bluuebunny/crossref_metadata_2025 huggingface dataset:
Threat‐Sensitive Behavioral Responses to Concentrations of Water‐Borne Cues from Predation
Authors: Kesavaraju Banugopan , Damal Kavitha , Juliano Steven A.
Published: February 2007

Aquatic organisms often detect predators via water‐borne chemical cues, and respond by showing reduced activity. Prey responses may be correlated with the concentration of predation cues, which would result in graded antipredator behavioral responses that adjust potentially costly behavioral changes to levels that are commensurate with the risk of predation. Larvae of the predatory mosquitoToxorhynchites rutilusprey upon other container‐dwelling insects, including larvae of the mosquitoOchlerotatus triseriatus. Previous work has established thatO. triseriatusreduce movement, foraging, and time below the surface, and increase the frequency of resting at the surface, in the presence of water‐borne cues from predation byT. rutilus. We tested whether these responses byO. triseriatusare threat sensitive by recording behavior of fourth instar larvae in two runs of an experiment in which we created a series of concentrations (100, 10, 1, 0.1, and 0.01% and 100, 70, 40, 20, and 10%) of water that had held eitherO. triseriatuslarvae alone (control) or aT. rutiluslarva feeding onO. triseriatus(predation). We also tested whether associated effects on time spent feeding are threat sensitive by determining whether frequencies of filtering or browsing are also related to concentration of cues. The frequencies of resting and surface declined, whereas frequency of filtering (but not browsing) increased more rapidly with a decrease in concentration of predation cues compared with control cues. Thus,O. triseriatusshows a threat sensitive behavioral response to water‐borne cues from this predator, adjusting its degree of behavioral response to the apparent risk of predation.
Cryopreservation of European Mouflon (Ovis Gmelini Musimon) Semen During the non‐Breeding Season is Enhanced by the Use of Trehalose
Authors: Berlinguer F , Leoni GG , Succu S , Mossa F , Galioto M , Madeddu M , Naitana S
Published: February 2007

Contents

The influence of trehalose on European mouflon spermatozoa cryopreservation during the non‐breeding season was tested. Semen was frozen in two different extenders: (a) recommended Tris‐based ram extender (CTR); (b) CTR extender supplemented with trehalose 0.147 mm (TRH). Sperm viability and acrosome integrity were assessed using propidium iodide and fluorescein isothiocynate labelled Pisum Sativum agglutinin. Trehalose significantly enhanced sperm viability after thawing compared with CTR extender (62.7% vs 51.8%; p < 0.05), whereas no differences were observed on acrosome integrity (42.9% vs 42.1%). Trehalose influence was also evidenced in the in vitro fertility test performed with sheep oocytes matured in vitro. Both fertilization rates (60.9% TRH vs 43.6% CTR; p < 0.05) and cleavage rates (58% TRH vs 39.8% CTR; p < 0.001) were higher for trehalose frozen semen compared with control extender frozen semen. A higher percentage of zygotes resulting from fertilization with trehalose cryopreserved semen presented the first cleavage earlier if compared with the group fertilized with control semen (48.7% vs 31.5%, respectively; p < 0.01). This result was confirmed by embryo kinetic development. Fertilization with trehalose cryopreserved semen leaded to an higher percentage of blastocysts (40.2% vs 27.8% CTR; p < 0.05), and enhanced in particular the number of blastocysts that developed on the day 6th of culture (28.6% vs 17% CTR; p < 0.05). Our data demonstrated that, during mouflon non‐breeding season, trehalose extender enhances spermatozoa viability and its in vitro fertilizing capacity, allowing the production of an higher number of blastocysts.
Measurement of Ovine Pregnancy‐Associated Glycoprotein (PAG) During Early Pregnancy in Lacaune Sheep
Authors: El Amiri B , Karen A , Sulon J , Melo de Sousa N , Alvarez‐Oxiley AV , Cognié Y , Szenci O , Beckers JF
Published: February 2007

Contents

This study describes ovine pregnancy‐associated glycoprotein (ovPAG) concentrations in 20 Lacaune sheep during early pregnancy. Measurements were performed by using semi‐purified ovPAG as standard, tracer and immunogens for antibody production in rabbits. Antisera R780 (against ovPAG57+59kDa) and R805 (against ovPAG558+61kDa) were used respectively in RIA‐780 and RIA‐805. Blood samples were collected at days 0, 18, 20, 22 and 25 after artificial insemination. From day 18 after breeding onward, the mean ovPAG concentration was significantly higher (p < 0.001) in plasma samples from pregnant ewes (n = 17) than in non‐pregnant ones (n = 3). The specific activity of the tracer was 11 760 Ci/mmol in RIA‐780 and 14 900 Ci/mmol in RIA‐805. The minimal detection limits for RIA‐780 and RIA‐805 were 0.2 ng/ml and 0.3 ng/ml, respectively. The intra‐assay CV of samples with low (1.0 ng/ml), medium (2.5 ng/ml) and high (4.0 ng/ml) PAG concentrations were 3%, 6% and 9% for RIA‐780 and 8%, 9% and 5% for RIA‐805. The inter‐assay CV in the same samples were 13%, 12% and 7% for RIA‐780 and 13%, 11% and 5% for RIA‐805. The recovery was higher than 95% in both assays. No cross‐reaction was observed with members of aspartic proteinase family as well as with other tested proteins. In both RIA‐780 and RIA‐805, inhibition of the binding of the tracer by antisera was parallel between standard curve and serial dilutions of pregnant ewe samples. In conclusion, the two homologous RIA systems are suitable for early quantification of ovPAG concentrations in ewe plasma samples from day 18 after breeding.
Does bronchopulmonary dysplasia change the postoperative outcome of herniorrhaphy in premature babies?
Authors: MELO‐FILHO ANTONIO ALDO , ASSUNÇÃO BRAGA ANGÉLICA DE FÁTIMA , REIS CALDERONI DAVI , VOLK SIDNEY , MARBA SERGIO , SBRAGIA LOURENÇO
Published: February 2007

Background:  Inguinal hernia is a common surgical condition in premature neonates. Because of physiological immaturity, they can present with lung‐related diseases, such as bronchopulmonary dysplasia (BPD), which may influence the time for operation and the postoperative outcome after hernia repair. The aim of this study was to analyze the role of BPD in the outcome of premature infants who underwent herniorrhaphy.

