bluuebunny/crossref_metadata_2025 huggingface dataset:
MRI Measurement of Granular Motion in a Rotating Drum
Authors: Kawaguchi Toshihiro , Tsutsumi Kenji , Tsuji Yutaka
Published: October 2006

It is generally difficult to measure the particle motion inside of dense granular flows or fluid‐particle flows. In the present paper, an MRI (Magnetic Resonance Imaging) technique is employed to measure the granular motion inside a rotating horizontal drum. A horizontal drum is half‐filled with a mixture of two different sizes of spherical particles, and is steadily rotated along its axis. A typical radial segregation phenomenon, i.e., smaller particles concentrate to the central part and larger particles distribute in the peripheral part, was observed in vertical cross sections. When a tapered drum was used, in addition to the radial segregation, an axial segregation was also observed. The effect of the inclination angle of the drum wall on the segregation phenomena was studied. Furthermore the effect of the rotational speed on the axial segregation phenomena was also studied.
Synthesis of single wall carbon nanotubes with defined 13C content
Authors: Kramberger C. , Löffler M. , Rümmeli M. , Grüneis A. , Schönfelder R. , Jost O. , Gemming T. , Pichler T. , Büchner B.
Published: October 2006

The synthesis of high quality isotope engineered SWCNT by means of laser ablation and the use of Pt‐Rh‐Re catalyst mixtures has been established. Optical absorption and Raman spectroscopy as well as transmission electron microscopy are utilized to characterize the obtained SWCNTs with regard to purity and yield. The absence of any ferromagnetic materials, as well as the remarkably low abundance of amorphous carbon renders this material ideal for magnetic studies. The controlled augmentation of 13C is conveniently confirmed by phonon softening and broadening observed in Raman spectroscopy. Isotope labelling at constant sample quality was achieved in the whole range from 1% 13C up to 98% 13C. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Precise, molecularly thin semiconductor shells: from nanotubes to nanocorrugated quantum systems
Authors: Prinz V. Ya.
Published: October 2006

This brief overview focuses on the fabrication methods and properties of semiconductor and metal nanoshells based on self‐rolling or buckling of strained ultrathin films. Previously, it was shown that thin epitaxial heterofilms (down to two monolayers for InGaAs/GaAs) can be controllably released from the substrates and converted into micro‐ and nanoshells, including tubes and corrugations. The diameter of the tubes obtained was down to 2 nm, and the period of the nanocorrugated systems was down to 10 nm. New results for quantum confinement in semiconductor and hybrid nanoshells and for fabrication of complex nanoshells are reported. Possible extension of this approach to the case of carbon shells is discussed. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Charge distribution of potassium intercalated Dy3N@C80 observed with core‐level and valence‐band photoemission
Authors: Shiozawa H. , Rauf H. , Grimm D. , Knupfer M. , Kalbac M. , Yang S. , Dunsch L. , Büchner B. , Pichler T.
Published: October 2006

A photoemission study of potassium intercalated trimetal‐nitride fullerene Dy3N@C80 is reported. A continuous electron doping to the carbon cage with increasing potassium intercalation levels is observed as shape changes in the carbon‐sensitive ultra‐violet photoemission spectrum. X‐ray photoemission shows that the valence electronic state of the trivalent Dy ions is not affected by the additional charge in the fullerene cage. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
In vitro evaluation of possible adverse effects of nanosized materials
Authors: Wick P. , Manser P. , Spohn P. , Bruinink A.
Published: October 2006

Nanoscaled materials, such as single walled carbon nanotubes (SWCNT), are increasingly used in a wide range of areas because of their unique characteristics. Presently, it is not clear to what extent these materials have an adverse effect if they are taken up by humans. Because of their dimensions and persistency, SWCNT have been compared with asbestos. In the present study, an in vitro system was used to compare the effects of SWCNT and asbestos. With the short term tests used, some similarities in the induced effects could be detected. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Cavity QED with a single QD inside an optical microcavity
Authors: Peter E. , Bloch J. , Martrou D. , Lemaître A. , Hours J. , Patriarche G. , Cavanna A. , Gérard J. M. , Laurent S. , Robert‐Philip I. , Senellart P.
Published: October 2006

To demonstrate strong coupling regime for a single quantum dot inside an optical microcavity, large oscillator strength quantum dots are needed. We show that quantum dots formed by the interface fluctuations of a thin GaAs quantum well are ideal systems for this purpose since they can present an oscillator strength larger than 100. By inserting a GaAs QD inside a state of the art microdisk microcavity, we demonstrate the strong coupling regime with a Rabi splitting of 400 µeV. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Towards a mid‐infrared polaron laser using InAs/GaAs self‐assembled quantum dots
Authors: Sauvage S. , Boucaud P. , Bras F. , Fishman G. , Ortéga J.‐M. , Gérard J.‐M. , Patriarche G. , Lemaître A.
Published: October 2006

A three level scheme based on S–P polaron intersublevel transitions in n‐doped InAs/GaAs self‐assembled quantum dots is proposed to obtain laser effect around 25 µm wavelength under optical pumping. Temperature dependence of the optical gain is theoretically analysed. Lasing effect is expected up to 300 K. To probe the T 2 decoherence time, one of the key parameter driving the laser performances, an optical Rabi oscillation experiment is performed on the pumping transition. Transmission variation is measured as a function of the pump pulse area and modelled by 2‐level optical Bloch equations considering inhomogeneous contributions. We show that the non‐monotonous population dependence and damping of the oscillation is only compatible with a T 2 ∼ 5 ps dephasing time, one order of magnitude longer than in quantum wells and one order of magnitude shorter than the 45 ps relaxation time of the S–P transition, demonstrating a non relaxation‐limited decoherence for the transition. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Growth of GaN quantum dots on nonpolar A ‐plane SiC by molecular‐beam epitaxy
Authors: Founta S. , Rol F. , Bellet‐Amalric E. , Sarigiannidou E. , Gayral B. , Moisson C. , Mariette H. , Daudin B.
Published: October 2006

