bluuebunny/crossref_metadata_2025_split huggingface dataset:
Androgen‐mediated cholesterol metabolism in LNCaP and PC‐3 cell lines is regulated through two different isoforms of acyl‐coenzyme A: Cholesterol Acyltransferase (ACAT)
Authors: Locke Jennifer A. , Wasan Kishor M. , Nelson Colleen C. , Guns Emma S. , Leon Carlos G. 
Published: November 2007

AbstractBACKGROUNDThe objective of this work was to determine the effect of an androgen agonist, R1881, on intracellular cholesterol synthesis and esterification in androgen‐sensitive (AS) prostate cancer (LNCaP) cells.METHODSWe investigated the activity and expression of cholesterol metabolism enzymes, HMG‐CoA‐reductase and ACAT in the LNCaP and PC‐3 (androgen‐independent control) models.RESULTSMicrosomal PC‐3 HMG‐CoA‐reductase activity was increased with R1881 despite having similar cholesterol levels while increased cholesterol levels in microsomes from LNCaPs treated with R1881 (L+) were associated with increased HMG‐CoA reductase activity. Increased intracellular cholesteryl esters (CE) found in (L+) were not associated with an increased ACAT1 activity. There was no effect from androgen treatment on ACAT1 protein expression in theses cells; however, ACAT2 expression was induced upon R1881 treatment. In contrast, we found an increase in the in vitro ACAT1 activity in PC‐3 cells treated with androgen (P+). Only ACAT1 expression was induced in P+. We further assessed the expression of STAT1α, a transcriptional activator that modulates ACAT1 expression. STAT1α expression and phosphorylation were induced in P+. To determine the role of the AR on ACAT1 expression and esterification, we treated PC‐3 cells overexpressing the androgen receptor with R1881 (PAR+). AR expression was decreased in PAR+ cells; ACAT1 protein expression and cholesterol ester levels were also decreased, however, ACAT2 remained unchanged. STAT1α expression was decreased in PAR+.CONCLUSIONSOverall, these findings support the importance of cholesterol metabolism regulation within prostate cancer cells and unravel a novel role for STAT1α in prostate cancer metabolism. Prostate 68: 20–33, 2008. © 2007 Wiley‐Liss, Inc.
Nonmedical prescribing: managing a hypertension clinic
Authors: Smalley Lorna 
Published: November 2007

AbstractOur series Nonmedical prescribing gives an overview of the work that can be done by nonmedical prescribers and what can be achieved. Here, a supplementary prescribing pharmacist in Derby describes her role in managing a clinic for patients with newly‐diagnosed hypertension. Copyright © 2007 Wiley Interface Ltd
DiGEM: value of glucose self‐monitoring in type 2 diabetes
Authors: Burrill Peter 
Published: November 2007

AbstractA randomised controlled trial published in a peer‐reviewed journal is considered to be the ‘gold standard’ of information about the effectiveness of a treatment; however, critical appraisal of trials is required in order to judge the value and implications of the results. Here, the author presents an appraisal of the DiGEM study, which considered the effectiveness of self‐monitoring of blood glucose in patients with noninsulin‐treated diabetes.Farmer A, Wade A, Goyder E, et al. Impact of self‐monitoring of blood glucose in the management of patients with non‐insulin treated diabetes: open parallel group randomised trial. BMJ 2007;335:132‐6. Copyright © 2007 Wiley Interface Ltd
Optimal QSAR Analysis of the Carcinogenic Activity of Aromatic and Heteroaromatic Amines
Authors: Fang Yaping , Feng Yi , Li Menglong 
Published: November 2007

AbstractAromatic and heteroaromatic amines are widely used in industrial chemicals and can be found in cooked foods and in tobacco smoke. In this study, Quantitative Structure–Activity Relationships (QSARs) are developed that correlate the observed carcinogenic activities of 80 aromatic and heteroaromatic amines. Principal Component Regression and stepwise linear regression techniques have been applied to construct the QSAR models. The performance of these two models is slightly superior compared to the previous reported based on the same dataset by multiple linear regression techniques. To improve the performance, Support Vector Regression (SVR) has been used to construct the QSARs and Genetic Algorithm (GA) has been used to select the most informational descriptors. Additionally, by introducing the concept of the weighting technique into the model, a new SVR, optimized sample‐weighted SVR is proposed. The optimal weighted coefficient is 0.2. The results suggest that approaches using GA selecting descriptors and weighting the descriptors can effectively improve the performance of the SVR models. The optimal Root Mean Square Error in Prediction is 0.799, which is relative smaller than other models. Jackknife‐testing procedure has been used to validate the models. The results indicate that the selected descriptors by GA and weighting technique are important and necessary to improve the performance of QSAR models by SVR.
Complete profiling and characterization of in vitro nefazodone metabolites using two different tandem mass spectrometric platforms
Authors: Li Austin C. , Shou Wilson Z. , Mai Ting T. , Jiang Xiang‐yu 
Published: November 2007

