Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic encephalopathy (HE) is a significant cause of morbidity and mortality in patients with advanced chronic liver disease. Current therapies are associated with inconvenient side-effects, high cost, and incomplete efficacy. The quanternary ammonium compound L-acyl-carnitine has been suggested as a potent, low-cost, and safe alternative therapy for patients with cirrhosis and HE. A systematic review of the literature assessing the use of carnitine in the treatment of HE identified three high-quality human trials for review. Analysis of the selected carnitine trials compared to currently accepted therapies suggests that L-acyl-carnitine is promising as a safe and effective treatment for HE, and further trials of this drug are warranted.
 ...
PMID:Is oral L-acyl-carnitine an effective therapy for hepatic encephalopathy? Review of the literature. 1827 Aug 33

Corydalis saxicola Bunting (Papaveraceae), a traditional folk medicine, has been used to treat hepatic diseases for a long time. Owing to its signicant clinical effectiveness against hepatitis, cirrhosis and hepatoma, C. saxicola and its preparation are widely applied. In this study, eight alkaloids, namely isocorydine, scoulerine, dehydrocheilanthifoline, dehydrodiscretamine, dehydroisoapocavidine, dehydrocavidine, palmatine and berberine, which have been previously proven to possess potential antitumour activity, were selected as the chemical markers of C. saxicola. To evaluate the quality of C. saxicola, a simple, accurate and reliable HPLC-DAD method was developed for the simultaneous determination of the above eight compounds. Separation was achieved on a Gemini C(18) column (5 microm, 250 x 4.6 mm i.d., Phenomenex Inc., CA, USA) with a gradient solvent system of 20 mM aqueous ammonium acetate-acetonitrile, at a flow-rate of 1.0 mL/min and detected at 270 and 280 nm. All eight calibration curves showed good linearity (R(2) > 0.9992). The method was reproducible with intra- and inter-day variations of less than 5%. The recovery was in the range of 96.09-102.80%. This assay was successfully utilised to quantify the eight alkaloids in C. saxicola from different locations. The results demonstrated that this method is simple, reliable and suitable for the quality control of this medicinal herb.
 ...
PMID:Simultaneous determination of eight bioactive alkaloids in Corydalis saxicola by high-performance liquid chromatography coupled with diode array detection. 1844 71

Cirrhosis represents the final stage of many chronic liver diseases and is associated to more or less pronounced hyponutrition, independently of the etiology, particularly at advanced stages. Its origin is multifactorial, with three factors contributing to it: a) limitation or decrease of intake; b) impairment in nutrients digestion or absorption; and c) the interference with nutrients metabolism. A poor nutritional status is associated with a poor survival prognosis. Whether caloric-protein malnourishment (CPM) is an independent predictor of mortality or only a marker of the severity of liver failure is subject to controversy. There is no consensus on which are the best diagnostic criteria for CPM in cirrhosis. Assessment of hyponutrition is extremely difficult since both the disease itself and the triggering or etiologic factors affect many of the parameters used. Metabolic impairments mimic a hypercatabolic state. These patients have decreased carbohydrate utilization and storage capacity and increased protein and fat catabolism leading to depletion of protein and lipid reserves. These abnormalities together with decreased nutrients intake and absorption are the bases for CPM. The most important metabolic impairment in patients with advanced liver disease is the change in amino acids metabolism. The plasma levels of branched amino acids (BAA) are decreased and of aromatic amino acids (AAA) are increased, which has therapeutic implications. Among the consequences of the structural impairments taking place in cirrhosis, we may highlight hepatic encephalopathy, defined as impaired central nervous system functioning that manifests as a series of neuropsychiatric, neuromuscular, and behavioral symptoms. These are due to the inability of the diseased liver to metabolize neurotoxins that accumulate in the brain affecting neurotransmitters and are attributed to the toxic effect of ammonium on the brain tissue. Nutritional therapy brings benefits in the different stages of the disease. In the short term, it improves nitrogen balance, decreases the hospital stay, and improves liver function. In the long term, it decreases the incidence and severity of encephalopathy and improves quality of life. Supplementation with enteral nutrition may improve protein intake, decrease the frequency of hospitalization, and improve the nutritional status, the immune function and the disease severity. Protein restriction is not indicated in compensated cirrhosis. A diet containing about 30 kcal/kg/d and 1.2 g of protein/kg/d is recommended. In acute encephalopathy temporary protein restriction may be needed, which should not last longer than 48 h and be minimized since even in patients with liver disease better outcomes are obtained without obtaining severe protein restriction. Oral supplementation with BAA slows the progression of liver disease and improves survival and quality of life. Supplementation should be done with fiber or diets with vegetable proteins, which bring high fiber content and less AAA, or either with dairy proteins in addition to a high ratio/nitrogen ratio.
 ...
PMID:[Liver cirrhosis and encephalopathy: clinical and metabolic consequences and nutritional support]. 1871 6

