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Biomedical subjects

G Baggio

Publications and source records attributed to G Baggio.

At least 91 records · Page 5Linked to original sources

Relationship between triglyceride-rich lipoprotein (chylomicrons and VLDL) and HDL2 and HDL3 in the post-prandial phase in humans.

In order to evaluate the relationship between triglyceride-rich lipoproteins (chylomicrons and VLDL) and HDL during alimentary lipaemia, 12 healthy volunteers, 6 male and 6 female (aged 20--40 yrs), were studied. Cholesterol, phospholipid, triglyceride and protein were evaluated in whole serum, VLDL, LDL and HDL (successively subfractionated in HDL2 and HDL3). Blood samples were collected in a fasting state, 4.5 and 9 h after a 1500 calorie meal (20% protein, 40% carbohydrate, 40% fat). A striking increase in triglyceride-rich lipoproteins after 4.5 h was observed in both sexes, but was more pronounced in males. An increase in phospholipid and triglyceride as well as a slight reduction in cholesterol was evident in HDL after 4.5 h. At the same time both lipids and proteins were decreased in HDL3 and increased in HDL2. This phenomenon is more evident in females, who showed a significantly higher basal HDL2 level. These results suggest a possible metabolic relationship in the post-prandial phase between triglyceride-rich lipoproteins and HDL, and an inverse correlation between HDL2 and HDL3.

Adult↗

[Heteroarylalkanoic acids with potential anti-inflammatory activity].

A series of (3-oxodihydro-1,2,4-benzothiadiazin-1,1-dioxide-3-yl)acetic acids [compounds of type (A)] and (1,2,4-benzothiadiazin-1,1-dioxide-3-yl)oxyacetic acids [compounds of type (B)] were synthesised and tested for antiinflammatory activity. Preliminary tests showed certain compounds to have a significant level of antiinflammatory activity in rat paw edema induced by carrageenan. It was found that the antiinflammatory activity of this series of compounds depends on the nature, number and position of the substituents on the benzene ring.

Acetates↗

Influence of bile acids and free fatty acids on physicochemical properties of LP-X.

In this study it is demonstrated, that incubation of both, bile acids and free fatty acids with LP-X, the abnormal plasmalipoprotein found in patients suffering from cholestasis or LCAT-deficiency, results in striking alterations of the physico-chemical and immunological properties of LP-X: 1. The cathodic mobility in agar is changed into an anodic mairation of the material. 2. The unique appearance of LP-X on electronmicrographs is altered by the incubation revealing fingerprint like structures. 3. The albumin portion of LP-X becomes immunologically detectable. 4. Bile salts cause marked changes in the hydrated density of the material as determined by zonal ultracentrifugation. 5. In vitro incubation of LP-X with postheparin plasma causes a complete disappearance of LP-X as judged by its typical migration on agar electrophoresis. All these alterations can be prevented or reversed by the addition of albumin in appropriate concentrations. These findinga are important in the light of studies designed to investigate the catabolic action of plasma lipolytic enzymes on LP-X, as well as for follow up studies of LP-X concentrations during the course of disease.

Bile Acids and Salts↗

Lipoprotein-X and diagnosis of cholestasis: comparison with other biochemical parameters and liver biopsy.

The presence or absence of histological signs of cholestasis (on the basis of liver specimens obtained by means of liver biopsy) was compared with total bilirubin, alkaline phosphatase, gamma-glutamyl transpeptidase, ornithine carbamoyltransferase, serum glutamic oxaloacetic transaminase levels and LP-X test in 157 patients suffering from different liver diseases. The LP-X test was positive in 93% of the 59 cases in whom histological evidence of cholestasis was observed and negative 95% of the 98 cases in whom histological examination was negative. LP-X concurs more frequently with the histological picture than do total bilirubin and alkaline phosphatase. These data confirm that LP-X test is more specific than the tests traditionally used to demonstrate or exclude cholestasis. An increment in gamma-GT levels was observed in 97% of the patients with a positive LP-X test. These clinical results have been discussed in the light of recent data regarding the mechanism of lipoprotein-X formation and the possible relationships between LP-X and gamma-glutamyl transpeptidase.

