Biomedical subjects

G Mingrone

Publications and source records attributed to G Mingrone.

At least 109 records · Page 6Linked to original sources

PubMed1993

Turnover and oxidation rates of plasma-free fatty acids in obese patients treated with dexfenfluramine.

In order to assess a possible direct metabolic effect of dexfenfluramine (dF) apart from its action on food intake reduction, 10 obese postmenopausal women and 10 obese men (BMI = 32.19 +/- 1.99 kg/m2) were studied in a single-blind fashion: 4 weeks on placebo (D-28 to D0) and 4 weeks on dF (D0 to D28). A balanced diet, computed on the basis of basal metabolic rate x 1.4, was followed throughout the study. The patients' alimentary diary was checked for compliance. FFA turnover and oxidation rate, using 1-14C palmitate intravenous infusion, was determined basally (D0), after single high-dose (30 mg, D1) and after long-term (15 mg b.i.d., D28) administration. Indirect calorimetric measurements were performed using a mass spectrometer, and the usual metabolic parameters were computed. The isotope method was used in order to assess plasma FFA oxidation rate. Plasma FFA were analyzed by high-performance liquid chromatography (HPLC) and specific activity was determined at 55, 60, 65 and 70 min by counting dpm in HPLC eluates corresponding to the retention time of palmitate. The turnover rate was not significantly modified after single high-dose dF administration when compared to basal values (6.24 +/- 1.62 at D1 vs. 5.63 +/- 2.07 mmol/kg/min at D0), but was significantly increased at D28 compared with D0 (6.35 +/- 1.96 mmol/kg/min; p < 0.05). A significant increase in FFA oxidation rate was observed with respect to basal values after dF administration both at D1 (0.81 +/- 0.33 at D1 vs. 0.61 +/- 0.21 mmol/kg/min at D0; p < 0.01) and at D28 (0.77 +/- 0.34 mmol/kg/min; p < 0.015).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Biliary lipid secretion: immunolocalization and identification of a protein associated with lamellar cholesterol carriers in supersaturated rat and human bile.

Feeding a 0.5% diosgenin plus 0.02% simvastatin diet to rats increases biliary cholesterol concentration and saturation to levels generally found in human native supersaturated bile. By using preparative ultracentrifugation, gel filtration chromatography, and electron microscopy, we isolated, purified, and identified lamellar structures (unilamellar vesicles and multilamellae) as a major biliary cholesterol transport in supersaturated human and rat bile. It was estimated that more than 60% of biliary cholesterol is transported in these lamellar carriers, which were identified by transmission electron microscopy as unilamellar vesicles and multilamellar bodies within bile canaliculi of rats with cholesterol supersaturated bile. By SDS-PAGE, a characteristic and constant protein profile was found associated to the purified lamellar carriers. One of these proteins, a 130-kDa protein, was isolated from human biliary lamellae and used for preparation of a rabbit polyclonal antibody, which cross-reacted with the homologous rat protein. By Western blotting, it was established that the purified low density fraction of bile-Metrizamide gradients, containing lamellae, was enriched with the 130-kDa protein. The 130-kDa protein was characteristically detected at the canalicular membrane by Western blotting of hepatic subcellular fractions and by immunohistochemistry of rat and human liver biopsies. Amino acid sequencing of the amino terminus of the 130-kDa protein demonstrated a complete identity with aminopeptidase N, a canalicular transmembrane hydrophobic glycoprotein. These studies show that biliary lipids may acquire an ordered multilamellar structure that is present in the canaliculi of rats with supersaturated bile. These biliary lamellae are similar to lamellar bodies and surfactant-like material frequently found in other epithelia, suggesting common biogenetic, structural, and functional properties. The identification of aminopeptidase N associated with biliary lamellae is consistent with the involvement of the canalicular membrane in the secretory mechanism of biliary lipids.

Amino Acid Sequence↗

PubMed1992

Metabolic effects and disposition of sebacate, an alternate dicarboxylic fuel substrate.

