Asano Yoshihiro , Mori Hidezo , Tomoike Hitonobu , Kitamura Soichiro , Hori Masatsugu , Kitakaze Masafumi
Published: September 2004

Background—

Although statins are reported to have a cardioprotective effect, their immediate direct influence on ischemia-reperfusion injury and the underlying mechanisms remain obscure. We investigated these issues an in vivo canine model.

Methods and Results—

Dogs were subjected to coronary occlusion (90 minutes) and reperfusion (6 hours) immediately after injection of pravastatin (0.2, 2, or 10 mg/kg), pitavastatin (0.01, 0.1, or 0.5 mg/kg), or cerivastatin (0.5, 5, or 50 μg/kg). Then myocardial phosphatidylinositol 3-kinase (PI3-K) and 5′-nucleotidase activities were measured, as well as infarct size. After 15 minutes of reperfusion, pravastatin caused dose-dependent activation of Akt and ecto-5′-nucleotidase in the ischemic zone, and the effect was significant at higher doses. Pitavastatin also significantly increased these activities, and its optimal dose was within the clinical range, whereas cerivastatin caused activation at the lowest dose tested. In all cases, both Akt and ecto-5′-nucleotidase showed activation in parallel, and this activation was completely abolished by wortmannin, a PI3-K inhibitor. The magnitude of the infarct-limiting effect paralleled the increase in Akt and ecto-5′-nucleotidase activity and was blunted by administration of wortmannin, α,β-methyleneadenosine-5′-diphosphate, or 8-sulfophenyltheophylline during reperfusion. Both collateral flow and the area at risk were comparable for all groups.

Conclusions—

Activation of ecto-5′-nucleotidase after ischemia by PI3-K activation may be crucial for immediate infarct-size limitation by statins. There seems to be an optimal dose for each statin that is independent of its clinical cholesterol-lowering effect.
Exaggerated Blood Pressure Responses During Mental Stress Are Prospectively Related to Enhanced Carotid Atherosclerosis in Middle-Aged Finnish Men
Authors: Jennings J. Richard , Kamarck Thomas W. , Everson-Rose Susan A. , Kaplan George A. , Manuck Stephen B. , Salonen J.T.
Published: September 2004

Background—

Hemodynamic reactions to mental stress may contribute to atherosclerosis. We previously observed cross-sectional relationships between blood pressure reactions to a standardized stress battery and carotid intima-media thickness (IMT) in the Kuopio Ischemic Heart Disease (KIHD) study. These are the first prospective results on this relationship.

Methods and Results—

Men from 4 age cohorts (42 to 60 years old at study onset) were challenged with a standardized mental stress battery, and heart rate and blood pressure reactions were assessed. Ultrasound measures of common carotid IMT were collected at this time and 7 years later as noninvasive markers of atherosclerosis. Data were collected from a sample of 756 men at both times. Systolic blood pressure reactions to mental stress at study onset were positively related to mean carotid IMT 7 years later (β=0.035,
P
=0.001, by blood pressure quartile, IMT=0.91, 0.93, 0.96, 1.00 mm) and to the progression of IMT (β=0.020,
P
=0.006, by blood pressure quartile, ΔIMT=0.08, 0.09, 0.11, 0.11 mm). Similar significant relations were shown for maximal IMT and plaque height. Diastolic blood pressure responses were less strongly related to carotid IMT than were systolic responses. Heart-rate responses were unrelated. Adjustment for standard risk factors did not substantially reduce the relation between systolic blood pressure reactivity and the progression of mean carotid IMT (standardized β=0.059,
P
=0.026), maximal carotid IMT (standardized β=0.084,
P
=0.006), or plaque height (standardized β=0.093,
P
=0.008).

Conclusions—

The degree of systolic blood pressure reactivity to mental challenge is prospectively related to carotid IMT in middle-aged and older men, independent of known risk factors.
Arterial Pressure Response to the Antioxidant Tempol and ET
B
Receptor Blockade in Rats on a High-Salt Diet
Authors: Williams Jan Michael , Pollock Jennifer S. , Pollock David M.
Published: September 2004

We hypothesized that increased superoxide contributes to mean arterial pressure (MAP) regulation in male Sprague-Dawley rats fed a high-salt diet and/or during endothelin (ET
B
) receptor blockade. Four groups on either a normal- or a high-salt diet were studied for 1 week: (1) control; (2) tempol, a superoxide dismutase mimetic, in their drinking water (1 mmol/L); (3) A-192621, an ET
B
antagonist, in their food (10 mg/kg daily); or (4) both tempol and A-192621. Without ET
B
blockade, tempol had no effect on MAP (telemetry) in rats on the normal-salt diet but significantly reduced MAP in rats on the high-salt diet (100±3 vs 112±2 mm Hg,
P
<0.05). On the normal-salt diet, A-192621 increased MAP with or without tempol. Under high-salt conditions, tempol attenuated the increase in MAP produced by A-192621, but only during the initial days of treatment. Plasma 8-isoprostanes were increased in all rats on the high-salt diet and were further increased after 3 days of A-192621 but not after 7 days; tempol inhibited the increase produced by A-192621 but had no influence on the increase produced by high salt. H
2
O
2
excretion was significantly higher in rats on a high-salt diet for the 7-day drug treatment compared with those on a normal-salt diet. Tempol further increased H
2
O
2
excretion in rats on a high-salt diet, an effect accelerated in A-192621–treated rats. These data suggest that blood pressure lowering by tempol in rats on a high-salt diet may be unrelated to reductions in superoxide and that renal H
2
O
2
may account for the limited ability of tempol to attenuate hypertension produced by ET
B
receptor blockade.
Mapping the Genetic Determinants of Hypertension, Metabolic Diseases, and Related Phenotypes in the Lyon Hypertensive Rat
Authors: Bilusic Marijo , Bataillard Alain , Tschannen Michael R. , Gao Li , Barreto Nadia E. , Vincent Madeleine , Wang Tao , Jacob Howard J. , Sassard Jean , Kwitek Anne E.
Published: September 2004

