Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coronary artery disease (CAD) is the leading cause of death worldwide and is commonly caused by a constellation of risk factors called the metabolic syndrome. We characterized a family with autosomal dominant early CAD, features of the metabolic syndrome (hyperlipidemia, hypertension, and diabetes), and osteoporosis. These traits showed genetic linkage to a short segment of chromosome 12p, in which we identified a missense mutation in LRP6, which encodes a co-receptor in the Wnt signaling pathway. The mutation, which substitutes cysteine for arginine at a highly conserved residue of an epidermal growth factor-like domain, impairs Wnt signaling in vitro. These results link a single gene defect in Wnt signaling to CAD and multiple cardiovascular risk factors.
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PMID:LRP6 mutation in a family with early coronary disease and metabolic risk factors. 1733 14

Osteonecrosis of the femoral head usually affects patients in their third to fifth decade of life. Common risk factors are alcohol, nicotine, corticosteroids, hyperlipidaemia and hypercoagulability. Depending on the stage of the osteonecrosis, the diagnosis is confirmed by radiographs, magnetic resonance imaging or scintigraphy. The ARCO classification (Association Research Circulation Osseous), which is based on older classifications recommended by Ficat/Arlet, Steinberg, Koo or Marcus/Enneking, is a valuable prognostic tool for finding an adequate treatment option. Transient osteoporosis of the hip is controversially discussed as a pre-stage of osteonecrosis or a self-limiting condition based on reflex dystrophy. Conservative and operative treatment options are reported in the literature. Recently published data favour core decompression as an effective procedure for early stage osteonecrosis and transient osteoporosis.
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PMID:[Transient osteoporosis and osteonecrosis of the femoral head. Risk factors, classification and differential diagnosis]. 1747 49

The aim of the study was to explore the role of tennis in the promotion of health and prevention of disease. The focus was on risk factors and diseases related to a sedentary lifestyle, including low fitness levels, obesity, hyperlipidaemia, hypertension, diabetes mellitus, cardiovascular disease, and osteoporosis. A literature search was undertaken to retrieve relevant articles. Structured computer searches of PubMed, Embase, and CINAHL were undertaken, along with hand searching of key journals and reference lists to locate relevant studies published up to March 2007. These had to be cohort studies (of either cross sectional or longitudinal design), case-control studies, or experimental studies. Twenty four studies were identified that dealt with physical fitness of tennis players, including 17 on intensity of play and 16 on maximum oxygen uptake; 17 investigated the relation between tennis and (risk factors for) cardiovascular disease; and 22 examined the effect of tennis on bone health. People who choose to play tennis appear to have significant health benefits, including improved aerobic fitness, a lower body fat percentage, a more favourable lipid profile, reduced risk for developing cardiovascular disease, and improved bone health.
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PMID:Health benefits of tennis. 1750 88

Cardiovascular disease, such as atherosclerosis, has been associated with reduced bone mineral density and fracture risk. A major etiologic factor in atherogenesis is believed to be oxidized phospholipids. We previously found that these phospholipids inhibit spontaneous osteogenic differentiation of marrow stromal cells, suggesting that they may account for the clinical link between atherosclerosis and osteoporosis. Currently, anabolic agents that promote bone formation are increasingly used as a new treatment for osteoporosis. It is not known, however, whether atherogenic phospholipids alter the effects of bone anabolic agents, such as bone morphogenetic protein (BMP)-2 and parathyroid hormone (PTH). Therefore we investigated the effects of oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (ox-PAPC) on osteogenic signaling induced by BMP-2 and PTH in MC3T3-E1 cells. Results showed that ox-PAPC attenuated BMP-2 induction of osteogenic markers alkaline phosphatase and osteocalcin. Ox-PAPC also inhibited both spontaneous and BMP-induced expression of PTH receptor. Consistently, pretreatment of cells with ox-PAPC inhibited PTH-induced cAMP production and expression of immediate early genes Nurr1 and IL-6. Results from immunofluorescence and Western blot analyses showed that inhibitory effects of ox-PAPC on BMP-2 signaling were associated with inhibition of SMAD 1/5/8 but not p38-MAPK activation. These effects appear to be due to ox-PAPC activation of the ERK pathway, as the ERK inhibitor PD98059 reversed ox-PAPC inhibitory effects on BMP-2-induced alkaline phosphatase activity, osteocalcin expression, and SMAD activation. These results suggest that atherogenic lipids inhibit osteogenic signaling induced by BMP-2 and PTH, raising the possibility that hyperlipidemia and atherogenic phospholipids may interfere with anabolic therapy.
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PMID:Atherogenic phospholipids attenuate osteogenic signaling by BMP-2 and parathyroid hormone in osteoblasts. 1752 49

