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)

This study was designed to determine whether male Mongolian gerbils (Meriones unguiculatus) develop atherosclerosis (AS) during long-term feeding of diets similar to those consumed by humans. Gerbils were fed diets containing 16% casein (C) or soy (S) protein +/- 0.1% cholesterol (CH) for 15 months. The energy contribution from protein, fat and carbohydrate was similar to the energy distribution reported for the average North American (NA) diet and the level of added dietary CH resembled the average NA intake. At mo 0, 3, 6, 9, 12 and 15, animals were killed and tissue sections were prepared for histologic examination. Microscopic observations of cardiovascular tissues did not reveal any evidence of AS in any of the diet groups. Liver fatty infiltration (FI) was evident in the C+CH and C groups at mo 3 and 9, respectively, and continued to occur at all subsequent sampling times. Livers from gerbils fed S+CH also began to exhibit FI at mo 9, while livers from S-fed gerbils did not show any significant morphologic changes. Biochemical liver total lipid results supported the histological liver findings. Other tissues examined did not reveal any morphological changes related to diet. The gerbil may be a useful animal model to study mechanisms which inhibit AS development.
Acta Cardiol 1990
PMID:Long-term feeding of casein or soy protein with or without cholesterol in Mongolian gerbils. I. Morphologic effects. 223 27

In clinical trials, all lipid-lowering agents have been associated with mild, asymptomatic elevations of alanine aminotransferase (ALT) and asparate aminotransferase enzymes. This, along with the fact that 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are hepatotoxic in some animals, led the US Food and Drug Administration (FDA) to recommend monitoring of liver enzymes for all lipid-lowering agents, except the bile acid sequestrants. Because the drugs act by different mechanisms, ALT elevations may be a pharmacodynamic effect related to lipid lowering, rather than a direct effect of the drug. Animal studies support this assumption. ALT elevations of 3 times the upper limit of normal occur in <3% of patients in clinical trials of lipid-lowering drugs. The elevations are transient and often dose-related, and they usually revert to normal while continuing therapy and have never been associated with hepatotoxicity. Confounding factors include alcohol, acetaminophen, and pre-existing liver disease, such as chronic hepatitis C and type II diabetes with fatty liver, which are both associated with mild, intermittent elevations of ALT. The more important issue is whether or not lipid-lowering agents are hepatotoxic. There are case reports of hepatotoxicity (cholestasis, jaundice, hepatitis, chronic active hepatitis, fatty liver, cirrhosis and acute liver failure) with all of the drugs, except cholestyramine. To date there are just 5 cases of documented liver failure linked to lovastatin. There is no evidence that monitoring reduces the rate of hepatotoxicity. Mild elevations of ALT that occur with many drugs, including HMG-CoA reductase inhibitors, do not predict hepatotoxicity. Liver enzyme elevations appear to be a class characteristic of lipid-lowering agents. Hepatotoxicity is a rare idiosyncratic reaction, occurring only with sustained released nicotinic acid.
Am J Cardiol 2000 Jun 22
PMID:Defining patient risks from expanded preventive therapies. 1085 89

As the prevalence of the metabolic syndrome increases, 2 comorbid conditions--hepatic steatosis and human immunodeficiency virus (HIV) lipodystrophy--have become difficult clinical challenges. Dyslipidemia in patients with nonalcoholic fatty liver disease or nonalcoholic steatohepatitis may improve with use of statins, fibrates, niacin, and thiazolidinediones, but the data are presently very limited. HIV lipodystrophy is associated with a marked risk of coronary artery disease (CAD), and more aggressive management of the dyslipidemia is likely necessary to improve the prognosis.
Am J Cardiol 2005 Aug 22
PMID:Management of dyslipidemia in patients with complicated metabolic syndrome. 1609 39

The purpose of the Liver Expert Panel was to provide advice to the National Lipid Association's (NLA) Safety Task Force in response to specific questions concerning liver-associated risks of statin therapy. The panel was composed of academic hepatologists with clinical and research interests in nonalcoholic fatty liver disease, lipid metabolic disorders, and drug hepatotoxicity.
Am J Cardiol 2006 Apr 17
PMID:An assessment of statin safety by hepatologists. 1658 33