We report on A ‐plane GaN quantum dots in AlN, grown on A ‐plane 6H SiC substrates by plasma‐assisted molecular‐beam epitaxy. AFM imaging revealed a strong alignment of the dots along the [1$ \bar 1 $00] direction that we correlated with the anisotropic morphology of the AlN buffer layer. A vertical correlation of these dots was evidenced by high resolution transmission electron microscopy on superlattice samples with an AlN spacer thickness of 5 nm. Time‐resolved spectroscopy performed on both C ‐plane and A ‐plane samples revealed much shorter radiative lifetimes for the A ‐plane dots, indicating a strong reduction of the internal electric field with respect to the one present in their C ‐plane counterparts. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Ultrafast emission under two‐photon excitation of biexcitons in CuCl quantum dots
Authors: Miyajima K. , Kagotani Y. , Saito S. , Ashida M. , Itoh T.
Published: October 2006

Time‐resolved photoluminescence spectra of biexcitons confined in CuCl quantum dots have been measured by means of an optical Kerr‐gate method. When the biexcitons are generated by resonant two‐photon excitation, a new ultrashort photoluminescence is observed. This result indicates that the resonant two‐photon excitation of the biexcitons induces a new transition process with a large optical nonlinearity which is characteristic for the direct generation. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Minimization of 𝓁2norm of the error signal in posicast input command shaping: a polynomial approach
Authors: Hurák Z. , Hromčík M. , Špiller M.
Published: October 2006

In this paper, design of a posicast input command shaper is formulated in discrete‐time domain as minimization of 𝓁2norm of the error sequence. This optimization task is solved by simple algebraic manipulation with polynomials, namely, solving two‐sided linear equations with polynomials and modular shift of a polynomial. Numerical examples are given to demonstrate properties of the optimal design in contrast with the classical Smith's design technique achieving complete cancellation of residual vibrations. Copyright © 2006 John Wiley & Sons, Ltd.
Quantifying spatial correlations in extinction risk for an aphid metapopulation
Authors: Hudgens Brian R.
Published: October 2006

Metapopulation persistence depends on dispersal offsetting local extinction risks. The mitigating power of dispersal to offset local extinction risks is substantially reduced if extinction risks are highly spatially correlated. Extinction risks are likely to be spatially correlated when mechanisms driving local extinction act on large spatial scales, such as climatic events or far‐ranging predators. In this paper I develop a method to quantify spatial correlations in local extinction risks within a region. I then show that colonies of the aphidAphis lugentiswithin clusters of their host plant,Senecio bigelovii, do not have strong spatial correlations in extinction risks, even though the primary mechanism for colony extinction is over‐predation by far‐ranging predators (ladybugs and syrphid flies). Consequently, dispersal potentially plays an important role offsetting local extinction. Aphids did experience a weak, but significantly positive correlation in extinction risk in one of the two years of this study as well as increasing extinction risks across all plant clusters in both years. These observations point to important gaps in our understanding of how population synchrony affects metapopulation persistence.
Is the law of reflux valid? Sweden, 1880-1913
Authors: HORTLUND PER
Published: October 2006

In the classical monetary debates, the Banking School held that notes would be equally demand-elastic whether supplied by many issuers or a single one. The Free Banking School held that notes would be less demand-elastic if supplied by a single issuer. These assertions have rarely, if ever, been subject to more stringent statistical testing. In this study the elastic properties of the note stock of the Swedish note banking system in 1880–95 is compared with those of the regime in 1904–13, when the Bank of Sweden held a note monopoly. Evidence suggests that notes did not become less elastic after monopolisation, thus lending support to the views of the Banking School.
Incidence and Predictors of Difficult and Impossible Mask Ventilation
Authors: Kheterpal Sachin , Han Richard , Tremper Kevin K. , Shanks Amy , Tait Alan R. , O’Reilly Michael , Ludwig Thomas A.
Published: October 2006

Background

Mask ventilation is an essential element of airway management that has rarely been studied as the primary outcome. The authors sought to determine the incidence and predictors of difficult and impossible mask ventilation.

Methods

A four-point scale to grade difficulty in performing mask ventilation (MV) is used at the authors' institution. They used a prospective, observational study to identify cases of grade 3 MV (inadequate, unstable, or requiring two providers), grade 4 MV (impossible to ventilate), and difficult intubation. Univariate and multivariate analyses of a variety of patient history and physical examination characteristics were used to establish risk factors for grade 3 and 4 MV.

Results

During a 24-month period, 22,660 attempts at MV were recorded. 313 cases (1.4%) of grade 3 MV, 37 cases (0.16%) of grade 4 MV, and 84 cases (0.37%) of grade 3 or 4 MV and difficult intubation were observed. Body mass index of 30 kg/m or greater, a beard, Mallampati classification III or IV, age of 57 yr or older, severely limited jaw protrusion, and snoring were identified as independent predictors for grade 3 MV. Snoring and thyromental distance of less than 6 cm were independent predictors for grade 4 MV. Limited or severely limited mandibular protrusion, abnormal neck anatomy, sleep apnea, snoring, and body mass index of 30 kg/m or greater were independent predictors of grade 3 or 4 MV and difficult intubation.

