bluuebunny/crossref_metadata_2025 huggingface dataset:
Interleukin‐6 and Interleukin‐8 Production by Mononuclear Cells of Chronic Alcoholics During Treatment
Authors: Martinez Francisca , Thomas Nicole M. , Darban Hamid , Cox Thomas J. , Wood Steve , Watson Ronald R.
Published: June 2007

Chronic alcohol consumption has been associated with suppression of a number of immune parameters. This study was designed to investigate the relationship between chronic alcohol ingestion and cessation with respect to release of interleukin‐6 (IL‐6) and interleukin‐8 (IL‐8) using highly specific and sensitive ELISA assays, as well as a functional assay, natural killer cell cytotoxic activity. ELISAs were developed to determine the amount of IL‐6 and IL‐8 release by peripheral blood mononuclear cells (PBMCs). Two groups of subjects were recruited: young (18–22 years old), nonalcoholic users (controls) and long‐term alcoholics (35–55 years old). Blood samples were collected at time 0 from all subjects and from alcoholics 28 days after treatment had begun and alcohol use had ceased. Then mitogen‐stimulated release of cytokines by peripheral blood cells was determined. The abstaining controls, and the alcoholics, after 30 days of abstinence, tended to produce lower amounts of IL‐6 and IL‐8, although these differences were not statistically significant. Natural killer cell activity was not statistically different between the young groups, yet appeared to increase once alcohol use discontinued. Some of the cells from the controls (abstainers) were incubated with ethanol (EtOH). Its content in sealed wells was measured after the time of incubation of PBMCs. When EtOH was serially diluted in plates, some well‐well diffusion was noted, but the maximum concentration of EtOH never fell below 0.3% from an initial concentration of 0.5%, and at no time was the EtOH concentration gradient completely lost, even after 66 hr of incubation. EtOH in vitro did not induce significant modulation of IL‐6 or IL‐8 release from subjects over the concentration range of ethanol tested (0.02–0.5%). Similarly, there was no statistically significant dependence of baseline (non‐stimulated) release of IL‐6 or IL‐8 on the presence of EtOH in culture medium.
Occurrence of Blood Acetaldehyde in Women During Ethanol Intoxication: Preliminary Findings
Authors: Fukunaga Tatsushige , Sillanaukee Pekka , Eriksson C. J. Peter
Published: June 2007

The question of gender differences regarding blood acetaldehyde levels during ethanol intoxication has not been clarified because of the difficulties in the determination of acetaldehyde levels. Although the blood acetaldehyde levels in men during normal ethanol oxidation are reported to be undetectable, no valid data on female blood acetaldehyde levels have yet been reported. Thus, in the present investigation, 13 young healthy nonalcoholic women, almost all of which took oral contraceptives regularly, were challenged with different doses of ethanol (0.34, 0.68, and 1.02 g/kg) during three different sessions. Venous blood acetaldehyde and ethanol levels were then determined by headspace gas chromatography involving appropriate correction for artefactual acetaldehyde formation during blood treatment and analytical procedures. Corrected blood acetaldehyde levels (mean 2 μM, range0–6 μM) were observed, predominantly at lower ethanol concentrations. Elevated acetaldehyde levels in women may explain why ethanol is less frequently abused and causes tissue damage more rapidly in women than men.
Effect of Ethanol Exposure on Circulating Levels of Insulin‐Like Growth Factor I and II, and Insulin‐Like Growth Factor Binding Proteins in Fetal Rats
Authors: Mauceri Helena J. , Unterman Terry , Dempsey Sandra , Lee Wei‐Hua , Conway Sonya
Published: June 2007

Maternal ethanol (ETOH) exposure is associated with impaired fetal growth. Because insulin‐like growth factors (IGFs) are thought to be important in the regulation of fetal somatic growth, we examined the influence of maternal ETOH exposure on fetal growth and plasma levels of IGF‐I, IGF‐II, and IGF binding proteins (IGFBPs) in the rat model. Control (A) dams were fed a standard rat chow ad libitum. ETOH (E) consuming dams were fed a 36% ETOH diet, and pair‐fed (P) dams were fed isocaloric amounts of a control liquid diet. All animals were killed on day 20 of gestation. Plasma concentrations of IGF‐I and ‐II were determined by radioimmunoassay after formic acid‐acetone extraction and heat inactivation of IGFBPs. Levels of IGFBPs in fetal plasma were estimated by Western ligand blotting after protein separation by SDS‐PAGE and electrotransfer to nitrocellulose. Membranes were probed with [125l]IGF‐l, and IGFBPs were identified by autoradiography, quantified by scanning densitometry and results expressed relative to corresponding IGFBPs in control fetal plasma.

Maternal weight gain from conception to 20 days of pregnancy was reduced for E compared to P and A dams (p < 0.05 E vs. P or A). The same pattern was reflected in fetal weight that tended to be lower in P compared with A pups, and was significantly reduced in E pups compared with both groups (p < 0.0001 E vs. P or A). Thus, fetal growth was more retarded in E animals despite equal caloric and protein intake by E and P dams.

Radioimmunoassay of fetal plasma revealed that there was no difference in circulating levels of IGF‐II in A (65.5 ± 8.7 ng/ml) and P (65.9 ± 9.8 ng/ml) plasma. However, levels of IGF‐II were higher in E (87.1 ± 6.2 ng/ml) than in corresponding P animals. At the same time, there were no differences in IGF‐I levels between any of the treatment groups. Western ligand blotting demonstrated that levels of 32–34 kDa IGFBPs were elevated in plasma of P compared with A fetal plasma, consistent with an effect of reduced maternal nutrition. In contrast, levels of32–34 kDa IGFBPs were reduced in E plasma compared with P and A (p < 0.04 and p < 0.02, respectively).

