Background:While mild itching may seem harmless,it can worsen over time,necessitating early treatment.Epicutaneous sensitization has recently gained attention.Oral exposure may promote immune tolerance,but ingestion a...Background:While mild itching may seem harmless,it can worsen over time,necessitating early treatment.Epicutaneous sensitization has recently gained attention.Oral exposure may promote immune tolerance,but ingestion after epicutaneous sensitization can trigger severe allergic responses.Therefore,this study focused on the initial stages of allergic symptoms before they become severe and investigated the mechanisms underlying food ingestion-induced mild itching following epicutaneous sensitization.Methods:Female mice were epicutaneously sensitized with ovalbumin(OVA).Scratching behavior was recorded,and serum and tissue samples were collected.Levels of OVA-specific immunoglobulin(Ig)E/IgG1,histamine,and mast cell protease-1(MCPT-1)were measured by ELISA.Histological analysis of skin tissues and immune cell infiltration was performed via staining.Results:OVA challenge following epicutaneous sensitization induced mild itching in the OVA group.Scratching behavior peaked between 1 and 2 h and persisted for 8 h before returning to baseline.This itching was accompanied by dynamic fluctuations in OVA-specific IgE and IgG1,histamine,and MCPT-1 levels.Histological analysis revealed increased epidermal thickness and granulocytic infiltration,particularly of mast cells and eosinophils,within 2 h of OVA challenge.Mast cell and eosinophil migration into the skin tissues was significant,with eosinophil migration into the dermis persisted despite normalization of histamine levels and mast cell degranulation.These results suggest that mast cells and eosinophils play significant roles even in mild itching.Conclusion:This study provides insights into the early immune responses involved in food allergies,contributing to a better understanding of how mild symptoms can progress to more severe reactions.展开更多
Objective To observe the clinical efficacy of ＂itching symptom＂ of allergic rhinitis treated from the perspective of ＂wind＂. Methods Forty patients were given acupuncture therapy, Fengchf （风池 GB 20, bilaterally...Objective To observe the clinical efficacy of ＂itching symptom＂ of allergic rhinitis treated from the perspective of ＂wind＂. Methods Forty patients were given acupuncture therapy, Fengchf （风池 GB 20, bilaterally）, Dazhui （大椎 GV 14）, Fengmen （风门 BL 12, bilaterally）, Feishu （肺俞 BL 13, bilaterally） and Shangyingxiang （上迎香 EX-HN8, bilaterally） were selected. After needle withdrawal, a fire cup was applied between GV 14 and BL 13, and the cup was retained for 10 min. Treatment for 15 times was considered as 1 course of treatment. Three days were free from treatment between 2 courses, and 3 courses were needed. The curative effect was evaluated after treatment ends, and follow-up visit was performed one year after treatment. Results The scores of nasal symptom and itching symptom after treatment ends and one year after treatment significantly reduced when compared with that before treatment （all P〈0.05）, the difference was not statistically significant when compared the scores of nasal symptom and itching symptom one year after treatment with that after treatment ends （both P〉O.O5）.According to the follow-up visit performed one year after treatment, the markedly effective and effective cases reduced, ineffective cases increased, and the total effective rate declined slightly. The serum IgE levels, after treatment ends I-（164.79±44.29） IU/mL and one year after treatment [（180.71±52.81）IU/ mL] , both significantly reduced when compared with that before treatment [（380.12±61.45） IU/mL, both P〈0.05] , the serum igE level one year after treatment increased when compared with that after treatment ends, but the difference was not statistically significant （P〉O.05）. Conclusion （1） Significant short-term and long-term curative effects have been obtained during the treatment of ＂itching symptom＂ of allergic rhinitis from the perspective of ＂wind＂, （2） the mechanism of action may be related with the decrease of serum IgE level, （3） it is indicated that there are correlations between allergic rhinitis and atopic diseases such as atopic dermatitis and allergic conjunctivitis, etc.展开更多
The averaging in optimal switching control problems is considered under the following two cases: the switching cost does not depend on ε and the switching cost vanishes as ε tends to zero. The value ...The averaging in optimal switching control problems is considered under the following two cases: the switching cost does not depend on ε and the switching cost vanishes as ε tends to zero. The value function of the original fast problem converges locally uniformly to the value function of the averaged problem under both cases. The ways of averaging turn out to be different between both cases.展开更多
