bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of an additional supraspinal component to the analgesic mechanism of action of buprenorphine
Authors: Ding Zhe , Raffa Robert B 
Published: April 2009

Background and purpose: Buprenorphine displays attributes of opioids, but also some features distinct from them. We examined spinal and supraspinal signal transduction of buprenorphine‐induced anti‐nociception in mice compared with morphine and fentanyl.Experimental approach: The opioid receptor antagonist naloxone,Pertussistoxin (PTX), Gzprotein antisense and nociceptin/orphanin‐FQ receptor agonist nociceptin, and antagonist, JTC‐801, were injected supraspinally (intracerebroventricular) and spinally (intrathecal). Also the cell‐permeable Ser/Thr protein phosphatase inhibitor okadaic acid was given supraspinally.Key results: Spinal naloxone (20 µg) or PTX (1 µg) attenuated morphine, fentanyl and buprenorphine (s.c.) anti‐nociception. Supraspinal naloxone or PTX attenuated morphine and fentanyl, but not buprenorphine anti‐nociception. Spinal Gzprotein antisense did not alter buprenorphine, morphine or fentanyl anti‐nociception and supraspinal Gz‐antisense did not alter morphine or fentanyl anti‐nociception. However, supraspinal Gz‐antisense (not random sense) reduced buprenorphine anti‐nociception. Peripheral JTC‐801 (1 mg·kg−1, i.p.) enhanced the ascending (3 mg·kg−1) and descending (30 mg·kg−1) portions of buprenorphine's dose–response curve, but only spinal, not supraspinal, nociceptin (10 nmol·L−1) enhanced buprenorphine anti‐nociception. Intracereboventricular okadaic acid (0.001–10 pg) produced a biphasic low‐dose attenuation, high‐dose enhancement of buprenorphine(3 or 30 mg·kg−1, s.c.) anti‐nociception, but did not affect morphine or fentanyl anti‐nociception.Conclusions and implications: Buprenorphine has an opioid component to its supraspinal mechanism of analgesic action. Our present results reveal an additional supraspinal component insensitive to naloxone, PTX and nociceptin/orphanin‐FQ, but involving Gzprotein and Ser/Thr protein phosphatase. These data might help explain the unique preclinical and clinical profiles of buprenorphine.
The local anaesthetics proadifen and adiphenine inhibit nicotinic receptors by different molecular mechanisms
Authors: Spitzmaul Guillermo , Gumilar Fernanda , Dilger James P , Bouzat Cecilia 
Published: April 2009

Background and purpose: Many local anaesthetics are non‐competitive inhibitors of nicotinic receptors (acetylcholine receptor, AChR). Proadifen induces a high‐affinity state of the receptor, but its mechanism of action and that of an analogue, adiphenine, is unknown.Experimental approach: We measured the effects of proadifen and adiphenine on single‐channel and macroscopic currents of adult mouse muscle AChR (wild‐type and mutant). We assessed the results in terms of mechanisms and sites of action.Key results: Both proadifen and adiphenine decreased the frequency of ACh‐induced single‐channel currents. Proadifen did not change cluster properties, but adiphenine decreased cluster duration (36‐fold at 100 µmol·L−1). Preincubation with proadifen decreased the amplitude (IC50= 19 µmol·L−1) without changing the decay rate of macroscopic currents. In contrast, adiphenine did not change amplitude but increased the decay rate (IC50= 15 µmol·L−1). Kinetic measurements demonstrate that proadifen acts on the resting state to induce a desensitized state whose kinetics of recovery resemble those of ACh‐induced desensitization. Adiphenine accelerates desensitization from the open state, but previous application of the drug to resting receptors is required. Both drugs stabilize desensitized states, as evidenced by the decrease in the number of clusters elicited by high ACh concentrations. The inhibition by adiphenine is not affected by proadifen, and the mutation αE262K decreases the sensitivity of the AChR only for adiphenine, indicating that these drugs act at different sites.Conclusions and implications: Two analogous local anaesthetics bind to different sites and inhibit AChR activity via different mechanisms and conformational states. These results provide new information on drug modulation of AChR.
Pharmacogenetic characterization of indacaterol, a novel β2‐adrenoceptor agonist
Authors: Sayers I , Hawley J , Stewart CE , Billington CK , Henry A , Leighton‐Davies JR , Charlton SJ , Hall IP 
Published: April 2009

