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Studio dell'effetto dell'attivazione del recettore GABAB sul consumo di alcol e sulle proprietà motivazionali dell'alcol nel ratto

GABA is a major inhibitory neurotransmitter in the brain. Recent preclinical evidence suggests that pharmacological activation of the GABAB receptor (one of the two receptorstypes to which GABA may bind) reduced alcohol intake and ameliorated alcohol in take and ameliorated alcohol withdrawal syndrome. The recent discovery of a modulatory binding site within the GABAB receptor, together with the synthesis of in vivo effective drugs with positive allosteric modulatory activity, provide novel tools for investigations on the role of the GABAB receptor in the mediation of alcohol-related behaviors. The aim of the present study was twofold: (a) investigating the effect of GABAB receptor direct agonists on alcohol�s reinforcing and motivational properties, and (b) extending the investigation to some GABAB receptor positive allosteric modulators (PAMs). Selectively bred, Sardinian alcohol preferring (sP) rats (an animal model of alcoholism) were initially trained to press a lever to gain access to alcohol (index of the reinforcing and motivational properties of alcohol) under standard procedure of oral alcohol self-administration. Injection of non-sedative doses of both baclofen (direct agonist) and GS39383 (PAM) resulted in statistically, dose-dependent reduction of the rats' responding on the, alcohol-associated lever. These data suggest that activation of the GABAB receptor-either by mean of direct agonists or PAMs - may suppress alcohol reinforcement and motivation to consume alcohol

Post-capitalist literature in urban morphology of the last decade. Its relationship with New Users and ICT.

The article is constructed hermeneutically through content analysis based on the grounded theory of post-capitalist literature. The methodology is qualitative and consists of a systematic review of the scientific literature, directed to verify its reference and resonance in urban morphology of the last decade and establish its relationship with new users and ICT. The analysis determines more comprehensive alternatives to reduce future socio-environmental problems generated by neoliberal practices. The results obtained display directions towards overcoming the system of consumerism, deepening the crisis of global capitalism, and transcending with inclusive alternatives that can lead us towards a more equitable and less harmful development for the population and its environment. Keywords: Post-capitalism, urban morphology, ICT, user.El artículo se construye de manera hermenéutica a través del análisis de contenido basado en teoría fundamentada de la literatura postcapitalista, la metodología es de orden cualitativa y consiste en una revisión sistemática de la literatura científica, dirigida a comprobar su referencia y resonancia en la morfología urbana de la última década y establecer su relación con los nuevos usuarios y las TIC. El análisis determina alternativas más íntegras para disminuir los futuros problemas socioambientales, generados por las prácticas neoliberales. Los resultados obtenidos se dirigen a: superar el sistema de consumismo, profundizar sobre la crisis del capitalismo global y trascender con alternativas inclusivas que pueden dirigirnos hacia un desarrollo más equitativo y menos dañino para la población y su entorno. Palabras clave: Postcapitalismo, morfología urbana, TIC, usuario.Peer Reviewe

Reduction by the Positive Allosteric Modulator of the GABAB Receptor, GS39783, of Alcohol Self-Administration in Sardinian Alcohol-Preferring Rats Exposed to the “Sipper” Procedure

The present study was designed to evaluate (a) alcohol self-administration behavior of selectively bred, Sardinian alcohol-preferring (sP) rats exposed to the so-called “sipper” procedure (characterized by the temporal separation between alcohol-seeking and -taking phases), and (b) the effect of the positive allosteric modulator of the GABAB receptor, GS39783, on alcohol self-administration in sP rats exposed to this procedure. To this end, sP rats were initially trained to lever-respond under a reinforcement requirement (RR) 55 (RR55) for alcohol. Achievement of RR55 resulted in the 20-min presentation of the alcohol (15%, v/v)-containing sipper bottle. Once stable levels of lever-responding and alcohol consumption were reached, rats were treated with 0, 25, 50, and 100 mg/kg GS39783 (i.g.) 60 min before the self-administration session. Rats displayed robust alcohol-seeking (as suggested by relatively short latencies to the first lever-response and high frequencies of lever-responding) and -taking (as suggested by alcohol intakes averaging approximately 1.5 g/kg) behaviors. Pretreatment with GS39783 inhibited both alcohol-seeking (the number of rats achieving RR55 and the mean RR value were virtually halved) and -taking (the amount of self-administered alcohol was reduced by approximately 60%). The results of the present study suggest the power of the “sipper” procedure in triggering high levels of alcohol-seeking and -taking behavior in sP rats. Further, these results extend to this additional procedure of alcohol self-administration the capacity of GS39783 to reduce the motivational properties of alcohol and alcohol consumption in sP rats

