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Remission of hair loss and induction of hair regrowth by botulinum neurotoxin A in mice
ARTICLE IN PRESS 42
Abstracts Toxins 2008 / Toxicon 51 (2008) 1–54
safety in the treatment of detrusor sphincter dyssynergia. Twelve adult patients with detrusor sphincter dyssynergia are randomly divided into three groups by a random table, four patients in each group. Depending on randomization, BOTOX 50,75 or 100 U will be administered. The results indicate that BOTOX 75 and 100 U statistically reduce postvoiding residual urine and detrusor pressure at Po0.05. The BOTOX 100 U group revealed statistically most reduction when comparing between all groups at Po0.05. Conclusion:The lowest effective dose of BOTOX in the treatment of detrusor sphincter dyssynergia is 75–100 U, which is slightly lower than in other studies. Keywords: Detrusor sphincter dyssynergia; Botulinum toxin type A 10.1016/j.toxicon.2008.04.125
6. Dermatological and cosmetic indications 124. Effects of botulinum toxin type A on histamineinduced itch and vasomotor responses in human skin Parisa Gazerani a, Natalia Pedersen b, Drewes Asbjørn Mohr b, Lars Arendt-Nielsen a a b
Aalborg University, Aalborg, Denmark Aalborg South Hospital, Aalborg, Denmark
Clinical evidences reveal the anti-pruritic effect of Botulinum toxin type A (BoNT/A). BoNT/A inhibits the release of acetylcholine as well as some other substances, which may be involved in pruritus. The present study investigated the effect of subcutaneous administration of BoNT/A on experimentally induced itch by histamine in human skin. Fourteen healthy male volunteers (26.372.6 years) received BoNT/A (5 U, BOTOXs, Allergan, US) and isotonic saline in the volar surface of either forearm. Histamineprick tests were performed 4 times at the treatment sites (before, day 1, day 3 and week 1 after treatments). The itch intensity (VAS0-10) and neurogenic inflammation were measured and the effect of treatments over trials was assessed by repeated ANOVA. BOTOXs significantly reduced the histamine-induced itch intensity (F1,39 ¼ 30.2, Po0.001) compared to saline. Flare area was smaller in BOTOXs-treated arm compared to saline (F1,39 ¼ 15.4, P ¼ 0.002). Findings from laser Doppler assessed blood flow (F1,26 ¼ 177.3, Po0.001) and thermo-images (F1,26 ¼ 27.6, Po0.001) clearly showed the suppressive effect of BOTOXs on histamine-induced vasomotor reactions compared to saline. BoNT/A reduced itch intensity and neurogenic inflammation to histamine-prick test in human skin. The findings can be applicable in future treatments of some pruritic conditions. Keywords: Histamine; Prick-test; BoNT/A; Itch 10.1016/j.toxicon.2008.04.126
125. Remission of hair loss and induction of hair regrowth by botulinum neurotoxin A in mice Siro Luvisetto, Stefano Cobianchi, Sara Marinelli, Flaminia Pavone CNR Institute of Neuroscience, Roma, Italy
The present research concerns the use of botulinum neurotoxin serotype A (BoNT/A) in preventing hair loss and favoring hair regrowth in subjects suffering alopecia areata. The model used was the relatively common form of hair loss, which arises spontaneously in C57BL/6 (B6) and B6 129Sv substrains. These mice initiate losing their hairs at the 3rd–4rd month of age, predominantly in the head–neck region, with alopecia quickly proceeding in a nuchal–caudal direction over all the back. We found that mice subjected to a single BoNT/A microinjection (15 pg/ mouse), subcutaneously into the alopecic area, showed a significant long-lasting reduction of hair loss and stimulation of the hair follicle regeneration. Because of numerous endogenous molecules like growth factors, cytokines, hormones and neuropeptides profoundly influencing the hair follicle cycle, we suggest that BoNT/A, which blocks the release of various presynaptic neuromediators, could inhibit hair loss and induce hair regrowth by blocking the release of pro-inflammatory factors responsible for neurogenic inflammation. We can hypothesize that BoNT/A application could be useful to treat the androgenetic alopecia and other forms, such as stress-induced hair loss, caused by neurogenic inflammation and/or autoimmune pathologies, by chemotherapies, and more generally by hormonal dysfunctions. Further studies will improve our knowledge about this relevant thematic of research. Keywords: BoNT/A; Alopecia; Mice 10.1016/j.toxicon.2008.04.127
126. Anhidrotic effect of intradermal injections of botulinum toxin—A comparison of different products and concentrations Alma Rystedt a, Carl Swartling b, Hans Naver c a b c
University Hospital in Uppsala, Uppsala, Sweden Carl, Uppsala, Sweden Hans, Uppsala, Sweden
Botulinum toxin (BoNT) is used in various fields of medicine, including treatment of hyperhidrosis. In the literature, dose–response has varied with respect to the BTX-containing products Botoxs, Dysports and Neuroblocs. We hypothesised that the dilution level of BoNT is of importance for the effect and we therefore investigated the anhidrosis after intradermal injections of each product in three different concentrations. Nine healthy subjects received injections, each one 0.1 ml, in the back. The anhidrotic areas were identified by an iodine-starch test after 3 weeks. When the three products were diluted to 100 U/ml level, the achieved mean anhidrotic areas were approximately the same. Furthermore, the lowest used concentrations for Botoxs (25 U/ml) and Neuroblocs (100 U/ml) led to the largest anhidrotic mean area per
