Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proteinase-activated receptor-2 (PAR2) may be an important regulator of skin mast cell function during cutaneous inflammation and hypersensitivity. However, little is known of the role of PAR2 in allergic pruritus, because mast cells, which are thought to be responsible for this symptom, can release a number of different pruritogens. In the present study, we investigated the effects of several agents on passive cutaneous anaphylaxis-induced scratching behavior in ICR mice. As a result, cetirizine and ketanserin produced dose-dependent inhibition of scratching behavior induced by passive cutaneous anaphylaxis. Combined cetirizine with ketanserin exhibited significant inhibitory effects for the number of passive cutaneous anaphylaxis-induced scratching behavior. Pretreatment of the experimental animals with PAR2-neutralizing antibody and protease inhibitor leupeptin significantly inhibited passive cutaneous anaphylaxis-induced scratching behavior. Furthermore, we found that topical application of tacrolimus significantly reduced the number of scratching behavior induced by passive cutaneous anaphylaxis in a dose-dependent manner. Combined cetirizine with tacrolimus also exhibited significant inhibitory effects for the number of passive cutaneous anaphylaxis-induced scratching behavior. Tacrolimus in doses of 3% and 10% significantly inhibited tryptase-induced scratching behavior. These results suggest that PAR2 may be involved in passive cutaneous anaphylaxis-induced scratching behavior and tacrolimus produces an anti-allergic pruritus effect in ICR mice.
 ...
PMID:Participation of proteinase-activated receptor-2 in passive cutaneous anaphylaxis-induced scratching behavior and the inhibitory effect of tacrolimus. 1957 80

Atopic dermatitis (AD) is a chronic relapsing eczematous skin disease characterized by pruritus and inflammation and accompanied by cutaneous physiological dysfunction (dry and barrier-disrupted skin). Most of the patients have atopic diathesis. A standard guideline for the management (diagnosis, severity classification and therapy) of AD has been established. In our guideline, the necessity of dermatological training is emphasized in order to assure diagnostic skill and to enable evaluation of the severity of AD. The definitive diagnosis of AD requires the presence of all three features: (i) pruritus; (ii) typical morphology and distribution; and (iii) chronic and chronically relapsing course. For the severity classification of AD, three elements of eruption (erythema/acute papules, exudation/crusts and chronic papules/nodules/lichenification) are evaluated in the most severely affected part of each of the five body regions (head/neck, anterior trunk, posterior trunk, upper limbs and lower limbs). The areas of eruption on the five body regions are also evaluated, and both scores are totaled (maximum 60 points). The present standard therapies for AD consist of the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation, topical application of emollients to treat the cutaneous physiological dysfunction, systemic antihistamines and anti-allergic drugs as adjunctive treatments for pruritus, avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. Tacrolimus ointment (0.1%) and its low-density ointment (0.03%) are available for adult patients and 2-15-year-old patients, respectively. The importance of the correct selection of topical corticosteroids according to the severity of the eruption is also emphasized. Furthermore, deliberate use of oral cyclosporine for severe recalcitrant adult AD is referred.
 ...
PMID:Guidelines for management of atopic dermatitis. 1978 16

Itching is the most important problem in atopic dermatitis and tacrolimus has been suggested to attenuate the itching by topical application. However, the anti-itch mechanism of tacrolimus has not been well elucidated. In the present study, an allergic dermatitis accompanied by frequent scratching behaviors was induced by repeated paintings with 2,4-dinitrofluorobenzene (DNFB) acetone solution onto the mouse ear and the effects of tacrolimus and dexamethasone on the dermatitis and associated scratching behavior were comparatively examined. Repeated DNFB paintings caused a typical dermatitis accompanied by elevated serum immunoglobulin E (IgE) and frequent scratching behaviors. Both tacrolimus and dexamethasone given topically for 10 days before the final challenge significantly inhibited the ear swelling and reduced the expression of interferon-gamma mRNA. Dexamethasone inhibited the accumulation of eosinophils completely, although tacrolimus did not. Both drugs did not affect the elevation of serum IgE levels. Tacrolimus significantly inhibited the scratching behavior, whereas dexamethasone failed to affect it. Repeated DNFB challenge depleted substance P in the dermis. Treatment with tacrolimus before the final challenge completely inhibited the recovery of substance P content, whereas dexamethasone facilitated the recovery. DNFB-induced ear swelling and scratching behavior were significantly inhibited by FK888, a tachykinin NK(1) receptor antagonist. Therefore, substance P seems to participate in the induction of ear swelling and scratching behavior upon final challenge with DNFB, and depletion of substance P by tacrolimus in the dermis contributes to its inhibition of ear swelling and scratching behavior at least in part.
 ...
PMID:Depletion of substance P, a mechanism for inhibition of mouse scratching behavior by tacrolimus. 1981 45