These data suggest that circulating levels of IGF‐II (but not IGF‐I) and specific IGFBPs are altered in growth‐retarded fetuses exposed to ETOH. Comparison to fetal plasma obtained from pair‐fed litters demonstrate that these effects on IGF and IGFBP levels are specific to ETOH, and not simply due to maternal nutrient intake. Taken together, these observations indicate that ETOH has unique effects on fetal IGF physiology compared with previously studied models of fetal growth retardation. Alterations in the expression and levels of IGFs and IGFBPs may contribute to ETOH‐induced fetal growth deficiency.
Nonsteroidal Antiinflammatory Drugs Lower Ethanol‐Mediated Liver Increase in Lipids and Thiobarbituric Acid Reactive Substances
Authors: de Piña Martha Zentella , Saldaña‐Balmori Yolanda , Hernández‐Tobías Aida , Piña Enrique
Published: June 2007

Four nonsteroidal antiinflammatory drugs–namely, acetylsalicylic acid, naproxen, nimesulide, and dipyrone–were assayed to search their capability in preventing the hepatic increase of triacylglycerols and thiobarbituric acid reactive substances, as an indication of lipid peroxidation, resulting from the acute intoxication of rats with ethanol. The four antiinflammatory compounds inhibited the ethanol‐mediated increase in triacylglycerols and thiobarbituric acid reactive substances. Furthermore, each one of these antiinflammatory drugs produced distinctive actions on blood ethanol levels: a temporal diminution with aspirin and naproxen, no changes with nimesulide, and an increase with dipyrone. It is concluded that the nonsteroidal antiinflammatory drugs contributed to controlling hepatic lipid peroxidation, and hence the oxidative stress promoted by ethanol intoxication.
Effect of Acute Alcohol Withdrawal on Sensitivity to Pro‐and Anticonvulsant Treatments in WSP Mice
Authors: Crabbe John C. , Merrill Catherine M. , Belknap John K.
Published: June 2007

Through the genetic technique of selective breeding, a mouse line [Withdrawal Seizure Prone (WSP)] has been developed that expresses severe handling‐induced convulsions (HIC) after cessation of chronic ethanol exposure. These mice also display rebound elevations in HIC after a single ethanol injection. In the current studies, we tested WSP mice in several paradigms. WSP mice were found to be marginally sensitive to the effects of acute doses of dizocilpine to reduce HIC. However, when tested during acute withdrawal from a single ethanol injection, WSP were more sensitive to this compound. Although N‐methyl‐d‐aspartate significantly elevated HIC in naive WSP mice, it was more effective at low doses when given during acute withdrawal. Withdrawing mice were slightly more sensitive than naive mice to kainic acid. Pentylenetetrazole elevated HIC in naive and withdrawing mice; it was marginally more effective in naive mice. Diazepam inhibited HIC in both naive and withdrawing mice, and was slightly more effective during acute withdrawal. This pattern of results suggests that acute alcohol withdrawal is accompanied by altered sensitivity to convulsants and anticonvulsants. These changes include enhanced sensitivity in at least two excitatory amino acid‐gated ion channel binding sites.
Biochemical Studies of a New Class of Alcohol Dehydrogenase Inhibitors from Radix puerariae
Authors: Keung Wing‐Ming
Published: June 2007

Two potent, reversible inhibitors of human alcohol dehydrogenase; (ADH) isozymes were isolated from Radix puerariae (RP, commonly, known as kudzu root) and identified as the isoflavones daidzein and genistein. The 4‐methoxy derivatives of daidzein (trivial name, for‐mononetin) and genistein (biochanin A), minor constituents of RP, were also shown to be ADH inhibitors. All of these isoflavones inhibit 1 the human ‐γ1γ2‐ADH isozyme competitively with respect to ethanol] and uncompetitively with respect to NAD+. A survey of more than 40 structurally related compounds revealed one more isoflavone (prunetin) and four flavones (7‐hydroxyflavone, apigenin, galangin, and kaempferol) that inhibit ADH. The isoflavone inhibitors, however, are far more potent than the flavone inhibitors. Among the isoflavones studied, genistein is the most potent with Ki, = 0.1 μM toward γ2γ2‐ ADH. Human ADH isozymes differ in their sensitivity to these inhibitors in the order γ2γ2‐, γ1γ1 > α1α1−,>− > xx‐ADH. These inhibitors, do not affect the β1β1,− and β2β2‐ADH isozymes at concentrations as high as 20 μM. Rat and rabbit class I ADHs are also inhibited by these. isoflavone inhibitors. The 7‐O‐glucosyl derivatives of daidzein, genistein, formononetin, and biochanin A do not inhibit ADH, but are potent aldehyde dehydrogenase inhibitors.
Effect of Alcohol, Acetaldehyde, and Salsolinol on β‐Endorphin Secretion from the Hypothalamic Neurons in Primary Cultures
Authors: Reddy B. V. , Sarkar Dipak K.
Published: June 2007

The effect of ethanol, acetaldehyde, and salsolinol on hypothalamic β‐endorphin secreting neurons is studied by using rat fetal hypothalamic neurons in primary culture. Exposure of these neuronal cells to different concentrations of ethanol (12.5–50 mM) and acetaldehyde (12.5‐50 μm) caused a concentration‐dependent increase in the secretion of β‐endorphin. Salsolinol (12.5–50 μm) did not cause any significant change in the secretion of β‐endorphin. Ethanol's effect was short‐lasting (2 hr). Acetaldehyde's effect on β‐endorphin secretion was greater and longer lasting, as compared with ethanol. Ethanol and salsolinol do not have any effect on cell viability, whereas higher concentrations of acetaldehyde appear to reduce the number of viable cells after 6 hr of treatment. None of the above treatments has any effect on cellular DNA content. These results suggest that ethanol is a potent stimulator of hypothalamic β‐endorphin. These results also show for the first time that ethanol's metabolite acetaldehyde is more potent in stimulating β‐endorphin secretion and may be significant in the ethanol regulated β‐endorphin secretion.
Leucine and Glucose Turnover in Chronic Alcoholics During Early Abstinence and After an Ethanol Load
Authors: Petermann Margarita , González Clara , Hirsch Sandra , de la Maza María Pía , Bunout Daniel
Published: June 2007

