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Biomedical subjects

E Bergamaschi

Publications and source records attributed to E Bergamaschi.

At least 73 records · Page 4Linked to original sources

[Treatment of ischemia in late thrombosis after aorto-iliaco-femoral reconstructions].

Late thrombosis of inserted prosthetic grafts for arterial reconstructive surgery is one of the most frequent late complication. Its incidence is influenced by many factors: hemodynamic conditions, quality of run-in and run-off, technical aspects of the primary repair. Progressive arteriosclerosis in femoral vessels was the cause of graft limb thrombosis in most instances. When graft occlusion does occur, there is, in a majority of patients, an immediate return of ischemia which often is severe and redo-operation is indicated to restore circulation. A new angiogram is mandatory, especially for the recognition of the inflow to the central anastomosis and for the evaluation of the distal run-off. Several surgical techniques are in use for redo-operation (graft thrombectomy with or without graft prolongation, partial or total replacement of the prosthesis, reconstruction by an extra-anatomical by-pass). Very important is the role of the deep femoral artery: in patients with a multi-level occlusive disease a patent deep femoral artery most often provides an effective inflow repair with a combined use of profundaplasty and lumbar sympathectomy. In this report of 188 late thrombosis, in a twenty year experience, at the Department of General and Cardiovascular Surgery, University of Milan, we made a redo-operation in 83% of the cases, according our preference in surgical procedures, to the partial substitution of the prosthesis with large profundaplasty. An associated lumbar sympathectomy was performed in 25% of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[The nephrotoxicity of ionic and nonionic contrast media in urography. An evaluation with immunoenzyme technics and monoclonal antibodies].

The nephrotoxicity of ionic and nonionic contrast media (cm) was evaluated in 52 patients undergoing pyelography. The contrast media were i.v. injected in 30'. Urine samples were collected before, 2 and 48 hours after the injection. Urinary albumin (alb) and retinol binding protein (RBP) excretion was evaluated by immunoenzymatic methods; alb and RBP were considered as indicators of glomerular permeability and of tubular reabsorption, respectively. The urinary excretion of brush-border antigen of proximal tubule (BBA) was also measured, as an indicator of microtissue damage, by a sensitive double-antibody ELISA with monoclonal antibodies. The results demonstrate ionic cm to have greater functional effects than nonionic ones, as suggested by the increased urinary excretion of both alb and RBP. However, tubular damage seemed to be more severe with nonionic agents, as suggested by BBA excretion. Although toxic damage had little significance for the patients' health, long-term effects are not to be excluded.

Adult↗

Hydrophobic interaction of alcian blue with soluble and erythrocyte membrane proteins.

Alcian Blue (AB), a cationic dye widely employed for monitoring negative surface charge variations on red blood cell (RBC), platelet and glomerular membranes of patients with nephrotic syndromes, was found in fact to aggregate with itself and precipitate in the pH range 7.0-7.8, i.e., at the physiological pH values used for performing the binding assay between the dye and cell surfaces. This aggregation appears to be essentially hydrophobic as it is insensitive to urea but fully prevented in presence of 2% zwitterionic detergent. In addition, AB binds to most RBC membrane proteins solubilized by urea-detergent extraction, again suggesting hydrophobic interaction. AB also interacts with freely soluble proteins such as haemoglobin and myoglobin; such binding is disrupted by ethylurea and/or 2% zwitterionic detergent, typical inhibitors of hydrophobic liaisons. AB also strongly binds to myoglobin with all the negative charges blocked by esterification of the carboxyl groups, again ruling out direct interaction via surface negative charges. It is concluded that AB binding to the RBC surface can hardly monitor variations in surface charge due to sialic acid residues but, at best, variations in surface hydrophobicity.

Adult↗

Effects of some monocyclic aromatic solvents and their metabolites on brain dopamine in rabbits.

Adult male rabbits were exposed to high concentrations (750 ppm, 12 hours daily for 7 days) of toluene, xylenes, styrene, ethylbenzene, vinyltoluene (3-methylstyrene), and 7-methyl-styrene vapours or were dosed with 4 mM/kg/day i.p. of hippuric, methylhippuric, mandelic, phenylglyoxylic, and 7-methyl-mandelic acids. Styrene, vinyltoluene and ethylbenzene caused a marked depletion of striatal and tuberoinfundibular dopamine. Such an effect was also caused by treatment with phenylglyoxylic and mandelic acids. Dopamine depletion was associated with an increase in homovanillic acid concentration in the same regions. These results indicate that dopamine metabolism is a target for the neurotoxic effects of some monocyclic aromatic hydrocarbons and their metabolites, a lateral vinyl- or ethyl-chain being crucial for the structure/activity relationship of such compounds.

