bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Prophetic Seer Potentiating Us in the Present
Authors: Thompson Curtis L. 
Published: November 2007

AbstractIn his book Radical Evolution Joel Garreau functions as a prophet and a seer. In presenting a narrative of the future that includes an optimistic view of human nature, he warns that because of the GRIN technologies (genetics, robotics, information technology, and nanotechnology) the quickening evolution of “The Curve” is upon us and could well soon culminate in the mind‐boggling social change of “The Singularity.” Garreau considers three scenarios of the technological future: the Heaven Scenario, the Hell Scenario, and the Prevail Scenario. The third wins favor because the heavenly envisionment with its evolution of a superintelligent human who could engineer a species with a greatly extended lifespan is too blissful and the hellish prognostication with its destruction of the human species within the next quarter century is too pernicious. Just right is the middle‐of‐the‐road perspective of the Prevail‐Transcend depiction of the future. This third view is indeed more appropriate than the first two scenarios, but a more nuanced form of the third perspective—emphasizing similarly the role of human freedom and responsibility in continuing to reshape human nature but drinking less deeply of the transhumanist elixir and more deeply of a pantransentheistic potion—would constitute a more suitable vision of the future.
A pilot study of pharmacokinetically guided dosing of oral methotrexate in the initial phase of psoriasis treatment
Authors: Hroch M , Chladek J , Simkova M , Vaneckova J , Grim J , Martinkova J 
Published: November 2007

AbstractBackground  Clinical studies of low‐dose oral methotrexate (MTX) in the treatment of psoriasis and rheumatoid arthritis document a large interpatient variability in the pharmacokinetics of MTX, including its polyglutamates (MTXPGs) in erythrocytes (RBC). This can be a factor contributing to the variability of therapeutic and toxic effects.Aim  This pilot trial aimed to investigate the MTXPG concentrations in RBC as well as their relation to therapeutic and adverse effects during the initial 4 months of pharmacokinetically guided therapy with a divided‐dose schedule (three doses of MTX separated by 12‐h intervals once a week).Subjects and methods  Sixteen psoriatic patients (4 men and 12 women; mean age, 53 years; range, 28–69 years) with moderate‐to‐severe chronic plaque psoriasis [mean Psoriasis Area and Severity Index (PASI) = 24; range, 9–42] were enrolled in the study. Concentrations of plasma MTX and that of MTXPGs in RBC were assayed using liquid chromatography methods. The area under the concentration–time curve of plasma MTX in the interval 0–8 h post‐dose (AUC0–8 h) was measured after a test bolus dose of 10 mg, and the starting weekly dose was individualized in order to achieve the target AUC0–8 h of 1800 nmol·h/L. The PASI, biochemistry, and haematology tests and MTXPGs levels in RBC were evaluated at baseline and at 4‐week intervals.Results  The AUC0–8 h achieved 1360 ± 425 nmol·h/L (mean ± SD: range, 778–2400 nmol·h/L). The mean (range) of individualized doses was 14.5 mg/week (7.5–22.5 mg). The mean (SD) steady‐state concentration of total MTXPGs observed between days 85 to 110 reached 113 (34.6) nmol/L (range, 66.1–174 nmol/L). The PASI decreased from 24·0 ± 8.0 (mean ± SD) at baseline to 8.0 ± 6.1 at day 110 (P < 0.001). Thirteen patients (87%) achieved a greater than 50% improvement in baseline PASI, and seven (47%) experienced a greater than 75% improvement. There was no relationship between the percent improvement from baseline PASI and the steady‐state concentration of MTXPGs in RBC. All patients tolerated MTX well. Throughout the study period, there was a continuous increasing trend in the geometric mean values of the mean corpuscular volume from 92.6 to 96.4 fL (P < 0.001) and of plasma homocysteine from 9.5 to 12.3 µmol/L (P < 0.005). The geometric mean serum alanine aminotransferase (ALT) activity slightly increased from 0.49 to 0.80 µkat/L (P < 0.05). However, only two patients had the ALT activity transiently elevated above twice the upper limit of normal.Conclusion  Results of this pilot trial show that the steady‐state levels of MTXPGs in RBC vary less than threefold between patients and did not correlate with the change in PASI observed after 4 months of therapy with an individualised weekly dose of MTX. Whether pharmacokinetically guided dosing can improve the results of psoriasis therapy with MTX should be prospectively tested in large controlled studies.
Anti‐inflammatory effect of pimecrolimus in the sodium lauryl sulphate test
Authors: Engel K , Reuter J , Seiler C , Mönting J Schulte , Jakob T , Schempp CM 
Published: November 2007

