Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biochemical and toxicological effects of occupational and dietary exposure of humans to cyanide poisoning from large-scale cassava processing and ingestion of cassava foods were investigated using spectrophotometric and enzymatic methods. Analysis of urinary and serum thiocyanate (cyanide metabolite) from workers in cassava processing industries, who were 'frequent' [those who eat cassava food(s) at least once a day] and 'infrequent' [those who eat cassava food(s) only occasionally] consumers of cassava-based diets, was carried out with the aid of questionnaries. The mean urinary thiocyanate level of the cassava processors (mean+/-S.D.; 153.50+/-25.21 micromo1/l) was 2.2 and 2.6 times higher than that of frequent (70.1+/-21.8 micromo1/l) and infrequent (mean+/-S.D.; 59.30+/-17.0 micromo1/l) cassava consumers, respectively. The mean serum thiocyanate levels rose to 126.73+/-12.4 micromo1/l for the former and 68.4+/-18.3 and 54.7+/-13.2 micromo1/l, respectively, for the latter. An increase in plasma activity by 10% above normal of aspartate aminotransferase (AST) was observed in 40% of the cassava processors, whereas it was within normal range in all consumers. The activities of alanine aminotransferase (ALT) and alkaline phosphatase (ALK.PHOS) were within the normal value in all cases studied. The blood glucose level of 50% of the cassava processors was 100 mg/ml or above while that of the consumers was in the range of 68-85 mg/100 ml. The total protein, serum albumin and creatinine levels were in the range for normal values for the processors and consumers. The health implications of these findings are discussed.
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PMID:Occupational and dietary exposures of humans to cyanide poisoning from large-scale cassava processing and ingestion of cassava foods. 1206 22

The objective was to study toxin-induced effects on physiological parameters in the rabbit and whether these parameters show dose-response and co-variation after administration of a recombinant fusion protein between staphylococcal enterotoxin (SE) and the Fab fragment of an antibody. Rabbits are very sensitive to SE toxins and the cardiovascular and immune effects are similar to those observed in septic shock in man. The test compound, r-C242 Fab-SEA, was administered intravenously to anaesthetised New Zealand white rabbits at doses in the range of 0.00005-50 microg/kg. All rabbits were checked for titres of anti-SEA antibodies before entering the experiment, since they could neutralise the effect of the test compound. Heart rate, blood pressure and body temperature were continuously monitored before and during 6 h after dosing. Immediately before the start of administration and 3 and 6 h during the experiment, blood gases (pO(2) and pCO(2)), pH, haematology, clinical chemistry, cytokine response (TNF-alpha) and trace elements (Mn, Cu, Zn, Se, Ag, Cd, Hg and Pb) were measured. No mortality occurred, but at 50 microg/kg severe adverse clinical signs developed. The decrease in blood pressure was weakly dose-related. Heart rate, ECG, body temperature, pCO(2) and pH were not affected by the treatment. pO(2) tended to increase as a function of time, but not in relation to dose. WBC and PLT decreased dose dependently. TNF-alpha was not affected by the treatment. The major effects on clinical chemistry were a dose-dependent increase in AST and creatinine. Potassium and urea showed dose dependent increases, mainly at higher doses, though these changes were of less value for drug selection purposes. Trace element changes were observed, including an increase in Mn and a decrease of Zn at all doses. The Cu/Zn ratio decreased below normal at low doses, whereas at high doses in which adverse effects developed, it increased above normal. Post mortem examination revealed minimal to moderate dose-related granulocytic infiltrate in the lungs. The present study showed dose-response and co-variation between several changes in cardiovascular, haematology, clinical chemistry and trace element parameters during the initial phase of toxin-induced effects preceding a possible lethal endpoint and associated patho-physiological changes.
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PMID:Effects of a superantigen-antibody recombinant fusion protein (r-C242 Fab-SEA) on toxicological responses in the anaesthetised rabbit. 1250 54

Parenteral nutrition (PN) is the only treatment for patients affected by chronic intestinal failure (CIF). Home parenteral nutrition (HPN) programs are started when patients need prolonged PN. Unfortunately, many patients on prolonged PN develop liver disease (LD). The aim of our study was to assess the prevalence of LD in our series of patients on HPN. We reviewed our records of patients discharged from the hospital on HPN for CIF. HPN was started when one parent was fully trained in the use of this treatment and if the social and familial home environment was reliable. All patients received total PN by a central venous catheter. All patients with abnormal AST, ALT, ALK, gammaGT, and bilirubin values for more than 3 months were considered affected by PN-related LD. Thirty-six patients (23 of whom were boys and 13 girls) were discharged on HPN. During the study period, for CIF, 16 were affected by short bowel syndrome (SBS), of whom 6 had ultra-short bowel; 16 with functional intestinal failure, and 4 with chronic intestinal pseudobstruction (CIPO). Mean duration of HPN was 2.1 years/patient. Nine of 36 patients (25%) on HPN for CIF showed LD. Seven of the 16 patients (43%) with LD were affected by SBS and 2 (12.5%) patients by functional intestinal failure. No patients with CIPO developed LD. In patients affected by SBS, the onset of LD was very earlier than in patients with ID.
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PMID:Prevalence of liver complications in pediatric patients on home parenteral nutrition: indications for intestinal or combined liver-intestinal transplantation. 1469 75

