bluuebunny/crossref_metadata_2025 huggingface dataset:
An experimental study on the effects of salamander larvae on isopods in stream pools
Authors: HUANG CHIFU , SIH ANDREW
Published: May 2006

SUMMARY 1. We used a combination of field surveys and field and laboratory experiments to examine the effects of predatory small‐mouthed salamander larvae, Ambystoma barbouri (Kraus and Petranka), on the density and microhabitat use of benthic isopods, Lirceus fontinalis (Rafinesque).

2. A survey of four field stations yielded a significant negative relationship between the densities of salamander larvae and isopods.

3. A field experimental manipulation of salamander density confirmed that salamanders reduce isopod density and isopod use of open micro‐habitat. Salamanders did not significantly affect the mean or coefficient of variation in isopod size.

4. A laboratory experiment showed that in the absence of refuges for isopods, salamanders were capable of eating large numbers of isopods; small isopods were particularly vulnerable to salamander predation.
Predicting the growth of age‐0 yellow perch populations from measures of whole‐lake productivity
Authors: ABBEY D.H. , MACKAY W.C.
Published: May 2006

SUMMARY.
1. The relationship was examined between four measures of lake productivity [total phosphorus (TP) and chlorophyll a (Chl a) concentrations, zooplankton density and biomass] and growth in length and weight of age‐0 yellow perch in ten central Alberta lakes.

2. In these lakes, average summer TP and Chl a levels were in the range 11–51 and 1.4–19.5 μg1−1, respectively. The interaction of TP and Chl a could explain 61% and 57% of the variance in total length and wet weight, respectively, of age‐0 yellow perch sampled at the end of August.

3. The ability to predict first year fish growth from lake productivity is strongest at low levels of productivity (TP<35μgl−1). In the lakes studied, fish community structure is more complex at high levels of productivity (TP>35μg1−1), and more data on complex community level interactions seem necessary to predict fish growth in these systems.
Morphological responses of Daphnia ambigua to different concentrations of a chemical extract from Chaoborus flavicans
Authors: HANAZATO TAKAYUKI , OOI TAKASHI
Published: May 2006

1. Daphnia ambigua were reared individually with eight different concentrations of a chemical extract from larvae of Chaohorus flavicans, and the frequency of appearance of helmeted individuals and the helmet sizes were determined in the instars 1–6.

2. The animals developed most marked helmets in the second instar in response to the extract. The frequency of the helmeted individuals and helmet size in the second instar increased with increasing chemical concentration, although their dose‐response curves differed between them.

3. The results may explain the cyclomorphosis of Daphnia, which develop the highest helmets in summer, when the predators are abundant and active, and the concentrations of the predator‐released chemicals would presumably be high.

4. The extract became toxic to Daphnia at the highest concentration prepared.
Long‐term patterns of invertebrate stream drift in an Australian temperate stream
Authors: SCHREIBER E.S.G.
Published: May 2006

1. Invertebrate stream drift was sampled bimonthly in the Acheron River, Victoria, Australia, over a period of 18 months. Replicated hourly samples were collected over a 25‐h period on each sampling date. A total of 194 taxa were identified in the drift. However, total drift density was dominated by few taxa.

2. Some evidence was obtained for a seasonal pattern in drift: this was most pronounced in relative abundances of individual taxa and the composition of the drift, rather than in total drift densities. Most of the commonly collected taxa reflected the seasonal pattern of total drift. However, some of the common taxa did not.

3. A small number of taxa showed behavioral drift, with a nocturnal increase in drift densities. One species of ‘Baetis’ drifted in high densities over short periods of time around dusk and dawn. It did not drift in higher densities during the night than during the day. The results emphasize the need for drift studies to be more rigorously designed than is typically the case.
Benthic insects in Swedish lake‐outlet streams: patterns in species richness and assemblage structure
Authors: MALMQVIST BJÖRN , ERIKSSON ÅSA
Published: May 2006

1. We studied how species richness of three hierarchical insect species groups, namely all benthic, lotic and filtering taxa, were related to a number of environmental variables in a data set from fifteen Swedish lake outlets.

2. In partial least‐squares analyses, we found that size‐related factors (stream width, discharge) and velocity‐related factors (current velocity, substratum particle size) were positively associated, and productivity‐related factors (chlorophyll a, seston energy, conductivity) negatively associated, with the species richness of the three groups.

3. The weak and negative relationship of richness with productivity largely negated theoretical predictions, whereas the species‐environment results corroborated earlier findings from running water systems.

4. The most important factors associated with the species composition of the lake outlets studied included pH, lake area, discharge, channel width and detritus.

5. Of the filter feeders, most species of blackflies (Diptera: Simuliidae) showed a negative relationship with pH.

6. A nested subset analysis demonstrated that species‐poor sites did not have a subset of species found at more species‐rich sites in any of the three hierarchical groups.
Role of PI3‐kinase/Akt signalling pathway in renal function and cell proliferation after renal ischaemia/reperfusion injury in mice
Authors: XIE LIPING , ZHENG XIANGYI , QIN JIE , CHEN ZHAODIAN , JIN YONGFENG , DING WEI
Published: May 2006

Background:  PI3K/Akt pathway has been shown to play a critical role in the regulation of mitogenic signalling, apoptosis, cell proliferation and survival in a variety of cells and tissues. The aim of the present study was to investigate the role of PI3K/Akt pathway in the renal ischaemia/reperfusion.

