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Biomedical subjects

L Polo

Publications and source records attributed to L Polo.

15 recordsLinked to original sources
PubMed2000

Polylysine-porphycene conjugates as efficient photosensitizers for the inactivation of microbial pathogens.

Porphycenes are electronic isomers of porphyrins which, when neutral, display no appreciable photosensitizing action towards Gram-negative bacteria. The covalent binding of oligomeric polylysine moieties, which are cationic at physiological pH values, endows porphycenes with a significant phototoxic activity against Gram-negative bacteria while retaining their photoefficiency against a variety of microbial pathogens, including Gram-positive bacteria, fungi and mycoplasmas. The effect of the polylysine moiety is dependent on both the polylysine concentration and the degree of oligomerization. A suitable interplay among the various parameters opens the possibility to obtain either a broad spectrum of antimicrobial activity or a selective action toward a specific pathogen while minimizing the damage to human fibroblasts.

Anti-Bacterial Agents↗
PubMed1999

Role of ground and excited singlet state oxygen in the red light-induced stimulation of Escherichia coli cell growth.

Irradiation of selected Escherichia coli defective strains with red-light induces a stimulation of the cell growth rate. Such effect is wavelength-dependent and is accompanied by a transient increase of the cell volume and some enzymic activities. The presence of oxygen appears to be essential for the occurrence of a significant photostimulatory effect. The results obtained upon irradiation in the presence of quenchers (tryptophan, histidine, azide) or enhancers (deuterium oxide) of singlet oxygen (1O2) strongly suggest that this activated oxygen derivative is generated by excitation of endocellular chromophores (possibly cytochromes). The reaction of 1O2 with nearby cellular targets could induce a sublethal cell damage which in turn promotes an accelerated cell metabolism.

Azides↗
PubMed1999

Photochemical and pharmacokinetic properties of selected flavins.

Some photochemical and pharmacokinetic properties of riboflavin, lumiflavin and the 2',3',4',5' tetraacetyl, tetrapropionyl, tetrabutiryl and tetrapalmitoyl esters of riboflavin have been studied. The esters are considerably more photostable than riboflavin but less so than lumiflavin, and appear to be photosensitizers with a behaviour similar to that of riboflavin, promoting photoreactions of biological targets even in the absence of molecular oxygen. The various flavins display important differences in their pharmacokinetic behaviour. Riboflavin, lumiflavin and the short-chain esters (the acetyl and propionyl esters) are rapidly cleared from serum, and recovered in comparable amounts from the liver and kidneys. These results are in agreement with their hydrophilic or moderately hydrophobic character. In contrast, the longer-chain butiryl and palmitoyl esters exhibit a prolonged retention in serum and undergo a significantly larger accumulation in the liver as compared with the kidneys; they are also found in the spleen. In all cases the tissue uptake of these esters becomes appreciable only after 24 h. These results are coherent with the highly hydrophobic character of these esters, which induce a slow release from serum lipoproteins and have a preferential clearance via the bile-gut pathway, showing affinity for the components of the reticuloendothelial system. These long-chain riboflavin esters will probably have a greater and more persistent risk of photoinduced hepatotoxicity than riboflavin, lumiflavin and the short-chain esters.

Animals↗
PubMed1997

Effects of heparin on the electrophysiological and mechanical properties of early embryonic chick hearts.

The effect of heparin (1-200 microg/ml) on several functional properties of 4-day-old embryonic hearts was studied. Intracellular recordings either from cells of the atrium, the atrio-ventricular canal or the ventricle were made on the isolated and perfused hearts. In all impaled myocardial cells, heparin produced an increment in the maximal rate of rise and amplitude of the action potentials and the duration was slightly diminished. In addition, heparin provoked a reduction in the spontaneous beating frequency, while the electrical excitability and the conduction velocity of the atrium and the ventricle were increased. The measurements of atrio-ventricular latency revealed that it was diminished, i.e. the propagation of impulses through the atrio-ventricular canal was improved. Simultaneously with these changes, heparin incremented the amplitude of contraction of either the atrium or the ventricle importantly.

Animals↗
PubMed1997

Effects of low power laser-irradiation on differential blood count and body temperature in endotoxin-preimmunized rabbits.

Low power laser irradiation has been shown to have various immune-modulatory effects under in vitro conditions but little is known about such effects in animal models. Escherichia coli endotoxin-preimmunized rabbits were used to determine the influence of transcutaneously applied low power laser light on differential blood count and rectal temperature. After three initial immunizations animals were either boostered with 5 ng/kg of endotoxin or injected with pyrogen-free saline and subsequently underwent irradiation using two different wavelengths of red laser light and sham irradiation, respectively. Differential blood count of laser-treated animals was characterized by significantly higher lymphocyte values and lower neutrophil values at twenty hours (boostered rabbits) and twenty-three hours (non-boostered rabbits) after irradiation. Differential blood cell counts returned to baseline values within 23 hours in the boostered animals, whereas in the non-boostered rabbits lymphocytes showed a trend to further increase. Recording of rectal temperature revealed a further rise after laser application, changes being of greater magnitude and longer duration in the non-boostered animals. These results seem to indicate that a single low power laser irradiation can modulate immune-responses depending on the immunological status of the organism.

