Liver retention

A large degree of variation is apparent in retention rates for americium in the liver among various animal species (Durbin 1973), as indicated by measured or estimated liver clearance half-times of approximately 5-16 days in rats, 152 days in baboons, 1-10 years in dogs, and 10 years in Chinese hamsters. A liver clearance half-time of 2 years has been estimated for humans (Griffith et al. 1983). Refer to Section 3.5.1 for information regarding toxicokinetic mechanisms that may play a role in interspecies differences in liver retention of americium. 

Significant interspecies differences are apparent regarding liver retention rates of absorbed americium (Durbin 1973 Griffith et al. 1983) (see Sections 3.4.2.4 and 3.5.1 for more detailed information). 

Lloyd RD, Mays CW. 1975. Determining liver retention of transuranium elements in living beagles. Radiat Environ Biophys 12 139-145. 

JTjgure 5. Liver retention of Mn 6 Mn-labeled meal in control (C) and Dawley (SD) and Wistar (W) rats. 

From injection studies in laboratory animals it was found that retention was dependent on the isotope, chemical form, and sex. In dogs plutonium-239 was retained longer than plutonium-237 (Bair et al. 1974). The retention of plutonium-242 and plutonium-244 was similar, and was longer than the retention time for plutonium-236 and plutonium-239 (Guilmette et al. 1978). In mice no difference was seen in fractional retention at low and high doses (Andreozzi et al. 1983). In hamsters more plutonium administered intravenously in an insoluble form (plutonium dioxide) was retained than plutonium administered in a soluble form (plutonium citrate) (Brooks et al. 1976b). Retention after intraperitoneal injection of mice and hamsters may be sex-dependent females retained more in the liver than males (Smith et al. 1976, 1978). However, retention after intravenous injection was not sex-dependent (Smith et al. 1978). Total retention and liver retention increased with age (Bruenger et al. 1980 David and Harrison 1984). 

The whole body retention of intravenously administered plutonium- 237 and/or -239 citrate in dogs varied from approximately 85% to almost 100% (Bair et al. 1974 Lloyd et al. 1976, 1984) with liver retention of about 25% (Bair et al. 1974 Lloyd et al. 1976, 1984 Stover et al. 1962) and skeletal retention of about 50% (Bruenger et al. 1980 Lloyd et al. 1978a, 1978b, 1984 . Liver retention was found to be dose- dependent (Stover et al 1962). In hamsters, the whole body retention of plutonium-239 dioxide was approximately 100% (Brooks et al. 1983). Plutonium was found to be retained for an indefinite time in the testes and ovaries of mice and rats (Green et al. 1977 Miller et al. 1989 Taylor 1977). Retention at the site of administration after exposure which simulated wounds was from 16 to 21 % of the administered dose (Dagle et al. 1984). 

The trend in liver retention (not Illustrated) does not show the pronounced uptake for trans-[Pt(NH3)2Cl2] as in the kidney. Thus, the chemlcal-blogical processes leading to tissue retention (and perhaps organ toxicity) appear quite different for the liver V8 kidney. In this context, it is worthwhile to note that while uptake of cis-[Pt(NH3)2CI2] in the kidney can lead to nephrotoxicity, reports of hepatotoxicity associated with cis-[Pt(NH3)2CI2] chemotherapy are rare. 

Europium and gadolinium show in vivo deposition in the skeleton of rats which is broadly comparable to that of americium and curium. However, the liver deposition of the two actinides appears to be almost double that of the two lanthanides (Durbin 1962). In the blood plasma in vivo (as discussed earlier) europium, gadolinium, americium and curium associate with transferrin to about 20% and the stability constants for their transferrin complexes appear to be similar, table 8. The long-term retention of the lanthanides in bone does not appear to have been studied in similar depth to that of the actinides, but animal studies appear to suggest that lanthanide retention time in bone may be a little shorter than for the actinides. By contrast, liver retention appears to be comparable for actinides and lanthanides, at least in rats and mice (Evans 1990). Although care will be needed in the interpretation of the data, it does... 

These dragp are used with caution in patients with tachycardia, cardiac arrhythmias, hypertension, hypotension, those with a tendency toward urinary retention, those with decreased liver or kidney function, and those with obstructive disease of the urinary system or gastrointestinal tract. The anticholinergic drugp are given with caution to the older adult. 

A diuretic is a drug that increases die secretion of urine (ie, water, electrolytes, and waste products) by die kidneys. Many conditions or diseases, such as heart failure, endocrine disturbances, and kidney and liver diseases can cause retention of excess fluid (edema). When die patient shows signs of excess fluid retention, die primary healdi care provider may order a diuretic. There are various types of diuretic drugs, and the primary healdi care provider selects the one that best suits die patient s needs and effectively reduces the amount of excess fluid in body tissues. 

This gene is broadly distributed in skeletal muscle, heart, uterus, and in a variety of non-muscle cells. The mRNA levels are particularly high in intestine, lung and spleen, whereas they are very low in liver, testes, kidney and pancreas. In the muscle tissue SERCA3 may be confined primarily to non-muscle cells (vascular smooth muscle, endothelial cells, etc.). The C-terminus of SERCA3 is Asp-Gly-Lys Lys-Asp-Leu-Lys (Table I) it may serve as a sorting signal for retention of the enzyme in the endoplasmic reticulum [57]. 

Primary biliary cirrhosis is characterized by progressive inflammatory destruction of the bile ducts. Immune-mediated inflammation of intrahepatic bile ducts results in remodeling and scarring, causing retention of bile within the liver and subsequent hepatocellular damage and cirrhosis. The number of patients affected with primary biliary cirrhosis is difficult to estimate because many people are asymptomatic and incidental diagnosis during routine health care visits is common. 

Solutions that contain sodium citrate/citric acid (Shohl s solution and Bicitra) provide 1 mEq/L (1 mmol/L) each of sodium and bicarbonate. Polycitra is a sodium/potassium citrate solution that provides 2 mEq/L (2 mmol/L) of bicarbonate, but contains 1 mEq/L (1 mmol/L) each of sodium and potassium, which can promote hyperkalemia in patients with severe CKD. The citrate portion of these preparations is metabolized in the liver to bicarbonate, while the citric acid portion is metabolized to C02 and water, increasing tolerability compared to sodium bicarbonate. Sodium retention is also decreased with these preparations. However, these products are liquid preparations, which may not be palatable to some patients. Citrate can also promote aluminum toxicity by augmenting aluminum absorption in the GI tract. 

Docetaxel Neutropenia (DLT), hyperlacrimation, fluid retention, nail disorders, myelosuppression Use with caution in liver dysfunction. Do not give if biliary tract is obstructed. Premedicate dexamethasone. 

The liver is the primary soft tissue site of initial accumulation of absorbed americium in humans. Americium taken up into skeletal muscle appears to have a longer retention half-time than americium in the liver. Therefore, at long times after exposure (years), the skeletal muscle will contain a larger fraction of the systemic americium burden than the liver (Filipy and Kathren 1996 Kathren 1994 Mclnroy et al. 

Predictions based on the model have been compared to observed time courses for lung, liver, and skeletal americium burden in dogs that inhaled americium oxide (Mewhinney and Griffith 1983). Data on lung retention for four humans who accidentally inhaled americium were also compared to model predictions. The empirical observations fell within predicted retention patterns for particle sizes (AMAD) 0.5 and 1.8 im (Mewhinney and Griffith 1983). 

Cohen N, Antonelli R, Lo Sasso T, et al. 1978. Effect of ethanol on the retention of americium-241 in the baboon liver. J Toxicol Environ Health 4 825-833. 

---