The complex nature of hypertension makes identifying the pathophysiology and its genetic contributions a challenging task. One powerful approach for the genetic dissection of blood pressure regulation is studying inbred rat models of hypertension, as they provide natural allele variants but reduced heterogeneity (both genetic and etiologic). Furthermore, the detailed physiologic studies to which the rat is amenable allow for the determination of intermediate phenotypes. We have performed a total genome scan in offspring of an F
2
intercross between the Lyon hypertensive (LH) and Lyon normotensive rat strains to identify linkage of anthropometric, blood pressure, renal, metabolic, and endocrine phenotypes. Quantitative trait locus (QTL) regions involved in blood pressure regulation, end-stage organ damage, body and organ weight, and lipid metabolism in the LH rat were identified on chromosomes 1, 2, 3, 5, 7, 10, 13, and 17, with 2 phenotypes associated with the metabolic syndrome identified on chromosomes 1 and 17. Regions on chromosomes 2, 13, and 17 were revealed to be important for blood pressure regulation. Regions on chromosome 17 were found to significantly contribute to both metabolic homeostasis and blood pressure regulation; 2 aggregates of a total of 23 QTLs were identified, including several “intermediate phenotypes.” These intermediate phenotypes may be used as closer surrogates to the mechanisms leading to hypertension and metabolic dysfunction in the LH rat.
Association Between Factor VII Polymorphisms and Blood Pressure
Authors: Sass Catherine , Blanquart Christine , Morange Pierre-Emmanuel , Pfister Michèle , Visvikis-Siest Sophie
Published: September 2004

The purpose this study was to determine whether Arg353Gln and −323Del/Ins polymorphisms of factor VII (FVII) are related to blood pressure levels and hypertension. Subjects were drawn from the Stanislas Cohort, a longitudinal, familial French cohort examined twice since 1994. The “blood pressure study” included 1342 subjects free of medication use that could affect blood pressure. The “hypertension study” included 645 normotensive and 77 hypertensive adult subjects. Association with hypertension was also studied in 547 hypertensives enrolled in a clinical trial and in 624 normotensives drawn from the Stanislas Cohort. In the “blood pressure study,” parents with the 353Gln or −323Ins allele had lower blood pressures than did noncarriers at each examination, independent of covariates (0.01≤
P
≤0.05, except for diastolic blood pressure [DBP] at baseline, where
P
=0.103). Similarly significant relations were observed in their offspring (
P
≤0.05, except for systolic blood pressure [SBP] at 5 years, where
P
=0.186). In a representative subgroup of 267 individuals, the −323Del/Ins polymorphism was significantly associated with plasma FVII levels in both parents and offspring (
P
<0.001). FVII levels in plasma were significantly correlated with SBP and DBP in parents but not in offspring. After inclusion of both FVII levels and the −223Del/Ins in the same model in parents, only FVII levels remained significantly associated with SBP and DBP. The “hypertension study” revealed that the 353Gln and −323Ins alleles were related to decreased risk (odds ratio [OR]=0.554, 95% confidence interval [CI], 0.362 to 0.848, and OR=0.475, 95% CI, 0.299 to 0.755, respectively). These results suggest that the FVII gene may be a susceptibility locus for hypertension.
The rise and fall of whiteness studies
Authors: Hartman Andrew
Published: September 2004

Over the last decade or so, the study of whiteness in the US has grown in both cultural and academic significance, attracting hostility from neo-conservative commentators. But there is also a critique to be had from the Left. For while the study of whiteness as a social construction - which takes its starting point from Du Bois - has demonstrated more clearly than ever how racism is at the core of US history and society, it has, for the most part, failed to take the issue of class into account. How and why this is is closely analysed here, in an examination of the work, in particular, of Ignatiev, Hale, Roediger and Saxton.
Differential dynamics of histone H3 methylation at positions K4 and K9 in the mouse zygote
Authors: Lepikhov Konstantin , Walter Jörn
Published: September 2004

Background

In the mouse zygote the paternal genome undergoes dramatic structural and epigenetic changes. Chromosomes are decondensed, protamines replaced by histones and DNA is rapidly and actively demethylated. The epigenetic asymmetry between parental genomes remains at least until the 2-cell stage suggesting functional differences between paternal and maternal genomes during early cleavage stages.

Results

Here we analyzed the timing of histone deposition on the paternal pronucleus and the dynamics of histone H3 methylation (H3/K4mono-, H3/K4tri- and H3/K9di-methylation) immediately after fertilization. Whereas maternal chromatin maintains all types of histone H3 methylation throughout the zygotic development, paternal chromosomes acquire new and unmodified histones shortly after fertilization. In the following hours we observe a gradual increase in H3/K4mono-methylation whereas H3/K4tri-methylation is not present before latest pronuclear stages. Histone H3/K9di-methylation is completely absent from the paternal pronucleus, including metaphase chromosomes of the first mitotic stage.