Animals↗

Exposure to hydrocarbons and renal disease: an experimental animal model.

The association between hydrocarbon exposure and chronic glomerulonephritis is still a controversial scientific issue. Recent epidemiological evidence suggests a role of exposure to hydrocarbons in the progression of glomerulonephritis towards chronic renal failure. The present experimental study on rats has been designed to assess the possible role of styrene in the progression of adriamycin (ADR) nephrosis, a well known model of renal fibrosis following nephrotic syndrome induced by ADR. Female Sprague-Dawley rats were exposed to styrene, 300 ppm, 6 h/day, 5 days/week for 12 weeks (group 1); treated with ADR, 2 mg/Kg, i.v., twice on day 1 and day 15 of the study (group 2); Additional groups of animals received both the styrene and ADR treatments (group 3) or served as controls (group 4). The urinary excretion of total and single proteins (albumin, Retinol-Binding Protein (RBP), Clara Cell 16 Kd protein (CC16), fibronectin) was measured monthly, whereas histopathology and determinations requiring blood sampling were carried out at the end of the experiment. A progressive increase in total proteinuria, falling in the nephrotic range already by the 6th week was observed in ADR-treated groups. Styrene exposure caused up to a 3- to 5-fold increase as compared to controls. Co-exposure to ADR and styrene also resulted in a proteinuria much greater than that caused by ADR alone. The interactive effect of styrene and ADR was statistically significant for albuminuria and urinary fibronectin. A similar response was observed for glomerular filtration rate at the end of the experiment, styrene-exposed animals showing hyperfiltration as compared to their respective control group. At the end of the experiment, histopathological scoring for interstitial infiltration and fibrosis was also significantly higher in styrene-treated animals as compared to their respective control groups. In ADR-treated rats, low molecular weight proteinuria (l.m.w.p.) was only slightly affected, suggesting minimal tubular dysfunction associated with extensive tubular atrophy. However, styrene-exposed animals showed l.m.w.p. higher than their respective controls. In summary, in this animal model we were able to confirm both styrene-induced microproteinuria, mainly albuminuria and minor increases in l.m.w.p., observed among occupationally exposed workers and the role of hydrocarbon exposure as a factor accelerating the progression of renal disease suggested by epidemiological investigations in patients suffering from chronic renal disease. Whereas in rats exposed to styrene only, microproteinuria was stable over time and minor histopathological changes were noted at the end of the experiment, evidence of a role of solvent exposure in the progression of ADR nephropathy was obtained in terms of both renal dysfunction and interstitial fibrosis. The mechanistic basis of styrene-ADR interaction is unclear. However, experimental evidence is consistent with epidemiological findings suggesting the need to avoid solvent exposure in patients suffering from renal diseases.

Albuminuria↗

[Indicators of pulmonary epithelial damage among workers at a foundry exposed to airborne pollutants].

Foundry ambient air contains very high concentrations of noxious substances, such as particulate matter and gaseous pollutants, which can target the respiratory epithelium. Serum concentrations of the 16-kDa Clara cell protein (CC16-S) may reflect both the integrity of the epithelial barrier and smoke-induced Clara cell toxicity. To evaluate whether CC16-S is a sensitive biomarker of early respiratory disturbances, it was determined in a group of 35 foundry male workers (aged 41.1 +/- 6.9 years) examined both prior to and at the end of their work-shift (06:00 a.m.-02:00 p.m.). Exposure to inhalable/respirable dusts and PAH was characterized; urinary excretion of 1-hydroxypyrene (1-OH-P) and naphtol was measured to assess exposure to pyrene and naphthalene, respectively. CC16 serum levels decreased at the end of the shift (10.7 +/- 3.82 micrograms/L vs. 8.39 +/- 3.05 micrograms/L; p < 0.01); such decrements were significantly larger in more exposed workers. Although smokers had lower baseline values as compared to non smokers, both subgroups showed an average decrease of 30% in CC16-S concentrations at the end of shift. CC16-S was also negatively correlated with 1-OH-P, but not with naphtol concentrations. Decreased CC16-S levels can result from citotoxicity and would represent an useful biomarker of pneumotoxicity in foundry workers exposed to complex mixtures.