Methods:  Four experimental groups, sham‐operative mice, vehicle‐delivered and wortmannin‐treated ischaemic/reperfusion injury mice, wortmannin‐treated normal mice were designed to examined serum blood urea nitrogen level, renal injury, proliferating cell nuclear antigen protein and Akt phosphorylation status at 30 min, 90 min, 24 h, 48 h of reperfusion after ischaemic treatment. Wortmannin or its vehicle was given intraperitoneally at 4 h before surgery. Blood urea nitrogen was measured, and immunohistochemistry and western blotting were used to detect the components of PI3K/Akt pathway in the ischaemic/reperfusion injury kidney.

Results:  PI3‐kinase inhibitor wortmannin imposes a deleterious effect on serum blood urea nitrogen level, renal function after renal ischaemia/reperfusion injury in mice. The renal cell proliferation increased after ischaemia/reperfusion injury in mouse, which could be inhibited by wortmannin. Phosphorylation of Akt was increased after ischaemia/reperfusion in the mouse kidney, and reduced by wortmannin administration.

Conclusion:  This primary study suggests that PI3‐kinase/Akt signalling pathway play an important role in the regulation of the renal repair after ischaemia/reperfusion injury.
The study of Western European cabinets
Authors: BLONDEL JEAN , THIEBAULT JEAN‐LOUIS
Published: May 2006

Abstract. We are still relatively unfamiliar with the structures and modes of behaviour of Western European cabinets and we need first to identify the range of the differences which exist with respect to two major dimensions along which cabinet governments can be located (collective v. hierarchical decision‐making and political representation v. administrative and/or specialist skills). A valuable test can be obtained by considering in detail the cases of a number of countries in which the traditions of cabinet government are known to be different from those of the British model, both because of the existence of coalitions and because of specific traditions of ‘administrative’ and even ‘bureaucratic’ government. Marked variations emerge with respect to four elements: ministerial expertise, the large autonomy of ministers, the authority of the prime minister or chancellor, and the relatively limited influence of the council of ministers as a deliberative body. Cabinet government is a flexible machinery which has given rise to a number of different models corresponding to different traditions and to different conditions in which the political system operates.
Sources of variation in working class formation
Authors: EAGLES MUNROE
Published: May 2006

Abstract. Using data from residents of three differentiated working class neighbourhoods in Sheffield, England, this study explores the relative plausibility of three analytical perspectives on the working class formation process (the ecological, sectoral, the socialization perspectives). Expectations drawn from each of these are used to account for observed variations among respondents on several measures of working class formation. The results of several tests provide some support for the ecological and (to a lesser extent) the sectoral perspectives. However, both seem to offer less satisfactory accounts of observed variations in class formation than the socialization perspective. Some suggestions for further research to build upon the findings presented here are offered.
Carl Schmitt and the contradictions of liberal democracy
Authors: BELLAMY RICHARD , BAEHR PETER
Published: May 2006

Abstract. This article examines the contradictions Schmitt holds to exist between liberalism and democracy. The authors first examine Schmitt's descriptions of liberalism and democracy. They then proceed to his analysis of the political domain, which provides the basis of his criticism of liberal democracy. Following an evaluation of his argument, they propose a democratic conception of liberalism which both draws on Schmitt's account of the political while defending the viability of the union of liberalism and democracy.
Evidence for Increased Oxidative Stress in Alcohol‐Dependent Patients Provided by Quantification of in Vivo Salicylate Hydroxylation Products
Authors: Thome Johannes , Zhang Jianjun , Davids Eugen , Foley Paul , Weijers Heinz‐Gerd , Wiesbeck Gerhard A. , Böning Jobst , Riederer Peter , Gerlach Manfred
Published: May 2006

The hypothesis of increased oxidative stress in alcohol‐dependent patients postulates that altered free radical metabolism is involved in the various symptoms associated with this disease, including brain atrophy, peripheral polyneuropathy, alcoholic liver fibrinogenesis, and cancer. Using an in vivo assay for quantitation of hydroxyl radical (.OH) levels in peripheral blood, we detected increased values in patients suffering from alcohol dependence when compared with non‐dependent control persons. The assay used in this study involves the injection of acetylsalicylic acid, which is metabolized in vivo by direct reaction with OH to 2,3‐dihydroxybenzoic acid (DHBA). The time curve for the concentration of the reaction product (2,3‐DHBA), determined by high‐performance liquid chromatography, thus estimates the OH radical level in the peripheral blood of individuals undergoing this test. For the first time, we used the intravenous application of acetylsalicylic acid to avoid artifacts arising from differences in gastrointestinal resorption, known to be disturbed in alcoholism. The areas under the 2,3‐DHBA time curves differed significantly (p < 0.05) between patients and controls (0.54 ± 0.27 vs. 0.36 ± 0.19 μM.h). This study presents further evidence for alterations in radical metabolism in vivo in patients suffering from alcohol dependence. The assay can also be used in further studies dealing with antioxidative treatment (radical scavengers) to evaluate the effectiveness of such therapy.
Cortical and Subcortical White Matter Damage without Wernicke's Encephalopathy after Recovery from Thiamine Deficiency in the Rat
Authors: Langlais Philip J. , Zhang Shu‐Xing
Published: May 2006

