Safety Pharmacology Screening: Practical Problems in Drug Development

1997 ◽  
Vol 16 (1) ◽  
pp. 41-65 ◽  
Author(s):  
Lawrence I. Mortin ◽  
Christopher J. Horvath ◽  
Michael S. Wyand
Keyword(s):  
Nonhuman Primates ◽  
Animal Species ◽  
Smooth Muscles ◽  
Electrolyte Balance ◽  
Large Animal ◽  
Toxicity Studies ◽  
General Pharmacology ◽  
Pharmacologic Effect ◽  
Immunologic Diseases ◽  
Species Specific

Undesired pharmacologic activities of novel drugs or biologies may limit development of a therapeutic prior to the characterization of any toxicologic effects. In rodent species, general pharmacology assays have traditionally been used to screen new agents for pharmacologic effects on the central and peripheral nervous systems, the autonomic nervous system and smooth muscles, the respiratory and cardiovascular systems, the digestive system, and the physiologic mechanisms of water and electrolyte balance. In large animal species, such as dogs and nonhuman primates, smaller numbers of animals per study limit their use for screening assays, but these species may play an important role in more detailed mechanistic studies. For drugs and biologies that must be tested in nonhuman primates because of species-specific action of the test agent, functional pharmacologic data are often collected during acute or subacute toxicity studies. This requires careful experimental design to minimize any impact pharmacologic effects or instrumentation may have on the assessment of toxicity. In addition, with many new therapies targeted at immunologic diseases, the pharmacologic effect of therapeutics on the immune system presents new challenges for pharmacologic profiling. The application of pharmacology assays by organ system in both rodent and large animal species are discussed, as well as practical issues in assessing pharmacology endpoints in the context of toxicity studies.

scholarly journals Intracellular calcium oscillations and activation in horse oocytes injected with stallion sperm extracts or spermatozoa

Reproduction ◽  
2003 ◽  
pp. 489-499 ◽  
Author(s):  
SJ Bedford ◽  
M Kurokawa ◽  
K Hinrichs ◽  
RA Fissore
Keyword(s):  
Embryonic Development ◽  
Intracellular Calcium ◽  
Intracytoplasmic Sperm Injection ◽  
Animal Species ◽  
Mammalian Species ◽  
Calcium Oscillations ◽  
Large Animal ◽  
Oocyte Activation ◽  
Mouse Oocytes ◽  
Species Specific

In oocytes from all mammalian species studied to date, fertilization by a spermatozoon induces intracellular calcium ([Ca(2+)](i)) oscillations that are crucial for appropriate oocyte activation and embryonic development. Such patterns are species-specific and have not yet been elucidated in horses; it is also not known whether equine oocytes respond with transient [Ca(2+)](i) oscillations when fertilized or treated with parthenogenetic agents. Therefore, the aims of this study were: (i) to characterize the activity of equine sperm extracts microinjected into mouse oocytes; (ii) to ascertain in horse oocytes the [Ca(2+)](i)-releasing activity and activating capacity of equine sperm extracts corresponding to the activity present in a single stallion spermatozoon; and (iii) to determine whether equine oocytes respond with [Ca(2+)](i) transients and activation when fertilized using the intracytoplasmic sperm injection (ICSI) procedure. The results of this study indicate that equine sperm extracts are able to induce [Ca(2+)](i) oscillations, activation and embryo development in mouse oocytes. Furthermore, in horse oocytes, injection of sperm extracts induced persistent [Ca(2+)](i) oscillations that lasted for >60 min and initiated oocyte activation. Nevertheless, injection of a single stallion spermatozoon did not consistently initiate [Ca(2+)](i) oscillations in horse oocytes. It is concluded that stallion sperm extracts can efficiently induce [Ca(2+)](i) responses and parthenogenesis in horse oocytes, and can be used to elucidate the signalling mechanism of fertilization in horses. Conversely, the inconsistent [Ca(2+)](i) responses obtained with sperm injection in horse oocytes may explain, at least in part, the low developmental success obtained using ICSI in large animal species.

