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)

Sixteen patients with allergic rhinitis were recruited into a double-blind crossover protocol studying the immediate effect of nedocromil sodium (NS) on the pattern of nasal symptoms and secretions after allergen challenge. After pretreatment with placebo or NS, allergen challenge resulted in pruritus, rhinorrhea, nasal congestion, and/or sneezing within 10 minutes in 12 of 16 subjects. Prostaglandin D2 (PGD2), a marker of mast cell degranulation, increased proportionately with symptom scores, remaining above the 95% confidence interval for 120 minutes after both pretreatments. No difference in PGD2 between the NS-treatment and placebo-treatment days was observed. Protein markers extravasated through the vasculature (albumin and IgG) or secreted by mucosal glands (lactoferrin) were assayed. Total protein, albumin, IgG, and lactoferrin all remained greater than 95% confidence interval for 100 minutes after allergen challenge in the placebo-pretreated group and 120 minutes in the NS-pretreated group. Although there appeared to be a trend for lower secretion of PGD2, albumin, and IgG in the NS-treated group, the overall differences did not achieve statistical significance. This protocol revealed that two topical 130 microliter doses of a 1% solution of NS failed to significantly reduce allergen-induced symptoms, PGD2 generation, or secretion of albumin, IgG, or lactoferrin when NS was compared with placebo. The anti-inflammatory and mast cell-stabilizing effects of NS may require more prolonged pretreatment before provocation to be effective.
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PMID:Effects of nedocromil sodium on allergen-induced rhinitis in humans. 131 Oct 8

Allergic rhinitis is characterized by a profuse rhinorrhea in addition to paroxysms of sneezing, nasal congestion, and pruritus. To define better the sources of nasal secretion produced during rhinitis, nasal allergen challenges were performed on nine atopic subjects with seasonal rhinitis. A single dose of allergen was sprayed into one side of the nose, and nasal lavages were collected bilaterally for 7 hours. Nasal lavages were assayed for protein (total protein, albumin, lactoferrin, and lysozyme) and mediator (histamine and prostaglandin D2) content. Protein concentrations increased and remained elevated above baseline levels in both ipsilateral and contralateral secretions for up to 3 hours after allergen challenge. The proportion of albumin relative to total protein (the albumin percent) increased on the ipsilateral side, whereas the relative proportions of lactoferrin and lysozyme (the lactoferrin percent and lysozyme percent) increased on the contralateral side. Prostaglandin D2, but not histamine, increased selectively on the ipsilateral side. These data suggest that the ipsilateral protein secretory response is due to allergen-induced mast cell mediator release causing increased vascular permeability, whereas the contralateral protein secretory response is primarily a reflex-induced glandular secretion.
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PMID:The pathophysiology of rhinitis. V. Sources of protein in allergen-induced nasal secretions. 171 3

The effects of topically applied prostaglandin (PG) D2 and BW245C, a potent PGD2 agonist, on intraocular pressure (IOP) were studied in normotensive human volunteers. Doses of 5 and 10 micrograms PGD2 induced a mean reduction in IOP of 0.8 and 1 mmHg, respectively. At a dose of 50 micrograms, hypotension was preceded by initial hypertension (4 mmHg at 0.5 h) and the magnitude of the mean IOP reduction during the hypotensive phase was 1.1 mmHg. The application of BW245C (2.5 micrograms) induced an IOP change similar to that observed following treatment with 50 micrograms PGD2. Side effects caused by these compounds included conjunctival hyperemia, itching, and foreign-body and mild burning sensations. However, miosis and signs of intraocular inflammation were not observed. These results indicate that although PGD2 and BW245C are effective in reducing human IOP, their clinical usefulness as anti-glaucoma drugs may be limited by the extraocular side effects.
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PMID:Effects of prostaglandin D2 and its analogue, BW245C, on intraocular pressure in humans. 193 72

Nasal challenges with pollen grains represent one of the techniques of provocation. However, the clinical criteria of positivity are not clearly established. Nasal challenges with increasing numbers of orchard-grass pollen grains were performed in 60 patients allergic to grass pollens and 20 normal subjects. Before any challenge, the nose was washed three times with saline and then lactose, and 50, 150, 450, 1350, and 4050 orchard-grass pollen grains were insufflated into the nostrils until a symptom score of 5 was reached. This score was mainly based on major symptoms of allergic rhinitis, for example, rhinorrhea, nasal obstruction, sneezes, and to a lesser extent, on minor symptoms, such as pruritus, conjunctivitis, and pharyngitis. Nasal secretions were obtained after each challenge by lavage. Histamine was titrated by a radioimmunoassay with a monoclonal antibody against acylated histamine. Prostaglandin D2 (PGD2) was assayed with an enzyme immunoassay with a polyclonal antibody against PGD2 methoxamine. None of the normal subjects had a symptom score greater than 2; 55/60 patients had a positive challenge. The release of PGD2 was significantly (p less than 0.001, Kruskal-Wallis test) correlated with a symptom score of 5; 74.5% of patients had a significant release of PGD2 in nasal secretions. In contrast, although 58.2% of patients had a release of histamine in nasal secretions when the challenge was positive, the correlation with symptom scores was not significant. PGD2 in nasal secretions increased 3.7-fold after a positive nasal challenge.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Correlation between symptoms and the threshold for release of mediators in nasal secretions during nasal challenge with grass-pollen grains. 246 5