The relative etiologic roles of ethanol and thiamine deficiency in the cortical atrophy and loss of cerebral white matter in chronic alcoholics are uncertain. The present study examined the distribution of degenerating axons within cortical and subcortical tracts 1 week after recovery from early to late symptomatic stages of thiamine deficiency in the absence of ethanol in Sprague‐Dawley rats. The brains of rats exposed to an early symptomatic stage of pyrithiamine‐induced thiamine deficiency, 12–13 days of treatment, contained degenerating axons in corpus callosum, anterior commissure, external and internal capsules, optic and olfactory tracts, and fomix and mammillothalamic tracts. A dense pattern of degenerating axons was evident in layers Ill‐IV of frontal and parietal cortex. Less intense and more evenly distributed degenerating axons were present in layers IV‐VI of frontal, parietal, cingulate, temporal, retrosplenial, occipital, and granular insular cortex. Neuronal counts in mamrnillary body nuclei and areal measurements of the mammillary body were unchanged from controls and the thalamus was relatively undamaged. In animals reversed at later and more advanced symptomatic stages of thiamine deficiency, 14–15 days of treatment, degenerating axons were found in other cortical regions and hippocampus and there was extensive neuronal loss and gliosis within mammillary body and medial thalamus. These results demonstrate that a single episode of thiamine deficiency can selectively damage cortical white matter tracts while sparing the thalamus and mammillary body and may be a critical factor responsible for the pathological and behavioral changes observed in alcoholics without Wernicke's encephalopathy.
Carbohydrate‐Deficient Transferrin as a Marker of Alcohol Consumption in Male Patients with Liver Disease
Authors: Rubio Mireia , Caballería Joan , Deulofeu Ramón , Caballería Llorenç , Gassó Marta , Parés Albert , Vilella Angels , Giménez América , Ballesta Antonio , Rodés Joan
Published: May 2006

Carbohydrate‐deficient transferrin (CDT) has been proposed as a marker of alcohol abuse. However, its value in patients with associated liver disease is still controversial. The aim of the study was to investigate the usefulness of CDT as a marker of alcohol consumption in patients with liver disease. We measured serum levels of CDT and those of commonly used hematological and biochemical markers, mean corpuscular volume (MCV), transaminases (AST and ALT), and γ‐glutamyltransferase in 179 male subjects divided into four groups: 45 active drinkers (13 with normal liver, 21 with fibrosteatosis, and 11 with liver cirrhosis), 45 abstinent chronic alcoholics (18 with and 27 without liver disease), 58 patients with nonalcoholic liver disease, and 31 healthy controls. Serum CDT in active alcoholics was 37.5 ± 3.6 units/liter, being significantly higher than that of abstinent alcoholics (20.3 ± 1.5 units/liter), patients with nonalcoholic liver disease (18.1 ± 1.1 units/liter), and controls (13.1 ± 0.8 units/liter). Contrary to the other markers, no significant differences were observed in CDT values in relation with the presence and severity of liver disease in either the active drinkers or in the abstinent alcoholics. The sensitivity and specificity of CDT as a marker of alcoholism in the series as a whole was 64% and 82%, respectively, similar to the best conventional marker, MCV (64 and 82%). In patients with liver disease, CDT maintained good sensitivity (72%) and specificity (83%). Receiver operating characteristic analysis confirmed that CDT had a similar diagnostic value to that of MCV, but better than γ‐glutamyltransferase and transaminases for the detection of alcohol abusers. The good diagnostic efficacy of CDT remained unchanged when analyzing only patients with liver disease. We conclude that serum CDT is a good marker of alcoholism and is less influenced than the currently used biochemical markers for associated liver disease. Thus, CDT is an effective laboratory test to detect alcohol abuse regardless of the presence of alcoholic liver disease.
Cost and Usage Impacts of Treatment Initiation: A Comparison of Alcoholism and Drug Abuse Treatments
Authors: Goodman Allen C. , Nishiura Eleanor , Humphreys R. Scott
Published: May 2006

An extensive literature on substance abuse and mental health treatments suggests that they often lead to decreased usage and/or spending on other medical treatments. We compare alcohol and drug abuse treatment costs with a model that decomposes total treatment costs into amount of treatment (outpatient visits or inpatient days) and costs per treatment. The analysis compares alcohol and drug abuse treatment costs regarding: (1) the incremental costs attributable to changed short‐term substance abuse and nonsubstance abuse treatments; (2) the impacts of current substance abuse treatments on short‐term nonsubstance abuse, long‐term substance abuse, and long‐term nonsubstance abuse treatments; and (3) the difference in inpatient and outpatient impacts. Our findings indicate that alcoholism and drug abuse treatment initiation have similar impacts on coincident and subsequent utilization and costs. For both treatments, the largest portions of the cost impacts occur for inpatient treatments, and for treatments that occur within 6 months of the initiation. The similarity of results suggests that it may often be reasonable to infer utilization and cost impacts for one type of care from studies that examine the other.
Activation of Arachidonic Acid‐Specific Phospholipase A2 in Human Neuroblastoma Cells after Chronic Alcohol Exposure: Prevention by GM1 Ganglioside
Authors: Basavarajappa Balapal S. , Saito Mitsuo , Cooper Thomas B. , Hungund Basalingappa L
Published: May 2006