The Wnt/beta-catenin signaling pathway affects several biological processes ranging from embryonic development, patterning, and postembryonic stem cell fate, to bone formation and insulin secretion in adulthood. beta-Catenin mediates canonical Wnt signaling by binding to and activating members of the T-cell factor (TCF) transcription factor family. Similar to the Wnt/beta-catenin pathway, oxidative stress influences fundamental cellular processes including stem cell fate and has been linked to aging and the development of age-related diseases. However, the molecular details of the pathogenetic effects of oxidative stress on the homeostasis of many different tissues remain unclear. beta-Catenin has been recently implicated as a pivotal molecule in defense against oxidative stress by serving as a cofactor of the forkhead box O (FOXO) transcription factors. In addition, it has been shown that oxidative stress is a pivotal pathogenetic factor of age-related bone loss and strength in mice, leading to, among other changes, a decrease in osteoblast number and bone formation. These particular cellular changes evidently result from diversion of the limited pool of beta-catenin from TCF- to FOXO-mediated transcription in osteoblastic cells. Fascinatingly, attenuation of Wnt-mediated transcription, resulting from an autosomal-dominant missense mutation in LRP6, a coreceptor for the Wnt-signaling pathway, has been linked recently genetically not only to premature osteoporosis, but also to coronary artery disease as well as several features of the metabolic syndrome including hyperlipidemia, hypertension, and diabetes, but not obesity. In this minireview, we highlight evidence linking the age-associated oxidative stress with FOXOs, Wnt/beta-catenin signaling, osteoblastogenesis, adipogenesis, osteoporosis, and several features of the metabolic syndrome. We hypothesize that antagonism of Wnt signaling by oxidative stress with increasing age may be a common molecular mechanism contributing to the development not only of involutional osteoporosis, but several pathologies such as atherosclerosis, insulin resistance, and hyperlipidemia, all of which become more prevalent with advancing age.
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PMID:Gone with the Wnts: beta-catenin, T-cell factor, forkhead box O, and oxidative stress in age-dependent diseases of bone, lipid, and glucose metabolism. 1762 81

Coronary heart disease and osteoporosis are common diseases in aging populations. Traditionally, these diseases have been considered as distinct and unrelated. However, nowadays there has been increasing evidence indicating a pathological link between these two disorders. Both diseases share etiological factors as hyperlipidemia, hypertension, diabetes, oxidative stress, inflammation, hyperhomocysteinemia. Statins, hypolipidemic drugs, not only reduce atherogenesis but also stimulate bone formation. Bisphosphonates, drugs used in osteoporosis treatment, have been shown to influence serum cholesterol levels and inhibit atherosclerotic plaque formation.
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PMID:[Coronary heart disease and osteoporosis: factors related to development of both diseases]. 1794 67

Cardiac transplantation has become an established intervention for end-stage heart disease. Clinical outcomes in older cardiac transplant patients have improved over the last decade and are almost similar to those in younger patients. Nevertheless, morbidity and mortality due to infections, cancer and chronic allograft vasculopathy remain problematic. On the other hand, older transplant patients seem to have lower incidences of acute rejection episodes than younger patients. Conventional immunosuppression with calcineurin-inhibiting drugs, azathioprine and corticosteroids is responsible for a number of adverse effects. Although these adverse effects can also be seen in younger patients, tolerance to these agents seems to decrease with increasing age. In particular, diabetes mellitus, osteoporosis and chronic renal insufficiency are associated with higher morbidity and mortality in older cardiac transplant patients. As the elderly become an ever-increasing segment of the cardiac transplant population, new and innovative immunosuppressive strategies will have to be developed and applied.Currently, the availability of new immunosuppressive drugs means more individualised immunosuppressive protocols can be used. New antibodies for induction therapy, a choice between ciclosporin and tacrolimus, and the advent of mycophenolate mofetil as well as proliferation signal inhibitors (everolimus, sirolimus) have changed immunosuppressive protocols dramatically. Therefore, a generalised protocol for all patients has been replaced by individualised immunosuppression depending on the patient group. Moreover, protocols can be modified during follow-up depending on the individual patient's requirements and problems. Hypertension and hyperlipidaemia could be influenced by the selection of tacrolimus over ciclosporin, and weaning of corticosteroids might have a positive impact on osteoporosis or diabetes. There is also no clear evidence that tacrolimus is associated with a higher risk for new onset of diabetes. Chronic renal insufficiency can be managed with calcineurin inhibitor-free immunosuppression consisting of mycophenolate mofetil and proliferation signal inhibitors. Both everolimus and sirolimus also seem to have a protective effect against the onset of graft vasculopathy and some sorts of cancer after cardiac transplantation. As a general rule, however, older cardiac transplant patients should be treated with lower doses and fewer immunosuppressive drugs to avoid over-immunosuppression.
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PMID:Immunosuppressive therapy in older cardiac transplant patients. 1795 59