Atopic dermatitis (AD) is chronically relapsing eczematous skin disorder having significant impact worldwide. Tacrolimus is the drug-of-choice which inhibits T-cell activation resulting in suppression of inflammation. However, despite being effective, most common adverse events of tacrolimus are low-and-variable bioavailability, burning sensation and pruritus at application site, which prompt for development of novel carrier that could effectively target tacrolimus to site-of-action without producing undesirable side-effects. Tacrolimus-loaded lipid-nanoparticles (T-LN) were prepared and optimized. DSC and FT-IR have been employed to study drug-excipient incompatibility and encapsulation of drug in lipid which was further confirmed by (1)H NMR. In vitro studies revealed much higher drug release, skin penetration and enhanced skin accumulation as compared to reference Protopic. In vitro and in vivo occlusion studies demonstrated similar occlusiveness for T-LN and reference however; T-LN showed significantly higher drug levels penetrating into deeper skin layers where dendritic cells responsible for immunopathogenesis of AD mainly reside. In-vivo skin retention demonstrated 3.36, 30.81 and 28.68-times higher stratum corneum, epidermal and dermal levels respectively compared to reference. Visualization of cutaneous uptake in-vivo using CLSM confirmed targeting to deeper skin layers and Draize test showed no skin irritation with PII 0.00. Thus T-LN displayed superior performance, effective skin targeting and improved safety as compared to reference.
 ...
PMID:Targeting tacrolimus to deeper layers of skin with improved safety for treatment of atopic dermatitis. 2063 47

Atopic dermatitis (AD) is a skin disorder having significant impact worldwide, characterized by itchy, erythematous and intensely pruritic rash with periods of remission. Tacrolimus is the drug-of-choice in treatment of many immune mediated dermatoses including AD. Despite being effective, most common adverse events of tacrolimus are burning sensation and pruritus at the application site prompting for development of novel carrier that could effectively target tacrolimus to site-of-action without producing undesirable toxic-effects. Tacrolimus loaded lipid nanoparticles (T-LN) were developed and evaluated comparatively for enhanced targeting potential to site of action and improved safety with commercially available ointment product, Protopic as reference. T-LN was successfully developed by high pressure homogenization technique. Significantly higher drug release and skin permeating properties were observed for T-LN as compared to reference. T-LN suppressed inflammatory response in vivo by 3.5 times more efficiently than reference, demonstrating its improved efficacy. Entrapment of tacrolimus in lipid nanoparticles avoided direct contact of drug with skin; alleviating drug related local side effects.
 ...
PMID:Safer than safe: lipid nanoparticulate encapsulation of tacrolimus with enhanced targeting and improved safety for atopic dermatitis. 2148 93

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by extreme pruritis and lichenified papules and plaques that may begin in or persist into adulthood. Topical corticosteroids are first-line prescription therapy for AD; they are efficacious and have a well established safety profile. The topical calcineurin inhibitors tacrolimus and pimecrolimus were approved by the US FDA in 2000 and 2001, respectively, as second-line topical therapy for AD. This review evaluates the available studies on the comparative effectiveness, safety, cost, and impact on quality of life of topical corticosteroids and topical calcineurin inhibitors for the treatment of adult AD. Tacrolimus was found to be as effective as class III-V topical corticosteroids for AD of the trunk and extremities, and more effective than low-potency class VI or VII corticosteroids for AD of the face or neck. Pimecrolimus was less effective than both tacrolimus and low-potency topical corticosteroids for moderate to severe AD. The short-term safety studies found that, compared with topical corticosteroid-treated adults, patients treated with topical calcineurin inhibitors had an increased frequency of application-site reactions, an equivalent infection risk, and a decreased risk of skin atrophy. The long-term safety of topical calcineurin inhibitors remains under investigation. Currently published studies that evaluated the comparative cost and quality-of-life effects compared tacrolimus with less potent topical corticosteroids despite the availability of equivalent potency corticosteroids. Further cost and quality-of-life studies are needed that compare topical calcineurin inhibitors with stronger classes of topical corticosteroids over longer time periods. The available clinical trials data do not suggest an efficacy advantage for topical calcineurin inhibitors over topical corticosteroids in adults with AD of the trunk and extremities, and there is not yet adequate evidence to support topical calcineurin inhibitors as first-line therapy for adult AD.
 ...
PMID:Comparative effectiveness of topical calcineurin inhibitors in adult patients with atopic dermatitis. 2226 4

Pruritus is a severe symptom that is difficult to treat in atopic dermatitis patients. Red ginseng (RG), a natural medicine, has various biological activities such as anti-inflammatory effects. In this study, we examined the efficacy of RG extract (RGE) and its mechanism on experimental atopic dermatitis in mice. The effects of RGE on vascular permeability and itching were first evaluated. Histamine-induced permeability and itching were significantly inhibited by embrocation with RGE as well as diphenhydramine, an antihistamine drug. Next, we assessed the therapeutic effect of topical RGE in a mouse model of atopic dermatitis. Dermatitis was induced by repeated application of 2,4-dinitrofluorobenzene (DNFB) acetone solution to the mouse ear. The effects of tacrolimus (a calcineurin blocker), dexamethasone (a corticosteroid), and RGE on dermatitis and associated scratching behavior were compared. Repeated DNFB application caused frequent scratching behaviors and ear swelling. Topical treatment with tacrolimus, dexamethasone, and RGE for 8 days before the final challenge with DNFB significantly inhibited ear swelling. Tacrolimus and RGE significantly inhibited scratching behavior, whereas dexamethasone failed to do so. DNFB-induced nerve growth factor expression and nerve fiber extension were significantly attenuated by tacrolimus and RGE, but not by dexamethasone. RGE may have the potential for treatment of atopic dermatitis.
 ...
PMID:Red ginseng inhibits scratching behavior associated with atopic dermatitis in experimental animal models. 2238 56

