bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cue‐conditioned alcohol seeking in rats following abstinence: involvement of metabotropic glutamate 5 receptors
Authors: Adams CL , Short JL , Lawrence AJ 
Published: January 2010

Background and purpose:  The current study was designed to: (i) examine whether functional interactions occur between receptors known to regulate alcohol self‐administration; and (ii) characterize relapse to alcohol seeking following abstinence.Experimental approach:  The selective cannabinoid CB1 receptor antagonist SR141716A (0.03–1.0 mg·kg−1 i.p.) resulted in a dose‐dependent reduction in ethanol self‐administration in ethanol‐preferring Indiana‐preferring rats. SR141716A was then co‐administered with either the selective glutamate metabotropic glutamate 5 (mGlu5) receptor antagonist 3‐[(2‐methyl‐1,3‐thiazol‐4‐yl)ethynyl]pyridine (MTEP) or the selective adenosine A2A receptor antagonist SCH58261.Key results:  When administered at individually sub‐threshold doses, a combination of SR141716A (0.1 mg·kg−1) and SCH58261 (0.5 mg·kg−1 i.p.) produced a reduction (28%) in ethanol self‐administration. Combinations of threshold doses of SR141716A (0.3 mg·kg−1) and SCH58261 (2.0 mg·kg−1, i.p.) caused an essentially additive reduction (68%) in alcohol self‐administration. A combination of individually sub‐threshold doses of CB1 and mGlu5 receptor antagonists did not affect alcohol self‐administration; however, combined threshold doses of SR141716A (0.3 mg·kg−1) and MTEP (1.0 mg·kg−1 i.p.) did reduce ethanol self‐administration markedly (80%). Cue‐conditioned alcohol seeking was attenuated by pretreatment with MTEP (1.0 mg·kg−1) co‐administered with SR141716A (0.3 mg·kg−1 i.p.). In contrast, SCH58261 (2.0 mg·kg−1) co‐administered with SR141716A (0.3 mg·kg−1 i.p.) did not reduce cue‐conditioned alcohol seeking.Conclusions and implications:  Adenosine A2A and cannabinoid CB1 receptors regulated alcohol self‐administration additively, but combined low‐dose antagonism of these receptors did not prevent cue‐conditioned alcohol seeking after abstinence. In contrast, combined low‐dose antagonism of mGlu5 and CB1 receptors did prevent relapse‐like alcohol seeking after abstinence, suggesting a prominent role for mGlu5 receptors in this paradigm.
Rimonabant (SR141716) induces metabolism and acquisition of fertilizing ability in human sperm
Authors: Aquila S , Guido C , Santoro A , Gazzerro P , Laezza C , Baffa MF , Andò S , Bifulco M 
Published: January 2010

Background and purpose:  The endocannabinoid system and the cannabinoid CB1 receptor have been identified in human sperm, and it is well known that endocannabinoids have pronounced adverse effects on male and female reproduction. In order to elucidate further the pathophysiological role of the endocannabinoid system in male fertility, we investigated the activity of the CB1 receptor antagonist rimonabant (SR141716) on the fertilizing ability of human sperm.Experimental approach:  We evaluated in vitro the effects of rimonabant on motility, survival, capacitation, acrosin activity and metabolism of human sperm. Particularly, capacitation was studied by using three different approaches: intracellular free Ca2+ content assay, cholesterol efflux assay and protein tyrosine phosphorylation analysis.Key results:  Rimonabant significantly increased sperm motility and viability through the induction of pAkt and pBcl2, key proteins of cell survival and metabolism, and it induced acrosome reaction and capacitation as well. Rimonabant reduced the triglyceride content of sperm, while enhancing lipase and acyl‐CoA dehydrogenase activities, implying an overall lipolytic action in these cells. Rimonabant also affected sperm glucose metabolism by decreasing phosphorylation of glycogen synthase kinase 3 and increasing glucose‐6‐phosphate dehydrogenase activity, suggesting a role in inducing sperm energy expenditure. Intriguingly, agonism at the CB1 receptor, with an anandamide analogue or a selective inhibitor of fatty acid amide hydrolase, produced opposing effects on human sperm functions.Conclusions and implications:  Our data suggest that blockade of the CB1 receptor by rimonabant induces the acquisition of fertilizing ability and stimulates energy expenditure in human sperm.
The role of kinin B1 and B2 receptors in the scratching behaviour induced by proteinase‐activated receptor‐2 agonists in mice
Authors: Costa Robson , Manjavachi Marianne N , Motta Emerson M , Marotta Denise M , Juliano Luiz , Torres Hugo A , Pesquero João B , Calixto João B. 
Published: January 2010

