bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scn2a sodium channel mutation results in hyperexcitability in the hippocampus in vitro
Authors: Kile Kara Buehrer , Tian Nan , Durand Dominique M. 
Published: November 2007

Summary
Purpose: To investigate in vitro, the cellular network activity of the hippocampus in Q54 mice that display spontaneous seizures because of a gain‐of‐function mutation of the Scn2a sodium channel gene.
Methods: Extacellular recordings were obtained from CA1 and CA3 pyramidal neurons in hippocampal slices prepared from Q54 transgenic and nontransgenic littermates (WT) under physiologic conditions as well as during periods of orthodromic stimulation of the Schaffer collaterals. Cerebral spinal fluid samples were analyzed and cresyl violet histology of the hippocampus was conducted.
Results: Increased spontaneous extracellular activity was found in both CA1 and CA3 regions of Q54 hippocampal slices. Q54 slices also demonstrated significantly greater spontaneous and afterdischarge activity as well as population spike amplitude and duration following tetanic stimulus in comparison to WT slices. Frequency analysis of tetanically stimulated recordings indicated high‐frequency components (100 and 200 Hz) unique to Q45 slices. Analysis of cresyl violet histology supports healthy Q54 slices up to 10 weeks, while Q54 cerebral spinal fluid shows elevated osmolarity.
Conclusion: Evidence for hyperexcitability and increased synaptic efficacy in Q54 mice was found by observing spontaneous activity as well as evoked activity. Response to tetanic stimulation included unique high‐frequency oscillations, and resulted in an increased population spike amplitude and duration. Histological assessment shows equivalent neuronal development in both experimental groups. The data support the hypothesis that modified Scn2a channels in Q54 mice result in network hyperexcitability of the hippocampus necessary for the development and maintenance of temporal lobe seizures.
Growing old with epilepsy: the neglected issue of cognitive and brain health in aging and elder persons with chronic epilepsy
Authors: Hermann Bruce , Seidenberg Michael , Sager Mark , Carlsson Cynthia , Gidal Barry , Sheth Raj , Rutecki Paul , Asthana Sanjay 
Published: November 2007

SummaryThe purpose of this review is to examine what is known about cognitive and brain aging in elders with chronic epilepsy. We contend that much remains to be learned about the ultimate course of cognition and brain structure in persons with chronic epilepsy and concern appears warranted. Individuals with chronic epilepsy are exposed to many risk factors demonstrated to be associated with abnormal cognitive and brain aging in the general population, with many of these risk factors present in persons with chronic epilepsy as early as midlife. We suggest that a research agenda be developed to systematically identify and treat known modifiable risk factors in order to protect and promote cognitive and brain health in aging and elder persons with chronic epilepsy.
A Haplotype Analysis ofCYP2E1Polymorphisms in Relation to Alcoholic Phenotypes in Mexican Americans
Authors: Yang Min , Tsuang John , Yvonne Wan Yu‐Jui 
Published: November 2007

