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Biomedical subjects

R Alinovi

Publications and source records attributed to R Alinovi.

At least 19 recordsLinked to original sources
PubMed2006

Flunisolide decreases exhaled nitric oxide and nitrotyrosine levels in asthmatic children.

BACKGROUND: Exhaled nitric oxide (FeNO) has been reported to be elevated in the oxidative stress involved in asthmatic patients, and the reaction of nitric oxide (NO) with superoxide anions results in the formation of nitrotyrosine. The purpose of this study was to investigate the effect of inhaled steroid treatment on nitrotyrosine levels collected by exhaled breath condensate (EBC) and on FeNO. METHODS: This was a single-blind placebo-controlled study. The lung function, FeNO, and nitrotyrosine levels were evaluated in 10 asthmatic children. RESULTS: The nitrotyrosine levels were stable during the placebo period (T0 = 1.16 ng/ml versus T1 = 1.05 ng/ml; NS.), whereas they decreased after the treatment with flunisolide (T2 = 1.14 ng/ml versus T3 = 0.88 ng/ml; P < .001). No significant reduction in FeNO levels was observed after placebo treatment (T0 = 38.4 ppb versus T1 = 34.7 ppb, NS.). In contrast, FeNO values decreased significantly being at T3 = 14.9 ppb (T1 versus T3; P = .024). CONCLUSIONS: This study shows that corticosteroid treatment reduces nitrotyrosine levels in EBC of asthmatic subjects.

Administration, Inhalation↗
PubMed2005

Analysis of oxidative stress in SK-N-MC neurons exposed to styrene-7,8-oxide.

Styrene-7,8-oxide (SO) is the main metabolite of styrene, a neurotoxic volatile organic compound used industrially. Here we report the novel observation that several markers of oxidative stress were affected in SK-N-MC cells exposed for 16 h to concentrations of SO that induce apoptotic cell death. The production of Thiobarbituric Acid Reactive Substances (TBARS), rose from 69.1 +/- 15.7 nmol/g protein (control) to 119.3 +/- 39.2 and 102.0 +/- 17.3 nmol/g protein after exposure to 0.3 and 1 mM SO, respectively. Carbonyl group levels were significantly enhanced by SO at both concentrations. The lower dose also decreased sulphydryl groups. SO caused a marked oxidative DNA damage, as shown by a fivefold increase in 8-hydroxy-2(')-deoxyguanosine (8-OHdG). In addition, SO exposure resulted in alterations of scavenging abilities, given the reduction of both glutathione (GSH) and glutathione-S-transferase (GST) activity. Induction of expression of the oxidative stress response gene heme-oxygenase-1 (HO-1) and an increased HO-1 activity were also observed. These data provide compelling evidence that oxidative stress significantly contributes to SO toxicity in neuronal cells.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2004

Exhaled breath condensate eicosanoids and sputum eosinophils in asthmatic children: a pilot study.

Cysteinyl leukotrienes (cys-LTs), LTB4 and 8-isoprostane are increased in the exhaled breath condensate (EBC) from asthmatic patients. The aim of this study was to investigate whether the measurement of cys-LTs, LTB4 and 8-isoprostane in EBC can reflect the level of airway inflammation assessed by induced sputum in asthmatic children sensitized to house dust mite (HDM) during natural avoidance of HDM allergens. Twelve children were evaluated at the time of admission (T0) and after 3 months of stay (T1) at the Istituto Pio XII (Misurina, Italian Dolomites 1756 m). Sputum eosinophil percentage and measurement of cys-LTs, LTB4 and 8-isoprostanes in the breath condensate at T0 and T1 were evaluated. Eosinophil percentage in induced sputum was 8.5 +/- 1.1% at T0 and 3.5 +/- 0.4% at T1 (p = 0.011). Neutrophil percentage in sputum was 1.1 +/- 0.5% at T0 and 1.5 +/- 1.0% at T1 (ns). Cys-LTs mean level was 14.24 +/- 4.53 pg/ml at T0 and 4.65 +/- 0.68 pg/ml at T1 (p = 0.0125). LTB4 level was 2.36 +/- 0.19 pg/ml at T0 and 2.41 +/- 0.23 pg/ml at T1 (ns). 8-Isoprostane level reduced from 17.47 +/- 3.18 pg/ml at T0 to 7.36 +/- 3.26 pg/ml at T1 (p = 0.003). This study show that exhaled cys-LTs and 8-isoprostane, as well as eosinophil percentage in induced sputum, are reduced after allergen avoidance in asthmatic children suggesting a potential application of EBC for the non-invasive evaluation of airway inflammation in asthma in allergic asthmatic children.