Methods:  Fifty‐two premature infants who underwent hernia repair from 1996 to 2004 at CAISM‐UNICAMP were included in this study. Seventeen babies had BPD and 35 did not. The features reviewed included: (i) associated preoperative morbidity; (ii) birth data and the hernia; and (iii) hernia diagnosis, surgery and postoperative outcome data. Three sets of analysis were undertaken. The first compared features with and without BPD. The second was an univariate analysis to detect associations between those features and postoperative complications. Finally, a multivariate analysis to determine the effect of BPD when adjusted for other factors.

Results:  Some features were different between the studied groups, such as birth weight, age at herniorrhaphy and time of preoperative mechanical ventilation. There was no statistical difference in weight at surgery, duration of postoperative ventilation and weight at discharge between those with BPD and those without. Univariate and multivariate analysis found no association between different studied variables, including BPD, and incidence of postoperative respiratory complications.

Conclusion:  These data suggest that all premature infants, with or without BPD, should be treated with equal concern regarding the possibility of postoperative pulmonary complications.
Deep sedation with intravenous infusion of combined propofol and ketamine during dressing changes and whirlpool bath in patients with severe epidermolysis bullosa
Authors: WU JUNZHENG
Published: February 2007

Continuous i.v. infusion of propofol, or propofol plus ketamine for deep sedation and analgesia was carried out in two patients with severe epidermolysis bullosa (EB) during extensive dressing changes and deep whirlpool baths. Intermittent small doses of narcotics were given as supplement for pain relief as needed. Both patients had typical features of severe EB, including extremity contractures, severe digit deformity, difficult airways, extensive blisters and broken skin with denuded areas and severe wound infections. SpO2 was roughly estimated by holding the probe around the earlobe periodically and no other monitors could be applied because of the skin conditions and the settings of the procedures. Retrospective anesthesia record review showed that the combined propofol and ketamine infusions provided satisfactory sedation with significantly reduced narcotic requirements compared with propofol alone. There were no noticeable side effects when ketamine was added. Ketamine appears to be a good addition to propofol and narcotics to provide sedation and analgesia when there are great concerns for respiration depression, apnea, difficult pain management and potential unstable hemodynamics during dressing changes and whirlpool baths in severe EB patients.
Probabilistic Voting and Accountability in Elections with Uncertain Policy Constraints
Authors: MEIROWITZ ADAM
Published: February 2007

We consider accountability in repeated elections with two long‐lived parties that have distinct policy preferences and different levels of valence. In each period the government faces a privately observed feasibility constraint and selects a publicly observed policy vector. While pure strategy equilibria do not exhibit tight control on government policy making, complete control is possible in mixed strategies. In optimal equilibria voters use reelection functions which depend on policy in a manner that causes the governing party to internalize voter preferences. In these optimal equilibria the voters use different reelection functions for different parties.
Crime and Punishment and Corruption: Who Needs “Untouchables?”
Authors: SILVA EMILSON C. D. , KAHN CHARLES M. , ZHU XIE
Published: February 2007

Becker's result that fines should be maximized is also applicable to some social environments where law enforcers are corrupt. If the regulated activity is legal, the principal may efficiently deter crime without an anti‐corruption unit. An opportunistic anti‐corruption unit, even when corrupt, becomes useful for the principal when the activity is illegal, since the principal's goal of maximizing fines motivates the unit to collect bribes from the enforcer, which subsequently induces the enforcer to be nearly completely honest, minimizing corruption. Therefore, we show that there is not necessarily an infinite regress originating with the puzzle of who polices the police.
Sexual function and satisfaction in heterosexual couples when men are administered sildenafil citrate (Viagra®) for erectile dysfunction: a multicentre, randomised, double‐blind, placebo‐controlled trial
Authors: Heiman JR , Talley DR , Bailen JL , Oskin TA , Rosenberg SJ , Pace CR , Creanga DL , Bavendam T
Published: February 2007

Objective  To investigate the effect of improvement in erectile dysfunction (ED) on sexual function and satisfaction measures in heterosexual couples in which the woman reports that sexual intercourse is unsatisfactory at least half of the time.

Design  Multicentre, double‐blind, placebo‐controlled study.

Setting  Outpatient medical clinics.

Population  Hundred and eighty men with ED and their female partners in whom sexual intercourse was satisfactory about half the time or less (score of ≤3 on the Female Partner of ED Subject Questionnaire question 3 [FePEDS Q3]).

Methods  Men were randomised to flexible‐dose sildenafil (25, 50, and 100 mg) or placebo as needed for 12 weeks.

