The Experts below are selected from a list of 246 Experts worldwide ranked by ideXlab platform
Takeshi Nakahara - One of the best experts on this subject based on the ideXlab platform.
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Inhibition of mite‐induced dermatitis, pruritus, and Nerve sprouting in mice by the endothelin receptor antagonist bosentan
Allergy, 2020Co-Authors: Makiko Kido-nakahara, Fumitaka Ohno, Masaki Takemura, Gaku Tsuji, Dugarmaa Ulzii, Bing Wang, Masutaka Furue, Takeshi NakaharaAbstract:Background Endothelin-1 (EDN1) can evoke histamine-independent pruritus in mammals and is upregulated in the lesional epidermis of atopic dermatitis (AD). EDN1 increases the production of interleukin 25 (IL-25) from keratinocytes to accelerate T helper type 2 immune deviation. Plasma EDN1 levels are positively correlated with the clinical severity and itch intensity of AD. Therefore, we hypothesized that the inhibition of EDN1 might be useful for treating atopic inflammation and itch and investigated the effects of the topical application of the EDN1 receptor antagonist bosentan on the skin inflammation and itch in a murine AD model. Methods We analyzed the mite-induced AD-like NC/Nga murine model, which was topically applied with bosentan or ethanol control every day for 3 weeks. We also subjected in vitro primary sensory neuron culture systems to Nerve Elongation and branching assays after EDN1 stimulation. Results Topical application of bosentan significantly attenuated the development of mite-induced AD-like skin inflammation, dermatitis scores, ear thickness, scratching bouts, and serum level of thymus and activation-regulated chemokine in NC/Nga mice. Bosentan application also significantly reduced the gene expression of Il13, Il17, and Ifng in the treated lesions. Histologically, the number of infiltrated dermal cells, the epidermal EDN1 expression, and the number of intraepidermal Nerve fibers were significantly inhibited upon bosentan application. While EDN1 significantly elongated the neurites of dorsal root ganglion cells in a dose- and time-dependent manner, bosentan treatment attenuated this. Conclusions EDN1 plays a significant role in mite-induced inflammation and itch. Topical bosentan is a potential protective candidate for AD.
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inhibition of mite induced dermatitis pruritus and Nerve sprouting in mice by the endothelin receptor antagonist bosentan
Allergy, 2020Co-Authors: Makiko Kidonakahara, Fumitaka Ohno, Masaki Takemura, Gaku Tsuji, Dugarmaa Ulzii, Bing Wang, Masutaka Furue, Takeshi NakaharaAbstract:Background Endothelin-1 (EDN1) can evoke histamine-independent pruritus in mammals and is upregulated in the lesional epidermis of atopic dermatitis (AD). EDN1 increases the production of interleukin 25 (IL-25) from keratinocytes to accelerate T helper type 2 immune deviation. Plasma EDN1 levels are positively correlated with the clinical severity and itch intensity of AD. Therefore, we hypothesized that the inhibition of EDN1 might be useful for treating atopic inflammation and itch and investigated the effects of the topical application of the EDN1 receptor antagonist bosentan on the skin inflammation and itch in a murine AD model. Methods We analyzed the mite-induced AD-like NC/Nga murine model, which was topically applied with bosentan or ethanol control every day for 3 weeks. We also subjected in vitro primary sensory neuron culture systems to Nerve Elongation and branching assays after EDN1 stimulation. Results Topical application of bosentan significantly attenuated the development of mite-induced AD-like skin inflammation, dermatitis scores, ear thickness, scratching bouts, and serum level of thymus and activation-regulated chemokine in NC/Nga mice. Bosentan application also significantly reduced the gene expression of Il13, Il17, and Ifng in the treated lesions. Histologically, the number of infiltrated dermal cells, the epidermal EDN1 expression, and the number of intraepidermal Nerve fibers were significantly inhibited upon bosentan application. While EDN1 significantly elongated the neurites of dorsal root ganglion cells in a dose- and time-dependent manner, bosentan treatment attenuated this. Conclusions EDN1 plays a significant role in mite-induced inflammation and itch. Topical bosentan is a potential protective candidate for AD.
Thay Q. Lee - One of the best experts on this subject based on the ideXlab platform.
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Ulnar collateral ligament insufficiency affects cubital tunnel syndrome during throwing motion: a cadaveric biomechanical study.
