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Biomedical subjects

I Freitas

Publications and source records attributed to I Freitas.

At least 19 recordsLinked to original sources
PubMed1998

Tumor microcirculation and its significance in therapy: possible role of omega-3 fatty acids as rheological modifiers.

Despite the great efforts to find new drugs or devices to suppress cancer cells, attempts to modify microcirculation and therefore the state of tumor cells and their surrounding normal tissues have not been given the attention they deserve. Solid tumors are composed of highly heterogeneous populations of malignant, stromal and inflammatory cells in a continuously adapting extracellular matrix. All of the above components interact and regulate each other to produce distinct microenvironments within the tumor mass. Abnormal microcirculation plays a particular role in the maintenance of this anomalous condition and favors the formation of metastasis, but on the other hand provides the therapist with an important site for intervention. In this brief overview we attempt to outline three aspects: (a) how the anomalous tumor blood flow provokes the nonuniform distribution of oxygen and nutrients within the tumor mass, thus determining different responses to the various cancer therapies; (b) how hemorheology is the clinical parameter most easily modified and (c) how omega-3 essential fatty acids are natural drugs that could be used in this sense beyond their antitumoral properties.

Animals↗
PubMed1996

Lysosomal exocytosis induced by hyperthermia: a new model of cancer death. III. Effect on liver metastasis.

The purpose of the present study was to evaluate by morphological approaches (light and electron microscopy), the effect of hyperthermic treatment in one case of human liver metastasis. The results demonstrate that hyperthermia causes a significant reduction of the metastatic cells circulating into sinusoids and the "normalization" of the hepatocytes substructure. The data are consistent with a direct and/or indirect action of the temperature on the presence of infiltrating tumor cells. Particular importance is attributed to a general activation of lysosomes present in neoplastic cells, Kupffer cells and hepatocytes.

Cell Death↗
PubMed1994

Quantitative comparison between the gel-film and polyvinyl alcohol methods for dehydrogenase histochemistry reveals different intercellular distribution patterns of glucose-6-phosphate and lactate dehydrogenases in mouse liver.

The precise histochemical localization and quantification of the activity of soluble dehydrogenases in unfixed cryostat sections requires the use of tissue protectants. In this study, two protectants, polyvinyl alcohol (PVA) and agarose gel, were compared for assaying the activity of lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G6PDH) in normal female mouse liver. Quantification of enzyme activity was determined cytophotometrically in periportal (PP), pericentral (PC) and midzonal (MZ) areas. No coloured reaction product was present in PVA media after the incubation period. In contrast, the agarose gels appeared to be highly coloured after incubation. As a consequence, sections incubated with gel media were less intensely stained than those incubated in PVA-containing media. The specific G6PDH reaction (test minus control) yielded approximately 75% less formazan in sections incubated by the agarose gel method than with the PVA method. Further, the amount of formazan deposits attributable to G6PDH activity was highest in the midzonal and pericentral zones of the liver lobule with PVA media, and Kupffer cells could be discriminated easily because of their high G6PDH activity. Significant zonal differences or Kupffer cells could not be observed when agarose gel films were used for the detection of G6PDH activity. The LDH localization patterns appeared to be more uniform after incubation with both methods: no significant differences in specific test minus control reactions were seen between PP, PC and MZ. However, less formazan production (33%) was detected in sections incubated with agarose gels when compared with those incubated with PVA media.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Tumor angiogenesis: evidence of new blood channels from plasma infiltrations.

Stroma formation in Ehrlich carcinoma, studied with histochemical and TEM techniques, is similar to wound healing. In this tumour mast cells, macrophages, adipocytes, platelets and fibrin seem to co-operate locally with malignant cells in regulating stroma formation. The gaps opened in the tumor parenchyma by plasma outpouring from local blood vessels seem to offer easy routes for endothelial cell migration towards ill-nourished areas, and may explain the irregular aspect of tumor microvascularity.

Animals↗
PubMed1991

Tumor hypoxia, reoxygenation and oxygenation strategies: possible role in photodynamic therapy.

The concept of hypoxia and its role in tumor therapy are currently under re-evaluation. Poor oxygenation is no longer visualized as an independent feature promoting necrosis and resistance to treatments, but rather as one of the several interdependent microenvironmental parameters associated with impaired blood perfusion. Tumor cells display several survival strategies and remain clonogenic for long periods in nutrient-deprived situations. Reoxygenation may cause lethal damage, improve the response to therapy, or else allow the cell variants adapted to hypoxia to resume proliferation with enhanced aggressiveness and resistance to treatment. The blood supply parameters, oxygenation status and metabolism of malignant cells are discussed here from the standpoint of tumor photodynamic therapy. The role of the tumor interstitial fluid as oxygen- and sensitizer-carrier is discussed. Techniques for assessing tumor oxygenation and for mapping hypoxic territories are described. Strategies for locally improving the oxygenation levels or for selectively destroying the hypoxic populations are outlined.

Humans↗
PubMed1985

Role of hypoxia in photodynamic therapy of tumors.

