bluuebunny/crossref_metadata_2025_split huggingface dataset:
PRECLINICAL STUDY: Route of administration affects the ability of naltrexone to reduce amphetamine‐potentiated brain stimulation reward in rats
Authors: Todtenkopf Mark S. , O'Neill Krystal S. , Kriksciukaite Kristina , Turncliff Ryan Z. , Dean Reginald L. , Ostrovsky‐Day Irina , Deaver Daniel R. 
Published: June 2009

ABSTRACTOpioid receptor antagonism has been shown to attenuate behavioral and neurochemical effects of amphetamine in humans and rodents. The effects of acute (oral or subcutaneous) or extended‐release naltrexone (XR‐NTX) were tested on the reward‐enhancing effects of amphetamine using the intracranial self‐stimulation (ICSS) paradigm. Acute exposure to drugs of abuse reduces the locus of rise (LOR) in the ICSS procedure, reflecting enhanced brain stimulation reward (BSR). Rats were treated once a day with naltrexone orally (PO; 5.0 mg/kg) or subcutaneously (SC; 0.5 mg/kg) for four consecutive days and tested with D‐amphetamine (0.5 mg/kg, intraperitoneal) in the ICSS paradigm 30 minutes later on days 1 and 4. Separate groups of rats received XR‐NTX (50 mg/kg, SC) or placebo microspheres (similar mass to XR‐NTX, SC) on day 0 and tested with D‐amphetamine in the ICSS paradigm on days 4, 14, 21, 28 and 41 after administration. Naltrexone plasma concentrations were determined for each amphetamine testing session using liquid chromatography‐mass spectrometry/mass spectrometry (LC‐MS/MS). In rats pretreated with naltrexone acutely, amphetamine‐potentiated BSR did not differ from vehicle‐pretreated rats on either day 1 or day 4 (25–30% decrease in LOR). In XR‐NTX‐pretreated rats, amphetamine‐potentiated BSR was reduced by 64 and 70% on days 4 and 14, respectively, compared to placebo microsphere‐treated controls. This effect dissipated by day 21. Naltrexone plasma concentrations were comparable across all treatment groups (14–30 ng/ml) on days 1, 4 and 14. In summary, an extended‐release formulation of naltrexone results in significant attenuation of psychostimulant‐enhanced BSR that is not observed with acute naltrexone.
PRECLINICAL STUDY: Electroacupuncture treatment reverses morphine‐induced physiological changes in dopaminergic neurons within the ventral tegmental area
Authors: Hu Ling , Chu Ning‐ning , Sun Lin‐lin , Zhang Rong , Han Ji‐Sheng , Cui Cai‐lian 
Published: June 2009

ABSTRACTChronic morphine administration decreases the size of dopamine (DA) neurons in the ventral tegmental area (VTA). These transient morphological changes are accompanied by a reduced sensitivity of morphine‐induced conditioned place preference (CPP) after chronic exposure to the drug. In this study we examined alterations in the firing rate of DAergic neurons by means of extracellular recording following chronic morphine exposure and applied 100 Hz electroacupuncture (EA) treatment to reverse the reduced firing rate of these neurons. In the first set of experiments we show that in rats, which received chronic morphine treatment for 14 days, a small dose of morphine was not able to induce a CPP response anymore. However, the sensitivity to morphine was reinstated by consecutive EA treatment for 10 days. The electrophysiological response of VTA DA neurons to morphine was markedly reduced in chronic morphine‐treated rats compared to saline‐treated controls. A substantial recovery of the reactivity of VTA DA neurons to morphine was observed in rats that received 100 Hz EA for 10 days. Our findings suggest that 100 Hz EA is a potential therapy for the treatment of opiate addiction by normalizing the activity of VTA DA neurons.
PRECLINICAL STUDY: Is withdrawal hyperalgesia in morphine‐dependent mice a direct effect of a low concentration of the residual drug?
Authors: Rubovitch Vardit , Pick Chaim G , Sarne Yosef 
Published: June 2009

