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Biomedical subjects

F Petrucci

Publications and source records attributed to F Petrucci.

At least 19 recordsLinked to original sources

Metal changes in CSF and peripheral compartments of parkinsonian patients.

BACKGROUND: Involvement of metals in the risk of developing Parkinson's disease (PD) has been suggested. In the present study, concentration of metals in cerebrospinal fluid (CSF), blood, serum, urine and hair of 91 PD patients and 18 controls were compared. METHODS: Blood and hair were microwave digested, while CSF, serum and urine were water-diluted. Elements quantification was achieved by Inductively Coupled Plasma Atomic Emission Spectrometry and Sector Field Inductively Coupled Plasma Mass Spectrometry. RESULTS: Some metal imbalances in PD were observed: i), in CSF, lower Fe and Si; ii), in blood, higher Ca, Cu, Fe, Mg and Zn; iii), in serum, lower Al and Cu; iv), in urine, lower Al and Mn, higher Ca and Fe; and v), in hair, lower Fe. The ROC analysis suggested that blood Ca, Fe, Mg and Zn were the best discriminators between PD and controls. In addition, hair Ca and Mg were at least 1.5 times higher in females than in males of patients and controls. A decrement with age of patients in hair and urine Ca and, with less extent, in urine Si was observed. Magnesium concentration in CSF decreased with the duration and severity of the disease. Elements were not influenced by the type of antiparkinsonian therapy. CONCLUSIONS: Variation in elements with the disease do not exclude their involvement in the neurodegeneration of PD.

Age Factors↗

Assessment of workers' exposure to palladium in a catalyst production plant.

Airborne particulate matter was collected and biomonitoring of workers was performed by sampling blood, urine and hair of 84 exposed subjects, 17 occasionally exposed employees, 21 controls from administrative offices and 25 unexposed people (external controls). Determination of Pd was performed using Quadrupole and High Resolution Inductively Coupled Plasma Mass Spectrometry. The Production of Catalysts Department and the Refining Service presented the highest levels of Pd in airborne matter collected by means of an area sampler. The highest level of soluble Pd (1.66 microg m(-3)) was found in the Production of Catalysts Department. The highest concentration of Pd in airborne matter, collected by means of personal devices (7.90 microg m(-3)) was found in the Refining Service. Hair showed a clear distribution pattern among departments, with values ranging from 0.60 to 5.54 microg g(-1). Administrative workers presented blood levels of Pd between 2 and 500 times higher than external controls. Only urine levels correlated with the measurements of airborne Pd collected with personal devices. A very strong association between airborne Pd collected by personal devices and Pd levels in hair (r(2)= 0.569, with p< or = 0.01) and urine (r(2)= 0.684, with p< or = 0.01) was found. On the basis of these findings: (i) blood results appear to be an unsuitable biological marker for occupational exposure to Pd; (ii) urine could be considered as a satisfactorily responsive bio-marker for occupational monitoring; and (iii) hair cannot be considered a good index of time-related exposure.

Adult↗

Biomonitoring of a worker population exposed to platinum dust in a catalyst production plant.

AIMS: To evaluate the occupational exposure to platinum in an industrial plant engaged in the production, recovery, and recycling of catalytic converters for the automotive traction and chemical industries. METHODS: Pt was determined in airborne particulate matter, and blood, urine, and hair of 106 exposed workers, 21 controls from the plant's administrative offices, and 25 unexposed subjects. RESULTS: The highest air Pt level was found in the department of the plant in which supports are coated with acid metal solutions, where values of 2.39 and 4.83 microg/m3 respectively were found in environmental airborne particulate matter and in air collected using personal sampler devices. The percentage of soluble Pt was also highest in this area, varying from 24% to 44% of the total. The biological data confirmed this trend, with mean concentrations in this site being higher than in other working areas: 1.86 microg/l (urine), 0.38 microg/l (blood), and 2.26 microg/kg (hair). The workers employed in the administrative sector, who were not directly exposed to Pt, had levels of contaminant lower than those of other workers, albeit 2-20 times higher than those of external controls. High correlations were obtained between Pt levels detected in airborne samples using personal devices and those found in urine and hair, but not in blood. CONCLUSIONS: The background level of Pt in all areas of the factory implies widespread exposure for the workers. The most reliable biomarker was urine. Hair cannot be considered a good index of time related exposure, at least until more reliable methods of washing can be found that are able to remove exogenous Pt completely.