Air Pollution, Indoor↗

[Lymphocyte subpopulations in workers exposed occupationally to styrene].

In a group of 32 workers occupationally exposed to styrene, the distribution of lymphocyte subsets was investigated by automated flow cytometry. The group under study consisted of 22 male and 10 female workers aged 39.7, D.S. = 10 years and employed for 6.8 years in factories manufacturing glass fibre-reinforced plastics. A control group (12 males and 7 females) recruited according to the same selection criteria was simultaneously examined. Environmental and biological monitoring was used to characterize styrene exposure. In styrene-exposed workers, phenotypic analysis of peripheral blood revealed a reduced proportion of T helper lymphocytes and a relative increase in the T suppressor subset, leading to a significant inversion of the helper/suppressor ratio (0.92) among heavily exposed workers (greater than 50 ppm, 8h-TWA) as compared to less exposed workers and controls (1.37 and 1.43 respectively). The proportion of natural killer (NK) T lymphocytes was significantly increased among styrene workers. The proportion of B lymphocytes was unchanged as compared to the control group. Dose-response relationships were clearly apparent for the observed increases in the prevalence of abnormalities: none of control subjects showed more than 2 (out of 8) abnormal values as compared to 20 and 40% of styrene workers belonging respectively to the low and high exposure group (p less than 0.007). Only a minority of controls exhibited abnormally high levels of both NK and suppressor T lymphocytes (0-5%), the corresponding figures for styrene workers being 7-10% (low exposure) and 45% (high exposure). As a whole, the findings support the hypothesis of the immunotoxicity of styrene, which could be due either to direct effects on lymphocytes or to indirect mechanisms possibly mediated by neuroendocrine changes.

Adult↗

[Environmental and biological monitoring of exposure to polycyclic aromatic hydrocarbons in workers of an electric steel foundry].

AIMS: To assess and classify exposure to Polycyclic Aromatic Hydrocarbons (PAHs) in some specific working areas of a steel foundry operating with a continuous casting process and evaluate biomonitoring data in different job tasks. METHODS: Exposure to dusts and six PAHs classified as carcinogenic by EU directives was studied in a cohort of 35 male foundry workers (aged 41.1 +/- 6.9 years), who were examined both prior to and at the end of the work-shift (06:00 a.m.-02:00 p.m.) in two different periods. The urinary excretion of 1-hydroxypyrene (1-OH-P) was measured as a biomarker of exposure to pyrene. RESULTS: PAHs concentrations ranged from 461.8 to 935.6 ng/m3 near the continuous casting area, whereas lower values were measured near the ladle furnace. End of shift 1-OH-P values were higher in 11 non-smoking workers involved in continuous casting process as compared to those employed in mantenance and furnace areas (median of the second determination: 5.70 microg/g creatinine--range: 1.24-21.24 vs 1.17 microg/g creatinine--range: 0.23-4.49; p< 0.001). 1-OH-P excretion was significantly correlated with both the sum of six carcinogenic PAHs and pyrene airborne concentrations. In two biomonitoring sessions, 9.1% and 34.3% of the workers respectively showed end-of-shift 1-OH-P values exceeding the occupational exposure limit (OEL) (4.4 microg/g creatinine or 2.3 micromol/mol(-1) creatinine) recommended for coke-oven workers. CONCLUSIONS: 1-OH-P is a useful biomarker in assessing PAH exposure and is associated with job category at a Steelplant. Due to exposure variability, to assess risk associated with PAHs exposure, biological monitoring should be carried out periodically.

Adult↗

[Carbon nanotubes (CNT) and nanoparticles (NP): interaction with lung epithelium and other biological systems].

Carbon nanotubes (CNT) and nanoparticles (NP) represent new classes of technological materials with innovative properties. Although inhalation is less likely for engineered nanomaterials (NM) compared with ambient or mineral dust particles, this can happen during bulk manufacture and handling of freely dispersable NP at workplace. Both environmental and engineered NP are able to cause oxidative stress, reactive oxygen species (ROS) generation, NF-kappaB activation, but some of the possible NM interactions with biological systems may result in additional forms of injury. NP can impair fagocytosis, can enhance macrophage sensitivity to chemotactic factors (MCP-1), thus worsening antigen-mediated inflammation. Metal NP (e.g. TiO2, Al2O3 and Fe3O4) can impair mitochondrial function, leading to a dramatic reduction of the intracellular glutathione pool, thus compromising cell viability and morphology. CNTs are a man-made form of crystalline carbon currently attracting intense research efforts because of their unique properties, that make them suitable for many uses in biomedicine and pharmacology. CNTs stimulate TNF-alpha production in the lung, inducing inflammatory reactions, but they can also cross cell membranes reacting with DNA and aminoacidic residues, leading to cell apoptosis. Larger CNTs could have features of conventional fibers and show the ability to stimulate mesenchymal cell growth and to cause lung granulomas formation and fibrotic reactions. These results suggest that NM are potentially hazardous to humans and that strict industrial hygiene measures should be taken to limit exposure during their manipulation.

