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Biomedical subjects

S Kimel

Publications and source records attributed to S Kimel.

30 records · Page 2Linked to original sources
PubMed1992

Glucose administration combined with photodynamic therapy of cancer improves therapeutic efficacy.

Both the scope and the levels of activity in basic research and in the clinical applications of PDT, have grown enormously during the past few years. Several studies have examined the synergism of hyperthermia and chemotherapeutic agents in combination with PDT to enhance tumor eradication. The present study investigates the synergism of glucose administration combined with phototherapy. The results of this study suggest that glucose administration is simple and well tolerated, and combined with PDT produces a larger percentage of animals cured than using PDT alone. Furthermore, the results indicate that this approach requires lower amounts of light and might enable dosage reduction of photosensitizer for optimal response, with minimal side effects, to the treatment of cancer.

Adenocarcinoma↗
PubMed1992

Demonstration of synergistic effects of hyperthermia and photodynamic therapy using the chick chorioallantoic membrane model.

The chick chorioallantoic membrane (CAM) model was used to study vascular effects of photodynamic therapy (PDT) and hyperthermia (HPT) and the synergism of these modalities. The CAM is a convenient medium for monitoring the modifications of the vasculature. It is possible to view the CAM and to examine structural changes of individual blood vessels in real time. Moreover, the CAM is a closed system which lends itself to mathematical modeling of the temporal and spatial temperature profile and in which HPT can be performed quantitatively and to a selected depth, using different lasers. A porphyrin-type photosensitizer solution was applied to areas of the CAM, defined by teflon O-rings placed on the surface. Uptake dynamics of the sensitizer into the CAM was determined by analyzing its fluorescence in vivo. The CAM area was irradiated with a dual-wavelength laser system composed of a dye laser at 644 nm (to induce PDT) and a CO2 laser at 10.6 microns (to bring about HPT). Damage to the CAM vasculature, due to combined PDT+HPT, was compared to the outcome of the separate modalities, and a synergistic effect of about 40% was observed.

Allantois↗
PubMed1991

Temperature effects on photosensitized processes.

The singlet-oxygen-mediated reaction of meso-tetraphenylporphine tetrasulphonate (TPPS4) with different chemical acceptors in buffered aqueous solution was studied as a function of temperature. Imidazole, tryptophan, dimethyl p-nitrosoaniline, (RNO) and furfuryl alcohol served as acceptors. The measurements were performed in real time by spectroscopic or electrochemical monitoring of the consumption of the various reagents, acceptors or dissolved oxygen as a function of the absorbed energy. The results show the following increases in the reaction rate over the temperature range 15-45 degrees C: tryptophan (86%), RNO (90%), furfuryl alcohol (150%) and imidazole (210%). The influence of temperature-correlated changes in the initial oxygen concentration and pH was investigated. Possible implications of the present results for the synergistic influence of hyperthermia and photodynamic therapy are discussed.

Indicators and Reagents↗
PubMed1990

Photochemotherapy of hypervascular dermal lesions: a possible alternative to photothermal therapy?

Continued improvement in the results of laser treatment of port wine stain, with reduction in scarring, will depend on the ability to use lasers to induce selective injury of only the abnormal blood vessels in the dermis while sparing the normal overlying epidermis. Photodynamic therapy, using an exogenous photosensitizing drug specifically activated by certain wavelengths of light, may be used to destroy selectively certain targets in biological systems. The current study demonstrates, in the chicken comb model, that photochemotherapy can be used to treat hypervascular dermal lesions while leaving the normal overlying epidermis completely intact.

Animals↗
PubMed1990

XeCl laser action at medium fluences on biological tissues: fluorescence study and simulation with a chemical solution.

A rat heart, isolated and perfused, was irradiated with a XeCl excimer laser at 308 nm. The evolution of the fluorescence spectrum was measured. For an incident energy E greater than 4 kJ m-2 per pulse the fluorescence changed with time in a complex and spectrally non-uniform way. The proposed interpretation is that the radiation acts on the cellular respiratory chain. Buffered solutions of NADH, cytochrome c and FAD, which play a role in the respiratory chain, were irradiated in order to simulate the in vivo findings. The conclusion of this study is that XeCl radiation introduces a modification in the functioning of the respiratory chain: it accelerates electron transfer, but this quickly leads to an interruption of the respiratory chain.

Animals↗
PubMed1990

In vivo tumor oxygen tension measurements for the evaluation of the efficiency of photodynamic therapy.