Conclusions

The authors observed the incidence of grade 3 MV to be 1.4%, similar to studies with the same definition of difficult MV. Presence of a beard is the only easily modifiable independent risk factor for difficult MV. The mandibular protrusion test may be an essential element of the airway examination.
Measurement of Carboxyhemoglobin and Methemoglobin by Pulse Oximetry
Authors: Barker Steven J. , Curry Jeremy , Redford Daniel , Morgan Scott
Published: October 2006

Background

A new eight-wavelength pulse oximeter is designed to measure methemoglobin and carboxyhemoglobin, in addition to the usual measurements of hemoglobin oxygen saturation and pulse rate. This study examines this device's ability to measure dyshemoglobins in human volunteers in whom controlled levels of methemoglobin and carboxyhemoglobin are induced.

Methods

Ten volunteers breathed 500 ppm carbon monoxide until their carboxyhemoglobin levels reached 15%, and 10 different volunteers received intravenous sodium nitrite, 300 mg, to induce methemoglobin. All were instrumented with arterial cannulas and six Masimo Rad-57 (Masimo Inc., Irvine, CA) pulse oximeter sensors. Arterial blood was analyzed by three laboratory CO-oximeters, and the resulting carboxyhemoglobin and methemoglobin measurements were compared with the corresponding pulse oximeter readings.

Results

The Rad-57 measured carboxyhemoglobin with an uncertainty of +/-2% within the range of 0-15%, and it measured methemoglobin with an uncertainty of 0.5% within the range of 0-12%.

Conclusion

The Masimo Rad-57 is the first commercially available pulse oximeter that can measure methemoglobin and carboxyhemoglobin, and it therefore represents an expansion of our oxygenation monitoring capability.
Recurrent Laryngeal Nerve Palsy after Anterior Cervical Spine Surgery
Authors: Audu Paul , Artz Greg , Scheid Sarah , Harrop James , Albert Todd , Vaccaro Alexander , Hilibrand Alan , Sharan Ashwini , Spiegal Joseph , Rosen Marc
Published: October 2006

Background

Vocal fold immobility (paresis or paralysis) from recurrent laryngeal nerve injury remains an important cause of morbidity after anterior cervical spine surgery. A maneuver involving endotracheal tube (ETT) cuff manipulation has been proposed to reduce its incidence. This study is a randomized, prospective, double-blind investigation to test the hypothesis that ETT cuff manipulation reduces the incidence of postoperative vocal fold immobility after anterior cervical spine surgery.

Methods

One hundred patients scheduled to undergo anterior cervical spine surgery were randomly assigned to one of two groups. After inducing general endotracheal anesthesia, patients in the intervention group had their ETT cuff pressures maintained at 20 mmHg or less. After placement of self-retaining retractors, the ETT cuff was deflated for 5 s and then reinflated. Patients in the control group had no further manipulation of their ETT once the cuff was inflated after intubation. Cuff pressures in both groups were recorded before skin incision (baseline) and after placement of self-retaining retractors (peak). Patients' vocal fold motion was evaluated by indirect laryngoscopy performed preoperatively and postoperatively. The examination was videotaped and reviewed by a blinded otolaryngologist. Postoperative vocal fold motion was graded as normal, paretic, or paralyzed.

Results

Complete data were available in 94 patients. The incidence of vocal fold paralysis was 3.2% (95% confidence interval, 0.7-9.4%). Cuff manipulation decreased ETT cuff pressure but did not reduce the incidence of vocal fold immobility (15.4% vs. 14.5%).

Conclusion

Endotracheal tube cuff deflation/reinflation and pressure adjustment do not reduce the incidence of vocal fold immobility in anterior cervical spine surgery.
Protective Ventilation Influences Systemic Inflammation after Esophagectomy
Authors: Michelet Pierre , D’Journo Xavier-Benoît , Roch Antoine , Doddoli Christophe , Marin Valerie , Papazian Laurent , Decamps Isabelle , Bregeon Fabienne , Thomas Pascal , Auffray Jean-Pierre
Published: October 2006

Background

Esophagectomy induces a systemic inflammatory response whose extent has been recognized as a predictive factor of postoperative respiratory morbidity. The aim of this study was to determine the effectiveness of a protective ventilatory strategy to reduce systemic inflammation in patients undergoing esophagectomy.

Methods

The authors prospectively investigated 52 patients undergoing planned esophagectomy for cancer. Patients were randomly assigned to a conventional ventilation strategy (n = 26; tidal volume of 9 ml/kg during two-lung and one-lung ventilation; no positive end-expiratory pressure) or a protective ventilation strategy (n = 26; tidal volume of 9 ml/kg during two-lung ventilation, reduced to 5 ml/kg during one-lung ventilation; positive end-expiratory pressure 5 cm H2O throughout the operative time).

Results

Plasmatic levels of interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor alpha were measured perioperatively and postoperatively. Pulmonary function and postoperative evolution were also evaluated. Patients who received protective strategy had lower blood levels of IL-1beta, IL-6, and IL-8 at the end of one-lung ventilation (0.24 [0.15-0.40] vs. 0.56 [0.38-0.89] pg/ml, P < 0.001; 91 [61-117] vs. 189 [127-294] pg/ml, P < 0.001; and 30 [22-45] vs. 49 [29-69] pg/ml, P < 0.05, respectively) and 18 h postoperatively (0.18 [0.13-0.30] vs. 0.43 [0.34-0.54] pg/ml, P < 0.001; 54 [36-89] vs. 116 [78-208] pg/ml, P < 0.001; 16 [11-24] vs. 35 [28-53] pg/ml, P < 0.001, respectively). Protective strategy resulted in higher oxygen partial pressure to inspired oxygen fraction ratio during one-lung ventilation and 1 h postoperatively and in a reduction of postoperative mechanical ventilation duration (115 +/- 38 vs. 171 +/- 57 min, P < 0.001).