Conclusion

Parallel to the epigenetic asymmetry in DNA methylation, chromatin modifications are also different between both parental genomes in the very first hours post fertilization. Whereas methylation at H3/K4 gradually becomes similar between both genomes, H3/K9 methylation remains asymmetric.
Localization of ABCG5 and ABCG8 proteins in human liver, gall bladder and intestine
Authors: Klett Eric L , Lee Mi-Hye , Adams David B , Chavin Kenneth D , Patel Shailendra B
Published: September 2004

Background

The molecular mechanisms that regulate the entry of dietary sterols into the body and their removal via hepatobiliary secretion are now beginning to be defined. These processes are specifically disrupted in the rare autosomal recessive disease, Sitosterolemia (MIM 210250). Mutations in either, but not both, of two genes ABCG5 or ABCG8, comprising the STSL locus, are now known to cause this disease and their protein products are proposed to function as heterodimers. Under normal circumstances cholesterol, but not non-cholesterol sterols, is preferentially absorbed from the diet. Additionally, any small amounts of non-cholesterol sterols that are absorbed are rapidly taken up by the liver and preferentially excreted into bile. Based upon the defects in sitosterolemia, ABCG5 and ABCG8 serve specifically to exclude non-cholesterol sterol entry at the intestinal level and are involved in sterol excretion at the hepatobiliary level.

Methods

Here we report the biochemical and immuno-localization of ABCG5 and ABCG8 in human liver, gallbladder and intestine using cell fractionation and immunohistochemical analyses.

Results

We raised peptide antibodies against ABCG5 and ABCG8 proteins. Using human liver samples, cell fractionation studies showed both proteins are found in membrane fractions, but they did not co-localize with caveolin-rafts, ER, Golgi or mitochondrial markers. Although their distribution in the sub-fractions was similar, they were not completely contiguous. Immunohistochemical analyses showed that while both proteins were readily detectable in the liver, ABCG5 was found predominately lining canalicular membranes, whereas ABCG8 was found in association with bile duct epithelia. At the cellular level, ABCG5 appeared to be apically expressed, whereas ABCG8 had a more diffuse expression pattern. Both ABCG5 and ABCG8 appeared to localize apically as shown by co-localization with MRP2. The distribution patterns of ABCG5 and ABCG8 in the gallbladder were very similar to each other. In the small intestine both ABCG5 and ABCG8 appear to line the brush border. However, at the level of the enterocyte, the cellular distribution patterns of ABCG5 and ABCG8 differed, such that ABCG5 was more diffuse, but ABCG8 was principally apical. Using standard deglycosylation methods, ABCG5 and ABCG8 do not appear to be glycosylated, suggesting a difference between human and mouse proteins.

Conclusion

We report the distribution patterns of ABCG5 and ABCG8 in human tissues. Cell fractionation studies showed that both proteins co-fractionated in general, but could also be found independent of each other. As predicted, they are expressed apically in both intestine and liver, although their intracellular expression patterns are not completely congruent. These studies support the concept of heterodimerization of ABCG5 and ABCG8, but also support the notion that these proteins may have an independent function.
Cyclin A and cyclin D1 as significant prognostic markers in colorectal cancer patients
Authors: Bahnassy Abeer A , Zekri Abdel-Rahman N , El-Houssini Soumaya , El-Shehaby Amal MR , Mahmoud Moustafa Raafat , Abdallah Samira , El-Serafi Mostafa
Published: September 2004

Background

Colorectal cancer is a common cancer all over the world. Aberrations in the cell cycle checkpoints have been shown to be of prognostic significance in colorectal cancer.

Methods

The expression of cyclin D1, cyclin A, histone H3 and Ki-67 was examined in 60 colorectal cancer cases for co-regulation and impact on overall survival using immunohistochemistry, southern blot and in situ hybridization techniques. Immunoreactivity was evaluated semi quantitatively by determining the staining index of the studied proteins.

Results

There was a significant correlation between cyclin D1 gene amplification and protein overexpression (concordance = 63.6%) and between Ki-67 and the other studied proteins. The staining index for Ki-67, cyclin A and D1 was higher in large, poorly differentiated tumors. The staining index of cyclin D1 was significantly higher in cases with deeply invasive tumors and nodal metastasis. Overexpression of cyclin A and D1 and amplification of cyclin D1 were associated with reduced overall survival. Multivariate analysis shows that cyclin D1 and A are two independent prognostic factors in colorectal cancer patients.

Conclusions

Loss of cell cycle checkpoints control is common in colorectal cancer. Cyclin A and D1 are superior independent indicators of poor prognosis in colorectal cancer patients. Therefore, they may help in predicting the clinical outcome of those patients on an individual basis and could be considered important therapeutic targets.
Norovirus gastroenteritis general outbreak associated with raw shellfish consumption in South Italy
Authors: Prato Rosa , Lopalco Pier Luigi , Chironna Maria , Barbuti Giovanna , Germinario Cinzia , Quarto Michele
Published: September 2004

Background

Despite Noroviruses (NV, previously "Norwalk-like viruses") being a leading cause of acute gastroenteritis outbreaks, the impact of NV infection is at present unknown and little information is available about strains circulating in Italy. In April 2002 an outbreak of gastroenteritis occurred in the province of Bari (South-east Italy), involving several households.

