Biomedical subjects

A Mezzetti

Publications and source records attributed to A Mezzetti.

At least 91 records · Page 5Linked to original sources

PubMed1993

Differences in the glutathione system of cultured aortic smooth muscle cells from young and aged rats.

We studied the relation between the glutathione (GSH) system and cell proliferation in a model of smooth muscle cells (SMC) derived from the thoracic aorta of 4-6-week-old (young) and 15-month-old (aged) rats. SMC from aged rats showed greater levels of total non-protein thiol compounds (T-SH), increased glutathione transferase (GST) and increased glutathione reductase (GSSG-Red) activities compared with cells from young rats. These changes were associated with an increased proliferation rate of SMC from aged rats. To evaluate the role of GSH on cell proliferation better, a specific inhibitor of gamma-glutamyl-cystein synthetase, DL-buthionine-SR-sulphoximine (BSO) was used. BSO showed a dose-dependent inhibition of cell growth, with an IC50 of 10(-4) M, after 48-72 h of incubation. Removal of BSO restored cell growth, further suggesting a link between GSH levels and vascular cell proliferation. The inhibitory effect of BSO was about two times greater on SMC from young than on SMC from aged rats. BSO showed 56% inhibition on the proliferation of SMC from young rats and 32% inhibition on SMC from aged rats (10(-4) M, 72 h of incubation). A parallel reduction of GSH levels of 38% and 19% for SMC from young and aged rats, respectively, was observed, suggesting that age-related factors may influence the involvement of GSH system in cell proliferation.

Aging↗

PubMed1993

Hypoxia-induced coronary flow changes in the perfused rat heart: effects of high L-carnitine concentrations.

1. Hemodynamic effects of physiological (0.04 and 0.07 mM) and high (8, 15 and 25 mM) L-carnitine (LC) concentrations were tested on the normally oxygenated and hypoxic perfused rat heart. 2. No effect was detected on aerobic hearts, whereas a dose-dependent rise in coronary flow (CF) during both the hyperemic and constrictive phases was observed in hypoxic hearts with 8, 15 and 25 mM LC. This action was apparently unrelated to a resting tension (RT) improvement, which was observed only with 25 mM LC. 3. When 11 mM glucose was replaced by 11 mM mannitol in the perfusion buffer, LC effects on the hyperemic phase were abolished; however, 25 mM LC resulted in CF-values still significantly higher than those detected without the drug, though RT was similar in these glucose-free groups. 4. It may be concluded that LC is ineffective on the perfused rat heart in aerobic conditions, whereas high LC concentrations can enhance CF only during hypoxia, these effects being independent of heart function improvements and partly unrelated to glucose presence.

Aerobiosis↗

PubMed1993

Myocardial antioxidant defenses during cardiopulmonary bypass.

In 31 male patients undergoing coronary bypass surgery who underwent different periods of cardioplegic hypothermic arrest, the activities of glutathione peroxidase, glutathione reductase, glutathione transferase, copper/zinc-containing and manganese-containing superoxide dismutases, and catalase were studied in the right atrial myocardium, before and 5 minutes after aortic cross-clamping. The levels of thiobarbituric acid reactive substances (TBARS) and nonproteic thiol compounds (NP-SH) were also assessed. Prolonged ischemia followed by reperfusion induced activation of the major myocardial antioxidant enzymes with marked NP-SH depression and TBARS increase, despite cold crystalloid cardioplegic protection. These changes were significantly related to the duration of the ischemic arrest, suggesting: (1) that reperfusion free radical generation is dependent on the severity of the previous ischemic period; and (2) the occurrence of myocardial oxidative stress during cardiopulmonary bypass.

Adult↗

PubMed1992

Heparin: does it act as an antioxidant in vivo?