Humans↗

[Biological indicators and reference values].

For biological indicators of exposure, effect or susceptibility, appropriate reference values should be available for a comparative evaluation at individual or at group level. Reference values can be either measured in the same subjects before the exposure starts (internal reference), or extrapolated from an appropriately selected group (external reference). In both cases, confounding factors as well as possible sources of variability (biological and analytical), must be taken into account and controlled. Proceeding from clinical chemistry to occupational and environmental medicine, different exclusion and partition criteria in producing reference values should be adopted. Whereas clinical chemistry is aimed at discriminating people as having or not diseases, preventive medicine deals with healthy subjects to prevent effects derived from abnormal exposure to xenobiotics. To this purpose, it is mandatory that general requirements are satisfied, such as the clear definition of the reference population, the conditions under which the specimens were obtained, the adequacy of the indicator itself to provide information, provided that all laboratory results were produced by adequately standardized methods under sufficient quality control. Since we are shifting from macro to microdoses, reference values would help in discriminating natural or man-made sources of exposure.

Biomarkers↗

Serum prolactin in subjects occupationally exposed to manganese.

To evaluate whether or not occupational exposure to manganese (Mn) affects basal levels of serum prolactin (PRL), a cross-sectional study was carried out in 31 occupationally-exposed workers, aged 39.2 years (DS 7.9) exposed to manganese (Mn) dusts for 14.5 years (range: 5 to 29 years) in a ferroalloy producing plant. Thirty-four industrial workers not exposed to neurotoxic chemicals and of comparable age composed the control group. Airborne Mn concentrations in dusts of the furnace area ranged 210 to 980 micrograms/m3, which is below the current American Conference of Governmental Industrial Hygienists (ACGIH)-recommended threshold limit value-time weighted average (TLV-TWA) of 1 mg/m3. Manganese concentrations in blood Mn (MnB) and in urine (MnU) were significantly higher in Mn-exposed workers as compared to control workers. The Mn-exposed workers showed significantly higher serum prolactin (PRL) levels with the geometric mean (GM) being 9.77 ng/ml with a geometric standard deviation (GSD) of 1.69 as compared to controls (GM 4.65 ng/ml, GSD 1.78, p < 0.001). Serum PRL was negatively related to age and positively correlated with both MnB and MnU. Dose-effect relationships were still significant in partial correlation analysis after control for age. The prevalence of abnormally high PRL values was consistent with a dose-response relationship. The observed increase in serum PRL among Mn-exposed workers suggests an impairment of tonic inhibition by tubero-infundibular dopaminergic neurons. The correlation between PRL and both MnB and MnU in samples collected at least 48 h from the last exposure suggests that such indices provide an estimation of the target dose.

Adult↗

Dopamine (DA) metabolism in PC12 cells exposed to manganese (Mn) at different oxidation states.

The present study was aimed at assessing the role of Mn valency state in Mn-induced changes in DA metabolism by PC12 cells. Mn(ll)Cl2, Mn(lll)Acetate, and Mn(IV)O2 were used for these experiments. PC12 cells were incubated for 3, 24 and 72 hours to Mn nominal concentrations ranging from 10-8 to 10(-4) M in 24-well plates containing 2 x 10(5) cells/well. Supernatants and cellular materials were then separated and immediately processed for the analysis of dopamine (DA), and its metabolite 3,4-di-hydroxy-phenylacetic acid (DOPAC). Lactate dehydrogenase (LDH) activity and MTT cleavage were measured as indices of cell death. In parallel experiments, Mn-containing medium (10(-5) M) was removed and cells incubated for further periods with Mn-free medium to evaluate the reversibility of observed changes. At the end of the experimental periods, none of Mn-exposed cultures showed appreciable reduction in cell viability as compared to their respective controls. After exposure to Mn(II) and Mn(III), irreversible and dose-dependent decreases in the medium but not in intra-cellular DA were apparent. Indeed, 10(-4) M Mn(II) caused the disappearance of DA and DOPAC from the medium. The same effect was caused by 10(-5) M Mn(III), the dose-effect relationship being shifted towards lower dose levels. Mn(IV) induced a parallel and dose-dependent decrease of DA and DOPAC concentrations in both intra- and extra-cellular compartments. Such an effect was reversible after removal of Mn from the medium. Multiple interferences on DA metabolism are caused by Mn. Mn(II) and Mn(III) seem to block DA secretion without affecting DA turnover rate. Mn(IV) seems to cause DA depletion and aspecific (secondary) changes in secretion rates. Further studies are necessary to understand the mechanisms underlying the differential effects of various Mn compounds on DA metabolism.