Abstracts Toxins 2008 / Toxicon 51 (2008) 1–54
safety in the treatment of detrusor sphincter dyssynergia. Twelve adult patients with detrusor sphincter dyssynergia are randomly divided into three groups by a random table, four patients in each group. Depending on randomization, BOTOX 50,75 or 100 U will be administered. The results indicate that BOTOX 75 and 100 U statistically reduce postvoiding residual urine and detrusor pressure at Po0.05. The BOTOX 100 U group revealed statistically most reduction when comparing between all groups at Po0.05. Conclusion:The lowest effective dose of BOTOX in the treatment of detrusor sphincter dyssynergia is 75–100 U, which is slightly lower than in other studies. Keywords: Detrusor sphincter dyssynergia; Botulinum toxin type A 10.1016/j.toxicon.2008.04.125
6. Dermatological and cosmetic indications 124. Effects of botulinum toxin type A on histamineinduced itch and vasomotor responses in human skin Parisa Gazerani a, Natalia Pedersen b, Drewes Asbjørn Mohr b, Lars Arendt-Nielsen a a b
Aalborg University, Aalborg, Denmark Aalborg South Hospital, Aalborg, Denmark
Clinical evidences reveal the anti-pruritic effect of Botulinum toxin type A (BoNT/A). BoNT/A inhibits the release of acetylcholine as well as some other substances, which may be involved in pruritus. The present study investigated the effect of subcutaneous administration of BoNT/A on experimentally induced itch by histamine in human skin. Fourteen healthy male volunteers (26.372.6 years) received BoNT/A (5 U, BOTOXs, Allergan, US) and isotonic saline in the volar surface of either forearm. Histamineprick tests were performed 4 times at the treatment sites (before, day 1, day 3 and week 1 after treatments). The itch intensity (VAS0-10) and neurogenic inflammation were measured and the effect of treatments over trials was assessed by repeated ANOVA. BOTOXs significantly reduced the histamine-induced itch intensity (F1,39 ¼ 30.2, Po0.001) compared to saline. Flare area was smaller in BOTOXs-treated arm compared to saline (F1,39 ¼ 15.4, P ¼ 0.002). Findings from laser Doppler assessed blood flow (F1,26 ¼ 177.3, Po0.001) and thermo-images (F1,26 ¼ 27.6, Po0.001) clearly showed the suppressive effect of BOTOXs on histamine-induced vasomotor reactions compared to saline. BoNT/A reduced itch intensity and neurogenic inflammation to histamine-prick test in human skin. The findings can be applicable in future treatments of some pruritic conditions. Keywords: Histamine; Prick-test; BoNT/A; Itch 10.1016/j.toxicon.2008.04.126
125. Remission of hair loss and induction of hair regrowth by botulinum neurotoxin A in mice Siro Luvisetto, Stefano Cobianchi, Sara Marinelli, Flaminia Pavone CNR Institute of Neuroscience, Roma, Italy
The present research concerns the use of botulinum neurotoxin serotype A (BoNT/A) in preventing hair loss and favoring hair regrowth in subjects suffering alopecia areata. The model used was the relatively common form of hair loss, which arises spontaneously in C57BL/6 (B6) and B6 129Sv substrains. These mice initiate losing their hairs at the 3rd–4rd month of age, predominantly in the head–neck region, with alopecia quickly proceeding in a nuchal–caudal direction over all the back. We found that mice subjected to a single BoNT/A microinjection (15 pg/ mouse), subcutaneously into the alopecic area, showed a significant long-lasting reduction of hair loss and stimulation of the hair follicle regeneration. Because of numerous endogenous molecules like growth factors, cytokines, hormones and neuropeptides profoundly influencing the hair follicle cycle, we suggest that BoNT/A, which blocks the release of various presynaptic neuromediators, could inhibit hair loss and induce hair regrowth by blocking the release of pro-inflammatory factors responsible for neurogenic inflammation. We can hypothesize that BoNT/A application could be useful to treat the androgenetic alopecia and other forms, such as stress-induced hair loss, caused by neurogenic inflammation and/or autoimmune pathologies, by chemotherapies, and more generally by hormonal dysfunctions. Further studies will improve our knowledge about this relevant thematic of research. Keywords: BoNT/A; Alopecia; Mice 10.1016/j.toxicon.2008.04.127
126. Anhidrotic effect of intradermal injections of botulinum toxin—A comparison of different products and concentrations Alma Rystedt a, Carl Swartling b, Hans Naver c a b c
University Hospital in Uppsala, Uppsala, Sweden Carl, Uppsala, Sweden Hans, Uppsala, Sweden
Botulinum toxin (BoNT) is used in various fields of medicine, including treatment of hyperhidrosis. In the literature, dose–response has varied with respect to the BTX-containing products Botoxs, Dysports and Neuroblocs. We hypothesised that the dilution level of BoNT is of importance for the effect and we therefore investigated the anhidrosis after intradermal injections of each product in three different concentrations. Nine healthy subjects received injections, each one 0.1 ml, in the back. The anhidrotic areas were identified by an iodine-starch test after 3 weeks. When the three products were diluted to 100 U/ml level, the achieved mean anhidrotic areas were approximately the same. Furthermore, the lowest used concentrations for Botoxs (25 U/ml) and Neuroblocs (100 U/ml) led to the largest anhidrotic mean area per