bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of the Estrogenic Activity of Phytoestrogens Isolated from Bourbon and Beer
Authors: Rosenblum E. R. , Stauber R. E. , Van Thiel D. H. , Campbell I. M. , Gavaler J. S.
Published: June 2007

Phytoestrogenic substances have previously been isolated and identified in two alcoholic beverages: bourbon and beer. To delineate the relative potencies of the estrogenic substances of plant origin thus far identified in these commonly consumed alcoholic beverages, we evaluated the ability of biochanin A, β‐sitosterol, genistein, and daidzein to bind to cytosolic estrogen receptor binding sites. The in vitro studies demonstrated that each of the contained substances was capable of effectively competing for cytosolic estrogen receptor binding sites of rat liver and uterus. Further, the two phytoestrogens constituents of bourbon, β‐sitosterol and biochanin A, were less potent than those present in beer. Given the high concentration of β‐sitosterol in bourbon, we chose to evaluate the estrogenicity of β‐sitosterol in vivo using ovariectomized rats. β‐sitosterol was administered either daily or intermittently at 3 doses, based on amounts previously determined to be present in bourbon. The in vivo studies demonstrated that β‐sitosterol is capable of producing a weak estrogenic effect only at the lowest dose (6.2 μg/dl) administered intermittently. These responses suggest that β‐sitosterol may be weakly estrogenic at low doses, but is unable to maintain such an effect at higher doses.
State‐Dependent Stimulus Control: Cueing Attributes of Ethanol “Hangover” in Rats
Authors: Gauvin David V. , Goulden Kevin L. , Holloway Frank A.
Published: June 2007

In Experiment 1, twelve Sprague‐Dawley rats were trained in a two‐choice food‐reinforced drug discrimination task (10‐min sessions) using the state‐dependent interoceptive stimulus attributes of ethan‐ol's (ETOH) delayed or rebound effects (EDE) versus “normal” basal homeostasis. Rats were injected with either 4 g/kg ETOH or equivalent volumes of saline (SAL) 18 hr before the sessions. Each rat was injected with an additional 1 ml/kg injection of SAL 15 min before the sessions. EDE training sessions were always followed by a “day off.” SAL sessions were conducted between36–96 hr after an EDE training session. Rats demonstrated>90% discriminative accuracy. Test sessions showed a time‐dependent, cyclic, return from the experimental “hangover” state to the “normal” state, by 48 hr. The acute (immediate) effects of ETOH and chlordiazepoxide (0.75 g/kg or 0.18 mg/kg, respectively; 15 min) did not cross‐generalize with the “hangover” state. Both these low‐dose ETOH and chlordiazepoxide pretreatments blocked the stimulus attributes of “hangover.” All subjects responded on the EDE‐appropriate lever at 5.6 mg/kg pentylenetetrazole and exhibited an increase in susceptibility to clonic seizures. In Experiment 2 blood alcohol concentration kinetics functions were quantified in three groups (n = 8/ group) of age‐matched cohorts to Experiment 1 subjects (2, 3, and 4 g/kg ETOH) using a head‐space gas chromatographic technique. The training stimulus state associated with 4 g/kg, at 18 hr postin‐jection intervals, in Experiment 1, did not produce any chromatogram peaks for ETOH or any its active metabolite (acetaldehyde, acetone, nor methanol). The present data demonstrated the saliency and “anxiogenic” dimensionality of experimentally induced “hangover.”
Decreased Postnatal Testosterone Surge in Male Rats Exposed to Ethanol During the Last Week of Gestation
Authors: McGivern Robert F. , Handa Robert J. , Redei Eva
Published: June 2007

Prenatal alcohol exposure in the rat is known to interfere with the neurobehavioral sexual differentiation of the male brain. Because normal sexual differentiation of the male brain requires adequate levels of perinatal testosterone, we examined the effect of prenatal ethanol exposure on (1) the postnatal surge of testosterone and (2) the in vitro secretion of testosterone in response to luteinizing hormone (LH) stimulation of testes from fetal alcohol exposed (FAE) animals and controls. Sprague‐Dawley dams were administered a fortified liquid diet containing 35% ethanol‐derived calories, a pair‐fed (PF) isocaloric liquid diet, or given ad libitum access to dry lab chow (CF). Dams were administered the liquid diets from days 7 or 14 through parturition. The postnatal surge of testosterone in FAE males was studied only in animals exposed to ethanol from day 14 through parturition. In the first experiment, FAE and PF males and females were delivered by cesarian section on day 22 of gestation (E22) and trunk blood collected at 0, 60, 120, and 240 min after parturition. Experiment 2 measured plasma testosterone in male pups that were killed at 0, 60, 120, 240, 360, and 480 min after delivery. Results showed that the postnatal testosterone surge of FAE males in both experiments was significantly attenuated compared with PF controls. No effect of prenatal ethanol was observed in female offspring. Female testosterone levels were several fold lower than male littermates, and no evidence of a postnatal testosterone surge was observed.

