bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACTAs 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

ABSTRACTKnowledge 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

ABSTRACTIn 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

ABSTRACTThe 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

ABSTRACTThe 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

ABSTRACTThe 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.
Haplotypes of the plasminogen activator gene associated with ischemic stroke
Authors: Saito Kosuke , Sato Naoyuki , Morita Akihiko , Takahashi Teruyuki , Soma Masayoshi , Usami Ron , Nakayama Tomohiro 
Published: October 2006

SummaryIschemic stroke (IS) is thought to be a multifactorial disorder associated with genetic backgrounds and environmental factors. In the circulating plasma, tissue plasminogen activator (tPA) catalyzes the reaction from plasminogen to plasmin. If there is a functional disability of tPA, induction of thrombosis and infarction disorders can occur. The aim of this study was to performa haplotype-based case-control study using single nucleotide polymorphisms (SNPs) in the human tPA gene, and to assess the association between the tPA gene and IS. We genotyped 182 IS individuals and 403 controls for five SNPs in the human tPA gene, rs7007329, rs732612, rs8178750, rs2020922, and rs4471024. Using these five SNPs, a haplotype-based case control study was performed. There were seven SNP combinations that exhibited significant differences in the overall distribution between the IS and control groups. Linkage disequilibrium analysis showed that the combination of rs7007329 and rs8178750 was useful in identification of the susceptibility haplotype. The frequency of the G-T haplotype at rs7007329-rs8178750 was significantly higher in the IS group (1.2%) as compared to the control group (0.0%) (p=0.003).Diplotype analysis also showeda significant association of the diplotype with the G-T haplotype at rs7007329-rs8178750 (OR:11.4, 95%CI:1.32–97.9, p=0.013). These results suggest that the G-T haplotype at rs7007329-rs8178750 of the tPA gene isa genetic marker for IS, and that tPA ora neighboring gene isa susceptibility gene for IS.
Psychological impact of testing for thrombophilic alterations
Authors: Razzaboni Elisabetta , Gremigni Paola , Bitti Pio Enrico , Favaretto Elisabetta , Palareti Gualtiero , Legnani Cristina 
Published: October 2006

SummaryWe investigated the psychological impact of testing for the presence of thrombophilic alterations. The enrolled subjects received counseling from a physician before blood sampling and after receiving results, with a view to provide clear information about the aim of thrombophilia screening (TS). Participants were requested to completea pre-test questionnaire during this interview and a post-test questionnaire 20 days after receiving theTS results. One hundred ninety-seven subjects completed the pre-test questionnaire and 140/197 (71.1%) returned the post-test one. The TS results were altered in 36 (25.7%, R506Q mutation n=19; G20210A mutation n=9; antithrombin deficiency n=1; LAC phenomenon n=4; hyperhomocysteinemia n=3) and normal in 104 subjects. We assessed: perceived health status (PHS), state of anxiety, health fears, depressive reactions, moods, perceived well-being, and perceived daily-life stress. For both groups, both at pre- and post-test, none of the psychological variable scores showed significant worsening, regardless of whether TS resulted altered or normal. Anxiety significantly (p≤0.05) decreased at post-test in the altered group and a nonsignificant improvement in PHS after TS result communication was recorded in both groups. Age was an important factor in mediating psychological impact. In conclusion, diagnosis of thrombophilic alterations seems to be well accepted in the short term and TS should not be discouraged for potential adverse psychological effects. However, the psychological impact over a longer period of receiving altered results needs to be further investigated. The relationship between absence of adverse psychological reactions and quality of counseling program provided before and after TS should also be investigated.
Identification of a new truncated form and deamidation products of fibrinopeptide B released by thrombin from human fibrinogen
Authors: Cardinali Barbara , Damonte Gianluca , Melone Luca , Salis Annalisa , Tosetti Francesca , Rocco Mattia , Profumo Aldo 
Published: October 2006

