Assessment of the safety and efficacy of topical copper chlorophyllin in women with photodamaged facial skin.

BACKGROUND: Chronic exposure to the sun causes the skin to prematurely age. Photodamaged skin is characterized by progressive damage to the dermal extracellular matrix with loss of collagen and degradation of elastin. Clinical manifestations of such photoaged or photodamaged skin include wrinkles and irregular pigmentation. Various cosmetic treatments including topical retinoids, growth factors, and skin lighteners have shown some benefit. Salts of copper chlorophyllin complex are semi-synthetic naturally derived compounds with anti-oxidant and wound healing activity that has not been previously tested in photodamaged skin. OBJECTIVES: This single-center pilot study was conducted to assess the efficacy and safety of a liposomal dispersion of topically applied sodium copper chlorophyllin complex in women with mild-moderate fine lines and wrinkles in the periocular areas and facial solar lentigenes over a course of 8 weeks. METHODS: Subjects were supplied with the test product, a topical gel containing chlorophyllin complex salts (0.066%), with directions to apply a pea-sized amount to the periocular areas, cheeks and nose every morning and evening. Clinical assessments were performed at screening/baseline and at week 8. Standardized digital photographs were taken and self-assessment questionnaires were conducted. RESULTS: Ten subjects completed the 8-week study. All clinical efficacy parameters showed statistically significant improvements over baseline at week 8. The study product was well tolerated. Subject questionnaires showed the test product was highly rated. CONCLUSIONS: In this pilot study, a topical formulation containing a liposomal dispersion of sodium copper chlorophyllin complex was shown to be clinically effective and well tolerated for the treatment of mild-moderate photodamage and solar lentigenes when used for 8 weeks.

Assessment of the hamster cheek pouch as a model for radiation-induced oral mucositis, and evaluation of the protective effects of keratinocyte growth factor using this model.

PURPOSE: Oral mucositis induced by radiotherapy impacts quality of life. Previous studies have reported on the use of the hamster as a model for radiation-induced oral mucositis; however, details regarding factors such as radiation dose response, effects on myeloperoxidase (MPO) activity and related histopathological changes remain unclear. In the present study using the hamster, we evaluated the dose dependency of radiation-induced oral mucositis and the effects of keratinocyte growth factor (palifermin). METHODS: Oral mucositis was induced in the cheek pouch by X-irradiation using single doses in the range 20-50 Gy. To evaluate the protective effect of palifermin, administration was carried out (5 mg/kg) on days 1, 2 and 3 or on days 9, 10 and 11 after single irradiation at a dose of 40 Gy. RESULTS: The oral mucositis score, MPO activity and histopathological findings of inflammation increased in a dose dependent manner. Palifermin treatment stimulated the proliferation of mucosal epithelial cells. Additionally, palifermin when administered on days 1, 2 and 3 after irradiation (40 Gy) reduced the severity of oral mucositis. CONCLUSIONS: The hamster was found to be a suitable model for radiation-induced oral mucositis, with excellent results regarding the evaluation of radiation dose response and drug reactivity.

Assessment of the effect of local application of amifostine on acute radiation-induced oral mucositis in guinea pigs.

The aim of present study was to assess the radioprotective effects of the local application of amifostine to treat acute buccal mucositis in guinea pigs. A total of 32 guinea pigs were randomized into four groups: (Group A) topically administered 50 mg of amifostine plus radiotherapy (RT); (Group B) 100 mg amifostine plus RT; (Group C) normal saline plus RT; and (Group D) normal saline plus sham RT. The opportunity for administration was 15 min before irradiation. When administered, the cotton pieces that had been soaked with 0.5 ml amifostine solution or saline were applied gently on the buccal mucosa of each guinea pig for 30 min. The animals in Groups A, B and C were irradiated individually with a single dose of 30 Gy to the bilateral buccal mucosa. Eight days after irradiation, the animals were scored macroscopically; they were then euthanized, and the buccal mucosal tissues were processed for hematoxylin-eosin staining and ICAM-1 immunohistochemical analysis. In Groups A and B, the mean macroscopic scores were 2.9 ± 0.6 and 2.4 ± 1.1, respectively. There was no significant difference between the two groups (P > 0.05). However, when they were separately compared with Group C (4.4 ± 0.7), a noticeable difference was obtained (P < 0.05). No mucositis was observed in Group D. Comparisons of the expression of ICAM-1 were in agreement with the macroscopic data. Histologically, superficial erosion, exudate and ulcer formation were all observed in the RT groups; only the severity and extent were different. The microscopic observations in the amifostine-treated groups were better than in Group C. The results demonstrated that topical administration of amifostine to the oral mucosa is effective treatment of acute radiation-induced mucositis.

