Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Blood purification, mainly plasma exchange (PE), was carried out for 13 cases of acute, and two cases of chronic postoperative liver failure. Four of thirteen acute cases (31%) survived. Although only one of eight with chronic liver disease survived, three of five without chronic liver disease survived. In most of those who lived, other organ failure occurred less often; total bilirubin and blood ammonia were less than 15 mg/dl and 200 micrograms/dl, respectively, before PE: and total bilirubin, blood ammonia, and branched chain amino acid/aromatic amino acid (BCAA/AAA) ratios recovered after five or fewer sessions of PE. Two chronic cases, treated for 1 and 4 years, respectively, were good candidates for liver or multiple organ transplantation. Although both died, PE was effective in reducing jaundice and in improving consciousness and general condition. Plasma exchange should be introduced early after assessing the changes in total bilirubin, blood ammonia, and coma grade in patients with acute postoperative liver failure. Plasma exchange could be useful as a chronic hepatic support system for those awaiting liver transplantation.
 ...
PMID:Blood purification for postoperative liver failure with special reference to chronic hepatic support for those awaiting liver transplantation. 175 Nov 73

The usefulness of newly device hybrid artificial liver system was evaluated in anhepatic dogs. The artificial liver module was composed of 60 to 80gm. primary cultured canine (Beagle) hepatocytes which were attached to 200 borocillicate glass plates. Total hepatectomy were done through cavo-caval and porto-caval shunt method using Anthron catheter to 14 dogs. Dogs were divided into following three groups. Group I; no treatment (n = 6) Group II; plasma perfusion (n = 4) Group III; treated with the artificial liver systems (n = 4) The survival times were 21.3 +/- 5.6, 27.8 +/- 4.0, and 55.0 +/- 11.3 hours in group I, II, and III, respectively. The longest survival time was 65 hours in one of group III dogs. APTT levels in group I and II increased more than 100 sec. within 24 hours. On the other hand it was maintained within 50 sec. during 54 hours treatment in group III. Ammonia levels in group I and II extremely increased over 2000ng/dl. In group III, it was less than 400ng/dl for 54 hours. Plasma amino acid levels in group I and II (Glutamine, Arginine, AAA) revealed significantly higher than in group III at 18 hours after operation. It is concluded that the newly device hybrid artificial liver system was useful for in vivo liver support.
 ...
PMID:[A hybrid artificial liver system composed of primary cultured canine hepatocytes]. 232 5

The goal of this study was to evaluate the presence of extrahepatic damage and the uniformity and reversibility of the histological findings in CCl4-induced liver cirrhosis in the rat. To verify these findings rats were sacrificed 2 and 10 weeks after a treatment consisting of ten intragastric doses of CCl4, administered weekly. All treated rats developed an irreversible micronodular cirrhosis with no damage to the brain, kidney and pancreas. Moreover, rats sacrificed 2 weeks after the last CCl4 dose showed a number of functional alterations usually observed in man. In particular, low branched chain/aromatic amino acids (BCAA/AAA) plasma ratio, high ammonia, low zinc and high insulin with normal blood glucose were obtained.
 ...
PMID:Carbon tetrachloride-induced experimental cirrhosis in the rat: a reappraisal of the model. 262 82

To clarify the clinical significance of specific plasma amino acid abnormalities occurring in liver disorders with portal-systemic shunting, plasma amino acids and insulin levels were measured in idiopathic portal hypertension (IPH), extrahepatic portal occulusion (EHPO), and liver cirrhosis (LC). Three branched chain amino acids (BCAA: valine + leucine + isoleucine) were decreased in all three diseases in comparison with controls. Since plasma insulin measured during oral glucose tolerance tests did not specifically rise in LC, reduction of BCAA is not merely ascribed to hyperinsulinemia. Either portal-systemic shunting or some extent of liver damage may contribute to a fall in BCAA. Two aromatic amino acids (AAA: phenylalanine + tyrosine), which were within the normal range in EHPO and IPH, showed a marked increase in LC. Thus, changes of AAA probably mainly reflect the severity of the liver disease. The molar ratio of BCAA/AAA (MR) significantly correlated with ICG k, ICG R15, PT and the sum of blood ammonia in an oral ammonia tolerance test which may reflect the degree of hepatic disorder. MR diminished in the following decreasing order: controls, EHPO, IPH and LC.
 ...
PMID:Plasma amino acid abnormalities in liver disease: comparative analysis of idiopathic portal hypertension, extrahepatic portal occlusion and liver cirrhosis. 277 20

