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)

S-adenosyl-L-methionine (SAMe), a molecule naturally present in several body tissues and fluids, is produced, by SAMe synthetase, from ATP and methionine. SAMe has a fundamental role, as methyl group donor, in transmethylation reactions in which the synthesis of membrane phospholipids (especially phosphatidylcholine) is mandatory for the maintenance of membrane fluidity. Another metabolic pathway involving SAMe, transsulphuration, is initiated with the release of -CH3 from the molecule and the formation of S-Adenosyl-homocysteine and then homocysteine and cysteine, a precursor of glutathione the main cellular antioxidant, responsible of detoxification of various compounds and xenobiotics. At last SAMe is implicated in aminopropylation process for the polyamine synthesis. The development of stable double salt of p-toluene sulphonic acid and sulphuric acid of SAMe enables the clinical use of the drug, as a therapeutical agent, for the treatment of a number of liver dysfunctions. In various animal and human models, including controlled trials, it has been demonstrated that SAMe can ameliorate some biochemical parameters and pruritus in cholestasis induced by a range of compounds (i.e. oestrogens, lithocolate, etc) and in intrahepatic cholestasis superimposed to chronic liver disease. Concerning alcohol toxicity, SAMe prevents, in ethanol fed baboons, depletion of glutathione levels, normalizes the mitochondrial enzymes and improves the histological hepatic lesions. In human healthy volunteers it has been recently demonstrated that SAMe, after ethanol ingestion, significantly lowers plasma concentration of ethanol and acetaldehyde as well. Finally, SAMe has been proposed, instead of N-acetylcysteine, as precursor of glutathione, in patients who present late after ingestion of an overdose of paracetamol.
 ...
PMID:[S-adenosyl-L-methionine (SAMe) and its use in hepatology]. 129 37

S-Adenosyl-L-methionine has been reported to induce beneficial effects in intrahepatic cholestasis of pregnancy. Because cholestasis of pregnancy has a high prevalence in Chile and a deleterious effect on fetal prognosis, we decided to verify the efficacy of S-adenosyl-L-methionine in this disease. Eighteen patients with pruritus that appeared during pregnancy and with elevated serum levels of bile salts (68.1 +/- 15.9 mumol/L; mean +/- S.E.M.) and ALT (226 +/- 50 KU/L) were enrolled in a prospective double-blind study comparing the effects of the drug with a placebo. S-Adenosyl-L-methionine, 900 mg, or placebo was administered in daily intravenous infusions for 20 days. Every 5 days liver function tests were done and pruritus was assessed using a preestablished score. No significant differences in pruritus or in serum levels of bile salts, ALT, bilirubin and alkaline phosphatases were seen during or after treatment between patients who received S-adenosyl-L-methionine (n = 9) or placebo (n = 9). No relevant adverse reactions were detected. Most patients had cesarean sections because of reasons unrelated to the therapeutic trial. All newborns had Apgar scores greater than 7 and normal postnatal development. Our patients had moderately severe to severe cholestasis of pregnancy as indicated by the onset of pruritus before wk 32 of pregnancy. Seven of nine multiparous patients had a past history of recurrent cholestasis of pregnancy. In this study, the administration of S-adenosyl-L-methionine during 20 days did not improve intrahepatic cholestasis of pregnancy.
 ...
PMID:S-adenosyl-L-methionine in the treatment of patients with intrahepatic cholestasis of pregnancy: a randomized, double-blind, placebo-controlled study with negative results. 205 Mar 26

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.
 ...
PMID:Role of S-adenosyl-L-methionine in the treatment of intrahepatic cholestasis. 208 76

Several non-opioid regulatory peptides have been described in normal human skin localized both in neural fibres and in cellular elements. These include substance P, neurokinin A, neurotensin, calcitonin gene-related peptide, vasoactive intestinal polypeptide, peptide histidine methionine, neuropeptide Y, somatostatin, galanin and atrial natriuretic peptide. In the present review the morphological aspects and distribution of peptidergic nerves in normal human skin are presented. The main functional roles on nociception, pruritus, cutaneous blood flow and sweat production are discussed in regard to neuropeptides. The relationships between neuropeptides, mast-cells and neurogenic inflammation are discussed in detail. Pathological conditions are reported in which an alteration in the peptidergic control might be of importance in their pathogenesis. Some working hypothesis are discussed.
 ...
PMID:[Neuropeptides and the skin: morphological, functional and physiopathological aspects]. 268 Sep 14

Patients with liver disease have increased plasma concentrations of the endogenous opioid peptides methionine enkephalin and leucine enkephalin. As an initial investigation to determine whether opioid peptides contribute to any of the clinical manifestations of hepatic disease nalmefene, a specific opioid antagonist devoid of agonist activity, was given to 11 patients with cirrhosis. They all experienced a severe opioid withdrawal reaction on starting the drug. In the nine patients with primary biliary cirrhosis pruritus was greatly alleviated, fatigue seemed to improve, and plasma bilirubin concentration, which had been rising, showed a modest fall in all except one patient. These results indicate that blocking opioid receptors has an effect on some of the metabolic abnormalities of liver disease.
 ...
PMID:Opioid peptides and primary biliary cirrhosis. 314 46

