Serum BPIFB4 levels classify health status in long-living individuals

People that reach extreme ages (Long-Living Individuals, LLIs) are object of intense investigation for increase/decrease of genetic variant frequencies, genetic methylation levels, protein abundance in serum and tissues. The aim of these studies is the discovery of the mechanisms behind LLIs extreme longevity and the identification of markers of well-being. We have recently associated a BPIFB4 haplotype (LAV) with exceptional longevity under a homozygous genetic model, and identified that CD34(+) of LLIs subjects express higher BPIFB4 transcript as compared to CD34(+) of control population. It would be of interest to correlate serum BPIFB4 protein levels with exceptional longevity and health status of LLIs

Efeitos da adição de diferentes fontes de enxofre na dieta de gatos adultos em parâmetros urinários e equilíbrio ácido-básico

A urolitíase é uma desordem comum na clínica veterinária, considerada como uma das maiores causas de morbidade. Esta desordem está intimamente associada ao pH urinário sendo que a nutrição desempenha papel fundamental no controle dessa doença, pois através da manipulação dietética é possível modificar o pH urinário. O enxofre é considerado um macroelemento com forte influência no equilíbrio ácido-básico e pode ser crucial para controlar o pH urinário em gatos. O objetivo deste estudo foi avaliar os efeitos da adição de diferentes fontes de enxofre (S) na dieta de gatos nos parâmetros urinários e no equilíbrio ácido-básico destes animais. 42 gatos adultos saudáveis foram divididos em 3 grupos e cada grupo de 14 gatos recebeu 7 dietas em um delineamento de blocos ao acaso. O sulfato de cálcio (CaSO4), a DL-metionina (DLM) e a metionina hidróxi-análoga (MHA) foram adicionados a uma dieta controle em dois níveis (1,28g S/kg e 2,56g S/kg) para formular outras 6 dietas experimentais. O equilíbrio ácido-básico foi avaliado por hemogasometria em amostras de sangue venoso. O DLM no teor mais alto e MHA diferiram da dieta controle em relação ao pH urinário (P<0,05). O sulfato de cálcio, embora não tenha diferido da dieta controle, demonstrou alterar o pH urinário apesar do seu equilíbrio eletrolítico nulo. Aparentemente, o efeito alcalinizante do cálcio não foi suficiente para anular a acidificação da urina pelo sulfato. Os tratamentos não apresentaram alteração do equilíbrio ácido-básico dos animais e não afetaram o consumo das dietas experimentais

Cannabis use in patients with early psychosis is associated with alterations in putamen and thalamic shape

Around half of patients with early psychosis have a history of cannabis use. We aimed to determine if there are neurobiological differences in these the subgroups of persons with psychosis with and without a history of cannabis use. We expected to see regional deflations in hippocampus as a neurotoxic effect and regional inflations in striatal regions implicated in addictive processes. Volumetric, T1w MRIs were acquired from people with a diagnosis psychosis with (PwP + C = 28) or without (PwP − C = 26) a history of cannabis use; and Controls with (C + C = 16) or without (C − C = 22) cannabis use. We undertook vertex‐based shape analysis of the brainstem, amygdala, hippocampus, globus pallidus, nucleus accumbens, caudate, putamen, thalamus using FSL FIRST. Clusters were defined through Threshold Free Cluster Enhancement and Family Wise Error was set at p < .05. We adjusted analyses for age, sex, tobacco and alcohol use. The putamen (bilaterally) and the right thalamus showed regional enlargement in PwP + C versus PwP − C. There were no areas of regional deflation. There were no significant differences between C + C and C − C. Cannabis use in participants with psychosis is associated with morphological alterations in subcortical structures. Putamen and thalamic enlargement may be related to compulsivity in patients with a history of cannabis use

Association of cannabis with glutamatergic levels in patients with early psychosis: Evidence for altered volume striatal glutamate relationships in patients with a history of cannabis use in early psychosis

