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)

While the pathomechanisms of respiratory atopy are rather well established, the role of IgE-mediated hypersensitivity in the elicitation and maintenance of eczematous skin lesions in atopic eczema is still controversial. Few diseases are characterized by an equally elevated production of IgE antibodies as atopic eczema. Many authors, however, regard this only as epiphenomenon. On the other hand, there is clearcut clinical evidence for exogenous elicitation of atopic eczema by contact with aero or food allergens. A variety of hypotheses may help to explain the participation of IgE antibodies in the induction of eczema: vasoactive mediators secreted by skin mast cells or basophils after allergen contact may produce itch, contact urticaria or a 'late-phase-reaction' with consequent eczematous skin changes further maintained by scratch responses. Recent investigations stress a possible role of Langerhans cells in the epidermis with a low affinity receptor for IgE with possible function for antigen presentation, mediator release or regulatory interactions. Certain cytokines such as interleukin-4 or gamma-interferon are able to enhance the expression of the IgE-receptor on the surface of Langerhans cells. IL-4 and gamma-interferon act synergistically in this respect on Langerhans cells, contrary to B cells. Furthermore lymphocytes may act directly via certain cytokines (e.g. histamine releasing factor, chemotactic factors etc.) on mast cells or eosinophil granulocytes in a proinflammatory sense. Eosinophils seem also to be involved in the inflammatory response in atopic eczema by releasing products such as major basic protein (MBP) or eosinophil cationic protein (ECP) which has been found to be elevated in severe atopic eczema.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Atopic eczema, Langerhans cells and allergy. 193 74

The etiology of atopic pruritus is unclear and seems mostly histamine-independent. In order to investigate non-mast cells as possible sources of pruritogenic agents, peripheral blood mononuclear cells from 12 atopic eczema patients and 12 controls were incubated in vitro for 24 h with phytohemagglutinin or concanavalin A (both at 10 micrograms/ml) or with medium alone, and each subject was tested with his own cell supernatants and lysates by prick testing and by application on tape-stripped skin. Histamine (0.1%) and substance P (500 microM) were tested in comparison, and reactions were observed for up to 24 h. Cell supernatants were also analysed for their contents of several cytokines. Lymphocyte cell extracts or supernatants failed to cause symptoms in controls but induced whealing in 6 and itching in 3 patients on prick testing within 5 min, lasting for 30 min in 2 patients and persisting for 6 h in 1 patient. Histamine caused itching in all controls and in 7 patients within 5 min on prick testing, with decreasing reactivity at later times. Substance P yielded results with lower values. With all three types of test reagents, fewer subjects reacted on tape stripped skin. High levels of interleukins 2 and 6, low levels of interferon and no detectable levels of interleukin 4 and tumour necrosis factor were measured in stimulated cell supernatants and extracts, with even lower levels in subjects exhibiting skin reactivity. These findings thus provide evidence that as yet unidentified mononuclear cell products may be involved in whealing and itching associated with atopic eczema.
 ...
PMID:Pruritogenic effects of mitogen-stimulated peripheral blood mononuclear cells in atopic eczema. 865 Oct 16

