Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 33
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Proc Natl Acad Sci U S A ; 118(5)2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33468630

RESUMO

Precise, quantitative measurements of the hydration status of skin can yield important insights into dermatological health and skin structure and function, with additional relevance to essential processes of thermoregulation and other features of basic physiology. Existing tools for determining skin water content exploit surrogate electrical assessments performed with bulky, rigid, and expensive instruments that are difficult to use in a repeatable manner. Recent alternatives exploit thermal measurements using soft wireless devices that adhere gently and noninvasively to the surface of the skin, but with limited operating range (∼1 cm) and high sensitivity to subtle environmental fluctuations. This paper introduces a set of ideas and technologies that overcome these drawbacks to enable high-speed, robust, long-range automated measurements of thermal transport properties via a miniaturized, multisensor module controlled by a long-range (∼10 m) Bluetooth Low Energy system on a chip, with a graphical user interface to standard smartphones. Soft contact to the surface of the skin, with almost zero user burden, yields recordings that can be quantitatively connected to hydration levels of both the epidermis and dermis, using computational modeling techniques, with high levels of repeatability and insensitivity to ambient fluctuations in temperature. Systematic studies of polymers in layered configurations similar to those of human skin, of porcine skin with known levels of hydration, and of human subjects with benchmarks against clinical devices validate the measurement approach and associated sensor hardware. The results support capabilities in characterizing skin barrier function, assessing severity of skin diseases, and evaluating cosmetic and medication efficacy, for use in the clinic or in the home.


Assuntos
Eletrônica , Pele/patologia , Água , Tecnologia sem Fio , Adolescente , Adulto , Pré-Escolar , Análise de Elementos Finitos , Humanos , Temperatura
2.
Front Immunol ; 11: 1740, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32903402

RESUMO

Background: Activation of protease-activated receptor-2 (PAR2) has been implicated in inflammation, pruritus, and skin barrier regulation, all characteristics of atopic dermatitis (AD), as well as Netherton syndrome which has similar characteristics. However, understanding the precise role of PAR2 on neuro-immune communication in AD has been hampered by the lack of appropriate animal models. Methods: We used a recently established mouse model with epidermal overexpression of PAR2 (PAR2OE) and littermate WT mice to study the impact of increased PAR2 expression in epidermal cells on spontaneous and house dust mite (HDM)-induced skin inflammation, itch, and barrier dysfunction in AD, in vivo and ex vivo. Results: PAR2OE newborns displayed no overt abnormalities, but spontaneously developed dry skin, severe pruritus, and eczema. Dermatological, neurophysiological, and immunological analyses revealed the hallmarks of AD-like skin disease. Skin barrier defects were observed before onset of skin lesions. Application of HDM onto PAR2OE mice triggered pruritus and the skin phenotype. PAR2OE mice displayed an increased density of nerve fibers, increased nerve growth factor and endothelin-1 expression levels, alloknesis, enhanced scratching (hyperknesis), and responses of dorsal root ganglion cells to non-histaminergic pruritogens. Conclusion: PAR2 in keratinocytes, activated by exogenous and endogenous proteases, is sufficient to drive barrier dysfunction, inflammation, and pruritus and sensitize skin to the effects of HDM in a mouse model that mimics human AD. PAR2 signaling in keratinocytes appears to be sufficient to drive several levels of neuro-epidermal communication, another feature of human AD.


Assuntos
Dermatite Atópica/metabolismo , Epiderme/inervação , Gânglios Espinais/metabolismo , Queratinócitos/metabolismo , Prurido/metabolismo , Receptor PAR-2/metabolismo , Animais , Animais Geneticamente Modificados , Sinalização do Cálcio , Dermatite Atópica/genética , Dermatite Atópica/imunologia , Modelos Animais de Doenças , Endotelina-1/metabolismo , Queratinócitos/imunologia , Fator de Crescimento Neural/metabolismo , Prurido/genética , Prurido/imunologia , Pyroglyphidae/imunologia , Receptor PAR-2/genética
3.
Acta Derm Venereol ; 100(14): adv00210, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32556347

RESUMO

A total of 185 elderly Japanese patients with mild to severe dementia were surveyed on itch, using multiple methods of evaluation including self-evaluation of itch conducted by patients as well as evaluation of scratching behavior and scratching marks on the body surface conducted by others. As a result, 36.8% self-evaluated that they were suffering from itch, whereas 53.5% were found to scratch. Of those who by themselves denied the presence of itch, 31.4% were found to scratch. Dry skin was found in 74.1%, the severity of which was positively correlated to the rating of scratching behavior and marks. These results indicate a high prevalence of pruritus in patients with dementia, and suggest that one should not solely rely on self-evaluation but should refer to additional clinical information such as scratching for evaluation of pruritus in patients with dementia. Skin care with moisturizer may be important to control itch in patients with dementia.


