bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of antimicrobial drug usage measures on the identification of heavy users, patterns of usage of the different antimicrobial classes and time‐trends evolution
Authors: CHAUVIN C. , QUERREC M. , PEROT A. , GUILLEMOT D. , SANDERS P.
Published: April 2008

Several measurement units are available to quantify antimicrobial usage in veterinary medicine, to obtain diverse measures such as the weight of active substance used, the live weight (LW) treated, the fraction of animals exposed, the number of treatments recorded or the cost represented. These measures can be applied to study practices variability between farms, to characterize patterns of usage of the different antimicrobial classes or to follow evolution of antimicrobial usage with time. An investigation was carried out to specifically explore the influence of measurement units on the conclusions obtained from such studies. Antimicrobial exposure was explored in a sample of turkey and chicken broiler flocks, using six different units [kg of active compound, treatments, days of administration, kg of LW treated, animal daily dose to treat 1 kg of LW (ADDkg) and euros] to compare flocks usage variability and patterns of use of the different antimicrobial classes. Time‐trends evolutions of macrolides usage in turkey broilers, characterized by percentage of flocks exposed and LW treated, were also compared. In all analyses, the measure gave different results without equivalences, highlighting the necessity for care in choosing the measurement unit and caution in interpreting the figures obtained.
Relative potency of ketamine and S(+)‐ketamine in dogs
Authors: DUQUE J. C. , OLESKOVICZ N. , GUIRRO E. C. B. P. , VALADÃO C. A. A. , SOARES V. E.
Published: April 2008

The aim of this study was to determine the relative potency of racemic ketamine and S(+)‐ketamine for the hypnotic effect and to evaluate the clinical anesthesia produced by equianesthetic doses of these two substances in dogs. One hundred and eight dogs were allocated in groups R2, R2.5, R3, R6, R9, R12, S2, S2.5, S3, S6, S9, and S12, to receive by intravenous route 2, 2.5, 3, 6, 9, and 12 mg/kg of ketamine or S(+)‐ketamine, respectively. A dose–effect curve was drawn with the dose logarithm and the percentage of dogs that presented hypnosis in each group. The curve was used to obtain a linear regression, to determine the effective doses 100 and the potency relationship. In another experimental phase, eight groups of five dogs received 3, 6, 9 and 12 mg/kg of ketamine or S(+)‐ketamine to evaluate the periods of latency, hypnosis, and total recovery. The times in which the dogs reached the sternal position, attempted to stand up for the first time, recovered the standing position, and started to walk were also recorded. The hypnotic dose for ketamine was 9.82 ± 3.02 (6.86–16.5) mg/kg and for S(+)‐ketamine was 7.76 ± 2.17 (5.86–11.5) mg/kg. The time of hypnosis was longer in R3 and the first attempt to stand up occurred early in R6 when compared with S3 and S6 respectively. When R9 (100% of hypnosis with ketamine) and S6 [100% of hypnosis with S(+)‐ketamine] were compared (1:1.5 ratio), the time to sternal position (12 ± 2.5 and 20.2 ± 5.6 min respectively) and the total recovery time (45 ± 5.5 and 60.2 ± 5.2 min respectively) were significantly shorter with S(+)‐ketamine. It was concluded that the potency ratio between ketamine and S(+)‐ketamine in dogs is smaller than the one reported in other species, and that the dose obtained after a reduction of 50%, as usually performed in humans, would not be enough to obtain equianesthetic effects in dogs.
Landing distance in a synchronic North American firefly
Authors: COPELAND JONATHAN , MOISEFF ANDREW , FAUST LYNN
Published: April 2008

Abstract The flash communication system of Photinus carolinus in Great Smoky Mountain National Park (Tennessee) is characterized by male firefly synchrony. Photinus carolinus males signal a conspecific female with synchronic trains of flashes. A solitary responding female attracts several males, which is not common in North American rover fireflies. The female and the group of males that she attracts are called a cluster. It is hypothesized that the first male attracted to the female would land closer to the female than would additional males because there would be less tendency for visual confusion. This hypothesis is explored under controlled conditions by replacing the responsive female with an appropriately flashing light‐emitting diode (LED) located in the center of a flat target area. When infra‐red videography is used to measure the first male and the additional males’ landing distances from the counterfeit female (LED), most fireflies land within 15 cm of the target LED, and the first male does not land closer than the additional males. It is suggested that cluster formation is a by‐product of male synchrony and is facilitated by the tendency of males to land near, but not on, females.
Selective regulation of sensitivity to odours of different behavioural significance in the American cockroach,Periplaneta americana
Authors: ZHUKOVSKAYA MARIANNA I.
Published: April 2008

AbstractOrally supplied octopamine significantly enhances the wing‐raising behaviour in male American cockroachesPeriplaneta americana, in response to periplanone B the main component of the sex pheromone, but not attraction. In addition, octopamine decreases the response to the general odorant, hexan‐1‐ol. The presence of a calling female, as well as octopamine treatment, eliminates the avoidance of hexanol by males. Electroantennogram responses to hexan‐1‐ol decreases after topical octopamine application.
Heart transplantation: Literature review 2006–2007
Authors: Mahle William T.
Published: April 2008

