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

Endothelin-1, a potent vasoconstrictor peptide with 21 amino acid residues, is released by the vascular endothelium. Plasma immunoreactive endothelin levels were measured in 23 patients with cirrhosis and in 20 healthy subjects. Concentrations were significantly lower in patients with non-uraemic cirrhosis than in normal subjects (19.4 +/- 8.9 pmol/l vs. 48.8 +/- 24.8 pmol/l, p less than 0.002). Plasma renin, aldosterone, atrial natriuretic peptide, arginine-vasopressin and catecholamines did not show significant correlations with plasma endothelin-1 levels. Furthermore, there were no significant differences in plasma endothelin levels for etiology of cirrhosis, presence of ascites or varices. These data suggest that low circulating endothelin may be involved in the development or maintenance of systemic vasodilatation in cirrhosis.
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PMID:Plasma endothelin levels in cirrhotic subjects. 138 39

New trends in tests for coagulation and fibrinolysis and advances in diagnosis for the hypercoagulable state and utilization of immunological techniques such as various polyclonal and monoclonal antibodies are reported. We discussed (1) the new markers for hypercoagulable states, (2) differential diagnosis of disseminated intravascular coagulation (DIC) and abnormalities of coagulation in liver cirrhosis (LC), and (3) new markers for fibrinolysis and vascular function. Thrombin-antithrombin III complex (TAT) levels were higher in thrombotic diseases than in healthy controls. Therefore, TAT should be a good marker for hypercoagulation as fibrinopeptide A (FPA) and soluble fibrin monomer complex (SFMC). Measurement of TAT, plasma-alpha 2 plasmin inhibitor complex (PIC), and D dimer were useful for differential diagnosis of DIC and liver cirrhosis. t-PA-PAI complex correlated well with t-PA, but not with fibrinolytic parameters such as PIC. The t-PA-PAI complex may be a good marker for the function of the vascular endothelium.
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PMID:[A new advance in theory of blood coagulation and fibrinolysis and its practical application]. 190 12

The authors report the results of postmortem histopathological studies in 12 patients who had been treated by endoscopic obliteration of esophagogastric varices with Bucrylate (isobutyl-2-cyanoacrylate). All patients had cirrhosis; 11 patients were Pugh classe C. Eleven patients had esophageal injections. Acute esophageal lesions were characterized by ulcerations in obliterated varices and diffusion of Bucrylate into the esophageal wall. Chronic lesions were characterized by disappearance of varices and Bucrylate, extending fibrosis of the esophageal wall and re-epithelialization of the mucosa. In one patient who had received gastric injections only, non ulcerated Bucrylate filled gastric varices were seen. Bucrylate seems to have a dual action on esophageal varices: immediate obliteration and acute necrosis of the vascular endothelium. Necrosis causes diffusion of Bucrylate through the esophageal wall, and later, secondary fibrosis whereas the product is progressively eliminated into the esophageal lumen.
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PMID:[Endoscopic obturation of esophagogastric varices with bucrylate. II. Morphologic study based on 12 autopsy cases]. 378 Nov 61

In 1987 it was demonstrated that the vascular endothelium produces nitric oxide, a gas that acts as highly labile but very potent relaxing factor for the vascular smooth muscle. During the last 5-6 years, a series of discoveries from many different avenues of research came together revealing the major biological role of NO as neurotransmitter in the nervous system and other parts of the body, as a potent vasodilating and cytoprotective substance, as mediator of endotoxin-induced cytotoxicity and as a substance involved in various disorders such as liver cirrhosis and reactions of the immune system. Recent studies suggest that in addition to VIP and ATP, NO may mediate non-adrenergic, non-cholinergic (NANC) inhibition of gastrointestinal smooth muscle and related inhibitory junction potentials. The identity of action of NO and NANC nerve stimulation has been supported by numerous in vitro and in vivo studies on esophagus, stomach, small intestine and colon of various species including humans.
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PMID:[Nitric oxide in regulation of gastrointestinal and biliary motility]. 797 89

Nitric oxide derived from vascular endothelium is a potent vasodilator that plays a key role in the homeostasis of blood pressure. Because cirrhotic patients tend to have low arterial pressure, we measured in 51 patients and 10 control subjects serum nitrite and nitrate levels as an index of in vivo nitric oxide generation. We also measured plasma endotoxin, a substance frequently increased in cirrhotic patients and known to induce nitric oxide synthesis. Cirrhotic patients showed significant increases in serum nitrite/nitrate and plasma endotoxin compared with controls. Values were particularly increased in patients with decompensated cirrhosis, as manifested by ascites with or without functional kidney failure. High serum nitrite/nitrate levels were associated with high plasma renin activity, high aldosterone and antidiuretic hormone levels and low urinary excretion of sodium. In addition, serum nitrite/nitrate levels significantly correlated with endotoxemia. Oral administration of colistin to 15 cirrhotic patients reduced significantly plasma endotoxin levels (p < 0.01) and serum nitrite/nitrate levels (p < 0.05). Because endotoxin enhances the expression of inducible nitric oxide synthase, our results suggest that circulating endotoxin in cirrhosis is responsible for excessive synthesis and release of nitric oxide by the vasculature. These findings might explain the hemodynamic dysfunction seen in cirrhotic patients.
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PMID:Increased serum nitrite and nitrate levels in patients with cirrhosis: relationship to endotoxemia. 822 20

