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Biomedical subjects

G Lupattelli

Publications and source records attributed to G Lupattelli.

At least 55 records · Page 3Linked to original sources

Blood rheology during bacterial infection in the elderly and early middle-aged.

The aim of this study was to ascertain if the hemorheological profiles in 35 elderly and 20 young to middle-aged patients returned to normal after bacterial infection. Erythrocyte sedimentation rates, fibrinogen levels, plasma viscosity, hematocrit, white blood cell count and filterability rates (through 5 mu diameter pore filters, using a low shear positive pressure Nuclepore filtration system) of red blood cells and unfractionated leucocytes were determined at the onset of acute bacterial infection, after 3 weeks at full clinical recovery, and again 2 weeks later at the end of convalescence. Our data confirm that rheological impairments exist at the onset of bacterial infection, and persist up to clinical recovery. At the end of convalescence the unfractionated leucocyte filterability rate was still significantly higher in the elderly patients, compared not only to our normal standard, but also to average values in the younger group.

Adult↗

Effect of prostaglandin E1 on low density lipoprotein apo-B-receptor binding in human, rat and swine liver in vitro.

The effect of PGE1 on low density lipoprotein (LDL) apo-B-receptor binding was examined in human, rat and swine liver. Autologous LDL (for humans and swines) and homologous LDL (for rats) were isolated by ultracentrifugation and labelled with 123I using Iodogen followed by purification with dialysis. LDL-concentrations of 0.1-6 micrograms protein/ml were used for direct binding assays investigating the specific binding of labelled LDL in presence of increasing PGE1-concentrations (100 pM to 100 microM). In separate experiments the effect of PGE1 on displacement of specifically bound 123I-LDL by unlabelled ones was studied. The binding capacities estimated by Scatchard analysis were similar for human and rat liver LDL-apo-B-receptor binding, however, swine liver exhibited a significantly (p less than 0.001) lower binding capacity for 123I-LDL. PGE1 significantly (p less than 0.01-0.001) increased the amount of 123I-LDL specifically bound to the liver apo-B-receptors and the binding affinity in all liver preparations of the 3 species in a dose-dependent manner. PGE1 also significantly increased competition of unlabelled LDL for 123I-LDL bound to its specific apo-B-receptors in a dose-dependent manner (p less than 0.01-0.001) with an ED50 of 123 +/- 64 nM for human liver, 901 +/- 102 nM for rat liver obtained during anaesthesia, 74 +/- 23 nM for rat liver obtained after decapitation and 941 +/- 121 nM for swine liver. In human liver iloprost (ED50 = 876 +/- 53 nM) and PGI2 (ED50 = 52 +/- 12 microM) were less effective than PGE1, PGE2 had no effect on LDL-induced competition. It is concluded that PGE1 renders LDL more sensitive for apo-B-receptor binding suggesting a potential hypolipidemic action of PGE1.

Adult↗

Comparison of different methods for LDL isolation and radioiodination on liver LDL receptor binding in vitro.

Lipoproteins were isolated either by immunoaffinity chromatography (LDL and VLDL) or ultracentrifugation (LDL). Purified lipoproteins were labeled with 123I using either Iodogen or iodine-monochloride (IC1) each followed by purification with gel-chromatography or dialysis (total of 4 combinations). Lipoprotein-concentrations of 0.1-6 micrograms protein/mL were used for direct binding assays investigating the specific binding of labeled lipoproteins (in the presence of a 50-fold excess of unlabeled lipoproteins) to human liver apo-B, E-receptors. In separate experiments displacement of bound 123I-lipoproteins (labeled by the methods mentioned) by unlabeled ones was studied. The binding capacities estimated by Scatchard analysis were similar to each other (141-163 ng protein bound/mg liver plasma membrane protein) independent from the method used for isolation and labeling. Also the affinity constants were very similar and ranged from 0.9 to 1.7 micrograms protein/L. It is concluded that immunoaffinity chromatography or ultracentrifugation for isolation of lipoproteins and the Iodogen or IC1-method for radiolabeling can be recommended to be equally good for in vitro receptor investigation.

Adult↗

Isradipine, a calcium-entry blocker, decreases vascular [125-I]low-density lipoprotein entry in hypercholesterolemic rabbits.

In 72 male rabbits aged 6 months, the endothelium of the abdominal aorta was abraded by a Fogarthy catheter. The animals were then fed a 1% cholesterol-supplemented diet for 4 weeks. In addition, half of the animals were treated for the entire period with isradipine (0.3 mg/kg daily), a dihydropyridine calcium antagonist; the other 36 animals served as controls. One hour and 3, 6, 12, 24, and 48 hours before the animals were killed, [125-I]low-density lipoprotein (LDL 10 microCi) was administered intravenously (i.v.) to six animals in each group. The [125-I]LDL entry was quantified in the abdominal aorta according to the type and presence of endothelial lining. Isradipine significantly reduced the [125-I]LDL entry at most time intervals. In parallel, an increase in vascular prostaglandin (PGI2) synthesis was noted, which might be the underlying mechanism for the decreased LDL entry.

