Search PubMed⌕ Search

Biomedical subjects

A Antonelli

Publications and source records attributed to A Antonelli.

At least 55 records · Page 3Linked to original sources
PubMed1999

Chromosome aberrations in lymphocytes and clastogenic factors in plasma detected in Belarus children 10 years after Chernobyl accident.

In 1996, 10 years after Chernobyl accident, a cytogenetic analysis was carried out to assess whether chromosome aberrant cells (CA) were still detectable in the lymphocytes and clastogenic factors (CFs) were present in the plasma of children coming from Gomel (Belarus), one of the most heavily contaminated regions. Furthermore, the possible contribution of plasmatic CFs to the amount of CA was investigated. The presence of CA was examined in the lymphocytes from 29 thyroid tumour-affected children and 41 healthy children (local controls). Thirty healthy children living in Pisa (Italy) were enrolled in the study as additional controls from an uncontaminated area. No significant difference was observed between the two control groups, whereas a significantly increased frequency of CA was found in the tumour-affected children, as compared with Gomel and Pisa controls (chi 2-test, p < 0.001). However, when soil contamination level was taken into account, the chromosome type CA frequency observed in tumour-affected children coming from the more contaminated areas (> 4 Ci/km2) resulted significantly higher than that in other children, either affected or not (p = 0.003). The presence of CFs was analyzed on the plasma ultrafiltrate from 41 children. 7/10 (70%) plasma samples from tumour-affected children and 17/23 (74%) Gomel controls resulted to possess clastogenic activity irrespective of soil contamination levels. No activity was detected in the plasma of eight Pisa controls (0%). The difference between both Gomel groups and Pisa controls was highly significant (p = 0.002). A borderline, but not statistically significant correlation (p = 0.08) was observed between basal CA frequency and CF potency, which became significant (p = 0.03) when only chromosome type of aberrations was considered. We conclude that, although the presence of CFs in the plasma of these children might be partly responsible of the cytogenetic effects observed, the main source of damage has considered to be do to the previous and/or continuous exposure to environmental radiocontaminants. Tumour-affected children may represent a subset of the population either more sensitive to clastogenic damage or exposed to higher levels of contaminants.

Adolescent↗
PubMed1999

Clinical and molecular studies of 73 Italian families with autosomal dominant cerebellar ataxia type I: SCA1 and SCA2 are the most common genotypes.

We clinically and genetically evaluated 73 Italian families with autosomal dominant cerebellar ataxia (ADCA) type I. Spinocerebellar ataxia (SCA) type 1 was the most common genotype (SCA1), accounting for 41% of cases (30 families), SCA2 was slightly less frequent (29%, 21 families), and the remaining families were negative for the SCA1, SCA2, and SCA3 mutations. Among the positively genotyped families, SCA1 was found most frequently in families from northern Italy (50%), while SCA2 was the most common mutation in families from the southern part of the country (56%). Slow saccades and decreased deep tendon reflexes were observed significantly more frequently in SCA2 patients, while increased deep tendon reflexes and nystagmus were more common in SCA1. In SCA1 and SCA2 families there was a significant inverse correlation between expansion size and age at onset. Analysis of triplet repeat numbers in parent-offspring pairs showed greater meiotic instability, which was associated with an earlier onset of the disease in SCA2 families than in SCA1 families.

Adult↗
PubMed1999

Yeast influence on volatile composition of wines.

Nine Saccharomyces cerevisiae and four Saccharomyces bayanus strains used in the production of Trebbiano wine were examined. The aim of this study is to evaluate the different abilities of various yeast strains in wine-making. The possibility of yeast discrimination on the basis of their volatile production is another possibility. Wine chemical analyses showed statistically significant differences depending on the yeast strain used. Some compounds such as 2-phenylethanol, 2-phenethyl acetate, ethyl lactate, 3-ethoxypropanol, and, to a lesser extent, diethyl succinate and propionic acid characterized examined Saccharomyces bayanus yeasts. Moreover, these strains did not produce any undesirable compounds, such as acetic acid and sulfur anhydride. For these reasons and because they synthesized malic acid, they could be more suitable for white wine production. The other yeasts showed great differences, which are difficult to correlate with the strain. However, some strains had peculiar characteristics, such as an uncommonly high concentration of n-propanol and 3-ethoxypropanol.

