Expression and pharmacology of endogenous Ca-v channels in SH-SY5Y human neuroblastoma cells

SH-SY5Y human neuroblastoma cells provide a useful in vitro model to study the mechanisms underlying neurotransmission and nociception. These cells are derived from human sympathetic neuronal tissue and thus, express a number of the Ca-v channel subtypes essential for regulation of important physiological functions, such as heart contraction and nociception, including the clinically validated pain target Ca(v)2.2. We have detected mRNA transcripts for a range of endogenous expressed subtypes Ca(v)1.3, Ca(v)2.2 (including two Ca(v)1.3, and three Ca(v)2.2 splice variant isoforms) and Ca(v)3.1 in SH-SY5Y cells; as well as Ca-v auxiliary subunits alpha(2)delta(1-3), beta(1), beta(3), beta(4), gamma(1), gamma(4-5), and gamma(7). Both high-and low-voltage activated Ca-v channels generated calcium signals in SH-SY5Y cells. Pharmacological characterisation using omega-conotoxins CVID and MVIIA revealed significantly (similar to 10-fold) higher affinity at human versus rat Ca(v)2.2, while GVIA, which interacts with Ca(v)2.2 through a distinct pharmacophore had similar affinity for both species. CVID, GVIA and MVIIA affinity was higher for SH-SY5Y membranes vs whole cells in the binding assays and functional assays, suggesting auxiliary subunits expressed endogenously in native systems can strongly influence Ca(v)2.2 channels pharmacology. These results may have implications for strategies used to identify therapeutic leads at Ca(v)2.2 channels

Recent aflatoxin survey data in milk and milk products: A review

Aflatoxin M1 (AFM1) occurrence in human and animal milk, infant formula, powdered milk, cheese and yoghurt represents a risk for health. The last four years (2010–2014) of data, as well as the most frequently and updated analytical methods applied for AFM1 quantification, are evaluated. Aflatoxin B1, considered the most potent toxic aflatoxin, is metabolised to form the monohydroxy derivative AFM1. This metabolized, expressed in the milk, is relatively stable, and it is not eliminated by heat treatments or pasteurisation, and thus represents a serious health concern

Protocadherin-1 is essential for cell entry by New World hantaviruses

International audienceThe zoonotic transmission of hantaviruses from their rodent hosts to humans in North and South America is associated with a severe and frequently fatal respiratory disease, hantavirus pulmonary syndrome (HPS)1,2. No specific antiviral treatments for HPS are available, and no molecular determinants of in vivo susceptibility to hantavirus infection and HPS are known. Here we identify the human asthma-associated gene protocadherin-1 (PCDH1)3-6 as an essential determinant of entry and infection in pulmonary endothelial cells by two hantaviruses that cause HPS, Andes virus (ANDV) and Sin Nombre virus (SNV). In vitro, we show that the surface glycoproteins of ANDV and SNV directly recognize the outermost extracellular repeat domain of PCDH1-a member of the cadherin superfamily7,8-to exploit PCDH1 for entry. In vivo, genetic ablation of PCDH1 renders Syrian golden hamsters highly resistant to a usually lethal ANDV challenge. Targeting PCDH1 could provide strategies to reduce infection and disease caused by New World hantaviruses

Pharmacological Modulation of GABA Function in Autism Spectrum Disorders: A Systematic Review of Human Studies

Autism spectrum disorders are an emerging health problem worldwide, but little is known about their pathogenesis. It has been hypothesized that autism may result from an imbalance between excitatory glutamatergic and inhibitory GABAergic pathways. Commonly used medications such as valproate, acamprosate, and arbaclofen may act on the GABAergic system and be a potential treatment for people with ASD. The present systematic review aimed at evaluating the state-of-the-art of clinical trials of GABA modulators in autism. To date there is insufficient evidence to suggest the use of these drugs in autistic subjects, even if data are promising. Of note, short-term use of all the reviewed medications appears to be safe. Future well designed trials are needed to elucidate these preliminary findings