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Biomedical subjects

M Palumbo

Publications and source records attributed to M Palumbo.

At least 109 records · Page 6Linked to original sources
PubMed1991

Nerve root recovery in complete injuries of the cervical spine.

Thirty-six patients with complete quadriplegia were reviewed. Twenty-two underwent surgery, and 14 did not. There were 11 burst fractures and 3 extension fracture-dislocations, which were treated with anterior decompression and rigid plate fixation. There were 22 flexion injuries that were treated with posterior stabilization using Kirschner-wire tension band fixation, Harrington compression hooks, or Halifax laminar hooks. The non-operative group was treated with skeletal traction with skull tongs for 6-12 weeks followed by the application of a hard collar or halo vest for 3 months. Of the 22 patients who underwent surgery, 32% descended one level and 18% two levels. In the nonoperative group, only one patient descended one level. It is concluded that the heretofore pessimistic outlook regarding complete quadriplegia is unwarranted and that a more aggressive approach may result in a better functional outcome.

Adolescent↗
PubMed1990

Relevance of ionic effects on norfloxacin uptake by Escherichia coli.

The uptake of the quinolone drug norfloxacin by Escherichia coli was investigated at initial rate kinetics at different pH and monovalent/divalent metal ion concentration. The results support a simple diffusion mechanism for quinolone incorporation into cells. The uptake process decreases under acidic conditions. The presence of Na+ or K+ ions does not affect the results to an appreciable extent, whereas divalent ions cause a dramatic decrease in drug incorporation. The antibacterial activity, evaluated under identical experimental conditions, shows a direct relationship with the uptake data. As a general explanation for the above results it is suggested that the ability of the drug to penetrate into cells is a function of its net charge. The molecule in the zwitterionic form exhibits maximum permeation properties, whereas the uptake is remarkably reduced when the drug bears a net charge as a result of ionization or complex formation with bivalent ions. These results allow further insight into the mechanism of quinolone access to the intracellular compartment.

Biological Transport↗
PubMed1990

The effect of the minor groove binding agent DAPI (4,6-diamidino-2-phenyl-indole) on DNA-directed enzymes: an attempt to explain inhibition of plasmid expression in Escherichia coli [corrected].

The activity of DAPI, on a number of DNA-directed enzymes involved in DNA topology, transcription, replication and repair, is reported in this paper. DAPI was always more inhibitory than ethidium bromide, in particular against RNA polymerase and DNA ligase, which seemed to be specifically affected. While the effect on RNA polymerase is likely due to a preferential occupancy of the promoter region, that on DNA ligase could rely upon a mechanism of steric hindrance in the minor groove. These phenomena, independently from an alteration of the tertiary structure of DNA by the ligand, can account for the previously reported inhibition of plasmid expression in Escherichia coli.

DNA Ligases↗
PubMed1990

Photobiological activity of 3,4'-dimethyl-8-methoxypsoralen, a linear furocoumarin with unusual DNA-binding properties.

The furocoumarin derivative 3,4'-dimethyl-8-methoxypsoralen (DMe-8-MOP) exhibits remarkable antiproliferative activity, but is devoid of skin phototoxicity. To gain insight into this peculiar behaviour we investigated non-covalent and covalent binding of DMe-8-MOP to calf thymus DNA, along with DNA-synthesis inhibition and mutagenic activity. The non-covalent interaction of DMe-8-MOP with the nucleic acid is quite poor as shown by equilibrium dialysis, spectroscopic, chiroptical and hydrodynamic techniques. However, it exhibits relevant photobinding ability to DNA using both isolated nucleic acid samples and cellular systems. Unlike the large majority of congeners, DMe-8-MOP undergoes predominantly photochemical monoaddition to the double helical polynucleotide. Upon examination of the products obtained by enzymatic hydrolysis of DMe-8-MOP photomodified DNA, the formation of an unusual furan side adduct is proposed, which could account for the peculiar photochemical and photobiological properties of the 3,4'-dimethyl furocoumarin derivative.

Animals↗
PubMed1990

N-methylmitomycin A cross-linking to nucleosomal structure.

The cross-linking reaction of N-methylmitomycin A to 175-bp calf thymus nucleosomes and to reconstituted core particles having known DNA sequences was examined using gel-electrophoresis techniques. The nucleosome structure, as the CAP-DNA complex, leads to a decreased covalent binding in comparison to protein-free DNA, suggesting, in addition to sequence specificity, precise geometrical requirements for bifunctional covalent addition of the drug to the nucleic acid.

Animals↗
PubMed1990

[Study of the properties of condensed forms of the complexes of linear and supercoiled DNA with mitoxantrone and bisantrene].

The effect of anthrachinone and anthracene derivatives on linear and circular superstranded molecules of DNA in conditions of their condensation was studied. It was shown that the compounds formed strong intercalation complexes with the molecules of the linear and circular superstranded DNA when the DNA molecules were in the condensed condition. The optical properties of the disperse liquid crystal phases formed of the complexes of the investigated compounds with the molecules of linear double-chain DNA differed. Moreover, the optical properties of the condensed phases formed of the complexes of the compounds with the molecules of linear and circular superstranded DNA also differed. The causes of the differences are discussed.

Anthracenes↗
PubMed1990

Anti-cancer activity of anthracycline antibiotics and DNA condensation.

Light scattering techniques were used to investigate the ability of a number of anthracyclines to cause compaction in double-stranded DNA and nucleosomes at physiological ionic strength. The structurally organized polynucleotide was efficiently condensed by all of the drugs examined, while no appreciable aggregation of free double-stranded DNA is observed under the same experimental conditions. A model for the process is proposed. Our results suggest the lack of a direct relationship between the critical concentration of free drug at which condensation of DNA occurs and the cytotoxic and anti-cancer properties exhibited by the various anthracycline derivatives.