Background and purpose:  Activation of the proteinase‐activated receptor‐2 (PAR‐2) induces scratching behaviour in mice. Here, we have investigated the role of kinin B1 and B2 receptors in the pruritogenic response elicited by activators of PAR‐2.Experimental approach:  Scratching was induced by an intradermal (i.d.) injection of trypsin or the selective PAR‐2 activating peptide SLIGRL‐NH2 at the back of the mouse neck. The animals were observed for 40 min and their scratching response was quantified.Key results:  I.d. injection of trypsin or SLIGRL‐NH2 evoked a scratching behaviour, dependent on PAR‐2 activation. Mice genetically deficient in kinin B1 or B2 receptors exhibited reduced scratching behaviour after i.d. injection of trypsin or SLIGRL‐NH2. Treatment (i.p.) with the non‐peptide B1 or B2 receptor antagonists SSR240612 and FR173657, respectively, prevented the scratching behaviour caused by trypsin or SLIGRL‐NH2. Nonetheless, only treatment i.p. with the peptide B2 receptor antagonist, Hoe 140, but not the B1 receptor antagonist (DALBK), inhibited the pruritogenic response to trypsin. Hoe 140 was also effective against SLIGRL‐NH2‐induced scratching behaviour when injected by i.d. or intrathecal (i.t.) routes. Also, the response to SLIGRL‐NH2 was inhibited by i.t. (but not by i.d.) treatment with DALBK. Conversely, neither Hoe 140 nor DALBK were able to inhibit SLIGRL‐NH2‐induced scratching behaviour when given intracerebroventricularly (i.c.v.).Conclusions and implications:  The present results demonstrated that kinins acting on both B1 and B2 receptors played a crucial role in controlling the pruriceptive signalling triggered by PAR‐2 activation in mice.
Herbs and Spices: Unexpected Sources of Antiepileptogenic Drug Treatments?
Authors: Wong Michael 
Published: January 2010