Adult↗

Trace and major elements in whole blood, serum, cerebrospinal fluid and urine of patients with Parkinson's disease.

Quantifications of Al, Ca, Cu, Fe, Mg, Mn, Si and Zn were performed in urine, serum, blood and cerebrospinal fluid (CSF) of 26 patients affected by Parkinson's disease (PD) and 13 age-matched controls to ascertain the potential role of biological fluids as markers for this pathology. Analyses were performed by Inductively Coupled Plasma Atomic Emission Spectrometry and Sector Field Inductively Coupled Plasma Mass Spectrometry. The serum oxidant status (SOS) and anti-oxidant capacity (SAC) were also determined. Results showed a decreasing trend for Al in all the fluids of PD patients, with the strongest evidence in serum. Calcium levels in urine, serum and blood of PD patients were significantly higher than in controls. Copper and Mg concentrations were significantly lower in serum of PD patients. Levels of Fe in urine, blood and CSF of patients and controls were dissimilar, with an increase in the first two matrices and a decrease in CSF. No significant difference was found in levels of Mn between patients and controls. Urinary excretion of Si was significantly higher in PD subjects than in controls. No clear difference between Zn levels in the two groups was found for serum, urine or CSF, but an increase in Zn levels in the blood of PD patients was observed. The SOS level in PD was significantly higher while the corresponding SAC was found to be lower in patients than in controls, in line with the hypothesis that oxidative damage is a key factor in the pathogenesis of PD. The results on the whole indicate the involvement of Fe and Zn (increased concentration in blood) as well as of Cu (decreased serum level) in PD. The augmented levels of Ca and Mg in the fluids and of Si in urine of patients may suggest an involuntary intake of these elements during therapy.

Aged↗

Biomonitoring of traffic police officers exposed to airborne platinum.

BACKGROUND: Over the past two decades there has been a substantial increase in environmental levels of palladium, platinum, and rhodium, the platinum group elements (PGEs), due to the widespread use of catalytic converters for automotive traction. AIM: To evaluate urinary platinum levels in occupationally exposed subjects. METHODS: A total of 161 employees from the Rome City Police Force were studied; 103 were traffic police involved in controlling streets with an average flow of vehicles, while the remaining 58 were control subjects engaged only in office work. Platinum quantification in the urine samples of these subjects was carried out by sector field inductively coupled plasma mass spectrometry. RESULTS: There were no statistically significant differences between platinum levels in the group of subjects engaged in traffic control and the control group (4.45 (2.42) ng/l v 4.56 (2.84) ng/l, respectively). CONCLUSIONS: Urinary levels were found to be higher than those reported for other urban populations, thus showing a progressive increase in human exposure to Pt.

Adult↗

High-throughput microwave-digestion procedures to monitor neurotoxic elements in body fluids by means of inductively coupled plasma mass spectrometry.

Microwave (MW) digestion procedures with high sample throughput (simultaneous digestion of 36 or 80 samples) and procedural simplicity (disposable plastic tubes, or re-usable liners with screw-cap) were investigated for their efficiency in routine analyses of biological samples. Different digestion vessel materials were tested for metal leaching/adsorption and thermal resistance: quartz, glass, polyethylene (PE) and polystyrene (PS). For the instrumental quantification of Al, Bi, Cd, Co, Cr, Hg, Mn, Mo, Ni, Pb, Sb, and Tl at ultra-trace levels in urine, serum, and whole blood, sector field inductively coupled plasma mass spectrometry (SF-ICP-MS) was used. The different pretreatment conditions and vessels were evaluated in terms of contamination risk, effective power of detection, accuracy, and precision. Results of analyses of serum, urine and whole blood certified reference materials (CRMs) were fully satisfactory for almost all the analytes. In the case of Hg, Mo, and Tl in serum digested in plastic containers the results were just below the lower limit of uncertainty of the certified range. On the basis of the present data the following MW procedures can be suggested: 1. for urine, digestion with nitric acid at atmospheric pressure in plastic vials; 2. for serum, digestion with nitric acid at atmospheric pressure in glass vessels; and 3. for whole blood, digestion under pressure in quartz tubes. Because of the levels of the procedural blanks, Bi was not measurable at the concentrations expected in human fluids, and Al was accurately detectable in whole blood only.

