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Objectives: Recently the use of glycolic-acid-containing cosmetics has received increased public interest in their supposed ability to reduce wrinkles, roughness, age spots and other skin damage. However, the safety of such products when used excessively or chronically, especially by photosensitive people, is being questioned. The purpose of this study was to examine the effects of glycolic acid alone or in combination with UVB on skin damage and inflammatory response., Method: Guinea pigs were treated with glycolic acid (from 1 to 7 mg/cm(2)) alone or in combination with UVB (0.4 or 3 J/cm(2)) for 14 days. Skin damage was evaluated by scoring the skin irritation value by the method of Draize and by histopathological observations. Cyclooxygenase 2 (COX-2) expression and prostaglandin E(2) (PGE(2)) production were also assessed., Results: Glycolic acid caused an increase in the level of skin damage in a dose- and time-dependent manner. Lower doses (1 and 3 mg/cm(2)) of glycolic acid mostly caused erythema and eschar, and these consequently formed scales, whereas higher doses (5 and 7 mg/cm(2)) of glycolic acid caused redness, edema and necrotic ulceration. Glycolic acid also increased the thickness of the epidermal layer, reduced the organization of the stratum corneum and eventually destroyed some parts of the epidermal layer at 7 mg/cm(2). UVB (0.4 and 3 J/cm(2)) caused redness and edema as well as reduced the integrity of the stratum corneum. Glycolic acid enhanced the UVB-induced skin damage. The magnitude of the damage caused by combined UVB and glycolic acid treatment was much greater than that caused by glycolic acid or UVB alone. Moreover, partial destruction of the epidermal layer was observed in skin treated with 3 J/cm(2) UVB and 3 mg/cm(2) glycolic acid. However, glycolic acid did not change the basal and UVB-induced PGE(2) production and COX-2 protein expression., Conclusion: These results show that glycolic acid causes skin damage in a dose- and time-dependent manner and that it enhances UVB-induced skin damage without accompanying PGE(2) production or COX-2 protein expression. Therefore, caution should be exercised by those using glycolic acid on a chronic basis or excessively. Moreover, those with photosensitive skins and those more exposed to the sun should be particularly careful., (Copyright 2002 S. Karger AG, Basel)

Head and neck cancer surgeons are often faced with the challenge of managing previously irradiated soft tissue that has poor vascularity and slower epithelialization. This study investigates the effect of supplemental basic fibroblast growth factor (bFGF) on flap vascularity, tissue oxygenation, and epidermal regeneration in nonirradiated (n = 40) and irradiated porcine skin flaps (n = 40). Supplemental bFGF increased vascularity in nonirradiated flaps by 80% (p = .005), with a trend to a higher tissue oxygen level by day 14. The irradiated bFGF-treated flaps did not show increased vascularity or higher tissue oxygen levels 2 weeks after surgery. However, in both irradiated and nonirradiated groups, epidermal regeneration increased by greater than 70% with supplemental bFGF (p < .002). The results of this study suggest that supplemental bFGF can increase tissue vascularity in nonirradiated tissues and epidermal regeneration in both nonirradiated and irradiated conditions.

Delayed postoperative wound healing in previously radiated cancer patients is a common and debilitating occurrence. Prior studies have given evidence that endothelial cell growth factor (ECGF) can accelerate neovascularization in soft tissue. To explore its effects in irradiated tissue, an ECGF-heparin formulation (7200 micrograms/mL) contained in Gelfoam was applied to previously irradiated (N = 38) and nonirradiated skin flaps (N = 38) on rabbit ears. Both peripheral neovascularization and flap viability were quantitatively documented by polar planimetry and digital angiography in all flaps. The ECGF-heparin flaps had a greater than twofold increase in both vascularity and viability when compared to their controls among the irradiated and nonirradiated flaps (P < .01). Also, the additional viability and vascularization effects from ECGF-heparin did not appear statistically altered by previous radiation. These results support the promising angiogenic effect of ECGF-heparin in previously irradiated surgical wounds.

