We describe here an approach to boost detection sensitivity and expand dynamic range in the quantitation of large molecules while maintaining analytical specificity using summation of MRM (SMRM) transitions and LC separation technique.
Serum Biomarkers Reveal Long-term Cardiac Injury in Isoproterenol-treated African Green Monkeys
In this study, we have used filter-aided sample preparation (FASP) and tandem mass tag (TMT) labeling to investigate serum protein alterations in isoproterenol-treated African green monkeys.
In Vivo Activity of Amodiaquine against Ebola Virus Infection
We investigated the potential anti-EBOV effect of amodiaquine in a well-characterized nonhuman primate model of EVD.
Increased stress associated with head-out plethysmography testing can exacerbate respiratory effects and lead to mortality in rats
The generalized stress inherent to head-out plethysmography testing exacerbated the respiratory effects of DSM421 and was possibly compounded by DSM421’s cardiovascular effects, thus artifactually resulting in moribundity and mortality in rats.
Preclinical evaluations to identify optimal linezolid regimens for tuberculosis therapy
Clinically relevant linezolid regimens were simulated in the in vitro hollow-fiber infection model (HFIM) system to identify the linezolid therapies that minimize toxicity, maximize antibacterial activity, and prevent drug resistance.
Preclinical Studies on the Pharmacokinetics, Safety, and Toxicology of Oxfendazole: Toward First in Human Studies
A 2-week study in rats identified target organs of oxfendazole toxicity to be bone marrow, epididymis, liver, spleen, testis, and thymus. Female rats had greater oxfendazole exposure and exhibited toxicities at lower doses than did males. Decreased white blood cell levels, a class effect of benzimidazole anthelmintics, returned to normal during the recovery period. The no observed adverse effect level was determined to be >5 but <25 mg/kg/d and the maximum tolerated dose 100 mg/kg/d. The highest dose, 200 mg/kg/d, resulted in significant toxicity and mortality, leading to euthanization of the main study animals in this group after 7 days. Oxfendazole did not exhibit genetic toxicology signals in standard Ames bacterial, mouse lymphoma, or rat micronucleus assays nor did it provoke safety concerns when evaluated for behavioral effects in rats or cardiovascular safety effects in dogs. These results support the transition of oxfendazole to First in Human safety studies preliminary to its evaluation in human helminth diseases
Tenofovir Disoproxil Fumarate: Toxicity, Toxicokinetics, and Toxicogenomics Analysis After 13 Weeks of Oral Administration in Mice
The goals of this study were to evaluate the molecular mechanism of TDF-induced toxicity in mice by correlating transcriptional changes with plasma drug levels and traditional toxicology end points.
Non-Clinical Safety Evaluation of Xoma 3AB, a Novel Triple Antibody Drug Product Targeting Botulinum Toxin Type a, in Sprague-Dawley Rats
The Role of Nonprofit Institutes in Pharmaceutical Development
When I describe to friends and colleagues what I do for a living, I typically get a response like, “So, you are really no different than a pharmaceutical company.” Exactly. And not at all. SRI International has played a major role in the development of therapeutics for a wide range of diseases over the years […]