Humans↗

Environmental risk of particulate and soluble platinum group elements released from gasoline and diesel engine catalytic converters.

A comparison of platinum-group element (PGE) emission between gasoline and diesel engine catalytic converters is reported within this work. Whole raw exhaust fumes from four catalysts of three different types were examined during their useful lifetime, from fresh to 80,000 km. Two were gasoline engine catalysts (Pt-Pd-Rh and Pd-Rh), while the other two were diesel engine catalysts (Pt). Samples were collected following the 91441 EUDC driving cycle for light-duty vehicle testing, and the sample collection device used allowed differentiation between the particulate and soluble fractions, the latter being the most relevant from an environmental point of view. Analyses were performed by inductively coupled plasma-mass spectrometry (ICP-MS) (quadrupole and high resolution), and special attention was paid to the control of spectral interference, especially in the case of Pd and Rh. The results obtained show that, for fresh catalysts, the release of particulate PGE through car exhaust fumes does not follow any particular trend, with a wide range (one-two orders of magnitude) for the content of noble metals emitted. The samples collected from 30,000-80,000 km present a more homogeneous PGE release for all catalysts studied. A decrease of approximately one order of magnitude is observed with respect to the release from fresh catalysts, except in the case of the diesel engine catalyst, for which PGE emission continued to be higher than in the case of gasoline engines. The fraction of soluble PGE was found to represent less than 10% of the total amount released from fresh catalysts. For aged catalysts, the figures are significantly higher, especially for Pd and Rh. Particulate PGE can be considered as virtually biologically inert, while soluble PGE forms can represent an environmental risk due to their bioavailability, which leads them to accumulate in the environment.

Air Pollutants↗

Platinum-group elements: quantification in collected exhaust fumes and studies of catalyst surfaces.

Automotive catalytic converters, in which Pt, Pd and Rh (platinum-group elements; PGEs) are the active components for eliminating several noxious components from exhaust fumes, have become the main source of environmental urban pollution by PGEs. This work reports on the catalyst morphology through changes in catalyst surface by scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDX) and laser-induced breakdown spectrometry (LIBS) from fresh to aged catalytic converters. The distribution of these elements in the fresh catalysts analysed (Pt-Pd-Rh gasoline catalyst) is not uniform and occurs mainly in a longitudinal direction. This heterogeneity seems to be greater for Pt and Pd. PGEs released by the catalysts, fresh and aged 30,000 km, were studied in parallel. Whole raw exhaust fumes from four catalysts of three different types were also examined. Two of these were gasoline catalysts (Pt-Pd Rh and Pd-Rh) and the other two were diesel catalysts (Pt). Samples were collected following the 91,441 EUDC driving cycle for light-duty vehicle testing. The results show that at 0 km the samples collected first have the highest content of particulate PGEs and although the general tendency is for the release to decrease with increasing number of samples taken, exceptions are frequent. At 30,000 km the released PGEs in gasoline and diesel catalysts decreased significantly. For fresh gasoline catalysts the mean of the total amount released was approximately 100, 250 and 50 ng km(-1) for Pt, Pd and Rh, respectively. In diesel catalysts the Pt release varied in the range 400-800 ng km-1. After ageing the catalysts up to 30,000 km, the gasoline catalysts released amounts of Pt between 6 and 8 ng km(-1), Pd between 12 and 16 ng km(-1) and Rh between 3 and 12 ng km(-1). In diesel catalysts the Pt release varied in the range 108-150 ng km(-1). The soluble portion of PGEs in the HNO3 collector solution represented less than 5% of the total amount for fresh catalysts. For 30,000 km the total amount of soluble PGEs released was similar or slightly higher than for 0 km.