Previous studies have shown that heparin antagonizes oxygen radical-mediated injury to endothelial cells, suggesting an antioxidant role of the drug. In the present investigation, the hypothesis that heparin exerts direct antioxidant effects was tested in several experimental models. We have found that 1, 3, 5, 10, 20, 40 and 80 U/mL of heparin do not scavenge superoxide anion, hydrogen peroxide, hydroxyl radical or the stable free radical 1,1-diphenyl-2-pycrylhydrazyl. Moreover, the drug is ineffective towards iron-driven linolenic acid peroxidation, autooxidation of brain homogenate and linolenic acid peroxidation mediated by human internal mammary artery homogenate. Specific studies on the potential iron-binding-inactivating capacity of heparin prove the drug to be totally ineffective. Finally, the loss of protein sulphydryls from human plasma induced by hypoxanthine-xanthine oxidase-generated oxygen radicals is not prevented by heparin. In conclusion, heparin, even at concentrations far higher than those usually used therapeutically, has no direct antioxidant properties. Thus, other mechanisms not strictly antioxidant-type must be involved in heparin-mediated cell protection against toxic oxygen metabolites.

Animals↗

PubMed1992

Glutathione-related enzyme activities and lipoperoxide levels in human internal mammary artery and ascending aorta. Relations with serum lipids.

The relation among glutathione-related enzyme activities, thiobarbituric acid-reactive substances of the human aorta and internal mammary artery, and serum lipids was studied in 40 male patients undergoing coronary revascularization. Glutathione peroxidase and glutathione reductase activities were significantly higher in the internal mammary artery, whereas glutathione transferase activity was elevated in the aortic wall. Moreover, non-selenium-dependent glutathione peroxidase activity was detectable only in the aorta. The levels of thiobarbituric acid-reactive substances were significantly higher in the aorta. A positive correlation was found among the activity of glutathione peroxidase, glutathione reductase, and thiobarbituric acid-reactive substances in the internal mammary artery and total cholesterol, low density lipoprotein cholesterol, and triglycerides. In the aortic wall, a positive correlation among the activity of glutathione peroxidase, glutathione transferase, thiobarbituric acid-reactive substances, and the previously mentioned serum lipids was evident. In contrast, high density lipoprotein cholesterol was inversely related to enzymatic activities and thiobarbituric acid-reactive substances in both the internal mammary artery and aorta. In conclusion, significant differences in the levels of glutathione-related enzyme activities and thiobarbituric acid-reactive substances in the internal mammary artery and aorta were found, suggesting a different ability of the two tissues to counteract oxidative stress: the glutathione-related antioxidant properties and the level of lipid peroxidation in the arterial tissue seem to be specifically influenced by serum lipids.

Adult↗

PubMed1992

Circadian variations in antioxidant defences and lipid peroxidation in the rat heart.

Circadian variations in antioxidant defences and lipid peroxidation were investigated in 12 rat hearts perfused during light (i.e., at 08.00, n = 6) and dark cycle (i.e., at 19.00, n = 6). Higher levels of non proteic thiol compounds (P < 0.01), glutathione transferase activity (P < 0.05) and lipid peroxidation (P < 0.01) were detected in evening-excised hearts, associated with a lower (P < 0.05) selenium-dependent glutathione peroxidase activity; superoxide dismutase and glutathione reductase activities, as well as vitamin E content, were similar in the two groups. Moreover, a greater release of thiobarbituric acid reactive substances (P < 0.01) and proteins (P < 0.05) was detected in the myocardial effluent of another group of 5 evening-excised hearts perfused with Krebs-Henseleit buffer containing 30 microM cumene hydroperoxide, as compared to 5 light-cycle hearts. In conclusion, a higher oxidative stress seems to be operative in the rat heart during early stages of the dark phase, in spite of the increase level of non proteic thiol compounds (namely, glutathione). An imbalance of antioxidant defences, and/or higher radical generation and unsaturation degree of biomembranes lipids, may be hypothesized to favour myocardial oxidative stress at the beginning of the motor activity phase in rats.

Animals↗

PubMed1992

Effects of high fat-, cholesterol-enriched diet on the antioxidant defence mechanisms in the rabbit heart.