The photodynamic therapy of tumors is based on a photosensitization reaction that produces oxygen-derived cytotoxic species. The availability of oxygen is therefore a necessary condition to obtain the desired effect. However, most tumors develop regions that have outgrown their vascular supply, and therefore present severe hypoxia. In many hypoxic, yet viable areas, oxygen partial pressures almost two orders of magnitude lower that in normal tissues have been measured by other authors. It is here suggested that hypoxic cells are resistant to the therapy and hence are a source of postirradiation recurrence of the tumors. Methods are reviewed and discussed that can be used to: (a) improve the tumor oxygenation status prior to, or during irradiation; (b) destroy hypoxic cells; and, (c) allow the reoxygenation of the tumor by using fractionated irradiation protocols which increase tumor photosensitivity. Hyperthermia, a therapy to which hypoxic cells are particularly sensitive, is discussed. Cellular and vascular parameters that should be considered when discussing the synergism between hyperthermia and photodynamic therapy are listed. The new research field of hypoxia mapping by nondestructive, noninvasive, imaging techniques is briefly discussed.

Cell Membrane↗
PubMed1984

The time-dependent behaviour of hematoporphyrin-derivative in saline: a study of spectral modifications.

Hematoporphyrin-Derivative (HpD), a widely-used tumor-specific photosensitizer, is a complex mixture of porphyrins whose composition has yet to be clarified. This paper reports on the behaviour of HpD in saline. From a spectroscopic point of view, the fresh solution is characterized by two main absorption peaks, attributable to monomeric and dimeric forms. With aging, a new porphyrin species (NPS) appears. To define the NPS, absorption, excitation and emission spectra were measured in different conditions and time-resolved fluorescence measurements were also performed. This species exhibits an absorption/excitation peak at 405 nm, an emission peak at 575 nm and a fluorescence decay time of approximately 3.5 ns. Its formation is strongly influenced by many environmental factors: in particular, gases diluted in the solution, temperature, pH and concentration. The presence of Oxygen and a pH value outside the 6-8 range may be considered inhibiting factors. The NPS seems to be quite important in the understanding of HpD tumor-specificity, since the presence of an emission band similar to the NPS one seems to be favoured in tumor cells as compared with normal cells.

Hematoporphyrin Derivative↗
PubMed1984

Time-resolved fluorescence spectroscopy of hematoporphyrin-derivative in human lymphocytes.

This paper reports on time-resolved microfluorimetric measurements on hematoporphyrin-derivative (HpD)-treated lymphocytes. HpD is at present widely used as a tumor-locating and photosensitizing drug. It is therefore of great importance to study the extent to which the HpD uptake process depends on cell functional and structural properties. Time-resolved fluorescence measurements in single cells are very useful in this respect, since they give information on the content of fluorescent molecules through fluorescence peak-intensity, and, indirectly, on the binding properties through the fluorescence decay times. In particular, we studied the dependence of HpD fluorescence on the cellular functional state. To this end, we performed in-cell fluorescence measurements on human lymphocytes, both in quiescent conditions and in the pre-replicative phase, after stimulation with phytohemagglutinin (PHA). We found a higher HpD content in stimulated lymphocytes. Moreover, we found a spectral band around 575 nm, corresponding to a particular porphyrin species, in which the differences between normal and stimulated lymphocytes are more striking. The porphyrin species emitting in this band seems to play a role in the specific interaction of HpD with tumors, since a similar emission band has also been found in tumor cells containing HpD.

Hematoporphyrin Derivative↗
PubMed1984

Spectroscopic studies of hematoporphyrin-derivative in culture medium.

This work reports on studies of hematoporphyrin-derivative (HpD) behaviour in culture medium. Absorption, excitation and emission spectra, together with time-resolved fluorescence measurements, were performed. In previous works, similar studies had been carried out on HpD in saline and in lymphocytes: a new porphyrin species (NPS) and the environmental conditions for its formation in saline were studied. A fluorescent emission similar to that presented by the NPS is reported to be more likely in tumor rather than in normal HpD-treated cells, it was also found in greater amounts in lymphocytes in the pre-replicative phase, as compared with quiescent ones. The higher NPS content in stimulated rather than in quiescent lymphocytes may be due either to a differential uptake, as compared with other HpD components, or to a differential formation rate in cells, because of different microenvironmental conditions. To distinguish between these two main assumptions, the formation of NPS in culture medium was studied. The process was very slow: no NPS appeared within the first 40 h. The incubation time of lymphocytes in culture medium added with HpD in the experiments performed was only 1 h and therefore a differential formation rate of NPS may explain the higher content found in stimulated lymphocytes.

Culture Media↗
PubMed1984

An automatic pulsed laser microfluorometer with high spatial and temporal resolution.

The paper describes an automatic pulsed laser microfluorometer with high spatial and temporal resolution, developed in our laboratories. The instrument consists of: (i) a nitrogen-laser-pumped dye-laser for the excitation of the fluorescence, (ii) a microscope with additional optics to focus the excitation beam on the sample and to collect the fluorescence, (iii) filters or monochromators to select the output wavelength, (iv) a fast photomultiplier tube to detect the signal, and (v) a dual time-scale microprocessor-controlled signal averager for the acquisition and processing of the signal. Examples are given that show the potential of the time-resolved fluorescence microscopy in studying, quantitatively and qualitatively, the properties of fluorescent molecules.

Animals↗