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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tight junctions create a highly selective diffusion barrier between epithelial and endothelial cells by preventing the free passage of molecules and ions across the paracellular pathway. Although the regulation of this barrier is still enigmatic, there is evidence that junctional transmembrane proteins are critically involved. Recent evidence confirms the notion that occludin, a four-pass integral plasma-membrane protein, is a functional component of the paracellular barrier. The overall hydrophilicity of occludin predicts two extracellular loops bounded by NH(2)- and COOH-terminal cytoplasmic domains. To date, the binding of the COOH terminus of occludin to intracellular proteins is well documented, but information concerning the function of the cytoplasmic NH(2) terminus is still lacking. Using yeast two-hybrid screening we have identified a novel interaction between occludin and the E3 ubiquitin-protein ligase Itch, a member of the HECT domain-containing ubiquitin-protein ligases. We have found that the NH(2)-terminal portion of occludin binds specifically to a multidomain of Itch, consisting of four WW motifs. This interaction has been confirmed by our results from in vivo and in vitro co-immunoprecipitation experiments. In addition, we provide evidence that Itch is specifically involved in the ubiquitination of occludin in vivo, and that the degradation of occludin is sensitive to proteasome inhibition.
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PMID:The tight junction-specific protein occludin is a functional target of the E3 ubiquitin-protein ligase itch. 1178 81

The Notch pathway is a conserved signal transduction cascade which is essential for pattern formation and the proper execution of a wide array of cell-fate decisions. As only modest differences in Notch pathway activity suffice to determine dramatic differences in cellular behavior, this pathway is tightly regulated by a variety of molecular mechanisms. Several recent studies now highlight the importance of the ubiquitination pathway in the control of Notch pathway activity. This review will summarize recent advances in understanding the function of four E3 ubiquitin ligases that regulate levels of the Notch receptor and other components of this pathway. These include Suppressor of deltex/Itch and Sel-10, which both regulate Notch, Neuralized, which regulates the Notch ligand Delta, and LNX, which regulates the Notch antagonist Numb.
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PMID:Protein degradation: four E3s for the notch pathway. 1181 85

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.
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PMID:Dysregulation of T lymphocyte function in itchy mice: a role for Itch in TH2 differentiation. 1187 57

Scabies ('Itch Mite') is truly a Great Neglected Disease that inflicts misery on millions. Molecular approaches, while still in their infancy, are providing a better understanding of the parasite and will have important implications for control and prevention. It has long been thought that dogs may act as a reservoir for human infections. However, genetic studies cast doubt over this supposition.
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PMID:The scourge of scabies. 1185 81

Topically applied aspirin has recently been reported to decrease histamine-induced itch in human volunteers. Our aim is to confirm this and to study the antipruritic ability of topical aspirin in inflamed skin. In 24 non-atopic volunteers, an inflammatory skin reaction was induced in forearm skin at 5 different sites by sodium lauryl sulphate contained in Finn Chambers. Aspirin 10%, aspirin 1%, mepyramine 5% and vehicle were applied to the inflamed and corresponding non-inflamed areas 20 min before itch induction with intradermal histamine injection. Itch and pain were scored on a visual analogue scale at regular intervals. Wheal and flare areas were measured. No difference in itch intensities was found after application of aspirin, mepyramine and vehicle, but more itch was induced in aspirin and mepyramine pretreated sites in inflamed skin compared to normal skin (p<0.05). In normal skin, flare areas were smaller after pretreatment with aspirin 10% (p<0.05) and mepyramine (p<0.001), as were wheal areas after mepyramine (p<0.01), compared to vehicle pretreatments. In inflamed skin, flare areas were smaller after pretreatment with aspirin 10% (p<0.01) and mepyramine (p<0.001), as were wheal areas after aspirin 10% (p<0.01), aspirin 1% (p<0.05) and mepyramine (p<0.001). We conclude that despite a significant skin penetration as measured by the influence on wheal and flare reactions, topically applied aspirin did not decrease histamine-induced itch in the model used.
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PMID:Topically applied aspirin decreases histamine-induced wheal and flare reactions in normal and SLS-inflamed skin, but does not decrease itch. A randomized, double-blind and placebo-controlled human study. 1201 95

Two cases of Dogger Bank Itch responding to oral cyclosporin (Neoral) are reported. The first, a 42-year-old shell-fisherman, presented with eczema on his face, forearms and hands. Oral prednisolone was ineffective and in subsequent years systemic steroids and topical clobetasol propionate allowed him to continue his work. In the shellfishing season of 1996, cyclosporin (Neoral) was introduced and the eczema was subsequently satisfactorily controlled. The second fisherman, aged 46, presented with an irritant eczema of the hands and forearms. Initial treatment with emollients and potent topical steroids had little effect. A subsequent course of cyclosporin provided good control of the eczema.
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PMID:Dogger Bank Itch and cyclosporin. 1217 83