We studied leucine turnover using a primed infusion of [1‐14C]‐l‐leucine and glucose turnover using a primed infusion of [6‐3H]‐d‐glucose in five alcoholic patients without liver damage and five age‐matched controls. Infusions were maintained for 6 hr, and at the end of the 3rd hour, a 0.8 g/kg iv ethanol load was administered in 20 min. Leucine flux, nonoxidative disposal and oxidation rates, and glucose rate of appearance were calculated during the 3rd and 6th hours of infusion. Ethanol disappearance rate and the percentage completely metabolized to CO2 and H2O in 3 hr were also calculated. Compared with controls, alcoholics had significantly higher basal leucine flux (55.6 ± 12 vs. 37.3 ± 9.3 μm/m2/min) and nonoxidative disposal (48.7 ± 8.7 vs. 31.1 ± 7.5 μm/m2/min). No differences were observed in basal glucose appearance rates in alcoholics and controls (397.6 ± 115.2 vs. 349.4 ± 120.6 μm/m2/min). Compared with controls, alcoholics had a higher alcohol disappearance rate (2.72 ± 0.59 vs. 1.84 ± 0.43 mm/kg/min) and percentage of ethanol metabolized to CO2 and H2O in 3 hr (40.6 ± 10.2 vs. 22.9 ± 6.9%). After the ethanol load, both leucine turnover and glucose rate of appearance decreased significantly only in alcoholics. There was a positive correlation between the change in leucine flux and ethanol disappearance rate and percentage metabolized to CO2 and H2O in alcoholics.
Small Animal Magnetic Resonance Imaging: A Means of Studying the Development of Structural Pathologies in the Rat Brain
Authors: Pentney Roberta J. , Alletto James J. , Acara Margaret A. , Dlugos Cynthia A. , Fiel Robert J.
Published: June 2007

Small animal magnetic resonance imaging (SAMRI) was developed to detect structural tissue changes associated with disease states in animal models. The disease state of particular interest here is that associated with long‐term alcohol abuse. The small animal model used for this study was the thiamine‐deficient Sprague‐Dawley rat, a model that provides a relatively rapid means of mimicking the a ventriculomegaly frequently found in human chronic alcohol abusers, a A custom‐designed coil tuned to the magnetic field of a 1.5 Tesla clinical magnetic resonance imager provided the technology necessary to delineate discreet regions of the rat brain with clarity. Adult, male rats were imaged, placed on a thiamine‐deficient pellet diet for ?6 weeks, and then reimaged. Treatment associated enlargement of the lateral ventricles identified in the images was verified by posttreatment histological analysis of the brains of these rats. The results demonstrated that SAMRI is capable of providing dramatic and reliable visual evidence of pathological structural changes in small tissue volumes with high resolution and reproducibility. Furthermore, the noninvasiveness of SAMRI allowed for imaging of the same animals over time, thereby reducing the numbers of animals needed for convincing documentation of the changes in ventricular size.
Chronic Ethanol Administration Impairs Degradation of Formaldehyde‐Treated Albumin by the Perfused Rat Liver
Authors: Rees Georgia M. , Miller Jacqueline A. , Casey Carol A. , Tuma Dean J.
Published: June 2007

Nonparenchymal cells of the liver appear to be important in the pathogenesis of various liver diseases, including that caused by ethanol. It is known that chronic ethanol administration impairs the process of receptor‐mediated endocytosis in hepatocytes. Liver endothelial cells are also actively endocytic cells, playing a prominent role in the clearance from the circulation of a variety of macro‐molecules. In this study, we assessed the effect of ethanol administration on this “scavenger” function of liver endothelial cells by measuring the degradation of formaldehyde‐treated albumin in isolated, perfused livers of ethanol‐fed rats. Rats were pair‐fed for 1 or 4 weeks with a liquid diet containing either ethanol as 36% of total calories or an isocaloric amount of carbohydrate. Chronic ethanol administration in this manner for 1 or 4 weeks significantly impaired the degradation of this endothelial cell iigand (by 60 ± 9% and 37 ± 9%, respectively). Liver perfusions were also performed on rats that had been administered ethanol acutely or in which ethanol was added to the perfusate. No acute effect of ethanol on the degradation of this Iigand was seen. These results demonstrate that chronic ethanol ingestion impairs receptor‐mediated endocytosis of formaldehyde‐treated albumin by liver endothelial cells, indicating that the adverse effects of ethanol on protein trafficking within the liver are not limited to the hepatocytes.
First‐Pass Metabolism of Ethanol Is Predominantly Gastric
Authors: Lim Robert T. , Gentry R. Thomas , Ito Daisuke , Yokoyama Hirokazu , Baraona Enrique , Lieber Charles S.
Published: June 2007

