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)

Patients with cirrhosis exhibit characteristic hemodynamic changes with a hyperkinetic circulation and an abnormal distribution of the blood volume and neurohumoral regulation. Their plasma and noncentral blood volumes are increased, and the central and arterial blood volume and systemic vascular resistance are decreased. A peripheral arterial vasodilatation may be of pathogenic importance to the low systemic vascular resistance as it directly correlates to the degree of central hypovolemia. It may therefore be an important element in the development of the low arterial blood pressure and hyperkinetic circulation in cirrhosis. Various vasodilators such as atrial natriurectic peptide, calcitonin gene-related peptide, adrenomedullin, and nitric oxide are among potential candidates in the arterial vasodilatation in cirrhosis. Besides enhanced sympathetic nervous activity, activation of the renin-angiotensin-aldosterone system, and elevated circulating vasopressin, endothelin-1 may also be implicated in the hemodynamic counter-regulation in cirrhosis. Recent research has focused on the assertion that the hemodynamic and neurohumoral abnormalities in cirrhosis are part of a general circulatory dysfunction influencing the course of the disease.
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PMID:Circulatory abnormalities in cirrhosis with focus on neurohumoral aspects. 935 62

Patients with cirrhosis and portal hypertension exhibit characteristic haemodynamic changes with a hyperkinetic systemic circulation, an abnormal distribution of the blood volume and neurohumoral dysregulation. Their plasma and noncentral blood volumes are increased, but the central and arterial blood volume and systemic vascular resistance are decreased. A systemic and splanchnic vasodilatation is of pathogenic importance to the low systemic vascular resistance and abnormal volume distribution. These are important elements in the development of the low arterial blood pressure and hyperkinetic circulation in cirrhosis. Various vasodilators such as nitric oxide, calcitonin gene-related peptide, and adrenomedullin are among potential candidates in the vasodilatation in cirrhosis. Besides reflex induced enhanced sympathetic nervous activity, activation of the renin-angiotensin-aldosterone system, and elevated circulation vasopressin, endothelin-1 may also be implicated in the haemodynamic counter-regulation in cirrhosis. Recent research has focused on the assertion that the haemodynamic and neurohumoral abnormalities in cirrhosis are part of a general circulatory dysfunction, influencing the course of the disease with reduction of kidney function and sodium-water retention as the outcome.
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PMID:Haemodynamics and fluid retention in liver disease. 975 6

Increased circulating levels of the neuropeptide calcitonin gene-related peptide (CGRP) have recently been described in cirrhosis. CGRP is formed by alternative transcription of the calcitonin/alpha-CGRP gene, which also gives rise to calcitonin (CT). This study was undertaken to determine circulating plasma concentrations of CT in patients with cirrhosis in relation to the severity of disease and the plasma level of CGRP. Moreover, the kinetics of CT was evaluated for different organ systems by determination of arteriovenous extraction. Thirty-nine patients with cirrhosis (Child-Turcotte classes A/B/C, n = 10/22/7) were studied under a hemodynamic investigation and compared with 13 control subjects without liver disease. CT and CGRP in arterial and organ venous plasma were determined by radioimmunoassays. In patients with cirrhosis, circulating CT was significantly increased versus control (12.1 v 6.9 pmol/L, P < .001) and a direct relation to the Child-Turcotte score was found (P < .005). The increased circulating CT was directly correlated with increased CGRP (r = .29, P < .05). No significant arteriovenous extraction of circulating CT was observed in the kidneys, hepatosplanchnic system, lower extremities, or peripheral circulation, but there was a substantial rate of pulmonary disposal and clearance (P < .005). It is concluded that in addition to thyroid production, increased circulating CT in cirrhosis is most likely due to overexpression of the calcitonin/alpha-CGRP gene, with relation to the severity of disease and possibly to an accompanying pulmonary dysfunction.
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PMID:Increased circulating calcitonin in cirrhosis. Relation to severity of disease and calcitonin gene-related peptide. 1064 63

In the liver, the autonomic nervous system plays an important role in degenerative and inflammatory changes. The aim of the present study was to investigate the distribution of neuronal fibres containing neuropeptides in livers of 5 patients with cirrhosis by immunocytochemical localization at the light and electron microscopical level of substance P (SP), neuropeptide Y (NPY), somatostatin (SOM), and calcitonin gene-related peptide (CGRP). In patients with alcoholic cirrhosis, a decreased number of neuronal fibres was found in the portal tract and fibrous septa as well as in the sinusoids of regenerative nodules. NPY- and SP-immunoreactive neuronal fibres were more numerous than CGRP-containing fibres. They were located mainly in portal tracts. These findings led to the conclusion that peptidergic innervation plays a role in inflammatory and fibrotic changes in cirrhotic liver.
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PMID:Immunocytochemical study on the liver innervation in patients with cirrhosis. 1114 32