Conclusion

A protective ventilatory strategy decreases the proinflammatory systemic response after esophagectomy, improves lung function, and results in earlier extubation.
No Sex Differences in Memory Formation during General Anesthesia
Authors: Stonell Christopher A. , Leslie Kate , He Cheng , Lee Leonard
Published: October 2006

Background

Women respond differently to anesthesia than men, initially recovering more rapidly, but having more postoperative morbidity. Studies on surgical patients report evidence of memory formation during anesthesia. However, sex differences in memory formation have not been explored. Therefore, the authors investigated sex differences in the implicit and explicit memory formation during general anesthesia.

Methods

With ethics committee approval, 120 consenting adult patients scheduled to undergo surgery during general anesthesia were recruited. Intraoperatively, 16 target words were presented to patients via headphones, and the Bispectral Index was recorded. Postoperatively, memory for presented words was tested using a word stem completion test. The test was divided into inclusion and exclusion parts, to delineate implicit and explicit memory contributions.

Results

Target and distracter hit rates were similar in men and women. For the whole study group, there was a significant difference between inclusion target hit rate (0.42) and base hit rate (0.39) (P = 0.01). Buchner's model suggested that this memory formation was attributable to both implicit and explicit memory. A Bispectral Index value greater than 50 was the only significant predictor of inclusion target hit rate. None of the patients were able to consciously recall the words presented during surgery.

Conclusions

Patients showed greater memory performance for words presented during general anesthesia than for words not presented. However, sex differences in memory formation were not observed. A relation between hypnotic state and memory during sevoflurane anesthesia was also established, suggesting that memory formation is possible even at hypnotic depths considered to be adequate anesthesia.
Effects of Desflurane in Senescent Rat Myocardium
Authors: Rozenberg Sandrine , Besse Sophie , Amour Julien , Vivien Benoît , Tavernier Benoît , Riou Bruno
Published: October 2006

Background

The myocardial negative inotropic effects of desflurane are less pronounced than those of other halogenated anesthetics, partly because of intramyocardial catecholamine store release. However, the effects of desflurane on aging myocardium are unknown, whereas aging is known to be associated with an attenuation of catecholamine responsiveness.

Methods

The effects of desflurane (1.9-9.3 vol%) were studied in left ventricular papillary muscle of adult and senescent rats (29 degrees C; 0.5 mm Ca; stimulation frequency 12 pulses/min). The inotropic effects were compared under low and high loads, using the maximum unloaded shortening velocity and maximum isometric active force, and without or with alpha- and beta-adrenoceptor blockade.

Results

Desflurane induced a moderate positive inotropic effect in adult rats but a negative inotropic effect in senescent rats. After alpha- and beta-adrenoceptor blockade, desflurane induced a comparable negative inotropic effect in adult and senescent rats. No lusitropic effect under low load was observed, whereas desflurane induced a slight but significant positive lusitropic effect under high load similar between the two groups of rats. This positive effect was abolished by adrenoceptor blockade.

Conclusion

The authors' study suggests that desflurane does not induce significant intramyocardial catecholamine release in senescent myocardium, a result that should be integrated in the well-known alteration in the catecholamine response during aging.
Store-operated Ca2+Influx in Airway Smooth Muscle
Authors: Prakash Y S. , Iyanoye Adeyemi , Ay Binnaz , Sieck Gary C. , Pabelick Christina M.
Published: October 2006

Background

Volatile anesthetics produce bronchodilation in part by depleting sarcoplasmic reticulum Ca stores in airway smooth muscle (ASM). Other bronchodilatory drugs are known to act via cyclic nucleotides (cyclic adenosine 3',5'-cyclic monophosphate, cyclic guanosine 3',5'-cyclic monophosphate). Intracellular Ca regulation in ASM involves plasma membrane Ca influx, including that triggered by sarcoplasmic reticulum Ca depletion (store-operated Ca entry [SOCE]). The authors hypothesized that anesthetics and bronchodilatory agents interact in inhibiting SOCE, thus enhancing ASM relaxation.

Methods

In enzymatically dissociated porcine ASM cells imaged using fluorescence microscopy, sarcoplasmic reticulum Ca was depleted by 1 microm cyclopiazonic acid in 0 extracellular Ca, nifedipine, and potassium chloride (preventing Ca influx through L-type channels and SOCE). Extracellular Ca was rapidly reintroduced to selectively activate SOCE in the presence or absence of 1 minimum alveolar concentration (MAC) halothane, isoflurane, or sevoflurane. Anesthetic interference with SOCE regulation by cyclic nucleotides was examined by activating SOCE in the presence of (1) 1 microm acetylcholine, (2) 100 microm dibutryl cyclic adenosine 3',5'-cyclic monophosphate, or (3) 100 microm 8-bromo-cyclic guanosine 3',5'-cyclic monophosphate.

Results

SOCE was enhanced by acetylcholine, whereas volatile anesthetics and both cyclic nucleotides partially inhibited Ca influx. Preexposure to 1 or 2 MAC anesthetic (halothane > isoflurane > sevoflurane) inhibited SOCE. Only halothane and isoflurane inhibited acetylcholine-induced augmentation of Ca influx, and significantly potentiated cyclic nucleotide inhibition such that no influx was observed in the presence of anesthetics and cyclic nucleotides.