In 7 rabbits fed on hyperlipidic diet (0.5% cholesterol, 5% peanut oil and 5% lard) for 4 weeks, the ventricular myocardium was tested for antioxidant defences and thiobarbituric acid reactive substances. Seven age-matched rabbits served as controls. The hearts were previously subjected to 45 min Langendorff perfusion to study coronary flow, developed tension and resting tension; coronary effluent values of CPK activity, pH and UV absorbance at 250 nm (i.e., low molecular weight ATP catabolites) were also investigated. After 4 weeks of diet, a significant rise of plasma cholesterol (P < 0.0001) and triglycerides (P < 0.0001) was observed. Total superoxide dismutase, catalase and glutathione transferase activities underwent a significant increase (P < 0.05) in the hyperlipidemic animals. On the contrary, a depression of glutathione reductase (P < 0.01) and selenium-dependent glutathione peroxidase (P < 0.01) activities, associated with decreased levels of non proteic thiol compounds (P < 0.01), was assessed. The selenium-independent glutathione peroxidase activity was not detectable in both groups. Thiobarbituric acid reactive substances levels were significantly increased in the hyperlipidemic rabbit myocardium (P < 0.01). Even though heart hemodynamics, CPK release and perfusate pH did not differ in control and experimental animals, higher 250 nm absorbance values (P < 0.05) were detected in the myocardial effluent of hyperlipidemic rabbits. In conclusion, high fat-, cholesterol-enriched diet induces an imbalance in the rabbit heart antioxidant defences, some of which are increased, whereas others are depressed, eventually resulting in enhanced myocardial lipid peroxidation. These biochemical changes are associated with higher perfusate values of UV absorbance at 250 nm, but not with significant CPK leakage or myocardial hemodynamics derangement.

Adenosine Triphosphate↗

PubMed1992

Captopril therapy in severe hypertension: effects of intravenous administration.

In 10 severe hypertensives the effects of intravenous administration of scalar doses of captopril were evaluated. The behaviour of blood pressure, heart rate, electrocardiographic pattern and left ventricular (LV) diastolic function, in basal condition (T0) and after 60 min of captopril infusion (T60), were analysed. Diastolic performance was assessed by pulsed wave Doppler echocardiography, evaluating transmitral peak flow velocities in early diastole (PEDV), late diastole (PLDV) and the PEDV/PLDV ratio. All patients showed an increase in LV mass (assessed by M-mode echocardiography) and altered diastolic performance, documented by high PLDV and low PLDV/PEDV ratio values. Clinical, haematological, urinary and biochemical data were also assessed for possible side effects. Captopril significantly reduced BP in 7 out of the 10 patients. Supine BP decreased from 212 +/- 15.3/126 +/- 5.6 to 171 +/- 17.7/98 +/- 11.8 mmHg (T0 vs. T60 P less than 0.0001). No electrocardiographic abnormality was observed during the study. The goal of antihypertensive effect was reached at 40-50 min after the onset of captopril therapy. Heart rate showed a small but constant decrease (from 76 +/- 7.7 to 72.8 +/- 5.7 beats/min, T0 vs. T60, P less than 0.05). Side effects of intravenous captopril were always mild and transient; no severe hypotension as 'first dose effect' was observed in our study. The echocardiographic data showed a significant decrease in LV end-systolic dimension after captopril infusion, while left atrial, LV diastolic dimension and fractional shortening remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Aortic glutathione-related antioxidant defences in rabbits subjected to suprarenal aortic coarctation hypertension.