A study was conducted to evaluate the effects of acute and subacute locoweed exposure on serum swainsonine concentrations and selected serum constituents in sheep. Thirteen mixed-breed wethers (BW = 47.5 +/- 9.3 kg) were assigned randomly to 0.2, 0.4, or 0.8 mg of swainsonine x kg BW(-1) x d(-1) treatments. During acute (24 h) and subacute (19 d) exposure, serum swainsonine was detected in all treatments and was greatest (P < 0.03) in the 0.8 mg treatment. Serum alkaline phosphate (ALK-P) activity was increased (P < 0.01) for the 0.8 mg treatment compared with baseline (0 h) by 7 h and continued to increase throughout the initial 22 h following acute exposure to locoweed. A linear increase (P < 0.01) in serum ALK-P activity was noted, with the rate being 3.00 +/- 0.56 U x L(-1) x h(-1). Serum ALK-P activity was increased (P < 0.05) across treatments on d 7 over d -19, -12, 0, 1, 21, and 26; on d 14 over d -19, -12, 0, and 26; and on d 19 over d -19, -12, 0, 1, 21, and 26. By d 20, approximately 48 h after last exposure to swainsonine, serum ALK-P activities were no longer different (P = 0.13) than baseline (d -19, -12, and 0), and by d 26 values had generally returned to baseline. No linear (P = 0.98), quadratic (P = 0.63), or cubic effects of swainsonine with time from exposure were noted for serum aspartate aminotransferase. Similar to serum ALK-P activities, serum aspartate aminotransferase activities were increased (P < 0.05) across treatment levels on d 7, 14, 19, 20, 21, and 26 over those on d -19, -12, 0, and 1. Total serum Fe was decreased (P < 0.05) within the initial 22 h following the swainsonine exposure. On d 21 (48 h after swainsonine feeding ended), serum Fe increased to 472 mg/L. Concentrations of ceruloplasmin were lower (P < 0.10) on d 14 and 19 following exposure to locoweed. Recovery of ceruloplasmin levels coincided with similar changes in serum Fe. There was a linear (slope = 0.33 mg x dL(-1) x d(-1); P < 0.01) effect with time of exposure to locoweed (i.e., swainsonine) on serum triglyceride concentrations. Rapid changes in serum ALK-P and Fe concentrations without parallel changes in other damage markers indicate that acute exposure to swainsonine induces metabolic changes that may impair animal production and health before events of cytotoxicity thought to induce clinical manifestation of locoism.
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PMID:Effects of locoweed on serum swainsonine and selected serum constituents in sheep during acute and subacute oral/intraruminal exposure. 1564 21

Ischemia-reperfusion injury (I/R-I), which is unavoidable in liver transplantation, impairs liver regeneration and predisposes to liver failure. The three major mitogen-activated protein-kinases (MAPKs): ERK, p38, and JNK, are critical in the transmission of signals triggered by proinflammatory cytokines, by stress, and by growth factors. JNK and p38alpha activation have been associated with apoptosis; p38beta with cell survival; and ERK with proliferation. Previous studies have demonstrated gender dimorphism in hepatocellular dysfunction after experimental trauma and hemorrhage. Female mice are protected to a much greater extent from I/R-I than male mice. We assessed the effects of 17beta-estradiol (17beta-E) on liver function, host survival, and cellular activation of MAPK in a murine model of I/R-I in reduced-size livers. C57BL/6 mice were subjected to 45 minutes of warm ischemia (70% of the liver mass). After reperfusion, the nonischemic lobes were excised. Vehicle, 17beta-E or the estrogen receptor antagonist ICI-182780, was delivered 1 hour before the injury. We evaluated AST and apoptosis as well as activation of JNK, p38, and ERK. Female mice showed a lower level of hepatocellular injury (AST = 445 +/- 82 IU/L) after I/R-I compared with male mice (AST = 1400 +/- 210). 17beta-E decreased the liver injury in male mice (AST = 522 +/- 77), an effect that was partially reversed by ICI-182,780 (910 +/- 92). A higher rate of apoptosis was observed in male animals given saline (enrichment factor = 7.22 +/- 0.8) versus those treated with 17beta-E (5.85 +/- 0.3, P < .05). A significant increase in liver regeneration, as assessed by the percentage of liver weight/body weight was demonstrated in females (184% +/- 24%) and male mice given 17beta-E (168% +/- 22%) compared with male mice given vehicle (9% +/- 4%). 17beta-E significantly down-regulated JNK and p38alpha activities, whereas I/R-I promoted p38beta and ERK activation. These results suggest that the cytoprotective effects of 17beta-E on I/R-I to reduced-size livers are associated with selective modulation of MAPK kinases.
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PMID:17beta-estradiol differentially activates mitogen-activated protein-kinases and improves survival following reperfusion injury of reduced-size liver in mice. 1580 58