Assuntos
Demência , Prurido , Idoso , Demência/diagnóstico , Demência/epidemiologia , Humanos , Japão/epidemiologia , Prevalência , Prurido/diagnóstico , Prurido/epidemiologia , Inquéritos e Questionários
4.
Acta Derm Venereol ; 99(3): 268-273, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30523352

RESUMO

Three clinical studies were conducted to test a newly-developed app for smartwatches, which included an algorithm to measure nocturnal scratching using acceleration data. The first study in 5 patients with atopic dermatitis demonstrated high reliability of the app for measurement of scratching compared with video monitoring (positive predictive value 90.2 ± 6.6%, sensitivity 84.6 ± 10.2%, correlation of scratching duration per h r = 0.851-0.901, p < 0.001). The second study in 20 patients with atopic dermatitis and 10 healthy volunteers showed that total scratching duration in patients was significantly longer than in healthy volunteers and correlated positively with Eczema Area and Severity Index (EASI) scores. In the third study, conducted in an open-entry manner in which 201 evaluable participants measured nocturnal scratching, those who self-reported itch or pruritic diseases had a significantly longer duration of scratching than those who did not. In conclusion, this app has a high reliability and potential clinical usefulness for measurement of nocturnal scratching.


Assuntos
Ritmo Circadiano , Computadores de Mão , Dermatite Atópica/diagnóstico , Aplicativos Móveis , Movimento , Prurido/diagnóstico , Sono , Adulto , Estudos de Casos e Controles , Dermatite Atópica/complicações , Dermatite Atópica/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prurido/etiologia , Prurido/fisiopatologia , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Fatores de Tempo
5.
J Invest Dermatol ; 137(1): 170-178, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27566399

RESUMO

Itch and pain are closely related but are distinct sensations. Intradermal injection of acid generates pain in both rodents and humans; however, few studies have addressed the intriguing question of whether acid (protons) can evoke itch like other algogens by spatial contrast activation of single nociceptors. Here, we report that (i) citric acid (0.2 mol/L) pH-dependently induced a scratching response in mice when applied intradermally to nape or cheek skin, (ii) acidified buffer elevated intracellular calcium levels in dorsal root ganglion pruriceptors, and (iii) injection of intradermal citric acid (pH 3.0) into the nape induced a pruritogen-like but not algogen-like c-Fos immunoreactivity pattern in the cervical spinal cord. Using pharmacological and genetic approaches, we identified potential acid-sensing channels/receptors involved in acidic citrate-evoked itch. Results indicate that TRPV1, but neither ASIC3 nor TRPA1, is involved in the acidic citrate-induced scratching response. Furthermore, one of the proton-sensing G-protein-coupled receptors, TDAG8, was highly (∼71%) expressed in Nppb+ dorsal root ganglion pruriceptors. Itch induced by acidic citrate, but not α-methyl-5-hydroxytryptamine, chloroquine, compound 48/80, or bile acid, was markedly decreased in TDAG8-/- mice. In a heterologous expression system, TDAG8 potentiated the acid-induced calcium response by regulating TRPV1. Thus, protons could evoke pruriception by acting on TDAG8 to regulate TRPV1 activation with its mechanism of future therapeutic relevance.


