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Osamu Ishikawa - One of the best experts on this subject based on the ideXlab platform.

  • efficacy of <B>BotulinumB> <B>ToxinB> B injection for raynaud s phenomenon and digital ulcers in patients with systemic sclerosis
    Acta Dermato-venereologica, 2017
    Co-Authors: Sei-ichiro Motegi, Chisako Fujiwara, Akiko Sekiguchi, Akihito Uehara, Kazuya Yamada, Sayaka Toki, Yuki Date, Tetsuya Nakamura, Osamu Ishikawa
    Abstract:

    The efficacy and safety of <B>BotulinumB> <B>ToxinB> B (BTX-B) for treatment of Raynaud's phenomenon and digital ulcers in patients with systemic sclerosis was assessed. A total of 45 patients with systemic sclerosis who had Raynaud's phenomenon were Blinded and divided randomly into 4 groups: a no-treatment control group, and 3 treatment groups, using 250, 1,000 or 2,000 international units (U) of BTX-B injections in the hand with more severe symptoms. Four weeks after injection, pain/numBness visual analogue scale scores and Raynaud's score in the groups treated with 1,000 and 2,000 U BTX-B were significantly lower than in the control group and the group treated with 250 U BTX-B. These Beneficial effects were sustained until 16 weeks after the single injection. At 4 weeks after injection skin temperature recovery in the group treated with 2,000 U BTX-B was significantly improved. The numBers of digital ulcers in the groups treated with 1,000 and 2,000 U BTX-B were significantly lower than in the control group. In conclusion, 1,000 and 2,000 U BTX-B injections significantly suppressed the activity of Raynaud's phenomenon and digital ulcers in patients with SSc without serious adverse events.

  • Efficacy of <B>BotulinumB> <B>ToxinB> B Injection for Raynaud’s Phenomenon and Digital Ulcers in Patients with Systemic Sclerosis
    Society for Publication of Acta Dermato-Venereologica, 2017
    Co-Authors: Sei-ichiro Motegi, Chisako Fujiwara, Akiko Sekiguchi, Akihito Uehara, Kazuya Yamada, Sayaka Toki, Yuki Date, Tetsuya Nakamura, Osamu Ishikawa
    Abstract:

    The efficacy and safety of <B>BotulinumB> <B>ToxinB> B (BTX-B) for treatment of Raynaud’s phenomenon and digital ulcers in patients with systemic sclerosis was assessed. A total of 45 patients with systemic sclerosis who had Raynaud’s phenomenon were Blinded and divided randomly into 4 groups: a no-treatment control group, and 3 treatment groups, using 250, 1,000 or 2,000 international units (U) of BTX-B injections in the hand with more severe symptoms. Four weeks after injection, pain/numBness visual analogue scale scores and Raynaud’s score in the groups treated with 1,000 and 2,000 U BTX-B were significantly lower than in the control group and the group treated with 250 U BTX-B. These Beneficial effects were sustained until 16 weeks after the single injection. At 4 weeks after injection skin temperature recovery in the group treated with 2,000 U BTX-B was significantly improved. The numBers of digital ulcers in the groups treated with 1,000 and 2,000 U BTX-B were significantly lower than in the control group. In conclusion, 1,000 and 2,000 U BTX-B injections significantly suppressed the activity of Raynaud’s phenomenon and digital ulcers in patients with SSc without serious adverse events

Roy S Chuck - One of the best experts on this subject based on the ideXlab platform.

  • <B>BotulinumB> <B>ToxinB> B-Induced Mouse Model of Keratoconjunctivitis Sicca
    2020
    Co-Authors: Olan Suwan-apichon, Kaevalin Lekhanont, Ram Rangsin, Michael Rizen, Samantha Herretes, Johann M G Reyes, Roy S Chuck
    Abstract:

    PURPOSE. To develop a mouse model of human chronic dry eye (keratoconjunctivitis sicca [KCS]). METHODS. Under direct visualization with an operating microscope, CBA/J mice received a transconjunctival injection of saline or 1.25, 5, or 20 milliunits (mU) of <B>BotulinumB> <B>ToxinB> B (BTX-B) into the lacrimal gland. The mice were either left unstressed or were suBjected to an air Blower for 5 h/d, 5 d/wk in fixed temperature and humidity conditions. Tear production and corneal fluorescein staining were evaluated in all groups Before injection and at several time points after. Tear production was measured with phenol red-impregnated cotton threads. Corneal fluorescein staining was photographed under coBalt Blue light with a digital camera fitted with a macro lens. RESULTS. BTX-B-injected mice displayed significantly decreased tear production until the 4-week time point. Throughout all time points, the addition of environmental Blower stress did not appear to alter tear production significantly. Linear regression models, used to evaluate the effects of various doses of BTX-B on tear production, showed that doses higher than 1.25 mU did not provide significantly different outcomes. After 3 days, saline-injected mice showed no corneal staining, whereas BTX-B-injected mice displayed various amounts of staining. At the early time point (day 3), there did not appear to Be an additional effect of the Blower on corneal fluorescein staining. However, at 1, 2, and 4 weeks, the Blower stress appeared to increase the amount of corneal fluorescein staining at each BTX-B dose, although not significantly. Furthermore, at 8 to 10 weeks, in the BTX B-injected groups, corneas had persistent staining, even though tear production had already returned to normal levels. Histopathologic analyses revealed no inflammatory cell infiltration of the stroma or acini of the lacrimal glands and conjunctivae of Both saline-injected and BTX-B-injected animals. CONCLUSIONS. Intralacrimal gland injection of BTX-B resulted in persistent corneal fluorescein staining within 3 days, and a significant decrease in aqueous tear production that persisted for 1 month. Intralacrimal gland injection of BTX-B suppressed lacrimation, thereBy estaBlishing a dry eye state. This animal model could Be a useful tool for investigating the pathogenesis of the chronic condition KCS in humans. (Invest Ophthalmol Vis Sci. 2006;47:133-139

  • effects of topical anti inflammatory agents in a <B>BotulinumB> <B>ToxinB> B induced mouse model of keratoconjunctivitis sicca
    Journal of Ocular Pharmacology and Therapeutics, 2007
    Co-Authors: Kaevalin Lekhanont, Choul Yong Park, Janine A Smith, Juan Castro Combs, Pisit Preechawat, Olan Suwanapichon, Ram Rangsin, Roy S Chuck
    Abstract:

    Purpose: The aim of this study was to compare the effects of topical nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroid, doxycycline, and artificial tears for the treatment of ocular sur...

  • Effect of topical olopatadine and epinastine in the <B>BotulinumB> <B>ToxinB> B-induced mouse model of dry eye.
    Journal of Ocular Pharmacology and Therapeutics, 2007
    Co-Authors: Kaevalin Lekhanont, Choul Yong Park, Juan Castro Combs, Ram Rangsin, Olan Suwan-apichon, Roy S Chuck
    Abstract:

    Purpose: The aim of this study was to compare the effect of topical olopatadine, epinastine, and luBricant eye drops on dry eye ocular surface disease in the <B>BotulinumB> <B>ToxinB> B (BTX-B)-induced mouse model of keratoconjunctivitis sicca. Methods: CBA/J mice were randomized into 3 experimental groups of 10 animals each. All mice received a transconjunctival injection of 0.05 mL of 20-mU BTX-B solutions into the left lacrimal gland. Three (3) days after intralacrimal gland injections, each group received treatment with twice-daily topical luBricant as a control, 0.1% olopatadine, or 0.05% epinastine eye drops. To monitor the progression of dry eye tear production, an ocular surface fluorescein staining score was evaluated in each of the 3 experimental groups. Results: Three (3) days after the intralacrimal gland injection of BTX-B, aqueous tear production was significantly decreased (1.95 ± 0.64 mm), compared to Baseline level (2.69 ± 0.66 mm; P < 0.001). Similarly, there was a statistically significant increa...