Adolescent↗
PubMed2003

Cysteinyl leukotrienes and 8-isoprostane in exhaled breath condensate of children with asthma exacerbations.

BACKGROUND: Cysteinyl leukotrienes (Cys-LTs) and isoprostanes are inflammatory metabolites derived from arachidonic acid whose levels are increased in the airways of asthmatic patients. Isoprostanes are relatively stable and specific for lipid peroxidation, which makes them potentially reliable biomarkers for oxidative stress. A study was undertaken to evaluate the effect of a course of oral steroids on Cys-LT and 8-isoprostane levels in exhaled breath condensate of children with an asthma exacerbation. METHODS: Exhaled breath condensate was collected and fractional exhaled nitric oxide (FE(NO)) and spirometric parameters were measured before and after a 5 day course of oral prednisone (1 mg/kg/day) in 15 asthmatic children with an asthma exacerbation. Cys-LT and 8-isoprostane concentrations were measured using an enzyme immunoassay. FE(NO) was measured using a chemiluminescence analyser. Exhaled breath condensate was also collected from 10 healthy children. RESULTS: Before prednisone treatment both Cys-LT and 8-isoprostane concentrations were higher in asthmatic subjects (Cys-LTs, 12.7 pg/ml (IQR 5.4-15.6); 8-isoprostane, 12.0 pg/ml (9.4-29.5)) than in healthy children (Cys-LTs, 4.3 pg/ml (2.0-5.7), p=0.002; 8-isoprostane, 2.6 pg/ml (2.1-3.0), p<0.001). After prednisone treatment there was a significant decrease in both Cys-LT (5.2 pg/ml (3.9-8.8), p=0.005) and 8-isoprostane (8.4 pg/ml (5.4-11.6), p=0.04) concentrations, but 8-isoprostane levels remained higher than in controls (p<0.001). FE(NO) levels, which fell significantly after prednisone treatment (p<0.001), did not correlate significantly with either Cys-LT or 8-isoprostane concentrations. CONCLUSION: After a 5 day course of oral prednisone there is a reduction in Cys-LT and 8-isoprostane levels in EBC of children with an asthma exacerbation, although 8-isoprostane levels remain higher than in controls. This finding suggests that corticosteroids may not be fully effective in reducing oxidative stress in children with an exacerbation of asthma.

Adolescent↗
PubMed1997

The assessment of biomarkers to detect nephrotoxicity using an integrated database.

Groups of industrial workers exposed to heavy metals (cadmium, mercury, and lead) or solvents were studied together with corresponding control groups. The cohorts were collected from several European centers (countries). Eighty-one measurements were carried out on urine, blood, and serum samples and the results of these analyses together with questionnaire information on each individual were entered into a central database using the relational database package Rbase. After the completion of the database construction phase, the data were exported in a format suitable for analysis by the statistical package SAS. The potential value of each test as an indicator of nephrotoxicity was then assessed. Rigorous exclusion criteria were applied which resulted in the elimination of some tests and samples from the dataset. The measurable contributions of smoking, gender, metal exposure, and site were either singly or in combination assessed by biomarkers for nephrotoxicity. The parameters measured included three urinary enzymes, six specific proteins, total protein, two extracellular matrix markers, four prostaglandins and anti-GBM antibodies, and beta 2-microglobulin in serum. The most sensitive renal tests included the urinary enzymes N-acetyl-beta-D-glucosaminidase (NAG) and intestinal alkaline phosphatase (IAP), brush border antigens, and urinary low-molecular-weight proteins. Of the newer tests investigated the prostaglandins were the most promising. Different patterns of biomarker excretion were observed following exposure to lead, cadmium, or mercury. The dataset provides a unique repository of data which could provide the basis of an enlarging source of information on normal human reference ranges and on the effects of exposure to toxins and the use of biomarkers for monitoring nephrotoxicity.