Objective:To investigate the activity of the active principle in the spines of the seed pods of Mucuna pruriens using contraction of guinea pig ileum as index of pharmacological activity. Methods:The active principle ...Objective:To investigate the activity of the active principle in the spines of the seed pods of Mucuna pruriens using contraction of guinea pig ileum as index of pharmacological activity. Methods:The active principle was extracted with 0.0015 M NaCl.Muscle strips of guinea pig ileum were prepared and contractile responses were measured using a Kymograph.Two sets of experiment were conducted:（1）.The contraction of the ileum in presence of different concentrations of histamine,2-methylhistamine and the extract of Mucuna pruriens.（2）.The contractile response of the ileum in presence of different concentrations of the extract and antagonists including diphenhydramine,atropine and methysergide.Results:（1） The extract of Mucuna pruriens hair, 2- methylhistamine and histamine produced dose dependent contraction of guinea pig ileum (Extract ED<sub>50</sub> = 13.0μg/mL,2-methylhistamine ED<sub>50</sub>=8.5μg/mL and histamine ED<sub>50</sub>=10.0μg/ mL).（2） Diphenhydramine,an H,antagonist competitively blocked the contractile response of the Mucuna pruriens extract（3） Coadminstration of the Mucuna pruriens extract either with different doses of antimuscarinic agent atropine or 5-hydroxytryptamine blocking agent methysergide did not alter the extract induced contractile response of the guinea pig ileum.Conclusion:These results demonstrate that the spines of Mucuna pruriens possess histamine activity which may contribute to its itching and painful irritation effects.展开更多
Background: Pruritus is a distressing symptom of cholestatic, inflammatory, and malignant liver diseases. It is a common symptom in many biliary and cholestatic disorders such as primary biliary cirrhosis (PBC). Sever...Background: Pruritus is a distressing symptom of cholestatic, inflammatory, and malignant liver diseases. It is a common symptom in many biliary and cholestatic disorders such as primary biliary cirrhosis (PBC). Several mechanisms are generally accepted as possible explanations to the underlying basis of itch. However, the exact pathophysiology of pruritus in liver diseases remains unclear. The cutaneous and central neurobiology of pruritus is complex and underlies a regulation of variable mechanisms. At present, not all mechanisms including neuromediators and receptors are known. Objective: Our objective is to evaluate whether the expression pattern of NGF and its receptor TrK A has a role in pruritus in a group of Egyptian cirrhotic patients. Patients and Methods: Forty Patients with liver cirrhosis were enrolled in the study depending on clinical evidence of stigmata of chronic liver disease (e.g. jaundice, ascites, palmar erythema, spider naevi, etc.) and ultrasonographic features of liver cirrhosis (e.g. coarse echo texture, shrunken liver, etc.). Patients were divided into two groups. Group (1): included 20 patients cirrhotic patients without pruritus. Group (2): included 20 patients cirrhotic patients with pruritus. A group of age and sex matched healthy twenty volunteers as a control. Results: After evaluation of histopathological using hematoxylin and eosin stained sections (H&E) was done. There was positive correlation between NGF protein expression and severity of pruritus in cirrhotic patients with pruritus (r = 0.876, p value ≤ 0.001). Also there was positive correlation between TrK A protein expression and severity of pruritus in cirrhotic patients with pruritus (r = 0.44, p value ≤ 0.05). Conclusions: We report, for the first time, role of these proteins (NGF/TrK A) in the mechanism of pruritus in cirrhotic patients and may provide a potential target for new treatment of pruritus in cirrhotic.展开更多
[Objectives]To observe and analyze the clinical efficacy and possible mechanism of Chuanbai antipruritic lotion"water film"wet compress combined with chloramphenicol prednisone liniment in the treatment of a...[Objectives]To observe and analyze the clinical efficacy and possible mechanism of Chuanbai antipruritic lotion"water film"wet compress combined with chloramphenicol prednisone liniment in the treatment of acute eczema.