Abstract:  The broad range of topics relevant to pediatric heart transplantation makes it difficult to follow the published literature consistently. Moreover, as the field of pediatric heart transplantation overlaps with mechanical support and heart failure the realm of journals of relevance continues to expand. This review will provide succinct summaries of the recent medical literature in the field of pediatric transplantation. In this review, we summarize important articles in the field of pediatric heart transplantation that have been published over the last two yr (2006 and 2007).
No infection with porcine endogenous retrovirus in recipients of acellular porcine aortic valves: a two‐year study
Authors: Gu Chunhu , Wei Xufeng , Wang Yunya , Chen Yu , Liu Jincheng , Wang Hongbin , Sun Guocheng , Yi Dinghua
Published: April 2008

Abstract:  Background:  Engineered tissue heart valves may become a promising therapeutics for heart valve disease. Compared with synthetic materials, acellular porcine scaffolds are considered as suitable matrices for tissue‐engineered heart valves for the mechanical and structural properties of native tissue. Whether acellular porcine scaffolds can cause infection in recipients with porcine endogenous retrovirus (PERV) is critical for evaluating the safety of transplantation of tissue‐engineered heart valves based on acellular porcine scaffolds. This study was completed to evaluate the risk of PERV transmission for application of acellular porcine aortic valves (PAVs).

Methods:  Native aortic valves obtained from Chinese pigs of different species were acellularized by our modified detergent‐enzymatic acellularization procedure. Polymerase chain reaction and reverse transcriptase polymerase chain reaction for pol sequences were used to detect PERV infection. In vitro, ovine endothelial cells (ECs) were inoculated and cocultured with supernatants of porcine aortic endothelial cells (PAECs) and acellualr PAVs, respectively. On 7th day, DNA and RNA of ovine ECs were isolated and tested for PERV. In vivo, acellular PAVs were implanted in the descending thoracic aorta in 40 sheep. Blood samples from the sheep and implanted acellular PAVs were collected 24 months after operation and tested for PERV.

Results:  All cells were removed from the PAVs. Acellularized PAVs were repopulated by autologous cells of the host 24 months after implantation. PERV was detected in all native PAVs, porcine blood samples, acellularized PAVs and ovine ECs inoculated with supernatants of PAECs; no PERV was detected in ovine ECs cocultured with acellularized PAVs, ovine blood samples, and implanted acellular PAVs.

Conclusions:  Acellularized PAVs processed by modified detergent‐enzymatic acellularization procedure can be used for cardiovascular tissue‐engineered grafts as matrix scaffolds without risk of PERV transmission.
Differential activation of mononuclear phagocytes in cerebellar malformation associated with Walker–Warburg syndrome
Authors: Ulfig Norbert , Steinbrecher Alice , Stoltenburg‐Didinger Gisela , Rezaie Payam
Published: April 2008

Walker–Warburg syndrome (WWS) is an autosomal recessive disorder with alterations affecting the CNS that are characteristic of type‐II lissencephaly and dysplasia/hypoplasia of the cerebellum. Other than these features, WWS is typically also accompanied by muscular dystrophy and abnormalities affecting the eyes. There is at present little information on the state of microglial and mononuclear phagocytic cell responses within the brain in WWS. In this case report, we present evidence for focal and differential activation of mononuclear phagocytes specifically confined to the dysplastic cerebellum of an infant at 5 months of age, diagnosed with WWS.
Mitochondrial changes in motor neurons of homozygotes of leucine 126 TT deletion SOD1 transgenic mice
Authors: Doi Koji , Nakano Toshiya , Kitayama Michio , Watanabe Yasuhiro , Yasui Kenichi , Fukada Yasuyo , Morino Shinichi , Kaidoh Toshiyuki , Nakashima Kenji , Inoué Takao
Published: April 2008

We investigated the time course of ultrastructural changes of mitochondria in the spinal cord of homozygotes of Leu126TTdel SOD1 (superoxide dismutase 1) with FLAG (signal sequence at the C‐terminal protein) transgenic mice (DF‐homo). Non‐Tg mice and wild‐type human SOD1 with FLAG epitope transgenic mice (WF) were investigated as controls for non‐onset Tg mice. Expansion and vacuolation of the mitochondrial matrix was exhibited in motor neurons in the anterior horns of DF‐homo Tg mice at the presymptomatic stage. Such mitochondrial degeneration became severe at the postsymptomatic stage. In contrast, expansion of the mitochondrial inner‐membrane space was not evident even at the terminal stage. Microvacuoles of cytoplasm and fibrillar inclusions were rarely shown from the early symptomatic stage. WF mice showed expansion and vacuolation of the mitochondrial inner membrane space at old age. Non‐Tgs showed no obvious change in mitochondria. Gold‐labeled human SOD1 immunoreactivity showed small amount of gold deposits in the vacuolated mitochondria. These results suggest that the expansion and vacuolation of mitochondrial matrix in the spinal cord of DF‐homo transgenic mice is the first pathological change, but that it is not directly caused by the aggregation of an abnormal human SOD1 protein in intermembrane space of mitochondria.
Pathological examination of spinal lesions in meningeal carcinomatosis
Authors: Kizawa Mayuki , Mori N. , Hashizume Y. , Yoshida M.
Published: April 2008

