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Biomedical subjects

E Bosisio

Publications and source records attributed to E Bosisio.

At least 37 records · Page 2Linked to original sources

Mean transit time, forced expiratory volume and age in healthy male smokers and non-smokers.

We studied 67 healthy males aged 20-30 years, 29 of them non-smokers and 38 smokers. In smokers, forced expiratory volume (FEV), 1 s forced expiratory volume (FEV1) and peak flow (PF) were significantly lower than in non-smokers, while the FEV1/FEV ratio, flows and mean transit time (MTT) compared well. MTT appeared directly related to age and negatively to FEV1/FEV, with no difference between the two groups, but MTT was directly related to FEV in non-smokers and negatively in smokers. Multiple regression analysis, MTT = a + b(FEV)+c(age), showed that parameters b and c were significantly different between smokers and non-smokers and, in the former, parameter b was negative. In non-smokers the effects of age and FEV on MTT were roughly the same, but in smokers MTT was influenced above all by age, probably because MTT measured the effects of continued smoking.

Adult↗

Correlation between plasma levels of fenofibrate and lipoprotein changes in hyperlipidaemic patients.

Eleven hyperlipidaemic patients received two formulations of fenofibrate (differing in in vitro dissolution) in randomized sequence, each for 6 weeks. Formulation N, giving a 2-3-fold higher plasma fenofibrate level compared to R, lowered both the cholesterol and triglyceride levels far more than R. Changes in the total and high density lipoprotein cholesterol levels were not significantly correlated with the fenofibrate level. A highly significant correlation was detected for triglycerides in Type IV patients, and for changes both in very low density lipoprotein (VLDL) cholesterol and triglycerides in the entire group of patients. In conditions of widely distributed steady state levels of an absorbable hypolipidaemic drug, a significant correlation may thus be detected between the plasma level and the reduction of VLDL - associated lipids.

Adult↗

Relationship of the phenotypic expression of the A-IMilano apoprotein with plasma lipid and lipoprotein patterns.

The plasma lipoprotein and apolipoprotein profile of 29 adult A-IMilano (A-IM) carriers and 29 age- and sex-matched non-affected subjects of the same kindred was examined, in order to investigate linkages between the lipid and apoprotein abnormalities and the phenotypic expression of the biochemical disorder. Carriers (A-IM+) showed a higher prevalence of hypertriglyceridemia (12 out of 29); they also had lower plasma total cholesterol, esterified cholesterol and phospholipids, compared to non-carriers. Lipoproteins were characterized by a significant enrichment of triglycerides in low and high density fractions (LDL and HDL), and by the expected striking reduction of HDL mass and cholesterolemia. Conversely, no significant alterations of the major circulating apolipoprotein levels, except for apo A-I and apo A-II, were noted in the A-IM+. The increased free cholesterol/esterified cholesterol ratio in plasma (most marked in HDL), was accompanied by a significant reduction of the lecithin cholesterol acyl transferase molar activity. Several correlations pertaining to lipids, lipoproteins and apoproteins were examined: cholesterol and triglycerides in HDL and, more remarkably, apoprotein A-I and C-III levels in plasma were significantly correlated in the A-IM+. While there was no significant prevalence of specific apo E phenotypes, plasma triglycerides and apo C-II levels were highly correlated in the carriers. The A-IM subjects, while in the presence of severe lipoprotein risk factors, may have alternative mechanisms of cholesterol disposal, potentially responsible for the apparently low prevalence of atherosclerosis.

Adolescent↗

Ventilatory response to carbon dioxide and to isometric muscle contraction after administration of placebo, propranolol, mepindolol and salbutamol.

Healthy males (23-29 years) volunteered as subjects. We studied the ventilatory response to carbon dioxide and to isometric exercise (50% of maximum voluntary contraction) after administration of propranolol (20 mg), mepindolol (5 mg), salbutamol (20 mg) and placebo (single dose orally). The increase of pulmonary ventilation (VE) activated by central (CO2) and reflex stimulus (hand-grip) did not differ statistically between the four drugs. Analysis of VE in terms of inspiratory drive (Vt/Ti) and timing ratio (Ti/Ttot) showed that during CO2 stimulation mepindolol and salbutamol increased VE predominantly by the increase of Vt/Ti, presumably through the direct stimulation on the respiratory center. During rebreathing, Ti/Ttot increased significantly after administration of placebo and propranolol, so VE increased by a rise of Vt/Ti and by an increase of an effective 'timing component' (Ti/Ttot). Propranolol does not modify the ventilatory response to CO2 and hand-grip when VE is analyzed in terms of Vt/Ti and Ti/Ttot.