[Methods]A total of 76 acute eczema cases admitted to Shiyan Taihe Hospital from January 2022 to March 2023 were divided into Western medicine treatment group and integrated traditional Chinese and Western medicine group.In the Western medicine treatment group,chloramphenicol and prednisone liniment was applied to the skin lesions and oral administration of cetirizine hydrochloride.The course of treatment in both groups was 2 weeks(w).The levels of interferon-γ(IFN-γ),interleukin-4(IL-4)and the ratio of IFN-γ/IL-4 in the peripheral blood of patients before and 2 weeks after treatment,as well as serum immunoglobulin E(IgE),anti-IgE antibody and histamine(HA)level,and with skin lesions disappearing time,skin oil,transepidermal water loss(TEWL),eczema area and severity index(EASI)score,total effective rate,degree of pruritus and traditional Chinese medicine quality of life scale(EPQOLS)score to evaluate the efficacy.[Results]Compared with the Western medicine treatment group at 2 w,the disappearance time of skin lesions in the integrated traditional Chinese and Western medicine group was shortened,TEWL,itching degree and EASI score,serum IgE and HA,and peripheral blood IL-4 levels were all decreased(P<0.05).IFN-γand IFN-γ/IL-4 ratio,anti-IgE antibody,EPQOLS score and total effective rate were all increased(P<0.05),and the difference was statistically significant.[Conclusions]Chuanbai antipruritic lotion"water film"wet compress combined with chloramphenicol prednisone liniment is an optimized and safe and efficient method for the treatment of acute eczema,which can quickly relieve the symptoms of inflammatory damage of eczema and restore the skin barrier function,dry dampness and relieve itch.Inhibition of the release of histamine active substances and regulation of immunity may be the main mechanisms.展开更多
Toll-like receptors （TLRs） are germline-encoded pattern-recognition receptors that initiate innate immune re- sponses by recognizing molecular structures shared by a wide range of pathogens, known as pathogen-associ...Toll-like receptors （TLRs） are germline-encoded pattern-recognition receptors that initiate innate immune re- sponses by recognizing molecular structures shared by a wide range of pathogens, known as pathogen-associated molecular patterns （PAMPs）. After tissue injury or cellular stress, TLRs also detect endogenous ligands known as danger-associated molecular patterns （DAMPs）. TLRs are expressed in both non-neuronal and neuronal cell types in the central nervous system （CNS） and contribute to both infectious and non-infectious disorders in the CNS. Following tissue insult and nerve injury, TLRs （such as TLR2, TLR3, and TLR4） induce the activation of microglia and astrocytes and the production of the proinflammatory cytokines in the spinal cord, leading to the development and maintenance of inflammatory pain and neu- ropathic pain. In particular, primary sensory neurons, such as nociceptors, express TLRs （e.g., TLR4 and TLR7） to sense exogenous PAMPs and endogenous DAMPs released after tissue injury and cellular stress. These neuronal TLRs are new players in the processing of pain and itch by increasing the excitability of primary sensory neurons. Given the prevalence of chronic pain and itch and the suffering of affected people, insights into TLR signaling in the nervous system will open a new avenue for the management of clinical pain and itch.展开更多
Nociception is an important physiological process that detects harmful signals and results in pain perception. In this review, we discuss important experimental evidence involving some TRP ion channels as molecular se...Nociception is an important physiological process that detects harmful signals and results in pain perception. In this review, we discuss important experimental evidence involving some TRP ion channels as molecular sensors of chemical, thermal, and mechanical noxious stimuli to evoke the pain and itch sensations. Among them are the TRPA1 channel, members of the vanilloid subfamily （TRPV1, TRPV3, and TRPV4）, and finally members of the melastatin group （TRPM2, TRPM3, and TRPMS）. Given that pain and itch are pro-survival, evolutionarily-honed protective mechanisms, care has to be exercised when developing inhibitory/modulatory com- pounds targeting specific pain/itch-TRPs so that physio- logical protective mechanisms are not disabled to a degree that stimulus-mediated injury can occur. Such events have impeded the development of safe and effective TRPV1- modulating compounds and have diverted substantial resources. A beneficial outcome can be readily accom- plished via simple dosing strategies, and also by incorpo- rating medicinal chemistry design features during compound design and synthesis. Beyond clinical use, where compounds that target more than one channel might have a place and possibly have advantageous features, highly specific and high-potency compounds will be helpful in mechanistic discovery at the structure-function level.展开更多
基金supported by JSPS KAKENHI Grant Number(22K11779).
