Structural and antitrypanosomal data of different carbasones of piperitone.

This article reports data on four carbazones of piperitone: semicarbazone 1, thiosemicarbazone 2, 4-phenyl semicarbazone 3 and 4-phenyl thiosemicarbazone 4 prepared directly in situ from essential oil of Cymbopogon schoenantus, whose GC-FID and GC-MS analysis revealed piperitone as major component (68.20%). The structures of hemi-synthesized compounds were confirmed by high throughput IR, MS, 1H and 13C NMR based spectrometric analysis. Their antiparasitic activities were evaluated in vitro on Trypanosoma brucei brucei (Tbb). The compound 3 (IC50=8.63±0.81 µM) and 4 (IC50=10.90±2.52 µM) exhibited antitrypanosomal activity, 2 had a moderate activity (IC50=74.58±4.44 µM) but 1 was void of significant activity (IC50=478.47 µM). The in vitro tests showed that all compounds were less cytotoxic against the human non cancer fibroblast cell line (WI38) (IC50>80 µM) while only 2 (IC50=21.16±1.37 µM) and 4 (IC50=32.22±1.66 µM) were cytotoxic against the Chinese Hamster Ovary (CHO) cells and toxic on Artemia salina (Leach) larvae. Piperitone 4-phenyl semicarbazone 3, the best antitrypanosomal compound, showed also a selectivity index (SI) higher than 7 on the larvae and the tested cells and therefore might be further studied as antitrypanosomal agent. Also, all compounds except 3 showed selectivity between the two tested cell lines (SI>2). This data reveals for the first time the antitrypinosomal properties of thiosemicarbazones, their cytotoxicity on mammalian cells as well as their activities against Tbb and A. salina Leach.

Atypical spatiotemporal signatures of working memory brain processes in autism.

Working memory (WM) impairments may contribute to the profound behavioural manifestations in children with autism spectrum disorder (ASD). However, previous behavioural results are discrepant as are the few functional magnetic resonance imaging (fMRI) results collected in adults and adolescents with ASD. Here we investigate the precise temporal dynamics of WM-related brain activity using magnetoencephalography (MEG) in 20 children with ASD and matched controls during an n-back WM task across different load levels (1-back vs 2-back). Although behavioural results were similar between ASD and typically developing (TD) children, the between-group comparison performed on functional brain activity showed atypical WM-related brain processes in children with ASD compared with TD children. These atypical responses were observed in the ASD group from 200 to 600 ms post stimulus in both the low- (1-back) and high- (2-back) memory load conditions. During the 1-back condition, children with ASD showed reduced WM-related activations in the right hippocampus and the cingulate gyrus compared with TD children who showed more activation in the left dorso-lateral prefrontal cortex and the insulae. In the 2-back condition, children with ASD showed less activity in the left insula and midcingulate gyrus and more activity in the left precuneus than TD children. In addition, reduced activity in the anterior cingulate cortex was correlated with symptom severity in children with ASD. Thus, this MEG study identified the precise timing and sources of atypical WM-related activity in frontal, temporal and parietal regions in children with ASD. The potential impacts of such atypicalities on social deficits of autism are discussed.

The usefulness of plasma histamine and different tryptase cut-off points in the diagnosis of peranaesthetic hypersensitivity reactions.

UNLABELLED: Anaesthetic hypersensitivity reactions can be IgE- or not IgE-mediated and are a challenge to find the causal agent. Histamine and tryptase determination are classically considered useful in the diagnosis of these reactions. The aim of our study was to assess the diagnostic usefulness of plasma histamine and different cut-off points of serum tryptase. METHODS: Patients suffering a reaction suggestive of hypersensitivity during general anaesthesia in Clínica Universidad de Navarra (2008-2012) were included. Serum tryptase and plasma histamine were measured at the time of the reaction and 2 h later. Baseline tryptase was also determined. Four to eight weeks after the reaction an allergological study was performed to all the drugs or products involved in the reaction. RESULTS: Sixty-five patients suffered an immediate hypersensitivity reaction during the period of the study. Thirty-seven patients (20 male) with median age 48 years (12-79) were included because they completed allergological study, and histamine and tryptase were correctly obtained. Elevated plasma histamine was observed in 34 cases (92%). Tryptase exceeded twice the basal values in 10 patients (31%). Using different cut-off points of tryptase, the number of patients with elevated tryptase would be 15 patients (41%) for a cut-off point of 5 µg/L; 12 patients (32%) for a cut-off point of 8.23 µg/L; nine patients (24%) for 10.5 µg/L; and eight patients (22%) for 11.4 µg/L. The median tryptase level for the IgE-mediated reactions was 9.0 µg/L (2-70 µg/L) and 4.0 µg/L (3-13 µg/L) in non-IgE-mediated reactions (P < 0.01). Median tryptase levels were higher in more severe reactions (grade 2 or 3) in comparison with grade 1. The best ratio for serum-tryptase-during-reaction/basal-serum-tryptase to discriminate between IgE and non-IgE reactions was 2.0. CONCLUSION: The best criterion for discriminating IgE- and non IgE-mediated hypersensitivity reactions in anaesthesia was a tryptase value exceeding twice the basal one.

Pathophysiology of sleep-dependent memory consolidation processes in children.