L-ornithine-L-aspartate (LOLA) is a stable salt of two natural nonessential L-amino acids: ornithine and aspartic acid. It is formulated and marketed in low and high doses. Low doses are used as a food supplement and high doses (above 5 g) as a medicinal product to lower blood ammonia concentration and to eliminate symptoms of hepatic encephalopathy associated with liver cirrhosis. The aim of this review is to present physiological roles of L-ornithine and L-aspartate in the human body, to assess conditions under which these amino acids could be deficient, to analyze consequences of these deficiencies, and to review the current state of knowledge on the effects of LOLA administration. The data used in this publication result from searches of different electronic databases such as Cochrane Trials Register, MEDLINE, PubMed, Medscape, or Google Scholar, with a cut-off date of November 29, 2009, using terms: L-ornithine-L-aspartate, ornithine aspartate, ornithine, Hepa-Merz, ornithine deficiency, hyperammonemia, hepatic encephalopathy, and liver cirrhosis. Both amino acids play key roles in ammonia detoxification and in proline and polyamine biosyntheses. Polyamines are considered critical for DNA synthesis and cell replication and have been shown to stimulate hepatic regeneration. Supplementation with ornithine in animal models demonstrated enhanced wound breaking strength and collagen deposition. It has been shown in vitro, in vivo and in perfused organs that urea synthesis from ammonia is limited by endogenous ornithine and that ornithine can pharmacologically promote urea formation to a greater degree than any ammonia supply. Administration of LOLA in high doses reduced high blood ammonia induced either by ammonium chloride or protein ingestion or existing as a clinical complication of cirrhosis. In health and with proper diet, L-ornithine and L-aspartate are synthesized de novo in sufficient quantities, but in the states of disease, tissue damage, organ insufficiency, excessive metabolic demand, growth, pregnancy, or urea cycle enzyme deficiencies, these amino acids need to be supplemented with the food. The review of available data indicate that there is direct and indirect (resulting from physiology) scientific rationale for dietary use of LOLA, depending on an individual's physiological, metabolic or pathological conditions. In conditional ornithine deficiency, daily supplementation with LOLA at doses about 1 g/day is safe and, as demonstrated in vitro, should be sufficient to saturate tissue ornithine concentration to prevent postprandial hyperammonemia and to stimulate tissue regeneration.
 ...
PMID:[Physiological functions of L-ornithine and L-aspartate in the body and the efficacy of administration of L-ornithine-L-aspartate in conditions of relative deficiency]. 2064 12

