Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metabolism of nitrendipine occurs principally in the liver. Therefore, an alteration of pharmacokinetics has to be discussed in patients with hepatic impairment. To evaluate steady-state plasma concentrations and pharmacokinetics, a low dose of nitrendipine (5 mg/day for 3 weeks) was administered orally to patients with different chronic liver diseases (fatty liver, n = 3; chronic hepatitis, n = 2; and cirrhosis of the liver, n = 5). Nitrendipine plasma concentrations were analyzed by using a gas-liquid chromatography procedure. Twenty-two days after beginning the study, steady-state plasma concentrations were lower than 1.0 microgram/L in one patient without liver disease and in seven patients with chronic liver diseases, in contrast to three patients with alcoholic cirrhosis (5.5, 1.3, and 2.9 micrograms/L). The maximum concentration (Cmax) was 2.3 micrograms/L in the patient without liver disease and 8.3 +/- 3.9 micrograms/L in the hepatic patients. The elimination half-life was prolonged in three of five patients with cirrhosis of the liver (35, 67, and 43 h), whereas in the other patients the half-life was in a normal range (4.2-21.3 h). The area under the concentration-time curve (AUC) was enhanced in three patients with liver cirrhosis (387, 69, and 126 h/micrograms/L); in the other seven hepatic patients, results were normal (35-49 h/micrograms/L). There were no alterations observed in any patient in blood pressure and laboratory data. Oral administration of a low dose of nitrendipine resulted in slightly enhanced steady state plasma concentrations only in patients with advanced cirrhosis of the liver. The half-life, AUC, and bioavailability also seem to be altered only in a more severe state of liver disease.
J Cardiovasc Pharmacol 1988
PMID:Disposition of nitrendipine in patients with chronic liver diseases. 246 69

This review includes the initial experience with NMR imaging of the liver, spleen, and pancreas at the University of California, San Francisco, using a prototype 0.35 Tesla system. This experience shows great promise for detection of hepatic metastases using T1-weighted pulse sequences. T2-weighted pulse sequences appear sensitive for detecting cavernous hemangioma of the liver and may allow tissue specific discrimination of the benign lesion from cancer. NMR is also suitable for evaluating diffuse metabolic alterations and is sensitive and specific for the diagnosis of iron overload. Detection of fatty liver requires use of chemical shift techniques as conventional NMR imaging pulse sequences are relatively insensitive. Motion artifacts and lack of an effective bowel contrast agent limits imaging of the pancreas and retroperitoneum, where CT remains the procedure of choice. The normal spleen has longer T1 and T2 relaxation times than liver or pancreas and NMR has not been successful in diagnosing splenic metastases or lymphoma on a routine basis. We conclude that NMR imaging will be valuable in the diagnosis of focal liver disorders; until fast scan techniques and effective magnetic contrast agents are available for oral and/or intravenous use, other abdominal applications will remain limited.
Cardiovasc Intervent Radiol 1986
PMID:Nuclear magnetic resonance of the liver, spleen, and pancreas. 300 15

Naringin, a bioflavonoid found in citrus fruit peel, is known to have an antioxidative effect, but its effect on atherosclerosis has not been studied. This study evaluated the effect of naringin on blood lipid levels and aortic fatty streaks, and its action mechanism in hypercholesterolemic rabbits. Male New Zealand white rabbits were fed a 0.25% cholesterol diet and divided into an untreated group (n = 4), a naringin-treated group (n = 5; 500 mg/kg per day), and a lovastatin-treated group (n = 5; 20 mg/kg per day). After 8 weeks, blood was sampled and analyzed biochemically. Aorta and liver were harvested and examined histologically. Cholesterol level in rabbits fed the 0.25% cholesterol diet reached 17 times normal and decreased in the rabbits fed naringin and lovastatin, whose effects were not statistically significant (p > 0.05). However, both naringin and lovastatin effectively decreased the area of fatty streak in thoracic aorta on macroscopic analysis (p < 0.05) and significantly reduced subintimal foam cell infiltration on microscopic morphometry (p < 0.05). These foam cells were macrophages on immunohistochemical analysis. Naringin treatment inhibited hypercholesterolemia-induced intercellular adhesion molecule-1 (ICAM-1) expression on endothelial cells. Hypercholesterolemia caused fatty liver and elevation of liver enzymes, which was prevented by naringin but not by lovastatin. Naringin significantly reduced fatty streak formation and neointimal macrophage infiltration and also inhibited the expression of ICAM-1 in endothelial cells, suggesting that suppression of ICAM-1 contributed to the antiatherogenic effect. Naringin, unlike lovastatin, has a hepatoprotective action.
J Cardiovasc Pharmacol 2001 Dec
PMID:Naringin has an antiatherogenic effect with the inhibition of intercellular adhesion molecule-1 in hypercholesterolemic rabbits. 1170 99