ABSTRACTWithdrawal of opioid drugs leads to a cluster of unpleasant symptoms in dependent subjects. These symptoms are stimulatory in nature and oppose the acute, inhibitory effects of opiates. The conventional theory that explains the opioid withdrawal syndrome assumes that chronic usage of opioid drugs activates compensatory mechanisms whose stimulatory effects are revealed upon elimination of the inhibitory opioid drug from the body. Based on previous studies that show a dose‐dependent dual activity of opiates, including pain perception, we present here an alternative explanation to the phenomenon of withdrawal‐induced hyperalgesia. According to this explanation, the residual low concentration of the drug that remains after cessation of its administration elicits the stimulatory withdrawal hyperalgesia. The goal of the present study was to test this hypothesis. In the present study we rendered mice dependent on morphine by a daily administration of the drug. Cessation of morphine application elicited withdrawal hyperalgesia that was completely blocked by a high dose of the opiate antagonist naloxone (100 mg/kg). Similarly, naloxone (2 mg/kg)‐induced withdrawal hyperalgesia was also blocked by 100 mg/kg of naloxone. The blockage of withdrawal hyperalgesia by naloxone suggested the involvement of opioid receptors in the phenomenon and indicated that withdrawal hyperalgesia is a direct effect of a residual, low concentration of morphine. Acute experiments that show morphine‐ and naloxone‐induced hyperalgesia further verified our hypothesis. Our findings offer a novel, alternative approach to opiate detoxifications that may prevent withdrawal symptoms by a complete blockage of the opioid receptors using a high dose of the opioid antagonist.
Targeting the allergen to oral dendritic cells with mucoadhesive chitosan particles enhances tolerance induction
Authors: Saint‐Lu N. , Tourdot S. , Razafindratsita A. , Mascarell L. , Berjont N. , Chabre H. , Louise A. , Van Overtvelt L. , Moingeon P. 
Published: June 2009

Background:  Sublingual immunotherapy (SLIT) efficacy could be improved by formulations facilitating allergen contact with the oral mucosa and uptake by antigen‐presenting cells (APCs).Methods:  Two types of chitosan microparticles, differing in size and surface charge, were tested in vitro for their capacity to improve antigen uptake and presentation by murine bone marrow‐derived dendritic cells (BMDCs) or purified oral APCs. T‐cell priming in cervical lymph nodes (LNs) was assessed by intravenous transfer of carboxyfluorescein diacetate succinimidyl ester‐labelled ovalbumin (OVA)‐specific CD4+ T cells and flow cytometry analysis. Ovalbumin‐sensitized BALB/c mice were treated sublingually with soluble or chitosan‐formulated OVA twice a week for 2 months. Airway hyperresponsiveness (AHR), lung inflammation and T‐cell responses in cervical and mediastinal LNs were assessed by whole‐body plethysmography, lung histology and Cytometric Bead Array technology, respectively.Results:  Only a mucoadhesive (i.e. highly positively charged) and microparticulate form of chitosan enhances OVA uptake, processing and presentation by murine BMDCs and oral APCs. Targeting OVA to dendritic cells with this formulation increases specific T‐cell proliferation and IFN‐γ/IL‐10 secretion in vitro, as well as T‐cell priming in cervical LNs in vivo. Sublingual administration of such chitosan‐formulated OVA particles enhances tolerance induction in mice with established asthma, with a dramatic reduction of both AHR, lung inflammation, eosinophil numbers in bronchoalveolar lavages, as well as antigen‐specific Th2 responses in mediastinal LNs.Conclusions:  Mucoadhesive chitosan microparticles represent a valid formulation for sublingual allergy vaccines.
CD40 and OX40 ligand are differentially regulated on asthmatic airway smooth muscle
Authors: Krimmer D. I. , Loseli M. , Hughes J. M. , Oliver B. G. G. , Moir L. M. , Hunt N. H. , Black J. L. , Burgess J. K. 
Published: June 2009

