Cannabis sativa has been associated with contradictory effects upon seizure states despite its medicinal use by numerous people with epilepsy. We have recently shown that the phytocannabinoid cannabidiol (CBD) reduces seizure severity and lethality in the well-established in vivo model of pentylenetetrazole-induced generalised seizures, suggesting that earlier, small-scale clinical trials examining CBD effects in people with epilepsy warrant renewed attention. Here, we report the effects of pure CBD (1, 10 and 100mg/kg) in two other established rodent seizure models, the acute pilocarpine model of temporal lobe seizure and the penicillin model of partial seizure. Seizure activity was video recorded and scored offline using model-specific seizure severity scales. In the pilocarpine model CBD (all doses) significantly reduced the percentage of animals experiencing the most severe seizures. In the penicillin model, CBD (≥10mg/kg) significantly decreased the percentage mortality as a result of seizures; CBD (all doses) also decreased the percentage of animals experiencing the most severe tonic-clonic seizures. These results extend the anti-convulsant profile of CBD; when combined with a reported absence of psychoactive effects, this evidence strongly supports CBD as a therapeutic candidate for a diverse range of human epilepsies.

The purpose of the present study was to examine newborns' behavioral and physiological reactions to the cry of another infant (labeled a reactive cry). 101 newborns of depressed (N=40) and non-depressed (N=61) mothers were assessed on the Brazelton Neonatal Behavioral Assessment Scale (NBAS, Brazelton and Nugent, 1995) and 89 of those infants also participated in an auditory task. Cardiovascular activity (heart period, parasympathetic tone, and recovery to basal activity) was obtained from a sub-sample of these infants (n=37). Vocal distress and regulatory behaviors were examined when newborns listened to another infant's cry and to a simulated sound (the control condition). ANOVAs indicated that newborns of depressed mothers showed lower basal parasympathetic tone. In addition, newborns of depressed mothers responded with less vocal distress to the cry sounds of another infant, and were delayed in physiological regulation following this sound. These findings suggest that newborns of depressed mothers show altered, possibly dysregulated, behavioral and physiological patterns during socio-emotional situations in comparison to newborns of non-depressed mothers.

Previous research has found that infants respond with more negative/protest as well as approach-type behaviors in response to the loss of maternal attention to a social-rival as compared to a non-social item. The purpose of the current research was to conceptually replicate the maternal inattention research with a different population and to extend on it by examining the relationships between infants' emotional responses and their temperament and physiology (brain activity). A baseline measure of infant EEG was collected after which mother-infant dyads (n=30) participated in two mother-ignoring conditions. Infants demonstrated more approach-style responses (maternal-directed gaze, proximity, and touch), higher reactivity levels (increased arousal, aggression, and disorganization), and more negative affect in the social-rival relative to the nonsocial condition. Approach-style (jealousy) responses were predictive of the infants' greater left frontal baseline EEG activity. Maternal reports of an infant's temperamental sociability and approach were not related to frontal EEG but several temperamental characteristics were associated with approach style responses during the social-rival condition. These findings collectively point to the emotion of jealousy in infants, as only during the social rival condition were associations between approach style responses and negative affect as well as left frontal EEG activity uncovered.

Summary Purpose: We assessed the anticonvulsant potential of the phytocannabinoid Delta(9)-tetrahydrocannabivarin (Delta(9)-THCV) by investigating its effects in an in vitro piriform cortex (PC) brain slice model of epileptiform activity, on cannabinoid CB1 receptor radioligand-binding assays and in a generalized seizure model in rats. Methods: Delta(9)-THCV was applied before (10 mumDelta(9)-THCV) or during (10-50 mumDelta(9)-THCV) epileptiform activity induced by Mg(2+)-free extracellular media in adult rat PC slices and measured using multielectrode array (MEA) extracellular electrophysiologic techniques. The actions of Delta(9)-THCV on CB1 receptors were examined using [(3)H]SR141716A competition binding and [(35)S]GTPgammaS assays in rat cortical membranes. Effects of Delta(9)-THCV (0.025-2.5 mg/kg) on pentylenetetrazole (PTZ)-induced seizures in adult rats were also assessed. Results: After induction of stable spontaneous epileptiform activity, acute Delta(9)-THCV application (>/=20 mum) significantly reduced burst complex incidence and the amplitude and frequency of paroxysmal depolarizing shifts (PDSs). Furthermore, slices pretreated with 10 mumDelta(9)-THCV prior to induction of epileptiform activity exhibited significantly reduced burst complex incidence and PDS peak amplitude. In radioligand-binding experiments, Delta(9)-THCV acted as a CB1 receptor ligand, displacing 0.5 nm [(3)H]SR141716A with a Ki approximately 290 nm, but exerted no agonist stimulation of [(35)S]GTPgammaS binding. In PTZ-induced seizures in vivo, 0.25 mg/kg Delta(9)-THCV significantly reduced seizure incidence. Discussion: These data demonstrate that Delta(9)-THCV exerts antiepileptiform and anticonvulsant properties, actions that are consistent with a CB1 receptor-mediated mechanism and suggest possible therapeutic application in the treatment of pathophysiologic hyperexcitability states.

SYED A.A., JONES N.A.G., BLISS R.D., ROBERTS J.T., MALLICK U.K., JOHNSON S.J., DOUGLAS S.F., PERROS P.& QUINTON R.(2009) European Journal of Cancer Care Metachronous testicular teratoma, testicular seminoma and papillary thyroid carcinoma occurring in a single individual: a report of two unrelated casesWe describe two unrelated men who both developed teratomas in one testis followed by seminomas in the contralateral testis followed by papillary thyroid carcinomas. Neither man had a family history of cancers. Although random occurrence is possible, genetic predisposition and/or environmental influence would seem a likely explanation for this previously unreported combination of tumours.

