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)

Osteoporosis is several times more common in patients with PBC compared with the general population. Maintaining adequate intake of calcium and vitamin D is important for prevention of bone loss. The use of bisphosphonates or vitamin K to improve bone mineral density in osteopenic patients seems promising and needs to be further evaluated. Patients with PBC may develop fat-soluble vitamin deficiencies, especially vitamins A and D; serum levels should be investigated in patients considered at risk with the aim of recommending appropriate replacement therapy. Finally, hyperlipidemia in PBC does not seem to be associated with an increased risk of atherogenesis. New therapies in this patient population are currently under investigation.
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PMID:Management of osteoporosis, fat-soluble vitamin deficiencies, and hyperlipidemia in primary biliary cirrhosis. 1459 36

Osteoporosis is associated with both atherosclerosis and vascular calcification. No mechanism yet explains the parallel progression of these diseases. Here, we demonstrate that osteoclasts (OCL) depend on lipoproteins to modulate cellular cholesterol levels and that this controls OCL formation and survival. Removal of cholesterol in OCL via high-density lipoprotein or cyclodextrin treatment dose-dependently induced apoptosis, with actin disruption, nuclear condensation and caspase-3 activation. One mechanism linked to the induction of OCL apoptosis was the cell-type-specific failure to induce HMG-CoA reductase mRNA expression, suggesting an absence of feedback regulation of de novo cholesterol biosynthesis. Furthermore, cyclodextrin treatment substantially suppressed essential M-CSF and RANKL-induced survival signaling pathways via Akt, mTOR and S6K. Consistent with these findings, cholesterol delivery via low-density lipoprotein (LDL) significantly increased OCL viability. Interestingly, OCLs from the LDL receptor (LDLR)-/- mouse exhibited reduced size and lifespan in vitro. Remarkably, LDLR+/+ OCL in lipoprotein-deficient medium phenocopied LDLR-/- OCL, while fusion and spreading of LDLR-/- OCL was rescued when cholesterol was chemically delivered during differentiation. With hyperlipidemia being associated with disease of the vascular system and bone, these findings provide novel insights into the selective lipoprotein and cholesterol dependency of the bone resorbing cell. Cell Death and Differentiation (2004) 11, S108-S118. doi:10.1038/sj.cdd.4401399 Published online 12 March 2004
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PMID:Osteoclast formation, survival and morphology are highly dependent on exogenous cholesterol/lipoproteins. 1524 77

Recent advances in immunosuppressive drug regimens have changed the outcome after liver transplantation significantly in the last two decades. However, chronic rejection and long-term graft survival remains a major problem. Side effects like drug-induced nephrotoxicity, hypertension, osteoporosis, hyperlipidaemia and neuropathy of some immunosuppressive agents play an essential role in long-term allograft and patient survival. This review outlines the current treatment of short- and long-term immunosuppression in liver transplanted patients, it summarizes the treatment of acute and chronic rejection, describes the complications and side effects of immunosuppressive therapy and points out the current use of immunosuppressive therapy in living-related liver transplantation.
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PMID:Immunosuppression and modulation in liver transplantation. 1524 Aug 45

Remedies for primary osteoporosis are increasing in brands but not always with concomitant improvements in efficacy and safety. Clinical studies suggest that nitrogen-containing bisphosphonates alone display sufficient practical effectiveness to survive as effective therapy. However, their less effectiveness in highly osteopenic patients due to their lack of genuine bone anabolic effect waits improvements. Pinpointing statins as the inducer of BMP-2 provoked a rush of clinical and laboratory studies to identify bone anabolic properties. Clinical studies, even if only through observational, suggest that under conventional dosing conditions for hyperlipemia, the liver-targeted statins now in use display insufficient bone anabolic effect, although laboratory studies seem to be clarifying the mechanisms underlying intrinsic bone anabolic properties. While incomplete, these studies indicate the possibility that, if bioavailability to bone could be improved by simply changing dosing methods and/or deliberate derivatization, the genuine anabolic properties of statins on bone could be extracted and put into therapeutic use.
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PMID:Osteoporosis requires bone-specific statins. 1532 Jul 48