Conclusions

These data indicate that volatile anesthetics prevent sarcoplasmic reticulum refilling by inhibiting SOCE and enhancing cyclic nucleotide blunting of Ca influx in ASM. Such interactions likely result in substantial airway relaxation in the presence of both anesthetics and bronchodilatory agents such as beta agonists or nitric oxide.
Risk factors for alcoholic liver disease
Authors: Bellentani Stefano , Saccoccio Gioconda , Masutti Flora , Giacca Mauro , Miglioli Lucia , Monzoni Adriana , Tiribelli Claudio
Published: October 2006

Alcoholic liver disease (ALD) is still a frequent disorder, even though its incidence appears to be decreasing. In spite of intense investigation, the precise mechanisms leading to ALD are still imprecisely known. This is due in part to the lack of a reliable animal model; in part to the difficulty of obtaining clinical data of adequate sample size and derived from unblased populations and finally from the lack of uniformity of the criteria used to define ALD. This paper will review what is known of the various pieces of this puzzle, with particular emphasis not only on the total amount of alcohol consumed, but also on drinking patterns and type of alcoholic beverage ingested. The other potential factors such as age, gender, genetic background, nutritional status, occupational hazards and viral diseases (especially HCV infection) will be touched upon.
Chronic dopaminergic signaling in the basal ganglia: a damage perspective on kinases and fos‐related antigens
Authors: O'Callaghan James P. , Miller Diane B. , Pennypacker Keith R.
Published: October 2006

Specific protein phosphorylation pathways have been shown to play a role in cellular adaptation responses underlying addiction to psychostimulants such as methamphetamine and cocaine. Transcriptional regulation through fos‐related antigens constitutes one element through which these dopaminergic agonists exert their persistent actions. In addition to their addictive properties, amphetamines are known to damage dopaminergic nerve terminals. Although not widely appreciated, protein phosphorylation cascades and fos‐related antigens also may play a role in the neurotoxic actions of substituted amphetamines such as methamphetamine. Here we document the involvement of the dopaminoceptive phosphoprotein, DARPP‐32, the fos‐related antigen, FRA‐2, and the growth associated protein kinase, MAP kinase, in the neurotoxic action of known dopaminergic neurotoxicants, including methamphetamine. The addictive and neurotoxic properties of psychostimulants may share some molecular signaling mechanisms.
NAALADase inhibition reduces alcohol consumption in the alcohol‐preferring (P) line of rats
Authors: McKinzie D. L. , Li T.‐K. , McBride W. J. , Slusher B. S.
Published: October 2006

N‐acetyl‐aspartyl‐glutamate (NAAG) is a major peptide component of the brain, with millimolar tissue levels of 0.1–5 nmol/mg wet weight. NAAG is hydrolyzed by the enzyme N‐acetylated alpha‐linked acidic dipeptidase (NAALADase; glutamate carboxypeptidase II; EC no. 3.4.17.21) to N‐acetyl‐aspartate (NAA) and glutamate. Recently, a potent and selective NAALADase inhibitor termed 2‐(phosphonomethyl)pentanedioic acid (2‐PMPA) was identified that has a 300 pM Ki for NAALADase inhibition. Given the accumulating evidence indicating an important role of the glutamate system in alcoholism and dependence, the objective of this study was to evaluate the effects of systemic administration of 2‐PMPA (50, 100 and 200 mg/kg; i.p.) upon the ethanol intakes of alcohol‐preferring (P) rats. Female P rats (n = 8) received daily 1‐hour scheduled access to a 10% (v/v) ethanol. In a within‐subjects design, 2‐PMPA treatments were tested once a week. Baseline ethanol drinking consisted of the mean of the 3 days prior to testing in which saline injections were given. Results indicated that, whereas the 200 mg/kg dose of 2‐PMPA had no effect on ethanol intake, both the 50 and 100 mg/kg doses significantly reduced ethanol consumption by approximately 25% (p< 0.05) during the 1‐hour access period. Body weights and 24‐hour water intakes were not altered at any of the doses. These data suggest that the NAAG/NAALADase system may be involved in neuronal systems regulating alcohol‐drinking behavior.
The dopamine D2 receptor (DRD2) gene–a genetic risk factor in heavy smoking?
Authors: Batra Anil , Gelfort Gisbert , Bartels Mathias , Smoltczyk Hanna , Buchkremer Gerhard , Riess Olaf , Schöls Ludger
Published: October 2006

Indications of a genetic predisposition to nicotine dependence have been derived from numerous epidemiological data and from individual genetic studies suggesting the involvement of the dopaminergic D2 receptor. Previous association studies defined the TaqlA polymorphism as a risk factor for addiction, in particular for alcoholism and tobacco dependence. Results of investigations into this polymorphism in 110 severely addicted smokers and a control group of 60 population‐matched German non‐smokers did not support these findings. However, our results indicate an association between the DRD2‐Fokl‐1 allele and the onset and intensity of smoking.
REVIEW: Non‐human primate models of inheritance vulnerability to alcohol use disorders
Authors: Barr Christina S. , Goldman David
Published: October 2006