Protective Effect of Resveratrol Against Kainate-Induced Temporal Lobe Epilepsy in Rats. Wu Z, Xu Q, Zhang L, Kong D, Ma R, Wang L. Neurochem Res 2009;34(8):1393–1400. Resveratrol (Res) is a phytoalexin produced naturally by several plants, which has multifunctional effects such as neuroprotection, anti-inflammatory, and anti-cancer. The present study was to evaluate a possible anti-epileptic effect of Res against kainate-induced temporal lobe epilepsy (TLE) in rat. We performed behavior monitoring, intracranial electroencepholography (IEEG) recording, histological analysis, and Western blotting to evaluate the anti-epilepsy effect of Res in kainate-induced epileptic rats. Res decreased the frequency of spontaneous seizures and inhibited the epileptiform discharges. Moreover, Res could protect neurons against kainate-induced neuronal cell death in CA1 and CA3a regions and depressed mossy fiber sprouting, which are general histological characteristics both in TLE patients and animal models. Western blot revealed that the expression level of kainate receptors (KARs) in hippocampus was reduced in Res-administrated rats compared to that in epileptic ones. These results suggest that Res is a potent anti-epilepsy agent, which protects against epileptogenesis and progression of the kainate-induced TLE animal. Curcumin Protects Against Electrobehavioral Progression of Seizures in the Iron-Induced Experimental Model of Epileptogenesis. Jyoti A, Sethi P, Sharma D. Epilepsy Behav 2009;14(2):300–308. The purpose of the study was to investigate whether dietary intake of curcumin can inhibit the onset and progression of seizures and their associated pathophysiology in experimental FeCl3-induced epileptogenesis. Curcumin was considered for this study because it can cross the blood–brain barrier and bind redox-active metal ions. It is also well known for its antioxidative, anticancer, and anti-inflammatory properties. In the present study, seizures were induced by intracortical injection of FeCl3 into young rats. Synchronized video/EEG recordings were obtained to diagnose the progression of seizures. Short-term treatment with a curcumin-supplemented diet (1500 ppm w/w) significantly inhibited the onset of grade III and IV seizures in rats with iron-induced epilepsy. The lower dose of curcumin (500 ppm) was not effective in inhibiting grade III seizures, but retarded the onset and progression of generalized seizures. The seizure-suppressing potential of curcumin is explained by the observed biochemical, behavioral, and ultrastructural results. Our results indicate that curcumin significantly prevents generalization of electroclinical seizure activity as well as the pathogenesis associated with iron-induced epileptogenesis.
Magnetic resonance imaging diagnosis of iron overload in a leukemic patient after allogeneic hematopoietic stem cell transplantation
Authors: Tan Cher Heng , Marcal Leonardo , Tan Dongfeng , Patnana Madhavi 
Published: January 2010

BACKGROUND: Iron overload (IO) is increasingly recognized as a common cause of hepatic dysfunction in leukemic patients who have undergone allogeneic hematopoietic stem cell transplantation. Magnetic resonance imaging (MRI) is a noninvasive method of making the diagnosis.CASE REPORT: A patient with acute lymphocytic leukemia presented with severe liver dysfunction during salvage chemotherapy for leukemia relapse after undergoing allogeneic hematopoietic stem cell transplantation. The liver dysfunction was originally attributed to graft‐versus‐host disease; however, findings on MRI and liver biopsy were consistent with hepatic IO.CONCLUSIONS: As illustrated by our case, MRI can be a reliable, noninvasive modality that should be employed in the work‐up of these patients.
The aptamer ARC1779 blocks von Willebrand factor–dependent platelet function in patients with thrombotic thrombocytopenic purpura ex vivo
Authors: Mayr Florian B. , Knöbl Paul , Jilma Bernd , Siller‐Matula Jolanta M. , Wagner Patricia G. , Schaub Robert G. , Gilbert James C. , Jilma‐Stohlawetz Petra 
Published: January 2010

BACKGROUND: In thrombotic thrombocytopenic purpura (TTP), ultralarge von Willebrand factor (VWF) multimers bind platelet (PLT) glycoprotein Ib and lead to the formation of disseminated fibrin‐poor, VWF‐rich PLT thrombi. The aptamer ARC1779 blocks binding of the VWF A1 domain to PLT glycoprotein Ib. We evaluated whether ARC1779 inhibits the excessive VWF activity and VWF‐mediated PLT function in patients with TTP.STUDY DESIGN AND METHODS: We studied the ex vivo concentration response curves for ARC1779 on PLT function analyzer (PFA‐100, Dade Behring) and cone‐and‐plate analyzer (CPA, Impact‐R) PLT function tests, agonist‐induced PLT aggregation, and VWF activity of TTP patients (n = 11, three in acute phase and eight in remission) and healthy controls (n = 44).RESULTS: VWF activity and VWF‐dependent PLT plug formation were increased in TTP patients relative to healthy controls, but agonist‐induced PLT aggregation was not. ARC1779 blocked collagen/adenosine 5′‐diphosphate (ADP)‐induced PLT plug formation as measured by PFA‐100 with an inhibitory concentration (IC)100 of approximately 1 µg/mL in citrate‐anticoagulated samples and approximately 3 to 4 µg/mL in hirudin‐anticoagulated samples. A similar concentration of ARC1779 was necessary to block shear‐dependent PLT adhesion in both TTP patients and healthy controls using the CPA assay (IC100 of approx. 1 µg/mL for both). ARC1779 blocked VWF activity with an IC90 of approximately 3 to 4 µg/mL in all subjects, but did not inhibit PLT aggregation by ADP, collagen, or arachidonic acid even at concentrations much greater than those that fully inhibited VWF‐dependent PLT function.CONCLUSIONS: ARC1779 potently and specifically inhibits VWF activity and VWF‐dependent PLT function. ARC1779 may be a promising novel therapeutic for the treatment of TTP.
Conversion to the buffy coat method and quality of frozen plasma derived from whole blood donations in Canada
Authors: Sheffield William P. , Bhakta Varsha , Jenkins Craig , Devine Dana V. 
Published: January 2010