Background and purpose:Indacaterol is a novel β2‐adrenoceptor agonist in development for the treatment of chronic obstructive pulmonary disease. The aim of this study was to investigate the comparative pharmacology of indacaterol in recombinant cells expressing the common polymorphic variants of the human β2‐adrenoceptor and in human primary airway smooth muscle (ASM) cells.Experimental approach:Chinese hamster ovarian‐K1 cell lines expressing high and low levels of the common human β2‐adrenoceptor variants were generated [Gly16‐Glu27‐Val34‐Thr164(GEVT), RQVT, GQVT] and also the rare GQVI variant. Human primary ASM cells were isolated from explants of trachealis muscle. Adenosine‐3′,5′‐cyclic‐monophosphate production was used as an outcome measure.Key results:In both the low‐ and high‐expression recombinant GEVT ‘wild type’ cell lines indacaterol is a high‐efficacy agonist. Salmeterol and formoterol were identified as low‐ and high‐efficacy agonists, respectively, and showed similar potencies to indacaterol irrespective of the β2‐adrenoceptor genotype. The I164 variant cell line was associated with a reduced capacity to generate adenosine‐3′,5′‐cyclic‐monophosphate in response to β2‐adrenoceptor agonist. In the human primary ASM cells indacaterol gave a maximal response intermediate between that of salmeterol and formoterol.Conclusions and implications:These data demonstrate that indacaterol is a high‐efficacy agonist in recombinant cell systems but acts with lower efficacy in human primary ASM cells. No marked genotype‐dependent effects were observed for common variants; however, changes in I164 receptor activity were identified, which were dependent on the level of expression of β2‐adrenoceptors.
Pan‐African eclogite facies metamorphism of ultramafic rocks in the Shackleton Range, Antarctica
Authors: ROMER T. , MEZGER K. , SCHMÄDICKE E. 
Published: April 2009

AbstractIn the Shackleton Range of East Antarctica, garnet‐bearing ultramafic rocks occur as lenses in supracrustal high‐grade gneisses. In the presence of olivine, garnet is an unmistakable indicator of eclogite facies metamorphic conditions. The eclogite facies assemblages are only present in ultramafic rocks, particularly in pyroxenites, whereas other lithologies – including metabasites – lack such assemblages. We conclude that under high‐temperature conditions, pyroxenites preserve high‐pressure assemblages better than isofacial metabasites, provided the pressure is high enough to stabilize garnet–olivine assemblages (i.e. ≥18–20 kbar). The Shackleton Range ultramafic rocks experienced a clockwise P–T path and peak conditions of 800–850 °C and 23–25 kbar. These conditions correspond to ∼70 km depth of burial and a metamorphic gradient of 11–12 °C km−1 that is typical of a convergent plate‐margin setting. The age of metamorphism is defined by two garnet–whole‐rock Sm–Nd isochrons that give ages of 525 ± 5 and 520 ± 14 Ma corresponding to the time of the Pan‐African orogeny. These results are evidence of a Pan‐African suture zone within the northern Shackleton Range. This suture marks the site of a palaeo‐subduction zone that likely continues to the Herbert Mountains, where ophiolitic rocks of Neoproterozoic age testify to an ocean basin that was closed during Pan‐African collision. The garnet‐bearing ultramafic rocks in the Shackleton Range are the first known example of eclogite facies metamorphism in Antarctica that is related to the collision of East and West Gondwana and the first example of Pan‐African eclogite facies ultramafic rocks worldwide. Eclogites in the Lanterman Range of the Transantarctic Mountains formed during subduction of the palaeo‐Pacific beneath the East Antarctic craton.
The concept of the epilepsy syndrome: How useful is it in clinical practice?
Authors: Beghi Ettore 
Published: May 2009

