Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many drugs besides lipid-lowering drugs affect serum lipid levels in either a potentially harmful or beneficial way, and may therefore increase or decrease the risk of cardiovascular disease. Diuretics, beta-blocking agents, progestogens, combined oral contraceptives containing 'second generation' progestogens, danazol, immunosuppressive agents, protease inhibitors and enzyme-inducing anticonvulsants adversely affect the lipid profile. They increase total cholesterol, low density lipoprotein cholesterol and triglycerides by up to 40, 50 and 300%, respectively, and decrease high density lipoprotein cholesterol by a maximum of 50%. Conversely, alpha-blocking agents, estrogens, hormone replacement therapy, combined oral contraceptives containing 'third generation' progestogens, selective estrogen receptor modulators, growth hormone and valproic acid show mostly beneficial effects on the lipd profile. Some drugs, for example, isotretinoin, acitretin and antipsychotics, mainly elevate triglyceride levels. Adverse or beneficial effects on serum cholesterol levels do not always translate into a higher or lower, respectively, incidence of cardiovascular disease. because these drugs may influence cardiovascular risk through multiple pathways. In some cases, excessive cholesterol levels occur, for example, with protease inhibitor therapy, and several cases of pancreatitis attributable to drug-induced hypertriglyceridaemia have been reported. Some general guidelines on the management of drug-induced dyslipidaemia can be given. Replacement of the dyslipidaemia-inducing drug by an equivalent alternative therapy is preferred. However, such alternatives are often difficult to find. If there is no equivalent alternative and treatment with the dyslipidaemia-inducing drug must be initiated, monitoring of serum lipid levels is important. If drug use is expected to be long term, the existing guidelines for the management of dyslipidaemia in the general population can be applied to drug-induced dyslipidaemia. In cases of extreme hyperlipidaemia, medication use should be reassessed.
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PMID:Drug-Induced lipid changes: a review of the unintended effects of some commonly used drugs on serum lipid levels. 1173 56

Three categories of highly active antiretroviral therapy (HAART)-associated major toxic effects have been identified: nucleoside-related toxic effects (e.g., neuropathy, myopathy, pancreatitis, hepatic steatosis, lactic acidosis, and possibly lipoatrophy), metabolic complications (e.g., fat redistribution, insulin resistance, and hyperlipidemia), and bone disease (e.g., osteopenia and/or osteoporosis). The toxic effects caused by nucleosides are hypothesized to be a result of mitochondrial injury and include myopathy, pancreatitis, liver failure, and lactic acidosis. Alterations in lactic acid metabolism range from common instances of asymptomatic lactic acidemia to rare occurrences of life-threatening lactic acidosis with hepatic steatosis. A metabolic syndrome consisting of lipodystrophy (i.e., fat redistribution), hyperlipidemia and insulin resistance has been observed, particularly with protease inhibitor treatment. Some additive interaction between protease inhibitors and nucleosides has also been described. The potential relationship of these metabolic abnormalities to increased risk of cardiovascular disease and diabetes has broad implications on long-term patient management. Lipodystrophy associated with HAART is generally accompanied by potentially serious abnormalities, including dyslipidemia (i.e., hypercholesterolemia and hypertriglyceridemia) and altered glucose metabolism (i.e., insulin resistance). Regimens of HAART may have adverse effects on bone metabolism, as indicated by emerging reports of osteopenia, osteoporosis, and avascular necrosis.
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PMID:Long-term exposure to lifelong therapies. 1183 99

Chronic infection with HIV type 1 is associated with alterations in macronutrient metabolism, specifically elevated plasma lipids, glucose and reduced insulin sensitivity. These alterations are most severe in patients at the later stages of AIDS, indicating a relationship with disease progression. Recently, a metabolic syndrome, termed lipodystrophy, has been described in successfully-treated HIV patients in whom the altered macronutrient metabolism of HIV infection appears to be amplified markedly, with concurrent alterations in adipose tissue patterning. This syndrome presents a paradox, as before the development of highly-active antiretroviral therapy (HAART) the most severe perturbations in metabolism were observed in the sickest patients. Now, the patients that respond well to therapy are showing metabolic perturbations much greater than those seen before. The implications of this syndrome are that, whilst life expectancy may be increased by reducing viral load, there are concomitant increases in the risk of cardiovascular disease, diabetes and pancreatitis within this patient population. The aetiology of the syndrome remains unclear. In a collaborative trial with the Chelsea and Westminster Hospital in London we have used stable-isotope-labelled fatty acids to examine the hypothesis that treatment with HAART causes a delayed clearance of dietary lipid from the circulation, resulting in the retention of lipid within plasma and the downstream changes in insulin and glucose homeostasis. This hypothesis would indicate a role for low-fat diets, exercise and drugs that reduce plasma lipid or insulin resistance, in modulating the response to antiretroviral therapy in HIV infection.
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PMID:The paradox of improved antiretroviral therapy in HIV: potential for nutritional modulation? 1200 87