  • <B>BotulinumB> <B>ToxinB> B induced mouse model of keratoconjunctivitis sicca
    Investigative Ophthalmology & Visual Science, 2006
    Co-Authors: Olan Suwanapichon, Kaevalin Lekhanont, Ram Rangsin, Michael Rizen, Samantha Herretes, Johann M G Reyes, Roy S Chuck
    Abstract:

    Purpose To develop a mouse model of human chronic dry eye (keratoconjunctivitis sicca [KCS]). Methods Under direct visualization with an operating microscope, CBA/J mice received a transconjunctival injection of saline or 1.25, 5, or 20 milliunits (mU) of <B>BotulinumB> <B>ToxinB> B (BTX-B) into the lacrimal gland. The mice were either left unstressed or were suBjected to an air Blower for 5 h/d, 5 d/wk in fixed temperature and humidity conditions. Tear production and corneal fluorescein staining were evaluated in all groups Before injection and at several time points after. Tear production was measured with phenol red-impregnated cotton threads. Corneal fluorescein staining was photographed under coBalt Blue light with a digital camera fitted with a macro lens. Results BTX-B-injected mice displayed significantly decreased tear production until the 4-week time point. Throughout all time points, the addition of environmental Blower stress did not appear to alter tear production significantly. Linear regression models, used to evaluate the effects of various doses of BTX-B on tear production, showed that doses higher than 1.25 mU did not provide significantly different outcomes. After 3 days, saline-injected mice showed no corneal staining, whereas BTX-B-injected mice displayed various amounts of staining. At the early time point (day 3), there did not appear to Be an additional effect of the Blower on corneal fluorescein staining. However, at 1, 2, and 4 weeks, the Blower stress appeared to increase the amount of corneal fluorescein staining at each BTX-B dose, although not significantly. Furthermore, at 8 to 10 weeks, in the BTX B-injected groups, corneas had persistent staining, even though tear production had already returned to normal levels. Histopathologic analyses revealed no inflammatory cell infiltration of the stroma or acini of the lacrimal glands and conjunctivae of Both saline-injected and BTX-B-injected animals. Conclusions Intralacrimal gland injection of BTX-B resulted in persistent corneal fluorescein staining within 3 days, and a significant decrease in aqueous tear production that persisted for 1 month. Intralacrimal gland injection of BTX-B suppressed lacrimation, thereBy estaBlishing a dry eye state. This animal model could Be a useful tool for investigating the pathogenesis of the chronic condition KCS in humans.

Axel T Brunger - One of the best experts on this subject based on the ideXlab platform.

  • <B>BotulinumB> neuro<B>ToxinB> B recognizes its protein receptor with high affinity and specificity
    Nature, 2006
    Co-Authors: Andreas Rummel, Thomas Binz, Axel T Brunger
    Abstract:

    <B>BotulinumB> <B>ToxinB>s, produced By Clostridia <B>BotulinumB>, are a potential Biological hazard to humans and a potential Bioweapons threat. The <B>ToxinB>s are potent inhiBitors of neurotransmitter release at synapses, and it is this property that causes the neuroparalytic syndrome known as Botulism. Two related papers now report the crystal structure of <B>BotulinumB> <B>ToxinB> B Bound to its receptor on the exposed surface of the neuron. This will provide insight into the high affinity and specificity of this interaction, and aid in the development of antiBotulism vaccines and drugs. One of two papers that descriBe how <B>BotulinumB> <B>ToxinB>s produced By Clostridium <B>BotulinumB> are potent inhiBitors of neurotransmitter release By elucidating the crystal structure of <B>BotulinumB> <B>ToxinB> B Bound to its receptor. <B>BotulinumB> neuro<B>ToxinB>s (BoNTs) are produced By Clostridium <B>BotulinumB> and cause the neuroparalytic syndrome of Botulism. With a lethal dose of 1 ng kg-1, they pose a Biological hazard to humans and a serious potential Bioweapon threat1. BoNTs Bind with high specificity at neuromuscular junctions and they impair exocytosis of synaptic vesicles containing acetylcholine through specific proteolysis of SNAREs (soluBle N-ethylmaleimide-sensitive fusion protein attachment protein receptors), which constitute part of the synaptic vesicle fusion machinery2,3. The molecular details of the <B>ToxinB>–cell recognition have Been elusive. Here we report the structure of a BoNT in complex with its protein receptor: the receptor-Binding domain of <B>BotulinumB> neuro<B>ToxinB> serotype B (BoNT/B) Bound to the luminal domain of synaptotagmin II, determined at 2.15 A resolution. On Binding, a helix is induced in the luminal domain which Binds to a saddle-shaped crevice on a distal tip of BoNT/B. This crevice is adjacent to the non-overlapping ganglioside-Binding site of BoNT/B. Synaptotagmin II interacts with BoNT/B with nanomolar affinity, at Both neutral and acidic endosomal pH. Biochemical and neuronal ex vivo studies of structure-Based mutations indicate high specificity and affinity of the interaction, and high selectivity of BoNT/B among synaptotagmin I and II isoforms. Synergistic Binding of Both synaptotagmin and ganglioside imposes geometric restrictions on the initiation of BoNT/B translocation after endocytosis. Our results provide the Basis for the rational development of preventive vaccines or inhiBitors against these neuro<B>ToxinB>s.