Journal of shoulder and elbow surgery, 2019Co-Authors: Teruhisa Mihata, Masashi Neo, Masaki Akeda, Michael Künzler, Michelle H. Mcgarry, Thay Q. LeeAbstract:Background In throwing athletes, cubital tunnel syndrome and insufficiency of the ulnar collateral ligament (UCL) are common pathologic processes of the elbow. The objective of this study was to investigate the effect of UCL tears on ulnar Nerve Elongation in the simulated throwing position. Methods Eight fresh frozen cadaveric upper limbs were tested at the simulated late cocking to acceleration phase in the throwing motion using an elbow testing system. Elbow valgus laxity and ulnar Nerve length and strain under 2 Nm of applied valgus torque (maximum torque in cadaveric elbow) were evaluated. Paired t-tests were used to compare all data between intact UCLs and UCLs after complete transection of the anterior oblique ligament. Linear regression analysis was used to investigate relationships between elbow valgus laxity and ulnar Nerve strain. Results Elbow valgus laxity significantly increased after transection of the UCL. Ulnar Nerve length after UCL transection was significantly greater than that in the intact condition at 60° (P = .006) and 90° of elbow flexion (P Conclusion Increased elbow valgus laxity due to UCL insufficiency may cause Elongation of the ulnar Nerve and exacerbate cubital tunnel syndrome during the throwing motion.
Kenji Takamori - One of the best experts on this subject based on the ideXlab platform.
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Itch and Nerve fibers with special reference to atopic dermatitis: Therapeutic implications
The Journal of dermatology, 2014Co-Authors: Mitsutoshi Tominaga, Kenji TakamoriAbstract:Nerve density in the epidermis is partly involved in itch sensitization in pruritic skin diseases, such as atopic dermatitis (AD). Epidermal innervation is thought to be regulated by the balance between Nerve Elongation factors (e.g. Nerve growth factor) and Nerve repulsion factors (e.g. semaphorin 3A). Semaphorin 3A (Sema3A) has been shown to inhibit Nerve growth factor (NGF)-induced sprouting of sensory Nerves, and epidermal Sema3A levels are lower in AD patients, concomitant with an increase in epidermal Nerve density. In addition, treatment with anti-NGF, Sema3A replacement, and several existing treatments, such as ultraviolet-based therapies, normalized the hyperinnervation in AD, resulting in suppression of itching. This review expands knowledge regarding potential therapeutic strategies for ameliorating intractable pruritus in AD.
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Sensitization of Itch Signaling: Itch Sensitization— Nerve Growth Factor, Semaphorins
Itch, 2014Co-Authors: Semaphorins Mitsutoshi Tominaga, Kenji TakamoriAbstract:Itch (or pruritus) has been defined as an unpleasant sensation that provokes the desire to scratch. Itch is also believed to signal danger from various environmental factors or physiological abnormalities. Therefore, it frequently accompanies a variety of inflammatory skin conditions and systemic diseases.Histamine is the best-known pruritogen in humans and also acts as an experimental itch-causing substance. Clinically, antihistamines, i.e., histamine H1-receptor blockers, are commonly used to treat all types of itching resulting from renal and liver diseases, as well as from serious skin diseases such as atopic dermatitis. However, antihistamines often lack efficacy in patients with chronic itch that may involve other agonists, including proteases, neuropeptides, cytokines, and opioids, and their cognate receptors, such as thermoreceptors, PARs, Mrgprs, and opioid receptors. Such pruritogenic mediators and modulators released in the periphery may directly activate itch-sensitive fibers, especially C-fibers, by binding to specific receptors on the Nerve terminals (Ikoma et al. 2006; Paus et al. 2006; Xiao and Patapoutian 2011). Nerve fibers are also activated by exogenous mechanical, chemical, and biological stimuli, resulting in itch responses (Akiyama et al. 2010; Tominaga and Takamori 2010).Histological analyses have shown that epidermal Nerve densities are increased in patients with atopic dermatitis and xerosis, suggesting that the higher density is partly responsible for itch sensitization in the periphery. Such hyperinnervation is probably caused by an imbalance of Nerve Elongation factors, such as Nerve growth factor (NGF), and Nerve repulsion factors, such as semaphorin 3A (Sema3A), produced by keratinocytes (Tominaga and Takamori 2010). These axonal guidance molecules may also act on keratinocytes, immune cells and vascular endothelial cells, and be indirectly involved in the modulation of itching. This chapter presents recent knowledge regarding itch sensitization associated with epidermal Nerve density controlled by NGF and Sema3A, especially in atopic dermatitis.