Wilson's disease is an inherited disorder leading to accumulation of copper in tissues, mainly in the liver and brain. Genetic defect is in the gene coding ATPase type P (ATP7B). The inheritance is autosomal recessive. Up to now, more then 500 mutations causing Wilson's disease were described. The most frequent mutation in Central Europe is mutation H1069Q. The manifestation of Wilson's disease is usually hepatic or neurologic. Hepatic form is manifested by acute or chronic hepatitis, steatosis or cirrhosis. Neurologic involvement is manifested usually after 20 year of age by motor disturbances (tremor, disturbed speech, problems with writing), which could progress into severe extrapyramidal syndrome with tremor, rigidity, dysartria, dysfagia and muscle contracture. Diagnosis is based on clinical and laboratory examinations (neurologic symptoms, liver disease, low serum ceruloplasmin levels, elevated free copper concentration in serum, high urine copper excretion, and presence of Kayser-Fleischer rings). Confirmation of diagnosis is done by hepatic copper concentration in liver biopsy or by genetic examination. Untreated disease leads to the death of a patient. Treatment is based on chelating agents decreasing the copper content by excretion into urine (D-penicillamine, trientine) or on agents preventing absorption of copper from food (zinc, ammonium-tetrahiomolybdene). Patients with asymptomatic Wilson's disease have to be treated as well. In Czech Republic either penicillamine or zinc are used. Liver transplantation is indicated in patients with fulminant liver failure or decompensated cirrhosis. Screening in families of affected patients (all siblings) is obvious.
 ...
PMID:[Wilson's disease]. 2066 62

Patients with liver cirrhosis show sleep disturbances. Insight into their relationship with hepatic encephalopathy (HE) can be obtained using animal models of HE. The aims of this work were to assess (1) whether rats with portacaval shunts (PCS), a model of HE, show alterations in sleep and if they are similar to those in patients with HE; (2) Whether hyperammonemia plays a role in these sleep alterations; and (3) the time course of sleep alterations in these animal models. Rats were subjected to PCS to induce HE. Another group of rats was fed an ammonium-containing diet to induce hyperammonemia. Polysomnographic recordings were acquired for 24 h and sleep architecture was analyzed in control, PCS, and hyperammonemic rats at 4, 7, and 11 weeks after surgery or diet, respectively. PCS rats show a significant reduction in rapid eye movement (REM) and non-rapid eye movement (NREM) sleep time and increased sleep fragmentation, whereas reduced sleep occurs at 4 weeks and worsens at 7 and 11 weeks, sleep fragmentation appears at 7 weeks and worsens at 11 weeks. Hyperammonemic rats show decreased REM sleep, starting at 7 weeks and worsening at 11 weeks, with no changes in NREM sleep or sleep fragmentation. Therefore, PCS rats are a good model to study sleep alterations in HE, their mechanisms, and potential treatment. Mild hyperammonemia mainly impacts mechanisms involved in REM generation and/or maintenance but does not seem to be involved in sleep fragmentation.
 ...
PMID:Progressive reduction of sleep time and quality in rats with hepatic encephalopathy caused by portacaval shunts. 2210 12

Hepatic encephalopathy is a major complication of cirrhosis. Ammonia and manganese have been associated with hepatic encephalopathy underlying mechanisms. Motor impairment and brain edema are common signs of hepatic encephalopathy. In the present study a model of liver damage in rats was combined with ammonia and manganese exposure to evaluate the role of these substances separately and their interactions on brain glutamine, water content and motor coordination. Additionally, we explored brain levels of each substance -Mn and ammonia- in the presence or absence of the other. Liver damage was induced by bile duct ligation. Rats were exposed to MnCl2 in drinking water (1 mg Mn/ml) and to ammonia in chow pellets containing 20% ammonium acetate (w/w). As expected, manganese and ammonia levels increased in the brain of cirrhotic rats exposed to these substances; in these animals, glutamine brain levels also increased and positively correlated with tissue water content in cortex. A three way-ANOVA showed that manganese favored ammonia and glutamine accumulation in brain, and possibly their subsequent deleterious effects, as evidenced by the fact that manganese and ammonia accumulation in the brain of cirrhotic rats severely affected motor function. These results suggest that even when controlling ammonia levels in cirrhotic patients, reduction of manganese intake is also a potential strategy to be considered in clinical practice.
 ...
PMID:Manganese and ammonia interactions in the brain of cirrhotic rats: effects on brain ammonia metabolism. 2229 Mar 16