To compare the prevalence of the metabolic syndrome (MS) using 3 definitions (World Health Organization [WHO], Adult Treatment Panel [ATP III], and International Diabetes Foundation [IDF]) in Korean subjects, we reviewed 6,196 participants (3,436 men and 2,760 women; mean age 51 +/- 11 and 49 +/- 12 years) who underwent a general health status evaluation and had findings of MS components, including serum insulin and microalbuminuria. The prevalence of the MS according to the WHO, ATP III, and IDF definitions (male and female) was 17.1% and 10.3%, 26% and 19.3%, and 22% and 25.4%, respectively. The degrees of agreement according to the k statistics (WHO and IDF, WHO and ATP III, and IDF and ATP III) were modest in both genders. The diagnosis of the MS was associated with a high odds ratio for nonalcoholic fatty liver disease but with a significantly varying prevalence of a Framingham risk score of >10%. The MS was seen in 10% to 30% of otherwise healthy middle-age Korean subjects presenting for health screening and the prevalence varied widely according to the criteria of its definition. The effect of the diagnosis of the MS in terms of cardiovascular risk varies significantly according to the criteria used. In conclusion, a universally accepted definition of the MS is needed for clinical and population-based studies.
Am J Cardiol 2009 Jun 15
PMID:A comparison of the prevalence of the MS and its complications using three proposed definitions in Korean subjects. 1953 84

Gamma-glutamyl transferase (GGT) is a second-generation enzymatic liver function test available for several decades, initially used as a sensitive indicator of alcohol ingestion, hepatic inflammation, fatty liver disease, and hepatitis. Longitudinal and cross-sectional investigational studies since 1990 have associated GGT with an increase in all-cause mortality, as well as chronic heart disease events such as congestive heart failure and components of the metabolic syndrome (abnormal body mass index and levels of high-density lipoprotein cholesterol, glucose, triglycerides, and systolic and diastolic blood pressure). In the upper reference range, GGT was found to be an independent biomarker of the metabolic syndrome, with a 20% per GGT quartile trend rise. Additionally, GGT was positively correlated with an 18% per quartile risk of cardiovascular events and a 26% per quartile increased risk of all-cause mortality. Furthermore, it may be considered a biomarker for "oxidative stress" associated with glutathione metabolism and possibly a "proatherogenic" marker because of its indirect relationship in the biochemical steps to low-density lipoprotein cholesterol oxidation. GGT is becoming an important addition to the multimarker approach to cardiovascular risk evaluation. It should be considered a valuable adjunct in stratifying patient risk and in assessing the aggressiveness of appropriate treatment, with hopes of preventing unnecessary cardiac events and deaths in future years.
Prev Cardiol 2010
PMID:Gamma-glutamyl transferase: a novel cardiovascular risk biomarker. 2002 25

Consumption of sugar-sweetened beverages has been associated with the development and maintenance of obesity, as well as the risk for multiple obesity-related comorbidities. Some experts have hypothesized that the effect is entirely associated with excess caloric intake, while others suggest that a component of sweeteners may have a physiologic impact on the development of hypertension, insulin resistance and nonalcoholic fatty liver disease. Chen et al. have presented the first, large-scale clinical trial, assessing the direct effect of modest changes in sweetened drink consumption on blood pressure in a racially diverse population. The study team utilized data from the PREMIER: Lifestyle Interventions for Blood Pressure Control trial, in which 810 adult subjects were randomized to three groups: advice only; comprehensive lifestyle modification aimed at weight loss, increased exercise and dietary sodium reduction; or comprehensive lifestyle modification with incorporation of the Dietary Approach to Stop Hypertension (DASH) diet. Sweetened drink intake was estimated from 24-h subject recall, assessed by unscheduled phone calls to subjects at baseline, 6 months and 18 months. Over the duration of the study, a reduction of one 12-oz serving of sugar-sweetened beverages per day was associated with an average of 1.8 mmHg reduction in systolic blood pressure and an average of 1.1 mmHg reduction in diastolic blood pressure.
Future Cardiol 2010 Nov
PMID:Sugar-sweetened beverages and hypertension. 2114 33