文摘Background:While mild itching may seem harmless,it can worsen over time,necessitating early treatment.Epicutaneous sensitization has recently gained attention.Oral exposure may promote immune tolerance,but ingestion after epicutaneous sensitization can trigger severe allergic responses.Therefore,this study focused on the initial stages of allergic symptoms before they become severe and investigated the mechanisms underlying food ingestion-induced mild itching following epicutaneous sensitization.Methods:Female mice were epicutaneously sensitized with ovalbumin(OVA).Scratching behavior was recorded,and serum and tissue samples were collected.Levels of OVA-specific immunoglobulin(Ig)E/IgG1,histamine,and mast cell protease-1(MCPT-1)were measured by ELISA.Histological analysis of skin tissues and immune cell infiltration was performed via staining.Results:OVA challenge following epicutaneous sensitization induced mild itching in the OVA group.Scratching behavior peaked between 1 and 2 h and persisted for 8 h before returning to baseline.This itching was accompanied by dynamic fluctuations in OVA-specific IgE and IgG1,histamine,and MCPT-1 levels.Histological analysis revealed increased epidermal thickness and granulocytic infiltration,particularly of mast cells and eosinophils,within 2 h of OVA challenge.Mast cell and eosinophil migration into the skin tissues was significant,with eosinophil migration into the dermis persisted despite normalization of histamine levels and mast cell degranulation.These results suggest that mast cells and eosinophils play significant roles even in mild itching.Conclusion:This study provides insights into the early immune responses involved in food allergies,contributing to a better understanding of how mild symptoms can progress to more severe reactions.
文摘Objective To observe the clinical efficacy of ＂itching symptom＂ of allergic rhinitis treated from the perspective of ＂wind＂. Methods Forty patients were given acupuncture therapy, Fengchf （风池 GB 20, bilaterally）, Dazhui （大椎 GV 14）, Fengmen （风门 BL 12, bilaterally）, Feishu （肺俞 BL 13, bilaterally） and Shangyingxiang （上迎香 EX-HN8, bilaterally） were selected. After needle withdrawal, a fire cup was applied between GV 14 and BL 13, and the cup was retained for 10 min. Treatment for 15 times was considered as 1 course of treatment. Three days were free from treatment between 2 courses, and 3 courses were needed. The curative effect was evaluated after treatment ends, and follow-up visit was performed one year after treatment. Results The scores of nasal symptom and itching symptom after treatment ends and one year after treatment significantly reduced when compared with that before treatment （all P〈0.05）, the difference was not statistically significant when compared the scores of nasal symptom and itching symptom one year after treatment with that after treatment ends （both P〉O.O5）.According to the follow-up visit performed one year after treatment, the markedly effective and effective cases reduced, ineffective cases increased, and the total effective rate declined slightly. The serum IgE levels, after treatment ends I-（164.79±44.29） IU/mL and one year after treatment [（180.71±52.81）IU/ mL] , both significantly reduced when compared with that before treatment [（380.12±61.45） IU/mL, both P〈0.05] , the serum igE level one year after treatment increased when compared with that after treatment ends, but the difference was not statistically significant （P〉O.05）. Conclusion （1） Significant short-term and long-term curative effects have been obtained during the treatment of ＂itching symptom＂ of allergic rhinitis from the perspective of ＂wind＂, （2） the mechanism of action may be related with the decrease of serum IgE level, （3） it is indicated that there are correlations between allergic rhinitis and atopic diseases such as atopic dermatitis and allergic conjunctivitis, etc.