Many animal species have been used to model certain aspects of alcohol use and addiction. However, there are complex behavioral and social features of alcohol use disorders that are not easily modeled in animal species. This review considers both the limitations and advantages of using a non‐human primate to model alcohol use disorders and discusses how non‐human primates can be particularly useful for studying how genetic variants interact with social factors, temperament and alcohol response as motivating factors for alcohol consumption and abstinence. Genetic variants in rhesus macaques (Macaca mulatta) that are functionally equivalent to those increasing addiction vulnerability in humans influence temperament, stress reactivity and alcohol response in addition to voluntary alcohol consumption. Non‐human primate models may also have translational value for understanding of how variants within addiction and abuse vulnerability genes influence alcohol‐induced neuroadaptation, neuropathology and treatment response.
PRECLINICAL STUDY: Ghrelin stimulates locomotor activity and accumbal dopamine‐overflow via central cholinergic systems in mice: implications for its involvement in brain reward
Authors: Jerlhag Elisabet , Egecioglu Emil , Dickson Suzanne L. , Andersson Malin , Svensson Lennart , Engel Jörgen A.
Published: October 2006

It is becoming increasingly apparent that there is a degree of neurochemical overlap between the reward systems and those regulating energy balance. We therefore investigated whether ghrelin, a stomach‐derived and centrally derived orexigenic peptide, might act on the reward systems. Central ghrelin administration (1 µg/µL, to the third ventricle) induced an acute increase in locomotor activity as well as dopamine‐overflow in the nucleus accumbens, suggesting that ghrelin can activate the mesoaccumbal dopamine system originating in the ventral tegmental area, a system associated with reward and motivated behaviour. The cholinergic afferents to the ventral tegmental area have been implicated in natural reward and in regulating mesoaccumbal dopamine neurons. The possibility that nicotinic receptors are involved in mediating the stimulatory and dopamine‐enhancing effects of ghrelin is supported by the findings that peripheral injection of the unselective nicotinic antagonist mecamylamine (2.0 mg/kg) blocked these ghrelin‐induced effects. Tentatively, ghrelin may, via activation of the acetylcholine–dopamine reward link, increase the incentive values of signals associated with motivated behaviours of importance for survival such as feeding behaviour. It will be important to discover whether this has therapeutic implications for compulsive addictive behaviours, such as eating behaviour disorders and drug dependence.
GENETIC STUDY: Analysis of variations in the tryptophan hydroxylase‐2 (TPH2) gene in cocaine dependence
Authors: Dahl John P. , Cubells Joseph F. , Ray Riju , Weller Andrew E. , Lohoff Falk W. , Ferraro Thomas N. , Oslin David W. , Kampman Kyle M. , Dackis Charles , Tang Yilang , Gelernter Joel , Kranzler Henry R. , O’Brien Charles P. , Berrettini Wade H.
Published: October 2006

While the exact physiological mechanisms underlying cocaine dependence remain unclear, a growing body of evidence indicates a role for the serotonergic neurotransmitter system in the pathology of this substance use disorder. The focus of the present study is to determine whether genetic variation in the tryptophan hydroxylase‐2 (TPH2) gene, which encodes the enzyme responsible for synthesis of the majority of the serotonin contained in neurons of the central nervous system, contributes to the pathophysiology of cocaine dependence. To examine this hypothesis, we used a case–control study design in which the genotype and allele distributions for six single nucleotide polymorphisms (SNPs) in the TPH2 gene were compared between cocaine‐dependent (n = 299) and control individuals (n = 208) of African descent. The results indicate that none of the SNPs in the TPH2 gene examined in this study associate with the cocaine‐dependent phenotype. This work suggests that variations in the TPH2 gene are not a risk factor for the development of cocaine dependence, but these findings require confirmation in larger, independent samples of cocaine‐dependent and control subjects.
CLINICAL AND IMAGING STUDY: Enhanced cue‐elicited brain activation in African American compared with Caucasian smokers: an fMRI study
Authors: Okuyemi Kolawole S. , Powell Joshua N. , Savage Cary R. , Hall Sandra B. , Nollen Nicole , Holsen Laura M. , McClernon F. Joseph , Ahluwalia Jasjit S.
Published: October 2006

Current evidence indicates that, although African Americans (AA) are more likely to attempt to quit smoking than Caucasians (CC) in any given year, success rates are lower for AA. However, factors contributing to these differences are not well known. In order to explore potential factors, this study assessed differences in attention to smoking cues between ethnic groups. Participants underwent morning functional magnetic resonance imaging scanning while viewing images of AA models and CC models who were either smoking (smoking cues) or engaging in everyday activities (neutral cues), interspersed with a fixation baseline period. The study was conducted at the Hoglund Brain Imaging Center of the University of Kansas Medical Center in Kansas City, KS. We studied 17 smokers (eight AA, nine CC) after 12‐hour abstinence and 17 non‐smokers (eight AA, nine CC) matched by age, gender, years of education, and handedness. The AA and CC smoking groups were also matched for number of cigarettes smoked per day. All results are P < 0.01, corrected for whole brain. There was a strong ethnicity by condition interaction among smokers in several a priori regions of interest. AA smokers showed a greater increase in response to smoking (versus neutral cues) than CC smokers in the medial prefrontal cortex, right lateral orbitofrontal cortex, and bilateral ventrolateral prefrontal cortex. In smoking versus baseline contrasts, additional areas of greater activation were found in AA, including the right amygdala and left caudate nucleus. No significant differences in cue‐elicited brain activation were found between AA and CC non‐smokers. These preliminary findings demonstrate variation in brain activation in response to smoking cues between AA and CC smokers in structures known to be associated with nicotine addiction. Differences in neural response may reflect fundamental differences in attention to smoking cues, which may in turn contribute to differences in effectiveness of nicotine dependence treatments among ethnic populations.
GENETIC STUDY: The polymorphism GABABR1 T1974C	[rs29230] of the GABAB receptor gene is not associated with the diagnosis of alcoholism or alcohol withdrawal seizures
Authors: Köhnke Michael , Schick Sandra , Lutz Ulrich , Köhnke Annette , Vonthein Reinhard , Kolb Werner , Batra Anil
Published: October 2006