Electrochemistry↗

Reference values for selected trace elements in serum of term newborns from the urban area of Rome.

Reference values for Al, Cd, Co, Cu, Li, Mn, Mo, Ni, Rb, Se and Zn, and indicative intervals for Sb are proposed in serum from cord blood of 143 term newborns of the urban area of Rome. On the basis of the eligibility criteria adopted, only babies with gestational age > 37 weeks and body weight at the delivery > 2500 g, i.e., "normal" term infants, were included in this study. With the exception of Cd, Li, Ni and Sb, experimental data for each of the other analytes were found to approach a normal distribution. The estimated references values (in ng/ml) were the following: Al, 1. 12-6.79; Cd, 0.10-0.52; Co, 0.20-0.43; Cu, 140-691; Li, 0.31-2.23; Mn, 0.79-3.26; Mo, 0.36-1.56; Ni, 0.20-3.15; Rb, 196-1302; Sb, 0. 10-1.48 (indicative range); Se, 20.2-69.7; and Zn, 318-1405. For several elements, the information available in the relevant literature does not allow adequate comparisons to be performed. This was actually possible only for Cu, Se and Zn. The correlations between the weights at birth (BW), gestational ages (GA) and elemental concentrations were elucidated. As expected, significant positive correlations were found for Cu and Se with GA and BW, respectively. Strong mutual associations were observed for several other elements, but their interpretation is still debatable.

Birth Weight↗

Activity of cisplatin and ICI 182,780 on estrogen receptor negative ovarian cancer cells: cell cycle and cell replication rate perturbation, chromatin texture alteration and apoptosis induction.

The activity of cisplatin (CP, range of concentrations 0.25-1 microg/ml), the pure steroidal antiestrogen compound ICI 182,780 (range of concentrations, 0.01-10 microM) and various combinations of, was investigated on an estrogen receptor negative ovarian cancer cell line (A2780 WT) and its CP-resistant derivative subline (A2780 CP3). CP markedly reduced A2780 WT cell growth but marginally affected A2780 CP3, whereas ICI 182,780 was effective on both cell lines. CP but not ICI 182,780 provoked a significant blockade in late S/G(2) phase in both cell lines, particularly in the parental line. Measuring the number of rounds of cell replications showed that CP diminished the cell replication rate of both cell lines, particularly in A2780 WT. Conversely, ICI 182,780 reduced the cell replication rate of A2780 CP3 but not A2780 WT cells. Both drugs provoked apoptosis in A2780 WT cells, as assessed by the appearance of large (50-300 kbp) DNA fragmentation. However, laser scanning cytometry showed that only CP induced a measurable alteration of chromatin texture in A2780 WT but not in A2780 CP3 cells. The combination CP and ICI 182,780 resulted in a synergistic inhibitory activity of cell growth with a CP potentiation up to 4 and 11-fold in A2780 WT and A2780 CP3 cells, respectively. This reflected an enhanced reduction of the cell replication rate and did not involve perturbations of the cell cycle other than those provoked by CP alone. Apoptosis induction and the level of CP-DNA adducts were not influenced by adding ICI 182,780 to CP in both cell lines.

Antineoplastic Combined Chemotherapy Protocols↗

Reference values for chromium, nickel and vanadium in urine of youngsters from the urban area of Rome.

