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References: Hair growth and hair loss

Cancer J Sci Am. 1996 Oct;2(5):273.
Protection from Radiation-Induced Alopecia with Topical Application of Nitroxides: Fractionated Studies

Cuscela D, Coffin D, Lupton GP, Cook JA, Krishna MC, Bonner RF, Mitchell JB.

Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

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 reverse similar75% compared with measurements in controls of reverse similar25%. Tempo-treated animals exhibited hair density values of reverse similar90% 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.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9166544&dopt=Abstract [PubMed - as supplied by publisher]

Biol Pharm Bull. 1997 May;20(5):586-8.
Norreticuline and reticuline as possible new agents for hair growth acceleration.

Nakaoji K, Nayeshiro H, Tanahashi T.

Sunstar Inc., Takatsuki, Osaka, Japan.

(S)-Norreticuline and (S)-reticuline have been shown to stimulate the proliferation of cultured cells from the murine hair apparatus significantly. Furthermore, these activities were found on cultured hair cells, but not on cultured keratinocytes or fibroblasts from murine skin. In addition, (S)-norreticuline significantly stimulated mouse hair regrowth. These results suggest that (S)-norreticuline and (S)-reticuline could have specific activities on hair apparatus cells and might be useful as active compounds for accelerating hair growth.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9178947&dopt=Abstract

Int J Dev Neurosci. 1997 Jul;15(4-5):619-29.
Implication of NMDA type glutamate receptors in neural regeneration and neoformation of synapses after excitotoxic injury in the guinea pig cochlea.

d'Aldin CG, Ruel J, Assie R, Pujol R, Puel JL.

INSERM U.254 Universite de Montpellier, Laboratoire de Neurobiologie de l'Audition-Plasticite synaptique, CHR Saint Charles, France.

In the adult mammalian cochlea, the ability of nerve fibres to regenerate has been observed following disruption of the organ of Corti by various means, or transsection of the cochlear nerve in the internal auditory meatus. Based upon the implication of glutamate as a neurotransmitter at synapses between sensory hair cells and terminal dendrites of the auditory nerve in the mammalian cochlea, we have developed, in a previous study, an in vivo model of neural regeneration and formation of synapses after the destruction of the afferent nerve endings by local application of the glutamate agonist alpha-amino-3-hydroxy-5-methyl-isoxazol-propionic acid (AMPA). In situ hybridization experiments performed during the re-innervation process revealed an overexpression of mRNA coding for NR1 subunit of N-methyl-D-aspartate (NMDA) receptors in the spiral ganglion neurons, suggesting that these receptors are implicated in neural regenerative processes. The present study has been designed to study the functional implication of NMDA receptors in the regrowth and synaptic repair of auditory dendrites in the guinea pig cochlea, by blocking the NMDA receptors during the period of normal functional recovery. In a first set of experiments, we recorded compound action potential after acute perilymphatic perfusion of cumulative doses (0.03-10mM) of DL 2-amino-5-phosphonovalerate (D-AP5), a NMDA antagonist, to determine the efficiency of the drug. In a second set of experiments, the auditory dendrites were destroyed by local application of the glutamate agonist AMPA. The blockage of NMDA by the antagonist D-AP5 applied with an osmotic micropump delayed the functional recovery and the regrowth of auditory dendrites. The findings of our study support the hypothesis that, in addition to acting as a fast transmitter, glutamate has a neurotrophic role via the activation of NMDA receptors.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9263038&dopt=Abstract

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