Liver Subject

In split liver transplantation (SLT) (R. Pichlmayr et al., 1989), it is possible to transplant segments V-VIII, which are left over in OSLT, into an adult. (400) This means that two recipients can be supplied with one donor organ. The surgical splitting of the donor liver subjects the organ to considerable stress, and therefore its quality has to meet particularly high standards. (366,426)... 

Gonzalez-Flecha B, Cutrin JC, Boveris A (1993) Time course and mechanisms of oxidative stress and tissue damage in rat liver subjected to in vivo ischemia-reperfusion. J Clin Invest 91 456-464... 

The effect of administration route on drug action is discussed in some detail by Benet (19) and by Rowland (20). Oral administration forces a first-pass route through the liver, subjecting the toxicant to enhanced metabolism. Other routes are weaker metabolically, though in some cases, skin can display up to 80% or more of liver metabolite activity. In the rat, for example, skin is more efficient than liver in degrading aryl carbamates. Our results support this thesis in terms of mean Log MW/LD50 values for phenol toxicity but not for carbamate toxicity. 

Some authorities question whether dmnkeimess can result from the inhalation of ethyl alcohol vapors. Experience has demonstrated that in any event such intoxication is indeed rare (281). There is no concrete evidence that the inhalation of ethyl alcohol vapor will cause cirrhosis. Liver function is definitely impaired during alcohol intoxication (282), making the subject more susceptible to the toxic effects of chlorinated hydrocarbons. 

Dibydropteridine reductase (from sbeep liver) [9074-11-7] Mr 52,000 [EC 1.6.99.7]. Purified by fractionation with ammonium sulfate, dialysed versus tris buffer, adsorbed and eluted from hydroxylapatite gel. Then run through a DEAE-cellulose column and also subjected to Sephadex G-lOO filtration. [Craine et al. J Biol Chem 247 6082 1972.]... 

Biotin can be synthesized by the human colon flora. The question to which extent this production contributes to covering the host-organism s requirements is, however, subject to discussion. In most foods of animal origin as well as in cereals, biotin prevails in the protein (= enzyme)-bound form as e-N-biotinyl-L-lysine (= biocytin). Brewer s yeast, liver, soya beans, and peanuts number among the biotin rich foods [1]. 

A special case for reduced bioavailabilty results from first-pass extraction that sometimes might be subjected to saturable Michaelis-Menten absorption kinetics. The lower the hepatic drug clearance is (Clhep) in relation to liver blood flow (Ql), or the faster the drug absorption rate constant (Ka), and the higher the dose (D) are, the more bioavailable is the drug (F). 

As mentioned above, many transcription factors are not always active. Rather the activity of transcription factors is often achieved by induced reversible modification. Most frequently is the addition of phosphate groups (phosphorylation) to Ser, Thr, or Tyr residues. For the AP-1 component c-Jun the phosphorylation at Ser63 and Ser73 enhances activity when cells are subjected to stress, e.g. radiation. Phosphorylation is, however, dispensable for c-Jun-dqDendent tissue homeostasis in the liver, indicating that certain activities do not require the regulatory enhancement. Jun-N-teiminal kinase and a kinase called RSK or p38 catalyze the phosphorylation of AP-1. 

Figure 16. Schematic of the geometry of a section of liver before (top) and after (bottom) being subjected to slow freezing. During slow freezing, ice forms in the sinusoids and water flows osmotically from the cells into the sinusoids. (The upper drawing is slightly modified from Rubinsky and Pegg, 1988.)...

At the doses used, there is blockage of the effects of as much as 25 mg of injected heroin. Toxicity in heroin addicts is low, but some reported subtle adverse effects of naltrexone such as decreased energy (Hollister et al. 1981). Nonaddicted obese subjects have been known to develop markedly elevated transaminase levels at doses of 300 mg/day (Mitchell et al. 1987). The inference has been drawn that high doses are potentially hepatotoxic (Pfohl et al. 1986), and the drug is contraindicated in liver failure or acute hepatitis. 