Hyperammonemia and sarcopenia (loss of skeletal muscle) are consistent abnormalities in cirrhosis and portosystemic shunting. We have shown that muscle ubiquitin-proteasome components are not increased with hyperammonemia despite sarcopenia. This suggests that an alternative mechanism of proteolysis contributes to sarcopenia in cirrhosis. We hypothesized that autophagy could be this alternative pathway since we observed increases in classic autophagy markers, increased LC3 lipidation, beclin-1 expression, and p62 degradation in immunoblots of skeletal muscle protein in cirrhotic patients. We observed similar changes in these autophagy markers in the portacaval anastamosis (PCA) rat model. To determine the mechanistic relationship between hyperammonemia and autophagy, we exposed murine C(2)C(12) myotubes to ammonium acetate. Significant increases in LC3 lipidation, beclin-1 expression, and p62 degradation occurred by 1 h, whereas autophagy gene expression (LC3, Atg5, Atg7, beclin-1) increased at 24 h. C(2)C(12) cells stably expressing GFP-LC3 or GFP-mCherry-LC3 constructs showed increased formation of mature autophagosomes supported by electron microscopic studies. Hyperammonemia also increased autophagic flux in mice, as quantified by an in vivo autophagometer. Because hyperammonemia induces nitration of proteins in astrocytes, we quantified global muscle protein nitration in cirrhotic patients, in the PCA rat, and in C(2)C(12) cells treated with ammonium acetate. Increased protein nitration was observed in all of these systems. Furthermore, colocalization of nitrated proteins with GFP-LC3-positive puncta in hyperammonemic C(2)C(12) cells suggested that autophagy is involved in degradation of nitrated proteins. These observations show that increased skeletal muscle autophagy in cirrhosis is mediated by hyperammonemia and may contribute to sarcopenia of cirrhosis.
 ...
PMID:Hyperammonemia-mediated autophagy in skeletal muscle contributes to sarcopenia of cirrhosis. 2289 79

An immature gray seal was presented with lethargy, weight loss, vomiting and hematuria. Hepatic disease and urinary tract infection were suspected. Abdominal ultrasound showed hyperechoic structures with marked acoustic shadowing spread throughout both kidneys, but incomplete visualization of the liver. Abdominal CT showed mineral densities scattered throughout both kidneys and poor delineation of the liver. Due to the poor quality of life, the seal was euthanized. Postmortem examination showed ammonium urate nephroliths, pyelonephritis, and hepatic cirrhosis. This case report emphasizes the difficulty of characterizing liver disease with conventional 2D-ultrasound and CT in a deep-chested animal with minimal intra-abdominal fat.
...
PMID:Imaging diagnosis-ultrasonographic and CT findings in a gray seal (Halichoerus grypus) with hepatic cirrhosis, pyelonephritis, and nephrolithiasis. 2357 75

Wilsons disease is an autosomal recessive genetic disorder in which copper accumulates in tissues, especially in the liver and the brain. The genetic defect affects the P type ATPase gene (ATP7B). More than 500 mutations causing Wilsons disease have been described. The most common mutation in Central Europe concerns H1069Q. The symptoms of Wilsons disease include hepatic or neurological conditions. The hepatic condition is manifested as steatosis, acute or chronic hepatitis or cirrhosis. The neurological conditions are most often manifested after the age of 20 as motor disorders (tremor, speech and writing disorders), which may result in severe extrapyramidal syndrome with rigidity, dysarthria and muscle contractions. The dia-gnosis is based on clinical and laboratory assessments (neurological signs, liver lesions, low ceruloplasmin, increased free serum copper, high Cu volumes in urine, KayserFleischer ring). The dia-gnosis is confirmed by a high Cu level in liver tissue or genetic proof. Untreated Wilsons disease causes death of the patient. If treated properly the survival rate approximates to the survival rate of the common population. The treatment concerns either removal of copper from the body using chelating agents excreted into the urine (Penicillamine, Trientine) or limitation of copper absorption from the intestine and reducing the toxicity of copper (zinc, ammonium tetrathiomolybdate). In the Czech Republic, Penicillamine or zinc is used. A liver transplant is indicated in patients with fulminant hepatic failure or decompensated liver cirrhosis. In the family all siblings of the affected individual need to be screened in order to treat any asymptomatic subjects.
 ...
PMID:[Wilsons disease]. 2390 62


<< Previous 1 2 3 4 5 6 7 Next >>