Itch is a major symptom of skin disease and is poorly understood, in part due to the lack of adequate small animal models. We show, using iontophoresis of histamine and capsaicin, that it is possible to induce scratching behaviour in both guinea pig and mouse. Use of iontophoresis may obviate the problems of induction of pain as well as itch when injection is used. The behavioural response to capsaicin, however, differs from that seen with histamine, raising the possibility that the use of scratch counts as a method of measuring itch severity needs to be set in the context of other responses. Naloxone partly inhibits scratching in mouse and guinea pig due to histamine. We also show that contact sensitization with 2-4 dinitrochlorobenzene (DNCB) can be used as a simple assay for chronic itch allowing study of scratching over at least a 15-h period. The characteristics of scratching (but not the time course) induced with DNCB are similar to those seen with histamine.
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PMID:Production of acute and chronic itch with histamine and contact sensitizers in the mouse and guinea pig. 1219 Sep 36

Itch is a subjective symptom; its magnitude (intensity) may be only estimated by the reports of patients or volunteers. We utilized a comparative screening method to identify and quantify the efficacy of topical antipruritics with a histamine-induced itch human model. Ten individuals responsive to histamine-induced itch sensation were enrolled. Both forearms served as test sites. Each test site was treated randomly either by histamine injection only or pretreated with a coded candidate formula for 30 min and then a histamine injection. Itch was experimentally induced in each test site by the intracutaneous injection of 100 microg histamine dihydrochloride dissolved in 1 ml normal saline. Itch magnitude was measured each minute after histamine injection for 20 min with a magnitude visual analogue scale. Itch duration was also recorded. Formulation D significantly (p < 0.05) decreased itch magnitude (within a 20-min test period), from 2.6 +/- 2.1 cm (mean +/- SD) to 2.2 +/- 2.1 cm (mean +/- SD) when compared to its vehicle control; it also significantly (p < 0.05) shortened itch duration (15.0 +/- 7.4 min; mean +/- SD) in comparison with its vehicle control (20.3 +/- 7.0 min; mean +/- SD). Of all the formulations tested, formulation D was the most effective antipruritic in decreasing histamine-induced itch. This method may act as a simple and robust screening procedure when evaluating potential antipruritics and allow a comparison among products. Until validated with disease-induced itch, e.g., atopic dermatitis, the model should be considered screening in nature.
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PMID:Screening topical antipruritics: a histamine-induced itch human model. 1221 82

Atopic eczema (AE) is a chronically pruritic inflammatory skin disease. Although the mediators and exact mechanisms eliciting and sustaining pruritus are not completely known, AE patients in clinical trials have been shown to benefit under treatment with morphine antagonists. Naltrexone (NAL) is a relatively pure morphine antagonist that blocks the effects of opioids twice as much as naloxone. NAL exhibits minimal pharmacological activity and displaces endorphines at mu- and kappa-receptors without its own intrinsic activity. NAL's excellent oral bioavailability and linear increases in the area under plasma concentration-time curve make it ideal for use in experimental studies. We designed our present experiments similar to former experiments evaluating both peripheral cutaneous sensations and central itch procession in order to gain more information about the possible distribution of opioid receptors and their involvement in the pathophysiology of pruritus. Eleven AE patients participated in our double-blind study. Either 25 mg of NAL (Nemexin) or a placebo (PLA) was given to the participants 60 min prior to the acetylcholine (ACH) injection [intracutaneous (i.c.) injection of 0.02 ml of 0.55 M]. A PLA stimulus with buffered saline served as control on the opposite forearm. We used laser Doppler flowmetry to measure the vasomotoric changes after ACH injection and recorded the duration and intensity of itch with a visual analogue scale (VAS). Following the evaluation of wheal and flare sensation, we obtained the area of itchy skin around the injection site (alloknesis) by gently stroking the surrounding skin with a brush in the centripetal direction towards the injection site. The results were planimetrically evaluated. Oral NAL reduced the perifocal itch significantly (P < 0.009). In four of our observations the area of alloknesis completely disappeared. Itch duration was reduced by 20 s and the intensity of itch was diminished, yet not significantly. NAL had no significant effects on cholinergic vasoreactions measured by the laser Doppler (P > 0.50) and especially failed to decrease the initial flux response, which is a typical sign of an altered vascular reaction (P > 0.25). The decrease of wheal (P = 0.008) and flare (P = 0.01) extension indicates an appropriate dosage of our treatment for this experiment. The most significant effects of NAL were observed in parameters of itch processing such as alloknesis (P = 0.009) and flare extension (P = 0.01). Therefore we favour the concept that NAL might have a stronger impact on central nervous mechanisms than on peripheral nociceptive structures.
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PMID:Efficacy of naltrexone on acetylcholine-induced alloknesis in atopic eczema. 1236 98

Pruritus is a common complaint among end stage renal disease patients and has been associated with poor outcome. We characterized this problem at our outpatient hemodialysis unit. Seventy patients were surveyed over a two-day period. A visual analog scale was used to evaluate the intensity of itching. Location of itching and temporal relationship to dialysis was assessed by questionnaire. Laboratory parameters were evaluated to differentiate between those who itched and those who did not itch. Seventy percent of patients reported pruritus either during and/or between hemodialysis sessions. Itch intensity ranged from mild to severe. Forty-five percent of patients itched in three or more areas with the back and legs most commonly reported. Laboratory parameters were unable to differentiate between patients who itched and those who did not itch. Itching remains a common problem in hemodialysis patients. New treatments for patients resistant to standard therapies are needed.
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PMID:Evaluation of uremic pruritus at an outpatient hemodialysis unit. 1238 Sep 6


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