Biomarkers↗
PubMed1997

Peripheral markers of catecholaminergic dysfunction and symptoms of neurotoxicity among styrene-exposed workers.

AIM: A cross-sectional investigation was carried out to assess possible relations between styrene-induced changes in three peripheral markers of catecholaminergic dysfunction and self-reported symptoms of neurotoxicity. SUBJECTS: Male workers (n = 46) aged 14-60 (mean 29.5) years who had been exposed to styrene for an average of 6 (0.2-29) years were recruited in glassfiber reinforced plastics plants. A control group of 30 blue-collar workers aged 22-52 (mean 35) years and with no history of exposure to chemicals was recruited from local industries. Styrene exposure ranged from 5 to 120 ppm (8 h-TWA), the median level being relatively low (25 ppm, 8 h-TWA). Styrene metabolites, mandelic and phenylglycoxylic acids (MAPGA) in the "next morning" urine spot samples ranged from 32.0 to 931.1 mg/g creatinine (median 186.5). METHODS: Platelet monoamine oxidases B (MAO B) and dopamine beta-hydroxylase (DBH) activities were assessed using methods based on HPLC and electrochemical detection. Plasma prolactin (PRL) was measured by a commercially available immunoassay. Questionnaire 16 (Q16) was used to survey self-reported symptoms. RESULTS: Although there was no difference in DBH activity between exposed workers and controls, the most highly exposed workers had significantly lower activity than control subjects. A tendency to lower platelet MAO B activity in exposed than in control subjects was observed. The prevalence of plasma DBH and platelet MAO B values below the lower reference limit was similar in the two groups. PRL values exceeding the upper reference limit were higher (14/46 vs 2/30) among styrene-exposed workers, who also exhibited significantly higher median levels (10.0 vs 5.7 micrograms/l) than control subjects. Although the number of reported symptoms was similar among exposed and control subjects, in the exposed group it was positively associated with urinary MAPGA (Rho = 0.30, P = 0.04). Of the three peripheral markers of catecholaminergic dysfunction, plasma DBH was the only parameter negatively related to both urinary MAPGA (F = 9.56, P = 0.003) and the number of reported symptoms (Rho = 0.23, P = 0.05). CONCLUSIONS: Plasma PRL appears to be a sensitive marker of styrene-induced tubero-infundibular dopaminergic dysfunction in male subjects. DBH in plasma and MAO B in platelets seem to be less suitable markers for biomonitoring effect at the individual level, although DBH was related to the number of reported symptoms and to internal dose. Further studies on a larger and more exposed population are necessary to clarify the significance of these markers for health and their predictive value with regard to both subjective disturbances and concurrently administered performance tests.

Adolescent↗
PubMed1996

Development and validation of new screening tests for nephrotoxic effects.