The diagnosis of systemic mastocytosis without urticaria pigmentosa has been made with increasing frequency since modern methods of histamine assay have been used clinically. We examined the incidence of urticaria-angioedema and mastocytosis over a recent 12-month period. Of 490 new patients we saw, 52 had urticaria-angioedema, and ten had evidence of excess histamine +/- PGD2, with at least ten mast cells per high-power field on skin biopsy. The average age was approximately 35 years; the male:female ratio was 1:4 for urticaria-angioedema and 1:2 for mastocytosis. Symptoms of mastocytosis included flushing, abdominal cramping/diarrhea, syncope, urticaria-angioedema, pruritus, and headache. Symptoms have typically been prevented by a combination of H1 and H2 antagonists, with addition of a cyclo-oxygenase inhibitor in syncopal cases. Acute hypotension has responded to epinephrine.
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PMID:Mastocytosis: one year's experience. 287 59

Nasal histamine (H), leukotriene C4 (I-LTC4) and SRS-A activity were studied in seven aspirin-(ASA)-intolerant patients (AIR) with rhinitis and in five ASA-tolerant control patients with chronic rhinitis after nasal provocation (NP) with a lysine acetylsalicylate solution. The same parameters were also studied after metabisulfite (MBS) NP in four sulfite-intolerant patients with rhinitis and in six control patients with chronic rhinitis. In six ASA-intolerant subjects and in four controls, we studied the PGD2 levels in nasal washes after ASA NP 0.2 mL of lysine acetylsalicylate solution (10 mg/mL) was sprayed intranasally in ASA-intolerant patients and controls and a 25-mg/mL MBS solution in sulfite intolerant patients and controls. Nasal wash fluids were obtained using 5 mL of 0.15 M saline before and 7 1/2, 15, 30, and 60 minutes after nasal provocation. The nasal provocation with ASA induced itching and sneezing in four out of seven intolerant subjects. In this subgroup histamine values in nasal wash fluids were significantly higher versus the remaining ASA-intolerant patients at 30 and 60 minutes (P less than .05 and P less than .01, respectively) and versus controls at 60 minutes (P less than .01). We found significantly higher I-LTC4 (P less than .01) and SRS-A levels in nasal washes collected from ASA-intolerant subjects versus controls at 60 minutes after nasal provocation. There was no significant increase in the mean PGD2 values in either the ASA-intolerant or control groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Study of mediators of anaphylaxis in nasal wash fluids after aspirin and sodium metabisulfite nasal provocation in intolerant rhinitic patients. 368 66

We present an unusual case of adult-onset systemic mastocytosis with biopsy-proven skin and bone manifestations with the rare presentation of lumbar fracture and osteopenia. The normal 24-hour urine histamine is surprising in this patient, but it does not rule out mastocytosis. It is a sensitive assay that can give false negative results if stored before the assay is performed. Also histamine and PGD2 metabolites are more sensitive and specific. It is surprising that our patient did not have gastrointestinal symptoms. In one prospective study of 16 patients with systemic mastocytosis in which 75% had bone marrow involvement as the most common extracutaneous site, 80% were found to have gastrointestinal symptomatology, indicating such symptoms to be more common than previously thought. The lack of pruritus is also surprising, as most cutaneous lesions of urticaria pigmentosa are pruritic. Symptoms of systemic mastocytosis, particularly pruritus may respond to antihistamines and the bone disease may not respond to calcium and hormone manipulation. The main role of the latter is to prevent further bone loss. We may consider the use of cromolyn or ketotifen if she does not respond. Close follow-up will be needed to check for progression, however she appears to have a good prognosis with skin involvement and no hematologic abnormalities.
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PMID:Systemic mastocytosis: a diagnostic challenge. 774 67