Reduced incidence and severity of acute radiation mucositis by WF10 (IMMUNOKINE) as adjunct to standard of cure in the management of head & neck cancer patients.

OBJECTIVE: To evaluate the role of WF10-immunotherapy in reducing oro-pharyngeal complications in head and neck cancer chemoradiotherapy. MATERIAL AND METHOD: Thirteen patients were enrolled and assigned either to WF10- (n = 6) or control group (n = 7). After completion of their initial (neoadjuvant) chemotherapy, patients received WF10 intravenous infusions at 0.5 mL/kg body weight/day for five consecutive days and repeated every 3 weeks, concomitantly to standard radiotherapy (6,600-7,500 cGy, 200 cGy/day). Control patients received radiotherapy alone. RESULTS: Patients in the WF10-group had a lower incidence of oro-pharyngeal complications grade > 2, including oral mucositis (1 vs. 5), dysphagia (2 vs. 7), oral pain (3 vs. 5), taste alteration (4 vs. 6) and weight loss (2 vs. 4). The statistical significances were achieved for the parameters of oral mucositis (p = 0. 048) and dysphagia (p = 0.009). CONCLUSION: WF10 appears to reduce severity of oro-pharyngeal complications associated with standard chemoradiotherapy for head and neck cancer.

Assessment by survival analysis of the radioprotective properties of propolis and its polyphenolic compounds.

The radioprotective effects of propolis and polyphenolic compounds from propolis on the radiation-induced mortality of mice exposed to 9 Gy of gamma-irradiation were studied. Intraperitoneal (i.p.) treatment of mice at doses of 100 mg kg(-1) body weight of propolis (water or ethanolic extract; WSDP or EEP) or its polyphenolic compounds (quercetin, naringin caffeic acid, chrysin) consecutively for 3 d before irradiation, delayed the onset of mortality and reduced the symptoms of radiation sickness. All test compounds provided protection against hematopoietic death (death within 30 d after irradiation). The greatest protection was achieved with quercetin; the number of survivors at the termination of the experiment was 63%. According to statistical analyses by the Kaplan-Meier method and the log-rank test, a significant difference between test components and control was found (p<0.001). Treatment with test components after lethal irradiation was ineffective. These results suggest that propolis and its polyphenolic compounds given to mice before irradiation protect mice from the lethal effects of whole-body irradiation.

Assessment of physical and antioxidant activity stability, in vitro release and in vivo efficacy of formulations added with superoxide dismutase alone or in association with alpha-tocopherol.

A topical formulation was added with different concentrations of superoxide dismutase (SOD) alone or in association with alpha-tocopherol (alpha-TOC). The physical stability was evaluated by rheological behavior of formulations stored at 4 degrees C, 30 degrees C/60% RH and 40 degrees C/70% RH for 6 months. SOD alone and formulations containing SOD 0.2%, 0.4% or 0.6% or SOD and alpha-TOC were stored in the same conditions and the enzymatic activity was evaluated by the superoxide anion scavenging using chemiluminescence measurement. In vitro release study was carried out using modified Franz diffusion cell and SOD formulations photoprotection against skin erythema was observed for 72 h. SOD and alpha-TOC formulation proved to be instable, since the interaction between the antioxidants led to both physical and enzymatic activity instability. SOD formulations showed to be physically stable and maintained the enzymatic activity for 6 months when stored at 4 and 30 degrees C/60% RH. Despite the fact of low SOD release from the formulation, it was effective in inhibiting the UVB-induced skin erythema for 48 h after a single application. Topical administration of antioxidants provides an efficient way to enrich the endogenous cutaneous protection system, and SOD formulations could be used for improving photoprotection of skin.