The definition, history, incidence, diagnosis, possible etiology and treatment of nausea and vomiting in early pregnancy, also called emesis gravidarum, are reviewed. The condition may involve nausea, retching and/or occasional vomiting in early pregnancy: severe vomiting is termed hyperemesis gravidarum. The condition was described as early as 2000 B.C. It occurs in 50-70% of pregnancies in Western societies, but is said to be rare in some primitive societies. A lower incidence of nausea and vomiting has been associated with spontaneous abortion before 20 weeks gestation. Among selected hormones measured in pregnant women, those with nausea and vomiting in early pregnancy had significantly lower cortisol and progesterone, but higher hCG, while those with vomiting in late pregnancy had significantly lower testosterone and hCG and higher dehydroepiandrosterone than unaffected women. Other factors proposed as causative agents include tissue polypeptide antigen, high LDLs and VLDLs, and low HDLs, gall bladder disease, and ovulation from the right ovary. Women who develop nausea while taking oral contraceptives also have a tendency to do so in pregnancy. Possibly the steroid load on the liver may explain the condition. In the absence of a theory to explain nausea in pregnancy, no specific treatment is known. Experimental use of S-adenosyl-L-methionine, a methyl donor active in estrogen conjugation, reverses some estrogen-induced liver changes, such as cholestasis, pruritus, and bile acid abnormalities in pregnancy.
 ...
PMID:Nausea and vomiting in pregnancy: a review. 361 96

The effect of various opioid or putative neurotransmitter peptides on histamine-induced itch and flare responses was studied in humans after intradermal injection. Significant enhancement of the histamine responses was induced by the stable methionine-enkephalin analogue FK 33-824, beta-endorphin and morphine. The putative neurotransmitters substance P and vasoactive intestinal polypeptide (VIP)--which moreover are potent histamine liberators--had no enhancing effect. The potentiation induced by FK 33-824 was induced neither by local pretreatment with Compound 48/80 to deplete the local stores of mast-cell-bound histamine, nor by oral pretreatment with indomethacin to inhibit prostaglandin formation in the skin. Thus, the enhancement did not seem to be due to histamine release or to prostaglandin formation and the mechanism of the effect remains to be shown. The specific morphine antagonist naloxone did not inhibit the potentiation by FK 33-824, which might indicate that ordinary opiate receptors were not involved. The results support the idea that pain and itch are qualitatively separate processes and suggest possible mechanisms of morphine-induced pruritus. The findings are of particular interest in view of recent reports on the presence of methionine-enkephalin in Merkel cells.
 ...
PMID:Potentiation of histamine-induced itch and flare responses in human skin by the enkephalin analogue FK-33-824, beta-endorphin and morphine. 618 98

Previous investigations have indicated that S-adenosyl-L-methionine (SAMe) leads to reversal of estrogen-induced bile flow impairment in rats. This randomized, single-blind clinical trial was performed to determine whether SAMe reverses intrahepatic cholestasis of pregnancy (ICP) which occurs in hypersensitive women associated with increased estrogen levels in late pregnancy. Eighteen women with ICP were randomly divided into three groups of six and treated for 20 days as follows: Group I received 200 mg per day of i.v. SAMe; Group II received 800 mg per day of i.v. SAMe; Group III served as control. At the beginning of the study, clinical and biochemical parameters were similar among groups. After 10 and 20 days of treatment with the higher dose of SAMe, the mean values of serum transaminases, conjugated bilirubin and total bile acids fell significantly in respect to initial levels; opposite results were found in the other two treatment groups. The final values of these selected parameters were lower in the group of subjects treated with 800 mg per day SAMe than in the other two groups of women. Pruritus graded on a 0 to 4+ scale significantly was reduced only in patients treated with the higher dose of SAMe. These results indicate a trend toward remission of ICP in women treated with 800 mg per day SAMe and suggest that SAMe administration may be a new therapeutic modality for ICP.
 ...
PMID:Reversal of intrahepatic cholestasis of pregnancy in women after high dose S-adenosyl-L-methionine administration. 670 1

S-adenosyl-L-methionine (ademethionine) has been recently proposed as a therapeutic agent for the treatment of intrahepatic cholestasis (IHC), a syndrome that overlaps with many different types of liver diseases. To obtain a global assessment of the results of the therapeutic efficacy of this compound, a meta-analysis of 6 controlled clinical trials with ademethionine in the symptomatic treatment of IHC of liver diseases and pregnancy was carried out. The therapeutic response to ademethionine treatment, for 15 to 30 days, proved to be superior to placebo, as assessed by resolution of pruritus, normalisation or 50% improvement in serum total bilirubin, serum conjugated bilirubin, alanine aminotransferase, gamma-glutamyl transpeptidase and alkaline phosphatase. At present, the therapeutic effect of ademethionine should be regarded as symptomatic, but long term studies on the effect of drug administration on the course of the disease and survival are being performed.
 ...
PMID:[A meta-analysis of therapeutic trials with ademetionine in the treatment of intrahepatic cholestasis]. 811 21

Intrahepatic cholestasis of pregnancy (ICP) is a syndrome usually manifesting during the third trimester of pregnancy and disappearing after delivery. Multiple factors seem to be involved in pathogenesis of the syndrome; however, ICP appears to take place in women congenitally hypersensitive to estrogens. Typical is pruritus, which may be followed by jaundice and associated with other less common symptoms. The biochemical parameters are characteristically altered: an increase in the levels of aminotransferases (AST, ALT), total bile acids and alkaline phosphatase is observed; while serum GGT are normal. Maternal prognosis is benign. By contrast, a higher risk of acute fetal distress and prematurity has been reported. Various drugs are used in the treatment of ICP. We present the case of a patient treated with S-adenosyl-L-methionine (SaMe). SaMe therapy has proved to be effective in improving the altered biochemical parameters, whose normalization was obtained before delivery.
 ...
PMID:[Intrahepatic cholestasis in pregnancy]. 911 20


1 2 Next >>