bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytoplasmic regions adjacent to the M3 and M4 transmembrane segments influence expression and function of α7 nicotinic acetylcholine receptors. A study with single amino acid mutants
Authors: Castelán Francisco , Mulet José , Aldea Marcos , Sala Salvador , Sala Francisco , Criado Manuel 
Published: October 2006

AbstractWe studied the role of the cytoplasmic regions adjacent to the M3 and M4 transmembrane segments of α7 nicotinic receptors in the expression of functional channels. For this purpose, a total of 50 amino acids were mutated throughout the mentioned regions. Mutants close to M3, from Arg294 to Leu321, showed slight modifications in the levels of α‐bungarotoxin binding sites and acetylcholine‐evoked currents. Exceptions were mutants located at two clusters (His296 to Pro300 and Ile312 to Trp316), which exhibited low expression levels. In addition, some mutants showed altered functional responses. Many mutants close to M4 showed increased receptor expression, especially the ones located at the hydrophobic face of a putative amphipathic helix. This effect seems to be the consequence of a combination of increased receptor biosynthesis, higher transport efficiency and delayed degradation, such that we postulate that elements in the amphipathic domain strongly influence receptor stability. Finally, some mutants in this region showed altered functional responses: elimination of positively charged residues (Arg424 and Arg426) increased currents, whereas the opposite was observed upon suppression of negatively charged ones (Glu430 and Glu432). These results suggest that the cytoplasmic regions close to M3 and M4 play important structural and functional roles.
Ethanol‐Related Behaviors in Serotonin Transporter Knockout Mice
Authors: Boyce‐Rustay Janel M. , Wiedholz Lisa M. , Millstein Rachel A. , Carroll Jenna , Murphy Dennis L. , Daws Lynette C. , Holmes Andrew 
Published: October 2006

Background:Increasing evidence supports a role for 5‐hydroxytryptamine (5‐HT) and the 5‐HT transporter (5‐HTT) in modulating the neural and behavioral actions of ethanol (EtOH) and other drugs of abuse.Methods:We used a 5‐HTT knockout (KO) mouse model to further study this relationship. 5‐Hydroxytryptamine transporter KO mice were tested for the sedative/hypnotic, hypothermia‐inducing, motor‐incoordinating (via accelerating rotarod), and depression‐related (via tail suspension test) effects of acute EtOH administration. Reward‐related effects of EtOH were assessed in 5‐HTT KO mice using the conditioned place preference (CPP) paradigm. 5‐Hydroxytryptamine transporter KO mice were tested for voluntary consumption of EtOH in a modified 2‐bottle choice test that measured the temporal organization of drinking over the circadian cycle via “lickometers.”Results:Replicating previous findings, 5‐HTT KO mice exhibited significantly increased sensitivity to EtOH‐induced sedation/hypnosis relative to wild‐type controls. Additionally, 5‐HTT KO mice showed motor‐coordination deficits at baseline and in response to EtOH. Hypothermic, pro‐depressive–like, and reward‐related effects of EtOH were no different across genotypes. Gross EtOH consumption was modestly reduced in 5‐HTT KO mice, due to significantly lesser consumption during the peak period of drinking in the early dark phase.Conclusions:Data extend the finding that loss of 5‐HTT gene function alters certain neural and behavioral effects of EtOH, with implications for better understanding the pathophysiology and treatment of alcoholism.
Time‐Dependent Alterations in Ethanol Intake in Male Wistar Rats Exposed to Short and Prolonged Daily Maternal Separation in a 4‐Bottle Free‐Choice Paradigm
Authors: Gustafsson Lisa , Nylander Ingrid 
Published: October 2006

