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)

Recent studies have established the clinical efficacy of S-adenosyl-L-methionine (SAMe) in the treatment of cholestasis associated with hepatic diseases, pregnancy and the administration of estrogen-containing oral contraceptives. In 4 clinical trials involving a total of 639 patients with cholestasis due to acute or chronic liver disease, SAMe in an intravenous dose of 800 mg/day or an oral regimen of 1.6 g/day for 2 weeks was superior to placebo in relieving the symptom of pruritus and in restoring serum total bilirubin and serum alkaline phosphatase towards normal. The drug is also effective in intrahepatic cholestasis of pregnancy (ICP), with intravenous administration of 800 mg/day for 2 weeks producing a substantial reduction in pruritus and an improvement in abnormal liver function indices. Moreover, SAMe treatment decreases the incidence of premature labour. SAMe appears to be the first safe and effective approach to the treatment of this syndrome, and also protects against the adverse hepatic effects of small doses of estrogen in patients with a history of ICP by normalising liver biochemistry and the oversaturated biliary lipid composition of the gallbladder bile. In animal models, SAMe reverses the pathological liver changes induced by xenobiotics such as taurolithocholate and alpha-naphthyl-isothiocyanate (ANIT) and the antipsychotic chlorpromazine. Several cooperative mechanisms appear to underlie the anticholestatic action of SAMe, the most important being the restoration of normal hepatocyte membrane fluidity and Na+, K+ ATPase activity, through a reversal of the reduction in phospholipid methylation produced by hepatotoxic agents. In addition, SAMe may act by promoting trans-sulphuration pathway reactions and consequently improving the detoxifying capacity of this metabolic system.
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PMID:Role of S-adenosyl-L-methionine in the treatment of intrahepatic cholestasis. 208 76

A health survey was conducted among spraymen exposed to 2.5% deltamethrin EC in the cotton fields. The subjects were exposed to deltamethrin at concentrations of 0.022-24.070 micrograms/m3 in respiratory zone air and of 0.013-0.347 micrograms/cm2 of skin contact. Results showed that one-half of the 44 subjects examined complained of itching and burning sensations on their faces. A few miliary red papules also appeared on the face of one subject but not sign of acute deltamethrin poisoning was evident on physical examination. There were no significant differences between the subjects examined and the controls in sodium, potassium, and urea contents in the serum, sodium potassium ATPase and serotonin in whole blood, and 3-methyl-4-hydroxymandelic acid and 5-hydroxyindoleacetic acid in the urine. Deltamethrin in the urine of spraymen was below the detection limit (0.20 microgram/liter) of the method used.
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PMID:Health survey among farmers exposed to deltamethrin in the cotton fields. 335 51

Although oral contraceptives (OCs) are yet to be legalized in Japan, it is estimated that at least 500,000 women were on pills in 1975. Intrahepatic cholestasis has been associated with OC in the Western countries, but only a few cases have been reported in Japan. A case of pill-related intrahepatic cholestasis in a 25-year old housewife will be presented in terms of clinical/pathological findings, changes in plasma and bile acid levels, and the effect of phenobarbital on bile stagnation. The patient had been taking 1 pill (Anovlar)/day, 25 days a month, for 5 months, and had experienced exhaustion, nausea, and constipation after 3 months of use; body itch and jaundice symptoms after 4 months. Cholangiography showed neither enlargement of the bile duct nor obstruction of the bile duct outside the liver. The condition was diagnosed as pill-related intrahepatic cholestasis. Total bilirubin was considerably raised; serum transaminase was moderately raised. Electromicroscopy showed the enlargement of bile canaliculi, which had electron dense bile content. Hepatic cellular peroxisome significantly increased. Plasma bile acid level, which was slightly raised initially, came down to the normal range when total bilirubin was back to normal with daily administration of phenobarbital 2 mg/kg. Studies which included experiments with rats as well as clinical-pathological results mentioned above suggested that bile stagnation was caused by ethinyl estradiol. By lowering bile canaliculi Na-K ATPase activity, ethinyl estradiol decreased bile acid independent of bile flow. Phenobarbital was effective for cholestasis by increasing bile canaliculi Na-K ATPase activity.
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PMID:[Intrahepatic cholestasis caused by oral contraceptives]. 714 55