Adult↗

HMGCoA reductase and cholesterol 7 alpha-hydroxylase in human liver.

The activities of HMGCoA reductase and cholesterol 7 alpha-hydroxylase were assayed in liver biopsies of patients with or without cholestyramine treatment. The active dephosphorylated form of HMGCoA reductase and the activity of cholesterol 7 alpha-hydroxylase were under the detection limits in untreated subjects. After cholestyramine treatment activities of both enzymes were stimulated and the active form of HMGCoA reductase became detectable in four out of the five tested patients. In two subjects who received cholestyramine, the effect of exogenously added [4-14C] cholesterol on cholesterol 7 alpha-hydroxylase was tested. In the presence of Tween 80, the detergent by which [14C]cholesterol was suspended, the enzyme activity was profoundly inhibited and synthesis of 7 alpha-hydroxycholesterol was extremely low.

Adult↗

Evaluation of enzyme activities by gas chromatography-mass spectrometry: HMGCoA reductase and cholesterol 7 alpha-hydroxylase.

Methods are described for the evaluation of HMGCoA reductase and cholesterol 7 alpha-hydroxylase activities. The methods are based on the measurement by selected-ion monitoring of mevalonate, formed from HMGCoA and of 7 alpha-hydroxycholesterol formed from cholesterol, respectively. The methods are as sensitive as those based on the use of radioisotopes but less time-consuming because quantitation is carried out on total lipid extracts. In the case of cholesterol 7 alpha-hydroxylase, the procedure does not require the use of exogenous cholesterol as the substrate, so problems related to its equilibration with endogenous microsomal cholesterol are avoided.

Animals↗

Effects of dietary proteins on the regulation of liver lipoprotein receptors in rats.

Female rats fed a 1.2% cholesterol diet with animal proteins (casein) develop a significant hypercholesterolemia, with a marked increase of very low density lipoprotein (VLDL)-associated cholesterol. Substitution of soy proteins for casein in the diet counteracts the increase of both total and VLDL cholesterol. Studies of liver receptor activity were carried out with both casein and soybean-cholesterol diets, to define the site of action of soy proteins. Binding of a cholesterol-rich lipoprotein fraction (beta-VLDL) to hepatic membranes is normal when a soybean-cholesterol diet is administered, and markedly reduced with casein-cholesterol. The activity of receptor-linked enzymes, HMG-CoA reductase, cholesterol 7 alpha-hydroxylase and acyl-CoA:cholesterol O-acyltransferase (ACATase), is differently affected by the two diets. HMG-CoA reductase activity is reduced by both diets with, however, significantly higher enzyme activities in the soybean-cholesterol-fed group. Both 7 alpha-hydroxylase and ACATase activity levels are significantly raised by casein-cholesterol but are in a normal range with soybean-cholesterol. These findings suggest that the hepatic receptor regulation of cholesterol metabolism is differently affected by animal and vegetable proteins in the diet.

Animals↗

Ventilatory volumes, flow rates, transfer factor and its components (membrane component, capillary volume) in obese adults and children.

We have studied the ventilatory volumes, flow rates, transfer factor and its components (membrane component and capillary volume) in 19 women and 23 children with moderate obesity. The adults showed restrictive defects, but the pulmonary volumes of children were within normal range. Peak flow, flows at 75 and 50% forced expiratory volume, in two groups, normalized for the forced expiratory volume, did not differ between the two groups. The transfer factor was reduced in adults, because of reduction of the alveolar volume, the membrane component was low in both groups; transfer factor and membrane component normalized for functional residual capacity were not different between the two groups. The capillary volume was greater in children than adults, because the excess body weight was greater for the children. In simple obesity, the main alteration is the decrease of distensibility of the chest wall that becomes worse as time goes on and is the cause for the alterations in ventilatory volume, flow and transfer factor.

Adult↗

The effect of cholestyramine on liver HMG-CoA reductase and cholesterol 7 alpha-hydroxylase in various laboratory animals.