Disodium sebacate is a 10-carbon-atom dicarboxylic acid, proposed as substrate for parenteral nutrition. We investigated its pharmacokinetic profile and thermogenic effect during a short-time infusion (5 h at 10 g/h) in 7 male volunteers. Sebacate in serum and urine was measured by high-performance liquid chromatography. A single-compartment model with two linear elimination routes was fitted. Metabolic measurements (VO2, VCO2, respiratory quotient, metabolic rate) were continuously performed for 8 h (5 h during and 3 h after the infusion) by a canopy indirect calorimeter. The apparent volume of distribution of sebacate was 8.39 +/- 0.69 liters, and the plasma fractional removal rate constant was 0.0086 +/- 0.00077 min-1. The average half-life and plasma clearance were 80.6 min and 72 ml/min, respectively. The increase in metabolic rate, the decrease in respiratory quotient and the changes in ketone body, glucagon and insulin levels during the infusion were not significant. 24-hour catecholamine excretion was within normal limits. Calories administered by sebacate seem to be available for utilization without relevant metabolic side effects.

Adult↗

PubMed1992

Tracer study of metabolism and tissue distribution of sebacic acid in rats.

The present study investigates the metabolic disposition of sebacic acid in rats. Three groups of experimental animals received different doses of disodium sebacate with 25 microCi of 14C-labeled molecule by intravenous injection. In the first group radioactivity plasma elimination curves were examined for two administered doses (80 and 160 mg). In the second group, expired 14CO2, urine tracer and feces tracer were counted after intravenous administration of 160 mg of sebacate. The animals of the third group were sacrificed at different times after intravenous administration of 160 mg of sebacate, and tracer elimination curves were obtained for several organs. The plasma half-life of sebacate is 38.71 min; about 35% of the administered tracer was excreted in the urine as unchanged sebacate; about 25% was eliminated as 14CO2 in expired air. Disposition of sebacate was complete within 4 h of administration. The sebacate half-life is longest in adipose tissue (135 min) and in liver (74 min), sites of likely transformation. In all other organs examined, the sebacate half-life is similar to that in plasma.

Absorption↗

PubMed1992

Analysis of serum conjugated bile acids by high performance liquid chromatography and mass spectrometry.

A high performance liquid chromatography (HPLC) mass spectrometry (MS) system for the analysis of glycine and taurine conjugated bile acids in human fasting and postprandial sera is described. Following purification on thin layer chromatograms conjugated bile acids were separated in a RP-18 5 microns column with methanol 0.02 M KH2PO4 buffer pH 5.10 as the mobile phase at a flow rate of 1 ml/min and assayed by direct injection MS. The bile acid fractions were assayed by MS. The amounts of conjugated bile acids in the postprandial sera of 15 subjects with normal liver function were significantly higher (p less than 0.05) than in fasting ones and the glycine/taurine ratio was about 1 for both. The method is better suited for a specific research area in experiments requiring a high level of accuracy.

Adult↗

PubMed1992

Effect of propionyl-L-carnitine in the treatment of diabetic angiopathy: controlled double blind trial versus placebo.

Diabetic angiopathy can be treated by medical or surgical means. In the initial stages of the disease (I and II according to Fontaine), pharmacological treatment aims at supplying ischaemic and therefore hypoxic regions with a sufficient quantity of energetic substrates for metabolic needs. A new method of treating peripheral vasculopathy was carried out in this study using propionyl-L-carnitine (PLC), a propionic ester of L-carnitine. The authors evaluated in a double-blind study the efficacy of chronic oral administration of PLC versus placebo. Twenty type II diabetic patients with peripheral angiopathy were enrolled in this study. They were divided into 2 groups of ten patients each. On termination of treatment, the ankle/arm pressure index, measured at rest, showed an improvement in the PLC treated group and a deterioration in the placebo group. The Windsor index, measured at 2, 5 and 10 min after exercise, showed a significant impairment in the PLC treated group with respect to the placebo group. The percent variation in walking distance, measured at various time intervals according to the protocol, showed a marked improvement in the PLC treated group. These results show that PLC significantly improves both walking distance autonomy and symptoms related to peripheral vasculopathy in diabetic patients. Like carnitine, PLC seems to act through a metabolic mechanism which results principally in preventing lactate formation in ischaemic tissue.

Administration, Oral↗

PubMed1991

Pharmacokinetic analysis of azelaic acid disodium salt. A proposed substrate for total parenteral nutrition.