Benign recurrent intrahepatic cholestasis is a rare autosomal recessive disorder characterized by repeated episodes of intense pruritus and jaundice. Each attack lasts from several weeks to months before resolving spontaneously. Patients are completely asymptomatic for months to years between symptomatic periods. The disorder does not lead to progressive liver disease. Although attacks seem to be associated with a viral prodrome, an inciting viral agent or toxin has not been defined. Genetic studies have mapped the defect of this disorder to the long arm of chromosome 18 and a gene that codes for a P-type ATPase, which appears to be involved in aminophospholipid transport. Therapy during symptomatic periods is supportive and aimed at relief of severe pruritus until the episode resolves spontaneously.
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PMID:Benign recurrent intrahepatic cholestasis. 1129 Dec 37

Many enveloped viruses exploit the class E vacuolar protein-sorting (VPS) pathway to bud from cells, and use peptide motifs to recruit specific class E VPS factors. Homologous to E6AP COOH terminus (HECT) ubiquitin ligases have been implicated as cofactors for PPXY motif-dependent budding, but precisely which members of this family are responsible, and how they access the VPS pathway is unclear. Here, we show that PPXY-dependent viral budding is unusually sensitive to inhibitory fragments derived from specific HECT ubiquitin ligases, namely WWP1 and WWP2. We also show that WWP1, WWP2, or Itch ubiquitin ligase recruitment promotes PPXY-dependent virion release, and that this function requires that the HECT ubiquitin ligase domain be catalytically active. Finally, we show that several mammalian HECT ubiquitin ligases, including WWP1, WWP2, and Itch are recruited to class E compartments induced by dominant negative forms of the class E VPS ATPase, VPS4. These data indicate that specific HECT ubiquitin ligases can link PPXY motifs to the VPS pathway to induce viral budding.
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PMID:HECT ubiquitin ligases link viral and cellular PPXY motifs to the vacuolar protein-sorting pathway. 1562 82

Moloney murine leukemia virus (MoMLV) Gag utilizes its late (L) domain motif PPPY to bind members of the Nedd4-like ubiquitin ligase family. These interactions recruit components of the cell's budding machinery that are critical for virus release. MoMLV Gag contains two additional L domains, PSAP and LYPAL, that are believed to drive residual MoMLV release via interactions with cellular proteins Tsg101 and Alix, respectively. We found that overexpression of Tsg101 or Alix failed to rescue the release of PPPY-deficient MoMLV via these other L domains. However, low-level expression of the ubiquitin ligase Itch potently rescued the release and infectivity of MoMLV lacking PPPY function. In contrast, other ubiquitin ligases such as WWP1, Nedd4.1, Nedd4.2, and Nedd4.2s did not rescue this release-deficient virus. Efficient rescue required the ubiquitin ligase activity of Itch and an intact C2 domain but not presence of the endophilin-binding site. Additionally, we found Itch to immunoprecipitate with MoMLV Gag lacking the PPPY motif and to be incorporated into rescued MoMLV particles. The PSAP and LYPAL motifs were dispensable for Itch-mediated virus rescue, and their absence did not affect the incorporation of Itch into the rescued particles. Itch-mediated rescue of release-defective MoMLV was sensitive to inhibition by dominant-negative versions of ESCRT-III components and the VPS4 AAA ATPase, indicating that Itch-mediated correction of MoMLV release defects requires the integrity of the host vacuolar sorting protein pathway. RNA interference knockdown of Itch suppressed the residual release of the MoMLV lacking the PPPY motif. Interestingly, Itch stimulation of the PPPY-deficient MoMLV release was accompanied by the enhancement of Gag ubiquitination and the appearance of new ubiquitinated Gag proteins in virions. Together, these results suggest that Itch can facilitate MoMLV release in an L domain-independent manner via a mechanism that requires the host budding machinery and involves Gag ubiquitination.
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PMID:Late domain-independent rescue of a release-deficient Moloney murine leukemia virus by the ubiquitin ligase itch. 1986 77