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Biomedical subjects

C Di Massimo

Publications and source records attributed to C Di Massimo.

At least 19 recordsLinked to original sources

Impairment of plasma nitric oxide availability in senescent healthy individuals: apparent involvement of extracellular superoxide dismutase activity.

To verify the potential involvement of the age-dependent modifications of EC-SOD activity in the impairment of plasma NO availability with advancing age, 40 healthy men divided into 4 age groups for the purpose of comparison (young: 27.4 +/- 1.5 years; middle: 50.8 +/- 2.2, years; old: 70.0 +/- 1.8 years; very old: 86.1 +/- 1.1 years) were enrolled in this study. Plasma samples were used for measurements of the stable end-product nitrite/nitrate (NOx), as an expression of NO availability, EC-SOD activity, thiobarbituric acid reactive substances (TBARS) as a marker of lipid peroxidation, low density lipoprotein (LDL) copper-mediated oxidation in vitro and total antioxidant capacity (TEAC). Our results indicated a significant age-related progressive decrease of plasma NOx content and EC-SOD activity and their values were positively correlated (r = 0.713, p < 0.001). Increased TBARS amount together with reduced lag time for in vitro oxidation of LDL and decreased content of TEAC were observed with advancing age. Finally, EC-SOD values were negatively correlated with plasma TBARS values (r = -0.855, p < 0.001). Findings of the present study suggest that the decrease of antioxidant defence strategies play a primary role by compromising NO availability in normally aged individuals, particularly through a progressive decrease of EC-SOD activity.

Adult↗

Flunarizine effects on oxidative stress in migraine patients.

Prophylactic activity of flunarizine in migraine is attributed to its antioxidant properties and to the relief of cerebral vasospasm in which nitric oxide (NO) is involved. We investigated the antimigraine activity of flunarizine and its influence on NO and oxidative marker bioavailability in 25 subjects suffering from migraine without aura and in 25 healthy controls. Urinary samples collected before and after treatment with flunarizine (5 mg orally per day for 6 months) were assayed for NO stable metabolites (NOx) and thiobarbituric acid reactive substances (TBARS). Urinary levels of NOx and TBARS were higher in migraine sufferers before treatment than in healthy controls. No differences were observed in NOx levels in migraine sufferers, before and after flunarizine treatment; urinary TBARS levels were decreased after flunarizine treatment (P < 0.05) and remained persistently higher than in healthy controls (P < 0.05). Our results suggest that flunarizine did not prevent NO-mediated vasodilatation, while it proved effective in limiting the oxidative reactions occurring in migraine sufferers.

Adult↗

Possible involvement of oxidative stress in exercise-mediated platelet activation.

In this study, we have attempted to verify whether a single bout of strenuous exercise performed by sedentary healthy individuals may interfere with the mechanisms controlling platelet sensitivity through exercise-related modifications of plasma oxidant/antioxidant equilibrium. Strenuous exercise resulted in an increased ADP- and collagen-evoked platelet aggregation associated with modified membrane fluidity and ion homeostasis. We also observed an enhanced plasma accumulation of secondary products of lipid peroxidation together with an increased susceptibility of low density lipoprotein (LDL) to in vitro oxidation and a decreased total plasma antioxidant potential. Notably, an acute elevation of nitrite/nitrate (NOx) amount was detected in plasma, whilst a decreased NOx content was measured in platelets. Findings of the current study suggest that oxidative stress induced by acute strenuous exertion may interfere with platelet responsiveness by promoting ox-LDL-mediated platelet activation and by decreasing platelet-derived nitric oxide bioactivity.

Adenosine Diphosphate↗

Possible involvement of plasma antioxidant defences in training-associated decrease of platelet responsiveness in humans.

The aim of this study was to evaluate in sedentary individuals the effects of a 20-week exercise training program on ex vivo platelet responsiveness and the possible involvement of plasma antioxidant defences in relation to the mechanisms controlling platelet sensitivity. A statistically significant decrease in ADP- and collagen-evoked platelet aggregation was observed after physical training together with an increase in plasma total antioxidant capacity (TEAC), superoxide dismutase activity, and high-density lipoprotein cholesterol (HDL-C) concentration. Additionally, a rise in lag time for in vitro low-density lipoprotein (LDL) oxidation as well as a decreased plasma level of secondary products of lipid peroxidation were observed after training, and the values for lag time were significantly correlated with TEAC and HDL-C. Nitrate/nitrite (NOx) content both in plasma and in platelet cytosol was significantly enhanced at the end of the training period and a significant positive correlation was found between plasma and intraplatelet NOx values. Furthermore, intraplatelet NOx content was positively correlated with HDL-C levels. The findings of the current study suggest that the improvement of antioxidant defences induced by moderate regular exercise may be involved in desensitising blood platelets most likely through the inhibition of LDL oxidation and the simultaneous enhancement of plasma and intraplatelet NOx bioavailability and HDL-C level.