Assuntos
Acidose/metabolismo , Formiatos/farmacologia , Prurido/metabolismo , Canais de Cátion TRPV/metabolismo , Acidose/genética , Análise de Variância , Animais , Comportamento Animal , Modelos Animais de Doenças , Injeções Intradérmicas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nociceptividade/efeitos dos fármacos , Prurido/induzido quimicamente , Prurido/patologia , Distribuição Aleatória , Reação em Cadeia da Polimerase em Tempo Real/métodos , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Estatísticas não Paramétricas , Canais de Cátion TRPV/genética
6.
J Invest Dermatol ; 136(1): 154-160, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26763435

RESUMO

Several thermosensitive transient receptor potential channels (transient receptor potential vanilloid type-1, -3; transient receptor potential cation channel, subfamily A, member 1) have been implicated in itch. In contrast, the role of transient receptor potential vanilloid type-4 (TRPV4) in itch is unknown. Therefore, we investigated if TRPV4, a temperature-sensitive cation channel, plays an important role in acute itch in mice. Four different pruritogens, including serotonin (5-hydroxytryptamine [5-HT]), histamine, SLIGRL (protease-activated receptors 2/mas-related G-protein-coupled receptor C11 agonist), and chloroquine (mas-related G-protein-coupled receptor A3 agonist), were intradermally injected into mice and itch-related scratching behavior was assessed. TRPV4 knockout mice exhibited significantly fewer 5-HT-evoked scratching bouts compared with wild-type mice. Notably, no differences between TRPV4 knockout and wild-type mice were observed in the number of scratch bouts elicited by SLIGRL and histamine. Pretreatment with a TRPV4 antagonist significantly attenuated 5-HT-evoked scratching in vivo. Using calcium imaging in cultured primary murine dorsal root ganglion neurons, the response of neurons after 5-HT application, but not other pruritogens, was significantly lower in TRPV4 knockout compared with wild-type mice. A TRPV4 antagonist significantly suppressed 5-HT-evoked responses in dorsal root ganglion cells from wild-type mice. Approximately 90% of 5-HT-sensitive dorsal root ganglion neurons were immunoreactive for an antibody to TRPV4, as assessed by calcium imaging. These results indicate that 5-HT-induced itch is linked to TRPV4.


Assuntos
Comportamento Animal/efeitos dos fármacos , Prurido/metabolismo , Canais de Cátion TRPV/metabolismo , Animais , Modelos Animais de Doenças , Histamina/efeitos adversos , Histamina/farmacologia , Imuno-Histoquímica , Injeções Intradérmicas , Masculino , Camundongos , Camundongos Endogâmicos , Camundongos Knockout , Prurido/induzido quimicamente , Prurido/patologia , Distribuição Aleatória , Receptor PAR-2/efeitos dos fármacos , Receptor PAR-2/metabolismo , Valores de Referência , Células Receptoras Sensoriais/efeitos dos fármacos , Serotonina/efeitos adversos , Serotonina/farmacologia , Canais de Cátion TRPV/genética
7.
Support Care Cancer ; 24(6): 2583-90, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26715293

RESUMO

PURPOSE: Malignant fungating tumors are neoplastic tumors associated with skin ulcers, which are susceptible to microbial colonization. Bacterial infection and proliferation may lead to malodor causing distress to patients. Metronidazole-an effective agent against anaerobes-may contribute to deodorization and improvement in quality of life (QOL). This study investigated the efficacy and safety of topical metronidazole 0.75 % gel for alleviation of malodor in anaerobically infected fungating neoplastic tumors. METHODS: This was a multicenter, open-label, non-controlled, phase III study including subjects aged 20 years or older with cutaneous fungating tumors releasing malodor (minimum score of 2 (mildly offensive smell) on a scale from 0 (no smell) to 4 (extremely offensive smell) based on investigator's assessment). Subjects applied metronidazole 0.75 % gel once or twice daily at the investigator's discretion for 14 days. Success was defined as an odor score of 0 or 1 at day 14, as assessed by the investigator. Patient satisfaction was assessed using a satisfaction questionnaire. Adverse events (AEs) that occurred after application of metronidazole 0.75 % gel were also reported. RESULTS: A total of 21 subjects at a median age of 65.0 years were enrolled. The success rate of deodorization at day 14 was 95.2 % (20/21 subjects). The patient satisfaction assessment showed that 71.4 % (15/21) of subjects were markedly or moderately improved. The treatment was well tolerated with only two AE cases of skin neoplasm bleeding (one mild and one moderate). CONCLUSIONS: Metronidazole 0.75 % gel is an effective and safe treatment for deodorization of malodorous fungating tumors.