SummaryAn epilepsy syndrome is a disorder characterized by a cluster of symptoms and signs customarily occurring in combination. A syndromic approach to the epilepsies would be of practical value for diagnostic, prognostic, and therapeutic purposes. However, despite considerable efforts by leaders in the field of epileptology and the improved knowledge of the clinical, genetic, imaging, and biologic aspects of epilepsy, there are no measurable objective criteria for recognizing seizure types and epilepsy syndromes as separate diagnostic entities with well‐defined prognostic and therapeutic aspects. The lack of pragmatic, evidence‐based instruments to devise a syndromic classification useful for clinical practice can be explained by the evolving concept of epilepsy syndrome, its dynamic characteristics, the poor prognostic predictivity, and the extremely complex genetic and pathophysiologic mechanisms underlying the epileptic phenomena. In addition, the results of the published reports on epilepsy syndromes are mostly biased by flaws in the study population, design, and statistical analysis. The Classification Core Group of the International League Against Epilepsy (ILAE), which is working on a new classification of the epilepsies, stated that the process of syndrome identification requires that an evidence‐based approach be applied to the published literature and future studies.
Acupuncture for Alcohol Dependence: A Systematic Review
Authors: Cho Seung‐Hun , Whang Wei‐Wan 
Published: April 2009

Background:  Acupuncture has been used in the treatment of substance‐related disorders for the past 30 years. However, a systematic review to assess the effect of various types of acupuncture for alcohol dependence has not yet been performed. The present systematic review assessed the results of randomized controlled trials (RCTs).Methods:  Nineteen electronic databases, including English, Korean, Japanese, and Chinese databases, were systematically searched for RCTs of acupuncture for alcohol dependence up to June 2008 with no language restrictions. The methodological qualities of eligible studies were assessed using the criteria described in the Cochrane Handbook.Results:  Eleven studies, which comprised a total of 1,110 individual cases, were systematically reviewed. Only 2 of 11 trials reported satisfactorily all quality criteria. Four trials comparing acupuncture treatment and sham treatments reported data for alcohol craving. Three studies reported that there were no significant differences. Among 4 trials comparing acupuncture and no acupuncture with conventional therapies, 3 reported significant reductions. No differences between acupuncture and sham treatments were found for completion rates (Risk Ratio = 1.07, 95% confidence interval, CI = 0.91 to 1.25) or acupuncture and no acupuncture (Risk Ratio = 1.15, 95% CI = 0.79 to 1.67). Only 3 RCTs reported acupuncture‐related adverse events, which were mostly minimal.Conclusions:  The results of the included studies were equivocal, and the poor methodological quality and the limited number of the trials do not allow any conclusion about the efficacy of acupuncture for treatment of alcohol dependence. More research and well‐designed, rigorous, and large clinical trials are necessary to address these issues.
The Impact of Chronic Cigarette Smoking on Recovery From Cortical Gray Matter Perfusion Deficits in Alcohol Dependence: Longitudinal Arterial Spin Labeling MRI
Authors: Mon Anderson , Durazzo Timothy C. , Gazdzinski Stefan , Meyerhoff Dieter J. 
Published: April 2009

Background:  Neuroimaging studies reported cerebral perfusion abnormalities in individuals with alcohol use disorders. However, no longitudinal magnetic resonance imaging (MRI) studies of cerebral perfusion changes during abstinence from alcohol have been reported.Methods:  Arterial spin labeling MRI was used to evaluate cortical gray matter perfusion changes in short‐term abstinent alcohol dependent individuals in treatment and to assess the impact of chronic cigarette smoking on perfusion changes during abstinence. Seventy‐six patients were scanned at least once. Data from 19 non‐smoking (17 males, 2 females) and 22 smoking (21 males, 1 female) patients scanned at 1 and 5 weeks of abstinence were used to assess perfusion changes over time. Twenty‐eight age‐equated healthy controls (25 males, 3 females) were scanned for cross‐sectional comparison, 13 of them were scanned twice. Given the age range of the cohort (28 to 68 years), age was used as a covariate in the analyses. Mean perfusion was measured in voxels of at least 80% gray matter in the frontal and parietal lobes and related to neurocognitive and substance use measures.Results:  At 1 week of abstinence, frontal and parietal gray matter perfusion in smoking alcoholics was not significantly different from that in non‐smoking alcoholics, but each group’s perfusion values were significantly lower than in controls. After 5 weeks of abstinence, perfusion of frontal and parietal gray matter in non‐smoking alcoholics was significantly higher than that at baseline. However, in smoking alcoholics, perfusion was not significantly different between the time‐points in either region. The total number of cigarettes smoked per day was negatively correlated with frontal gray matter perfusion measured at 5 weeks of abstinence. Lobar perfusion measures did not correlate significantly with drinking severity or cognitive domain measures at either time‐point.Conclusion:  Although cerebral perfusion in alcohol dependent individuals shows improvement with abstinence from alcohol, cigarette smoking appears to hinder perfusion improvement.
Immunoglobulin‐E Reactivity to a Glycosylated Food Allergen (Peanuts) Due to Interference With Cross‐Reactive Carbohydrate Determinants in Heavy Drinkers
Authors: Vidal C. , Vizcaino L. , Díaz‐Peromingo J.A. , Garrido M. , Gomez‐Rial J. , Linneberg A. , Gonzalez‐Quintela A. 
Published: April 2009

