Insight, animal

Bader M, Peters J, Baltatu O et al (2001)Tissue renin-angiotensin systems new insights from experimental animal models in hypertension research. J Mol Med 79 76-102... 

The parathyroid glands in FHH are reset to maintain a higher than normal serum calcium concentration owing to impaired suppression of PTH release in the face of hypercalcemia (e.g., resistance to CaQ+) (Fig. 2). Similarly the kidneys show a reduced calciuric response to hypercalcemia, which contributes to the hypercalcemia by promoting inappropriately reabsorption of calcium. Mouse models of FHH and NSHPT result from targeted inactivation of one or both CaR alleles, respectively [1,3]. These animals have provided valuable insights into the alterations in tissue function resulting from loss of the receptor. 

In-vitro models can provide preliminary insights into some pharmacodynamic aspects. For example, cultured Caco 2 cell lines (derived from a human colorectal carcinoma) may be used to simulate intestinal absorption behaviour, while cultured hepatic cell lines are available for metabolic studies. However, a comprehensive understanding of the pharmacokinetic effects vfill require the use of in-vivo animal studies, where the drug levels in various tissues can be measured after different dosages and time intervals. Radioactively labelled drugs (carbon-14) may be used to facilitate detection. Animal model studies of human biopharmaceutical products may be compromised by immune responses that would not be expected when actually treating human subjects. 

Chronic animal studies of organophosphates are few in number, but those that do exist provide a useful base from which to draw toxicological insight. In rats and mice exposed orally to tricresyl phosphate for 2 years, endocrine effects were found in a dose-response pattern and hepatic effects were found. Ovarian interstitial hyperplasia was also observed but was not dose related. No chronic-duration MRLs could be derived because of the limited number of studies. Tricresyl phosphate, a component of certain hydraulic fluids, produced no evidence of carcinogenic activity in assays with rats and mice (NTP 1994). However, another component, tributyl phosphate, was associated with an increased incidence of bladder tumors in rats and mice (FMC 1994a, 1994b). 

The yellow coloration in the Monarch as well as the larva of three other species of butterfly from South Florida is exclusively due to the specific accumulation of exceptionally high levels of lutein producing a pigmented epidermis. This active accumulation, reminiscent of the specific accumulation that occurs in the primate macula, indicates that butterfly larva is an excellent animal model for the study of carotenoid transport and binding. As such, elucidation of the mechanism of transport and binding of lutein in the epidermis and other tissues of these butterfly larvae may provide insight into xanthophyll uptake within the human eye (Bhosale et al. 2004). 

Insights from the clinic, animal models, and lesion studies... 

Bioluminescence, the phenomenon of biological light emission, has fascinated mankind for many centuries. Scientists have been intrigued by it, and for many years have tried to answer simple questions like how and why certain animals and bacteria bioluminesce. This research has led to new insights in (molecular) biology and biochemistry. For example, in the 1960s, McCapra studied the chemical mechanisms of bioluminescence and devised a model for firefly luciferin the acridan esters (Fig. 1) [1-5],... 

The composition of myelin changes during development 68 Spontaneous mutations in experimental animals provide insights about the structure and assembly of myelin 68 Myelin components exhibit great heterogeneity of metabolic turnover 69... 

Spontaneous mutations in experimental animals provide insights about the structure and assembly of myelin. The myelin mutants often have names relating to their characteristic tremor due to the myelin deficit, e.g. shiverer, jimpy, quaking and trembler mice (Table 4-2). Although some of the mutants have been studied for many years [1], it is only recently that recombinant DNA techniques have led to identification of the primary genetic defects in most of them. Some of them are good... 

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