Primate Vocal Communication and the Evolution of Speech

2021 ◽  
Vol 30 (1) ◽  
pp. 55-60
Author(s):  
Julia Fischer
Keyword(s):  
Nonhuman Primate ◽  
Nonhuman Primates ◽  
Vocal Communication ◽  
Internal State ◽  
Multiple Sources ◽  
Primate Communication ◽  
Evolution Of Speech ◽  
Primate Vocal Communication ◽  
Species Specific ◽  
Shed Light

Studies of nonhuman primate communication are often motivated by the desire to shed light on the evolution of speech. In contrast to human speech, the vocal repertoires of nonhuman primates are evolutionarily highly conserved. Within species-specific constraints, calls may vary in relation to the internal state of the caller or social experience. Receivers can use signalers’ calls to predict upcoming events or behavioral dispositions. Yet nonhuman primates do not appear to express or comprehend communicative or informative intent. Signalers are sensitive to the relation between their own actions and receivers’ responses, and thus, signaling behavior can be conceived as goal directed. Receivers’ ability to integrate information from multiple sources renders the system flexible and powerful. Researchers who take a linguistic or biological perspective on nonhuman primate communication should be aware of the strengths and limitations of their approaches. Both benefit from a focus on the mechanisms that underpin signaling and responses to signals.

scholarly journals The ship of the desert. The dromedary camel (Camelus dromedarius), a domesticated animal species well adapted to extreme conditions of aridness and heat

Rangifer ◽  
1990 ◽  
Vol 10 (3) ◽  
pp. 231 ◽  
Author(s):  
S. Bornstein
Keyword(s):  
Animal Species ◽  
Physiological Adaptation ◽  
Dromedary Camel ◽  
Large Animal ◽  
Water Losses ◽  
Evaporative Water ◽  
Ambient Temperatures ◽  
Adaptive Mechanisms ◽  
Adaptation To Heat ◽  
Arabian Camel

The dromedary camel (Camel dromedarius) is extremely well adapted to life in hot and arid lands. In terms of physiological adaptation to heat and water deprivation it surpasses by far every other large animal of which data have been collected. None of the adaptive mechanisms to cope with the environmental stresses are unique to the Arabian camel, but the efficiency of its adaptation is superior. At high ambient temperatures the camels adapt to the scarcity of water by reducing their faecal, urinary and evaporative water losses. During dehydration, the kidneys reduce water losses both by decreasing the glomerual filtration rate and by increasing the tubular reabsorption of water. Also their ability of regulating their body temperature from 34.5-40.7 °C conserves a lot of water, when most needed.

scholarly journals Species-Specific Knowledge About the Environment: A Biophilosophical View

1969 ◽  
Vol 1 (1) ◽  
Author(s):  
Alfredo Pereira Junior
Keyword(s):  
Animal Species ◽  
Specific Knowledge ◽  
Animal Brain ◽  
The World ◽  
Von Uexküll ◽  
Species Specific

The biological work of Jacob von Uexkull (1934) raised an hypothesis that different animal species living in the same environment would have different knowledge about it. He suggested that each species perceives the world according to the structure of their effectors. In this essay I discuss mechanisms in the animal brain possibly responsible for the "embodied" or "pragmatic" character of cognition.

scholarly journals Large animal models of stroke and traumatic brain injury as translational tools

2018 ◽  
Vol 315 (2) ◽  
pp. R165-R190 ◽  
Author(s):  
Annabel J. Sorby-Adams ◽  
Robert Vink ◽  
Renée J. Turner
Keyword(s):  
Traumatic Brain Injury ◽  
Ischemic Stroke ◽  
Brain Injury ◽  
Animal Models ◽  
Animal Species ◽  
Experimental Models ◽  
Clinical Translation ◽  
Large Animal ◽  
Large Animal Models ◽  
Significant Burden

Acute central nervous system injury, encompassing traumatic brain injury (TBI) and stroke, accounts for a significant burden of morbidity and mortality worldwide. Studies in animal models have greatly enhanced our understanding of the complex pathophysiology that underlies TBI and stroke and enabled the preclinical screening of over 1,000 novel therapeutic agents. Despite this, the translation of novel therapeutics from experimental models to clinical therapies has been extremely poor. One potential explanation for this poor clinical translation is the choice of experimental model, given that the majority of preclinical TBI and ischemic stroke studies have been conducted in small animals, such as rodents, which have small lissencephalic brains. However, the use of large animal species such as nonhuman primates, sheep, and pigs, which have large gyrencephalic human-like brains, may provide an avenue to improve clinical translation due to similarities in neuroanatomical structure when compared with widely adopted rodent models. This purpose of this review is to provide an overview of large animal models of TBI and ischemic stroke, including the surgical considerations, key benefits, and limitations of each approach.