Oral consumption of alcohol results in much lower blood alcohol concentrations (BACs) than does the same dose administered intravenously, suggesting significant first‐pass metabolism (FPM). The questions remain, however, (1) whether this difference truly represents FPM or simply reflects slower absorption of alcohol, and (2) if there is FPM, is it mainly of gastric or hepatic origin. To study this, rats were given the same dose alcohol (1 g/kg) by either intragastric intubation or by intravenous, intraportal, and intraduodenal infusions at a rate that mimicked the loss of alcohol from the stomach. Higher BAC levels after intravenous than intragastric alcohol indicated true FPM. Higher levels after intraportal or intraduodenal infusions (in fact, comparable to those obtained with the intravenous route) demonstrated negligible FPM when the route of delivery bypassed the stomach, yet included the liver. Furthermore, rats that had developed portosystemic shunts after ligation of the portal vein exhibited blood alcohol curves and FPM equivalent to those of sham‐operated controls, indicating that FPM is not dependent on first‐pass flow through the liver, but reflects gastric metabolism. The absence of significant hepatic FPM is attributable to the saturation of hepatic alcohol dehydrogenase by recirculating alcohol, resulting in no appreciable increase in metabolism secondary to newly absorbed alcohol. Finally, the in vivo gastric metabolism of alcohol in pylorus‐ligated rats was demonstrated by significantly lower BACs when alcohol was administered intragastrically than when an amount identical to that lost from the ligated stomach was given intraportally. Thus, the lower BACs with oral as opposed to intravenous alcohol are not simply a consequence of slow absorption, but result from FPM occurring predominantly in the stomach.
The Natural History of Outpatient Alcohol and Drug Abuse Treatment in a Private Healthcare Setting
Authors: Pettinati Helen M. , Belden Portia Payne , Evans Bradley D. , Ruetsch Charles R. , Meyers Kathleen , Jensen Jacqueline M.
Published: June 2007

Managed healthcare has had a major impact on the delivery of alcohol and drug abuse treatment services in the private setting, primarily by shitting patient enrollment from inpatient to outpatient treatment programs. The purpose of this study was to investigate the natural history of outpatient alcohol and drug abuse treatment in a private, nonprofit healthcare setting. Patient profiles at pretreatment, their attendance record in a 6‐week outpatient program, and their outcome in the year after treatment were evaluated in 120 patients with a DSM‐III‐R diagnosis of alcohol and/or cocaine dependence. There were 70 outpatients who successfully completed the program, and 50 who did not. Two subtypes of outpatient treatment failures were identified: Ss who prematurely left treatment against medical advice (n = a), and Ss who attended treatment but continued heavy use of substances (Treatment Resistant, n= 27). A logistic regression revealed that younger age, multiple prior treatments, and employment problems were related to outpatient treatment failure. Outpatient failures did not immediately seek alternative treatment, and most of them continued heavy substance use in the year post‐treatment i.e., 82% vs. 43% successful completers (X2= 13.8, df= 1, p < 0.01). Thus, there were a clinically relevant number of outpatient failures (42%), either because of lack of program attendance or continued substance use throughout treatment These behaviors were related to continued heavy use of substances in the year after treatment
Efficacy of Buspirone in Alcohol Dependence: A Review
Authors: Malec T. S. , Malec E. A. , Dongier M.
Published: June 2007

The five published controlled studies on the effects of buspirone in alcoholism treatment are reviewed. They have been conducted mostly in alcoholics with comorbid anxiety. Significant differences in favor of the medication were observed in several psychopathological measures (anxiety, depression, hostility, interpersonal sensitivity, and global psychopathology). In only two studies were alcohol craving and consumption found influenced. Metaanalysis showed positive effects of buspirone on treatment retention, as well as on anxiety. It can be concluded that the main effect of buspirone in the treatment of alcoholism is not on ethanol consumption pew se, but on associated psychopathological symptoms. A favorable safety profile and a lack of interaction with alcohol make buspirone a useful pharmacological adjunct in the treatment of alcoholism.
Ethanol Ingestion Inhibits Cell‐Mediated Immune Responses of Unprimed T‐Cell Receptor Transgenic Mice
Authors: Schodde Holly , Hurst Stephen , Munroe Melissa , Barrett Terrence , Waltenbaugh Carl
Published: June 2007

This paper introduces a transgenic ug) mouse in which the majority of the CWbearing T cells have T‐cell receptors that react with ovalbumin (OVA) as a model for ethanol research. Although these Tg animals were bred onto the BALB/c genetic background, a strain generally considered to be nonpreferring in ethanol consumption, we determined that BALB/c mice would consume an ethanol‐containing liquid diet, without significant mortality, and assessed alteration of specific immune responses. BALB/c, C57BU6 (B6), or (BALB/c x C57BL6)F1 hybrid (CB6F1) mice were fed LED containing 35,30,25, or 20% ethandaerived calories. Significant mortalii (>40%) was seen only in Wc and pronounced weight loss was seen in BALB/c, B6, CBEIFl mice when they were fed the diet containii the greatest ethanol concentration (LED35). Diets containing lesser amounts of ethanol did not cause mortalii. Liquid diets containing ≥30% ethand‐derhred calories significantly impaired the chicken γ‐globulbspecnic delayed hypersensitivity responses in Wc, B6, and CB6Flmice without significantly affecting the humoral immune response to sheep red Mood cells. We show that immunization of the Tg mice is not required for the development of a vigorous “debyed hypersensitivity” response to OVA or the I‐A'‐restricted peptide OVL323–399 in mice fed standard solid lab chow or liquid control diet. In marked contrast, OVA Tg mice fed ethand show a profound inhibition of this immune response, indicating that ethand‐induced inhibition of cell‐mediated immunity occurs independently of antigen priming.
Morphometric Characteristics of Human Hepatocellular Peroxisomes in Alcoholic Liver Disease
Authors: Craemer Dirk De , Pauwels Marina , Van den Branden Christiane
Published: June 2007