Within the framework of an European Commission-funded project, groups of industrial workers exposed to heavy metals (cadmium, mercury and lead) or solvents were studied together with corresponding control groups. Eighty-one measurements were carried out on urine and serum samples and the scientific results together with individual questionnaire information were entered into a central database. Data obtained was assessed centrally and individually in subsidiary studies. The measurable contributions were assessed either singly or in combination, of smoking, gender, metal exposure and site, to nephrotoxicity. The potential value of each test as an indicator of nephrotoxicity was then assessed on the basis of sensitivity and specificity. A number of new tests including prostaglandins and for extracellular matrix components were investigated as well as established tests for renal damage and dysfunction. The data obtained from this comprehensive study emphasises the value of noninvasive biomarkers for the early detection of nephrotoxicity due to environmental toxins. The urinary profile varied with the type of environmental/occupational toxin. By careful selection of a small panel of markers they can be used to indicate the presence of renal damage, the principal region affected, and to monitor the progress of disease and damage. Biomarkers were also used to confirm and tentatively establish safe exposure levels to nephrotoxins.

Biomarkers↗
PubMed1994

Does occupational cobalt exposure determine early renal changes?

A cohort of workers occupationally exposed to cobalt (Co) dusts was examined to assess possible subclinical renal effects attributable to Co. Cross-sectional investigations involved 26 workers with a mean age of 34.2 (S.D., 8.3), chronically-exposed (median, 3.5 years; range, 0.9-11) to Co dusts in hard-metal manufacturing factories. Thirty-five healthy control workers, with a mean age of 32.4 (S.D., 4.6) were also examined. Individual interviews were used to exclude subjects with renal or systemic diseases, intake of nephrotoxic drugs, and exposure to known nephrotoxins. Exposure levels, assessed by ambient and biological monitoring, showed an estimated exposure approaching the ACGIH-recommended TLV of 50 micrograms/m3. Immunochemical methods were used to measure urinary albumin, retinol-binding protein (RBP), beta 2-microglobulin (beta 2m), and tubular brush-border antigens. The prevalence of abnormal values for early markers of renal dysfunction was similar in Co-exposed workers and in controls. However, within the reference interval, the cumulated frequency distribution for beta 2m was shifted towards higher values in the exposed group. No relationship was detected between renal markers and either intensity or duration of exposure. In spite of a limited number of observations, these findings suggest that the kidney is not a target organ during occupational exposure to Co.

Adult↗
PubMed1994

Urinary excretion of tubular brush-border antigens among lead exposed workers.

The brush-border of the human renal proximal tubule is extremely sensitive to toxic, ischaemic and inflammatory insults. A monoclonal antibody to a brush-border antigen (BB-50) had been shown to identify increased urinary excretion of BB-50 (UBB-50) among workers exposed to heavy metals and hydrocarbons as well as patients on cisplatin and patients with early diabetic nephropathy. This study describes the use of this antibody to quantify UBB-50 among lead exposed workers. The study population consisted of 154 workers from a factory manufacturing lead stabilisers. Of these 91 workers had less than 6 months of exposure and formed the control group. The remaining 63 workers with a median exposure of 3 years formed the exposed group. Several blood lead (PbB) indices were used as exposure indices. These include the most recent PbB (PbBrec), a time-integrated blood lead index (PbBint), an absolute change in recent PbB (PbB delta), a relative change in PbB (PbB delta%), as well as the number of times the PbB measurements were above 40, 50 and 60 micrograms/100 ml (PbB40, PbB50, PbB60 respectively). Urinary levels of beta-2-microglobulin (U beta 2m), alpha-1-microglobulin (U alpha 1m), retinol binding protein (URBP), albumin (UAlb), activity of total N-acetyl-D-beta-glucosaminidase (NAG-T) and heat stable NAG isoenzyme (NAG-B) were measured along with the serum beta 2m (S beta 2m). Through stepwise analysis, UBB-50 was best correlated with PbBint, PbB40 and PbB delta% (r2, 0.271). Of these, PbBint and PbB40 had about twice the contribution to the variation in UBB-50.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Multiple interferences on catecholamine metabolism by tetrahydroisoquinolines (TIQs).

