Biomedical subjects

P Cozzi

Publications and source records attributed to P Cozzi.

39 records · Page 3Linked to original sources

PubMed1977

New broad-spectrum alkylthio cephalosporins.

A series of 7-substituted alkyl-thio-acylaminocephalosporins with the following general formula were prepared and tested for in vitro antibacterial activity: (formula: see text). We tried in our research to find any relationship between antibacterial activity and pharmacokinetic properties on the one hand, and chemical structure on the other. The most interesting products were also studied for their in vivo antibacterial activity in experimental acute systemic infections in the mouse.

Animals↗

PubMedDate not supplied

A new class of cytotoxic DNA minor groove binders: alpha-halogenoacrylic derivatives of pyrrolecarbamoyl oligomers.

DNA minor groove binders represent a class of cytotoxic antitumor agents whose DNA sequence specificity may lead to a high selectivity of action. Tallimustine, benzoyl nitrogen mustard derivative of distamycin A, showed excellent antitumor activity in preclinical tests but also a severe myelotoxicity. Novel nitrogen mustard derivatives of distamycin showing improved activity profile were recently identified. In particular, cinnamic nitrogen mustard and cinnamic ethyl half-mustard analogs of tallimustine showed increased potency and more favorable cytotoxicity/myelotoxicity ratio. However a series of alpha-halogenoacrylamido derivatives of distamycin-like frames showed an activity profile substantially improved in comparison to tallimustine. In particular PNU-166196, alpha-bromo-acrylamido derivative of four pyrrole distamycin-like frame ending with a guanidino moiety, showed high cytotoxic potency even on tumor cell lines resistant to alkylating agents and camptothecin, broad antitumor activity and myelotoxicity dramatically reduced in comparison to tallimustine. This compound was found to bind to minor groove TA-rich sequences but appeared unreactive in classical in vitro DNA alkylation assays. With respect to the apparent lack of DNA alkylation we speculated that an intracellular reactive nucleophilic species, e.g. glutathione (GSH), could activate the reactivity of the compound leading to alkylation of DNA in vivo. Recent evidence of both covalent interaction of PNU-166196 with plasmidic DNA in the presence of GSH and of enhanced cytotoxicity in tumor cells characterized by high levels of GSH were obtained. PNU-166196, in view of its excellent activity profile and its outstanding favorable cytotoxicity/myelotoxicity ratio, was selected for clinical development and is undergoing phase I studies.

Acrylamides↗

PubMedDate not supplied

Incidence of sepsis in central venous catheter-bearing patients with hematologic malignancies: preliminary results.

BACKGROUND: Indwelling central venous catheters (CVCs) are essential devices in the management of patients with hematological disorders treated with chemotherapy. However, their nature predisposes patients to unwanted complications. METHODS: CVC-related complications were retrospectively analyzed in 227 hematologic patients who were consecutively admitted to our hematology department between May 2002 and April 2004. Patients' diagnoses comprised acute myeloid leukemia (36.8%), acute lymphoid leukemia (7.3%), lymphoproliferative disorders (28.3%), multiple myeloma (19.5%), myeloproliferative syndromes (5%) and others (3.1%). The CVCs used were polyurethane three lumen 7-Fr (111 patients) for chemotherapy and 12-Fr (114 patients) for chemotherapy and peripheral blood stem cell apheresis, plus two tunneled catheters. RESULTS: The pathological events were: bacteriaemias (n=46); occlusions (n=10); exit tunnel infections (n=8); thrombosis (n=6); lung emboli (n=2). Among febrile patients the bacteriemia frequency was 20%, of which 13.6% were CVC-related (with a higher incidence in leukemia patients (p=0.027). Among the isolates, gram-positive bacteria were found in 29 cases (23 CVC-related cases), and gram-negative bacteria in 16 cases (8 CVC-related cases). Only one patient had Candida albicans sepsis. At univariate and multivariate analysis significant risk factors for infection (p<0.0001) were only the number of days/catheters and neutropenia duration. CONCLUSIONS: In our hematologic patients, the CVC complications were mainly septic, with only 10.1% of CVC-related bacteriemias, despite prolonged catheterization duration. Acute leukemia patients were at major risk for sepsis, probably due to a more severe neutropenia and prolonged catheterization duration.

Journal Article↗