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Kathrin Herrmann, Paul Flecknell
Pain has a profound effect on an animal's wellbeing. In Germany, researchers using animals have been legally required since 1972 to reduce any possible pain, suffering, distress or lasting harm to an absolute minimum. To evaluate how these provisions have been implemented in practice, an assessment of refinements to experimental techniques was conducted by retrospectively reviewing 684 surgical interventions described in 506 animal research applications that were sent to the German competent authorities for approval in 2010...
September 14, 2018: ALTEX
Wen Y Chung, Joseph J Wanford, Rohan Kumar, John D Isherwood, Richard D Haigh, Marco R Oggioni, Ashley R Dennison, Giuseppe Ercoli
An ex vivo, porcine spleen perfusion model was established to study the early events occurring in the spleen prior to the onset of bacterial sepsis, using organs retrieved from animals slaughtered for food production. Porcine spleens were harvested from adult pigs and connected to a normothermic extracorporeal perfusion circuit. A constant perfusion of heparinized blood was performed for 6 hours. After injection of Streptococcus pneumoniae to the circuit serial samples of both blood and spleen biopsies were collected and analysed...
August 3, 2018: ALTEX
Roberta De Souza Santos, Aaron P Frank, Biff F Palmer, Deborah J Clegg
Cell culture has enhanced our understanding of cellular physiology and constitutes an important tool in advancing mechanistic insight. Researchers should be reminded, however, that there are limitations in extrapolating data derived from cultured cells to questions focusing on the impact of sex. In this Opinion, we highlight two underappreciated aspects of cell culture systems regarding sex: how cell culture media alters the sex hormone environment, and how the innate sex of the cell is often not factored into the overall analysis...
July 27, 2018: ALTEX
Pilar Prieto, Rabea Graepel, Kirsten Gerloff, Lara Lamon, Magdalini Sachana, Francesca Pistollato, Laura Gribaldo, Anna Bal-Price, Andrew Worth
The replacement of animals in acute systemic toxicity testing remains a considerable challenge. Only animal data are currently accepted by regulators, including data generated by reduction and refinement methods. The development of Integrated Approaches to Testing and Assessment (IATA) is hampered by an insufficient understanding of the numerous toxicity pathways that lead to acute systemic toxicity. Therefore, central to our work has been the collection and evaluation of the mechanistic information on eight organs identified as relevant for acute systemic toxicity (nervous system, cardiovascular system, liver, kidney, lung, blood, gastrointestinal system and immune system)...
July 12, 2018: ALTEX
Aldo Dekker, Froukje Van Hemert-Kluitenberg, Anna H Oosterbaan, Kimberly Moonen, Laure Mouton
Titration of foot-and-mouth disease cattle challenge virus in cattle tongue has been the standard for many years in many countries, although for all other applications titration in animals has be replaced by in vitro methods. The objective of the analysis was the replacement of in vivo titration of cattle challenge virus by in vitro titration. Using data from 32 in vivo titration experiments together with the in vitro titration results, obtained by plaque count on primary lamb or pig kidney cells, of the same samples, as well as data from the virus isolation control chart used in the laboratory, we show that the repeatability of the in vitro titration is much higher than the repeatability of the in vivo titration...
July 12, 2018: ALTEX
Brian D Chapron, Alenka Chapron, Brian Phillips, Miracle C Okoli, Danny D Shen, Edward J Kelly, Jonathan Himmelfarb, Kenneth E Thummel
The role of megalin in the regulation of renal vitamin D homeostasis has previously been evaluated in megalin-knockout mice and rat proximal tubule epithelial cells. We revisited these hypotheses that were previously tested solely in the rodent models, this time using a 3-dimensional proximal tubule microphysiological system incorporating primary human proximal tubule epithelial cells. Using this human cell-derived model, we confirmed that 25OHD3 is transported into the human proximal tubule epithelium via megalin-mediated endocytosis while bound to vitamin D binding protein...
July 8, 2018: ALTEX
Fabian A Grimm, Alexander Blanchette, John S House, Kyle Ferguson, Nan-Hung Hsieh, Chimeddulam Dalaijamts, Alec A Wright, Blake Anson, Fred A Wright, Weihsueh A Chiu, Ivan Rusyn
Assessing inter-individual variability in responses to xenobiotics remains a substantial challenge, both in drug development with respect to pharmaceuticals and in public health with respect to environmental chemicals.  Although approaches exist to characterize pharmacokinetic variability, there are no methods to routinely address pharmacodynamic variability.  In this study, we aimed to demonstrate the feasibility of characterizing inter-individual variability in a human in vitro model. Specifically, we hypothesized that genetic variability across a population of iPSC-derived cardiomyocytes translates into reproducible variability in both baseline phenotypes and drug responses...
July 8, 2018: ALTEX
Lindsey K Borton, Kelly P Coleman
Pyrogenicity presents a challenge to clinicians, medical device manufactures, and regulators. A febrile response may be caused by endotoxin contamination, microbial components other than endotoxin, or chemical agents that generate a material-mediated pyrogenic response. While test methods for the assessment of endotoxin contamination and some microbial components other than endotoxin are well-established, material-mediated pyrogens remain elusively undefined. This review presents the findings of literature searches conducted to identify material-mediated pyrogens associated with medical devices...
