Carcinogenicity Evaluation of Baclofen in TgrasH2 Mice.

Baclofen is a γ-aminobutyric acid-B receptor agonist used for control of spastic muscle activity and as a treatment for alcohol abuse. The review of the nonclinical database suggested a data gap for potential carcinogenicity following long-term use. Regulatory requirements for pharmaceutical safety testing of cancer-causing potential have historically included 2-year rodent studies in rats and mice.

Intranodal Angiomyomatous Hamartoma in a Cynomolgus Monkey.

We describe here an angiomyomatous hamartoma in the right axillary lymph node of a three-year-old male cynomolgus monkey ( Macaca fascicularis), used as a control subject in a short-term toxicity study. This is a very rare lesion that has been reported almost exclusively in inguinal lymph nodes, and to date only in human beings. In the present case, light microscopy revealed partial replacement of the lymph node parenchyma by a disorganized, irregular vascular network, sparsely distributed smooth muscle cells, and a fibro-adipocytic stroma.

Species-specific inflammatory responses as a primary component for the development of glomerular lesions in mice and monkeys following chronic administration of a second-generation antisense oligonucleotide.

Chronic administration of drisapersen, a 2'-OMe phosphorothioate antisense oligonucleotide (AON) to mice and monkeys resulted in renal tubular accumulation, with secondary tubular degeneration. Glomerulopathy occurred in both species with species-specific characteristics. Glomerular lesions in mice were characterized by progressive hyaline matrix accumulation, accompanied by the presence of renal amyloid and with subsequent papillary necrosis.

Development of a Delayed-Type Hypersensitivity (DTH) Model in the Cynomolgus Monkey.

Although a T-dependent antibody response (TDAR) assay is generally recommended as the first-line immune function assay in nonclinical immunotoxicity evaluation, second-line assays such as delayed-type hypersensitivity (DTH) to measure cell-mediated responses can provide helpful additional information. In this study, male Cynomolgus monkeys were injected intramuscularly either once or twice with 1 mg Keyhole Limpet Hemocyanin (KLH) or twice with a commercially available tetanus vaccine (40 IU tetanus toxoid + 0.06 mg aluminum hydroxide).

Industry-contract research organization pathology interactions: a perspective of contract research organizations in producing the best quality pathology report.

This article provides observations on the features of sponsor-contract research organization communication that will achieve the best quality pathology report based on our collective experience. Information on the test article and any anticipated findings should be provided, and initial slide examination should be done with knowledge of treatment group (but may be followed by blinded review of target tissues to determine no-effect levels). Only a pathologist should write or revise the pathology report or the pathology section of the overall study report.

Effect of folate supplementation on clinical chemistry and hematologic changes related to bidisomide administration in the rat.

In a chronic toxicity study in the rat, bidisomide administered as a dietary admixture produced a dose-related lowering of reticulocytes and leucocytes. Plasma alanine aminotransferase activity was increased at 300 mg/kg and decreased at 900 mg/kg. The potential mechanisms of these effects were investigated by comparing the responses in groups of male Sprague-Dawley rats receiving a control diet, or 300 or 1200 mg/kg/day bidisomide.

A simple method for performing routine histopathological examination of the cardiac conduction tissue in the dog.

In standard toxicity studies, the cardiac conduction tissue is not systematically sampled and examined for histopathological changes. Most methods described use serial sectioning perpendicular to the long axis of the sinoauricular node (SAN) and atrioventricular node (AVN). Dozens of slides are needed to allow examination of a significant portion of the SAN and AVN.

Fasting for 24 h reveals liver microsteatosis after continuous i.v. infusion of milacemide in the rat.

Milacemide (2-n-pentylaminoacetamide) hydrochloride was administered by continuous i.v. infusion for up to 7 days, at 300 and 600 mg/kg per day to male Sprague-Dawley rats.