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)

Ascites is the most common complication of cirrhosis and is associated with 50% mortality at 2 years if patients do not receive orthotopic liver transplantation. Recently the International Ascites Club defined ascites into three groups: In grade I ascites fluid is detected only by ultrasound; in grade II, ascites is moderate with symmetrical distention of the abdomen; and in Grade 3 ascites is large or tense with marked abdominal distention. About 10% of patients with ascites are refractory to treatment with diuretics. In refractory ascites, patients do not respond to highest doses of diuretics (spironolactone 400 mg/day and furosemide 160 mg/ day) or develop side effects (hyperkalemia, hyponatremia, hepatic encephalopathy, or renal failure) that prohibit their use. Patients may be treated either by repeated large volume paracentesis plus albumin or transjugular intrahepatic portosystemic shunts (TIPS). Dilutional hyponatremia in cirrhotic patients is defined as serum sodium < or = 130 mEq/L in the presence of an expanded extracellular fluid volume, as indicated by the presence of ascites and/or edema. This complication of cirrhotic patients with ascites has recently gained attention given that several reports indicate that when serum sodium concentration is combined with the Model for End-Stage liver disease (MELD) it improves the prognostic accuracy of MELD score in patients awaiting orthotopic liver transplant (OLT). The first step in the management of dilutional hyponatremia is fluid restriction and discontinuation of diuretics. Water restriction at 1,000 mL/day helps prevent the progressive decrease in serum sodium concentration but usually does not correct hyponatremia in most cases. Actually are developing drugs that are active orally and act by selectively antagonizing the specific receptors (V2 receptor) of arginine vasopressin. These agents act in the distal collecting ducts of the kidneys, by increasing solute free water excretion and, thus, improving serum sodium concentration in hyponatremic patients.
 ...
PMID:[Refractory ascites and dilutional hyponatremia: current management and new aquaretics]. 1706 87

The presence of dilutional hyponatremia has a poor prognosis for survival in patients with cirrhosis and ascites. Effective and safe treatments are needed to improve prognosis in patients with cirrhosis and dilutional hyponatremia. The initial approach to management includes fluid restriction, low sodium diet, and minimizing the use of diuretics. In addition, the use of hypertonic saline should be avoided in patients with cirrhosis and dilutional hyponatremia. Furthermore, patients should be placed on the top of the list for liver transplantation if they are appropriate candidates. Although V2 arginine vasopressin receptor antagonists that selectively enhance solute-free water excretion in patients with cirrhosis seem very promising, two points must be considered in relation to the available data. First, although the results of phase-2 studies are encouraging, the efficacy and safety of these compounds should be further evaluated. Second, the clinical utility of these agents in cirrhosis has only been assessed in short-term studies. The long-term effects of these drugs remain unknown. Future research with these compounds should not only focus on the effects on serum sodium, but also on treatment and prevention of recurrence of ascites. In addition, the possible beneficial effects of these drugs in the prevention of hepatic encephalopathy would be worth studying.
 ...
PMID:Hyponatremia in cirrhosis: clinical features and management. 1707 68

The glycosylation profile of von Willebrand factor (VWF) is known to strongly influence its plasma levels. VWF contains several carbohydrate structures, including O-linked glycans that primarily consist of sialylated T antigen (NeuAc(alpha2-3)Gal-(beta1-3)-[NeuAc(alpha2-6)]GalNAc). It is not yet known whether O-linked carbohydrates affect VWF levels. We developed an immunosorbent assay based on neuraminidase incubation allowing subsequent binding of peanut agglutinin (PNA) to desialylated O-linked T antigen on VWF. An inverse relation was found between PNA binding and VWF antigen levels in healthy individuals (n = 111; Pearson rank = -0.43; P < .001). A similar inverse association was observed in randomly selected plasma samples from our diagnostic laboratory: 252% +/- 125% for VWF levels less than 0.5 U/mL (n = 15); 131% +/- 36% for VWF levels between 0.5 and 1.5 U/mL (n = 32); and 92% +/- 40% for VWF levels more than 1.5 U/mL (n = 19). Reduced or increased PNA binding was also observed in patients with increased (liver cirrhosis) or reduced (von Willebrand disease [VWD] type 1) VWF antigen levels, respectively. VWD type 1 patients further displayed increased ratios of propeptide over mature VWF antigen levels (0.38 +/- 0.18 versus 0.17 +/- 0.03 for patients and controls, respectively; P < .001), which is indicative of reduced VWF survival in these patients. Of interest, a linear relation between PNA binding and propeptide/VWF ratio was observed (Spearman rank = 0.47), suggesting a potential association between O-linked glycosylation and VWF survival. Finally, we detected a marked decrease in PNA binding in post-DDAVP (1-deamino-8-D-arginine vasopressin) samples from various patients, indicating that the O-linked glycosylation profile of VWF stored in endothelial storage organelles may differ from circulating VWF.
 ...
PMID:Variations in glycosylation of von Willebrand factor with O-linked sialylated T antigen are associated with its plasma levels. 1709 Jun 49