For elucidation of the mechanism of spinal cord disorders associated with meningeal carcinomatosis, we investigated meningeal infiltration and parenchymal, vascular, and radicular damage in spinal cords subjected to pathological autopsy. Spinal cords were collected from 24 patients with a histopathological diagnosis of meningeal carcinomatosis. Infiltration from the subarachnoid space into the spinal cord occurred primarily along the perivascular tissue, and infiltration from the anterior median fissure to the anterior horn was found along the central artery in cases of marked meningeal dissemination. Meningeal dissemination was particularly evident with small cell carcinoma of lung, breast cancer and melanoma, and direct infiltration from the meninges into the spinal cord was found. Direct infiltration into the nerve roots was frequently observed, and infiltration was more evident in the dorsal roots than in the ventral roots, with loss of nerve fibers. Circular necrosis of the white matter in the periphery of the spinal cord was noted in cases of marked meningeal dissemination, which probably resulted from circulatory disturbance secondary to tumor infiltration. In cases of marked dorsal radiculopathy, there was secondary ascending degeneration of the posterior funiculus in cases of marked dorsal radiculopathy. These pathological changes associated with spinal cord disorders are important findings in reviewing spinal cord symptoms and radiographic findings in meningeal carcinomatosis.
Venous congestive myelopathy: Three autopsy cases showing a variety of clinicopathologic features
Authors: Matsuo Koushun , Kakita Akiyoshi , Ishizu Nobutaka , Endo Kohtaro , Watanabe Yumiko , Morita Takashi , Takahashi Hitoshi
Published: April 2008

We describe three patients with progressive myelopathy, in whom autopsy revealed spinal cord pathology compatible with that of venous congestive myelopathy (VCM) associated with dural arteriovenous fistula (AVF), formerly known as angiodysgenetic necrotizing myelopathy (Foix–Alajournine syndrome). In these three patients, common symptoms were gait disturbance and sensory disturbance of the extremities, and these symptoms slowly worsened. The clinical diagnoses varied and included spinal cord intramedullary tumor, cervical spondylosis and multiple sclerosis. At autopsy, all the patients showed enlarged, tortuous venous vessels on the dorsal surfaces of the spinal cord at the affected levels. In the affected spinal cord parenchyma, necrotic lesions manifested by various degrees of neuronal loss and gliosis, with increased numbers of hyalinized vessels, were evident. The presence or absence of associated spinal dural AVF could not be identified histopathologically. Even with the help of modern neurological examination methods, early and accurate clinical diagnosis of VCM is sometimes difficult. When encountering patients with progressive myelopathy, VCM, although recognized as rare, should be considered as an important differential diagnosis.
Riluzole blocks persistent Na+and Ca2+currents and modulates release of glutamate via presynaptic NMDA receptors on neonatal rat hypoglossal motoneuronsin vitro
Authors: Lamanauskas Nerijus , Nistri Andrea
Published: April 2008

The neuroprotective agent riluzole is used for the symptomatic treatment of motoneuron disease, which strongly affects the brainstem nucleus hypoglossus. The mechanism of action of riluzole was investigated using, as a model, patch‐clamp recording from hypoglossal motoneurons of the neonatal rat brainstem slice preparation. In the presence of riluzole (10 µm), theta‐rhythm oscillations evoked by nicotine continued even though the persistent inward current (comprising sodium and calcium components) was halved, but they disappeared when the high frequency of spontaneous glutamatergic currents waned. Riluzole fully inhibited the persistent sodium current and partly depressed a tetrodotoxin (TTX)‐insensitive slow current antagonized by Mn2+or Cd2+. Repetitive firing was inhibited by riluzole without changing single action potentials. In the presence of TTX, riluzole depressed miniature glutamatergic currents occurring at high rate. Synaptic transmission with low release probability became sensitive to riluzole if release was stimulated by high potassium solution. Miniature current frequency was depressed by the N‐methyl‐d‐aspartic acid (NMDA) receptor antagonistd‐amino‐phosphonovaleriate (50 µm), which fully occluded the action of riluzole. As riluzole is a protein kinase C (PKC) inhibitor, the PKC antagonist chelerythrine (2.5 µm) mimicked the effect of riluzole and prevented it. In summary, riluzole blocked the persistent sodium current fully, and the calcium one partly, plus it decreased glutamatergic transmission probably via inhibition of PKC that regulated presynaptic NMDA receptors having a facilitatory effect on glutamate release. Controlling NMDA receptor function and, thus, excitatory transmitter release via modulation of PKC suggests a novel potential target to contrast glutamate excitotoxicity in this motor nucleus.
Glomerular activation patterns and the perception of odor mixtures
Authors: Grossman Kimberly J. , Mallik Atul K. , Ross Jessica , Kay Leslie M. , Issa Naoum P.
Published: April 2008

Odor mixtures can produce several qualitatively different percepts; it is not known at which stage of processing these are determined. We asked if activity within the first stage of olfactory processing, the glomerular layer of the olfactory bulb, predicts odor mixture perception. We characterized how mice respond to components after training to five different mixture ratios of pentanal and hexanal, and found two types of responses: elemental perception and overshadowing. We then used intrinsic signal imaging to observe glomerular activity in response to the same mixtures and their components. As has been previously described, glomerular activity patterns produced by mixtures resemble the linear combination of responses to components. Mice trained to identify mixtures with more hexanal than pentanal recognized hexanal but not pentanal when the odorants were presented alone (overshadowing). Consistent with these behavioral responses, the imaged activity pattern in response to mixtures was similar to that produced to hexanal alone. Moreover, there was no significant effect of glomerular inhibition in the imaged response. In contrast, the glomerular activity patterns did not predict elemental perception: when trained to identify mixtures with more pentanal than hexanal, mice recognized both components equally well, even with highly overlapping activation patterns. This suggests that spatial activity patterns within the olfactory bulb are not always sufficient to specify component recognition in mixtures.
Secure Versus Fragile High Self‐Esteem as a Predictor of Verbal Defensiveness: Converging Findings Across Three Different Markers
Authors: Kernis Michael H. , Lakey Chad E. , Heppner Whitney L.
Published: April 2008