Antibiotics, Antineoplastic↗
PubMed1989

[Changes in the lymphocyte subpopulations in a patient with orthotopic transplant of the liver].

Earlier experimental studies have shown that the cyclosporin immunosuppressive effect (CsA) can be modulated by drug timing as well as dose. More specifically treatment during the night was constantly associated with a statistically significant improvement in the prevention or delay of allograft rejection. The present study reports on the circadian variations in T-lymphocyte subpopulations in the peripheral blood of a patient given an orthotopic liver allograft and treated with CsA and steroids. In particular, a statistically significant circadian rhythm (p = 0.012) was observed for the T-helper (OKT4) subset with a peak time (acrophase) occurring during the night at 4:27 A.M. In this patient, CsA treatment was, therefore, adapted to the T-helper cycle with the aim of marching CsA blood level variations to that curve. The results suggest that CsA timing can provide a tool for daily dose reduction and then improve the success rate of drug treatment.

Antigens, Surface↗
PubMed1989

Diethylaminopropionamido-hydroxy-anthraquinones as potential anticancer agents: synthesis and characterization.

A number of new 9,10-anthracenediones were obtained, bearing one or two hydroxyl groups and one positively charged side chain at different positions of the aromatic ring system (compounds 1-5 in Chart 1). These derivatives resemble the anticancer agents mitoxantrone and ametantrone. The synthesis started from dihydroxy- or amino-hydroxy-9,10-anthracenediones, which were converted into the nitro-derivatives. After reduction to the corresponding amines and acylation with 3-chloropropionyl chloride, substitution with diethylamine led to the final diethylaminopropionamido derivatives. The new anthracenediones cause a quite relevant inhibition of cell growth in vitro and will be tested as possible anticancer agents.

Anthraquinones↗
PubMed1988

Pyrrolocoumarin derivatives: DNA-binding properties.

The spectroscopic and DNA-binding properties of a number of pyrrolocoumarin derivatives, including linear tricyclic, angular tricyclic, linear tetracyclic and angular tetracyclic compounds were investigated. The compounds we examined form non-covalent complexes with duplex DNA, probably of the intercalation type. The binding constants are comparable with the constants found for the furocoumarin analogues. Although for some of the compounds the photoreactivity with DNA is comparable with that of 8-MOP, pyrrolocoumarins behave as monofunctional reagents. This fact is explained in terms of an increased delocalization of the 4',5' double bond in the pyrrole moiety. Denaturation-renaturation experiments and HPLC analysis of the photoadducts confirm that pyrrolocoumarins are essentially monofunctional DNA-photobinding agents.

Coumarins↗
PubMed1988

A further insight into the mechanism of action of anthracycline antibiotics.

The uptake of Adriamycin (ADM) by eucaryotic and procaryotic cells and the interaction of the antibiotic with structurally organized DNA were investigated. The aim of this work was to understand why ADM is endowed with very low antibiotic activity in spite of being highly cytotoxic for mammalian cells, and to get a further insight into the mechanism of action of this compound. Spectrophotometric, fluorometric, chiroptical, and electron microscopic techniques were used. The drug was shown to concentrate in mammalian cells but failed to do so in bacteria and penetrated rather poorly in Candida albicans. The chromatin binding affinity of ADM appeared to be substantially reduced with respect to the affinity for free DNA. Complex stereochemistry was also influenced by the presence of nucleosomal arrangements in the polynucleotide. In addition, evidence was obtained that the antibiotic tended to accumulate at specific (linker) chromatin regions and to cause extensive compaction of organized DNA. The observed phenomena may play a relevant role in the mode of drug action in eucaryotic cells and help to explain the lack of antibacterial activity by ADM in spite of the apparent attainment of great enough intracellular levels to affect DNA template function.

Bacteria↗
PubMed1987

Bis-substituted hydroxy-anthracenediones: DNA binding and biological activity.

Three new hydroxy-9,10-anthracenedione derivatives (compounds 1-3 in Figure 1), bearing two charged or polar side chains at positions 2 and 4/5 of the tricyclic system, have been investigated for their DNA binding, cytotoxic and genotoxic activity. The interaction mode with nucleic acids is intercalative for compounds 1 and 2, while external and intercalative binding probably coexist for compound 3. Complexation of the nucleic acid occurs in all cases in a cooperative manner, so that drug binding favours further binding to double helical DNA. The scale of the intrinsic binding constant is discussed in terms of the nature and position of the side chain. Cell growth and DNA synthesis inhibition data match quite well with DNA affinity. Alkaline elution experiments show a correlation between drug cytotoxicity and DNA damage. Our results indicate that the position and number of OH groups, as well as of charged side chains, play an important role in modulating drug affinity for DNA and the consequent biological effects.

Anthraquinones↗
PubMed1986

Structural properties of hyaluronic acid in moderately concentrated solutions.

The solution properties of hyaluronic acid having various d.p. values have been examined at physiological pH and ionic strength by light-scattering techniques at various concentrations. The angular dependence of Kc/R0 was linear at low concentrations, whereas substantial curvature was present at small angles on increasing the concentration. This phenomenon was affected by the conditions of centrifugation. Moreover, the function Kc/R0 exhibited a maximum value at concentrations of polymer inversely related to the molecular weight. The maximum concentration was always higher than the critical concentration. Ageing, molecular-weight distribution, and polymer purity influenced the light-scattering response. A model is proposed in which the polysaccharide chains intertwine at relatively low concentrations of polymer and become entangled at high concentration, eventually leading to a non-homogeneous polymer network.

Animals↗