The prevalence of non-alcoholic fatty liver disease (NAFLD) ranges from 17% to 33% in the general population. It is frequently associated with obesity (60-90%), dyslipidemia (27-92%), diabetes (28-55%) and arterial hypertension (22%); in the presence of the metabolic syndrome, its incidence is 2-fold higher. NAFLD can be considered as an early mediator of the atherosclerotic process with which it shares some pathogenetic mechanisms (insulin resistance, oxidative stress, endothelial dysfunction, inflammatory activation). Patients with NAFLD are usually asymptomatic, high values of liver enzyme tests being the most common finding. Although liver biopsy is the current gold standard for diagnosis of NAFLD, it is not a practical screening tool given the cost, time-consuming nature and potential morbidity of this procedure. Ultrasound is a relatively inexpensive technique of liver imaging. Patients with NAFLD exhibit a higher mortality rate than the general population. The most frequent causes of death are represented by liver-related diseases, malignant neoplasms and cardiovascular disease, the latter being as frequent as malignant neoplasms. Data on cardiac abnormalities in patients with NAFLD are scarce. Abnormalities in left ventricular geometry and diastolic function have been described in patients with NAFLD as well as a more severe coronary artery disease characterized by vulnerable plaques, though observed in small cohort studies. According to the available evidence, NAFLD should be taken into consideration by cardiologists because its identification allows a better risk stratification in both primary and secondary prevention. Its correlation with coronary artery disease strongly suggests that NAFLD plays a proatherogenic role per se, in addition to the well known atherosclerotic risk factors. The finding of increased fatty liver content should prompt to assess the coexistence of other risk factors as well as to tailor the appropriate therapeutic regimen in order to reduce fatty liver content.
G Ital Cardiol (Rome) 2010 Sep
PMID:[Non-alcoholic fatty liver disease: a new challenge for cardiologists]. 2134 25

The relationship between metabolic disorders and obstructive sleep apnea (OSA) is multidirectional. Obesity is recognized as the strongest risk factor for OSA. It is unknown whether metabolic syndrome and insulin resistance/type 2 diabetes mellitus contribute to the development or aggravation of OSA, although this is likely. Conversely, OSA may be a risk factor for metabolic disorders. Strong evidence suggests that OSA may increase the risk of developing insulin resistance, glucose intolerance and type 2 diabetes mellitus. OSA has also been associated with the development and/or aggravation of obesity, dyslipidemia, metabolic syndrome and nonalcoholic fatty liver disease - a liver manifestation of metabolic syndrome. In addition, metabolic disorders are confounding factors in OSA. Metabolic disorders and OSA share common intermediate pathogenic pathways, including alterations in autonomic nervous system regulation, increased inflammatory activity, and alterations in adipokine levels and endothelial dysfunction, which may be involved in the interplay between these conditions. Overall, this complexity makes it especially difficult to reveal and understand the links between OSA and metabolic and cardiovascular disorders. The International Diabetes Federation has recently published clinical practice recommendations suggesting that OSA patients should be routinely screened for markers of metabolic disturbance and cardiovascular risk, such as waist circumference, blood pressure, and fasting lipid and glucose levels. It also recommends that the possibility of OSA should be considered in the assessment of all patients with type 2 diabetes mellitus and metabolic syndrome.
Adv Cardiol 2011
PMID:Metabolic disorders associated with obstructive sleep apnea in adults. 2200 90

Mipomersen is an antisense oligonucleotide inhibitor of apolipoprotein (apo) B-100 currently in phase 3 of development for the treatment of hyperlipidemia in patients with a high risk for cardiovascular disease. The drug acts by inhibiting the production of apoB-100, which is the structural core for all atherogenic lipids, including low-density lipoprotein cholesterol (LDL-C). The agent has been shown to produce significant reductions in LDL-C from baseline values compared with placebos. Clinical trials have demonstrated that mipomersen reduces LDL-C up to 44% in patients with familial hypercholesterolemia and patients with significantly elevated LDL despite taking maximum doses of statins. Unlike other medications that target apoB-100, such as microsomal triglyceride transfer proteins, mipomersen does not cause hepatic steatosis or intestinal steatosis and does not affect dietary fat absorption. Adverse side effects encountered with mipomersen include flu-like symptoms, injection site reactions, and elevated liver transaminases. If future studies continue to show such promising results, mipomersen would likely be a viable additional lipid-lowering therapy for patients who are at high cardiovascular risk, intolerant to statins, and/or not at target lipid levels despite maximum doses of statin therapy. Clinical outcome studies looking at cardiovascular disease end points still need to be done.
Cardiol Rev
PMID:Mipomersen: a safe and effective antisense therapy adjunct to statins in patients with hypercholesterolemia. 2229 57


1 2 3 Next >>