Animals↗

Are leucocyte-derived free radicals involved in ischaemia in human legs?

Leucocyte-derived free radicals were monitored in 30 stage II peripheral vascular disease (PVD) patients in an open placebo-controlled study. Linked to a transcutaneous oxygen pressure (TcPO2) monitor, they performed two consecutive standard treadmill tests (5 min, 2 km h-1, 12% slope) before and after 15-days treatment with placebo or a leucocyte-derived free radical scavenger (Piroxicam, 20 mg day-1), the second test being carried out at the TcPO2 half-recovery time. Blood samples were collected at baseline, at the maximum walking times and the TcPO2 half recovery times. The total and differential leucocyte counts, the percentage of cells with pseudopodia or cytoplasmatic irregularities, the filterability rates (using a positive pressure Nuclepore filter system) of the main leucocyte subfractions and plasma oxidant activity were monitored. Compared with values before treatment and with the placebo-treated group Piroxicam therapy significantly (P less than 0.001) reduced the final half-recovery time, the percentage of cells with pseudopodia and the level of plasma oxidant activity (P less than 0.01) and kept the granulocyte filterability rate stable, showing leucocyte-derived free radicals are involved in peripheral ischaemia.

Exercise↗

Prostaglandin E1 decreases the low-density-lipoprotein entry into rabbit arterial wall.

1. In 72 male rabbits fed a 1% cholesterol supplemented diet the effect of a 4 weeks daily infusion of prostaglandin E1 (PGE1, 20 micrograms kg-1 min-1 over 2 h) on [125I]-low density lipoprotein (LDL) accumulation (10 microCi; 0.5 mg protein ml-1) was examined versus sham-treatment after removal of the endothelium of the abdominal aorta by a Fogarthy catheter. 2. The uptake of [125I]-LDL was significantly (P less than 0.01) higher in endothelium-free aortic segments (showing the highest peak maximum at around 12 h after 125I-injection) as compared to aortic segments with endothelium intact (showing the lowest uptake of [125I]-LDL with the peak maximum at 48 h, last control time). Segments with the endothelium restored showed a similar LDL-retention curve to segments with endothelium however, being again significantly (P less than 0.01) higher. 3. PGE1-treatment caused reduction in LDL-accumulation, being significantly (P less than 0.001) pronounced in segments without endothelium and in segments with endothelium restored. 4. The findings indicate a beneficial effect of PGE1 in lipid metabolism by decreasing the LDL-influx into the arterial wall in-vivo.

Alprostadil↗

Bacterial infection and peripheral vascular disease.

Whole blood filterability was monitored in 16 nondiabetic peripheral vascular disease (PVD) patients within forty-eight hours of onset of bacterial infection, after ten to seventeen days antibiotic therapy and again, ten days later, after convalescence. The whole blood filterability rate was constantly disturbed before infection in these patients; the impairment worsened significantly (as was expected during infection), but after convalescence the whole blood filterability rate did not return to preinfection levels. This further significant impairment in whole blood filterability was inversely correlated with a reduction in the patients' pain-free walking time as determined by a standard treadmell test performed after convalescence and compared with their average times before infection.

Bacterial Infections↗

Low density lipoprotein receptors: preliminary results on "in vivo" study.

Plasmatic levels of low density lipoproteins (LDL) are regulated by the receptor pathway and most LDL receptor are located in the liver. A receptor defect due to genetic mutations of the LDL receptor gene is the cause of familial hypercholesterolemia (F. H.), a disease characterized by high cholesterol levels and premature atherosclerosis. Injection of autologous radiolabelled LDL, followed by hepatic scintiscanning, can be used to obtain "in vivo" quantification of hepatic receptor activity, both in normal and hypercholesterolemic patients. In this study we observed no hepatic increase of radioactivity in patients affected by F. H., confirming the liver receptor defect. Scintigraphy is a non-invasive technique which can be used to diagnose this disease and to monitor the efficacy of hypolipidemic therapy.

Humans↗

Indium-111-labeled low-density lipoprotein binds with higher affinity to the human liver as compared to iodine-123-low-density-labeled lipoprotein.

The interaction of 111In-low-density lipoprotein (LDL) and 123I-LDL with human liver-plasma membranes was investigated and compared. LDLs were isolated by sequential ultracentrifugation and radiolabeled either with 123I (using lodogen or iodine-monochloride) each followed by purification with gel-chromatography or dialysis) or 111In (using cyclic DTPA-anhydride). LDL concentrations of 0.1 to 32 micrograms protein/ml were used for direct binding assays investigating the specific binding of labeled LDL (in the presence of a 50-fold excess of unlabeled LDL) to human liver apoB-receptors. In separate experiments, displacement of bound 111In-(123I)-LDL by unlabeled LDL was studied. Human liver plasma membranes bound 239 +/- 26 ng protein of 111In-LDL/mg protein and 148 +/- 18 ng protein of 123I-LDL/mg protein specifically (p less than 0.001). The corresponding dissociation constants were 0.6 +/- 0.2 and 1.2 +/- 0.7 micrograms protein/ml, respectively (p less than 0.001). The capacity of unlabeled LDL to displace bound 111In-LDL was four times higher than that for 123I-LDL (IC50: 1.7 +/- 0.7 versus 7.7 +/- 1.0 micrograms protein/ml). No significant differences among the different methods of iodination of LDL were found. The findings show that 111In-labeled lipoproteins might be a better ligand for lipoprotein-receptor binding studies as compared to radioiodinated lipoprotein products.

