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)

Narrow proton nuclear magnetic resonance (1H-NMR) linewidths from plasma have been associated with the presence of malignancy (Fossel et al., New Engl. J. Med. (1986) 315, 1369-1376). In that study, subjects and controls were not fasted. In the present study, 1H-NMR methyl and methylene linewidths were measured in plasma from normolipemic individuals without cancer both during fasting and every 90 min after eating a fat meal. Plasma lipoprotein levels were measured in order to relate results to postprandial lipemia. Methyl, methylene, and average 1H-NMR linewidths were strongly positively correlated with high-density lipoprotein levels and inversely correlated with triacylglycerol-rich lipoprotein levels in both the fasting and postprandial states. Linewidths decreased postprandially, reaching a nadir at the peak of plasma triacylglycerol levels. This study demonstrated that postprandial lipemia can lead to narrowing of plasma methyl and methylene resonances comparable to that reported for subjects with cancer.
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PMID:Proton nuclear magnetic resonance methyl and methylene linewidths from plasma decrease during postprandial lipemia. 259 73

An increase in the plasma levels of apoprotein B-containing lipoproteins is the basis of the magnetic resonance (MR) test for cancer. The narrow MR line width reported by Fossel and co-workers to be associated with the presence of malignant disease is due to a relative increase of very low density lipoprotein. In contrast, the plasma from healthy controls, which has a much broader spectrum, has a higher proportion of high density lipoprotein. However, plasma from patients with hyperlipidemia unrelated to cancer also show narrow MR line widths and are therefore a confounding variable. We used magnetic resonance spectroscopy (MRS) to assess the plasma from 253 patients with a range of lipid related diseases and cancer, and 28 controls. A significant difference (p less than or equal to 0.0005) of 10 Hz exists between the mean line width of the controls and hyperlipidemics without malignant disease. However, in patients with solid tumours a difference of 7 Hz (p less than or equal to 0.0005) in the mean values is recorded although there is an overlap of 6 Hz compared with the controls. Moreover the MRS method was not found to distinguish patients with lymphomas from the control population. The index was not found to be related to patient age or tumour burden.
NMR Biomed 1988 Feb
PMID:Hyperlipidemia as a biochemical basis of magnetic resonance plasma test for cancer. 327 22

A reproducible, fairly narrow-sized population of rat lymph chylomicrons, approximately 100 nm, was isolated by centrifugation and combined with low levels of [1-13C]oleic acid for NMR studies. The carboxyl chemical shift was monitored as a function of aqueous pH to characterize the ionization behavior of the fatty acid in these particles. The titration curves were very similar to those for oleic acid in equivalent-sized emulsion particles composed of egg phosphatidylcholine and triolein. A simple partition-ionization model was fitted to the data to derive values for apparent ionization constant, expressed as pKapp, of 7.4-7.5 and the "true" surface to core partition coefficient of approximately 7 for oleic acid in chylomicrons. The fatty acid in chylomicrons thus appeared to be largely associated with the surface regions of these particles. Addition of bovine serum albumin to the samples showed that near physiologic pH much of the fatty acid was bound to the albumin at fatty acid to albumin-binding stoichiometries as high as 5.1 and with mass ratios of greater than 2 in favor of the lipid or lipoprotein particles. Lowering the pH of the medium shifted the distribution of fatty acid away from albumin so that at pH 5 with the emulsion, virtually all the fatty acid was associated with the lipid. The behavior observed under physiologic conditions is consistent with the rapid clearance and redistribution of fatty acid generated in these particles by lipolytic processes. However, under conditions of severe acidosis, hyperlipidemia, and hypoalbuminemia a significant portion of fatty acids might be retained in triglyceride-rich lipoproteins and their remnants and affect subsequent metabolism.
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PMID:The ionization and distribution behavior of oleic acid in chylomicrons and chylomicron-like emulsion particles and the influence of serum albumin. 333 52