ABSTRACT
Why is it that many individuals verbally rationalize and distort self‐esteem threatening information? We examined whether such verbal defensiveness (Feldman Barrett, Williams, & Fong, 2002) differs as a function of whether individuals' high self‐esteem is secure or fragile. Our findings indicated that individuals whose self‐esteem was stable, not contingent, or congruent with high implicit self‐esteem exhibited especially low amounts of verbal defensiveness. In contrast, verbal defensiveness was considerably higher when individuals' high self‐esteem was unstable, contingent, or paired with discrepant low implicit self‐esteem. Discussion centers on why the possession of well‐anchored and secure high self‐esteem obviates defensiveness directed toward enhancing, maintaining, or bolstering feelings of self‐worth.
A possible mechanism for the beneficial effect of ethanol in essential tremor
Authors: Manto M. , Laute M.‐A.
Published: April 2008

Background: Essential tremor is one of the most common movement disorders in elderly people. The hypothesis of a disregulation ofN‐methyl‐d‐aspartate (NMDA) pathways has been suggested. It was shown experimentally that infusion of NMDA in cerebellar nuclei down‐regulates glutamate release.

Methods: We assessed the effects of intranuclear administration of harmaline on the NMDA‐mediated regulation of glutamate in rats using reverse dialysis. We hypothesized that ethanol, which improves essential tremor in the clinic, antagonizes the effect of harmaline upon glutamatergic transmission. We tested the interaction of ethanol and harmaline upon glycerol (a marker of membrane turn‐over), lactate, and pyruvate concentrations.

Results: Harmaline increased the concentrations of glutamate and impaired the NMDA‐mediated regulation of glutamate. Ethanol decreased the concentrations of glutamate during NMDA stimulation in case of pre‐administration with harmaline. Concentrations of glycerol rose with harmaline. Glycerol levels markedly decreased during NMDA infusion when inhibitors of nitric oxide synthase, α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate antagonists or NMDA antagonists were administered. Harmaline increased lactate/pyruvate ratios during NMDA infusion but these ratios returned to normal values in presence of ethanol.

Discussion: We provide a possible mechanism for the beneficial effect of ethanol on essential tremor. The concept of glutamatergic disregulation underlying essential tremor is highlighted. Consequences for our understanding of essential tremor are discussed.
Probation and Parole: Overworked, Misunderstood, and Under‐Appreciated: But Why?
Authors: PAPAROZZI MARIO , DEMICHELE MATTHEW
Published: April 2008

Abstract: Historically, the efficacy of probation and parole policies and practices have been judged by the general public, politicians, and many professional insiders by sensationalised crimes involving individuals sentenced to community supervision. The probation and parole profession has not established mechanisms to clearly articulate its public value; doing so would foster the development of policies and practices that derive more from empirical research evidence and sound theory than political faddism. The failure within the probation and parole profession to come to broad agreement regarding desired outcomes and to establish evidence‐based and/or theoretically‐sound professional principles has created a policy lacuna that is too often filled by elected officials who lack an understanding of the history, science, and philosophy of probation and parole. Probation and parole agencies should focus on producing publicly‐valued results and disseminating easily‐understood information that justifies their important niche within America's criminal justice system.
DEEP DIVISION IN THE CHLOROPHYCEAE (CHLOROPHYTA) REVEALED BY CHLOROPLAST PHYLOGENOMIC ANALYSES1
Authors: Turmel Monique , Brouard Jean‐Simon , Gagnon Cédric , Otis Christian , Lemieux Claude
Published: April 2008

The Chlorophyceae (sensu Mattox and Stewart) is a morphologically diverse class of the Chlorophyta displaying biflagellate and quadriflagellate motile cells with varying configurations of the flagellar apparatus. Phylogenetic analyses of 18S rDNA data and combined 18S and 26S rDNA data from a broad range of chlorophycean taxa uncovered five major monophyletic groups (Chlamydomonadales, Sphaeropleales, Oedogoniales, Chaetophorales, and Chaetopeltidales) but could not resolve their branching order. To gain insight into the interrelationships of these groups, we analyzed multiple genes encoded by the chloroplast genomes of Chlamydomonas reinhardtii P. A. Dang. and Chlamydomonas moewusii Gerloff (Chlamydomonadales), Scenedesmus obliquus (Turpin) Kütz. (Sphaeropleales), Oedogonium cardiacum Wittr. (Oedogoniales), Stigeoclonium helveticum Vischer (Chaetophorales), and Floydiella terrestris (Groover et Hofstetter) Friedl et O’Kelly (Chaetopeltidales). The C. moewusii, Oedogonium, and Floydiella chloroplast DNAs were partly sequenced using a random strategy. Trees were reconstructed from nucleotide and amino acid data sets derived from 44 protein‐coding genes of 11 chlorophytes and nine streptophytes as well as from 57 protein‐coding genes of the six chlorophycean taxa. All best trees identified two robustly supported major lineages within the Chlorophyceae: a clade uniting the Chlamydomonadales and Sphaeropleales, and a clade uniting the Oedogoniales, Chaetophorales, and Chaetopeltidales (OCC clade). This dichotomy is independently supported by molecular signatures in chloroplast genes, such as insertions/deletions and the distribution of trans‐spliced group II introns. Within the OCC clade, the sister relationship observed for the Chaetophorales and Chaetopeltidales is also strengthened by independent data. Character state reconstruction of basal body orientation allowed us to refine hypotheses regarding the evolution of the flagellar apparatus.
ISOLATION AND CHARACTERIZATION OF THE PHYTOENE DESATURASE GENE AS A POTENTIAL SELECTIVE MARKER FOR GENETIC ENGINEERING OF THE ASTAXANTHIN‐PRODUCING GREEN ALGA CHLORELLA ZOFINGIENSIS (CHLOROPHYTA)1
Authors: Huang Junchao , Liu Jin , Li Yantao , Chen Feng
Published: April 2008