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An Update on Peripheral Mechanisms and Treatments of Itch
Biological & pharmaceutical bulletin, 2013Co-Authors: Mitsutoshi Tominaga, Kenji TakamoriAbstract:Histamine H1-receptor blockers are used to treat all types of itch resulting from serious skin diseases such as atopic dermatitis, as well as from renal and liver diseases. However, they often lack efficacy in chronic itch, a profound clinical problem that decreases quality of life. The development of effective treatments requires a full understanding of the fundamental mechanisms of itch. Recent studies have indicated that the pathogenic mechanisms of itch also involve agonists other than histamine, including proteases, neuropeptides, cytokines, and opioids, as well as their cognate receptors. Release of these pruritogenic mediators and modulators into the periphery may directly activate itch-mediating C-fibers via specific receptors on the Nerve terminals. Histological observations have shown increased epidermal Nerve densities in patients with atopic dermatitis, suggesting that the higher density is at least partly responsible for itch sensitization. This hyperinnervation is likely induced by an imbalance between Nerve Elongation and repulsion factors produced by keratinocytes. Neuronal matrix metalloproteinases are also involved in the penetration of Nerve fibers into the extracellular matrix. Moreover, itch-mediating fibers such as gastrin-releasing peptide(+) (GRP(+)) and Mas-related G-protein coupled receptor A3(+) (MrgprA3(+)) fibers are present in the skin. Clinically, emollients or UV-based therapies can partly control epidermal Nerve density, but new substances and classes of antipruritic drugs are needed. This review highlights recent knowledge regarding epidermal Nerve fibers that are partly involved in itch sensitization, and discuss peripheral mechanisms and treatments of itch, especially in atopic dermatitis.
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Topically applied semaphorin 3A ointment inhibits scratching behavior and improves skin inflammation in NC/Nga mice with atopic dermatitis.
Journal of dermatological science, 2012Co-Authors: Osamu Negi, Mitsutoshi Tominaga, Atsuko Kamo, Suhandy Tengara, Hideoki Ogawa, Kenichi Taneda, Yasushi Suga, Kenji TakamoriAbstract:Abstract Background Epidermal hyperinnervation in atopic dermatitis (AD) is activated directly by various external stimuli, causing enhanced itching. Nerve density is regulated by the Nerve repulsion factor semaphorin 3A (Sema3A), along with Nerve Elongation factors. Objective To investigate the effects of Sema3A ointment in the NC/Nga mouse model of AD. Methods An AD-like phenotype was induced by repeated application of Dermatophagoides farinae body (Dfb) ointment to the dorsal skin of NC/Nga mice. Vaseline, heparinoid, betamethasone, tacrolimus and recombinant Sema3A ointments were applied to the lesional skin once a day for 4 days. Transepidermal water loss (TEWL) was measured before and after each treatment. We also scored the degree of dermatitis and recorded videos to observe scratching behavior. Subsequently, we collected skin samples from these mice for histological analyses. Results Topical application of Sema3A, betamethasone and tacrolimus ointments significantly inhibited scratching behavior and improved dermatitis scores in Dfb-treated mice compared with control mice, whereas vaseline and heparinoid had no effects. A significant improvement of TEWL was observed only in Sema3A ointment-treated mice. Moreover, Sema3A ointment reduced the densities of PGP9.5- and substance P-immunoreactive Nerve fibers in the epidermis and the numbers of inflammatory cells, such as CD4 immunoreactive T cells and eosinophils, and improved acanthosis in the Dfb-treated mice compared with controls. Conclusion Sem3A ointment may have therapeutic efficacy in patients with pruritus and dermatitis of AD.
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Mechanisms Regulating Epidermal Innervation in Pruritus of Atopic Dermatitis
Skin Biopsy - Perspectives, 2011Co-Authors: Mitsutoshi Tominaga, Kenji TakamoriAbstract:Histamine, the best-known pruritogen in humans, is also regarded as an experimental itch-causing substance. Clinically, antihistamines, i.e., H1-receptor blockers, are used to treat all types of itch resulting from renal and liver diseases, as well as from serious skin diseases such as atopic dermatitis. Antihistamines, however, often lack efficacy in patients with chronic itch involving other agonists, including proteases, neuropeptides, cytokines, and opioids, as well as their cognate receptors, including thermoreceptors, PAR-2, and opioid receptors. Release of these pruritogenic mediators and modulators into the periphery may directly activate itch-sensitive C-fibers by binding to specific receptors on the Nerve terminals (Ikoma et al., 2006; Paus et al., 2006). Nerve fibers can also be activated by exogenous mechanical, chemical, or biological stimuli, resulting in itch responses (Tominaga and Takamori, 2010). Histological examination has shown increased epidermal Nerve densities in patients with atopic dermatitis (AD), suggesting that this higher density may be at least partly responsible for the intense itching in the skin. Such hyperinnervation is probably caused by an imbalance of Nerve Elongation factors (e.g. Nerve growth factor, amphiregulin, and gelatinase) and Nerve repulsion factors (e.g. semaphorin 3A and anosmin-1) produced by keratinocytes (Tominaga and Takamori, 2010; Tengara et al., 2010). Using a unique system of culturing rat dorsal root ganglion (DRG) neurons, consisting of Boyden chambers and extracellular matrix (ECM), we recently demonstrated that neuronal matrix metalloproteinase-2 (MMP-2) is involved in the penetration of sensory Nerve fibers into basement membrane through modulation by axonal guidance molecules and/or ECM (Tominaga et al., 2009a). Clinically, psoralenUVA (PUVA) therapy may reduce epidermal hyperinnervation in patients with AD by normalizing abnormal Sema3A and NGF expression in the epidermis, decreasing in visual analog scale (VAS) scores of pruritus severity (Tominaga et al., 2009c). Such anti-Nerve growth effects have been observed in the dry skin of acetone-treated mice following exposure to narrowband-UVB and excimer lamps (Kamo et al., 2011a). These findings may help understand the mechanisms by which UV-based therapy modulate epidermal innervation. This chapter presents recent knowledge regarding the relationship between pruritus and epidermal Nerve density, especially in AD.
