Biology and postnatal development of organ systems of cynomolgus monkeys (Macaca fascicularis).

Background: The cynomolgus macaque has become the most used non-human primate species in nonclinical safety assessment during the past decades.

Methods: This review summarizes the biological data and organ system development milestones of the cynomolgus macaque available in the literature.

Results: The cynomolgus macaque is born precocious relative to humans in some organ systems (e.

Discovery of novel and potent leukotriene B4 receptor antagonists. Part 1.

The inhibition of LTB(4) binding to and activation of G-protein-coupled receptors BLT1 and BLT2 is the premise of a treatment for several inflammatory diseases. In a lead optimization effort starting with the leukotriene B(4) (LTB(4)) receptor antagonist (2), members of a series of 3,5-diarylphenyl ethers were found to be highly potent inhibitors of LTB(4) binding to BLT1 and BLT2 receptors, with varying levels of selectivity depending on the substitution. In addition, compounds 33 and 38 from this series have good in vitro ADME properties, good oral bioavailability, and efficacy after oral delivery in guinea pig LTB(4) and nonhuman primate allergen challenge models.

Effects of LTB4 receptor antagonism on pulmonary inflammation in rodents and non-human primates.

Asthma, chronic obstructive pulmonary disease (COPD) and acute lung injury/acute respiratory distress syndrome (ALI/ARDS) are characterized by neutrophilic inflammation and elevated levels of leukotriene B4 (LTB4). However, the exact role of LTB4 pathways in mediating pulmonary neutrophilia and the potential therapeutic application of LTB4 receptor antagonists in these diseases remains controversial. Here we show that a novel dual BLT1 and BLT2 receptor antagonist, RO5101576, potently inhibited LTB4-evoked calcium mobilization in HL-60 cells and chemotaxis of human neutrophils.

Microbiological evaluation of a newly constructed animal facility.

Newly constructed animal facilities require microbiological evaluation prior to occupation to ensure that all facets of the design not only function accordingly and that the building is ready for introduction of new, healthy animal species and personnel. Our objective was to perform microbiological monitoring to ensure the integrity of systems implemented within our facility, both new and those transferred from existing facilities. This monitoring included environmental sampling of the autoclaves, cage washers, tunnel washers, and water system to ensure operant conditions.

Refinements in the care and use of animals in toxicology studies-regulation, validation, and progress.

During the past decade, important advances have been made in the humane care and use of laboratory animals used in toxicology studies, and there is strong international interest by the pharmaceutical sector in continuing with this progress. Because of the potential influence on human health, safety studies are highly regulated, and implementing refinements in laboratory animal care and use may require an initial validation study to demonstrate a lack of effect on study outcome. This paper provides an overview of issues surrounding implementation of animal care refinements in toxicology laboratory settings, including regulatory constraints, conducting validation studies, current progress in refinements, and areas for future consideration.