MUFAs may have cardioprotective effects because several epidemiologic studies reported that olive oil enriched with MUFAs lowered LDL cholesterol concentrations and coronary artery disease (CAD)5 risk (, ). However, reports from epidemiologic studies and meta-analyses have not consistently supported the hypothesis that MUFA consumption lowers risk of CAD (). Although previous randomized clinical trials evaluated the effect of dietary MUFAs on CAD risk factors such as LDL cholesterol, little is known about the effects of dietary MUFAs on CAD risk in a community setting. Furthermore, some previous studies reported that long-chain MUFAs and very-long-chain MUFAs may lead to cardiac lipotoxicity and coronary atherosclerosis (, ). These results suggest that long-chain MUFAs could have unfavorable influence on CAD via inflammation, apoptosis of myocardium, and dyslipidemia (ie, LDL particle enrichment with cholesteryl oleate) (). Our group has previously reported a positive relation of red blood cell (RBC) cis palmitoleic (16:1n–7) acid with CAD and an inverse relation of cis vaccenic acid (18:1n–7) with CAD, which are 2 MUFAs from de novo lipogenesis (). However, limited data are available on the association between other individual long-chain MUFAs and CAD risk. Therefore, we examined whether individual RBC long-chain and very-long-chain MUFAs are each associated with risk of CAD in participants in the Physicians’ Health Study (PHS


(b) CB1 cannabinoid receptor crosstalk with other extracellular signalling pathways

CB1 receptors have been shown to crosstalk with growth factor and neurotrophin signalling events at different levels (figure 3). CB1 receptor activation is associated to changes in growth factor expression, and can regulate tyrosine kinase growth factor receptors by direct transactivation mechanisms. In the adult nervous system, CB1 receptor expression is involved in the regulation of the levels of the neurotrophin brain-derived neurotrophic factor (BDNF), and thus CB1-deficient mice have reduced hippocampal BDNF levels under basal circumstances, which could explain some of the neuronal plasticity and emotional alterations shown in those animals []. Transactivation of growth factor receptors with tyrosine kinase activity (EGFR, Trk B and others) has been shown to be involved in some CB1 receptor-mediated neurodevelopmental actions []. CB1 receptor-induced transactivation can be mediated by growth factor or cytokine (e.g. TNFα) expression or their processing and shedding from inactive membrane-bound precursors [,]. Moreover, transactivation can occur via cytosolic tyrosine kinases of the Src family and this mechanism may influence interneuron migration []. Growth factor levels are also regulated by cannabinoid signalling under different neurodegenerative paradigms, such as hippocampal and striatal excitotoxicity, in which BDNF, fibroblast growth factor 2 (FGF2) and epidermal growth factor (EGF) are tuned by CB1 receptors []. Reciprocally, FGF receptors promote axonal growth and guidance via DAGL activation and 2AG generation [].

CB1 receptor activation can also lead to the regulation of small G proteins and subsequent control of cytoskeleton and microtubule dynamics, which may be responsible for cannabinoid actions on neuritogenesis and synaptogenesis. Activation of CB1 receptors can induce either neurite outgrowth or retraction []. CB1 receptors are enriched in the axonal growth cones of GABAergic interneurons at late gestation and, when activated, they induce a chemorepulsive collapse of axonal growth cones by activating RhoA [,]. CB1 receptor-induced neurite outgrowth in neuroblastoma Neuro2A cells occurs via Rap1, Src and the signal transducer and activator of transcription 3 (STAT 3) [,]. CB1 receptor activation and IL6 receptor signalling exert a synergistic effect in cAMP–responsive element binding protein (CREB) and STAT3 activation that enforces neurite outgrowth []. In the retina, the CB1 receptor induces growth cone collapse in a mechanism involving the intracellular trafficking of the deleted in colorectal cancer receptor []. Nerve growth factor-induced neurite outgrowth of PC12 cells is inhibited by CB1 receptor modulation of Trk A/Rap1/B-Raf-mediated sustained ERK activation []. The recent demonstration that recruitment of the Gi-interacting protein GRIN (G-protein-regulated inducer of neurite outgrowth) upon CB1 receptor activation can determine the signalling output of FGF stimulation, by allowing Sprouty-mediated inhibition of ERK signalling [], may reconcile the apparent conflicting results of CB1 receptors mediating a positive or inhibitory action in neurite outgrowth and ERK activation. In summary, further investigation on the role of recently described CB1 receptor interacting proteins (i.e. CRIP1, AP3 and others) will shed light on cannabinoid signalling mechanisms [] and may clarify the different neurodevelopmental actions of CB1 receptor activity. Importantly, the different kinetics and intensity of signal transduction pathways engaged by the CB1 receptor in a particular cellular context can induce different NP cell fate decisions, for example from proliferation and self-renewal (acute ERK activation) to neural differentiation (sustained ERK activation).

rodent model for investigating the cardiac electrical substrates of the increased vulnerability to arrhythmias that characterizes anxiety.

Given the increased likelihood of cardiovascular alterations in high anxious individuals, it is not only important to understand the mechanistic bases of this association, but also to develop therapeutic treatments for anxiety that could desirably improve cardiovascular function. Indeed, conventional anti-anxiety medications, such as benzodiazepines, do not seem to provide direct benefits on cardiovascular health. Recent investigations have started to draw attention to the role of the endocannabinoid (ECB) system in the pathophysiology of affective disturbances such as anxiety and depression,. The endogenous cannabinoid ligand anandamide (AEA) activates the two major cannabinoid receptors, type 1 (CB1) and type 2 (CB2). Following rapid on-demand biosynthesis, AEA is inactivated by cellular uptake followed by intracellular hydrolysis by fatty acid amide hydrolase (FAAH), which also cleaves the noncannabinoid fatty acid ethanolamides oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). Converging preclinical studies indicate that pharmacological inhibition of FAAH augments brain AEA levels and elicits anxiolytic-like effects in a CB1 receptor-dependent manner,,,,, providing support for the potential utility of FAAH inhibitors in the treatment of anxiety disorders (for reviews see:,). Available data suggest that the ECB system also plays a role in the regulation of cardiac function and might be a promising therapeutic target for a variety of cardiac dysfunction conditions (for reviews see:,). CB1 and CB2 receptors are expressed in cardiac myocytes,. Preliminary preclinical evidence indicates that activation of the ECB pathway with exogenous AEA protects the heart from arrhythmias induced by adrenaline administration or ischemia-reperfusion procedure in rats. Intriguingly, chronic administration of URB694, a second generation FAAH inhibitor with improved metabolic stability and selectivity,, has recently been shown to prevent the adverse behavioral and cardiac effects of repeated social stress exposure in rats. Taken together, these findings prompt further investigation aimed at determining whether inhibition of FAAH activity may represent a viable pharmacological strategy for the treatment of the comorbidity of cardiovascular disease with anxiety and mood disorders.

Overall Rating:

  • Positive: 1
  • Mixed: 0
  • Negative: 0

Filter by:

Higher vitamin D levels cut colorectal cancer risk by 31% | Daily Mail Online

The report, led by the Harvard, adds weight to a theory which had not been proven. Three quarters of Americans and a fifth of Brits are vitamin D deficient, and colorectal cancer rates are rising.

No contributions of this type has been made yet.

No contributions of this type has been made yet.

No contributions of this type has been made yet.

No contributions of this type has been made yet.

Have Something to Add? Sign In Easily with Facebook