As the inhibitory neurotransmitter gamma aminobutyric acid (GABA) modulates ethanol consumption, alcohol withdrawal symptoms and seizure generation by interacting with the GABAB receptor, the genes encoding for the GABAB receptor can be considered as candidate genes for alcoholism and alcohol withdrawal seizures (AWS). As the polymorphism GABABR1 T1974C[rs29230] of the GABAB receptor gene had been associated with alcoholism and EEG abnormalities in prior studies, the present examination investigated if the polymorphism is associated with the diagnosis of alcoholism or AWS. After genotyping the allele and genotype frequencies of a group of alcoholics with a history of AWS (n = 69) were compared with the results of a group of alcoholics with only mild withdrawal symptoms (n = 97). Additionally a group of healthy controls (n = 101) was compared with individuals with the diagnosis of alcoholism (n = 220). As no significant differences were found between the compared groups, this study gave no further evidence for GABABR1 T1974C[rs29230] as a candidate for alcoholism or AWS.
CLINICAL STUDY: Fluctuations in (R,S)‐methadone pharmacokinetics and response among long‐term methadone maintenance patients
Authors: Mitchell Timothy B. , Dyer Kyle R. , Newcombe David , Somogyi Andrew A. , White Jason M.
Published: October 2006

Knowledge of how methadone disposition may fluctuate during the course of maintenance treatment is presently limited. This study investigated long‐term fluctuations in methadone pharmacokinetics in five methadone maintenance patients who participated in two 24‐hour testing sessions separated by at least one year. Results indicated substantial fluctuations between sessions in dose‐corrected average steady‐state plasma (R)‐methadone concentrations (Cav), ranging from a 51% decrease to a 466% increase. These fluctuations were not consistently associated with changes in methadone dose or self‐reported withdrawal status. The plasma (S)‐:(R)‐methadone Cav ratio increased significantly (12%, P = 0.04) between the sessions, suggesting a different pattern of long‐term change in the pharmacokinetics of each enantiomer over time. The pronounced and variable fluctuations in methadone disposition evident in these patients highlight the need for an individualized approach to patient dosing and monitoring.
PRECLINICAL STUDY: Effects of aqueous, methanolic and chloroform extracts of rhizome and aerial parts of Valeriana officinalis L. on naloxone‐induced jumping in morphine‐dependent mice
Authors: Sharifzadeh Mohammad , Hadjiakhoondi Abbas , Khanavi Mahnaz , Susanabadi Maryam
Published: October 2006

In the present study, the effects of rhizomes and aerial parts extracts of Valeriana officinalis L. on morphine dependence in mice have been investigated. Animals were treated subcutaneously with morphine (50, 50 and 75 mg/kg) three times daily (10 am, 1 pm and 4 pm) for 3 days, and a last dose of morphine (50 mg/kg) was administered on the fourth day. Withdrawal syndrome (jumping) was precipitated by naloxone (5 mg/kg) which was administered intraperitoneally 2 hours after the last dose of morphine. To study the effects of the aqueous, methanolic and chloroform extracts of both aerial parts and rhizome of the V. officinalis L. on naloxone‐induced jumping in morphine‐dependent animals, 10 injections of morphine (three administrations each day) for dependence and a dose of 5 mg/kg of naloxone for withdrawal induction were employed. Intraperitoneal injection of different doses (1, 5, 25 and 50 mg/kg) of aqueous, methanolic and chloroform extracts of the rhizome of V. officinalis L. 60 minutes before naloxone injection decreased the jumping response dose‐dependently. Pre‐treatment of animals with different doses (1, 5, 25, 50 and 100 mg/kg) of aqueous and methanolic extracts of aerial parts of V. officinalis L. 60 minutes before naloxone injection caused a significant decrease on naloxone‐induced jumping. The chloroform extract of the aerial parts of V. officinalis L. did not show any significant changes on jumping response in morphine‐dependent animals. It is concluded that the extracts of V. officinalis L. could affect morphine withdrawal syndrome via possible interactions with inhibitory neurotransmitters in nervous system.
PRECLINICAL STUDY: Different effects of chronic phencyclidine on brain‐derived neurotrophic factor in neonatal and adult rat brains
Authors: Semba Jun’ichi , Wakuta Maki , Suhara Tetsuya
Published: October 2006

The N‐methyl‐D‐aspartate (NMDA) receptor and brain‐derived neurotrophic factor (BDNF) are both known to play major roles in the normal development of the brain. We have hypothesized that the chronic blockade of NMDA with phencyclidine (PCP) may have a different effect on BDNF synthesis at different stages of development. In an acute experiment, rat pups and adult rats were injected with PCP (2.5, 5 or 10 mg/kg) at postnatal day (PD) 15 or 49, respectively. In a chronic experiment, rat pups were injected daily from PD 5 to PD 14 with PCP (2.5, 5 or 10 mg/kg), while adult rats were injected daily with the same dose from PD 39 to PD 48. BDNF levels in the hippocampus, striatum and frontal cortex were determined by ELISA assay 24 hours after the last injection. Chronic PCP treatment of neonatal rats induced a dose‐dependent decrease in BDNF in the hippocampus but not in the frontal cortex and striatum. Single injection of PCP to rat pups showed a slight reduction of BDNF in the hippocampus but only at higher doses. In contrast to neonatal brain, neither acute nor chronic injection of PCP influenced BDNF in adult brain. These findings suggest that chronic blockade of NMDA receptor in the early neonatal period has an inhibitory effect on BDNF synthesis in the hippocampus and may impair normal neurodevelopment in rat pups.
REVIEW: Genetically selected Marchigian Sardinian alcohol‐preferring (msP) rats: an animal model to study the neurobiology of alcoholism
Authors: Ciccocioppo Roberto , Economidou Daina , Cippitelli Andrea , Cucculelli Marino , Ubaldi Massimo , Soverchia Laura , Lourdusamy Anbarasu , Massi Maurizio
Published: October 2006