In the control of acute rejection, attention is being focused more and more on the long-term adverse effects of the immunosuppressive agents used. Since cardiovascular disease is the main cause of death in renal transplant recipients, optimal control of cardiovascular risk factors is essential in the long-term management of these patients. Unfortunately, several commonly used immunosuppressive drugs interfere with the cardiovascular system. In this review, the cardiovascular adverse effects of the immunosuppressive agents currently used for maintenance immunosuppression are thoroughly discussed. Optimising immunosuppression means finding a balance between efficacy and safety. Corticosteroids induce endothelial dysfunction, hypertension, hyperlipidaemia and diabetes mellitus, and impair fibrinolysis. The use of corticosteroids in transplant recipients is undesirable, not only because of their cardiovascular effects, but also because they induce such adverse effects as osteoporosis, obesity, and atrophy of the skin and vessel wall. Calcineurin inhibitors are the most powerful agents for maintenance immunosuppression. The calcineurin inhibitor ciclosporin (cyclosporine) not only induces these same adverse effects as corticosteroids but is also nephrotoxic. Tacrolimus has a more favourable cardiovascular risk profile than ciclosporin and is also less nephrotoxic. It has little or no effect on blood pressure and serum lipids; however, its diabetogenic effect is more prominent in the period immediately following transplantation, although at maintenance dosages, the diabetogenic effect appears to be comparable to that of ciclosporin. The diabetogenic effect of tacrolimus can be managed by reducing the dose of tacrolimus and early corticosteroid withdrawal. The effect of tacrolimus on endothelial function has not been completely elucidated. The proliferation inhibitors azathioprine and mycophenolate mofetil (MMF) have little effect on the cardiovascular system. Yet, indirectly, by inducing anaemia, they may lead to left ventricular hypertrophy. MMF is an attractive alternative to azathioprine because of its higher potency and possibly lower risk of malignancies. Sirolimus also induces anaemia, but may be promising because of its antiproliferative features. Whether the hyperlipidaemia induced by sirolimus counteracts its beneficial effects is, as yet, unknown. It may be combined with MMF, however, initial attempts resulted in severe mouth ulcers.
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PMID:Effect of immunosuppressive agents on long-term survival of renal transplant recipients: focus on the cardiovascular risk. 1534 97

Although long-term continuation medical treatment is needed in chronic diseases, such as osteoporosis, and hypertension, hyperlipemia, since there are no subjective symptoms much, an understanding of the necessity for medication is hard to be obtained. Furthermore, in elderly people, it has two or more chronic diseases, and since the medicine of varieties is taken in many cases, medication compliance tends to become bad. Explanation with a disease sufficient in a chronic-disease patient and medication counseling of elderly people is useful to improvement in compliance, and safety reservation of a patient.
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PMID:[Medication counseling in the oral medicine of osteoporosis and complications with elderly people]. 1557 6

Recent studies suggest that statins and beta-blockers which are widely prescribed for the treatment of hyperlipidemia and hypertension play an important role in bone metabolism. Statins inhibit HMG-CoA reductase and its down-stream mevalonate pathway. They modulate osteoclastic and osteoblastic activity, since metabolites of mevalonate are critically involved in bone cell biology. Sympathetic nervous system also controls bone formation via its direct effects on osteoblasts. Administration of beta-blockers may lead to an increase bone mass and reduce the risk of fracture. Statins and beta-blockers could have anabolic effects on bone metabolism and may be potential therapeutic implications for osteoporosis.
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PMID:[Anabolic effects of statin and beta-blocker on bone metabolism]. 1557 80

