Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The levels of 5-hydroxytryptamine (serotonin, 5-HT) and substance P (SP) were assayed (using high performance liquid chromatography-electron capture and radioimmunoassay methods) in the peripheral blood of 17 patients with known mid-gut carcinoids, 16 of whom had hepatic metastases. All patients had supranormal basal levels of 5-HT and SP. The clinical and hormonal changes induced by two provocation tests, intravenous pentagastrin (PG) and calcium infusion, were compared. Pentagastrin caused flushing in all the patients, induced gastrointestinal symptoms in all but one of the patients with hepatic involvement, and universally elevated circulating 5-HT levels. Pretreatment with a 5-HT2-receptor blocking agent, ketanserin, abolished the gastrointestinal effects but had virtually no influence on either 5-HT levels or flushing induced by intravenous pentagastrin. In contrast, calcium infusion induced carcinoid symptoms in only two of six patients, and this was consistently associated with stimulation of circulating serotonin levels. The authors conclude that 1) 5-HT may be responsible for the gastrointestinal symptoms in carcinoid patients, but it does not seem to play any role in flushing; 2) ketanserin may be a useful therapeutic agent in alleviating gastrointestinal symptoms in carcinoid patients; 3) differential responses to PG suggests that SP is released from a site different from that of 5-HT; 4) it is possible that SP may contribute to the mediation of flushing, but it cannot be the sole agent causing this symptom; and 5) the pentagastrin test with measurements of 5-HT levels in peripheral blood seems to be superior to calcium infusion as a provocative test in documenting the diagnosis of carcinoid disease.
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PMID:The pentagastrin test in the diagnosis of the carcinoid syndrome. Blockade of gastrointestinal symptoms by ketanserin. 257 77

A tumor substrain secreting a large amount of serotonin [5-hydroxytryptamine (5-HT); CAS: 50-67-9; 3-(2-amino-ethyl)indol-5-ol] and a minute amount of histamine (CAS: 51-45-6) has been isolated from the previously established strain of transplantable gastric carcinoid of Mastomys (Praomys) natalensis secreting both histamine and 5-HT. Mastomys bearing a large growing transplant and excreting a large amount of 5-hydroxy-indoleacetic acid [(5-HIAA) CAS: 54-16-0] were associated often with reddening of the nose, lower lip, auricles, hands, and feet. Soon after the animals were anesthetized by ether or other volatile anesthetics, the tinges of red of the above-mentioned exposed parts abruptly turned bright red and rapidly spread over the neck, upper chest, and epigastric area. The reddening was transient, lasting 1.5-5 minutes, thereby fulfilling the criteria of flushing. The severity of ether-provoked flushing in tumor-bearing Mastomys paralleled the urinary excretion levels of 5-HIAA. The ether-provoked flushing was prevented completely by sc injection of either ketanserin (150 micrograms) or somatostatin (20 micrograms). The same ether-provoked flushing as found in tumor-bearing Mastomys could be reproduced in normal ones by constant infusion of 20 mg 5-HT/kg/24 hours (i.e., doses comparable to those released from a transplanted tumor) through an osmotic minipump implanted subcutaneously.
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PMID:Novel flushing provoked by volatile anesthetics in Mastomys natalensis bearing a transplantable substrain of gastric carcinoid that predominantly secretes serotonin. 620 24

In this report we present the history of a patient with symptomatic carcinoid syndrome. During flushing he suffered from variant angina. The observation of coronary spasm due to excess 5-hydroxytryptamine (5-HT) is discussed with regard to the discharge of 5-HT from clotting platelets in the coronary arteries.
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PMID:Evidence for coronary spasm during flushing in the carcinoid syndrome. 646 96

The carcinoid syndrome is a rare clinical entity mainly characterized by flushing and diarrhoea. It is due to different biological mediators produced by tumours that arise from enterochromaffin cells. Such tumours are typically located in the ileum, have a long course and become symptomatic only in the presence of overt liver metastases. Among the involved mediators, the role of serotonin (5-hydroxytryptamine, 5-HT) has been ascertained in the pathogenesis of diarrhoea, while it remains controversial in that of flushing. Ketanserin is a 5HT-2 antagonist with no mixed receptor agonist-antagonist activity. We report the case of a severely distressing carcinoid syndrome fully dominated by ketanserin. The patient was a 75-year-old man, who came to our attention because of marked weight loss, impossibility to feed and almost continuous diarrhoea due to liver colonization of a mid ileum carcinoid tumour, previously resected at the age of 65. Sustained facial and trunk flushing also presented several times daily. Ketanserin, 20 mg twice a day orally, was administered and then increased up to 40 mg daily with no side effects and progressive complete control of both diarrhoea and flushing. It is suggested that ketanserin, due to its availability and tolerability, should first be considered for palliative relief of carcinoid syndrome. The literature on this subject is extensively reviewed.
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PMID:[Symptomatic relief of carcinoid syndrome by ketanserin. A case]. 763 30

