Search

Using the Elaborated Intrusion Theory of Desire and the Self-Regulatory Executive Function model of psychopathology as bases, this study explored whether metacognitive beliefs and desire thinking (DT) are associated with higher levels of Compulsive Sexual Behavior (CSB). A total of 1185 participants from the general population were included in the study (mean ± SD age = 25.32 years ± 5.58; age range = 18-19 years; females = 76.7 %). Metacognitive beliefs, DT, CSB, anxiety and depressive symptoms were assessed. Correlation analyses and path analyses were run. Results of the path analysis showed that positive metacognitive beliefs about DT were associated with DT-Imaginal Prefiguration (DT-IP), which in turn was positively associated with DT-Verbal Perseveration (DT-VP). The latter was strongly and positively associated with negative metacognitive beliefs about DT, which in turn was linked to CSB. Moreover, DT-VP was also found to be directly linked to the outcome variable and positive metacognitive beliefs about DT were also directly linked to DT-VP and negative metacognitive beliefs about DT. The total Coefficient of Determination (0.45) indicated a good fit to the observed data. Metacognitive beliefs and DT may be potential maintenance factors in CSB. Metacognitive beliefs and DT could also be considered as potential therapeutic targets in clinical interventions aimed at reducing the severity of CSB., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Desire thinking is a conscious and voluntary cognitive process that is closely linked to levels of craving and addictive behaviors. The Desire Thinking Questionnaire (DTQ) can be used to measure desire thinking in all age groups as well as in addicts. This measurement has also been translated into several languages. This study aimed to test the psychometric properties of the Chinese version of the DTQ (DTQ-C) among adolescent mobile phone users., Methods: One thousand and ninety-seven adolescents who own a mobile phone and are younger than 18 years old completed the DTQ-C and a battery of questionnaires assessing the big five personality traits, negative affect, brooding, self-control, craving, and problematic mobile phone use (PMPU). The psychometric analyses of the DTQ-C were conducted, including exploratory factor analysis (EFA), confirmatory factor analysis (CFA), reliability, and validity analysis., Results: The EFA revealed a 10-item two-factor structure (i.e., verbal perseveration and imaginal prefiguration) that was confirmed by the CFA. The results of CFA showed fit indexes of χ 2 /df = 4.83, CFI = 0.967, TLI = 0.954, RMSEA = 0.059, SRMR = 0.032. The total scale had internal consistency reliabilities of 0.93, which demonstrated that DTQ-C presented good reliability. The two dimensions were correlated with PMPU (r verbal perseveration  = 0.54; r imaginal prefiguration  = 0.45), neuroticism (r verbal perseveration  = 0.18; r imaginal prefiguration  = 0.14), conscientiousness (r verbal perseveration  = -0.19; r imaginal prefiguration  = -0.18), depression (r verbal perseveration  = 0.22; r imaginal prefiguration  = 0.16), anxiety (r verbal perseveration  = 0.26; r imaginal prefiguration  = 0.22), stress (r verbal perseveration  = 0.15; r imaginal prefiguration  = 0.10) and self-control (r verbal perseveration  = -0.29; r imaginal prefiguration  = -0.26), which demonstrated that DTQ-C presented good concurrent validity. The two factors of DTQ-C correlated weakly with brooding (ranging from 0.08 to 0.10). The principal component factor analysis of the two dimensions of desire thinking and craving showed that craving and desire thinking belonged to different dimensions. Both of which showed good divergent validity of desire thinking. Additionally, an examination of incremental validity revealed that two factors were both positively associated with PMPU beyond demographic characteristics, big five personality traits, negative affect, and self-control (B verbal perseveration  = 0.49 and B imaginal prefiguration  = 0.13)., Conclusions: It has been found that the 10-item DTQ-C is a reliable and valid measure of desire thinking in Chinese adolescent mobile phone users., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: According to the recent adaptation of the I-PACE model, desire thinking and craving might be closely related to problematic Internet pornography use. The overall aim of the present study was to investigate the role of two components of desire thinking (imaginal prefiguration and verbal perseveration) and craving in problematic Internet pornography use. Furthermore, we examined gender differences in the underlying mechanism linking desire thinking to problematic Internet pornography use., Method: A total of 414 Italian adults (mean age = 27.55 years, SD = 