Fermentation↗
PubMed1999

Efficient inhibition of macrophage TNF-alpha production upon targeted delivery of K48R ubiquitin.

K48R ubiquitin (K48R-Ub) is an analogue of native ubiquitin that does not form polyubiquitin chain conjugates. Targeted delivery of this recombinant mutant ubiquitin to human macrophages results in an intracellular increase in the ubiquitin analogue. IkappaBalpha polyubiquitination and degradation were significantly inhibited in K48R-Ub targeted macrophages upon stimulation with lipopolysaccharide. The ability to reduce IkappaBalpha degradation was also associated with a reduced production of TNF-alpha, the gene of which is under NF-kappaB control. At a concentration of 0.1 microM, dexamethasone was less effective than K48R-Ub in preventing IkappaBalpha depletion and TNF-alpha release. These data suggest that ubiquitin analogues are potent suppressors of TNF-alpha release in macrophages.

Anti-Inflammatory Agents↗
PubMed1999

Insulin: new roles for an ancient hormone.

Recent research has greatly expanded the domain of insulin action. The classical action of insulin is the control of glucose metabolism through the dual feedback loop linking plasma insulin with plasma glucose concentrations. This canon has been revised to incorporate the impact of insulin resistance or insulin deficiency, both of which alter glucose homeostasis through maladaptive responses (namely, chronic hyperinsulinaemia and glucose toxicity). A large body of knowledge is available on the physiology, cellular biology and molecular genetics of insulin action on glucose production and uptake. More recently, a number of newer actions of insulin have been delineated from in vitro and in vivo studies. In sensitive individuals, insulin inhibits lipolysis and platelet aggregation. In the presence of insulin resistance, dyslipidaemia, hyper-aggregation and anti-fibrinolysis may create a pro-thrombotic milieu. Preliminary evidence indicates that hyperinsulinaemia per se may be pro-oxidant both in vitro and in vivo. Insulin plays a role in mediating diet-induced thermogenesis, and insulin resistance may therefore be implicated in the defective thermogenesis of diabetes. In the kidney, insulin spares sodium and uric acid from excretion; in chronic hyperinsulinaemic states, these effects may contribute to high blood pressure and hyperuricaemia. Insulin hyperpolarises the plasma membranes of both excitable and non-excitable tissues, with consequences ranging from baroreceptor desensitisation to cardiac refractoriness (prolongation of QT interval). Under some circumstances insulin is vasodilatory-the mechanism involving both the sodium-potassium pump and intracellular calcium transients. Finally, by crossing the blood-brain barrier insulin exerts a host a central effects (sympatho-excitation, vagal withdrawal, stimulation of corticotropin releasing factor), collectively resembling a stress reaction. Description and understanding of these new roles, their interactions, the interplay between insulin resistance and hyperinsulinaemia, and their implications for cardiovascular disease have only begun.

Animals↗
PubMed1999

Autoantibodies to CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase) in Caucasian patients with diabetes: effects on insulin release from human islets.

