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Biomedical subjects

L Mazzanti

Publications and source records attributed to L Mazzanti.

At least 163 records · Page 9Linked to original sources

Plasma membrane changes associated with rat liver regeneration.

The lipid composition and fluidity of plasma membranes have been studied at different stages of liver regeneration (4, 15 and 24 h after surgery). The phospholipid and fatty acid composition is not modified, whereas the cholesterol/phospholipid ratio is lower with respect to control membranes. The modification of the physical properties of the membranes has been studied directly by EPR analysis and indirectly by temperature dependence and cooperativity of some membrane-bound enzymes (Mg2+-ATPase, (Na+ + K+)-ATPase and 5'nucleotidase). Surgical operation or anaesthesia alone causes an early increase in fluidity; such an effect appears to be markedly reduced at a later stage. There seems to be a marked effect of regeneration on plasma membrane fluidity 15 h after partial hepatectomy when several parameters--surface fluidity, cholesterol/phospholipid ratio, and 5'-nucleotidase activity in the presence of concanavalin A -- are modified and indicate an increase in membrane fluidity. It is suggested that this modification of membrane properties could be related to the proliferative process.

Adenosine Triphosphatases↗

Effect of anesthetics on membrane fluidity tested by two different techniques: EPR spin labels and polarization of perylene fluorescence.

We have investigated the effect of n-butanol on the spectroscopic properties of two types of probes, that are usually employed to detect membrane fluidity, in mitochondrial phospholipid vesicles and mitochondrial membranes. Although both a spin label (16-doxylstearate) and the fluorescent probe perylene detect a higher immobilization of the membrane in comparison with phospholipid vesicles, the effect of butanol in the case of the membrane is strikingly different with the two techniques employed, showing increased fluidity in the case of the spin label and decreased fluidity with the fluorescent probe.

Anesthetics↗

Noradrenergic innervation of the heart in untreated and daunomycin-pretreated animals.

The innervation of guinea-pig and rat cardiac tissue consists of thin noradrenergic axons running parallel to the myocardial fibres and producing well-developed fluorescent networks which are denser in guinea-pig tissue. Transverse sections of arterial vessels exhibit a marked polar-like disposition of adrenergic nerves, which mainly appear to be concentrated in two opposite areas. Tissue sections from daunomycin-treated animals fluoresced a striking orange-red. This drug-specific fluorescence emanated from all parts of the ventricular tissue, with particular intensity in the nuclei. Neither the density nor the shape of the adrenergic nerves were affected by treatment with the drug. Despite penetration and storage of the antibiotic into the ventricular tissue, cardiotoxicity was not found in the present study.

Adrenergic Fibers↗

Molecular mechanism of general anesthesia: II. Spin label studies on synaptic membranes.

In this communication we report the effects of general anesthetics on the mobility and order of spin labeled stearic acid derivatives in synaptic membranes and in bilayers formed from the lipids extracted therefrom. The anesthetics studied abolish the immobilization induced by synaptic membrane proteins on the membrane lipids : this effect, observed particularly in the bilayer core, is interpreted as a labilization of lipid-protein interactions induced by anesthetics.

Anesthesia, General↗

Molecular mechanism of general anesthesia: I. Fluorescence studies in mitochondrial membranes.

We have tested the working hypothesis that anesthetics, by labilizing lipid-protein interactions, induce conformational changes in membrane proteins involved in the transmission of neural impulses. In the first communication of this series we report that general anesthetics induce changes in the fluorescence of the probes ANS and NPN in model membranes, lipid vesicles and mitochondria. The changes observed concern the quantumyield but not the position of the emission maximum. Such changes may be interpreted as due to fluidization of the membrane core (NPN), accompanied by variable effects in the membrane surface(ANS).

Anesthesia, General↗

Molecular mechanism of general anesthesia: III. Kinetic studies on erythrocyte ghost acetylcholinesterase.

General anesthetics inhibit erythrocyte membrane-bound acetylcholinesterase. Release of the membrane-bound enzyme by sonication into a soluble form induces a loss of sensitivity to anesthetics. Reconstitution of the solubilized enzyme with phospholipids restores its inhibition by anesthetics. The results suggest that anesthetic inhibition of acetylcholinesterase is mediated through the lipid bilayer.

Acetylcholinesterase↗

Lipid protein interactions in mitochondria. VIII. Effect of general anesthetics on the mobility of spin labels in lipid vesicles and mitochondrial membranes.

We have studied the effect of general anesthetics on the mobility of two stearic acid spin labels (5-doxyl stearic acid and 16-doxyl stearic acid) in bovine heart mitochondria and in phospholipid vesicles made from either mitochondrial lipids or commercial soybean phospholipids. The general anesthetics used include nonpolar compounds (alcohols, halothane, pentane, diethyl ether, chloroform) and the amphiphatic compound, ketamine. All anesthetics tested increase the mobility of the spin labels in phospholipid vesicles to a limited extent up to a concentration where the ESR spectra become those of free spin labels. On the other hand, anesthetics have a pronounced effect on mitochondrial membranes at concentrations as low as those known to produce general anesthesia; the effect is lower near the bilayer surface (5-doxyl stearic acid) and very strong in the bilayer core (16-doxyl stearic acid). The effects of anesthetics are mimicked by the detergent, Triton X-100. We suggest that the discrepancy between the action of anesthetics in mobilizing the spin labels in lipid vesicles and in membranes results from labilization of lipid protein interactions.

Anesthetics↗

Conformational effects on the activity of drugs. 7. Synthesis and pharmacological properties of 2-(p-nitrophenyl)-substituted morpholines.