Production of testosterone from testes was studied using an automated perfusion system. The secretory testosterone response to LH stimulation of testes on day 18 (E18) of gestation and at birth (E22) was similar in testes from FAE animals to that observed in testes from PF and CF controls. The response of all testes to a pulse of LH (5 nM) delivered over a 5‐min period (flow rate = 200 μl/min) from animals at E18 was significantly greater than the response observed at day 22. No morphological abnormalities were detected by visual inspection of electron photomicrographs of testes from FAE animals at E18 or E22. The in vitro response to LH of testes from FAE animals indicates that the reduction in the postnatal testosterone surge in FAE animals is not due to a decrease in testicular sensitivity to LH.
Alterations in Activity Following Alcohol Administration During the Third Trimester Equivalent in P and NP Rats
Authors: Riley Edward P. , Barron Susan , Melcer Ted , Gonzalez David
Published: June 2007

There is considerable variation in the consequences of alcohol abuse during pregnancy on infant outcome. Although it is clear that a number of factors contribute to this variability, one hypothesis that has received recent attention is the role of genetic differences in response to alcohol. This study examined activity levels in the alcohol‐preferring (P) and alcohol‐nonpreferring (NP) rats following neonatal alcohol exposure. Although these lines were selectively bred for differences in voluntary alcohol consumption, they also differ in their sensitivity and tolerance to alcohol. The P and NP offspring were artificially reared and administered ethanol (either 6 or 4 g/kg/day) from postnatal day 4 (PN 4) until PN 10 via intragastric cannula. An artificially reared isocaloric maltose group and a normally reared control group were also included. From PN 18 to PN 21, subjects were tested daily for 30 min in an automated activity monitor. Exposure to either the 4 or 6 g/kg dose of ethanol resulted in overactivity in P rats. However, only the 6 g/kg dose group displayed overactivity among the NP offspring. Furthermore, the level of overactivity displayed by the alcohol‐exposed P rats was significantly greater than that displayed by the alcohol‐exposed NP rats. These data suggest that genetic differences in response to alcohol may be a predictor for the behavioral teratogenic effects of alcohol.
Optical Spectroscopy and Cerebral Vascular Effects of Alcohol in the Intact Brain: Effects on Tissue Deoxyhemoglobin, Blood Content, and Reduced Cytochrome Oxidase
Authors: Barbour Randall L. , Gebrewold Asefa , Altura Burton M.
Published: June 2007

Dose‐response effects of acute ethanol infusions were studied, noninvasively, in the unopened brain to examine the hypothesis that ethanol can induce stroke‐like events as a consequence of cerebral vasospasm and tissue ischemia. By using a single sending and receiving fiber, an optical backscatter measurement (500–800 nm) was used to monitor the levels of deoxyhemoglobin (DH), reduced cytochrome oxidase (rCO), and relative tissue blood content in a closed cranium preparation. Anesthetized rats were prepared by cannulating a branch of the internal carotid artery and subjected to either bolus infusions (1.25 or 2.5 μm ethanol in Ringers/g tissue) or to constant infusions of 5 or 10% ethanol at various rates (0.30–2.92 μm/g/min). To facilitate optical penetration, a portion of the left parietal cranium was shaved to a translucent appearance. Results showed that low, bolus doses of ethanol typically produced a slight increase (5–10%) in the oxyhemoglobin signal, indicating that vasodilation had probably occurred. Higher doses, however, produced a prompt and significant reduction in the hemoglobin signal, increased levels of DH, and a rise in rCO suggesting a vasoconstrictor response leading to ischemia had occurred, followed by recovery within 3–5 min. Constant infusions of ethanol produced a similar cerebral vascular response, in a dose‐related manner, but of a more sustained nature. At levels of 50–60% of the maximum bolus dose, the effect was more pronounced, accompanied by an increase in the levels of rCO (by 50–90%). Control experiments using identical volumes/flow rates of Ringers solution produced no significant alterations in the optical spectrum. Overall, these data indicate that, depending on dose: (a) ethanol can induce vasodilatory or vasoconstrictor effects in the intact brain; (b) the more pronounced effects involve vasospasm in the cortical microcirculation leading to global ischemia; and (c) optical measurements permit direct noninvasive assessment of the cerebral vascular effects of alcohol and, potentially, other substances of abuse
Kinetic Interactions Between 4‐Methylpyrazole and Ethanol in Healthy Humans
Authors: Jacobsen D. , Sebastian C. S. , Dies D. F. , Breau R. L. , Spann E. G. , Barron S. K. , McMartin K. E.
Published: June 2007

4‐Methylpyrazole (4‐MP), a potent inhibitor of alcohol dehydrogenase activity, is a candidate to replace ethanol as the antidote for methanol and ethylene glycol intoxications, because It has a longer duration of action and apparently fewer adverse effects. To study a probable mutual inhibitory effect between ethanol and 4‐MP on their elimination, two studies were performed in healthy human volunteers using double‐blind crossover designs. In study A, 4‐MP in the presumed therapeutic dose range of 10 to 20 mg/kg caused a 40% reduction in the rate of elimination of ethanol in 12 subjects given 0.5 to 0.7 g/kg of ethanol. These data suggest that such doses of CMP inhibit alcohol dehydrogenase activity in humans in vivo and would be effective at blocking methanol or ethylene glycol metabolism. In study B, ethanol (0.6 g/kg followed by 0.2 g/kg twice) significantly decreased the rate of elimination of 4‐MP (5 mg/kg, given intravenously to four subjects). These moderate doses of ethanol also inhibited the rate of urinary excretion of 4‐carboxypyrazole, the primary metabolite of 4‐MP in humans. Data suggest that ethanol inhibits 4‐MP metabolism, thereby increasing the duration of therapeutic blood levels of CMP in the body. This mutual interaction may have clinical implications, because most self‐poisoned patients have also ingested ethanol. Theoretically, methanol and ethylene glycol might also show such interactions with 4‐MP.
Hostility Is Associated with a Low Prolactin Response to Meta‐chlorophenylpiperazine in Abstinent Alcoholics
Authors: Handelsman Leonard , Holloway Karen , Kahn Rene S. , Sturiano Christopher , Rinaldi Paul J. , Bernstein David P. , Siever Larry , Gabriel Steven , Cooper Thomas B.
Published: June 2007