文摘The averaging in optimal switching control problems is considered under the following two cases: the switching cost does not depend on ε and the switching cost vanishes as ε tends to zero. The value function of the original fast problem converges locally uniformly to the value function of the averaged problem under both cases. The ways of averaging turn out to be different between both cases.
文摘Objective:To investigate the activity of the active principle in the spines of the seed pods of Mucuna pruriens using contraction of guinea pig ileum as index of pharmacological activity. Methods:The active principle was extracted with 0.0015 M NaCl.Muscle strips of guinea pig ileum were prepared and contractile responses were measured using a Kymograph.Two sets of experiment were conducted:（1）.The contraction of the ileum in presence of different concentrations of histamine,2-methylhistamine and the extract of Mucuna pruriens.（2）.The contractile response of the ileum in presence of different concentrations of the extract and antagonists including diphenhydramine,atropine and methysergide.Results:（1） The extract of Mucuna pruriens hair, 2- methylhistamine and histamine produced dose dependent contraction of guinea pig ileum (Extract ED<sub>50</sub> = 13.0μg/mL,2-methylhistamine ED<sub>50</sub>=8.5μg/mL and histamine ED<sub>50</sub>=10.0μg/ mL).（2） Diphenhydramine,an H,antagonist competitively blocked the contractile response of the Mucuna pruriens extract（3） Coadminstration of the Mucuna pruriens extract either with different doses of antimuscarinic agent atropine or 5-hydroxytryptamine blocking agent methysergide did not alter the extract induced contractile response of the guinea pig ileum.Conclusion:These results demonstrate that the spines of Mucuna pruriens possess histamine activity which may contribute to its itching and painful irritation effects.
文摘Background: Pruritus is a distressing symptom of cholestatic, inflammatory, and malignant liver diseases. It is a common symptom in many biliary and cholestatic disorders such as primary biliary cirrhosis (PBC). Several mechanisms are generally accepted as possible explanations to the underlying basis of itch. However, the exact pathophysiology of pruritus in liver diseases remains unclear. The cutaneous and central neurobiology of pruritus is complex and underlies a regulation of variable mechanisms. At present, not all mechanisms including neuromediators and receptors are known. Objective: Our objective is to evaluate whether the expression pattern of NGF and its receptor TrK A has a role in pruritus in a group of Egyptian cirrhotic patients. Patients and Methods: Forty Patients with liver cirrhosis were enrolled in the study depending on clinical evidence of stigmata of chronic liver disease (e.g. jaundice, ascites, palmar erythema, spider naevi, etc.) and ultrasonographic features of liver cirrhosis (e.g. coarse echo texture, shrunken liver, etc.). Patients were divided into two groups. Group (1): included 20 patients cirrhotic patients without pruritus. Group (2): included 20 patients cirrhotic patients with pruritus. A group of age and sex matched healthy twenty volunteers as a control. Results: After evaluation of histopathological using hematoxylin and eosin stained sections (H&E) was done. There was positive correlation between NGF protein expression and severity of pruritus in cirrhotic patients with pruritus (r = 0.876, p value ≤ 0.001). Also there was positive correlation between TrK A protein expression and severity of pruritus in cirrhotic patients with pruritus (r = 0.44, p value ≤ 0.05). Conclusions: We report, for the first time, role of these proteins (NGF/TrK A) in the mechanism of pruritus in cirrhotic patients and may provide a potential target for new treatment of pruritus in cirrhotic.