Cognitive impairments are often associated with abnormal sleep activity in developmental disorders and pathologies of childhood. Besides, accumulated evidence indicates that post-training sleep benefits to the consolidation of recently learned information in healthy adults and children. Although sleep-dependent consolidation effects in children are clearly established for declarative memories, they remain more debated in the procedural memory domain. Nowadays, recent experimental data suggest close interactions between the development of sleep-dependent plasticity markers, cortical maturation and cognition in children. In the present review, we propose that studying sleep and memory consolidation processes in developmental disorders and acquired childhood pathologies can provide novel, enlightening clues to understand the pathophysiological mechanisms subtending the disruption of long-term cerebral plasticity processes eventually leading to cognitive and learning deficits in children.

Impact of focal interictal epileptiform discharges on behaviour and cognition in children.

It is hypothesised that focal interictal epileptiform discharges (IED) may exert a deleterious effect on behaviour and cognition in children. This hypothesis is supported by the abnormally high prevalence of IED in several developmental disorders, like specific language impairment, and of cognitive and behavioural deficits in epileptic children after excluding confounding factors such as underlying structural brain lesions, drug effects, or the occurrence of frequent or prolonged epileptic seizures. Neurophysiological and functional neuroimaging evidence suggests that IED may impact cognition through either transient effects on brain processing mechanisms, or through more long-lasting effects leading to prolonged inhibition of brain areas distant from but connected with the epileptic focus (i.e. remote inhibition effect). Sustained IED may also impair sleep-related learning consolidation processes. Nowadays, the benefits of anti-epileptic treatment aimed at reducing IED are not established except in specific situations like epileptic encephalopathies with continuous spike and waves during slow-wave sleep. Well-designed pharmacological studies are still necessary to address this issue.

Effects of free fatty acids on the metabolic response to oral fructose in lean healthy humans.

OBJECTIVE: To study the effects of an experimental increase in plasma FFA concentration on fructose to glucose conversion, total hepatic glucose output and glycaemic response to oral fructose. SUBJECTS: Six healthy subjects (three men, three women; age: 24.3 +/- 2.3 years; BMI: 21.6 +/- 0.8 kg/m2). DESIGN: Each subject absorbed 0.5 g/kg of 13C-enriched fructose and randomly received either a triglyceride-heparin infusion or saline. MEASUREMENTS: Total hepatic glucose output was traced with 6,6-2H2-glucose. Appearance in plasma of glucose synthesized from fructose was calculated from the isotopic enrichment in 13C of plasma glucose. Substrates oxidation was assessed with indirect calorimetry. RESULTS: The triglycerides-heparin infusion increased FFA concentration before fructose as compared to saline (1086 +/- 40 vs 451 +/- 67 microM; p < 0.001) and lipid oxidation was 15% and 70% increased before and during fructose, respectively as compared to saline. Total hepatic glucose output, plasma appearance of glucose synthesized from fructose and glycaemic response were not affected. Glycogen storage over the first 3 h following fructose was increased (6.2 +/- 2.1 g vs 0.3 +/- 2.1 g; p < 0.01). CONCLUSION: Triglycerides-heparin infusion did not stimulate plasma glucose appearance from fructose. Liver glucose-6-phosphate could have been produced in excess and diverted towards glycogen synthesis.

d-amphetamine and fixed-interval performance: effects of operant history.

Sixteen rats were initially exposed for 50 sessions to either a fixed-ratio 40 or an interresponse-time-greater-than-11-second food reinforcement schedule, then shifted to a fixed-interval 15-second food reinforcement schedule. Animals with fixed-ratio 40 histories lever pressed at much higher rates under the fixed-interval schedule than did animals with inter-response-time-greater-than-11-second histories. This difference persisted across 93 sessions of fixed-interval exposure. The effects of d=amphetamine were assessed after 15 and 59 sessions of fixed-interval exposure. On both occasions, the low-rate responding of animals with interresponse-time-greater-than-11-second histories was typically increased by all doses of the drug, while the high-rate responding of animals with fixed-ratio 40 histories was typically decreased by all doses of the drug. These results suggest that control response rate under the fixed-interval schedule, which may be affected by a history of responding under another schedule, is the primary determinant of the relative effects of d-amphetamine.

Effects of feeding regimen on ethanol intake by guinea pigs.

During daily two-hr sessions, guinea pigs licked a drinking tube filled with either 0 (tap water), 2,4 or 8% (v/v) ethanol solution under three feeding regimens. Consumption of each solution was highest when sufficient food to maintain subjects at 90% of free-feeding weight was provided during sessions, lower when the same food ration was provided after sessions, and lowest when ad lib access to food was provided within and between sessions. However, this decrease in consumption across feeding regimens was inversely related to ethanol concentration. Under all feeding regimens, volume of solution consumed decreased with increasing ethanol concentration while milligrams ethanol consumed increased with ethanol concentration. These results are similar in some respects to previous findings with rats and monkeys, suggesting that further studies of oral ethanol self-administration by guinea pigs may be merited.

Effects of d-amphetamine and chlordiazepoxide on positive conditioned suppression.

Six rats lever-pressed under a variable-interval 80-sec food reinforcement schedule. After responding had stabilized, an 8-sec tone terminating with food delivery was superimposed on the variable-interval schedule on the average once every five minutes without regard to the animal's behavior. This positive conditioned suppression procedure consistently reduced responding during the pre-food stimulus (tone). Neither d-amphetamine (0.5, 1.0, 2.0 mg/kg) nor chlordiazepoxide (7.5, 15, 30 mg/kg) significantly affected the relative suppression produced by the tone. Instead, both drugs produced generally non-selective effects, similarly affecting response rate in the presence and absence of the tone.