6.13; age range = 18-58; 53.6 % men) participated in this study. Participants completed an online survey to assess problematic Internet pornography use, pornography craving, desire thinking and problematic Internet use. Path analyses and a multi-group approach were used to test the relationships among variables and to explore gender differences., Results: Imaginal prefiguration was associated to pornography craving which, in turn, was associated to verbal perseveration as proximal antecedent of problematic Internet pornography use, above and beyond the effect of age, relationship status, and problematic Internet use. Two paths significantly differed between men and women: the path between verbal perseveration and problematic Internet pornography, which for women was weaker and did not reach significance; and the path between problematic Internet use and problematic Internet pornography use that was not significant for women., Conclusions: In line with the I-PACE model, the present study provided support for the potential role of desire thinking in problematic Internet pornography use as a specific Internet-use disorder and expanded the literature in the field by testing unexplored gender differences. Preventive and clinical implications are discussed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Desire thinking is a conscious and voluntary cognitive process that consists of perseverative focus on information, memories, and prefiguration of images related to a desired target. The Desire Thinking Questionnaire (DTQ) is acknowledged as a reliable and valid tool to measure desire thinking in both adults and adolescents. The aim of the present study was to examine the psychometric properties of the DTQ in Turkish adolescent sample., Methods: A convenience sample of 200 adolescents completed the Turkish version of the DTQ (DTQ-T) and an Exploratory Factor Analysis (EFA) was performed. Subsequently, a convenience sample of 701 adolescents completed the DTQ-T and a battery of questionnaires assessing personality traits, affect, boredom, impulsivity, and Internet Gaming Disorder (IGD). A Confirmatory Factor Analysis (CFA) was performed on the DTQ-T and validity was determined by examining correlations with other measures., Results: A 9-item two-factor structure was observed in the EFA. An 8-item two-factor structure was established in the CFA. Results demonstrated that the DTQ-T yields adequate levels of reliability and concurrent validity. Additionally, an examination of incremental validity showed that DTQ-T significantly predicted IGD when controlling for personality traits, affect, boredom, and impulsivity., Conclusions: The 8-item DTQ-T was found to be a reliable and valid measure of desire thinking among Turkish adolescents. Desire thinking may be a feasible target for mental health workers to alleviate the symptoms of IGD., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The Metacognitions about Online Gaming Scale (MOGS) measures maladaptive metacognitions about online gaming. The purpose of the present study was to evaluate psychometric properties of the MOGS, including its factor structure, reliability, and predictive validity among Iranian adolescents. The scale was administered to 769 Iranian adolescents (577 male, mean age = 16.39 ± 1.68 years) with an age range of 15-19 years. The participants completed the Persian-translated version of the MOGS, the Big Five Inventory-10, the Depression, Anxiety and Stress Scale 21, the Video-Game Related Cognitions Scale, the Motives for Online Gaming Questionnaire, and the Problematic Online Gaming Questionnaire. The results of the Exploratory Factor Analysis (n = 350) and Confirmatory Factor Analysis (n = 419) confirmed three-factors similar to the parent version, including "negative metacognitions about uncontrollability of online gaming" (N-MOGU), "negative metacognitions about dangers of online gaming" (N-MOGD), and "positive metacognitions about online gaming" (P-MOG). The Persian MOGS's reliability showed a suitable internal consistency for the P-MOG, the N-MOGU, the N-MOGD, and the total score in both confirmatory and exploratory samples (range 0.79 to 0.93). A hierarchical regression analysis showed that the Persian MOGS predicted 33.9% of the variance in problematic online gaming independently of personality traits, anxiety, depression, stress, and both gaming-related cognitions and gaming motives. Furthermore, the results of analyses of variance with follow-up Bonferroni pairwise comparisons showed that interaction between the factors of MOGS and types of game and tools of gaming was significant. The findings provide evidence that the Persian MOGS among Iranian adolescents appears psychometrically appropriate to be used by researchers and practitioners dealing with the prevention