Peroxidation of lipids is another factor which must be considered in the safety evaluation of liposome administration. Smith and coworkers (1983) demonstrated that lipid peroxides can play an important role in liver toxicity. Allen et al. (1984) showed that liposomes protected by an antioxidant caused less MPS impairment than liposomes subjected to mild oxidizing conditions. From the study of Kunimoto et al. (1981) it can be concluded that the level of peroxidation in freshly prepared liposome preparations and those on storage strongly depends both on the phospholipid fatty acid composition and on the head group of the phospholipid. Addition of appropriate antioxidants to liposomes composed of lipids which are liable to peroxidation and designed for use in human studies is therefore necessary. 

Novotna E, David A, Malek B. 1979. [An epidemiological study of hepatic tumor incidence in subjects working with trichloroethylene. I. Negative result of retrospective investigations in subjects with primary liver cancer. ] Prac Lek 31 121-123. (Czech)... 

A small but variable proportion of the carotenoids with one or two P-ionone rings (mainly P-carotene) are cleaved in the enterocytes to produce retinol (vitamin A). This process is very tightly controlled, so that too much vitamin A is not produced, although the control mechanism is not clear. Some cleavage of P-carotene can also occur in the liver, but this does not account for the turnover of P-carotene in the body. Small amounts of carotenoids are subject to enterohepatic circulation, but this does not account for losses. 

There has been considerable interest recently in the role of NO in many disorders. The role of NO in liver disease has been the subject of a detailed review recently to which interested readers are referred (Stark and... 

Gerli, G., Locatelli, G.F., Mongiat, R., Zenoni, L., Agostoni, A., Moschini, G., Zafiropoulos, D., Bruno, S., Rossi, S., Vignati, A. Tarolo, G. and Podda, M. (1992). Erythrocyte antioxidant activity, serum caeruloplasmin, and trace element levels in subjects with alcoholic liver disease. Am. J. Clin. Pathol. 97, 614-618. 

Alcohol abuse is a major clinical problem in many countries and has been the subject of investigation for many years by those interested in determining the molecular basis of ethanol-induced liver dam e (see Lieber, 1990). These intensive and extended efforts have revealed much about the metabolism of ethanol in the liver and about the toxicity of its primary oxidative product, acetaldehyde. They have not, however, folly elucidated the molecular mechanisms that lead to the typical features of alcoholic liver injury steatosis, necrosis and eventually cirrhosis. 

Hepatic reperfusion injury is not a phenomenon connected solely to liver transplantation but also to situations of prolonged hypoperfusion of the host s own liver. Examples of this occurrence are hypovolemic shock and acute cardiovascular injur) (heart attack). As a result of such cessation and then reintroduction of blood flow, the liver is damaged such that centrilobular necrosis occurs and elevated levels of liver enzymes in the serum can be detected. Particularly because of the involvement of other organs, the interpretation of the role of free radicals in ischaemic hepatitis from this clinical data is very difficult. The involvement of free radicals in the overall phenomenon of hypovolemic shock has been discussed recently by Redl et al. (1993). More specifically. Poll (1993) has reported preliminary data on markers of free-radical production during ischaemic hepatitis. These markers mostly concerned indices of lipid peroxidation in the serum and also in the erythrocytes of affected subjects, and a correlation was seen with the extent of liver injury. The mechanisms of free-radical damage in this model will be difficult to determine in the clinical setting, but the similarity to the situation with transplanted liver surest that the above discussion of the role of XO activation, Kupffer cell activation and induction of an acute inflammatory response would be also relevant here. It will be important to establish whether oxidative stress is important in the pathogenesis of ischaemic hepatitis and in the problems of liver transplantation discussed above, since it would surest that antioxidant therapy could be of real benefit. 

Shu, Y., Cheng, Z. N., Liu, Z. Q. et al. (2001). Interindividual variations in levels and activities of cytochrome P-450 in liver microsomes ofChinese subjects. Acta Pharmacologica Sinica, 22(3),... 

In the foregoing example, the drug was administered to a healthy subject who had normal kidney and liver function. The estimated biological half-life in this... 

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