Search PubMed⌕ Search

Biomedical subjects

F Petrucci

Publications and source records attributed to F Petrucci.

At least 37 records · Page 2Linked to original sources

[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↗

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↗

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↗

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↗

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↗

Clinical, analytical and pharmacokinetic aspects in cancer chemotherapy with platinum coordination compounds.

A survey of investigations performed by our group over the last few years whose goal was to obtain analytical, clinical and pharmacokinetic data concerning cancer chemotherapy with Pt-based drugs is reported. From this standpoint the use of inductively coupled-plasma atomic emission spectrometry for determining Pt levels in biological samples is discussed, particularly as regards: 1) the amelioration of sample introduction procedures into the torch in the case of micro-sampling and 2) the investigation of plasma drug distribution by means of liquid chromatography techniques. Clinical studies evaluated therapeutic response and toxicity during regional and systemic treatments with Cisplatin and Carboplatin against solid tumors in adults as well as in children. Several pharmacokinetic parameters such as plasma half-lives for free and protein-bound drug, tissues exposure as determined by AUC and urinary excretion are examined.

Adolescent↗

Occupational exposure to antiproliferative drugs in health care workers.

A survey is presented of the information available on the occupational hazard caused by exposure to anticancer drugs. Emphasis is laid on the need for stricter and safer measures to protect the sanitary personnel, who should also be constantly and thoroughly informed on the risk run when manipulating antiproliferative agents. Possible strategies for effectively preventing occupational diseases in this field are finally outlined.

Abnormalities, Drug-Induced↗

Relaxin: a mammotropic hormone promoting growth and differentiation of the pigeon crop sac mucosa.

The pigeon crop sac is responsive to local administration of mammotropic hormones independently of systemic hormonal influences. We showed previously in mice that relaxin promotes growth of the mammary gland only after pre-treatment with estrogen. In this study we investigated whether relaxin, locally administered, has a stimulatory effect without estrogen pre-treatment. The results of this study show that relaxin stimulates the crop sac mucosa causing changes in its gross appearance and histological modifications indicating enhanced growth and differentiation of the mucosal epithelium. The effects of relaxin are dose-related, as demonstrated by the increases of the wet and dry weights, the [3H]thymidine and [3H]uridine uptakes of the mucosa, and the histochemically detectable DNA content of the mucosal epithelium. These results strengthen the idea that relaxin should be included in the list of mammotropic hormones.

Animals↗

Determination of Pt in biological samples by inductively coupled plasma atomic emission spectrometry (ICP-AES) with electrothermal vaporization (ETV).

An electrothermal sample vaporization device was combined with an inductively coupled plasma spectrometer for the determination of Pt in biological samples (serum, urine, tissues). A commercial graphite furnace for atomic absorption was connected to an ICP torch using an electrically heated quartz tube. The argon gas stream was slightly modified. Sample aliquots up to 100 microL were dried at 120 degrees C, ashed at 1400 degrees C and subsequently heated to 2700 degrees C. The aerosol obtained was transported into a 2.2 kW argon ICP by means of a carrier gas flowing at 1.4 L/min. The detection limit was found to be 0.25-0.5 micrograms/L, depending upon the matrix. These values are one order of magnitude better than those obtained using conventional nebulizers. The precision (RSD) at 50 micrograms/L ranged from 0.04 to 0.07 and the accuracy (evaluated as recovery) was 103.2% to 105.3%. Because the matrix effects could not be neglected, different calibration curves were prepared for each kind of medium. The analytical capabilities of the method described were found to be suitable for the determination of Pt used in routine monitoring during chemotherapy with Cisplatin and other Pt-based compounds.

Hot Temperature↗

Chemotherapeutic agent cisplatin monitoring in biological fluids by means of inductively-coupled plasma emission spectrometry (ICP-AES).

The antitumoral agent cis-diamminedichloroplatinum (II) was administered at doses of 40 mg m-2 body surface area daily for 5 days via continuous i.v. infusion in association with etoposide (VP-16-213). The Pt concentration in serum up to 30 days from the beginning of the therapy was monitored by inductively-coupled plasma emission spectrometry. Results lead to two main conclusions: the analytical technique employed is suitable for measurements of Pt in biological fluids with the necessary precision (0.95-2.5%), accuracy (recovery 98.5-101.7%) and detection power (0.002-0.004 mg/l); there were effective Pt plasma concentrations for a greater length of time (with peak value 2.0 mg/l towards the end of treatment) than those achieved by other therapies so far adopted. On the other hand, toxic side effects, in particular gastrointestinal toxicity, myelosuppression and nephrotoxicity, were found to be not worse than those generally caused by the administration of the chemotherapeutic compound at lower doses. Both aspects were deeded to be essential prerequisites for better exploiting the drug's effectiveness.

Body Fluids↗

The local administration of relaxin induces changes in the microcirculation of the rat mesocaecum.

The clinical improvement of Raynaud's disease during pregnancy has been attributed to the increased relaxin (RLX) level in blood. Therefore we investigated the effect of topical porcine RLX (NIH-RXN-Pl) on the microcirculation of the mesocaecum of Wistar male rats, under direct microscope observation as judged by two observers. The hormone was applied locally to avoid systemic interferences either alone or after norepinephrine (NE) and promethazine (PM). The drugs were coded and the results were recorded independently by two observers. Porcine RLX induced rapid dilatation of the veins of the rat mesocaecum in a dose-related manner. The arteriolas and capillary flows were unchanged, while the venular flow was progressively reduced. The observed effects were sustained and disappeared with tissue wash-out. The RLX effects were reversed by addition of NE; conversely high doses of RLX were able to oppose the NE and PM vasospasm. We conclude that the local administration of RLX influences the microcirculation, possibly through an action on the smooth muscle of the venulae. The effects seems antagonistic with those of NE and PM.

Administration, Topical↗