and treatment of problematic online gaming., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Desire Thinking (DT) is a voluntary cognitive process aimed at orienting to prefigure images, information, and memories about positive target-related experience. It comprises of two components: Imaginal Prefiguration and the Verbal Perseveration. DT has been found to be positively associated with alcohol use, gambling, nicotine use, and problematic Internet use. Despite this, neither qualitative nor quantitative reviews have been undertaken to critically summarize findings about the association between DT and addictive behaviours. The aim of this systematic review and meta-analysis is to evaluate the strength of the association between DT and addictive behaviours., Method: In accordance to PRISMA criteria, a research was conducted on PubMed and PsycInfo. A manual search of reference lists was also run. Search terms were: "addiction / gambling / alcohol / tobacco / nicotine / drug / cocaine / marijuana / cannabis / opioid / heroin / methadone / internet" AND "Desire Thinking"., Results: Ten studies were included. Both components of DT were found to be associated with addictive behaviours (alcohol use, nicotine use, gambling, problematic Internet use) in both clinical and community samples. The strength of the association between Verbal Perseveration and addictive behaviours appears to be stronger for alcohol and nicotine use than Internet use. The association between DT and addictive behaviours is not moderated by age., Conclusion: DT is present across different addictive behaviours. The assessment of DT and tailored interventions aimed to reduce the propensity to engage in DT should be considered in the treatment of addictive behaviours., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Research has indicated that craving is one of the strongest predictors of treatment outcome and relapse in Alcohol Use Disorders (AUD) but there is little consensus on the factors that may influence its activation and escalation. Research has also shown that desire thinking is an important cognitive process which may exacerbate craving in problem drinkers. The aim of present study was to explore, for the first time, the role of desire thinking in prospectively predicting relapse, craving and binge drinking in patients receiving treatment for AUD. One hundred and thirty-five patients admitted to two rehabilitation centres and two outpatient services for addiction and mental health problems were administered baseline, treatment completion and three months follow-up measures of anxiety and depression, AUD severity, binge drinking frequency, craving and desire thinking. Results indicated that the verbal perseveration component of desire thinking at treatment completion was the only significant predictor of relapse at follow-up over and above baseline AUD severity and binge drinking frequency. Furthermore, the imaginal prefiguration component of desire thinking and craving levels at treatment completion were found to predict craving levels at follow-up independently of AUD severity and binge drinking frequency at baseline. Finally, both the imaginal prefiguration and verbal perseveration components of desire thinking at treatment completion were found to be the only predictors of binge drinking frequency at follow-up independently of AUD severity and binge drinking frequency at baseline. Treatments for AUD should aim to reduce desire thinking in people to enhance clinical outcomes and reduce relapse risk., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Both positive smoking outcome expectancies and metacognitions about smoking have been found to be positively associated with cigarette use and nicotine dependence. The goal of this study was to test a model including nicotine dependence and number of daily cigarettes as dependent variables, anxiety and depression as independent variables, and smoking outcome expectancies and metacognitions about smoking as mediators between the independents and dependents., Methods: The sample consisted of 524 self-declared smokers who scored 3 or above on the Fagerstrom Test for Nicotine Dependence (FTND: Uysal et al., 2004)., Results: Anxiety was not associated with either cigarette use or nicotine dependence but was positively associated with all mediators with the exception of stimulation state enhancement and social facilitation. Depression, on the other hand, was found to be positively associated with nicotine dependence (and very weakly to cigarette use) but was not associated with either smoking outcome expectancies or metacognitions about smoking. Only one smoking outcome expectancy (negative affect reduction) was found to be positively associated with nicotine dependence but not cigarette use. Furthermore