alpha-Tocopherol and three derivatives in which the phytol chain is modified or deleted were exam... more alpha-Tocopherol and three derivatives in which the phytol chain is modified or deleted were examined for their effect on cultured keratinocyte arachidonic acid metabolism. 2,2,5,7,8-Pentamethyl-6-hydroxychromane (PMC), in which the phytol chain is replaced by a methyl group, inhibited basal, bradykinin (BK)- and A23187-stimulated prostaglandin E2 (PGE2) synthesis with an apparent Ki of 1.3 microM. The Ki of the analogue with six carbon atoms in the side chain (C6) was 5 microM while that of the C11 analogue was 10 microM. No effect of alpha-tocopherol was observed. The mechanism of inhibition was studied using PMC. The effect of PMC on phospholipase and cyclooxygenase activity was assayed using stable isotope mass measurements of PGE2 formation, which assesses arachidonate release and cyclooxygenase metabolism simultaneously. BK-stimulated formation of PGE2, derived from endogenous phospholipid, was decreased 60% by 5 microM PMC and eliminated by 50 microM PMC, compared with contro...
ABSTRACT Benzoporohyrin derivative monoacid ring A (BPD) is a lipophilic photosensitizer with a m... more ABSTRACT Benzoporohyrin derivative monoacid ring A (BPD) is a lipophilic photosensitizer with a maximum absorption peak at 690 nm. When liposomally formulated, it distributes in human plasma almost exclusively to the lipoprotein fraction. In experimental animals and humans, it demonstrates good selectivity for tumors as well as other hyperproliferative tissues or cells. In experimental animal tumour models we have found maximum selectivity between tumour and normal surrounding tissue to occur within the first hour following intravenous administration, providing an opportunity for very early PDT following injection. Early clinical trial results from treatment of patients with cutaneous cancerous lesions have shown encouraging efficacy at levels of drug between 0.35 and 0.5 mg/kg. In addition, studies on patients with psoriasis indicate that BPD and light may be used to clear psoriatic plaques.
Lasers in Otolaryngology, Dermatology, and Tissue Welding, 1993
ABSTRACT This is a preliminary report of an ongoing clinical trial involving patients with malign... more ABSTRACT This is a preliminary report of an ongoing clinical trial involving patients with malignant skin tumors. Fifteen patients with malignant skin tumors received an infusion of 0.25 - 0.5 mg/kg of BPD-MA three to four hours prior to irradiation of their tumors with 50 - 150 J/cm2 of 690 nm laser light from an argon pumped tunable dye laser. Tumor response was assessed clinically for up to three months following treatment. In addition, daily serial phototesting of normal skin to filtered light from a xenon arc lamp emitting UVA and visible (UVA/VIS) light was carried out before and after BPD-MA infusion to determine the dose of light required each day to produce `minimal erythema' in normal skin. Complete follow-up data are available for 64 cutaneous tumors in the first fifteen patients treated. A complete clinical tumor response was noted in 63% of the tumors treated, with a partial response (> 50% reduction in tumor area) in 11%. Sensitivity to UVA/VIS light was drug dose-dependent and maximal on the day of treatment. The estimated mean duration of photosensitivity to UVA/VIS light ranged from 2.4 days for the lowest BPD-MA dose (0.25 mg/kg) to 5.4 days for the highest dose (0.5 mg/kg). Cutaneous photosensitivity due to BPD-MA appears to be short-lived. Complete responses for malignant skin tumors have been achieved using BPD-MA doses of 0.25 - 0.5 mg/kg in combination with 50 - 150 J/cm2 of 690 nm laser light.
The inflammation produced by exposure to ultraviolet (UV) light has been well documented clinical... more The inflammation produced by exposure to ultraviolet (UV) light has been well documented clinically and histologically. However, the mechanisms by which mediators induce this clinical response remain poorly defined. It is clear that photochemistry occurring after UV absorption must be responsible for initiating these events. Some of these underlying mechanisms have been defined. After exposure to UV light, the formation of prostaglandins and the release of histamine are increased. In addition to an increase in the quantity of these mediators, an increase in sensitivity of irradiated tissue to agonist stimulation also occurs. This increased sensitivity may cause tissue to respond to agonist levels previously present. Phospholipase activity also increases, making more substrate available for prostaglandin formation. Oxygen radical-induced peroxidation of membrane lipids caused by irradiation may contribute to increased phospholipase activity. Oxygen-free radicals also participate in sunburn cell formation and in UV-induced decreases in Langerhans cell numbers. Several enzymatic and non-enzymatic mechanisms are present in skin for reducing these highly reactive oxygen species.
Coronary artery bypass grafting for atherosclerotic heart disease is commonly performed throughou... more Coronary artery bypass grafting for atherosclerotic heart disease is commonly performed throughout the world. Complications of coronary artery bypass grafting include saphenous neuralgia due to injury to the saphenous nerve during harvest of the saphenous vein. Dermatologic complications of coronary revascularization are infrequently reported and include an eruption overlying the vein donor-site scar. We describe two cases of saphenous vein donor site dermatitis associated with sensory peripheral neuropathy in the distribution of the dermatitis. Histopathologic studies revealed a subacute spongiotic dermatitis. The course of the eruption was characterized by exacerbations and remissions with gradual resolution of both the dermatitis and neuropathy over a 1- to 2-year period. Our cases are unique because the dermatitis developed in the area of the neurologic changes. We propose that the dermatitis may be a trophic change secondary to saphenous neuralgia.