SummaryQuantification of fibrinopeptides release is widely used to investigate fibrinogen activation, and standard chromatographic or capillary electrophoretic procedures are readily available. However, in the analyses of fibrinopeptide mixtures derived from the action of thrombin on human fibrinogen, a few unidentified peaks are usually present. The composition of these peaks was studied by reverse-phase HPLC/MS, revealing a single major anomalous peptide having a molecular mass of 1384.4. A further MS/MS analysis allowed the identification of this form, as a Nterminally truncated fibrinopeptideB (fpB) lacking the first two residues (pyroglutamic acid and glycine). This previously unidentified, relatively low-abundance form (∼7%) has been found consistently in our fibrinopeptides preparations, and analysis of the parent Bβ-chain suggest that it is likely present in circulating fibrinogen. In addition, deamidated forms of all fpB species (including desArgB), resulting from the conversion of asparagine to aspartic acid, were also identified. Overall, these previously unreported forms constitute a substantial amount of fpB (up to ∼17% of the total), and should be taken into account for a reliable quantitative analysis of fpB release.
Amplified anticoagulant activity of tissue factor-targeted thrombomodulin
Authors: Wu Chenliang , Vincelette Jon , Martin-McNulty Baby , Alexander Serene , Larsen Brent , Light David , McLean Kirk , Wang Yi-Xin 
Published: October 2006

SummaryTissue factor (TF) exposure isa potent pro-thrombotic trigger that initiates activation of the coagulation cascade, while thrombomodulin (TM) is a potent anticoagulant protein that limits the extent of activation. Both TF neutralizing antibodies and soluble TM (sTM) are effective anticoagulants. We have developed a novel anticoagulant fusion protein, Ab(TF)-TM, by fusing a TF-neutralizing single-chain antibody, Ab(TF), to an active fragment of TM. Ab(TF)-TM is a novel anticoagulant targeting to sites of TF exposure with a dual mechanism of action. The Ab(TF) portion of the molecule inhibits TF/factor VIIa mediated activation of FIX and FX, and the TM portion of the molecule acts as a cofactor for activation of protein C. In-vitro coagulation assays show that Ab(TF)-TM more potently inhibits TF-initiated coagulation (prothrombin time) than can its individual components, Ab(TF) (20-fold) and sTM (80-fold) alone, or in combination (10-fold). In contrast, the potency of Ab(TF)-TM in the activated partial thromboplastin and thrombin clotting time assays was similar to sTM alone. Ina rat model of disseminated intravascular coagulation (DIC), intravenous injection of a human TF-containing thromboplastin reagent (0.5 ml/kg) resulted in an immediate death in ∼60% of the animals and a clinical score of ∼2.5. Pre-injection of Ab(TF)-TM or Ab(TF) and sTM, given alone or in combination, showed dose-dependent efficacy. At a dose of 0.7 nmol/kg, Ab(TF)-TM completely prevented death and reduced clinical scores by 79%, while neither Ab(TF) nor sTM, given alone or in combination, showed significant therapeutic effects. Calculated effective doses that reduced mortality by 50% relative to that in the control group (ED50, nmol/kg) were 0.21 for Ab(TF)-TM, 3.2 for an equimolar mixture of Ab(TF) and sTM, 4.3 for sTM and 20 for Ab(TF). Thus, Ab(TF)-TM presented 10– to 100-fold enhancement of the anticoagulant potency, relative to the ED50 in Ab(TF) and sTM given either alone or in combination, in a rat DIC model.
Folic acid administration and antibodies against homocysteinylated proteins in subjects with hyperhomocysteinemia
Authors: Undas Anetta , Stïpień Ewa , Glowacki Rafal , Tisończyk Joanna , Tracz Wieslawa , Jakubowski Hieronim 
Published: October 2006

SummaryGrowing evidence indicates that elevated total homocysteine (tHcy) levels can elicit autoimmune response in vivo. Antibodies against Nε-Hcy-proteins have been shown to be associated with stroke and premature myocardial infarction. The aim of the current study was to investigate the effect of treatment with folic acid on anti-Nε-Hcy-albumin and -hemoglobin antibodies. We recruited 20 apparently healthy men and 12 male patients with documented coronary artery disease (CAD). All participants had plasma fasting tHcy levels >15 µM. At baseline, and after three and six months of treatment with folic acid 1 mg daily, we determined tHcy, serum folate and vitamin B12 levels, along with serum anti-Nε-Hcy-albumin and -hemoglobin IgG antibodies using the home-made immunoenzymatic assays. Both groups did not differ with regard to age, tHcy, folate, lipid profile, and CRP. The only significant difference between healthy subjects and CAD patients was levels of antibodies against Nε-Hcy-albumin. As expected, folic acid administration led to significant decreases in tHcy and increases in folate levels in both groups. Levels of both anti-Nε-Hcy-albumin and -hemoglobin antibodies fell markedly following a three-month folic acid administration in healthy subjects, but not in CAD patients, without any changes at six months in either group. Folic acid administration resulted in a loss of significant correlations between tHcy and antibodies both following three and six months of the therapy in healthy subjects, in contrast to CAD patients. Carriers of the methylenetetrahydrofolate reductase (MTHFR) 677T allele with CAD had significantly higher levels of anti-Nε-Hcy-albumin before and during folic acid administration as compared to healthy subjects. In conclusion, our findings suggest that Hcy-related autoimmune response is resistant to folic acid administration in CAD patients, while in healthy subjects reduced tHcy levels are associated with suppressed production of antibodies against Nε-Hcyproteins. These observations might explain at least in part the failure of vitamin therapy to reduce the risk of cardiovascular events as recently reported.
Antibody profile and clinical course in primary antiphospholipid syndrome with pregnancy morbidity
Authors: Ruffatti Amelia , Tonello Marta , Del Ross Teresa , Cavazzana Anna , Grava Chiara , Noventa Franco , Tona Francesco , Iliceto Sabino , Pengo Vittorio 
Published: October 2006