Background:  N‐glycans in plant and invertebrate glycoproteins can induce extensive IgE cross‐reactivity therefore limiting the specificity of in vitro allergy tests. IgE sensitization to N‐glycans (cross‐reactive carbohydrate determinants, CCDs) may be increased in heavy drinkers, who therefore show IgE reactivity to aeroallergens, latex, and Hymenoptera venoms. The peanut, a CCD‐bearing allergen, is the leading cause of severe food allergic reactions in many populations.Aim of the study:  To investigate the potential interference of CCDs with determinations of IgE to peanuts in heavy drinkers.Methods:  We determined IgE to peanuts and IgE to a CCD marker (MUXF3, the N‐glycan from bromelain) in 41 heavy drinkers admitted to the hospital and 54 healthy controls. None of the participants reported symptoms of peanut allergy. In cases with positive (≥0.35 kU/l) IgE to peanuts, we performed inhibition assays with a neoglycoprotein consisting of MUXF3 molecules coupled to bovine serum albumin (MUXF3‐BSA) and a similar neoglycoprotein lacking xylose and fucose (MM‐BSA). In the same cases, we screened for IgE to a panel of recombinant nonglycosylated peanut allergens. SDS‐PAGE immunoblotting and inhibition assays were performed in selected cases.Results:  The prevalence of positive IgE to peanuts was 22 and 3.7% in heavy drinkers and healthy controls, respectively (p < 0.001). Peanut‐IgE positivity was closely related to the presence of IgE to CCDs. In most (8/9) heavy drinkers with positive IgE to peanuts, reactivity was inhibited by preincubation with MUXF3‐BSA, but not with MM‐BSA. IgE binding to multiple bands on immunoblotting studies was also inhibited by MUXF3‐BSA preincubation. IgE to nonglycosylated recombinant peanut allergens was uniformly negative.Conclusion:  Heavy drinking is associated with clinically asymptomatic IgE reactivity to peanuts, a relevant food allergen, in relation to CCD interference.
Ethanol Attenuates Spatial Memory Deficits and Increases mGlu1a Receptor Expression in the Hippocampus of Rats Exposed to Prenatal Stress
Authors: Van Waes Vincent , Enache Mihaela , Zuena Annarita , Mairesse Jérôme , Nicoletti Ferdinando , Vinner Elisabeth , Lhermitte Michel , Maccari Stefania , Darnaudéry Muriel 
Published: April 2009

Background:  Although it is generally believed that chronic ethanol consumption impairs learning and memory, results obtained in experimental animals are not univocal, and there are conditions in which ethanol paradoxically improves cognitive functions. In the present work, we investigated the effects of prenatal stress and of chronic ethanol exposure during adulthood on spatial memory in rats.Methods:  Rats were subjected to a prenatal stress delivered as 3 daily 45‐minute sections of restraint stress to the mothers during the last 10 days of pregnancy (PRS rats). After 7 months of ethanol exposure (ethanol 10%, oral intake), memory performances were evaluated in a spatial discrimination test in control and PRS male rats. Then, the oxidative damages and the expression of metabotropic glutamate (mGlu) receptors were assessed in their hippocampus.Results:  Chronic ethanol exposure resulted in a reduced performance in a spatial recognition task in control animals. Unexpectedly, however, the same treatment attenuated spatial memory deficits in rats that had been subjected to prenatal stress. This paradigm of ethanol administration did not produce detectable signs of oxidative damage in the hippocampus in either unstressed or PRS rats. Interestingly, ethanol intake resulted in differential effects in the expression of mGlu receptor subtypes implicated in mechanisms of learning and memory. In control rats, ethanol intake reduced mGlu2/3 and mGlu5 receptor levels in the hippocampus; in PRS rats, which exhibited a constitutive reduction in the levels of these mGlu receptor subtypes, ethanol increased the expression of mGlu1a receptors but did not change the expression of mGlu2/3 or mGlu5 receptors.Conclusion:  Our findings support the idea that stress‐related events occurring before birth have long‐lasting effects on brain function and behavior, and suggest that the impact of ethanol on cognition is not only dose‐ and duration‐dependent, but also critically influenced by early life experiences.
Ethanol‐Responsive Genes (Crtam, Zbtb16, and Mobp) Located in the Alcohol‐QTL Region of Chromosome 9 Are Associated With Alcohol Preference in Mice
Authors: Weng Julia , Symons Melissa N. , Singh Shiva M. 
Published: April 2009

