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)

The efficacy, safety and usefulness of murine anti-endotoxin monoclonal IgM antibody "E5, an intravenous dose of 2 mg/kg" were evaluated in 88 patients with suspected Gram-negative sepsis from 37 institutes in Japan. Out of these, 74 patients were evaluable for the efficacy, 85 for safety and 75 for clinical usefulness. In assessing the efficacy, the patients were divided into 3 groups based on the plasma endotoxin levels (Endospecy with new PCA treatment of plasma): H group with a level of above 9.8 pg/ml and M group with a level of 3.0-9.8 pg/ml and L group with a level of below 3.0 pg/ml. 1. The efficacy rates as assessed following administration of E5 were 73.1% in the H group, 70.4% in the M group and 38.1% in the L group being higher in the groups with significantly high plasma endotoxin levels. 2. In both the H and M groups in whom plasma endotoxin levels were significantly high, the majority of the patients showed rapid reduction of the levels after administration of E5. 3. In all groups, improvement in body temperature, pulse rate, blood TNF-alpha and blood IL-6 was observed after treatment with E5. In the H and M groups with an endotoxin level of > or = 3.0 pg/ml, improvement in platelet count as well as in CRP was noted. The H group showed also improvement in WBC. 4. Improvement in the shock score was noted in all the groups but was more outstanding in the H and M groups in the early stage of treatment. 5. Side effects were seen in 5 (5.9%) of 85 patients and all thought to be allergic in symptoms such as rash, itching, fever and flare. 6. The reaction to the prick test performed before administration of E5 was negative in all these 5 patients. For 3 of the 5 patients, anti-E5 IgE antibody was measured. In all of them, the IgE levels were higher than those of healthy controls. Also, in 47.6% of patients, an elevation of anti-E5 IgG antibody was noted two weeks after the administration. 7. Clinical laboratory abnormalities were observed in 3 (3.5%) of 85 patients. They were an elevation of S-GOT.S-GPT and lowering of BUN, increased Al-p and decreased CH50, increased neutrophilia (%) and were all slight in the degree of the changes. 8. The clinical usefulness of E5 was evaluated for 75 patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Phase II study of edobacomab (E5) in the treatment of gram-negative sepsis]. 813 82

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.
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PMID:Pathophysiology of perennial allergic rhinitis. 921 57

The currently available respiratory topical corticosteroids are all effective at reducing the nasal symptoms of itch, sneezing, rhinorrhoea and obstruction associated with allergic rhinitis. The mechanism of action of corticosteroids is related to their anti-inflammatory activities. They have been documented to prevent fluid exudation and reduce the number of circulating inflammatory cells, including lymphocytes, mast cells, basophils, eosinophils, macrophages, and neutrophils. This occurs through multiple mechanisms, e.g. eosinophil infiltration is suppressed by preventing cytokine production, reducing local mechanisms of tissue infiltration, and decreasing eosinophil survival. Furthermore, corticosteroids also reduce preformed and newly-generated mediators (e.g. histamine, tryptase, prostanoids, leukotrienes), and inhibit production of cytokines and chemokines by inflammatory cells (e.g. IL-1 through IL-6, IL-8, RANTES, TNF-alpha, IFN-gamma and GM-CSF). The currently available corticosteroids differ pharmacologically. Fluticasone propionate appears to have the greatest affinity for the glucocorticoid receptor, and binds more quickly and dissociates more slowly from the receptor compared with other corticosteroids, suggesting a more prolonged duration of action. Its increased specificity for respiratory tissue may lead to greater potency with less potential for systemic adverse effects. Fluticasone propionate has been compared with other corticosteroids in animal models for relative topical and systemic potency, and according to these data, it has the most favourable risk-benefit ratio.
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PMID:The pharmacological basis for the treatment of perennial allergic rhinitis and non-allergic rhinitis with topical corticosteroids. 921 61