Akiko Sekiguchi - One of the best experts on this subject based on the ideXlab platform.

  • Suppression of neuropeptide By <B>BotulinumB> <B>ToxinB> improves imiquimod-induced psoriasis-like dermatitis via the regulation of neuroimmune system.
    Journal of dermatological science, 2020
    Co-Authors: Syahla Nisaa Amalia, Akihiko Uchiyama, Hritu Baral, Yuta Inoue, Sahori Yamazaki, Chisako Fujiwara, Akiko Sekiguchi, Yoko Yokoyama, Sachiko Ogino, Ryoko Torii
    Abstract:

    ABstract Background Psoriasis is a multifactorial disease arises from a complex interaction of genetics, immune system, and environmental aspects. IL-23/Th17 immune axis has Been considered as a primary modulator in psoriasis. In addition, several findings imply that nervous system may take a part in the pathogenesis of psoriasis, suggesting that nervous system, through its neuropeptide, may interact with immune system and lead to the formation of psoriasis. OBjective We aimed to ascertain the role of neuropeptides secreted from neurons in the pathogenesis of psoriasis in vivo. Methods The release of neuropeptide was inhiBited By injecting <B>BotulinumB> <B>ToxinB> B (BTX-B) on Imiquimod (IMQ)-induced psoriasis-like dermatitis mice model. Quantification of skin dermatitis, infiltrating inflammatory cells, and the production of cytokines at the lesional skin area were performed By PSI score, immunostaining, and real-time PCR. We also tested the effect of selective CGRP antagonist (CGRP8−37) on psoriasis-like dermatitis in IMQ-treated mice. Results BTX-B injection significantly suppressed PSI score and reduced the numBer of CD4+ T cells, CD11c+ dendritic cells, and the production of IL-17A/F in the lesional skin. The expressions of PGP9.5+ nerve fiBers and neuropeptides (SP, CGRP) were also significantly reduced following BTX-B injection. Additionally, CGRP antagonist also suppressed the development of IMQ-induced psoriasis-like dermatitis in mice. Conclusion The suppression of neuropeptide secretion in the skin By BTX injection might inhiBit nerve elongation, the infiltration of immune cells, as well as IL-17 production, resulting in the improvement of psoriasis. Neuropeptide inhiBitor could also Be applied to the treatment of psoriasis.

  • efficacy of <B>BotulinumB> <B>ToxinB> B injection for raynaud s phenomenon and digital ulcers in patients with systemic sclerosis
    Acta Dermato-venereologica, 2017
    Co-Authors: Sei-ichiro Motegi, Chisako Fujiwara, Akiko Sekiguchi, Akihito Uehara, Kazuya Yamada, Sayaka Toki, Yuki Date, Tetsuya Nakamura, Osamu Ishikawa
    Abstract:

    The efficacy and safety of <B>BotulinumB> <B>ToxinB> B (BTX-B) for treatment of Raynaud's phenomenon and digital ulcers in patients with systemic sclerosis was assessed. A total of 45 patients with systemic sclerosis who had Raynaud's phenomenon were Blinded and divided randomly into 4 groups: a no-treatment control group, and 3 treatment groups, using 250, 1,000 or 2,000 international units (U) of BTX-B injections in the hand with more severe symptoms. Four weeks after injection, pain/numBness visual analogue scale scores and Raynaud's score in the groups treated with 1,000 and 2,000 U BTX-B were significantly lower than in the control group and the group treated with 250 U BTX-B. These Beneficial effects were sustained until 16 weeks after the single injection. At 4 weeks after injection skin temperature recovery in the group treated with 2,000 U BTX-B was significantly improved. The numBers of digital ulcers in the groups treated with 1,000 and 2,000 U BTX-B were significantly lower than in the control group. In conclusion, 1,000 and 2,000 U BTX-B injections significantly suppressed the activity of Raynaud's phenomenon and digital ulcers in patients with SSc without serious adverse events.

  • Efficacy of <B>BotulinumB> <B>ToxinB> B Injection for Raynaud’s Phenomenon and Digital Ulcers in Patients with Systemic Sclerosis
    Society for Publication of Acta Dermato-Venereologica, 2017
    Co-Authors: Sei-ichiro Motegi, Chisako Fujiwara, Akiko Sekiguchi, Akihito Uehara, Kazuya Yamada, Sayaka Toki, Yuki Date, Tetsuya Nakamura, Osamu Ishikawa
    Abstract:

    The efficacy and safety of <B>BotulinumB> <B>ToxinB> B (BTX-B) for treatment of Raynaud’s phenomenon and digital ulcers in patients with systemic sclerosis was assessed. A total of 45 patients with systemic sclerosis who had Raynaud’s phenomenon were Blinded and divided randomly into 4 groups: a no-treatment control group, and 3 treatment groups, using 250, 1,000 or 2,000 international units (U) of BTX-B injections in the hand with more severe symptoms. Four weeks after injection, pain/numBness visual analogue scale scores and Raynaud’s score in the groups treated with 1,000 and 2,000 U BTX-B were significantly lower than in the control group and the group treated with 250 U BTX-B. These Beneficial effects were sustained until 16 weeks after the single injection. At 4 weeks after injection skin temperature recovery in the group treated with 2,000 U BTX-B was significantly improved. The numBers of digital ulcers in the groups treated with 1,000 and 2,000 U BTX-B were significantly lower than in the control group. In conclusion, 1,000 and 2,000 U BTX-B injections significantly suppressed the activity of Raynaud’s phenomenon and digital ulcers in patients with SSc without serious adverse events

Chisako Fujiwara - One of the best experts on this subject based on the ideXlab platform.

  • Suppression of neuropeptide By <B>BotulinumB> <B>ToxinB> improves imiquimod-induced psoriasis-like dermatitis via the regulation of neuroimmune system.
    Journal of dermatological science, 2020
    Co-Authors: Syahla Nisaa Amalia, Akihiko Uchiyama, Hritu Baral, Yuta Inoue, Sahori Yamazaki, Chisako Fujiwara, Akiko Sekiguchi, Yoko Yokoyama, Sachiko Ogino, Ryoko Torii
    Abstract:

    ABstract Background Psoriasis is a multifactorial disease arises from a complex interaction of genetics, immune system, and environmental aspects. IL-23/Th17 immune axis has Been considered as a primary modulator in psoriasis. In addition, several findings imply that nervous system may take a part in the pathogenesis of psoriasis, suggesting that nervous system, through its neuropeptide, may interact with immune system and lead to the formation of psoriasis. OBjective We aimed to ascertain the role of neuropeptides secreted from neurons in the pathogenesis of psoriasis in vivo. Methods The release of neuropeptide was inhiBited By injecting <B>BotulinumB> <B>ToxinB> B (BTX-B) on Imiquimod (IMQ)-induced psoriasis-like dermatitis mice model. Quantification of skin dermatitis, infiltrating inflammatory cells, and the production of cytokines at the lesional skin area were performed By PSI score, immunostaining, and real-time PCR. We also tested the effect of selective CGRP antagonist (CGRP8−37) on psoriasis-like dermatitis in IMQ-treated mice. Results BTX-B injection significantly suppressed PSI score and reduced the numBer of CD4+ T cells, CD11c+ dendritic cells, and the production of IL-17A/F in the lesional skin. The expressions of PGP9.5+ nerve fiBers and neuropeptides (SP, CGRP) were also significantly reduced following BTX-B injection. Additionally, CGRP antagonist also suppressed the development of IMQ-induced psoriasis-like dermatitis in mice. Conclusion The suppression of neuropeptide secretion in the skin By BTX injection might inhiBit nerve elongation, the infiltration of immune cells, as well as IL-17 production, resulting in the improvement of psoriasis. Neuropeptide inhiBitor could also Be applied to the treatment of psoriasis.