Background: Previous studies have shown that maternal separation can be used in animal studies of early environmental influence on adult ethanol intake. These studies have shown that short daily separations result in low ethanol intake, whereas prolonged separations relate to an enhanced risk for a high ethanol intake. The aim of the present study was to further examine the long‐term effects of early‐life events on ethanol intake.Methods: Rat pups were exposed to 15 minutes (MS15) or 360 minutes (MS360) of daily maternal separation during postnatal days 1 to 21 or kept under normal animal facility rearing (AFR) conditions. In adulthood, male rats were given free access to 5, 10, and 20% ethanol, in addition to water, in a 4‐bottle‐choice paradigm.Results: No differences in total ethanol intake or preference between the 3 experimental groups were found. The 54‐day drinking period was divided into acquisition, stabilization, and maintenance phases for analysis of time and group differences. The MS15 rats increased ethanol intake over time; they mostly consumed 5% ethanol and had a low intake of 20% ethanol throughout the experiment. MS360 rats increased ethanol intake, changed preference from 5% to 20% ethanol, and had a higher increase in intake of 20% ethanol over time. The ethanol intake and preference in the AFR rats were more similar to that of the MS360 rats.Conclusions: Time‐dependent changes were observed in the preferred choice of low versus high ethanol concentrations in MS15 and MS360 rats. The results support previous findings suggesting that MS15 can be used as a model for environmental protective factors and that MS360 represents a risk environment for acquisition of a high adult ethanol intake.
Environmental Cues, Alcohol Seeking, and Consumption in Baboons: Effects of Response Requirement and Duration of Alcohol Abstinence
Authors: Weerts Elise M. , Goodwin Amy K. , Kaminski Barbara J. , Hienz Robert D. 
Published: October 2006

Background:Environmental stimuli (cues) that have been paired with alcohol drinking may evoke classically conditioned states that in turn influence alcohol consumption and relapse to heavy drinking. Animal models using chained schedules of alcohol reinforcement may be useful for examining such complex interactions.Methods:Alcohol drinking was established in 4 baboons. A sequence of lights and tones was presented during daily 3‐hour sessions. First, cues were presented alone and no programmed contingencies were in effect. Second, cues were paired with 3 linked components consisting of different behavioral contingencies leading to and concluding with access to alcohol for self‐administration in the last component (i.e., a chained schedule of alcohol reinforcement). Third, the effects of withholding alcohol access (i.e., forced abstinence) and increasing the number of lever responses required per drink were evaluated.Results:Cues paired with a chained schedule of alcohol reinforcement engendered behaviors that brought baboons into contact with alcohol‐related cues and occasioned operant responding that facilitated access to alcohol (alcohol seeking) during components that preceded alcohol access. Increasing the response requirement for each drink decreased the number of drinks and volume of alcohol consumed, but did not alter alcohol seeking. On the first session after 14 days of alcohol abstinence, latency to complete the operant requirement that produced alcohol access was decreased while both alcohol self‐administration and volume of alcohol consumed were increased.Conclusions:Alcohol self‐administration and consumption were sensitive to increases in response requirement and duration of alcohol abstinence, while seeking was only enhanced by duration of alcohol abstinence. This animal model may be useful to further examine the interactions between environmental cues and behaviors associated with seeking and consumption of alcohol and to evaluate the efficacy of potential alcohol treatment drugs on these behaviors.
Chronic Alcohol Accentuates Nutritional, Metabolic, and Immune Alterations During Asymptomatic Simian Immunodeficiency Virus Infection
Authors: Molina Patricia E. , McNurlan Margaret , Rathmacher John , Lang Charles H. , Zambell Kirsten L. , Purcell Jeanette , Bohm Rudolf P. , Zhang Ping , Bagby Gregory J. , Nelson Steve 
Published: October 2006

Background: Alcohol abuse has been reported to have a high prevalence in the human immunodeficiency virus (HIV)‐infected population. However, its impact on disease progression is unknown. Studies dissecting the drug‐induced or alcohol‐induced metabolic derangements that are likely to alter the course of disease progression are lacking. This is particularly important because of the substantial reduction in morbidity and mortality of patients on highly active antiretroviral therapy (HAART). HIV infection has become a more chronic disease during which alcohol‐induced metabolic alterations may become more prevalent and pronounced.Methods: The present study used a model of chronic intragastric alcohol administration initiated 3 months before intravenous simian immunodeficiency (SIV) inoculation and continued thereafter throughout the course of SIV infection, to investigate the impact of chronic alcohol binge‐like consumption during the initial 10‐month asymptomatic phase of SIV infection in nonhuman primate rhesus macaques. Anthropometric, metabolic, biochemical, nutritional, and immune state indicators were examined before infection and at 3‐month intervals in asymptomatic chronic alcohol‐treated SIV‐infected macaques and time‐matched isocaloric and uninfected controls.Results: Intravenous SIVΔB670 infection resulted in increased viral load, decreased circulating CD4+/CD8+ lymphocyte ratio, and increased lymphocyte proliferation (Ki67/CD3+). Chronic alcohol/SIV+ animals showed a higher viral load at 3 months post‐SIV infection as well as a significant and early decrease in caloric intake and nitrogen balance associated with a change in food choice. Rates of skeletal muscle protein synthesis and breakdown, mRNA expression of IGF‐I, myostatin, or the ubiquitin ligase muscle atrophy F‐box protein (MAFbx) did not differ from basal during the 10‐month asymptomatic period of infection. However, muscle TNF‐α mRNA expression was markedly increased at 10 months post‐SIV infection in alcohol/SIV+ animals.Discussion: These findings suggest that chronic alcohol accelerates nutritional and metabolic dysregulation during SIV infection and may favor a skeletal muscle proinflammatory state, possibly conducive to subsequent muscle wasting.
Reinforcing Effects of Central Ethanol Injections in Newborn Rat Pups
Authors: Nizhnikov Michael E. , Varlinskaya Elena I. , Spear Norman E. 
Published: October 2006