Assuntos
Infecções Bacterianas/tratamento farmacológico , Metronidazol/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Úlcera Cutânea/tratamento farmacológico , Administração Cutânea , Adulto , Idoso , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/uso terapêutico , Infecções Bacterianas/microbiologia , Infecções Bacterianas/patologia , Feminino , Humanos , Masculino , Metronidazol/efeitos adversos , Pessoa de Meia-Idade , Odorantes/prevenção & controle , Satisfação do Paciente , Qualidade de Vida , Neoplasias Cutâneas/microbiologia , Neoplasias Cutâneas/patologia , Úlcera Cutânea/microbiologia , Úlcera Cutânea/patologia , Resultado do Tratamento
8.
J Clin Invest ; 124(6): 2683-95, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24812665

RESUMO

In humans, pruritus (itch) is a common but poorly understood symptom in numerous skin and systemic diseases. Endothelin 1 (ET-1) evokes histamine-independent pruritus in mammals through activation of its cognate G protein-coupled receptor endothelin A receptor (ETAR). Here, we have identified neural endothelin-converting enzyme 1 (ECE-1) as a key regulator of ET-1-induced pruritus and neural signaling of itch. We show here that ETAR, ET-1, and ECE-1 are expressed and colocalize in murine dorsal root ganglia (DRG) neurons and human skin nerves. In murine DRG neurons, ET-1 induced internalization of ETAR within ECE-1-containing endosomes. ECE-1 inhibition slowed ETAR recycling yet prolonged ET-1-induced activation of ERK1/2, but not p38. In a murine itch model, ET-1-induced scratching behavior was substantially augmented by pharmacological ECE-1 inhibition and abrogated by treatment with an ERK1/2 inhibitor. Using iontophoresis, we demonstrated that ET-1 is a potent, partially histamine-independent pruritogen in humans. Immunohistochemical evaluation of skin from prurigo nodularis patients confirmed an upregulation of the ET-1/ETAR/ECE-1/ERK1/2 axis in patients with chronic itch. Together, our data identify the neural peptidase ECE-1 as a negative regulator of itch on sensory nerves by directly regulating ET-1-induced pruritus in humans and mice. Furthermore, these results implicate the ET-1/ECE-1/ERK1/2 pathway as a therapeutic target to treat pruritus in humans.


Assuntos
Ácido Aspártico Endopeptidases/metabolismo , Endotelina-1/metabolismo , Metaloendopeptidases/metabolismo , Prurido/etiologia , Prurido/metabolismo , Adulto , Animais , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Ácido Aspártico Endopeptidases/genética , Endotelina-1/administração & dosagem , Endotelina-1/genética , Enzimas Conversoras de Endotelina , Feminino , Gânglios Espinais/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Metaloendopeptidases/antagonistas & inibidores , Metaloendopeptidases/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Prurido/genética , Receptor de Endotelina A/metabolismo , Transdução de Sinais , Pele/inervação , Pele/metabolismo , Pele/patologia , Regulação para Cima
9.
J Allergy Clin Immunol ; 133(2): 448-60, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24373353

RESUMO

BACKGROUND: Although the cytokine IL-31 has been implicated in inflammatory and lymphoma-associated itch, the cellular basis for its pruritic action is yet unclear. OBJECTIVE: We sought to determine whether immune cell-derived IL-31 directly stimulates sensory neurons and to identify the molecular basis of IL-31-induced itch. METHODS: We used immunohistochemistry and quantitative real-time PCR to determine IL-31 expression levels in mice and human subjects. Immunohistochemistry, immunofluorescence, quantitative real-time PCR, in vivo pharmacology, Western blotting, single-cell calcium imaging, and electrophysiology were used to examine the distribution, functionality, and cellular basis of the neuronal IL-31 receptor α in mice and human subjects. RESULTS: Among all immune and resident skin cells examined, IL-31 was predominantly produced by TH2 and, to a significantly lesser extent, mature dendritic cells. Cutaneous and intrathecal injections of IL-31 evoked intense itch, and its concentrations increased significantly in murine atopy-like dermatitis skin. Both human and mouse dorsal root ganglia neurons express IL-31RA, largely in neurons that coexpress transient receptor potential cation channel vanilloid subtype 1 (TRPV1). IL-31-induced itch was significantly reduced in TRPV1-deficient and transient receptor channel potential cation channel ankyrin subtype 1 (TRPA1)-deficient mice but not in c-kit or proteinase-activated receptor 2 mice. In cultured primary sensory neurons IL-31 triggered Ca(2+) release and extracellular signal-regulated kinase 1/2 phosphorylation, inhibition of which blocked IL-31 signaling in vitro and reduced IL-31-induced scratching in vivo. CONCLUSION: IL-31RA is a functional receptor expressed by a small subpopulation of IL-31RA(+)/TRPV1(+)/TRPA1(+) neurons and is a critical neuroimmune link between TH2 cells and sensory nerves for the generation of T cell-mediated itch. Thus targeting neuronal IL-31RA might be effective in the management of TH2-mediated itch, including atopic dermatitis and cutaneous T-cell lymphoma.