In the assessment of human health risk, the obtainment of reference values in biological tissues and/or fluids is crucial to estimate the type and magnitude of occupational and environmental exposure. In this context, urine is the major excretion route for many noxious substances that have entered the organism and can be viewed as one of the most useful materials for biomonitoring campaigns. In this study, reference concentration ranges for Cr, Ni and V in urine were achieved in a sub-population of 131 youngsters, aged 6-10, attending primary schools in the urban area of Rome. Subjects under drug therapy or affected by any pathological diseases were not included in this investigation. Strict precautions against contamination or loss of the analytes of interest were adopted for all steps. Determinations were performed by means of high resolution inductively coupled plasma mass spectrometry. In general, the natural log-transformed concentration data for the three elements investigated conformed to a satisfactorily normal distribution. The estimated reference ranges were as follows (microg g(-1) creatinine): Cr, 0.07-0.76; Ni, 0.20-1.23; V, 0.02-0.22. The sex of the youngsters was tentatively treated as a statistical explanatory variable using the Fischer F-test on variance.

Child↗

cis-Diamminedichloroplatinum(II) given in low-dose continuous infusion with concurrent radiotherapy to patients affected by inoperable lung carcinoma: a pharmacokinetic approach.

The pharmacokinetics of cis-diamminedichloro platinum(II) (cisplatin), given as a continuous infusion with concurrent radiotherapy to patients with locally advanced inoperable non-small-cell lung carcinoma, was investigated in 16 cases. The regimen, repeated for 6 consecutive weeks, consisted of weekly 10-Gy radiotherapy given in five fractions from Monday to Friday, and concurrent 100-h infusion of cisplatin delivered at a daily dose of 4 mg/m2 by a central venous catheter and a portable pump. Throughout the weeks of therapy the platinum levels were determined in plasma and in ultrafiltered plasma by respectively inductively coupled plasma atomic emission spectrometry and inductively coupled plasma mass spectrometry. Mean levels of platinum in plasma ([Pt]tot ) increased from the 1st to the 6th week of infusion, while mean levels of platinum in ultrafiltered plasma ([Pt]uf), 110 microg/l, showed no marked variation throughout the therapy. [Pt]uf ranged from 16% to 22% of the total Pt. Mean levels of Pt in ultrafiltered plasma were of the same order of magnitude as those found to be active in vitro as radiopotentiators. Pt decay levels were measured for 24 h at the end of the 1st and 5th weeks of infusion, allowing the calculation of the Pt half-life and the area under the decay curves. The mean value of the area under the decay curve, plotting [Pt]tot against time (AUC), in the range 0-24 h from the end of the 5th week of infusion, was about twice that from the end of the 1st week; by contrast, the mean AUC values did not vary for the [Pt]uf against time curves. The mean values of the alpha half-life of Pt in the ultrafiltered plasma were in accordance with those published in the literature; however, an unexpected very long beta half-life was found (more than 100 h). Thus it was suggested that Pt species other than free cisplatin were present in the ultrafiltered plasma; such species probably involve metal bound to low-molecular-mass proteins. Throughout the therapy, the toxic effects in all patients were negligible, and 75% of them had an objective locoregional reduction of disease. In only 2 cases was progression of disease observed within the irradiated area. On the basis of these data, it can be concluded that cisplatin at a level of 110 microg/l in the ultrafiltered plasma, in the reported scheme of continuous intravenous infusion, has an enhancing effect on radiation and avoids concentration peaks of platinum not bound to protein.

Adult↗

Use of the stable isotope 65Cu test for the screening of Wilson's disease in a family with two affected members.