Epidemiological studies have reported that women with osteoporosis present an increased risk of cardiovascular events and that lipid lowering therapy (statins) could be associated with a decreased risk of fracture. We investigated whether women with atherogenic lipid profile have lower lumbar and femoral bone mineral density (BMD) and higher prevalence of osteopenia than those with normal lipid levels. The study included 52 overweight early postmenopausal women, with no history of hormone replacement therapy, or any current or past pathology or treatment that could alter bone or lipid metabolism. Atherogenic lipid profile or hyperlipidemia was defined as hypercholesterolemia (> or = 240 mg/dl) or high low-density lipoprotein cholesterol (high-LDLc > or = 160 mg/dl) or high lipoprotein (a) [high-Lp (a) > or =25 mg/dl], and low-BMD as t-score <-1 SD at lumbar o femoral site. The results show that women with hyperlipidemia had lower mean-adjusted BMD (mean+/-SEM) at lumbar (0.865+/-0.020 vs. 0.958+/-0.028 g/cm2, p = 0.007) and femoral neck (0.712+/-0.015 vs. 0.796+/-0.021, p = 0.004 g/cm2) than those with normal lipid levels. Hypercholesterolemia group had higher prevalence of low-BMD at lumbar spine (82.6% vs. 55.2%, p = 0.04, OR: 3.8; 95% CI: 1.04-14.2) and femoral neck (65.2% vs. 37.9%, p = 0.05, OR: 3.1; 95% CI: 0.98-9.6). The high-LDLc group had also higher prevalence low-BMD at femoral neck (75% vs. 39%, p = 0.01, OR: 4.7; 95% CI: 1.26-17.5), and the high-Lp (a) group at lumbar spine (87% vs. 51.7% p = 0.007, OR: 6.2; 95% CI: 1.5-25.6). Women with hyperlipidemia had higher prevalence of low BMD at lumbar spine (81.8% vs. 42.1%, p = 0.003, OR: 6.2; 95% CI: 1.7-22) and femoral neck (60.6% vs. 31.6%, p = 0.04, OR: 3.3; 95% CI: 1.01-11.0). In conclusion, early postmenopausal women with atherogenic lipid profile, defined as cholesterol > or =240 mg/dl or LDLc > or = 160 mg/dl or Lp(a) > or = 25 mg/dl have lower lumbar and femoral BMD and have an increased risk of osteopenia than those with normal lipid profile, suggesting that hyperlipidemia could be associated with osteoporosis and bone status should be evaluated in women with hyperlipidemia.
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PMID:Atherogenic lipid profile and elevated lipoprotein (a) are associated with lower bone mineral density in early postmenopausal overweight women. 1567 90

Regucalcin was discovered in 1978 as a Ca(2+)-binding protein that does not contain EF-hand motif of Ca(2+)-binding domain. The name regucalcin was proposed for this Ca2(2+)binding protein, which can regulate liver cell functions related to Ca(2+). The regucalcin gene is localized on chromosome X, and the organization of the regucalcin gene consists of seven exons and six introns. AP-1 and NFI-A1 can bind to the promoter region of the rat regucalcin gene to mediate the Ca(2+) response for transcriptional activation. Regucalcin plays a pivotal role in maintaining intracellular Ca(2+) homeostasis due to activating Ca(2+) pump enzymes in the plasma membrane (basolateral membrane), microsomes (endoplasmic reticulum) and mitochondria of many cell types. Regucalcin has a suppressive effect on Ca(2+) signaling from the cytoplasm to the nucleus in the proliferative cells. Also, regucalcin has been demonstrated to transport to nucleus, and it can inhibit nuclear protein kinase, protein phosphatase, and deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) synthesis. Regucalcin can control enhancement of cell proliferation due to hormonal stimulation. Moreover, overexpression of regucalcin suppresses cell death and apoptosis in the cloned rat hepatoma cells induced by various signaling factors. Regucalcin plays a multifunctional role in the regulation of cellular function in liver, kidney cortex, heart and brain. Moreover, regucalcin-overexpressing rat has been shown to induce bone loss and hyperlipidemia with increasing age, indicating a pathophysiologic role. Regucalcin transgenic rat may be useful as an animal model in osteoporosis and hyperlipidemia. Thus, regucalcin plays a pivotal role in maintaining cell homeostasis and function. Regucalcin gene expression-related diseases may be found in human.
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PMID:Role of regucalcin in maintaining cell homeostasis and function (review). 1570 26

Postmenopausal osteoporosis is caused by an increased bone loss after menopause. Both estrogen and bisphosphonate have a potent anti-resorptive effect on bone and are proved to be useful for treatment of osteoporosis. Treatment regimen for osteoporosis should be determined after considering presence of estrogen-deficiency related symptoms such as climacteric symptoms, hyperlipidemia and so on. From the view point of gynecologist, HRT should be chosen first for prevention and treatment of postmenopausal osteoporosis.
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PMID:[How to chose HRT or bisphosphonate for postmenopausal osteoporosis?]. 1577 78


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