Hygiene's competitive challenge to dentistry.
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Canada↗
Biomedical subjects
D Coffin
Publications and source records attributed to D Coffin.
In vivo radiation protection by nitric oxide modulation.
Drugs that affect blood flow have been shown to be whole body radiation protectors. Using NG-nitro-L-arginine, a specific inhibitor of nitric oxide synthase, and the NO-releasing agent (C2H5)2N[N(O)NO-]Na+ (DEA/NO), we have studied the ability of NO to modulate whole body radiation toxicity in C3H mice. NG-Nitro-L-arginine given to mice between 15 and 60 min prior to radiation afforded significant protection from whole body irradiation, e.g., the estimated whole body irradiation dose required to kill 50% of mice by 30 days after radiation (LD50/30) in mice treated with NG-nitro-L-arginine 60 min before irradiation was 1051 cGy compared with a whole body radiation LD50/30 of 822 cGy in control mice (P < 0.00001). Treatment of mice with DEA/NO prior to whole body irradiation also significantly reduced toxicity; the estimated whole body radiation LD50/30 was 1063 and 945 cGy in mice treated with DEA/NO 10 or 30 min before irradiation, respectively (P < 0.00001 for radiation LD50/30 of either DEA/NO-treated group compared with control). Measurement of [14C]etanidazole binding to bone marrow demonstrated that DEA/NO and NG-nitro-L-arginine exacerbated bone marrow hypoxia. Perturbations of NO levels have profound effects on in vivo radiosensitivity of normal tissues. We hypothesize that alterations in regional blood flow may underlie the changes in radiosensitivity that we have observed.
Amino Acid Oxidoreductases↗
Sulfuric acid and streptococci clearance from respiratory tracts of mice.
The inhalation of 15 mg/cu m (3.2mu count median diameter) of H2SO4 aerosol for four hours after exposure to radioactive aerosol resulted in a reduction in the rate of clearance of nonviable streptococci from the lungs and noses of mice. A second exposure to H2SO4 lasting 90 minutes (15 mg/cu m, 3.2mu count median diameter) for four days prior to the radioactive aerosol resulted in a reduced rate of clearance of nonviable streptococci from the noses but not the lungs. Neither of these exposure regimens caused an alteration in the rate of reduction of viable streptococci from the lungs or noses. Inhalation of 1.5 mg/cu m of H2SO4 (0.6mu coung median diameter) for four daily 90-minute exposures prior to, or for four hours after exposure to Streptococcus caused no alteration in the normal rate of clearance of viable or nonviable streptococci from the noses or lungs.
Aerosols↗
Carcinogenicity of organic fractions of particulate pollutants collected in New York City and administered subcutaneously to infant mice.
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Adenoma↗
Protection from radiation-induced alopecia with topical application of nitroxides: fractionated studies.
PURPOSE: Hair loss resulting from irradiation of the head and neck or from whole brain irradiation often leads to cosmetic, social, and psychological problems for the radiotherapy patient. Few successful clinical interventions are available. We have shown that nitroxides (stable free radicals) afford radiation protection against single-dose radiation-induced alopecia in a guinea pig model. Here we determine if topical nitroxide application provides protection from fractionated radiation treatment. MATERIALS AND METHODS: Two symmetrical and contralateral areas (3 x 5 cm) of skin on the dorsal trunk of guinea pigs were shaved to a hair length of 0.25 cm. A 2 mL solution containing 70 mg/mL nitroxide (Tempo or Tempol) in 70% ethanol was topically applied to the skin surface of one side; 70% ethanol was applied to the contralateral (control) side 10 minutes before irradiation. Animals were placed in a special jig that held skin without decreasing blood flow to the treatment area and fractionated external beam radiation (7 Gy) was delivered daily for eight fractions over 10 days via a 4 MeV linear accelerator. Alopecia (hair density) was scored weekly for 13 to 14 weeks after radiotherapy, using a standardized reference with respect to hair loss and regrowth in the treatment field. RESULTS: After radiation treatment, dry desquamation and gradual hair loss were observed for both control and nitroxide-treated skin; however, over weeks 4 to 11 postirradiation hair loss was much more pronounced in control animals when compared with nitroxide-treated animals. Hair density measurements for Tempol treatment over weeks 9 to 13 were approximately 75% compared with measurements in controls of approximately 25%. Tempo-treated animals exhibited hair density values of approximately 90% compared with 12% in controls over weeks 11 to 14. Tempol and Tempo treatments resulted in significant radioprotection. Histologic evaluation showed that radiation treatment alone in ethanol controls resulted in a marked decrease in the number of hair follicles and poor development of remaining follicles; however, nitroxide pretreatment resulted in no appreciable decrease in hair follicles and hair follicles appeared mature. This was also observed in unirradiated ethanol controls. Electron paramagnetic resonance studies revealed that topical nitroxide application did not result in measurable systemic concentrations of either drug. CONCLUSIONS: The results of this study suggest that topical application of nitroxides may be useful in a clinical setting to reduce the undesirable toxicity of radiation-induced alopecia.
Administration, Topical↗