Calcium animal models

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. 

Once in the serum, aluminium can be transported bound to transferrin, and also to albumin and low-molecular ligands such as citrate. However, the transferrrin-aluminium complex will be able to enter cells via the transferrin-transferrin-receptor pathway (see Chapter 8). Within the acidic environment of the endosome, we assume that aluminium would be released from transferrin, but how it exits from this compartment remains unknown. Once in the cytosol of the cell, aluminium is unlikely to be readily incorporated into the iron storage protein ferritin, since this requires redox cycling between Fe2+ and Fe3+ (see Chapter 19). Studies of the subcellular distribution of aluminium in various cell lines and animal models have shown that the majority accumulates in the mitochondria, where it can interfere with calcium homeostasis. Once in the circulation, there seems little doubt that aluminium can cross the blood-brain barrier. 

Dimercaprol is FDA-approved as single-agent treatment of acute poisoning by arsenic and inorganic mercury and for the treatment of severe lead poisoning when used in conjunction with edetate calcium disodium (EDTA see below). Although studies of its metabolism in humans are limited, intramuscularly administered dimercaprol appears to be readily absorbed, metabolized, and excreted by the kidney within 4-8 hours. Animal models indicate that it may also undergo biliary excretion, but the role of this excretory route in humans and other details of its biotransformation are uncertain. 

In addition, gelatin peptides have shown to accelerate absorption of dietary calcium in animal models increasing calcium bioavailability (Kim et al., 1998). Jung et al. (2006) reported that fish bone peptides (FBP) could inhibit the formation of insoluble Ca salts in neutral pFI. During the experimental period, Ca retention was increased and loss of bone mineral was decreased by FBP II supplementation in ovariectomized rats. The levels of femoral total Ca, bone mineral density, and strength were also significantly increased by the FBP diet to levels similar to those of the casein phosphopeptide diet group. 

Song, Y., Bowersox S.S., Connor, D.T., Dooley D.J., Lotarski S.M., Malone Th., Miljanich G., Millerman E., Rafferty M.F., Rock D., Roth B. D., Schmidt, J., Stoehr, S., Szoke, B. G., Taylor, Ch., Vartanian, M., Wang, Y.-X. (S)-4-Methyl-2-(methylamino)pentanoic acid [4,4-bis(4-fluorophenyl)-butyl]amide hydrochloride, a novel calcium channel antagonist, Is efficacious in several animal models of pain, J. Med. Chem. 2000, 43, 3474-3477. 

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