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

Contact irritant dermatitis can be defined by four interrelated elements: skin barrier disruption, epidermal skin changes, cytokine release, and nerve ending changes. The predominant symptom of eczema relates to the fourth constituent, which produces pruritic symptoms that are often neglected when using pre-formulated topical steroids and immunomodulators. Although the induction of pruritus with proteinases and cytokines demonstrates the close connections between immune and neurotrophic factors in the pathophysiology of pruritus, agents that specifically affect the cutaneous nerve endings are often beneficial for use in patients affected by dermatitis. Besides avoiding triggering factors, agents such as pramoxine, phenol, camphor, and menthol are extremely valuable in allaying patients' symptoms of pruritus. Indeed, therapeutic remedies, which incorporate anti-pruritic agents in their formulation, may be advantageous for the bulk of patients with contact irritant dermatitis.
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PMID:Contact irritant dermatitis and anti-pruritic agents: the need to address the itch. 1285 65

MUC1 is expressed by glandular epithelial cells. It is overexpressed in the majority of breast tumours, making it a potential target for immune therapy. The objectives of the present study were to evaluate the anti-tumour activity and tolerance of repeated administration of TG1031 (an attenuated recombinant vaccinia virus containing sequences coding for human MUC1 and the immune stimulatory cytokine IL-2) in patients with MUC1-positive metastatic breast cancer. This was an open-label, randomised study comparing two dose levels, 5 x 10E6 and 5 x 10E7, with 14 patients in each arm. The treatment was administered intramuscularly every 3 weeks for the first 4 doses and every 6 weeks thereafter, until progression. Two patients had a partial tumour regression ( > 50%), and 15 patients had stable disease as their best overall response until at least the 5th injection. Partial regression lasted for 11 months in one patient and for 12 months in the second patient who then underwent surgical resection of her hepatic metastases. The most frequent adverse events included inflammation at injection site: 7 patients, itching or pain at injection site: 5 patients, and moderate fever: 6 patients. One responding patient developed antinuclear, anti-DNA, and increased anti-TPO antibodies after the fifth injection, and which resolved at the end of treatment. The treatment regimes were well tolerated with a low toxicity profile. Although clinical efficacy remains limited, this study demonstrates the potential use of MUC1-based immune therapy in breast cancer.
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PMID:Metastatic Breast Tumour Regression Following Treatment by a Gene-Modified Vaccinia Virus Expressing MUC1 and IL-2. 1297 34

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease. Its main features are eczematous skin lesions with a typical distribution and severe pruritus. Allergens, skin irritants, systemic or local infections, environmental pollutants and hormonal changes have a role in the pathophysiology of AD. A further important trigger factor for both intrinsic and extrinsic AD is emotional stress. Recently published observations point to direct psychoneuroimmunological and -endocrinological mechanisms: Psychological stress causes a transient increase of peripheral blood eosinophil count and an increase in both CD8+/CD11b+ and CLA+ T-cells. In addition, stress changes the cytokine and the hormone profile with increased levels of IFN-gamma and IL-5, and decreased levels of cortisol in AD patients in contrast to healthy controls. These findings underline the role of immunological changes and a possible suppressed hypothalamic-pituitary-adrenal (HPA) axis closing the loop for the final aggravation of AD.
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PMID:[Atopic dermatitis and psychological stress]. 1451 38

The Th2 cytokine inhibitor, suplatast tosilate (300 mg/day) was administered to 45 cases of patients with atopic dermatitis for 8 weeks. The clinical scores, peripheral blood eosinophil counts, serum LDH levels, total IgE levels, serum eosinophil cationic protein (ECP) levels, and serum IL-5 levels before and after the treatment were observed and comparatively evaluated. The results of this study were summarized as follows. 1) Temporary improvements were found in the severity score, itching score, and sleeplessness score. All evaluated scores decreased significantly for all observation periods at 2, 4, 6 and 8 weeks after administration of suplatast tosilate compared with those before the administration. 2) In severe group, there was a significant improvement of severity score of lower limb. In moderate group there were significant improvements of severity score of head, face, neck and of upper limb. There were significant improvements of severity score of trunk and upper limbs in mild group. 3) The peripheral blood eosinophil counts and serum LDH levels significantly diminished compared with those before administration, but no significant difference was found in total IgE levels and serum ECP levels. 4) The serum IL-5 levels decreased after administration, however, there was no statistical significance. 5) The positive correlations between delta-severity score and delta-peripheral eosinophil count, delta-serum LDH levels, delta-serum ECP levels were found. 6) The positive correlations between delta-peripheral eosinophil count and delta-serum LDH levels, delta-serum ECP levels were observed. 7) There was no sign of adverse effects of the drug. From the above mentioned results, we confirmed the high efficacy of suplatast tosilate in the treatment of atopic dermatitis.
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PMID:[The effect of suplatast tosilate on the patients with atopic dermatitis--relationship between clinical symptoms and immunological parameters]. 1468 38