Dietary digestible carbohydrates are able to modulate lipogenesis, by modifying the expression of genes coding for key lipogenic enzymes, like fatty acid synthase. The overall objective of the Nutrigene project (FAIR-CT97-3011) was to study the efficiency of various carbohydrates to modulate the lipogenic capacity and relevant gene expression in rat and human species (control and obese subjects) and to understand the underlying molecular mechanisms involved in the regulation of lipogenic genes by carbohydrates. Key cellular mediators (namely SREBP-1c and 2, AMP activated protein kinase, cholesterol content) of the regulation of lipogenic gene expression by glucose and/or insulin were identified and constitute new putative targets in the development of plurimetabolic syndrome associated with obesity. In humans, hepatic lipogenesis and triglyceride synthesis, assessed in vivo by the use of stable isotopes, was promoted by a high-carbohydrate diet in non obese subjects, and in non alcoholic steatotic patients, but was not modified in the adipose tissue of obese subjects. Non digestible/fermentable carbohydrates, such as fructans, were shown to decrease hepatic lipogenesis in non obese rats, and to lessen hepatic steatosis and body weight in obese Zucker rats. If confirmed in obese humans, this would allow the development of functional food able to counteract the metabolic disturbances linked to obesity.
Nutr Metab Cardiovasc Dis 2001 Aug
PMID:Study of the regulation by nutrients of the expression of genes involved in lipogenesis and obesity in humans and animals. 1189 44

The metabolic syndrome is intended to identify patients who have increased risk of diabetes and/or a cardiac event due to the deleterious effects of weight gain, sedentary lifestyle, and/or an atherogenic diet. The National Cholesterol Education Program's Adult Treatment Panel III definition uses easily measured clinical findings of increased abdominal circumference, elevated triglycerides, low high-density lipoprotein-cholesterol, elevated fasting blood glucose and/or elevated blood pressure. Three of these five are required for diagnosis. The authors also note that other definitions of metabolic syndrome focus more on insulin resistance and its key role in this syndrome. This review focuses on how treatment might affect each of the five components. Abdominal obesity can be treated with a variety of lower calorie diets along with regular exercise. Indeed, all of the five components of the metabolic syndrome are improved by even modest amounts of weight loss achieved with diet and exercise. For those with impaired fasting glucose tolerance, there is good evidence that a high fiber, low saturated fat diet with increased daily exercise can reduce the incidence of diabetes by almost 60%. Of note, subjects who exercise the most, gain the most benefit. Metformin has also been shown to be helpful in these subjects. Thiazolidinedione drugs may prove useful, but further studies are needed. Although intensified therapeutic lifestyle change will help the abnormal lipid profile, some patients may require drug therapy. This review also discusses the use of statins, fibrates, and niacin. Likewise, while hypertension in the metabolic syndrome benefits from therapeutic lifestyle change, physicians should also consider angiotensin converting enzyme inhibitor drugs or angiotensin receptor blockers, due to their effects on preventing complications of diabetes, such as progression of diabetic nephropathy and due to their effects on regression of left ventricular hypertrophy. Aspirin should be considered in those with at least a 10% risk of a coronary event over 10 years. Finally, three related conditions, nonalcoholic fatty liver disease, polycystic ovary syndrome and protease inhibitor associated lipodystrophy improve with therapeutic lifestyle change. Although metformin is shown to be useful with polycystic ovary syndrome, the data supporting drug therapy for the other syndromes is less convincing. More robust studies are needed before any firm recommendations can be made.
Expert Rev Cardiovasc Ther 2004 Mar
PMID:Treatment of metabolic syndrome. 1515 70

