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Biomedical subjects

G Mingrone

Publications and source records attributed to G Mingrone.

At least 127 records · Page 7Linked to original sources

Influence of sodium salts of saturated medium chain length (C6, C9, C10 and C12) dicarboxylic acids on the uterine horn of rat in vitro.

The influence of the sodium salt of some dicarboxylic acids (adipic acid, C6; azelaic acid, C9; sebacic acid, C10; dodecandioic acid, C12) on both spontaneous and evoked activity of uterine horn of rats has been studied in vitro. Spontaneous activity of uterine muscle was inhibited by dicarboxylic salts (DS) causing the total abolition of mechanical events at concentrations of 64 x 10(-3) M-C6, 40 x 10(-3) M-C9, 32 x 10(-3) M-C10 and 24 x 10(-3) M-C12. Dicarboxylic salts antagonized the maximal isometric contraction of the uterine horn induced by administration of acetylcholine, oxytocin or prostaglandins (PGF2 alpha). The amount of antagonism was dependent upon the concentration of DS used. Dicarboxylic salt showed an aspecific inhibitory effect on the uterine horn which progressively increased with their chain length (C12 greater than C10 greater than C9 greater than C6). The results suggested that the inhibitory effects of DS on smooth muscle could be due to a cellular membrane hyperpolarization.

Acetylcholine↗

[Lipid lipoperoxidation and atherosclerosis].

The concepts of free radicals, radical reactivity and the mechanism of their production in biological systems are discussed. Emphasis is placed on the mechanisms of lipid damage by initiation, propagation and termination. The free radicals may play a part in the pathogenesis of atherosclerosis.

Arteriosclerosis↗

Prediction of lithogenic character of human bile by a quaternary system.

The lithogenic character of human gallbladder bile was investigated by a mathematical model on the basis of a clinical data set. Each bile was described by means of the quaternary system bile salts--phospholipids--free fatty acids--cholesterol. Reporting a set of bile samples on the tetrahedron of concentrations, a clear separation emerged between the control bile, the bile from patients with gallstones, and the bile of subjects with gallbladder dyskinesia. This group was characterized by a largely increased content of free fatty acids.

Adult↗

Netilmicin pharmacokinetics in uremic patients undergoing hemodialysis.

The pharmacokinetics of netilmicin after i.v. administration were studied in 10 adult hemodialyzed patients during and after a dialysis session. The mean interdialysis half-life was 49.6 h, whereas during dialysis this value was reduced to 5.02 h. The mean volume of distribution of netilmicin was about 20% of the total body weight. The dialyzer clearance of netilmicin, measured at 60 and 150 min after the beginning of the session, was about 50 ml/min; this means that 60-65% of the drug may be lost during the 4.5 h standard dialysis. The total body clearance of netilmicin was similar to the dialyzer clearance values, suggesting that the drug is eliminated almost entirely by hemodialysis and that its renal elimination in our patients is negligible. In conclusion, in uremic hemodialyzed patients netilmicin behaves like other aminoglycosides.

Half-Life↗

Distribution of radiolabelled azelaic cid in eye membranes and fluids of rabbits.

A direct cytotoxic effect of azelaic acid on melanocytes of human melanoma has been demonstrated. In view of a possible future therapeutic employment of this drug in the treatment of primary ocular melanoma, we investigated the route of choice of azelaic acid administration in rabbits. Our results evidenced a suden and direct blood absorption of topically (by retrobulbar injection) administered azelaic acid. This is in agreement with the high water solubility of azelaic acid sodium salt. These preliminary reports indicate that the elective route of azelaic administration in primitive eye melanoma is intravenously by continuous infusion.

Animals↗

The possible role of free fatty acids in the pathogenesis of cholesterol gallstones in man.

The lipid composition of hepatic and gallbladder bile was examined in 20 patients with cholesterol gallstones and in 20 control subjects. Lipid fractions other than bile salts, phospholipids and cholesterol were found to be present, i.e., sterol esters, non-identified fractions and, above all, free fatty acids. The latter probably originated from biliary phospholipids via activity of phospholipases, present in the gallbladder wall. No significant difference in amount and pattern of free fatty acids and phospholipids was found in hepatic bile between patients with gallstones and controls. On the contrary, we observed relevant differences in the lipid composition of gallbladder bile. In this way, we consider that the bile becomes lithogenic inside the gallbladder as a consequence of release of free fatty acids, particularly if these are constituted by saturated chains. In fact, these can compete with cholesterol in the solubilization in biliary micelles. On the other hand, free fatty acids can be directly toxic for the gallbladder wall and produce a cholecystitis.

