PubMed Health⌕ Search

Biomedical subjects

J D Spikes

Publications and source records attributed to J D Spikes.

At least 19 recordsLinked to original sources
PubMed1992

Quantum yields and kinetics of the photobleaching of hematoporphyrin, Photofrin II, tetra(4-sulfonatophenyl)-porphine and uroporphyrin.

Porphyrins used as sensitizers for the photodynamic therapy (PDT) of tumors are progressively destroyed (photobleached) during illumination. If the porphyrin bleaches too rapidly, tumor destruction will not be complete. However, with appropriate sensitizer dosages and bleaching rates, irreversible photodynamic injury to the normal tissues surrounding the tumor, which retain less sensitizer, may be significantly decreased. This paper surveys the quantum yields and kinetics of the photobleaching of four porphyrins: hematoporphyrin (HP), Photofrin II (PF II), tetra(4-sulfonatophenyl)porphine (TSPP) and uroporphyrin I (URO). The initial quantum yields of photobleaching, as measured in pH 7.4 phosphate buffer in air, were: 4.7 x 10(-5), 5.4 x 10(-5), 9.8 x 10(-6), and 2.8 x 10(-5) for HP, PF II, TSPP and URO respectively; thus, the rates of photobleaching are rather slow. Low oxygen concentration (2 microM) significantly reduced the photobleaching yields. However, D2O increased the yields only slightly, and the singlet oxygen quencher, azide, had no effect, even at 0.1 M. Photosensitizing porphyrins in body fluids, cells and tissues may be closely associated with various photooxidizable molecules and electron acceptors and donors. Therefore, selected model compounds in these categories were examined for their effects on porphyrin photobleaching. A number inhibited and/or accelerated photobleaching, depending on the compound, the porphyrin and the reaction conditions. For example, 1.0 mM furfuryl alcohol increased the photobleaching yields of HP and URO more than 5-fold, with little effect on PF II or TSPP. In contrast, the electron acceptor, methyl viologen, increased the photobleaching yield of TSPP more than 10-fold, with little accelerating effect on the other porphyrins. These results suggest that the mechanism(s) of the photobleaching of porphyrin photosensitizers in cells and tissues during PDT may be complex.

Dihematoporphyrin Ether↗
PubMed1991

Presence of blood significantly decreases transmission of 630 nm laser light.

Application of 630 nm light in the presence of blood is often necessary during photodynamic therapy, particularly for proposed intravascular applications. The effect of blood on transmission of 630 nm light was studied using a three dimensional irradiation model and an integrating sphere for measuring light transmitted in any direction through blood layers of different hematocrit (25 to 75) and thickness (.15 to .98 mm). There was an inverse relationship between transmission and hematocrit and transmission and blood thickness, p = .000 for both. At a physiologic hematocrit of 46, transmission through blood layers of .98, .41, .28, and .15 mm were 21%, 33%, 29%, and 58% respectively. These blood thicknesses or more are likely in the clinical environment, and can be expected to result in significant transmission losses. The marked absorption of 630 nm light by blood indicates that removal of the blood or correction for power loss should be employed when 630 nm light is applied in a blood containing environment.

Absorption↗
PubMed1990

Photothermal sensitizers: possible use in tumor therapy.

Photothermal damage of tissues or endotissular compartments may be induced by pulsed irradiation of either endogenous chromophores (e.g. hemoglobin, melanin) or externally added dyes; the latter should have short triplet lifetimes and mainly decay from electronically excited states by nonradiative pathways. Potential photothermal sensitizers are some metallo derivatives of porphyrins and porphyrinoid compounds, azo dyes and triphenylmethane derivatives. These dyes have the additional property of significant absorbance at wavelengths longer than 600 nm, which can penetrate deep into biological tissues. Spatial confinement of the photothermal process depends on the absorption coefficient of the photoexcited chromophore and its thermal relaxation time. Present evidence indicates that the selective photothermal damage of macromolecules or subcellular organelles requires pulsed excitation at picosecond or nanosecond regimes, while microsecond or millisecond domains are effective in the case of cells or similar structures. The possible use of photothermal sensitization in the treatment of tumors is briefly discussed.