Hyponatremia, which is often due to dysregulation of arginine vasopressin, occurs frequently in hospitalized patients and is associated with increased morbidity and mortality. Nonosmotic secretion of arginine vasopressin is central to the pathophysiology of hyponatremia in patients with euvolemic hyponatremia (due to, for example, the syndrome of inappropriate secretion of antidiuretic hormone) and those with hypervolemic hyponatremia secondary to congestive heart failure or cirrhosis with ascites. Arginine vasopressin-receptor antagonists, a novel class of agents that block the action of arginine vasopressin on V2 receptors in the renal collecting ducts, may provide specific correction of sodium and water imbalance in hyponatremia by promoting free water clearance while sparing electrolytes (aquaresis). Arginine vasopressin antagonism would treat hyponatremia directly, as opposed to other therapies that do not address the effects of arginine vasopressin dysregulation directly.
 ...
PMID:Vasopressin dysregulation and hyponatremia in hospitalized patients. 1771 57

Several fluid retentive states such as heart failure, cirrhosis of the liver, and syndrome of inappropriate antidiuretic hormone secretion are associated with inappropriate elevation in plasma levels of arginine vasopressin (AVP), a neuropeptide that is secreted by the hypothalamus and plays a critical role in the regulation of serum osmolality and in circulatory homeostasis. The actions of AVP are mediated by three receptor subtypes V1a, V2, and V1b. The V1a receptor regulates vasodilation and cellular hypertrophy while the V2 receptor regulates free water excretion. The V1b receptor regulates adrenocorticotropin hormone release. Conivaptan is a nonpeptide dual V1a/V2 AVP receptor antagonist. It binds with high affinity, competitively, and reversibly to the V1a/V2 receptor subtypes; its antagonistic effect is concentration dependent. It inhibits CYP3A4 liver enzyme and elevates plasma levels of other drugs metabolized by this enzyme. It is approved only for short-term intravenous use. Infusion site reaction is the most common reason for discontinuation of the drug. In animals conivaptan increased urine volume and free water clearance. In heart failure models it improved hemodynamic parameters and free water excretion. Conivaptan has been shown to correct hyponatremia in euvolemic or hypervolemic patients. Its efficacy and safety for short-term use have led to the Food and Drug Administration (FDA) approval of its intravenous form for the correction of hyponatremia in euvolemic and hypervolemic states. Despite its ability to block the action of AVP on V1a receptors, no demonstrable benefit from this action was noted in patients with chronic compensated heart failure and it is not approved for this indication. Consideration should be given to further evaluation of its potential benefits in patients with acute decompensated heart failure.
 ...
PMID:Conivaptan: a dual vasopressin receptor v1a/v2 antagonist [corrected]. 1791 59

Hyponatremia is the most frequently encountered electrolyte disturbance in hospitalized patients. It is usually caused by dysregulation of arginine vasopressin (AVP) homeostasis which accompanies disorders associated with water retention such as congestive heart failure and cirrhosis, or follows euvolemic states such as syndrome of inapprioprate secretion of antidiuretic hormone. Available therapy, i.e. restriction of fluid intake, saline and diuretics, is often ineffective with unpredictable results and potentially serious side effects. Recent clinical trials with non-peptide AVP receptor antagonists (vaptans) have indicated that these drugs are effective in the treatment of hyponatremia. Vaptans lead to aquaresis, an electrolyte-sparing excretion of free water, that results in the correction of serum sodium concentration. Until now the Food and Drug Administration in the USA has approved the use of intravenous conivaptan for treatment of euvolemic hyponatremia. In this article, we review results from recent clinical trials on vaptans (lixivaptan, tolvaptan, conivaptan and satavaptan) which showed their efficacy in the treatment of hyponatremia.
 ...
PMID:[Vasopressin antagonists in treatment of hyponatremia]. 1801 83