Among the sequence of events which occur during photodynamic therapy (PDT) are depletion of oxygen and disruption of tumor blood flow. In order to more clearly understand these phenomena we have utilized transcutaneous oxygen electrodes to monitor tissue oxygen disappearance. These results provide, for the first time, non-invasive real-time information regarding the influence of light dose on tissue oxygenation during irradiation. Measurements were conducted on transplanted VX-2 skin carcinomas grown in the ears of New Zealand white rabbits. Rabbits were treated with Photofrin II and tumors were irradiated with up to 200 kJ/m2 (500 W/m2) of 630-nm light. Substantial reductions in tumor oxygen tension were observed upon administration of as little as 20 kJ/m2. For a series of brief irradiations, oxygen tension was modulated by the appearance of laser light. Tissue oxygen reversibility appeared to be dependent upon PDT dose. Long-term, irreversible tissue hypoxia was recorded in tumors for large (200 kJ/m2) fluences. These results suggest that transcutaneous oxygen tension may be useful as a general indicator of the effectiveness of PDT and as an in situ predictor of the energy required to elicit tumor damage.

Animals↗
PubMed1989

Singlet oxygen generation of porphyrins, chlorins, and phthalocyanines.

The production of singlet oxygen was measured indirectly for three classes of photosensitizers: porphyrins (Photofrin II, TPPS4), chlorins (MACE, DACE), and a phthalocyanine (CASPc). Buffered solutions of sensitizers and singlet oxygen acceptors were irradiated with a CW dye laser and the oxygen depletion was monitored electrochemically with a Clark-type microelectrode. A comparison of oxygen-depletion rate constants and quantum efficiencies yields the order of efficiency of the sensitizers: TPPS4 greater than MACE greater than PII greater than DACE greater than CASPc. For singlet oxygen acceptors the order was: furfuryl alcohol greater than imidazole greater than tryptophan. CHO cell suspensions were also used as acceptors. Here the order of efficiency (per absorbed photon) was PII greater than MACE approximately CASPc. Expressed in terms of oxygen depletion per cell the order was CASPc approximately PII greater than MACE. When performing cell clonogenicity studies the order of efficiencies, expressed as percentage cell kill per unit weight of sensitizer, was CASPc greater than PII greater than MACE approximately DACE. The discrepancy between the efficiencies of sensitizers to generate singlet oxygen and their cytotoxicity was explained in terms of photodegradation (for the chlorins), intracellular localization (for PII), and contributions from a Type I mechanism (for CASPc).

Animals↗
PubMed1988

An acute light and electron microscopic study of ultraviolet 193-nm excimer laser corneal incisions.

The 193-nm ultraviolet beam from an argon fluoride excimer laser was focused on the corneas of rabbits to produce incisions of the type necessary for radial keratotomy. The energy densities used were in two ranges, 1.0 to 2.1 J/cm2 per pulse and 200 to 700 mJ/cm2 per pulse. The eyes were enucleated and fixed for histologic and electron microscopic examination immediately after exposure. Structural analysis of the higher energy density exposures showed ridging on the surface of the cornea, micro-pitting on the stromal surface inside the cut, and denudation of the endothelium under the ablation zone. The lower energy density incisions did not exhibit significant surface ridging or endothelial cell loss but did exhibit significant stromal swelling during the laser exposure thus making it difficult to produce incisions of a precisely controlled depth. Beam profile measurements and infrared thermal measurements of the cornea surface during laser exposure were made.

Animals↗
PubMedDate not supplied

Photodynamic parameters in the chick chorioallantoic membrane (CAM) bioassay for topically applied photosensitizers.

The relative efficacy of Photofrin-based photodynamic therapy (PDT) has been compared with that of the second-generation photosensitizers 5-aminolevulinic acid (ALA), sulfonated chloro-aluminum phthalocyanine (AlPcSn), benzoporphyrin derivative monoacid ring A (BPD-MA), and lutetium texaphyrin (Lutex). PDT-induced vascular damage in the chick chorioallantoic membrane (CAM) is measured following topical application of the photosensitizers. In order to make meaningful comparisons, care is taken to keep treatment variables the same. These include light dose (5 and 10 J/cm2), power density (33 and 100 mW/cm2), and drug uptake time (30 and 90 min). The drug dose ranges from 0.1 microgram/cm2 for BPD to 5000 micrograms/cm2 for ALA. Results are also analyzed statistically according to CAM vessel type (arterioles versus venules), vessel diameter, and vessel development (embryonic age). For each photosensitizer, the order of importance for the various PDT parameters is found to be unique. The differences between the sensitizers are most likely due to variation in biophysical and biochemical characteristics, biodistribution, and uptake kinetics.

Administration, Topical↗