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D Milosavljevic

Publications and source records attributed to D Milosavljevic.

9 recordsLinked to original sources
PubMed2002

Peroxisome proliferator-activated receptor (PPAR) agonists decrease lipoprotein lipase secretion and glycated LDL uptake by human macrophages.

Lipoprotein lipase (LPL) acts independently of its function as triglyceride hydrolase by stimulating macrophage binding and uptake of native, oxidized and glycated LDL. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors expressed in monocyte/macrophages, where they control cholesterol homeostasis. Here we study the role of PPARs in the regulation of LPL expression and activity in human monocytes and macrophages. Incubation of human monocytes or macrophages with PPARalpha or PPARgamma ligands increases LPL mRNA and intracellular protein levels. By contrast, PPAR activators decrease secreted LPL mass and enzyme activity in differentiated macrophages. These actions of PPAR activators are associated with a reduced uptake of glycated LDL and could influence atherosclerosis development associated with diabetes.

Biological Transport↗
PubMed2001

Preferential reduction of very low density lipoprotein-1 particle number by fenofibrate in type IIB hyperlipidemia: consequences for lipid accumulation in human monocyte-derived macrophages.

The combined (mixed) type IIB phenotype is typically associated with premature atherosclerosis and characterised by concomitant elevation of plasma levels of atherogenic triglyceride-rich lipoproteins, consisting of very low density lipoprotein (VLDL)-1 (Sf 60-400), VLDL-2 (Sf 20-60), and intermediate density lipoprotein (IDL) (Sf 12-20), as well as small dense LDL. After dietary stabilisation, type IIB patients received micronised fenofibrate (267 mg/day) for up to 12 months. At baseline (T0), patients (n=11) displayed fasting triglyceride, cholesterol and apoB levels of 308+/-13, 350+/-17 and 187+/-9 mg/dl, respectively. Micronised fenofibrate (M-fenofibrate) induced marked reductions in plasma triglyceride (TG) (-61%, P<0.0001), total cholesterol (-32%, P=0.0005) and apolipoprotein (apo) B (-33%, P<0.001) at 12 months (T12); similar effects were seen after 3 months (T3) of treatment. These changes resulted from significant reductions in VLDL-1 (-75%, P=0.00001), VLDL-2 (-46%, P=0.002) and LDL (-33%, P<0.0003); IDL concentrations were unchanged. At baseline, VLDL-1 constituted the major TG-rich lipoprotein (TRL) fraction (50% of total mass), but only 25% at T12. These drug effects were accompanied by marked increase in HDL-C (+20%, P=0.018). Quantitative changes in triglyceride-rich lipoproteins were accompanied by significant qualitative modifications in particle size and chemical composition (VLDL-1: TG, -10.7%, P<0.001; FC, +59%, P=0.0002; PL, +19%, P=0.033; VLDL-2: FC, +11%, P=0.027; IDL: FC, +14%, P=0.0004; PL, +12%, P=0.002). Reduction in the TG content of VLDL-1 was reflected in a shift of particle size distribution to smaller diameters (mean 45.4 and 42.3 nm, respectively, at T0 and T12). We evaluated the relative atherogenicity of TRL subfractions by determining their capacity, when normalised to equal particle numbers (as apoB 100 content), to induce lipid accumulation in human monocyte-derived macrophages. Among TRL subfractions, VLDL-1 (100 microg apoB/ml) possessed the highest capacity to induce macrophage lipid loading (up to sevenfold increase in TG content, P<0.001; free cholesterol, up to 1.7-fold; P<0.05). At 100 microg apoB/ml, cellular TG loading from VLDL-1 was twofold greater than that for VLDL-2 (P<0.01), and fivefold greater than for IDL (P<0.01). Despite drug-induced changes in the qualitative properties of TRL subfractions, the activity of VLDL-1, VLDL-2 and IDL as ligands which lead to induction of macrophage lipid accumulation, at equivalent particle numbers, was not detectably altered. By contrast, the fibrate-mediated reduction in the number of circulating VLDL-1 and VLDL-2 particles (four and twofold, respectively) resulted in marked decrease in cellular lipid loading. Considered together, these findings suggest that fenofibrate may act at systemic and arterial levels to reduce the cardiovascular risk associated with VLDL subfractions in patients with a combined hyperlipidemic (type IIB) phenotype. Indeed, we speculate that reductions in circulating levels of VLDL-1 and VLDL-2 may diminish intimal penetration of these particles and thus their propensity to enhance arterial macrophage lipid accumulation and foam cell formation. Finally, fenofibrate further attenuated the atherogenic lipid profile in these patients by inducing marked reduction in LDL and elevation in cardioprotective HDL.

