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)

Based on our new finding that an inflammation in which tumor necrosis factor (TNF) is primed or triggered (ontogenic inflammation) can regulate the homeostasis in ontogenesis, we have identified a new lipopolysaccharide from wheat flour (LPSw) that can induce ontogenic inflammation in adult mice. LPSw can prime adult mice to produce TNF when given orally or percutaneously, suggesting that it may maintain homeostasis in adults. LPSw can cure experimental animals of diabetes, hyperlipidemia, ulcer, and herpes. It can also stimulate bone resorption and egg-laying, and shows a strong analgesic effect that is blocked by naloxone. This effect even allows a release from drug addiction. Suppression of serum cholesterol level by oral uptake of LPSw in Watanabe heritable hyperlipidemic (WHHL) rabbit was also observed. Infection of toxoplasma was prevented by oral uptake of LPSw. The realization that a single oral or percutaneous administration of LPSw may be a cure for multiple intractable diseases may lead to the presentation of a nontoxic type of Coley's toxin, which is known to be an efficient cancer treatment, but has high toxicity.
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PMID:Oral or percutaneous administration of lipopolysaccharide of small molecular size may cure various intractable diseases: a new version of Coley's toxin. 147 70

The hyperlipidemia accompanying infection has been attributed to production of tumor necrosis factor. This cytokine inhibits adipose tissue lipoprotein lipase, which could decrease clearance of lipoproteins. Infections also increase hepatic lipogenesis. We now have demonstrated that tumor necrosis factor-alpha stimulates lipid synthesis in vivo. 2 h after administration of tumor necrosis factor (25 micrograms/200 g), plasma triglycerides increase 2.2-fold and remain elevated for 17 h. Plasma cholesterol also increases, but this effect appears after 7 h. Tumor necrosis factor rapidly stimulates incorporation of tritiated water into fatty acids in the liver (1-2 h), which persists for 17 h. Also, tumor necrosis factor stimulates hepatic sterol synthesis. Of note, tumor necrosis factor treatment does not stimulate lipid synthesis in other tissues, including adipose tissue. Labeled fatty acids rapidly increase in the plasma, raising the possibility that stimulation of hepatic lipogenesis by tumor necrosis factor contributes to the hyperlipidemia of infection.
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PMID:Tumor necrosis factor-alpha stimulates hepatic lipogenesis in the rat in vivo. 359 72

Infection of 10-day-old chicken embryos with an avian retrovirus. Rous-associated virus type 7, resulted in a disease characterized by stunting and hyperlipidemia. By 20 days after hatch, infected chickens were smaller than hatchmates and developed ataxia and obesity over the next 30 days. Histological examinations of livers from infected chickens revealed a diffuse panlobular fatty infiltrate involving an accumulation of fat in microdroplets. Electron microscopic examinations of livers from infected chickens revealed hepatocytes with swollen mitochondria that lacked cristae. The thyroid and pancreas were infiltrated with lymphoblastoid cells by 1 week after hatch. An examination of the blood revealed a mild anemia, a frank lipemia, and high levels of uric acid. This syndrome induced by Rous-associated virus type 7 in chickens may be useful for elucidating the nature of several diseases, including that found in the fatty liver and kidney syndrome of chickens and that observed in a strain of obese chickens.
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PMID:Rous-associated virus type 7 induces a syndrome in chickens characterized by stunting and obesity. 629 59

Infection-induced hyperlipidemia develops due to a combination of factors, one of which is decreased clearance of lipids from the bloodstream due to depressed synthesis of lipoprotein lipase (LPL). Recently, the peroxisome proliferator activated receptors (PPARs) have been shown to be important in the regulation of LPL, particularly PPARgamma. PPARgamma and its heterodimerization partner, RXR alpha have been shown to be transcriptional activators of LPL in co-transfection analysis. Therefore, we hypothesized that the decrease in LPL expression during endotoxemia may be a result of depressed PPARgamma expression. In these studies, we examined the effect of endotoxin or its proximal mediator, tumor necrosis factor (TNF), on the expression of PPARgamma in white (WAT) and brown adipose tissue (BAT) in CD-1 mice. We report that treatment with endotoxin, but not TNF, transiently decreased PPARgamma mRNA levels 4 hr after treatment. However, endotoxin or TNF treatment decreased PPARgamma protein levels after 18 hr, which was at a time when LPL mRNA levels were also depressed. These data suggest that decreased PPARgamma expression following endotoxin or TNF treatment may contribute to the hyperlipidemia due to decreased expression of LPL, which would impair triglyceride clearance.
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PMID:Decreased expression of murine PPARgamma in adipose tissue during endotoxemia. 920 56