文摘[Objectives]To observe and analyze the clinical efficacy and possible mechanism of Chuanbai antipruritic lotion"water film"wet compress combined with chloramphenicol prednisone liniment in the treatment of acute eczema.[Methods]A total of 76 acute eczema cases admitted to Shiyan Taihe Hospital from January 2022 to March 2023 were divided into Western medicine treatment group and integrated traditional Chinese and Western medicine group.In the Western medicine treatment group,chloramphenicol and prednisone liniment was applied to the skin lesions and oral administration of cetirizine hydrochloride.The course of treatment in both groups was 2 weeks(w).The levels of interferon-γ(IFN-γ),interleukin-4(IL-4)and the ratio of IFN-γ/IL-4 in the peripheral blood of patients before and 2 weeks after treatment,as well as serum immunoglobulin E(IgE),anti-IgE antibody and histamine(HA)level,and with skin lesions disappearing time,skin oil,transepidermal water loss(TEWL),eczema area and severity index(EASI)score,total effective rate,degree of pruritus and traditional Chinese medicine quality of life scale(EPQOLS)score to evaluate the efficacy.[Results]Compared with the Western medicine treatment group at 2 w,the disappearance time of skin lesions in the integrated traditional Chinese and Western medicine group was shortened,TEWL,itching degree and EASI score,serum IgE and HA,and peripheral blood IL-4 levels were all decreased(P<0.05).IFN-γand IFN-γ/IL-4 ratio,anti-IgE antibody,EPQOLS score and total effective rate were all increased(P<0.05),and the difference was statistically significant.[Conclusions]Chuanbai antipruritic lotion"water film"wet compress combined with chloramphenicol prednisone liniment is an optimized and safe and efficient method for the treatment of acute eczema,which can quickly relieve the symptoms of inflammatory damage of eczema and restore the skin barrier function,dry dampness and relieve itch.Inhibition of the release of histamine active substances and regulation of immunity may be the main mechanisms.
基金supported by the US National Institutes of Health (R01-DE17794, R01-NS54362 and R01-NS67686)
文摘Toll-like receptors （TLRs） are germline-encoded pattern-recognition receptors that initiate innate immune re- sponses by recognizing molecular structures shared by a wide range of pathogens, known as pathogen-associated molecular patterns （PAMPs）. After tissue injury or cellular stress, TLRs also detect endogenous ligands known as danger-associated molecular patterns （DAMPs）. TLRs are expressed in both non-neuronal and neuronal cell types in the central nervous system （CNS） and contribute to both infectious and non-infectious disorders in the CNS. Following tissue insult and nerve injury, TLRs （such as TLR2, TLR3, and TLR4） induce the activation of microglia and astrocytes and the production of the proinflammatory cytokines in the spinal cord, leading to the development and maintenance of inflammatory pain and neu- ropathic pain. In particular, primary sensory neurons, such as nociceptors, express TLRs （e.g., TLR4 and TLR7） to sense exogenous PAMPs and endogenous DAMPs released after tissue injury and cellular stress. These neuronal TLRs are new players in the processing of pain and itch by increasing the excitability of primary sensory neurons. Given the prevalence of chronic pain and itch and the suffering of affected people, insights into TLR signaling in the nervous system will open a new avenue for the management of clinical pain and itch.
基金supported by the National Institutes of Health,USA(DE018549,UL1TR001117,P30AR066527,and AR48182 to WL,AR48182-S1 to WL as co-investigatorF33DE024668 and K12DE022793 to YC)+1 种基金the US Department of Defense(W81XWH-13-1-0299 to WL)the Harrington Discovery Institute,Cleveland OH(to WL)
文摘Nociception is an important physiological process that detects harmful signals and results in pain perception. In this review, we discuss important experimental evidence involving some TRP ion channels as molecular sensors of chemical, thermal, and mechanical noxious stimuli to evoke the pain and itch sensations. Among them are the TRPA1 channel, members of the vanilloid subfamily （TRPV1, TRPV3, and TRPV4）, and finally members of the melastatin group （TRPM2, TRPM3, and TRPMS）. Given that pain and itch are pro-survival, evolutionarily-honed protective mechanisms, care has to be exercised when developing inhibitory/modulatory com- pounds targeting specific pain/itch-TRPs so that physio- logical protective mechanisms are not disabled to a degree that stimulus-mediated injury can occur. Such events have impeded the development of safe and effective TRPV1- modulating compounds and have diverted substantial resources. A beneficial outcome can be readily accom- plished via simple dosing strategies, and also by incorpo- rating medicinal chemistry design features during compound design and synthesis. Beyond clinical use, where compounds that target more than one channel might have a place and possibly have advantageous features, highly specific and high-potency compounds will be helpful in mechanistic discovery at the structure-function level.