In seven rabbits subjected to suprarenal aortic coarctation hypertension, the segments above and below the coarctation were tested for the antioxidant defences (i.e. acid-soluble thiol compounds, selenium-dependent and selenium-independent glutathione peroxidase, glutathione reductase, glutathione transferase) and thiobarbituric acid-reactive substances. Seven sham-operated rabbits served as controls. Systolic blood pressure proximal to the ligature increased significantly with respect to pre-operative values after 16 days (117 +/- 8.3 vs 71.7 +/- 5.2 mmHg, P less than 0.05), while pressure distal to the ligature remained normotensive. Higher values of acid-soluble thiol compounds, thiobarbituric acid-reactive substances and increased activities of selenium-dependent glutathione peroxidase, glutathione reductase and glutathione transferase were assayed in the suprarenal with respect to the subrenal segment in both groups. However, the values of the upper segments were more elevated in the experimental group than in controls, but no differences were observed in the lower segments. Glutathione peroxidase activity assayed with cumene hydroperoxide was higher than the activity assayed with hydrogen peroxide in the hypertensive segments, but no differences were detected in the substenotic and control segments. Furthermore, an isoenzymatic form of glutathione transferase, analogous to rat 8-8 glutathione transferase isoenzyme, was detected by immunodiffusion in the hypertensive aorta. The following conclusions may be drawn: (1) a biochemical gradient in glutathione-related enzymes, acid-soluble thiol compounds and thiobarbituric acid-reactive substances between the proximal and distal aorta seems to exist in control rabbits; (2) suprarenal aortic coarctation induces a significant increase in glutathione-related antioxidant defences and thiobarbituric acid-reactive substances of the hypertensive aortic wall.

Animals↗

PubMed1991

Regional distribution of glutathione-related antioxidant defences in the normal rabbit aorta.

In 6 normal rabbits, the aortic arch, the descending thoracic and the abdominal aorta were tested for non proteic thiol compounds, selenium-dependent and selenium-independent glutatione peroxidase, glutatione reductase, glutatione transferase and thiobarbituric acid reactive substances. The aortic arch showed the greatest content of non proteic thiol compounds and thiobarbituric acid reactive substances, associated to the highest activities of glutathione-related enzymes. However, not significant differences were detectable between aortic arch and descending thoracic aorta, except for the glutathione transferase activity (0.395 +/- 0.031 vs 0.330 +/- 0.053 U/mg protein, p less than 0.05). Furthermore, both aortic arch and descending thoracic aorta showed significantly higher values of non proteic thiol compounds (46.05 +/- 10.15% and 33 +/- 13.5%, p less than 0.05), selenium-dependent glutathione peroxidase activity (70.35 +/- 26% and 54.3 +/- 9.5%, p less than 0.05), glutathione reductase activity (25.4 +/- 7% and 18.4 +/- 4.5%, p less than 0.05) and thiobarbituric acid reactive substances (65.8 +/- 18% and 47.2 +/- 17%, p less than 0.05) with respect to the abdominal aorta. The selenium-independent glutathione peroxidase activity was not detectable. In conclusion, a biochemical gradient in glutathione-related antioxidant defences and thiobarbituric acid reactive substances proceeding from the proximal to the distal segments seems to exist in the normal rabbit aorta. These results could contribute to explain the non homogeneous distribution of experimental atherosclerosis in the rabbit aorta.

Animals↗

PubMed1990

Glutathione peroxidase, glutathione reductase and glutathione transferase activities in the human artery, vein and heart.

The continuous exposure to blood components, including prooxidants, makes the blood vessel wall susceptible to oxidative stress and free radical mediated reactions (Henning and Chow, 1988; Stamm et al., 1989; Halliwell and Gutteridge, 1984). Free radicals can be produced extracellularly via the respiratory bursts of activated neutrophils, or intracellularly, via oxidation of hypoxanthine by xanthine oxidase (Henning and Chow, 1988; Stamm et al., 1989; Rubanyi, 1988). Microsomal enzymes such as lipoxygenase and cyclooxygenase may also be a source of reactive species of oxygen (Henning and Chow, 1988; Stamm et al., 1989; Rubanyi, 1988; Mason et al., 1980). It has been proposed that free radicals are involved in the initiation and progression of various cardiovascular diseases including arteriosclerosis (Henning and Chow, 1988; Stamm et al., 1989; Yagi, 1988; Jürgens et al., 1987). Thus the adequacy of the defence systems against free radicals is critical for the susceptibility of blood vessel wall to oxidative damage. Among the enzymatic systems capable of protecting the cell against oxidative injury, selenium dependent glutathione peroxidase (Se-GSH-px), glutatione reductase (GSSG-rx) and glutathione transferase (GST) play a crucial role (Flohe' et al., 1976; Mannervik and Danielson, 1988). Using glutathione (GSH) as a cofactor, Se-GSH-px reduces H2O2 to water and organic hydroperoxides to the corresponding alcohols (Flohe' et al., 1976). This reaction leads to conversion of GSH into its oxidized form (GSSG). In the presence of NADPH, GSSG-rx is able to reduce the oxidized glutathione.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Sodium cromoglycate in the treatment of eosinophilic gastroenteritis.