Background: Newborn rat pups readily ingest ethanol of low to moderate concentrations and are sensitive to its reinforcing effects. Given that early ethanol exposure can promote its future abuse, it is vital to discover the mechanisms behind reinforcing effects of ethanol at this stage of life.Methods: Cesarean‐delivered 3‐ to 4‐hour‐old rat pups were exposed to lemon odor (unconditioned stimulus) either paired or explicitly unpaired with central injections of saline or ethanol (25, 50, 100, 200, or 400 mg%) in a volume of 1 μL. One hour following conditioning subjects were tested on a surrogate nipple providing water in the presence of lemon odor. Reinforcement from ethanol's central effects was indexed by significantly greater attachment time on a lemon‐scented nipple in paired subjects than in unpaired or saline controls.Results: Rats centrally injected with 25 to 200 mg% ethanol in the presence of lemon odor spent significantly more time attached to a lemon‐scented surrogate nipple providing water than did their saline‐injected or unpaired counterparts. Those injected with 400 mg% ethanol did not differ from their corresponding controls. No detectable brain alcohol content was found in the assay of whole brain for ethanol levels.Conclusions: These results indicate that 3‐ to 4‐hour‐old rat pups find central injections of 25 to 200 mg% ethanol reinforcing. This procedure virtually eliminates ethanol's chemosensory or caloric attributes as the source of ethanol reinforcement. The present classical olfactory conditioning paradigm can be used to further study mechanisms of this apparently pharmacological reinforcement by ethanol in newborn rat pups.
Brain Stimulation for Epilepsy: Stimulating Results?
Authors: Garcia Paul 
Published: October 2006

Long-Term Follow-Up of Patients with Thalamic Deep Brain Stimulation for Epilepsy Andrade DM, Zumsteg D, Hamani C, Hodaie M, Sarkissian S, Lozano AM, Wennberg RA Neurology 2006;66:1571–1573 The authors describe long-term follow-up (mean, 5 years) in patients with anterior (AN) (n = 6) or centromedian (n = 2) thalamic deep brain stimulation (DBS) for epilepsy. Five patients (all AN) had 50% seizure reduction, although benefit was delayed in two until years 5 to 6, after changes in antiepileptic drugs. DBS electrode implantation in AN patients was followed by seizure reduction 1 to 3 months before active stimulation, raising the possibility of a beneficial microthalamotomy effect. Hippocampal Electrical Stimulation in Mesial Temporal Lobe Epilepsy Tellez-Zenteno JF, McLachlan RS, Parrent A, Kubu CS, Wiebe S Neurology 2006;66:562–565 Background Adjustable, reversible therapies are needed for patients with pharmacoresistant epilepsy. Electrical stimulation of the hippocampus has been proposed as a possible treatment for mesial temporal lobe epilepsy (MTLE). Methods Four patients with refractory MTLE whose risk to memory contraindicated temporal lobe resection underwent implantation of a chronic stimulating depth electrode along the axis of the left hippocampus. The authors used continuous, subthreshold electrical stimulation (90 μsec, 190 Hz) and a double blind, multiple cross-over, randomized controlled design, consisting of three treatment pairs, each containing two 1-month treatment periods. During each treatment pair the stimulator was randomly turned ON 1 month and OFF 1 month. Outcomes were assessed at monthly intervals in a double blind manner, using standardized instruments and accounting for a washout period. The authors compared outcomes between ON, OFF, and baseline periods. Results Hippocampal stimulation produced a median reduction in seizures of 15%. All but one patient's seizures improved; however, the results did not reach significance. Effects seemed to carry over into the OFF period, and an implantation effect cannot be ruled out. The authors found no significant differences in other outcomes. There were no adverse effects. One patient has been treated for 4 years and continues to experience substantial long-term seizure improvement. Conclusion The authors demonstrate important beneficial trends, some long-term benefits, and absence of adverse effects of hippocampal electrical stimulation in mesial temporal lobe epilepsy. However, the effect sizes observed were smaller than those reported in non-randomized, unblinded studies.
Is Posttraumatic Epilepsy the Best Model of Posttraumatic Epilepsy?
Authors: Mazarati Andrey 
Published: October 2006

