In vitro and in vivo safety evaluation of Dipteryx alata Vogel extract

<p>Abstract</p> <p>Background</p> <p><it>Dipteryx alata </it>Vogel popularly known as "baru" is an important commercial leguminous tree species from the Brazilian Cerrado, which possess medicinal properties, besides its fruits consumption by animals and humans. The use of the "naturally occurring plants" as herbal remedies and foods mainly from leaves, seeds, flowers and roots of plants or extracts require precautions before ensuring these are safe and efficacious. The objective of this study was to evaluate the safety of <it>D. alata </it>barks extract.</p> <p>Methods</p> <p>Vegetal drugs of <it>D. alata </it>barks were submitted to quality control assays and further to the safety assays under 1) <it>in vitro </it>parameter by <it>Salmonella </it>(Ames) mutagenicity, and 2) <it>in vivo </it>parameter on the pregnancy of rats.</p> <p>Results</p> <p>The extract was non-mutagenic to any of the assessed strains TA97a, TA98, TA100 and TA102 even after metabolic activation (+S9). All <it>in vivo </it>parameters (reproductive ability evaluation, physical development of rat offsprings, and neurobehavioral development assays) showed no changes related to control group.</p> <p>Conclusion</p> <p><it>D. alata </it>barks extract is neither mutagenic by the Ames test nor toxic in the pregnancy of rats, with no physical-neurobehavioral consequences on the rat offsprings development.</p

Mouse Leydig cells express multiple P2X receptor subunits

ATP acts on cellular membranes by interacting with P2X (ionotropic) and P2Y (metabotropic) receptors. Seven homomeric P2X receptors (P2X1–P2X7) and seven heteromeric receptors (P2X1/2, P2X1/4, P2X1/5, P2X2/3, P2X2/6, P2X4/6, P2X4/7) have been described. ATP treatment of Leydig cells leads to an increase in [Ca2+]i and testosterone secretion, supporting the hypothesis that Ca2+ signaling through purinergic receptors contributes to the process of testosterone secretion in these cells. Mouse Leydig cells have P2X receptors with a pharmacological and biophysical profile resembling P2X2. In this work, we describe the presence of several P2X receptor subunits in mouse Leydig cells. Western blot experiments showed the presence of P2X2, P2X4, P2X6, and P2X7 subunits. These results were confirmed by immunofluorescence. Functional results support the hypothesis that heteromeric receptors are present in these cells since 0.5 μM ivermectin induced an increase (131.2 ± 5.9%) and 3 μM ivermectin a decrease (64.2 ± 4.8%) in the whole-cell currents evoked by ATP. These results indicate the presence of functional P2X4 subunits. P2X7 receptors were also present, but they were non-functional under the present conditions because dye uptake experiments with Lucifer yellow and ethidium bromide were negative. We conclude that a heteromeric channel, possibly P2X2/4/6, is present in Leydig cells, but with an electrophysiological and pharmacological phenotype characteristic of the P2X2 subunit

Zebrafish disease models in drug discovery: from preclinical modelling to clinical trials

Numerous drug treatments that have recently entered the clinic or clinical trials have their genesis in zebrafish. Zebrafish are well established for their contribution to developmental biology and have now emerged as a powerful preclinical model for human disease, as their disease characteristics, aetiology and progression, and molecular mechanisms are clinically relevant and highly conserved. Zebrafish respond to small molecules and drug treatments at physiologically relevant dose ranges and, when combined with cell-specific or tissue-specific reporters and gene editing technologies, drug activity can be studied at single-cell resolution within the complexity of a whole animal, across tissues and over an extended timescale. These features enable high-throughput and high-content phenotypic drug screening, repurposing of available drugs for personalized and compassionate use, and even the development of new drug classes. Often, drugs and drug leads explored in zebrafish have an inter-organ mechanism of action and would otherwise not be identified through targeted screening approaches. Here, we discuss how zebrafish is an important model for drug discovery, the process of how these discoveries emerge and future opportunities for maximizing zebrafish potential in medical discoveries

Measurement of the spin structure of the deuteron in the DIS region

Ageev ES, Alexakhin VY, Alexandrov Y, et al. Measurement of the spin structure of the deuteron in the DIS region. Phys.Lett. B. 2005;612(3-4):154-164.We present a new measurement of the longitudinal spin asymmetry Ad and the spin-dependent structure function g(1)(d) of the deuteron in the range 1 < Q(2) < 100 GeV2 and 0.004 < x < 0.7. The data were obtained by the COMPASS experiment at CERN using a 160 GeV polarised muon beam and a large polarised (LiD)-Li-6 target. The results are in agreement with those from previous experiments and improve considerably the statistical accuracy in the region 0.004 < x < 0.03. (c) 2005 Elsevier B.V. All rights reserved