Neonatal animals

Children s Susceptibility. No studies were located in which comparisons were made between the sensitivity of children and adults to the toxicity of americium. Animal studies indicate that juvenile dogs are less susceptible than adults to americium-induced bone cancer (Lloyd et al. 1999). No direct evidence was located to indicate that the pharmacokinetics of americium in children may be different from that in adults. Based on dosimetric considerations related to differences in the parameters of available models, as well as studies in animals, it seems likely that children may be more susceptible to americium toxicity than are adults by virtue of age-related differences in pharmacokinetics. Absorption of ingested americium may be as much as 200 times greater in neonatal animals than in adults. (Bomford and Harrison 1986 David and Harrison 1984 Sullivan et al. 1985). 

Sullivan MF. 1980a. Absorption of actinide elements from the gastrointestinal tract of neonatal animals. Health Phys 38 173-185. 

Neonatal animals have been found to absorb 20-40 times more thorium through the gastrointestinal tract than adult animals (Sullivan et al. 1980a, 1980b, 1983) indicating that children may be more susceptible to both the chemical and radiological effects of thorium than adults. 

Metabolism may be mediated by intestinal microflora, epithelial enzymes, or liver enzymes preceding entry into the systemic circulation. Chloramphenicol is well absorbed when administered orally to calves less than 1 week old, but it is inactivated by microflora when administered to ruminants. Similar observations have been made after oral administration of amoxicillin, ampicillin, and cephalexin therapy in young calves (11). On the other hand, trimethoprim, which is extensively metabolized in the liver and may undergo some metabolism in the rumen, shows higher systemic availability in the newborn calf and kid, due probably to the lower metabolic activity in the neonatal animal. 

Explain how a chemical might be less toxic in a neonatal animal. 

Alterations to the development of the embryo, fetus, or neonatal animal, either morphological or functional, and caused by chemicals is termed "developmental toxicology." The result may involve interference with normal growth, homeostasis, development, differentiation, and/or behavior. 

Treatment of neonatal animals, or those subjected to partial hepatectomy, with single doses of dimethylnitrosamine, leads to hepatic tumors, as in these cases the liver cells are actively dividing and are more susceptible. It has been found that the liver cells in culture are susceptible at particular stages in the cell cycle. 

Chemicals that require metabolic activation may be less toxic in neonatal animals as a result of reduced levels of enzyme activity. However levels of protection may also be reduced. 

While all of the above-mentioned studies were performed using adult models, the effects of focal ischemia on SVZ or SGZ precursor cells were also investigated in neonatal animals. Unilateral hypoxic-ischemic injury elicited an increase of BrdU+ cells in ipsilateral hippocampus, mainly DG, and the number of BrdU+ neuronal cells was also increased in DG, while the number of oligodendrocytes decreased (Bartley et al. 2005). Ischemia also upregulated progenitor cell proliferation in neonatal SVZ, peri-infarct striatum (Plane et al. 2004), and cortex (Fagel et al. 

The neuroprotective effects of other compounds have also been demonstrated to be enhanced when combined with hypothermia. Guan et al. (6) evaluated the efficacy of hypothermia in combination with insulinlike growth factor (IGF) using a modified Levine hypoxic-ischemic model (right carotid ligation plus 10 min of hypoxia in neonatal animals). In this study, the use of hypothermia resulted in a significant extension of the therapeutic time window. Recovery in a cool vs a warm environment (23 C vs 31 C) extended the effectiveness of IGF-1 by up to 4 h. 

This compound, Sn-MPCh, decreases effectively plasma billirubin levels in both adult and neonatal animals and is under current evaluation as an alternative to phototherapy... 

Large concentrations of MSG administered by gavage or intravenous injection causes focal lesions in the hypothalamus of rodents and rabbits. These occur only hours after exposure. The mouse appears to be the most sensitive species affected. Neonatal animals are more sensitive to MSG neurotoxicity. Neuronal damage occurs in neonatal mice when plasma levels reach between 100 and dOOpmoldl. In adults, the plasma levels have to reach >630nmoldl before similar effects are noted. None of the primate studies were able to demonstrate hypothalamic lesions after exposure to MSG. 

Plasma albumin concentration is decreased in the presence of hepatic cirrhosis, liver abscess, acute pancreatitis, gastrointestinal disease, the nephrotic syndrome and chronic renal failure. Hypoalbuminaemia is a characteristic of neonatal animals, apart from foals, whereas the plasma concentration of cq-acid glycoprotein is markedly elevated in newborn piglets. Hyperbilirubinaemia could further decrease the albumin binding capacity of acidic drugs and some basic drugs in neonatal animals. 

Supportive measures that would complement antimicrobial effectiveness and assist recovery of the animal from the infection should be provided. In neonatal animals, care must be taken to avoid a too-rapid rate of intravenous fluid administration. Fever may serve a useful purpose in infectious diseases, and the change in body temperature may be used to assess the progress of the infection. In the presence of an infectious diseased, the only indication for an antipyretic drug, e.g. aspirin or paracetamol (acetaminophen) in dogs but not in cats metamizole (dipyrone) or sodium salicylate administered intravenously to horses, is to decrease body temperature to below a dangerous level, 41°C (105.8°F). Concurrent therapy with a NSAID and an aminoglycoside antibiotic increases the risk of nephrotoxicity. If the infection is suspected to be contagious, the diseased and in-contact animals should be isolated. 

The Bioavailability and Disposition of Antimicrobial Agents in Neonatal Animals... 

Baggot, J.D. Short, C.R. (1984) Drug disposition in neonatal animals, with particular reference to the foal. Equine Veterinary Journal, 16, 364-367. 

---