The associative striatum, an established substrate in psychosis, receives widespread glutamatergic projections. We sought to see if glutamatergic indices are altered between early psychosis patients with and without a history of cannabis use and characterise the relationship to grey matter. 92 participants were scanned: Early Psychosis with a history of cannabis use (EPC\u2009=\u200929); Early Psychosis with minimal cannabis use (EPMC\u2009=\u200925); Controls with a history of cannabis use (HCC\u2009=\u200916) and Controls with minimal use (HCMC\u2009=\u200922). Whole brain T1 weighted MR images and localised proton MR spectra were acquired from head of caudate, anterior cingulate and hippocampus. We examined relationships in regions with known high cannabinoid 1 receptor (CB1R) expression (grey matter, cortex, hippocampus, amygdala) and low expression (white matter, ventricles, brainstem) to caudate Glutamine+Glutamate (Glx). Patients were well matched in symptoms, function and medication. There was no significant group difference in Glx in any region. In EPC grey matter volume explained 31.9% of the variance of caudate Glx (p\u2009=\u20090.003) and amygdala volume explained 36.9% (p\u2009=\u20090.001) of caudate Glx. There was no significant relationship in EPMC. The EPC vs EPMC interaction was significant (p\u2009=\u20090.042). There was no such relationship in control regions. These results are the first to demonstrate association of grey matter volume and striatal glutamate in the EPC group. This may suggest a history of cannabis use leads to a conformational change in distal CB1 rich grey matter regions to influence striatal glutamatergic levels or that such connectivity predisposes to heavy cannabis use

Association of cannabis with glutamatergic levels in patients with early psychosis: Evidence for altered volume striatal glutamate relationships in patients with a history of cannabis use in early psychosis

he associative striatum, an established substrate in psychosis, receives widespread glutamatergic projections. We sought to see if glutamatergic indices are altered between early psychosis patients with and without a history of cannabis use and characterise the relationship to grey matter. 92 participants were scanned: Early Psychosis with a history of cannabis use (EPC = 29); Early Psychosis with minimal cannabis use (EPMC = 25); Controls with a history of cannabis use (HCC = 16) and Controls with minimal use (HCMC = 22). Whole brain T1 weighted MR images and localised proton MR spectra were acquired from head of caudate, anterior cingulate and hippocampus. We examined relationships in regions with known high cannabinoid 1 receptor (CB1R) expression (grey matter, cortex, hippocampus, amygdala) and low expression (white matter, ventricles, brainstem) to caudate Glutamine+Glutamate (Glx). Patients were well matched in symptoms, function and medication. There was no significant group difference in Glx in any region. In EPC grey matter volume explained 31.9% of the variance of caudate Glx (p = 0.003) and amygdala volume explained 36.9% (p = 0.001) of caudate Glx. There was no significant relationship in EPMC. The EPC vs EPMC interaction was significant (p = 0.042). There was no such relationship in control regions. These results are the first to demonstrate association of grey matter volume and striatal glutamate in the EPC group. This may suggest a history of cannabis use leads to a conformational change in distal CB1 rich grey matter regions to influence striatal glutamatergic levels or that such connectivity predisposes to heavy cannabis use

Cannabidiol modulation of hippocampal glutamate in early psychosis.

BACKGROUND Emerging evidence supports the antipsychotic effect of cannabidiol, a non-intoxicating component of cannabis, in people with psychosis. Preclinical findings suggest that this antipsychotic effect may be related to cannabidiol modulating glutamatergic signalling in the brain. AIM The purpose of this study was to investigate the effects of cannabidiol on the neurochemical mechanisms underlying psychosis. METHODS We investigated the effects of a single oral dose of cannabidiol (600 mg) in patients with psychosis, using a double-blind, randomised, placebo-controlled, repeated-measures, within-subject cross-over design. After drug administration, 13 patients were scanned using proton magnetic resonance spectroscopy to measure left hippocampal glutamate levels. Symptom severity was rated using the Positive and Negative Syndrome Scale 60 min before drug administration (pre-scan), and 270 min after drug administration (post-scan). Effects of cannabidiol on hippocampal glutamate levels, symptom severity, and correlations between hippocampal glutamate and symptoms were investigated. RESULTS Compared to placebo, there was a significant increase in hippocampal glutamate (=0.035), and a significantly greater decrease in symptom severity (=0.032) in the psychosis patients under cannabidiol treatment. There was also a significant negative relationship between post-treatment total Positive and Negative Syndrome Scale score and hippocampal glutamate (=0.047), when baseline Positive and Negative Syndrome Scale score, treatment (cannabidiol vs placebo), and interaction between treatment and glutamate levels were controlled for. CONCLUSIONS These findings may suggest a link between the increase in glutamate levels and concomitant decrease in symptom severity under cannabidiol treatment observed in psychosis patients. Furthermore, the findings provide novel insight into the potential neurochemical mechanisms underlying the antipsychotic effects of cannabidiol