AbstractThis paper describes the complete profiling and characterization of in vitro metabolites of the antidepressant agent nefazodone (NEF) generated by human liver microsome (HLM). Two new metabolic pathways (biotransformation) for NEF have been discovered by the characterization of three new metabolites, including two new metabolites (M24, M25) formed due to the N‐dealkylation reaction that occurred between the triazolone and propyl units, and one new metabolite (M26) formed due to the O‐dearylation reaction that occurred on the phenoxyethyl unit. These metabolites were initially detected by a 4000 Q‐Trap instrument and then confirmed by exact mass measurement using an LTQ‐Orbitrap. Both instruments proved to be capable of providing complete in vitro metabolite information in a single liquid chromatography/tandem mass spectrometry (LC/MS/MS) analysis, although each had its advantages and disadvantages. One noticeable disadvantage of the 4000 Q‐Trap was the reduced quality of isotopic pattern in the enhanced mass scan (EMS) spectrum when it was used as survey scan to trigger multiple dependent product ion scans. The problem was especially exacerbated for minor metabolites with low signal intensity. On the other hand, the LTQ‐Orbitrap maintained excellent isotopic pattern when used as a full scan survey scan. Twenty‐six metabolites were detected and identified. The formation of these new metabolites was also confirmed by analyzing duplicate incubations at different time points. Copyright © 2007 John Wiley & Sons, Ltd.
MHC I expression and synaptic plasticity in different mice strains after axotomy
Authors: Sabha Mario , Emirandetti Amanda , Cullheim Staffan , De Oliveira Alexandre Leite Rodrigues 
Published: November 2007

AbstractThe success of axonal regeneration has been attributed to a co‐operation between the severed neurons and the surrounding environment, including non‐neuronal cells and the extracellular matrix. Important differences regarding the regeneration potential after injury have been described among inbred mice strains. To date, there is only limited knowledge of how such variation can be linked with the genetic background. It has recently been demonstrated that MHC class I molecules have an influence on the spinal cord synaptic plasticity elicited by a peripheral lesion, and the regenerative capacity following such a lesion. Therefore, in the present work we compared the MHC I expression after axotomy in three isogenic mice strains, namely C57BL/6J, Balb/cJ, and A/J, and investigated the fine ultrastructure of the synaptic elimination process that follows such lesion. The results show that C57BL/6J mice, that have a comparatively poor regenerative potential, display a lower upregulation of MHC I in the spinal cord, coupled with a slower synaptic stripping. On the other hand, A/J mice, which have been shown to have a stronger axonal regrowth potential, showed a clear upregulation of MHC I and a sharp acute loss of afferents, at 1 week after lesion. Our results suggest that a more prominent expression of MHC I in the first week after lesion may positively influence the regenerative outcome associated with a more effective axonal regrowth. Synapse 62:137–148, 2008. © 2007 Wiley‐Liss, Inc.
CART receptor binding in primary cell cultures of the rat nucleus accumbens
Authors: Jones Douglas C. , Kuhar Michael J. 
Published: November 2007

AbstractSpecific cocaine‐amphetamine regulated transcript (CART) receptor binding has been reported in AtT20 and PC12 cells. In this study, receptor binding has been examined in primary cell cultures of several rat brain regions. Utilizing125I‐CART 61–102 as a ligand and CART 55–102 as a displacer, significant levels of specific binding compared with nonspecific binding were found in the nucleus accumbens. Specific CART binding was substantially lower in hippocampal, hypothalamic, and pituitary cells. The specific binding was saturable with aKdof 1.43 ± 0.25 nM and aBmaxof 49.03 ± 2.33 fmol/mg protein. The binding was also highly specific for CART 55–102 as other inactive CART peptide fragments, unrelated peptides, γ‐aminobutyric acid, or cocaine showed no affinity for the receptor at 10 μM concentrations. Furthermore, addition of the GTP analog, Gpp(NH)p, significantly decreased specific binding but addition of an ATP analog did not, suggesting that the receptor is a g‐protein coupled receptor. This is the first demonstration of CART peptide receptor binding in primary cell cultures of the rat brain. Synapse 62:122–127, 2008. © 2007 Wiley‐Liss, Inc.
Dopamine partial agonist actions of the glutamate receptor agonists LY 354,740 and LY 379,268
Authors: Seeman Philip , Caruso Carla , Lasaga Mercedes 
Published: November 2007