We report a case of bullous mastocytosis in a 30-month-old girl, who developed disseminated pruritic urticarial and bullous lesions on the trunk accompanied by episodes of vomiting and generalized flushing. Her problems began at the age of 6 months. Her stool was repeatedly positive for occult blood. Histamine and 5-hydroxytryptamine were measured in the urine and serum; urine 5-hydroxytryptamine levels were elevated. In addition, trypsin and chymotrypsin levels were raised in the blister fluid. Metachromatic staining of the mast cells in a skin biopsy specimen confirmed the diagnosis. A combination of oral disodium cromoglycate and ketotifen produced a dramatic improvement of the cutaneous and gastrointestinal features.
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PMID:[Bullous mastocytosis in a child]. 917 60

Paraneoplastic syndromes are frequently associated with various types of malignant tumors but are fairly rare in the course of hepatocellular carcinoma (HCC). We describe the clinical case of a 76 year old man with chronic hepatitis C infection related to liver disease who had suffered for several months from chronic runny but blood and mucus-free diarrhea, together with progressive weight loss and flushing of the face. Serological tests made on admission confirmed the chronic liver disease and showed an increase of serum levels of some neuroendocrine hormones, i.e. 5-hydroxytryptamine and vasoattive intestinal peptide. Ultrasound and CT scans led to the diagnosis of HCC. The diarrhea and the increase in some neuroendocrine hormones were therefore interpreted as expression of a paraneoplastic-like neuroendocrine syndrome that had preceded the onset of HCC by some months. The patient died a few months after the diagnosis of HCC, from total portal vein thrombosis and consequent liver and renal failure. This clinical report draws the attention to the possibility of paraneoplastic syndrome expression before the clinical onset of HCC and to the role that neuroendocrine hormones may have on the growth and spread of HCC.
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PMID:[Diarrhea as first clinical manifestation of hepatocellular carcinoma]. 1235 85

Cumulative addition of atropine to the organ bath containing endothelium-intact (+E) rat aorta, which was precontracted with phenylephrine (PE, 1 microM) and subsequently relaxed with carbachol (1 microM), caused biphasic changes in the vascular contractility of +E rat aortic rings. Low concentrations of atropine (10 nM-1.0 microM) caused progressive restoration of contraction to PE; whereas at higher concentrations (1-100 microM), atropine caused progressive relaxation. Atropine-induced aortic relaxation was significantly inhibited upon endothelium removal by either rubbing or saponin treatment, but considerable relaxation still persisted in the range of 30-100 microM atropine. Similar findings were also obtained when the nitric oxide (NO) generation was inhibited with 300 microM NO synthase inhibitor, L-NAME. Atropine-induced relaxation was also observed when 5-hydroxytryptamine (5-HT) was used as the agonist and the atropine-relaxation was more potent at lower concentrations of PE and 5-HT. However, atropine had no effect on the contraction elicited by KCl or prostaglandin F(2 alpha). Also, atropine-induced relaxation was not affected by indomethacin (1-10 microM), nicotine (10-100 microM) or hexamethonium (30 microM). Pretreatment of +E aorta with tetraethylammonia (TEA, 3-10 mM) or 4-aminopyridine (4-AP, 1-3 mM) showed prominent inhibitory effect on atropine-induced relaxation; on the other hand, preincubation with glibenclamide (1-10 microM), BaCl(2) (1-30 microM) or 2 microM charybdotoxin and apamin, had little effect on the relaxation induced by atropine. When added to tissues after relaxation to atropine, TEA and 4-AP concentration-dependently reversed the relaxation in -E aorta, whereas in +E aorta, TEA up to 30 mM and 4-AP up to 10 mM only partially affected atropine-induced relaxation. Although TEA and 4-AP potentiated the PE-contraction, such potentiation is unlikely to contribute to the change in sensitivity to atropine-induced relaxation, since in the presence of 15 mM KCl, which also potentiated PE-contraction to a comparable extent, the atropine-relaxation remains unchanged. Scopolamine also acts like atropine, except that the effect of scopolamine was smaller than that of atropine and is primarily endothelium-dependent. Atropine-induced relaxation also occurs in medium artery (renal artery) and small muscular artery (mesenteric artery). In conclusion, atropine-relaxation is mediated in part via voltage-dependent K(+) channels in both smooth muscle and endothelium and forms the mechanistic basis for the observed vasodilation, reduced blood pressure and facial flushing following atropine overdose.
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PMID:In vitro relaxation of vascular smooth muscle by atropine: involvement of K+ channels and endothelium. 1280 79