Azelaic acid was the first dicarboxylic acid proposed as an alternative energy substrate in total parenteral nutrition. In this study, the pharmacokinetics of azelaic acid were investigated in 12 healthy volunteers, 7 receiving a constant infusion (10g over 90 min) and 5 a bolus dose (1g). The 24h urinary excretion and plasma concentration in blood samples taken at regular intervals were assayed by gas-liquid chromatography. Experimental data were analysed by a 2-compartment nonlinear model that describes both tubular secretion and cellular uptake in Michaelis-Menten terms. A high value of urinary excretion (mean 76.9% of infused dose) and a mean clearance of 8.42 L/h were found, suggesting the presence of tubular secretion. Estimating the population mean of the pharmacokinetic model parameters gave a maximal cellular uptake of 0.657 g/h. The model predicts that 90% of the maximal uptake should be reached in the plateau phase of a constant infusion of 2.2 g/h. The presence of extensive and rapid losses through urinary excretion, and the low estimated value of the maximal cellular uptake, indicate that azelaic acid is not suitable as an energy substrate for total parenteral nutrition.

Adult↗

PubMed1990

[Traumatic perforation of the duodenum. Diagnostic and therapeutic problems].

The treatment of traumatic ruptures of the duodenum is one of the greatest controversies in surgery. The injury mechanisms, diagnostic criteria and factors underlying the prognosis are analysed and indications suggested for the various types of intervention. The problem relating to the operating technique are specified.

Duodenum↗

PubMed1990

A glucagon-secretin-like peptide stimulates the intrinsic nervous plexus of guinea pig gallbladder.

The role of vasoactive intestinal peptide (VIP), as a possible neurotransmitter of the intrinsic nerve plexus in the guinea pig gallbladder, was investigated by monitoring spontaneous contractile activity. VIP receptor antagonist (4 Cl-D-Phe6, Leu 17)-VIP did not produce any effect on muscular tone and spontaneous activity, whereas (N-Ac-Tyr1, D-Phe2)-GRF-(1-29)-NH2, (14-GRF analog), which is known to stimulate digestive enzyme secretion by interacting with the VIP-preferring receptors, greatly increased the amplitude and frequency of waves as well as the muscular tone. Since VIP receptor antagonist acts selectively as a competitive antagonist for the action of VIP, we conclude that the gallbladder inhibitory intrinsic plexus neurotransmitter is not VIP, but a member of the glucagon-secretin family of peptides.

Animals↗

PubMed1990

Serum and biliary lipid pattern in rabbits feeding a diet enriched with unsaturated fatty acids.

Adult male New Zealand white rabbits were fed for 3 months a stock diet supplemented with 6% (w/w) soybean oil heated at 240 degrees C for 60 min. After the first month of treatment a significant increase in total lipid content of serum was observed mainly due to the cholesterol ester fraction. Simultaneously, grossly induced atherosclerosis and marked liver damage were histologically and clinically demonstrated. Lipid peroxide values, performed by thiobarbituric acid test in lipid extracts from liver, aorta and bile showed a significant increase as compared to controls. Lipoperoxidation rate increased with the duration of feeding. Parallel to this there was a marked reduction in the activities of glutathione peroxidase, superoxide dismutase and catalase in liver and aorta, all enzymes involved in the mechanism of detoxification of lipid peroxides. The results are in agreement with the hypothesis that lipid peroxidation can play a significant role in the pathogenesis of atherosclerosis.

Animals↗

PubMed1990

Free fatty acids stimulate mucin hypersecretion by rabbit gall-bladder epithelium in vitro.

1. Mucin, a high-molecular-weight glycoprotein secreted by the gall-bladder and biliary duct epithelium, is a well-known nucleation-prompting factor in experimental and human gall-stone disease. 2. Free fatty acids when incubated in vitro (micellar suspension with 1 mmol/l Tween 40) with rabbit gall-bladders can promote abundant mucus secretion. 3. The hexosamine content of rabbit gall-bladder walls, measured by gas-liquid chromatography, was significantly higher in gall-bladders incubated with fatty acids than in control tissues. 4. The biochemical data were supported by ultrastructural findings showing numerous droplets with a translucent content in the perinuclear cytoplasm. Exocytosis was also seen in treated gall-bladders, confirming the secretory nature of the vesicles. 5. These results suggest that free fatty acids, which appear in high amounts when bile lecithins are hydrolysed by phospholipase, play an active role in the gall-stone formation.

Acetylgalactosamine↗

PubMed1990

Toxicity of disodium sebacate.