Allergen specific nasal challenge (ASNC) is an optimal model to study the pathophysiological mechanisms sustaining allergic inflammation, particularly the cytokine pattern. Antihistamines have been accepted as a highly effective therapy for allergic rhinitis. The aim of this double blind, randomised, placebo controlled study was the evaluation of symptoms and cytokines, during the early phase, after a single dose of mizolastine (10 mg), fexofenadine (120 mg) or placebo, using the model of ASNC. A total of 30 patients with allergic rhinitis underwent nasal challenge 6 hours after treatment. The following parameters were evaluated 30 minutes after ASNC (i.e. early phase): nasal symptoms (rhinorrhea, itching, sneezing, obstruction), and cytokine pattern, including IL1, IL6, and TNFalpha. Mizolastine was associated with early phase reduction of: i) clinical symptoms (p < 0.03), ii) cyotkine levels of IL1 (p = 0.003), IL6 (p < 0.007), and TNF_ (p < 0.003) in comparison with placebo group. Fexofenadine significantly inhibited IL6 (p < 0.004) and TNFalpha (p < 0.004) levels in comparison with placebo. The present findings demonstrate that mizolastine exerts a significant effect on early phase events, reducing symptoms and pro-inflammatory cytokines. Fexofenadine reduces TNFalpha and IL6 levels only. These effects appear to be clinical relevant for mizolastine.
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PMID:Mizolastine and fexofenadine modulate cytokine pattern after nasal allergen challenge. 1518 Mar 56

T cell-derived cytokines are important in the development of an effective immune response, but when dysregulated they can promote disease. Here we identify a four-helix bundle cytokine we have called interleukin 31 (IL-31), which is preferentially produced by T helper type 2 cells. IL-31 signals through a receptor composed of IL-31 receptor A and oncostatin M receptor. Expression of IL-31 receptor A and oncostatin M receptor mRNA was induced in activated monocytes, whereas epithelial cells expressed both mRNAs constitutively. Transgenic mice overexpressing IL-31 developed severe pruritus, alopecia and skin lesions. Furthermore, IL-31 receptor expression was increased in diseased tissues derived from an animal model of airway hypersensitivity. These data indicate that IL-31 may be involved in promoting the dermatitis and epithelial responses that characterize allergic and non-allergic diseases.
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PMID:Interleukin 31, a cytokine produced by activated T cells, induces dermatitis in mice. 1518 96

The turnover of Jun proteins, like that of other transcription factors, is regulated through ubiquitin-dependent proteolysis. Usually, such processes are regulated by extracellular stimuli through phosphorylation of the target protein, which allows recognition by F box-containing E3 ubiquitin ligases. In the case of c-Jun and JunB, we found that extracellular stimuli also modulate protein turnover by regulating the activity of an E3 ligase by means of its phosphorylation. Activation of the Jun amino-terminal kinase (JNK) mitogen-activated protein kinase cascade after T cell stimulation accelerated degradation of c-Jun and JunB through phosphorylation-dependent activation of the E3 ligase Itch. This pathway modulates cytokine production by effector T cells.
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PMID:Jun turnover is controlled through JNK-dependent phosphorylation of the E3 ligase Itch. 1535 65

Tacrolimus ointment (Protopic, Fujisawa) is an effective agent in a class of topical immunomodulators. Its mechanism of action is based on calcineurin inhibition, which results in decreased T-cell activation and inflammatory cytokine release. Tacrolimus ointment is safe and effective for short- and long-term treatment of atopic dermatitis (AD) in pediatric and adult patients. The most common adverse events associated with its use are a transient burning sensation and pruritus at the site of application. Unlike topical corticosteroid agents, tacrolimus ointment does not cause a reduction in collagen synthesis or skin thickness. Because tacrolimus ointment does not cause skin atrophy, it may be safely used for months or years on all skin areas, including the face and intertriginous areas.
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PMID:Tacrolimus ointment (Protopic) for atopic dermatitis. 1555 Sep 92

