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)

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.
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PMID:Distinct serum cytokines in AIDS-related skin diseases. 1018 88

Ultraviolet radiation causes inflammation characterized by erythema and swelling, but also exhibits antiinflammatory effects which have led to the use of ultraviolet B radiation (UVBR) and psoralen plus ultraviolet A (PUVA) in the treatment of psoriasis, chronic severe atopic dermatitis and uremic pruritus. In inflammatory dermatoses, a pathogenic role of nitric oxide (NO) derived from inducible nitric oxide synthase (iNOS) has been suggested. To elucidate how UVBR regulates iNOS expression in skin under inflammatory conditions, we investigated the effect of UVBR on NO production and iNOS expression in cultured murine keratinocyte Pam 212 cells stimulated with interferon-gamma (IFN-gamma) or tumor necrosis factor-alpha (TNF-alpha). Low doses of UVBR significantly suppressed IFN-gamma- or TNF-alpha-induced NO production. UVBR also downregulated IFN-gamma- or TNF-alpha-induced iNOS expression at both the mRNA level and the protein level. These findings suggest the possibility that the down-regulatory effect of UVBR on IFN-gamma- or TNF-alpha-induced iNOS expression may, in part, explain the antiinflammatory and therapeutic properties of UVBR in inflammatory dermatoses.
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PMID:Ultraviolet B radiation downregulates inducible nitric oxide synthase expression induced by interferon-gamma or tumor necrosis factor-alpha in murine keratinocyte Pam 212 cells. 1092 73

AIDS is known to cause a shift of cytokines in the periphery. However, predominant cytokines in skin of patients with HIV-associated skin diseases have not been clearly defined. We hypothesized that there are distinct cytokine profiles that distinguish among the different clinical manifestations of AIDS-related skin diseases. To test this hypothesis, lesional and non-lesional skin was biopsied from 53 HIV+ patients with Kaposi's sarcoma (KS), psoriasis, and pruritus due to eosinophilic folliculitis, and from HIV negative controls with psoriasis or KS prior to therapy. Immunohistochemistry was performed with antibodies to tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, interferon (IFN)-gamma, and interferon-inducible protein (IP)-10. HIV positive individuals included 10 with psoriasis, 14 with pruritus, and 15 with Kaposi's sarcoma. HIV negative controls included 12 with psoriasis and two with KS. Semi-quantitative analysis of cytokine staining was confirmed by optical density using a digital imaging system on four representative skin sections from each disease. Optical density analyses were conducted using ANOVA and t-tests. We found that epidermis overlying HIV+ Kaposi's sarcoma was hyperproliferative and was highest in IP-10, IFN-gamma, and IL-10 (P=0.0001). HIV+ pruritus was significantly highest in TNF-alpha (P=0.0001) staining. HIV+ psoriasis represented an intermediate state for all four cytokines. Normal skin adjacent to lesions showed the same relative patterns, with lower intensities. Skin diseases seen frequently in the setting of HIV and immunodeficiency have relatively distinct levels and patterns of cytokine expression that may reflect immune dysfunction, reactivity to HIV and to opportunistic infections.
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PMID:Cytokine expression patterns distinguish HIV associated skin diseases. 1101 55