BACKGROUND: Canada converted from the platelet‐rich plasma (PRP) method to the buffy coat (BC) method of processing whole blood donations between 2006 and 2008. We measured coagulation variables in plasma units during this transition, in 2006 (PRP only), 2007 (BC and PRP), and 2008 (BC only) to test the hypothesis that this conversion would not affect frozen plasma (FP) quality.STUDY DESIGN AND METHODS: Fresh‐frozen plasma (FFP; frozen within 8 hr of collection) or FP (frozen within 24 hr of collection) units were shipped on dry ice from 12 plasma manufacturing sites, thawed, and characterized using an automated coagulation analyzer, at a single testing site.RESULTS: FP made by the BC method (FP‐BC) exhibited fibrinogen, Factor (F)V, ABO‐matched FVIII, and antithrombin levels at least as high as FP made by the PRP method (FP‐PRP) and supported global clotting, as measured by prothrombin time or activated partial thromboplastin time, to an indistinguishable extent as FP‐PRP. FP‐BC and FP‐PRP did not differ in ABO‐matched FVIII levels, but both contained 30% to 35% less FVIII than FFP. There was no discernible effect of the site of manufacturing on plasma quality. FP‐BC units leukoreduced by centrifugation contained more FV activity than those leukoreduced by filtration, but the difference was unlikely to be of clinical significance.CONCLUSION: Our data suggest that no reduction in FP quality, at least in the characteristics we tested, accompanied the switch from the PRP to the BC method processing of whole blood donations in Canada.
Prevalence of HLA antibodies in remotely transfused or alloexposed volunteer blood donors
Authors: Kakaiya Ram M. , Triulzi Darrell J. , Wright David J. , Steele Whitney R. , Kleinman Steven H. , Busch Michael P. , Norris Philip J. , Hillyer Christopher D. , Gottschall Jerome L. , Rios Jorge A. , Carey Patricia , Glynn Simone A. 
Published: January 2010

BACKGROUND: HLA antibody testing of previously transfused or pregnant donors may help reduce the risk of transfusion‐related acute lung injury (TRALI). However, the prevalence of HLA antibodies in transfused donors has not been well characterized.STUDY DESIGN AND METHODS: Transfusion and pregnancy history was obtained from consenting donors. HLA Class I and II antibody testing was performed by multiantigen bead Luminex platform. Cutoff values for Class I and II antibodies used normalized background ratios of 10.8 and 6.9, respectively. Linear probability models were used to evaluate potential associations between HLA alloimmunization and donor characteristics.RESULTS: A total of 7920 donors (2086 males and 5834 females) were tested. HLA antibody prevalence did not significantly differ between 895 transfused (1.7%) and 1138 nontransfused males (1.0%; odds ratio [OR], 1.75; 95% confidence interval [CI], 0.80‐3.82]. Prevalence in 45 transfused nulliparous females (4.4%; 95% CI, 0.1%‐11.8%) was not different from the 1.6% prevalence in 1732 nontransfused nulliparous females (OR, 2.94; 95% CI, 0.68‐12.74). Transfused parous females had higher prevalence than nontransfused counterparts (p = 0.004; OR, 1.39; 95% CI, 1.07‐1.80). In a linear probability model, the estimated additive risk of transfusion‐induced alloimmunization was only 0.8% (95% CI, −0.2% to 1.8%; p = 0.10). Donor transfusion history showed that 58% of transfusions occurred more than 10 years previously.CONCLUSION: Transfused volunteer blood donors do not appear to have a significantly higher prevalence of HLA antibodies than their nontransfused counterparts. Thus, in an effort to reduce TRALI risk, ascertaining past history of transfusion and testing these donors for HLA antibodies is not necessary.
Neonatal alloimmune thrombocytopenia caused by an antibody specific for a newly identified allele of human platelet antigen‐7
Authors: Koh Yangsook , Taniue Atsuko , Ishii Hiroyuki , Matsuyama Nobuki , Amakishi Etsuko , Hayashi Tomoya , Furuta Rika A. , Fukumori Yasuo , Hirayama Fumiya , Yoshimura Keiji , Nagamine Tomoko , Tamai Susumu , Nakano Susumu 
Published: January 2010