The prolactin response to the administration of serotonin agonists is an index of central nervous system serotonin (5HT) activity. This index is blunted in association with hostile aggression in personality‐disordered individuals without substance abuse. We tested whether prolactin response to the partial 5HT agonist meta‐chlorophe‐nylpiperazine (MCPP) (0.35 mg/kg PO) was associated with measures of trait hostility in alcoholics who were completing a 3‐week rehabilitation program alter medical detoxification. We also tested whether the same 5HT index differed in the group of alcoholics compared with the healthy volunteers. The prolactin response to MCPP was inversely associated with the main index of trait hostility and was similarly inversely associated with an index of depression. There was, however, no difference in neuroendocrine or temperature responses to MCPP between the alcohol‐dependent group and the healthy volunteers.
Biological Markers of Alcohol Consumption and Effect of Calcitonin in Nonalcoholic Men: A Prospective, Double‐Blind Study
Authors: Elomaa Ville‐Veikko , Löyttyniemi Eliisa , Kärkkäinen Päivi , Salaspuro Mikko , Laitinen Kalevi
Published: June 2007

The objective of this study was to study the ability of biological markers of alcohol consumption in differentiating subjects below weekly consumption of 400 or 600 g of absolute ethanol from those above, and to study the effect of intranasal calcitonin on alcohol drinking. A prospective 12‐week double‐blind study that used anonymous data collection with drinking diaries was done. The drug that was studied (calcitonin or placebo) was used during study weeks5–8. This study was performed at the research unit of a university hospital. The subjects consisted of 59‐nine men aged 26 to 57 years who considered themselves as regular but modest drinkers and were recruited by advertisements. The measurements were obtained from monthly questionnaires and daily anonymous diaries for alcohol drinking data, and biological markers of alcohol consumption (aspartate ami‐notransferase, alanine aminotransferase, y‐glutamyt transpepti‐dase, beta hexosaminidase, and carbohydrate deficient transferrin). The results indicated intranasal calcitonin with a dose of 2001U three times a week had no effect on alcohol use. All biological markers studied had only a modest ability to differentiate those with weekly alcohol consumption of 400 or 600 g or over from those below these limits. The areas under receiver operating characteristic (ROC) curve with the limit 400 g/week were 0.71 for aspartate aminotransferase, 0.61 for alanine aminotransferase, 0.74 for γ‐glutamyl transpepti‐dase, 0.68 for β‐hexosaminidase, and 0.78 for carbohydrate deficient transferrin. Respective numbers for the 600‐g limit were more uniform. As evaluated by ROC analysis, carbohydrate deficient transferrin was the best biological marker to find men with weekly alcohol consumption over 400 g. lntranasal salmon calcitonin had no affect on alcohol drinking.
Carbohydrate‐Deficient Transferrin as an Indicator of Drinking Status During a Treatment Outcome Study
Authors: Anton Raymond F. , Moak Darlene H. , Latham Patricia
Published: June 2007

Biological markers of alcohol consumption have been used in both clinical and research settings to aid in the identification of relapse drinking. Although carbohydrate‐deficient transferrin (CDT) has been shown to be a sensitive and specific marker for the identification of heavy drinkers, little data are available as to its utility as a marker for relapse drinking during treatment, particularly in comparison with the more widely used serum γ‐glutamyltransferase (GGT). CDT and GGT were measured in 35 male alcoholics before entering, and every 4 weeks during, a 12‐week outpatient treatment trial combining pharmacotherapy and cognitive behavioral therapy. CDT and GGT were again measured 14 weeks after completion of treatment. During the 12‐week treatment period, CDT showed a significant difference in those individuals who abstained from drinking (30% decrease), compared with those who relapsed (10% increase). GGT decreased on average in all individuals, and the change from treatment entry did not dier significantly across the drinking outcome groups. The change in CDT, but not GGT, from study entry to termination, significantly correlated with total alcohol consumption during the trial. At the 14‐week posttreatment, follow‐up evaluation CDT showed about a 60% elevation and GGT showed a 30% elevation, on average, from study entry values in those individuals who had relapse drinking by self and/or collateral report. The change in both markers differed between those individuals who remained abstinent or relapsed during the poststudy period. In general, the change in CDT from pretreatment levels seemed more sensitive to drinking status during treatment and follow‐up than GGT. This indicates that CDT may be a more sensitive marker for evaluating drinking status during both clinical and research treatment trials.
Bulimia Nervosa and Substance Dependence: Association and Family Transmission
Authors: Kaye Walter H. , Lilenfeld Lisa R. , Plotnicov Katherine , Merikangas Kathleen R. , Nagy Linda , Strober Michael , Bulik Cynthia M. , Moss Howard , Greeno Catherine G.
Published: June 2007

Alcohol and drug use disorders are common among women with bulimia newosa (BN) and their family members. However, it is not known whether there is a familial relationship between BN and substance use disorders. We compared 47 women with BN and 44 non‐eating‐disordered community control women, and their first‐degree relatives (177 and 190, respectively). BN probands were stratified by the presence (43%) or absence (57%) of lifetime alcohol and/or drug dependence. The first‐degree relatives of substance‐dependent BN probands had significantly higher lifetime rates of alcohoWdrug dependence (38%), compared with relatives of nonsubstance‐depen‐dent BN probands (10%) or relatives of community controls (18%). These data suggest that BN and substance dependence are transmitted independently in families.
Serum and Ascitic Levels of Soluble Intercellular Adhesion Molecule‐1 in Patients with Alcoholic Liver Cirrhosis: Relation to Biochemical Markers of Disease Activity and Alcohol Intake
Authors: Nagy István , Mándi Yvette
Published: June 2007

