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Biomedical subjects

M Palumbo

Publications and source records attributed to M Palumbo.

At least 127 records · Page 7Linked to original sources

Clinical comparative study on the activity of cefamandole in the treatment of serious staphylococcal infections caused by methicillin-susceptible and methicillin-resistant strains.

Ninety-two microbiologically documented staphylococcal infections were treated with cefamandole in an open comparative study on the clinical efficacy of this cephalosporin in the therapy of infections caused by both methicillin-susceptible and methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus spp. The majority of the episodes (86 of 92) were treated with cefamandole alone, and six were treated with cefamandole in association with other antibiotics. In the evaluable S. aureus infections, 34 of 46 (73.9%) due to methicillin-susceptible strains and 12 of 16 (75%) due to methicillin-resistant strains responded to therapy. In particular, among the patients infected by methicillin-susceptible S. aureus 6 of 9 cases of septicemia, 0 of 2 cases of endocarditis, 2 of 2 cases of pneumonia, 2 of 3 osteoarticular infections, 8 of 12 cases of peritonitis in patients with chronic renal failure in continuous ambulatory peritoneal dialysis (CAPD), 13 of 15 skin-soft tissue infections, and 3 of 3 urinary tract infections responded to therapy. Among those due to methicillin-resistant strains, cure was achieved in 2 of 4 cases of septicemia, 0 of 1 case of endocarditis, 9 of 10 skin-soft tissue infections, and 1 of 1 urinary tract infection. In the evaluable infections caused by coagulase-negative staphylococci, 9 of 11 (81.8%) due to methicillin-susceptible and 15 of 17 (88.2%) due to methicillin-resistant strains responded to therapy. In particular, among patients infected by methicillin-susceptible, coagulase-negative staphylococci, 4 of 4 cases of septicemia, 0 of 1 case of endocarditis, 1 of 1 case of pneumonia, 1 of 1 case of peritonitis in CAPD, 2 of 3 infections of skin-soft tissue, and 1 of 1 urinary tract infection responded to therapy. Among patients infected by methicillin-resistant, coagulase-negative staphylococci were cured 5 of 6 cases os septicemia, 6 of 6 cases of peritonitis (in CAPD), 4 of 4 infections of skin-soft tissue, and 0 of 1 urinary tract infection.

Adult↗

Adult polycystic liver disease in childhood. A case report.

A case of adult type polycystic liver disease in a child is reported. The entire right hepatic lobe was involved whereas the left lobe was normal. Spleen, kidneys and pancreas did not show cystic alterations. Diagnostic examinations and histologic findings are illustrated. The patient underwent right hepatectomy. The adult and childhood types of congenital polycystic liver disease are discussed.

Cysts↗

Antitumor activity of new anthraquinone derivatives.

Seven new 9,10-anthracenedione derivatives bearing positively-charged side chains at different positions of the condensed ring system have been investigated in their interaction with DNA and their biological effects, including antitumor activity in the P 388 mouse miniscreen. The drug's affinity for DNA was found to be related to the efficacy of inhibition of cell growth and nucleic acid synthesis for a number of cell lines. Moreover, alkaline elution experiments showed a close relationship between mutagenic potential and cytotoxicity. With the exception of one, all compounds behaved like intercalating agents, as shown by the unwinding of supercoiled plasmid DNA. DNA appeared, therefore, to be the more important target for drug action. The marginal in vivo activity shown by two substances in this series suggests a number of possible structural modifications which may increase their therapeutic efficacy.

Animals↗

A search for potential antitumor agents: biological effects and DNA binding of a series of anthraquinone derivatives.

In an effort to establish a relationship between mechanism of binding and affinity to DNA, cytotoxic activity, and genotoxic activity, we have studied four new anthracenedione derivatives bearing charged side chain groups at various positions of the polycyclic aromatic system. Cytotoxicity, genotoxicity, and thermodynamic DNA binding parameters were shown to be directly related, indicating the polynucleotide as an important target for drug action, rather than a minor, subterminal interacting site. This finding was further supported by the observation of extensive anthraquinone accumulation occurring in the nuclear compartment. The relative binding affinities of the drugs are discussed in terms of nature and position of side-chain substituents. Different binding modes were found: three compounds intercalate into the nucleic acid double helix, and one interacts with the exterior of the macromolecule. The biological results suggest that the mode of complex formation plays a less relevant role than DNA binding efficiency.