In this study, we tested a new artificial liver device using liver pieces in 8-h hemoperfusion of comatous porcine blood and compared two alternative tissue preparations. Acute hepatic coma in the pigs was induced by complete devascularization of the liver. The animals were killed in stage IV coma (15-25 h after the operation), and 1 l blood was perfused over 200 g fresh or DMSO-preserved liver cubes. After the devascularization GOT, GPT, GLDH, AP, LDH, SDH, bilirubin, free fatty acid, and bile acid levels in serum increased progressively. Ammonia concentrations underwent a rapid increase in the first 9 h of coma development from 126.0 +/- 9.9 to 321.9 +/- 62.2 mumol/l. Most of the amino acids in serum were elevated and molar ratio of BCAA/AAA declined from 3.87 +/- 0.79 to 0.92 +/- 0.24. In the course of hemoperfusion ammonia was removed from the perfusate to 71% of the initial values using fresh and to 39% using preserved tissue. Correspondingly, there was an increase in urea concentrations. Amino acid metabolism was ameliorated during the perfusion; Fischer's quotient increased from 0.91 +/- 0.15 to 1.38 +/- 0.14 (fresh liver) and from 0.89 +/- 0.14 to 2.11 +/- 0.44 (preserved liver); neuroexcitatory amino acids Asp and Glu were markedly elevated. Energy charge of the liver cells increased and reached levels exceeding 0.5 in both experimental groups, a balanced energy metabolism was maintained and suggests active metabolization by the liver pieces. In comparison with fresh tissue, preserved liver cubes proved effective. We consider our artificial liver device capable of temporary hepatic support in acute necrosis of the liver and suppose that its efficiency can be potentiated by combining this system with other procedures.
 ...
PMID:Successful treatment of hepatic coma by a new artificial liver device in the pig. 408 14

The aims of this study were: 1. the assessment of the nitrogen balance (NB) in both compensated and encephalopathic cirrhotics, 2. the evaluation of the efficacy of a new therapeutic approach: amino acid solutions enriched with branched chain (BCAA) but poor in aromatic (AAA) amino acids. Solutions containing only BCAA were also employed: 42 cirrhotics were divided into the following groups: 1st group (26 cases), cirrhosis without hepatic encephalopathy (HE); 2nd group (16 cases), cirrhosis with HE. Six patients (23%) in the 1st group showed a positive NB at the beginning; 20 (77%) were negative; 18 of them were fed an oral diet (0.8 g protein/kg/day; 35 cal/kg/day) as a result of which they were brought into a positive NB within 5 days (from - 7.38 +/- 0.95 to + 3.67 +/- 0.46 g N/24 h). In two cases the diet failed to give a positive NB, so it was replaced by a BCAA enriched solution infusion (NB raised from - 1.0 +/- 5.4 g N/24 h). Patients in the 2nd group were put on total parenteral nutrition (TPN); two cases receiving glucose alone achieved a positive NB only when BCAA enriched solutions were added (from - 4.0 to + 3.0 g N/24 h). Four patients treated for 3 days with BCAA alone did not achieve a positive NB; in these cases likewise, BCAA enriched solutions were added in order to achieve a positive NB (from - 0.8 to + 4.2 g N/24 h); all 14 cases treated from the beginning with glucose + BCAA enriched solutions became positive, on average, within 5 days (from - 4.82 +/- 0.89 to + 3.15 +/- 0.61 g N/24 h). In addition to the NB, other parameters (blood ammonia, BCAA/AAA ratio, blood urea, electroencephalograms) and clinical symptoms were beneficially influenced by these solutions.
 ...
PMID:Negative nitrogen balance in cirrhotics. (A correct therapeutic approach). 729 72

Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome characterized predominantly by augmented neuronal inhibition and probably neuronal damage. Several theories concerning the pathogenesis of HE have been proposed; none of these theories is necessarily exclusive. Furthermore, the validity of none of them has been definitively proved experimentally. In this review article an important role of endotoxin and tumor necrosis factor-alpha (TNF) in the pathogenesis of HE is suggested. The involvement of endotoxin and TNF in the pathogenesis of HE seems to be very convincing; it may explain many of the derangements seen in HE. It also seems to be in strong relation to the main theories about HE, the ammonia theory, the GABAergic theory, the benzodiazepine theory, and the AAA/false neurotransmitter theory, where these theories may represent some of the mechanisms whereby TNF may cause inhibition and damage to the CNS in HE, or may represent accompanying features to elevated levels of endotoxin and TNF, with no important role in the pathogenesis of HE. The possible involvement of endotoxin and TNF in the pathogenesis of HE may possess an important clinical application, for serum LPS and TNF concentrations may be of important diagnostic and prognostic value in HE, and treatment with antibodies against endotoxin and against TNF may have potentially beneficial therapeutic effects in this serious and potentially fatal disease.
 ...
PMID:Endotoxin and tumor necrosis factor-alpha in the pathogenesis of hepatic encephalopathy. 796 64