Background: CD40 and OX40 Ligand (OX40L) are cell‐surface molecules expressed on airway smooth muscle (ASM) that can enhance inflammatory cell activation and survival. The aim of this study was to examine the effect of tumour necrosis factor‐alpha (TNF‐α) and interferon‐gamma (IFN‐γ) on ASM CD40 and OX40L expression.Methods: CD40 and OX40L expression on human ASM cells from asthmatic and nonasthmatic donors following stimulation with TNF‐α and/or IFN‐γ was measured using cell‐surface enzyme‐linked immunosorbent assay (ELISA) and flow cytometry. Involvement of signalling pathway was investigated with pharmacological inhibitors. Soluble TNF receptor levels were quantified by ELISA.Results: Interferon‐γ and TNF‐α synergistically increased CD40 expression to a greater extent on asthmatic than on nonasthmatic ASM. In contrast, IFN‐γ reduced TNF‐α‐induced OX40L expression to a similar extent in both cell types. TNF‐α and IFN‐γ induced CD40 via nuclear factor‐κB (NF‐κB) and signal transducer and activator of transcription‐3 in both cell types and modulated OX40L via NF‐κB and c‐Jun N terminal kinase in nonasthmatic cells. Similar effects on the induction of OX40L in asthmatic cells were seen with NF‐κB, but these were not statistically significant. The reduced OX40L expression with TNF‐α and IFN‐γ involved extracellular regulated kinase 1/2 activation.Conclusion: Asthmatic ASM may modulate airway inflammation locally by increasing CD40 and OX40L expression in response to cytokines. IFN‐γ may regulate ASM pro‐inflammatory actions by differentially modulating ASM CD40 and OX40L expression.
Longitudinal trends of total and allergen‐specific IgE throughout childhood
Authors: Matricardi P. M. , Bockelbrink A. , Grüber C. , Keil T. , Hamelmann E. , Wahn U. , Lau S. 
Published: June 2009

Background:  The development and the quantitative relationship between allergen‐specific IgE (S‐IgE) responses and total IgE (T‐IgE), during childhood and adolescence have not been described and understood in detail. The objective of this study was to describe and compare the longitudinal trends of serum levels of S‐IgE and T‐IgE during childhood.Methods:  We analysed data from participants in the MAS birth cohort study at 2, 5, 7 and 10 years of age (n = 273) and at 1, 3, 5, 6, 7, 10 and 13 years (n = 84). Total‐IgE and the overall level of specific‐IgE against nine locally relevant airborne and food allergens were determined by FEIA (ImmunoCAP). Allergic rhino‐conjunctivitis and asthma were ascertained by questionnaires.Results:  Longitudinal patterns of T‐IgE levels from age 1 to 13 years were highly heterogeneous (declining, flat or increasing with different profiles). From 5 years of age, logarithmic (log10) transformed values of T‐IgE and of S‐IgE levels tend to follow a parallel trend, so that their relation remained constant throughout school age. A flat trend of T‐IgE vs a constantly increasing trend of T‐IgE was associated with a low or, respectively, high rate of wheezing at 13 years of age.Conclusions:  Beginning at the age of 5 years, total serum IgE levels in children from an industrialized country evolved in parallel with overall S‐IgE levels. Therefore, variations in T‐IgE levels at school age closely reflect variations in overall S‐IgE levels. Further studies are required to strengthen the biological and clinical implication of this novel finding.
Blockade of CCR4 in a humanized model of asthma reveals a critical role for DC‐derived CCL17 and CCL22 in attracting Th2 cells and inducing airway inflammation
Authors: Perros F. , Hoogsteden H. C. , Coyle A. J. , Lambrecht B. N. , Hammad H. 
Published: June 2009

Background:  As Th2 type lymphocytes orchestrate the cardinal features of allergic asthma, inhibiting their recruitment to the lungs could be of therapeutic benefit. Although human Th2 cells express the CCR4 chemokine receptor and increased production of CCR4 ligands has been found in asthmatic airways, studies in animals have reached contradictory conclusions on whether blocking this pathway would be beneficial.Objective:  As a lack of efficacy might be due to differences between mouse and man, we readdressed this question using a humanized severe combined immunodeficiency model of asthma.Methods:  Mice received peripheral blood mononuclear cells from house dust mite (HDM) allergic asthmatic patients and then underwent bronchial challenge with HDM.Results:  This resulted in marked allergic inflammation and bronchial hyper‐reactivity. Administration of CCR4 blocking antibody abolished the airway eosinophilia, goblet cell hyperplasia, IgE synthesis and bronchial hyperreactivity. In this chimeric system, human CD11c+ dendritic cells (DCs) were the predominant source of CCR4 ligands, suggesting that DC‐derived chemokines attract Th2 cells. In separate experiments using human DCs, in vitro exposure to HDM of DCs from HDM allergic patients but not healthy controls caused CCL17 and CCL22 release that resulted in chemoattraction of polarized human Th2 cells in a CCR4‐dependent way.Conclusions:  Taken together, our data provide proof of concept that CCR4 blockade inhibits the salient features of asthma and justify further clinical development of CCR4 antagonists for this disease.
‘ERAD'icating Mislocalized Proteins in an Acromesomelic Dwarfism Disorder
Authors: Kang MH 
Published: June 2009