Phytoene desaturase (PDS) is a rate‐limiting enzyme in carotenoid biosynthesis. Algal PDS is inhibited by some herbicides, leading to the bleaching of the cells due to destruction of chl. Specific point mutations in PDS confer resistance to the herbicide norflurazon, suggesting that mutated PDS could be used as a dominant selectable marker for genetic engineering of algae, for which very few selective markers are available. In this study, we report the isolation and characterization of the PDS gene from the astaxanthin‐producing green alga Chlorella zofingiensis Dönz. The open reading frame (ORF) of this PDS gene, interrupted by six introns, encoded a polypeptide of 558 amino acid residues. The deduced protein sequence showed significant homology to phytoene desaturases of algae, cyanobacteria, and higher plants. Expression of the PDS gene in Escherichia coli demonstrated that the enzyme was able to convert phytoene to ζ‐carotene. The PDS gene in Chlorella was shown to be up‐regulated by high light and glucose treatment. With a single amino acid change (L516R), the mutated PDS‐L516R was still active and exhibited ∼36‐fold greater resistance to the bleaching herbicide norflurazon than the unaltered enzyme. Thus, the modified PDS gene could be a useful tool for genetic engineering of carotenoid biosynthesis in C. zofingiensis and perhaps also in other algae.
Consistent, High‐Level Ethanol Consumption in Pig‐Tailed Macaques via a Multiple‐Session, Limited‐Intake, Oral Self‐Dosing Procedure
Authors: Weed Michael R. , Wilcox Kristin M. , Ator Nancy A. , Hienz Robert D.
Published: April 2008

Background: Alcohol abuse is a major public health burden that can lead to many adverse health effects such as impaired hepatic, gastrointestinal, central nervous system and immune system function. Preclinical animal models of alcohol abuse allow for experimental control over variables often difficult to control in human clinical studies (e.g., ethanol exposure before or during the study, history of other drug use, access to medical care, nutritional status, etc). Nonhuman primate models in particular provide increased genetic, anatomic and physiologic similarity to humans, relative to rodent models. A small percentage of macaques will spontaneously consume large quantities of ethanol; however, most nonhuman primate models of “voluntary” ethanol intake produce relatively low daily ethanol intake in the majority of monkeys.

Methods: To facilitate study of chronic exposure to high levels of ethanol intake, a macaque model has been developed that induces consistent, daily high‐level ethanol consumption. This multiple‐session procedure employed 4 drinking sessions per day, with sessions occurring once every 6 hours.

Results: The group average alcohol consumption was 4.6 g/kg/d (SEM 0.4), roughly twice the group average consumption of previous reports. Ethanol drinking sessions produced group mean blood ethanol levels of 95 mg/dl after 60 minutes, and fine motor control was impaired up to 90 minutes after a drinking session.

Conclusion: This model of multiple‐session, limited access, oral ethanol self‐dosing produced consistent, high‐level ethanol consumption with each session qualifying as a “binge” drinking session using the definition of “binge” provided by the NIAAA (>80 mg/dl/session). This model of ethanol drinking in macaques will be of great utility in the study of immunological, physiological and behavioral effects of ethanol in nonhuman primates.
No Role of Matrixmetalloproteinase‐3 Genetic Promoter Polymorphism 1171 as a Risk Factor for Cirrhosis in Alcoholic Liver Disease
Authors: Stickel Felix , Österreicher Christoph H. , Halangk Juliane , Berg Thomas , Homann Nils , Hellerbrand Claus , Patsenker Eleonora , Schneider Vreni , Kolb Armin , Friess Helmut , Schuppan Detlef , Puhl Gero , Seitz Helmut K. , Leathart Julian L. B. , Day Christopher P.
Published: April 2008

Background:  As only a minority of alcoholics develop cirrhosis, polymorphic genes, whose products are involved in fibrosis development were suggested to confer individual susceptibility. We tested whether a functional promoter polymorphism in the gene encoding matrix metalloproteinase‐3 (MMP‐3; 1171 5A/6A) was associated liver cirrhosis in alcoholics.

Methods:  Independent cohorts from the UK and Germany were studied. (i) UK cohort: 320 alcoholic cirrhotics and 183 heavy drinkers without liver damage and (ii) German cohort: 149 alcoholic cirrhotics, 220 alcoholic cirrhotics who underwent liver transplantation and 151 alcoholics without liver disease. Patients were genotyped for MMP‐3 variants by restriction fragment length polymorphism, single strand confirmation polymorphism, and direct sequencing. In addition, MMP‐3 transcript levels were correlated with MMP‐3 genotype in normal liver tissues.

Results:  Matrix metalloproteinase‐3 genotype and allele distribution in all 1023 alcoholic patients were in Hardy–Weinberg equilibrium. No significant differences in MMP‐3 genotype and allele frequencies were observed either between alcoholics with or without cirrhosis. There were no differences in hepatic mRNA transcription levels according to MMP‐3 genotype.