Pruritus is one of the major unsolved problems for patients receiving regular hemodialysis. In this study, we conducted a 6 month prospective and crossover trial to investigate the effect of polymethylmethacrylate (PMMA) membrane for renal itching. We also examined the role of the tumor necrosis factor (TNF)-alpha system for pruritus in hemodialysis patients. We assessed the degree of skin itching and measured circulating levels of TNF-alpha and soluble TNF receptors (sTNFR-I, sTNFR-II) in 19 patients using hemodialysis, complicated by prolonged severe pruritus for 6 months. Serum sTNFR-I and II levels were significantly elevated in hemodialysis patients compared to normal subjects. Serum sTNFR-II levels were significantly and negatively correlated with serum albumin (r = -0.602, p = 0.007). A significant positive relationship was also found between sTNFR-I and erythropoietin dosage (r = 0.554, p = 0.016). However, no association was found between the degree of pruritus and circulating sTNFR-I and II values. Skin itching scale was significantly decreased from 2.7 +/- 0.2 to 2.1 +/- 0.3 following the use of PMMA membrane for 3 months (p < 0.05). In contrast, there was no change in itching scales during 3 months of conventional therapy (2.2 +/- 0.3 versus 2.2 +/- 0.3, p = NS). PMMA itself did not affect serum TNF-alpha and sTNFR values as well as conventional dialyzer membranes. These findings suggested that the PMMA dialyzer can improve renal itching not mediated through the modification of the TNF-alpha system.
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PMID:Polymethylmethacrylate efficacy in reduction of renal itching in hemodialysis patients: crossover study and role of tumor necrosis factor-alpha. 1145 73

Treatment of onchocerciasis with diethylcarbamazine (DEC) or ivermectin is associated with a posttreatment reaction characterized by fever, tachycardia, hypotension, lymphadenopathy, and pruritus. To investigate the role of the Wolbachia bacterial endosymbiont of Onchocerca volvulus in these reactions, serum samples collected before and after treatment with either anthelmintic were assessed for evidence of Wolbachia DNA. By use of real-time quantitative polymerase chain reaction, Wolbachia DNA was detected in both groups-with significantly higher levels in those who received DEC (P <.0001). In the ivermectin group, there was a significant correlation between levels of bacterial DNA and serum tumor necrosis factor-alpha (P =.013). Peak DNA levels correlated with reaction scores (P =.048). Significant correlations were also seen between Wolbachia DNA and the antibacterial peptides calprotectin (P =.021) and calgranulin B (P <.0001). These findings support a role for Wolbachia products in mediating the inflammatory responses seen following treatment of onchocerciasis and suggest new targets for modulating these reactions.
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PMID:Bacterial endosymbionts of Onchocerca volvulus in the pathogenesis of posttreatment reactions. 1192 Feb 98

There is no effective medical treatment for primary sclerosing cholangitis (PSC), a chronic cholestatic liver disease that usually progresses to cirrhosis and liver failure. The aim of this study was to determine the safety and efficacy of etanercept, an inhibitor of tumor necrosis factor, in the treatment of PSC. Ten patients with clinically active PSC were studied. All had elevated serum alkaline phosphatase levels, cholangiograms that were diagnostic of PSC, and liver histology consistent with PSC. Five patients had elevated serum bilirubin levels, five had pruritus, eight had failed to respond to ursodiol and/or methotrexate, and six had rapidly recurring dominant bile duct strictures. Patients were to receive etanercept, 25 mg subcutaneously twice weekly, for 6 months if there were no side effects and for 1 year if there was evidence of efficacy after 6 months. Biochemical tests of liver function did not improve in any patient. Mean serum bilirubin levels increased significantly, from 2.0 to 3.6 mg/dl (P = 0.026). Two of the five patients with pruritus had resolution of pruritus during treatment with etanercept, recurrence when etanercept was stopped, and resolution when it was restarted, although there was little change in liver enzymes or bilirubin levels. There was no decrease in the rate of stricture formation and there were no side effects. Etanercept, at the dosage used, was well tolerated but not effective in the treatment of PSC. It may be helpful in treating pruritus due to cholestasis.
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PMID:A pilot study of etanercept in the treatment of primary sclerosing cholangitis. 1499 26