AbstractBackground  Pimecrolimus is a calcineurin inhibitor used for the topical treatment of inflammatory skin diseases. We have shown previously that pimecrolimus cream is not effective on intact skin in the ultraviolet erythema test.Objective  To test the anti‐inflammatory effect of pimecrolimus cream after damage of the skin barrier by sodium lauryl sulphate (SLS) in a randomised, placebo‐controlled, observer‐blinded study.Methods  SLS (3% v/v) was applied under occlusion on the back of 36 healthy volunteers for 24 h. Subsequently, the test areas were treated for 24 h with pimecrolimus cream, 1% hydrocortisone in a hydrophilic ointment, and the vehicle alone over three consecutive days. One control area remained untreated. The erythema index and the transepidermal water loss (TEWL) served as readout parameters to assess the SLS‐induced skin irritation.Results  Pimecrolimus cream and 1% hydrocortisone cream significantly reduced the SLS‐induced erythema. The two test preparations did not have a significant effect on the TEWL.Conclusion  After damage to the skin barrier by SLS, pimecrolimus seems to penetrate into the skin as shown by a reduction of the irritation‐induced erythma. These data further support the notion that pimecrolimus is selectively effective in the treatment of skin disorders with an impaired function of the epidermal barrier.
Hypolipidemic and antioxidant effects of ethanolic extract from dried calyx ofHibiscus sabdariffain alloxan‐induced diabetic rats
Authors: Farombi E.O. , Ige O.O. 
Published: November 2007

AbstractThe present study investigated the hypolipidemic and antioxidant effects of ethanolic extract ofHibiscus sabdariffaL (HSE) in rats treated with alloxan. The results were compared with the standard hypolipidemic drug lovastatin. HSE at doses of 100 and 200 mg/kg elicited dose‐dependent effects on the biomarkers evaluated. In alloxan‐treated rats, HSE at the dose of 200 mg/kg significantly attenuated the elevated blood glucose concentration by 57%. Lovastatin (10 mg/kg) similarly reduced the glucose level in alloxan‐treated rats by 48%. HSE reduced the alloxan‐induced increases in cholesterol, very low‐density lipoprotein cholesterol (VLDL‐C), low‐density lipoprotein cholesterol (LDL‐C) and atherogenic index by 29%, 36%, 40%, and 32%, respectively while lovastatin decreased the alloxan‐induced increases in the parameters by 25%, 23%, 28%, and 31%, respectively. HSE (200 mg/kg) and lovastatin (P < 0.01) decreased the alloxan‐induced increases in the lipid profiles both in the liver and the kidneys. HSE at 200 mg/kg attenuated the alloxan‐induced decrease in the activities of superoxide dismutase (SOD), catalase (CAT) and the level of glutathione (GSH) by 36%, 44%, and 64% in the liver and by 20%, 43%, and 85% in the kidney of rats. Lovastatin similarly increased SOD, CAT and GSH by 32%, 29%, and 64% in the liver and by 17%, 26%, and 73% in the kidney of alloxan‐treated rats. HSE (200 mg/kg) significantly decreased the alloxan‐mediated increase in malondialdehyde (MDA) and protein carbonyl (PC) levels in the liver by 44% and 43% and in the kidneys by 45% and 38%, respectively, while lovastatin decreased the alloxan‐induced elevation in MDA and PC in the liver by 42% and 41% and in the kidney by 45% and 33%, respectively. While HSE at a dose of 200 mg/kg and lovastatin normalized the activity of phosphatidate phosphohydrolase in the liver, the extract and lovastatin did not elicit significant changes in the kidney enzyme activity in rats treated with alloxan. Overall, our data demonstrate that HSE possesses strong hypolipidemic as well as antioxidant properties in alloxan‐induced diabetic rats and as suchHibiscus sabdariffacould be useful in preventing the development of atherosclerosis and possible related cardiovascular pathologies associated with diabetes.
Animal models of anxiety in mice
Authors: Bourin Michel , Petit‐Demoulière Benoit , Nic Dhonnchadha Brid , Hascöet Martine 
Published: November 2007