Infection, inflammation and trauma induce marked changes in the plasma levels of a wide variety of proteins (acute phase response), and these changes are mediated by cytokines. The acute phase response is thought to be beneficial to the host. The host's response to injury also results in dramatic alterations in lipid metabolism and circulating lipoprotein levels which are mediated by cytokines. A large number of cytokines including TNF, the interleukins, and the interferons increase serum triglyceride levels. This rapid increase (1-2 h) is predominantly due to an increase in hepatic VLDL secretion while the late increase may be due to a variety of factors including increased hepatic production of VLDL or delayed clearance secondary to a decrease in lipoprotein lipase activity and/or apolipoprotein E levels on VLDL. In animals other than primates, cytokines also increase serum cholesterol levels, most likely by increasing hepatic cholesterol. Cytokines increase hepatic cholesterol synthesis by stimulating HMG CoA reductase gene expression and decrease hepatic cholesterol catabolism by inhibiting cholesterol 7 alpha-hydroxylase, the key enzyme in bile acid synthesis. Injury and/or cytokines also decrease HDL cholesterol levels and induce alterations in the composition of HDL. The content of SAA and apolipoprotein J increase, apolipoprotein A1 may decrease, and the cholesterol ester content decreases while free cholesterol increases. Additionally, key proteins involved in HDL metabolism are altered by cytokines; LCAT activity, hepatic lipase activity, and CETP levels decrease. These changes in lipid and lipoprotein metabolism may be beneficial in a number of ways including: lipoproteins competing with viruses for cellular receptors, apolipoproteins neutralizing viruses, lipoproteins binding and targeting parasites for destruction, apolipoproteins lysing parasites, redistribution of nutrients to cells involved in the immune response and/or tissue repair, and lipoproteins binding toxic agents and neutralizing their harmful effects. Thus, cytokines induce marked changes in lipid metabolism that lead to hyperlipidemia which represents part of the innate immune response and may be beneficial to the host.
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PMID:Beneficial effects of cytokine induced hyperlipidemia. 955 31

To define the extent and time course of HIV-proteinase inhibitor (PI) effects on serum lipid levels 148 patients on triple combination therapy including PIs and 91 patients on therapy with two nucleosides as a control group were evaluated. In the PI group there was a significant increase in total cholesterol after 3, 6 and 12 months compared to the baseline level (198, 204 and 203 vs. 176 mg/dl). The increase in triglycerides was 25.5% from the baseline at month 3. Indinavir had a significantly higher impact on cholesterol levels than saquinavir. No changes in lipids were seen in the control group. It was concluded that hyperlipidemia is associated with PI use, becomes evident within 3 months of treatment and seems to be substance specific.
Infection
PMID:Hyperlipidemia under treatment with proteinase inhibitors. 1021 34

Kidney transplant recipients require careful follow-up in both the early (< 6 months) and late posttransplant periods. Monitoring should focus on graft function and the most common complications of immunosuppression therapy. Infections, especially CMV infection, require particular attention in the first few months after transplantation, when immunosuppression is most intense. In both the early and the late posttransplant periods, an emphasis should be placed on intensive management of CVD risk factors (e.g., hypertension, hyperlipidemia, cigarette smoking). Screening for malignancies known to occur with a high incidence after transplantation is also important. With the improved short-term survival rates brought about by new, potent immunosuppressive agents, emphasis has now shifted to the prevention and treatment of posttransplant complications in kidney transplant recipients. A heightened awareness of these complications, along with a cooperative effort between primary care physicians and transplant programs, offers the best hope for further improvement in outcomes after kidney transplantation.
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PMID:Care of the kidney transplant recipient. Vigilant monitoring creates the best outcome. 1236 Jun 61

Apolipoprotein E2, which has an R158 for C substitution, has reduced affinity for the LDL receptor and is associated with type III hyperlipoproteinemia in humans. Consistent with these observations, we have found that following adenovirus-mediated gene transfer, full-length apoE2 aggravates the hypercholesterolemia and induces hypertriglyceridemia in E-deficient mice and induces combined hyperlipidemia in C57BL/6 mice. Unexpectedly, the truncated apoE2-202 form that has an R158 for C substitution when expressed at levels similar to those of the full-length apoE2 normalized the cholesterol levels of E-deficient mice without induction of hypertriglyceridemia. The apoE2 truncation increased the affinity of POPC-apoE particles for the LDL receptor, and the full-length apoE2 had a dominant effect in VLDL triglyceride secretion. Hyperlipidemia in normal C57BL/6 mice was prevented by coinfection with equal doses of each, the apoE2 and the apoE2-202-expressing adenoviruses, indicating that truncated apoE forms have a dominant effect in remnant clearance. Hypertriglyceridemia was completely corrected by coinfection of mice with an adenovirus-expressing wild-type lipoprotein lipase, whereas an inactive lipoprotein lipase had a smaller effect. The findings suggest that the apoE2-induced dyslipidemia is not merely the result of substitution of R158 for C but results from increased secretion of a triglyceride-enriched VLDL that cannot undergo lipolysis, inhibition of LpL activity, and impaired clearance of chylomicron remnants. Infection of E(-)(/)(-)xLDLr(-)(/)(-) double-deficient mice with apoE2-202 did not affect the plasma cholesterol levels, and also did not induce hypertriglyceridemia. In contrast, apoE2 exacerbated the hypercholesterolemia and induced hypertriglyceridemia, suggesting that the LDL receptor is the predominant receptor in remnant clearance.
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PMID:Molecular mechanisms of type III hyperlipoproteinemia: The contribution of the carboxy-terminal domain of ApoE can account for the dyslipidemia that is associated with the E2/E2 phenotype. 1292 33

