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Biomedical subjects

L Brunelli

Publications and source records attributed to L Brunelli.

At least 19 recordsLinked to original sources

Modulation of catalase peroxidatic and catalatic activity by nitric oxide.

Previously, we found that catalase enhanced the protection afforded by superoxide dismutase to Escherichia coli against the simultaneous generation of superoxide and nitric oxide (Brunelli et al., Arch. Biochem. Biophys. 316:327-334, 1995). Hydrogen peroxide itself was not toxic in this system in the presence or absence of superoxide dismutase. We therefore investigated whether catalase might consume nitric oxide in addition to hydrogen peroxide. Catalase rapidly formed a reversible complex stoichiometrically with nitric oxide with the Soret band shifting from 406 to 426 nm and two new peaks appeared at 540 and at 575 nm, consistent with the formation of a ferrous-nitrosyl complex. Catalase consumed more nitric oxide upon the addition of hydrogen peroxide. Conversely, micromolar concentrations of nitric oxide slowed the catalase-mediated decomposition of hydrogen peroxide. Catalase pretreated with nitric oxide and hydrogen peroxide regained full activity after dialysis. Our results suggest that catalase can slowly consume nitric oxide while nitric oxide modestly inhibits catalase-dependent scavenging of hydrogen peroxide. The protective effects of catalase in combination with superoxide dismutase may result from two actions; reducing peroxynitrite formation by scavenging nitric oxide and by scavenging hydrogen peroxide before it reacts with superoxide dismutase to form additional superoxide.

Catalase↗

The comparative toxicity of nitric oxide and peroxynitrite to Escherichia coli.

The reactivity and toxicity of nitric oxide is modest in comparison to oxidants derived from nitric oxide. Exposure of Escherichia coli to 1 mM nitric oxide under aerobic or anaerobic conditions did not decrease viability of the bacteria. Peroxynitrite (1 mM), the reaction product of superoxide and nitric oxide, was completely bactericidal after 5 s. The nitrovasodilator, 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1), slowly decomposes to release both nitric oxide and superoxide and thereby produces peroxynitrite. SIN-1 killed E. coli in direct proportion to its concentration with an LD50 of 0.5 mM. Copper, zinc superoxide dismutase (50-400 units/ml) provided substantial but not complete protection against SIN-1 killing. Catalase (500-10,000 units/ml) partially protected in direct proportion to its concentration, while inactivated catalase was not protective. Superoxide dismutase and catalase together completely protected E. coli against SIN-1 toxicity. Oxy-hemoglobin eliminated both SIN-1 and peroxynitrite toxicity. The bactericidal activity of SIN-1 was further enhanced by pterin plus xanthine oxidase. Pterin plus xanthine oxidase alone or together with Fe3+ ethylenediamine tetraacetate produced no significant decrease in E. coli viability. Hydrogen peroxide was not directly toxic to the bacteria, but E. coli pretreated with hydrogen peroxide were more susceptible to peroxynitrite, SIN-1, and the aerobic oxidation products of nitric oxide. Hydrogen peroxide pretreatment did not increase significantly the toxicity of nitric oxide under anaerobic conditions. Our results suggest that peroxynitrite is far more toxic to E. coli than nitric oxide or its by products from aerobic oxidation.

Escherichia coli↗

Activation of the intracellular glutathione system by oxydative stress during cardiopulmonary bypass and myocardial perfusion.

The glutathione (GSH) system is the main defence of tissues against free radicals and red blood cells (RBC) are the most efficient sites for GSH redox cycle activation. Total GSH was assayed during cardiopulmonary bypass (CPB) in RBC and serum from the coronary sinus, peripheral arteries and veins in 18 children corrected of their cardiac defect. Our conclusions are: (1) RBC-GSH redox cycle is activated during heart ischaemia and reperfusion; (2) the activation of intracellular GSH system is preponderant compared with the extracellular one; (3) variations in intraerythrocytic total GSH during heart ischaemia and perfusion are detectable in peripheral veins and arteries, which can be the convenient sites for monitoring changes in the GSH cycle; and (4) increased total GSH levels are present in RBC before aortic crossclamping: at the beginning of mechanical ventilation in veins and, when CPB is started, also in arteries.

Biomarkers↗

Influence of dietary manipulation on incidence of atopic disease in infants at risk.

Of 5,500 newborn infants whose family histories were screened, 900 were found to have anamnestic risk. Cord-blood IgE was evaluable in 4,677 of these newborns, of which 394 had levels > or = 1 IU/mL; 84 infants had both anamnestic risk and elevated cord-blood IgE levels. Parents of infants with anamnestic risk were informed of their child's risk of atopy. Additionally, for 391 infants at two of the three participating hospitals, a preventive diet was prescribed that recommended breastfeeding for the first 6 months of life, with maternal diet restricted to no more than 200 dL of cow milk per day, no more than one egg per week, and no tomato, fish, shellfish, nuts, or foods allergenic to the mother. Only soy formula was recommended, and introduction of solid foods was also carefully prescribed. Furthermore, doctors recommended against exposure to tobacco smoke, animal allergens, and early entrance into daycare. Evaluable infants whose parents complied with the prescribed diet were found to have a lower incidence of atopy during the first year of life (13.3%, n = 158) than infants whose parents had ignored the prescribed diet (54.7%, n = 86) or infants whose parents were offered no dietary recommendations (28.9%, n = 218). Differences between the compliant group and the two groups with unrestricted diets were significant, indicating that this prescribed diet may protect against or delay onset of food allergies during the first year of life.