Conclusions:  Matrix metalloproteinase‐3 1171 promoter polymorphism plays no role in the genetic predisposition for liver cirrhosis in alcoholics. Stringently designed candidate gene association studies are required to exclude chance observations.
Tolerance to Disulfiram Induced by Chronic Alcohol Intake in the Rat
Authors: Tampier Lutske , Quintanilla María Elena , Israel Yedy
Published: April 2008

Background:  Disulfiram, an inhibitor of aldehyde dehydrogenase used in the treatment of alcoholism, is an effective medication when its intake is supervised by a third person. However, its therapeutic efficacy varies widely, in part due to the fact that disulfiram is a pro‐drug that requires its transformation into an active form and because it shows a wide range of secondary effects which often prevent the use of doses that ensure full therapeutic effectiveness. In this preclinical study in rats we report the development of tolerance to disulfiram induced by the chronic ingestion of ethanol, an additional source of variation for the actions of disulfiram with possible therapeutic significance, We also addresses the likely mechanism of this effect.

Methods:  Wistar‐derived rats bred for generations as high ethanol drinkers (UChB) were trained for either 3 days (Group A) or 30 days (Group B) to choose between ethanol (10% v/v) or water, which were freely available from 2 bottles on a 24‐hour basis. Subsequently, animals in both groups were administered disulfiram or cyanamide (another inhibitor of aldehyde dehydrogenase) and ethanol intake in this free choice paradigm was determined. Animals were also administered a standard dose of 1 g ethanol/kg (i.p) and arterial blood acetaldehyde was measured.

Results:  Disulfiram (12.5 and 25 mg/kg) and cyanamide (10 mg/kg) markedly inhibited ethanol intake (up to 60 to 70%) in animals that had ethanol access for only 3 days (Group A). However both drugs were inactive in inhibiting ethanol intake in animals that had consumed ethanol for 30 days (Group B). Following the injection of 1 g ethanol/kg, arterial blood acetaldehyde levels reached levels of 150 and 300 μM for disulfiram and cyanamide respectively, values which were virtually identical regardless of the length of prior ethanol intake of the animals.

Conclusions:  Chronic ethanol intake in high‐drinker rats leads to marked tolerance to the aversive effects of disulfiram and cyanamide on ethanol intake despite the presence of consistently high levels of blood acetaldehyde. These findings may have implications for the use of disulfiram for the treatment of alcoholism in humans.
Validity of the Obsessive Compulsive Drinking Scale in a Heavy Drinking Population
Authors: Connor Jason P. , Jack Alyssa , Feeney Gerald F.X. , Young Ross McD.
Published: April 2008

Background:  The Obsessive Compulsive Drinking Scale [OCDS; Anton et al., Alcohol Clin Exp Res 19 (1995), 92] is the most widely used measure of alcohol craving. There are no studies which comprehensively investigate the construct and concurrent validity of the OCDS in a severe alcohol dependent population.

Methods:  Three hundred and seventy alcohol‐dependent patients were referred to a hospital‐based alcohol treatment program. All participants completed the OCDS, the Alcohol Use Disorders Identification Test [AUDIT; Saunders et al., Addiction 88 (1993), 791] and provided demographic and alcohol consumption data.

Results:  The sample was randomly split into 2. Exploratory factor analysis and confirmatory factor analysis were conducted on these subsamples. Both analyses identified a 4‐factor solution (compulsions, interference, obsessions and resisting obsessions). All factors showed sound internal consistency. Neither the factor scores nor the total OCDS score was related to baseline alcohol problems (AUDIT) or consumption.

Conclusions:  There was some support for the construct validity of the OCDS in this clinical group. Concurrent validity of the scale was not supported by these cross‐sectional data. Future research should examine the predictive utility of the OCDS over time.
A Longitudinal Analysis of Alcohol Outlet Density and Assault
Authors: Livingston Michael
Published: April 2008

Background:  The majority of studies that have examined the local‐level relationship between alcohol outlet density and violence have utilized cross‐sectional data. These studies have consistently demonstrated that there is a spatial link between outlets and violence, but because of their design they have not been able to determine whether changes in outlet density result in changes in rates of violence. The few studies that have examined this question over time have found that the violence rates are related to changes in outlet density. This study provides further evidence of this link and examines the characteristics of regions in which changes in outlet density are most strongly associated with changes in violence rates.

Methods:  The study examined 9 years of data measuring alcohol outlet density (using liquor licensing records) and alcohol‐related violence (using police recorded night‐time assaults) from 186 postcodes in the metropolitan area of Melbourne, Australia. The relationships between 3 types of alcohol outlet density and alcohol‐related violence were assessed using fixed‐effects models. The postcodes were then grouped into 5 clusters based on their socio‐demographic profile and separate fixed‐effects models were fitted to assess whether the relationships between outlets and violence differed based on the type of region being examined.

Results:  The initial models found overall positive relationships between all 3 types of alcohol outlets and violence. When separate models were developed for postcode clusters, they demonstrated that the link between outlet density and violence was significant in all neighborhood types, but the specific relationships varied substantially.

