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Biomedical subjects

I Rosenthal

Publications and source records attributed to I Rosenthal.

At least 37 records · Page 2Linked to original sources
PubMed1990

Preferential uptake of a water-soluble phthalocyanine by atherosclerotic plaques in rabbits.

This study is the first demonstration of preferential accumulation of a water soluble phthalocyanine dye in atheromatous plaques in the rabbit. Two groups of rabbits with diet-induced atheromatous plaques were killed 4 and 24 h following intravenous administration of copper phthalocyanine tetrasulfonate. Uptake of the dye by plaque-containing and normal appearing aortae was evaluated macroscopically and quantitatively by extraction of the dye from the tissues. The concentration of the dye in the atheromatous plaques was 2.6 and 1.7 times higher than in the normal vessel wall at 4 and 24 h, respectively. The concentration of the dye in normal appearing aortae in the 2 study groups was similar to that of aortae of control rabbits which were fed a normal diet and exposed to the dye for the same time periods. We conclude that copper phthalocyanine accumulates preferentially in atheromatous plaques in rabbits. These findings provide a basis for the utilization of phthalocyanines for plaque identification and for photodynamic therapy of atherosclerosis.

Animals↗
PubMed1990

[Value of etomidate for the temporary clamping in early surgery, in normotension, of ruptured intracranial aneurysms. Preliminary study of 8 cases].

For 8 cases of aneurysmal ruptures in patients between twenty two and sixty-six years old, with clinical grade I or II, without diabetes neither high blood pressure, all of them underwent before the third day, with EEG monitoring, the surgical technic requires a temporary clipping of the carrying vessel (extreme times: 2 min 30 and 16 min), with a normal mean blood pressure. mean (ASBP) The circulatory cerebral brain protection is obtained with vascular filling before the clipping time and administration of Etomidate, (0.4 mg.kg-1) as soon as the aneurysm is exposed. For etomidate the posology is. The total required dose of Etomidate was about 98 mg. In all cases this protocol well tolerated (no neurological deficit) enables a good brain protection without cardio-vascular inconveniences of high barbiturate posologies. The waking up is very quick and allows a very early neurological check-up and a return to the presurgery tensional pattern too.

Adult↗
PubMed1989

Inhibition of human lymphocyte stimulation by visible light and phthalocyanine photosensitization: mitogen and wavelength dependency.

Mitogenic stimulation of human peripheral blood lymphocytes is inhibited by phthalocyanine photosensitization using visible light. The mechanism of inhibition was studied using stimulating agents differing in their mode of action. Stimulation by the plant lectin phytohemagglutinin (PHA) was the least sensitive to inhibition by photosensitization, followed by the tumor promoter phorbol myristate acetate (PMA) and the calcium ionophore A23187. Mitogenic stimulation could also be inhibited by light only, but higher fluences were needed. The order of efficacy was blue greater than red greater than green light, and the response to A23187 was least affected, followed by an increased inhibition of the response to PHA and PMA stimulation. Possible targets and mechanisms for these effects are discussed.

Calcimycin↗
PubMed1989

Synthesis and photocytotoxicity of some new substituted phthalocyanines.

Some new, ring-substituted phthalocyanines have been synthesized and underwent preliminary testing for photodynamic activity using the colony forming ability of Chinese hamster cells in culture as an endpoint. Using 4-(3-N,N-diethylaminopropyl)phthalonitrile as a precursor, the previously unknown metal-free 2,9,16,23-tetra-(3-N,N-diethylaminopropyl)phthalocyanine was prepared and converted to its zinc (II) and its cationic water-soluble 2,9,16,23-tetramethylammonium zinc (II) iodide derivatives. Other new phthalocyanine derivatives tested, include a 2,9,16,23-tetra(2-hydroxymethyl-2-methylbutoxy)phthalocyaninato zinc (II) and 2,3,9,10,16,17,23,24-octahydroxyphthalocyaninato zinc (II) derivatives. Boron tribromide cleavage of the newly prepared and fully characterized 2,3,9,10,16,17,23,24-octamethoxyphthalocyanine gave the unstable metal-free octahydroxyphthalocyanine, which could only be characterized by ultraviolet-visible, NMR and IR spectroscopy.