The Basidiomycete fungus Agaricus blazei Murill has traditionally been used as a health food for the prevention of cancer, diabetes, hyperlipidemia, arteriosclerosis and chronic hepatitis. In the present study, we examined the antitumor activities of various substances isolated from the lipid fraction of A. blazei. Tumor growth was retarded by the oral administration of the lipid fraction extracted from A. blazei with a chloroform/methanol mixture in sarcoma 180-bearing mice. The substance with the antitumor activity in the lipid fraction was isolated via silica gel column chromatography, eluted with an acetonitrile/methanol (3:2) mixture and identified as ergosterol by direct comparison of the (1)H NMR and mass spectrometry spectral data of an authentic sample. The oral administration of ergosterol to sarcoma 180-bearing mice significantly reduced tumor growth at doses of 400 and 800 mg/kg administered for 20 d without side effects, such as the decreases in body, epididymal adipose tissue, thymus, and spleen weights and leukocyte numbers induced by cancer chemotherapy drugs. Ergosterol had no cytotoxicity against tumor cells. To clarify the antitumor activity of ergosterol, we examined the effects of ergosterol on tumor-induced angiogenesis using two in vivo models. Intraperitoneal administration of ergosterol at doses of 5, 10 and 20 mg/kg for 5 consecutive d inhibited the neovascularization induced by Lewis lung carcinoma cell-packed chambers, suggesting that either ergosterol or its metabolites may be involved in the inhibition of tumor-induced neovascularization. Therefore, we further examined the inhibitory effects of ergosterol on Matrigel-induced neovascularization. Female C57BL/6 mice were subcutaneously inoculated with Matrigel containing acidic fibroblast growth factor and heparin with or without ergosterol. Ergosterol inhibited the Matrigel-induced neovascularization, suggesting that ergosterol directly inhibits Matrigel-induced neovascularization. From these results, it seems likely that the antitumor activity of ergosterol might be due to direct inhibition of angiogenesis induced by solid tumors. This is the first report of ergosterol as an antiangiogenic substance.
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PMID:Isolation of an antitumor compound from Agaricus blazei Murill and its mechanism of action. 1134 91

The design of safe sweeteners is very important for people who are affected by diabetes, hyperlipemia, and caries and other diseases that are linked to the consumption of sugars. Sweet proteins, which are found in several tropical plants, are many times sweeter than sucrose on a molar basis. A good understanding of their structure-function relationship can complement traditional SAR studies on small molecular weight sweeteners and thus help in the design of safe sweeteners. However, there is virtually no sequence homology and very little structural similarity among known sweet proteins. Studies on mutants of monellin, the best characterized of sweet proteins, proved not decisive in the localization of the main interaction points of monellin with its receptor. Accordingly, we resorted to an unbiased approach to restrict the search of likely areas of interaction on the surface of a typical sweet protein. It has been recently shown that an accurate survey of the surface of proteins by appropriate paramagnetic probes may locate interaction points on protein surface. Here we report the survey of the surface of MNEI, a single chain monellin, by means of a paramagnetic probe, and a direct assessment of bound water based on an application of ePHOGSY, an NMR experiment that is ideally suited to detect interactions of small ligands to a protein. Detailed surface mapping reveals the presence, on the surface of MNEI, of interaction points that include residues previously predicted by ELISA tests and by mutagenesis.
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PMID:Probing the surface of a sweet protein: NMR study of MNEI with a paramagnetic probe. 1146 46

One new flavonoide was isolated from Vicia amoena Fisch. On the basis of spectral (UV, MS, NMR) and chemical reactions, it was elucidated to be kaempferol-3-O-beta-D-mannoside, named amoenin(A3). Moreover, five known compounds have been isolated and identified as quercetin, kaempferol, quercetin-3-O-alpha-L-rhamoside, quercetin-3-O-beta-D-glucoside, kaempferol-3, 7-O-alpha-L-dirhamoside. The total flavonoides showed significant effects on inducing hyperlipidemia and increasing micro-blood vessel elasticity.
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PMID:[Studies on the chemical constitutens of Vicia amoena Fisch]. 1159 20