Animals↗

Conformational state of lacrimal proteins adsorbed on contact lenses.

A circular dichroism study has been performed to investigate the conformational properties of lysozyme adsorbed onto new and worn hydrophilic contact lenses. Whereas the native state of the protein is retained immediately after adsorption, lysozyme appears to be substantially denatured in worn lenses. These findings support the hypothesis of an immune response, due to lysozyme denaturation, for reported eye diseases in contact lens wearing patients. Regeneration processes to remove adsorbed proteins leave on the lens traces of potentially noxious materials. A reasonably frequent lens replacement is accordingly recommended.

Adsorption↗

Photobiological properties of some water-soluble 5-MOP and 8-MOP derivatives.

The photobiological properties of a number of water-soluble psoralen derivatives have been investigated. The compounds are characterized by the presence of protonated diethylaminoalkyloxy side-chains at position 5 or 8. Thus they are strictly related to the photochemotherapeutic agents 5-MOP and 8-MOP. Inhibition of DNA synthesis by the above compounds has been evaluated in mouse skin in vivo and in Ehrlich ascites tumor cells. In the latter experiments, inhibition of tumor transmitting capacity has been demonstrated by injection of irradiated cells into healthy animals. Finally, skin erythema formation has been studied in albino guinea pigs. The photobiological responses were quite remarkable in all cases. In general, derivatives at position 5 exhibit stronger antiproliferative effects, while the 8 isomers display higher skin phototoxicity.

5-Methoxypsoralen↗

DNA-binding of water-soluble furocoumarins: a thermodynamic and conformational approach to understanding different biological effects.

The interaction of two water-soluble furocoumarins, 8-(omega-diethyl aminopropyloxy)psoralen hydrochloride (I) and its 5-isomer (II), with DNA has been investigated by spectroscopic, equilibrium dialysis, hydrodynamic and chiroptical techniques. Both compounds intercalate into the polynucleotide double helix. From the dependence of the binding on ionic strength, ion release and binding free energy corrected for counterion release have been quantitatively estimated. It is shown that the differences in DNA-affinity observed for compounds I and II arise primarily from non electrostatic contributions. The binding process is exothermic, with slightly different van't Hoff enthalpies for the examined furocoumarins. Helix lengthening and dichroic effects indicate different intercalation geometries for the isomeric compounds. These studies allow a possible explanation for the finding that isomer I exhibits largely better DNA-photobinding properties, while isomer II is by far more effective as an antiviral agent.

Animals↗

Antiviral properties of psoralen derivatives: a biological and physico-chemical investigation.

Two isomeric psoralen derivatives (I and II in Fig. 1) bearing charged side chains, have been tested for activity against Herpes Simplex Virus type 1 (HSV-1) in the absence of u.v. irradiation. Striking differences have been observed both in antiviral and cytotoxic activity for the examined compounds, I being appreciably more effective. Metabolic and biochemical studies, as well as physico-chemical measurements indicate DNA as the major target. The different biological behaviour can be fully explained in terms of a modified affinity of the drugs toward DNA. The molecular basis for these findings probably stems from slightly different intercalation geometries, as shown by chiroptical studies. Comparable binding affinities for viral and cellular DNA fully account for lack of selective toxicity found in vivo. The present approach is proposed as a tool for the investigation of structure-function relationships in drug models.

Animals↗

New anthracenedione derivatives: interaction with DNA and biological effects.

Two anthracenedione derivatives [1 - (omega - diethylaminopropylamido) - 4 - hydroxy - 9,10 - anthracenedione hydrochloride (I) and 1 - (omega - diethylaminopropylamido) - 2 - methoxy - 4 - hydroxy - 9, 10 - anthracenedione hydrochloride (II)], having an electron-rich planar chromophore and an amino-substituted side chain, have been synthesized. Their binding ability to DNA was investigated by means of spectroscopic, equilibrium dialysis and fluorescence measurements. Their inhibition efficiency on nucleic acid synthesis was also evaluated both in mouse and human cells. Our results indicate that, in comparison with adriamycin, compound I shows a slightly weaker complexation ability to DNA, while compound II interacts with DNA at a substantially lower level. These data match quite well with the biological response on the inhibition of DNA and RNA synthesis exhibited by the above mentioned compounds; in fact compound I is slightly less efficient than adriamycin and about ten times more efficient than compound II. The close relationship between the results of physicochemical and biological studies is discussed.

Animals↗