Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-1 (IL-1), a cytokine released from macrophages by endotoxin stimulation, has been shown to upregulate the genetic expression of the hepatocyte growth factor (HGF). The present study was conducted to determine whether plasma HGF is increased in patients with systemic inflammatory response syndrome (SIRS). The plasma levels of HGF, endotoxin, and beta-glucan were measured in 41 surgical patients without hepatic diseases, 18 of whom had been diagnosed with sepsis, and 33, with nonseptic SIRS. The plasma HGF was found to be significantly increased in the 18 patients with sepsis, at 0.69 +/- 0.47 ng/ml (mean +/- SD), and in the 23 patients with nonseptic SIRS, at 0.49 +/- 0.37 ng/ml, compared to values in 40 normal controls, at 0.10 +/- 0.03 ng/ml (P < 0.001). No significant correlations were observed between the plasma levels of HGF and endotoxin (r = 0.02) or beta-glucan (r = -0.05) in any of the patients; however, plasma HGF was significantly correlated with the WBC count (r = 0.34, P < 0.05) and with total bilirubin (r = 0.45, P < 0.01). Plasma HGF was also strongly correlated with alanine transaminase (ALT) in 8 patients with ALT levels higher than 50 U/l (r = 0.70), but there was no such correlation in 33 patients with ALT levels of 50 U/l or less (r = 0.30). Thus, although the clinicopathologic significance of HGF is not well understood, the present findings indicate that plasma HGF increases in response to infection or inflammation.
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PMID:Plasma hepatocyte growth factor levels are increased in systemic inflammatory response syndrome. 872 43

Graft failure and extrahepatic organ complications, which frequently develop after transplantation, may be related to inflammatory mediators stimulated by endotoxin (ET). The role of endotoxemia after liver transplantation is controversial and may depend upon differences in the ET assay method used in the various contradicting studies. While the standard Limulus amebocyte lysate (LAL) is reactive for ET and beta-glucan, a novel turbidimetric assay method enables separate determinations of ET and beta-glucan. Beagle dogs undergoing orthotopic liver transplantation were divided into two groups. In Group I (n = 6) the grafts were transplanted immediately and in Group II (n = 6) grafts were preserved for 48 h in University of Wisconsin (UW) solution. Animals received cyclosporine immunosuppression and were followed for 14 days. Daily measurements of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) were performed. Samples for ET and beta-glucan measurement were collected serially and processed using the turbidimetric assay method. While no graft failure was seen in Group I, three of six Group II animals died from graft failure within 1 day after transplantation. Preservation and reperfusion injury was much more severe in the Group II grafts than in Group I grafts. While endotoxemia could not be detected, postoperative beta-glucan levels (undetectable pretransplant) were seen in both groups. Beta-glucan levels were much higher in Group II grafts than in Group I grafts, and correlated with the severity of liver damage. In conclusion, this study shows that beta-glucan, instead of ET, appears during the early posttransplant period. We believe that posttransplant elevation of beta-glucan is related to liver damage, especially endothelial damage by preservation and reperfusion.
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PMID:Beta-glucan reflects liver injury after preservation and transplantation in dogs. 1008 78

The effects of glucan and liposomized glucan, alone or co-administered with vitamin C, and empty liposomes on hepatic fibrosis in mice infected with Mesocestoides corti (M. vogae) tetrathyridia were studied. Preparations were administered every third day from day 7 to day 31 post-infection (p.i.), nine doses in total. Activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and cholesterol levels were measured in sera collected on days 11, 15, 21, 28, 32, 42, 50 and 65 p.i. Liver fibrosis was studied on the same days by measuring hydroxyproline concentration, which is considered a marker for collagen content. Larvicidal effects of the glucan and liposome preparations were estimated on day 65 p.i. in the liver and peritoneal cavity. Glucan formulations significantly enhanced collagen content, most prominently after administration of liposomized glucan in combination with vitamin C. Activities of both enzymes and cholesterol levels were slightly modified after administration of glucan alone. Liposomized glucan with vitamin C significantly increased ALT and AST activity and cholesterol levels up to days 28-32 p.i., after which they plateaued or declined. The most pronounced decrease was after administration of liposomized glucan and vitamin C. The same pattern of biochemical parameters in serum was observed after administration of empty liposomes, however, collagen content was not modified significantly. Larval counts in the liver and the peritoneal cavity were significantly reduced after treatment with either glucan formulation, but were unaffected following treatment with empty liposomes. In summary, intense fibrosis in the liver of mice treated with liposomized glucan and vitamin C did not result in the most extensive parenchymal cell injury but, rather in the highest efficacy of treatment. Liposomal lipids were probably utilized in the reparation of the damaged parenchymal cells, while glucan stimulated phagocytic cells.
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PMID:Modulation of liver fibrosis and pathophysiological changes in mice infected with Mesocestoides corti (M. vogae) after administration of glucan and liposomized glucan in combination with vitamin C. 1289 80