BACKGROUND:Neonatal alloimmune thrombocytopenia (NAIT) is a neonatal disorder characterized by maternal alloimmunization against fetal platelet (PLT) antigens inherited from the father. A healthy 30‐year‐old Japanese woman (Hit) gave birth to her second child after an uneventful pregnancy. Nine hours after birth, the infant presented with severe petechiae and a PLT count of 6 × 109/L.STUDY DESIGN AND METHODS:To elucidate the maternal cause of NAIT in the infant, serologic and genetic studies, including PLT genotyping and sequence‐based analysis, were conducted. Additionally, serologic screening for the new PLT antigen was performed.RESULTS:Serum from the NAIT infant's mother contained antibodies directed against a human PLT antigen (HPA) of the newborn. Using five‐cell‐lineage flow cytometry, we localized the antigen to a PLT glycoprotein (GP). Subsequent monoclonal antibody immobilization of PLT antigen assay and PLT immunofluorescence inhibition experiments localized the antigen to the GPIIIa subunit of the GPIIb/IIIa complex. GPIIIa localization was confirmed by sequence‐based typing studies, which identified a 1297C>T (407proline>serine substitution) mutation on the ninth exon of the GPIIIa gene. This mutation identified the third allele of HPA‐7. Anti‐Hitareacted with mutated GPIIIa‐transfected cells but not with stable transfectants expressing wild‐type GPIIIa. Serologic screening for Hitain the Japanese population revealed a phenotypic frequency of approximately 0.0015.CONCLUSIONS:We identified a new third allele of HPA‐7, which is characterized by a 1297C>T mutation in the GPIIIa gene. This 1297C>T allele was found in 0.15% of the Japanese population. An antibody against this antigen could be the cause of severe NAIT.
Monozygotic twins are discordant for chronic periodontitis: white blood cell counts and cytokine production after ex vivo stimulation
Authors: Torres de Heens Gaudy L. , Loos Bruno G. , Van Der Velden Ubele 
Published: January 2010

Torres de Heens GL, Loos BG, van der Velden U. Monozygotic twins are discordant for chronic periodontitis: white blood Cell Counts and Cytokine production after ex vivo stimulation. J Clin Periodontol 2010; 37: 129–136. doi: 10.1111/j.1600‐051X.2009.01485.x.AbstractObjectives: The aim of this study was to investigate the extent of concordance in the number of leucocytes and their cytokine secretion after ex vivo stimulation in a twin population discordant for the amount of periodontal breakdown.Material and Methods: Venous blood was collected from 18 adult twin pairs (10 monozygotic and eight dizygotic twins). Each twin pair consisted of a diseased twin (proband) and his/her co‐twin. In venous blood, leucocytes were counted. The cytokines interleukin (IL)‐1β, IL‐6, IL‐8, IL‐10 and IL‐12p40 were assessed after stimulation of monocytic cells, while IL‐13 and interferon (IFN)‐γ were determined after lymphocytic stimulation.Results: In the study population as a whole, probands showed higher total numbers of leucocytes and lower IL‐12p40 levels compared with their co‐twins. In monozygotic twins, no difference was found in the leucocyte counts, but probands secreted more IL‐6 than their co‐twins; an opposite trend was found for IL‐12p40.Conclusion: The results suggest that the observed discordance in periodontal breakdown in the studied monozygotic twin population may be related to the relatively high levels of IL‐6 and the low levels of IL‐12p40 secretion after ex vivo stimulation of whole‐blood cell cultures. This cytokine secretion profile may be regarded as a risk indicator of periodontitis.
Association between interleukin‐6 polymorphisms and periodontitis in Indian non‐smokers
Authors: Franch‐Chillida Fernando , Nibali Luigi , Madden Isobel , Donos Nikos , Brett Peter 
Published: January 2010