June 14, 2018: ALTEX
Alexander Edwards, Lottie Roscoe, Christopher Longmore, Fiona Bailey, Bushra Sim, Carol Treasure
Skin sensitisers are substances that can elicit allergic responses following skin contact and the process by which this occurs is described as skin sensitisation. Skin sensitisation is defined as a series of key events, that form an adverse outcome pathway (AOP). Key event three in the AOP is dendritic cell activation that can be modelled by the human Cell Line Activation Test (h-CLAT) and is typified by changes in cell surface markers CD54 and CD86 in dendritic cells. The h-CLAT is accepted at a regulatory level (OECD Test-Guideline (TG)442E) and can be used to assess skin sensitisation potential as part of an integrated approach to testing and assessment (IATA)...
June 13, 2018: ALTEX
Ann-Cathrin Volz, Larissa Hack, Franziska B Atzinger, Petra J Kluger
Vascularized adipose tissue models are highly demanded as alternative to existing animal models to elucidate the mechanisms of widespread diseases, screen for new drugs or asses corresponding safety levels. Standardly used animal-derived sera therein, are associated to ethical concerns, the risk of contaminations and many uncertainties in their composition and impact on cells. Therefore their use should be completely omitted. In this study we developed a serum-free, defined co-culture medium and implemented it to set up an adipocyte-endothelial cell (EC) co-culture model...
June 13, 2018: ALTEX
Rita Palmeira-de-Oliveira, Rita Monteiro Machado, José Martinez-de-Oliveira, Ana Palmeira-de-Oliveira
The HET-CAM (Hen's Egg Test-Chorioallantoic Membrane) assay is an in vitro alternative to the in vivo Draize Rabbit Eye test that mimics vascular changes in the chorioallantoic membrane. This qualitative method assesses the irritancy potential of chemicals. The CAM responds to injury with an inflammatory process similar to that in the rabbit eye's conjunctival tissue. Regarding topical toxicity assessment of medical devices, ISO 10993-10 states that any skin or eye irritant material shall be directly labelled as a potential vaginal irritant without animal testing, suggesting that the irritation potential for the eye and the vaginal epithelia is similar...
March 11, 2018: ALTEX
Johannes Delp, Simon Gutbier, Stefanie Klima, Lisa Hoelting, Kevin Pinto-Gil, Jui-Hua Hsieh, Michael Aichem, Karsten Klein, Falk Schreiber, Raymond R Tice, Manuel Pastor, Mamta Behl, Marcel Leist
The (developmental) neurotoxicity hazard is still unknown for most chemicals. Establishing a test battery covering most of the relevant adverse outcome pathways may close this gap, without requiring a huge animal experimentation program. Ideally, each of the assays would cover multiple mechanisms of toxicity. One candidate test is the human LUHMES cell-based NeuriTox test. To evaluate its readiness for larger-scale testing, a proof of concept library assembled by the U.S. National Toxicology Program (NTP) was screened...
January 21, 2018: ALTEX
Marcel Leist, Jan G Hengstler
Methods papers are important for the progress of biomedical research, as they provide the essential tools to explore new questions and help to better answer old ones. However, it is often not clear how a methods paper differs from a methods protocol. Confusion between these two very different types of publication is widespread. The resultant misunderstanding contributes to a relatively poor reputation of methods research in biology despite the fact that many Nobel prizes have been awarded specifically for method development...
2018: ALTEX
Hanna Vuorenpää
No abstract text is available yet for this article.
2018: ALTEX
Julika Fitzi-Rathgen
No abstract text is available yet for this article.
2018: ALTEX
Andras-Laszlo Nagy, Cornel Catoi, Carmen Socaciu, Adela Pintea, Nechita A Oros, Cristina Coman, Dumitrita Rugina, Cristian T Matea, Teodora Mocan, Teresa Coccini, Uliana De Simone, Isabella De Angelis, Alessia Bertero, Yula Sambuy, Francesca Caloni
No abstract text is available yet for this article.
2018: ALTEX
Megan Chesnut, Takashi Yamada, Timothy Adams, Derek Knight, Nicole Kleinstreuer, George Kass, Thomas Luechtefeld, Thomas Hartung
No abstract text is available yet for this article.
2018: ALTEX
Lucy Meigs, Lena Smirnova, Costanza Rovida, Marcel Leist, Thomas Hartung
For a long time, the discussion about animal testing vs its alternatives centered on animal welfare. This was a static warfare, or at least a gridlock, where life scientists had to take a position and make their value choices and hardly anyone changed sides. Technical advances have changed the frontline somewhat, with in vitro and in silico methods gaining more ground. Only more recently has the economic view begun to have an impact: Many animal tests are simply too costly, take too long, and give misleading results...
2018: ALTEX
Alice Krebs, Johanna Nyffeler, Jörg Rahnenführer, Marcel Leist
Many types of assays in cell biology, pharmacology and toxicology generate data in which a parameter is measured in a reference system (negative control) and then also under conditions of increasing stress or drug exposure. To make such data easily comparable, they are normalized, i.e., the initial value of the system (e.g., viability or transport function) is set to 100%, and all data are indicated relative to this value. Then, curves are fitted through the data points and summary data of the system behavior are determined...
2018: ALTEX
Andrey Poloznikov, Irina Gazaryan, Maxim Shkurnikov, Sergey Nikulin, Oxana Drapkina, Ancha Baranova, Alexander Tonevitsky
Most common drug development failures originate from either bioavailability problems, or unexpected toxic effects. The culprit is often the liver, which is responsible for biotransformation of a majority of xenobiotics. Liver may be modeled using "liver on a chip" devices, which may include established cell lines, primary human cells, and stem cell-derived hepatocyte-like cells. The choice of biological material along with its processing and maintenance greatly influence both the device performance and the resultant toxicity predictions...
2018: ALTEX
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