AbstractBecause glutamate compounds alter the release of dopamine and prolactin, the present study examined whether group II metabotropic receptor agonists, LY 354,740 and LY 379,268, had any direct in vitro action on dopamine D2 receptors on rat striatal tissue, cloned D2Long receptors, and prolactin release from anterior pituitary cells. In competition versus the D2‐specific ligand [3H]domperidone, LY 354,740 had a dissociation constant of 24 nM at D2High(the functional high‐affinity state of dopamine D2 receptors), while the value for LY 379,268 was 21 nM. LY 354,740 also stimulated by 50% the incorporation of [35S]‐GTP‐γ‐S at a concentration of 120 nM, but its maximal stimulation was only 22% of the maximum elicited by dopamine. LY 379,268 stimulated by 50% the incorporation of [35S]‐GTP‐γ‐S at 280 nM, but its maximal stimulation was also only 22% of the maximum elicited by dopamine. However, both LY 354,740 and LY 379,268 potently inhibited the dopamine‐induced incorporation of [35S]‐GTP‐γ‐S with inhibitory Ki values of 43 nM and 30 nM, respectively. The release of prolactin from rat isolated anterior pituitary cells in culture was 50% inhibited by 20 nM LY 379,268 and by 100 nM LY 354,740. These Ki values are similar to those known for the mGluR II receptor, suggesting that these compounds may have both glutamate and dopamine actions in vivo. The dopamine agonist and antagonist actions of these compounds indicate that these drugs have properties of a dopamine partial agonist, and may, therefore, have antipsychotic action. Synapse 62:154–158, 2008. © 2007 Wiley‐Liss, Inc.
In vivo effects of fenthion on oxidative processes by the modulation of glutathione metabolism in the brain of Oreochromis niloticus
Authors: Piner Petek , Sevgiler Yusuf , Üner Nevin 
Published: November 2007

AbstractThe present study was designed to understand the oxidative stress potential of fenthion, an organophosphate (OP) pesticide and its involvement in glutathione metabolism modulated buthionine sulfoximine (BSO, 50 mg/kg) and N‐acetylcysteine (NAC, 100 mg/kg) in the brain of fish, Oreochromis niloticus. A sublethal fenthion concentration (0.45 mg/L) was applied for 24, 48, and 96 h together with injection with BSO or NAC; following treatment, recovery periods for 24, 48, and 96 h were allowed. Total glutathione (tGSH), oxidized glutathione (GSSG), lipid peroxidation, protein level, and GSH‐related enzyme activities were analyzed by using spectrophotometric methods. Fenthion in applied concentration did not change GSH levels, but increased GSSG levels. BSO application in fenthion exposure caused a depletion in GSH, while increasing the GSSG levels. Glutathione peroxidase (GPx; EC 1.11.1.9) specific activity increased in fenthion‐applied groups at 24‐h treatment. γ‐Glutamylcysteinyl synthetase (γ‐GCS; EC 6.3.2.2) was not detected in the brain. NAC injection in fenthion treatment decreased GSH and increased GSSG levels and GST activity. In conclusion, fenthion in sublethal concentration induced an oxidative stress processes in brain. BSO application provided an evidence for the involvement of fenthion in GSH metabolism. NAC elevated the fenthion‐induced effects in spite of its antioxidant properties. Recovery period for 96 h was not adequate to eliminate the fenthion‐induced changes. © 2007 Wiley Periodicals, Inc. Environ Toxicol 22: 605–612, 2007.
Influence of intracellular Ca2+, mitochondria membrane potential, reactive oxygen species, and intracellular ATP on the mechanism of microcystin‐LR induced apoptosis in Carassius auratus lymphocytes in vitro
Authors: Zhang H. , Zhang J. , Chen Y. , Zhu Y. 
Published: November 2007