The activity of HMG-CoA reductase and cholesterol 7 alpha-hydroxylase was assayed in the liver of rats, rabbits, hamsters and guinea pigs at the minimum of the day cycle and after one night fasting. The amount of HMG-CoA reductase, as determined after its complete dephosphorylation in vitro was of the same order of magnitude in the tested species. The dephosphorylated active form of the enzyme was detectable only in the rat. Cholesterol 7 alpha-hydroxylase activity was also much higher in the rat. Cholestyramine treatment stimulated the activity of both enzymes. In particular, the ratio between active and inactive HMG-CoA reductase in rabbits, hamsters and guinea pigs became of the same order of magnitude of that found in rats.

Animals↗

Influence of species and sex on cholesterol 7 alpha-hydroxylase activity in experimental animals.

Cholesterol 7 alpha-hydroxylase activity was evaluated measuring by selected ion monitoring the amount of 7 alpha-hydroxycholesterol formed from endogenous microsomal cholesterol and from exogenously added [4-14C]cholesterol in incubations of liver microsomes. The enzyme activity was determined in female rats, hamsters and guinea pigs and results were compared with those obtained in male rats. The results suggest that there is no difference between male and females as far as the activity of the enzyme from endogenous cholesterol is concerned at least in rat liver. Moreover, saturation of the enzyme by the endogenous substrate was observed in all female animals in contrast to the male rat for which the enzyme was found to be not saturated, as already reported by others. From molar radioactivity of 7 alpha-hydroxycholesterol obtained during incubations with [4-14C]cholesterol, differences were also evidenced in the equilibration of the substrate with the endogenous pool of cholesterol. In the male rat, equilibration depended upon the concentration of radioactive cholesterol added to the medium and reached completion at 60 microM concentration. In female animals, molar radioactivity of 7 alpha-hydroxycholesterol was always linearly correlated with that of cholesterol in the medium but it was always lower than that one. This indicates that in the tested female animals only part of exogenously added cholesterol is accessible to the substrate pool of the enzyme.

Animals↗

3-Hydroxy-3-methylglutaric acid (HMGA) reduces dietary cholesterol induction of saturated bile in hamster.

3-Hydroxy-3-methylglutaric acid (HMGA) is a competitive inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCoAR) and strongly reduces cholesterol biosynthesis both in vitro and in vivo. Since the effects of this compound on biliary lipid composition are hitherto unknown, we have investigated whether it prevents dietary cholesterol induction of saturated bile in the hamster. Female Golden Syrian hamsters have been divided into four groups and treated for 10 weeks as follows: I) Standard diet, containing 0.8 mg cholesterol/g food; II) Standard diet plus HMGA (100 mg/kg b.w./day per os); III) Lithogenic diet containing 2.4 mg cholesterol/g food; IV) Lithogenic diet plus HMGA as above. The results indicate that HMGA is effective in reducing both bile cholesterol supersaturation and hypercholesterolemia. Inhibition of hepatic cholesterogenesis at the level of mevalonate synthesis by HMGCoAR and reduction of intestinal cholesterol absorption may be responsible for these effects.

Animals↗

Ventilatory pattern during handgrip on normal man.

We studied the ventilatory response to an isometric handgrip (50% maximum voluntary contraction) in 7 young normal subjects. VE increased significantly during isometric contraction due to increases in Vt/Ti (the mean inspiratory flow) and Ti/Ttot (the timing component of ventilation). The increase in Vt/Ti is greater than that in Ti/Ttot; thus, the contribution of the neural inspiratory drive is predominant in increasing the pulmonary ventilation during a handgrip.

Hand↗

Defective hydroxylation of phenformin as a determinant of drug toxicity.

The kinetics of phenformin and its metabolite, p-hydroxyphenethylbiguanide, was studied in eight diabetic patients with varying degrees of renal impairment. Plasma and urinary phenformin and p-hydroxyphenethylbiguanide levels were determined by the multiple selected ion monitoring technique. Phenformin half-lives were unrelated to the degree of renal impairment, whereas reduced renal clearances of insulin and creatinine were significantly correlated with a prolonged half-life of the metabolite. The excretion of p-hydroxyphenethylbiguanide was quite variable (between 4.9% and 27% of total urinary drug loss), probably due to a genetic polymorphism of hepatic mechanisms for hydroxylation. A reduced formation of the metabolite was concomitant with marked increases in the amount of circulating phenformin. A positive reciprocal correlation was detected between areas under the plasma curve of phenformin and both the renal clearance of the unchanged drug and the percentage of metabolite formation. A reduced hydroxylation of phenformin seems, therefore, to be responsible for the high plasma levels of the drug previously described in toxic patients.

Aged↗