Adaptation, Physiological↗

Urinary nitric oxide metabolites and lipid peroxidation by-products in migraine.

Enhanced endothelium nitric oxide (NO) and superoxide anion release may cause migraine through related cerebral blood flow changes. Thirty subjects suffering from migraine with and without aura and 20 healthy controls were investigated. Urine samples collected for 24 h during and after the migraine attack, and during the headache-free period, were assayed for urinary NO stable metabolites (NOx) and thiobarbituric acid reactive substances (TBARS). During the headache-free period urinary NOx and TBARS levels were higher in migraine sufferers than in controls (NOx 0.77 +/- 0.14 vs. 0.28 +/- 0.15 mmol/mmol creatinine, P < 0.05; TBARS 0.40 +/- 0.19 vs. 0.26 +/- 0.13 micro mol/mol creatinine, P < 0.05). Also, NOx excretion was higher during the headache-free period than during or after the migraine attack (P < 0.05). Urinary TBARS were increased during the attack with respect to the headache-free period (P < 0.05). No differences were observed in the same parameters between sufferers of migraine with and without aura. Urinary NOx and TBARS might be promising as markers of their systemic levels to evaluate the increased vulnerability to oxidative stress in migraine sufferers.

Adult↗

Influence of acute exercise on human platelet responsiveness: possible involvement of exercise-induced oxidative stress.

The aim of this study was to evaluate in sedentary male subjects the effects of an acute bout of strenuous and moderate exercise on ex vivo platelet responsiveness and its possible relationship with exercise-associated modifications of oxidant-antioxidant status. An increased ADP- and collagen-evoked platelet aggregation associated with modified membrane fluidity and ion homeostasis was observed after exhaustive exercise. After moderate exercise, we found a decrease of platelet aggregation evoked by low concentrations of agonists. Strenuous exercise, but not moderate exertion, resulted in the enhanced accumulation of secondary products of lipid peroxidation, decreased total antioxidant capacity, including a diminished superoxide dismutase activity, and increased susceptibility of low-density lipoprotein (LDL) to in vitro oxidation. Acute elevation of plasma nitrite/nitrate (NOx) content was observed following each single session of physical test, whilst the platelet NOx content was decreased after strenuous exercise and increased after moderate exercise. Findings of the present study suggest that oxidative stress induced by acute strenuous exercise may interfere with platelet responsiveness most likely by promoting oxidized LDL-mediated platelet activation and by decreasing plasma and platelet-derived nitric oxide (NO) bioactivity. Moreover, our results further suggest that platelet responsiveness following an acute moderate physical stressor may depend on the efficiency of plasma and intraplatelet NO to desensitize platelets to agonist stimulation.

Adenosine Diphosphate↗

Helicobacter pylori infection and migraine.

The study is aimed to ascertain whether the Helicobacter pylori (Hp) infection is responsible for the vulnerability to oxidative stress observed in migraineurs. Hp serological positivity was assessed by ELISA evaluation of specific IgA and IgG antibodies in 30 subjects (11 males and 19 females) suffering from migraine without aura during the headache-free period. The Hp infection was detected in 16.7% of migraineurs. Plasma accumulation of peroxidative substances (TBA-RS), an index of systemic oxidative status, was increased in migraineurs without Hp infection with respect to controls (P< 0.001), while no significant differences of TBA-RS were found in migraineurs with or without Hp infection. Unmodified values of plasma nitrite/nitrate concentrations, expression of systemic nitric oxide (NO), were obtained in migraineurs in comparison to controls indicating that Hp infection does not modify the plasma oxidative status and the systemic NO bioavailability of migraineurs. In conclusion, our results do not support any specific correlation between Hp infection and migraine.

Adult↗

Possible involvement of increased susceptibility of LDL to oxidation in age-related platelet activation.

Fifteen long-lived and fifteen young healthy subjects were enrolled in this study to verify the involvement of age-associated oxidative challenge in the mechanisms that control platelet activation. Our results showed in old subjects an enhancement of ex vivo platelet responsiveness to ADP and collagen, measured both in whole blood and in platelet rich plasma, an increased cytosolic calcium content, a decreased membrane fluidity and a lower intraplatelet nitrate/nitrite (NO(x)) amount. Additionally, an increased plasma content of peroxidative by-products (TBARS) and a decreased antioxidant plasma capacity together with a reduced lag time for in vitro oxidation of low density lipoprotein (LDL) and a diminished plasma NO(x) bioavailability were observed in aged subjects. Lag time for LDL oxidation was negatively correlated with plasma TBARS level, and positively correlated with intraplatelet NO(x) content. Findings of this study may support the speculation that advancing age increases the susceptibility of LDL to oxidative modifications and favors platelet activation by oxidized LDL-induced decrease of nitric oxide bioactivity.