The type II transmembrane glycoprotein CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase) has been proposed as a mediator of insulin secretion from pancreatic beta-cells and as a candidate for autoimmune reactions in type 2 diabetes. We evaluated the presence of anti-CD38 autoantibodies in Caucasian patients with diabetes and investigated the effect of these antibodies on insulin secretion from isolated human pancreatic islets. The presence of anti-CD38 autoantibodies was evaluated by using Western blot analysis in 236 patients with type 2 diabetes (mean age 63 years), in 160 patients with type 1 diabetes (mean age 38 years), and in 159 nondiabetic subjects. Anti-CD38 autoantibody titers at least 3 SD above the mean value of the control group were found in 9.7% of type 2 diabetic patients and in 13.1% of type 1 diabetic patients (chi2 = 15.9, P = 0.0003 vs. 1.3% of control subjects). No significant differences were observed in sex distribution, current age, age at diabetes onset, BMI, fasting serum glucose, or glycemic control between anti-CD38+ and anti-CD38-diabetic patients in either the type 2 or type 1 diabetic groups. The effect of 23 anti-CD38- and 13 anti-CD38+ sera on insulin secretion at low (3.3 mmol/l) or high (16.7 mmol/l) medium glucose concentrations was evaluated in isolated human pancreatic islets. Data are medians (interquartile range). The anti-CD38+ sera potentiated insulin release both at low [95 (64) vs. 23 (12) microU/ml of control incubations, respectively, P < 0.0001] and high [271 (336) vs. a control of 55 (37) microU/ml, respectively, P = 0.001] medium glucose concentrations, whereas the anti-CD38- sera did not. Furthermore, in the pooled data from all 36 tested sera, insulin levels in the islet incubation medium were directly related to the anti-CD38 antibody titer. We conclude that autoantibodies to CD38 are associated with both type 1 and type 2 diabetes in Caucasian subjects. These autoantibodies exert a stimulatory effect on insulin secretion by cultured human islets. The role of this autoimmune reaction in the pathogenesis of diabetes remains to be elucidated.

ADP-ribosyl Cyclase↗
PubMed1998

Cytogenetic damage in lymphocytes of healthy and thyroid tumor-affected children from the Gomel region (Belarus).

During 1994, 19 thyroid tumor-affected children and 17 healthy children from the Gomel region, one of the areas most polluted by the Chernobyl fallout, were analysed for (i) the presence of in their urine and (ii) chromosome aberrations (CA) in circulating lymphocytes. They were compared with 35 healthy children from Pisa, Italy. Tumor-affected children showed significantly (p<0.05) higher levels in their urine as compared to healthy controls from the Gomel region. No radioactivity was found in urine from the Pisa controls. CA frequency was significantly higher in tumor-affected children compared to the Gomel controls, but was not significantly different between Gomel and Pisa controls. However, dicentric chromosomes were found in a significantly (p<0.01) greater proportion in both affected and healthy Gomel children (3.4 and 1.3/1000 cells, respectively) as compared to the Pisa controls (0.4/1000 cells). Multiple regression analysis showed that the proportion of cells with acentric fragments, dicentric and ring chromosomes was significantly correlated (p<0.05) with the amount of excreted in their urine. These findings suggest that children from the Gomel region were still being exposed to radionuclides, which makes it possible to study a dose-effect relationship.

Adolescent↗
PubMed1998

Completion total thyroidectomy in children with thyroid cancer secondary to the Chernobyl accident.