Defective cellular trafficking of missense NPR‐B mutants is the major mechanism underlying acromesomelic dysplasia‐type MaroteauxHume et al. (2009)Human Molecular Genetics 18: 267–277
A Controlled SCID: Bringing Reticular Dysgenesis to a Halt
Authors: Kang MH 
Published: June 2009

Reticular dysgenesis (aleukocytosis) is caused by mutations in the gene encoding mitochondrial adenylate kinase 2Pannicke et al. (2009) Nature Genetics 41: 101–105Human adenylate kinase 2 deficiency causes a profound hematopoietic defect associated with sensorineural deafnessLagresle‐Peyrou et al. (2009)Nature Genetics 41: 106‐111
Incidence of pancreas graft thrombosis using low‐molecular‐weight heparin
Authors: Schenker Peter , Vonend Oliver , Ertas Neslihan , Wunsch Andreas , Schaeffer Michael , Rump Lars‐Christian , Viebahn Richard 
Published: June 2009

Abstract:  Introduction:  Simultaneous pancreas–kidney transplantation is the current treatment of choice for patients with type I diabetes and end stage renal disease. Vascular graft thrombosis (VGT) after pancreas transplantation is the main cause of early graft loss.Methods:  A total of 188 consecutive pancreas transplantations were performed between January 2000 and December 2006. A retrospective study was carried out in order to compare incidence of VGT and relaparotomy‐for‐bleeding rate of once daily fixed dose low‐molecular‐weight‐heparin (LMWH) to dose‐adjusted intravenous unfractionated heparin (UFH).Results:  Fifty‐eight patients receiving LMWH and 129 receiving UFH were identified. There were 7% (4/58) VGTs in the LMWH and 17% (22/129) in the UFH group (p = 0.047). The frequency of major bleeding requiring relaparatomy was not significantly different in the groups related to LMWH and UFH, respectively (6.9% vs. 7.8%). One yr patient and pancreas graft survival was 98.9/89.6% in the LMWH and 97.8/74.4% in the UFH group. Donor and recipient characteristics were similar.Conclusion:  In our experience once daily fixed dose LMWH might not be inferior to dose‐adjusted intravenous heparin in preventing pancreas graft thrombosis.
From words to action – influence of two organ donation campaigns on knowledge and formal decision making
Authors: Krekula Linda Gyllström , Malenicka Silvia , Linder Margareta , Tibell Annika 
Published: June 2009

Abstract: Introduction: In Sweden, two donation campaigns have been carried out; one short term (STC) during October 2001, and one long term (LTC) between the years 2003–2005. The goal was not only to inform the public but also to create a positive attitude, make people talk about donation and formally declare their decision.Methods: The effects of the two campaigns were evaluated through three opinion polls.Results: The willingness to donate was widespread (86%) before and after the campaigns. The LTC increased the knowledge of the Donor Card (24–35%, p < 0.001) and the National Donor Registry (19–40%, p < 0.001). The LTC focused on making people register, still though, only a small increase of registrants was found (11–14%, p = 0.043). The proportion expecting the question of organ donation if their relative was to die under circumstances that made organ donation possible increased (73–79%, p = 0.002). No corresponding increase was found regarding the number having informed a relative about their decision (20–23%, ns).Conclusion: The LTC was successful in increasing the expectation for the donation request. It also improved the knowledge of the Card and the Registry and slightly increased the number having registered. However, neither of the campaigns succeeded in making people inform their relatives.
Impact of induction therapy on bacterial infections and long‐term outcome in adult intestinal and multivisceral transplantation: a comparison of two different induction protocols: daclizumab vs. alemtuzumab
Authors: Kimura Takuya , Lauro Augusto , Cescon Matteo , Zanfi Chiara , Dazzi Alessandro , Ercolani Giorgio , Grazi Gian Luca , Vivarelli Marco , Ravaioli Matteo , Del Gaudio Massimo , Cucchetti Alessandro , Zanello Matteo , LaBarba Giuliano , Pironi Loris , Lazzarotto Tiziana , Pinna Antonio Daniele 
Published: June 2009