Aged↗
PubMed2001

Conscious sedation with midazolam or propofol does not alter left ventricular diastolic performance in patients with preexisting diastolic dysfunction: a transmitral and tissue Doppler transthoracic echocardiography study.

UNLABELLED: The effects of midazolam and propofol on left ventricular (LV) diastolic function have not been evaluated in humans. We tested the hypothesis that midazolam and propofol alter LV diastolic function evaluated with transmitral and tissue Doppler transthoracic echocardiography in patients with normal LV systolic function in the presence and absence of preexisting diastolic dysfunction. After IRB approval and informed consent, patients (n = 34) with normal or reversed transmitral blood flow velocity E-to-A ratios received 3 escalating doses of midazolam (0.025, 0.05, and 0.1 mg/kg) or propofol (0.25, 0.5, and 1.0 mg/kg) over 10 s at 5-min intervals. Hemodynamic variables and indices of diastolic function were recorded 3 min after each dose of midazolam and propofol. Patients with diastolic dysfunction demonstrated decreased ratios of peak transmitral E-to-A wave velocity and their corresponding time-velocity integrals as compared with normal patients. Reductions in anterior and posterior mitral annulus E/A ratios were also present. Midazolam and propofol did not further alter indices of LV diastolic function in patients with impaired early LV filling. The results indicate that sedation with midazolam or propofol does not affect indices of LV diastolic performance in healthy patients and those with preexisting diastolic dysfunction. IMPLICATIONS: Sedation with midazolam or propofol does not alter indices of left ventricular diastolic function in healthy patients and those with preexisting left ventricular filling abnormalities as evaluated by transthoracic echocardiography.

Adult↗
PubMed1999

Lipoprotein response to a National Cholesterol Education Program step II diet with and without energy restriction.

This study examined the efficacy of a National Cholesterol Education Program (NCEP) step II diet (25% fat with < 7% saturated fat [SFA]) with and without moderate energy restriction. We tested the hypothesis that moderate energy restriction would improve the lipid profile resulting from an isoweight NCEP step II diet. Twenty hypercholesterolemic subjets (10 men and 10 postmenopausal women) consumed the following three controlled diets, each of 4 weeks' duration, as outpatients: (1) high-fat, high-saturated-fat diet to establish baseline lipids and isoweight energy requirements, (2) NCEP step II diet at isoweight energy, and (3) NCEP step II diet with an energy level 15% less than isoweight. The NCEP step II diet at isoweight energy reduced total cholesterol (TC) by 4% (P = .015), high-density lipoprotein cholesterol (HDL-c) by 13% (P < .0001), and HDL2-c by 40% (P < .0001). The TC:HDL-c ratio increased from 4.9 to 5.5 (P < .0001) and was increased in 19 of 20 subjects. Apolipoprotein B (apo B)-containing lipoproteins changed reciprocally: low-density lipoprotein cholesterol (LDL-c) decreased 4% (P = .008) and very-low-density lipoprotein cholesterol (VLDL-c) increased 29% (P < .0001). Apo B levels did not change. Compared with the NCEP isoweight diet the NCEP hypocaloric diet significantly reduced VLDL-c (-9%, P = .014) and apo B (-5%, P = .015). There was an additional reduction in TC (-4%, P = .073) and LDL-c (-4%, P = .126) with no change in HDL-c (P = .807). These data indicate that a NCEP step II diet with energy restriction produces a more desirable lipoprotein response than a NCEP step II isoweight diet. Neither NCEP step II diet improved the TC:HDL-c ratio.

Adult↗
PubMed1997

Assessment of the potency and intrinsic activity of systemic versus intrathecal opioids in rats.