Animals↗
PubMed1996

Liposome-delivered 131I-labelled Zn(II)-phthalocyanine as a radiodiagnostic agent for tumours.

131I-Zn(II)-phthalocyanine (ZnPc) incorporated into unilamellar liposomes has been systemically injected to mice bearing a transplanted MS-2 fibrosarcoma. Biodistribution studies show that the pharmacokinetic behaviour of 131I-ZnPc is very similar to that defined for the parent molecule ZnPc including a serum half-life of ca. 12 h, a high recovery from liver and spleen and minimal accumulation in kidney and brain. The most important pharmacokinetic parameter is represented by the high tumour/ muscle ratio of 131I-ZnPc concentration (ca. 9 at 24 h post-injection). These results suggest the possible use of the radiolabelled derivative for a real-time non-invasive monitoring of the ZnPc concentration in the tumour and peritumoural tissue during photodynamic therapy.

Animals↗
PubMed1995

Effect of the delivery system on the biodistribution of Ge(IV) octabutoxy-phthalocyanines in tumour-bearing mice.

The pharmacokinetic properties of the Ge(IV)-octabutoxy-phthalocyanines (GePc) with two axially ligated triethylsiloxy (GePcEt) or trihexyl-siloxy (GePcHex) chains were studied in BALB/C mice bearing a transplanted MS-2 fibrosarcoma. The GePcs were delivered to mice after incorporation into unilamellar liposomes of dipalmitoyl phosphatidylcholine (DPPC) or in an emulsion of Cremophor-EL. The Cremophor delivered GePcs were cleared from the blood circulation at a much slower rate than the liposome-delivered GePcs. At the same time, Cremophor induced a slower and reduced uptake of the GePcs in the liver and spleen while it greatly enhanced the uptake in the tumour as compared to liposomes. Maximum tumour uptake was observed at 24 h post-injection and was equivalent to 0.67 and 0.50 nmol/g, respectively, for the Cremophor delivered GePcHex and GePcEt. The corresponding values for the liposome-delivered drugs were approximately one fourth of that observed with Cremophor.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1995

Effect of axial ligation and delivery system on the tumour-localising and -photosensitising properties of Ge(IV)-octabutoxy-phthalocyanines.

Four Ge(IV)-octabutoxy-phthalocyanines (GePcs) bearing two alkyl-type axial ligands were assayed for their pharmacokinetic properties and phototherapeutic efficiency in Balb/c mice bearing an intramuscularly transplanted MS-2 fibrosarcoma. The GePcs were i.v. injected at a dose of 0.35 mumol kg-1 body weight after incorporation into either Cremophor emulsions or small unilamellar liposomes of dipalmitoyl-phosphatidylcholine (DPPC). Both the nature of the delivery system and the chemical structure of the phthalocyanine were found to affect the behaviour of the GePcs in vivo. Thus, Cremophor-administered GePcs invariably yielded a more prolonged serum retention and a larger association with low-density lipoproteins (LDLs) as compared with the corresponding liposome-delivered phthalocyanines. This led to a greater efficiency and selectivity of tumour targeting. These effects were more pronounced for those GePcs having relatively long alkyl chains (hexyl to decyl) in the axial ligands. Maximal tumour accumulation (0.67 nmol per g of tissue) was found for Ge-Pc(hexyl)2 at 24 h after injection. Consistently, the Ge-Pc(hexyl)2, administered via Cremophor, showed the highest phototherapeutic activity towards MS-2 fibrosarcoma.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1995

Unusually high affinity of Zn(II)-tetradibenzobarrelenooctabutoxy-phthalocyanine for low-density lipoproteins in a tumor-bearing mouse.

An important factor in determining the efficacy of photosensitizing compounds in photodynamic therapy of tumors is the level to which tumors take up the photosensitizers after systemic injection. This parameter seems to be related to the transport modalities of the photosensitizer in the bloodstream. In this work the photosensitizer Zn(II)-tetradibenzobarrelenooctabutoxyphthalocyanine was shown to have an unprecedentedly high association with low-density lipoproteins (71% of the phthalocyanine in the plasma) when delivered in Cremophor micelles to tumor-bearing mice. This was accompanied by a particularly high tumor uptake at 24 h post-injection.

Animals↗
PubMed1992

The distribution of the tumour photosensitizers Zn(II)-phthalocyanine and Sn(IV)-etiopurpurin among rabbit plasma proteins.

Zn-phthalocyanine (ZnPc) and Sn-etiopurpurin (SnET2) incorporated in unilamellar liposomes or solubilized in a Cremophor-EL emulsion have been incubated in vitro with rabbit plasma or intravenously administered to rabbits. Ultracentrifugation and chromatographic analysis of the plasma showed that ZnPc and SnET2 are mainly released to lipoproteins; within the lipoprotein family, both dyes are preferentially bound by low-density (LDL) and high-density (HDL) lipoproteins. The amount of dye bound with these two lipoprotein classes was related to their relative concentration in the plasma; in most cases a larger amount of photosensitizer was bound to HDL as compared to LDL on a protein concentration basis.

1,2-Dipalmitoylphosphatidylcholine↗