Patients with cirrhosis and portal hypertension exhibit characteristic hemodynamic changes with hyperkinetic systemic circulation, abnormal distribution of blood volume and neurohumoral dysregulation. Their plasma and noncentral blood volumes are increased. Splanchnic vasodilation is of pathogenic significance to the low systemic vascular resistance and abnormal volume distribution of blood, which are important elements in the development of the concomitant cardiac dysfunction, recently termed 'cirrhotic cardiomyopathy'. Systolic and diastolic functions are impaired with direct relation to the degree of liver dysfunction. Significant pathophysiological mechanisms are reduced beta-adrenergic receptor signal transduction, defective cardiac excitation-contraction coupling and conductance abnormalities. Vasodilators such as nitric oxide and calcitonin gene-related peptide are among the candidates in vasodilation and increased arterial compliance. Reflex-induced, enhanced sympathetic nervous system activity, activation of the renin-angiotensin aldosterone system, and elevated circulation vasopressin and endothelin-1 are implicated in hemodynamic counter-regulation in cirrhosis. Recent research has focused on the assertion that the hemodynamic and neurohumoral abnormalities in cirrhosis are part of a general cardiovascular dysfunction, influencing the course of the disease with the reduction of organ function, with sodium and water retention as the outcome. These aspects are relevant to therapy.
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PMID:Splanchnic and systemic hemodynamic derangement in decompensated cirrhosis. 1124 Mar 79

This study investigated the incidence and severity of hepatic osteodystrophy in patients with posthepatitic liver cirrhosis, and the role of hepatocellular injury in bone loss. Twenty-four patients (15 females and 9 males, mean age 49 +/- 13 years) with posthepatitic cirrhosis were enrolled in this study. The control group consisted of 22 healthy age and sex matched adults. The bone mineral density (BMD) was evaluated by dual energy x-ray absorptiometry of the L1-L4 vertebral bodies. A detailed questionnaire was used to assess the epidemiological findings. A statistically significant decrease in BMD of the patients was observed. There were no significant differences in the alkaline phosphatase, parathyroid hormone, calcitonin, 25-hydroxyvitamin D, osteocalcin, free testosterone, luteinizing hormone, follicle stimulating hormone, and estradiol levels, oral calcium intake, urinary calcium, phosphorus and hydroxypyroline excretion between patients and controls. The control group smoked more cigarettes, consumed more coffee and meat, and were exposed the sun light for a longer period than the study group. Multiple regression analysis showed that osteopenia depends significantly on the extent of liver disease. The data shows that the patients with posthepatitic cirrhosis had osteopenia, and that cirrhosis was a direct and independent risk factor.
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PMID:Osteodystrophy in posthepatitic cirrhosis. 1167 84

Patients with cirrhosis and portal hypertension exhibit characteristic haemodynamic changes with a hyperkinetic systemic circulation, abnormal distribution of the blood volume, and neurohumoral dysregulation. Moreover, the circulating levels of several vasoactive substances may be elevated. Splanchnic vasodilatation is of pathogenic significance for the low systemic vascular resistance and abnormal volume distribution, which are important elements in the development of the concomitant cardiac dysfunction, recently termed cirrhotic cardiomyopathy. The systolic and diastolic functions are impaired with direct relation to the degree of liver dysfunction. Significant pathophysiological mechanisms seem to include a reduced beta-adrenergic receptor signal transduction, defective cardiac excitation-contraction coupling, and conductance abnormalities. Various vasodilators. such as nitric oxide and calcitonin gene-related peptide, are among candidates in the vasodilatation and the increased arterial compliance recently described in advanced cirrhosis. Reflex-induced enhanced sympatho-adrenal activity, activation of the renin-angiotensin-aldosterone system, and elevated circulating vasopressin and endothelin-1 are implicated in the haemodynamic counter-regulation in cirrhosis. Recent research has focused on the assertion that the haemodynamic and neurohumoral abnormalities in cirrhosis are part of a general cardiovascular dysfunction influencing the course of the disease, with reduction of organ function and sodium-water retention as the outcome. These aspects are relevant to therapy.
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PMID:Vasoactive substances in the circulatory dysfunction of cirrhosis. 1168 31