In order to further evaluate the role of cytokines in the induction of atopic pruritus, leukocytes from 10 atopic eczema patients or 10 nonallergic controls were stimulated in vitro with mite or birch pollen antigen for 1 and 4 days. Subjects were prick-tested with the supernatants, and whealing and itching were evaluated 20 and 60 min later. The supernatants were also examined for the contents of GM-CSF, IL-2, IL-6 and IL-8 by ELISA and TNFalpha. Two hours prior to testing, the antihistamine cetirizine (20 mg) or a placebo tablet were given to the patients according to a randomized, double-blind study protocol. After pricking with antigen-stimulated leukocyte supernatants, 6 of 10 patients but no controls reacted mostly at 20 min with whealing and/or pruritus. In the cetirizine-treated group, no decrease in these skin reactions was seen compared to placebo. Analysis for cytokines showed increased levels of IL-8 in allergen-stimulated samples, with no correlation to the induction of itching or whealing by these supernatants. IL-6 levels were low and variable, and GM-CSF, IL-2 and TNFalpha levels were always below standard values. These data show that leukocytes selectively release IL-8 in response to in vitro antigen stimulation. They furthermore provide additional support for the concept that as yet to be identified products play a role in atopic pruritus.
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PMID:Role of antigen-induced cytokine release in atopic pruritus. 962 7

Medical examinations were performed in a group of 51 Polish farmers heavily exposed to flax dust during harvesting and scutching (threshing) and in a group of 50 healthy urban dwellers not exposed to organic dusts (controls). The examinations included: interview concerning the occurrence of respiratory disorders and work-related symptoms, physical examination, X-ray examination of chest, lung function tests, oxymetric examinations, determination of the concentration of cytokines (IL-1alpha IL-6, TNFalpha) in blood serum and allergological tests with microbial antigens associated with organic dust, comprising: skin prick test with 4 antigens, agar-gel precipitation test with 12 antigens and test for specific inhibition of leukocyte migration with 4 antigens. As many as 32 farmers (62.7%) reported the occurrence of work-related symptoms during harvesting, transporting and scutching of flax. The most common complaint was general weakness reported by 15 farmers (29.4%), followed by headache reported by 14 (27.5%), blocking of the nose - by 11 (21.6%), dry cough, shivering, and eyes itching - each by 10 (19.8%), chest tightness and hoarseness - each by 9 (17.6%). No control subjects reported these work-related symptoms. The mean spirometric values in the examined group of farmers were within a normal range and did not show a significant post-shift decline. In contrast, a significant post-shift decline of oxymetric values was found among flax farmers. The farmers showed a frequency of the positive early skin reactions to environmental allergens in the range of 0-19.6%, a frequency of positive precipitin reactions in a range of 0-56.9%, and frequency of positive reactions of leukocyte migration inhibition in a range of 7.8-21.6%. The members of the control group responded to the majority of allergens with a significantly lower frequency of positive results compared to the farmers. Elevated concentrations of IL-1alpha and IL-6, but not TNFalpha, were found in blood sera of flax farmers. In conclusion, farmers engaged in harvesting and scutching of flax represent a group of elevated professional risk because of high incidence of work-related symptoms and high frequency of allergic reactions to bacteria and fungi associated with organic dust.
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PMID:Effects of exposure to flax dust in Polish farmers: work-related symptoms and immunologic response to microbial antigens associated with dust. 1115 40

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.
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PMID:Desloratadine: A new, nonsedating, oral antihistamine. 1129 78

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

Subjective/objective symptoms (itching, papula, erythema, lichenification, desquamation, scratching, erosion) and the levels of IgE, LDH, interleukin (IL) -6, thymus and activation-regulated chemokine (TARC) were compared before and after administering olopatadine hydrochloride (ALLELOCK tablets) to 17 atopic dermatitis (AD) patients. Subject/objective symptoms improved significantly after administering the agent, and the total dosage of the combined topical steroids was also significantly decreased after administration (p<0.05), although IgE, IL-6 and LDH levels did not change, TARC was significantly decreased (p<0.05). The correlation between the levels of IgE, IL-6, LDH and TARC before and after the administration was examined. There was a positive correlation between IgE and TARC (r=0.62, p<0.01) and between IL-6 and TARC (r=0.78, p<0.01). Olopatadine hydrochloride is therefore useful in improving the symptoms in AD, and TARC may be used as an indicator of the symptom improvement.
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PMID:[Examination of effectiveness of olopatadine hydrochloride in atopic dermatitis]. 1586 20