Animals↗

Peripheral markers of neurochemical effects among styrene-exposed workers.

Monoamine oxidase B (MAO-B) activity in platelets, serum dopamine-beta-hydroxylase (DBH) activity, and serum prolactin (PRL) were measured during a cross-sectional investigation in workers occupationally exposed to styrene. The study group consisted of 53 workers (33 men and 20 women) employed for 9.3 years on average (range 1-22) in reinforced plastics plants. Sixty industrial workers with no known exposure to chemicals and comparable as to age, sex and confounding variables were recruited as controls. The activities of MAO-B in platelet-rich plasma and of DBH in serum from exposed and control subjects were measured within the same run, using methods based on the liquid-chromatographic determination of the reaction products. Serum PRL was determined by both EIA and RIA. Blood samples had been collected between 8:00 and 9:00 a.m. A lower DBH activity was found in exposed as compared to control workers (GM: 7.25 U/ml serum vs. 10.11 U/ml serum; p < 0.01), whereas MAO-B activity was significantly lower in a heavily exposed subgroup (10.1 vs. 13.8 U/10(7) platelets; p = 0.05), but not in the whole sample (p = 0.07). Serum PRL was higher both in male (GM: 8.90 ng/ml vs. 6.05 ng/ml; p < 0.01) and female (GM: 12.6 ng/ml vs. 9.33 ng/ml; p < 0.05) styrene-exposed workers as compared to their respective controls. Dose-response relationships were found for abnormally low DBH and abnormally high PRL values, with a threshold occurring at metabolite levels corresponding to 8h-TWA styrene concentrations in air around 25 ppm. In summary, this study shows that long-term exposure to relatively low levels of styrene can affect DBH activity and basal serum PRL. Owing to its sensitivity, PRL is a useful biomarker to show impairments of dopaminergic control on pituitary secretion. Since DBH is expression of catecholamine secretion, its decreased activity could represent an indirect index of altered turnover rate of the physiological substrate (i.e.dopamine) at the neuronal level. However, a direct interference by styrene metabolites on enzyme activity cannot be ruled out. Platelet MAO-B activity seems to be less sensitive to styrene exposure.

Adult↗

Pilot study of peripheral markers of catecholaminergic systems among workers occupationally exposed to toluene.

In a pilot study, serum dopamine beta-hydroxylase (DBH), platelets monoamine oxidase type B (MAO B) activities and basal plasma prolactin (PRL) were measured, among 10 workers occupationally exposed to toluene and 10 control subjects, preceding and immediately following vacation. Six exposed subjects were employed in an adhesive tape making industry and 4 in a paint making industry. Their median basal levels of urinary hippuric acid were 0.44 mmole/mmole creatinine (cr) (range 0.23-1.97) and 0.18 mmole/mmole cr (range 0.15-0.19) respectively, the second to last morning of the work week, preceding vacation. The level of basal urinary hippuric acid among the control group was 0.26 mmole/mmole cr (range 0.03-0.38). The workers from the adhesive tape plant reported a significantly higher number of symptoms experienced frequently (Kruskal, Wallis, p < 0.05). On a group basis, serum DBH was lowest among the workers from the adhesive tape plant, who had the highest levels of basal urinary hippuric acid. In addition, a negative relation was observed between hippuric acid and serum DBH, preceding and following vacation (Rho = -0.46, p = 0.05; Rho = -0.51, p = 0.03). The observed changes in serum DBH activity are consistent with its decrease in human, following long-term exposure to styrene, another aromatic hydrocarbon. The findings of this pilot study, on a limited number of individuals suggest that DBH may be a sensitive peripheral bioindicator. Further studies of larger groups should be done to confirm the decrease in serum DBH activity with toluene exposure and explore whether this alteration is related to the neurotoxic impairments associated with exposure.

Adult↗