Assuntos
Interleucinas/imunologia , Prurido/imunologia , Receptores de Interleucina/imunologia , Células Th2/imunologia , Animais , Canais de Cálcio/imunologia , Células Cultivadas , Feminino , Gânglios Espinais/citologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas do Tecido Nervoso/imunologia , Receptores de Interleucina/genética , Células Receptoras Sensoriais/imunologia , Pele/imunologia , Canal de Cátion TRPA1 , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/imunologia , Canais de Potencial de Receptor Transitório/imunologia
10.
Biol Pharm Bull ; 36(8): 1235-40, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23902966

RESUMO

The unique physiological features of histamine-sensitive C-fibers and spinothalamic tract neurons support the hypothesis of itch specific pathway, whereas subsequent studies on cowhage-induced itch have provided evidence against it, suggesting the presence of multiple neural pathways for itch. Not only peripheral pruritogens but also spinal neural receptors are involved in the control of itch, and will be the target of treatment. Itch sensitization in chronic pruritus is another crucial factor that needs to be considered in the treatment. Neuropathic itch is the type of itch that occurs when nerve fibers are damaged or injured and spontaneous firing of nerves takes place, and plays a major role in itch accompanying some pathological conditions such as herpes zoster. The complexity of itch is due to the broad range of mediators involved and the large variety of neural mechanisms behind.


Assuntos
Prurido/fisiopatologia , Analgésicos/uso terapêutico , Animais , Antipruriginosos/uso terapêutico , Humanos , Fenômenos Fisiológicos do Sistema Nervoso , Vias Neurais/fisiopatologia , Prurido/etiologia
11.
Pain ; 154(6): 897-904, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23582153

RESUMO

When a newly developed experimental method to vibrate vellus hairs on human skin was applied to the face and arm in healthy subjects, intense itch was reproducibly induced on the face, but not on the arm, without any flare reactions. In contrast to histamine-induced itch, mechanically evoked itch was not characterized as burning or stinging by any subjects, and was resistant to histamine H1-receptor antagonists. When the stimulation was continued for 10 min, mechanically evoked itch reached the maximum intensity within 10 s, but gradually attenuated after 60 to 90 s and was rarely perceivable at the end of stimulation. When the stimulation was discontinued at 90 s, mechanically evoked itch rapidly attenuated after the end of stimulation, but took more than 10 min before it completely diminished. These results indicate a possible involvement of C-tactile neurons in mechanically evoked itch because they have consistent characteristics such as low mechanical thresholds, intermediate adaptation, after discharge, favorable response to slowly moving stimuli, and fatigue during repeated mechanical stimulation, although it needs to be confirmed by future microneurographic studies. Touch-alloknesis was present in the adjacent skin area until mechanically evoked itch completely diminished, supporting the hypothesis that itch sensitization can be caused by a continuous activation of peripheral itch neurons whether or not they are histamine-sensitive C nerves. In conclusion, this study provides direct evidence of mechanosensitive nerves involved in itch in human skin. The purity of mechanically evoked itch without any pain-related sensory components is a major advantage for investigating the differentiation of itch from pain.


Assuntos
Estimulação Física/métodos , Prurido/etiologia , Percepção do Tato/fisiologia , Tato/fisiologia , Adulto , Método Duplo-Cego , Feminino , Histamina/farmacologia , Antagonistas dos Receptores Histamínicos H1/farmacologia , Humanos , Masculino , Prurido/induzido quimicamente , Limiar Sensorial/efeitos dos fármacos , Limiar Sensorial/fisiologia , Pele/efeitos dos fármacos , Pele/inervação , Tato/efeitos dos fármacos , Percepção do Tato/efeitos dos fármacos , Vibração
14.
J Invest Dermatol ; 132(7): 1886-91, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22418875