Adult↗

Influence of aging and exercise-induced stress on human platelet function.

Ten healthy nonsmoking old men (age 52-70 years, OM) and ten healthy nonsmoking young men (age 20-30 years, YM) were submitted to an exercise test on a bicycle ergometer to examine the combined influence of aging and exercise-induced stress on platelet function. Data were analyzed by two-way ANOVA test to determine the statistical significance of differences between baseline, after exercise and after recovery values, and by Mann-Whitney test to compare differences between young and old groups. Our results show in OM at rest an increased platelet aggregability induced by the higher values of intraplatelet basal free calcium (143.3 +/- 4.8 vs. 121.5 +/- 6.0 nM, p < 0.05) and a statistically significant increase of plasma oxidative by-products evaluated as thiobarbituric acid-reactive substances (TBA-RS: 5.9 +/- 0.7 vs. 1.5 +/- 0.1 micromol/l, p < 0.05). Further, significant modifications of calcium and TBA-RS levels were found in both groups because of exercise-induced stress. The positive relationships between calcium amount and plasma values of TBA-RS in OM before (r = 0.728, p = 0.017) and after (r = 0.772, p = 0.009) physical test and in YM only at the end of exercise (r = 0.853, p = 0.002), underline that oxidative stress may modulate platelet function by influencing calcium homeostasis and platelet membrane permeability.

Adult↗

In vitro short-term response of human erythrocytes to implant materials used in maxillo-facial rigid internal fixation.

A short-term in vitro experimental study was performed to analyze the effects of metallic miniplates used in maxillo-facial rigid internal fixation on some functional features of human erythrocytes that represent a pivotal rheological component for correct blood flow in the tissular area surrounding metallic implants. In our working conditions, no interference on osmotic fragility, intracellular ATP content and spontaneous hemolysis was observed. Conversely, a statistically significant increase of rigidity in the deeper lipid region of erythrocyte membrane was verified. On the basis of our results, the in vitro erythrocyte modifications after 18 h of whole blood/metallic device contact are relatively small and negligible.

Biocompatible Materials↗

Oxidative stress and platelet responsiveness in migraine.

The aim of this study is to investigate whether oxidative stress may represent a pivotal determinant of the altered functional features of platelets in migraineurs during the headache-free period. Twenty-three patients with migraine with aura, free of attack, and 23 healthy volunteers were enrolled for the study. The involvement of an oxidative condition appears confirmed by the statistically significant increase (p < 0.001) of plasma levels of thiobarbituric acid-reactive substances which may be considered a marker for oxidative stress and themselves strong-pro-oxidants. Such oxidative status seems to induce in platelets of migraineurs increased membrane rigidity (p < 0.001), reduced cytosolic calcium in the resting condition and after thrombin stimulation (p < 0.001), and decreased aggregatory responses to ADP and collagen. These findings indicate that the "in vitro" anomalous platelet behavior in migraineurs, observed in headache-free periods, may be considered as the transient expression of the exhausted platelets to "in vivo" stimulation and probably related to an increased vulnerability to oxidative stress.

Adult↗

Platelet responsiveness in migrainous children during headache-free period.

Results of this study confirm the link between migraine and alterations of platelet responsiveness. Our data suggest that in migraineurs the perturbated platelet microviscosity, analyzed by means of fluorescence polarization, appears responsible for the decrease of stimulation-induced influx of external calcium through the platelet membrane. These findings suggest that platelet membrane microviscosity may be considered as a more significant platelet marker of migraine rather than the well-known and nonspecific phenomenon of platelet hyperaggregation, evaluated by time-transmittance variations induced by adenosine diphosphate and collagen.

Blood Platelets↗

Influence of a selective 5HT1-receptor agonist GR43175 on platelet responsiveness.

The possible interaction of sumatriptan, a selective 5HT1-receptor agonist, with platelet responsiveness has been investigated. Stimulation of platelet rich plasma with sumatriptan (1-100 microM) did not induce shape change, aggregation or modification of intraplatelet cytosolic calcium levels. Total inhibition of aggregation induced by 20 microM 5HT was observed in platelets preincubated for 20 min with 100 microM sumatriptan. In the same model, platelet stimulation with 4 microM adenosine 5'-diphosphate (ADP), concentration known to induce an irreversible single-phase curve, determined a decrease of aggregatory response. Concentrations from 1 microM to 50 microM of sumatriptan did not influence the aggregatory response induced by 5HT and ADP. These effects appear not to be determined by modifications of platelet calcium homeostasis. The possibility to modulate platelet responsiveness by sumatriptan offers a further approach for evaluating the probable link between platelet behaviour and pathophysiology of migraine.

