Biomedical subjects

S Caroli

Publications and source records attributed to S Caroli.

At least 37 records · Page 2Linked to original sources

PubMed1996

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↗

PubMed1996

The Role of Chirocephalus diaphanus in the Early Recognition of Environmental Pollution by Trace Elements

A study was undertaken to evaluate whether the fairy shrimp Chirocephalus diaphanus (Crustacea: Anostraca) could be considered as a species capable of biomonitoring environmental contamination by accumulating trace elements. This preliminary investigation aimed at assessing the levels of As, Cd, Cu, Hg, Pb, Se, and Zn in natural waters as well as in adults and cysts of fairy shrimps sampled from five different sites in central Italy. Trace elements were determined by inductively coupled plasma (ICP)-based spectrometry. In particular, ICP-mass spectrometry (ICP-MS) was resorted to in most cases due to its high detection power. Pretreatment of samples (adults and cysts) consisted basically in the HNO3-assisted microwave digestion of the material. The highest levels of trace elements were found in the anostracan cysts, with concentration ranges (μg/g) of 0.464-3.11 for As, up to 0.820 for Cd, 2.62-13.0 for Cu, 0.011-0.213 for Hg, 0.966-8.46 for Pb, 0.295-2.45 for Se, and 16.4-50.4 for Zn. On the other hand, the lowest concentrations were found in natural waters, with values close to the ICP-MS detection power for some elements. These data are probative of a bioconcentration process, the extent of which is proportional to the environmental level of each element. This may turn out to be useful in planning biological monitoring and assessing ecotoxicological consequences which might ensue from the diffusion of the exploitation of such organisms in aquaculture.

Journal Article↗

PubMed1996

Stability of Mercury Dilute Aqueous Solutions: An Open Issue

In the framework of the activities of the European Commission Reference Laboratory (CRL) for residues at the Istituto Superiore di Sanita a number of analytical quality control trials on determination of trace analytes are being carried out. As regards trace elements it soon became apparent that the stability of Hg dilute aqueous solutions is rather unsatisfactory. An investigation was thus undertaken to ascertain the conditions under which the concentration of this metal does not appreciably change. Mercury solutions were prepared in high purity deionized water in the concentration range 1-10 ng g-1 and the effect of various amounts of HNO3 and K2Cr2O7 (alone or in combination) was elucidated by measuring the variations with time in the actual concentration of Hg. Determinations were performed by both inductively coupled plasma atomic emission spectrometry and inductively coupled plasma mass spectrometry. Results show that solutions added with 5% (w/w) HNO3 and 0.01% (w/w) K2Cr2O7 do not undergo any significant alteration in the nominal content of the analyte for at least 1 month. Similar conclusions are reached in the case of solutions enriched in CaCO3, NaCl, NaNO3, KH2PO4, KNO3, and Mg(NO3)2.6H2O to mimic acid digests of meat samples. The improvement ensuing from the adoption of this approach on the performance of the Hg analytical quality control trials is discussed in detail.

Journal Article↗

PubMed1995

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↗

PubMed1995

[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↗

PubMed1995

[Platinum-based antineoplastic agents: biomedical applications and therapeutic aspects].

A survey of investigations performed over the last decade concerning analytical, clinical and pharmacological data on cancer chemotherapy with Pt-based drugs is reported. From this standpoint discussion focuses on clinical studies aimed at evaluating therapeutic response and toxicity during regional and systemic treatment of cisplatin against solid tumors in adults as well as in children. Concurrent treatments with locoregional hyperthermia in the case of limb tumors or with radiotherapy in the case of lung carcinoma are also dealt with.

Adult↗

PubMed1995

Clinical pharmacokinetics of cumulative very high dose of cisplatin in chemotherapy resistant solid tumors.