Investigations of the acute toxicity of disodium sebacate after oral, i.p. and i.v. administration were carried out on 220 Wistar rats (110 males and 110 females) and 204 New Zealand rabbits (102 males and 102 females). No oral acute toxicity was found. On the contrary LD50 +/- s.e. of 5500 +/- 830 mg/kg b.w. and 6000 +/- 850 mg/kg b.w. were found respectively for rats and rabbits after i.p. sebacate administration. When sebacate was given i.v., the median lethal dose +/- s.e. was 560 +/- 86.5 mg/kg b.w. for rats and 1400 +/- 267.2 mg/kg b.w. for rabbits. Similar results were obtained in corresponding groups of animals (in total 220 rats and 204 rabbits) given oral, i.p. and i.v. saline solutions with added glucose in order to obtain the same value of osmolarity and sodium ion concentration. The above results appear indicative of low toxicity of disodium sebacate, and suggest that the toxic effects found could be due to the sodium content of the compound administered. Similarly, subacute and chronic toxicity was investigated in forty rats and forty rabbits (twenty males and twenty females) fed disodium sebacate incorporated into pellets. When compared to the control animals, no significant differences in biological parameters (clinical, chemical and haematological values, growth curves and histological findings for the different organs) were observed in the test groups during the treatment period. In addition, fetal toxicity, teratogenicity and neonatal toxicity were investigated in twenty female rats and twenty female rabbits. Sebacic acid did not show any teratogenic effect and the development of the fetuses was regular.

Animals↗

PubMed1989

Spontaneous contractile activity of guinea-pig gall-bladder in vitro.

Some parameters of rhythmic mechanical and electrical events of guinea-pig gall-bladder were investigated. Pressure-volume (P-V) responses, extracellular electrical activity and gall-bladder morphology were recorded. Rhythmic gall-bladder activity consisted of waves of pressure at intraluminal volumes between 0.5 and 1.8 ml. The pressure waveforms developed in a single contraction were usually oscillatory, containing two or more peaks which were more or less separated. The maximum amplitude value of phasic pressure waves was 1.8 +/- 0.6 cmH2O. Bursts of spike potentials appeared at three equidistant electrodes along the longitudinal diameter of the bladder with variable delays indicating absence of propagation of the fast electrical activity. By analysing the morphological changes of gall-bladder silhouette during the P-V curve it was evident that the maximum amplitude and duration of contractile events occurred when the whole muscular wall was stretched. Tetrodotoxin added to the bath solution did not abolish rhythmic activity--indicating its myogenic nature--and shifted the P-V curve to the left of the control, confirming the inhibitory role of the intrinsic nervous plexus of guinea-pig gall-bladder.

Animals↗

PubMed1989

Lumbar chemical sympathectomy in end stage of arterial disease: early and late results.

Hemodynamic variables were used to evaluate the effectiveness of lumbar chemical sympathectomy in 20 patients with ischemic foot lesions. Early clinical improvement was obtained in 68% of the cases. The two-year cumulative limb salvage rate was 52%. Results indicate that lumbar chemical sympathectomy offers the same benefits as surgical sympathectomy and represents a useful alternative in patients with advanced ischemic disease of the lower limb, decreasing the rate and the level of amputations.

Aged↗

PubMed1989

Azelaic acid--biochemistry and metabolism.

Medium chain length dicarboxylic acids (DA) from C8 to C13 are competitive inhibitors of tyrosinase in vitro. The introduction of electron acceptor groups or electron donor groups into the 2 and/or the 8 position of the molecule enhances or reduces respectively the inhibitory effects of DA. In addition to tyrosinase, DA can reversibly inhibit thioredoxin reductase, NADPH cytochrome P450 reductase, NADH dehydrogenase, succinic dehydrogenase and H2CoQ-Cytochrome C oxidoreductase. Among DA, azelaic acid (AA, C9 dicarboxylic acid) is extensively used because: 1) it is much cheaper than other DA; 2) it has no apparent toxic or teratogenic or mutagenic effect; 3) when administered perorally to humans, at the same concentrations as the other DA, it reaches much higher serum and urinary concentrations. Serum concentrations and urinary excretion obtained with intravenous or intra-arterial infusions of AA are significantly higher than those achievable by oral administration. Together with AA, variable amounts of its catabolites, mainly pimelic acid, are found in serum and urine, indicating an involvement of mitochondrial beta-oxidative enzymes. Short-lived serum levels of AA follow a single 1 h intravenous infusion, but prolonging the period of infusion with successive doses of similar concentration produces sustained higher levels during the period of administration. These levels are consistent with the concentrations of AA capable of producing a cytotoxic effect on tumoral cells in vitro. AA is capable of crossing the blood-brain barrier: its concentration in the cerebrospinal fluid is normally in the range of 2-5% of the values in the serum.