Background:  Previously, our group identified cytotoxic and regulatory T‐cell molecule (Crtam), zinc finger and BTB domain containing 16 (Zbtb16), and myelin‐associated oligodendrocytic basic protein (Mobp) as ethanol‐responsive genes in the mouse brain by gene expression profiling. In this study, we used a genetic co‐segregation analysis to assess the association of Crtam, Zbtb16, and Mobp with the alcohol preference (AP) phenotype in the alcohol‐preferring C57BL/6J (B6) and alcohol avoiding DBA/2J (D2) strains of mice.Methods:  Semi‐quantitative reverse transcription‐polymerase chain reaction (RT‐PCR) was used to confirm previous microarray analysis results that Crtam, Zbtb16, and Mobp brain mRNA levels in the B6 and D2 strains are altered by ethanol treatment. The association of the 3 genes with AP was assessed in a F2 population (n = 427) derived from the reciprocal crosses involving the B6 and D2 strains. Each F2 individual was assessed for their AP using the 2 bottle choice test and genotyped for Crtam, Zbtb16, and Mobp single nucleotide polymorphisms (SNPs) that differ between B6 and D2 mice.Results:  Semi‐quantitative RT‐PCR analysis confirmed that Crtam, Zbtb16, and Mobp are ethanol‐responsive genes. The SNP analyses show that alleles of the 3 genes co‐segregate with the AP phenotype in F2 mice, where individuals homozygous for the B6 allele have higher AP than those homozygous for the D2 allele. Also, the Crtam–Zbtb16 loci that are tightly linked and the Mobp locus act in an additive fashion in determining the relative AP phenotype.Conclusion:  Our results are consistent with the hypothesis that Crtam, Zbtb16, and Mobp may be involved in AP in mice. The nature of this association remains to be established and may reflect a direct effect of these genes or an indirect effect caused by linked genes on mouse chromosome 9.
Three‐Year Chemical Dependency and Mental Health Treatment Outcomes Among Adolescents: The Role of Continuing Care
Authors: Sterling Stacy , Chi Felicia , Campbell Cynthia , Weisner Constance 
Published: April 2009

Background:  Few studies have examined the effects of treatment factors, including the types of services [chemical dependency (CD), psychiatric, or both], on long‐term outcomes among adolescents following CD treatment, and whether receiving continuing care may contribute to better outcomes. This study examines the effect of the index CD and ongoing CD and psychiatric treatment episodes, 12‐step participation, and individual characteristics such as CD and mental health (MH) severity and gender, age, and ethnicity, on 3‐year CD and MH outcomes.Methods:  Participants were 296 adolescents aged 13 to 18 seeking treatment at 4 CD programs of a nonprofit, managed care, integrated health system. We surveyed participants at intake, 1 year, and 3 years, and examined survey and administrative data, and CD and psychiatric utilization.Results:  At 3 years, 29.7% of the sample reported total abstinence from both alcohol and drugs (excluding tobacco). Compared with girls, boys had only half the odds of being abstinent (OR = 0.46, p = 0.0204). Gender also predicted Externalizing severity at 3 years (coefficients 18.42 vs. 14.77, p < 0.01). CD treatment readmission in the second and third follow‐up years was related to abstinence at 3 years (OR = 0.24, p = 0.0066 and OR = 3.33, p = 0.0207, respectively). Abstinence at 1 year predicted abstinence at 3 years (OR = 4.11, p < 0.0001). Those who were abstinent at 1 year also had better MH outcomes (both lower Internalizing and Externalizing scores) than those who were not (11.75 vs. 15.55, p = 0.0012 and 15.13 vs. 18.06, p = 0.0179, respectively).Conclusions:  A CD treatment episode resulting in good 1‐year CD outcomes may contribute significantly to both CD and MH outcomes 3 years later. The findings also point to the value of providing a continuing care model of treatment for adolescents.