AbstractAmong the multiple possibilities to study human pathologies, animal models remain one of the most used pathways. They allow to access to unavailable answers in human patients and to learn about mechanisms of action of drugs. Primarily developed with rats, animal models in anxiety have been adapted with a mixed success for mice, an easy‐to‐use mammal with better genetic possibilities than rats. In this review, we have focused on the most used animal models in anxiety in mice. Both conditioned and unconditioned models are described, to represent all types of animal models of anxiety. Behavioural studies require strong care for variable parameters, linked to environment, handling or paradigm; we have discussed about this topic. Finally, we focused on the consequences of re‐exposure to the apparatus. Test–retest procedures can bring in new answers, but should be deeply studied, to revalidate the whole paradigm as an animal model of anxiety.
The mechanisms of vasorelaxant effect of leptin on isolated rabbit aorta
Authors: Şahin Ayşe Saide , Bariskaner Hulagu 
Published: November 2007

AbstractIn the present study, we analysed the effects of leptin on rabbit aorta and the mechanisms underlying these effects. Leptin (10−12–10−9 m) induced concentration‐dependent relaxation in intact rabbit aorta rings precontracted with phenylephrine (10−6 m). Removal of endothelium abolished the effects of leptin. Pretreatment of rings with Nω‐nitro‐l‐arginine methyl ester (10−4 m 20 min) or catalase (1200 U/mL 20 min) significantly reduced the relaxant response to leptin when compared with the control group. The incubation of brefeldin A (3.5 × 10−5 m 90 min), indomethacin (10−5 m 20 min), tetraethylammonium (10−4 m 20 min), and glibenclamide (10−5 m, 20 min) did not affect the leptin‐induced vasodilation. These results suggest that leptin relaxes the rabbit aorta. The relaxation is mediated by endothelium‐derived nitric oxide and hydrogen peroxide.
Analysis of drug transporter expression in human intestinal Caco‐2 cells by real‐time PCR
Authors: Maubon Nathalie , Le Vee Marc , Fossati Lina , Audry Mathilde , Le Ferrec Eric , Bolze Sebastien , Fardel Olivier 
Published: November 2007

AbstractExpression of drug transporters corresponds to a crucial parameter in intestinal Caco‐2 cells widely used for investigating drug absorption. In order to characterize it in an accurate, reproducible and comparative manner, we analyzed mRNA levels of 19 influx and efflux drug transporters through real‐time quantitative polymerase chain reaction assays combined with the use of a total RNA reference standard. Profiles of transporter expression were found to be significantly correlated in two independent Caco‐2 cell clones and in human small intestine, which may support the use of Caco‐2 cells for investigating intestinal drug transport. Several transporters were nevertheless quantitatively expressed at higher (MRP2, MRP3, MRP4, MRP5, MRP6, OATP‐A, OATP‐B, OCT1 and MCT1) or lower (BCRP) levels in Caco‐2 cells comparatively to small intestine. Moreover, MDR1, MRP2, OATP‐A and PEPT1 mRNA relative expression were found to differ in the two analyzed Caco‐2 cell clones by at least a twofold factor, highlighting that some variations in transporter expression may occur in Caco‐2 cells depending on cell origin, and therefore underlining the interest of carefully characterizing transporter levels in any Caco‐2 cell clone before its use for drug transport assays.
Dose‐response effect of ellagic acid on circulatory antioxidants and lipids during alcohol‐induced toxicity in experimental rats
Authors: Devipriya Nagarajan , Sudheer Adluri Ram , Menon Venugopal P. 
Published: November 2007

