Enhanced prefrontal serotonin 2A receptor signaling in the subchronic phencyclidine mouse model of schizophrenia

Prefrontal serotonin 2A receptors (5‐HT_2ARs) have been linked to the pathogenesis and treatment of schizophrenia. Many antipsychotics fully occupy 5‐HT_2AR at clinical relevant doses, and activation of 5‐HT_2A receptors by lysergic acid diethylamide (LSD) and LSD‐like drugs induces a schizophrenia‐like psychosis in humans. Subchronic phencyclidine (PCP) administration is a well‐established model for schizophrenia‐like symptoms in rodents. The aim of the present study was to investigate whether subchronic PCP administration changes expression, binding, or functionality of cortical 5‐HT_2ARs. As a measure of 5‐HT_2AR functionality, we used the 5‐HT_2AR agonist 2,5‐dimethoxy‐4‐iodoamphetamine (DOI)‐induced head‐twitch response (HTR) and mRNA expression of the immediate‐early genes (IEGs) activity‐related cytoskeletal associated‐protein (Arc), c‐fos, and early growth response protein 2 (egr‐2) in the frontal cortex. Mice were treated with PCP (10 mg/kg) or saline for 10 days, followed by a 5‐day washout period. The PCP pretreatment increased the overall induction of HTR and frontal cortex IEG mRNA expression following a single challenge with DOI. These functional changes were not associated with changes in 5‐HT_2AR binding. Also, binding of the 5‐HT_1AR and the 5‐HT transporter was unaffected. Finally, basal mRNA level of Arc was increased in the prefrontal cortex after subchronic PCP administration as revealed with in situ hybridization. Together these findings indicate that PCP administration produces changes in the brain that result in an increase in the absolute effect of DOI. Therefore, neurotransmission involving the 5‐HT_2AR could contribute to the behavioral deficits observed after PCP treatment. © 2013 Wiley Periodicals, Inc.     

Comparison study of full and subthreshold bulimia nervosa: Personality,clinical characteristics,and short-term response to therapy

Abstract

This study compared symptomatological and personality differences between individuals with threshold bulimia nervosa (BN; n=39) and those with subthreshold BN (n=39) and their short-term response to a brief outpatient intervention. Participants were matched using a pairwise matching procedure, taking into account age, age of onset, and duration of the disorder. Both groups received the same brief outpatient psychoeducational therapy. The same assessment measures were used before and after treatment. With the exception of some clinical and psychopathological symptoms (higher depression and phobic anxiety in threshold BN), there were no significant between-group differences on scales of general psychopathology or personality traits. At the end of treatment, there were no significant between-group differences on abstinence rates for binge eating and vomiting, number of sessions attended, or dropout rates. Threshold BN and subthreshold BN share common psychopathological symptoms and personality traits. No differences in therapy outcome were observed for the two groups after a brief group psychoeducational intervention.     

Impact of mindfulness training on attentional control and anger regulation processes for psychotherapists in training

Abstract

Objectives: Little empirical literature focuses on psychotherapists' cultivation of internal states of mind necessary for controlling attention and responding empathically to the client. We explore the effects of mindfulness training on emotional and attentional measures in Spanish resident intern psychiatrists and clinical psychologists. Method: One hundred and three residents were assigned to an experimental group (n = 60) that completed an 8-week mindfulness training versus a wait-list control group (n = 43). We evaluated emotional variables (sadness, anxiety, and anger, using standard instruments), state of mindfulness (using the Mindfulness Awareness Attention Scale), and attentional control variables using objective measures such as a continuous performance task and the Stroop task before and after mindfulness training. Results: Our study provides data that suggest that mindfulness training significantly improves measures of trait anger and attentional control. Conclusions: Further research is needed to replicate these findings, explore the effects of mindfulness training on other aspects of emotional regulation and cognition, and evaluate the impact of these effects within clinical situations.     