Animals↗

PubMed1989

First exchange neutrophilia is not always an index of peritonitis during CAPD.

To date, the medical literature suggests that CAPD patients with peritonitis have an increase in the dialysate white cell count (greater than 100 cells mL) with neutrophilia (greater than 50%). In order to explore the differential composition of the peritoneal fluid cells (P.F.C.), we have followed 21 patients (PTS) twice a month over a 30-month period. Nine hundred and fifty samples obtained either from the 24 hours (hrs) drained CAPD fluid, or from the "First Morning Exchange" (F.M.E.) during the same day, when possible, were estimated with the "Millipore Filter" (5-8 Micron (lw) pore size), stained by the Papanicolau method. The results can be so summarized: (1) 13 PTS (62%) showed constantly a low polynuclear count (3-32%); (2) 8 non-infected PTS (38%) showed constantly a higher neutrophilia (40-80%); and (3) from time to time the PTS of the two groups showed a higher neutrophilia and an increased cellularity during clinical infection. In all the samples, the differential P.F.C. count was not affected by the dialysate composition and no difference was observed between the 24 hrs samples and the F.M.E. samples made on the same day. Differential peritoneal cell count may be useful when there are important changes in the stable individual composition.

Adult↗

PubMed1989

A hemostasis study in CAPD patients during fibrinolytic intraperitoneal therapy with urokinase (UK).

Catheter obstruction due to fibrin deposits during CAPD can cause poor outflow of peritoneal fluid and recurrent peritonitis. In order to treat this complication, 75,000 IU of diluted Urokinase (UK) were infused into catheters obstructed by fibrin in 10 CAPD patients (4 of which had peritonitis), without adverse reactions. After 60 minutes, a 2 liter exchange of peritoneal fluid was performed. In all the cases a normal outflow was restored. Hemostasis parameters (PT, PTT, TT, Fibrinogen, FDP, Fibrin monomers, BT, AT III) and blood cells count (RBC, HGB, HCT, WBC, PTL), were assayed before and two hours after the UK infusion, and did not show any significant variation, except for a decrease of white blood cells, which remained, however, within the normal range. No peritonitis episode occurred in the follow-up period. UK fibrinolytic therapy is safe and effective in treating fibrin obstruction of CAPD catheters without catheter removal and prevents recurrent peritonitis.

Catheters, Indwelling↗

PubMed1988

Free fatty acids: a stimulus for mucin hypersecretion in cholesterol gallstone biles.

The concentration of free fatty acids, phosphatidylcholine and lysophosphatidylcholine, and the fatty acid composition as well as the levels of the mucins, analyzed by an improved GLC method, were examined in ten biles from patients with cholesterol gallstones (pathological biles) and in ten control biles. In pathological biles the amounts of free fatty acids and phosphatidylcholine, were significantly higher (8.99 +/- 1.09) vs. 2.75 +/- 0.62 micrograms/mg) and lower (6.62 +/- 0.71 vs. 21.91 +/- 3.86 micrograms/mg), respectively, than in control biles, indicating that a relationship exists between the two lipid fractions. Lysophosphatidylcholine concentrations remained unchanged in the two groups (1.02 +/- 0.55 micrograms/mg in pathological biles vs. 1.32 +/- 0.57 micrograms/mg in control biles). The increased levels of free fatty acids were directly correlated (r = 0.73, P less than 0.05) with biliary hypersecretion of mucus glycoproteins. Acetylglucosamine and acetylgalactosamine were significantly higher in pathological biles than in control biles (1.91 +/- 0.67 vs. 0.60 +/- 0.13 microgram/mg). The nucleating potency of the increased amounts of mucins, coupled with lowered levels of phosphatidylcholine, might play a very important role in stone formation and precipitation.

Adult↗