Franch‐Chillida F, Nibali L, Madden I, Donos N, Brett P. Association between interleukin‐6 polymorphisms and periodontitis in Indian non‐smokers. J Clin Periodontol 2010; 37: 137–144. doi: 10.1111/j.1600‐051X.2009.01501.x.AbstractAim: Genetic polymorphisms (SNPs) in the interleukin‐6 (IL‐6) gene have been associated with the presence of periodontitis. The aim of this study was to investigate the association between five SNPs in the IL‐6 promoter region and the periodontal status of a rural Indian population.Materials and Methods: Two hundred and fifty‐one systemically healthy volunteers were clinically assessed by a single calibrated examiner and divided into: healthy individuals and periodontitis patients based on the European Workshop on Periodontitis definitions and on a recently suggested definition, which takes into account age and clinical attachment levels. Their genomic DNA was analysed blindly using real‐time polymerase chain reaction to study IL‐6 variants. The association between genetic factors and the presence of periodontitis was assessed by logistic regression.Results: The IL‐6−174 GG genotype was associated with periodontitis in non‐smokers and older subjects (>45 years old). No statistically significant associations were detected between IL‐6 haplotypes and periodontal status, after adjusting for confounders.Conclusions: The IL‐6−174 polymorphism showed some evidence of an association with the periodontal status in non‐smokers and older subjects in this rural Indian population. This association might be mediated by the effect of IL‐6 on inflammatory responses.
Compromised periodontal status in an urban Sri Lankan population with type 2 diabetes
Authors: Preshaw Philip M. , De Silva Nimali , McCracken Giles I. , Fernando Devaka J. S. , Dalton Caroline F. , Steen Nick D. , Heasman Peter A. 
Published: January 2010

Preshaw PM, de Silva N, McCracken GI, Fernando DJS, Dalton CF, Steen ND, Heasman PA. Compromised periodontal status in an urban Sri Lankan population with type 2 diabetes. J Clin Periodontol 2010; 37: 165–1171. doi: 10.1111/j.1600‐051X.2009.01519.x AbstractAim: To determine the prevalence of periodontitis in an urban population of Sri Lankans with type 2 diabetes (T2DM) and to compare the data with those from a population of adults without diabetes.Methods: Demographic data and a diabetes profile were recorded for a population of urban Sri Lankan adults with T2DM including duration of diabetes, blood pressure; percentage glycosylated haemoglobin, fasting blood glucose level, total cholesterol; triglycerides, low‐ and high‐density lipoproteins. The clinical examination comprised an oral soft tissue examination, full‐mouth probing depths (PD), gingival recession (GR), clinical attachment levels and bleeding on probing (BoP).Results: Two hundred and eighty‐five individuals with T2DM and 72 controls were examined. 33.3% of T2DM patients were diagnosed with chronic periodontitis compared with 21.7% of controls (p=0.077). Subjects with T2DM had significantly more sites with PD4 and 5 mm (p<0.01), and higher mean GR and BoP scores (p<0.01).Conclusion: This urban Sri Lankan population of subjects with T2DM demonstrated a compromised periodontal status compared with non‐diabetic controls.