Hepatocellular peroxisomes harbor one of the metabolic pathways for ethanol metabolism (i.e., catalase in the presence of H2O2‐gen‐erating enzymes). We studied the morphometric characteristics of these organelles in 26 biopsy samples of patients with different alcohol‐induced lesions (12 with steatosis, 5 with hepatitis, and 9 with cimhosis) and compared the findings with those obtained in seven control livers. All 33 human liver biopsy samples were stained for catalase activity to facilitate peroxisomal identification. Morphometric analysis of the peroxisomes was performed on calibrated electron micrographs. The numerical density of the peroxisomes was significantly increased to 183%, whereas the mean peroxisomal diameter (dcircle) revealed a significant decrease to 89%. This resulted in a normal volume density of the peroxisomal compartment, whereas the surface density was significantly induced. Peroxisomal shape was not different between alcoholic and control livers. When alcoholic livers were divided into three subgroups according to his‐topathological findings, similar morphometric results were obtained when compared with control livers, although significancy was sometimes lost. No differences in peroxisomal characteristics were found among alcoholic subgroups. The mean peroxisomal diameter per human liver (alcoholic and control) was inversely correlated to the numerical density. It is concluded that the peroxisomal adaptation in human alcoholic liver is such as to create an efficient environment for a presumably increased peroxisomal metabolism.
Gender Differences in Phagocytic Responses in the Blood and Liver, and the Generation of Cytokine‐Induced Neutrophil Chemoattractant in the Liver of Acutely Ethanol‐Intoxicated Rats
Authors: Spitzer Judy A. , Zhang Ping
Published: June 2007

Phagocytosis by circulating and liver‐recruited polymorphonuclear leukocytes (PMNs) and Kupffer cells was studied in acutely ethanol‐intoxicated, age‐matched male and female rats. Acute ethanol intoxication in female rats is associated with a more effective phagocytic PMN response in the circulating blood, but with lower phagocytic activities by liver‐recruited PMNs and Kupffer cells than in their male counterparts. Endotoxin [lipopolysaccharide (LPS)] treatment (consisting of a Wmin intravenous infusion of a nonlethal dose) of acutely ethanol‐intoxicated male and female rats results in enhanced phagocytic responses in liver‐sequestered PMNs and Kupffer cells, but not in circulating PMNs. However, the LPS challenge elicits a lesser phagocytic response in liver PMNs and Kupffer cells of female rats than in males. Significant gender differences exist in the extent of hepatic PMN infiltration in ethanol plus LPS‐treated rats, which is paralleled by very similar difterences in CDll b/c adhesion molecule expression in circulating PMNs and cytokine‐induced neutrophil chemoattractant generation by hepatocytes and Kupffer cells. Taken together, these data indicate a smaller phagocytic response to fight infection in the liver of acutely alcohol‐intoxicated female rats, but also a mechanism to afford some protection against neu‐trophil‐associated tissue injury.
Effects of Prenatal Ethanol Exposure on Voltage‐Dependent Calcium Entry into Neonatal Whole Brain‐Dissociated Neurons
Authors: Lee Young‐Hee , Spuhler‐Phillips Karen , Randall Patrick K. , Leslie Steven W.
Published: June 2007

The effect of prenatal ethanol exposure on voltage‐dependent calcium entry into neonatal‐dissociated neurons was studied. Dissociated whole brain cells were isolated from neonates of prenatally ethanol‐treated (ET), pair‐fed (PF) control, and ad libitum (AL) control groups and loaded with bra‐2. Prenatal ethanol exposure resulted in a significant reduction of calcium entry into K+‐depolarized cells, compared with AL and PF control treatments. Initially, in dissociated cells from AL control animals, it was found that nifedipine (1 μM), ω‐agatoxin (100 nM), and ω‐conotoxin (500 nM), to a much lesser extent, significantly inhibited the 45 mM KCI‐stimulated calcium entry. To determine the inhibitory action of prenatal ethanol exposure on N‐1P‐1and L‐type voltage‐dependent calcium channels, treatment of neonatal‐dissociated neurons with different combinations of ω‐conotoxin, ω‐agatoxin, and nifedipine, respectively, was compared in the prenatal ethanol and control treatment groups. The inhibition of K+‐stimulated increase in calcium entry by prenatal ethanol exposure was significantly less in the presence or absence of single antagonist conditions (ET < AL and PF). There was no apparent interaction of ethanol exposure and antagonist condition. However, the reduced calcium entry after prenatal ethanol exposure was superseded by the stronger inhibition in dual and triple antagonist conditions. The magnitude of the calcium response inhibition by the antagonist combinations was similar among the ET, PF, and AL groups. Thus, these results suggest that prenatal ethanol exposure decreases voltage‐dependent calcium entry into neonatal‐dissociated neurons in a manner that does not seem to involve the selective inhibition of any individual N‐, P‐, or L‐type calcium channel.
Effect of Chronic Maternal Ethanol Administration on Nitric Oxide Synthase Activity in the Hippocampus of the Mature Fetal Guinea Pig
Authors: Kimura Karen A. , Parr Ann M. , Brien James F.
Published: June 2007