Human neuroblastoma cells were exposed to ethanol (EtOH; 100 mM) in culture for various time periods. It was found that chronic EtOH exposure increased the arachidonyl‐specific phospholipase A2 (PLA2) activity significantly in both cytosol (1.6‐fold) and membrane (2.2‐fold) fractions when 1‐palmitoyl‐2‐arachidonyl‐sn‐glycero‐3‐phosphocholine was used as a substrate. This arachidonyl‐specific PLA2 activity progressively increased with increasing duration of EtOH exposure and reached peak level at 72‐hr EtOH exposure (chronic). A significant amount of the PLA2 activity was associated with the membrane fraction. No significant difference in PLA2 activity was observed when 1‐palmitoyl‐2 oleoyl or linoleoyl‐sn‐glycero‐3‐phosphocholine was used as a substrate. It was also found that co‐treatment of neuroblastoma cells with ganglioside GM1 reduced the EtOH‐induced activation of arachidonyl‐specific PLA2 activity. The present results indicate that arachidonic acid‐specific PLA2 may play a role in adaptation mechanism to chronic EtOH in cultured neuroblastoma cells. Ganglioside GM1, in part, may exert its neuroprotective effects by modulating arachidonyl‐specific PLA2 activity in chronic EtOH‐exposed neuroblastoma cells.
Violence, Suicidality, and Alcohol/Drug Use Involvement in Adolescent Females with a Psychoactive Substance Use Disorder and Controls
Authors: Mezzich Ada C. , Giancola Peter R. , Tarter Ralph E. , Lu Sandy , Parks Susan M. , Barrett Cristin M.
Published: May 2006

This study had three aims: (1) to determine the relations between behavioral dysregulation, negative affectivity, and familial impairment with violence and suicidality (i.e., severity of ideation and attempts) in a sample of adolescent females with a psychoactive substance use disorder and controls; (2) to determine whether these relations are mediated by internalizing (depression/anxiety) and externalizing (nonviolent antisocial behavior) symptomatology; and (3) to determine whether severity of alcohol/drug use involvement moderates the relations between the mediating variables with violence and suicidality. Multiple behavioral, psychiatric interview, and self‐report measures were used to index behavioral dysregulation, negative affectivity, familial impairment, internalizing and externalizing symptomatology, and violence and suicidality in one hundred sixty‐one 14‐ to 18‐year‐old adolescent females with a psychoactive substance use disorder and in 80 controls. Structural equation modeling was used to determine the proposed relations. Results indicated that behavioral dysregulation, negative affectivity, and familial impairment were related to violence, whereas only familial impairment was related to suicidality. Internalizing symptomatology mediated the relation between familial impairment and suicidality, and was related to violence, whereas externalizing symptomatology mediated the relations between behavioral dysregulation, negative affectivity, and familial impairment with violence. Severity of alcohol/drug use involvement did not moderate the relations between internalizing or externalizing symptomatology with suicidality or violence. Nevertheless, the relation between internalizing symptomatology and suicidality was stronger in females with a greater degree of alcohol/drug use involvement, compared with those with a milder degree of involvement Therefore, from a prevention standpoint, behavioral dysregulation, negative affectivity, familial impairment, as well as internalizing and externalizing symptoms, may serve as clinical „points of intervention” for altering the development of violence and suicidality in high risk and substance abusing youth.
Fetal Alcohol Exposure and Temporal Vulnerability: Regional Differences in Alcohol‐Induced Microencephaly as a Function of the Timing of Binge‐Like Alcohol Exposure During Rat Brain Development
Authors: Maier Susan E. , Chen Wei‐Jung A. , Miller Jennifer A. , West James R.
Published: May 2006

In humans, microcephaly (small head for body size) is a common feature of fetal alcohol syndrome. An analogous measure, termed microencephaly (small brain for body size), can be used for evaluating the detrimental effects of the differential timing of alcohol exposure on brain development in animal model systems. Timed‐pregnant rats were exposed to binge‐like alcohol during either the first 10 days (first trimester equivalent) or second 10 days of gestation (second trimester equivalent), or the combination of first and second trimesters equivalent for prenatal treatments. Offspring from some of the animals exposed to alcohol during the combined first and second trimesters equivalent were raised artificially from postnatal day (P) 4 through P9 (part of the third trimester equivalent), and also received binge‐like alcohol during this period, producing animals that were exposed to alcohol during all three trimesters equivalent. Offspring from untreated dams were also raised artificially and received alcohol only from P4 to P9, thus creating animals that were exposed to alcohol only during part of the third trimester equivalent. All pups were perfused on P10. Appropriate controls (nutritional and normally reared) were used for every alcohol treatment combination. Peak blood alcohol concentrations were not different among the treatment groups for a given sampling time. Significant somatic growth deficits occurred in offspring exposed to alcohol for the equivalent of all three trimesters, compared with offspring exposed to alcohol during other periods. Brain growth in offspring also was significantly affected by the timing of alcohol exposure. The whole brain, forebrain, and cerebellum to body weight ratios of pups exposed to alcohol during the third trimester had more significant brain growth deficits than pups in groups exposed to alcohol during other times of brain development. Although alcohol exposure during the third trimester had a significant detrimental impact on overall brain growth, significant differences in temporal vulnerability were also found for the brainstem to body weight ratios. Offspring of dams exposed to alcohol during the first trimester had the same magnitude of deficit as those exposed to alcohol during the third trimester, and those two groups were significantly deficient compared with the groups exposed to alcohol at other times, suggesting some differential vulnerability of this region to alcohol‐induced injury at different times of development. This study is the first thorough examination of microencephaly and gross regional vulnerability of the developing brain as related to temporal factors of alcohol exposure in an animal
Ethanol Effects on Cultured Embryonic Hippocampal Neuronal Calcium Homeostasis Are Altered by Nerve Growth Factor
Authors: Webb B. , Heaton M. B. , Walker D. W.
Published: May 2006