The role of adhesion molecules; the intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) as mediators in development of skin allergy caused by giardiasis and the controlling role of the cytokine interleukin (IL)-6 over these adhesion molecules were studied. The work included 25 symptomatic giardiasis patients with skin allergy manifested by diffuse urticaria, pruritus, wheal and erythema, and had positive serum anti-Giardia immunoglobulin (Ig) E measured as mean optical density (OD) value by enzyme linked immunosorbent assay (ELISA), employed as an evidence of allergic sensitization (G.I). They were compared with 30 symptomatic giardiasis patients (G.II) and 20 apparently healthy control subjects (G.III), both latter groups had negative serum anti-Giardia IgE. The mean OD value of anti-Giardia IgE was significantly increased in G.I (P < 0.01) & insignificantly different in GIII (P > 0.05) compared with G.III. Serum levels of soluble forms of adhesion molecules; sICAM-1 & sVCAM-1, and IL-6 were determined by ELISA. sICAM-1 & sVCAM-1 serum levels were significantly increased (P < 0.001) in G.I compared with G.III and showed insignificant difference (P > 0.05) between Gs. II & III. Serum IL-6 significantly increased in G.I (P < 0.001) & G.II (P < 0.05) compared with G.III, and was significantly higher (P < 0.001) in G.I than G.II. Serum IL-6 correlated positively with serum sICAM-1 (P < 0.01) and sVCAM-1 (P < 0.001) in G.I. The results are discussed.
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PMID:Human giardiasis as an etiology of skin allergy: the role of adhesion molecules and interleukin-6. 1558 2

Skincare formulations for the improvement of aging skin are increasingly important consumer products. Here, we review available data on one such agent - 2-dimethylaminoethanol (DMAE) or deanol - that has recently been evaluated in a placebo-controlled trial. DMAE is an analog of the B vitamin choline and is a precursor of acetylcholine. Although the role of acetylcholine as a neurotransmitter is well known, growing evidence points to acetylcholine as a ubiquitous cytokine-like molecule that regulates basic cellular processes such as proliferation, differentiation, locomotion, and secretion in a paracrine and autocrine fashion. Indeed, this modulatory role may contribute to the cutaneous activity of DMAE. In a randomized clinical study, 3% DMAE facial gel applied daily for 16 weeks has been shown to be safe and efficacious (p < 0.05) in the mitigation of forehead lines and periorbital fine wrinkles, and in improving lip shape and fullness and the overall appearance of aging skin. These effects did not regress during a 2-week cessation of application. Beneficial trends (p > 0.05 but </= 0.1) were noted in the appearance of coarse wrinkles, under-eye dark circles, nasolabial folds, sagging neck skin, and neck firmness. Application was found to be well tolerated, with no differences in the incidence of erythema, peeling, dryness, itching, burning, or stinging between the DMAE and placebo groups. An open-label extension of the trial showed that the long-term application of DMAE gel for up to 1 year was associated with a good safety profile. The acute skin-firming effects of DMAE have been confirmed by quantitative measures of cutaneous tensile strength. In vitro studies in peripheral blood lymphocytes indicate that DMAE is a moderately active anti-inflammatory agent. Although its mechanisms of action in the skin remain to be elucidated, evidence suggests that the skin is an active site of acetylcholine synthesis, storage, secretion, metabolism, and receptivity. Muscarinic acetylcholine receptors have been localized to keratinocytes, melanocytes and dermal fibroblasts, whereas nicotinic acetylcholine receptors have been found in keratinocytes. The role of acetylcholine and the role of DMAE as a modulator of acetylcholine-mediated functions in the skin remain to be elucidated.Thus, the benefits of DMAE in dermatology include a potential anti-inflammatory effect and a documented increase in skin firmness with possible improvement in underlying facial muscle tone. Studies are needed to evaluate the relative efficacy of DMAE compared with other skin-care regimens (e.g., topical antioxidant creams, alpha-hydroxy acids).
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PMID:The role of dimethylaminoethanol in cosmetic dermatology. 1567 89


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