Predisposition to Alcohol Drinking and Alcohol Consumption Alter Expression of Calcitonin Gene-Related Peptide, Neuropeptide Y, and Microglia in Bed Nucleus of Stria Terminalis in a Subnucleus-Specific Manner

Excessive alcohol consumption is often linked to anxiety states and has a major relay center in the anterior part of bed nucleus of stria terminalis (BNST). We analyzed the impact of (i) genetic predisposition to high alcohol preference and consumption, and (ii) alcohol intake on anterior BNST, namely anterolateral (AL), anteromedial (AM), and anteroventral (lateral + medial subdivisions: AVl, AVm) subnuclei. We used two rat lines selectively bred for low- and high-alcohol preference and consumption, named Sardinian alcohol-non preferring (sNP) and -preferring (sP), respectively, the latter showing also inherent anxiety-related behaviors. We analyzed the modulation of calcitonin gene-related peptide (CGRP; exerting anxiogenic effects in BNST), neuropeptide Y (NPY; exerting mainly anxiolytic effects), and microglia activation (neuroinflammation marker, thought to increase anxiety). Calcitonin gene-related peptide-immunofluorescent fibers/terminals did not differ between alcohol-naive sP and sNP rats. Fiber/terminal NPY-immunofluorescent intensity was lower in BNST-AM and BNST-AVm of alcohol-naive sP rats. Activation of microglia (revealed by morphological analysis) was decreased in BNST-AM and increased in BNST-AVm of alcohol-naive sP rats. Prolonged (30 consecutive days), voluntary alcohol intake under the homecage 2-bottle “alcohol vs. water” regimen strongly increased CGRP intensity in BNST of sP rats in a subnucleus-specific manner: in BNST-AL, BNST-AVm, and BNST-AM. CGRP area sum, however, decreased in BNST-AM, without changes in other subnuclei. Alcohol consumption increased NPY expression, in a subnucleus-specific manner, in BNST-AL, BNST-AVl, and BNST-AVm. Alcohol consumption increased many size/shapes parameters in microglial cells, indicative of microglia de-activation. Finally, microglia density was increased in ventral anterior BNST (BNST-AVl, BNST-AVm) by alcohol consumption. In conclusion, genetic predisposition of sP rats to high alcohol intake could be in part mediated by anterior BNST subnuclei showing lower NPY expression and differential microglia activation. Alcohol intake in sP rats produced complex subnucleus-specific changes in BNST, affecting CGRP/NPY expression and microglia and leading to hypothesize that these changes might contribute to the anxiolytic effects of voluntarily consumed alcohol repeatedly observed in sP rats

Multi‑parametric MRI in the diagnosis and scoring of gastrointestinal acute graft‑versus‑host disease

Objectives Acute gastrointestinal graft-versus-host disease (GI-aGVHD) is a severe complication of allogeneic hematopoietic stem cell transplantation (HSCT). Diagnosis relies on clinical, endoscopic, and pathological investigations. Our purpose is to assess the value of magnetic resonance imaging (MRI) in the diagnosis, staging, and prediction of GI-aGVHD-related mortality. Methods Twenty-one hematological patients who underwent MRI for clinical suspicion of acute GI-GVHD were retrospectively selected. Three independent radiologists, blinded to the clinical findings, reanalyzed MRI images. The GI tract was evaluated from stomach to rectum by analyzing fifteen MRI signs suggestive of intestinal and peritoneal inflammation. All selected patients underwent colonoscopy with biopsies. Disease severity was determined on the basis of clinical criteria, identifying 4 stages of increasing severity. Disease-related mortality was also assessed. Results The diagnosis of GI-aGVHD was histologically confirmed with biopsy in 13 patients (61.9%). Using 6 major signs (diagnostic score), MRI showed 84.6% sensitivity and 100% specificity in identifying GI-aGVHD (AUC = 0.962; 95% confidence interval 0.891–1). The proximal, middle, and distal ileum were the segments most frequently affected by the disease (84.6%). Using all 15 signs of inflammation (severity score), MRI showed 100% sensitivity and 90% specificity for 1-month related mortality. No correlation with the clinical score was found. Conclusion MRI has proved to be an effective tool for diagnosing and scoring GI-aGVHD, with a high prognostic value. If larger studies will confirm these results, MRI could partly replace endoscopy, thus becoming the primary diagnostic tool for GI-aGVHD, being more complete, less invasive, and more easily repeatable. Key Points • We have developed a new promising MRI diagnostic score for GI-aGVHD with a sensitivity of 84.6% and specificity of 100%; results are to be confirmed by larger multicentric studies. • This MRI diagnostic score is based on the six MRI signs most frequently associated with GI-aGVHD: small-bowel inflammatory involvement, bowel wall stratification on T2-w images, wall stratification on post-contrast T1-w images, ascites, and edema of retroperitoneal fat and declivous soft tissues. • A broader MRI severity score based on 15 MRI signs showed no correlation with clinical staging but high prognostic value (100% sensitivity, 90% specificity for 1-month related mortality); these results also need to be confirmed by larger studies