The neurotoxic effect of acute ethanol treatment (AET) may lead to an alteration in the regulation of calcium (Ca2+) homeostasis in hippocampal neurons. Ca2+ homeostasis could be affected by AET when neurons are at rest or after depolarizing activity during synaptic transmission. It has been shown that nerve growth factor (NGF) can ameloriate some types of neurotoxicity by stabilizing Ca2+ homeostasis. Previously, we observed that ethanol (EtOH) changed unstimulated (basal) and potassium (K+)‐stimulated intracellular calcium ([Ca2+]i) in embryonic septohippocampal neurons (Webb et al., Brain Res. 729:176‐189,1996). The purpose of the present study is to determine the effects of NGF and EtOH on neuronal Ca2+ homeostasis in cultured embryonic hippocampal neurons. The hypotheses tested were the following: EtOH alters Ca2+ homeostasis in hippocampal neurons; NGF modulates Ca2+ homeostasis in hippocampal neurons; and NGF treatment alters the effect of EtOH on [Ca2+]1, in hippocampal neurons. Our results indicated that hippocampal neuronal cultures treated with EtOH had lower basal [Ca2+]1 than untreated neurons. EtOH decreased K+‐stimulated (30 mM KCl) changes in [Ca2+]1 in a dose‐dependent manner. During K+ stimulation, 20 ng/ml of NGF slowed and reduced the increase in [Ca2+]1. Hippocampal neurons treated with NGF increased or did not change basal [Ca2+]1 and did not change or increase K+‐stimulated [Ca2+], in response to EtOH. These responses were dose‐related and indicated that NGF could alter the response of hippocampal neurons to EtOH. In conclusion, AET results in the alteration of Ca2+ homeostasis in unstimulated and depolarized cultured embryonic hippocampal neurons. NGF and EtOH independently and collectively affected the regulation of Ca2+ homeostasis in this neuronal population. Changes in [Ca2+]1 can disrupt normal cellular function and contribute to cell death. Therefore, alteration of Ca2+ homeostasis may be an underlying mechanism involved in EtOH toxicity. NGF may ameliorate the toxic effects of EtOH by regulating Ca2+ homeostasis.
Organotypic Brain Slice Cultures for Functional Analysis of Alcohol‐Related Disorders: Novel Versus Conventional Preparations
Authors: Thomas Mark P. , Davis Margaret I. , Monaghan Daniel T. , Morrisett Richard A.
Published: May 2006

Assessment of long‐term alterations in neural function and phenotype has usually involved culture techniques that utilize dissociated preparations. Recently, we have approached such topics in alcohol research by using brain slice cultures, also known as explant or organotypic preparations. In this symposium presentation, two preparations will be discussed, and examples of the particular advantages of these preparations will be presented in relation to alcohol research. First, we use the hippocampal explant preparation for assessment of long‐term alterations in N‐methyl‐D‐aspartate receptor (NMDAR) function due to chronic ethanol exposure and subsequent withdrawal. This preparation displays many synaptic, structural, and enzymatic phenotypes indicative of normal neural preparations. Patch clamp recordings reveal NMDAR‐mediated excitatory postsynaptic current (EPSC) elicited upon stimulation of Schaffer collateral fibers and recorded from CA1 pyramidal cells. Long‐term ethanol exposure followed by subsequent withdrawal resulted in a specific enhancement of NMDAR‐mediated synaptic responses which preceded the expression of epileptiform events that occurred after prolonged withdrawal periods. Second, we describe a novel explant preparation, derived from horizontal slices of the entire forebrain and midbrain of the rat. These long‐term explants displayed multiple normal phenotypes including Nissl, AChE, TH, and GFAP staining. Electrophysiologically, these explants displayed a functional corticostriatal pathway recorded with field and patch clamp techniques and elicited by synaptic stimulation. Taken together, these explant preparations display utility for long‐term study of ethanol effects on neural systems, especially relating to withdrawal hyperexcitability as well as systems involved in drug‐seeking behavior.
Optical Monitoring of Living Brain Tissue
Authors: Hosokawa T. , Ohta M. , Koyama A. , Saito K. , Fine A.
Published: May 2006

Optical methods can usefully augment classical techniques such as electrical recording for investigating cellular and network physiology. Here, recent developments in optical methods–including confocal and nonlinear fluorescence imaging, semiconductor array imaging, and improved fluorescent indicators of ion concentration and transmembrane electrical potential–are briefly reviewed, and examples are offered that may suggest potential applications to experimental studies in alcoholism research.
Adenoviral‐Mediated Interferon‐γ Gene Therapy Augments Pulmonary Host Defense of Ethanol‐Treated Rats
Authors: Kolls Jay K. , Lei Dinghua , Stoltz David , Zhang Ping , Schwarzenberger Paul O. , Ye Peng , Bagby Greg , Summer Warren R. , Shellito Judd E. , Nelson Steve
Published: May 2006