Tacrolimus is a macrolide immunosuppressant that has been demonstrated to inhibit T-lymphocyte activation without the side-effects of corticosteroids. The safety profile of tacrolimus makes it a promising therapeutic option for dermatitis. To evaluate and compare the therapeutic ability of tacrolimus 0.1% ointment and mometasone furoate 0.1% ointment in patients with chronic hand eczema and positive patch tests. Thirty adults with chronic hand eczema and positive patch test reaction to relevant contact allergens were treated with tacrolimus 0.1% ointment or mometasone furoate 0.1% ointment in a single-centre, randomized comparative study. The scores of the evaluated clinical parameters (erythema, infiltration, vesiculation, desquamation, presence of cracks and itching) did not differ between Groups A and B at any of the four time points (p>0.05).On the other hand, in both groups, a significant difference was detected in all parameters between baseline and Day 90 recorded values. Tacrolimus is a promising alternative therapy for contact dermatitis patients as it is effective from the first month of treatment, well tolerated and offers similar therapeutic results to topical corticosteroid therapy.
 ...
PMID:Tacrolimus 0.1% vs mometasone furoate topical treatment in allergic contact hand eczema: a prospective randomized clinical study. 2240 3

We report a case of rheumatoid arthritis (RA) complicated with interstitial pneumonia that deteriorated after the administration of abatacept. A 55-year-old man developed RA and interstitial pneumonia. Although interstitial pneumonia was improved by high-dose glucocorticoids, various disease-modifying antirheumatic drugs including infliximab were ineffective for his arthritis. Tacrolimus was effective but was discontinued due to refractory itching and diarrhea. After 2 months, he was registered on the Phase III trial of abatacept in Japan because of worsening of arthritis. From 2 days after the abatacept administration, frothy sputum frequently appeared, but sputum culture was negative. On 13 days after the administration, the interstitial shadow was deteriorated by chest CT as compared with that of 2 months before, and he was dropped out from the trial. On 27 days after the administration, the dose of prednisolone was increased from 2 to 10 mg/day for his arthritis. On 44 days after the administration, the interstitial pneumonia improved. Abatacpet might be the cause of the deterioration of the interstitial pneumonia, but other possibilities such as discontinuation of tacrolimus, flare-up of RA itself or viral infection should be considered. This is the first report of deteriorated interstitial pneumonia after the abatacept administration in the literature. Further cases are needed to identify the relation between abatacept and interstitial pneumonia, however this possibility should be always kept in mind when we use abatacept.
 ...
PMID:[A case of rheumatoid arthritis complicated with deteriorated interstitial pneumonia after the administration of abatacept]. 2312 86

Use of immunosuppressors in the treatment of atopic dermatitis is an important innovation that reinforces the therapeutic arsenal in this chronic disease. Two such drugs are used topically for the treatment of atopic dermatitis. Tacrolimus exists in pommade form at a concentration of 0.1% for adults and 0.03% for children. Pimecrolimus, another calcineurine inhibitor with similar efficacy and tolerability, is not marketed in France. These products inhibit cytokine production by antigen-stimulated T lymphocytes. Their clinical efficacy has been demonstrated in many studies in the United States and Europe. They are particularly valuable for patients whose clinical course is marked by disease persistence and frequent flares, which would otherwise require almost continuous topical corticosteroid treatment. Topical calcineurine inhibitors may also have a significant benefit in patients with involvement of sensitive skin areas, such as around the eyes, face, neck and genital area, where systemic absorption and the risk of skin atrophy are particular concerns. The most frequent adverse effects are a local erythema-like reaction with burning and pruritus at the outset of treatment. No significant increase in bacterial or viral infections has been noted by comparison with control groups, and no systemic impact has been reported. However, these drugs should not be used in patients with a history of Kaposi-Juliusberg disease or in patients with herpes. Photoprotection measures must be respected. New trials with tacrolimus show that atopic lesions can be controlled by treating subclinical inflammation twice weekly between flares, thereby preventing flares and prolonging the flare-free interval. This new therapeutic approach is called proactive treatment. The efficacy of oral cyclosporine at 4-5 mg/kg/day in severe forms of atopic dermatitis is now well demonstrated. There is consistent evidence that oral cyclosporin is beneficial in patients whose disease is not adequately controlled by conventional topical therapies, leading to a significant improvement in health-related quality of life. Other immunosuppressors like methotrexate and some biologics (omalizumab, retuximab, etc.) show good efficacy during flares of severe forms, but larger comparative studies are needed before recommending these new treatments in severe atopic dermatitis.
 ...
PMID:[Place of immunosuppressors in atopic dermatitis]. 2347 53


<< Previous 1 2 3 4 5 Next >>