Adult↗

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

Because of the known advantages of coupling high performance liquid chromatography with mass spectrometry (HPLC-MS) in biological fluids, studies on the reversed-phase HPLC-MS system for direct analysis of conjugated bile acids in human bile samples are described. Ten samples of gallbladder bile of apparently healthy subjects were examined. The amounts of each tauro- and glycoconjugated bile acid as trifluoracetate were determined by mass fragmentography. Quantitation of at least 1 ng of each bile acid was possible.

Animals↗

Metabolism of straight saturated medium chain length (C9 to C12) dicarboxylic acids.

A method utilizing thin-layer chromatography, high performance liquid chromatography, and mass spectrometry was developed for the quantification of C9, C10, C11, and C12 dicarboxylic acids in serum, urine, and feces of human volunteers and rats after oral administration of the acids. The method allowed good resolution and measurement of the dicarboxylic acids at nanogram levels. In humans, excretion was independent of the dosage; about 60% of C9, 17% of C10, 5% of C11, and 1% of C12 were excreted in the urine during the first 12 hours after administration. The concentration of the acids in serum peaked between 2 and 3 hours. Excretion was also independent of dosage in rats. About 2.5% of C, 2.1% of C10, 1.8% of C11, and 1.6% of C12 were excreted in the urine over a period of 5 days. The serum concentration and the urinary excretion of the diacids reached a maximum at the second day after the oral dose. In both humans and rats, the dicarboxylic acids found in serum and urine were 2, 4, or 6 carbon atoms shorter than the corresponding administered diacid. This indicates that there was beta-oxidation of the ingested diacids to some extent. The administration of [1,9-14C]azeliac acid and of [10,11-3H]dodecandioic acid confirmed the occurrence of beta-oxidation, and led to elucidation of the fate of the ingested diacids that were not excreted as such in the urine.

Administration, Oral↗

Lipid composition in jaundiced rat liver by radio-thin-layer chromatography and photodensitometry.

In vitro hepatic synthesis of lipids starting from (1-14C)acetate was investigated for 14 days in rats with biliary obstruction by ligation of the common bile duct using radio-thin-layer chromatography (radio-TLC). This study was correlated with a quantitative assay of the various hepatic lipids using TLC correlated with photodensitometry. Hepatic total lipid synthesis increased progressively with time. With concern to the single fractions, the major modifications were verified on the 3rd day with a decreased incorporation of the labelled acetate into the triglycerides. On the other hand, using photodensitometry, they demonstrated a percentage increase. These variations can be justified by the presence of a feedback mechanism. The syntheses of cholesterol and the other fractions were maximum during this period. Histologic examination revealed, especially on the 3rd day, a neoformation of biliary ductules and on the 14th day, a regression of these histological changes.

Acetates↗

In vitro study of liver slices lipid 1-14C-acetate incorporation in hyperlipoproteinemic subjects.

The aim of the present study is to determine the "in vitro" rate of 1-14C-acetate incorporation into lipids in human liver slices from patients with various types of hyperlipoproteinemia. Hepatic tissue from type IIa hyperlipemic patients incorporated labelled acetate into free cholesterol at a higher rate than normolipidemic patients. In type IIb patients the incorporation was increased into hepatic free cholesterol, triglycerides and FFA. The liver of pre-beta hyperlipoproteinemic subjects incorporated 1-14C-acetate into triglycerides to a greater extent than hepatic tissue from controls. Triglyceride synthesis was highly elevated in type IV hyperlipoproteinemic patients with diabetes. In all cases, there was no significant correlation between increased hepatic triglyceride synthesis (dpm/mg of extracted lipids) and insulin response (microunits/ml) to oral glucose ingestion (75 g). The present data indicates that in the presence of disturbances in lipid and carbohydrate metabolism one observes an alteration of lipid synthesis in the liver. The in vitro incorporation of 1-14C-acetate into hepatic cholesterol and/or triglyceride in patients with primary hyperlipoproteinemia is increased. Thus the elevated serum cholesterol and triglyceride levels of these patients could be explained on the basis of an increased lipoprotein synthesis in the liver.

Acetates↗

Bile acid content of gallbladder bile and stones in type IIb and IV hyperlipoproteinemia.

We examined the bile acid composition of gallbladder bile using reversed-phase high performance liquid chromatography (HPLC), in normolipemic and hyperlipidemic (types IIb and IV) patients with cholelithiasis and compared them with normal subjects. Similarly, bile acid composition was determined n the gallstones of these patients. No free bile acids were found in any of the samples examined. We observed that gallbladder bile and gallstones of patients with type IV hyperlipidemia showed a significant increase in the percentage of glyco-conjugated bile acids and reduction in taurine conjugates. Based on this finding we postulate that in addition to biliary lipid composition bile acid composition may also play a role in the pathogenesis of cholesterol gallstone formation.