Adolescent↗

Long-term trial with colestipol plus clofibrate in familial hypercholesterolemia.

Twenty subjects with familial hypercholesterolemia (12 Type IIa and 8 Type IIb), previously treated with Colestipol for 16 months, were subjected to therapy with Colestipol (15 g/day) + clofibrate (2 g/day) for 15 months. During the second treatment period these patients continued to follow the isocaloric hypocholesterolemic diet initiated during the original trial. In Type IIa patients, the association of these drugs enhanced the decrease in plasma cholesterol levels. The total mean decrease was -40 +/- 17 mg/dl (P less than 0.05). In Type IIb patients, on the other hand, the association of clofibrate with Colestipol induced an increase in plasma cholesterol levels. The total mean increase was +24 +/- 7 mg/dl (P less than 0.05). A markedly significant decrease in plasma triglyceride levels was observed in this group (- 107 +/- 30; P less than 0.01). These results seem to indicate that, in Type IIa, clofibrate increased the resin's hypocholesterolemic effect. In Type IIb, on the other hand, the association of these drugs did not seem to be indicated since a marked hypotriglyceridemic effect was accompanied by an increase in plasma cholesterol levels. These results are briefly discussed in the light of recent data obtained on the effects of Colestipol and clofibrate on lipoprotein metabolism.

Adult↗

Two-dimensional immunoelectrophoresis of unconcentrated cerebrospinal fluid.

The two-dimensional immunoelectrophoresis on cellulose acetate, already utilized for serum proteins, has been applied to CSF proteins. The technical modifications which allow the use of unconcentrated CSF are described. By utilizing a particularly suitable supporting medium, a good separation of proteins is achieved; consequently narrow-based peaks are obtained and the isoantigens can be displayed as distinct components in spite of closely similar migration velocities. The preliminary results of this method are given. Particulary interesting appears a beta-migrating protein and the gamma-migrating oligoclonal bands. The first may present an anodic cleavage suggesting that it may be the beta1C/beta1A-globulin. If this hypothesis is confirmed, the relative concentrations of the two components can be investigated. No clear-cut peaks corresponding to the gamma-migrating oligoclonal bands have been observed, their place being taken by a low precipitation line continuous with the IgG peak. The reasons for this phenomenon may be tentatively ascribed to a local specificity of these IgG.

Beta-Globulins↗

[Heteropolycyclic systems. VII. 4-Dialkylaminoalkyl-2,3,3a,4-tetrahydro-1H-pyrrolo[2,1c] [1,2,4]benzothiadiazine-5,5-dioxides and their benzene-substituted derivatives. Cardiovascular effects in the anesthetized rat].

A series of 4-dimethylaminoethyl and 4-diethylaminoethyl derivatives of 2,3,3a,4-tetrahydro-1H-pyrrolo[2,1-c] [1,2,4] benzothiadiazine-5,5-dioxide substituted or unsubstituted in the benzene ring was prepared and subjected to preliminary investigation using the cardiovascular system of the anesthesized rat. Introduction of a basic group in the alkyl chain on N4 gives compounds with good hypotensive activity, this being most pronounced for (III, IV a and XIV) and an increase in differential pressure, marked for (V a, X, XII). These effects are sometimes accompanied by some bradycardizing activity, most marked for (V a) and (X). The results therefore confirm that derivatives of tetrahydropyrrolbenzothiazine have cardiovascular activity. Structure-activity relationships are discussed.

Animals↗

[Heteropolycyclic systems. VI. 4-Propyl-2,3,3a,4-tetrahydro-1H-pyrrolo(2,1c)(1,2,4)benzothiadiazine-5,5-dioxide and its derivatives. Cardiovascular effects of 4-alkyltetrahydropyrrolobenzothiadiazine in the anesthetized rat].