Methods

A retrospective cohort study was performed in order to assess risk factors associated with illness. All households where a case occurred were included in the study. Faecal specimens were collected from ill individuals. NV-specific RT-PCR was performed. Eleven samples of mussels were collected from fish-markets involved in the outbreak. A nested PCR was used for mussel samples.

Results

One hundred and three cases, detected by means of active surveillance, met the case definition. Raw shellfish eating was the principal risk factor for the disease, as indicated by the analytic issues (Risk Ratio: 1.50; IC 95%: 1.18 – 1.89; p < 0.001). NVs were found by means of RT-PCR of all the stool specimens from the 24 patients tested. Eleven samples of shellfish from local markets were tested for the presence or NVs; six were positive by nested PCR and genotypes were related to that found in patients' stools.

Conclusion

This is the first community outbreak caused by NVs related to sea-food consumption described in Italy. The study confirms that the present standards for human faecal contamination do not seem to be a reliable indicator of viral contaminants in mussels.
The effect of oxythioquinox exposure on normal human mammary epithelial cell gene expression: A microarray analysis study
Authors: Gwinn Maureen R , Whipkey Diana L , Weston Ainsley
Published: September 2004

Background

Inter-individual variation in normal human mammary epithelial cells in response to oxythioquinox (OTQ) is reported. Gene expression signatures resulting from chemical exposures are generally created from analysis of exposures in rat, mouse or other genetically similar animal models, limiting information about inter-individual variations. This study focused on the effect of inter-individual variation in gene expression signatures.

Methods

Gene expression was studied in primary normal human mammary epithelial cells (NHMECs) derived from four women undergoing reduction mammoplasty [Cooperative Human Tissue Network (National Cancer Institute and National Disease Research Interchange)]. Gene transcription in each cell strain was analyzed using high-density oligonucleotide DNA microarrays (HuGeneFL, Affymetrix™) and changes in the expression of selected genes were verified by real-time polymerase chain reaction at extended time points (ABI). DNA microarrays were hybridized to materials prepared from total RNA that was collected after OTQ treatment for 15, 60 and 120 min. RNA was harvested from the vehicle control (DMSO) at 120 min. The gene expression profile included all genes altered by at least a signal log ratio (SLR) of ± 0.6 and p value ≤ 0.05 in three of four cell strains analyzed.

Results

RNA species were clustered in various patterns of expression highlighting genes with altered expression in one or more of the cell strains, including metabolic enzymes and transcription factors. Of the clustered RNA species, only 36 were found to be altered at one time point in three or more of the cell strains analyzed (13 up-regulated, 23 down-regulated). Cluster analysis examined the effects of OTQ on the cells with specific p53 polymorphisms. The two strains expressing the major variant of p53 had 83 common genes altered (35 increased, 48 decreased) at one or more time point by at least a 0.6 signal log ratio (SLR). The intermediate variant strains showed 105 common genes altered (80 increased, 25 decreased) in both strains.

Conclusion

Differential changes in expression of these genes may yield biomarkers that provide insight into inter-individual variation in cancer risk. Further, specific individual patterns of gene expression may help to determine more susceptible populations.
Overview of the diagnostic value of biochemical markers of liver fibrosis (FibroTest, HCV FibroSure) and necrosis (ActiTest) in patients with chronic hepatitis C
Authors: Poynard Thierry , Imbert-Bismut Françoise , Munteanu Mona , Messous Djamila , Myers Robert P , Thabut Dominique , Ratziu Vlad , Mercadier Anne , Benhamou Yves , Hainque Bernard
Published: September 2004

Background

Recent studies strongly suggest that due to the limitations and risks of biopsy, as well as the improvement of the diagnostic accuracy of biochemical markers, liver biopsy should no longer be considered mandatory in patients with chronic hepatitis C. In 2001, FibroTest ActiTest (FT-AT), a panel of biochemical markers, was found to have high diagnostic value for fibrosis (FT range 0.00–1.00) and necroinflammatory histological activity (AT range 0.00–1.00). The aim was to summarize the diagnostic value of these tests from the scientific literature; to respond to frequently asked questions by performing original new analyses (including the range of diagnostic values, a comparison with other markers, the impact of genotype and viral load, and the diagnostic value in intermediate levels of injury); and to develop a system of conversion between the biochemical and biopsy estimates of liver injury.

Results

A total of 16 publications were identified. An integrated database was constructed using 1,570 individual data, to which applied analytical recommendations. The control group consisted of 300 prospectively studied blood donors. For the diagnosis of significant fibrosis by the METAVIR scoring system, the areas under the receiver operating characteristics curves (AUROC) ranged from 0.73 to 0.87. For the diagnosis of significant histological activity, the AUROCs ranged from 0.75 to 0.86. At a cut off of 0.31, the FT negative predictive value for excluding significant fibrosis (prevalence 0.31) was 91%. At a cut off of 0.36, the ActiTest negative predictive value for excluding significant necrosis (prevalence 0.41) was 85%. In three studies there was a direct comparison in the same patients of FT versus other biochemical markers, including hyaluronic acid, the Forns index, and the APRI index. All the comparisons favored FT (P < 0.05). There were no differences between the AUROCs of FT-AT according to genotype or viral load. The AUROCs of FT-AT for consecutive stages of fibrosis and grades of necrosis were the same for both moderate and extreme stages and grades. A conversion table was constructed between the continuous FT-AT values (0.00 to 1.00) and the expected semi-quantitative fibrosis stages (F0 to F4) and necrosis grades (A0 to A3).