Animals↗
PubMed1988

Release of clotting factors from photosensitized endothelial cells: a possible trigger for blood vessel occlusion by photodynamic therapy.

Photodynamic treatment of solid tumors results in the occlusion of blood vessels in the treated tissue. We hypothesize that this process is triggered by the release of one or more clotting factors from the photodamaged endothelial cells. Experimental evidence is presented that immediately after photodynamic treatment, cultured endothelial cells start releasing clotting factors into the medium in a dose range of minimal cytotoxicity.

Adrenal Medulla↗
PubMed1988

Recovery of Chinese hamster cells following photosensitization by zinc tetrahydroxyphthalocyanine.

The phthalocyanine dyes are attractive sensitizers for photodynamic therapy of cancer. The light fluence response curves for photocytotoxicity of zinc tetrahydroxyphthalocyanine were constructed using the colony-forming ability of Chinese hamster cells as an end-point. The survival curve of cells photosensitized to white light by this dye has a pronounced shoulder followed by an exponential decline. Postillumination hypertonic treatment (0.5 M NaCl for 20 min at 37 degrees C) enhanced log-phase killing, although to a lesser extent than after exposure to ionizing radiation. While such an enhancement usually indicates that the cells are able to repair potentially lethal damage, delayed trypsinization of photosensitized cells in plateau-phase failed to show a significant increase in cell survival. Thus, the repair of such a damage in plateau-phase is apparently absent. Experiments with split light fluence indicated that log-phase cells can repair sublethal damage during a 24 h interval, as evidenced by the reappearance of the shoulder on the split-dose survival curve.

Animals↗
PubMed1988

Combined action of phthalocyanine photosensitization and gamma-radiation on mammalian cells.

The response of Chinese hamster cells and human lymphocytes to the combined action of photosensitization by chloroaluminium phthalocyanine tetrasulfonate and gamma-radiation was studied using colony-forming ability and [3H]thymidine incorporation following mitogenic stimulation respectively, as endpoints. The action of both treatments was usually additive regardless of the sequence of application. However, in human lymphocytes irradiated at low temperature, the photosensitization interacted synergistically with the subsequent ionizing radiation; in this experiment the initial photosensitization reduced the yield of micronuclei produced by gamma-radiation.

Animals↗
PubMed1987

Mechanism of uptake of sulfonated metallophthalocyanines by cultured mammalian cells.

The uptake of several metallophthalocyanine tetrasulfonates by cultured Chinese hamster cells was studied. Uranyl- and chloraluminium were taken up at the highest rate followed by Ni-, Zn-, Cu-, Co- and dichlorosilicon-phthalocyanine tetrasulfonate. The uptake from the growth medium containing 10% serum in which only 15% of the dye is not bound to serum proteins was 5--18-fold slower than in the absence of serum, suggesting that most of the uptake is of free dye. Using gel filtration to separate tightly protein-bound dye from the free dye, binding curves were constructed that varied in slope and saturation values for the different compounds. At saturation, the number of dye molecules bound per serum albumin molecule varied from 1 for vanadyl- and cobalt-, to 4 for uranyl-phthalocyanine tetrsulfonate. Absorption spectra of the various phthalocyanines indicated that under physiological conditions, all dyes, with the exception of chloroaluminum- and dichlorosilicon-phthalocyanine tetrasulfonate, were aggregated. The rate of uptake was unrelated to the state of aggregation. The rate of uptake was temperature dependent at intervals longer than 1 h. At shorter times, very little temperature dependence was observed. These results suggest that the uptake process takes place in two steps. The first step is passive, involving binding of metallophthalocyanine tetrasulfonate to a receptor on the cell membrane, while the second one is active and involves internalization of the bound dye.