Effect of articaine on calcium transport in sarcoplasmic reticulum membranes isolated from medial pterygoid muscle

Local anesthetics used in dentistry have myotoxic effects. Articaine, also known as carticaine, is one of the local anesthetics most widely used in clinical dentistry. The aim of this work was to describe its effect on the sarcoplasmic reticulum Ca-ATPase isolated from medial pterygoid muscle. Ca-ATPase enzymatic activity was determined by a colorimetric method and ATP-dependent calcium uptake with a radioisotopic technique. Articaine inhibited both Ca-ATPase activity and calcium uptake in a concentration-dependent manner. Both inhibitory effects became evident at articaine concentrations lower than those employed in clinical dentistry. Half-maximal inhibitory concentrations (K) were 15.1 +/- 1.8 mM (n = 6) and 25.2 +/- 1.6 mM (n = 6) for enzymatic activity and calcium uptake, respectively. Preincubation of sarcoplasmic reticulum membranes with articaine enhanced Ca-ATPase activity in the absence of calcium ionophore, suggesting an ionophoric-like effect of the local anesthetic. We conclude that the inhibitory effect of articaine on the sarcoplasmic reticulum Ca-ATPase isolated from medial pterygoid muscle is due to a direct interaction of the anesthetic with the enzyme and to the increased membrane permeability to calcium induced by this drug.     

New thiazolyl-pyrazoline derivatives bearing nitrogen mustard as potential antimicrobial and antiprotozoal agents

A new series of N-substituted pyrazoline derivatives 6a–g , 7a–g , 8a–g , and 9a–g was synthetized by reaction of hydrazine derivatives and chalcone–thiazole hybrids bearing nitrogen mustard 5a–g . The chalcones 5a–g were obtained by Claisen–Schmidt condensation of thiazole-2-nitrogen mustard 3 and selected acetophenones 4a–g . These new compounds 6/7/8/9a–g were screened for their antifungal activity against Cryptococcus neoformans, with IC₅₀ values of 3.9–7.8 µg/ml for the N-3,5-dichlorophenyl pyrazolines 9e – g . Interestingly, those compounds show low cytotoxic effects toward erythrocytes (RBC). In addition, N-acetyl ( 6a,b ) and N-formyl pyrazolines ( 7a , 7b , 7c , and 7g ) showed inhibitory activity against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus, and vancomycin-intermediate S. aureus, with the most important minimum inhibitory concentration values ranging from 31.25 to 125 µg/ml. Regarding the antiprotozoal activity, thiazolyl-pyrazolines 9g , 8f , and 7c display high activity against Plasmodium falciparum, Leishmania (V) panamensis, and Trypanosoma cruzi, with EC₅₀ values of 11.80, 6.46, and 4.98 μM, respectively, and with 7c being approximately 2.6-fold more potent than benznidazole with a selectivity index of 1.61 on U-937 human cells, showing promising potential as a novel antitrypanosomal agent.     

Maximal heart rate assessment in recreational football players: A study involving a multiple testing approach

This study aimed at examining the suitability of a standard treadmill test (TT), popular intermittent field tests, and small‐sided football matches to induce maximal heart rate (HR_max) in recreational football players. Sixty‐six inactive untrained male subjects (age: 39.3 ± 5.8 years, VO_2max: 41.2 ± 6.2 mL kg^?1 min^?1, body mass: 81.9 ± 10.8 kg, height: 173.2 ± 6.4 cm) were evaluated. On separate occasions, the players were randomly submitted to a progressive VO_2max TT, to the Yo‐Yo intermittent endurance level 1 (YYIE1) and level 2 (YYIE2) tests, to the Yo‐Yo intermittent recovery level 1 (YYIR1) test, and to 7v7 (43 × 27 m pitch, 83 m²/player) football matches (45 minutes; 2‐4 matches/player). To ensure data consistency, exercise HR was recorded using the same HR monitors in all the experimental conditions. A total of 73%, 24%, 18%, 17%, and 30% of the players achieved their HR_max during the YYIE1, YYIE2, YYIR1, TT, and the small‐sided football matches, respectively. The probability of achieving HR_max increased proportionally to test duration, with 7.8 minutes as the cutoff time. Variations in HR_peak of ±2 b min^?1 should be regarded as of practical relevance. YYIE1 HR_peak provided the most accurate estimation of a subject's individual HR_max and much higher probability of reaching HR_max. Nevertheless, the results of this study suggest caution in considering a reference test for HR_max assessment in this population. The use of confirmation tests is still highly advisable when the test duration is shorter than 7.8 minutes. In this regard, field tests seem to be suitable and accurate for individual HR_max assessment in recreational football players.     

Carotid web: the challenging diagnosis of an under-recognized entity

Journal of Neurology - Determining the cause of acute ischemic stroke is crucial for patient management, particularly for preventing future stroke. In recent years, carotid web (CW), a...