Conclusions

Based on these results, the use of the biochemical markers of liver fibrosis (FibroTest) and necrosis (ActiTest) can be recommended as an alternative to liver biopsy for the assessment of liver injury in patients with chronic hepatitis C. In clinical practice, liver biopsy should be recommended only as a second line test, i.e., in case of high risk of error of biochemical tests.
Antitumor Vaccination of Patients With Glioblastoma Multiforme: A Pilot Study to Assess Feasibility, Safety, and Clinical Benefit
Authors: Steiner Hans Herbert , Bonsanto Matteo Mario , Beckhove Philipp , Brysch Michael , Geletneky Karsten , Ahmadi Rezvan , Schuele-Freyer Rebecca , Kremer Paul , Ranaie Golamreza , Matejic Dejana , Bauer Harald , Kiessling Marika , Kunze Stefan , Schirrmacher Volker , Herold-Mende Christel
Published: September 2004

Purpose

Prognosis of patients with glioblastoma is poor. Therefore, in glioblastoma patients, we analyzed whether antitumor vaccination with a virus-modified autologous tumor cell vaccine is feasible and safe. Also, we determined the influence on progression-free survival and overall survival and on vaccination-induced antitumor reactivity.

Patients and Methods

In a nonrandomized study, 23 patients were vaccinated and compared with nonvaccinated controls (n = 87). Vaccine was prepared from patient's tumor cell cultures by infection of the cells with Newcastle Disease Virus, followed by gamma-irradiation, and applied up to eight times. Antitumor immune reactivity was determined in skin, blood, and relapsed tumor by delayed-type hypersensitivity skin reaction, ELISPOT assay, and immunohistochemistry, respectively.

Results

Establishment of tumor cell cultures was successful in approximately 90% of patients. After vaccination, we observed no severe side effects. The median progression-free survival of vaccinated patients was 40 weeks (v 26 weeks in controls; log-rank test, P = .024), and the median overall survival of vaccinated patients was 100 weeks (v 49 weeks in controls; log-rank test, P < .001). Forty-five percent of the controls survived 1 year, 11% survived 2 years, and there were no long-term survivors (≥ 3 years). Ninety-one percent of vaccinated patients survived 1 year, 39% survived 2 years, and 4% were long-term survivors. In the vaccinated group, immune monitoring revealed significant increases of delayed-type hypersensitivity reactivity, numbers of tumor-reactive memory T cells, and numbers of CD8+ tumor-infiltrating T-lymphocytes in secondary tumors.

Conclusion

Postoperative vaccination with virus-modified autologous tumor cells seems to be feasible and safe and to improve the prognosis of patients with glioblastomas. This could be substantiated by the observed antitumor immune response.
The Individual Within the Group: Balancing the Need to Belong With the Need to Be Different
Authors: Hornsey Matthew J. , Jetten Jolanda
Published: September 2004

Many theorists have wrestled with the notion of how people balance their need to be included in social groups with their need to be different and distinctive. This question is particularly salient to researchers from the social identity perspective, who have traditionally viewed individual differentiation within groups as being inimical to group identification. In this article we present a number of strategies that people can use to balance their need to belong and their need to be different, without violating social identity principles. First, drawing from optimal distinctiveness theory, we discuss 4 ways in which the need for belonging and the need to be different can be resolved by maximizing group distinctiveness. We then discuss 4 ways in which it is possible to achieve individual differentiation within a group at the same time demonstrating group identification. These strategies are discussed and integrated with reference to recent empirical research and to the social identity perspective.
It's Beyond My Control: A Cross-Temporal Meta-Analysis of Increasing Externality in Locus of Control, 1960-2002
Authors: Twenge Jean M. , Zhang Liqing , Im Charles
Published: September 2004

Two meta-analyses found that young Americans increasingly believe their lives are controlled by outside forces rather than their own efforts. Locus of control scores became substantially more external (about .80 standard deviations) in college student and child samples between 1960 and 2002. The average college student in 2002 had a more external locus of control than 80% of college students in the early 1960s. Birth cohort/time period explains 14% of the variance in locus of control scores. The data included 97 samples of college students (n = 18,310) and 41 samples of children ages 9 to 14 (n = 6,554) gathered from dissertation research. The results are consistent with an alienation model positing increases in cynicism, individualism, and the self-serving bias. The implications are almost uniformly negative, as externality is correlated with poor school achievement, helplessness, ineffective stress management, decreased self-control, and depression.
Structure-activity relationship studies on chalcone derivatives: potent inhibition of platelet aggregation
Authors: Ko Horng-Huey , Hsieh Hsin-Kaw , Liu Cheng-Tsung , Lin Hsien-Chen , Teng Che-Ming , Lin Chun-Nan
Published: September 2004