AbstractEllagic acid (EA) is a naturally occurring polyphenolic compound that exhibits antioxidative, anti‐inflammatory, anti‐hyperlipidaemic and anticarcinogenic activities in a wide range of assays both in vitro and in vivo. It occurs in various foods such as strawberries, grapes, walnuts, etc. The aim of this study was to assess the effect of ellagic acid on alcohol‐induced changes in the circulatory antioxidative status, micronutrients and lipid levels in a dose‐dependent fashion. Female albino Wistar rats weighing 150–170 g were used to assess the effects of EA against alcohol‐induced damage. Three different concentrations of EA (30, 60 and 90 mg/kg body weight) were tested against 20% alcohol via intragastric administration. At the end of the experimental duration of 45 days, we evaluated endogenous antioxidants: both enzymatic (superoxide dismutase, catalase and glutathione peroxidase) and non‐enzymatic (vitamin C and E, and reduced glutathione) status, micronutrients, viz. copper and zinc, and lipids: cholesterol, triglycerides, free fatty acids and phospholipids in the circulation. The body weight gain of both alcohol‐fed rats and EA‐treated rats were also inferred. EA significantly inhibits alcohol‐induced toxicity by improving body weight, restoring antioxidant status, modulating micronutrients and attenuating the lipid levels in the circulation. The greatest inhibitory effect was observed with 60 mg/kg body weight of EA in all the biochemical assessments. The results support the hypothesis that EA at the concentration of 60 mg/kg body weight decreases the intensity of alcohol‐induced toxicity and could be developed as a potential drug for alcohol abuse in the near future.
Differential parenting and sibling jealousy: Developmental correlates of young adults’ romantic relationships
Authors: RAUER AMY J. , VOLLING BRENDA L. 
Published: November 2007

AbstractData from a survey of 200 young adults assessed whether the early nonshared environment, specifically parental differential treatment, was associated with romantic relationship distress through its effects on sibling jealousy, attachment styles, and self‐esteem. Individuals who received equal affection from their parents in comparison to their sibling reported equal jealousy between themselves and their sibling, had higher self‐esteem, more secure attachment styles, and less romantic relationship distress. Receiving differential parental affection, regardless of whether the participant or their sibling was favored, was associated with more negative models of self and others, which in turn were associated with greater romantic relationship distress. Results indicate that early within‐family experiences may be particularly relevant for later healthy romantic relationship functioning.
Prevalence and cost of nonadherence with antiepileptic drugs in an adult managed care population
Authors: Davis Keith L. , Candrilli Sean D. , Edin Heather M. 
Published: November 2007

Summary
Purpose: This study assessed the extent of refill nonadherence with antiepileptic drugs (AEDs) and the potential association between AED nonadherence and health care costs in an adult‐managed care population.
Methods: Retrospective claims from the PharMetrics database were analyzed. Inclusion criteria were: age ≥21, epilepsy diagnosis between January 01, 2000 and March 12, 2005, ≥2 AED prescriptions, and continuous health plan enrollment for ≥6 months prior to and ≥12 months following AED initiation. Adherence was evaluated using the medication possession ratio (MPR). Patients with an MPR <0.8 were classified as nonadherent. Multivariate regression was used to assess the effect of AED nonadherence on annualized cost outcomes. Regression covariates included patient demographics, Charlson Comorbidity Index (CCI), and follow‐up duration.
Results: Among patients meeting all inclusion criteria (N = 10,892), 58% were female, mean age was 44 years, mean CCI was 0.94, and mean follow‐up was 27 months. Mean MPR was 0.78 and 39% of patients were nonadherent. AED nonadherence was associated with an increased likelihood of hospitalization (odds ratio [OR]= 1.110, p = 0.013) and emergency room (ER) admission (OR = 1.479, p < 0.0001), as well as increased inpatient and ER costs of $1,799 and $260 (both p = 0.001), respectively, per patient per year. Outpatient and other ancillary costs were not significantly affected by nonadherence. A large net positive effect of nonadherence on total annual health care costs remained (+$1,466, p = 0.034) despite an offset from reduced prescription drug intake.
Discussion: Adherence with AEDs among adult epilepsy patients is suboptimal and nonadherence appears to be associated with increased health care costs. Efforts to promote AED adherence may lead to cost savings for managed care systems.
Valproate‐induced thrombocytopenia: a prospective monotherapy study
Authors: Nasreddine Wassim , Beydoun Ahmad 
Published: November 2007