Assessment by cytogenetic analysis of the radioprotection properties of propolis extract.

Propolis obtained from honeybee hives has been used in folk medicine as an anti-inflammatory, anti-carcinogenic or immunomodulatory agent. In animal studies, the radioprotector effect of propolis has been attributed to its free-radical scavenging properties. The present study was carried out to show the protective properties of propolis extract against DNA damage induced by gamma irradiation. The evaluation of the radioprotective effect of propolis has been carried out by the analysis of chromosome aberration induction after several doses of gamma rays. The results of an analysis in the presence of ethanol extract of propolis (EEP) were compared with the dose-effect calibration curve for gamma-rays by analysis of chromosome aberrations without propolis, a decrease in the radiation-induced chromosome aberrations has been observed to be higher than 50% for all the doses.

Incorporation of labelled N-acylethanolamine (NAE) into rat brain regions in vivo and adaptive properties of saturated NAE under x-ray irradiation.

Regional distribution of exogenous N-palmitoylethanolamine in the rat brain was investigated in the study. Possible protective and adaptive effect of N-stearoylethanolamine under 2 Gy whole-body X-irradiation and changes of brain lipid composition were also studied. It was found that after per os administration to rats N-([9,10-3H]-palmitoyl)-ethanolamine was primarily accumulated in hypothalamus, pituitary and adrenal glands and the label amount in brain was 0.95% of the oral dose. Quantities of palmitic acid in total brain phospholipids and plasmalogen form of phosphatidylcholine were increased; free cholesterol and diacyl form of phosphatidylcholine were decreased in 2 weeks after irradiation. 11-OH-corticosteroid level in the blood of exposed rats was decreased in comparison with control animals. N-stearoylethanolamine pre-treatment prevented from increasing the plasmalogen form of phosphatidylcholine and decreasing its diacyl form and restored 11-OH-corticosteroid level in the blood of irradiated rats. Recovering of brain free cholesterol level was observed when N-stearoylethanolamine was post-treated. So, the accumulation of N-([9,10-3H]-palmitoyl)ethanolamine in brain indicates its penetration through blood-brain barrier and suggests the possible role of saturated N-acylethanolamines in brain functioning, particularly, in stress response regulation of the organism by hypothalamus-pituitary-adrenal system. N-stearoylethanolamine treatment of irradiated rats causes protective effect concerning the of irradiation induced changes in the brain lipid composition and in 11-OH-corticosteroid level and modifies phospholipid fatty acid composition.

Assessment of the protective effect of amifostine on radiation-induced pulmonary toxicity.

