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)

Anion gap (AG) is a calculated value commonly used in clinical practice. It approximates the difference between the concentration of unmeasured anions (UA) and unmeasured cations (UC) in serum. At present, the reference range of anion gap has been lowered from 8-16 to 3-11 mmol/l because of the changes in technique for measuring electrolyte. However, clinicians and textbooks still refer and use the old reference value of 8-16 mmol/l. This may lead to misinterpretation of the value of anion gap. Our study updated the value of anion gap in clinical diagnosis and laboratory evaluation. Criteria for using anion gap were also suggested. We analyzed serum electrolyte using the Beckman Synchron CX5. The anion gap was calculated from the formula: [Na(+)-(Cl(-)+HCO(3)(-))]. We estimated the reference range using the non-parametric percentile estimation method. The reference range of anion gap obtained from 124 healthy volunteers was 5-12 mmol/l, which was low and confirmed the reports from other studies (3-11 mmol/l) using ion-selective electrode. From the retrospective study on the 6868 sets of serum electrolyte among hospitalized patients, we found the incidences of normal, increased, and decreased anion gaps were 59.5%, 37.6%, and 2.9%, respectively. The mean and central 90% range of increased anion gap were 16 and 13-20 mmol/l, which was lower than those reported in previous study (25 and 19-28 mmol/l). Anion gap exceeding 24 mmol/l was rare. The mean and central 90% range of decreased anion gap were 3 and 2-4 mmol/l, which were lower than those reported in previous study (6 and 3-8 mmol/l). The value of less than 2 mmol/l was rare. The most common causes of increased anion gap (hypertensive disease, chronic renal failure, malignant neoplasms, diabetes mellitus and heart diseases) and decreased anion gap (liver cirrhosis and nephrotic syndrome) in this study were similar to those in previous studies. We found two cases of IgG multiple myeloma with anion gap of 2 mmol/l. In conclusion, clinicians and laboratorians can use the anion gap as clue in quality control. They can check the incidences of increased and decreased anion gap. If one finds high incidence of increased anion gap (>24 mmol/l) or decreased anion gap (<2 mmol/l), one should check the quality control of electrolyte and whether the patients were hypoalbuminemia or hyperglobulinemia. An anion gap exceeding 24 mmol/l will suggest the presence of metabolic acidosis. It is very rare to find anion gap with the negative sign.
 ...
PMID:Update on value of the anion gap in clinical diagnosis and laboratory evaluation. 1136 34

The psychoactive properties of cannabinoids, the biologically active constituents of the marijuana plant, have long been recognized. Recent research has revealed that cannabinoids elicit not only neurobehavioral, and immunological, but also profound cardiovascular effects. Similar effects can be elicited by the endogenous ligand arachidonyl ethanolamine (anandamide) and 2-arachidonoyl-glycerol. The biological effects of cannabinoids are mediated by specific receptors. Two cannabinoid receptors have been identified so far: CB1-receptors are expressed by different cells of the brain and in peripheral tissues, while CB2-receptors were found almost exclusively in immune cells. Through the use of a selective CB1 receptor antagonist and CB1 receptor-knockout mice the hypotensive and bradycardic effects of cannabinoids in rodents could be attributed to activation of peripheral CB1 receptors. In hemodynamic studies using the radioactive microsphere technique in anesthetized rats, cannabinoids were found to be potent CB1-receptor dependent vasodilators in the coronary and cerebrovascular beds. Recent findings implicate the endogenous cannabinoid system in the pathomechanism of haemorrhagic, endotoxic and cardiogenic shock. Finally, there is evidence that the extreme mesenteric vasodilation, portal hypertension and systemic hypotension present in advanced liver cirrhosis are also mediated by the endocannabinoid system. These exciting, recent research developments indicate that the endogenous cannabinoid system plays an important role in cardiovascular regulation, and pharmacological manipulation of this system may offer novel therapeutic approaches in a variety of pathological conditions.
 ...
PMID:[Cardiovascular effects of cannabinoids]. 1214 Aug 59

Although cannabinoids have been recreationally employed for thousands of years, it was not until the discovery of their specific receptors, in the early nineties, that the molecular basis of cannabinoid activity have began to be understood. Growing research in this field has demonstrated not only that the action of cannabinoids in mammals is mainly receptor-mediated, but also that endogenous cannabinoids, such as anandamide, are produced, metabolized, and taken up across the cell membrane through a facilitated uptake process. The exogenous administration of cannabinoids, as well as the manipulation of their endogenous levels have been related to a variety of effects, such as analgesia, impairment of cognition and learning, appetite enhancement and peripheral vasodilation. Hence, the endocannabinoid system, including the CB1 and CB2 receptors, the metabolizing enzyme fatty acid amide hydrolase and the anandamide transporter, is a potential target for the development of novel therapeutic drugs in the treatment of various conditions, such as pain, feeding disorders and vascular disease among others. Although most of the research in the field of cannabinoids has been focused on their effects in the central nervous system, a growing line of evidence indicates that cannabinoids can also play a major role in the control of physiopathological functions in the cardiovascular system. In this context, endocannabinoids have been proposed as novel possible hypotensive agents, and have been involved in the hypotension observed in septic shock, acute myocardial infarction and cirrhosis. In addition, a protective role for endocannabinoids has been described in ischemia.
 ...
PMID:Cannabinoid system as a potential target for drug development in the treatment of cardiovascular disease. 1532 Apr 76