Cisplatin was administered to seven patients with advanced cancer in divided doses of 40 mg/m2 body surface daily for 5 consecutive days. The pharmacokinetics of total Pt was studied on the days 1, 3 and 5 of infusion. The renal function was assessed through the parameters usually applied in the clinical practice (serum creatinine level, creatinine clearance, urinary volume). Pt pharmacokinetics and the renal function did not show modifications outside the normal range. However, on day 5 of treatment patients showed increased alpha-half life and AUC of plasma Pt, as well as decreased Pt total body clearance and Pt renal clearance, associated to a significant (although still within normal range) increase in serum creatinine and a decrease in urinary volume. Moreover, a correlation between Pt pharmacokinetics and renal parameters (measured as the difference between the values of days 1 and 5 of treatment) was also found: the increase in creatinine was directly related to a decrease in Pt renal clearance and inversely related to Pt peak level in urine, while the latter was inversely related to a reduction of Pt renal clearance. It was concluded that very high doses of cisplatin are well tolerated in patients, although some parameters might suggest early impairment of the renal function.

Aged↗

PubMed1994

The adoption of good laboratory practice principles by Italian test facilities.

The principles of good laboratory practice (GLP) can be considered as a code of general behaviour potentially applicable to all experimental studies, although they were first conceived for harmonizing the conduct and assessment of toxicological tests designed to evaluate the impact of chemical substances on human health and the environment. From a general standpoint, therefore, GLP criteria aim at generating credible, comparable and cost-effective experimental information that can in turn make the decision-making process easier and sounder. On the other hand, of equal importance at the global level is the availability of and access to the wealth of critically assessed, self-consistent chemical data thus produced. Under both respects a key role is played by the activities undertaken under the aegis of international bodies such as the Organisation for Economic Cooperation and Development (OECD), the Commission of the European Union (CEU) and the International Register of Potentially Toxic Chemicals of the United Nations Environment Programme (IRPTC-UNEP). This cultural and scientific humus has been incorporated into legal provisions by most industrial countries to regulate production and commercialization of chemical substances. As regards Italy, the act DLvo no. 120 of 27 January 1992 focuses on the adoption of GLP principles by national test facilities and covers all possible categories of chemicals, namely industrial substances, pharmaceuticals, cosmetics, pesticides, food additives and still others. Accordingly, the compliance status with GLP principles of a test facility is ascertained by inspections carried out by public officers following a detailed procedure which will eventually result in the above acknowledgement provided that no major deviations in the laboratory performance are detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Italy↗

PubMed1994

Critical selection of toxicological data on chemicals. The example of the International Register of Potentially Toxic Chemicals data bank.

Although chemicals provide important benefits, they can also represent hazards to human health or the environment. However, due to number of chemicals involved, clearly no country can deal alone with the evaluation of existing scientific, technical and legal information on chemicals. This implies a need for countries to work together to assess the risk posed by chemicals and to share the results in a compatible and understandable way. In 1973 the governing council of United Nations Environment Programme (UNEP) decided to proceed with the creation of the International Register of Potentially Toxic Chemicals (IRPTC). The core activity of IRPTC is the collection of information on chemicals into a computerized data bank and the dissemination of these data in the form of chemical data profiles. The data profiles focus on selected chemicals with a potential to affect human health and the environment, excluding chemicals whose sole use is as a pharmaceutical or which are radioactive substances. The data collection and selection activities of IRPTC are driven by two key issues: data quality and data quantity. The objective of IRPTC in this respect is to provide decision-makers and other users with the most pertinent data available to substantiate their assessment of hazard. Providing reliable and detailed data in manageable amounts was the strategy chosen to achieve this objective.(ABSTRACT TRUNCATED AT 250 WORDS)

Databases, Factual↗

PubMed1994

The management of information: storage and retrieval of data.

Internationally harmonized and cost-effective control of chemicals marketed worldwide greatly depend both on the generation of and easy access to reliable and comparable experimental information. Stored data are of use only if information can be retrieved quickly in an understandable form. Some models and theories of information retrieval (e.g. fuzzy set theory, probabilistic approach, artificial intelligence) are briefly discussed first, then followed by applications (such as indexing and clustering techniques). Finally the structure of databases is briefly reviewed.

Database Management Systems↗

PubMed1994

A pilot study on colon cancer occurrence as related to serum selenium levels.