Animals↗
PubMed1990

Chlorins as photosensitizers in biology and medicine.

The photodynamic therapy (PDT) of tumors involves illumination of the tumorous area following the administration of a tumor-localizing photodynamic sensitizer. Hematoporphyrin derivative (HPD) and Photofrin II (a purified form of HPD), the main sensitizers used clinically for PDT to date, are complex mixtures of porphyrins; furthermore, these preparations absorb light very poorly in the red region of the spectrum (wavelengths greater than 600 nm) where light penetration into mammalian tissues is greatest. Thus there is considerable interest in identifying new sensitizers that localize more effectively in tumors, absorb more strongly at longer wavelengths and can be prepared in high purity. Much of this interest has been directed towards chlorins (reduced porphyrins), which typically absorb strongly in the red. This review summarizes research that has been carried out on selected types of chlorins, some of which may have important applications as sensitizers for PDT.

Animals↗
PubMed1989

The chemistry, photophysics and photosensitizing properties of phthalocyanines.

Phthalocyanines (Pcs) and naphthalocyanines (Ncs) are being extensively studied as photosensitizers for photodynamic therapy (PDT) of cancer. They strongly absorb clinically useful red light, with maxima around 670 nm and 770 nm respectively. Chelated with appropriate diamagnetic metal ions, they exhibit high triplet yields and long triplet lifetimes. Energy transfer from the triplet dye to ground-state oxygen to yield singlet oxygen appears to be the main photosensitizing pathway in biological systems. Underivatized Pcs and Ncs can be incorporated in liposomes for in vivo administration. Sulphonation renders the dyes water soluble but also enhances dimerization to yield photochemically inactive aggregates. Tumour retention and cell membrane penetration of the dyes are strongly affected by the polarity of the macrocycle as well as the nature of the central metal ion and axial ligands. Among the sulphonated dyes, amphiphilic mono- and disulphonated derivatives exhibit particularly good cell membrane-penetrating properties, although the more highly sulphonated dyes show better tumour retention in vivo. At least in vitro, Pc dyes are more photoactive than the corresponding Nc dyes, which probably reflects the lower photostability of the latter.

Indoles↗
PubMed1978

Recommendations for future research on ultraviolet radiation carcinogenesis.

Recommendations for future research on photocarcinogenesis were developed during an international conference on UVR carcinogenesis. Areas covered in the recommendations include research at the molecular biology level, human (especially epidemiologic aspects), physical (including instrumentation), and biologic studies (stressing animal models). The recommendations also propose the establishment of central supply and service sources for photocarcinogenesis research as well as the establishment of interdiscipilinary training programs related to research in photocarcinogenesis.

Animals↗
PubMed1977

Time of appearance and histology of tumors induced in the dorsal skin of C3Hf mice by ultraviolet radiation from a mercury arc lamp.

The time course of skin tumor induction was determined in hair-clipped inbred agouti C3Hf mice irradiated three times per week with a medium-pressure quartz-mercury lamp; 4 different UV doses were used. Although the ears were also exposed to the radiation, in the 3 groups given the highest doses no ear tumors were observed by the time each animal had developed at least 1 tumor on its back. No tumors were found in the animals receiving the lowest UV dose. In the group receiving the highest dose, males developed tumors earlier than did females; this trend continued in the lower dose groups. Many tumors that developed in the back skin were well-differentiated squamous cell carcinomas. Others were less well-differentiated squamous cell carcinomas. Others were less well defined so that the cell of origin was difficult to determine. In the group receiving the highest UV dose, the squamous cell carcinomas were few, whereas at the lower doses they predominated.

Animals↗