Animals↗
PubMed1987

Effect of light fluence rate on mammalian cells photosensitization by chloroaluminium phthalocyanine tetrasulphonate.

Phthalocyanines are photosensitizers evaluated for use in photodynamic therapy of cancer. As such, the dependence of the bioresponse on the light fluence rate may be of clinical importance. The effect of the fluence rate of white light from 0.165 to 3.3 kJ m-2 min-1 was studied in Chinese hamster cells and human lymphocytes, using as endpoints colony-forming ability and inhibition of [3H]thymidine incorporation following mitogenic stimulation and dye-photoactivation, respectively. Using Chinese hamster cells exposed to photoexcited chloroaluminium phthalocyanine tetrasulphonate in PBS solution, cytotoxicity was diminished as the fluence rate was reduced. In human lymphocytes changing the fluence rate between 0.33 and 3.3 kJ m-2 min-1 affected the response in a way similar to that of Chinese hamster cells. Human lymphocytes, when exposed to incremental increasing light fluences, 4 h after a conditioning dose, were able to recover from phthalocyanine-induced photodamage, as evidenced by the reappearance of a shoulder on the dose-effect curve. This recovery process during a protracted light exposure, could explain the reduced sensitivity to phthalocyanine photosensitization, compared to exposure at high fluence rates.

Animals↗
PubMed1986

Photohemolysis of human erythrocytes induced by aluminum phthalocyanine tetrasulfonate.

The phthalocyanines are a new class of photosensitizers with promising properties for use in photodynamic therapy of cancer [E. Ben-Hur and I. Rosenthal (1985) Int. J. Radiat. Biol., 47, 145--147]. The ability of aluminum phthalocyanine tetrasulfonate (AlPCS) to cause membrane damage upon light exposure was tested using photohemolysis of human erythrocytes as an endpoint. AlPCS was found to be quite efficient in causing red blood cell lysis. Photohemolysis dependency on the light fluence had a characteristic sigmoidal shape. The light fluence required for 50% hemolysis was inversely proportional to AlPCS concentration. Neither singlet oxygen nor hydroxyl radicals appear to be involved in the photohemolysis induced by AlPCS. This is inferred from the observation that exposure of erythrocytes in the presence of D2O or glycerol did not affect the light fluence response curve. These data suggest that photosensitization by AlPCS can cause membrane damage and that this damage may be responsible for cell killing.

Erythrocyte Membrane↗
PubMed1986

Photodynamic treatment of transplantable bladder tumors in rodents after pretreatment with chloroaluminum tetrasulfophthalocyanine.

Chloroaluminum tetrasulfophthalocyanine (AlPCS) was used as a photosensitizer for the photodynamic treatment of transplantable N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) induced urothelial tumors. Two groups of six rats each were injected with AlPCS (three micrograms./gm. body weight) and 24 hours after injection underwent photodynamic treatment with red light (greater than 590 nm., 360 joules/cm.2). Tumors examined four hours (Group I) and 24 hours (Group II) after the completion of phototreatment showed extensive hemorrhagic necrosis. Tumors treated with AlPCS alone showed no changes. In two other groups of six rats each, blood flow to tumors treated with AlPCS alone (Group III) and AlPCS plus light (Group IV) was measured using the radioactive microsphere technique. AlPCS plus light resulted in a significant decrease (p less than .05) in tumor blood flow within 10 minutes of completion of phototreatment while AlPCS alone had no effect on tumor blood flow. These findings are similar to those observed when higher doses (10 micrograms./gm. to 20 micrograms./gm. body weight) of hematophorphyrin derivative (HpD) and light were used for phototreatment of FANFT induced tumors. AlPCS is a stable sulfonated derivative of tetraazotetrabenzoporphyrin which absorbs maximally in the red portion of the visible spectrum, a region with good tissue penetration properties. These studies suggest the AlPCS may be a useful new agent for photodynamic therapy of cancer.

Animals↗