Main outcome measures  Primary: FePEDS Q3 (‘Over the past four weeks, when you had sexual intercourse, how often was it satisfactory for you?’) scored as 0 (no sexual activity) and 1 (almost never or never) to 5 (almost always or always). Secondary, partners: Sexual Function Questionnaire, Female Sexual Function Index (FSFI), and ED Inventory of Treatment Satisfaction (EDITS) partner version (EDITS‐Partner). Secondary, men: International Index of Erectile Function (IIEF), General Efficacy Questions, event log data, Self‐Esteem And Relationship questionnaire, and EDITS. Secondary, partners and men: Dyadic Adjustment Scale.

Results  The intention‐to‐treat population included 85 sildenafil recipients (mean age 59 ± 12 years) and 91 placebo recipients (mean age 57 ± 11 years). Most partners (aged 20–79 years; mean, 54 years) were postmenopausal. Sildenafil compared with placebo couples had greater improvement in the primary outcome (FePEDS Q3 [P < 0.0001]) and in sexual function, intercourse success rates, and secondary sexual satisfaction measures (FSFI satisfaction domain [P < 0.0001] and IIEF satisfaction domains [P < 0.001]) and had higher treatment satisfaction (EDITS and EDITS‐Partner; P < 0.0001). Several predictors of improvement were identified, and improvement in one member of the couple correlated positively with improvement in the other member.

Conclusions  The interdependence of sexual function and sexual satisfaction measures between members of couples consisting of men with ED and sexually healthy women reporting infrequent satisfactory sexual intercourse underscores the importance of including partners in ED treatment discussions.
Propionate increases neuronal histone acetylation, but is metabolized oxidatively by glia. Relevance for propionic acidemia
Authors: Nguyen Nga H. T. , Morland Cecilie , Gonzalez Susana Villa , Rise Frode , Storm‐Mathisen Jon , Gundersen Vidar , Hassel Bjørnar
Published: February 2007

In propionic acidemia, propionate acts as a metabolic toxin in liver cells by accumulating in mitochondria as propionyl‐CoA and its derivative, methylcitrate, two tricarboxylic acid cycle inhibitors. Little is known about the cerebral metabolism of propionate, although clinical effects of propionic acidemia are largely neurological. We found that propionate was metabolized oxidatively by glia: [3‐14C]propionate injected into mouse striatum or cortex, gave a specific activity of glutamine that was 5–6 times that of glutamate, indicating metabolism in cells that express glutamine synthetase, i.e., glia. Further, cultured cerebellar astrocytes metabolized [3‐14C]propionate; cultured neurons did not. However, both cultured cerebellar neurons and astrocytes took up [3H]propionate, and propionate exposure increased histone acetylation in cultured neurons and astrocytes as well as in hippocampal CA3 pyramidal neurons of wake mice. The inability of neurons to metabolize propionate may be due to lack of mitochondrial propionyl‐CoA synthetase activity or transport of propionyl residues into mitochondria, as cultured neurons expressed propionyl‐CoA carboxylase, a mitochondrial matrix enzyme, and oxidized isoleucine, which becomes converted into propionyl‐CoA intramitochondrially. The glial metabolism of propionate suggests astrocytic vulnerability in propionic acidemia when intramitochondrial propionyl‐CoA may accumulate. Propionic acidemia may alter both neuronal and glial gene expression by affecting histone acetylation.
Aβ Oligomers – a decade of discovery
Authors: Walsh Dominic M. , Selkoe Dennis J.
Published: February 2007

Converging lines of evidence suggest that progressive accumulation of the amyloid β‐protein (Aβ) plays a central role in the genesis of Alzheimer’s disease, but it was long assumed that Aβ had to be assembled into extracellular amyloid fibrils to exert its cytotoxic effects. Over the past decade, data have emerged from the use of synthetic Aβ peptides, cell culture models, β‐amyloid precursor protein transgenic mice and human brain to suggest that pre‐fibrillar, diffusible assemblies of Aβ are also deleterious. Although the precise molecular identity of these soluble toxins remains unsettled, accumulating evidence suggests that soluble forms of Aβ are indeed the proximate effectors of synapse loss and neuronal injury. Here we review recent progress in understanding the role of soluble oligomers in Alzheimer’s disease.
Formation of glycerol from glucose in rat brain and cultured brain cells. Augmentation with kainate or ischemia
Authors: Nguyen Nga H.T. , Gonzalez Susana Villa , Hassel Bjørnar
Published: February 2007

An increase in the concentration of glycerol in the ischemic brain is assumed to reflect degradation of phospholipids of plasma membranes. However, glycerol could, theoretically, be formed from glucose, which after glycolytic conversion to dihydroxyacetone phosphate, could be converted to glycerol‐3‐phosphate and hence to glycerol. We show here that 13C‐labeled glycerol accumulate in incubation media of cultured cerebellar granule cells and astrocytes incubated with [13C]glucose, 3 mmol/L, demonstrating the formation of glycerol from glucose. Co‐incubation of cerebellar granule cells with kainate, 50 µmol/L, led to increased glucose metabolism and increased accumulation of [13C]glycerol. Accumulation of [13C]glycerol and its precursor, [13C]glycerol‐3‐phosphate, was evident in brain, but not in serum, of kainate‐treated rats that received [U‐13C]glucose, 5 µmol/g bodyweight, intravenously and survived for 5 min. Global ischemia induced by decapitation also caused accumulation of [13C]glycerol and [13C]glycerol‐3‐phosphate. These results show that glycerol can be formed from glucose in brain; they also demonstrate the existence of a cerebral glycerol‐3‐phosphatase activity. Ischemia‐induced increases in brain glycerol may, in part, reflect an altered metabolism of glucose, in which glycerol formation, like lactate formation, acts as a redox sink.
The 20S proteasome isolated from Alzheimer’s disease brain shows post‐translational modifications but unchanged proteolytic activity
Authors: Gillardon Frank , Kloß Alexander , Berg Matthias , Neumann Manuela , Mechtler Karl , Hengerer Bastian , Dahlmann Burkhardt
Published: February 2007

