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Biomedical subjects

L Mazzanti

Publications and source records attributed to L Mazzanti.

At least 109 records · Page 6Linked to original sources

Structural and functional modifications induced by ketamine on synaptosomes in the rat.

This study correlates previous observations on the effects of a general anaesthetic (2-chlorophenyl-2-methylaminocyclohexanone, trade name Ketalar), administered in vivo on the functional properties of synaptosomes from the brain of the rat, with structural modifications detected using freeze-fracture electron microscopy. The anaesthetized rats exhibited a fluidization of the synaptic membranes, as probed by stearic acid spin labels, accompanied by a decrease in the activity of acetylcholinesterase. The freeze-fracture images of synaptosomes from anaesthetized rats showed a clear statistical increase in the number of vesicles with aggregated intramembrane particles, without any significant change of the particle diameter. The hypothesis that a perturbation of the lipid protein interaction is a primary effect, in the mechanism of action of anaesthetics, is supported at present only by indirect evidence.

Acetylcholinesterase↗

Sodium metabolism in offspring of hypertensive parents.

Intracellular sodium concentration and Na+/K(+)-ATPase activity were studied in erythrocytes obtained from members of 14 families with one hypertensive parent and from age-matched control subjects, as part of a study on the genetic and environmental determinants of essential hypertension. We found reduced Na+/K(+)-ATPase activity, increased intracellular Na+ concentration, and reduced urinary Na+ excretion in hypertensive patients as compared with the control subjects. In the offspring of hypertensive parents an increase in intracellular Na+ concentration and a decrease in Na+/K(+)-ATPase activity were observed, with a significant correlation relating such parameters. Normotensive spouses did not differ from the normotensive control adults in any of the parameters studied, suggesting no influence of shared family environment in our family group. These data suggest that there is a strong genetic influence contributing to familiar alterations in cation transport, although long-term studies are needed to evaluate the influence of environmental determinants.

Adolescent↗

Modifications induced by gestational diabetes mellitus on cellular membrane properties.

Alterations in erythrocyte plasma membrane properties (enzymatic activities and membrane fluidity) have been observed in patients affected by insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). In order to verify whether these alterations are present also in gestational diabetes mellitus (GDM) we studied the plasma membranes obtained from two different cellular types (erythrocyte from both mother and cord blood and placenta syncytiothrophoblast cell) of 16 healthy pregnant women and 15 women affected by GDM. The following determinations were performed on the membrane preparations: Na+/K(+)-ATPase activity, acetyl-cholinesterase (AchE) activity, membrane fluidity and cholesterol:phospholipid ratio. We observed a reduction of both enzymatic activities and a decrease of membrane fluidity in maternal and cord blood erythrocytes and in syncytiotrophoblast plasma membranes in GDM pregnant women in comparison with controls. The cholesterol to phospholipid ratio was significantly lower in the erythrocyte membranes of women affected by GDM than in normal pregnant women, while it was increased in the cord blood erythrocyte membranes and in placental membranes in GDM in comparison with controls. The present study found, in GDM patients, a membrane alteration similar to the abnormality reported in IDDM and NIDDM (i.e. decreased Na+/K(+)-ATPase activity), while opposite modifications were observed with regard to other membrane activities and properties. The different membrane alterations observed in GDM with respect to IDDM and NIDDM might be linked to the different degree of metabolic control, on the contrary the reduced Na+/K(+)-ATPase activity might be a primary event in the pathogenesis of diabetes mellitus per se and might constitute a signal of high risk of developing the disease later in the women affected by GDM during pregnancy.

Acetylcholinesterase↗

In vitro effect of magnesium on the Na/K-ATPase isolated from human placenta.

Magnesium (Mg) is an activator of many cellular processes, among which is cation transport. An imbalance of cation transport may be involved in several diseases, as well as during pregnancy. Since the action of Mg in vivo in preventing gestational diseases is known, as well as its role in vitro on some cation transport activities, we studied the action of increasing concentrations of Mg on the activity of the enzyme Na/K-ATPase isolated from placental tissue of six normotensive women, at term. Incubation in a medium with increasing concentrations of Mg resulted in a significant activation of the enzyme, which was related to Mg concentration. The study demonstrates the action of Mg in vitro on isolated enzymes, and suggests the use of enzyme purification as a model for the study of cation transport in pregnancy.

Dose-Response Relationship, Drug↗

Effect of magnesium-deficient diet on cation transport in pregnant rabbits.