The heat-induced changes in blood circulation in human forearm skin were studied. With the use of laser Doppler flowmetry, it was possible to noninvasively monitor the velocity and volume of red cells, and thus the flow rate of red cells or blood flow in the human skin. When the skin surface was heated at 35 degrees -43 degrees C for 60 min, the laser Doppler flow (LDF) changed dynamically, indicating that the blood flow in human forearm skin could increase as much as 15-20 times during heating at 43 degrees C. Such an increase in laser Doppler flow resulted from dilation of arterioles and recruitment of capillaries, and also to a lesser extent, from an increase in the velocity of red cell flux. The increase in the velocity of red cell flux implies that arteriovenous anastomoses exist in the human forearm skin, in contradiction to the common view that human forearm skin is devoid of arteriovenous anastomosis.

The effect of one to five multiple heatings on blood flow in the RIF-1 tumour, skin and muscle of C3H mice was studied. When heated for 1 h at 43.5 degrees C the tumour blood flow increased 1.8 times, and rapidly decreased after the heating to less than half the control value. The 2nd-5th heatings at 43.5 degrees C, applied at 1- or 3-day intervals, caused no further significant change in the tumour blood flow. In the skin and muscle the blood flow increased 5 times when heated for 1 h at 43.5 degrees C, and remained at 1.5-2.0 times of control for 1-3 days after the heating. The blood flow in the skin and muscle, particularly in the skin, was further increased by the 2nd-5th heatings applied at 3-day intervals, but not at 1-day intervals, albeit the additional increase was very small. Consequently, whereas the tumour blood flow was 5-6 times greater than that in the skin and muscle before heating, it was only about 1.5-2.0 times greater than that in the skin and muscle during the 1st heating. The tumour blood flow became more or less similar to the normal tissue blood flow during the 2nd-5th heatings given at 3-day intervals. The decline in the vascular response in normal and tumour tissues to the 2nd-5th heatings suggested development of vascular thermotolerance.

The changes in blood flow in the skin and in the periphery of RIF-1 tumours of C3H mice could be monitored continuously during heating with the use of the laser doppler flowmetry. The laser probe was placed gently on the skin or tumour surface and the change in blood flow was quantified from the output signal from the monitor during the heating of the tissues with temperature-controlled water. The blood flow in the tumour increased significantly during the first 20-30 min of heating at 42.5-44.5 degrees C and then began to decline during the second half of one hour of heating. The skin blood flow either continuously increased or remained elevated during 1 h heating at 42.5-44.5 degrees C. These results were generally similar to the previous reports on the heat-induced changes in blood flow in the skin and tumours measured by other methods.

The effect of Fluosol DA 20%, an emulsion of perfluorochemicals, in combination with carbogen (95% O2 and 5% CO2) breathing on the response of mouse tumors to radiation was studied. When A/J mice bearing SCK tumors in the right hind limb were injected iv with Fluosol DA 20% at 12 ml/kg and exposed to carbogen for 1 h before and during the irradiation of tumors, the response of tumors to a single dose of X irradiation was significantly enhanced. The dose modification factors for growth delay and cure of SCK tumors were 2.10 +/- 0.01 (SE) and 1.86 +/- 0.18 (SE), respectively. Such a treatment slightly increased the radiation-induced skin damage by a factor of 1.17 +/- 0.02 (SE), resulting in a therapeutic gain of 1.79 +/- 0.01 (SE) for the growth delay and 1.59 +/- 0.09 (SE) for the curability. Carbogen breathing alone also increased the response of tumor and skin to radiation, but it was far less effective than the combination of Fluosol DA 20% and carbogen breathing. It was concluded that iv injection of Fluosol DA 20% in conjunction with carbogen breathing significantly increased the O2 transport to hypoxic areas in the SCK tumors and thus significantly enhanced the tumoricidal effect of radiation on SCK tumors.

The changes in blood flow in the skin and muscle of rat by single, two or six heatings, were measured with the radioactive microsphere method. The blood flow rose continuously during the 2 h heatings at temperatures up to 43.0 degrees C and 44.0 degrees C in the skin and muscle, respectively. When heated at higher temperatures, the blood flow increased and then decreased. When heated twice at 43.5 degrees C for 1 h each, the magnitude of the increase in blood flow by the second heating varied depending on the time interval between the two heatings; e.g., the second heating on the 14th day after the first heating induced an increase in blood flow much greater than that by the first heating. When the heating at 43.5 degrees C for 1 h was repeated at intervals of five days, the second and third heatings were as effective as the first heating in increasing the skin blood flow. In the muscle, the second and third heatings were 2-3-fold more effective than the first heating in raising the blood flow. The heat-induced increase in blood flow in the skin and muscle gradually diminished from the fourth heating. The tissue temperature varied considerably during heating with a water bath at a constant temperature, due probably to the changes in blood flow.