Female↗

Drinking habits among high school students in Perugia, Italy, in 1981 and 1988: time trends and correlates.

The prevalence of alcohol consumption among 9th (14-15 years old) and 13th grade (18-19 years old) high school students in Perugia, Italy, was investigated in 1981 and 1988. Wine was the most popular beverage, although its use declined in the 7-year period. Beer consumption remained stable, but it was at a lower level than wine. Overall, alcohol consumption showed a slight decline among both 9th and 13th graders. However, the proportion of excessive drinkers increased, and a growing phenomenon of drunkenness among students was observed. Alcohol consumption was positively associated with sex and smoking and negatively associated with father's education and knowledge of the health hazards of alcohol abuse by multivariate analysis.

Adolescent↗

HIV and HBV infection in intravenous drug addicts from northeastern Italy.

Three hundred and two intravenous drug addicts (IVDA) from five towns in Northeastern Italy were studied. Of the males, 37/249 (14.8%) were homosexuals and of the females, 29/53 (54.7%) were prostitutes; 118 (39.0%) were alcoholics. AST levels were abnormal in 31.8%, ALT in 45.7%, GTP in 36.4%, and bilirubin in 14.6%. The prevalence of HBsAg (13.9%) and HBeAg (21.4% of HBsAg positive) was significantly higher than in 2,983 controls (4.2% and 6.3%, p less than .001 and p less than .02, respectively). Of the HBsAg positive subjects, 51.7% had anti-HDV antibodies. Among 260 HBsAg negative cases, 146 (56.2%) were anti-HBs and anti-HBc positive, 76 (29.2%) were anti-HBc positive and anti-HBs negative (25 anti-HBe positive and 51 anti-HBe negative), and 38 had no HBV markers. Anti-HIV ELISA positive subjects came to 70.5% (triplicate determination with absolute concordance) and Western blot analysis confirmed the results in 99.1% of ELISA positive and 100% of ELISA negative subjects. The prevalence of anti-HIV was significantly higher in anti-HBc positive than negative cases (p less than .02), even excluding HBsAg positive subjects. Cases negative for HIV and HBV had a significantly lower median duration of drug abuse than those with past or present infection (36 vs 60 months, p less than .001). HIV-related diseases were present in 56.3% of the cases (120/213; PGL in 94, ARC in 24, and AIDS in two).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Stainable iron in gastric and duodenal mucosa of primary hemochromatosis patients and alcoholics.

The presence of iron in gastric and duodenal mucosa was investigated with Perl's stain in endoscopic biopsies from 13 patients with overt primary hemochromatosis, 10 chronic heavy alcohol abusers, and 10 patients with nonulcer dyspepsia. In the primary hemochromatosis patients marked iron deposition was found in cells at the base of glands in the gastric body and antrum in nine cases, and in crypt cells and Brunner gland cells of the duodenum in six. Iron was detected in the lamina propria of the stomach in five and duodenum in four cases. A similar distribution of iron overload, usually of lesser degree, was also observed in five alcoholics. Serum ferritin levels and the degree of gastric and/or duodenal iron deposits did not correlate in either hemochromatosis patients or alcoholics. No gastric or duodenal siderosis was observed in nonulcer dyspepsia cases. The absence of gastric and duodenal stainable iron in some hemochromatosis patients and its presence in some alcoholics suggests that the diagnostic value of upper gastrointestinal biopsy in primary hemochromatosis is limited.

Adult↗

Clinical, biochemical and histological features of primary haemochromatosis: a report of 67 cases.

In 67 patients (mean age 51 years, range 26-79), at diagnosis of primary haemochromatosis (PH), grade III or IV liver iron overload was present in all cases, cirrhosis in 85%, transferrin saturation greater than 80% in 75%, serum ferritin greater than 1000 micrograms/l in 84%, and overt diabetes in 48%. Alcohol intake was greater than 150 g/day in 11 patients; six were chronic hepatitis B surface antigen (HBsAg) carriers. HLA-A3 and B7 antigens were present in 64% and 23% versus respectively 22% (p less than 0.01) and 9% (p less than 0.025) in controls. Iron overload was found in the stomach, duodenum, skin and bone marrow in 57, 43, 45 and 59% of the patients studied. Sixty-three patients were followed for 1-260 months (median 24); 43 received regular iron-depleting treatment and 20 did not because of liver failure, cancer or refusal. Cumulative survival was 79%, 67% and 61% at 1, 4 and 10 years, respectively. Ten patients died from hepatocellular carcinoma and two from extrahepatic cancer. The early high mortality rate was due to some cases of advanced disease or cancer. Cumulative survival in the regularly treated group was 95% at 1 year and 91% at 4 and 10 years, which was higher than in the untreated group.

Adult↗

Effect of ascorbic acid on desferrioxamine-induced urinary iron excretion in idiopathic hemochromatosis.

The effect on urinary iron excretion (UIE) of vitamin C administered orally 2 h after the start of an 8-hour desferrioxamine (DF) i.v. infusion was studied in 12 patients with untreated idiopathic hemochromatosis (IH). Mean +/- SEM basal UIE of 324.6 +/- 84.6 micrograms/24 h increased after a 1-gram i.v. DF infusion to 8,778.5 +/- 1,191.4 micrograms/24 h; when vitamin C 1 or 2 g were added to DF i.v. infusion, there were further increases to 11,241.5 +/- 1,486.1 (p less than 0.01) and 13,531.2 +/- 1,697.2 micrograms/24 h (p less than 0.05 versus the last value), respectively. Basal UIE did not significantly increase after oral vitamin C administration alone. No side effects were observed.

Adult↗