BACKGROUND/AIMS: An improved method for the study of copper metabolism in Wilson's disease, using a stable, rather than radioactive, copper isotope (65Cu) has recently been described. We report on the use of this method for the study of a family with two members affected by Wilson's disease. SUBJECTS: The family comprised parents and four siblings: one 20-year-old male and three females, aged 22, 17 and 5 years, respectively. The boy and the 17-year-old girl both presented with liver cirrhosis. Diagnosis of Wilson's disease was suggested by elevated liver copper content and/or low caeruloplasmin levels and Kayser-Fleischer ring. METHODS: All family members were given an oral dose of 3 mg of 65Cu. Blood samples were taken at 0, 1, 2, 6, 24, 48, and 72 hours. In 4 subjects, additional blood samples were drawn at 7, 14 and 21 days after dosage. The ratio 65Cu:63Cu in serum was determined in all samples by means of Inductively Coupled Plasma Mass Spectrometry. RESULTS: The diagnosis of Wilson's disease was confirmed in the two symptomatic members by the unequivocal decrease observed in the 65Cu percent enrichment, which approached zero by 72 hours. In contrast, Wilson's disease could be definitely excluded in both siblings, one of whom only 5 years old, on the evidence of net secondary peaks, showing normal incorporation of 65Cu into caeruloplasmin. These findings were later confirmed by genetic analysis. Parents, who carried defective genes with different mutations, also showed different abnormalities of copper metabolism. CONCLUSIONS: The oral test with the stable copper isotope 65Cu is a safe, non invasive option able to exclude Wilson's disease in patients with a difficult diagnosis or in a presymptomatic stage. However, positive tests must still be confirmed by copper dosage in liver biopsies, as heterozygotes can present with severe alterations of copper metabolism, without developing symptoms of the disease. The use of this test in conjunction with genetic analysis on a larger number of heterozygous subjects may add to the understanding of the Wilson's disease defect.

Adolescent↗

Tamoxifen synergizes the antiproliferative effect of cisplatin in human ovarian cancer cells: enhancement of DNA platination as a possible mechanism.

We investigated the chemosensitizing activity of tamoxifen (TAM) on estrogen receptor negative ovarian cancer cell lines sensitive (A2780 WT) and resistant to cisplatin (CP) (A2780 CP3). Our results showed that the treatment of both cell lines with the association TAM + CP (concentration range 0.01-1 microN and 0.1-1 microgram/ml, respectively) results in a synergistic antiproliferative activity and a complete reversal of the acquired CP-resistant phenotype. We demonstrated that in A2780 cells the addition of TAM to CP treatment is able to significantly enhance at every tested CP dose (P < 0.001) the amount of platinum (Pt) bound to the DNA. Since Pt-DNA levels in the genome are clearly related to the growth inhibitory effect of CP (correlation value = 0.97, P < 0.001) in our experimental model, we hypothesized that TAM could act synergistically with CP and overcome the acquired CP-resistance by enhancing Pt binding to the DNA. We suggest that, from a clinical point of view, TAM may be usefully included in CP-based chemotherapy regimens for ovarian cancer patients since plasma concentrations of the drug capable of in vitro CP resistance modulation are achievable in vivo. A prospective clinical trial to verify the clinical usefulness of combined TAM + CP treatment in ovarian cancer patients refractory to prior Pt-based chemotherapy is now underway in our department.

Antineoplastic Agents↗

Determination of platinum in plasma of patients affected by inoperable lung carcinoma treated with radiotherapy and concurrent low-dose continuous infusion of cis-dichlorodiammine platinum(II).

Platinum microquantities were determined in plasma of patients affected by lung carcinoma during treatment with radiotherapy (RT) and concurrent low-dose continuous infusion of cis-dichlorodiammineplatinum(II) (CDDP). RT was given at 50 Gy in continuous course; CDDP was continuously infused at 4 mg/m2 daily for 100 h/week for 5 weeks, and the infusions were separated by 68 h of rest. The percentage of free drug versus total drug in plasma was about 3%. It did not vary with therapy duration and was not significantly different from that found in 5-day continuous infusions at much higher daily doses. Nevertheless, maximal values of free Pt in plasma were very low and agreed with the low level of CDDP toxicity encountered on the present administration schedule.

Carcinoma↗

[Handling of biological material before trace element determination].

The various steps of the analytical process are taken into account with particular reference to problems arising in sampling biological materials, their storage, pretreatment, digestion (when necessary) and determination. Emphasis is laid on the fact that the availability of analytical equipment with exceptional detection power is not always flanked by an equivalent ability to control phenomena of contamination and/or loss of analytes as well as to check and guarantee the accuracy of experimental data. In this context, proper use of the most popular analytical techniques for the determination of trace elements and the adoption of strict procedural conditions for data reliability are briefly discussed.

Animals↗