Age-dependent

Other drugs such as the neuroleptic, haloperidol, inhibit the induction of hsp70 mRNA in rodent neurons (Sharp et al.. 1992). Although this observation needs to be confirmed in the human population, it raises the possibility that an age-dependent defect in the production of HS proteins is exacerbated by a drug which is commonly used in demented elderly patients. The potential for certain pharmacologic agents to inhibit the HS response could increase the risk for untoward effects of atherosclerosis and hypoxia. A similar concern may be raised with certain calcium channel blockers which also have been found to reduce the synthesis of HS proteins in cardiac myocytes (Low-Friedrich and Schoeppe, 1991). 

Enhancement of the human HS response may eventually be a clinical goal in dealing with the aging population which may be more susceptible to environmental stress. Several investigators have now shown an age-dependent defect in the regulation of the HS response at the transcriptional level (Fargnoli et al., 1990). This defect has been observed in human peripheral blood lymphocytes and in... 

Blake, M.J., Udelsman, R., Feulner, G.J., Norton, D.D., Holbrook, N.J. (1991). Stress induced heat shock protein 70 expression in adrenal cortex An ACTH-sensitive. age-dependent response. Proc. Natl. Acad. Sci. USA 88, 9873-9877,... 

An additional study reported age-dependent effects. Lakshmana and Raju (1994) found that oral treatment of rat pups with endosulfan from postnatal days 2-10 resulted in changes in the concentration of noradrenalin, dopamine, and serotonin in various brain areas that differed either in magnitude or direction from changes seen in pups treated from postnatal days 2-23. While the results from this study do not necessarily indicate that neonates are more sensitive to the toxic effects of endosulfan, they do show that the duration of exposure in neonates is an important parameter to consider. 

G. F. Webb, Theory of Nonlinear Age-Dependent Population Dynamics (1985)... 

The impact of gender on the onset of anaphylaxis is age-dependent. In children, boys predominate whereas after puberty this relationship reverses (fig. 3). Similar observations have been described for allergic asthma but not atopic eczema previously [41]. 

Wolfe MF, Kendall RJ. 1998. Age-dependent toxicity of terbufos and diazinon to European starlings (Stumis vulgaris) and red-winged blackbirds (Agelaiusphoeniceus). Environ Toxicol Chem 17 1300-1312. 

Gomi, F., Utsumi, H., Hamada, A, and Matsuo, M. (1993). Aging retards spin clearance from mouse brain and food restriction prevents its age-dependent retardation. Life Sci. 52, 2027-2033. 

Esat TM, Yokoyama Y (1999) Rapid fluctuations in the uranium isotope composition of the oceans (abstract). Eos Transactions AGU 80(46(Fall meeting supl)) 581 Fomes WL, DeMaster DJ, Smith CR (2001) A particle introduction experiment in Santa Catalina Basin sediments Testing the age-dependent mixing hypothesis. J Marine Res 59(1) 97-112 Francois R, Bacon MP (1994) Heimich events in the North Atlantic radiochemical evidence. Deep-Sea Res 141 315-334... 

Simpson HJ, Trier RM, Toggweiler JR, Mathieu G, Deck BL, Olsen CR, Hammond DE, Fuller C, Ku TL (1982) Radionuclides in Mono Lake, California. Science 216 512-514 Smith CR, Berelson W, Demaster DJ, Dobbs FC, Hammond D, Hoover DJ, Pope RH, Stephens M (1997) Latitudinal variations in benthic processes in the abyssal equatorial Pacific control by biogenic particle flux. Deep-Sea Res Part II-Topical Studies in Oceanography 44(9-10) 2295 Smith CR, Pope RH, Demaster DJ, Magaard L (1993) Age-dependent mixing of deep-sea sediments. Geochim Cosmochim Acta 57(7) 1473-1488... 

Congenital hypothyroidism is still seen in the United States, and all newborns in the United States undergo screening with a TSH level. As soon as the hypothyroid state is identified, the newborn should receive the full LT4 replacement dose. The replacement dose of LT4 in children is age-dependent. In newborns, the usual dose is 10 to 17 mcg/kg per day. LT4 tablets may be crushed and mixed with breast milk or formula. Serum FT4 levels (target 1.6-2.2 ng/dL or 20.59-28.31 pmol/L) are used for dose titration in infants because the TSH level may not respond to treatment as it does in older children and adults. By 6 months of age, the required dose is reduced to 5 to 7 mcg/kg per day, and from ages 1 to 10 years, the dose is 3 to 6 mcg/kg per day. After age 12, adult doses can be given. 

ICRP. 1989. Age-dependent doses to members of the public from intake of radionuclides Part 1. International Commission on Radiological Protection. Oxford Pergamon Press, 67-68, 75-89. 

Leggett RW, Eckerman KF, Williams LR. 1982. Strontium-90 in bone A case study in age-dependent dosimetric modeling. Health Phys 43 3 07-322. 

The O Flaherty Model simulates the age-dependence of lead kinetics on such factors as absorption efficiency, excretion efficiency, uptake into bone and loss from bone, and partitioning between plasma and red blood cells. The model does not incorporate age, dose rate, or time dependence of lead accumulation in every organ (e g., kidney) because the complex patterns of lead accumulation in certain tissues are not known (O Flaherty 1991a) (see Section 2.4.1). However, the basic model structure allows for additional modules to be incorporated, depending on its intended use in risk assessment. For example, additional modules that are currently being developed are a pregnancy model and a model of net bone loss in older women and men. 

The Leggett Model simulates the age-dependence of lead kinetics on such factors as bone turnover rates, partitioning between soft tissues and excreta, removal half-times in liver, kidneys, and red blood cells, and the deposition fraction in brain. The model structure represents a compromise between biological realism and practical considerations regarding the quantity and quality of information available to determine parameter values (Leggett 1993). 

The effect was greater in younger animals which is consistent with age dependence of lead neurotoxicity. 

Jett DA, Kuhlmann AC, Farmer SJ, et al. 1997. Age-dependent effects of developmental lead exposure on performance in the Morris water maze. Pharmacol Biochem Behav 57(l-2) 271-279. 

Kirov, R. Moyanova, S. (1998a). Age-dependent effect of ketanserin on the sleepwaking phases in rats. Int.J. Neurosci 93, 257-64. 

Haidar, C. Gupta, D. (1990). Sex- and age-dependent nature of the cytoplasmic 5 alpha-dihydrotestosterone (DHT) binding site/receptor in bovine pineal gland. J. Pineal Res. 8, 289-95. 

Eva, C., Ferrero, P., Rocca, P., Funaro, A., Bergamasco, B., Ravizza, L. and Genazzani, E. (1989) [3H] A-methylscopolamine binding to muscarinic receptors in human peripheral blood lymphocytes characterization, localization on T-lymphocyte subsets and age-dependent changes. Neuropharmacology 28, 719-726. 

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