A series of 4-propylderivatives of 2,3,3a,4-tetrahydro-1H-pyrrolo[2,1-c] [1,2,4]benzothiadizine-5,5-dioxide substituted or unsubstituted in the benzene ring was synthesized. Derivatives of these compounds together with those of the corresponding 4-methyl and 4-ethyl derivatives prepared previously were tested for cardiovascular effects in the anesthesized rat. All the compounds studied showed hypotensive activity which was particularly intense for compounds (X), (XIX), (XXII), (XXV), and produced an increase in differential pressure marked for (XXV) and (XXVIII) which was often accompanied by pronounced bradycardia (XVII), (XVIII) and (XIX). The results prove that derivatives of 2,3,3a,4-tetrahydro-1H-pyrrolo-[2,1-c][1,2,4]benzothiadiazine-5,5-dioxide have hypotensive and bradycardizing activity. Structure-activity relationships are discussed.

Animals↗

Isolation and characterization of lipoprotein-X from the pig.

In vitro incubation of pig bile with pig whole serum resulted in the formation of "LP-X like" material migrating towards the cathode on agar-gel electrophoresis. As in all other species studied so far, LP-X occurred also in the serum of bile duct ligated pigs, however, relatively late (48-72h) after the operation. In parallel, alterations of some serum parameters and of the protein-lipid composition of the different lipoporotein fractions were observed. While the electrophoretic behaviour, the protein-lipid and apoprotein composition of pig LP-X were comparable to those found in man, dog and rat, it sedimated in most instances at the density 1.063 g/ml.

Alkaline Phosphatase↗

Effect of lipoprotein-X on hepatic cholesterol synthesis.

The effect of different lipoproteins (lipoprotein-X and lipoprotein-B; LP-X and LP-B) on hepatic cholesterol synthesis was studied in vivo in rats. Lipoproteins were continuously infused into rats for 16 hours so that 24 mg cholesterol/100 g body weight were applied. Serum cholesterol level was nearly doubled after the infusion period. Lipoprotein electrophoresis revealed the predominance of the infused lipoprotein in the serum. LP-B infusion caused a reduction of cholesterol synthesis (42% of control values) and reduced the increased cholesterol synthesis of bile fistula rats to values below normal. LP-X did not reduce hepatic cholesterol synthesis significantly nor did it normalize the enhanced synthesis following biliary diversion. However, hepatic free cholesterol concentration increased after LP-X infusion. The effect of LP-X on liver cholesterol synthesis is similar to that of lecithin: cholesterol dispersions. The failure of LP-X to exert a feedback inhibition on cholesterol synthesis may therefore contribute to the mechanism of hypercholesterolemia in obstructive jaundice.

Animals↗

Prevalence of coronary artery disease and peripheral artery disease in patients with different types of primary hyperlipidemia.

The prevalence of coronary artery disease (CAD) and peripheral artery disease (PAD) was studied in 280 (203 males, 77 females) patients with different types of primary hyperlipoproteinemia. In primary hyperbetalipoproteinemia the prevalence of CAD (45% for Type IIa and 47% for Type IIb) is significatly higher than that in the other types of hyperlipoproteinemia (38% for Type IV and 17% for Type V). On the other hand, PAD prevalence is much higher in hypertriglyceridemia (21% in Type IIb and 20% in Type V) than in hypercholesterolemia alone (9% in Type IIa). These results suggest ths atherosclerotic complications are concerned. Moreover, the high frequency of PAD found in hypertriglyceridemia can be related to the high occurrence of diabetes in these patients. The effects of other major risk factors of atherosclerosis (smoking and hypertension) were also evaluated. Our results indicate that the association of hypercholestolemia and hypertension is more dangerous than the co-occurence of hypercholesterolemia and smoking.