The proinflammatory cytokine tumor necrosis factor (TNF) alpha signals both cell survival and death. The biological outcome of TNFalpha treatment is determined by the balance between NF-kappaB and Jun kinase (JNK) signaling; NF-kappaB promotes survival, whereas JNK enhances cell death. Critically, identity of a JNK substrate that promotes TNFalpha-induced apoptosis has been outstanding. Here we show that TNFalpha-mediated JNK activation accelerates turnover of the NF-kappaB-induced antiapoptotic protein c-FLIP, an inhibitor of caspase-8. This is not due to direct c-FLIP phosphorylation but depends on JNK-mediated phosphorylation and activation of the E3 ubiquitin ligase Itch, which specifically ubiquitinates c-FLIP and induces its proteasomal degradation. JNK1 or Itch deficiency or treatment with a JNK inhibitor renders mice resistant in three distinct models of TNFalpha-induced acute liver failure, and cells from these mice do not display inducible c-FLIP(L) ubiquitination and degradation. Thus, JNK antagonizes NF-kappaB during TNFalpha signaling by promoting the proteasomal elimination of c-FLIP(L).
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PMID:The E3 ubiquitin ligase itch couples JNK activation to TNFalpha-induced cell death by inducing c-FLIP(L) turnover. 1646 5

Pruritus is synonymous with itching. Many medical conditions are complicated by chronic pruritus compromising the patient's quality of life. The majority of pruritic stimuli are transmitted through C fibers into the lateral spinothalamic tract and then into the somatic sensory cortex where the itching is detected. Histamine, substance P, and tumor necrosis factor a play significant roles in the perception of pruritus. Medical conditions in adults with significant pruritus will be defined in this review.
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PMID:What lies beneath the surface of the itch in adults? 1747 98

Collectively, new developments in the field of medical dermatology will ultimately lead to improved patient care. We review several new findings in the dermatologic literature including the following: new questions regarding the malignant potential of anti-tumor necrosis factor agents, which are widely used for the treatment of moderate to severe psoriasis as well as psoriatic arthritis; anti-interleulin-12, a promising anticytokine for the treatment of psoriasis; diagnostic advances in the detection of latent Mycobacterium tuberculosis; advances in the primary prevention of human papillomavirus and herpes zoster; and new therapeutic options with existing medications for neuropathic pain and pruritus.
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PMID:Recent advances in medical dermatology. 1791 Jul 4

Uremic pruritus is one of the common complications in long-term dialysis patients. Recently, researchers reported that immunohypothesis with high serum level of cytokines could be the cause of uremic pruritus. Polymethylmethacrylate (PMMA) artificial kidney (AK) has been reported to adsorb more serum cytokines than other high-flux AKs. In July 2006, 30 patients with severe uremic pruritus from 300 chronic hemodialysis (HD) patients in a single center entered this prospective study. Their dialyzers were changed to PMMA AK for 4 weeks. The severity of pruritus was evaluated every week using the results of a questionnaire (pruritus score). Laboratory assays including predialysis serum blood urea nitrogen (BUN), creatinine, beta2-microglobulin (beta2M), calcium, phosphate, intact parathyroid hormone (iPTH), total CO(2), ferritin, hematocrit, high-sensitivity C-reactive protein (hsCRP), IL-1beta, IL-2, IL-6, IL-18, tumor necrosis factor-alpha (TNF-alpha), Kt/V, and beta2M clearance were measured before and at the end of 4 weeks of PMMA AK use. PMMA AK was effective in reducing the pruritus score from 23.46 +/- 11.94 to 7.38 +/- 6.42 (P < 0.001). The effect of uremic pruritus relief appeared after 1 week of PMMA AK use. There were no significant differences in the laboratory assay results including predialysis serum BUN, Cr, beta2M, calcium, phosphate, calcium-phosphate product, iPTH, total CO(2), ferritin, hematocrit, hsCRP, IL-1beta, IL-2, IL-6, IL-18, TNF-alpha, Kt/V, and beta2M clearance. The mechanism for the beneficial effect of PMMA AK on uremic pruritus remains to be determined. PMMA AK may be a useful adjuvant therapy in chronic HD patients with severe uremic pruritus.
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PMID:Uremic pruritus, cytokines, and polymethylmethacrylate artificial kidney. 1842 97


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