AbstractMicrocystin‐LR (MCLR), the most toxic microcystin up to date, could induce apoptosis in many kinds of fish and mammalian cells. For the fish immunotoxicity, it was found that MCLR could induce apoptosis in Carassius auratus lymphocytes in vitro. So this study focused on the role of intracellular Ca2+, mitochondrial membrane potential, reactive oxygen species (ROS), and intracellular ATP in response to the mechanisms of MCLR‐induced apoptosis in fish lymphocytes. MCLR (10 nM) administration resulted in a massive elevation in ROS, intracellular Ca2+, decreased ATP, and rapid mitochondrial membrane potential (ΔΨm) disruption. When compared to controls, both a fourfold significant (P < 0.001) elevation in O2− in 1.5 h and an approximately twofold increase in Ca2+ in 0.5 h were observed. After 6 h of treatment, an approximately 30% decrease for ΔΨm but about 75% decline for ATP were found. Together, the results demonstrated that MCLR‐induced apoptosis was associated with a massive calcium influx, resulting in O2− elevation, ΔΨm disruption, and ATP depletion. This study provided a possible cytotoxic mechanism of fish lymphocytes caused by MCLR. © 2007 Wiley Periodicals, Inc. Environ Toxicol 22: 559–564, 2007.
Comparison of patient satisfaction with community‐based vs. hospital psychiatric services
Authors: Henderson C. , Phelan M. , Loftus L. , Dall'Agnola R. , Ruggeri M. 
Published: November 2007

Objective: Previous work suggests that psychiatric patients are more satisfied with community‐based than with hospital‐based services, but it is not clear how far these findings can be generalized to routine services. The aim of this study was to compare the satisfaction of patients with psychosis between a hospital‐based service in London, UK and a community‐based service in Verona, Italy.Method: The Verona Service Satisfaction Scale (VSSS) was used to measure satisfaction among patients with psychosis in Nunhead (London) and South Verona.Results: Satisfaction across all dimensions was higher in South Verona than in Nunhead. Sociodemographic and service use differences between the two groups were insufficient to explain this difference.Conclusion: This study suggests that experimental findings that patients prefer community‐based to hospital psychiatric services can be generalized to routine services.
Attempted suicide and major public holidays in Europe: findings from the WHO/EURO Multicentre Study on Parasuicide
Authors: Jessen G. , Jensen B. F. , Arensman E. , Bib‐Brahe U. , Crepet P. , Leo D. De , Hawton K. , Haring C. , Hjelmeland H. , Michel K. , Ostamo A. , Salander‐Renberg E. , Schmidtke A. , Temesvary B. , Wasserman D. 
Published: November 2007

Objective: The aim of the study was to examine the relationship between suicide attempts and major public holidays in Europe.Method The analysis was based on data on 24388 suicide attempts by persons aged 15 years or older in the period 1989–1996. Data from 13 centres (representing 11 countries) participating in the WHO/EURO Multicentre Study on Parasuicide were analysed. The analysis of the fluctuation of suicide attempts around public holidays was based on the daily number of suicide attempts for each centre. For each day in the period under examination a mean number of suicide attempts (μ) was calculated. The analysis was based on the assumption that the data followed a Poisson distribution. The observed number of daily suicide attempts was compared with the expected number of attempts. A multiplicative model for the expected number in each centre was developed.Results: Before Christmas there were fewer suicide attempts than expected, and after Christmas there were approximately 40% more attempts than expected. In addition, more attempts than expected were registered on New Year's Day. In countries where people have the day off work on Whit Monday there were significantly fewer attempts during the 3 days before, but where Whit Monday is a normal working day significantly fewer attempts occurred on the Monday to Wednesday after Whit Sunday.Conclusion: There appears to be a transposition of a significant number of suicide attempts from before (and during) a major public holiday until after it. The division of holidays into non‐working and working days showed that a ‘holiday effect’ could only be found around major public holidays, particularly Christmas, Easter and Whitsun. These findings support the theory of the ‘broken‐promise effect’ for major public holidays.
Assessing varying degrees of lethality in depressed adolescent suicide attempters
Authors: Nasser E. H. , Overholser J. C. 
Published: November 2007