The 24-hour urinary excretion of 5-hydroxyindoleacetic acid in women with post-menopausal flushing attacks was compared with that of a control group of post-menopausal women without flushing attacks. The results were normal in the women with post-menopausal flushing, and it is concluded that 5-hydroxytryptamine is not a factor in the pathogenesis of post-menopausal flushing.
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PMID:The urinary excretion of 5-hydroxyndoleacetic acid in patients with menopausal flushing. 1374 43

The effects of endotoxin (ET) on spontaneous contractility and of carbachol- and alpha-methyl-5-hydroxytryptamine-(alpha-M-5-HT; 5-HT2 receptor agonist) induced contractions of smooth muscle preparations from the bovine abomasal antrum were investigated in vitro. Preparations from the abomasal antrum of freshly slaughtered healthy dairy cows were cut parallel to the longitudinal and circular fibres, suspended in isolated organ baths, and contractility was recorded and analyzed, using digitalized data. The traits maximum amplitude, time till maximum amplitude, frequency, basal tone, and area under curve were calculated. The contractile effect of Carbachol (CH) was concentration dependent. Repeated administration of CH (3.75 x 10(-6) M), each time interrupted by flushing of the organ baths, did not reveal any significant effect on contractility traits of CH-induced contractions. Endotoxin (10 micrograms/ml; lipopolysaccharide from E. coli, O26:B6) significantly reduced some of the spontaneously occurring contractility traits and of carbachol-(3.75 x 10(-6) M) and alpha-M-5-HT-induced (2.14 x 10(-5) M) contractions. The effects of higher and lower concentrations of ET occurred less consistently. The inhibitory effect of endotoxin was more pronounced after 6 hours as compared to 2 hours of incubation. The results of the present study (i) support the hypothesis of a possible role of endotoxin in reducing motility of the abomasum during the development of spontaneous abomasal displacement in dairy cows, and (ii) may serve as the basis for the development of an in vitro model of abomasal displacement with endotoxemia for future studies on the effect of motility modulating drugs.
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PMID:Effect of endotoxins on contractility of smooth muscle preparations from the bovine abomasal antrum. 1498 52

A novel approach for in-line solid-phase extraction capillary electrophoresis (SPE-CE) for basic analytes was developed. The method is based on the use of a weak cation-exchange monolith synthesised in situ in the front end of the CE capillary via photoinitiated polymerization to form poly(methacrylic acid-co-ethylene glycol dimethacrylate), which was used to create the SPE phase in-line with the CE separation capillary. The monolithic SPE material exhibited a surface area of 23.1 m2/g and a capacity of 403 nM for dopamine. Adsorption of the analytes as protonated, cationic species onto the SPE phase was achieved using an electrolyte of 6 mM phosphate and 12 mM sodium ion, buffered at pH 7.0, which is above the pKa of the monolith but below the pKa of the analytes. Elution of the analytes from the SPE phase was achieved using an electrolyte with a pH below that of the pKa of the monolith, namely 12 mM phosphate and 12 mM sodium ion, buffered at pH 3.0. Due to the discontinuous electrolyte combination, analytes were simultaneously eluted and focused as the electrophoretically mobilised pH step boundary moved through the SPE monolith, after which the analytes were separated by conventional CZE in the remainder of the capillary. Quantitative extraction from a solution of 0.5 microg/ml dopamine and epinephrine was achieved when flushing up to 15 column volumes of sample through the capillary. The limits of detection (S/N=3) for dopamine and epinephrine were 3.7 and 4.3 ng/ml, and this method provided a sensitivity enhancement for dopamine of 462 times compared to CZE using hydrodynamic injection. The developed method was used to preconcentrate a test mixture of neurotransmitters comprising dopamine, epinephrine, 5-hydroxytryptamine, metanephrine and also histamine. The applicability of this approach to real life samples was demonstrated by using a urine sample from a healthy person to detect dopamine at sub-ppm levels.
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PMID:Capillary electrophoresis of neurotransmitters using in-line solid-phase extraction and preconcentration using a methacrylate-based weak cation-exchange monolithic stationary phase and a pH step gradient. 1798 Mar 75


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