Microengineered systems with iPSC-derived cardiac and hepatic cells to evaluate drug adverse effects

Hepatic and cardiac drug adverse effects are among the leading causes of attrition in drug development programs, in part due to predictive failures of current animal or in vitro models. Hepatocytes and cardiomyocytes differentiated from human induced pluripotent stem cells (iPSCs) hold promise for predicting clinical drug effects, given their human-specific properties and their ability to harbor genetically determined characteristics that underlie inter-individual variations in drug response. Currently, the fetal-like properties and heterogeneity of hepatocytes and cardiomyocytes differentiated from iPSCs make them physiologically different from their counterparts isolated from primary tissues and limit their use for predicting clinical drug effects. To address this hurdle, there have been ongoing advances in differentiation and maturation protocols to improve the quality and use of iPSC-differentiated lineages. Among these are in vitro hepatic and cardiac cellular microsystems that can further enhance the physiology of cultured cells, can be used to better predict drug adverse effects, and investigate drug metabolism, pharmacokinetics, and pharmacodynamics to facilitate successful drug development. In this article, we discuss how cellular microsystems can establish microenvironments for these applications and propose how they could be used for potentially controlling the differentiation of hepatocytes or cardiomyocytes. The physiological relevance of cells is enhanced in cellular microsystems by simulating properties of tissue microenvironments, such as structural dimensionality, media flow, microfluidic control of media composition, and co-cultures with interacting cell types. Recent studies demonstrated that these properties also affect iPSC differentiations and we further elaborate on how they could control differentiation efficiency in microengineered devices. In summary, we describe recent advances in the field of cellular microsystems that can control the differentiation and maturation of hepatocytes and cardiomyocytes for drug evaluation. We also propose how future research with iPSCs within engineered microenvironments could enable their differentiation for scalable evaluations of drug effects.     

New resource for the computation of cartilage biphasic material properties with the interpolant response surface method

Cartilage material properties are important for understanding joint function and diseases, but can be challenging to obtain. Three biphasic material properties (aggregate modulus, Poisson's ratio and permeability) can be determined using an analytical or finite element model combined with optimisation to find the material properties values that best reproduce an experimental creep curve. The purpose of this study was to develop an easy-to-use resource to determine biphasic cartilage material properties. A Cartilage Interpolant Response Surface was generated from interpolation of finite element simulations of creep indentation tests. Creep indentation tests were performed on five sites across a tibial plateau. A least-squares residual search of the Cartilage Interpolant Response Surface resulted in a best-fit curve for each experimental condition with corresponding material properties. These sites provided a representative range of aggregate moduli (0.48–1.58 MPa), Poisson's ratio (0.00–0.05) and permeability (1.7 × 10^? 15–5.4 × 10^? 15 m⁴/N s) values found in human cartilage. The resource is freely available from https://simtk.org/home/va-squish.     

1,3,5-Tri-O-acetyl-2-deoxy- α, β-D-ERYTHRO-Pentofuranose from 2-Deoxy-D-ERYTHRO-Pentose

Abstract

A convenient, high-yield synthesis of 1,3,5-tri-O-acetyl-2-deoxy-α. β-D-erythro-pentofuranose from 2-deoxy-D-erythro-pentose is described.     

The changing criteria of social networks in a Cajun Community

The Zhi Mä Funeral Ceremony of the Na‐Khi of Southwest China. Joseph F. Rock. Studia Instituti Anthropos, Vol. 9. St. Gabriel's Mission Press, Vienna‐Mödling, 1955. 228 pp., 10 pls.

Mythen und Mysterien. Magie und Religian der Tibeter. M. Hermanns. Verlag Balduin Pick, Köln, 1956. 400 pp., 49 figs., 1 map.

Oracles and Demons of Tibet. René de Nebesky‐Wojkowitz. Mouton &; Co., ‘s‐Gravenhage, 1956. 666 pp., 10 pls., 25 figs.

Die Lamaistische Kunst in der Umwelt von Tibet. Siegbert Hummel. Otto Harrassowitz, Leipzig, 1955. 149 pp., 134 figs., 1 map.

El Monte. Igbo Finda, Ewe Orisha, Vititinfinda. Notas sobre la religión, la magía, las supersticiones y el folklore de los negros criollos y del pueblo de Cuba. Lydia Cabrera. Ediciones C. R., Habana 1954. 564 pp., 25 pls.

Die Hieroglyphen der Maya‐Handschriften. Günter Zimmermann. Universität Hamburg, Abhandlungen aus dem Gebiet der Auslandskunde, Band 62, Reihe B: Völkerkunde, Kulturgeschichte und Sprachen, Band 34. Verlag Cram, de Gruyter &; Co., Hamburg, 1956. 174 pp., 8 pls., ca. 2000 text ill.

Das Indianerbuch. Geb. F. A. Brockhaus Verlag. Leipzig 1956. Eva Lips. 443 PP., 32 pls., 11 text ill., 6 maps. Cloth bound DM 10.80.

Das doppelte Geschlecht. Ethnologische Studien zur Bisexualität in Ritus und Mythos. Hermann Baumann. Berlin 1955. 420 pp., 5 maps.

Von Fremden Völkern und Kulturen. Beiträge zur Völkerkunde. Hans Plischke zum 65. Geburtstage gewidmet von seinen Kollegen und Freunden, Schülern und Mitarbeitern. Herausgegeben von W. Lang, W. Nippold und G. Spannaus. Droste‐Verlag, Düsseldorf, 1955. 284 pp., 30 figs., 2 maps.

Die Wiener Schule der Völkerkunde — The Vienna School of Ethnology. Festschrift anlässlich des 25‐jährigen Bestandes des Institutes für Völkerkunde der Universität Wien (1929–1954). Herausgeber J. Haekel, A. Hohenwart‐Gerlachstein und A. Slawik, Wien 1956. VIII+ 568 S., 11 Taf., 21 Textill, und 2 Karten. $ 8.60.

Das Problem des Völkertodes. Eine Studie zur historischen Bevölkerungsbiologie. Ilse Schwidetzky. Ferdinand Enke Verlag, Stuttgart 1954. 165 pp. This and the following review have been held over from former times, when these contributions were apt to prove rather exhaustive. Reviews are now heavily cut down irrespective of the significance of the work presented.     

Benzyloxybenzylammonium chlorides: Simple amine salts that display anticonvulsant activity

Several antiepileptic drugs exert their activities by inhibiting Na⁺ currents. Recent studies demonstrated that compounds containing a biaryl-linked motif (Ar-X-Ar′) modulate Na⁺ currents. We, and others, have reported that compounds with an embedded benzyloxyphenyl unit (ArOCH₂Ar′, OCH₂ = X) exhibit potent anticonvulsant activities. Here, we show that benzyloxybenzylammonium chlorides (⁺H₃NCH₂C₆H₄OCH₂Ar′ Cl^?) displayed notable activities in animal seizure models. Electrophysiological studies of 4-(2′-trifluoromethoxybenzyloxy)benzylammonium chloride (9) using embryonic cortical neurons demonstrated that 9 promoted both fast and slow inactivation of Na⁺ channels. These findings suggest that the potent anticonvulsant activities of the earlier compounds were due, in part, to the benzyloxyphenyl motif and provide support for the use of the biaryl-linked pharmacophore in future drug design efforts.