The aim of the study was to investigate the effect of short-term treatment with fluticasone propionate on the response to nasal allergen challenge in patients with allergic rhinitis. Responses to nasal allergen challenge were assessed subjectively by recording symptom scores on visual analogue scales, and objectively by measuring histamine, PGD2 and LTC4 in nasal lavage and by measuring nasal inspiratory peak flow following challenge. Nasal allergen challenge resulted in an increase in all symptom scores (P < 0.05); an increase in histamine and PGD2 (P < 0.05), and a decrease in nasal inspiratory peak flow at 1 h, 5 h and 7 h following challenge (P < 0.05). The allergen-induced changes in symptom scores, mediator levels and nasal inspiratory peak flow were attenuated by treatment with fluticasone propionate (P < 0.05 for all parameters measured). Post-challenge nasal obstruction was decreased by 45%; sneezing, itching and rhinorrhoea by 73, 78 and 80% respectively in the group as a whole comparing scores whilst on fluticasone propionate with those on no therapy. Fluticasone propionate, 200 micrograms twice daily for 2 weeks is effective in reducing significantly the early and late response to nasal allergen challenge.
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PMID:Effect of short-term treatment with fluticasone propionate nasal spray on the response to nasal allergen challenge. 789 87

The therapeutic utility of cyclooxygenase (CO) inhibitors, such as ketorolac, in reducing the inflammatory events associated with allergic conjunctivitis is not unexpected since prostanoids (PG) elicit conjunctival redness (PGD2, PGE2, PGF2 alpha), edema (PGD2, TxA2), eosinophil infiltration (PGD2, PGJ2) and mucous cell discharge (PGD2, PGJ2, TxA2). Recently, topically administered ketorolac has also been reported to alleviate the itching associated with allergic conjunctivitis. This was viewed as intriguing since CO inhibitors are not regarded as useful for treating itching dermatoses and PGs do not elicit itching when applied to the skin. In order to investigate the antipruritic activity of ketorolac, we developed a model for reproducibly measuring ocular surface itch responses. The model involves itch-scratch responses to pruritogens applied locally to the ocular surface. Painful and foreign body stimuli do not produce an itch-scratch response. Unlike reported skin studies, PGE2 was a potent itch-producing substances in the conjunctiva. PGD2 was weakly pruritogenic but PGF2 alpha and the TxA2-mimetic U-46619 were inactive. The PG precursor arachidonic acid was also a potent pruritogen and its effects were inhibited by ketorolac pretreatment. Ketorolac also dose-dependently inhibited the itching associated with experimental allergic conjunctivitis. It appears that PGs are potent itch-producing substances in the conjunctiva and the anti-itch efficacy of ketorolac in allergic conjunctivitis appears to involve inhibition of conjunctival PG biosynthesis from arachidonic acid.
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PMID:The pruritogenic and inflammatory effects of prostanoids in the conjunctiva. 859 Feb 66

Topically administered ketorolac (Acular), a cyclooxygenase inhibitor, has recently been reported as clinically beneficial for treating allergic conjunctivitis. The ability of ketorolac to relieve the itching associated with allergic conjunctivitis is intriguing because cyclooxygenase inhibitors are not regarded as useful in treating allergic dermatoses and prostaglandins (PG) do not elicit an itch response in human skin. To gain further insight into the mechanisms involved in the antipruritic activity of ketorolac, we used a method of reproducibly assessing ocular surface itch responses in the guinea pig. The measurement of conjunctival pruritus involved a recently developed behavioral model whereby hind limb scratching episodes directed toward the afflicted area were quantified. Itch-scratch episodes have previously been delineated from foreign body and pain sensations, which do not evoke such a behavioral response. Ketorolac significantly inhibited the itching associated with experimental allergic conjunctivitis. The basis of this antipruritic activity may be ascribed to preventing the biosynthesis of itch-producing PGs because ketorolac inhibited arachidonic acid-induced pruritus. In contrast to skin studies, PGE2 and PGI2 were found to be potent pruritogens at the guinea pig ocular surface. PGD2 was a weak pruritogen, and PGF2 alpha and the thromboxane-mimetic U-46619 produced no meaningful response. Further studies involving selective agonists and antagonists suggested that EP1 receptors, IP receptors and PGD2-sensitive receptors may mediate prostanoid-induced conjunctival itching. No evidence for the involvement of other prostanoid receptor subtypes was obtained. Although the EP1 receptor antagonist AH 6809 and the DP receptor antagonist BW A868C inhibited PGE2- and PGD2-induced itching, respectively, neither antagonist alone significantly affected the itching associated with experimental allergic conjunctivitis. A combination of AH 6809 and BW A868C, however, did exhibit antipruritic activity. It appears that for effective relief of itching in allergic conjunctivitis, it is not sufficient to block the effects of a single pruritogenic PG. It is preferable to reduce the participation of all pruritogenic PGs by either using combined receptor antagonists or by using a cyclooxygenase inhibitor such as ketorolac to block their biosynthesis.
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PMID:Characterization of receptor subtypes involved in prostanoid-induced conjunctival pruritus and their role in mediating allergic conjunctival itching. 885 86


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