Background: Studies regarding the association between the 4 polymorphisms ofCYP2E1(CYP2E1*1D,*5B,*6, and*1B) and alcoholism are inconsistent and inconclusive. The purpose of the present study was to clarify previously discordant studies by haplotype analysis in the Mexican American population.Methods: The 4 polymorphisms ofCYP2E1were studied in 334 alcoholics and 365 controls. Genotype, allele, and haplotype frequency comparisons between alcoholics and controls were assessed. Patterns of linkage disequilibrium (LD) atCYP2E1were determined. Reconstructed haplotypes were tested for associations with clinical phenotypes (age onset of drinking, Maxdrinks, and smoking status).Results: No significant associations between the 4 polymorphisms ofCYP2E1and alcoholism were revealed by single allele tests. High LD was found between theCYP2E1 c2andCalleles in Mexican Americans. Eleven haplotypes were present in the 699 participants. The 6 main haplotypes with frequencies higher than 1% made up 97% of the total halpotypes. The frequency of subjects carrying H6 (1C‐c2‐C‐A2) was significantly higher in alcoholics than in controls (p = 0.0001). In contrast, the frequencies of H7 (1C‐c2‐C‐A1) and H10 (1C‐c2‐D‐A1) were significantly lower in alcoholics than in controls (p = 0.0072 for H7 andp = 0.0407 for H10). The frequency of H6 was significantly higher in alcoholics who had late onset of drinking than in nonalcoholic controls. Furthermore, the frequencies of H6 haplotype were also consistently higher in groups who had high number of maximum drinks (9 to 32 drinks) than in controls. When smokers are excluded, the frequencies of H6, H7, and H9 (1C‐c2‐D‐A2) showed statistically significant differences between alcoholics and controls (p < 0.05). Moreover, the association between H6 and alcoholism become more robust when smokers are excluded. Furthermore, the frequency of H1 (1C‐c1‐D‐A2) in alcoholic‐smokers was much higher than in alcoholic‐nonsmokers (p = 0.0028). In contrast, alcoholic‐smokers carried less H2 (1C‐c1‐D‐A1) in comparison with alcoholic‐nonsmokers (p = 0.0417). The H3 (1D‐c2‐C‐A2) frequency in alcoholic‐smokers was much lower than in alcoholic‐nonsmokers (p = 0.0042) and control‐smokers (p = 0.0363).Conclusions: Our data demonstrate that carrying haplotype H6 might enhance susceptibility to developing alcoholism, but possessing the H7 or H10 haplotype appears to decrease this susceptibility. The H6, H7, and H9 haplotypes may play certain roles in different clinical phenotypes in Mexican American alcoholics. In addition, our data suggest that the H1, H2, and H3 haplotypes are associated with alcohol drinking and smoking. These results support that haplotype analysis is much more informative than single allele analysis. Our findings clearly indicate the importance of H6 haplotype in alcohol drinking in Mexican Americans.
Alcohol Consumption Before Sleep Is Associated With Severity of Sleep‐Disordered Breathing Among Professional Japanese Truck Drivers
Authors: Sakurai Susumu , Cui Renzhe , Tanigawa Takeshi , Yamagishi Kazumasa , Iso Hiroyasu 
Published: November 2007

Background:  Alcohol consumption as well as overweight is known to aggravate the severity of sleep‐disordered breathing (SDB), but little is known about alcohol consumption in truck drivers. The aim of this study was to examine the relationship between alcohol consumption and SDB among truck drivers.Methods:  We conducted a cross‐sectional study of 1,465 men aged 20–69 years who were registered with the Japanese Trucking Association. The 3% oxygen desaturation index (3%ODI) was selected as an indicator of SDB, representing the number of desaturation events per hour of recording time in which blood oxygen fell by ≥3% based on overnight pulse‐oximetry. Participants completed a self‐administered questionnaire including alcohol consumption on the same night for SDB assessment.Results:  The prevalence of 3%ODI ≥5, ≥10, and ≥15/h was 25.4%, 11.1%, and 6.6% respectively. The multivariable odds ratios (OR) of 3%ODI ≥ 10/h were 1.5(0.9–2.5) for 0.5 to <1.0 g of alcohol intake/kg and 3.4(1.8–6.6) for ≥1.0 g of alcohol intake/kg compared with non‐drinkers. Similar associations with alcohol consumption were observed for 3%ODI ≥5 and ≥15/h. The relation between alcohol consumption (≥1.0 g of alcohol intake/kg) and 3%ODI ≥ 10/h tended to be more evident among men with body mass index (BMI) <23.4 kg/m2 than those with BMI ≥ 23.4 kg/m2 [11.4 (3.2–41) vs. 1.2 (0.6–2.7), p = 0.18 for interaction]. A similar trend was observed for 3%ODI ≥ 5/h.Conclusions:  The prevalence of undiagnosed SDB and the significant association of alcohol consumption with SDB severity emphasize the need for SDB screening and alcohol modification as well as weight control to prevent and control SDB among truck drivers.
Acute Ethanol Potentiates the Clock‐Speed Enhancing Effects of Nicotine on Timing and Temporal Memory
Authors: Meck Warren H. 
Published: November 2007

Background: Acute ethanol administration potentiates some of the behavioral effects of nicotine, although the extent of this effect is unknown. The present investigation assessed the ability of ethanol to potentiate nicotine’s effect on the overestimation of multisecond durations as a result of an increase in the speed of an internal clock.Methods: Adult male rats were exposed to the acute effects of ethanol (0.0, 0.5, 1.5, and 3.0 g/kg; IG) which was given 10 minutes prior to the administration of nicotine (0.0, 0.3, 0.6, and 1.0 mg/kg; IP). The effects of these combined treatments on timing and temporal memory were assessed using 18‐ and 36‐second peak‐interval procedures with separate visual/spatial cues for responding.Results: When administered alone, ethanol had no consistent effect on peak time, but decreased peak rate, and increased peak spread as a function of dose. In contrast, nicotine alone shifted the peak times of the response distributions leftward in a proportional manner as a function of dose. When administered after pretreatment with ethanol, nicotine’s effect on the horizontal placement of the peak functions was potentiated.Conclusions: The observation that ethanol pretreatment potentiates the clock‐speed enhancing effects of subsequently administered nicotine is discussed in terms of the role of α7‐nicotinic acetylcholine receptors and dopamine–glutamate interactions in cortico‐striatal circuits thought to subserve interval timing.
Formic Acid, a Novel Metabolite of Chronic Ethanol Abuse, Causes Neurotoxicity, Which Is Prevented by Folic Acid
Authors: Kapur Bhushan M. , Vandenbroucke Arthur C. , Adamchik Yana , Lehotay Denis C. , Carlen Peter L. 
Published: November 2007