Alcohol has long been recognized as an immunosuppressive drug and a risk factor for a spectrum of infectious diseases. Among these infections, bacterial pneumonias are most closely correlated with alcohol abuse. One potential mechanism of ethanol‐induced immunosuppression is through its ability to suppress alveolar macrophage production of tumor necrosis factor (TNF‐α). This defect can be reversed by priming macrophages with interferon‐γ (IFN‐γ). We hypothesized that macrophage priming in vivo in a model of acute ethanol intoxication could augment pulmonary host defenses. To test this hypothesis, we used adenoviral‐mediated gene transfer of the IFN‐γ gene. This strategy resulted in prolonged expression of IFN‐γ in vivo. Moreover, in a model of acute ethanol intoxication, this vector significantly enhanced lipopolysaccharide‐induced TNF‐α responses and lung polymorphonuclear leukocyte recruitment. Furthermore, pulmonary host defenses againstKlebsiella pneumoniaewere were significantly augmented. These enhanced host defenses were not reversed with pretreatment with a polyclonal anti‐TNF‐α antibody, suggesting that IFN‐γ's effect was through a non‐TNF‐α‐dependent mechanism. These data demonstrate that ethanol‐induced suppression of pulmonary host defenses can be reversed with IFN‐γ gene therapy.
Effects of Ethanol on Recombinant Glycine Receptors Expressed in Mammalian Cell Lines
Authors: Valenzuela C. Fernando , Cardoso Rita A. , Wick Marilee J. , Weiner Jeff L. , Dunwiddie Thomas V. , Harris R. Adron
Published: May 2006

We examined the effects of acute ethanol exposure on recombinant human glycine receptors transiently transfected into HEK 293 cells and stably transfected into Ltk− fibroblast‐like cells. In our study of the effects of ethanol, we used the whole‐cell patch‐clamp configuration. Relatively low concentrations of ethanol (25 mM and 50 mM) did not affect glycine‐gated currents in any of the cell lines studied. Higher concentrations of ethanol (100 mM and 200 mM) significantly potentiated glycine responses only in stably transfected Ltk− cells expressing α1 and α2 subunits and in HEK 293 cells transiently expressing α2 subunits. Cells stably expressing α1 versus α2 glycine receptors were modulated equally by ethanol. Both glycine α1 and glycine α1β receptors transiently expressed in HEK 293 cells were insensitive to all concentrations of ethanol tested; however, there was a trend toward potentiation at 100 and 200 mM ethanol concentrations. A population of cells (41–87%) that was sensitive to the potentiating effects of 100 and 200 mM ethanol (defined as more than 10% potentiation) was identified in both cell lines tested. In these sensitive cells, ethanol (100 and 200 mM) produced significant potentiation, independent of the cell line and the glycine receptor sub‐unit tested. Together with published results from studies with Xenopus oocytes, these data indicate that the sensitivity of recombinant glycine receptors to ethanol depends upon the expression system.
Reversal of Ethanol‐Induced Testosterone Suppression in Peripubertal Male Rats by Opiate Blockade
Authors: Emanuele M. A. , LaPaglia N. , Steiner J. , Jabamoni K. , Hansen M. , Kirsteins L. , Emanuele N. V.
Published: May 2006

Teenage drinking is a major problem in the United States, as well as abroad. Besides psychosocial implications, ethanol (EtOH) has detrimental effects on the reproductive system. Clinical problems associated with reduced reproductive hormones include osteoporosis, decreased muscle function, anemia, altered immune function, prostate involution, and decreased reproductive abilities. Education coupled with strategies aimed at preventing these deleterious consequences even in the face of continued EtOH intake is extremely important. We have tested the possibility that naltrexone, a drug currently used in patients to decrease alcohol craving, might also prevent the fall in the male hormone, testosterone, caused by EtOH exposure. Rats aged 35 days old (prepubertal), 45 days old (midpubertal), and 55 days old (late pubertal) were injected (intraperitoneally) with either saline, EtOH, naltrexone, or EtOH plus nabexone. In the two older age groups, EtOH significantly suppressed testosterone, which was prevented by administration of naltrexone. In the youngest animals, there was no treatment effect presumably due to low basal levels of testosterone. EtOH similarly reduced luteinizing hormone (LH), but this suppression was not prevented by naltrexone. There was no consistent effect of any treatment on hypothalamic concentration of pro‐LH releasing hormone (RH) (LHRH), LHRH, or on steady‐state levels of LHRH mRNA. We conclude that, as animals progress through puberty, EtOH suppresses LH and testosterone. The testosterone decline can be prevented by opiate blockade with naltrexone, an effect primarily seen at gonadal level. Thus, naltrexone, a drug already used clinically to reduce EtOH intake, also has protective physiological effects on the endocrine system.
A Review: Acute and Chronic Effects of Ethanol and Alcoholic Beverages on the Pancreatic Exocrine Secretion In Vivo and In Vitro
Authors: Niebergall‐Roth E. , Harder H. , Singer M. V.
Published: May 2006

Whereas oral or intraduodenal ethanol causes a moderate stimulation of pancreatic bicahonate and enzyme output, intravenous ethanol inhibits basal and hormonally stimulated pancreatic exocrine secretion in humans, dogs, cats, pigs, rabbits, and rats. This inhibition could be mediated by inhibitory cholinergic mechanisms or be the result of a direct cellular effect of ethanol. In vitro investigations have specified several signaling molecules that may be involved in the action of ethanol on stimulus‐secretion coupling in the exocrine pancreas, including cyclic adenosine monophosphate, intracellular calcium, and cholecystokinin and somatostatin receptors. In difference to pure ethanol solutions and distilled spirits, beer strongly stimulates pancreatic enzyme output, probably by nonalcoholic fermentation products. During chronic alcoholism, the ethanol‐induced inhibition is replaced by an enhanced enzyme output that causes intraductal protein precipitation. In vitro investigations suggest that this increase is reversible after alcohol withdrawal. The occurrence of protein precipitates is considered to be a crucial step in the development of chronic alcoholic pancreatitis in humans. Other ethanol‐induced secretory alterations that may contribute to the development of alcoholic pancreatitis are a decreased secretion of trypsin inhibitor, an increased cholinergic tone, and changes in the concentration of lithostathine.
Polysomnographic and Subjective Sleep Predictors of Alcoholic Relapse
Authors: Brower Kirk J. , Aldrich Michael S. , Hall Janette M.
Published: May 2006