Endothelin, one of the most potent vasoconstrictors known today, is released by the vascular endothelium. Patients after liver transplantation and patients with liver cirrhosis show significantly higher plasma endothelin concentrations and significantly reduced results in the quantitative liver function tests (ICG-HL, GEC, Lidocaine-HL, MEGX) compared with healthy control persons. The plasma endothelin concentrations were better correlated with the more liver bloodflow dependent function tests (ICG-HL, Lidocaine-HL) than with the more metabolic-capacity dependent function tests (GEC, MEGX). As cyclosporine A in vitro can increase the liberation of endothelin, we conclude that in patients after liver transplantation an endothelin mediated cyclosporine induced hepatotoxicity might be the reason for the demonstrated association.
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PMID:[Increased plasma endothelin concentrations in patients after liver transplantation and in liver cirrhosis]. 847 3

Prostaglandins (PGs) are arachidonic acid (AA) derivatives via the PG endoperoxyde H synthase (PGHS) complex. Two PGHS isoforms have been recognized, constitutive (PGHS-1) and inducible (PGHS-2), respectively. Within the kidney, vascular endothelium mainly produces PGI2; the whole glomerulus synthesizes several prostanoids, the predominant AA metabolite in humans being PGI2; tubules and medullary interstitial cells produce mainly PGE2. Renal PGs modulates the action of other hormones and autacoids involved in the regulation of renal hemodynamics, glomerular filtration and the renal handling of sodium and water. Renal PGs are, at least in part, excreted into urine. Measurement of urinary PGs or their metabolites has been found to provide a reliable estimation of basal as well as stimulated PG synthesis. Patients with cirrhosis of the liver show an increased renal synthesis of vasodilating PGs, as indicated by the high urinary excretion of PGs and/or their metabolites. Administration of nonsteroidal anti-inflammatory drugs (NSAIDs) to these patients causes a profound reduction in renal blood flow and glomerular filtration rate, a reduction in sodium excretion, and an impairment of free water clearance. These data clearly indicate that the increased renal synthesis of vasodilating PGs has a relevant role in maintaining renal hemodynamics, sodium and water excretion in a clinical setting characterized by a reduction of effective plasma volume and a striking activation of the major vasoconstricting systems, namely the renin-angiotensin-aldosterone, the sympathetic nervous system, and vasopressin. Patients with hepato-renal syndrome have a reduced renal synthesis of vasodilating PGE2 in the setting of a striking activation of endogenous vasoconstrictors and a maintained or increased renal production of thromboxane A2. Therefore, an imbalance between vasoconstricting systems and the renal vasodilator PGE2 was proposed to explain the renal failure observed in this condition. The urinary excretion of 2-3-dinor 6-keto-PGF1 alpha, an index of systemic PGI2 synthesis, is increased in patients with cirrhosis and hyperdynamic circulation, thus raising the possibility that systemic synthesis of PGI2 may contribute to the arterial vasodilatation of these patients. Finally, administration of exogenous prostanoids to patients with cirrhosis is not effective either in ameliorating renal function or in preventing the deleterious effect of NSAIDs.
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PMID:Arachidonic acid derivatives and renal function in liver cirrhosis. 935 64

Hypotension, low systemic vascular resistance and reduced sensitivity to vasoconstrictor are features of hyperdynamic syndrome in portal hypertension (PH) and are pathogenetic factors triggering most serious clinical complications of liver cirrhosis. Nitric oxide (NO) is a powerful vasodilating agent, released from vascular endothelium cell and effecting relaxation of vascular smooth muscle. An increased release of NO has been proposed to play a role in the pathogenesis of vasodilation and vascular hypocontractility associated with PH. In agreement with this hypothesis, the whole-body production of NO has been found to be increased in PH, and the measurement of NOS mRNA expression in different organs suggest that the splanchnic vascular system is a major source of NO release. Consequently, NO could play a role in the development of the splanchnic hyperaemia, collateral circulation and portal hypertensive gastropathy. Furthermore, increased generation of NO in central circulation likely accounts for pulmonary vasorelaxation and cardiac dysfunction found in cirrhosis. By contrast, PH-associated endothelial dysfunction seems to invalidate the capability of intrahepatic and intrarenal vasculature to produce NO. A deficient NO release in these vascular territories might contribute to enhancement of PH and development of the hepatorenal syndrome. Overall NO hyperproduction is either the cause (induction of iNOS) or the consequence (stimulation of ecNOS) of the hyperdynamic syndrome. This incertitude results from the yet undefined significance of mild and transitory activation of the endotoxin-cytokines axis for iNOS induction and contradictory data on specific iNOS and ecNOS activities. A contribution of each isoform of NOS to pathogenesis of the hyperdynamic syndrome probably depends on the model of PH in animal studies and the aetiology or severity of cirrhosis in human studies.
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PMID:The role of nitric oxide in portal hypertensive systemic and portal vascular pathology. 939 80

