A5042601716- Immunotoxicology and immune responses
- Animal testing and alternatives
- Bone Metabolism and Diseases
- Bone health and osteoporosis research
- Bone health and treatments
- Carcinogens and Genotoxicity Assessment
- Pancreatic function and diabetes
- Diabetes Treatment and Management
- Microbial infections and disease research
- Biosimilars and Bioanalytical Methods
- Pancreatitis Pathology and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Metabolism, Diabetes, and Cancer
- Diabetes Management and Research
- CAR-T cell therapy research
- Cancer Research and Treatments
- Hip disorders and treatments
- Risk Perception and Management
- TGF-β signaling in diseases
- Streptococcal Infections and Treatments
- Pharmaceutical studies and practices
- Statistical Methods in Clinical Trials
- dental development and anomalies
- Veterinary Pharmacology and Anesthesia
- Clinical Laboratory Practices and Quality Control
Eli Lilly (United States)
2014-2025
Centre for Innovation in Regulatory Science
2012
Iowa State University
1995-1998
University of Münster
1990
Fischer 344 rats (60/sex/group) were given daily subcutaneous injections of recombinant human parathyroid hormone (PTH)(1-34) for 2 years at doses 0, 5, 30, or 75 microg/kg. Treatment caused substantial increases in bone mass consistent with the known pharmacologic effects once-daily administration. As determined by quantitative computed tomography (QCT) and histomorphometry, was markedly increased. Substantial new formation resulted a large decrease marrow space accompanied altered...
A long-term study was conducted in female F344 rats to determine the relative importance of dose, treatment duration, and age at initiation on incidence teriparatide [rhPTH[1-34)]-induced bone proliferative lesions. Treatment groups consisted different combinations dose (0, 5, or 30 μg/kg/d), duration (6, 20, 24 months) (2 6 months age). The primary endpoints were neoplasms effects mass structure as evaluated by quantitative computed tomography histomorphometery. Significant increases tumors...
Abstract OVX monkeys treated for 18 months with 1 or 5 μg/kg/d teriparatide [PTH (1–34)] had significantly stronger proximal femora relative to ovariectomized controls. Teriparatide enhancement of cortical area, width, and trabecular bone volume seemed more than compensate the dose-dependent increase in porosity. Beneficial effects treatment on femur persisted beyond period may extend marrow. Introduction: We conducted a detailed quantitative analysis monkeys. increased mass, enhanced...
The Cause of Death in Non-Rodents (CODN) Working Group is an initiative under the Scientific and Regulatory Policy Committee (SRPC) Society Toxicologic Pathology (STP), focused on understanding existing practices expectations among pharmaceutical companies, academic entities, contract research organizations (CROs) when it comes to identifying reporting “Cause Death” (COD) or moribundity for early unplanned necropsies non-rodent animal species (mainly non-human primates [NHP] dogs) within...
Haemophilus parasuis is a common cause of polyserositis and polyarthritis in swine. Little known about the mucosal systemic sites replication lesions which follow an aerosol exposure to H. parasuis. In this experiment 5–week-old cesarean-derived, colostrum-deprived (CDCD) pigs were inoculated intranasally with inoculum containing 2 × 10 9 colony-forming units Two principals one control pig necropsied at 12, 36, 84, 108 hours postinoculation (PI) samples obtained for bacteriologic culture...
Skeletal effects are described for near-lifetime treatment of young, female rats with recombinant human PTH (1-34) (PTH). Rats (5-8 wk age) were administered 0, 5, 30, or 75 microg/kg x d sc up to 2 yr, as part an oncogenicity evaluation, which is required by regulatory agencies potential chronic therapies. Proliferative lesions observed in the skeleton Vahle et al. (1 ); this paper, we describe quantitative bone data study. In appendicular skeleton, stimulated trabecular and endocortical...
Abstract In rats, teriparatide [rhPTH(1-34)] causes marked increases in bone mass and osteosarcoma. primates, lesser mass, osteosarcomas have not been reported. Previous studies primates were designed to detect tumors did include a prolonged post-treatment observation period determine whether would arise after cessation of treatment. Ovariectomized (OVX), skeletally mature, cynomolgus monkeys (n = 30 per group) given for 18 mo at either 0 or 5 μg/kg/d subcutaneously. After treatment,...
The International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats Mice proposal (INHAND) has been operational since 2005. A Global Editorial Steering Committee manages the overall objectives project, development harmonized terminology each organ system is responsibility Organ Working Groups, drawing upon experts from North America, Europe, Japan. Great progress made with 9 systems published to date--respiratory, hepatobiliary, urinary, central/peripheral nervous...
The tumorigenic potential of dulaglutide was evaluated in rats and transgenic mice. Rats were injected sc twice weekly for 93 weeks with 0, 0.05, 0.5, 1.5, or 5 mg/kg corresponding to 7, 20, 58 times, respectively, the maximum recommended human dose based on plasma area under curve. Transgenic mice dosed 0.3, 1, 3 26 weeks. Dulaglutide effects limited thyroid C-cells. In rats, diffuse C-cell hyperplasia adenomas statistically increased at 0.5 greater (P ≤ .01 mg/kg), carcinomas numerically...
Industry representatives on the ICH S1B(R1) Expert Working Group (EWG) worked closely with colleagues from Drug Regulatory Authorities to develop an addendum S1B guideline carcinogenicity studies that allows for a weight-of-evidence (WoE) assessment in some cases, rather than conducting 2-year rat study. A subgroup of EWG composed regulators have published this issue detailed analysis Prospective Evaluation Study (PES) conducted under auspices EWG. Based experience gained through process,...
We report the consequences of prolonged treatment with recombinant human parathyroid hormone (1-34) (PTH) in male and ovariectomized female rats mature skeletons. Intact osteopenic, ovariectomized, F-344 were evaluated after 1 year 0, 8, or 40 μg/kg/day s.c. PTH. Males females about 6 months age at study initiation; (Ovx) for 5 weeks before initiation PTH treatment. did not affect survival either intact males females. Qualitative histopathology showed expected changes associated aging...
LY2541546 is a humanized monoclonal antibody (IgG4) that has been optimized for neutralizing activity against sclerostin. In 5-week and 6-month nonclinical safety studies in rats, caused dose-dependent reversible decreases platelet counts accompanied by accelerated production, increased megakaryocytes, altered megakaryocyte morphology. These treatment-related effects resulted primary hemostasis as manifested prolonged bleeding after phlebotomy or incidental toenail break. some cases, the...
The INHAND Proposal (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats Mice) has been operational since 2005. A Global Editorial Steering Committee (GESC) manages the overall objectives project development harmonized terminology each organ system is responsibility Organ Working Groups (OWG), drawing upon experts from North America, Europe Japan.Great progress made with 9 systems published to date - Respiratory, Hepatobiliary, Urinary, Central/Peripheral...
Glucagon-like peptide-1 (GLP-1) receptor agonists, used for the treatment of type 2 diabetes, have caused hyperplasia/neoplasia thyroid C cells in rodent carcinogenicity studies. Studies monkeys not identified an effect GLP-1 agonists on cells; however, group sizes were small. Dulaglutide is a once-weekly, long-acting human agonist recently approved United States and European Union. The objective this study was to determine whether dulaglutide altered C-cell mass monkeys. Male cynomolgus (20...