Hideaki E. Takahashi - One of the best experts on this subject based on the ideXlab platform.
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Proximal Nerve Elongation vs Nerve grafting in repairing segmental Nerve defects in rabbits.
Microsurgery, 2004Co-Authors: Jiang Baoguo, Minoru Shibata, Hironori Matsuzaki, Hideaki E. TakahashiAbstract:Segmental Nerve defects have been repaired with Nerve grafts. However, regenerating fibers must go through two coaptation sites, and donor site morbidities are inevitable. We elongated the distal Nerve segment using a tissue expander and reconnected the Nerve. We compared these results with those of Nerve grafting. Nerve injury models were created in the median Nerves of both forelimbs in 27 rabbits. The right Nerve was repaired by Elongation, and the left by tibial Nerve grafting. The length of the Elongation was the same as that of the graft in each animal. Eight rabbits had a 10-mm segment repaired, 9 had a 15-mm segment repaired, and 10 had a 20-mm segment repaired. Evaluated outcomes were Nerve conduction velocity, contractile force of the flexor muscle, axons number, and fiber diameter. The elongated and grafted groups did not differ substantially on any outcome. Distal Nerve Elongation could be an alternative to Nerve grafting for repairing large Nerve defects.
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Proximal Nerve Elongation vs Nerve grafting in repairing segmental Nerve defects in rabbits.
Microsurgery, 2004Co-Authors: Jiang Baoguo, Minoru Shibata, Hironori Matsuzaki, Hideaki E. TakahashiAbstract:If segmental Nerve defects could be repaired by elongating the proximal or distal segments, Nerve grafting might be unnecessary. We elongated a 40-mm proximal segment of an injured median Nerve, in the rabbit right forelimb, at a rate of 1 mm/day for 10 days in 10 rabbits and for 15 days in another 10. On the left forelimb of the same rabbits, a 10- for 15-mm segment of the median Nerve was removed, and a 10- for 15-mm segment, respectively, of the tibial Nerve was grafted in its place. Four months after the initial surgery, Nerve conduction velocity (NCV), contractile strength of the flexor digitorum superficialis (FDS), axon count, and axon diameter did not differ significantly between the 10-mm groups but were better in the 15-mm grafted group. Elongating the proximal Nerve segment may be an alternative to grafting in repairing segmental defects of less than 10 mm.
Teruhisa Mihata - One of the best experts on this subject based on the ideXlab platform.
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Ulnar collateral ligament insufficiency affects cubital tunnel syndrome during throwing motion: a cadaveric biomechanical study.
Journal of shoulder and elbow surgery, 2019Co-Authors: Teruhisa Mihata, Masashi Neo, Masaki Akeda, Michael Künzler, Michelle H. Mcgarry, Thay Q. LeeAbstract:Background In throwing athletes, cubital tunnel syndrome and insufficiency of the ulnar collateral ligament (UCL) are common pathologic processes of the elbow. The objective of this study was to investigate the effect of UCL tears on ulnar Nerve Elongation in the simulated throwing position. Methods Eight fresh frozen cadaveric upper limbs were tested at the simulated late cocking to acceleration phase in the throwing motion using an elbow testing system. Elbow valgus laxity and ulnar Nerve length and strain under 2 Nm of applied valgus torque (maximum torque in cadaveric elbow) were evaluated. Paired t-tests were used to compare all data between intact UCLs and UCLs after complete transection of the anterior oblique ligament. Linear regression analysis was used to investigate relationships between elbow valgus laxity and ulnar Nerve strain. Results Elbow valgus laxity significantly increased after transection of the UCL. Ulnar Nerve length after UCL transection was significantly greater than that in the intact condition at 60° (P = .006) and 90° of elbow flexion (P Conclusion Increased elbow valgus laxity due to UCL insufficiency may cause Elongation of the ulnar Nerve and exacerbate cubital tunnel syndrome during the throwing motion.