A pilot study was undertaken in order to assess the relationship between selenium status and occurrence of colon cancer in a selected population group. The opportunity for starting the programme occurred in 1992 after some information attained from health control laboratories that noted human colon cancer death rates much higher than normal in a well defined geographical area of central Italy (province of Terni). Element levels in serum and healthy and neoplastic colon tissues were determined for twenty subjects affected by the disease. A hydride generation-based method with inductively-coupled plasma atomic emission spectrometry (ICP-AES) detection was developed for the determination of Se in acid-digested samples. The mean values observed in the three types of samples led to the following conclusion: i) Se levels in serum of subjects affected by colon cancer are significantly lower (0.063 +/- 0.018 microgram/ml) than those reported previously for the national average (0.089-0.093 microgram/ml); ii) there is a considerable difference in Se levels between the healthy and neoplastic tissues (0.098 +/- 0.030 microgram/g vs 0.158 +/- 0.065 microgram/g).

Colonic Neoplasms↗

PubMed1993

Association of serum copper and zinc with serum electrolytes and with selected risk factors for cardiovascular disease in men aged 55-75 years. NFR Study Group.

Serum Cu (S-Cu) and Zn (S-Zn) levels were determined in 1468 out of 1856 male subjects aged 55-75 years living in the Rome area who participated, between 1989 and 1990, in the second examination in an epidemiological (New Risk Factors) survey. Mean S-Cu and S-Zn concentrations were 15.98 mumol/l (mean +/- 2SD: 10.38-21.58 +/- mumol/l) and 13.69 mumol/l (mean +/- 2SD: 8.94-18.44 mumol/l), respectively. S-Cu levels were directly related to serum calcium levels (S-Ca), serum magnesium levels (S-Mg), daily cigarette consumption, total cholesterol and age (years). S-Zn levels were directly related to S-Ca, S-Mg and cholesterol and inversely related to age. A weak inverse linear relationship existed between S-Zn and S-Cu. After adjustment for body mass index (BMI), smoking habit, alcohol consumption and blood biochemistry in a multiple linear regression model, the relationship of S-Cu (direct) and S-Zn (inverse) to age remained statistically significant.

Aged↗

PubMed1993

Aluminium content of infant formulas.

An investigation was undertaken in order to assess Al concentration levels in infant formulas. Eligibility criteria were defined and strictly adhered to. An overall strategy was worked out to guarantee reliability and representativity of experimental data, in particular by minimizing all possible sources of chemical contamination or loss. The study was carried out by means of Inductively-Coupled Plasma Atomic Emission Spectrometry (ICP-AES). In cow's milk-based infant formulas as made up for consumption (about 13% in the final solution), Al levels of between 0.03-0.85 mg/L were detected. Higher amounts were present in soya-based formulas, with concentrations ranging from 0.39 to 1.01 mg/L.

Aluminum↗

PubMed1993

Analytical problems in the quantification of elements in water bodies.

The main aspects of element analysis in natural waters are briefly surveyed. Particular attention is devoted to sampling, pretreatment and storage problems, as well as pitfalls, followed by a detailed discussion on the most flexible and powerful routine analytical techniques. A number of examples are also given to illustrate the major sectors of investigation presently being explored. Future trends and needs are finally outlined.

Fresh Water↗

PubMed1991

Outline of the ISS code for the classification of chemical substances for use in compiling a national inventory.

A coding system for categorizing all types of compounds was developed specifically as part of the National Inventory of Chemical Substances to be applied by the Istituto Superiore di Sanità (ISS) in order to comply with the EEC present legal provisions on chemicals in trade. A number of applications were also described to illustrate the coverage and the adaptability of the code.

Chemical Phenomena↗

PubMed1990

Reference values for essential and toxic elements in human milk.