BACKGROUND: One measure of an opioid's efficacy is its ability to retain its analgesic effect as the intensity of a noxious stimulus is increased. A few studies have assessed the ability of either spinal or systemic opioids to produce analgesia using low- and high-intensity stimulation. There are little data available to show whether there are differences in efficacy between systemic and intrathecal opioid administration. The purpose of this study was to assess the relative efficacy of several clinically useful opioids systemically and spinally and to determine whether intrathecal administration resulted in greater efficacy than systemic administration. METHODS: Groups of rats were administered multiple doses of meperidine, morphine, hydromorphone, fentanyl, sufentanil, or buprenorphine either subcutaneously or intrathecally via implanted catheters. Noxious radiant heat was applied sequentially to each hindpaw, one at low intensity (adjusted to a mean withdrawal latency of 10 s) and one at high intensity (adjusted to a mean withdrawal latency of 5 s). Paw withdrawal latencies were recorded; dose-response curves for each intensity and each route of administration were graphically recorded, and ED50s were calculated. Ratios of high-to low-stimulus intensity ED50s were calculated for both routes of administration for each drug, and the ratios of subcutaneous-to-intrathecal ED50s for low-intensity stimulation were calculated to assess the relative systemic versus spinal potencies for each drug. RESULTS: The ratios of the high-to-low intensity ED50s were meperidine, 11.8, morphine, 6.1, hydromorphone, 2.6, fentanyl, 2.3, sufentanil, 1.8, and buprenorphine, 24.0. For intrathecal administration, there was uniformity of the high- to low-intensity ED50 ratios for the agonist drugs (meperidine, 2.1; morphine, 2.1; hydromorphone, 1.9; fentanyl, 1.8; sufentanil, 1.6). For morphine and hydromorphone, the systemic ED50 doses were several hundred times the intrathecal ED50s whereas the systemic-to-spinal ED50 ratios for the other drugs were 20 or less. CONCLUSIONS: As intensity of noxious stimulation is increased, the more potent opioid agonists, administered systemically, produce antinociception with lesser increases in dose compared with lower potency drugs such as meperidine or morphine. When given spinally all opioid agonists tested, including morphine and meperidine, demonstrated good efficacy, as measured by their ability to provide antinociception for high versus low intensity stimulation.

Administration, Cutaneous↗
PubMed1994

High-density lipoprotein subfractions measured in stored serum.

We compared the effects of freezing serum on the determination of high-density lipoprotein (HDL) subfractions by two dual-precipitation methods, heparin and manganese chloride/dextran sulfate (HM/DS) (Gidez et al., J Lipid Res 1982;23:1206-23) and DS/DS (Warnick et al., Clin Chem 1982;28:1574), and by ultracentrifugation. Storing serum for 1 month at -70 degrees C resulted in reduced HDL3-cholesterol by ultracentrifugation and reduced total and HDL3-cholesterol by the DS/DS method. There was no change in either total HDL-cholesterol or HDL3-cholesterol with the HM/DS method. Additional studies involving only HM/DS indicated that total HDL-cholesterol in serum stored at 4 degrees C begins to decline after 3 days (-3.1 +/- 3.5%, P < 0.1). HDL was stable at -20 degrees C for 2 weeks but both total and HDL3-cholesterol decreased significantly after 1 month. Storage of serum at -70 degrees C resulted in no changes for 1 year; however, at 18 months, HDL3-cholesterol was reduced 13% (P = 0.002). We conclude that HDL subfractions can be determined accurately in serum as well as in plasma after storage at -70 degrees C for up to 1 year.

Blood Preservation↗
PubMed1988

Suxamethonium dosage in electroconvulsive therapy.

A double-blind study was conducted in 52 patients who received a total of 180 electroconvulsive therapy treatments. Patients were allocated randomly to receive doses of 15 mg, 25 mg or 50 mg of suxamethonium. Those who received suxamethonium 50 mg took significantly longer to breathe again compared with patients who received the lower doses, and were significantly more likely to have a very well modified convulsion than patients who received suxamethonium 15 mg. There were no differences among the groups in the incidences of muscle pains after treatment. We conclude that all three doses were acceptable; however, a dose of 25 mg had practical advantages over 50 mg and theoretical advantages over 15 mg.

Adult↗
PubMed1983

Determination of organ area. Application to thyroid.

A method has been developed for the quantification of a projected organ area using a standard gamma camera with pinhole collimation and computer processing of two vertically displaced images. Formulae have been derived expressing the uniquely determined quadratic relationship between object area and aperture distance with respect to projective image areas. This technique is extremely simple and its successful application to thyroid imaging is described.

Humans↗