Nitric oxide is a novel messenger that is involved in neuronal cell‐cell communication and seems to play a neurotrophic role in normal brain development Chronic prenatal ethanol exposure can produce central nervous system (CNS) teratogenesis, in which one of the target sites is the hippocampus. The main objective of our study was to test the following hypothesis: chronic matemal administration of an ethanol dosage regimen that produces CNS teratogenesis decreases nitric oxide synthase (NOS) activity in the fetal hippocampus. The ontogeny of NOS activity in the hippocampus of the developing guinea pig was further elucidated at two prenatal and two postnatal ages. The effects of chronic maternal oral administration of 4 g of ethanoVkg maternal body weight/day, isocaloric sucrose and pair feeding, or water [given as two equally divided doses 2 hr apart from gestational day (GD) 2 to GD 61] on body, brain, and hippocampal weights and hippocampal NOS activity were determined in the mature fetal guinea pig at GD 62 (term, about GD 68). NOS activity in the 25,000 × g supernatant fraction of hippocampal homogenate was measured using an optimized radiometric assay, based on the oxidation of l‐[14C]arginine to l‐[14C]citrulilne. For the chronic ethanol regimen, the matemai bid ethanol concentration at 1 hr after the second divided dose on OD 57 was 167 ± 45 mg/dI. Chronic matemal administration of ethanol decreased fetal body, brain, and hippocampai weights, compared with the isocaloric‐sucrose/pair‐fed and water treatment groups. The rate of l‐[14C]cibulline formation and NOS activity in the fetal hippocampus were decreased in the ethanol treatment group, compared with the isocaioric‐sucrose/ pair‐fed and water treatment groups. There was no difference in the rate of l‐[14C]citruIline formation, NOS activity, and fetal hippocampal and body weights between the isocaioric‐sucrose/pair‐fed and water treatment groups; however, fetal brain weight was decreased in the isocaloric‐sucrose group, compared with the water group. Data of this study support the research hkothesis by demonstrating that chronic matemal administration of ethanol decreases fetal hippocampal NOS activity that is comlated with restricted growth of this brain region.
Ethanol‐Induced Inhibition of Cell Proliferation Is Modulated by Insulin‐Like Growth Factor‐I Receptor Levels
Authors: Resnicoff Mariana , Cui Shijun , Coppola Domenico , Hoek Jan B. , Rubin Raphael
Published: June 2007

Ethanol inhibits the tyrosine autophosphorylation of the insulin‐like growth factor (IGF)‐1 receptor, an action that correlates with the inhibition of IGF‐I‐stimulated cell proliferation [J. Biol. Chem. 268:21777–21782 (1993)l. In the current study, the IGF‐I‐dependent proliferation of mouse BALB/c3T3 cells was completely inhibited by ethanol, but the growth of BALB/c3T3 cells that overexpress the IGF‐l receptor (p6 cells) was only partially inhibited by ethanol. BALB/ c3T3 cells that simultaneously overexpress both the IGF‐I receptor and IGF‐I were insensitive to growth inhibition by ethanol. In p6 cells, increasing concentrations of IGF‐l overcame the inhibition of IGF‐l receptor tyrosine autophosphorylation in the presence of ethanol. The importance of the IGF‐I receptor as a specific target for ethanol was further investigated in C6 rat glioblastoma cells that respond mitogenically to both epidermal growth factor (EGF) and IGF‐I. The mitogenic response of C6 cells to EGF was abrogated In cells expressing antisense mRNA to the IGF‐l receptor. Thus, EGF action in these cells is dependent on activation of an IGF‐I/lGF‐I receptor au‐tocrine pathway. Indeed, EGF stimulated an increase in IGF‐l receptor levels by more than 100%. Ethanol completely inhibited the prollferation of C6 cells in response to either EGF or IGF‐I. However, ethanol did not directly interfere with EGF receptor function, because EGF‐induced cell proliferation was unaffected by ethanol when added exclusively during a 1‐hr exposure to EGF. Ethanol did not interfere with the EGF‐induced increase in IGF‐I receptor expression. The addition of both EGF and IGF‐I overcame the inhibitory action of ethanol. In conclusion, the potency of ethanol as an inhibitor of IGF‐I‐mediated cell proliferation correlates with the level of IGF‐I receptors. In contrast to its effect on the IGF‐I receptor, ethanol has no direct effect on EGF receptor activation.
A Latent Growth Curve Analysis of Prosocial Behavior Among Rural Adolescents
Authors: Carlo Gustavo , Crockett Lisa J. , Randall Brandy A. , Roesch Scott C.
Published: June 2007

The present study was designed to investigate stability and changes in prosocial behavior and the parent and peer correlates of prosocial behavior in rural adolescents. Participants were from a rural, low SES community in the Eastern United States. The participants were in 7th, 8th, and 9th grades at Time 1 and 10th, 11th, and 12th grades at Time 4, and completed measures of prosocial behavior and quality of parent and peer relationships. Latent growth curve modeling revealed that despite moderate stability in individual differences in prosocial behavior and slight increases in quality of peer and parent relationships, level of prosocial behavior declined until late high school with a slight rebound in grade 12. Furthermore, increases in the quality of peer relationships predicted decreases in prosocial behavior for girls but not boys. Discussion focuses on continuity and change in prosocial behavior and the gender‐based relations between quality of parent and peer relationships and prosocial behaviors in adolescence.
Friendship Influences During Early Adolescence: The Special Role of Friends' Grade Point Average
Authors: Cook Thomas D. , Deng Yingying , Morgano Emily
Published: June 2007

This study examines how a wide variety of diverse friendship group attributes affect changes in indicators of school performance, social behavior, and mental health between early seventh and late eighth grade. Nine hundred and one middle school students named their friends. Independent data from these friends were used to construct friendship groups that were then characterized in terms of their mean level on measures of academic performance, social behavior, psychological closeness, and structure. Two novel conclusions emerge from the study. First, nearly all the friendship effects are domain‐specific. That is, peer attributes in the school domain affect individual school performance outcomes, while peer attributes in the social behavior domain affect individual social behavior. Second, friends' grade point average (GPA) is the most powerful single friendship attribute. It has the largest total effect, the most consistent effects within its own school performance domain, and the sole reliable cross‐domain impact—on an index of negative social behavior that taps into acting out and drug use. The within‐domain peer effects mostly replicate past findings, though the methodological controls used here are more extensive than in past studies and so provide a stronger causal warrant.
Adolescents' Peer Crowd Identification in the Netherlands: Structure and Associations with Problem Behaviors
Authors: Delsing Marc J. M. H. , Ter Bogt Tom F. M. , Engels Rutger C. M. E. , Meeus Wim H. J.
Published: June 2007