Background: Methanol is endogenously formed in the brain and is present as a congener in most alcoholic beverages. Because ethanol is preferentially metabolized over methanol (MeOH) by alcohol dehydrogenase, it is not surprising that MeOH accumulates in the alcohol‐abusing population. This suggests that the alcohol‐drinking population will have higher levels of MeOH’s neurotoxic metabolite, formic acid (FA). FA elimination is mediated by folic acid. Neurotoxicity is a common result of chronic alcoholism. This study shows for the first time that FA, found in chronic alcoholics, is neurotoxic and this toxicity can be mitigated by folic acid administration.Objective: To determine if FA levels are higher in the alcohol‐drinking population and to assess its neurotoxicity in organotypic hippocampal rat brain slice cultures.Methods: Serum and CSF FA was measured in samples from both ethanol abusing and control patients, who presented to a hospital emergency department. FA’s neurotoxicity and its reversibility by folic acid were assessed using organotypic rat brain hippocampal slice cultures using clinically relevant concentrations.Results: Serum FA levels in the alcoholics (mean ± SE: 0.416 ± 0.093 mmol/l,n = 23) were significantly higher than in controls (mean ± SE: 0.154 ± 0.009 mmol/l,n = 82) (p < 0.0002). FA was not detected in the controls’ CSF (n = 20), whereas it was >0.15 mmol/l in CSF of 3 of the 4 alcoholic cases. Low doses of FA from 1 to 5 mmol/l added for 24, 48 or 72 hours to the rat brain slice cultures caused neuronal death as measured by propidium iodide staining. When folic acid (1 μmol/l) was added with the FA, neuronal death was prevented.Conclusions: Formic acid may be a significant factor in the neurotoxicity of ethanol abuse. This neurotoxicity can be mitigated by folic acid administration at a clinically relevant dose.
Alcohol Accelerates Loss of Muscle and Impairs Recovery of Muscle Mass Resulting From Disuse Atrophy
Authors: Vargas Roberto , Lang Charles H. 
Published: November 2007

Background:  Muscle disuse atrophy is observed in patients recovering from trauma and there is an increased risk and severity of injury in patients abusing alcohol (EtOH). However, the interaction of EtOH and disuse on muscle protein balance has not been examined. Therefore, the present study addressed the hypothesis that EtOH accelerates the disuse atrophy and/or impairs the accretion of muscle protein during muscle recovery.Methods:  To address this aim, disuse atrophy was induced in rats by 3 days of unilateral hindlimb immobilization (casting), using the contralateral leg as control, with EtOH or saline being orally gavaged twice, each day during this period. In a separate study, EtOH‐treated rats received Velcade to inhibit proteasomal degradation. Finally, in the last study, rats had 1 limb casted for 5 days, the cast removed, and EtOH or saline gavaged twice daily during a 5‐day recovery period. Muscle protein metabolism was assessed using surrogate markers of protein synthesis [i.e., phosphorylation of 4E‐binding protein 1 (BP1) and S6 kinase 1 (S6K1)] and protein degradation (i.e., mRNA content of the ubiquitin E3 ligases atrogin‐1 and MuRF1).Results:  Ethanol alone did not decrease muscle weight in the uncasted muscle. However, the loss of mass of immobilized muscle from EtOH‐gavaged rats was 80% greater than in the animals not receiving EtOH. This atrophic response was not associated with a change in Akt, 4E‐BP1 or S6K1 phosphorylation among groups. In contrast, immobilization alone increased both atrogin‐1 and MuRF1 mRNA, and EtOH further increased their expression in immobilized muscle. The proteasome inhibitor Velcade attenuated atrophy produced by EtOH + disuse. When administered during the recovery period, EtOH prevented the normal accretion of muscle mass. This EtOH effect was associated with increased atrogin‐1 mRNA, a reduction in 4E‐BP1 and S6 phosphorylation, and an increased AMP‐activated kinase phosphorylation.Conclusions:  Based on the changes in these surrogate markers, our data suggest that EtOH accelerates disuse atrophy by stimulating ubiquitin‐mediated proteolysis, and blunts repletion of muscle protein during recovery from disuse by increasing proteolysis and decreasing protein synthesis.
Ethanol dependence of α1‐antitrypsin C‐terminal Lys truncation mediated by basic carboxypeptidases
Authors: Matthiessen H. Peter , Willemse Johan , Weber Alfred , Turecek Peter L. , Deiteren Kathleen , Hendriks Dirk , Ehrlich Hartmut J. , Schwarz Hans‐Peter 
Published: November 2007