OBJECTIVE: To evaluate the usefulness of submitting children with thyroid cancer secondary to nuclear accidents to a completion total thyroidectomy. DESIGN: A case series consisting of patients living and operated on in Belarus whose parents had asked for a clinical evaluation in a western European center. SETTING: A tertiary care referral center. PATIENTS: The conditions of 47 children from Gomel, Belarus, with differentiated thyroid carcinoma following the nuclear accident at Chernobyl, Ukraine, were evaluated at the University of Pisa, Pisa, Italy. In approximately half of the cases, the treatment in Belarus consisted of a hemithyroidectomy. After a complete evaluation, the decision was made to reoperate on 19 of them by performing a completion total thyroidectomy. The preoperative evaluation revealed that 5 (26%) of the 19 patients who had undergone a hemithyroidectomy had unilateral recurrent nerve palsy and that 2 (10.5%) had hypoparathyroidism. INTERVENTIONS: Neck ultrasonography was used for the preoperative localization of thyroid residuals, thyroid nodules, suspicious lymph nodes, and a guided fine-needle aspiration biopsy specimen. The circulating thyroglobulin measurement was obtained before reoperation. An iodine 131 whole-body scan (WBS) was performed and circulating thyroglobulin levels were obtained after completion of the thyroidectomy during withdrawal of levothyroxine sodium therapy. MAIN OUTCOME MEASURE: The number of patients with a recurrence of thyroid cancer and lung or lymph node metastases after the completion total thyroidectomy. RESULTS: The results of the histologic examination were positive for papillary thyroid cancer in 6 (28.6%) of 21 patients, 3 with residual cancer in the remaining thyroid lobe and 3 with metastatic lymph node disease. A posttherapy WBS demonstrated lung metastases in 5 (28%) of 18 patients and lymph node metastases in 6 (33%) of 18 patients; the results of a posttherapy WBS were negative for metastases in 7 (39%) of 18 patients. Hypoparathyroidism developed in 4 (21%) of 19 patients who underwent a completion total thyroidectomy; unilateral laryngeal nerve palsy developed in 1 (5.2%) of these 19 patients. Among 22 children who previously underwent total thyroidectomy in Belarus, a diagnostic WBS showed lung metastases in 10 (45%) of the children and lymph node metastases alone in 3 (14%) of the children; the results of a diagnostic WBS were negative for metastases in 9 (41%) of the children. Statistical analysis showed a nonsignificant (P>.05) difference in the prevalence of lung and lymph node metastases in patients who previously underwent total thyroidectomy compared with patients who underwent completion total thyroidectomy. CONCLUSION: Completion total thyroidectomy allowed for the diagnosis and treatment of recurrent thyroid cancer and lung or lymph node metastases in 61% (11/18) of the patients in whom residual differentiated thyroid carcinoma was not previously recognized.

Adolescent↗
PubMed1998

Effects of poly(ADP-ribose) polymerase inhibition on cell death and chromosome damage induced by VP16 and bleomycin.

Poly(ADP-ribose) polymerase (PARP) is a DNA-binding protein involved in cellular response to various genotoxic agents. To understand the role of PARP in the mechanisms which lead from specific DNA damage to cell death, we studied the effects of PARP inhibition in human lymphoblasts damaged with bleomycin (BLM) and VP16. These agents can induce DNA breakage but through different mechanisms, enabling the study of the different effects of PARP in inducing apoptosis in damaged cells. We demonstrate that in lymphoblasts VP16 treatment induces apoptosis to a greater extent than BLM treatment, and that PARP inhibition reduces VP16-induced apoptosis whereas it has no effect on BLM-induced apoptosis. After VP16 treatment with PARP inhibition, a reduction in the depletion of the proliferative compartment and a G2/M phase arrest are observed. Therefore, the increase in cell viability and the reduction in chromosome damage may both be the result of a prolonged DNA repair time. Hence, PARP appears to play a significant role in VP16-induced apoptosis and not in BLM-induced apoptosis. Since apoptosis is important in tumor treatment these findings might be useful when considering the combined employment of PARP inhibition with antineoplastic drugs.

Apoptosis↗
PubMed1997

2',3'-Dideoxycytidine cytotoxicity in human macrophages.

Human macrophages when cultured for several weeks in the presence of therapeutically relevant 2',3'-dideoxycytidine (ddC) concentrations show a time-dependent decay in mitochondrial DNA content. This decay is associated with a reduction of Rhodamine 123 fluorescence, a marker for mitochondrial membrane potential suggesting that impairment of mitochondrial functions occurs. Mitochondrial metabolic impairment was confirmed by direct evaluation of lactate production, which is markedly increased in cells treated with ddC. The activity of protein kinase C and intracellular free Ca2+ upon addition of phorbol 12-myristate 13-acetate (PMA) were lower in the drug-treated cells compared to controls. A 50% reduction in O2-release was also found upon PMA stimulation. Fluorescent latex beads, yeast and bacteria phagocytosis were normal, but intracellular bacteria killing was markedly impaired in ddC-exposed macrophages. Thus, ddC exerts a delayed mitochondrial toxicity also on differentiated macrophages with impairment of several metabolic properties and O2 production causing a reduced ability of these phagocytic cells to kill phagocytosed bacteria.