Plant-derived cannabinoids (phytocannabinoids) are compounds with emerging therapeutic potential. Early studies suggested that cannabidiol (CBD) has anticonvulsant properties in animal models and reduced seizure frequency in limited human trials. Here, we examine the anti-epileptiform and anti-seizure potential of CBD using in vitro electrophysiology and an in vivo animal seizure model, respectively. CBD (0.01-100 muM) effects were assessed in vitro using the Mg(2+)-free and 4-aminopyridine (4-AP) models of status epilepticus-like epileptiform activity in hippocampal brain slices via multi-electrode array (MEA) recordings. In the Mg(2+)-free model, CBD decreased epileptiform local field potential (LFP) burst amplitude (in CA1 and dentate gyrus (DG) regions) and burst duration (in all regions) and increased burst frequency (in all regions). In the 4-AP model, CBD decreased LFP burst amplitude (in CA1, only at 100 muM CBD), burst duration (in CA3 and DG), and burst frequency (in all regions). CBD (1, 10 and 100 mg/kg) effects were also examined in vivo using the pentylenetetrazole (PTZ) model of generalised seizures. CBD (100 mg/kg) exerted clear anticonvulsant effects with significant decreases in incidence of severe seizures and mortality in comparison to vehicle-treated animals. Finally, CBD acted with only low affinity at cannabinoid CB(1) receptors and displayed no agonist activity in [(35)S]GTPgammaS assays in cortical membranes. These findings suggest that CBD acts to inhibit epileptiform activity in vitro and seizure severity in vivo. Thus, we demonstrate the potential of CBD as a novel anti-epileptic drug (AED) in the unmet clinical need associated with generalised seizures.

The acute hippocampal brain slice preparation is an important in vitro screening tool for potential anticonvulsants. Application of 4-AP or removal of external Mg(2+) ions induces epileptiform bursting in slices which is analogous to electrical brain activity seen in status epilepticus states. We have developed these epileptiform models for use with multi-electrode arrays (MEAs), allowing recording across the hippocampal slice surface from 59 points. We present validation of this novel approach and analyses using two anticonvulsants, felbamate and phenobarbital, the effects of which have already been assessed in these models using conventional extracellular recordings. In addition to assessing drug effects on commonly-described parameters (duration, amplitude and frequency), we describe novel methods using the MEA to assess burst propagation speeds and the underlying frequencies that contribute to the epileptiform activity seen. Contour plots are also used as a method of illustrating burst activity. Finally, we describe hitherto unreported properties of epileptiform bursting induced by 100muM 4-AP or removal of external Mg(2+) ions. Specifically, we observed decreases over time in burst amplitude and increase over time in burst frequency in the absence of additional pharmacological interventions. These MEA methods enhance the depth, quality and range of data that can be derived from the hippocampal slice preparation compared to conventional extracellular recordings. It may also uncover additional modes of action that contribute to anti-epileptiform drug effects.

EEGs were examined in data collected from 348 1-week, 1-month and 3-month-old infants of depressed and non-depressed mothers across several studies. Both the percentage of infants exhibiting spectral peaks and the frequency in Hz at which those peaks were exhibited increased with age. Consistent with previous studies, infants of depressed mothers exhibited greater left frontal EEG power, suggesting greater relative right frontal EEG activity than infants of non-depressed mothers. This profile was apparent across a narrow frequency range, which shifted from 3-9Hz at 1 week of age to 4-9Hz by 3 months of age.

Recent studies have shown associations between maternal psychopathology and inhibited behaviors in infants. Moreover, physiological factors have been identified as affecting the continuity of behavioral inhibition across childhood. The purpose of the present study was to examine electroencephalogram (EEG) activity and inhibited behavior in 12-month-old infants of depressed versus non-depressed and mothers. Repeated measures MANOVAs indicated that the infants of mothers with stable psychopathology had greater relative right frontal EEG asymmetry, a pattern that typically accompanies greater negative affect and greater withdrawal behaviors. Infants of affectively ill mothers also showed more proximal behaviors toward a stranger and a novel toy than infants of well mothers, but fewer non-proximal behaviors toward their mothers. These results are discussed within a framework of behavioral inhibition for infants exposed to early psychopathologies in their mothers.

Multiple lines of evidence support a role for CD8(+) T cells in control of acute/early HIV replication; however, features of the primary HIV-specific CD8(+) T cell response that may impact on the efficiency of containment of early viral replication remain poorly defined. In this study, we performed a novel, comprehensive analysis of the kinetics of expansion of components of the HIV-specific CD8(+) T cell response in 21 acutely infected individuals. Epitope-specific T cell responses expanded asynchronously during primary infection in all subjects. The most rapidly expanded responses peaked as early as 5 days following symptomatic presentation and were typically of very limited epitope breadth. Responses of additional specificities expanded and contracted in subsequent waves, resulting in successive shifts in the epitope immunodominance hierarchy over time. Sequence variation and escape were temporally associated with the decline in magnitude of only a subset of T cell responses, suggesting that other factors such as Ag load and T cell exhaustion may play a role in driving the contraction of HIV-specific T cell responses. These observations document the preferential expansion of CD8(+) T cells recognizing a subset of epitopes during the viral burst in acute HIV-1 infection and suggest that the nature of the initial, very rapidly expanded T cell response may influence the efficiency with which viral replication is contained in acute/early HIV infection.