A series of 1-(p-nitrophenyl)-2-aminoethanol derivatives and their morpholine analogues have been synthesized and pharmacologically investigated in order to confirm some pharmacological observations made with the N-isopropyl-substituted compounds. In agreement with the previously obtained results, the weak alpha-adrenergic-stimulating activity and the potentiating effect on the responses to norepinephrine found in the open-chain compounds persist in their corresponding semirigid cyclic analogues. The results are discussed in the light of common knowledge of the structure-activity relationships of alpha-adrenergic drugs.

Adrenergic alpha-Antagonists↗

Effect of long-term GH administration on pituitary-thyroid function in idiopathic hypopituitarism.

Twenty-four euthyroid children with idiopathic pituitary dwarfism were studied. The euthyroid state for seven of these patients was determined by negative physical examinations, normal plasma T4 assays and normal 131I uptakes. For the other children, thyroid function was evaluated with T3 and T4 assays and on the basis of the TRH test. Each of the children was treated with HGH in one of three different ways. The first group (five cases) was given a HGH dose, ranging from 12.4 to 17.2 IU/m2//week. The second and third groups (nine and ten cases, respectively) were treated with 10 and 20 IU/m2/week, respectively. Treatment was carried out for periods ranging from 6 months to 6 years. After no less than 6 months of treatment, and at intervals of 6 months (or some multiple of 6 months) plasma T3 and T4 assays, as well as a TRH test were performed in each patient. In some patients one of the indices was once beyond the upper or lower limit of the normal range (none of the children presented simultaneous abnormal levels of more than one index during the controls). This value, however, returned to within normal limits at the following control. There was no correlation between T3, T4 and TSH with the duration of HGH therapy. There was no significant difference between the groups of children treated with the different HGH doses. These data seem to demonstrate that the risk of inducing an alteration in thyroid function in hypopituitary patients during HGH treatment is very slight, and that the irregularly abnormal thyroid indices observed in some of the children during one of the controls might be an expression of their metabolic status at that moment.

Adolescent↗

Biophysical studies on agents affecting the state of membrane lipids: biochemical and pharmacological implications.

The phospholipid requirement of membrane-bound enzymes may depend on several reasons. In our laboratory we have investigated lipids (1) as a bidimensional medium required for the movement of Coenzyme Q, a lipid-soluble cofactor of the mitochondrial respiratory chain, and (2) as a hydrophobic environment necessary to impose the proper conformation to membrane-bound enzymic proteins. We have found that Coenzyme Q, once reduced by NADH dehydrogenase, must cross the inner mitochondrial membrane; only quinones having long isoprenoid side chains can easily cross phospholipid bilayers, and this is the reason why a short chain quinone such as CoQ-3 inhibits NADH oxidation. The incapability of short quinones to cross lipid bilayers is due to their disposition in the lipid bilayer, stacked within the phospholipids. The conformational role of lipids has been investigated indirectly observing the kinetics of membrane-bound enzymes, e.g. the mitochondrial ATPase, and directly by circular dichroism. Lipid removal or lipid perturbation with organic solvents induce a decrease of alpha-helical content in mitochondrial proteins, and give rise to a series of kinetic changes in ATPase, including uncompetitive inhibition, increased activation energy, and loss of cooperativity in oligomycin inhibition. The recognition of a conformational role of lipids has allowed us to postulate a working hypothesis for the mechanism of action of general anesthetics. Such drugs have been found by us, by means of spin labels and fluorescent probes, to disrupt lipid protein interactions in several membranes, including synaptic membranes. The loosening of such interactions is believed to induce conformational changes, which will alter ion transport systems necessary to the propagation of neural impulses. Conformational changes induced by anesthetics have been found by us both directly by circular dichroism and indirectly by enzyme kinetics. The conformational effect of anesthetics is not directly exerted on the proteins but is mediated through the lipids. In agreement with this hypothesis we have found that membrane-bound acetylcholinesterase is inhibited by anesthetics, whereas the solubilized enzyme is not inhibited. However, binding of the solubilized enzyme to phospholipids restores anesthetic inhibition.

Acetylcholinesterase↗

Hypophyso-gonadal function in the diabetic child.

14 diabetic boys (five with a family history of diabetes and nine without) and 29 "short normal" boys were studied. A gonadal function test (2.000 IU of hCG i.m. for 3 days and plasma testosterone assay before and after the hCG administration) as well as an LH-RH test (50 microgram i.v.) were carried out. While basal testosterone level turned out to be similar in the two groups of children, it was significantly lower (p less than 0.01) after hCG than the mean value of the control group. This difference was mainly observed in those patients with a family history of diabetes. In the diabetic children, basal LH level was normal and the pituitary LH reserve was lower than in the control group. Both basal FSH level and FSH pituitary reserve were lower than in normal children. These data show that an alteration in the hypothalamus-pituitary-gonadal function is already evident in the diabetic child.

Adolescent↗

Histochemical studies of noradrenergic innervation of the liver in untreated and daunomycin-pretreated guinea-pigs.

The pattern of noradrenergic innervation of guinea-pig hepatic tissue was examined by using the fluorescence method of Falk et al. (1962). The distribution of monoaminergic nerve fibers in untreated animals was clearly evident at the level of the portal vein, the hepatic artery and the bile duct. The hepatic artery was the most densely innervated. Mast cells and Kupffer cells had no connection with the adrenergic fibres. In daunomycin-pretreated animals, the hepatic cells appeared to be deep red in colour owing to the presence of the antibiotic. Some noradrenergic nervous fibres, never previously described, were unexpectedly distinguishable in the liver parenchyma against the background red colour of daunomycin-pretreated tissue. They appeared to be contiguous to the hepatocytes and were of different shapes: comma-like, V-like, or like a string of pearls. The nature and the functional role of these elements is briefly discussed.

Adrenergic Fibers↗