Chronic neurodegenerative diseases are characterized by the accumulation of aggregated protein species, and functional impairment of the ubiquitin proteasome system has been hypothesized to contribute to neuronal cell loss. Decreased proteolytic activity of the 20S proteasome has been shown postmortem in crude brain lysates from Alzheimer’s disease (AD) patients. In the present study, we demonstrate, however, that catalytic activity of the 20S proteasome increases during chromatographic purification from AD brains as compared with age‐matched controls. By two‐dimensional difference gel electrophoresis we detected pI shifts in several proteasome subunits in AD samples pointing to differential post‐translational modifications. Moreover, we identified N‐terminal acetylation and dephosphorylation of subunit α7 in AD by tandem mass spectrometry. Thus, reduced peptidase activity in AD brain extracts is not an intrinsic property of the 20S proteasome, but may be resulting from the presence of endogenous inhibitory proteins or substrates. Post‐translational modifications of non‐catalytic subunits in situ may contribute to the trend towards enhanced hydrolytic activity of the isolated 20S proteasome after removal of the endogenous inhibitors.
Glutamate‐induced activation of nitric oxide synthase is impaired in cerebral cortexin vivoin rats with chronic liver failure
Authors: Rodrigo Regina , Erceg Slaven , Rodriguez‐Diaz Jesus , Saez‐Valero Javier , Piedrafita Blanca , Suarez Isabel , Felipo Vicente
Published: February 2007

It has been proposed that impairment of the glutamate‐nitric oxide‐cyclic guanosine monophosphate (cGMP) pathway in brain contributes to cognitive impairment in hepatic encephalopathy. The aims of this work were to assess whether the function of this pathway and of nitric oxide synthase (NOS) are altered in cerebral cortexin vivoin rats with chronic liver failure due to portacaval shunt (PCS) and whether these alterations are due to hyperammonemia. The glutamate‐nitric oxide‐cGMP pathway function and NOS activation by NMDA was analysed byin vivomicrodialysis in cerebral cortex of PCS and control rats and in rats with hyperammonemia without liver failure. Similar studies were done in cortical slices from these rats and in cultured cortical neurons exposed to ammonia. Basal NOS activity, nitrites and cGMP are increased in cortex of rats with hyperammonemia or liver failure. These increases seem due to increased inducible nitric oxide synthase expression. NOS activation by NMDA is impaired in cerebral cortex in both animal models and in neurons exposed to ammonia. Chronic liver failure increases basal NOS activity, nitric oxide and cGMP but reduces activation of NOS induced by NMDA receptors activation. Hyperammonemia is responsible for both effects which will lead, independently, to alterations contributing to neurological alterations in hepatic encephalopathy.
The Liverpool Adverse Events Profile: Relation to AED Use and Mood
Authors: Panelli Rosemary June , Kilpatrick Christine , Moore Susan M. , Matkovic Zelko , D'Souza Wendyl J. , O'Brien Terence J.
Published: February 2007

Summary: Purpose:The Liverpool Adverse Events Profile (LAEP) is used as a systematic measure of adverse effects from antiepileptic drugs (AEDs). This study evaluated LAEP in newly diagnosed seizure patients, and examined the relation between LAEP, anxiety, and depression.

Methods:Seizure patients seen in the two First Seizure Clinics were categorized into group A (AEDs commenced after assessment), group B (AEDs commenced before assessment), and group C (no AEDs). LAEP and the Hospital Anxiety and Depression Scale (HADS) were completed at baseline (n = 164) and 3 months (n = 103). Each LAEP symptom was assessed for baseline frequency, 3‐month frequency, and frequency change over a 3‐month period. Global scores for LAEP and HADS were analysed at baseline and 3 months.

Results: Symptom‐reporting patterns were similar between groups. However, increased frequency over a 3‐month period occurred for 12 symptoms in group A, 10 in group B, and one in group C. Global LAEP and HADS showed no significant group differences at baseline or changes over a 3‐month period. Multiple regression revealed that HADS scores predicted LAEP global scores better than did AED status. Multivariate analyses of variance demonstrated that increased reporting of 16 of 19 LAEP symptoms was significantly related to higher anxiety and depression rates.

Conclusions:In a First Seizure Clinic, LAEP detects changes in specific symptom frequencies when used as a repeated, symptom‐by‐symptom measure. Increased symptom frequency is associated with diagnostic category/AED treatment, anxiety, and depression. Global LAEP scores do not illustrate differences in symptom reporting between patients.
Postsurgical Health‐related Quality of Life (HRQOL) in Children Following Hemispherectomy for Intractable Epilepsy
Authors: Griffiths Stephanie Y. , Sherman Elisabeth M. S. , Slick Daniel J. , Eyrl Kim , Connolly Mary B. , Steinbok Paul
Published: February 2007