The present article provides an up‐to‐date review summarizing almost 18 years of research in genetically selected Marchigian Sardinian alcohol‐preferring (msP) rats. The results of this work demonstrate that msP rats have natural preference for ethanol characterized by a spontaneous binge‐type of drinking that leads to pharmacologically significant blood ethanol levels. This rat line is highly vulnerable to relapse and presentation of stimuli predictive of alcohol availability or foot‐shock stress can reinstate extinguished drug‐seeking up to 8 months from the last alcohol experience. The msP rat is highly sensitive to stress, shows an anxious phenotype and has depressive‐like symptoms that recover following ethanol drinking. Interestingly, these animals have an up‐regulated corticotrophin releasing factor (CRF) receptor 1 system. Clinical studies have shown that alcoholic patients often drink ethanol in the attempt to self‐medicate from negative affective states and to search for anxiety relief. We propose that msP rats represent an animal model that largely mimics the human alcoholic population that due to poor ability to engage in stress‐coping strategies drink ethanol as a tension relief strategy and for self‐medication purposes.
REVIEW: Modulation of high alcohol drinking in the inbred Fawn–Hooded (FH/Wjd) rat strain: implications for treatment
Authors: Overstreet David H. , Rezvani Amir H. , Cowen Michael , Chen Feng , Lawrence Andrew J.
Published: October 2006

The Fawn–Hooded rat (FH/Wjd) is an inbred alcohol‐preferring rat strain, unlike most of the other strains that were selectively bred for high alcohol intake and preference. It was chosen for study some 16 years ago because of a reported mutation that disrupted platelet serotonin function. Although the FH/Wjd rat has high alcohol intake (>5 g/kg/day) and preference (>65%), interbreeding with an alcohol‐non‐preferring inbred strain suggested that these measures are unrelated to the serotonin abnormality. Similarly, the exaggerated immobility of the FH/Wjd rats in the forced swim test did not correlate with the high alcohol intake. Many compounds have been tested in the FH/Wjd rats after both acute and chronic treatment and a substantial number of them have proved effective. However, as the case with opiate antagonists, tolerance to the effects of the drug can develop. An up‐regulation of opioid receptors accompanied the chronic treatment and this mechanism may account for the development of tolerance. Tolerance to opiate antagonists has also been demonstrated in two of the selectively bred alcohol‐preferring rat lines, but it is unknown whether this process may contribute to the relapses seen in individuals being treated with naltrexone. Other drugs that reliably decrease alcohol intake in the FH/Wjd rats include the 5‐hydroxytryptamine‐2A receptor antagonist, amperozide, the mGlu5 receptor antagonist 3‐[(2‐methyl‐1,3‐thiazol‐4‐yl)ethynyl]pyridine (MTEP) and herbal derivatives such as ibogaine, St. John’s wort and kudzu extract. Thus, studies in the FH/Wjd rat have led to the discovery of a wide variety of targets for the development of novel agents to treat alcoholism. The fact that several of these drugs were shown to reduce alcohol intake in some of the selectively bred alcohol‐preferring rat lines and/or alcohol‐preferring vervet monkeys increases our confidence that they are good candidates for further development.
Response of onion (Allium cepa L.) plants to fertilizers, weed competition duration, and planting times in the central Jordan Valley
Authors: QASEM JAMAL R.
Published: October 2006

The competitive ability of onion with weeds and the effects of weeds on onion crop growth and yield were investigated in three field experiments carried out in the central Jordan Valley during the 1997–1998 growing season. Fertilizer application to the onion plants in the presence of weeds significantly lowered the onion yield and reduced the bulb diameter, compared to the unfertilized, weed‐infested onion crop. Weed competition and onion yield reduction increased with an increase in the fertilizer rate. All weed‐free treatments with or without fertilizer gave a significantly higher onion yield than any of the fertilized, weedy plots. The highest yield of onion was obtained from the weed‐free plots with a moderate application of fertilizer. Weed competition reduced the growth, bulb yield, and size of onion in the plots established from bulbs, seedlings, and seeds when compared to the relevant weed‐free controls. The effect increased with competition duration and was more pronounced in direct‐seeded onion than in the other two types of planting material. However, onion grown from bulbs or seedlings gave better growth, bulb weight, and number and was more competitive than the direct‐seeded onion. The results showed that the minimum number of days of weed competition needed for a significant reduction in onion growth was 42 days when propagated from bulbs or seedlings and 21 days after direct‐seeding. Onion grown from bulbs tolerated weed competition better and produced a higher bulb yield than that obtained from direct‐seeded or transplanted onion, irrespective of the planting dates. December was found to be the best planting time for onion that was grown from bulbs and seedlings, while November was the best planting time for direct‐seeded onion, provided the plots were weed‐free throughout the growing season.