The present paper examined the underlying structure of Dutch adolescents' peer crowd identification and its relations with delinquency, aggression, depression, and anxiety. Questionnaire data were gathered from 2,334 adolescents between ages 12 and 19. Exploratory and confirmatory factor analyses revealed four clearly interpretable crowd‐identification dimensions: Alternative, Urban, Conventional, and Achievement Oriented. Identification with the Alternative and Urban dimensions was found to be positively related to depression, delinquency, and aggression. With regard to the Urban dimension, also a positive association was found with anxiety. Identification with the Conventional‐ and Achievement Oriented dimensions was found to be negatively related to delinquency. A negative associations was also found between the Achievement Oriented dimension and aggression. Roughly the same pattern of associations was found for boys and girls, and younger and older adolescents. Our results generally confirm findings from studies relating adolescent crowd identification to adjustment performed in the United States and Australia.
Periodontal disease increases the risk of severe pre‐eclampsia among pregnant women
Authors: Canakci Varol , Canakci Cenk Fatih , Yildirim Abdulkadir , Ingec Metin , Eltas Abubekir , Erturk Ayşe
Published: June 2007

Aim: To evaluate the possible link between the severity of periodontal disease and pre‐eclampsia and to correlate this link to clinical periodontal parameters and interleukin (IL)‐1β, tumour necrosis factor‐α (TNF‐α), and prostaglandins (PGE2) levels in both gingival crevicular fluid (GCF) and serum.

Material and Methods: Fifty‐nine pregnant women (20 mild pre‐eclampsia, 18 severe pre‐eclampsia, and 21 healthy pregnant women) were included in the study. Dental and periodontal recordings as well as GCF and blood samples were obtained within 48 h preceding delivery.

Results: The results of multivariate logistic regression showed a highly significant association between mild to severe pre‐eclampsia and severe periodontal disease (p<0.001). After adjusting for potential confounders (smoking, body weight, socioeconomic status, education level, and age), severe pre‐eclamptic women were 3.78 (1.77–12.74) times more likely to present severe periodontal disease than normotensive pregnant women. This odds ratio (OR) was 2.43 (1.13–8.19) for mild pre‐eclamptic women. IL‐1β, TNF‐α, and PGE2 levels in both serum and GCF were also significantly higher in the pre‐eclamptic groups than the normotensive women.

Conclusions: These results indicate that the presence and severity of periodontal disease seems to increase the risk for not only the occurrence but also the severity of pre‐eclampsia in pregnant women.
QSAR Study on the Relaxant Agents from Some Mexican Medicinal Plants and Synthetic Related Organic Compounds
Authors: Ramírez‐Galicia Guillermo , Garduño‐Juarez Ramón , Hemmateenejad Bahram , Deeb Omar , Estrada‐Soto Samuel
Published: June 2007

Quantitative Structure–Activity Relationship studies were performed to describe and predict the antispasmodic activity of some molecules isolated from Mexican Medicinal Flora as well as for some synthetic ones based on stilbenoid bioisosteres. The relaxant activity of these molecules was taken from experiments on rat and guinea‐pig ileum tissues. Given that there is some evidence of species‐specific on the relaxant effects, two data sets were proposed, one for rat ileum and the other for guinea‐pig ileum. These data were statistically treated in order to find a Quantitative Structure–Activity Relationship model that could describe the corresponding biological models. The goodness of prediction for the best models was measured in terms of the Leave‐One‐Out Cross‐Validation R2 (LOO q2) and the correlation coefficients of regressions through the origin (RTO R20). Results show that papaverine activity could not be used as reference in rat ileum tests; however, this molecule can be used as a good reference molecule in guinea‐pig ileum tests. Our study shows that MATS5p and R8m+ descriptors are the most important descriptors in predicting the rat ileum activity and that atomic polarizability is the main atomic property. On the other hand, the R3u GETAWAY descriptor turns out to be important in predicting the guinea‐pig ileum activity where the influence/distance of substituents on these molecules could describe the observed activity.
A First Course in Mind, Brain, and Education
Authors: Blake Peter R. , Gardner Howard
Published: June 2007

ABSTRACT— We describe what may well be the first course devoted explicitly to the topic of Mind, Brain, and Education (MBE). In the course, students examine four central topics (literacy, numeracy, emotion/motivation, and conceptual change) through the perspectives of psychology, neuroscience, genetics, and education. We describe the pedagogical tools we use to develop the skills critical for synthesizing information across the disciplines associated with MBE.
Determination of Major/ Minor and Trace Elements in Seamount Phosphorite by XRF Spectrometry
Authors: Wang Xiaohong , Li Guohui , Zhang Qin , Wang Yimin
Published: June 2007

In this paper, a method developed to determine the major, minor and trace elements, including carbon and the four halogens, in seamount phosphorite involving a modern XRF spectrometry technique is described. Ultra‐fine (99% v/v < 40 μm) powder samples (4 g) were directly pressed into pellets (Φ= 30 mm). For elements having an analytical line lower in energy than the energy of Fe Kα line absorption edge, the inter‐element absorption‐enhancement effects were corrected using an influence coefficient method. For the other elements, the matrix effects were corrected using the ratio of element peak to Rh Kα Compton peak (for I, Rh K|3 Compton peak was used instead). The relative standard deviation was smaller than 1.0% for the major elements (except C, Na and Cl). The detection limit levels of C, F, Cl, Br and I were 30, 20, 0.8, 0.2 and 0.3 (μg g−1 respectively for 100 s count time of background. The accuracy of this method was tested by evaluating determinations on three certified reference materials. The direct analysis of major and minor elements in geological materials by pressed pellet without any chemical procedures makes XRF spectrometry a particularly environment‐friendly analytical technique.
Multi‐Element Reference Samples of Black Shale
Authors: Petrov Lev L. , Kornakov Yuri N. , Korotaeva Irina la. , Anchutina Elena A. , Persikova Luidmila A. , Susloparova Vera E. , Fedorova Irina N. , Shibanov Viktor A.
Published: June 2007