We tested peptide immunotherapy in cat-allergic humans, using a formation of two synthetic peptides, IPC-1 and IPC-2, each of which is 27 amino acids long and contains T cell-reactive regions of Fel d 1, the major cat allergen. In this exploratory, randomized, double-blind, parallel-group study, 42 subjects received s.c. injections of treatment peptides 250 micrograms or placebo weekly for four consecutive weeks. Changes in immediate- and late-phase skin test reactivity, and in antigen-driven cytokine synthesis were assessed. Epicutaneous (end-point titration) and intradermal tests were performed with cat extract (ALK SQ Cat Hair) containing Fel d 1, before the first injection, then 2, 6 and 24 weeks after the fourth and last injection of peptides or placebo. IL-4, IL-10 and IFN-gamma expression by circulating peripheral blood mononuclear cells (PBMC) in response to cat extract was measured using short-term bulk culture of PBMC and short-term limiting dilution analysis. Subjects who received peptide immunotherapy did not tolerate significantly more cat extract containing Fel d 1 in the skin tests 2, 6 or 24 weeks after the last injection than they did at baseline, and their late-phase responses did not decrease significantly compared to baseline. Substantial IL-4, IL-10 and IFN-gamma responses were observed following primary culture of cat antigen-stimulated PBMC; however, the intensity of cytokine synthesis and the IFN-gamma: IL-4 ratio were unchanged in peptide- and placebo-treated groups 6 and 24 weeks after the last injection. A few hours after the injections, subjects receiving peptides reported more allergic rhinitis and asthma symptoms and more pruritus than those receiving placebo. We conclude that under the conditions tested, peptide immunotherapy did not reduce immediate- or late-phase skin reactivity to cat extract containing Fel d 1 or modify cat antigen-specific cytokine production significantly.
 ...
PMID:Fel d 1 peptides: effect on skin tests and cytokine synthesis in cat-allergic human subjects. 898 78

Allergic rhinitis involves an early phase, largely mediated through mast cells, and a late phase which involves cellular infiltration and mediator release. In the early phase, mast cells release mediators as a result of antigen cross-linking adjacent immunoglobulin E molecules bound to mast cell surfaces. This results in an accumulation of histamine which gives rise to the characteristic symptoms of rhinitis--sneezing, itching, rhinorrhoea and congestion. The late phase of the allergic response (hours after challenge) involves infiltration of the nasal epithelium by eosinophils, basophils, monocytes and T-lymphocytes, which release leukotrienes, kinins, histamine and a host of other mediators. The most important part of the late-phase response is probably mediated via the production of cytokines (IL-4, IL-5, IL-6, IL-8, GM-CSF and RANTES) by mast cells, TH2 lymphocytes or epithelial cells. The infiltration of tissues by cells normally present only in the blood is brought about by the production of adhesion molecules, such as VCAM-1 and E-selectin, which cause circulating eosinophils, basophils and T-lymphocytes to adhere to endothelial cells before moving through the endothelium into the tissue (diapedesis). Neuronal reflexes also play a role in the allergic response, both by mediating local responses to mediators and possibly playing a part in the activation of T-lymphocytes. The allergic response has also been shown to be less intense in a hot, humid environment, and more marked in a cold, dry environment, possibly due to changes in osmolality of the nasal surface fluid. Similar factors may play a role in the aetiology of non-allergic rhinitis.
 ...
PMID:Pathophysiology of perennial allergic rhinitis. 921 57

To determine whether common skin diseases associated with human immunodeficiency virus (HIV) were distinguishable based on the pattern of serum cytokine expression, we studied patients with psoriasis, pruritus, and Kaposi's sarcoma (KS) for levels of tumor necrosis factor (TNF)-alpha, interferon-gamma (IFN-y), interleukin (IL)-10, and IL-4. Thirty-two HIV-positive (HIV+) patients including 8 with KS, 11 with psoriasis, and 13 with pruritus along with 16 HIV-negative subjects with psoriasis were studied. IFN-gamma levels were highest in sera of HIV+ patients with psoriasis (p = 0.040). By contrast, TNF-alpha and IL-10 levels were highest in sera of HIV+ patients with pruritus (p = 0.012). Detectable levels of all cytokines in these patients were remarkably higher than for healthy adults. These results suggest that common skin diseases associated with HIV infection and AIDS can be distinguished by the production of unique cytokines.
 ...
PMID:Distinct serum cytokines in AIDS-related skin diseases. 1018 88