BACKGROUND: Patients with hereditary emphysema are treated with α1‐antitrypsin (α1‐proteinase inhibitor [A1PI]) concentrates. High‐resolution isoelectric focusing (IEF) analysis of A1PI shows that commercial A1PI products have different glycoisoform band patterns predominantly caused by varying degrees of C‐terminal Lys truncation at position 394 from the A1PI molecule. Basic carboxypeptidases (CPs) are a group of enzymes that specifically cleave C‐terminal basic amino acids (Arg or Lys) from peptides and proteins.STUDY DESIGN AND METHODS: In this study, whether A1PI is a substrate for basic CPs was investigated. CPN and CPU, two CPs present in plasma, and CPM, a GPI‐anchored membrane protein highly expressed in lung tissues, were included.RESULTS: Basic CPs are able to mediate the C‐terminal Lys truncation of A1PI although with a very low efficiency. However, presence of ethanol, for example, during Cohn fractionation, renders A1PI highly susceptible to cleavage by CP with the extent of Lys truncation depending on the ethanol concentration. This ethanol concentration dependence elegantly explains the varying amounts of des‐Lys A1PI present in commercial preparations purified from different Cohn fractions.CONCLUSIONS: The cause of C‐terminal truncation of A1PI present in products used for augmentation therapy has been identified, and it has been shown that A1PI becomes a substrate for CPs, specifically CPN, because of the presence of ethanol during Cohn fractionation.
Predicting donation among an Irish sample of donors and nondonors: extending the theory of planned behavior
Authors: McMahon Roz , Byrne Molly 
Published: November 2007

BACKGROUND: Research has indicated the ability of the Theory of Planned Behavior to predict blood donation. This study tested an extended version of the Theory of Planned Behavior (attitude, subjective norm, and perceived behavioral control with the addition of past behavior, moral norm, self‐identity, and anticipated regret) in predicting donation intention and behavior among donors and nondonors and if forming implementation intentions improved attendance at a mobile blood donation clinic.STUDY DESIGN AND METHODS: This study used a cross‐sectional follow‐up design. A questionnaire was distributed to 600 staff and students at the National University of Ireland, Galway, before the arrival of a mobile clinic to Galway city. Half of these participants were invited to make implementation intentions specifying how, where, and when they planned to donate blood. A second questionnaire measuring reported attendance at the clinic was distributed 2 weeks after the first questionnaire.RESULTS: A total of 172 eligible donors returned questionnaires (29% response rate). The extended Theory of Planned Behavior accounted for 51 percent of the variance in intention to donate in the future: anticipated regret, attitude, perceived behavioral control, self‐identity, and subjective norm significantly predicted intention. Donors differed from nondonors: they possessed more favorable attitudes toward blood donation, had a greater sense of donor identity, and believed more strongly in a moral obligation to donate blood than nondonors. Those who made implementation intentions were no more likely to donate that those who had not.CONCLUSION: Owing to the different factors influencing the donation decision for donors and nondonors, separate strategies to promote donation should be designed for these subgroups, targeting the elements most pertinent to each group.
Quality control of blood irradiation with a teletherapy unit: damage to stored red blood cells after cobalt‐60 gamma irradiation
Authors: Góes E.G. , Ottoboni M.A. , Palma P.V.B. , Morais F.R. , Pelá C.A. , Borges J.C. , Covas D.T. 
Published: November 2007