Previous studies indicate that subjectively reported and objectively measured sleep abnormalities at baseline can increase the risk of relapse in treated alcoholics. However, previous studies did not include both subjective and objective sleep measures in the same group of patients. We utilized polysomnography and the Sleep Disorders Questionnaire to determine if baseline polysomnography increased the ability to predict relapse beyond the prediction with subjective measures alone, after controlling for nonsleep variables that were associated with relapse. We followed 74 patients with a DSM‐III‐R diagnosis of alcohol dependence, of whom 36 relapsed to at least some drinking during an average follow‐up interval of 5 months. Univariate analyses revealed that relapsed patients did not differ from abstinent patients at baseline in demographics or psychiatric co‐morbidity, but they had more prior treatment episodes for alcoholism, more difficulty falling asleep, more complaints of abnormal sleep, and, on polysomnography, longer sleep latencies, shorter rapid eye movement sleep latencies, and less stage 4 sleep percentage than abstinent patients. With a series of logistic regression analyses, which controlled for age and gender, we demonstrated that sleep measures improved the prediction model compared with non‐sleep variables alone, and that polysomnography‐measured sleep latency was the most significant predictor variable. We conclude that subjective and objective measures of baseline sleep are predictors of relapse in treated alcoholic patients. These data also suggest that neurophysiological dysfunction contributes strongly to the etiology of relapse. Finally, sleep disturbance warrants clinical attention as a target of alcoholism treatment.
MOLECULAR BASIS FOR THE ROLE OF IRON IN EXPERIMENTAL ALCOHOLIC LIVER INJURY
Authors: Tsukamoto Hidekazu
Published: May 2006

The role of hepatic macrophage‐derived cytokines such as TNFα in the pathogenesis of ALD is plausible. However, the mechanism of TNFα upregulation is not well understood. Our studies to date offer a unique hypothesis that liver injury, induced by ethanol and a high‐fat diet in the intragastric infusion model, primes hepatic macrophages for NF‐κB activation and expression of TNFα, other cytokines, and chemokines, which are under the transcriptional regulation of this factor via enhanced heme turnover and nonheme iron storage by these cells.
Measuring Drinking Context
Authors: Knibbe Ronald
Published: May 2006

This paper is based on the session entitled “Measuring Drinking Context” that was held on May 12, 1997 at the International Workshop on Consumption Measures and Models for Use in Policy Development and Evaluation, Bethesda, MD. The session chair was Ronald Knibbe; presenters were Deborah Dawson, Tim Stockwell, Paul Gruenewald, and Eric Single; and discussants were Kathryn Graham, Thomas Greenfield, Thomas Harford, Michael Hilton, and Harold Holder.
Alcohol and Fetal Damage
Authors: Allebeck Peter , Olsen Jørn
Published: May 2006

Since the identification of fetal alcohol syndrome in the end of the 1960s, substantial evidence has accumulated on a number of adverse effects that alcohol consumption during pregnancy may have on the fetus. Long‐term effects on child development has also been observed. Although the various types of effects are well documented, less is known about threshold levels of consumption, under which there is no risk of damage. Few studies have assessed the risk associated with high episodic drinking. From a theoretical point of view, binge drinking in critical stages in organ formation may constitute a particularly high risk for adverse outcomes.
Chronic Ethanol Exposure Increases 3H‐GABA Release in Rat Hippocampus by Presynaptic Muscarinic Receptor Modulation
Authors: Hu Ming , Walker Don W. , Vickroy Thomas W. , Peris Joanna
Published: May 2006

Background: Chronic ethanol treatmcnt (CET) for 28 weeks significantly increases electrically‐stimulated 3H‐GABA release from hippocampal slices. This increase in GABA release may be one of the mechanisms by which CET decreases the magnitude of long‐term potentiation (LTP) in the hippocampus. The present study examined whether CET increases GABA release via an alteration in heterologous presynaptic cholinergic regulation.

Methods: Animals were treated with ethanol or sucrose diet for 28 weeks followed by either no withdrawal or a 48‐hr withdrawal period. The electrically‐stimulated 3H‐GABA release from preloaded superfused hippocampal slices of naive and CET rats was measured.

Results: Carbachol increased 3H‐GABA release in a concentration‐dependent manner, and atropine modulated 3H‐GABA release in a biphasic concentration‐dependent manner. Atropine (10 μM) significantly blocked the effects of carbachol. Oxotremorine, a selective muscarinic receptor agonist, also incrcased 3H‐GABA release. Mecamylamine, a selective nicotinic antagonist, did not modulate 3H‐GABA releasc and did not block the effects of carbachol. The effects of these agents were also tested in rats 0 or 48 hrs after withdrawal from CET. The biphasic effects of atropine were decreased, whereas the facilitating effects of carbachol were significantly incrcased. There were no changes in the effects of these agents on 3H‐acetylcholine release from hippocampal slices of CET rats compared to sucrose‐treated rats.