one smoking outcome expectancy (negative social impression) was found to be positively associated with cigarette use (but not to nicotine dependence). All metacognitions about smoking were found to be positively associated with nicotine dependence. Moreover, negative metacognitions about uncontrollability were found to be positively associated with cigarette use., Conclusions: Metacognitions about smoking appear to be a stronger mediator than smoking outcome expectancies in the relationship between negative affect and cigarette use/nicotine dependence. The implications of these findings are discussed., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Desire thinking is a conscious and voluntary cognitive process orienting to prefigure images, information and memories about positive target-related experience. Desire thinking has been found to be associated with both craving and alcohol use in clinical and non-clinical populations, however its role in predicting craving and problematic drinking patterns has never been investigated using a longitudinal design. The central aim of the present study was to explore the role of desire thinking at Time 2 (3months post-baseline) in predicting craving and binge drinking and Time 3 (6months post-baseline), controlling for levels of both these constructs and Time 1 (baseline). One hundred and thirty three non-hazardous drinkers were assessed on craving and binge drinking at Times 1 and 3, and on desire thinking at Time 2. Findings showed that desire thinking at Time 2 predicted craving and binge drinking at Time 3, controlling for craving and binge drinking at Time 1. Furthermore, the imaginal prefiguration component of desire thinking at Time 2 was found to mediate the relationship between craving at Times 1 and 3; conversely the verbal perseveration component of desire thinking at Time 2 was found to mediate the relationship between binge drinking at Times 1 and 3. The implications of these findings are discussed., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: Recent research has suggested that metacognitions may play a role across the spectrum of addictive behaviours. The goal of our studies was to develop the first self-report scale of metacognitions about online gaming., Method: We conducted two studies with samples of online gamers (n=225, n=348) to test the structure and psychometric properties of the Metacognitions about Online Gaming Scale and examined its capacity to predict weekly online gaming hours and Internet addiction., Results: Exploratory and confirmatory factor analyses supported a three-factor solution: positive metacognitions about online gaming, negative metacognitions about the uncontrollability of online gaming, and negative metacognitions about the dangers of online gaming. Internal consistency, predictive and divergent validity were acceptable. All the factors of the Metacognitions about Online Gaming Scale correlated positively with weekly online gaming hours and Internet addiction. Regression analyses showed that negative metacognitions about the uncontrollability of online gaming and levels of Internet addiction were the only significant predictors of weekly online gaming hours, and that positive metacognitions about online gaming and negative metacognitions about the uncontrollability of online gaming were the only significant predictors of Internet addiction., Conclusions: The Metacognitions about Online Gaming Scale was shown to possess good psychometric properties, as well as predictive and divergent validity within the populations that were tested., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Over the last twenty years metacognitive theory has provided a novel framework, in the form of the Self-Regulatory Executive Function (S-REF) model, for conceptualizing psychological distress (Wells & Matthews, 1994, 1996). The S-REF model proposes that psychological distress persists because of unhelpful coping styles (e.g. extended thinking and thought suppression) which are activated and maintained as a result of metacognitive beliefs., Objective: This paper describes the S-REF model and its application to addictive behaviors using a triphasic metacognitive formulation., Discussion: Evidence on the components of the triphasic metacognitive formulation is reviewed and the clinical implications for applying metacognitive therapy to addictive behaviors outlined., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Introduction: The aim of this study was to provide an overview of the construct of desire thinking and test a metacognitive model of desire thinking and craving, based on the work of Spada, Caselli and Wells (2012; 2013), which aims to explain the perseveration of desire thinking., Method: We conducted two studies involving four clinical samples (total N = 493) and a community sample (N = 494) presenting with different addictive behaviors. The relationships among variables were examined by testing the fit of path models within each sample., Results: In the model presented it was proposed that positive metacognitions about desire thinking are associated with, in turn, imaginal prefiguration and verbal perseveration, marking the activation of desire thinking. Verbal perseveration is then associated to negative metacognitions about desire thinking and craving denoting the pathological escalation of desire thinking. Finally, a direct association between positive metacognitions about desire thinking and negative metacognitions about desire thinking would mark those occasions where target-achieving behaviour runs as an automatized schemata without the experience of craving. Results indicated a good model fit in the clinical sample and a variation in the model structure in the community sample., Conclusion: These findings provide further support for the application of metacognitive theory to desire thinking and craving in addictive behaviors., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objectives: Recent research has suggested that metacognitions may play a role in smoking. The goal of the current set of studies was to develop the first self-report instrument of metacognitions about smoking., Method: We conducted three studies with samples of smokers (n = 222, n = 143, n = 25) to test the structure and psychometric properties of the Metacognitions about Smoking Questionnaire and examined its capacity to predict smoking behaviour., Results: Exploratory and confirmatory factor analyses supported a four-factor solution: positive metacognitions about cognitive regulation, positive metacognitions about emotional regulation, negative metacognitions about uncontrollability, and negative metacognitions about cognitive interference. Internal consistency, predictive and divergent validity, and temporal stability were acceptable. The metacognition factors correlated positively with daily cigarette use and levels of nicotine dependence, and contributed to the prediction of these outcomes over and above smoking outcome expectancies., Conclusions: The Metacognitions about Smoking Questionnaire was shown to possess good psychometric properties, as well as predictive and divergent validity within the populations that were tested. The metacognition factors explained incremental variance in smoking behaviour above smoking outcome expectancies., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Desire thinking is a voluntary cognitive process involving verbal and imaginal elaboration of a desired target. A desired target can relate to an object, an internal state or an activity, such as gambling. This study investigated the role of desire thinking in gambling in a cohort of participants recruited from community and clinical settings. Ninety five individuals completed a battery of self-report measures consisting of the Hospital Anxiety and Depression Scale (HADS), the Gambling Craving Scale (GCS), the Desire Thinking Questionnaire (DTQ) and the South Oaks Gambling Screen (SOGS). Correlation analyses revealed that gender, educational level, recruitment source, anxiety and depression, craving and desire thinking were correlated with gambling. A hierarchical multiple regression analysis revealed that both recruitment source and desire thinking were the only independent predictors of gambling when controlling for all other study variables, including craving. These findings are discussed in the light of metacognitive therapy (MCT)., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Rumination is an abstract, persistent, and repetitive thinking style that can be adopted to control negative affect. Recent studies have suggested the role of rumination as direct or indirect cognitive predictor of craving experience in alcohol-related problems., Aims: The goal of this study was to explore the effect of rumination induction on craving across the continuum of drinking behaviour., Methods: Participants of three groups of alcohol-dependent drinkers (N=26), problem drinkers (N=26) and social drinkers (N=29) were randomly allocated to two thinking manipulation tasks: distraction versus rumination. Craving was measured before and after manipulation and after a resting phase., Results: Findings showed that rumination had a significant effect on increasing craving in alcohol-dependent drinkers, relative to distraction, but not in problem and social drinkers. This effect was independent of baseline depression and rumination and was maintained across the resting phase., Conclusions: Rumination showed a direct causal impact on craving that is specific for a population of alcohol-dependent drinkers., (© 2013.)