The imbalance of cation transport is considered to play an important role in the development of hypertension, and this also applies to hypertension during pregnancy. Magnesium (Mg) is one of the factors that regulate cation transport across the cell membrane. We therefore studied the effect of a magnesium-deficient diet on the activity of erythrocyte Na/K-ATPase and Mg-ATPase from six pregnant rabbits and compared the results to those obtained from six controls on a normal diet. None of the rabbits on the deficient diet developed hypertension or intrauterine growth retardation; nevertheless the activity of both enzymes was significantly reduced compared to the group on the normal diet. Since the reduced activity of these enzymes can determine sodium or calcium retention in the cell, Mg deficiency could be the basis of the onset of some forms of hypertension in pregnancy.

Animals↗

[Effect of HMG-CoA reductase inhibitors on the erythrocyte membrane].

We studied 10 patients affected by primary hypercholesterolemia treated with placebo for 1 month and with simvastatin (20 mg die) for 6 months during a double-blind clinical trial. At 1-month intervals we determined the following parameters in the serum: total and HDL-cholesterol, triglycerides, apolipoprotein A1 and B. At the same time intervals, we also determined the cholesterol and phospholipid concentration, the Na+/K+ ATPase activity and the fluidity of the erythrocyte membranes. Our results demonstrated the following modifications in the erythrocyte membranes during simvastatin treatment: 1) an initial increase in the cholesterol concentration and in the cholesterol/phospholipid ratio, with a significant decrease only after 4 months; 2) a similar behaviour of membrane fluidity, with an initial decrease and an elevation after 4 months; 3) an increase in the Na+/K+ ATPase activity only after 4 months. We hypothesize that simvastatin not only inhibits the hepatic synthesis of cholesterol, but also modifies the cholesterol exchange between plasma and the erythrocyte membrane.

Cholesterol↗

Modifications induced by general anesthetics on Na+/K+ ATPase obtained from human placenta.

Previously it was demonstrated that thiopental in vivo anesthesia didn't affect the Na+/K(+)-ATPase activity of syncythiotrophoblast plasma membrane, while affecting other enzymatic activity. The aim of the present work was to investigate if this lack of effect of thiopental on the Na+/K+ ATPase activity might be due to its specificity of action on definite membrane proteins or if the binding sites of the anesthetic to this enzyme might be masked within the membrane. Temperature dependence of the Na+/K(+)-ATPase activity and of a spin label paramagnetic maleimide derivative (MSL,2,2,6,6-tetramethylpiperidin-1-oxyl-4-maleimide), which shows a selective binding to the reduced sulfhydryl groups of proteins were investigated. This report shows that a Na+/K(+)-ATPase membranous preparation obtained from placental tissue is strongly inhibited by thiopental.

Anesthetics↗

Bronchial reactivity and sex hormone: study in a Turner's population.

Respiratory function and bronchial reactivity was studied by carbachol challenge in 41 patients with Turner's syndrome and in 46 controls. In patients and controls the personal and family history of atopic illnesses was evaluated; reactivity to skin allergen tests was studied in patients only. Patients with Turner's syndrome had less allergy skin test reactivity; no difference was found in allergic symptoms between patients and controls despite the patients having a more positive family history of atopy (P less than 0.05). Respiratory function variables were higher in patients than in controls, and bronchial reactivity as expressed by the results of carbachol testing was higher in Turner's patients than in controls (P less than 0.01). Bronchial reactivity was significantly reduced after 6 months of estrogenic therapy (P less than 0.05) in subjects with Turner's syndrome, while the same did not occur in patients who did not receive estrogen treatment. This study of pulmonary function and bronchial reactivity in Turner's patients may help understand the effects of sex hormones in the regulation of bronchial tone and of bronchial response to constrictive agents.

Adolescent↗

Effects of sport (football) on growth: auxological, anthropometric and hormonal aspects.

There are very few data available on the relationship between sporting activities, endocrine levels and changes in anthropometric measurements during growth. In order to study these relationships, we have made measurements of growth, changes in physical conformation and the plasma levels of several hormones [cortisol, dehydroepiandrosterone sulphate (DHEA-S), testosterone, growth hormone, somatomedin C, insulin, glycaemia and haemoglobin A1C] in 175 boys, aged 10-16 years, who have played football at a competitive level and in 224 boys, severing as controls, who have never performed sporting activities regularly. The football players were divided into prepubertal and pubertal subjects (10-11.99 years, 12-13.99 years and 14-16 years, chronological and bone age groups). Our results showed no significant differences in the growth indices between prepubertal athletes and controls, but the plasma level of DHEA-S was significantly higher (P less than 0.05) in the athletes. Pubertal football players, however, were significantly taller than the control subjects, particularly at 14-16 years chronological age. There were no such significant differences when bone age was considered. The pubertal football players were also more advanced in all biological indices of maturity, i.e. pubic hair, testicular volume and bone age. The increase in DHEA-S in pubertal football players, already seen in prepubertals, was also combined with a significant increase in testosterone, growth hormone and cortisol levels. Thus, in football players the DHEA-S level is already higher during prepuberty. This increase thus precedes all other indices of growth and maturation associated with puberty. We hypothesize that, while not excluding the possible influence of selection, as ours is a cross-sectional study, adrenal hyperactivity may be mainly responsible for the earlier onset of pubertal growth and maturity in exercising males.