Anti-HIV Agents↗
PubMed1997

Reproductive potential: its influence on the susceptibility of a species to pesticides.

Acute lethal concentration estimates (72-hr LC50) and population growth rates (7-day instantaneous rate of increase) of two mite species, an herbivore, the two-spotted spider mite Tetranychus urticae Koch, and the generalist predator mite Iphiseius degenerans Berlese, were developed after exposure to two pesticides, dicofol and Neemix. For each pesticide, LC50 estimates for both species were similar, yet the two species exhibited completely different susceptibility when population growth rate was the endpoint evaluated; I. degenerans was much more susceptible than T. urticae to either pesticide. For example, populations of I. degenerans became extinct after exposure to 250-ppm azadirachtin, the active ingredient in Neemix, while T. urticae populations became extinct after exposure to 1000 ppm. A similar relationship was found for dicofol. The no observable effect concentration (NOEC) for population growth rates after Neemix exposure was 4 ppm for I. degenerans and 125 ppm for T. urticae. These NOEC values were equivalent to the acute LC2 for the immature stage of I. degenerans and the acute LC65 for the immature stage of T. urticae. Consequently, populations of T. urticae were able to compensate for high losses of individuals while I. degenerans populations could not compensate for losses. An analysis of reproduction data indicated that unexposed T. urticae produced four to five times more offspring than I. degenerans. This in itself was important because it indicated that I. degenerans was intrinsically more susceptible than T. urticae because similar effects on reproduction would be more devastating to the species with a lower reproductive rate. Results indicate that a species' reproductive potential can greatly influence its susceptibility to toxicants.

Animals↗
PubMed1997

Increased microbicidal activity of human monoblastoid cells upon long-term exposure to dideoxycytidine.

2',3'-Dideoxycytidine (ddC) is a nucleoside analogue currently used in AIDS therapy. We had previously found that long term exposure of U937 human monoblastoid cells to ddC induces the selection of drug-resistant cells (U937-R). In the present work we investigated some important biochemical properties and functional activities of these resistant cells. The results obtained show that U937-R maintained the properties of cell aggregation, adhesion and differentiation. Basal respiration, protein kinase C activity, superoxide anion release and intracellular free calcium were all increased in the drug-resistant line. Phagocytosis of fungi (Candida albicans) and bacteria (Staphylococcus aureus and Salmonella anatum) were similar in U937 and U937-R cells. Killing of C. albicans was significantly higher in drug-resistant cells (29.07 +/- 2.23% of killing vs 19.07 +/- 2.01 in the control; p < 0.001). Similarly, the bacterial killing was enhanced in U937-R cells (34.07 +/- 8.06% vs 22.60 +/- 4.41% in the control; p < 0.05). Thus, the results presented in this paper provide evidence of an increased microbicidal activity of human monocytic cells upon long term exposure to ddC, most likely due to an increased oxidative metabolism.

Blood Bactericidal Activity↗
PubMed1997

Intravenous immunoglobulin versus corticosteroid in treatment of Graves' ophthalmopathy.