The objective of this study was to assess the radioprotective effects of amifostine in the rat model of radiation-induced lung injury using fractionated doses of radiation, to determine whether amifostine given before irradiation protects tumor from radiation cytotoxicity, and to determine whether changes in plasma levels of transforming growth factor (TGF)-beta correlate with radioprotective effect of amifostine. R3230 AC mammary adenocarcinoma was transplanted on the right posterior chest wall of female Fisher-344 rats. Both tumor-bearing and non-tumor-bearing animals were irradiated to the tumor or right lung using 4 MV photons and fractionated dose of 35 Gy/5 fractions/5 days. Animals with tumors and those without were randomized into 4 groups, respectively (8 to 10 rats per group), to receive (1) radiation alone; (2) radiation + amifostine; (3) amifostine alone; (4) sham radiation. Amifostine (150 mg/kg) was given intraperitoneally 30 minutes before each fraction of irradiation. The tumor size was measured twice a week. Breathing rate was assessed every 2 weeks. TGF-beta levels in plasma were assessed monthly after treatment. Six months after irradiation, animals were euthanized and lung tissue was processed for hydroxyproline content analysis. A significant increase in breathing frequency started 9 weeks after irradiation in animals that received radiation only. In the radiation + amifostine group, there was both a delay and a significantly lower peak in breathing frequency (P < .001). Hydroxyproline content was higher in the radiation-alone group than in rats given amifostine prior to radiation (P < .05). The TGF-beta levels in plasma showed an increase from 1 to 3 months after radiation, peaking at 2 months in the rats with (2.80 +/- 0.23) or without (5.32 +/- 1.21) amifostine compared to sham irradiation. TGF-beta levels were significantly lower at 1 to 3 months in rats receiving amifostine plus radiation versus those receiving radiation alone. Tumor growth delay and regrowth rate after radiation were not different between radiation-alone and radiation + amifostine groups. This study confirms the protective effect of amifostine in reducing radiation-induced pulmonary toxicity. No tumor protection was demonstrated after fractionated radiotherapy. The reduction in pulmonary injury with amifostine in paralleling lower plasma levels of TGF-beta, suggesting that monitoring plasma levels of this cytokine may reflect the efficacy of an intervention aimed at preventing radiation-induced lung injury.

A pilot study of dermofilm in acute radiation-induced desquamative skin reactions.

Dermofilm (Innovatec, Australia Pty Ltd) is a topical preparation containing hydrophilic and lipophilic agents that enhance the barrier functions of damaged skin. It has been assessed in a pilot study of 50 patients with desquamative skin reactions to establish whether it is a suitable candidate to test against an existing, widely used alternative in a randomized controlled trial. Symptomatic improvement, compliance and healing time were the study endpoints. Symptomatic improvement occurred in 49 patients and compliance with the prescribing instructions was uniform. The range of healing times observed at all sites was large but a relationship with the size of the initial desquamated area was noted. It is concluded that a randomized trial comparing Dermofilm with a widely used and cheaper alternative would require a multicentre effort involving approximately 400 patients (200 per arm). Other trial design considerations are discussed.

[Assessment of the genetic risk of radiation by irradiation data from laboratory mammals]. / Otsenka geneticheskogo riska radiatsii po dannym oblucheniia u laboratornykh mlekopitaiushchikh.

An attempt has been made to assess quantitatively genetic risk of radiation for man based on mammalian (mostly mouse) data and using the direct method proposed by UNSCEAR. The parameter employed was induction of reciprocal translocations. Two assumptions were made: human radiosensitivity equals that of the mouse; and dose-response is linear. From observations with acute gamma irradiation the estimate of risk per 10(-2) Gy was as follows: 39 translocation heterozygotes are expected among one million F1 conceptions, 5 cases of multiple congenital anomalies, 25 abortions recorded and 49 unrecorded. Chronic gamma irradiation at dose rates of 1.3 X 10(-5), 1.7 X 10(-4) and 1.0 X 10(-4) Gy/min was 3 to 10 times less effective. Exposure to 4.2 GeV deuterons proved inferior in effectiveness to gamma irradiation. Chronic exposure to 4.1 MeV neutrons delivered at 8 X 10(-4) Gy/min showed 7 times the effectiveness of chronic gamma irradiation. Administration of tritiated water (from 37 to 37 X 10(2) kBq/g b.w.) to rats entailed a risk of the same order of magnitude as external chronic gamma irradiation. Reduction of genetic risk was achieved by pretreatment with either AFT-, ATP-serotonin mixtures or the molecular combinations, Adeturon and Cytriphos. Study of interspecies differences in genetic radiosensitivity showed decline in the following order: rat-rabbit-mouse-Syrian hamster. A dose-rate effect was most clearly seen in the rat, and least clearly in the rabbit. In female mice, examination of oocyte depletion indicated primary follicles to be highly susceptible to acute gamma irradiation; decrease in sensitivity was observed beginning with stage 4. Chronic gamma irradiation was found to be less effective.