In an effort to develop potent antiplatelet agents with anti-inflammatory action, a novel series of anti-inflammatory chalcones was screened to evaluate their antiplatelet effects. Structure-activity relationships and mode of action were investigated and characterized. The antiplatelet effects of the chalcones on washed rabbit platelets and human platelet-rich plasma were evaluated. Arachidonic acid-induced platelet aggregation was potently inhibited by almost all the chalcone derivatives. Collagen-induced platelet aggregation was potently inhibited by all the chalcone derivatives at 300 μm, except for compound 4 at 100 μm. Compounds 6, 7 and 9 significantly inhibited the aggregation of washed rabbit platelets induced by platelet-activating factor at 300 μm. Of the compounds tested in human platelet-rich plasma, compounds 2, 8 and 9 showed significant inhibition of secondary aggregation induced by adrenaline. It is concluded that the antiplatelet effect of 2, 8 and 9 is mainly owing to an inhibitory effect on thromboxane formation. The inhibitory effect of 6, 7 and 9 on platelet aggregation induced by platelet-activating factor could be owing to a calcium antagonizing effect or inhibition of intracellular calcium mobilization.
Nasal administration of albuterol: an alternative route of delivery
Authors: Hussain Anwar A , Dakkuri Adnan , Lai Yih-Loong , Traboulsi Ashraf , Hussain Munir A
Published: September 2004

The use of metered-dose inhalers for the delivery of albuterol, a β2-selective adrenergic agonist, is associated with drawbacks, especially in children and the elderly. This investigation was designed to assess the effectiveness of albuterol delivered intranasally and to compare this delivery route with intratracheal and intravenous delivery. Three parameters of pulmonary function (peak maximal expiratory flow, maximal expiratory flow at 50% vital capacity, and total lung capacity) in anaesthetized, artificially ventilated guinea pigs were used to determine the degree of protection produced by albuterol against bronchoconstrictor responses provoked by acetylcholine. The heart rate was also measured. Although intranasal albuterol induced a slower protective action during the very initial phase of absorption, the drug was shown to be equally effective when administered either intranasally or intratracheally. In contrast, despite a significant effect initially in the case of intravenous albuterol, its ability to influence pulmonary function faded rather rapidly. No statistically significant differences in heart rate could be detected among the different treatment groups. In conclusion, intranasal albuterol may offer an alternative to metered-dose inhalers for the treatment of acute bronchospasm and for prevention of exercise-induced asthma, especially for children and the elderly.
Cloned human 5-HT1A receptor pharmacology determined using agonist binding and measurement of cAMP accumulation
Authors: Sharif Najam A , Drace Colene D , Williams Gary W , Crider Julie Y
Published: September 2004

Twenty agonists and nine antagonists were evaluated for their ability to compete for [3H]-8-hydroxy-2-(di-n-propylamino)tetralin ([3H]-8-OH-DPAT) binding to the cloned human serotonin-1A (ch-5-HT1A) receptor expressed in Chinese hamster ovary cells and for their ability to alter adenylyl cyclase activity in the same cells. The most potent full agonists of high affinity included N,N-dipropyl-5-carboxamidotryptamine (pEC50 = 9.6 ± 0.1), MDL 73005EF (pEC50 = 9.3 ± 0.2), 5-methyl-urapidil (pEC50 = 9.2 ± 0.1), 5-carboxamidotryptamine (pEC50 = 9.1 ± 0.2), R(+)-8-OH-DPAT (pEC50 = 8.6 ± 0.1) and BMY-7378 (pEC50 = 8.6 ± 0.1). WB-4101 (pEC50 = 8.3 ± 0.2; IA = 79%), clozapine (pEC50 = 8.1 ± 0.3; IA = 29%), (buspirone (pEC50 = 7.6 ± 0.2; IA = 79%), quipazine (pEC50<5; IA = 45%) and R-DOI (pEC50<5; IA = 31%) were weaker agonists with partial agonist properties. The most potent antagonists were WAY-100,635 (pKi = 10.2 ± 0.1), methiothepin (pKi = 8.8 ± 0.2), spiperone (pKi = 8.7 ± 0.2) and NAN-190 (pKi = 8.5 ± 0.2). The receptor affinities and functional potencies were well correlated (r = 0.88; P<0.0001). Our binding data correlated well with the pharmacology of endogenous 5-HT1A receptors in the rabbit iris-ciliary body (r = 0.91; P<0.001) and rat hippocampus (r = 0.93, P<0.0001). Our functional cAMP data correlated well with other cAMP accumulation data (r = 0.8, P<0.01 vs calf hippocampus) but less so with [35S]-GTP-yS binding to the ch-5-HT1A receptor as a functional activity read-out (r = 0.58, P<0.05). The present study provides a detailed pharmacological characterization of the ch-5-HT1A receptor using binding and functional assays.
Reversal of cancer multidrug resistance by green tea polyphenols
Authors: Mei Yuying , Qian Feng , Wei Dongzhi , Liu Jianwen
Published: September 2004