RESUMO

Lightly touching normal skin near a site of itch can elicit itch sensation, a phenomenon known as alloknesis. To investigate the neural mechanisms of alloknesis, we have developed an animal model. Low-threshold mechanical stimulation of the skin normally does not elicit any response in naive C57/BL6 mice. Following acute intradermal (i.d.) injection of histamine in the rostral back, mechanical stimulation 7 mm from the injection site elicited discrete hindlimb scratch bouts directed toward the stimulus. This began at 10 minutes and peaked 20-40 minutes post histamine injection, declining over the next hour. Histamine itself elicited bouts of scratching not associated with the mechanical stimulus, which ceased after 30 minutes. Histamine- and touch-evoked scratching was inhibited by the µ-opiate antagonist naltrexone. Touch-evoked scratching was observed following i.d. 5-HT (5-hydroxytryptamine), a protease-activated receptor (PAR)-4 agonist, and an MrgprC11 agonist BAM8-22, but not chloroquine or a PAR-2 agonist. The histamine H1 receptor antagonist terfenadine prevented scratching and alloknesis evoked by histamine, but not 5-HT, a PAR-4 agonist or an MrgprC11 agonist. In mice with experimental dry skin, there was a time-dependent increase in spontaneous and touch-evoked scratching. This animal model appears to be useful to investigate neural mechanisms of itch and alloknesis.


Assuntos
Modelos Animais de Doenças , Prurido/etiologia , Tato , Animais , Histamina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Naltrexona/farmacologia , Oligopeptídeos/farmacologia , Fragmentos de Peptídeos/farmacologia , Receptores de Trombina/fisiologia
15.
Int Arch Allergy Immunol ; 158(2): 191-5, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22286689

RESUMO

BACKGROUND: Urticaria is mainly caused by mast cell-derived histamine through the histamine H(1) receptor. Antihistamines are occasionally used on demand upon a recurrence of urticaria; therefore, rapidly acting agents should be explored. The onset of action is assumed to depend on time to maximum concentration (T(max)), but the speed of action needs to be evaluated not only through blood concentration analysis but also by measuring in vivo effectiveness. METHODS: In this study, we chose two representative second-generation antihistamines (bepotastine and fexofenadine) with relatively short T(max) values and evaluated their effects on histamine-induced skin responses using both visual and laser Doppler imaging scales. RESULTS: Suppression of histamine-induced flare and itch was observed 3 and 6 h after administration of both antihistamines. Attenuation of itch was seen 30 min after the administration of each drug and thereafter until 6 h. In addition, bepotastine suppressed flare formation after only 30 min following application. CONCLUSION: These results suggest that antihistamines suppress histamine-induced itch and flare, followed by wheal formation, and that bepotastine suppresses skin symptoms sooner after administration than fexofenadine does, which is relatively consistent with the T(max) results.


Assuntos
Piperidinas/uso terapêutico , Prurido/tratamento farmacológico , Piridinas/uso terapêutico , Terfenadina/análogos & derivados , Urticária/tratamento farmacológico , Adulto , Feminino , Histamina/efeitos adversos , Antagonistas não Sedativos dos Receptores H1 da Histamina/farmacologia , Antagonistas não Sedativos dos Receptores H1 da Histamina/uso terapêutico , Humanos , Masculino , Piperidinas/farmacologia , Piridinas/farmacologia , Pele/efeitos dos fármacos , Pele/patologia , Terfenadina/farmacologia , Terfenadina/uso terapêutico
18.
Semin Cutan Med Surg ; 30(2): 64-70, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21767766

RESUMO

Itch has been described for many years as an unpleasant sensation that evokes the urgent desire to scratch. Studies of the neurobiology, neurophysiology, and cellular biology of itch have gradually been clarifying the mechanism of itch both peripherally and centrally. The discussion has been focused on which nerves and neuroreceptors play major roles in itch induction. The "intensity theory" hypothesizes that signal transduction on the same nerves leads to either pain (high intensity) or itch (low intensity), depending on the signal intensity. The "labeled-line coding theory" hypothesizes the complete separation of pain and itch pathways. Itch sensitization must also be considered in discussions of itch. This review highlights anatomical and functional properties of itch pathways and their relation to understanding itch perception and pruritic diseases.