This study investigated the relative contribution of the Big 5 personality factors and alcohol metacognitions in predicting weekly levels of alcohol use in binge drinking university students. No research to date has investigated whether either of these constructs predicts levels of weekly alcohol use in binge drinkers. A sample of university students (n=142) who were classified as binge drinkers were administered the following self-report instruments: NEO-Five Factor Inventory (NEO-FFI; Costa & McCrae, 1992), Positive Alcohol Metacognitions Scale (PAMS; Spada & Wells, 2008), Negative Alcohol Metacognitions Scale (NAMS; Spada & Wells, 2008), and Khavari Alcohol Test (KAT; Khavari & Farber, 1978). Pearson product-moment correlations showed that weekly levels of alcohol use were negatively correlated with agreeableness and conscientiousness and positively correlated with positive alcohol metacognitions about cognitive self-regulation, negative alcohol metacognitions about uncontrollability and negative alcohol metacognitions about cognitive harm. A hierarchical regression analysis revealed that conscientiousness and positive alcohol metacognitions about cognitive self-regulation were the only two significant predictors of weekly levels of alcohol use when controlling for gender. These findings show that being male, low on conscientiousness and high on positive alcohol metacognitions about cognitive self-regulation raises the risk for increased weekly levels of alcohol use in binge drinking university students. The implications of these findings are discussed., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Desire thinking is a voluntary cognitive process involving verbal and imaginal elaboration of a desired target. Recent research has highlighted the role of desire thinking in the maintenance of addictive, eating and impulse control disorders. The goal of this research project was to develop the first self-report measure of desire thinking. In Study 1 we constructed the Desire Thinking Questionnaire (DTQ) and conducted a preliminary factor analysis which identified two factors. The first factor concerned the perseveration of verbal thoughts about desire-related content and experience and was named 'Verbal Perseveration'. The second factor concerned the tendency to prefigure images about desire-related content and experience and was named 'Imaginal Prefiguration'. In Study 2 we performed a confirmatory factor analysis which provided support for this two factor solution, with both factors achieving adequate internal consistency. Divergent validity was also established through correlation analyses. In Study 3 the temporal stability of the DTQ was examined and confirmed. Finally, in Study 4, the predictive validity of the DTQ in a sample of alcohol abusers was investigated. The DTQ was shown to possess good psychometric properties, as well as divergent and predictive validity. This self-report measure may aid future research into desire thinking and craving, as well as facilitate assessment and case formulation within the context of addictive, eating and impulse control disorders., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

This study investigated the role of negative emotions and metacognitions in predicting problem drinkers' drinking status (absence or presence of drinking) and level of weekly alcohol use at 3, 6 and 12 months after a course of treatment. A total of 70 problem drinkers with a DSM-IV diagnosis of alcohol abuse participated in the study. Depressive symptoms were assessed with the Beck Depression Inventory and symptoms of anxiety were measured with the state anxiety sub-scale of the State-Trait Anxiety Inventory. Metacognitions were measured with the Meta-Cognitions Questionnaire. Results indicated that beliefs about need to control thoughts predicted: (1) drinking status at 3 and 6 months; and (2) level of weekly alcohol use at 3, 6 and 12 months. The contribution of metacognition was independent of negative emotions and initial level of weekly alcohol use. The results support the role of metacognition in problem drinking. Given that metacognitions are a possible risk factor for drinking status and level of weekly alcohol use it is suggested that treatment for problem drinking could target this variable.

Recently an innovative novel class angiotensin-AT1 antagonist has been developed by Rottapharm. In this study, we present a validated method for detecting CR 3834 in biological matrices using high-performance liquid chromatography (HPLC) with diode array detection. After oral administration (30mg/kg) to Wistar rats, the plasma and urine concentrations of CR 3834 and its potential metabolic products were determined. Moreover, the plasmatic time course in rats has been determined after intravenous (IV) administration of CR 3834 (5mg/kg). Biological samples (0.5ml of plasma and 1ml of urine) were purified using solid-phase extraction (SPE) of analytes and the internal standard Idebenone, 2,3-dimethoxy-5-methyl-6-(10-hydroxydecyl)-1-4-benzoquinone. A chromatographic separation was performed on an Adsorboshere C18 at 25 degrees C, with a pre-column of the same matrix; the eluent was made up of acetonitrile/acidified water with CF3COOH (pH 2.01) in ratio of 75:25 (v/v); the flow rate was 1.0ml/min and a 100microl loop. The lower limit of detection (LOD) was taken as 25ng/ml in plasma and 50ng/ml in urine samples. The lower limit of quantification (LOQ) was taken as 0.1 and 0.2microg/ml in plasma and urine samples, respectively. The procedures were validated according to international standards with a good reproducibility and linear response (r=0.9916 in plasma; r=0.9997 in urine). The coefficients of variation inter assay ranged between 2.579 and 4.951% in plasma, and between 0.813 and 2.460% in urine. Mean recovery for CR 3834 was 79% in plasma and 97% in urine samples. The experiments performed demonstrated that the method presented was suitable for determining this new angiotensin-AT1 antagonist in rat plasma and urine.