HIV protease inhibitors decrease mortality and improve quality of life in patients with HIV infection. However, these drugs have been associated with serum lipid elevations, which may pose an increased risk of cardiovascular disease and pancreatitis. Treatment of protease inhibitor-related hyperlipidaemia (PIH) is complicated by drug interactions, which significantly increase concentrations of most 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins). Although pravastatin and atorvastatin effectively lower cholesterol and triglyceride concentrations in HIV-infected patients, a significant number of patients did not achieve their National Cholesterol Education Program low density lipoprotein concentration goals. Nonetheless, due to the increased risk of rhabdomyolysis with elevated statin concentrations, atorvastatin should be considered a second-line agent. The limited available PIH data supports the fact that pravastatin and atorvastatin are well-tolerated in HIV-infected individuals. More data are needed on the appropriate starting doses, maximum safe doses, role of combination statin-fibrate therapy, documentation of coronary heart disease benefit and incidence of myotoxicity and hepatotoxicity. Pravastatin has an acceptable risk-benefit ratio in PIH, while theoretical toxicity concerns exist with atorvastatin.
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PMID:Risk-benefit of HMG-CoA reductase inhibitors in the treatment of HIV protease inhibitor-related hyperlipidaemia. 1290 55

The challenges of the epidemic are not limited to concerns about bulk and weight. The disabilities caused by obesity are physiologic and psychosocial. The increased waist to hip girth is associated with increased risk of cardiovascular disease, hyperlipidemia, hypertension, and diabetes. Obesity also has been related directly to increased risk of sleep apnea, cancer, gallbladder disease, musculoskeletal disorders, severe pancreatitis, bacterial panniculitis, diverticulitis, infertility, urinary incontinence, and idiopathic intracranial hypertension. The psychosocial factors and quality of life in the obese population also have been documented. Although there is some debate, the obese have been found to be twice as likely to suffer from anxiety, impaired social interaction,and depression when compared with the nonobese population. Although advances in obesity surgery have resulted in long-term, lasting treatment of this disease and some of its comorbidities (ie, diabetes, hypertension, sleep apnea), There is a pressing need to develop a comprehensive medical and nutrition plan to reduce the prevalence of this newly identified disease state. Some draw parallels to tobacco and the morbidity and mortality associated with its use. Perhaps there are similarities in these two epidemics. Both start with education of the population as to the morbidities and mortality associated with the disease. As with tobacco, this education is especially important for youth. Without a plan of education to promote nutrition and increased physical activity, and continued research into the causes of obesity, the prevalence of obesity will continue to rise in the United States.
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PMID:Epidemiology of obesity in the United States. 1582 34

To explore whether the placenta contributes to the lipoprotein metabolism of pregnant women, we took advantage of the fact that placental proteins are encoded from the fetal genome and examined the associations between lipids of 525 pregnant women and the presence, in their newborns, of genetic polymorphisms of LPL and apolipoprotein E (APOE), two genes expressed in placenta. After adjustment for maternal polymorphisms, newborn LPL*S447X was associated with lower triglycerides (-21 +/- 9 mg/dl), lower LDL-cholesterol (LDL-C; -12 +/- 5 mg/dl), lower apoB (-14 +/- 4 mg/dl), higher HDL-C (5 +/- 2 mg/dl), and higher apoA-I (9 +/- 4 mg/dl) in their mothers; newborn LPL*N291S was associated with higher maternal triglycerides (114 +/- 31 mg/dl); and newborn APOE*E2 (compared to E3E3) was associated with higher maternal LDL-C (14 +/- 6 mg/dl) and higher maternal apoB (14 +/- 5 mg/dl). These associations (all P < 0.05) were independent of polymorphisms carried by the mothers and of lipid concentrations in newborns and were similar in amplitude to the associations between maternal polymorphisms and maternal lipids. Such findings support the active role of placental LPL and APOE in the metabolism of maternal lipoproteins and suggest that fetal genes may modulate the risk for problems related to maternal dyslipidemia (preeclampsia, pancreatitis, and future cardiovascular disease).
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PMID:Lipoprotein metabolism of pregnant women is associated with both their genetic polymorphisms and those of their newborn children. 1610 48