The overexpression of intercellular adhesion molecule‐1 (ICAM‐1) has been shown to be involved in the pathogenesis of various necro‐inflammatory diseases, including alcoholic hepatitis. Shedding of this molecule from cell surfaces results in a circulating form, soluble CAM‐1 (SICAM‐1). In this work, the serum and ascitic concentrations of SICAM‐1 were studied in relation to clinical and laboratory data in patients with alcoholic liver cirrhosis of different disease activities. Elevated circulating concentrations of this adhesion molecule were found in all cirrhotic patients, the highest in those with superimposed sewere alcoholic hepatitis, and the levels in regularly drinking cirrhotics without severe alcoholic hepatitis were likewise significantly higher than in those who had stopped drinking. The serum SICAM‐1 concentration was best related to the serum AST activity, and also exhibited significant correlations with the pro‐thrombin activity, serum bilirubin, albumin, peripheral leukocyte count, Maddrey's discriminant function value, Child grading, and antecedent alcohol consumption. Multivariate regression analysis revealed that the serum AST and prothrombin activities were independent predictors of the circulating SICAM‐1 concentration. The concentration of SICAM‐1 in the uninfected ascitic fluid of cirrhotics was about seven times lower than that in the serum; the ratio of its ascitic and serum levels was lower than that of the ascitic and serum total protein concentrations. These data contradict a significant in‐traperitoneal production of the molecule. It is concluded that the serum SICAM‐1 level may be useful as a marker for the current disease activity (the severity of underlying acute necroinflammatory reactions) in alcoholic liver cirrhosis.
Mechanism of Ethanol Inhibition of NMDA Receptor Function in Primary Cultures of Cerebral Cortical Cells
Authors: Bhave Sanjiv V. , Snell Lawrence D. , Tabakoff Boris , Hoffman Paula L.
Published: June 2007

Ethanol is a potent inhibitor of the function of the N‐methyl‐o‐aspar‐tate (NMDA) subtype of glutamate receptor in various neuronal preparations. In primary cultures of cerebellar granule cells, ethanol was suggested to interact with the glycine co‐agonist site of the receptor by a mechanism involving protein kinase C. In the present study, the interaction of ethanol with various sites on the NMDA receptor was examined in primary cultures of cerebral cortical cells from ernbryonic rats. NMDA receptor function was determined by measuring increases in intracellular Ca2+ with fura‐2 fluorescence. Ethanol inhibited the function of the NMDA receptor in cerebral cortical cells, but in contrast to the results in cerebellar granule cells, phorbol ester treatment did not inhibit the NMDA response, and ethanol did not alter the effect of glycine on NMDA receptor function. Ethanol also did not affect inhibition of the NMDA response by Mg2+ or dizo‐cilpine. The results support the hypothesis that the mechanism of ethanol inhibition of NMDA receptor function can vary in neurons from different brain regions.
Chronic Ethanol Treatment Reduces the Responsiveness of the Hypothalamic‐Pituitary‐Thyroid Axis to Central Stimulation
Authors: Zoeller R. Thomas , Fletcher Donald L. , Simonyi Agnes , Rudeen P. Kevin
Published: June 2007

The hypothalamic‐pituitary‐thyroid (HPT) axis functions abnormally in man and animals chronically exposed to ethanol. The most consistent observation in humans is that the thyrotropin response to thyrotropin‐releasing hormone (TRH) is blunted. We have tested the hypothesis that chronic ethanol treatment in rats leads to a diminished responsiveness of the hypothalamus to central stimulation. Animals were maintained on 1 of 3 diets for 4 weeks: (1) laboratory chow and water provided ad libitum (chow‐fed), (2) Sustacal chocolate liquid diet with vitamin mixture containing 5% (w/v) ethanol provided ad libitum (ethanol), or (3) Sustacal chocolate liquid diet with vitamin mixture containing sucrose substituted isocalorically (35%) for ethanol and provided in amounts matched to a weight‐paired, ethanol‐treated animal (pair‐fed). At the end of 4 weeks, the animals were evaluated for their response to a single injection of ethanol (3 g/kg, ip) and/or exposure to 5°C. Chronic ethanol treatment produced an increase in TRH mRNA in neurons of the paraventricular nucleus and fully blocked the thyrotropic response to cold exposure. However, chronic ethanol‐treated animals did not exhibit altered basal levels of triiodothyronine or thyrotropin, nor did they have an altered response to a single injection of ethanol. These data demonstrate that chronic alcohol exposure alters functioning of the hypo‐thalamic‐pituitary‐thyroid axis at least in part by affecting TRH neurons of the paraventricular nucleus.
Fabrication of Functionally Graded and Aligned Porosity in Thin Ceramic Substrates With the Novel Freeze–Tape‐Casting Process
Authors: Sofie Stephen W.
Published: June 2007

Functionally graded and continuously aligned pore structures have been fabricated by a modified tape‐casting process for use as solid oxide fuel cell electrodes, catalysts, sensors, and filtration/separation devices. Pore gradients from <5 to 100 μm and aligned pore tubules have been directly fabricated in various ceramic materials with thin substrate sections approximately 500–1500 μm utilizing both low‐toxicity aqueous‐based slips and organic solvents. This process allows for the generation of pores without the use of thermally fugitive pore formers in a single processing step with no need for tape lamination. The incorporation of tape casting, unidirectional solidification, and the freeze‐drying process results in uniformly acicular pores aligned with the direction of the moving carrier film. Processing and microstructure variability will be discussed as it pertains to the effects of solids loading, freezing temperatures, and solvent type. Applications for this ceramic processing technology will also be discussed.
Effects of scaling and root planing and sub‐antimicrobial dose doxycycline on oral and systemic biomarkers of disease in patients with both chronic periodontitis and coronary artery disease
Authors: Tüter Gülay , Kurtiş Bülent , Serdar Muhittin , Aykan Tuba , Okyay Kaan , Yücel Ayşegül , Toyman Utku , Pınar Selin , Cemri Mustafa , Çengel Atiye , Walker Stephen G. , Golub Lorne M.
Published: June 2007