alpha-Tocopherol and three derivatives in which the phytol chain is modified or deleted were exam... more alpha-Tocopherol and three derivatives in which the phytol chain is modified or deleted were examined for their effect on cultured keratinocyte arachidonic acid metabolism. 2,2,5,7,8-Pentamethyl-6-hydroxychromane (PMC), in which the phytol chain is replaced by a methyl group, inhibited basal, bradykinin (BK)- and A23187-stimulated prostaglandin E2 (PGE2) synthesis with an apparent Ki of 1.3 microM. The Ki of the analogue with six carbon atoms in the side chain (C6) was 5 microM while that of the C11 analogue was 10 microM. No effect of alpha-tocopherol was observed. The mechanism of inhibition was studied using PMC. The effect of PMC on phospholipase and cyclooxygenase activity was assayed using stable isotope mass measurements of PGE2 formation, which assesses arachidonate release and cyclooxygenase metabolism simultaneously. BK-stimulated formation of PGE2, derived from endogenous phospholipid, was decreased 60% by 5 microM PMC and eliminated by 50 microM PMC, compared with contro...
ABSTRACT Benzoporohyrin derivative monoacid ring A (BPD) is a lipophilic photosensitizer with a m... more ABSTRACT Benzoporohyrin derivative monoacid ring A (BPD) is a lipophilic photosensitizer with a maximum absorption peak at 690 nm. When liposomally formulated, it distributes in human plasma almost exclusively to the lipoprotein fraction. In experimental animals and humans, it demonstrates good selectivity for tumors as well as other hyperproliferative tissues or cells. In experimental animal tumour models we have found maximum selectivity between tumour and normal surrounding tissue to occur within the first hour following intravenous administration, providing an opportunity for very early PDT following injection. Early clinical trial results from treatment of patients with cutaneous cancerous lesions have shown encouraging efficacy at levels of drug between 0.35 and 0.5 mg/kg. In addition, studies on patients with psoriasis indicate that BPD and light may be used to clear psoriatic plaques.
Lasers in Otolaryngology, Dermatology, and Tissue Welding, 1993
ABSTRACT This is a preliminary report of an ongoing clinical trial involving patients with malign... more ABSTRACT This is a preliminary report of an ongoing clinical trial involving patients with malignant skin tumors. Fifteen patients with malignant skin tumors received an infusion of 0.25 - 0.5 mg/kg of BPD-MA three to four hours prior to irradiation of their tumors with 50 - 150 J/cm2 of 690 nm laser light from an argon pumped tunable dye laser. Tumor response was assessed clinically for up to three months following treatment. In addition, daily serial phototesting of normal skin to filtered light from a xenon arc lamp emitting UVA and visible (UVA/VIS) light was carried out before and after BPD-MA infusion to determine the dose of light required each day to produce `minimal erythema' in normal skin. Complete follow-up data are available for 64 cutaneous tumors in the first fifteen patients treated. A complete clinical tumor response was noted in 63% of the tumors treated, with a partial response (> 50% reduction in tumor area) in 11%. Sensitivity to UVA/VIS light was drug dose-dependent and maximal on the day of treatment. The estimated mean duration of photosensitivity to UVA/VIS light ranged from 2.4 days for the lowest BPD-MA dose (0.25 mg/kg) to 5.4 days for the highest dose (0.5 mg/kg). Cutaneous photosensitivity due to BPD-MA appears to be short-lived. Complete responses for malignant skin tumors have been achieved using BPD-MA doses of 0.25 - 0.5 mg/kg in combination with 50 - 150 J/cm2 of 690 nm laser light.
The inflammation produced by exposure to ultraviolet (UV) light has been well documented clinical... more The inflammation produced by exposure to ultraviolet (UV) light has been well documented clinically and histologically. However, the mechanisms by which mediators induce this clinical response remain poorly defined. It is clear that photochemistry occurring after UV absorption must be responsible for initiating these events. Some of these underlying mechanisms have been defined. After exposure to UV light, the formation of prostaglandins and the release of histamine are increased. In addition to an increase in the quantity of these mediators, an increase in sensitivity of irradiated tissue to agonist stimulation also occurs. This increased sensitivity may cause tissue to respond to agonist levels previously present. Phospholipase activity also increases, making more substrate available for prostaglandin formation. Oxygen radical-induced peroxidation of membrane lipids caused by irradiation may contribute to increased phospholipase activity. Oxygen-free radicals also participate in sunburn cell formation and in UV-induced decreases in Langerhans cell numbers. Several enzymatic and non-enzymatic mechanisms are present in skin for reducing these highly reactive oxygen species.
Coronary artery bypass grafting for atherosclerotic heart disease is commonly performed throughou... more Coronary artery bypass grafting for atherosclerotic heart disease is commonly performed throughout the world. Complications of coronary artery bypass grafting include saphenous neuralgia due to injury to the saphenous nerve during harvest of the saphenous vein. Dermatologic complications of coronary revascularization are infrequently reported and include an eruption overlying the vein donor-site scar. We describe two cases of saphenous vein donor site dermatitis associated with sensory peripheral neuropathy in the distribution of the dermatitis. Histopathologic studies revealed a subacute spongiotic dermatitis. The course of the eruption was characterized by exacerbations and remissions with gradual resolution of both the dermatitis and neuropathy over a 1- to 2-year period. Our cases are unique because the dermatitis developed in the area of the neurologic changes. We propose that the dermatitis may be a trophic change secondary to saphenous neuralgia.
Uploads
Papers by Luciann Hruza