We compared the effectiveness of systemic corticosteroids with the use of high-dose intravenous immunoglobulin (IVIG) in the treatment of Graves' ophthalmopathy. This was performed as a prospective, nonrandomized study including a blinded ophthalmological and orbital computed tomographic (CT) evaluation. The two groups of patients were not significantly different in relation to sex composition, age distribution, duration of Graves' disease, and ophthalmopathy and previous hyperthyroidism. All patients were followed up by endocrinologic evaluation and blinded ophthalmological (before therapy = B, at the end of therapy = E, and 6 months after the end = 6M) and orbital CT (B and E) evaluations. Twenty-seven patients treated with IVIG were followed up after the end of treatment for an average of 21 months (range 12 to 48 months). Soft tissue involvement (NOSPECS) improved or disappeared in 32 of 35 (90%) patients treated with IVIG and in 25 of 27 (92.5%) patients treated with corticosteroids. Diplopia improved or disappeared in 22 of 29 (75%) patients treated with IVIG and in 16 of 20 (80%) patients treated with corticosteroids. The results observed by clinical evaluation were confirmed with orbital CT score in 30 IVIG patients and in the corticosteroid-treated patients; a significant reduction of extraocular muscle thickness was observed after treatment in both groups. Proptosis improved or disappeared in 20 of 31 (65%) patients treated with IVIG and in 15 of 24 (62%) patients treated with corticosteroids. Mean values of proptosis evaluated by Hertel's exophthalmometer showed a slight reduction both in IVIG as well as in corticosteroid-treated patients. It is interesting to observe that in 28 IVIG-treated patients in whom it was possible to evaluate soft tissue involvement, proptosis and diplopia in the period between the fifth and sixth month from the start of therapy, the most important part of the amelioration (if responders) was already obtained at that time. Responder patients were defined in relation to the decrease in the highest NOSPECS class or grade. Among IVIG-treated patients 26 of 34 (76%) responded; while in the corticosteroid group 18 of 27 (66%) responded to treatment. The prevalences of patients who responded to the treatments were not significantly different in the two groups (Chi-square). The initial values of the subjective eye score were similar in the two groups, and a significant reduction was observed in both. Major side effects requiring discontinuation of the corticosteroid therapy were observed in two patients with hemorrhagic gastritis and in one patient with manic-depressive psychosis. Among 15 patients submitted to the evaluation of bone mineral content before and after corti-costeroid therapy, 4 presented signs of osteoporosis and 3 a reduction of bone mineral content. Moderate and minor side effects were more frequently noted in steroid-treated patients than in the IVIG group. These data suggest that IVIG is safe and effective in reducing the eye changes in patients with Graves' ophthalmopathy.

Adrenal Cortex Hormones↗
PubMed1996

Pulmonary function, smoking habits, and high resolution computed tomography (HRCT) early abnormalities of lung and pleural fibrosis in shipyard workers exposed to asbestos.

To evaluate the presence of asbestos-related pleural and parenchymal abnormalities and their correlation with pulmonary function and smoking habits, 119 asbestos-exposed asymptomatic workers (mean age, 46.2 years; mean duration of asbestos exposure, 8.6 years; mean latency time, 21.6 years) with normal standard P.A chest radiographs were submitted to HRCT, CO-diffusing capacity and pulmonary function tests. HRCT scans were normal only in 31 (26%) examined workers; 31 (26%) subjects showed both pleural and parenchymal involvement, and 50 (42%) and seven (6%) had exclusively pleural and parenchymal abnormalities, respectively. Based on CO-diffusing capacity and pulmonary function tests, no significant difference was demonstrated between workers with pleural lesions and subjects with normal pleura; however, lower values of FVC were observed in the nonsmoking workers with parenchymal abnormalities in comparison with nonsmoking subjects with normal parenchyma (78.2 vs. 89.7% of predicted values; p = 0.03 by student's two-tailed t test), and lower values of FEV1/FVC in the smokers with parenchymal lesions with respect to smokers with normal parenchyma (93.7 vs. 100.2% of predicted values; p = 0.005 by students' two-tailed t test). In conclusion, our results demonstrate that HRCT may detect early parenchymal abnormalities which correlate with exposure to asbestos and respiratory function impairment, including a reduction in obstructive indices in smokers occupationally exposed to asbestos, without any clinically evident disease.

Adult↗