Objectives: This study evaluated the effects of scaling and root planing (SRP) ± sub‐antimicrobial dose doxycycline (SDD) on gingival crevicular fluid (GCF) levels of matrix metalloproteinase (MMP) ‐1, ‐8, ‐13 and on serum levels of high‐sensitivity C‐reactive protein (HsCRP) and lipid fractions in patients with both chronic periodontitis (CP) and coronary artery disease (CAD).

Material and Methods: Thirty‐six patients were randomly distributed into two groups (Placebo or SDD; 6 weeks) and both received two regimens of SRP. At baseline and 6 weeks, GCF and blood were collected and clinical indices were recorded. MMPs, HsCRP and lipid fractions were assayed.

Results: There were statistically significant improvements for all clinical parameters, GCF volumes, GCF MMPs and serum levels of HsCRP, apolipoprotein‐A (APO‐A), high‐density lipoprotein (HDL) and lipoprotein‐a between pre‐ and post‐treatment in both groups. Between groups, there were statistically significant greater improvements in pocket depth (PD), gingival index (GI), APO‐A and HDL, favouring the group receiving SDD adjunctive to SRP (p < 0.05).

Conclusion: Greater improvement was detected for PD and GI, and for serum levels of APO‐A and HDL cholesterol when using SRP+SDD compared with SRP+placebo in this study. An investigation with larger numbers of patients and a longer duration of drug treatment is needed to confirm these preliminary findings.
Melatonin attenuates arsenite‐induced apoptosis in rat brain: involvement of mitochondrial and endoplasmic reticulum pathways and aggregation of α‐synuclein
Authors: Lin Anya M. Y. , Fang S. F. , Chao P. L. , Yang C. H.
Published: June 2007

Abstract:  In the present study, the protective effect of melatonin on sodium arsenite (arsenite)‐induced apoptosis was investigated. Local infusion of arsenite elevated lipid peroxidation and depleted glutathione content in the infused substantia nigra (SN), as well as reduced striatal dopamine content. Systemic administration of melatonin diminished arsenite‐induced oxidative injury. Furthermore, melatonin attenuated arsenite‐induced increases in heat shock protein 70 and heme oxygenase‐1 as well as phosphorylation of p38 mitogen‐activated protein kinase and elevations in cyclooxygenase II and inducible nitric oxide synthase expression. Inhibition by melatonin of arsenite‐induced apoptosis was determined by its attenuation of DNA fragmentation and terminal deoxytransferase‐mediated dUTP‐nick end labeling's positive cells in the infused SN of melatonin‐treated rats. Melatonin reduced arsenite‐induced apoptosis through mitochondrial and endoplasmic reticulum (ER) pathways. In the mitochondrial pathway, systemic melatonin inhibited arsenite‐induced elevations in Bcl‐2 and cytosolic cytochrome c as well as arsenite‐induced reductions in procaspase‐3 levels and elevations in active caspase‐3 levels in the infused SN. Regarding the ER pathway, melatonin attenuated arsenite‐induced elevations in activating transcription factor‐4, CCAAT/enhancer binding protein (C/EBP) homologues protein, X‐bon binding protein (XBP‐1) and cytosolic immunoglobulin binding protein (BIP) as well as reductions in procaspase 12 levels. Moreover, aggregation of α‐synuclein was reduced in the arsenite‐infused SN of melatonin‐treated rats. Our in vitro data showed that melatonin ameliorated arsenite‐induced lipid peroxidation. Taken together, our data suggest that melatonin is neuroprotective against arsenite‐induced oxidative injury in the nigrostriatal dopaminergic system of rat brain. Furthermore, the neuroprotective effects by melatonin on arsenite‐induced apoptosis were mediated via inhibiting both mitochondrial and ER pathways. Accordingly, melatonin may be therapeutically useful for the treatment of arsenite‐induced apoptosis in central nervous system.
A Novel Three‐Dimensional In Vitro System to Study Trophoblast–Endothelium Cell Interactions
Authors: Aldo Paulomi B. , Krikun Graciela , Visintin Irene , Lockwood Charles , Romero Roberto , Mor Gil
Published: June 2007

Introduction

Pregnancy complications have been linked to improper trophoblast migration and failure of spiral artery transformation. Endothelial cells play an essential role in directing trophoblast migration and transformation, although by an unknown mechanism. We describe a novel in vitro model to evaluate endothelial–trophoblast interaction and signaling in a three‐dimensional system.

Method of study

Immortalized human endometrial endothelial cell line and first trimester trophoblast cells were co‐cultured. Endothelial transformation into vessel‐like structures occurred in MatrigelTM OpenLab Image Analysis software was used to monitor labeled trophoblast migration and endothelium transformation. Cytokine/chemokine production was determined using Multiplex.

Results

Trophoblast migrates toward endothelial cells in Matrigel, aligns on top of the endothelium within 4–8 hr and achieves complete replacement of the endothelium by 72–96 hr. Lipopolysaccharide treatment damages the endothelium and disrupts endothelium–trophoblast interaction.