Adult↗

Blood rheology during induced ischaemia of the lower limbs.

The filterability rate of whole blood, the red and white blood cell sub-populations, and the erythrocyte and leucocyte count variations were studied during exercise in 20 male non-diabetic smokers, all with Stage II peripheral vascular disease (PVD), and 20 matched controls. A controlled ischaemia was induced using treadmill exercise. Blood samples were taken at rest, at the onset of calf pain and at haemodynamic recovery from peak exercise. Leucocytes were counted, separated using Ficoll-Hypaque into their sub-populations by centrifugation, and adherence to Petri dishes, re-suspended in buffer and filtered through 5 micron pore diameter filters. Whole blood filterability and the leucocyte count were significantly increased at the onset of calf pain. A significant increase was observed in the filterability of the monocyte sub-fraction and this persisted throughout the recovery period.

Blood Viscosity↗

Platelet scintigraphy and survival in juvenile stroke patients.

In the present study the prevalence of active atherosclerotic lesion sites in the carotid and femoral arteries as well as the platelet survival in a selected group of 33 patients (8 males, 25 females) below the age of 50 after juvenile stroke has been examined. In the patients studied a high frequency (80%) of positive (visible) carotid artery lesions with a platelet uptake ratio (PUR) ranging from 1.07-1.79 as well as an extremely shortened platelet survival were monitored. In-vitro platelet function tests, however, did not show significant abnormalities. No correlation between PUR, platelet survival, platelet function and the clinical situation could be assessed. These findings indicate that in this highly selected group of patients in-vivo haemostatic balancing seems to be severely impaired.

Adult↗

Reactive oxygen metabolites in peripheral arterial occlusive disease.

Plasma oxidant activity (marker of reactive oxygen metabolites) and the unfractionated leucocyte filterability rate (determined through 5 micron pore diameter Nuclepore filters, using a positive pressure system) were monitored in 15 stage II peripheral vascular disease (PVD) patients before and after ischaemia was induced by treadmill exercise (12 degrees slope/2 km/hour). Plasma oxidant activity increased (+ 115%) significantly (p less than 0.001) at the maximum walking time, correlating (r = 0.79) with a significant (p less than 0.001) impairment (+23%) in the unfractionated leucocyte filterability rate. At the transcutaneous oxygen pressure (tcPO2) half recovery time the plasma oxidant activity approached basal values but the unfractionated leucocyte filterability rate remained significantly (p less than 0.001) impaired (+16%). It returned to basal values at the full tcPO2 recovery time. These results show reactive oxygen metabolites are released during ischaemia of the lower limbs and are correlated with a significant impairment in the flow properties of leucocytes.

Arterial Occlusive Diseases↗

[In vivo flow of autologous radioactively labeled low-density lipoproteins (LDL) in human blood vessels].

Following 123I-labelling and reinjection of autologous low-density lipoproteins (LDL) to patients with clinically manifest atherosclerosis and/or hyperlipoproteinaemia (HLP), an investigation was carried out of whole body kinetics and local kinetics over atherosclerotic lesions and areas of increased LDL entry identified by "hot spots" in the 123I-LDL scintigram. In patients with HLP the number and frequency of "hot spots" was higher than in normolipaemics. The time course of 123I-LDL influx into atherosclerotic lesion sites until scintigraphic visualization of "hot spots" exhibited three different types of LDL uptake among the patients. In the majority of patients LDL kinetics was characterized by entry into the vessels with the maximal radioactivity measured as early as within 60 minutes after reinjection. In some patients maximal radioactivity over lesion sites was discovered after 20 hours or even later. Morphological evaluation revealed that in comparison to control tissue, fatty streaks and lipid lesions show by far the highest 123I-LDL accumulation. Ex vivo measurement of the deposition of 125I-LDL in de- and re-endothelialized rabbit aortic segments exhibited a significantly (p less than 0.01 - p less than 0.001) higher 125I-LDL retention as compared with endothelialized segments (after i.v.-injection).

Adult↗

Effects of 3-glucosaminoglycan sulfate on hemorheologic parameters in hyperlipidemic peripheral vascular disease (PVD) patients: a preliminary double-blind crossover study.

The effects of 3-glucosaminoglycan sulfate on lipids and the hemorheologic parameters were observed in a preliminary double-blind crossover study in 30 hyperlipidemic peripheral vascular disease (PVD) patients. Parenteral administration of the test drug was associated with a reduction in serum lipids, especially in triglyceride levels, and a lowering of fibrinogen, plasma viscosity, and whole blood viscosity levels. These effects justify the drug's use in the treatment of PVD, especially when associated with hypertriglyceridemia and hemorheologic disturbances.

Adult↗