Sirolimus (SRL) has become an option in kidney transplantation, especially among patients who develop chronic allograft nephropathy (CAN). This study sought to evaluate the safety and efficacy of SRL in 103 kidney recipients of mean age 40 years, including 78 recipients of organs from deceased donors. The major reason for conversion was calcineurin inhibitor (CNI) nephrotoxicity (42.3%) followed by CAN (35.4%). A preconversion kidney biopsy was performed in 89 patients with CAN diagnosed in 51. Mean time to conversion was 40.5 months. The new therapy was: SRL/mycophenolate mofetil (MMF)/prednisone (Pred) in 79 patients; SRL/tacrolimus (TAC)/Pred in 15; and other SRL combinations in 9. The target SRL trough level was 5.0 to 8.0 ng/mL. To evaluate the impact of conversion on renal function, we compared the proteinuria and inverse serum creatinine at 3 months before conversion, at conversion, and at 1, 3, 6, 12, and 24 months postconversion. The overall mean follow-up time was 13.2 months. The analysis showed significant improvement in renal function at month 1 postconversion (P<.05) with stabilization thereafter. The SRL/MMF combination frequently induced anemia and/or leukopenia (n=23). Infections included pneumonia (n=10), herpes zoster (n=7), herpes simplex (n=3), cytomegalovirus (n=2), histoplasmosis (n=2), tuberculosis (n=2), and neurocryptococcosis (n=1). Reasons for SRL discontinuation were myelotoxicity (n=4), infection (n=3), nephrotoxicity (n=3), gastrointestinal intolerance (n=3), myopathy (n=1), pneumonitis (n=1), hyperlipidemia (n=1), and other reasons (n=3). Graft loss occurred in 29 patients due to CAN (n=21) followed by death (cardiovascular, n=2; infectious, n=2), acute rejection (n=3), and infection following immunosuppression withdrawal (n=1). We concluded that SRL represented an option but reducing associated immunosuppression should strongly be considered to minimize the frequent side effects, especially infections.
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PMID:Posttransplantation conversion to sirolimus-based immunosuppression: a single center experience. 1808 30

Renal transplant recipients have increased mortality rates when compared with the general population. The new immunosuppressive drugs have improved short-term patient survival up to 95% at 1-2 years, but these data have to be confirmed in long-term follow-up. Furthermore, no particular regimen has proved to be superior over others with regard to patient survival. Cardiovascular diseases are the most common cause of mortality in renal transplant recipients and while no immunosuppressive drug has been directly associated with cardiovascular events, immunosuppressive drugs have different impacts on traditional risk factors. Corticosteroids and ciclosporin are the agents with the most negative impact on weight gain, blood pressure and lipids. Tacrolimus increases the risk of new-onset diabetes mellitus. Sirolimus and everolimus have the most impact on risk factors for post-transplant hyperlipidaemia. Modifications in immunosuppression could improve the cardiovascular profile but there is little evidence regarding the beneficial effects of these changes on patient outcomes. Malignancies are also an increasing cause of mortality, overtaking cardiovascular disease in some series. Induction therapy, azathioprine and calcineurin inhibitors (CNIs) are probably the immunosuppressive agents most linked with post-transplant malignancies. Mycophenolate mofetil (MMF) has no negative impact on the incidence of malignancies. Target of rapamycin (mTOR) inhibitors have antioncogenic properties and they are associated with a lower incidence of malignancies. In addition, these agents have been recommended for use to decrease the dose or withdrawal of CNIs in patients with malignancies. Infections are still an important cause of morbidity and mortality in renal transplant recipients. Some immunosuppressive agents such as MMF increase the incidence of cytomegalovirus infection and the need for prophylactic measures in risk recipients. The use of potent immunosuppressive therapy has resulted in the appearance of BK virus nephropathy, which progresses to graft failure in a high percentage of patients. Although first associated with tacrolimus and MMF immunosuppression, recent data suggest that BK nephropathy appears with any kind of triple therapy. In conclusion, reducing risk factors for patient death should be a major target to improve outcomes after renal transplantation. Effort should be made to control cardiovascular diseases, malignancies and infections with improved use of immunosuppressive drugs. Preliminary results with belatacept suggest its safety and efficacy, and open new perspectives in the immunosuppression of de novo renal transplant recipients.
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PMID:Immunosuppressive drugs in kidney transplantation: impact on patient survival, and incidence of cardiovascular disease, malignancy and infection. 1985 26


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