Summary:  Health‐related quality of life (HRQOL) is an important outcome measure in clinical research. Given the psychosocial and behavioral difficulties associated with pediatric epilepsy, evaluating HRQOL in this patient population is of particular importance. Though HRQOL has been examined in pediatric patients receiving focal resection or pharmacological (antiepileptic drug; AED) treatment, it has not been assessed in patients receiving hemispherectomy (HE) for intractable epilepsy. The current study evaluated HRQOL in a sample of pediatric HE cases (N = 26) using previously validated questionnaires relative to surgical (N = 30) and nonsurgical (N = 84) comparison groups. Compared with focal resection and nonsurgical patients, parents of children who received HE reported similar levels of HRQOL. In surgical cases, worse HRQOL was correlated with residual seizure frequency. In both surgical and nonsurgical cases, female gender, higher AED load, and lower functional independence predicted worse HRQOL. Interestingly, HE status (i.e., having undergone HE) predicted fewer epilepsy‐related limitations. Consistent with previous findings, AED load, in addition to lower functional abilities, appear particularly detrimental to life quality in pediatric epilepsy. HE, however, is not associated with increased risk for poor HRQOL. When considered in light of the multiple, significant risk factors for poor outcome associated with HE, children who undergo the procedure fare surprisingly well.
A Comparison of Self‐reported Quality of Life between Patients with Epilepsy and Neurocardiogenic Syncope
Authors: Santhouse Jacqueline , Carrier Christine , Arya Sanjay , Fowler Helen , Duncan Susan
Published: February 2007

Summary:  Epilepsy and neurocardiogenic syncope share a final common pathway of loss of consciousness and consequent social disruption. We compared 52 patients with syncope, 96 with epilepsy and 100 controls. Epilepsy and syncope patients expressed significantly higher levels of anxiety and depression and reported significantly less good quality of life (QoL) compared with controls. There were no significant differences on any of the QoL parameters measured between the syncope and epilepsy patients. These findings suggest the main contributor to poor QoL in epilepsy may be the unpredictable loss of control that is the hallmark of the condition.
Effect of Interictal Spikes on Single‐Cell Firing Patterns in the Hippocampus
Authors: Zhou Jun‐Li , Lenck‐Santini Pierre‐Pascal , Zhao Qian , Holmes Gregory L.
Published: February 2007

Summary:  Purpose: The interictal EEG spike(s) is the hallmark of the epileptic EEG. While focal interictal spike (IS) have been associated with transitory cognitive impairment, with the type of deficit dependent on where in the cortex the IS arises, the mechanism by which IS result in transitory dysfunction is not known. The purpose of this study was to determine the effect of IS on single‐cell firing patterns in freely moving rats with a prior history of seizures.

Methods: We studied IS in two seizure models; pilocarpine‐induced status epilepticus and recurrent flurothyl models. The effect of spontaneous hippocampal spikes on action potentials (APs) of CA1 cells in rats walking in a familiar environment was investigated using 32 extracellular electrodes. We also compared the effect of spikes on two types of hippcampal cells; place cells that discharge rapidly only when the rat's head is in a specific part of the environment, the so‐called firing field, and interneurons, which are a main source of inhibition in the hippocampus.

Results: IS were associated with a decreased likelihood of AP compared with IS‐free portions of the record. Compared to pre‐IS baseline, IS were followed by significant decreases in CA1 APs for periods up to 2 s following the IS in both models. When occurring in flurries, IS were associated with a pronounced decrease in APs. The response to IS was cell‐dependent; IS resulted in decreases in AP firing after the IS in interneurons but not place cells.

Conclusions: This study demonstrates that IS have substantial effects on cellular firing in the hippocampus and that these effects last far longer than the spike and slow wave. Furthermore, the effect of IS on cellular firing was cell specific, affecting interneurons more than place cells. These findings suggest that IS may contribute to seizure‐induced cognitive impairment by altering AP firing in a cell‐specific manner.
Two‐Year Outcome of Alcohol Interventions in Swedish University Halls of Residence: A Cluster Randomized Trial of a Brief Skills Training Program, Twelve‐Step–Influenced Intervention, and Controls
Authors: Ståhlbrandt Henriettæ , Johnsson Kent O. , Berglund Mats
Published: February 2007

Background: High‐risk alcohol consumption among university students is well documented. Several types of intervention have proved to be effective in reducing alcohol consumption. This study examines the 2‐year outcome of 2 different alcohol intervention programs at university halls of residence.

Methods: Ninety‐eight university halls of residence (with 556 students) were cluster randomized to 2 different intervention groups: a brief skills training program (BSTP) with interactive lectures and discussions, a twelve‐step–influenced (TSI) program with didactic lectures by therapists trained in the 12‐step approach, and a control group. All students completing the baseline assessment received personalized feedback by mail. Students responded to mailed follow‐up questionnaires after 1, 2, and 3 years, including alcohol use disorders identification test (AUDIT; years 2 and 3), short index of problems (SIP), and estimated blood alcohol concentration (eBAC).

Results: All groups significantly reduced their AUDIT scores from baseline to the second year follow‐up, with no significant differences between the groups. Seventy‐seven percent of the students belonged to a population with high‐risk consumption, using the AUDIT cut‐off scores of 8 and 4 for men and women, respectively. Students with high‐risk alcohol consumption showed significant differences in AUDIT score reduction in favor of the BSTP compared with controls, and had a tendency to show better results than the TSI intervention (p=0.06). Similar trends could be seen using SIP and eBAC. The TSI did not differ significantly from the control group within the group of students with high‐risk alcohol consumption.

Conclusions: This study suggests that a BSTP is effective as an intervention in students with high‐risk alcohol consumption.
Regulation of Platelet‐Derived Growth Factor Signaling Pathway by Ethanol, Nicotine, or Both in Mouse Cortical Neurons
Authors: Wang Ju , Gutala Ramana , Sun Dongxiao , Ma Jennie Z. , Sheela Rani CS , Ticku Maharaj K. , Li Ming D.
Published: February 2007

Background: The higher incidence of smoking among alcoholic subjects suggests the presence of common molecular mechanisms underlying nicotine and alcohol use and abuse. However, these mechanisms are largely unknown. By using cultured fetal mouse cortical neurons as a model system, we sought to identify genes and pathways that are modulated in the cells by ethanol, nicotine, or both.