Cannabinoids, the active ingredients of Cannabis sativa, have been used by humans as hallucinogens and therapeutic agents for thousands of years. These agents are now known to act through the cannabinoid CB1 and CB2 receptors. The recent discovery of endogenous cannabinoids and the fact that they are involved in the pathology of hypotension associated with hemorrhage, sepsis, cirrhosis, and myocardial infarction indicate that cannabinoids play a greater role in human and animal pathophysiology than initially anticipated. Anandamide is the first of the endogenous cannabinoid ligands discovered. Its intravenous administration produces a characteristic three-phase response in the circulatory systems of experimental animals: In phase 1--a short-lasting decrease in heart rate and systemic blood pressure is related to activation of vanilloid TRPV1 receptors. In phase 2 an increase in blood pressure involves multiple mechanisms, both central (probably through the rostral ventrolateral medulla) and peripheral (vascular, Ca2+-dependent). In phase 3 there is a prolonged decrease in blood pressure and sometimes bradycardia, related to the activation of cannabinoid CB1 and vanilloid TRPV1 receptors. On the basis of this three-phase mechanism, the present paper intends to describe the participation of anandamide in the circulatory system under physiological and pathophysiological conditions. It also discusses the possibility of applying cannabinoid ligands as new therapeutic agents for the treatment of some pathologies.
 ...
PMID:[Influence of anandamide, the endogenous agonist of cannabinoid receptors on the circulatory system]. 1592 5

Cardiac contractility in cirrhosis is normal at baseline but hyporesponsive to stimuli, a phenomenon known as 'cirrhotic cardiomyopathy'. The pathogenesis remains unclear. Endocannabinoids are vasoactive, but have not previously been examined in the cirrhotic heart. We therefore aimed to systematically clarify a possible role of endocannabinoids in the pathogenesis of cirrhotic cardiomyopathy. Cirrhosis was induced in Sprague-Dawley rats by bile duct ligation; controls underwent a sham operation. At 4 weeks after operation, isolated left ventricular papillary muscle contractility was studied. Dose-response curve for a beta-adrenergic agonist isoproterenol was constructed in the presence and absence of a CB-1 antagonist AM251 (1 microM). Cirrhotic muscles had a blunted response to isoproterenol, which was completely restored by AM251. Dose-response curves to anandamide, and CB-1 and CB-2 protein and mRNA expression in Western blot and reverse transcriptase-polymerase chain reaction experiments were not significantly different between cirrhotic and sham muscles. Force-frequency relationship studies were performed in cirrhotic and normal muscles. At higher frequencies, anandamide reuptake blockers (VDM11 and AM404) significantly enhanced muscle relaxation in cirrhotic muscles, but not in controls. This effect was completely blocked by AM251 and pertussis toxin, whereas tetrodotoxin partially reversed it. Taken together, these results indicate a pathogenic role for increased local (neuronal) production of endocannabinoids, mediated by a G(i)-protein-dependent CB-1-responsive pathway in cirrhotic cardiomyopathy. The increased tachycardia-stress-induced release of endocannabinoids may help explain why contractility is normal at baseline but attenuated with stress.
 ...
PMID:Role of endocannabinoids in the pathogenesis of cirrhotic cardiomyopathy in bile duct-ligated rats. 1602 38

Hepatic fibrosis, the common response associated with chronic liver diseases, ultimately leads to cirrhosis, a major public health problem worldwide. We recently showed that activation of hepatic cannabinoid CB2 receptors limits progression of experimental liver fibrosis. We also found that during the course of chronic hepatitis C, daily cannabis use is an independent predictor of fibrosis progression. Overall, these results suggest that endocannabinoids may drive both CB2-mediated antifibrogenic effects and CB2-independent profibrogenic effects. Here we investigated whether activation of cannabinoid CB1 receptors (encoded by Cnr1) promotes progression of fibrosis. CB1 receptors were highly induced in human cirrhotic samples and in liver fibrogenic cells. Treatment with the CB1 receptor antagonist SR141716A decreased the wound-healing response to acute liver injury and inhibited progression of fibrosis in three models of chronic liver injury. We saw similar changes in Cnr1-/- mice as compared to wild-type mice. Genetic or pharmacological inactivation of CB1 receptors decreased fibrogenesis by lowering hepatic transforming growth factor (TGF)-beta1 and reducing accumulation of fibrogenic cells in the liver after apoptosis and growth inhibition of hepatic myofibroblasts. In conclusion, our study shows that CB1 receptor antagonists hold promise for the treatment of liver fibrosis.
 ...
PMID:CB1 cannabinoid receptor antagonism: a new strategy for the treatment of liver fibrosis. 1725 52