Assuntos
Vias Aferentes/fisiopatologia , Prurido/fisiopatologia , Células Receptoras Sensoriais/fisiologia , Pele/fisiopatologia , Vias Aferentes/fisiologia , Animais , Encéfalo/fisiologia , Encéfalo/fisiopatologia , Humanos , Pele/inervação , Medula Espinal/fisiologia , Medula Espinal/fisiopatologia
19.
Semin Cutan Med Surg ; 30(2): 127-37, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21767775

RESUMO

Pruritus (itch) is a major symptom in many dermatologic as well as systemic diseases and has a dramatic impact on the quality of life in these patients. The symptom of itch has to be treated on the basis of its pathophysiology and its underlying disease. In daily practice, a "quick" diagnosis of the underlying disease is often difficult, although a rapid relief of the itch is desired. We often treat patients on the basis of the symptomatology. A rational therapeutic ladder for a symptomatic therapy is useful until the final diagnosis has been confirmed. There are probably many subtypes of pruritus, just as there are many diseases that cause itch. The pathophysiology in many subtypes of pruritus is still poorly understood, hindering a rapid and targeted treatment strategy. An extensive diagnostic workup is often required to determine the final cause(s) of the itch. Thus, in daily life, physicians often start with a more or less rational therapeutic strategy to combat the debilitating itch. We present possible therapeutic ladders that form the basis for effective therapeutic itch strategies in various diseases. On the basis of our current knowledge about the different pathophysiologies of itch, on clinical trials or case reports, and our own clinical experience, we aim to present therapeutic ladders for the rapid as well as long-term management of itch. Finally, we summarize current exciting developments of experimental strategies in itch research and in clinical development for itch therapy.


Assuntos
Prurido/tratamento farmacológico , Prurido/etiologia , Algoritmos , Anticonvulsivantes/uso terapêutico , Antidepressivos/uso terapêutico , Doença Crônica , Glucocorticoides/uso terapêutico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Antagonistas de Entorpecentes , Fototerapia , Prurido/diagnóstico , Receptores Opioides/agonistas
20.
CNS Neurosci Ther ; 17(6): 742-9, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20950328

RESUMO

Targets for antipruritic therapies are now expanding from the skin to the central nervous system. Recent studies demonstrate that various neuronal receptors in the spinal cord are involved in pruritus. The spinal opioid receptor is one of the best-known examples. Spinal administration of morphine is frequently accompanied by segmental pruritus. In addition to µ-opioid receptor antagonists, κ-opioid receptor agonists have recently come into usage as novel antipruritic drugs, and are expected to suppress certain subtypes of itch such as hemodialysis- and cholestasis-associated itch that are difficult to treat with antihistamines. The gastrin-releasing peptide receptor in the superficial dorsal horn of the spinal cord has also received recent attention as a novel pathway of itch-selective neural transmission. The NMDA glutamate receptor appears to be another potential target for the treatment of itch, especially in terms of central sensitization. The development of NMDA receptor antagonists with less undesirable side effects on the central nervous system might be beneficial for antipruritic therapies. Drugs suppressing presynaptic glutamate-release such as gabapentin and pregabalin also reportedly inhibit certain subtypes of itch such as brachioradial pruritus. Spinal receptors of other neuromediators such as bradykinin, substance P, serotonin, and histamine may also be potential targets for antipruritic therapies, given that most of these molecules interfere not only with pain, but also with itch transmission or regulation. Thus, the identification of itch-specific receptors and understanding itch-related circuits in the spinal cord may be innovative strategies for the development of novel antipruritic drugs.


Assuntos
Neurotransmissores/fisiologia , Prurido/tratamento farmacológico , Prurido/fisiopatologia , Medula Espinal/fisiologia , Animais , Desenho de Fármacos , Células Secretoras de Gastrina/efeitos dos fármacos , Células Secretoras de Gastrina/fisiologia , Humanos , Receptores da Bradicinina/efeitos dos fármacos , Receptores da Bradicinina/fisiologia , Receptores de Glutamato/efeitos dos fármacos , Receptores de Glutamato/fisiologia , Receptores Histamínicos/efeitos dos fármacos , Receptores Histamínicos/fisiologia , Receptores da Neurocinina-1/efeitos dos fármacos , Receptores da Neurocinina-1/fisiologia , Receptores Opioides/efeitos dos fármacos , Receptores Opioides/fisiologia , Receptores de Serotonina/efeitos dos fármacos , Receptores de Serotonina/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...