We present here a novel integrative metabonomic approach to probe toxic effects of drugs in experimental animals using alpha-naphthylisothiocyanate (ANIT) as a model hepatotoxicant. Male Han-Wistar rats were dosed with ANIT (150 mg/kg, n = 25), and plasma and liver samples were collected for NMR and magic-angle spinning (MAS) NMR spectroscopy at 3, 7, 24, 31, and 168 h postdosing. Urine was collected continuously for 3 days prior to dosing and up to 168 h postdose. Histopathology and plasma clinical chemistry was also performed at all time points. Liver samples were analyzed either intact by 600 MHz 1H MAS NMR techniques or using high resolution (liquid state) 1H NMR of water-acetonitrile extracts. These data were related to sequential 1H NMR measurements in urine and plasma using pattern recognition methods. 1D 1H NMR spectra were data-reduced and analyzed using principal components analysis (PCA) to show the time-dependent biochemical variations induced by ANIT toxicity. From the eigenvector loadings of the PCA, those regions of the 1H NMR spectra and hence the combinations of endogenous metabolites marking the main phase of the toxic episode were identified. The ANIT-induced biochemical manifestations included a hepatic lipidosis associated with hyperlipidaemia; hyperglycaemia and glycosuria; increased urinary excretion of taurine and creatine; a shift in energy metabolism characterized by increased plasma ketone bodies with reduced urinary excretion of tricarboxylic acid cycle intermediates and raised hepatic bile acids leading to bile aciduria. The integration of metabolic data derived from several sources gives a holistic approach to the study of time-related toxic effects in the intact system and enables the characterization of key metabolic effects during the development and recovery from a toxic lesion.
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PMID:NMR and pattern recognition studies on the time-related metabolic effects of alpha-naphthylisothiocyanate on liver, urine, and plasma in the rat: an integrative metabonomic approach. 1159 32

We present the patient with 1-month history of mild hypertension, who was admitted to our department with suspicion of coronary heart disease. He had family history of hypertension and coronary heart disease, hyperlipidaemia and he has been smoker for several years. During the diagnostic exertion test chest pain together with an unusual high blood pressure was found (240/140 mmHg). The results of catecholamines and their metabolites in 24-urine collection, abdominal ultrasonography and NMR revealed pheochromocytoma in the left adrenal gland, which was removed successfully. Particular clinical examination allowed to include the patient to the group with low-symptomatic pheochromocytoma. Abdominal USG, which had been done prior to the exertion test, didn't reveal any incidental tumor in the adrenal glands. The abnormal hypertensive reaction during exertion test was the main decision of the urine catecholamines and their metabolites determination. Pheochromocytoma should be included to the differential diagnosis in all patients with chest pain and high blood pressure during diagnostic exertion test.
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PMID:[Low-symptomatic pheochromocytoma]. 1195 7

The synthesis and characterization of Co(II) and Co(III) 2,6-pyridinedicarboxylate (dipic(2-)) complexes are reported. Solid-state X-ray characterizations were performed on [Co(H(2)dipic)(dipic)].3H(2)O and [Co(dipic)(mu-dipic)Co(H(2)O)(5)].2H(2)O. Two coordination modes not previously observed in dipicolinate transition metal complexes were observed in these complexes; one involves metal coordination to the short C-O (C=O) bond, and the other involves metal coordination to a protonated oxygen atom. Solution studies, including paramagnetic NMR and UV-vis spectroscopy, were done showing the high stability and low lability of the Co(III) complex, whereas the Co(II) complexes exhibited ligand exchange in the presence of excess ligand. The [Co(dipic)(2)](2-) complex has pH dependent lability and in this regard is most similar to the [VO(2)dipic](-) complex. The [Co(dipic)(2)](2-) was found to be effective in reducing the hyperlipidemia of diabetes using oral administration in drinking water in rats with STZ-induced diabetes. Oral administration of VOSO(4) was used as a positive control for metal efficacy against diabetes. In addition to providing a framework to evaluate structure-function relationships of various transition metal complexes in alleviating the symptoms of diabetes, this work describes novel aspects of structural and solution cobalt chemistry.
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PMID:Cobalt(II) and cobalt(III) dipicolinate complexes: solid state, solution, and in vivo insulin-like properties. 1223 Mar 90

Microorganisms producing squalene synthase inhibitors were screened from soils. A high producer was selected and identified as a Streptomyces species. Two active inhibitors were obtained from culture broths via a series of purification processes involving solvent extraction, WK-10 cation-exchange column chromatography, HP-20 adsorption column chromatography, silica-gel column chromatography, preparative HPLC, and crystallization. The inhibitors were confirmed as macrolactins A and F with molecular weights of 402 by UV-absorption spectrometry, fast atom bombardment mass spectometry, and 13C- and 1H-NMR analyses. Kinetic results for macrolactins A and F showed that they appear to be noncompetitive inhibitors of rat liver squalene synthase with IC50 values of 1.66 and 1.53 micromol/L, respectively. Since mammalian squalene synthase was used, these inhibitors have significant potential as therapeutic agents for hyperlipemia and suppression of cholesterol biosynthesis.
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PMID:Characteristics of the squalene synthase inhibitors produced by a Streptomyces species isolated from soils. 1473 15


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