This paper describes the creation of two new reference samples of black shale, SCHS‐1 and SLg‐1, collected in the Bodaibo Region of Irkutsk District (Siberia, Russia). These samples have been developed as State Standard Samples to meet the requirements of Russia's Normative Documents, so that they can be recognised by the Russian State Certification Agency and included on the State Register of certified reference materials. SCHS‐1 was produced from shale of the Khomolkho suite; SLg‐1 represents the average composition of the Sukhoy Log gold deposit (within Au mineralisation). The homogeneity was assessed by applying the concept of potential inhomogeneity, and the inhomogeneity uncertainties (σinhom) for the indicator elements that were estimated experimentally by silicate XRF analysis. It was found that a majority of the indicator elements was characterised by σinhom/Δp < 1/8 (Δp is the permissible certification uncertainty), and so σinhom was neglected for the indicator elements and all other elements that were included in their respective group. The value of σinhom calculated for Fe (σinhom,Fe/Δp > 1 /8) was taken into consideration for the noble metals and their associated elements (e.g., Ag, As, Au, etc.). More than fifty laboratories (thirty‐seven from Russia) were involved in the interlaboratory experiment (ILE) to analyse these reference samples. The data obtained from the ILE allowed SCHS‐1 and SLg‐1 to be certified for, fifty‐one and forty‐three elements, respectively, as State Standard Samples.
Investigations into the Preparation of Ultra‐Fine Particle Size Geochemical Reference Materials
Authors: Wang Yimin , Gao Yushu , Wang Xiaohong , Wu Shuqi , Gu Tiexin
Published: June 2007

Although over recent years, sensitivity and precision of modern analytical techniques have continuously improved, traditional analytical specification for the particle size of samples has remained at 74 μm (‐200 mesh). For this reason, the uncertainty caused by inhomogeneity in test portions of the sample itself has become a more and more significant contribution to the total analytical uncertainty. Therefore, to reduce this total uncertainty, the first step is to improve the homogeneity by reducing the particle size of a sample. For this purpose, we have investigated a method for the preparation of ultra‐fine reference materials. Using the modern ultra‐fine crushing technique (jet mill), six marine sediment samples MSAn and MSCS‐1 to 5 were prepared and the particle distributions of these samples were measured using a laser particle‐analyser. The average particle size of these samples was 4–5 (im and the largest particle size was less than 30 (im. MSAn will be used as the sample for a future GeoPT(tm) proficiency testing round and MSCS‐1 to 5 will be prepared as reference materials. All geochemical laboratories are welcome to participate in this co‐operative research programme. The processing and use of ultra‐fine samples (< 30 μm) will have a significant influence on the future development of geoanalytical techniques as a consequence of the potential reduction in the mass of test portion and the development of new geoanalytical systems.
A Reflection on Mg, Cd, Ca, Li and Si Isotopic Measurements and Related Reference Materials
Authors: Carignan Jean , Cardinal Damien , Eisenhauer Anton , Galy Albert , Rehkamper Mark , Wombacher Frank , Vigier Nathalie
Published: June 2007

This contribution aims to report the reflections we had with the scientific community during two international workshops on reference materials for stable isotopes in Davos (2002) and Nice (2003). After evaluating the isotopic homogeneity of some existing reference materials, based on either certificates, literature data or specific inter‐laboratory rounds, we confirm these as primary reference materials or propose new ones relative to which stable isotope compositions should be reported. We propose DSM‐3 for Mg, NIST SRM 915a for Ca, L‐SVEC for Li and NBS28 for Si. Cadmium does not yet have a well identified delta zero material, although three commercial mono‐elemental Cd solutions have yielded the same isotopic composition relative to one another. In order to scale the linearity of any mass spectrometer, some secondary reference materials are also proposed: Cambridge‐1 solution for Mg, the “Münster‐Cd” and JEPPIM Cd solutions for Cd and the “Big Batch” silicate for Si. The team from Nancy propose to prepare a mixed spike solution for Li isotopes. Well‐characterised natural samples such as ocean or continental waters, diatoms, sponges, rocks and minerals are needed to validate the entire analytical procedure, particularly to take into account the effect of sample mineralisation and of chemical manipulations for elemental separation prior to analysis.
Accurate and High‐Precision Measurement of Lithium Isotopes in Two Reference Materials by MC‐ICP‐MS
Authors: Millot Romain , Guerrot Catherine , Vigier Nathalie
Published: June 2007

We report here a newly developed method for measurement of Li isotopes by use of multi‐collector ICP‐MS (Neptune) allowing rapid and high precision determination of Li isotope ratios at low levels of lithium (15–20 ng). The lithium reference sample solution IRMM‐016 was analysed over a period of ten months with an external reproducibility of 0.24% (2s, n = 52). Chemical separation of Li from matrix was performed on the seawater sample IRMM BCR‐403, for which a mean δ7Li value of + 31.0 ± 0.1 % (2s/√n, n = 31) was obtained. This mean value is in good agreement with those previously published for other seawater samples. BCR‐403 seawater being readily available, we propose that this seawater sample be used as a reference sample for Li isotope measurements.