Liver determinants

The relative rates of activation and detoxification of methyl paraoxon within the liver determine whether net activation or detoxification will occur (Sultatos 1987). Sex-differences have been observed in acute... 

Once cirrhosis is diagnosed, disease progression is relentless, regardless of the initial insult to the liver. Determining the specific cause of cirrhosis requires examination of both physical presentation and past medical history. An accurate social history is particularly important because few factors in the physical and laboratory examination aid in determining disease etiology. Understanding the cause of a patient s cirrhosis is imperative because it can affect therapeutic options and treatment decisions. 

It seems established that the presence of amine oxidase in the body, and especially that in the liver, determines the oral efficacy of 0-phenylethylamines. In general those compounds of this nature having an alpha carbon atom adjacent to that bearing the amine— that is, /S-phenylisopropylamine—are not deaminated by amine oxidase (134), are active on oral administration, and are excreted in the urine as such following oral or parenteral administration (28, 102, 132, 151). 

In turn the steady-state enzyme concentration in the liver determines the baseline hepatic intrinsic clearance, CLint, for the metabolism of a drug substrate by the enzyme. When substrate concentration, S, is low relative to the Michaelis constant, Km, for a particular biotransformation,... 

Furr, H.C. Amedee-Manesme, O. Clifford, A.J. Bergen, H.R. 3rd. Jones, A.D. Anderson, D.P. Olson, J.A. 1989. Vitamin A concentrations in liver determined by isotope dilution assay with tetradeuterated vitamin A and by biopsy in generally healthy adult humans. Am. J. Clin. Nutr. 49 713-716. 

The availability of substrates (ammonia and amino acids) in the liver determines the amount of urea synthesized. Urea excretion increases with increased protein intake and decreases with decreased protein intake. 

Lievens P, Versieck J, Cornells R, et al. 1977. The distribution of trace elements in normal human liver determined by semi-automated radiochemical neutron activation analysis. J Radioanal Chem 37 483-496. 

Adair, W.L. Keller, R.K. (1982) Dolichol Metabolism in Rat Liver. Determination of the Subcellular Distribution of Dolichyl Phosphate and its Site and Rate of de novo Biosynthesis , Journal of Biological Chemistry, 257, 8990-6... 

Primary or secondary liver cancer is a major cause of cancer-related mortality worldwide and local tumor growth within the liver determines survival in a great number of patients [1]. Although surgical resection is considered to be the only curative treatment for hepatocellular carcinoma (HCC) or metastases confined to the liver, only a small number of patients are candidates for this type of treatment. In most cases, hepatic resection is not a therapeutic option owing to the size, number, or location of the lesions. Therefore, a number of palliative local treat-... 

Fio. 9. Effect of azaeerine on the pyridine nucleotide level of mouse liver. Determinations were made on a 6% (w/w) trichloroacetic acid extract of mouse liver. Each value represents the pooled samples of two mice. Curve 1, saline control curve 2, asaserine-injected animals. From Narrod et al. (ttO). 

The dosage of flucytosine is 150—200 mg/kg orally in four portions every six hours. A 1% flucytosine solution has been developed for intravenous adrninistration. In some countries, a 10% ointment is also available. In patients with normal renal function, flucytosine is seldom toxic, but occasionally severe toxicity may be observed (leukopenia and thrombocytopenia). Plasma levels should be determined and the dose in patients with impaired renal function should be checked. Liver function tests (transaininases and alkaline phosphatase) should be performed regularly. In some patients with high flucytosine plasma levels, hepatic disorders have been observed (24). 

The liver plays an important role in the endocrine system. The concentrations of hormones in plasma, and the activity of the glands which secrete them, are determined by the rate at which they are deactivated by the liver. The liver also has a major function in female reproduction since it is the target tissue of ovarian estrogen, to which it responds by producing the yolk protein vitellogenin. " Xenobiotics that affect either of these functions can therefore be considered to be potential endocrine disrupters. 

Toxic effects often disappear after the cessation of the exposure, but they can also be permanent. The tissue s ability to regenerate is one of the most important factors that determines the nature of toxic effects. For example, liver tissue has a remarkable capacity to regenerate, and therefore liver injur> is often reversible. On the other hand, neuronal cells do not regenerate at all, thus neuronal injury is irreversible. It is true that neuronal cells can compensate for possible losses, but only to a minor degree. In particular, chronic effects tend to be irreversible. ... 

The e. posure route partly determines the distribution of the chemical in die body. Like tlie chemical benzene, a single chemical may follow multiple routes of e. posure. The liver, like the skin, acts as a filter. The liver is the primary dcto.xification site. To.xicants that arc absorbed into the lungs, skin, mouth, and esophagus may temporarily bypass the liver however, toxicants absorbed tluougli the stomach and intestines follow the blood s direct path to tlie liver. 

The procedure for recalculating the HI by effect and by mechanism of action is briefly described later. If one of the effect-specific luizard indices exceeds unity, consideration of tlic mechanism of action might be warranted. A strong case is required, however, to indicate that two compounds which produce adverse effects on the same organ system (c.g., liver), altliough by different mechanisms, should not be treated as dose additive. Any such determination should be reviewed. 

G. P. Blanch, A. Glausch, V. Schurig, R. Serrano and M. J. Gonzalez, Quantification and determination of enantiomeric ratios of chkal PCB 95, PCB 132 and PCB 149 in shark liver samples (C. coelolepis) from the Atlantic ocean , 7. High Resolut. Chromatogr. 19 392-396 (1996). 

Gel permeation ehromatography (GPC)/normal-phase HPLC was used by Brown-Thomas et al. (35) to determine fat-soluble vitamins in standard referenee material (SRM) samples of a fortified eoeonut oil (SRM 1563) and a eod liver oil (SRM 1588). The on-line GPC/normal-phase proeedure eliminated the long and laborious extraetion proeedure of isolating vitamins from the oil matrix. In faet, the GPC step permits the elimination of the lipid materials prior to the HPLC analysis. The HPLC eolumns used for the vitamin determinations were a 10 p.m polystyrene/divinylbenzene gel eolumn and a semipreparative aminoeyano eolumn, with hexane, methylene ehloride and methyl tert-butyl ether being employed as solvent. 

In the case of dmg interactions involving metabolic inhibition, little increase in the substrate concentration is expected when the inhibition constant (K ) determined in in vitro studies using human liver samples is larger than the inhibitor concentration in vivo. Various approaches have been adopted using mathematical models in attempts to quantitatively predict in vivo dmg interactions from in vitro data [5]. 

The effect of a statin is usually determined by measuring fasting plasma lipids and lipoproteins after 4-6 weeks of treatment. Liver enzymes and eventually creatine kinase (in case of myositis liver enzymes are usually also elevated) are measured simultaneously to exclude side effects related to liver and muscles. After the treatment goal has been reached, blood sampling is usually performed 1-2 times a year. 

Administration may result in nausea, vomiting, headache, diarrhea, abdominal pain, and skin rash. Abnormal liver function tests may be seen and may require follow-up tests to determine if liver function has been affected. 

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