Objective: Understanding the lethality of suicide attempts and its relation to other psychological variables may improve clinical judgement with regard to suicide risk.Method: The lethality of suicidal behaviour was examined in 60 hospitalized adolescent in‐patients who had recently attempted suicide. Subjects were divided into non‐lethal, low‐lethal and high‐lethal groups based on the qualities of their suicidal acts.Results: The groups did not differ in terms of hopelessness, depression, substance abuse or self‐esteem. Moreover, they did not differ significantly in diagnoses of major depression. adjustment disorder, substance abuse and bipolar disorder. The group of high‐lethal attempters was the only group with several individuals diagnosed with a major depressive episode and comorbid attention deficit disorder. The high‐lethal group also reported the strongest desire to end their lives.Conclusion: Based on lethality of suicide attempts, adolescent suicide attempters can be differentiated in terms of the wish to die as well as some instances of diagnostic comorbidity. However, they may not be differentiated in terms of severity of depression or hopelessness, demographic variables and other aspects of suicidal behaviour.
The fertility and fecundity of patients with psychoses
Authors: McGrath J. J. , Hearle J. , Jenner L. , Plant K. , Drummond A. , Barkla J. M. 
Published: November 2007

Objective: Previous research has suggested that patients with schizophrenia have fewer offspring compared to the general population. Reduced fertility in a disorder with a strong genetic component and an apparently stable incidence has implications for models of genetic transmission. There is also a need to obtain contemporary estimates of the prevalence of parenthood among subjects with psychotic disorders in order to inform service planning. The aim of this study was to determine the fertility and fecundity of a representative sample of individuals with psychoses who were in contact with mental health services, and to explore the interactions between age at first diagnosis and fertility.Method All clients of two community mental health clinics and an extended‐care psychiatric hospital were surveyed. Data on diagnosis, age at first diagnosis, and the number and age of offspring were collected. Based on interviews with the proband and chart review, a genogram of the probands’ family was drawn that identified sex, age, affected status and the number of offspring for each patient and their siblings.Results: In total, 36% of all patients were parents. Most women with psychoses (59%) were mothers. Patients with psychoses had fewer offspring compared to their unaffected same‐sex siblings. This was especially the case for men with non‐affective psychoses. Higher levels of fertility were associated with a later age at first diagnosis.Conclusion: The consistent finding of reduced ‘reproductive fitness’ in those with non‐affective psychoses needs to be incorporated in the genetic epidemiology of these disorders. Despite this reduction in fertility and fecundity, many patients with psychoses are parents. Services need to remain mindful of the special needs of these patients.
Subjective and external assessments of quality of life in schizophrenia: relationship to insight
Authors: Doyle M. , Flanagan S. , Browne S. , Clarke M. , Lydon D. , Larkin C. , O'Callaghan E. 
Published: November 2007

Objective: This study assessed the manner in which insight influenced schizophrenic patients’ evaluation of their objective life conditions and the concurrent validity between patients’ and clinicians’ assessments of patients’ global quality of life.Method: Forty out‐patients who fulfilled DSM‐III‐R criteria for schizophrenia were independently interviewed using the Lancashire Quality of Life Profile and the Standard of Living Interview. Insight was assessed using a self‐report questionnaire, the Insight Scale.Results: For insightful patients there was a significant but modest correlation between objective and subjective indicators of quality of life. Likewise, a significant correlation between subjective and external evaluations of global quality of life was limited to those individuals who had good insight. Conclusion: Diminished insight may limit the usefulness of the self‐report methodology for assessing quality of life for some individuals with schizophrenia.
Seasonal affective disorders among rural Finns and Lapps
Authors: Saarijärvi S. , Lauerma H. , Helenius H. , Saarilehto S. 
Published: November 2007

Saarijärvi S, Lauerma H, Helenius H, Saarilehto S. Seasonal affective disorders among rural Finns and Lapps.We investigated the prevalence of seasonal affective disorder (SAD) and subsyndromal SAD (S‐SAD) in rural populations in south‐western and northern Finland by using the Seasonal Pattern Assessment Questionnaire (SPAQ). A total of 1710 SPAQs were analysed. The prevalences of overall SAD and S‐SAD were 12.0% and 27.1%, respectively. Winter SAD (W‐SAD) was the most common type, with prevalences of 9.5%, for W‐SAD and 18.4% for W‐S‐SAD. The prevalences of overall and winter SAD did not differ between Finns living in northern and south‐western Finland. Among the Lapps, W‐SAD cases were less frequent than among the Finns in Lapland. Overall seasonality correlated significantly with female gender, high body mass index, high level of education and young age.