In the past two decades, cannabinoids have emerged as crucial mediators in a variety of pathophysiological conditions. Awareness of their critical functions in liver pathophysiology is only recent, probably given the low level of expression of cannabinoid receptor type 1 (CB1 receptor) and type 2 (CB2 receptor) in normal liver. However, it has been shown that non-alcoholic fatty liver disease and cirrhosis are associated to a marked upregulation of the hepatic endocannabinoid system, including increases in endocannabinoids and in hepatic CB receptors, both in humans and in rodents. Consequently, a growing number of cannabinoid-related hepatic effects are being unravelled. Hence, hepatic CB1 receptors enhance liver steatogenesis in a mouse model of high fat-induced obesity, and contribute to peripheral arterial vasodilation in cirrhosis, thereby promoting portal hypertension. In addition, CB1 and CB2 receptors elicit dual opposite effects on fibrogenesis associated to chronic liver injury, by promoting pro- and antifibrogenic effects, respectively. Therefore, endocannabinoid-based therapies may open novel therapeutic avenues in the treatment of chronic liver diseases.
 ...
PMID:Endocannabinoids as novel mediators of liver diseases. 1675 9

There are at least two types of cannabinoid receptors, CB1 also named CNR1 and CB2 also named CNR2, both coupled to G proteins. CB1 receptors exist primarily on central and peripheral neurons. CB2 receptors are present mainly on immune cells. Endogenous agonists for cannabinoid receptors (endocannabinoids) have also been discovered, the most important being arachidonoyl ethanolamide (anandamide), 2-arachidonoyl glycerol (2-AG), and 2-archidonyl glyceryl ether. Following their release, endocannabinoids are removed from the extracellular space and then degraded by intracellular enzymic hydrolysis. CB1/CB2 agonists are already used clinically as antiemetic or to stimulate appetite. Potential therapeutic uses of cannabinoid receptor agonists include the management of multiple sclerosis, spinal cord injury, pain, inflammatory disorders, glaucoma, bronchial asthma, vasodilatation that accompanies advanced cirrhosis, and cancer.
 ...
PMID:Therapeutic potential of cannabinoid receptor ligands: current status. 1681 Mar 44

CB1 and CB2 are multifunctional cannabinoid-specific receptors considered to be involved in inhibition of tumor development. To elucidate their roles in hepatocarcinogenesis, we analyzed the expression of these receptors in tumor and matched nontumorous tissues of human hepatocellular carcinoma (HCC) samples. In situ hybridization analysis showed overexpression of CB1 mRNAs in 8 of 13 (62%) HCC samples, and of CB2 mRNAs in 7 of 13 (54%). Immunohistochemical analysis of 64 HCC samples showed the expression of CB1 and CB2 receptors to increase from normal liver to chronic hepatitis to cirrhosis. Marked expression of CB1 and CB2 receptors was noted in the majority of cirrhotic liver samples (86 and 78%, respectively). In HCC, high expression of CB1 and CB2 receptors was observed in 29 (45%) and 33 (52%) cases, respectively. Clinicopathological evaluation indicated a significant correlation between CB1 and CB2 expression and two clinicopathological parameters such as the histopathological differentiation (P = 0.021 and 0.001, respectively), portal vein invasion (P = 0.015 and 0.004, respectively). Univariate analysis indicated that disease-free survival was significantly better in HCC patients with high versus those with low CB1 and CB2 expression levels (P = 0.010 and 0.037, respectively). Our results indicate that CB1 and CB2 have potential as prognostic indicators and suggest possible beneficial effects of cannabinoids on prognosis of patients with HCC.
 ...
PMID:Overexpression of cannabinoid receptors CB1 and CB2 correlates with improved prognosis of patients with hepatocellular carcinoma. 1707 88

Chronic liver injury exposes the patient to liver fibrosis and its end stage, cirrhosis, is a major public health problem worldwide. In western countries, prevailing causes of cirrhosis include chronic alcohol consumption, hepatitis C virus infection and non-alcoholic steatohepatitis. Current treatment of hepatic fibrosis is limited to withdrawal of the noxious agent. Nevertheless, suppression of the cause of hepatic injury is not always feasible and numerous efforts are directed at the development of liver-specific antifibrotic therapies. Along these lines, the authors recently demonstrated that the endocannabinoid system shows promise as a novel target for antifibrotic therapy during chronic liver injury. Indeed, cannabinoid receptors CB1 and CB2 promote dual pro- and antifibrogenic effects, respectively. Therefore, endocannabinoid-based therapies, combining CB2 agonists and CB1 antagonists may open novel therapeutic perspectives for the treatment of chronic liver diseases.
 ...
PMID:Cannabinoid receptors as new targets of antifibrosing strategies during chronic liver diseases. 1729 97


1 2 3 Next >>