A Model of Posttraumatic Epilepsy Induced by Lateral Fluid-Percussion Brain Injury in Rats Kharatishvili I, Nissinen JP, McIntosh TK, Pitkänen A Neuroscience 2006;140:685–697 Although traumatic brain injury is a major cause of symptomatic epilepsy, the mechanism by which it leads to recurrent seizures is unknown. An animal model of posttraumatic epilepsy that reliably reproduces the clinical sequelae of human traumatic brain injury is essential to identify the molecular and cellular substrates of posttraumatic epileptogenesis, and perform preclinical screening of new antiepileptogenic compounds. We studied the electrophysiologic, behavioral, and structural features of posttraumatic epilepsy induced by severe, non-penetrating lateral fluid-percussion brain injury in rats. Data from two independent experiments indicated that 43% to 50% of injured animals developed epilepsy, with a latency period between 7 weeks to 1 year. Mean seizure frequency was 0.3 ± 0.2 seizures per day and mean seizure duration was 113 ± 46 s. Behavioral seizure severity increased over time in the majority of animals. Secondarily generalized seizures comprised an average of 66 ± 37% of all seizures. Mossy fiber sprouting was increased in the ipsilateral hippocampus of animals with posttraumatic epilepsy compared with those subjected to traumatic brain injury without epilepsy. Stereologic cell counts indicated a loss of dentate hilar neurons ipsilaterally following traumatic brain injury. Our data suggest that posttraumatic epilepsy occurs with a frequency of 40% to 50% after severe non-penetrating fluid-percussion brain injury in rats, and that the lateral fluid percussion model can serve as a clinically relevant tool for pathophysiologic and preclinical studies.
The many faces of blue nevus: A clinicopathologic study
Authors: Ferrara Gerardo , Soyer H. Peter , Malvehy Josep , Piccolo Domenico , Puig Susana , Sopena Juan , Zalaudek Iris , Argenziano Giuseppe 
Published: October 2006

Background:  In recent years, several histopathologic variants of blue nevus have been identified, whose clinical and dermoscopic correlates need further clarification.Methods:  A comparative evaluation of histopathologic and dermoscopic features was carried out on 52 melanocytic proliferations belonging to the morphologic spectrum of blue nevus.Results:  On dermoscopy, all lesions showed a homogeneous, structureless pigment pattern, with a curious variety of colors (blue, white–blue, black, brown, and polychromatic). Histopathologically, the majority of blue lesions were common blue nevi (11/19); the majority of white–blue lesions were ‘hypochromic’ (sclerotic, hypomelanotic, and amelanotic) blue nevi (17/22); all the black lesions were ‘compound’ blue nevi (2/2); the majority of brown lesions were combined blue nevi (3/4); the unusual polychromatic dermoscopic appearance was often associated with a histopathologic diagnosis of deep penetrating nevus (2/5).Conclusion:  A dermoscopic–pathologic approach now allows us to identify ‘blue’ (common) blue nevi, ‘white’ (hypochromic) blue nevi, ‘black’ (compound) blue nevi, ‘brown’ (combined) blue nevi, and ‘polychromatic’ (deep penetrating) blue nevi. A better recognition of the many dermoscopic faces of blue nevi is expected to give a morphologic guideline for the clinical management of these lesions.
Endogenous Transforming Growth Factor‐β Inhibits Toll‐Like Receptor Mediated Activation of Human Uterine Natural Killer Cells
Authors: Eriksson Mikael , Meadows Sarah K. , Wira Charles R. , Sentman Charles L. 
Published: October 2006

