Dietary triacylglycerols with palmitic acid in the sn-2 position modulate levels of N-acylethanolamides in rat tissues

BACKGROUND: Several evidences suggest that the position of palmitic acid (PA) in dietary triacylglycerol (TAG) influences different biological functions. We aimed at evaluating whether dietary fat with highly enriched (87%) PA in sn-2 position (Hsn-2 PA), by increasing PA incorporation into tissue phospholipids (PL), modifies fatty acid profile and biosynthesis of fatty acid-derived bioactive lipids, such as endocannabinoids and their congeners. STUDY DESIGN: Rats were fed for 5 weeks diets containing Hsn-2 PA or fat with PA randomly distributed in TAG with 18.8% PA in sn-2 position (Lsn-2 PA), and similar total PA concentration. Fatty acid profile in different lipid fractions, endocannabinoids and congeners were measured in intestine, liver, visceral adipose tissue, muscle and brain. RESULTS: Rats on Hsn-2 PA diet had lower levels of anandamide with concomitant increase of its congener palmitoylethanolamide and its precursor PA into visceral adipose tissue phospholipids. In addition, we found an increase of oleoylethanolamide, an avid PPAR alpha ligand, in liver, muscle and brain, associated to higher levels of its precursor oleic acid in liver and muscle, probably derived by elongation and further delta 9 desaturation of PA. Changes in endocannabinoids and congeners were associated to a decrease of circulating TNF alpha after LPS challenge, and to an improved feed efficiency. CONCLUSIONS: Dietary Hsn-2 PA, by modifying endocannabinoids and congeners biosynthesis in different tissues may potentially concur in the physiological regulation of energy metabolism, brain function and body fat distribution

Longitudinal assessment of brain-derived neurotrophic factor in Sardinian psychotic patients (LABSP): a protocol for a prospective observational study

Brain-derived neurotrophic factor (BDNF) plays a crucial role in neurodevelopment, synaptic plasticity and neuronal function and survival. Serum and plasma BDNF levels are moderately, but consistently, decreased in patients with schizophrenia (SCZ) compared with healthy controls. There is a lack of knowledge, however, on the temporal manifestation of this decline. Clinical, illness course and treatment factors might influence the variation of BDNF serum levels in patients with psychosis. In this context, we propose a longitudinal study of a cohort of SCZ and schizophrenic and schizoaffective disorder (SAD) Sardinian patients with the aim of disentangling the relationship between peripheral BDNF serum levels and changes of psychopathology, cognition and drug treatments

High-density lipoprotein contribute to G0-G1/S transition in Swiss NIH/3T3 fibroblasts

High density lipoproteins (HDLs) play a crucial role in removing excess cholesterol from peripheral tissues. Although their concentration is lower during conditions of high cell growth rate (cancer and infections), their involvement during cell proliferation is not known. To this aim, we investigated the replicative cycles in synchronized Swiss 3T3 fibroblasts in different experimental conditions: i) contact-inhibited fibroblasts re-entering cell cycle after dilution; ii) scratch-wound assay; iii) serum deprived cells induced to re-enter G1 by FCS, HDL or PDGF. Analyses were performed during each cell cycle up to quiescence. Cholesterol synthesis increased remarkably during the replicative cycles, decreasing only after cells reached confluence. In contrast, cholesteryl ester (CE) synthesis and content were high at 24h after dilution and then decreased steeply in the successive cycles. Flow cytometry analysis of DiO-HDL, as well as radiolabeled HDL pulse, demonstrated a significant uptake of CE-HDL in 24h. DiI-HDL uptake, lipid droplets (LDs) and SR-BI immunostaining and expression followed the same trend. Addition of HDL or PDGF partially restore the proliferation rate and significantly increase SR-BI and pAKT expression in serum-deprived cells. In conclusion, cell transition from G0 to G1/S requires CE-HDL uptake, leading to CE-HDL/SR-BI pathway activation and CEs increase into LDs

Interactions between calliphoridae dipters and Helicodiceros muscivorus

This article reports on the experimental results of a research programme dealing with the reproductive strategies of Helicodiceros muscivorus (L. fil.) Engler(Araceae: Aroideae). In particular, the role played by the odorous mixture emanated by the vegetable species as olfactory information received by the insects, and the importance of that specific biological activity in governing the behavioural choices made by the pollinating insects is studied