Abstract:  Introduction:  Induction therapy with daclizumab or alemtuzumab has been recently introduced for intestinal transplantation; however, the impact of such induction therapy on bacterial infections remains to be clarified. The purpose of this study was to evaluate the impact of induction therapy on the incidence of bacterial infections and long‐term patient survival.Patients and methods:  Over the past seven yr, we performed 39 intestinal (ITx) and multivisceral (MTVx) transplants in 38 adult patients. In the early period, daclizumab was used for induction, and tacrolimus and steroids were administered for maintenance [daclizumab and tacrolimus (DT) group; n = 11]. From 2002, we used alemtuzumab for induction, with low‐dose tacrolimus maintenance [alemtuzumab and tacrolimus (AT) group; n = 23]. The incidence of bacterial infections and patient outcome were compared between the two groups.Results:  There were no significant differences in recipient and donor demographics, procedure (ITx vs. MTVx), and cold and warm ischemic time between the two groups. Within 30 d after ITx, bacterial infections were observed in seven patients (64%) in the DT and in 14 patients (64%) in the AT group. Between 30 and 180 d after ITx, a total of 17 episodes of bacterial infections were observed in the DT and 26 episodes in the AT group. Three patients in the DT and eight in the AT group died, and all of the deaths were related to infectious complications except one each in DT and AT.Conclusion:  There was no difference in incidence of bacterial infections and long‐term patient survival between the two groups.
Outcome of hepaticojejunostomy for biliary tract obstruction following liver transplantation
Authors: Langer F.B. , Györi G.P. , Pokorny H. , Burghuber C. , Rasoul‐Rockenschaub S. , Berlakovich G.A. , Mühlbacher F. , Steininger R. 
Published: June 2009

Abstract:  Background:  Strictures and concrements are the most common biliary complications following liver transplantation. Endoscopic treatment might not lead to a definitive cure in all patients, especially in strictures involving the biliary bifurcation. The aim of this study was to determine the efficacy and the long‐term outcome of hepaticojejunostomy (HJS) for post‐transplant biliary tract obstruction.Material and methods:  Thirty‐seven patients were retrospectively studied for resolving of cholestasis and the incidence of recurring biliary obstruction.Results:  Surgery was performed because of anastomotic strictures in 11, ischemic strictures at the donor common bile duct in seven, strictures involving the bile duct bifurcation in 10, hepatolithiasis without strictures in one and biliary cast formation diagnosed by endoscopic retrograde cholangiography or T‐tube cholangiography in eight patients. Cholestasis instantly improved in 82% of the patients. After a long‐term follow‐up of median 33 months (range 3–149), 28 of the patients (76%) required no further intervention for recurring biliary obstruction following HJS. Anastomotic strictures were observed in six (16%), recurring biliary concrements in two patients (5%).Conclusion:  HJS did prevent recurrent biliary obstruction in the majority of the patients. We therefore recommend early HJS for complicated post‐transplant biliary tract obstruction not treatable by a limited number of endoscopic interventions.
Anticonvulsants in bipolar disorders: current research and practice and future directions
Authors: Bowden Charles L 
Published: June 2009

Objectives: To determine the clinical effectiveness of drugs with anticonvulsant properties for interventions in persons with bipolar disorder and to place these findings in the context of clinicians’ practices and their implications for future research to more effectively manage bipolar disorders.Methods: Major electronic databases were searched up to February 2009 for clinical trial data, both original studies and reviews, on drugs with anticonvulsant properties studied for bipolar disorders.Results: Valproate, principally as divalproex, has strong evidence for effectiveness in mania, moderately strong evidence for benefits in prophylaxis of recovered states, and recent proof‐of‐concept evidence for benefits in bipolar depression. Lamotrigine has strong evidence for evidence for effectiveness in maintenance treatment of bipolar disorder, principally for benefits in depressive states. Lamotrigine has been established as ineffective in mania and has lacked efficacy in acute bipolar depression in most randomized trials. Carbamazepine has strong evidence for effectiveness in mania, but lacks adequate studies in other aspects of bipolar disorder treatment. Its adverse effect profile and pharmacokinetic interference with a wide range of drugs, including many employed in bipolar disorder, warrants limitation of use to patients who have responded inadequately to other regimens.Conclusions: Three drugs, valproate, lamotrigine, and carbamazepine, have strong evidence‐based support for use in clinical states of bipolar disorder. Other anticonvulsant drugs investigated in bipolar disorder either have evidence of lack of benefits in bipolar disorder or have been inadequately studied to determine possible effectiveness.