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  • 1
    Electronic Resource
    Electronic Resource
    Glycine: a new anti-inflammatory immunonutrient (1999)
    Springer
    Cellular and molecular life sciences 56 (1999), S. 843-856 
    Details
    ISSN: 1420-9071
    Keywords: Key words. Glycine; immunoregulation; anti-inflammatory; glycine receptor.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The mechanism of the immunosuppressive effects of glycine and its pathophysiological applications are discussed in this review. Glycine has been well characterized in spinal cord as an inhibitory neurotransmitter which activates a glycine-gated chloride channel (GlyR) expressed in postsynaptic membranes. Activation of the channel allows the influx of chloride, preventing depolarization of the plasma membrane and the potentiation of excitatory signals along the axon. Glycine has recently been shown to have similar inhibitory effects on several white blood cells, including hepatic and alveolar macrophages, neutrophils, and lymphocytes. Pharmacological analysis using a GlyR antagonist strychnine, chloride-free buffer, and radiolabeled chloride has provided convincing evidence to support the hypothesis that many white blood cells contain a glycine-gated chloride channel with properties similar to the spinal cord GlyR. Molecular analysis using reverse transcription-polymerase chain reaction and Western blotting has identified the mRNA and protein for the β subunit of the GlyR in total RNA and purified membrane protein from rat Kupffer cells. Dietary glycine is protective in rat models against endotoxemia, liver ischemia-reperfusion, and liver transplantation, most likely by inactivating the Kupffer cell via this newly identified glycine-gated chloride channel. Glycine also prevents the growth of B16 melanomas cell in vivo. Moreover, dietary glycine is protective in the kidney against cyclosporin A toxicity and ischemia-reperfusion injury. Glycine may be useful clinically for the treatment of sepsis, adult respiratory distress syndrome, arthritis, and other diseases with an inflammatory component.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s000180050030
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  • 2
    Electronic Resource
    Electronic Resource
    Gentle organ manipulation during harvest as a key determinant of survival of fatty livers after transplantation in the rat (1999)
    Springer
    Transplant international 12 (1999), S. 351-359 
    Details
    ISSN: 1432-2277
    Keywords: Key words Liver transplantation ; Organ harvest ; Kupffer cells ; Ethanol ; Gadolinium chloride
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Both in situ organ manipulation during harvest and steatosis reduce survival after liver transplantation via mechanisms involving Kupffer cells; thus, their effect on survival was compared here. Moderate steatosis was induced by a single dose of ethanol to Lewis rats, while long-term administration of ethanol yielded severe steatosis in donor animals. After minimal dissection during the first 12 min, livers were either manipulated gently or left alone for 13 min subsequently. Orthotopic liver transplantation was performed after 1 h of cold storage in UW solution. Ethanol increased hepatic lipid content to a level of moderate or severe steatosis that reduced survival after transplantation from 100 % to approximately 70 % (P 〈 0.05). However, gentle manipulation decreased survival to approximately 30 % (P 〈 0.05) in livers from normal, saline-treated rats and in livers from rats fed a high-fat control diet. Moreover, after short- or long-term ethanol administration, manipulation of fatty livers decreased survival from 70 % to approximately 13 % (P 〈 0.05). Further, manipulation elevated serum transaminases, total bilirubin, and necrosis significantly about 2- to 20-fold in fatty grafts after transplantation. At the end of harvest, trypan blue distribution time and hypoxia assessed from 2-nitroimidazole binding were elevated significantly about two- to fourfold by manipulation of fatty grafts. Gadolinium chloride, a Kupffer cell toxicant, blocked the detrimental effects of manipulation. These data demonstrate for the first time that, while steatosis is detrimental for survival, organ manipulation plays a much greater role than fat in mechanisms of primary nonfunction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050239
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  • 3
    Electronic Resource
    Electronic Resource
    Generation of lipid free radicals by adherent leukocytes from transplanted rat liver (1998)
    Springer
    Transplant international 11 (1998), S. 353-360 
    Details
    ISSN: 1432-2277
    Keywords: Key words Liver transplantation ; rat ; free radicals ; Free radicals ; liver transplantation ; rat ; Adherent leukocytes ; free radicals