Adolescent↗

Altered cellular Ca2+ and Na+ transport in diabetes mellitus.

Platelet intracellular Ca2+ concentration ([Ca2+]i) and its response to stimuli (ADP and thrombin) were studied in 15 insulin-dependent and 22 non-insulin-dependent diabetes mellitus patients with the fluorescent probe Fura 2. The activity of Ca2(+)-ATPase and Na(+)-K(+)-ATPase, membrane fluidity, and cholesterol and phospholipid content were also determined in platelet membranes. Compared with control subjects, diabetic patients showed 1) increased platelet [Ca2+]i in the resting state, 2) higher Ca2+ levels after stimulation with thrombin and ADP, due entirely to increased resting concentrations, 3) reduced activity of Na(+)-K(+)-ATPase, 4) increased activity of Ca2(+)-ATPase, 5) higher fluidity of the platelet membrane, and 6) increased membrane concentration of total phospholipids. Na(+)-K(+)-ATPase activity was inversely related to platelet [Ca2+]i in each group studied, whereas Ca2(+)-ATPase activity was positively correlated with intracellular Ca2+ levels. The data obtained in diabetic subjects suggest an abnormality in Ca2+ and Na+ transport across the platelet membrane that might be responsible for the reported platelet hyperreactivity to stimuli in diabetes.

Adenosine Diphosphate↗

Cyclosporin effect on sodium and potassium transport across erythrocytes in rheumatoid arthritis.

The aim of the present work was to evaluate the action of cyclosporin (CsA) both in vivo and in vitro on the active sodium transport across the erythrocyte membrane of rheumatoid arthritis (RA) patients. The in vivo study was performed on 20 patients affected by refractory RA and treated with CsA (5 mg/kg/die) or with azathioprine (2 mg/kg/die) before and after 7 days' therapy. The control group was formed of 25 healthy subjects. RA patients before treatment showed increased intra-erythrocyte Na+ concentration and decreased Na+, K+ ATPase activity in comparison with normal subjects. A rise in the activity of the sodium pump and a reduction in the intra-erythrocyte Na+ concentration were observed after cyclosporin treatment, but not after azathioprine. The in vitro study was performed on intact RBCs and on erythrocyte membranes from 15 healthy subjects and from 12 patients affected by classical RA, in the presence or absence of CsA (0.5-1-2 micrograms/ml). CsA (0.5 micrograms/ml) increased the Na+, K+ ATPase activity in intact RBCs and in erythrocyte membranes from both groups of subjects. Intracellular Na+ was decreased only in erythrocytes from RA patients after addition of 0.5 micrograms/ml CsA. A direct action of CsA on the membrane hydrophobic environment of the Na+, K+ ATPase is hypothesized on the basis of the present results.

Adult↗

[In vitro structural aspects of the human trophoblastic cell].

Maternal- fetal exchanges are mainly regulated by trophoblast, which displays an active role during embryo growth. Trophoblast organization into a syncytial layer involves structural and functional steps that may be monitored and better elucidated by "in vitro" studies. In light of this, we have carried out morphological and biochemical analyses in order to evaluate 1) the syncytiotrophoblast formation in culture (48 h, 5-30 days) the Na+/K+ATPase activity and 3) the plasmalemmal microviscosity changes occurring during "in vitro" trophoblast production. Morphological and biochemical modulations have been pointed out.

Cells, Cultured↗

Direct oxidation of glutamate by mitochondria from porcine adrenal cortex.

1. Mitochondria isolated from porcine adrenal cortex under State 3 conditions oxidized succinate with a rate of 47 +/- 4.48 na oxygen/min/mg/protein and with ADP:O ratio 0.98 +/- 0.09. In the presence of 15 microM deoxycorticosterone the rate of succinate oxidation was 36.8 +/- 3.08 na oxygen/min/mg/protein. 2. Under the same conditions the rate of glutamate oxidation was 22.8 +/- 2.21 and 16.8 +/- 0.65 na oxygen/min/mg/protein, respectively. ADP:O ratio was 1.45 +/- 0.14. 3. Introduction of trace amounts of malate into the mitochondria oxidizing glutamate only slightly increased the rate of O2 uptake. 4. The glutamate dehydrogenase activity in these mitochondria was 12.5 +/- 0.69 nmol/min/mg.