In this study we tried to investigate the effect of fructose-1,6-diphosphate and HTK solution on protecting primary cardiac muscle cells of rat with cold preservation. The primary cardiac muscle cells of rat were cultured in vitro with four preservation solutions respectively: 0.9% sodium chloride solution (group A), FDP (group B), HTK solution (group C) and a mixture of FDP and HTK solution (group D). The cells were preserved for 6, 8 and 10 h at 0-4 degrees C. The values of AST and LDH-L and the Na+-K+ ATPase activity in cardiac muscle cells were detected, and the survival rate of cardiac muscle cells was detected with trypan blue staining. The values of AST and LDH-L in group C and group D were remarkable lower those in group A and group B (P<0.001), while the Na+-K+ ATPase activity and the survival rate of cells in group C and group D were much higher than those in group A and group B (P<0.001). The values of AST and LDH-L after 6 hours in group D decreased much more than those in group C (P<0.01), while the Na+-K4 ATPase activity and the survival rate of cells in group D improved more than those in group C (P<0. 01). Both of the HTK solution and the mixture of HTK and FDP solution have an evident effect on protecting the primary cardiac muscle cells of rat in vitro with cold preservation, Compared with the HTK solution, the mixture solution has a better short-term protective effect.
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PMID:The effect of fructose-1, 6-diphosphate and HTK solution on protecting primary cardiac muscle cells of rat with cold preservation. 1620 Dec 75

Cutaneous leg ulcers are common in sickle cell anaemia and their risk might be genetically determined. Sickle cell anaemia patients were studied to examine the relationship of leg ulcers with haemolysis and with single nucleotide polymorphisms (SNPs) in candidate genes that could affect sickle vasoocclusion. Leg ulcer patients had lower haemoglobin levels and higher levels of lactate dehydrogenase, bilirubin, aspartate transaminase and reticulocytes than did control patients with sickle cell anaemia but without leg ulcers. Age-adjusted comparisons showed that sickle cell anaemia-alpha thalassaemia was more frequent among controls than cases. These results strongly suggested that the likelihood of having leg ulcers was related to the intensity of haemolysis. 215 SNPs in more than 100 candidate genes were studied. Associations were found with SNPs in Klotho, TEK and several genes in the TGF-beta/BMP signalling pathway by genotypic association analyses. KL directly or indirectly promotes endothelial nitric oxide (NO) production and the TEK receptor tyrosine kinase is involved in angiogenesis. The TGF-beta/BMP signalling pathway modulates wound healing and angiogenesis, among its other functions. Haemolysis-driven phenotypes, such as leg ulcers, could be improved by agents that reduce sickle erythrocyte density or increase NO bioavailability.
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PMID:Sickle cell leg ulcers: associations with haemolysis and SNPs in Klotho, TEK and genes of the TGF-beta/BMP pathway. 1668 47

Chronic shortage of donor organs has led to acceptance of steatotic livers as grafts, although there is a higher risk of primary graft dysfunction. We herein report the beneficial impact of Polysol, a newly developed preservation solution, on cold storage of steatotic rat livers. Dietary hepatic steatosis was induced in Wistar rats by 2-day fasting and subsequent 3-day re-feeding with a fat-free, carbohydrate-rich diet. Fatty livers were retrieved, flushed and then stored at 4 degrees C for 24 hours with either HTK or Polysol. Functional integrity of the grafts was evaluated by isolated reperfusion with oxygenated Krebs-Henseleit buffer at 37 degrees C for 45 minutes in both groups. Polysol preservation resulted in significant reductions of not only parenchymal (AST (IU/L); 6728+/-824 in HTK vs. 3107+/-718 in Polysol; P < 0.001) but also mitochondrial (GLDH (IU/L); 3189+/-773 vs. 1282+/-365; P < 0.01) enzyme release throughout reperfusion. Moreover, PVP (16.9+/-2.7 vs. 7.8+/-1.5 mmHg; P < 0.05), hepatic O2 consumption (0.291+/-0.047 vs. 1.056+/-0.053 micromol/g liver/min; P < 0.001), tissue ATP content (0.695+/-0.086 vs. 1.340+/-0.157 micromol/g dry-liver; P < 0.005), bile production (0.79+/-0.11 vs. 4.08+/-0.66 microL/g liver/45-min; P < 0.001), malondialdehyde into the perfusate (1.922+/-0.198 vs. 0.573+/-0.094 nmol/L; P < 0.0001) and wet/dry-weight ratio of the liver tissues (5.20+/-0.31 vs. 3.85+/-0.15; P < 0.005) were all better preserved by Polysol. In line with these benefits, electron microscopy revealed that Polysol preservation substantially suppressed deleterious mitochondrial alterations in steatotic livers. In conclusion, cold storage using Polysol resulted in significantly better integrity and function of steatotic livers. Polysol, therefore, may be a new alternative especially for "marginal" organs.
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PMID:Impact of polysol, a newly developed preservation solution, on cold storage of steatotic rat livers. 1711 34