The aim of this study was to examine the effect and mechanism of green tea polyphenols (TP) on reversal of multidrug resistance (MDR) in a carcinoma cell line. Using the MTT assay, TP was examined for its modulating effects on the drug-resistant KB-A-1 cells and drug-sensitive KB-3–1 cells. When 10 μg mL−1 (-)-epigallocatechin gallate (EGCG) or 40 μg mL−1 TP were present simultaneously with doxorubicin (DOX), the IC50 of DOX on KB-A-1 cells decreased from 10.3 ± 0.9 μg mL−1 to 4.2 ± 0.2 and 2.0 ± 0.1 μg mL−1, respectively. TP and EGCG enhanced the DOX cytotoxicity on KB-A-1 cells by 5.2-and 2.5-times, respectively, but did not show a modulating effect on KB-3–1 cells. This indicated that both TP and EGCG had reversal effects on the MDR phenotype in-vitro. A KB-A-1 cell xenograft model was established, and the effect of TP on reversing MDR in-vivo was determined. Mechanistic experiments were conducted to examine the uptake, efflux and accumulation of DOX. Cloning and expression of the nucleotide binding domain of the human MDR1 gene in Escherichia coli was established, and by using colorimetry to examine the activity of ATPase to hydrolyse ATP, the ATPase activity of target nucleotide binding domain protein was determined. TP exerted its reversal effects through the inhibition of ATPase activity, influencing the function of P-glycoprotein, and causing a decreased extrusion of anticancer drug and an increased accumulation of anticancer drug in drug resistant cells. Using reverse transcription-polymerase chain reaction, the inhibitory effect of TP on MDR1 gene expression was investigated. Down-regulation of MDR1 gene expression was the main effect, which resulted in the reversal effect of TP on the MDR phenotype. TP is a potent MDR modulator with potential in the treatment of P-glycoprotein mediated MDR cancers.
Encapsulation of naturally occurring flavonoids into liposomes: physicochemical properties and biological activity against human cancer cell lines
Authors: Goniotaki M , Hatziantoniou S , Dimas K , Wagner M , Demetzos C
Published: September 2004

Liposomes consisting of egg phosphatidylcholine were prepared by a thin-film hydration method followed by sonication and were used to investigate the percentage encapsulation of four flavonoids (quercetin, rutin, isoscutellarein and isoscutellarein diglycoside). The lipid recovery and the flavonoid-to-lipid molar ratio were measured using high-performance thin-layer chromatography/flame ionization detection and UV-vis spectroscopy. Differential scanning calorimetry was used to study the effect of the flavonoids on the phase transition temperature and on the enthalpy of the main phase transition of dipalmitoylphosphatidylcholine bilayers, and their ability to influence the membrane fluidity. The final liposomal formulation incorporating flavonoids, as well as free flavonoids, were tested for their activity against human cancer cell lines using the sulforhodamine B assay. The results showed that the encapsulation efficiency varied from 95% (0.21 flavonoid-to-lipid molar ratio) to 37.5% (0.09 flavonoid-to-lipid molar ratio) for isoscutellarein and its glycoside, respectively. The differential scanning calorimetry data showed close thermal and dynamic effects depending on the structure of the flavonoids, and suggest that there is a relationship between flavonoid molecular structure and the interaction with model membranes. Liposomal isoscutellarein showed improved growth inhibiting activity against all cell lines tested in comparison with that of its free form, which was inactive (>100 μM).
Asiatic acid derivatives enhance cognitive performance partly by improving acetylcholine synthesis
Authors: Kim So Ra , Koo Kyung Ah , Lee Mi Kyeong , Park Hyeung-geun , Jew Sang-sup , Cha Kyung-hoe , Kim Young Choong
Published: September 2004

Thirty-six semi-synthesized derivatives of asiatic acid were examined to determine if they had cognitive-enhancing activity in a passive avoidance test. Among the compounds tested, AS-2, AS-2–9–006 and AS-9–006 significantly alleviated scopolamine-induced memory impairment at doses of 1 and 10 mg kg−1. Furthermore, AS-2 and AS-2–9–006 (1 mg kg−1 administered four times daily) enhanced cognitive performance as determined in a water maze test. These three asiatic acid derivatives did not show any significant effect on the learning process in active avoidance tests. AS-2, AS-2–9–006 and AS-9–006 enhanced cholineacetyltransferase activity in a cholinergic neuroblastoma cell line, S-20Y, in-vitro. Therefore, AS-2, AS-2–9–006 and AS-9–006 may have therapeutic value in alleviating certain memory impairment observed in dementia.
Degradation of berenil (diminazene aceturate) in acidic aqueous solution
Authors: Campbell Michael , Prankerd Richard J , Davie Ashley S , Charman William N
Published: September 2004

The trypanocide berenil was assessed for chemical stability over the pH range 1–8 at 37°C and 0.2 m ionic strength. It was found to be sufficiently unstable under acid conditions that its therapeutic efficacy is most likely severely compromised when administered orally. At pH 3, the half-life was 35 min, decreasing to 1.5 min at pH 1.75. Reaction rate constants were corrected for the effects of buffer catalysis and were found to range from 2.00 min−1 at pH 1 to 6.1 × 10−6 min−1 at pH 8. The pH-rate profile displayed a region (pH 1–4) where specific acid catalysis was dominant, followed by a transitional region (pH 5–7), and finally a region (pH > 7) where uncatalysed degradation was most important. It is recommended that berenil be enteric coated for formulations to be used in treating Third World parasitic diseases.
Pluronic block copolymers and Pluronic poly(acrylic acid) microgels in oral delivery of megestrol acetate
Authors: Alakhov Valery , Pietrzynski Grzegorz , Patel Kishore , Kabanov Alexander , Bromberg Lev , Hatton T Alan
Published: September 2004