SummaryIn women diagnosed as having category I primary obstetric antiphospholipid syndrome, clinical characteristics and the risk of subsequent thromboembolic events and further unsuccessful pregnancy has not been clearly documented. Women with unexplained obstetric complications and no definite autoimmune systemic diseases were tested for lupus anticoagulant (LA), IgG/ IgM anticardiolipin (aCL) and IgG/IgM anti-human β2-Glycoprotein I (aβ2GPI) antibodies and diagnosed as having primary antiphospholipid syndrome (APS) in classification category I on the basis of more than one laboratory criteria present in any combination. Characteristics at the time of diagnosis and risk factors for subsequent clinical events during a mean follow-up of 6.3 years were evaluated. Fifty-three of 600 women studied were found to fulfil obstetric criteria and had more than one positive laboratory test at the time of diagnosis. All the women were a CL and aβ2GPI positive, and 16 were also LA positive. This latter group (triple positivity) had distinct features and had more frequently experienced previous thromboembolism (OR= 122.5, 95% CI 16–957, p<0.001).They also had an increased rate of late pregnancy loss (OR=16.2, 95%CI 0.9–292, p=0.01), and a higher IgG aβ2GPI titer at diagnosis (median, 25th and 75th percentile were 118, 37–962, vs. 23, 18–32, respectively, p<0.0001). During follow-up, the rate of thromboembolic events was significantly higher in the group of women with triple positivity and/ or previous thromboembolism (OR=57.5, 95% CI 2.7–1160, p=0.0004) which were the only independent predictors of TE in the multivariate model. Recurrent pregnancy loss took place in seven out of 47 women who had a new pregnancy. Triple positivity and/or previous thromboembolism were again the only independent markers (OR=34.4, 95% CI 3.5–335.1, p=0.003) of an unsuccessful new pregnancy. In conclusion, in primary APS with pregnancy morbidity in classification category I, quite different groups of patients may be identified on the basis of laboratory tests. Triple positivity and/or a history of thromboembolism predict new TE events and new unsuccessful pregnancies.
Identification of functional polymorphisms of the thromboxane A2 receptor gene in healthy volunteers
Authors: Fontana Pierre , Gandrille Sophie , Remones Véronique , Dupont Annabelle , Reny Jean-Luc , Aiach Martine , Gaussem Pascale 
Published: October 2006

SummaryThromboxane A2 receptor (TP) is an important actor in vascular physiology and plays a crucial role in the platelet activation process. Genetic polymorphisms of the gene coding for the TP have been described, but their impacts on platelet function tests are unknown. The aim of this study was to investigate the relationship between genetic polymorphisms of the coding sequence of the TP gene and platelet function tests. We investigated 100 healthy volunteers twice, one week apart by performing platelet aggregation and secretion tests. We sequenced the coding region of the TP gene and confronted the genetic variants with the phenotypic results. We identified five single nucleotide polymorphisms (SNP); one of them, T1712C, replaces Leu by Pro at position 133 of the isoform β of the TP. Homozygosity for the minor allele of the C795T, C924T or the G1686A SNP was associated with a decreased expression of CD62P when platelets were stimulated with the TP agonist U46619. As C795T and C924T have been linked to clinical disorders in which TxA2 plays a key role, the possible role of the G1686A and T1712C SNP should also be examined in selected diseases.