Adult↗

"In vitro" study of liver slices lipid (1-14C) acetate incorporation in experimental diabetes.

The effect of insulin deficiency on lipid synthesis in the liver of normal rats, diabetic rats by alloxan and pancreatectomized rats was studied in vitro using (1-14C) acetate as lipid precursor. Insulin deficiency induces an increased incorporation of (1-14C) acetate into triglycerides in rat liver. This is particularly evident in pancreatectomized rats with respect to alloxan diabetic rats. It is concluded that in experimental diabetes an atherogenous metabolic pattern is elaborated by the liver.

Acetates↗

Comparative effects of chenodeoxycholic acid and ursodeoxycholic acid on lipid synthesis in rat liver.

Chenodeoxycholic and ursodeoxycholic acids reduce significantly the hepatic synthesis of lipids in rats. The present study has been carried out using (1-14C)acetate and evaluating its incorporation into different lipidic fractions of the liver by thin-layer radiochromatography. Ursodeoxycholic acid proved to be more active than chenodeoxycholic acid: in addition to a significant decrease of the hepatic incorporation of the acetate into cholesterol and triglycerides an increase of the hepatic incorporation of the acetate into phospholipids has been observed. The exogenous administration of bile acids diminishes the hepatic synthesis of cholesterol and therefore its biliary excretion; it enriches the bile acid and phospholipid pool in the liver and bile. By this way the action of bile acids establishes in the liver a condition which induces such an increase of availability of mixed micelles in the bile as to make it unsaturated in cholesterol.

Animals↗

Reversed-phase high-performance liquid chromatographic separation and quantification of individual human bile acids.

The reversed-phase high-performance liquid chromatographic separation and quantification of individual bile acids is described. Taurine- and glycine-conjugated bile acids were separated and detected directly by an ultraviolet absorbance detector operating at 200 nm. Simultaneous quantitation of at least 100 ng of each conjugated bile acid is possible. Carboxylic (free and glycine-conjugated) bile acids were esterified with p-bromophenacyl-bromide. The reaction, using N,N-diisopropylethylamine as catalyst, yields quantitatively the strongly absorbing p-bromophenacyl esters whch can be determined by absorbance measurement at 254 nm. Simultaneous quantitation of less than 20 ng of each bile acid is possible. The present method is applied to the quantitation of individual bile acids in ten human gallbladder bile samples.

Acetophenones↗

[Celiac disease: association with rheumatoid arthritis and diabetes mellitus. Apropos of a clinical case].

A case of coeliac disease accompanied by serum-negative rheumatoid arthritis and (subsequently) by diabetes mellitus is described. The appearance of a similar clinical and sympatomatological enteric and articular picture in one of the patient's brothers is seen as evidence that the link between the components of the three-fold syndrome is to be found in common genetic factors, with an onset in the form of a cellular and biohumoral immunological disorder.

Adolescent↗

[Bile lipid composition in subjects with blood lipid disorders (types II and IV). Effect of a new hypolipemic drug (Etofibrate)].

The biliary lithogenous index before and after treatment with Etofibrate, a new hypolipaemizing substance, has been assessed in dyslipidaemic subjects (ypes II and IV). Etofibrate is the result of the association of a molecule of clofibrate and one of nicotinic acid. An analysis of relative molar concentrations of biliary lipides showed that subjects with type IV and IIb dyslipidaemia produced lithogenous bile in base condition, unlike subjects with type IIa dyslipidaemia. After 28 days of treatment with Etofibrate (900 mg/die) a clear-cut increase was observed in the biliary lithogenous index in all types of dyslipidaemia examined.

Adult↗

Lipid synthesis from the liver in patients with psoriasis.

In psoriatic patients with hyperlipidemia we studied the hepatic lipid synthesis from (1-(14)C)-acetate in human liver biopsy specimens in vitro by a thin-layer radio-chromatography. In psoriatics type IV (according to Fredrickson) a significant increase in (1-(14)C)-acetate hepatic incorporation especially into phospholipids (25%) and triglycerides (52%) was observed; in type IIb increased lipogenesis was phospholipids (24.5%), free cholesterol (44.4%) and triglycerides (29%). Abnormal lipid metabolism often coexists with glucose intolerance in psoriasis; no correlation between hyperinsulinemia and augmented (1-(14)C)-acetate incorporation into hepatic triglycerides was found.

Adult↗