Animal models usefulness

Gene therapy for rectification of defects in the enzymes of the urea cycle is an area of active investigation. Encouraging preliminary results have been obtained, for example, in animal models using an adenoviral vector to treat citrullinemia. 

Alini M et al (2008) Are animal models useful for studying human disc disorders/degenera-tion Eur Spine J 17(1) 2—19... 

During the 1970 s and early 1980 s a large number of test methods were developed to measure the toxic potency of the smoke produced from burning materials. The ones most widely used are in refs. 29-32. These tests differ in several respects the conditions under which the material is burnt, the characteristics of the air flow (i.e. static or dynamic), the type of method used to evaluate smoke toxicity (i.e. analytical or bioassay), the animal model used for bioassay tests, and the end point determined. As a consequence of all these differences the tests result in a tremendous variation of ranking for the smoke of various materials. A case in point was made in a study of the toxic potency of 14 materials by two methods [33]. It showed (Table I) that the material ranked most toxic by one of the protocols used was ranked least toxic by the other protocol Although neither of these protocols is in common use in the late 1980 s, it illustrates some of the shortcomings associated with small scale toxic potency of smoke tests. 

Detailed studies have also been made on the toxicity of HC1, an irritant gas often present in fires. It does not cause baboon or rat incapacitation up to very high exposure doses which are sufficient (or very close) to cause eventual death [12]. Furthermore, a recent study has shown that the effects of irritants are heavily dependent on the animal model used [13]. 

The acute toxicity of emorfazone was found to be equal to or less than that of aminopyrine depending on animal models used [45]. From chronic toxicity tests [46,47], safe doses of 30 mg/kg per day (rats) or 120 mg/kg per day (dogs) were deduced. In rats, no significant effects of (3) on the reproductive activity or newborn development were observed [48-50], nor were adverse effects on the embryos found when (3) was given to rabbits, rats or mice during the period... 

Cognitive enhancing effects of 5-HT3 receptor antagonists have been observed in several animal models, using both normal animals and animals in which a cognitive deficit has been induced by the administration of the muscarinic antagonist scopolamine [41]. An example is the Wisconsin test, in which marmosets learn to discriminate which of two objects conceal a food reward and, after learning this, the task is reversed such that the food is hidden beneath the other object. Treatment with ondansetron has been shown to enhance the ability of marmosets to learn the reversal task. 

Alexandrakis, G., Jalali, S., and Gloor, P. (1998). Diagnosis of Fusarium keratitis in an animal model using the polymerase chain reaction. Br. J. Ophthalmol. 82,306-311. 

Mechanism of tolerance. The molecular events involved in the development of tolerance to carbamazepine have not been clearly identified. However, in a preclinical animal model using amygdala-kindled seizures, S. R. B. Weiss and colleagues (1995) in our laboratory have found that the variety of seizure-induced adaptive changes that usually emerge following seizures fail to do so with development of tolerance to the anticonvulsant effects of carbamazepine. The loss of these adaptive changes, such as increases in... 

By inserting hydrophobic antiobesity compounds into the liposomal bilayers, marine phospholipids would boost the effect of the inserted hydrophobic antiobesity compounds. When marine phospholipids are served as liposomal drinks, they would be more effective than adding into solid foods or feeds. These facts were borne out by Okada et al. (2011). They carried out the following experiment. Brown seaweed (Undaria pinnatifida) lipid containing fucoxanthin (UL) encapsulated into scallop midgut gland phospholipids (PL) liposomes were prepared to see the promotional effect of marine phospholipid liposome on antiobesity. Animal model used in their study was 3-week-old male diabetic-obese... 

A second animal model uses H-ros transgenic mice (Oncomouse ) which spontaneously develop mammary and salivary tumors.97 This model is considered to be more relevant to human cancer in that tumor initiation and growth is endogenous, in contrast to nude mouse tumor explants. Mice with palpable tumors between 50 and 350 mm3 were treated with either the ester prodrug 18c (40 mg/kg, once daily, s.c.) or vehicle, and the size of the tumors monitored over time.44 While... 

Time-course analysis in a rabbit iliac artery model disclosed <20% stent re-endothelialization at four days, <40% at seven days, and near-complete endothelialization at 28 days following stent implantation (18). The re-endothelialization process has been studied in several other animal models using different types of injuries with very controversial results, suggesting, in part, a diversity in the response and capacity of vascular healing. 

Two organochlorine pesticides have also been evaluated in animal models using early life stage exposures. Methoxychlor (Chapin et al., 1997) and heptachlor (Smialowicz et al., 2001) were evaluated for immunotoxicity after perinatal plus juvenile exposure of rats. In the case of methoxychlor, T cell-dependent antibody responses were depressed persistently in males but not females (Chapin et al., 1997). For heptachlor, early exposure of Sprague-Dawley rats, using doses relevant to human exposure, produced persistent impairment of antibody responses in males but not females. No adult-exposure immunotoxicity was observed at the doses examined, suggesting that there is an increased susceptibility of the prenatal and/or early postnatal life stages to this pesticide (Smialowicz et al., 2001 Smialowicz, 2002). 

Endogenous opioids and exogenously administered delta opioid receptor agonists have been demonstrated to have antidepressant-like effects in animal models used to evaluate novel antidepressant compounds. This chapter reviews some of the previous research investigating the role of the opioid system, and more specifically the delta opioid receptor system, in clinical depression and in animal models used to study human depression and antidepressant treatments. In addition, this chapter discusses the interpretation of animal models of depression and their uses in the evaluation of new potential therapeutics. 

Experiments and data presented in this chapter demonstrate that delta opioid agonists have antidepressant-like effects in animal models used to measure antidepressant activity. The antidepressant-like effects can be separated from other behavioral effects produced by these compounds, such as locomotor stimulation, convulsions, and learning impairments. This separation lends validity to this potential target for depression by eliminating effects or sources that may produce false positives. These compounds should be tested in other models of antidepressant activity to confirm these findings in the forced swim test. 

A more relevant study for biopharmaceuticals is the repeat-dose study where exaggerated clinical doses are given to an animal model using the intended clinical route of administration. For most biopharmaceuticals this is the intravenous route of administration. Interesting exceptions are Lucentis and Pulmozyme , given intraocularly and by inhalation, respectively, in the pivotal repeat-dose studies. 

Fig. 1. Qualitative prediction of compound properties in humans from animal models using in vitro and in vivo data.

Drug metabolism and pharmacokinetics, which normally include bio-analytical chemistry, to assess the delivery and disposition profile of the leads in animal models using the route of administration projected for clinical studies... 

Many proteins, polypeptides, oligonucleotides, and other large molecules are immunogenic in the animal models used in pharmacology and toxicology evalu-... 

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