Because of the relative ease of embryonic manipulation and observation, the ability to produce a great number of genetic mutations, efficient screening methods, and the continued advance of molecular genetic tools, such as the progress in sequencing and mapping of the zebrafish genome, the use of zebrafish (Danio rerio) as a biomedical model organism continues to expand. However, studies involving zebrafish husbandry and veterinary care struggle to keep pace with scientific progress. This article outlines some of the current, acceptable methods for providing anesthesia and euthanasia and provides some examples of how performance-based approaches can be used to advance the relatively limited number of anesthetic and euthanizing techniques available for zebrafish.
Dose-response studies often form integral parts of pharmacological investigations of drug activity and efficacy and of toxicological investigations of drug and chemical safety.Standardized dose-response study protocols, statistical models, model fitting techniques, and computer programs are widely available for such applications. Many studies how ever, require nonstandard models and model fitting procedures to adequately describe the resulting data. Maximum likelihood analysis can accommodate a wide variety of model structures in a unified manner. This presentation illustrates how general purpose nonlinear regression analysis routines, such as those that are available in SAS or in BMDP, can be used to obtain maximum likelihood model solutions and associated er ror analyses for nonstandard model fitting situations. This reduces the need for special purpose computer programs for individual modeling applications. Methodological con siderations in the application of nonlinear regression modeling procedures to maximum likelihood estimation are discussed. The methodology is illustrated with several model ing situations.
Sulfur mustard (HD; 2,2′‐dichlorodiethyl sulfide) can produce incapacitating blisters in humans following dermal exposure. Most non‐human animal models, however, do not form the large fluid‐filled blisters observed in humans. Many models, nevertheless, do produce similar damage at the dermal/epidermal junction when evaluated by histopathology. In this study, it was observed that the hairless guinea pig (HGP) exhibits similar histopathological responses following exposure to HD vapor. Two sets of HGPs were exposed percutaneously for various lengths of time to HD vapor. In one set, the HGPs were sacrificed 24 h after exposure, and skin specimens were collected and processed for histopathology. In the other set, light reflectance was measured at skin test sites 4, 5, 6 and 24 h after exposure, to assess erythema. The Nikolsky’s sign test was also performed 24 h after exposure by rotating a metal disk glued to the skin test site and inspecting the skin for loss of epidermis. Probit analysis of data indicated that the exposure durations that produced a 50% incidence of microblisters and Nikolsky’s sign were ca. 7.5 and 4.5 min, respectively. Maximum erythema was observed 6 h following a 6 min exposure. Operating parameters for assessing the efficacies of skin protectants have been characterized.
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