The present study investigated the circulating levels and cerebral fluxes of calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and neuropeptide Y (NPY) and their relation to cerebral blood flow (CBF) during normoventilation and hyperventilation in patients with fulminant hepatic failure (FHF). Sixteen patients with FHF were studied and compared to six patients with cirrhosis of the liver. CBF was measured by the (133)Xe wash-out technique. Blood samples were obtained simultaneously from the artery and internal jugular bulb. Concentrations of CGRP and VIP were higher in FHF than in cirrhosis, 87 (55-218) vs. 29 (21-42) pmol/L, and 11 (6-29) vs. 5 (3-9)pmol/L, respectively. NPY was normal, none of the measures were related to CBF, and there was no detectable net brain fluxes. Hyperventilation did not alter any of the measures. CGRP and VIP in FHF seem to reflect hemodynamic changes in the systemic rather than in the cerebral circulation.
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PMID:Circulating levels of neuropeptides (CGRP, VIP, NPY) in patients with fulminant hepatic failure. 1188 8

The endocannabinoid anandamide and cannabinoid (CB) receptors have been implicated in the hypotension in various forms of shock and in advanced liver cirrhosis. Anandamide also activates vanilloid TRPV(1) receptors on sensory nerve terminals, triggering the release of calcitonin gene-related peptide which elicits vasorelaxation in isolated blood vessels in vitro. However, the contribution of TRPV(1) receptors to the in vivo hypotensive effect of anandamide is equivocal. We compared the cardiac performance of anaesthetized TRPV(1) knockout (TRPV(1)(-/-)) mice and their wild-type (TRPV(1)(+/+)) littermates and analysed in detail the haemodynamic effects of anandamide using the Millar pressure-volume conductance catheter system. Baseline cardiovascular parameters and systolic and diastolic function at different preloads were similar in TRPV(1)(-/-) and TRPV(1)(+/+) mice. The predominant hypotensive response to bolus intravenous injections of anandamide and the associated decrease in cardiac contractility and total peripheral resistance (TPR) were similar in TRPV(1)(+/+) and TRPV(1)(-/-) mice, as was the ability of the CB(1) receptor antagonist SR141716 to completely block these effects. In TRPV(1)(+/+) mice, this hypotensive response was preceded by a transient, profound drop in cardiac contractility and heart rate and an increase in TPR, followed by a brief pressor response, effects which were unaffected by SR141716 and were absent in TRPV(1)(-/-) mice. These results indicate that mice lacking TRPV(1) receptors have a normal cardiovascular profile and their predominant cardiovascular depressor response to anandamide is mediated through CB(1) receptors. The role of TRPV(1) receptors is limited to the transient activation of the Bezold-Jarisch reflex by very high initial plasma concentrations of anandamide.
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PMID:Haemodynamic profile and responsiveness to anandamide of TRPV1 receptor knock-out mice. 1512 5

Chronic liver diseases commonly result in liver fibrosis, and eventually liver cirrhosis. In the last decade, a new theory explaining liver fibrosis has been established. Accordingly, the development of liver fibrosis due to chronic liver diseases is thought to be mediated by inflammatory cells. They release fibrogenic mediators such as transforming growth factors (TGF)-beta, which are considered to be responsible for the activation and transformation of fat-storing cells. Recently, the involvement of mast cells and peripheral and autonomic nervous system in the fibrogenesis has been suggested. This study was aimed to establish the presence and distribution of mast cells and nerve fibers in the rat liver in the light of their implication in liver inflammatory and fibrotic disorders. Mast cells and afferent (sensory) fibers were detected immunohistochemically. An immunofluorescent method was applied to demonstrate tryptase and serotonin (SER) in the mast cells, while the primary sensory neuronal processes were identified by using antibodies against their marker calcitonin gene-related peptide (CGRP) and the proinflammatory mediator substance P (SP). The portal tracts and fibrous septa contained numerous mast cells, which exhibited strong immuno-reactivity to tryptase and SER. SER-positive nerve fibers were also found. It is generally accepted that no nerve fibers are present in the hepatic lobules, but the current investigation clearly demonstrates availability of CGRP-, SP, and SER-immunoreactive nerve fibers there. Our results indicate that in the rat liver portal tracts and hepatic lobules there are numerous mast cells, sensory and autonomic nerve fibers, which may be involved in liver injury by the inflammatory mediators they release.
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PMID:Relevance of mast cells and hepatic lobule innervation to liver injury. 1547 May 32


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