Dependable reference values (RVs) for the concentration ranges of health-related elements in human biological fluids and organs are to date of acknowledged importance for an early recognition of pathological states. On the other hand, the present lack of reliable data on levels to be considered as baseline values for elements of major concern from a toxicological, environmental and nutritional point of view demands the development of experimental procedures capable of satisfying the requirements of detection power, specificity and applicability on a large scale necessary to generate vast amounts of reliable measurements. As part of an overall monitoring program, an investigation was undertaken with the following two aims: a) the present suitability of inductively-coupled plasma atomic emission spectrometry (ICP-AES) to identify and quantitate minor and trace elements in human milk with the necessary accuracy and precision; b) assessment of RV concentrations for Al, Ba, Cd, Cr, Cu, Fe, Li, Mg, Mn, Ni, Pb and Zn. Four population groups were selected (each with 9 subjects) resulting from the various combinations of smokers and non-smokers from an urban or a rural environment. Strict eligibility criteria were adopted in order to select only women in good health, no known occupational exposure and whose nutritional habits could be described in detail. A scrupolous and systematic approach was adopted to minimize every possible source of elemental contamination from the sampling step onwards. Digestion of samples was attempted both with mixtures of strong acids and by resorting to acid-assisted mineralization in a microwave oven. Both methods were satisfactory for subsequent introduction into the torch of the ICP-AES system. The outcome of this pilot study gave the following median RVs for concentration (in mg/kg): Al, 0.14; Ba, 0.013; Cd, 0.002; Cr, 0.016; Cu, 0.40; Fe, 0.72; Li, 0.004; Mg, 29.4; Mn, 0.006; Ni, 0.05; Pb, 0.016; and Zn, 3.08.

Female↗

PubMed1989

A pharmacokinetic study of high-dose continuous infusion cisplatin in children with solid tumors.

The pharmacokinetics of cisplatin were investigated in 14 patients, aged 10 months through 13 years who were affected by solid malignant tumors. High-dose cisplatin (40 mg/m2/d) was administered with repeated courses for five days as a continuous intravenous (IV) infusion. Total platinum (Pt) levels in plasma and urine and free (protein-unbound) Pt levels in plasma ultrafiltrate were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES). Areas under the concentration v time curve (AUCs) for mean total and free Pt levels were calculated for the 120-hour period of infusion and for the 384 and 120 hours following its completion, respectively. Half-lives of total and free Pt in plasma were calculated for the 216 hours following completion of infusion in five patients at their first course. The fraction of the administered Pt dose excreted in urine as Pt was determined for the five-day period of infusion and seven-day period after its completion. A total of 36 courses were studied. Maximum average Pt levels were reached after 120 hours of infusion: at the first course, 3.22 and 0.17 micrograms/mL for total and free Pt, respectively. Platinum levels declined according to a biexponential model, with initial half-lives of 18.3 and 16.9 minutes, and terminal half-lives of 81.9 and 59.0 hours as determined for total and free Pt, respectively. In the second and third courses studied there was a progressive increase in mean Pt plasma levels. Consequently, the free drug exposure as measured by AUC increased in all patients with repeated courses: 47.7% for the second and 124.4% for the third course, when compared with the first. At the same time, the mean fraction of the dose excreted in the urine for the 12-day period considered, was 44.1% for the first course, 36.2% for the second, and 28.4% for the third. The progressive enhancement of tissue exposure to the free cytotoxic drug, resulting from a reduced renal clearance of Pt with sequential courses of cisplatin, produced mainly increased toxicity while therapeutic effect progressively diminished.

Adolescent↗

PubMed1989

Selenium intake with diet in Italy: a pilot study.

Selenium is an element essential to man. The main environmental pathway of Se-exposure for the general population is through food. As is true for all essential elements, not only deficient but also excessive exposure results in adverse health effects. Between these extremes there is a range of safe and adequate Se intakes. In 1980 the Italian National Research Council recommended 50-200 micrograms/day as an interval adequate to meet nutritional requirements, being at the same time below the threshold of toxic effects. Therefore the evaluation of dietary Se intake has become very important. The purpose of this work is the estimation of dietary intakes of Se using data on the amount and composition of an average Italian diet. Complete meals from a factory canteen were analyzed and calculations of weekly intake of Se carried out. Analyses were performed by means of Inductively-coupled Plasma Atomic Emission Spectrometry. The results obtained, related to the average and indicative food consumption of Italian people, showed that the daily intake is well within the recommended range.

Diet↗