Conclusions:  Changes in the number of alcohol outlets in a community are linked to changes in the amount of violence the community experiences. This relationship varies across the clusters of suburbs examined, with packaged liquor outlets consistently associated with violence in suburban areas and general (hotel) and on‐premise (nightclubs, restaurants, and bars) licenses associated with violence in inner‐city and inner‐suburban areas.
Elevated Cerebrospinal Fluid Tau Protein Levels in Wernicke’s Encephalopathy
Authors: Matsushita Sachio , Miyakawa Tomohiro , Maesato Hitoshi , Matsui Toshifumi , Yokoyama Akira , Arai Hiroyuki , Higuchi Susumu , Kashima Haruo
Published: April 2008

Objective:  Limited neuronal cell loss is seen in the neuropathology of Wernicke’s encephalopathy (WE), but the extent of neuronal damage has not been well studied. Moreover, there is still a debate as to whether alcohol itself causes brain damage in humans. Although, it is difficult to examine the extent of neuronal damage in living patients, recent studies have revealed that total tau protein levels in the cerebrospinal fluid (CSF) reflect the rate of neuronal degeneration. Therefore, we hypothesized that the elevated CSF total tau in patients with WE was due to neuronal damage and thus we examined CSF total tau protein in patients with WE, as well as in those with alcohol withdrawal delirium (WD) and Korsakoff syndrome (KS). We also examined CSF total tau in nonalcohol dependent patients with Alzheimer’s disease (AD) as a disease control.

Methods:  CSF samples were obtained from 13 acute WE patients with alcohol dependence, 9 WD patients with alcohol dependence and 16 KS patients with alcohol dependence, and from 20 nonalcohol dependent AD patients. CSF was also obtained from 10 of the WE patients after their disease had progressed to the chronic stage. CSF tau protein levels in all samples were determined by sandwich enzyme‐linked immunosorbent assay. Tau phosphorylated at threonine 181 (p‐tau181) and amyloid β‐protein ending at amino acid 42 (Aβ42) in CSF were also determined for comparison between acute WE with AD.

Results:  Total tau was significantly elevated in acute WE and decreased on long‐term follow‐up, but was not elevated in WD or KS. The patterns of p‐tau181 and Aβ42 differed between acute WE and AD.

Conclusions:  Intense neuronal cell death occurs transiently in WE, and the mechanism differs from that in AD. Neuronal damage is generally unaccompanied in WD. These results suggest that CSF total tau is a useful biological marker for WE.
The Subjective, Rather Than the Disinhibiting, Effects of Alcohol Are Related to Binge Drinking
Authors: Rose Abigail Katherine , Grunsell Laura
Published: April 2008

Background:  Evidence suggests that alcohol‐related problems are associated with impulsivity and disinhibited behavior. Less certain is whether disinhibited behavior is due to an impulsive disposition or alcohol’s ability to disinhibit some people more than others. There are a range of disinhibited behaviors associated with alcohol, including excessive alcohol consumption, bingeing. The study tested whether nondependent alcohol bingers showed more disinhibition after placebo and/or alcohol relative to nonbingers and whether this was related to enhanced motivation to drink following a priming dose of alcohol.

Methods:  Twenty participants (10 bingers) attended the laboratory twice. Baseline measures included impulsivity, alcohol‐related cognitions, alcohol urge, and mood. Participants were preloaded with alcohol (male: 0.6 g/kg, female: 0.5 g/kg) and placebo (counterbalanced). After a 20‐minute rest, participants completed 2 impulsivity tasks (Two Choice & Time Estimation) separated by second urge and mood ratings.

Results:  Bingers did not show greater impulsivity characteristics but were more concerned about their drinking (p = 0.02) and ability to control drinking (p = 0.04). A priming effect was found: alcohol urge increased after alcohol but not placebo (p = 0.006). Bingers reported greater tolerance to the sedative (p = 0.05) and lightheaded (p = 0.04) effects of alcohol, relative to nonbingers. Binge status was not associated with impulsivity task performance, while preload type (alcohol/placebo) supported only marginal associations.

Conclusions:  Risk of binge drinking in nondependent individuals is not strongly affected by impulsive personality characteristics or alcohol’s ability to induce behavioral disinhibition. However, alcohol did lead to a priming effect and bingers were more tolerant to the sedative and lightheaded effects of alcohol relative to placebo. Risk of binge drinking is associated with the subjective effects of a priming dose of alcohol.
Anomalies of Left Coronary Artery Origin Affecting Surgical Repair of Hypoplastic Left Heart Syndrome and Shone Complex
Authors: Saroli Tania , Gelehrter Sarah , Gomez‐Fifer Carlen A , Van Der Velde Mary E , Bove Edward L , Ensing Gregory J
Published: April 2008

There has traditionally been less concern regarding coronary anomalies with left‐sided congenital heart lesions such as hypoplastic left heart syndrome (HLHS)
or Shone complex than with other lesions. However, coronary anomalies in this setting can profoundly affect surgical intervention, particularly when surgical repair involves the ascending aorta. We describe four patients with congenital left‐sided heart lesions in which left coronary artery (LCA) anomalies substantially affected intervention and outcome. In the first two cases, the coronary anomalies were not identified prospectively and resulted in surgical injury directly to the coronary or to its surrounding region. In the latter two cases, successful identification of the coronary anomaly preoperatively allowed for modification of surgical technique and/or intervention. We conclude that detailed coronary artery assessment should be part of the routine echocardiographic evaluation of congenital left‐sided heart lesions that require surgery.
Quantitative analysis of association between herpesviruses and bacterial pathogens in periodontitis
Authors: Saygun I. , Kubar A. , Şahin S. , Şener K. , Slots J.
Published: April 2008

Background and Objective:  The development of human periodontitis may depend upon cooperative interactions among herpesviruses, specific pathogenic bacteria and tissue‐destructive inflammatory mediators. This study sought to identify associations among human cytomegalovirus, Epstein–Barr virus and six putative periodontopathic bacteria in periodontitis lesions.