Osteopontin (OPN) plays a pivotal role in various immune responses and inflammatory diseases. OPN is expressed in various granulomatous diseases; however, the cellular and molecular role of OPN in these diseases is not well known. We analyzed the role of OPN in a beta-glucan-induced hepatic granuloma model. First, we found that neither OPN deficiency nor overexpression of OPN affected the number and the size of hepatic granulomas at day 7, indicating that OPN is not involved in the formation of hepatic granulomas at the early stages. Importantly, OPN did not influence the liver tissue damage as defined by alanine aminotransferase and aspartate aminotransferase levels at early stages. Second, OPN deficiency resulted in the reduction of IL-12 and IFN-gamma production at early stages. Third, at late stages, OPN deficiency resulted in a decrease in the number and size of hepatic granulomas, and a reduction of liver tissue injury. This was due to the reduction of the cellular recruitment including macrophages, CD4 T cells and dendritic cells into the liver, and the reduction of tumor necrosis factor (TNF)-alpha production in the liver. In contrast, overexpression of OPN resulted in the persistence of granuloma formation. These data suggest that OPN affects the persistence of hepatic granuloma formation. Our results indicate that OPN up-regulates the production of IL-12 and IFN-gamma within the granulomas at early stages, and OPN has an additional role in the regulation of cellular recruitment and TNF-alpha production at late stages that determine the severity of liver tissue injury.
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PMID:Osteopontin affects the persistence of beta-glucan-induced hepatic granuloma formation and tissue injury through two distinct mechanisms. 1497 21

Caspofungin (CAS) is the first of a new class of antifungal agents, the echinocandins, that interfere with fungal cell wall synthesis by inhibition of glucan synthesis. Here, we report the results of 31 patients treated with CAS following allogeneic SCT. CAS was administered as a second-line agent to patients with invasive fungal infection (IFI) (n=15) or fever of unknown origin (n=16) who were recalcitrant to or intolerant of prior antifungal therapy. Unsuccessful first-line regimes included amphotericin B (n=17), liposomal amphotericin B (n=5), fluconazole (n=3), itraconazole (n=1), and voriconazole (n=2). All patients received concomitant immunosuppressive therapy for graft-versus-host disease. In 23 patients, cyclosporin A (CSA) and CAS were administered concurrently without any major side effects detected. Observed increases in GPT were not clinically significant. Normalization of serum creatinine and significant reductions in C-reactive protein were observed in response to CAS. Favorable outcome to CAS were documented in eight of 15 patients with IFI and in 15 of 16 patients with fever of unknown origin. CAS is a promising alternative in patients with IFI and fever of unknown origin in the setting of allogeneic SCT.
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PMID:Caspofungin as second-line therapy for fever of unknown origin or invasive fungal infection following allogeneic stem cell transplantation. 1575 83