The serum levels of eosinophil cationic protein (ECP), soluble E-selectin (sE-selectin), soluble CD14 (sCD14) and interleukin (IL)-4 are known to be elevated in patients with atopic dermatitis (AD). However, little is known of the mutual relationship between these factors. To elucidate the clinical and mutual relevance of these markers, we examined the serum levels of ECP, sE-selectin, sCD14 and IL-4 as compared with eruption scores, itch scores, total IgE and numbers of peripheral eosinophils in patients with AD (n = 43), non-atopic eczema (n = 24) and urticaria (n = 13) and in normal individuals (n = 45). In 27 patients with AD the levels of these markers were compared before and after treatment. Levels of ECP were elevated only in the patients with AD, whereas the sE-selectin levels were higher not only in AD but also in non-atopic eczema in a severity-dependent manner. The levels of both markers significantly diminished after treatment. Significant correlations existed between ECP levels and numbers of eosinophils, sE-selectin levels and itch scores, and sE-selectin levels and IgE levels. No significant changes were observed in the sCD14 and IL-4 levels. Taken together, sE-selectin and ECP are good but distinct serum markers that reflect different clinical features of AD.
 ...
PMID:Soluble E-selectin and eosinophil cationic protein are distinct serum markers that differentially represent clinical features of atopic dermatitis. 1021 70

Desloratadine is a new, selective, H(1)-receptor antagonist that also has anti-inflammatory activity. In vitro studies have shown that desloratadine inhibits the release or generation of multiple inflammatory mediators, including IL-4, IL-6, IL-8, IL-13, PGD(2), leukotriene C(4), tryptase, histamine, and the TNF-alpha-induced chemokine RANTES. Desloratadine also inhibits the induction of cell adhesion molecules, plateletactivating factor-induced eosinophil chemotaxis, TNF-alpha-induced eosinophil adhesion, and spontaneous and phorbol myristate acetate-induced superoxide generation in vitro. In animals desloratadine had no effect on the central nervous, cardiovascular, renal, or gastrointestinal systems. Desloratadine is rapidly absorbed, has dose-proportional pharmacokinetics, and has a half-life of 27 hours. The absorption of desloratadine is not affected by food, and the metabolism and elimination are not significantly affected by the subject's age, race, or sex. There are no clinically relevant interactions between desloratadine and erythromycin, ketoconazole, or grapefruit juice. Desloratadine is not a significant substrate of the P-glycoprotein transport system. Once daily administration of desloratadine rapidly reduces the nasal and nonnasal symptoms of seasonal allergic rhinitis, including congestion. In patients with seasonal allergic rhinitis and concomitant asthma, desloratadine treatment was also associated with significant reductions in total asthma symptom score and use of inhaled beta(2)-agonists. Use of desloratadine in patients with chronic idiopathic urticaria was associated with significant reductions in pruritus, number of hives, size of the largest hive, and interference with sleep and daily activities. Clinical experience in over 2300 patients has shown that the adverse event profile of desloratadine is similar to that of placebo; desloratadine has no clinically relevant effects on electrocardiographic parameters, does not impair wakefulness or psychomotor performance, and does not exacerbate the psychomotor impairment associated with alcohol use.
 ...
PMID:Desloratadine: A new, nonsedating, oral antihistamine. 1129 78

The atopic dermatitis is a chronic inflammatory skin illness, with remissions and exacerbations, itch, and association with allergic rhinitis and asthma. There is a complex interrelationship of genetic, environmental, pharmacological and psychological factors that contribute to the development and severity of the illness: Different manifestations of immunological disorders are an increment in the number of IgE antibodies toward common antigens, an increment in the liberation of proinflammatory mediators by basophils and mast cells, peripheral and local eosinophilia, biphasic activity Th1/Th2 with the liberation of cytokines (IL-4, IL-5, IL-13), GM-CSF and the IFN-gamma caused by the cells Th1. an increment in the liberation of major basic protein, eosinophil cationic protein besides the expression of chemotactic factors by the monocytes (RANTES, eotaxin, vasoactive intestinal peptide, etc.). In 1980, Hanifin and Rajka made public the diagnostic criteria for the atopic dermatitis and it has been universally accepted as an standard for the diagnosis. Leung reported that a knowledge about the immunopathological bases of the atopic dermatitis has important clinical implications for the diagnosis and possible treatment there are multiple choices for a treatment because of the complexity of the illness. Among these are thalidomide and transfer factor as an immunomodulator treatment with acceptable safety and clinical efficacy.
 ...
PMID:[New concepts about atopic dermatitis]. 1139 66