Several Pluronic-based formulations were studied in-vitro and in a rat model with respect to the release and bioavailability of megestrol acetate (MA) after oral administration. It was demonstrated that an aqueous, micellar formulation comprising a mixture of a hydrophobic (L61) and a hydrophilic (F127) Pluronic copolymer, significantly enhanced the bioavailability of MA administered orally at relatively low doses (1–7 mg kg−1). Pluronic-based microgels (spherical gel particles of sub-millimetre size) were introduced as MA vehicles. The microgels comprised a cross-linked network of poly(acrylic acid) onto which the Pluronic chains were covalently attached. Microgels of Pluronic L92 and poly(acrylic acid) fabricated into tablet dosage forms exhibited dramatically lowered MA initial burst release. The MA release was pH-dependent owing to the pH sensitivity of the microgel swelling, with the drug retained by the microgel at pH 1.8 and released slowly at pH 6.8. In the rat model, a significant increase in MA bioavailability was observed when the microgel-formulated MA was administered orally at a high dose of 10 mg kg−1, owing to the enhanced retention of the microgel. The study of the microgel passage through the gastrointestinal tract demonstrated the microgel retention characteristic of a very high molecular weight polymer and the absence of any systemic absorption of the polymer.
Decrease in oral bioavailability of ciclosporin by intravenous pulse of methylprednisolone succinate in rats
Authors: Konishi Hiroki , Sumi Masaki , Shibata Nobuhito , Takada Kanji , Minouchi Tokuzo , Yamaji Akira
Published: September 2004

We examined the effects of high-dose methylprednisolone on the bioavailability of orally administered ciclosporin in rats. To emulate the clinical protocol of methylprednisolone pulse therapy, methylprednisolone sodium succinate (MPS), a prodrug of methylprednisolone, was intravenously administered as repeated doses (66.3 mg kg−1) for 3 days. The area under the blood ciclosporin concentration versus time curve after oral administration was significantly reduced by 60% by pulse treatment with MPS. Based on our previous finding that the total body clearance of ciclosporin was reduced by about 20% by the same methylprednisolone pulse protocol, the extent of reduction in the oral bioavailability of ciclosporin was estimated to be approximately 50%, indicating a drug interaction between high-dose methylprednisolone and orally administered ciclosporin, which affected the absorption process. In rats treated with MPS, an in-situ efflux experiment using rhodamine-123 demonstrated that the reverse transport function of P-glycoprotein (P-gp) in the small intestine was significantly enhanced, although there was no significant increase in the intestinal microsomal activity of triazolam α- and 4-hydroxylation, metabolic probes for CYP3A. In addition, a significant decrease was observed in the amount of secreted bile acids serving as an enhancer of gastrointestinal absorption of ciclosporin in MPS treatment. To directly estimate the absorptive capacity, an in-situ absorption test was conducted using a closed-loop of small intestine in control and MPS-treated rats. Intestinal absorption of ciclosporin was significantly decreased, not only in the absence of bile flow but also by treatment with MPS, which well reflected the change in the in-vivo pharmacokinetic behaviour of ciclosporin after methylprednisolone pulsing. These results demonstrate that bioavailability of ciclosporin is markedly reduced by MPS pulse treatment, and the mechanism of this interaction was confirmed to involve enhancement of small-intestinal P-gp function and decrease in bile secretion.
Protective effects of the Chinese prescription Hachimi-jio-gan against diabetic oxidative stress
Authors: Kim Hyun Young , Yokozawa Takako , Cho Eun Ju , Yamabe Noriko
Published: September 2004

We used rats with streptozotocin (STZ)-induced diabetes to investigate the effects of Hachimi-jiogan on diabetic oxidative stress. Oral administration of Hachimi-jio-gan, at a dose of 50, 100 or 200 mg kg−1 (body weight) daily, for 10 days to rats with STZ-induced diabetes resulted in significant dose-dependent decreases in serum levels of glucose and glycosylated protein, implying that Hachimi-jio-gan improves the abnormal glucose metabolism that leads to oxidative stress. Hachimi-jio-gan also showed a tendency to reduce the urine volume and significantly reduced the elevated urinary protein level. Moreover, rats with STZ-induced diabetes had high serum levels of superoxide and nitrite/nitrate. However, the administration of Hachimi-jio-gan dose-dependently reduced the overproduction of radicals associated with diabetes, suggesting the role of Hachimi-jio-gan as a radical scavenger that could protect against diabetic oxidative stress. Furthermore, thiobarbituric acid-reactive substance levels in serum and hepatic and renal mitochondria were dose-dependently lower in the Hachimi-jio-gan-treated groups than in the control diabetic group, which implies that Hachimi-jio-gan would alleviate the oxidative stress associated with diabetes through the inhibition of lipid peroxidation. These results indicate that Hachimi-jio-gan is a potential therapeutic agent that will reduce the damage caused by oxidative stress involved in diabetes.
Deconstructing ‘globalisation’ in Ireland
Authors: Smith Nicola Jo-Anne
Published: September 2004

English

The Irish Republic has been widely hailed as a ‘showpiece of globalisation’. This article argues that although Ireland has experienced considerable change in recent years, there is little evidence to suggest that its economy has indeed been ‘globalised’. Yet the discursive construction of globalisation may in itself play an independent causal role in shaping political outcomes. The article thus also explores the role of ideas about globalisation in shaping Irish policy change.
The new regulatory state and relational capacity
Authors: Jayasuriya Kanishka
Published: September 2004

English

Globalisation has transformed the internal architecture of the state, leading to the emergence of a new form of regulatory state that operates through mechanisms of metagovernance – that is, the governance of governance. This has important implications for various models of policy capacity. Conventional accounts of policy capacity embody an attribute model of capacity that seeks to identify a set of transformative powers over policy and structure. In contrast, the new regulatory state requires that capacity be understood as a relational term that structures various sites of governance and links dispersed regulatory resources and agents.