The peroxisome proliferator-activated receptor (PPAR) family of genes plays a major role in metabolic regulation. Unfortunately, the results of two recent, large event trials of PPAR agonists have been mixed. High rates of crossover to statin use confound the interpretation of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial, which found a less than expected reduction in coronary and stroke events with fenofibrate. Of concern, nonsignificant increases in coronary and sudden deaths, thrombotic events, and pancreatitis occurred in the fenofibrate group. The PROspective pioglitAzone Clinical Trial In macroVascular Events (PROACTIVE) also found a reduction in coronary and stroke events with pioglitazone compared with placebo in a population with diabetes and cardiovascular disease, but this benefit was counterbalanced by an increase in congestive heart failure as well as symptomatic edema. Further research is needed to determine the role of PPAR agonists in the prevention of cardiovascular disease.
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PMID:Update on PPAR agonists: the clinical significance of FIELD and PROACTIVE. 1716 49

The use of fibrates in the management of lipoprotein disorders has a history dating back to the mid-1960s. This group of drugs has now been tested in several large long-term trials with cardiovascular end points. Overall, there is good evidence for the reduction of cardiovascular disease in primary prevention studies and in those of subjects with manifest disease. More recent trials have suffered from high interference due to 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) introduction, particularly in their placebo control groups. However, there is very good evidence for overall safety from a combined study of >20,000 patients in these controlled clinical trials lasting approximately 5 years. Abdominal pain has been observed more frequently in the statin vs placebo group. Myopathy, liver enzyme elevations, and cholecystitis have been potential adverse reactions of interest. However, these have occurred at a very low rate and are rarely found to be statistically more frequent in the active-treatment group compared with the subjects taking placebo. The recent Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study found a slightly higher incidence of pancreatitis, deep venous thrombosis, and pulmonary embolism. Small creatinine and homocysteine elevations are observed in many patients taking fibrates, and the effect of this on long-term outcomes is under study. The FIELD study also described a significant reduction in the rates of progression of proteinuria and vascular retinopathy with fibrate therapy. To date, there has been no study exclusive to patients with elevated triglycerides, raising the question of the potential benefit of these drugs in patients with the lipid abnormalities most effectively treated with fibrates.
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PMID:Expert commentary: the safety of fibrates in lipid-lowering therapy. 1736 73

With current dietary therapy, life expectancy in glycogen storage disease (GSD) has improved considerably and more children reach adulthood. Notwithstanding intensive dietary therapy, moderate to severe hyperlipidaemia is still observed frequently. There is limited information about the type and extent of hyperlipidaemia. We studied the lipid profile in 20 patients, aged 8-54 years, of the three (types I, III and IX) most common forms of adult GSD. Hyperlipidaemia was shown to be type-specific, affecting predominantly patients with GSD type Ia, who showed marked combined hypercholesterolaemia and hypertriglyceridaemia. By contrast, a heterogeneous distribution of HDL was found in patients with GSD I and III. There was no significant difference in Apo Al and Apo B concentrations between groups. In addition, mass measurements of the fractions of VLDL1, VLDL2 and IDL were raised in all patients with GSD Ia by comparison with all other patients with GSD. Patients with GSD type Ia have lipid concentrations and individual mass measurements that are consistent with ranges found in patients who have a significant risk of atherosclerosis. Accumulated evidence, however, suggest GSD type Ia patients do not have an increased risk of atherosclerotic cardiovascular disease (CVD) but the reason remains unknown. Intervention to reduce their lipid levels could therefore be on the basis of seeking to prevent the risk of pancreatitis rather than that of CVD.
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PMID:Serum lipid and lipoprotein profile of patients with glycogen storage disease types I, III and IX. 1740 2

Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be "Curecumin".
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PMID:Curcumin as "Curecumin": from kitchen to clinic. 1790 May 36


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