Flow rates of double‐lumen over‐the‐wire catheters for high‐volume fluid resuscitation in large animal species

2022 ◽  
Author(s):  
Juliana H. Giffoni ◽  
Raffaella B. C. Teixeira ◽  
Raphael R. Wenceslau ◽  
Melina A. F. Abrantes ◽  
Jéssica G. Oliveira ◽  
...  
Keyword(s):  
Fluid Resuscitation ◽  
Animal Species ◽  
High Volume ◽  
Large Animal ◽  
Double Lumen ◽  
Flow Rates ◽  
The Wire

259 EFFECTS OF BIPHASIC PACING IN LARGE ANIMAL SPECIES.

2006 ◽  
Vol 54 (1) ◽  
pp. S302.4-S302 ◽  
Author(s):  
F. Tondato ◽  
L. Rougée ◽  
G. K. Ostrander ◽  
M. Ungs ◽  
M. M. Mower
Keyword(s):  
Animal Species ◽  
Large Animal

scholarly journals Evolution of species-specific major seminal fluid proteins in placental mammals by gene death and positive selection

2015 ◽  
Vol 84 (3) ◽  
pp. 217-235 ◽  
Author(s):  
Camille Meslin ◽  
Michel Laurin ◽  
Isabelle Callebaut ◽  
Xavier Druart ◽  
Philippe Monget
Keyword(s):  
Amino Acids ◽  
Positive Selection ◽  
Statistical Power ◽  
Animal Species ◽  
Seminal Fluid ◽  
Domestic Animal ◽  
Secreted Proteins ◽  
Seminal Fluid Proteins ◽  
Species Specific ◽  
Complex Substance

The seminal fluid is a complex substance composed of a variety of secreted proteins and has been shown to play an important role in the fertilisation process in mammals and also in Drosophila. Several genes under positive selection have been documented in some rodents and primates. Our study documents this phenomenon in several other mammalian taxa. We study the evolution of genes that encode for 20 proteins that are quantitatively predominant in the seminal fluid of at least one out of seven domestic animal species. We analyse the amino acid composition of these proteins for positive selection and for the presence of pseudogenes. Genes that disappeared through pseudogenisation include KLK2 in cattle, horse and mice. Traces of positive selection are found in seven genes. The identified amino acids are located in regions exposed to the protein surface, suggesting a role in the interaction of gametes, with possible impact on the process of speciation. Moreover, we found no evidence that the predominance of proteins in seminal fluid and their mode of evolution are correlated, and the uncoupled patterns of change suggest that this result is not due solely to lack of statistical power.

Cloth-Based Hybridization Array System for Expanded Identification of the Animal Species Origin of Derived Materials in Feeds

2007 ◽  
Vol 70 (12) ◽  
pp. 2900-2905 ◽  
Author(s):  
JOHANNA MURPHY ◽  
JENNIFER ARMOUR ◽  
BURTON W. BLAIS
Keyword(s):  
Mitochondrial Dna ◽  
Dna Sequences ◽  
Microscopic Examination ◽  
Animal Species ◽  
Specific Detection ◽  
Animal Feeds ◽  
Species Origin ◽  
Pcr Products ◽  
Species Specific ◽  
Immunoenzymatic Assay

A cloth-based hybridization array system (CHAS) previously developed for the detection of animal species for which prohibited materials have been specified (cattle, sheep, goat, elk, and deer) has been expanded to include the detection of animal species for which there are no prohibitions (pig and horse) in Canadian and American animal feeds. Animal species were identified by amplification of mitochondrial DNA sequences by PCR and subsequent hybridization of the amplicons with an array of species-specific oligonucleotide capture probes immobilized on a polyester cloth support, followed by an immunoenzymatic assay of the bound PCR products. The CHAS permitted sensitive and specific detection of meat meals from different animal species blended in a grain-based feed and should provide a useful adjunct to microscopic examination for the identification of prohibited materials in animal feeds.

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