Methods: Primary cerebral cortical cultures were prepared from the brains of 14‐day‐old C57BL/6 mouse fetuses and exposed to ethanol (75 mM), nicotine (0.1 mM), or both for 5 consecutive days. A homeostatic pathway‐focused microarray consisting of 638 sequence‐verified genes was used to measure transcripts differentially regulated by ethanol, nicotine, or both in 5 drug‐treated cortical neuron samples and 5 control samples. Quantitative real‐time reverse transcriptase‐polymerase chain reaction analysis was used to verify the mRNA expression levels of genes of interest detected from the microarray experiments.

Results: Through a pathway‐focused cDNA microarray and balanced experimental design, we identified 65, 111, and 81 significantly regulated genes in the ethanol, nicotine, and ethanol/nicotine‐treated neurons, respectively. Of them, the genes of Akt2, Nsg1, Pdgfa, Pfn1, Rbbp7, and Tcfeb were comodulated. The genes differentially expressed in 1 or more treatment groups could be classified into 4 major clusters, with each cluster consisting of genes involved in different biological processes. The platelet‐derived growth factor (PDGF) signaling pathway was significantly regulated by all 3 treatments, but by different mechanisms, which may lead to different cellular consequences.

Conclusions: Our results indicate that the PDGF pathway represents one of the major biochemical mechanisms in the cellular and molecular responses to each drug in cortical neurons. Finally, we demonstrated that the pathway‐focused microarray system used in the present study is a valuable tool for dissecting the mechanisms of complex signaling pathways such as the PDGF pathway.
Alcohol Dehydrogenase Genetic Polymorphisms, Low‐to‐Moderate Alcohol Consumption, and Risk of Breast Cancer
Authors: Visvanathan Kala , Crum Rosa M. , Strickland Paul T. , You Xiaojun , Ruczinski Ingo , Berndt Sonja I. , Alberg Anthony J. , Hoffman Sandra C. , Comstock George W. , Bell Douglas A. , Helzlsouer Kathy J.
Published: February 2007

Background: In vitro, human isoenzymes encoded by genes homozygous for the ADH1C*1 or ADH1B*2 alleles metabolize ethanol to acetaldehyde at a faster rate than those homozygous for the ADH1C*2 or ADH1B*1 allele. Because alcohol is a known risk factor for breast cancer, we evaluated the joint association of genetic variants in ADH and alcohol consumption in relation to breast cancer.

Methods: A nested case–control study of 321 cases and matched controls was conducted. Five single nucleotide polymorphisms (SNPs) in the ADH1C and ADH1B genes were genotyped. Logistic regression was used to assess odds ratios (ORs) and 95% confidence limits (CIs) for each SNP. Haplotype analysis of all 5 SNPs was also undertaken.

Results: Among drinkers, the median intake of total alcohol was 13 g/wk (10th–90th percentiles; 4.5–135.9) in cases and 18 g/wk (10th–90th percentiles; 4.5–104.1) in controls. Women who drank alcohol tended to be at an increased risk of developing breast cancer compared with those who did not drink (OR=1.40%, 95% CI 0.97–2.03), particularly those who were premenopausal at the time of breast cancer diagnosis (OR=2.69%, 95% CI: 1.00–7.26). Of the known functional alleles, breast cancer risk was not significantly increased among carriers of at least 1 ADH1C*1 or ADH1B*2 allele, when compared with those homozygous for the genotype at each locus. However, breast cancer risk tended to be lower among women who inherited the G allele at ADH1B IVS1+896A>G (OR=0.62, 95% CI 0.37–1.04). Overall haplotype frequencies were not significantly different between cases and controls.

Conclusions: In this study low levels of alcohol are associated with a modest increase in breast cancer risk that is not altered by known functional allelic variants of the ADH1B and 1C gene. The protective association conferred by the G allele at ADH1B IVS1+896A>G needs further evaluation.
Deficits in Eye Movement Control in Children With Fetal Alcohol Spectrum Disorders
Authors: Green Courtney R. , Munoz Douglas P. , Nikkel Sarah M. , Reynolds James N.
Published: February 2007

Background: Prenatal exposure to alcohol can result in a spectrum of adverse developmental outcomes in offspring, collectively termed fetal alcohol spectrum disorders (FASD). Deficits in executive function—the psychological processes involved in controlling voluntary goal‐oriented behavior—are prevalent in FASD. Oculomotor tasks have been designed as highly sensitive tools to evaluate components of executive function. Because of the extensive overlap in the brain areas controlling eye movements and those affected in FASD, we hypothesized that individuals with FASD display specific neurobehavioral abnormalities that can be quantified with eye movement testing.

Methods: Subjects (8–12 years old) were instructed to look either toward (prosaccade) or away from (antisaccade) a stimulus that appeared in the peripheral visual field. Two fixation conditions were used. In the gap condition, the central fixation point (FP) was removed before the appearance of the peripheral stimulus; in the overlap condition, the FP remained illuminated. Saccadic reaction times (SRTs, time from stimulus appearance to saccade initiation), direction errors (saccades made in the incorrect direction relative to instruction), and express saccades (short‐latency: SRT=90–140 ms) were measured to assess automatic and volitional saccade control.

Results: Compared with controls, FASD children had elongated reaction times, excessive direction errors, and no express saccades. Metric analysis of correct prosaccades revealed a trend toward increased saccadic duration and decreased saccadic velocity in FASD subjects.