TIQs are thought to be formed by condensation between dopamine and certain metabolites of ethanol, organic solvents and anesthetic gases. Described here are experiments aimed at evaluating TIQs interference with catecholamine synthesis. Rat adrenal pheochromocytoma (PC12) cell lysates were exposed to benzyl-TIQ and phenyl-TIQ. The activities of tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) were measured by HPLC-based methods following exposure to variable concentrations of TIQs. The effects of TIQs on DBH activity were also assessed in human serum. Dixon plot analyses revealed that TIQs act on TH as competitive inhibitors with different affinity. Ki for benzyl- and phenyl-TIQ were 5 and 3 microM respectively. DBH activity in serum exposed to benzyl- and phenyl-TIQ ranging from 0.2 to 20 microM rose respectively by 12.5% to 58% for benzyl- and by 7.8% to 26% for phenyl-TIQ. Such TIQs interferences with catecholamine metabolism seem to account for dopamine (DA) depletion observed in parallel in vitro experiments on PC12 cells. The dose-dependent inhibition of TH and the increased activity of DBH together with the relatively low effective doses of TIQs suggest this mechanism as a possible explanation of the selective toxicity of styrene and other solvents to dopaminergic systems observed in rabbits following experimental exposure and suspected to occur in occupationally-exposed workers.

Animals↗
PubMed1993

Reversible tubular proteinuria precedes microalbuminuria and correlates with the metabolic status in diabetic children.

Early tubular alterations were studied in 53 children with insulin-dependent diabetes mellitus (IDDM), 32 of whom were followed at regular 6-monthly intervals for 3 years. The urinary levels of retinol-binding protein (RBP), beta 2-microglobulin and brush border antigens (BBA) (determined by monoclonal enzyme immunoassay) were taken as indices of functional and cellular tubular alterations; urinary albumin was considered an early marker of glomerular alterations. All indices of tubular alterations were higher in IDDM children than in 368 normal children, while albuminuria was unchanged. Urinary levels of BBA, however, varied widely during follow-up, with 25 of the 32 IDDM patients who were followed at regular intervals having pathological values for BBA on at least one occasion, followed by normalization. Metabolic alteration was found to be the main cause of this variability, since a high statistical correlation was found between urinary BBA and fructosamine (P < 0.001) and between RBP and the stable fraction of glycosylated haemoglobin (P < 0.001). The data confirm that transient tubular proteinuria occurs in diabetic children before any other marker of renal involvement such as microalbuminuria. The maintenance of good metabolic control is essential to normalize this early abnormality that can be considered a reversible sign of functional renal involvement.

Adolescent↗
PubMed1992

Nephropathies and exposure to perchloroethylene in dry-cleaners.

Even in specific risk groups, the relation between exposure to organic solvents and chronic renal diseases remains controversial. Thus, in a collaborative European study, we assessed the renal effects of occupational exposure to perchloroethylene (PCE) in dry-cleaners compared with matched controls who were simultaneously examined. Single high and low molecular weight proteins, kidney-derived antigens and enzymes, and prostanoids were measured in urine. beta 2-microglobulin, creatinine, laminin fragments, and anti-glomerular basement membrane antibodies were also measured in serum. A canonical function based on 23 such variables correctly classified 93% of individuals as either PCE-exposed or controls; with 13 markers, group membership was identified in 87% of subjects. Increased high molecular weight protein in urine was frequently (17/50 vs 1/50, p less than 0.0001) associated with tubular alterations. Changes were consistent with diffuse abnormalities along the nephron in workers exposed to low levels of PCE (median 15 parts per million). Generalised membrane disturbances might account for the increased release of laminin fragments, fibronectin, and glycosaminoglycans, for high molecular weight proteinuria, and for the increased shedding of epithelial membrane components from tubular cells with different location along the nephron (brush-border antigens and Tamm-Horsfall glycoprotein). These findings of early renal changes indicate that solvent-exposed subjects, especially dry-cleaners, need to be monitored for the possible development of chronic renal diseases.

Adolescent↗
PubMed1992

Reference values for early markers of renal damage.