Conclusion

We report a novel three‐dimensional in vitro and in vivo system of trophoblast–endothelium cell interaction. Significant changes in endothelial cells’ phenotype are observed upon differentiation in Matrigel. These changes may be necessary for endothelium to direct trophoblast migration and transformation.
Topochemical Models for Prediction of Telomerase Inhibitory Activity of Flavonoids
Authors: Dureja Harish , Madan Anil Kumar
Published: June 2007

In the present study, the relationship between the topochemical indices and telomerase inhibitory activity of flavonoids has been investigated. Three topochemical indices, Wiener's topochemical index (a distance‐based topochemical descriptor), molecular connectivity topochemical index (an adjacency‐based topochemical descriptor) and superadjacency topochemical index (an adjacency cum distance‐based topochemical descriptor) were used for the present investigation. The values of the Wiener's topochemical index, molecular connectivity topochemical index and superadjacency topochemical index for each of the 30 analogues comprising the data set were computed using an in‐house computer program. Resultant data was analysed and suitable models were developed after identification of the active ranges. Subsequently, a biological activity was assigned to each analogue involved in the data set using these models, which was then compared with the reported telomerase inhibitory activity. Statistical significance of proposed models was investigated using intercorrelation analysis. Accuracy of prediction using proposed models was found to vary from 80% to 83%.
ANN‐QSAR Model of Drug‐binding to Human Serum Albumin
Authors: Deeb Omar , Hemmateenejad Bahram
Published: June 2007

Quantitative structure–activity relationship study was performed to understand drug binding to human serum albumin. This study was performed on 94 different human serum albumin drug and drug‐like compounds by using the principal component‐artificial neural network modeling method, with application of eigenvalue ranking factor selection procedure. The results obtained by principal component‐artificial neural network gives better regression models with good prediction ability using a relatively low number of principal components in comparison to other quantitative structure–activity relationship studies on the same data set of compounds. A 0.8497 coefficient of determination was obtained using principal component‐artificial neural network with six extracted principal components.
QSAR Study on the Antinociceptive Activity of Some Morphinans
Authors: Ramírez‐Galicia Guillermo , Garduño‐Juárez Ramón , Hemmateenejad Bahram , Deeb Omar , Deciga‐Campos Myrna , Moctezuma‐Eugenio Juan Carlos
Published: June 2007

Quantitative structure–activity relationship studies were performed to describe and predict the antinociceptive activity of 31 morphinan derivatives reported by the US Drug Evaluation Committee in 2005 and 2006. From these, three data sets were constructed and several models were calculated following the multiple linear regression and Leave‐One‐Out Cross‐Validation (LOO‐CV) tests. In general, these models achieved good descriptive power (approximately 92%) as well as predictive power (approximately 76%), but were unable to predict an external validation set of morphinan derivatives. When artificial neural networks were applied to these models, an improvement of the predictive and external validation values was obtained. It was observed that the results of the NN models are significantly better that those obtained by multiple linear regression. In spite that the problem under investigation can be handled adequately by a linear model, a neural network does bring slight improvements in the predictive power.
Further Characterisation of the 91500 Zircon Crystal
Authors: Wiedenbeck Michael , Hanchar John M. , Peck William H. , Sylvester Paul , Valley John , Whitehouse Martin , Kronz Andreas , Morishita Yuichi , Nasdala Lutz , Fiebig J. , Franchi I. , Girard J.‐P. , Greenwood R.C. , Hinton R. , Kita N. , Mason P.R.D. , Norman M. , Ogasawara M. , Piccoli P.M. , Rhede D. , Satoh H. , Schulz‐Dobrick B. , Skår O. , Spicuzza MJ. , Terada K. , Tindle A. , Togashi S. , Vennemann T. , Xie Q. , Zheng Y.‐F.
Published: June 2007

This paper reports the results from a second characterisation of the 91500 zircon, including data from electron probe microanalysis, laser ablation inductively coupled plasma‐mass spectrometry (LA‐ICP‐MS), secondary ion mass spectrometry (SIMS) and laser fluorination analyses. The focus of this initiative was to establish the suitability of this large single zircon crystal for calibrating in situ analyses of the rare earth elements and oxygen isotopes, as well as to provide working values for key geochemical systems. In addition to extensive testing of the chemical and structural homogeneity of this sample, the occurrence of banding in 91500 in both backscattered electron and cathodoluminescence images is described in detail. Blind intercomparison data reported by both LA‐ICP‐MS and SIMS laboratories indicate that only small systematic differences exist between the data sets provided by these two techniques. Furthermore, the use of NIST SRM 610 glass as the calibrant for SIMS analyses was found to introduce little or no systematic error into the results for zircon. Based on both laser fluorination and SIMS data, zircon 91500 seems to be very well suited for calibrating in situ oxygen isotopic analyses.
Comparison of Silver and Gold Inquarting in the Fire Assay Determination of Palladium/Platinum and Rhodium in Geological Samples
Authors: Suominen Meeri , Kontas Esko , Niskavaara Heikki
Published: June 2007

The classical lead fire assay is still the most important method for the pre‐concentration and separation of Ag, Au and some of the platinum‐group elements (PGE) in the analysis of geological materials. The most frequently used fire assay procedure is the determination of Au, Pd and Pt with Ag as collector. When Au is used instead of Ag as a collector, Pd, Pt, Rh and possibly Ir can also be determined. In this study the recoveries by Au and Ag collectors, also called inquarts, were compared in the fire assay analysis of Pd, Pt and Rh in geological reference materials. The amount of gold to be added was optimised. Variable recoveries were obtained with Ag inquart for Rh, but a 2 mg inquart of Au gave good recoveries for all three of these elements in the analysis of reference samples of different geological materials. A procedure, alternative to scorification, to overcome interferences caused by base metals in the cupellation step is presented. The procedure involves cutting the Pb button into pieces and analysing the pieces separately. Prior to this, a homogeneity study of the lead button was made, and it showed that Pd, Pt and Rh were evenly distributed in the Pb button. All determinations were made using inductively coupled plasma‐atomic emission spectrometry (ICP‐AES).
Problems and Suggestions Concerning the Notation of Cadmium Stable Isotope Compositions and the Use of Reference Materials
Authors: Wombacher Frank , Rehkämper Mark
Published: June 2007