Conclusion: These results reflect deficits in executive function and motor control, and are consistent with dysfunction of the frontal lobes, possibly due to disrupted inhibitory mechanisms. Therefore, eye movement tasks may be powerful and easy tools for assessing executive function deficits in FASD.
Association Between Change in Bone Mineral Density and Decline in Usual Walking Speed in Elderly Community‐Dwelling Japanese Women During 2 Years of Follow‐Up
Authors: Kwon Jinhee , Suzuki Takao , Yoshida Hideyo , Kim Hunkyung , Yoshida Yuko , Iwasa Hajime , Sugiura Miho , Furuna Taketo
Published: February 2007

OBJECTIVES: To investigate the association between change in bone mineral density (BMD) and change in usual walking speed in elderly community‐living Japanese women during 2 years of follow‐up.

DESIGN: Longitudinal cohort study.

SETTING: Community‐based.

PARTCIPANTS: A total of 182 women aged 70 to 84 who completed a baseline survey and a follow‐up survey 2 years later.

MEASUREMENTS: An interview, anthropometric measurements, blood analysis, and physical performance tests were performed at baseline and at follow‐up 2 years later. BMD was evaluated using dual‐energy X‐ray absorptiometry measured at the forearm. Annual percentage changes in BMD and usual walking speed during the 2‐year follow‐up period were calculated; annual percentage changes in BMD were summarized in quartiles. The association between annual bone loss rate and decline in usual walking speed was analyzed using multiple linear regression adjusted for changes in muscle strength, balance capability, and other potential confounders.

RESULTS: Change in BMD was significantly related to change in usual walking speed during the 2‐year follow‐up. After multivariate adjustment, usual walking speed declined significantly more in elderly women whose BMD decreased (−3.5% change in walking speed in the first quartile of percentage change in BMD and −3.1% in the second quartile) than in women whose BMD increased (+1.5% in fourth quartile).

CONCLUSION: Elderly women whose BMD decreased had a significantly greater decline in usual walking speed than women whose BMD increased, even after multivariate adjustment of potential confounders.
Reactive oxygen species and antioxidant mechanisms in human tissues and their relation to malignancies
Authors: KARIHTALA PEETER , SOINI YLERMI
Published: February 2007

Reactive oxygen species (ROS) are formed in mammalian cells as a consequence of aerobic respiration. Despite multiple conserved redox modulating systems, a given proportion of ROS continuously escape from the mitochondrial respiratory chain, being sufficiently potent to damage cells in various ways, including numerous carcinogenic DNA mutations. Oxidative stress resulting from an imbalanced ratio between ROS production and detoxification may also disturb physiological signal transduction, lead to chain reactions in lipid layers, and damage DNA repair enzymes. The significance of ROS and antioxidant systems in carcinogenesis is still complicated and in many ways contradictory. Enhanced antioxidant mechanisms in tumor cells in vivo have been implicated in chemoresistance and lead to poor prognosis, whereas most in vitro studies have reported tumor‐suppressing properties of antioxidant enzymes. The present review aims to clarify the significance of oxidative stress and the role of cell redox state modulating systems in human malignancies in light of the current literature.
Effect of the different phosphorylated Smad2 protein localizations on the invasive breast carcinoma phenotype
Authors: LIAPIS GEORGE , MYLONA ELENI , ALEXANDROU PARASKEVI , GIANNOPOULOU IOANNA , NIKOLAOU IRINI , MARKAKI SOFIA , KERAMOPOULOS ANTONIOS , NAKOPOULOU LYDIA
Published: February 2007

Smad2 participates in the TGF‐β signaling pathway, where it cooperates with transcription factors to regulate expression of defined genes. The purpose of this study was to investigate the expression pattern of phosphorylated Smad2 (pSmad2) in association with clinicopathological parameters and biological markers of proliferation and invasion. Immunohistochemistry was applied on paraffin‐embedded sections from 164 patients with invasive breast carcinomas to detect the expression of the proteins pSmad2, ER, PR, Ki67, topoisomerase IIa, ERK2, catenin‐p120, MMP‐14 and TIMP‐2. pSmad2 protein was detected in the nuclei of the malignant cells (68.1%) and in the tumor fibroblasts (55.2%). Nuclear pSmad2 was inversely correlated with histological grade and LN (p=0.047 and p=0.05) as well as with Ki67 and topoIIa (p=0.003 and p=0.021, respectively). There was also an inverse relation between nuclear pSmad2 and normal immunoexpression of the adhesion molecule catenin‐p120 (p=0.028). Both nuclear and stromal pSmad2 were positively correlated with ERK2 of tumor fibroblasts (p=0.008 and p=0.0001, respectively), while stromal pSmad2 was furthermore related to stromal MMP‐14 and tumor TIMP‐2 (p=0.006 and p=0.022, respectively). Patients with high expression of cancerous pSmad2 tended to have a better prognosis, although statistic significance was never reached. pSmad2 was found to play a dual role, according to its distribution. Nuclear localization was thus found to be related to a less aggressive tumor phenotype, whereas stromal location was associated with an invasive phenotype.
Expression of neuroendocrine markers in non‐small cell lung cancer
Authors: SØRHAUG SVEINUNG , STEINSHAMN SIGURD , HAAVERSTAD RUNE , NORDRUM IVAR S. , MARTINSEN TOM C. , WALDUM HELGE L.
Published: February 2007