BACKGROUND: Previous publications have documented the damage caused to red blood cells (RBCs) irradiated with X‐rays produced by a linear accelerator and with gamma rays derived from a 137Cs source. The biologic effects on RBCs of gamma rays from a 60Co source, however, have not been characterized.STUDY DESIGN AND METHODS: This study investigated the effect of 3000 and 4000 cGy on the in vitro properties of RBCs preserved with preservative solution and irradiated with a cobalt teletherapy unit. A thermal device equipped with a data acquisition system was used to maintain and monitor the blood temperature during irradiation. The device was rotated at 2 r.p.m. in the irradiation beam by means of an automated system. The spatial distribution of the absorbed dose over the irradiated volume was obtained with phantom and thermoluminescent dosimeters (TLDs). Levels of Hb, K+, and Cl‐ were assessed by spectrophotometric techniques over a period of 45 days. The change in the topology of the RBC membrane was investigated by flow cytometry.RESULTS: Irradiation caused significant changes in the extracellular levels of K+ and Hb and in the organizational structure of the phospholipid bilayer of the RBC membrane. Blood temperature ranged from 2 to 4°C during irradiation. Rotation at 2 r.p.m. distributed the dose homogeneously (92%‐104%) and did not damage the RBCs.CONCLUSIONS: The method used to store the blood bags during irradiation guaranteed that all damage caused to the cells was exclusively due to the action of radiation at the doses applied. It was demonstrated that prolonged storage of 60Co‐irradiated RBCs results in loss of membrane phospholipids asymmetry, exposing phosphatidylserine (PS) on the cells' surface with a time and dose dependence, which can reduce the in vivo recovery of these cells. A time‐ and dose‐dependence effect on the extracellular K+ and plasma‐free Hb levels was also observed. The magnitude of all these effects, however, seems not to be clinically important and can support the storage of irradiated RBC units for at last 28 days.
Incest indices from microsatellite genotypes of mother‐child pairs
Authors: Wenk Robert E. 
Published: November 2007

BACKGROUND: Suspected incestuous paternity is encountered infrequently and investigation may be complicated by absence of the suspected father. Incest indices (IIs) can be calculated from microsatellite (STR) types of only a mother and child, but could be misleading. Therefore, the method was evaluated.STUDY DESIGN AND METHODS: Combined incest indices (CIIs) of 50 randomly mated (RM) mothers and their children were compared with those of 50 simulated incestuous (SI) mothers and their children. Each CII was calculated from 18 individual locus IIs. Combined indices were categorized as “diagnostic” (<0.010 and >100 for RM and SI cases, respectively), “indicative” (CII was directionally correct but not erroneously diagnostic), and “misleading” (>1.0 in RM and <0.01 in SI). The relative importance was determined of each of the three variables contributing to the CII.RESULTS: In 41 cases (41%), CIIs attained diagnostic values. Fifty‐two CIIs were indicative. CIIs were misleading in 3 RM cases and 4 SI cases. The number of mother‐child (M‐C) STR genotype similarities was the most important determinant of CIIs. Infrequent alleles in M‐C similarities were important in raising CIIs in SI. The kind of M‐C genotype similarity was the least important variable.CONCLUSIONS: Study of 18 STR loci produces diagnostic CIIs in only two of five suspected incest cases. Study of approximately 33 independent STRs would assure that greater than 97.5 percent of cases will have diagnostic CIIs if incest occurred. Study of loci that are more informative than typical STRs would be advantageous.
Effects of Bacillus thuringiensisδ‐endotoxin‐fed Helicoverpa armigera on the survival and development of the parasitoid Campoletis chlorideae
Authors: Sharma H.C. , Dhillon M.K. , Arora R. 
Published: November 2007

AbstractWith the deployment of transgenic crops expressing δ‐endotoxins from Bacillus thuringiensis (Bt) for pest management, there is a need to generate information on the interaction of crop pests with their natural enemies that are important for regulation of pest populations. Therefore, we studied the effects of the Bt δ‐endotoxins Cry1Ab and Cry1Ac on the survival and development of the parasitoid Campoletis chlorideae Uchida (Hymenoptera: Ichneumonidae) reared on Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) larvae fed on Bt toxin‐intoxicated artificial diet. The H. armigera larvae fed on artificial diet impregnated with Cry1Ab and Cry1Ac at LC50 (effective concentration to kill 50% of the neonate H. armigera larvae) and ED50 (effective concentration to cause a 50% reduction in larval weight) levels before and after parasitization resulted in a significant reduction in cocoon formation and adult emergence of C. chlorideae. Larval period of the parasitoid was prolonged by 2 days when fed on Bt‐intoxicated larvae. No adverse effects were observed on female fecundity. The observed effects appeared to be indirect in nature, because no Bt proteins were detected through enzyme‐linked immunosorbent assay in the C. chlorideae larvae, cocoons, or adults fed on Cry1Ab‐ or Cry1Ac‐treated H. armigera larvae. The effects of Bt toxin proteins on C. chlorideae were due to early mortality of H. armigera larvae, that is, before completion of parasitoid larval development.