Notations for Cd stable isotope compositions and the use of reference materials are discussed. It is proposed that Cd stable isotope data should be reported as variations of the 114Cd/110Cd ratio/ using either the δ114/110Cd or ε114/110Cd notations. Future publications should report results for BAM‐1012 Cd, the only currently available international Cd isotope reference material. It is also recommended that “Münster Cd” and a range of specified geological reference materials are used as additional reference materials. The final choice of a primary “zero‐delta” reference standard remains the most important outstanding question.
Reference Materials in Geoanalytical Research ‐Review for 2004 and 2005
Authors: Jochum Klaus Peter , Willbold Matthias
Published: June 2007

This review gives an overview of the use and development of reference materials of geochemical and environmental interest in the literature of the years 2004 and 2005. In these years the performance of existing methods has been improved and new geochemical applications using new techniques have been developed. Accordingly, there was an increasing need for new reference materials, especially for in situ microanalysis and for precise stable isotope measurements. In addition, there was a notable trend for further characterisation of existing reference materials, mainly for the platinum‐group elements. This review focuses on five topics: reference materials for platinum‐group elements, reference glasses for in situ microanalysis, zircon reference materials, isotopic reference materials, and the development and certification of reference materials.
Trace Element Determination by ICP‐AES and ICP‐MS: Developments and Applications Reported During 2004 and 2005
Authors: Linge Kathryn L.
Published: June 2007

This review describes significant developments in trace element determination using inductively coupled plasma‐atomic emission spectrometry (ICP‐AES) and inductively coupled plasma‐mass spectrometry (ICP‐MS) that were reported in 2004 and 2005. It focuses on the application of ICP techniques to geological and environmental samples; fundamental studies in ICP‐MS and ICP‐AES instrumentation are not included. The literature reviewed indicated that the majority of new publications concerned advances in ICP‐MS analysis rather than ICP‐AES. However, ICP‐AES developments are still being published, particularly in the areas of sample preconcentration and sample introduction. The trend in increasing publication of developments in hyphenated speciation techniques looks set to persist as knowledge of elemental speciation becomes critical for many environmental studies. Collision or reactions cells were the most reported technique for spectral interference removal in ICP‐MS, probably reflecting the growing adoption of cell instruments in laboratories during the last few years.
Chemical Characterisation of Chromites by XRF Spectrometry
Authors: Gazulla Maria Fernanda , Barba Antonio , Gómez María Pilar , Orduña Monica
Published: June 2007

The present study was undertaken to establish and validate a methodology for determining the chemical composition of chromite ores, as no detailed information could be found in the literature. Chromite ores from South Africa, Kazajistan and Mongolia were analysed. X‐ray fluorescence (XRF) spectrometry was used for chemical characterisation. Sample preparation in the form of fused beads was optimised in terms of sample:flux ratio, type of flux, type of release agent, fusion temperature and time. Calibration and validation samples were prepared from mixtures of reference materials. The proposed methodology was then used in an interlaboratory test for preparing a new chromite‐rich reference material.

L'analyse présentée id a été entreprise afin d'établir et de valider une méthodologie pour déterminer la composition chimique de minerals de chromite, car aucune information détaillée là dessus ne pouvait etre trouvée dans la littérature. Des minerals de chromite d'Afrique du Sud, du Kazakhstan et de Mongolie ont été analysés par spectrométrie de Fluorescence de Rayons X (XRF) afin d'être caractérisés chimiquement. La préparation des échantillons afin d'obtenir des perles fondues a été optimisée en termes du rapport “échantillon/fondant”, type de fondant, d'agent mouillant, température et durée de fusion. La calibration et la validation ont été faites à partir de mixtures de matériau de référence. La méthodologie proposée a été ensuite appliquée à un test d'inter‐comparaison en vue de préparer un nouveau matériau de référence riche en chromite.
Hyperventilation‐induced hypocapnic alkalosis slows the adaptation of pulmonary O2 uptake during the transition to moderate‐intensity exercise
Authors: Chin Lisa M. K. , Leigh Ryan J. , Heigenhauser George J. F. , Rossiter Harry B. , Paterson Donald H. , Kowalchuk John M.
Published: June 2007