Microdialysis in intact and denervated striatum of unilaterally 6-hydroxydopamine (6-OHDA) lesioned rats was used to investigate whether CR 3394, N-[2-(3,5-dimethyl-1-adamantyl)ethyl]acetamidine, an adamantane derivative with preferential selectivity for the NR2B subunit of the NMDA receptor, has dopamine releasing properties in vivo. We also investigated whether this NMDA antagonist can potentiate the effects of L-Dopa on extracellular dopamine in these animals. After systemic injection, there was no significant effect of CR 3394 on extracellular dopamine, at all doses studied (1, 5 and 20 mg/kg i.p.), in either intact or in denervated striatum. On the other hand, striatal perfusion with 100 microM of the compound elicited release of dopamine in intact, but not in denervated striatum. In denervated striatum of the 6-OHDA-lesioned rats, CR 3394 (5 mg/kg) significantly enhanced the dopamine release induced by L-Dopa administration (25 mg/kg i.p.) in combination with benserazide (10 mg/kg i.p.). In particular, the onset of action of L-Dopa was potentiated. However, when combined with a subthreshold dose of L-Dopa (5 mg/kg), the effects of CR 3394 were lost. We conclude that CR 3394, like other NR2B receptor antagonists, has dopamine releasing properties in vivo. It enhances the effects of suprathreshold doses of L-Dopa in the denervated striatum, but not of low doses of L-Dopa. Therefore, future studies are necessary to establish the potential of selective NR2B receptor antagonists as L-Dopa-sparing agents.

This paper aims to discuss the validation and family determinants affecting the longevity of Sardinian centenarians, using a genealogical approach. This preliminary study presents the first results of a genealogical tree reconstruction of selected centenarians aged 105 and over, from certain areas. These are mostly situated in the province of Nuoro, an area with the highest rate of centenarians and where the female-to-male sex ratio tends to be male-biased. An accurate centenarian age validation was performed that required a meticulous examination of numerous civil status records and parish registers. An important finding was that longevity occurs among the ascendants of a particular branch of the family. The data used are still provisional but, should it apply to other validated cases, it would provide empirical evidence of a genetic component in longevity. A more thorough examination of the data available may yield deeper insights into the role played by endogamy and consanguinity.