Itch is an E3 ubiquitin ligase that is disrupted in nonagouti-lethal or itchy mice. Itch deficiency leads to severe immune and inflammatory disorders and constant itching of the skin. Here we show that Itchminus sign/minus sign T cells show an activated phenotype and enhanced proliferation. Production of the type 2 T helper (TH2) cell cytokines interleukin 4 (IL-4) and IL-5 by Itchminus sign/minus sign T cells was augmented upon stimulation, and the TH2-dependent serum concentrations of immunoglobulin G1 (IgG1) and IgE in itchy mice were also increased. Molecularly, Itch associated with and induced ubiquitination of JunB, a transcription factor that is involved in TH2 differentiation. These results provide a molecular link between Itch deficiency and the aberrant activation of immune responses in itchy mice.
 ...
PMID:Dysregulation of T lymphocyte function in itchy mice: a role for Itch in TH2 differentiation. 1187 57

Atopic dermatitis is a common, chronic, relapsing cutaneous disease with typical cellular and humoral immunologic abnormalities that can result in significant physical and psychological morbidity to the patient. Atopic dermatitis typically begins in childhood and can often persist through adolescence into adulthood. Although there are a variety of treatments for atopic dermatitis, many patients' symptoms do not improve or they have adverse reactions to medications, requiring the search for other, effective therapeutic agents. A number of inflammatory and immunological abnormalities have long been noted in patients with atopic dermatitis. Although great strides have been made in understanding the causes, the complex pathophysiology of atopic dermatitis is still not completely understood. Most notably, patients with atopic dermatitis often have an elevation of serum immunoglobulin (Ig) E levels, depressed cellular immunity, elevated blood eosinophilia, and increased interleukin (IL)-4 production. In addition, peripheral blood mononuclear cells of patients with atopic dermatitis produce reduced levels of interferon-gamma spontaneously and in response to stimuli. Due to this constellation of features, atopic dermatitis was initially viewed as a prototypical type 2 helper T lymphocyte (T(h2)) disease. These immunological findings led to a number of clinical trials with recombinant interferon-gamma in patients who had severe, unremitting atopic dermatitis. Treatment with recombinant interferon-gamma was postulated to be able to correct the immunological imbalances in patients with atopic dermatitis by decreasing serum IgE levels, IL-4 levels, restoring immune balance, and thereby leading to clinical improvement. Initial open-label studies, a double-blind placebo trial, and long-term open-label studies have demonstrated the clinical efficacy and tolerability of recombinant interferon-gamma in a subset of patients with severe, unremitting atopic dermatitis. Patients receiving treatment often had marked decreases in severity of clinical parameters: erythema, edema/indurations, pruritus, excoriations, dryness, lichenification and associated reduction in total body surface area involvement. Surprisingly, treatment with recombinant interferon-gamma did not lower serum IgE levels refuting the hypothesized mechanism by which interferon-gamma would bring about clinical improvement in patients with atopic dermatitis. Instead, decreases were noted in absolute white blood cell and eosinophil counts that tended to correlate with clinical improvement. Although the exact mechanism by which recombinant interferon-gamma brings about clinical changes in patients with atopic dermatitis is unknown, recombinant interferon-gamma should be considered a possible therapy for patients with atopic dermatitis.
 ...
PMID:Atopic dermatitis: the role of recombinant interferon-gamma therapy. 1197 38


1 2 3 4 5 6 7 8 9 10 Next >>