Adenosine Diphosphate↗

Platelet changes in classic migraine.

We investigated some ultrastructural aspects of platelet activity in patients with classic migraine during an attack-free period. We focused on the production of malondialdehyde (MDA), the intracellular concentration of Ca++ and the membrane phospholipid structure using a DPH (1,6 diphenyl-1,3,5 hexatriene) fluorescent probe. Our study comprised 20 patients with classic migraine and 5 healthy controls, from whom 10 cc samples of blood were collected in test tubes containing sodium citrate (1/9 cc). We found no significant differences in MDA production between migraineurs and controls either before or after stimulation with thrombin. The same applies to the concentration of intracellular Ca++ (Ca++i). The membrane lipid composition assessed by DPH fluorescent probe was normal both in migraineurs and in controls. Our findings suggest no intrinsic activation of platelet aggregation.

Adolescent↗

Artificial intelligence and the supervision of bioprocesses (real-time knowledge-based systems and neural networks).

The ability to supervise and control a highly non-linear and time variant bioprocess is of considerable importance to the biotechnological industries which are continually striving to obtain higher yields and improved uniformity of production. Two AI methodologies aimed at contributing to the overall intelligent monitoring and control of bioprocess operations are discussed. The development and application of a real-time knowledge-based system to provide supervisory control of fed-batch bioprocesses is reviewed. The system performs sensor validation, fault detection and diagnosis and incorporates relevant expertise and experience drawn from both bioprocess engineering and control engineering domains. A complementary approach, that of artificial neural networks is also addressed. The development of neural network modelling tools for use in bioprocess state estimation and inferential control are reviewed. An attractive characteristic of neural networks is that with the appropriate topology any non-linear functional relationship can be modelled, hence significantly reducing model-process mismatch. Results from industrial applications are presented.

Artificial Intelligence↗

Rheological features of erythrocytes in acute myocardial infarction.

There is evidence that oxidative insult plays a role in the development of acute myocardial infarction. Significance has also been attributed to changes in viscosity of the blood and in the deformability and aggregation of erythrocytes affecting their rheological behavior. In a group of patients with myocardial infarction we found a decreased erythrocyte filtration and an increased blood viscosity with no significant change in plasma viscosity. These changes were accompanied by alterations in the microviscosity of the erythrocyte membrane assessed by measuring the polarization of specific fluorescent molecules. From our data it is evident that there is an increase in the rigidity of the membrane at the lipid/protein boundary, with an associated increase in the fluidity of the deep lipid core of the membrane, while no changes were observed in the dynamic behavior of the membrane proteins. These physico-chemical perturbations in the membrane could be the basis for the decreased filtration of erythrocytes. We found, however, no evidence of lipid peroxidation in the erythrocyte membrane.

Adenosine Triphosphate↗

Interaction of neomycin with human erythrocytes.

This study has been undertaken to verify if neomycin, known to be toxic because it interacts with membrane-bound phosphatidylinositol-4,5-biphosphate, may lead to an extensive perturbation of the membrane organization of human erythrocytes. By comparison, the effects induced by a non toxic aminocyclitol antibacterial agent as spectinomycin were examined. Our data exclude extended alterations of the membrane and hence large structural changes of the whole cell for both the drugs probably as a consequence of the extreme difficulty of penetration because of their selective hydrophilic features. However, only neomycin seems to present a binding on negatively charged regions of erythrocyte membranes, that could be responsible of its remarkable toxicity.

Erythrocyte Membrane↗

Aging of human erythrocytes: the role of membrane perturbations induced by in vitro ATP-depletion.

The in vitro metabolic depletion of the erythrocytes has been often utilized to mimic the oxidative stress responsible of their in vivo senescence process. The present study is focused to detect the extent to which the modifications of the whole cell and/or of its membrane, consequent to in vitro ATP-depletion, could trigger a mechanism similar to that verified during in vivo aging. From our data it appears that the shape changes and the increased osmotic fragility could be related to physico-chemical alterations that take place at membrane level. Main alterations concern the significant decrease of negative charges of membrane surface, as evidenced by fluorescence intensity enhancement of membrane-associated ANS, and of the increase of fluidity in the lipid/protein membrane region, suggesting a close analogy with the progressive in vivo senescence of the RBC. Furthermore, the ATP-depletion erythrocyte can efficiently remove exogenous hydrogen peroxide differently from old RBC that showed, as well reported, a severe decrease of enzymic protection against oxidative insult.

Adenosine Triphosphate↗