Problem  Toll‐like receptors (TLRs) recognition is an important means for the innate immune system to rapidly respond to pathogen invasion. Our aim was to determine whether uterine natural killer (uNK) cell cytokine production induced by stimulation through TLRs could be regulated by endogenous transforming growth factor (TGF)‐β in human endometrium.Method of study  Single cells were isolated from human endometrium, and interferon (IFN)‐γ production by endometrium cells and uNK cells was determined after stimulation by TLR agonists. The role of TGF‐β in regulating this response was tested by blocking TGF‐β function using antibodies or a specific inhibitor, SB431542.Results  TGF‐β blockade increased TLR agonist induced IFN‐γ by uNK cells. The regulation of uNK cell cytokine production was observed when uNK cells were incubated with agonists for TLR2 (PGN) or TLR3 (polyI:C). Blockade of TGF‐β or TGF‐β receptor signaling had no effect on constitutive cytokine production in the absence of TLR agonists.Conclusion  The results indicate that endogenous TGF‐β alters cytokine responses of uNK cells in human endometrium in response to TLR agonists. These data suggest that uNK cell responses to microbial pathogens in the endometrium are regulated by the amount of biologically active TGF‐β present within the human endometrium.
What does the community think about lifespan extension technologies? The need for an empirical base for ethical and policy debates
Authors: Lucke Jayne , Ryan Bree , Hall Wayne 
Published: October 2006

Objectives:  This paper examines public understandings of possibilities for increasing life expectancy, interest in taking up lifespan‐extending interventions, and motivations influencing these intentions. Methods:  Structured interviews were conducted with 31 adults, aged 50 and over. Results:  Participants believed that technological advances would increase life expectancy but questioned the value of quantity over quality of life. Life in itself was not considered valuable without the ability to put it to good use. Participants would not use technologies to extend their own lifespan unless the result would also enhance their health. Conclusions:  These findings may not be generalisable to the general public but they provide the first empirical evidence on the plausibility of common assumptions about public interest in ‘anti‐ageing’ interventions. Surveys of the views of representative samples of the population are needed to inform the development of a research agenda on the ethical, legal and social implications of lifespan extension.
Prevalence and determinants of dietary supplement and non‐prescription medicine use by men and women over 53 years old in Taiwan. Results from a population‐based cross‐sectional survey
Authors: Tsai Alan C , Liou Jenn‐Chang , Chang Jack M C , Chuang Yi‐Li , Lin Shu‐Hui , Lin Yu‐Hsuan 
Published: October 2006

Objectives:  This study investigated the prevalence and determinants of the use of dietary supplements and non‐prescription medicines by older adults in Taiwan. Methods:  Data are from the 1999 Survey of Health and Living Status of the Elderly in Taiwan. The survey involved a national random sample of 2360 men and 2080 women, 53 years or older. Results:  Overall, 32.4% of elderly men and 42.7% of elderly women used at least one kind of dietary supplement during the past 12 months. Approximately 16% of elderly men and 19% of elderly women used multivitamin and mineral supplements, 10.5 and 22% used calcium, and 10 and 14% used vitamin E, respectively. Conclusions:  The rates of supplement use are generally lower than those observed in the USA but comparable to that in other industrialised countries. Elderly who are females or who are more highly educated or physically more active are more frequent supplement users.
Information technology and sustainable change within the domain of local practice
Authors: Ibrahim Rahimah , Barnett Karen , Buys Laurie 
Published: October 2006

Objectives:  To explore the local service delivery level when information technology (IT) was introduced into a non‐profit residential aged care facility. Methods:  Theoretical sampling provided participants from occupational groups staffing day‐to‐day work activities. Twenty‐two participants were interviewed about the compulsory use of computers in daily routines, and the role of IT in service delivery. Findings:  Analysis of interview data identified five themes. Three related to local service delivery issues that stemmed from the restructuring of daily work practices. Two themes, which enforced the change at local level, related to the idea of sustainability. Conclusion:  IT was regarded as part of the new focus in aged care towards outcome‐related goals such as efficiency, fiscal sustainability and quality. Nonetheless, these outcomes were perceived by the staff to be separate from the care given to the residents, indicating that staff could not yet reconcile the new procedural requirements with their caregiving practice.