Effect of acute administration of Pistacia lentiscus L. essential oil on rat cerebral cortex following transient bilateral common carotid artery occlusion

<p>Abstract</p> <p>Background</p> <p>Ischemia/reperfusion leads to inflammation and oxidative stress which damages membrane highly polyunsaturated fatty acids (HPUFAs) and eventually induces neuronal death. This study evaluates the effect of the administration of <it>Pistacia lentiscus </it>L. essential oil (E.O.), a mixture of terpenes and sesquiterpenes, on modifications of fatty acid profile and endocannabinoid (eCB) congener concentrations induced by transient bilateral common carotid artery occlusion (BCCAO) in the rat frontal cortex and plasma.</p> <p>Methods</p> <p>Adult Wistar rats underwent BCCAO for 20 min followed by 30 min reperfusion (BCCAO/R). 6 hours before surgery, rats, randomly assigned to four groups, were gavaged either with E.O. (200 mg/0.45 ml of sunflower oil as vehicle) or with the vehicle alone.</p> <p>Results</p> <p>BCCAO/R triggered in frontal cortex a decrease of docosahexaenoic acid (DHA), the membrane highly polyunsaturated fatty acid most susceptible to oxidation. Pre-treatment with E.O. prevented this change and led further to decreased levels of the enzyme cyclooxygenase-2 (COX-2), as assessed by Western Blot. In plasma, only after BCCAO/R, E.O. administration increased both the ratio of DHA-to-its precursor, eicosapentaenoic acid (EPA), and levels of palmytoylethanolamide (PEA) and oleoylethanolamide (OEA).</p> <p>Conclusions</p> <p>Acute treatment with E.O. before BCCAO/R elicits changes both in the frontal cortex, where the BCCAO/R-induced decrease of DHA is apparently prevented and COX-2 expression decreases, and in plasma, where PEA and OEA levels and DHA biosynthesis increase. It is suggested that the increase of PEA and OEA plasma levels may induce DHA biosynthesis via peroxisome proliferator-activated receptor (PPAR) alpha activation, protecting brain tissue from ischemia/reperfusion injury.</p

The Oral History of Vic Salerno

<p>AEA, anandamide; PEA, palmitoylethanolamide; OEA, oleoylethanolamide; 2-AG, 2-arachidonoylglycerol. Values are means ± SD, n = 10.</p><p>* P< 0.05.</p><p>Visceral adipose tissue N-Acylethanolamides (NAEs), 2-AG and fatty acid concentrations in phospholipids (PL), triacylglycerols (TAG) and non esterified fatty acids (NEFA), in rats fed Lsn-2 PA or Hsn-2 PA for 5 weeks.</p

An activator of voltage-gated K+ channels Kv1.1 as a therapeutic candidate for episodic ataxia type 1

Loss-of-function mutations in the KCNA1(Kv1.1) gene cause episodic ataxia type 1 (EA1), a neurological disease characterized by cerebellar dysfunction, ataxic attacks, persistent myokymia with painful cramps in skeletal muscles, and epilepsy. Precision medicine for EA1 treatment is currently unfeasible, as no drug that can enhance the activity of Kv1.1-containing channels and offset the functional defects caused by KCNA1 mutations has been clinically approved. Here, we uncovered that niflumic acid (NFA), a currently prescribed analgesic and anti-inflammatory drug with an excellent safety profile in the clinic, potentiates the activity of Kv1.1 channels. NFA increased Kv1.1 current amplitudes by enhancing the channel open probability, causing a hyperpolarizing shift in the voltage dependence of both channel opening and gating charge movement, slowing the OFF-gating current decay. NFA exerted similar actions on both homomeric Kv1.2 and heteromeric Kv1.1/Kv1.2 channels, which are formed in most brain structures. We show that through its potentiating action, NFA mitigated the EA1 mutation-induced functional defects in Kv1.1 and restored cerebellar synaptic transmission, Purkinje cell availability, and precision of firing. In addition, NFA ameliorated the motor performance of a knock-in mouse model of EA1 and restored the neuromuscular transmission and climbing ability in Shaker (Kv1.1) mutant Drosophila melanogaster flies (Sh5). By virtue of its multiple actions, NFA has strong potential as an efficacious single-molecule-based therapeutic agent for EA1 and serves as a valuable model for drug discovery