Material and Methods:  Fifteen periodontitis patients (nine with aggressive periodontitis and six with chronic periodontitis) and 15 periodontally normal subjects were included in the study. In each study subject, a microbiological sample was collected, using a curette, from the deepest periodontal probing depth of the dentition. A real‐time TaqMan® polymerase chain reaction assay was employed to determine the subgingival counts of human cytomegalovirus, Epstein–Barr virus, Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum and Campylobacter rectus. Statistical analysis was performed using the Student's t‐test, the Pearson correlation coefficient test and the single variable logistic regression test for odds ratio‐based risk calculation.

Results:  Human cytomegalovirus was detected in eight periodontitis lesions and in one normal periodontal site, Epstein–Barr virus was detected in nine periodontitis lesions and in two normal periodontal sites, and the study bacteria were detected in 6–15 periodontitis lesions and in 1–11 normal periodontal sites. Correlations were found between counts of human cytomegalovirus and Epstein–Barr virus, between counts of human cytomegalovirus and P. gingivalis, T. forsythia and C. rectus, and between counts of Epstein–Barr virus and P. gingivalis and T. forsythia. Human cytomegalovirus and Epstein–Barr virus counts were also positively associated with the level of periodontal attachment loss, probing pocket depth and gingival bleeding on probing.

Conclusion:  This study confirmed that periodontal human cytomegalovirus and Epstein–Barr virus are associated with major periodontopathic bacteria and with the severity of periodontal disease. The finding of abundant herpesviruses in periodontitis lesions redefines the pathogenic paradigm of the disease. Understanding the interplay between herpesviruses and specific bacterial species in the pathogenesis of periodontitis may form the basis for new approaches to preventing, reducing or delaying tissue breakdown from periodontal infections.
Going with the Flow: Trafficking‐Dependent and ‐Independent Regulation of Serotonin Transport
Authors: Steiner Jennifer A. , Carneiro Ana Marin D. , Blakely Randy D.
Published: April 2008

Antidepressant‐, cocaine‐ and 3,4‐methylenedioxymethamphetamine‐sensitive serotonin (5‐hydroxytryptamine, 5‐HT) transporters (SERTs) are expressed on presynaptic membranes of 5‐HT‐secreting neurons to provide efficient uptake of the biogenic amine after release. SERTs also support 5‐HT transport across platelet, placental, gastrointestinal and pulmonary membranes and thus play a critical role in central nervous system and peripheral nervous system 5‐HT signaling. SERTs are subject to multiple levels of posttranslational regulation that can rapidly alter 5‐HT uptake and clearance rates. Specific cell surface receptors are now known to regulate SERT trafficking and/or catalytic function, with pathways activating protein kinase C, protein kinase G and p38 mitogen‐activated protein kinase receiving the greatest attention. Remarkably, disease‐associated mutations in SERT not only impact basal SERT activity but also selectively impact one or more SERT regulatory pathway(s). In this review, we describe both trafficking‐dependent and trafficking‐independent modes of SERT regulation and also the suspected roles played in regulation by SERT‐associated proteins. Elucidation of the SERT ‘regulome’ provides important depth to our understanding of the likely origins of 5‐HT‐associated disorders and may help orient research to develop novel therapeutics.
S‐nitrosylated proteins of a medicinal CAM plant Kalanchoe pinnata– ribulose‐1,5‐bisphosphate carboxylase/oxygenase activity targeted for inhibition
Authors: Abat Jasmeet K. , Mattoo Autar K. , Deswal Renu
Published: April 2008

Nitric oxide (NO) is a signaling molecule that affects a myriad of processes in plants. However, the mechanistic details are limited. NO post‐translationally modifies proteins by S‐nitrosylation of cysteines. The soluble S‐nitrosoproteome of a medicinal, crassulacean acid metabolism (CAM) plant, Kalanchoe pinnata, was purified using the biotin switch technique. Nineteen targets were identified by MALDI‐TOF mass spectrometry, including proteins associated with carbon, nitrogen and sulfur metabolism, the cytoskeleton, stress and photosynthesis. Some were similar to those previously identified in Arabidopsis thaliana, but kinesin‐like protein, glycolate oxidase, putative UDP glucose 4‐epimerase and putative DNA topoisomerase II had not been identified as targets previously for any organism. In vitro and in vivo nitrosylation of ribulose‐1,5‐bisphosphate carboxylase/oxygenase (Rubisco), one of the targets, was confirmed by immunoblotting. Rubisco plays a central role in photosynthesis, and the effect of S‐nitrosylation on its enzymatic activity was determined using NaH14CO3. The NO‐releasing compound S‐nitrosoglutathione inhibited its activity in a dose‐dependent manner suggesting Rubisco inactivation by nitrosylation for the first time.
The Electrophoretic Deposition of Lanthanum Manganite Powders for a Cathode‐Supported Solid Oxide Fuel Cell in Planar and Tubular Configurations
Authors: Krkljuš Ivana , Branković Zorica , Đuriš Katarina , Vukotić Vesna , Branković Goran , Bernik Slavko
Published: April 2008

The purpose of this research was to obtain porous, high‐quality cathodes for solid oxide fuel cells in both planar and tubular shapes. To accomplish this, cathodic electrophoretic deposition of the LaMnO3powder (synthesized by the modified sol–gel method proposed by Pechini) was performed. The optimal sintering temperatures were 1200°C and 1300°C for the tubular and planar configurations, respectively. Single‐phase deposits with about 40% porosity were obtained in both configurations. The cathode quality was confirmed by depositing an electrolyte layer of YSZ. After the cosintering of both layers, an extremely dense electrolyte layer was obtained, and the cathode layer retained its high porosity.