Neuroendocrine (NE) differentiation is reported in some cases of non‐small cell lung cancer (NSCLC). The aim of this study was to evaluate the expression of NE markers in NSCLC using novel sensitive methods. 20 cases of NSCLC were examined using immunohistochemical (IHC) and immunoelectron microscopy (IEM) methods. In addition, circulating levels of the NE markers chromogranin A (CgA) and neuron‐specific enolase (NSE) were measured. Using conventional IHC methods, two tumours (10%) showed immunoreactivity for synaptophysin (SYN), one (5%) for Cg and four (20%) for neural cell adhesion molecule (NCAM). Adding the tyramide signal amplification (TSA) technique, the number of immunoreactive tumours for both SYN and CgA increased to five (25%). No increased immunoreactivity was achieved for NCAM. Nine tumours (45%) were immunoreactive for SYN, CgA or NCAM. Using IEM, one of five representative samples that revealed IHC reactivity for CgA showed immunogold labelling of CgA in cytoplasmic vesicles. Elevated levels of circulating CgA or NSE did not correlate with positive IHC findings. In conclusion, using sensitive IHC methods NE differentiation was seen in a greater proportion of NSCLC than previously reported. Sensitive methods may improve our understanding of the tumour biology and represent an important diagnostic tool for future therapeutic modalities.
Comparison of objective and sensory skin irritations of several cosmetic preservatives
Authors: Lee Eunyoung , An Susun , Choi Dongwon , Moon Seongjoon , Chang Ihseop
Published: February 2007

There are many cosmetic ingredients, such as preservatives and fragrances, known to elicit adverse effects. The aim of this study was to investigate the side‐effects of cosmetic preservatives, by evaluating objective and subjective skin irritation. The method comprised of 2 parts. In part 1, we tried to compare 24‐hr patch test results with the sensory irritation potential of several preservatives. In part 2, skin cumulative irritation test for 21 days and sensory irritation test were performed to compare various combinations of preservatives in 4 types of formulations. Our data showed that methylparaben, ethylparaben, propylparaben, butylparaben, phenoxyethanol (PE) and chlorphenesin (CPN) have similar objective skin irritation potential at the minimal inhibitory concentration of each preservative, but CPN has higher potential than other preservatives in subjective irritation. Sensory irritation of preservatives changed according to formulation type, and PE combined with CPN highly increased irritation. There was correlation between antimicrobial activity and skin objective irritation but not sensory irritation. Influence on skin sensory irritation varies with the combination of preservatives. Therefore, for the development of new preservatives and cosmetics, it is important to evaluate skin sensory irritation of preservatives used in cosmetic products according to the type of formulations.
Benzophenone 4: an emerging allergen in cosmetics and toiletries?
Authors: Hughes T. Merion , Stone Natalie M.
Published: February 2007

Chemical ultraviolet (UV) filters have, over the last few decades, been increasingly used not only in conventional sunscreen products but also in many cosmetics and toiletries. Allergic contact dermatitis as well as photoallergic contact dermatitis reactions have been well documented as a consequence of such use. Over a 3‐year period, we recorded the number of positive patch test reactions to a selection of chemical UV filters that we added to our usual cosmetics/facial series. Our objective was to investigate whether any of these filters produced significant numbers of positive patch test results in the absence of photostimulation. Our results show that not only did benzophenone 4 (2‐hydroxy‐4‐methoxybenzophenone‐5‐sulphonic acid: sulisobenzone) produce significantly more positive patch test results than the other UV filters that were tested, but also it was the third most frequently positive result overall. Our findings would support the inclusion of benzophenone 4 when patch testing to investigate likely contact dermatitis from cosmetics and toiletries.
Lymphomatoid contact dermatitis induced by gold earrings
Authors: Conde‐Taboada Alberto , Rosón Elena , Fernández‐Redondo Virginia , García‐Doval Ignacio , De La Torre Carlos , Cruces Manuel
Published: February 2007

Metallic gold has long been regarded as a relatively safe material when in contact with the skin and mucosal membranes, with only sporadic reports of allergic contact dermatitis or stomatitis. This is probably due to its stability and low tendency to ionization. Lymphomatoid reactions have been described in cutaneous responses to several products. We report a patient who developed bilateral nodules on the earlobes at the sites of piercing earrings. Histologically, these lesions presented a lymphomatoid appearance, with a T‐cell diffuse infiltrate. The patch test demonstrated a strong reaction to 1% gold sodium thiosulfate.
Comparison of reactivity to allergens using the TRUE Test and IQ chamber system
Authors: Lazarov Aneta , David Michael , Abraham David , Trattner Akiva
Published: February 2007

The reproducibility of the patch test is of great importance to its diagnostic utility. The objective of this study was to quantitatively and qualitatively compare the reproducibility of patch test reactions between the manufacturer‐loaded TRUE Test® (TT) panel and the investigator‐loaded IQ® Chamber (IQC) system using the European Standard Series (ESS) (Chemotechnique Diagnostics, Malmö, Sweden). Consecutive patients were simultaneously patch tested with 21 allergens using the TT and IQC system. The concordance and discordance of the 2 methods were analysed. Testing was performed in 207 patients (85 men and 122 women) who yielded 317 positive reactions, 188 with the IQ system and 129 with the TT. A total of 204 tests were positive with both methods, showing a positive concordance rate of 64.4%, with IQC producing more positive results. A high concordance rate of positive results was achieved for Cl+ Me− isothiazolinone (81.5%), nickel sulfate (79%), formaldehyde (76.9%), and paraphenylenediamine (PPD) (72.7%); a moderate concordance was noted for quaternium 15 (66.7%), potassium dichromate (64.3%), and fragrance mix (58.1%); and a low concordance was noted for cobalt chloride (27.6%) and Balsam of Peru (18.2%). The IQC and the TT are similar in finding allergy to allergens with high concordance. The IQC system has an advantage in detecting clinically relevant reactions to allergens that have a moderate and a low concordance.