Type I (T1) diabetes, also called insulin dependent diabetes mellitus (IDDM), is characterized by little or no insulin production and hyperglycemia. One of the less well known complications of T1-diabetes is bone loss which occurs in humans and animal models. This complication is receiving increased attention because T1-diabetics are living longer due to better therapeutics, and are faced with their existing health concerns being compounded by complications associated with aging, such as osteoporosis. Both male and female, endochondrial and intra-membranous, and axial and appendicular bones are susceptible to T1-diabetic bone loss. Exact mechanisms accounting for T1-diabetic bone loss are not known. Existing data indicate that the bone defect in T1-diabetes is anabolic rather than catabolic, suggesting that anabolic therapeutics may be more effective in preventing bone loss. Potential contributors to T1-diabetic suppression of bone formation are discussed in this review and include: increased marrow adiposity, hyperlipidemia, reduced insulin signaling, hyperglycemia, inflammation, altered adipokine and endocrine factors, increased cell death, and altered metabolism. Differences between T1-diabetic- and age-associated bone loss underlie the importance of condition specific, individualized treatments for osteoporosis. Optimizing therapies that prevent bone loss or restore bone density will allow T1-diabetic patients to live longer with strong healthy bones.
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PMID:Understanding the pathology and mechanisms of type I diabetic bone loss. 1797 93

Quality of care of many diseases, such as diabetes, hypertension, hyperlipidemia, and osteoporosis, can be assessed effectively from information in usual medical records concerning blood tests, blood pressure, bone density, etc. However, quality of care of rheumatoid arthritis (RA), as well as most rheumatic diseases, cannot be assessed from usual medical records. The primary basis for this problem involves limitations of laboratory tests and the absence of a single "gold standard" measure in RA Therefore, indices which include laboratory tests, joint counts, and patient questionnaires have been developed. These indices are collected in all RA clinical trials and other clinical research, but not in usual clinical care, a phenomenon which may limit severely possible assessment and improvement of quality and patient outcomes. Patient questionnaires and joint counts, rather than laboratory tests or radiographs in a medical record, are the best measures to assess and monitor RA patient status. Patient questionnaires are the most significant clinical prognostic markers for severe long-term RA outcomes, such as work disability, costs and premature mortality, and are more cost-effective and easily-collected than formal quantitative joint counts in busy clinical settings. The value of patient questionnaires and joint counts in RA is reviewed in three examples from the authors' research concerning premature mortality in RA, changes in patient clinical status between 1985 and 2000, and a QUEST-RA global perspective, to better evaluate the structure, processes, and outcomes of RA care.
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PMID:Assessment of quality of rheumatoid arthritis care requires joint count and/or patient questionnaire data not found in a usual medical record: examples from studies of premature mortality, changes in clinical status between 1985 and 2000, and a QUEST-RA global perspective. 1802 12

Most of the patients who are candidate to liver transplant have varying degrees of hyponutrition. That is why they may be subsidiary to receive nutritional therapy so as to improve their nutritional status and the transplant outcomes. However, preoperative support is difficult to perform in many cases due to multiple factors among which the patients clinical situation, the diagnostic requirements, the therapeutic regimens, and extra-hospital care of the "stable" candidates may be listed. In the post-surgical phase, the patients must receive nutritional support in the same way other patients submitted to major surgery do. Early enteral nutrition is the most appropriate method in most of the cases, for which intraoperative placement of a transpyloric access to the digestive tract is recommended, usually through a naso-jejunal tube. Enteral nutrition should be maintained until nutritional requirements may appropriately be covered by oral feeding. Immunosuppressive therapy importantly contributes to the development of such problems after transplantation through its secondary metabolic-nutritional effects. The patients require nutritional follow-up not only to assess the evolution of their nutritional status but also to detect, prevent, and treat late-onset impairments such as obesity, hyperlipidemia, or osteoporosis, which commonly occur in these patients.
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PMID:[Liver transplant. Nutritional implications]. 1871 9


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