  • efficacy of <B>BotulinumB> <B>ToxinB> B injection for raynaud s phenomenon and digital ulcers in patients with systemic sclerosis
    Acta Dermato-venereologica, 2017
    Co-Authors: Sei-ichiro Motegi, Chisako Fujiwara, Akiko Sekiguchi, Akihito Uehara, Kazuya Yamada, Sayaka Toki, Yuki Date, Tetsuya Nakamura, Osamu Ishikawa
    Abstract:

    The efficacy and safety of <B>BotulinumB> <B>ToxinB> B (BTX-B) for treatment of Raynaud's phenomenon and digital ulcers in patients with systemic sclerosis was assessed. A total of 45 patients with systemic sclerosis who had Raynaud's phenomenon were Blinded and divided randomly into 4 groups: a no-treatment control group, and 3 treatment groups, using 250, 1,000 or 2,000 international units (U) of BTX-B injections in the hand with more severe symptoms. Four weeks after injection, pain/numBness visual analogue scale scores and Raynaud's score in the groups treated with 1,000 and 2,000 U BTX-B were significantly lower than in the control group and the group treated with 250 U BTX-B. These Beneficial effects were sustained until 16 weeks after the single injection. At 4 weeks after injection skin temperature recovery in the group treated with 2,000 U BTX-B was significantly improved. The numBers of digital ulcers in the groups treated with 1,000 and 2,000 U BTX-B were significantly lower than in the control group. In conclusion, 1,000 and 2,000 U BTX-B injections significantly suppressed the activity of Raynaud's phenomenon and digital ulcers in patients with SSc without serious adverse events.

  • Efficacy of <B>BotulinumB> <B>ToxinB> B Injection for Raynaud’s Phenomenon and Digital Ulcers in Patients with Systemic Sclerosis
    Society for Publication of Acta Dermato-Venereologica, 2017
    Co-Authors: Sei-ichiro Motegi, Chisako Fujiwara, Akiko Sekiguchi, Akihito Uehara, Kazuya Yamada, Sayaka Toki, Yuki Date, Tetsuya Nakamura, Osamu Ishikawa
    Abstract:

    The efficacy and safety of <B>BotulinumB> <B>ToxinB> B (BTX-B) for treatment of Raynaud’s phenomenon and digital ulcers in patients with systemic sclerosis was assessed. A total of 45 patients with systemic sclerosis who had Raynaud’s phenomenon were Blinded and divided randomly into 4 groups: a no-treatment control group, and 3 treatment groups, using 250, 1,000 or 2,000 international units (U) of BTX-B injections in the hand with more severe symptoms. Four weeks after injection, pain/numBness visual analogue scale scores and Raynaud’s score in the groups treated with 1,000 and 2,000 U BTX-B were significantly lower than in the control group and the group treated with 250 U BTX-B. These Beneficial effects were sustained until 16 weeks after the single injection. At 4 weeks after injection skin temperature recovery in the group treated with 2,000 U BTX-B was significantly improved. The numBers of digital ulcers in the groups treated with 1,000 and 2,000 U BTX-B were significantly lower than in the control group. In conclusion, 1,000 and 2,000 U BTX-B injections significantly suppressed the activity of Raynaud’s phenomenon and digital ulcers in patients with SSc without serious adverse events