CR3465 (L-Tyrosine, N-[(2-quinolinyl)carbonyl]-O-(7-fluoro-2-quinolinylmethyl) sodium salt) is a potent antagonist of [3H]leukotriene D4 ([3H]LTD4) binding to guinea pig lung preparations, its Ki (4.7+/-0.7 nM) being comparable with that of montelukast (5.6+/-0.6 nM). In tracheal strips from standard or ovalbumin-sensitized guinea pigs, CR3465 caused parallel rightward shifts in the concentration-response curves obtained with either LTD4 or antigen (pA(2), 8.74 and 8.15). Intravenous (i.v.) administration of the agent both antagonized (ED50, 9.9+/-1.9 microg/kg) and reverted LTD4 -induced bronchoconstriction of anesthetized guinea pigs. CR3465 reduced inflammatory infiltrates in the bronchoalveolar lavage fluid after antigen challenge of sensitized animals, and proved also active in inhibiting phosphodiesterase 3 (PDE3) and phosphodiesterase 4 (PDE4) activities exhibited by human platelets and neutrophils (IC50, 2.01+/-0.07 and 4.7+/-0.5 microM). In line with properties shown by phosphodiesterase inhibitors, CR3465 reduced the contractile response of guinea pig airways to histamine and decreased N-formyl-Met-Leu-Phe (fMLP)-induced degranulation of human neutrophils (IC50, 13.8 microM). Oral administration (20 mg/kg) of the compound in rats produced a significant (37%) ex vivo inhibition of tumor necrosis factor-alpha (TNF-alpha) release from lipopolysaccharide-stimulated whole blood. Pharmacokinetic data in the rat demonstrated approximately 100% bioavailability of the agent. We conclude that CR3465 represents a potent leukotriene CysLT1 receptor antagonist with enhanced effects, being also useful for counteracting spasmogenic and inflammatory stimuli other than those elicited by cysteinyl-leukotrienes (Cys-LTs).

Although changes in airway responsiveness in pulmonary inflammation are commonly related to the action of infiltrated leukocytes, our previous report suggested a direct role of inflammatory cytokines in LPS-induced lung hyporesponsiveness. The aim of this study was to define if cytokines detected in the BALF (bronchoalveolar lavage fluid) of intratracheal LPS-treated mice could be, at least in part, responsible for 5-HT (5-hydroxytryptamine) lung hyporeactivity. Our results show that intratracheal instillation of LPS induced a time-dependent increase in IL-(interleukin-)1beta, IL-6, and TNF (tumor necrosis factor)alpha in the BALF. Cytokine production was paralleled by 5-HT lung hyporesponsiveness, and intratracheal administration of TNFalpha proved to be very efficient in inhibiting 5-HT responsiveness. In addition, systemic treatment with rolipram, an inhibitor of TNFalpha production, was paralleled by a significant recovery of lung responsiveness. On the contrary, IL-1beta and IL-6 were not demonstrated to play a relevant role in 5-HT hyporesponsiveness. It is concluded that TNFalpha could be a crucial mediator of LPS-induced lung hyporesponsiveness.

Although it is commonly accepted that the anti-inflammatory effect of nonsteroidal anti-inflammatory drugs (NSAIDs) is mainly associated to their ability to inhibit the cyclooxygenase (COX) enzyme system, several results indicate that non-COX mechanisms could be important in the therapeutical effect of these drugs. The aim of this study was to define if NSAIDs could exert, at least in part, their anti-inflammatory effect by inhibiting the activities of human polymorphonuclear leukocytes (PMNs) triggered by chemotactic stimuli and, if so, to understand the relationship of this effect with COX inhibition. A unique opportunity to dissociate the inhibition of prostaglandin (PG) synthesis from other therapeutical properties of NSAIDs is constituted by ketoprofen isomers being the S-isomer 100 time more potent than R-isomer on COX inhibition. Our results show that R- and S-ketoprofen, independently of their potency as PG inhibitors, proved very efficacious in selective inhibition of interleukin-8 (IL-8) chemotaxis. Inhibition of IL-8 chemotaxis was not restricted to ketoprofen isomer as it could be observed also with drugs belonging to different classes of NSAIDs and it was obtained at drug concentration superimposable to plasma levels after therapeutic administration in patients. Reduction of IL-8 migration by ketoprofen isomers was paralleled by selective inhibition of PMN response in terms of intracellular calcium concentration ([Ca(2+)]i) increase and extracellular signal regulated kinase(ERK)-2 activation, two intracellular mediators reported to be critical for PMN activities. It is concluded that inhibition of IL-8 chemotaxis could represent a new clinical target for ketoprofen isomers and, in fact, contribute to the anti-inflammatory activity of NSAIDs.