Two patients suffering from eosinophilic gastroenteritis (EG) were treated with sodium cromoglycate (SCG). Before treatment they showed enteric and cutaneous symptoms, such as abdominal pain, nausea, vomiting, diarrhoea and recurrent urticaria and angioedema. The histological findings were a notable amount of eosinophilic infiltration in the lamina propria and gastric glands, a villous shortening and thickening and weak eosinophilic inflammation in the duodenum. The patients were treated with 300 mg SCG, 4 times daily, for 4/5 months. During treatment, the clinical symptoms disappeared and at the end of treatment a reduced inflammation with an almost complete decrease of eosinophilic infiltration was observed. The results provide evidence of SCG efficacy in the treatment of EG and suggest its employment as an alternative to the steroids commonly used in EG.

Adult↗

PubMed1990

Effect of ischaemia-reperfusion on glutathione peroxidase, glutathione reductase and glutathione transferase activities in human heart protected by hypothermic cardioplegia.

The activities of glutathione peroxidase (GSH-px), glutathione reductase (GSSG-rx) and glutathione transferase (GST) were measured in myocardial specimens obtained from right atria of patients subjected to different period of ischaemic arrest (aortic clamping ranging from 10 min to 90 min) followed by 60 min. of reperfusion, during open heart surgery 41-90 min. period of aortic clamping induced a significant increase of GSH-px activity with both H2O2 (p less than 0.05) and cumene hydroperoxide (p less than 0.025) as substrates when compared with baseline levels. Aortic clamping and reperfusion, however did not significantly change the myocardial activities of glutathione transferase and glutathione reductase. It is suggested that the increase of GSH-px in ischaemic-reperfused human hearts may render the myocardium less susceptible to oxidative attack particularly during the reoxygenation period when the level of active oxygen species is greatly elevated.

Female↗

PubMed1988

Effect of ischemia and reperfusion on antioxidant enzymes and mitochondrial inner membrane proteins in perfused rat heart.

Experiments were performed to investigate the effects of 60 min severe global ischemia followed by 30 min reperfusion on the antioxidant enzymatic system in the isolated perfused rat heart. Ischemia induced a significant increase of cytoplasmic and mitochondrial selenium-dependent glutathione peroxidase (EC 1.11.1.9) activity. In reperfused hearts, only the mitochondrial form showed a further significant increase. Glutathione reductase (EC 1.6.4.2) was increased in ischemic hearts, whilst the reperfused hearts showed a decrease towards the level found in aerobic hearts. Mitochondrial superoxide dismutase (EC 1.15.1.1) activity was depressed in ischemic as well as in reperfused hearts, though the cytoplasmic form was unmodified. Catalase (EC 1.11.1.6), glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and glutathione transferase (EC 2.5.1.18) activities were unchanged throughout the experiment. Ischemia and reperfusion induced a significant fall in tissue-reduced glutathione content concomitant with an increase of its oxidized form. We have also studied the mitochondrial inner membrane proteins for both molecular weight, with Coomassie blue, and thiol status, with monobromobimane stain, using a sodium dodecyl sulfate polyacrylamide gel electrophoresis technique. Neither ischemia nor reperfusion effected any relevant modification of the molecular weight of the mitochondrial inner-membrane proteins either in the presence or absence of a reducing agent. However, two of these proteins with an apparent molecular weight of 52,0000 and 12,000 showed a decrease in the monobromobimane stain, probably due to the oxidation of their thiol groups.