Abnormal macrophage response to microbial stimulus in a 43-year-old man with a severe form of atherosclerosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>New evidence indicates infections are emerging as risk factors for atherosclerosis although their specific role in the development and progression of atherosclerosis is still unclear.</p> <p>Case presentation</p> <p>A 43-year-old Caucasian man who had been treated for four years for multiple sclerosis progressively manifested systemic hypertension, polycythemia, peripheral arterial occlusion with intermittent claudication, and persistent headaches. In 2006, an instrumental analysis (magnetic resonance imaging) of our patient revealed widespread fibrocalcific atherosclerotic lesions which accounted for all his current symptoms, including those related to microbial stimulus. Two particular aspects were of interest, namely a lack of conventional cardiovascular risk factors and a negative family history for cardiovascular events. His chemical blood tests all yielded negative findings although a low positive hepatitis C virus-ribonucleic acid titer was detected. The titer had progressively increased and worsening atherosclerosis threatened the life of our patient. Interferon therapy was not appropriate for our patient due to the severe adverse effects observed shortly after its administration.</p> <p>Conclusions</p> <p>The reaction of individual cells to infections may provide an explanation as to why individuals with a similar microbial burden, corrected for the presence of other risk factors, display a different susceptibility to developing or worsening atherosclerosis. The identification of susceptible individuals and the treatment even of silent infections may provide an additional tool against atherosclerosis and its clinical complications. The evaluation of cell susceptibility before and after the correction of risk factors may contribute to the assessment of the efficacy of drug therapy.</p

Symptomatic remission and recovery in major psychosis: Is there a role for BDNF? A secondary analysis of the LABSP cohort data

Remission, relapse prevention, and clinical recovery are crucial areas of interest in schizophrenia (SCZ) research. Although SCZ is a chronic disorder with poor overall outcomes, years of research demonstrated that recovery is possible. There are considerable data linking brain-derived neurotrophic factor (BDNF) to SCZ, however, evidence on the role of BDNF in remission in SCZ is scarce. This secondary analysis of the Longitudinal Assessment of BDNF in Sardinian patients (LABSP) data aimed to investigate the relationship between serum BDNF levels and symptomatic remission, simultaneous clinical and functional remission, and recovery in patients with SCZ. A total of 105 patients with SCZ or schizoaffective disorder were recruited for a longitudinal assessment of BDNF levels over 24 months. Longitudinal data were analyzed using mixed-effects linear regression models. The study found significant associations between use of long acting injectables (chi 2 = 7.075, df = 1, p = 0.008), baseline serum BDNF levels (U = 701, z = -2.543, p = 0.011), and "childhood" (U = 475, z = -2.124, p = 0.034) and "general" (U = 55, z = -2.014, p = 0.044) subscales of the Premorbid Adjustment Scale (PAS) with patients maintaining remission and recovery. The diagnosis of SCZ was significantly associated with lower BDNF levels for patients with simultaneous clinical and functional remission (Z = 2.035, p = 0.0419) and recovery (Z = 2.009, p = 0.0445) compared to those without. There were no significant associations between remission in the entire sample and longitudinal serum BDNF levels or genetic variants within the BDNF gene. These findings provide further insight into the complex relationship between BDNF and SCZ

A Secondary Analysis of the Complex Interplay between Psychopathology, Cognitive Functions, Brain Derived Neurotrophic Factor Levels, and Suicide in Psychotic Disorders: Data from a 2-Year Longitudinal Study

Identifying phenotypes at high risk of suicidal behaviour is a relevant objective of clinical and translational research and can facilitate the identification of possible candidate biomarkers. We probed the potential association and eventual stability of neuropsychological profiles and serum BDNF concentrations with lifetime suicide ideation and attempts (LSI and LSA, respectively) in individuals with schizophrenia (SCZ) and schizoaffective disorder (SCA) in a 2-year follow-up study. A secondary analysis was conducted on a convenience sample of previously recruited subjects from a single outpatient clinic. Retrospectively assessed LSI and LSA were recorded by analysing the available longitudinal clinical health records. LSI + LSA subjects consistently exhibited lower PANSS-defined negative symptoms and better performance in the BACS-letter fluency subtask. There was no significant association between BDNF levels and either LSI or LSA. We found a relatively stable pattern of lower negative symptoms over two years among patients with LSI and LSA. No significant difference in serum BDNF concentrations was detected. The translational viability of using neuropsychological profiles as a possible avenue for the identification of populations at risk for suicide behaviours rather than the categorical diagnosis represents a promising option but requires further confirmation