Worldwide contamination of food-crops with mycotoxins: Validity of the widely cited 'FAO estimate' of 25.

Prior to 1985 the Food and Agriculture Organization (FAO) estimated global food crop contamination with mycotoxins to be 25%. The origin of this statement is largely unknown. To assess the rationale for it, the relevant literature was reviewed and data of around 500,000 analyses from the European Food Safety Authority and large global survey for aflatoxins, fumonisins, deoxynivalenol, T-2 and HT-2 toxins, zearalenone and ochratoxin A in cereals and nuts were examined. Using different thresholds, i.e. limit of detection, the lower and upper regulatory limits of European Union (EU) legislation and Codex Alimentarius standards, the mycotoxin occurrence was estimated. Impact of different aspects on uncertainty of the occurrence estimates presented in literature and related to our results are critically discussed. Current mycotoxin occurrence above the EU and Codex limits appears to confirm the FAO 25% estimate, while this figure greatly underestimates the occurrence above the detectable levels (up to 60-80%). The high occurrence is likely explained by a combination of the improved sensitivity of analytical methods and impact of climate change. It is of immense importance that the detectable levels are not overlooked as through diets, humans are exposed to mycotoxin mixtures which can induce combined adverse health effects.

Endocannabinoid regulation of inward rectifier potassium (Kir) channels.

The inward rectifier potassium channel Kir2.1 (KCNJ2) is an important regulator of resting membrane potential in both excitable and non-excitable cells. The functions of Kir2.1 channels are dependent on their lipid environment, including the availability of PI(4,5)P2, secondary anionic lipids, cholesterol and long-chain fatty acids acyl coenzyme A (LC-CoA). Endocannabinoids are a class of lipids that are naturally expressed in a variety of cells, including cardiac, neuronal, and immune cells. While these lipids are identified as ligands for cannabinoid receptors there is a growing body of evidence that they can directly regulate the function of numerous ion channels independently of CBRs. Here we examine the effects of a panel of endocannabinoids on Kir2.1 function and demonstrate that a subset of endocannabinoids can alter Kir2.1 conductance to varying degrees independently of CBRs. Using computational and Surface plasmon resonance analysis, endocannabinoid regulation of Kir2.1 channels appears to be the result of altered membrane properties, rather than through direct protein-lipid interactions. Furthermore, differences in endocannabinoid effects on Kir4.1 and Kir7.1 channels, indicating that endocannabinoid regulation is not conserved among Kir family members. These findings may have broader implications on the function of cardiac, neuronal and/or immune cells.

Direct Regulation of Hyperpolarization-Activated Cyclic-Nucleotide Gated (HCN1) Channels by Cannabinoids.

Cannabinoids are a broad class of molecules that act primarily on neurons, affecting pain sensation, appetite, mood, learning, and memory. In addition to interacting with specific cannabinoid receptors (CBRs), cannabinoids can directly modulate the function of various ion channels. Here, we examine whether cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), the most prevalent phytocannabinoids in Cannabis sativa, can regulate the function of hyperpolarization-activated cyclic-nucleotide-gated (HCN1) channels independently of CBRs. HCN1 channels were expressed in Xenopus oocytes since they do not express CBRs, and the effects of cannabinoid treatment on HCN1 currents were examined by a two-electrode voltage clamp. We observe opposing effects of CBD and THC on HCN1 current, with CBD acting to stimulate HCN1 function, while THC inhibited current. These effects persist in HCN1 channels lacking the cyclic-nucleotide binding domain (HCN1ΔCNBD). However, changes to membrane fluidity, examined by treating cells with TX-100, inhibited HCN1 current had more pronounced effects on the voltage-dependence and kinetics of activation than THC, suggesting this is not the primary mechanism of HCN1 regulation by cannabinoids. Our findings may contribute to the overall understanding of how cannabinoids may act as promising therapeutic molecules for the treatment of several neurological disorders in which HCN function is disturbed.