Review of Rodent Euthanasia Methods.

The optimal choice of euthanasia method for laboratory rodents depends on a number of factors, including the scientific goals of the study, the need to minimize animal pain and/or distress, applicable guidelines and laws, the training and proficiency of personnel, and the safety and emotional needs of the personnel performing the euthanasia. This manuscript aims to provide guidance to researchers so they may select the method of euthanasia that results in minimal experimental confounds, such as the creation of artifact and alteration of tissues and analytes. Specific situations addressed include euthanasia of large numbers of rodents and euthanasia of neonates.

PDK1 attenuation fails to prevent tumor formation in PTEN-deficient transgenic mouse models.

PDK1 activates AKT suggesting that PDK1 inhibition might suppress tumor development. However, while PDK1 has been investigated intensively as an oncology target, selective inhibitors suitable for in vivo studies have remained elusive. In this study we present the results of in vivo PDK1 inhibition through a universally applicable RNAi approach for functional drug target validation in oncogenic pathway contexts.

Purine derivatives as potent gamma-secretase modulators.

The development of a novel series of purines as gamma-secretase modulators for potential use in the treatment of Alzheimer's disease is disclosed herein. Optimization of a previously disclosed pyrimidine series afforded a series of potent purine-based gamma-secretase modulators with 300- to 2000-fold in vitro selectivity over inhibition of Notch cleavage and that selectively reduces Alphabeta42 in an APP-YAC transgenic mouse model.

Validation of the use of nonnaive surgically catheterized rats for pharmacokinetics studies.

Although large animals, such as dogs and nonhuman primates, often are used for more than 1 pharmacokinetics study, common practice is to use only naive rodents for pharmacokinetics studies. We undertook a series of studies to validate whether surgically cannulated nonnaive rats could be used again after a 7-d washout. When vascular catheters are cared for appropriately, we find that they remain patent for more than 2 wk, with negligible drug carryover.

Helicobacter-induced chronic active lymphoid aggregates have characteristics of tertiary lymphoid tissue.

Susceptible strains of mice that are naturally or experimentally infected with murine intestinal helicobacter species develop hepatic inflammatory lesions that have previously been described as chronic active hepatitis. The inflammatory infiltrates in some models of chronic autoimmunity or inflammation resemble tertiary lymphoid organs hypothesized to arise by a process termed lymphoid organ neogenesis. To determine whether hepatic inflammation caused by infection with helicobacter could give rise to tertiary lymphoid organs, we used fluorescence-activated cell sorting, immunohistochemistry, and in situ hybridization techniques to identify specific components characteristic of lymphoid organs in liver tissue sections and liver cell suspensions from helicobacter-infected mice.

Biomethod for Obtaining Gastric Juice and Serum From the Unanesthetized Guinea Pig (Cavia porcellus).

Blood sample collection and gastric intubation of guinea pigs have been considered difficult techniques that require anesthesia. We developed methods to sample blood and gastric juice from manually restrained, unanesthetized guinea pigs. To collect gastric juice, the guinea pig is restrained in vertical position by an assistant, who keeps the guinea pig's head in extreme dorsoflexion by use of a strip of gauze looped around the top incisors.