Impaired urinary dilution leading to water retention and hyponatremia may occur in patients with cardiac failure, cirrhosis, pregnancy, oxytocin administration, hypothyroidism, glucocorticoid, and mineralocorticoid deficiency. The mechanisms for these defects predominantly involve the nonosmotic stimulation of arginine vasopressin release with up-regulation of aquaporin 2 water channel expression and trafficking to the apical membrane of the principal cells of the collecting duct. These perturbations are reversed by V2 vasopressin receptor antagonists. In contrast, urinary concentration defects leading to polyuria are vasopressin resistant. They may involve several factors, such as impaired countercurrent concentration secondary to down-regulation of Na-K-2Cl cotransporter. Vasopressin-resistant down-regulation of aquaporin 2 expression has also been described as a factor in impaired urinary concentration.
 ...
PMID:Vasopressin and aquaporin 2 in clinical disorders of water homeostasis. 1851 89

Impaired urinary dilution leading to water retention and hyponatremia may occur in patients with cardiac failure, cirrhosis, pregnancy, hypothyroidism, glucocorticoid and mineralocorticoid deficiency. The mechanisms for these defects predominantly involve the non-osmotic stimulation of arginine vasopressin release with upregulation of aquaporin 2 water channel expression and trafficking to the apical membrane of the principal cells of the collecting duct. These perturbations are reversed by V2 vasopressin receptor antagonists. In contrast, urinary concentration defects leading to polyuria are vasopressin-resistant. They may involve several factors, such as impaired counter-current concentration secondary to downregulation of Na-K-2Cl co-transporter. Vasopressin-resistant downregulation of aquaporin 2 expression has also been described as a factor in impaired urinary concentration.
 ...
PMID:Molecular mechanisms of clinical concentrating and diluting disorders. 1865 7

Hyponatremia is a frequent complication of advanced cirrhosis related to an impairment in the renal capacity to eliminate solute-free water that causes a retention of water that is disproportionate to the retention of sodium, thus causing a reduction in serum sodium concentration and hypo-osmolality. The main pathogenic factor responsible for hyponatremia is a nonosmotic hypersecretion of arginine vasopressin (or antidiuretic hormone) from the neurohypophysis related to circulatory dysfunction. Hyponatremia in cirrhosis is associated with increased morbidity and mortality. There is evidence suggesting that hyponatremia may affect brain function and predispose to hepatic encephalopathy. Hyponatremia also represents a risk factor for liver transplantation as it is associated with increased frequency of complications and impaired short-term survival after transplantation. The current standard of care based on fluid restriction is unsatisfactory. Currently, a new family of drugs, known as vaptans, which act by antagonizing specifically the effects of arginine vasopressin on the V2 receptors located in the kidney tubules, is being evaluated for their role in the management of hyponatremia. The short-term treatment with vaptans is associated with a marked increase in renal solute-free water excretion and improvement of hyponatremia. Long-term administration of vaptans seems to be effective in maintaining the improvement of serum sodium concentration, but the available information is still limited. Treatment with vaptans represents a novel approach to improving serum sodium concentration in cirrhosis.
 ...
PMID:Hyponatremia in cirrhosis: pathogenesis, clinical significance, and management. 1867 3

Hypervolemic hyponatremia is common in patients with decompensated cirrhosis, resulting from solute-free water retention caused by the stimulation of V2 receptors of the distal nephron by relatively high circulating levels of arginine vasopressin (AVP, a nonapeptide). A nonosmotic secretion of AVP by the hypothalamo-neurohypophysial system is responsible for high plasma AVP concentrations. This hypersecretion of AVP is triggered by a decrease in effective arterial blood volume and arterial pressure caused by splanchnic/systemic vasodilation. Hyponatremia is an independent predictor of mortality in patients with cirrhosis; however, it is still unknown if hyponatremia by itself plays a role or if it is a simple marker of the severity of liver disease. Pharmacological treatments of hypervolemic hyponatremia using drugs that antagonize the binding of AVP to V2 receptors are under evaluation in patients with cirrhosis.
 ...
PMID:Hyponatremia in cirrhosis. Pathophysiology, prevalence, prognostic value, treatment. 1931 78


<< Previous 1 2 3 4 5 6 7 8 Next >>