The radioprotective effect of 5-thio-D-glucose on mouse skin was studied. Intraperitoneal injection of A/J mice with 1.5 g/kg of 5-thio-D-glucose 2 hr prior to X irradiation of the foot reduced early foot skin damage through Day 40 postirradiation by a dose modification factor of 1.3 +/- 0.1. Similarly, late foot deformity during Days 60-90 postirradiation was reduced by a factor of 1.2 +/- 0.1. The radioprotective effect of 5-thio-D-glucose was also compared with that of WR-2721, an aminothiol radioprotector, in CDF1 mice. An intraperitoneal injection of 1.5 g/kg of 5-thio-D-glucose reduced early radiation-induced skin damage by a dose modification factor of 1.2 +/- 0.1 as compared to that of 1.5 +/- 0.2 by 0.65 g/kg of WR-2721 in this strain of mice. 5-Thio-D-glucose is also known to specifically kill and radiosensitize hypoxic tumor cells. Consequently, this drug may be a useful radiotherapy adjuvant, reducing normal tissue damage and enhancing tumor control by minimizing hypoxic protection.

The effects of local heating or cooling on skin microcirculation in volar aspect of human forearms was studied using laser Doppler flowmetry. When the skin was heated to 40 degrees C from a normal temperature of 32 degrees C, red cell flow (laser Doppler flow, blood flow) momentarily increased several fold and then temporarily decreased. The flow subsequently resumed a gradual increase reaching 10-15 times that of control in 30-40 min. When the skin temperature was returned to 32 degrees C after 60 min of heating, the blood flow momentarily declined but soon increased for several minutes before it began its major descent. When cooled from 32 degrees C to 5 degrees C, the flow momentarily decreased, but soon increased, surpassing the pre-cooling level. The flow began to decline when the cooling was prolonged for more than 15-20 min. The changes in flow corresponded well with the changes in number (volume) and speed of red cells. Laser Doppler flowmetry was found to be very useful for continuously monitoring microcirculatory blood flow in human skin.

In experimental animal systems, hyperthermia at therapeutic temperature (43-45 degrees C) causes a profound increase in blood flow in normal tissues while it induces only meager and temporal increases in blood flow in tumors. A severe vascular occlusion and hemorrhage usually follows the increase in blood flow in the tumors at the above temperatures. Another pronounced physiological change in tumors by heat is a prompt decrease in intratumor pH. The decrease in intratumor pH would accentuate the thermokilling of tumor cells and also possibly inhibit repair of thermodamage and development of thermotolerance in tumors. The temperature in tumors may rise higher than that in normal tissues during heating because of inefficient heat dissipation from the tumor as a result of decrease blood flow or vascular occlusion. Thus, the differential effects of heat on vascular function and pH in tumors and normal tissues may result in a greater damage in tumors than in surrounding normal tissues. Further investigation is urgently needed to find out whether similar physiological changes occur in human tumors and normal tissues by hyperthermia.

Vascular change by the combined treatments of radiation and hyperthermia was studied. The legs of rats were irradiated with 2000 rad of X rays in a single dose and heated at 43.0 degrees C for 1 hr at various times after irradiation, and the blood flow and vascular volume in the skin and muscle were determined with 125I-microspheres and 51Cr-RBC methods, respectively. Irradiation alone caused an immediate increase in blood flow and vascular volume in skin and muscle followed by a second increase during 2-4 weeks postirradiation. Heating also caused an immediate and profound increase in blood flow and vascular volume. When tissues were irradiated first and heated the increase in blood flow and vascular volume was generally greater than that caused by irradiation or heat alone for about 4 weeks postirradiation. The combined effects were either additive or more than additive depending on the interval between the irradiation and heating during this period. Hyperthermia at 40 days postirradiation increased the blood flow and vascular volume only slightly above that of the irradiated control, indicating that the combined effect of irradiation and hyperthermia became less than additive. It was concluded that the thermosensitivity of irradiated blood vessels in skin and muscle for 3-4 weeks postirradiation was at least similar or greater than that of unirradiated controls. The thermosensitivity of vessels appeared to decline 40 days after irradiation.