Animals↗

PubMed1988

Gallbladder kinetics in obese patients. Effect of a regular meal and low-calorie meal.

Gallbladder contractility has been studied in 21 obese patients (greater than 130% ideal weight) and 30 nonobese subjects before and at regular intervals after the administration of a regular solid-liquid meal, and after a low-calorie, low-fat meal used conventionally for weight-loss purposes (Modifast). Gallbladder volume was determined by means of real-time ultrasonography, using a linear array scanner with a 3.5 MHZ probe. In seven of the obese patients, gallbladder contractility was also evaluated after a 10-day regimen with Modifast. The obese group showed a statistically significant greater gallbladder fasting volume and blunted contractility than controls both after the ordinary and the low-calorie meal. The 10-day low-calorie regimen was associated with a statistically significant increment in fasting gallbladder volume, while the percent volume reduction after Modifast did not change. It is suggested that, in addition to metabolic factors, gallbladder hypocontractility in the obese may contribute to the high incidence of cholesterol gallstones noted in these patients. A low-calorie, low-fat diet augmenting gallbladder volume may favor bile stasis and therefore the likelihood of developing gallstones.

Adult↗

PubMed1988

Effect of ketanserin, a selective antiserotoninergic drug, on human anal canal pressure.

The effect of Ketanserin, a new antiserotoninergic drug, on human anal pressure in vivo was investigated. Anal pressure was recorded continuously in 14 normal subjects by a low-compliance water perfused probe with two recording points at the sphincter level. After a 30-min basal tracing Ketanserin (10 mg IV as bolus) or placebo was administered in a double blind manner, and the recording continued for 1 h. The results show that Ketanserin induced a 30% fall in anal pressure soon after its administration which was statistically significant when compared with the placebo (p less than 0.01). This effect lasted up to 40 min of recording and was followed by a return to control values within 1 h.

Adult↗

PubMed1988

Gallbladder contraction and its relationship to interdigestive duodenal motor activity in normal human subjects.

Gallbladder volume and interdigestive gastric and duodenal motor activity were evaluated simultaneously in 12 normal subjects. After overnight fasting, gallbladder volume was monitored every 4 min in each subject by means of real-time ultrasonography, and gastroduodenal motor activity was measured by means of a probe consisting of three polyvinyl catheters with one side opening for each catheter, placed 15 cm apart and constantly perfused with deionized water. Real-time ultrasonography and intestinal manometry were performed by different investigators and continued until at least two consecutive spontaneous phase III activities of migrating motor complexes were observed. The results show a cyclic variation of gallbladder volume, which reached its minimum value before the end of phase II in the proximal duodenum and its maximum in early phase II, 25 min after the beginning of phase III. These results suggest that there is a relationship between the cyclic gallbladder volume changes, which occur during fasting in humans, and with the various phases of duodenal migrating motor complex.

Digestion↗

PubMed1988

Gallbladder emptying in duodenal ulcer patients having undergone Billroth II gastrectomy.

There is an increased incidence of gallstones in patients who have undergone Billroth II (BII) gastrectomy for duodenal ulcer. To explore the mechanisms underlying this, we examined changes in gallbladder volume induced by a meal and by intravenous administration of cerulein, in 13 BII patients and in 13 normal subjects. Gallbladder volume was measured by real-time ultrasonography. In the fasting state, gallbladder volumes were significantly larger in BII patients than in controls. The percent decrease in gallbladder volume after the meal was significantly less and maximum volume reduction observed throughout the study occurred sooner in BII patients than in controls. In contrast, the kinetics and magnitude of the reduction in gallbladder volume induced by cerulein were similar in the two groups. These findings suggest that the altered gallbladder response to a meal is due to impaired postprandial stimulation of gallbladder following BII gastrojejunostomy.

Adult↗