Arachidonic acid (AA) can undergo monooxygenation or epoxidation by enzymes in the cytochrome P450 (CYP) family in the brain, kidney, lung, vasculature, and the liver. CYP-AA metabolites, 19- and 20-hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatrienoic acids (EETs) and diHETEs have different biological properties based on sites of production and can be stored in tissue lipids and released in response to hormonal stimuli. 20-HETE is a vasoconstrictor, causing blockade of Ca(++)-activated K(+) (KCa) channels. Inhibition of the formation of nitric oxide (NO) by 20-HETE mediates most of the cGMP-independent component of the vasodilator response to NO. 20-HETE elicits a potent dilator response in human and rabbit pulmonary vascular and bronchiole rings that is dependent on an intact endothelium and COX. 20-HETE is also a vascular oxygen sensor, inhibits Na(+)/K(+)-ATPase activity, is an endogenous inhibitor of the Na(+)-K(+)-2Cl(-)cotransporter, mediates the mitogenic actions of vasoactive agents and growth factors in many tissues and plays a significant role in angiogenesis. EETs, produced by the vascular endothelium, are potent dilators. EETs hyperpolarize VSM cells by activating KCa channels. Several investigators have proposed that one or more EETs may serve as endothelial-derived hyperpolarizing factors (EDHF). EETs constrict human and rabbit bronchioles, are potent mediators of insulin and glucagon release in isolated rat pancreatic islets, and have anti-inflammatory activity. Compared with other organs, the liver has the highest total CYP content and contains the highest levels of individual CYP enzymes involved in the metabolism of fatty acids. In humans, 50-75% of CYP-dependent AA metabolites formed by liver microsomes are omega/omega-OH-AA, mainly w-OH-AA, i.e. 20HETE, and 13-28% are EETs. Very little information is available on the role of 19- and 20-HETE and EETs in liver function. EETs are involved in vasopressin-induced glycogenolysis, probably via the activation of phosphorylase. In the portal vein, inhibition of EETs exerts profound effects on a variety of K-channel activities in smooth muscles of this vessel. 20-HETE is a weak, COX-dependent, vasoconstrictor of the portal circulation. EETs, particularly 11,12-EET, cause vasoconstriction of the porto-sinusoidal circulation. Increased synthesis of EETs in portal vessels and/or sinusoids or increased levels in blood from the meseneric circulation may participate in the pathophysiology of portal hypertension of cirrhosis. CYP-dependent AA metabolites are involved in the pathophysiology of portal hypertension, not only by increasing resistance in the porto-sinusoidal circulation, but also by increasing portal inflow through mesenteric vasodilatation. In patients with cirrhosis, urinary 20-HETE is several-fold higher than PGs and TxB2, whereas in normal subjects, 20-HETE and PGs are excreted at similar rates. Thus, 20-HETE is probably produced in increased amounts in the preglomerular microcirculation accounting for the functional decrease of flow and increase in sodium reabsorption. In conclusion, CYP-AA metabolites represent a group of compounds that participate in the regulation of liver metabolic activity and hemodynamics. They appear to be deeply involved in abnormalities related to liver diseases, particularly cirrhosis, and play a key role in the pathophysiology of portal hypertension and renal failure.
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PMID:Role of cytochrome P450-dependent arachidonic acid metabolites in liver physiology and pathophysiology. 1462 96

Endothelial adhesion molecules (AM) play an important role in the pathogenesis of several diseases namely infections, neoplasms and chronic inflammatory diseases. Because alcoholic hepatitis and even atherosclerosis are considered as inflammatory diseases and ethanol may modulate inflammatory response, several researchers have investigated the link between ethanol consumption, endothelial AM and the development of both processes. In vitro, animal and human studies have analysed the effects of ethanol and non-alcoholic components of alcoholic beverages on inflammatory biomarkers of atherosclerosis such as monocyte and endothelial AM. These studies have shown that both ethanol and non-alcoholic components of alcoholic beverages, mainly polyphenols, reduce intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin expression of vascular endothelium, as well as monocyte adhesion to this endothelium. These data suggest that moderate alcohol intake has an anti-inflammatory effect on the cardiovascular system and reduces early serum markers of atherosclerosis. However, at higher doses ethanol may exert an inflammatory effect. In fact, chronic alcoholics exhibit significantly higher serum levels of endothelial AM than abstainers and moderate drinkers. In addition, an upregulation of E-selectin, ICAM-1 and VCAM-1 is also detected in liver biopsies obtained from patients with alcoholic hepatitis and cirrhosis. The clinical usefulness of the measurement of serum endothelial AM is discussed.
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PMID:The effect of alcohol consumption on endothelial adhesion molecule expression. 1469 Aug 73


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