Dermatitis is a group of highly pruritic chronic inflammatory skin diseases which represents a major public-health problem worldwide. The prevalence of dermatitis has increased in recent years affecting up to 20% of the general population. Acute skin lesions are characterized by extensive degrees of intercellular edema of the epidermis (spongiosis) and a marked perivenular inflammatory cell infiltrate in the dermis. Keratinocytes within eczematous lesions exhibit a modified expression of proinflammatory cytokines, chemokines and cell-surface molecules. The pathophysiological puzzle of dermatitis is far from being elucidated completely, but skin infiltration of activated memory/effector T cells are thought to play the pivotal role in the pathogeneses. The aim of this study was the set-up of organotypic models mimicking the symptoms of eczematous dermatitis to provide a tool for therapeutic research in vitro. Therefore activated T cells (ATs) were integrated in organotypic skin and epidermis equivalents (SE, EE). These models enabled the reproduction of several clinical hallmarks of eczematous dermatitis: (1) T cells induce keratinocyte apoptosis, which leads to a reduced expression of the adhesion molecule E-cadherin (E-cad) and disruption of the epidermal barrier. (2) Expression of intercellular adhesion molecule-1 (ICAM-1) allows the attachment of leukocytes to epidermal cells. (3) Upregulation of neurotrophin-4 (NT-4) in the epidermis is thought to mediate pruritus in lesions by supporting nerve outgrowth. (4) Elevated levels of pro-inflammatory cytokines (IL-1alpha and IL-6) and chemokines (IL-8, IP-10, TARC, MCP-1, RANTES and eotaxin) amplify the inflammatory response and lead to an influx of secondary immunocells into the skin. The therapeutics dexamethasone and FK506 markedly reduce cytokines/chemokines production and epidermal damaging in these models. These data underline that activated memory/effector T cells induce eczematous changes in this HaCaT cell based organotypic skin equivalent. Furthermore it can be concluded that these models make it possible to investigate targets of therapeutics in skin.
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PMID:In vitro reproduction of clinical hallmarks of eczematous dermatitis in organotypic skin models. 1595 7

Smoking causes a variety of adverse effects on organs that have no direct contact with the smoke itself such as the liver. It induces three major adverse effects on the liver: direct or indirect toxic effects, immunological effects and oncogenic effects. Smoking yields chemical substances with cytotoxic potential which increase necro-inflammation and fibrosis. In addition, smoking increases the production of pro-inflammatory cytokines (IL-1, IL-6 and TNF- alpha) that would be involved in liver cell injury. It contributes to the development of secondary polycythemia and in turn to increased red cell mass and turnover which might be a contributing factor to secondary iron overload disease promoting oxidative stress of hepatocytes. Increased red cell mass and turnover are associated with increased purine catabolism which promotes excessive production of uric acid. Smoking affects both cell-mediated and humoral immune responses by blocking lymphocyte proliferation and inducing apoptosis of lymphocytes. Smoking also increases serum and hepatic iron which induce oxidative stress and lipid peroxidation that lead to activation of stellate cells and development of fibrosis. Smoking yields chemicals with oncogenic potential that increase the risk of hepatocellular carcinoma (HCC) in patients with viral hepatitis and are independent of viral infection as well. Tobacco smoking has been associated with suppression of p53 (tumour suppressor gene). In addition, smoking causes suppression of T-cell responses and is associated with decreased surveillance for tumour cells. Moreover, it has been reported that heavy smoking affects the sustained virological response to interferon (IFN) therapy in hepatitis C patients which can be improved by repeated phlebotomy. Smoker's syndrome is a clinico-pathological condition where patients complain of episodes of facial flushing, warmth of the palms and soles of feet, throbbing headache, fullness in the head, dizziness, lethargy, prickling sensation, pruritus and arthralgia.
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PMID:Heavy smoking and liver. 1703 78


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