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The production of free radicals in blood correlates with primary nonfunction of transplanted livers, but the source of the free radicals is unknown. The purpose of this study was to determine if adherent leukocytes in the transplanted liver are responsible for the radicals detected in blood. First, a new method to harvest adherent leukocytes from the liver without enzymatic digestion was developed and characterized by transplanting livers from ethanol-treated rats, which increases primary nonfunction, and from saline-treated controls. Free radicals were then detected in isolated leukocytes using the spin-trapping technique and electron spin resonance (ESR) spin spectroscopy. Livers were perfused with a balanced salt solution (200 ml), followed by a Ca2 + -free solution containing EGTA and heparin (400 ml). Perfusion with Ca2 + -free buffer removed greater than 90 % of all adherent leukocytes from saline-treated livers and nearly 80 % of all leukocytes from fatty livers without removing Kupffer cells. Transplanted fatty livers from rats given ethanol contained significantly more adherent leukocytes (5.0 × 107 cells/liver) than grafts from control donors (3.2 × 107 cells/liver) and almost double the number of adherent neutrophils and monocytes. Moreover, adherent white blood cells from transplanted livers produced the same three free radical species that have been detected previously in blood; however, cells from ethanol-treated livers produced about five times more radical adducts. These data show that adherent white blood cells produce free radicals that are important in the mechanism of primary graft nonfunction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050157
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  • 4
    Electronic Resource
    Electronic Resource
    Amino acids in rinse effluents as a predictor of graft function after transplantation of fatty livers in rats (1999)
    Springer
    Transplant international 12 (1999), S. 168-175 
    Details
    ISSN: 1432-2277
    Keywords: Key words Liver transplantation ; Survival ; Amino acids ; Organ preservation ; Primary nonfunction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There are too few reliable markers by which one can predict future function of a liver before implantation. Consequently, the purpose of this study was to test the hypothesis that amino acids in rinse–effluents could predict transplant outcome in marginal fatty livers from rats. Amino acids were measured in the rinse effluent from the livers immediately after harvest and graft preparation or cold storage. Amino acids in the effluent were twice as high in ethanol-treated animals compared to those in nonfatty controls. Ethanol-treated fatty livers survived for no longer than 7 days after transplantation while 83 % of nonfatty controls survived (P 〈 0.05). In subsequent studies, the cold-storage time was decreased to 6 h to determine whether failing fatty livers released more amino acid than grafts that would function normally. There was a significant increase in amino acids in the effluent of fatty grafts compared to controls. Moreover, the sum of the four selected amino acids (alanine, valine, histidine, leucine) was lower than 23 nmol/g liver in functional livers, whereas failing grafts had totals significantly higher than 25 nmol/g liver. The sum of the four amino acids correlated well with 24 h post-transplant serum AST levels (r = 0.78, P 〈 0.0001). So we can conclude that amino acid release can serve as a useful marker of graft viability and reliably predicts survival.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050206
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  • 5
    Electronic Resource
    Electronic Resource
    Effect of aging on oxidative metabolism and conjugation in perfused livers of an inbred strain of mice: A pilot study (1985)
    Springer
    Age 8 (1985), S. 3-8 
    Details
    ISSN: 1574-4647
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A study was carried out to examine the possibility that altered mitochondrial function with aging might cause changes in hepatic rates of oxygen uptake and β-oxidation of fatty acids. Livers of 2–4 month and 20–25 month old CBA mice were perfused, and rates of respiration and ketogenesis were measured. Livers of old mice had significantly decreased rates of oxygen utilization (190 ± 16 vs 151 ± 9 μmol/gm/hr, p.05) and significantly lower rates of ketogenesis as indicated by rates of acetoacetate and β-hydroxybutyrate production (84 ± 8 vs 63 ± 7, p 〈.05). To determine whether NADPH supply, which is largely derived from β-oxidation of fatty acids in the fasted state, might be rate limiting for mixed-function oxidation in aged mice, rates of p-nitroanisole O-demethylation were measured in livers of young and old mice. Age had no effect on mixed-function oxidation of p-nitroanisole. Rates of glucuronidation of p-nitrophenol were also not affected by age; however, rates of sulfation of p-nitrophenol were significantly higher in livers of old (7.2 ±.6) than in young (3.5 ± 0.8) mice. This pilot study raises the possibility that the disposition of ingested fatty acids and xenobiotic compounds requiring sulfation may be significantly altered with aging. Moreover, it demonstrates that the perfused mouse livers can be used as a model in aging studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02431935
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