Summary
Purpose: The frequency of valproate (VPA)‐induced thrombocytopenia varied widely in previous studies, due to methodological differences. Our objective was to evaluate the relationship between trough VPA plasma levels and platelet counts and assess risk factors for the development of thrombocytopenia.
Methods: Patients with refractory partial epilepsy were enrolled in this double‐blind, multicenter, concentration–response trial that evaluated the efficacy and safety of high versus low trough plasma VPA concentrations following administration of divalproex sodium as monotherapy. Trough VPA concentrations and concomitant platelet counts were drawn at baseline and intermittently throughout the 24‐week trial. Bivariate correlations and multivariate stepwise regression analysis were performed between platelet counts and multiple variables. A logistic regression analysis was done to determine the probability of developing thrombocytopenia at various VPA levels.
Results: A total of 851 VPA levels and concomitant platelet counts were analyzed in 265 patients. Of these, 17.7% of patients experienced at least one episode of thrombocytopenia (platelet count ≤ 100,000/μl) after exposure to divalproex sodium. A significant negative correlation was found between VPA levels and platelet counts. Women were significantly more likely to develop thrombocytopenia. The probability of developing thrombocytopenia substantially increased at trough VPA levels above 100 μg/ml in women and above 130 μg/ml in men.
Discussion: Our data strongly support a causal relationship between rising plasma VPA levels and reduced platelet counts, with additional risk factors including female gender and lower baseline platelet counts.
EPSP depression following neocortical seizures in cat
Authors: Nita Dragos A. , Cissé Youssouf , Timofeev Igor 
Published: November 2007

Summary To study the possible mechanism(s) underlying unresponsiveness following neocortical seizures, we recorded excitatory postsynaptic potentials (EPSPs) of cortical neurons evoked by ipsilateral cortical stimulation before and after spontaneous or elicited seizures. Regular‐spiking neurons (n = 32) were intracellularly recorded in association area five of cats under ketamine–xylazine or barbiturate anesthesia. Compared with control responses, cortically evoked EPSPs were characterized by decreased amplitude after electrographic seizures. Synaptic responses and intrinsic properties were measured by applying extracellular electrical stimuli followed by intracellular hyperpolarizing current pulses. The input resistance decreased during seizures but quickly recovered to control level after the paroxysms, whereas the amplitude of evoked EPSPs remained lower following seizures, generally for 2–12 min, suggesting that the decreased EPSPs were not due to an alteration of intrinsic response. Data demonstrate a long‐lasting decreased synaptic responsiveness following generalized spike‐wave seizures slowly recovering in time.
Acculturation and Alcohol Among Latino Adults in the United States: A Comprehensive Review
Authors: Zemore Sarah E. 
Published: November 2007

Background:  In light of the inconsistent evidence associating acculturation with drinking outcomes among Latinos in the United States, the current paper comprehensively reviews the literature on this topic.Methods:  Studies were eligible for review if they (1) were published in a refereed journal, (2) were published in English, (3) sampled Latino/Hispanic adults aged 18+, (4) examined self‐reported drinking behavior, alcohol‐related problems, and/or alcohol abuse/dependence, and (5) reported original results or unique analyses from a larger dataset. The review includes only studies using composite scales of acculturation. Studies were identified via electronic databases (i.e., PSYCHINFO, ETOH, and PUBMED) using search terms, and combinations thereof, including “acculturat*,”“alcohol*,”“Latino,” and “Hispanic.” This search was supplemented by recursive checking and author searches. Thirty‐two articles were identified and coded on methodological characteristics; results from 24 disaggregating genders and using appropriate outcomes were summarized.Results:  Higher acculturation was very consistently associated with higher odds of drinking among women, even controlling for demographic covariates. The evidence for women also suggested associations between higher acculturation and heavier drinking on other outcomes, including total volume, drinking frequency, typical quantity, heavy/problem drinking, drinking problems, and abuse/dependence, despite some null results. Relationships were weaker and ambiguous among men. Some evidence suggested that highly acculturated men are (compared with peers low on acculturation) more prone to drink, and perhaps as a result, can show higher consumption and problems. However, results also implied that, among male drinkers, higher acculturation may be associated with a lighter drinking pattern. Important study limitations were identified, including low power, aggregation of nondrinkers with drinkers, restrictive sampling, measurement issues, and analytical issues.Conclusions:  The pattern of results suggests important associations between acculturation and drinking outcomes—particularly for women—but conclusions are tempered by serious methodological limitations. The review urges further research, particularly large‐scale, longitudinal studies, addressing these limitations.