The effect of voluntary hyperventilation‐induced hypocapnic alkalosis (RALK) on pulmonary O2 uptake () kinetics and muscle deoxygenation was examined in young male adults (n= 8) during moderate‐intensity exercise. Subjects performed five repetitions of a step‐transition in work rate from 20 W cycling to a work rate corresponding to 90% of the estimated lactate threshold during control (CON; , ∼40 mmHg) and during hyperventilation (RALK; , ∼20 mmHg). was measured breath‐by‐breath and relative concentration changes in muscle deoxy‐ (ΔHHb), oxy‐ (ΔO2Hb) and total (ΔHbtot) haemoglobin were measured continuously using near‐infrared (NIR) spectroscopy (Hamamatsu, NIRO 300). The time constant for the fundamental, phase 2, response (τ) was greater (P < 0.05) in RALK (48 ± 11 s) than CON (31 ± 9 s), while τHHb was similar between conditions (RALK, 12 ± 4 s; CON, 11 ± 4 s). The ΔHbtot was lower (P < 0.05) in RALK than CON, prior to (RALK, −3 ± 5 μmol l−1; CON, −1 ± 4 μmol l−1) and at the end (RALK, 1 ± 6 μmol l−1; CON, 5 ± 5 μmol l−1) of moderate‐intensity exercise. Although slower adaptation of during RALK may be related to an attenuated activation of PDH (and other enzymes) and provision of oxidizable substrate to the mitochondria (i.e. metabolic inertia), the present findings also suggest a role for a reduction in local muscle perfusion and O2 delivery.
Abolition of Ca2+‐mediated intestinal anion secretion and increased stool dehydration in mice lacking the intermediate conductance Ca2+‐dependent K+ channel Kcnn4
Authors: Flores Carlos A. , Melvin James E. , Figueroa Carlos D. , Sepúlveda Francisco V.
Published: June 2007

Intestinal fluid secretion is driven by apical membrane, cystic fibrosis transmembrane conductance regulator (CFTR)‐mediated efflux of Cl– that is concentrated in cells by basolateral Na+−K+−2Cl– cotransporters (NKCC1). An absolute requirement for Cl– efflux is the parallel activation of K+ channels which maintain a membrane potential that sustains apical anion secretion. Both cAMP and Ca2+ are intracellular signals for intestinal Cl– secretion. The K+ channel involved in cAMP‐dependent secretion has been identified as the KCNQ1–KCNE3 complex, but the identity of the K+ channel driving Ca2+‐activated Cl– secretion is controversial. We have now used a Kcnn4 null mouse to show that the intermediate conductance IK1 K+ channel is necessary and sufficient to support Ca2+‐dependent Cl– secretion in large and small intestine. Ussing chambers were used to monitor transepithelial potential, resistance and equivalent short‐circuit current in colon and jejunum from control and Kcnn4 null mice. Na+, K+ and water content of stools was also measured. Distal colon and small intestinal epithelia from Kcnn4 null mice had normal cAMP‐dependent Cl– secretory responses. In contrast, they completely lacked Cl– secretion in response to Ca2+‐mobilizing agonists. Ca2+‐activated electrogenic K+ secretion was increased in colon epithelium of mice deficient in the IK1 channel. Na+ and water content of stools was diminished in IK1‐null animals. The use of Kcnn4 null mice has allowed us to demonstrate that IK1 K+ channels are solely responsible for driving intestinal Ca2+‐activated Cl– secretion. The absence of this channel leads to a marked reduction in water content in the stools, probably as a consequence of decreased electrolyte and water secretion.
Why some of us get fat and what we can do about it
Authors: Levin Barry E.
Published: June 2007

There is a widespread obesity epidemic in the developed world which is having an adverse impact on the health of affected individuals. Many of the afflicted have a genetic predisposition to become obese. These individuals become obese when they over consume highly palatable, calorically dense foods which are readily available at low cost. Once obesity occurs, fewer than 10% of affected individuals can sustain significant weight loss permanently. The hypothesis of this review is that some obesity‐prone individuals have an inborn reduction in their ability to sense and respond to inhibitory signals from adipose stores and other organs which should limit their intake of energy when it exceeds their metabolic needs. Furthermore, the physiological processes which drive all of us to seek and ingest food and limit energy expenditure during periods of negative energy balance provide an irresistible drive to regain lost adipose stores in weight‐reduced obese individuals. For this reason, prevention of obesity and the identification factors which promote the development of neural pathways which enhance the negative feedback signals from the periphery should be a major focus of ongoing research in this field.
Decrease in PIP2–channel interactions is the final common mechanism involved in PKC‐ and arachidonic acid‐mediated inhibitions of GABAB‐activated K+current
Authors: Sohn Jong‐Woo , Lim Ajin , Lee Suk‐Ho , Ho Won‐Kyung
Published: June 2007

We showed in our previous study that in hippocampal CA1 neurons the stimulation of muscarinic receptors inhibited the GIRK current (IGIRK) via a PLC/PKC pathway, whereas group I metabotropic glutamate receptors (mGluR) inhibitedIGIRKvia a PLA2/arachidonic acid pathway. In this study, we present evidence that receptor‐mediated signalling pathways activated by the two Gq‐coupled receptors (GqPCRs) converge on the inhibition of GIRK channel–PIP2interaction.IGIRKwas activated in acutely isolated hippocampal CA1 neurons by repetitive application of baclofen, a GABABreceptor agonist, with a 2–3 min interval. When both CCh and DHPG were pretreated before the secondIGIRKactivation, the magnitude of the secondIGIRKwas 52.2 ± 2.5% of the firstIGIRK, which was not significantly different from the magnitude of inhibition by CCh or DHPG alone. This result shows that the effects of muscarinic receptor and group I mGluR stimulation onIGIRKare not additive but occlusive, suggesting that each pathway may converge to a common mechanism that finally regulatesIGIRK. To test the involvement of PIP2in this mechanism, the effect of CCh and DHPG onIGIRKwas tested in cells loaded with exogenous PIP2. The inhibition ofIGIRKby CCh or DHPG was almost completely abolished in PIP2‐loaded cells. We confirmed that the inhibition ofIGIRKby direct application of phorbol ester or arachidonic acid was also completely reversed in PIP2‐loaded cells. These results indicate that the decrease in PIP2–channel interactions is the final common mechanism responsible for GqPCR‐induced inhibitions ofIGIRKmediated by PKC and arachidonic acid.