Adrenal Cortex↗

Calcium and sodium transport in gestational hypertension.

The enzymatic activities of Na+/K+ ATPase and Ca2+ ATPase were determined on erythrocyte membranes from 9 normotensive and 9 gestational hypertensive pregnant women near term. A reduction in the activity of the Na+/K+ ATPase and a relative increase in the activity of the Ca2+ ATPase were found in the hypertensive patients, possibly due to a conformational alteration of erythrocyte membranes. This observation supports the possible role of the transmembrane cation transport in the pathogenesis of gestational hypertension.

Adult↗

Modifications induced by diabetes on the physicochemical and functional properties of erythrocyte plasma membrane.

Increasing evidence suggests that in experimental diabetes an impairment in Na+,K+-ATPase activity plays a central role in the pathophysiology of diabetic complications, while only a few data are available with regard to human subjects. We studied the erythrocyte membrane Na+,K+-ATPase activity and membrane fluidity in insulin-dependent and non-insulin-dependent diabetic subjects. A significant decrease in the enzyme activity and in fluorescence polarization values was found in both groups compared with normal subjects. Neither Na+,K+-ATPase activity nor membrane fluidity was found to be related to metabolic control, assessed by means of fasting blood glucose levels and HbA1c. On the contrary, a significant correlation was observed between Na+,K+-ATPase activity and membrane fluidity in both insulin-dependent and non-insulin-dependent diabetic subjects. The present work provides evidence that a reduction in the Na+,K+-ATPase activity is present in the plasma membranes of insulin-dependent and non-insulin-dependent diabetics. Furthermore, it suggests that the change in enzyme activity might be related to modifications in membrane fluidity.

Adult↗

Morphological development of the human placenta in normal and complicated gestation: a quantitative and ultrastructural study.

In order to evaluate the structural potentialities of the placenta, we analyzed placentas in the following conditions: normal full term gestation, hypertensive status, twin pregnancy and abortion at 8-12 weeks of gestation, comparing cell structures, surface organization and tissue reaction. We quantitatively evaluated (1) the arborization of the placental villous tree, and (2) the microvillous density per unit of surface area, paralleling these data with ultrastructural and immunohistochemical features. In early gestation (8-12 weeks of pregnancy) the limited degree of branching of placental villi parallels a reduced number of clefts per unit of surface area (0.7/1,000 microns2), if compared with controls (2.7/1,000 microns2). In the full term twin placenta, the number of furrows is 2.26/1,000 microns2: this value reflects a low arborization potentiality, testifying to a low placental maturity. On the contrary, a high branching of the placental villous tree is present at term in hypertension. In this gestational condition, the number of sulci of 3.1/1,000 microns2 reveals a compensatory attitude of the placenta, aiming to sustain the impaired fetal-maternal metabolic interchange. In all these cases, syncytiotrophoblastic microvilli are reduced in number in comparison with the normal placenta, and this is likely to be an expression of a low trophoblastic maturation degree. The placenta is a barrier with a highly specialized function that conditions fetal outgrowth, and microenvironmental modifications are promptly faced by this structure through morphofunctional modulations.

Female↗

[Hypertension and syncytiotrophoblast: morpho-structural aspects].

Hypertension is a pathological condition that involves maternal fetal relationship. In hypertension placenta displays a syncytiotrophoblast plasmalemma with aspects of anomalous behaviour concerning Intramembranous Particles (IMP) and actin content of microvilli cytoskeleton. Decrease of syncytiotrophoblast microvilli IMP and microvilli actin further sustain the tendency of hypertensive placenta to show some features of immaturity that might deeply influence fetal-maternal exchanges during pregnancy associated with pathological status.

Calcium↗

Molecular alterations induced by hypertension in pregnancy on syncythiotrophoblast plasma membranes from human placenta.

To evaluate the possible functional relationships between hypertensive status and syncythiotrophoblast plasma membrane behaviour we have carried out a freeze-fracturing and biochemical investigation to assess: 1) ultrastructurally, relations between number and diameter of Intramembrane Particles (IMP) and hypertensive conditions; 2) biochemically, actin content of microvilli in this pathological status. Our data in vitro show a decrease of IMP in hypertension before and after Ca++ addition and a decrease of actin in microvilli of hypertensive placenta. These observations seem to be in agreement with the hypothesis of a possible structural immaturity in hypertensive placenta and may represent morphological signs of placental insufficiency.

Actins↗