Reducing Effect of Saikosaponin A, an Active Ingredient of Bupleurum falcatum, on Intake of Highly Palatable Food in a Rat Model of Overeating

Recent lines of experimental evidence have indicated that saikosaponin A (SSA)—a bioactive ingredient of the medicinal plant, Bupleurum falcatum L.—potently and effectively reduced operant self-administration of chocolate and reinstatement of chocolate-seeking behavior in rats. The present study was designed to assess whether the protective properties of SSA on addictive-like, food-related behaviors generalize to a rat model of overeating of palatable food. To this end, rats were habituated to feed on a standard rat chow for 3 h/day; every 4 days, the 3-h chow-feeding session was followed by a 1-h availability of highly palatable, calorie-rich Danish butter cookies or Oreo chocolate cookies. Even though fed, rats consumed large amounts of cookies; intake of calories from cookies (consumed in 1 h) was even larger than that of calories from chow (consumed in 3 h). SSA (0, 0.25, 0.5, and 1 mg/kg, i.p.) was administered 10 min before cookie presentation. Treatment with SSA resulted in a dose-related decrease in intake of both butter and chocolate cookies. Administration of the cannabinoid CB1 receptor antagonist/inverse agonist, rimonabant (0, 0.3, 1, and 3 mg/kg, i.p.; tested as reference compound), produced a similar reduction in intake of butter cookies. These results (a) contribute to the set-up and validation of a rat model of overeating, characterized by the intake of large amounts of unnecessary calories and (b) provide an additional piece of evidence to the anorectic profile of SSA in rats

Clinical global impression-severity score as a reliable measure for routine evaluation of remission in schizophrenia and schizoaffective disorders

Aims: This study aimed to compare the performance of Positive and Negative Syndrome Scale (PANSS) symptom severity criteria established by the Remission in Schizophrenia Working Group (RSWG) with criteria based on Clinical Global Impression (CGI) severity score. The 6-month duration criterion was not taken into consideration. Methods: A convenience sample of 112 chronic psychotic outpatients was examined. Symptomatic remission was evaluated according to RSWG severity criterion and to a severity criterion indicated by the overall score obtained at CGI-Schizophrenia (CGI-SCH) rating scale (≤3) (CGI-S). Results: Clinical remission rates of 50% and 49.1%, respectively, were given by RSWG and CGI-S, with a significant level of agreement between the two criteria in identifying remitted and non-remitted cases. Mean scores at CGI-SCH and PANSS scales were significantly higher among remitters, independent of the remission criteria adopted. Measures of cognitive functioning were largely independent of clinical remission evaluated according to both RSWG and CGI-S. When applying RSWG and CGI-S criteria, the rates of overall good functioning yielded by Personal and Social Performance scale (PSP) were 32.1% and 32.7%, respectively, while the mean scores at PSP scale differed significantly between remitted and non-remitted patients, independent of criteria adopted. The proportion of patients judged to be in a state of well-being on Social Well-Being Under Neuroleptics-Short Version scale (SWN-K) were, respectively, 66.1% and 74.5% among remitters according to RSWG and CGI-S; the mean scores at the SWN scale were significantly higher only among remitters according to CGI-S criteria. Conclusions: CGI severity criteria may represent a valid and user-friendly alternative for use in identifying patients in remission, particularly in routine clinical practic

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