Diabetes mellitus and advanced liver disease are associated with each other more frequently than expected by chance, and such an association carries a significant risk of morbidity and mortality. A metabolic pathway leading to advanced liver disease via fatty liver and steatohepatitis has been demonstrated, further supporting the possibility that cirrhosis may be a late complication of diabetes. In addition, an interaction between hepatitis C virus (HCV) and insulin resistance increases the overall prevalence of associated diseases, through largely unidentified mechanisms. Extensive prospective monitoring of non-alcoholic fatty liver disease cases, analysis of insulin signaling in HCV-infected patients using molecular biology techniques, and intervention studies, will help to clarify the mechanisms of action of the possible clinical strategies, the predictive value of biochemical, histological, and clinical markers, and the effectiveness of treatments available.
Nutr Metab Cardiovasc Dis 2007 Jan
PMID:Diabetes and liver disease: an ominous association. 1716 82

We present a rare case of a 63-year-old woman, the oldest one in the literature, with supradiaphragmatic ectopic liver that mimics a pulmonary nodule. The chest roentgenogram and chest computer tomography showed a lobulated tumor nearby the diaphragm. Pathological examination of the resected tumor disclosed only remarkable fatty liver change. Ectopic liver should be kept in mind to differentiate for the pulmonary tumor nearby the diaphragm.
Thorac Cardiovasc Surg 2007 Jun
PMID:Supradiaphragmatic ectopic liver: delayed traumatic hepatic hernia mimics pulmonary tumor. 1754 66

Although the definition of the phenotype is imprecise, cardiometabolic syndrome (CMS) includes a constellation of complex diseases such as type 2 diabetes, dislipidemias, central obesity and hypertension, proinflammatory and prothrombotic states, ovarian polycystosis and fatty liver. The genetics of each disease is complex in itself and varies in spectrum from monogenic and syndromic models of inheritance, usually rare, to the most common polygenic and multifactorial forms. In addition, human studies using the candidate-gene approach indicate that common genetic variants of several genes are associated with the development of CMS. Genome-wide scans have also provided several chromosomal regions associated with some of the components of CMS. In addition, through comparative genomics animal models can generate a map for candidate loci in humans and a promising approach is offered by bioinformatic tools for gene prioritization. Lastly, the involvement of genes whose products are already the targets for approved drugs, such as SLC6A4, PPARalpha and PPARgamma , in the development of CMS suggests new avenues for CMS pharmacological treatment.
Ther Adv Cardiovasc Dis 2007 Oct
PMID:Genetics of the cardiometabolic syndrome: new insights and therapeutic implications. 1912 94

Statins are among the most widely prescribed drugs in the western world and play a significant role in reducing cardiovascular risk. However, concern regarding their hepatic safety profile has meant that patients with concurrent liver pathology are often denied such benefits. In this review we consider the evidence for and against the prescription of statins to patients with nonalcoholic fatty liver disease, a group typically associated with high cardiovascular risk. Contrary to current opinion, we find that there is considerable evidence for and little evidence against the prescription of statins to this population and suggest that the guidelines advising against their use in these patients should be reviewed.
Cardiovasc Ther 2009
PMID:Prescribing statins to patients with nonalcoholic fatty liver disease: real cardiovascular benefits outweigh theoretical hepatotoxic risk. 1955 26

Cardiovascular disease is as common in individuals with chronic liver disease as in the general population. Moreover, recent data suggest that patients with nonalcoholic fatty liver disease (NAFLD) may have a cardiovascular risk greater than that conferred by the conventional risk factors. There is unequivocal evidence that cardiovascular disease is an important cause of morbidity and mortality in this patient population and thus requires consideration of aggressive therapy with lipid-lowering agents such as statins. Because all statins are hepatically cleared and can cause elevations in liver biochemistries, there is a concern that patients with underlying liver disease may be at increased risk for hepatotoxicity. However, recent data, along with an assessment of statin safety by the Liver Expert Panel, suggest that statins are generally well tolerated in patients with chronic liver disease such as NAFLD, primary biliary cirrhosis, and hepatitis C virus. These drugs also appear to be safe in patients with stable/compensated cirrhosis. However, decompensated cirrhosis and acute liver failure should be considered contraindications for lipid-lowering therapy as these patients are unlikely to benefit because of their generally grave prognosis. Although routine hepatic biochemical test monitoring is recommended, the cost-effectiveness of this approach has been questioned. The benefit of statins in patients with underlying liver disease who are otherwise important candidates for statin therapy far outweighs the risk of a very rare event of serious liver injury.
Curr Treat Options Cardiovasc Med 2009 Aug
PMID:Use of statins in patients with liver disease. 1962 60


1 2 3 Next >>