The portacaval anastomosis (PCA) rat model and human cirrhosis have many metabolic and nutritional abnormalities in common, such as growth retardation, hepatic and gonadal atrophy, and hyperammonemia. The severity of these abnormalities is variable and may be related to a number of factors, including portal pressure, portosystemic shunting, dietary intake, and how efficiently food is used. Therefore, this rat model was used to study these variables with the intent of gaining insights for improving the management of portal hypertension and malnutrition in human cirrhosis. A nonsuture end-to-side PCA (N = 100) or sham surgery (N = 71) was performed in 100 male rats. Four weeks after surgery, body and organ weights, food intake, serum ammonia, and serum amino acids were measured at death. In a subgroup of rats, (sham 7; PCA 34) portal venous pressure, degree of portosystemic shunting, and organ and body weights were obtained at death. Growth, liver weight, and testes weight were decreased, ammonia levels were higher, and the ratios of branched chain to aromatic amino acid (BCAA/AAA) were lower in the PCA group compared to the sham animals (P < 0.05). Since spleen weights correlated with portal pressure (P = 0.01), the PCA animals were then divided into those with preserved and those with low portal pressures based on spleen weight. The PCA group with preserved portal pressure had better growth, larger livers and testes, lower serum ammonia, and higher BCAA/AAA levels than the PCA group with low portal pressure; improvements associated with normal amounts of food intake and better food efficiency than the low pressure animals (P < 0.05 or better). Sham animals had no portosystemic shunting, while 100% shunting occurred in both PCA groups regardless of the portal pressure. In conclusion, preservation of portal pressure after portacaval anastomosis provides metabolic and nutritional benefits, which are independent of portosystemic shunting and associated with normal dietary intake and better preserved food efficiency.
 ...
PMID:Preservation of portal pressure improves growth and metabolic profile in the male portacaval-shunted rat. 1235 33

FeaR is an AraC family regulator that activates transcription of the tynA and feaB genes in Escherichia coli. TynA is a periplasmic topaquinone- and copper-containing amine oxidase, and FeaB is a cytosolic NAD-linked aldehyde dehydrogenase. Phenylethylamine, tyramine, and dopamine are oxidized by TynA to the corresponding aldehydes, releasing one equivalent of H2O2 and NH3. The aldehydes can be oxidized to carboxylic acids by FeaB, and (in the case of phenylacetate) can be further degraded to enter central metabolism. Thus, phenylethylamine can be used as a carbon and nitrogen source, while tyramine and dopamine can be used only as sources of nitrogen. Using genetic, biochemical and computational approaches, we show that the FeaR binding site is a TGNCA-N8-AAA motif that occurs in 2 copies in the tynA and feaB promoters. We show that the coactivator for FeaR is the product rather than the substrate of the TynA reaction. The feaR gene is upregulated by carbon or nitrogen limitation, which we propose reflects regulation of feaR by the cyclic AMP receptor protein (CRP) and the nitrogen assimilation control protein (NAC), respectively. In carbon-limited cells grown in the presence of a TynA substrate, tynA and feaB are induced, whereas in nitrogen-limited cells, only the tynA promoter is induced. We propose that tynA and feaB expression is finely tuned to provide the FeaB activity that is required for carbon source utilization and the TynA activity required for nitrogen and carbon source utilization.
...
PMID:Finely tuned regulation of the aromatic amine degradation pathway in Escherichia coli. 2401 33

Hyperammonemia and severe amino acid imbalances play central role in hepatic encephalopathy (HE). In the article is demonstrated that the main source of ammonia in cirrhotic subjects is activated breakdown of glutamine (GLN) in enterocytes and the kidneys and the main source of GLN is ammonia detoxification to GLN in the brain and skeletal muscle. Branched-chain amino acids (BCAA; valine, leucine, and isoleucine) decrease due to activated GLN synthesis in muscle. Aromatic amino acids (AAA; phenylalanine, tyrosine, and tryptophan) and methionine increase due to portosystemic shunts and reduced ability of diseased liver. The effects on aminoacidemia of the following variables that may affect the course of liver disease are discussed: nutritional status, starvation, protein intake, inflammation, acute hepatocellular damage, bleeding from varices, portosystemic shunts, hepatic cancer, and renal failure. It is concluded that (1) neither ammonia nor amino acid concentrations correlate closely with the severity of liver disease; (2) BCAA/AAA ratio could be used as a good index of liver impairment and for early detection of derangements in amino acid metabolism; (3) variables potentially leading to overt encephalopathy exert substantial but uneven effects; and (4) careful monitoring of ammonia and aminoacidemia may discover important break points in the course of liver disease and indicate appropriate therapeutic approach. Of special importance might be isoleucine deficiency in bleeding from varices, arginine deficiency in sepsis, and a marked rise of GLN and ammonia levels that may appear in all events leading to HE.
...
PMID:Ammonia and amino acid profiles in liver cirrhosis: effects of variables leading to hepatic encephalopathy. 2522 Aug 75


1