In Vitro Cytogenetic Assays: Chromosomal Aberrations and Micronucleus Tests.

Chromosome damage is a very important indicator of genetic damage relevant to environmental and clinical studies. Detailed descriptions of the protocols used for detection of chromosomal aberrations induced by genotoxic agents in vitro both in the presence or absence of rat liver-derived metabolizing systems are given in this chapter. Structural chromosomal aberrations that can be observed and quantified at metaphases are described here.

Vehicle Systems and Excipients Used in Minipig Drug Development Studies.

Minipigs have been used for dermal drug development studies for decades, and they are currently more frequently considered as the second nonrodent species for pivotal nonclinical studies, in lieu of the dog or nonhuman primate, for compounds delivered via standard systemic routes of administration. Little is known about the tolerability of different excipients in minipigs; sharing knowledge of excipient tolerability and compositions previously used in nonclinical studies may avoid testing of inadequate formulations, thereby contributing to reduced animal usage. This article reviews vehicles employed in the Göttingen(®)minipig based on the combined experience from a number of pharmaceutical companies and contract research organizations.

Spontaneous glomerulonephritis in Göttingen minipigs.

The Göttingen minipig is one of the nonrodent species recommended by various regulatory authorities for safety assessment of drugs in preclinical studies. In such studies, knowledge of background pathology is critical in order to evaluate the potential renal toxicity. In the present study, the authors report 4 cases of glomerulonephritis out of 154 microbiologically defined Göttingen minipigs microscopically evaluated in preclinical studies.

Function of the hypothalamo-pituitary-adrenal axis and humoral immune mechanisms during experimental allergic encephalomyelitis in SJL/J mice.

Objectives: In the present work, a method to induce experimental allergic encephalomyelitis (EAE) in female SJL/J mice was developed and validated in our laboratory. Although the latter is a popular animal model to mimic human multiple sclerosis, it remains to be clarified if: (1) the measurement of circulating antibodies against myelin antigens can be used as an index to predict the development of clinical EAE, as well as the severity of disease, and (2) the genetic susceptibility of this strain is associated with altered hypothalamo-pituitary-adrenal (HPA) function.

Methods And Results: We observed that SJL/J mice display a strong humoral response to immunization with myelin basic protein (MBP), as assessed by the titration of circulating anti-MBP antibodies.