Cannabidiol modulation of hippocampal glutamate in early psychosis

BACKGROUND Emerging evidence supports the antipsychotic effect of cannabidiol, a non-intoxicating component of cannabis, in people with psychosis. Preclinical findings suggest that this antipsychotic effect may be related to cannabidiol modulating glutamatergic signalling in the brain. AIM The purpose of this study was to investigate the effects of cannabidiol on the neurochemical mechanisms underlying psychosis. METHODS We investigated the effects of a single oral dose of cannabidiol (600 mg) in patients with psychosis, using a double-blind, randomised, placebo-controlled, repeated-measures, within-subject cross-over design. After drug administration, 13 patients were scanned using proton magnetic resonance spectroscopy to measure left hippocampal glutamate levels. Symptom severity was rated using the Positive and Negative Syndrome Scale 60 min before drug administration (pre-scan), and 270 min after drug administration (post-scan). Effects of cannabidiol on hippocampal glutamate levels, symptom severity, and correlations between hippocampal glutamate and symptoms were investigated. RESULTS Compared to placebo, there was a significant increase in hippocampal glutamate (=0.035), and a significantly greater decrease in symptom severity (=0.032) in the psychosis patients under cannabidiol treatment. There was also a significant negative relationship between post-treatment total Positive and Negative Syndrome Scale score and hippocampal glutamate (=0.047), when baseline Positive and Negative Syndrome Scale score, treatment (cannabidiol vs placebo), and interaction between treatment and glutamate levels were controlled for. CONCLUSIONS These findings may suggest a link between the increase in glutamate levels and concomitant decrease in symptom severity under cannabidiol treatment observed in psychosis patients. Furthermore, the findings provide novel insight into the potential neurochemical mechanisms underlying the antipsychotic effects of cannabidiol

S152. CANNABIDIOL INDUCED MODULATION OF MEDIOTEMPORAL ACTIVITY DURING A VERBAL MEMORY TASK IN FIRST-EPISODE PSYCHOSIS

Background Global neurocognitive impairments are a central feature of psychosis. Deficits in verbal memory in particular are the most consistently reported of these impairments from the first-episode of psychosis (FEP). Neuroimaging studies in psychosis have largely identified reductions in neural activation during various memory and learning related tasks, particularly in the medial temporal lobe, compared to healthy controls. Tetrahydrocannabinol (THC) and cannabidiol (CBD), both components of the cannabis plant that act through the endocannabinoid (eCB) system in the brain, have been found to induce direct and opposite neural effects during similar tasks in healthy samples, when compared to each other. Additionally, CBD has been shown to have antipsychotic properties, and may suppress THC induced psychotic symptoms and their directly associated functional abnormalities in healthy individuals. Thus far, the effects of CBD on the neural substrates implicated in memory and learning, and those underlying psychotic symptoms in FEP cohorts is unknown. Methods 17 FEP patients were initially recruited to the study. A double-blind, randomized, placebo controlled, repeated measures, within subject cross over design, with at least a one-week washout period between scans was employed. Participants were given identical capsules of either CBD (600mg), or placebo (PLB), then scanned using a block design fMRI paradigm, while performing a verbal paired associate learning task. 13 participants completed scanning, and were included in the analysis of the data. An ROI mask of the hippocampus, striatum, and parahippocampal gyrus was used in the data analysis, and all results were thresholded for less than one false positive over the whole map. Results A CBD related decrease in activity was observed in the left hippocampus (p = 0.0024) and the right parahippocampal gyrus (p = 0.0024) during the recall condition, within the FEP group. No significant differences between PLB and CBD functional activity were observed during the encoding condition. No significant differences were observed between FEP participant performances on the CBD and PLB study days. Discussion These findings provide robust evidence of the modulatory effect of an acute dose of CBD on the neural substrates underlying learning and memory, supporting a role for the eCB system in the abnormalities observed in psychosis, and its potential as a target for treatment