Previous studies have shown that donor hypernatremia and possibly recipient hyponatremia negatively impact graft function after orthotopic liver transplant (OLT). The purpose of this retrospective investigation was to determine whether measured differences in serum sodium values between cadaveric donors and OLT recipients (DeltaNa(+)) influence immediate postoperative allograft function and short-term patient outcomes. Two hundred and fifty patients that underwent OLT from January 2001 to December 2005 were included in this study. The DeltaNa(+) for each donor recipient pair was correlated with standard postoperative liver function tests as well as recipient length of intensive care unit stay (LOICUS), length of hospital stay (LOHS) and recipient survival. The relationship between donor hypernatremia (serum sodium >or= 155 mEq/mL), recipient hyponatremia (serum sodium level <or= 130 mEq/mL), and postoperative outcomes were analyzed as well. Adjustments were made for baseline potential confounders, including model for end-stage liver disease (MELD) score, preservation solution used (HTK vs. UW), recipient and donor demographics and cold ischemia time (CIT). DeltaNa(+) as well as donor hypernatremia and recipient hyponatremia were not found to be associated with immediate postoperative allograft function, intraoperative blood product usage, LOICUS, LOHS or short-term patient survival. However, both the preoperative MELD score and HTK preservation solution used were significantly associated with several patient outcomes. A higher MELD score was associated with both increased red blood cell (RBC) (P < 0.001) and fresh frozen plasma (FFP) usage (P = 0.002), elevated postoperative total bilirubin levels (P < 0.001), increased LOHS (P = 0.04), and a higher 30-day post transplant mortality (P = 0.02). The use of HTK preservation solution was associated with higher mean postoperative aspartate aminotransferase levels (P = 0.02) and decreased mean RBC (P < 0.001) and FFP usage (P = 0.009) compared to UW preservation solution use.
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PMID:Association between donor-recipient serum sodium differences and orthotopic liver transplant graft function. 1816 40

Asiatic acid is a triterpenoid component possessing antioxidative, anti-inflammatory and hepatoprotective activity. In this issue, we explored the protective effects of asiatic acid and the relative mechanism in the D-galactosamine/lipopolysaccharide (D-GalN/LPS)-induced hepatotoxicity in hepatocytes and kupffer cells co-cultured system. The cultures were pretreated with asiatic acid for 12 h, followed by D-GalN/LPS exposure for 12 h. Asiatic acid reduced aspartate aminotransferase and lactate dehydrogenase generation and increased cell viability in a concentration-dependent manner. Meanwhile, the effects of asiatic acid in leukotriene C(4) synthase (LTC(4)S) expression and cellular redox status including reactive oxygen species and GSH content were detected. The results showed that D-GalN/LPS induced the increase of reactive oxygen species followed by extracellular signal-regulated kinase 1/2 (ERK 1/2) and nuclear factor-kappaB (NF-kappaB) activation. Treatment with ERK 1/2 specific inhibitor 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene (U0126) abolished the ERK1/2 protein phosphorylation and blunted LTC(4)S expression. Reactive oxygen species signaling pathway inhibitor pyrrolidine dithiocarbamate (PDTC) inhibited reactive oxygen species generation and NF-kappaB activation, which in turn blocked LTC(4)S expression and attenuated the injury. Asiatic acid can protect the hepatocytes against D-GalN/LPS-induced hepatotoxicity. During which, the cell redox was ameliorated and increased expression of LTC(4)S was reversed by the pretreatment of asiatic acid. Taken together, asiatic acid can protect against D-GalN/LPS-induced hepatotoxicity partly via redox-regulated LTC(4)S expression pathway.
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PMID:Protective effects of asiatic acid against D-galactosamine/lipopolysaccharide-induced hepatotoxicity in hepatocytes and kupffer cells co-cultured system via redox-regulated leukotriene C4 synthase expression pathway. 1908 74


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