Pressure ulcers (PU) cause morphological and functional alterations in the skin and visceral organs. In this study we investigated the role of oxidative damage in PUs and the probable beneficial effect of beta-glucan treatment against this damage. beta-glucan is known to have immunomodulatory effects. Experiments were carried on Wistar albino rats. PU was induced by applying magnets over steel plates that were implanted under the skin, to compress the skin and cause ischemia where removing the magnets cause reperfusion of the tissue. Within the first 12 h, rats were subjected to 5 cycles of ischemia/reperfusion (I/R), followed by 12 h ischemia. This protocol was repeated for 3 days. In treatment groups, twice a day during reperfusion periods, beta-glucan was either applied locally (25 mg/kg) as an ointment on skin, or administered orally (50 mg/kg) as a gavage. At the end of the experimental periods, tissue samples (skin, liver, kidney, lung, stomach, and ileum) were taken for the measurement of malondialdehyde (MDA)--an index of lipid peroxidation--and glutathione (GSH)--a key antioxidant--levels. Neutrophil infiltration was evaluated by the measurement of tissue myeloperoxidase activity, while collagen contents were measured for the evaluation of tissue fibrosis. Skin tissues were also examined microscopically. Liver and kidney functions were assayed in serum samples. Local treatment with beta-glucan inhibited the increase in MDA and MPO levels and the decrease in GSH in the skin induced by PU, but was less efficient in preventing the damage in visceral organs. However, systemic treatment prevented the damage in the visceral organs. Significant increases in creatinine, BUN, ALT, AST, LDH and collagen levels in PU group were prevented by beta-glucan treatment. The light microscopic examination exhibited significant degenerative changes in dermis and epidermis in the PU group. Tissue injury was decreased especially in the locally treated group. Thus, supplementing geriatric and neurologically impaired patients with adjuvant therapy of beta-glucan may have some benefits for successful therapy and improving quality of life.
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PMID:Pressure ulcer-induced oxidative organ injury is ameliorated by beta-glucan treatment in rats. 1654 2

The protective effect of beta-glucan against oxidative injury caused by acetaminophen was studied in mice liver. BALB-c mice (25-30 g) were pre-treated with beta-d-glucan (50 mg/kg, p.o.) for 10 days and on the 11th day they received an overdose of acetaminophen (900 mg/kg, i.p.). Four hours after the acetaminophen injection, mice were decapitated and their blood was taken to determine serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and tumor necrosis factor-alpha (TNF-alpha) levels. Tissue samples of the liver were taken for histological examination or for the determination of levels of malondialdehyde, an end product of lipid peroxidation; glutathione (GSH), a key antioxidant; and myeloperoxidase activity, an index of tissue neutrophil infiltration. The formation of reactive oxygen species in hepatic tissue samples was monitored by using the chemiluminescence technique with luminol and lucigenin probes. Acetaminophen caused a significant decrease in the GSH level of the tissue, which was accompanied with significant increases in the hepatic luminol and lucigenin chemiluminescence values, malondialdehyde level, MPO activity and collagen content. Similarly, serum ALT, AST levels, as well as LDH and TNF-alpha, were elevated in the acetaminophen-treated group when compared with the control group. On the other hand, beta-d-glucan treatment reversed all these biochemical indices, as well as histopathological alterations that were induced by acetaminophen. In conclusion, these results suggest that beta-d-glucan exerts cytoprotective effects against oxidative injury through its antioxidant properties and may be of therapeutic use in preventing acetaminophen toxicity.
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PMID:Acetaminophen-induced toxicity is prevented by beta-D-glucan treatment in mice. 1682 97