Conclusion

: These results suggest that presynaptic muscarinic receptors facilitate GABA release, whereas nicotinic receptors do not play a significant role in modulating GABA release in hippocampus. CET selectively alters presynaptic muscarinic regulation of GABA release in hippocampus and may help us to further understand the mechanism underlying the disruption of LTP by CET.
Relative Versus Absolute Carbohydrate‐Deficient Transferrin as a Marker of Alcohol Consumption in Patients With Acute Alcoholic Hepatitis
Authors: Halm Ulrich , Tannapfel Andrea , Mössner Joachim , Berr Frieder
Published: May 2006

Background: Carbohydrate‐deficient transferrin has been described as a sensitive and specific marker for alcohol consumption. This study investigated the usefulness of carbohydrate‐deficient transferrin as a marker of alcohol consumption in acute alcoholic hepatitis.

Methods: Absolute concentrations (U/l) and relative values (%) of carbohydrate‐deficient transferrin dctermined in serum with commercial assays, as well as conventional markers for alcohol consumption, were compared with the alcohol consumption (as estimated by a questionaire) in patients with acute alcoholic hepatitis (n= 19), alcoholic liver cirrhosis (n= 37), and nonalcoholic liver diseases (n= 16).

Results: The concentration of carbohydrate‐deficient transferrin was increased (p < 0.001) in nonabstaining paticnts (median intake 80 g alcohol/day) with alcoholic liver cirrhosis (45.7 ± 30 U/l), but not in patients with acute alcoholic hepatitis (20.0 ± 7.8 U/l) despite higher alcohol consumption (median 130 gid), nor in abstaincrs with alcoholic livcr cirrhosis (19.4 ± 6.0 U/l) or nonalcoholic liver disease (18.5 ± 6.7 U/l). However, the relative values of carbohydrate‐deficient transferrin were increased both in acute alcoholic hepatitis (7.9 ± 2.1%) and nonabstainers with alcoholic liver cirrhosis (7.4 ± 2.8%), but not in abstaincrs with alcoholic liver cirrhosis (4.6 ± 3.5%) or nonalcoholic liver disease (3.8 ± 0.9%) (p < 0.001). In acute alcoholic hepatitis, the sensitivity and specificity were only 32% and 87% for absolute concentrations, rcspcctively, but 79% and 97% for relative values of carbohydrate‐deficient transferrin. The concentrations of carhohydrate‐deficient and total transferrin in serum were strongly correlated (r= 0.60; p= 0.008).

Conclusions: The relative value (% of total), but not the absolute concentration, of carbohydrate‐deficient transferrin in serum is a useful marker of alcohol consumption in acute alcoholic hepatitis.
Ethanol‐Associated Olfactory Stimuli Reinstate Ethanol‐Seeking Behavior After Extinction and Modify Extracellular Dopamine Levels in the Nucleus Accumbens
Authors: Katner Simon N. , Weiss Friedbert
Published: May 2006

Background

: Alcohol craving or automatic behavioral responses provoked by alcohol‐related cues are thought to contribute to relapse risk in abstinent individuals. However, there is to date only limited direct experimental evidence that supports this hypothesis. The present study employed an operant response‐reinstatement model to examine the effects of ethanol‐associated environmental stimuli on alcohol‐seeking behavior and extracellular dopamine (DA) levels in the nucleus accumbens (NAcc).

Methods

: Male Wistar rats were prepared with intracerebral guide cannulae for microdialysis and trained to operantly self‐administer ethanol in the presence of discrete olfactoIy discriminative stimuli (SΔ's) signaling the availability of ethanol (10% wiv) versus a nonrewarding stimulus (a 50 μM quinine HCl solution). After the discrimination learning phase, responding for ethanol (and quinine) was extinguished by withholding the drinking solutions as well as the corresponding SΔ's. After reaching and maintaining an extinction criterion of ≤ 5 responsesisession, the rats were exposed noncontingently to the ethanol and nonrcward SΔ's but without the availability of ethanol or quinine.

Results

: The ethanol SΔ's, but not nonreward SΔ's, elicited significant recovery of responding. Exposure to the operant chamber during a 20 min “waiting period” before presentation of the SΔ's was associated with a small but significant increase in dialysate DA levels. Subsequent exposure to the ethanol SΔ and onset of the reinstatement session was accompanied by a small but significant decrease in DA efflux. Exposure to the nonreward SΔ did not alter DA levels.

Conclusions

: The behavioral data confirm that ethanol‐predictive discriminative stimuli reliably elicit ethanol‐seeking behavior after extinction. The increase in DA efflux during the waiting period confirms earlier findings and suggests that anticipation of access to ethanol activates mesolimbic DA neurons. The decrease in DA efflux after onset of the reinstatement session in animals that were presented with the ethanol SΔ's may reflect neurochemical events associated with the mismatch between the predicted (i.e., ethanol availability) and actual (i.e., absence of ethanol) stimulus events. This possibility is supported by the lack of changes in DA efflux in rats that were presented with the nonreward SΔ's, a test condition that did not involve such a mismatch. Overall, the findings provide further evidence for a role of conditioning processes in the control of alcohol‐seeking behavior and, by extension, support the hypothesis that conditioned responses to drug‐related stimuli may be an important factor in chronic alcohol abuse and relapse.