Adult↗

Improved assessment of plasma lipoprotein patterns. III. Direct measurement of lipoproteins after gel-electrophoresis.

Based on a previously described technique [Clin. Chem. 19, 737 (1973)] of precipitating plasma lipoproteins with polyanions after their electrophoretic separation in gels, a new method is presented for measuring normal plasma lipoproteins densitometrically. The method is fast and easy; the CV for beta-, pre-beta-, and alpha-lipoproteins was less than 5% in one series. Results are linearly related to concentration up to 10 g of total lipoprotein per liter. No unusual equipment is required. Standardization is done with the aid of a commercially available filter. Total plasma cholesterol and cholesterol calculated from quantified lipoprotein fractions were highly (r = 0.963) correlated.

Adult↗

Formation of lipoprotein-X. Its relationship to bile compounds.

In this study we have demonstrated that in native bile, lipids are organized in the form of a lipoprotein (bile LP) carrying albumin as apoprotein. The lipid composition of bile LP is almost identical to lipoprotein-X (LP-X, the characteristic lipoprotein of cholestasis). However, it differs from LP-X inits protein/lipid ratio and immunological and electrophoretic characteristics. Bile lipoprotein can be converted into "LP-X-like" material in vitro by adding albumin or serum to native bile. The LP-X-like material formed in vitro has physicochemical and chemical characteristics similar or identical to LP-X isolated from serum. As bile lipoprotein can be converted into LP-X-like material by the addition of albumin to bile, LP-X can be converted into bile-LP-like particles by adding bile salts to a LP-X-positive serum. Furthermore, experimental connection of the common bile duct to the vena cava is followed after a few hours by the appearance of LP-X-like material in the plasma. These facts taken together strongly suggest that bile LP is a precursor lipoprotein for LP-X and that it refluxes into the plasma pool under cholestatic conditions.

Animals↗

[Long term treatment of familial hypercholesterolemia with Colestipol, a new anionic exchange resin (author's transl)].

Results relative to long term treatment with Colestipol (a new resin sequestering bile acids) in 23 subjects with familial hypercholesterolemia, 12 with Type II A, 8 with Type II B and 3 homozygotes are reported. The patients had previously undergone treatment with clofibrate together with a hypocholesterolemic diet. After six weeks with placebo, the patients were given 15 g/die active drug for a period of 12 months and a double dose (30 g/die) for a successive period of 4 months. During the experimental trial the same hypocholesterolemic, isocaloric diet which had been followed during the previous hypolipidemic treatment was maintained. In the entire group taken as a whole, the total mean decrease was --56,9 +/- 15 mg/dl (P less than 0,01) after 12 months of 15 g/die Colestipol and --62,8 +/- 13 mg/dl (P less than 0,01) during the following 4 months with 30 g/die Colestipol. The difference between the two periods of treatment (15 g and 30 g/die) is not statistically significant. During the active drug treatment a slight but not statistically significant triglyceride increase was observed. The increase was most marked in the Type II B patients: the triglyceride variations in this group could be partly caused by slight variations in mean body weight. Starting from a mean basal value of 3,9 +/- 0,2 mg/dl, serum uric acid showed a significant increase which was maintained throughout the entire period of treatment, reaching a peak of 5,6 +/- 0,3 mg/dl (P less than 0,001) at the twelfth month. During the experimental trial no significant modifications were observed in the hematological routine analysis and liver functional tests, no malabsorption syndrome and no signs of toxicity were seen. Most frequent side effects were constipation, nausea, metheorism which, with the exception of four cases, which were withdrawn from the study, were reported as being transitory and mild. In conclusion, since Colestipol treatment significantly lowers cholesterol levels in patients with familial hypercholesterolemia and does not manifest any toxicity or serious side effects, it can be used effectively in the long term treatment of this disease which is characterized by an elevated frequency of cardiovascular complications.

Adult↗