beta-Glucans are glucose polymers with a variety of stimulatory effects on the immune system. The objective of this study was to determine the effect of prophylactic oral administration of soluble Saccharomyces cerevisiae-derived beta-1,3/1,6-glucan (SBG) on the outcome of experimental endotoxaemia and shock-associated organ injury. Male Wistar rats were pretreated with SBG orally (SBGpo, 20 mg/kg/day) for 14 days, subcutaneously (SBGsc, 2 mg/kg/day) for 3 days, or vehicle (placebo). Rats were anaesthetized and subjected to endotoxaemia by intravenous infusion of Escherichia coli lipopolysaccharide (LPS) (6 mg/kg) or saline infusion (sham). We observed significant levels of plasma beta-glucan in the SBGpo group (P<0 x 5), although the SBGsc group had levels approximately 40-fold higher despite a 10-fold lower dose. SBG prophylaxis caused enhanced blood pressure recovery following LPS-induced blood pressure collapse. Oral treatment with SBG attenuated the LPS-induced rise in plasma creatinine levels (P<0 x 05), indicating protection against renal injury. SBG also attenuated the plasma levels of aspartate aminotransferase and alanine aminotransferase (SBGpo, P<0 x 01; SBGsc, P<0 x 01), indicating protection against LPS-induced hepatic injury. A moderate increase in baseline interleukin (IL)-1beta levels was observed in the SBGsc group (P< 0 x 05). In the LPS-challenged rats, plasma levels of proinflammatory cytokines was moderately reduced in both SBG-treated groups compared to placebo. SBG treatment, particularly oral administration, had a striking effect on the haemodynamics of LPS-treated rats, although only a minute fraction of the orally administered beta-glucan translocated to the circulation. Enhanced organ perfusion may thus be responsible for the attenuated levels of indicators of kidney and liver injury seen in SBG-treated rats.
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PMID:Oral and systemic administration of beta-glucan protects against lipopolysaccharide-induced shock and organ injury in rats. 1734 15

We tested the hypothesis that laminarin (LAM), a beta (1-3) polysaccharide extracted from brown algae, can modulate the response to a systemic inflammation. Male Wistar rats (n=7 per group) were fed a standard diet (control) or a diet supplemented with LAM for 25 days (5% during 4 days followed by 10% during 21 days). Thereafter, Escherichia coli lipopolysaccharides (LPS; 10 mg/kg i.p.) were injected and the animals were sacrificed 24 h after LPS challenge. The hypothermia, hyperglycemia and hypertriglyceridemia occurring early after LPS administration were less pronounced in LAM-treated rats than in controls. The increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) activities - reflecting hepatic alterations - was lessened after LPS injection in LAM-treated rats compared to control rats. LAM treatment decreased serum monocytes number, nitrite (NO2) and tumor necrosis factor-alpha (TNF-alpha). LAM also modulated intra-hepatic immune cells: it lowered the occurrence of peroxidase-positive cells (corresponding to monocytes/neutrophils) and, in contrast, it increased the number of ED2-positive cells, corresponding to resident hepatic macrophages, i.e. Kupffer cells. In conclusion, the hepatoprotective effect of marine beta (1-3) glucan during endotoxic shock may be linked to its immunomodulatory properties. We propose that both lower recruitment of inflammatory cells inside the liver tissue and lower secretion of inflammatory mediators play a role in the tissue protective effect of LAM. These effects could be due to a direct effect of beta-glucan on immune cells, or to an indirect effect through their dietary fibre properties (fermentation in the gut).
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PMID:Dietary supplementation with laminarin, a fermentable marine beta (1-3) glucan, protects against hepatotoxicity induced by LPS in rat by modulating immune response in the hepatic tissue. 1827 7

In this study, we analyzed a water-soluble polysaccharide MP-I isolated from Mytilus coruscus. MP-I was obtained by hot-water extraction, anion-exchange and gel-permeation chromatography. Complete hydrolysis, periodate oxidation, methylation analysis, as well as Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) spectroscopy were conducted to elucidate its structure. MP-I was subjected to investigate the protective effect on carbon tetrachloride (CCl(4)) induced liver damage in male Kunming mice. Based on the data obtained, MP-I was found to be an alpha-(1-->4)-D-glucan, branched with a single alpha-D-glucose at the C-6 position every eight residue, on average, along the main chain. Based on the calibration with Dextran, the glucan had a molecular weight of about 1.35 x 10(6) Da. Pharmacological studies revealed that MP-I could decrease serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and hepatic malondialdehyde aldehydes (MDA) levels, increase the hepatic total superoxide dismutase (T-SOD) activity, and improve hepatic damage in the CCl(4) induced liver injury in mice in a dose-dependent manner. The results suggest that the possible mechanism is due to its antioxidant activity of MP-I.
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PMID:Characterization and protection on acute liver injury of a polysaccharide MP-I from Mytilus coruscus. 1796 34


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