In addition to the difficulties related to the definition of a reference population and hence of reference limits, special methodological problems have to be dealt with when early markers of renal damage are applied to monitor groups at risk. The urinary excretion of both high and low molecular weight proteins, as measured by sensitive immunoassays, is routinely applied in health surveillance programmes aimed at preventing the occurrence of adverse renal effects resulting from exposure to nephrotoxic chemicals, among which are several metals. Owing to the large intra-individual variability experimentally demonstrated for all indicators of renal impairment, carefully standardized sampling conditions must be adopted. At the individual level, repeated measurements should be performed before a diagnosis of renal disease or dysfunction is established. In fact, several physiological conditions may account for transient changes in renal function, leading to measured levels greatly exceeding reference limits.

Albuminuria↗
PubMed1992

Urinary excretion of brush border antigens and other proteins in children with vesico-ureteric reflux.

This study was designed to evaluate the occurrence and the type of proteinuria in 82 children with vesico-ureteric reflux (VUR) with or without renal scars. The urinary excretion of the high molecular weight protein albumin was taken as an index of glomerular alterations and the excretion of retinol-binding protein (RBP), beta 2-microglobulin and brush border antigens (BBA) (measured by monoclonal antibody-based enzyme-linked immunosorbent assay) was taken as an index of tubular alterations. All such markers were increased in children with VUR and were related to the degree of renal function. Patients showing reduced creatinine clearance had very high levels of albuminuria, microproteinuria and BBA, with all these variables reciprocally correlated. In children with normal renal function however, only microproteins (not albumin or BBA) were slightly increased, thus indicating an isolated tubular defect without involvement of the proximal segment of the tubule. However, microprotein excretion did not correlate with the grade of scarring (99mtechnetium-dimercaptosuccinic acid scan), both RBP and beta 2-microglobulin excretion being normal in 75% of children with radioisotopic signs of renal lesions but increased in 17% of children without scars. Therefore, tubular proteinuria identifies different groups of children with VUR but is not related to renal scarring. Prospective studies will define the usefulness of proteinuria as a reliable indicator of renal outcome.

Adolescent↗
PubMed1992

Rat model of perchloroethylene-induced renal dysfunctions.

To investigate whether perchloroethylene (PCE) can induce renal disturbances and to compare morphological alterations with functional data, two groups of 12 male and female Fischer-344 mature rats were treated daily with PCE (500 mg/kg body wt in corn oil, p.o.) for 4 weeks. Sex- and age-matched control groups received corn oil only. Weekly, the urinary excretion of albumin (Alb), alpha 2 mu-globulin (alpha 2 mu) and retinol-binding protein (RBP) was measured in 24-hr urine samples using immunoassays specific for rat proteins. N-acetylglucosaminidase (NAG) activity was measured by a colorimetric assay. Electrophoretic analysis of proteinuria included SDS-PAGE and isoelectric-focusing of Alb purified from serum and urine. Weekly histopathology comprised light and electron microscopy. In the male rat, a trend toward progressive albuminuria (up to 15 times the pair-fed controls) was observed, together with transient increases in alpha 2 mu and NAG; RBP showed a twofold increase at the end of treatment. Histopathology failed to demonstrate glomerular changes, whereas it displayed alpha 2 mu accumulation and mild lesions in the S2 segment of proximal tubules. Thus, in the male rat, the selective damage to S2 was associated with "glomerular" proteinuria, the alpha 2 mu cortical content being closely correlated with albuminuria (n = 9, r = 0.92, P < 0.001). In the female rat, only minor, although statistically significant (P < 0.05), increases were recorded for Alb, whereas urinary alpha 2 mu reached up to four times the control values. As a whole, these findings suggest that PCE, like other hydrocarbons, selectively affects the tubular segment S2 in the rat. A competition with alpha 2 mu for tubular uptake could explain enhanced albuminuria. Owing to the species specificity of alpha 2 mu, caution should be exercised in extrapolating these findings to man.

Albuminuria↗