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)

Eosinophilic endocarditis is a potentially lethal complication of chronic peripheral blood hypereosinophilia. We hypothesized that eosinophil peroxidase (EPO), an abundant eosinophil (EO) cationic granule protein, promotes eosinophilic endocarditis by binding to negatively charged endocardium, and there generating cytotoxic oxidants. Using an immunocytochemical technique, we demonstrated endocardial deposition of EPO in the heart of a patient with hypereosinophilic heart disease. Because EPO preferentially oxidizes Br- to hypobromous acid (HOBr) rather than Cl- to hypochlorous acid (HOCl) at physiologic halide concentrations, we characterized the Br(-)-dependent toxicity of both activated EOs and purified human EPO towards several types of endothelial cells and isolated working rat hearts. In RPMI supplemented with 100 microM Br-, phorbol myristate acetate-activated EOs, but not polymorphonuclear leukocytes, caused 1.8-3.6 times as much 51Cr release from four types of endothelial cell monolayers as in RPMI alone. H2O2 and purified human EPO, especially when bound to cell surfaces, mediated extraordinarily potent, completely Br(-)-dependent cytolysis of endothelial cells that was reversed by peroxidase inhibitors, HOBr scavengers, and competitive substrates. We further modeled eosinophilic endocarditis by instilling EPO into the left ventricles of isolated rat hearts, flushing unbound EPO, then perfusing them with a buffer containing 100 microM Br- and 1 microM H2O2. Acute congestive heart failure (evidenced by a precipitous decrement in rate pressure product, stroke volume work, aortic output, and MVO2 to 0-33% of control values) ensued over 20 min, which deletion of EPO, Br-, or H2O2 completely abrogated. These findings raise the possibility that EPO bound to endocardial cells might utilize H2O2 generated either by overlying phagocytes or endogenous cardiac metabolism along with the virtually inexhaustible supply of Br- from flowing blood to fuel HOBr-mediated cell damage. By this mechanism, EPO may play an important role in the pathogenesis of eosinophilic endocarditis.
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PMID:Bromide-dependent toxicity of eosinophil peroxidase for endothelium and isolated working rat hearts: a model for eosinophilic endocarditis. 198 18

We compared the rise in nasal airway resistance (NAR) provoked by topical application of substance P (SP) and of methacholine (MCH) in seventeen patients suffering from rhinitis and fourteen control subjects. Challenges with SP or MCH were separated by a week or more. NAR was measured by posterior rhinomanometry before and 10 min after intranasal administration of SP (10-40 nmol) or MCH (3-12 mumol). The two groups of subjects had similar baseline levels of NAR and similar small responses to buffered saline. Substance P but not MCH provoked cutaneous flushing in all subjects. Both SP and MCH provoked a significantly greater increase in NAR in patients suffering from rhinitis than in control subjects. The increase in NAR was dose-dependent, and on a molar basis, SP was 375-500-fold more potent than MCH. Pretreatment with 200 micrograms of a topically active anticholinergic agent, oxytropium bromide, prevented the rise in NAR caused by 12 mumol of MCH but not that caused by 40 nmol of SP in six patients suffering from rhinitis. We conclude that SP is absorbed across the nasal mucosa and causes cutaneous vasodilation, that MCH and SP cause a greater rise in NAR in patients suffering from rhinitis than in control subjects, that SP is about 500-fold more potent than MCH in increasing NAR, and that the rise in NAR caused by SP is not mediated by postganglionic parasympathetic mechanisms.
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PMID:Nasal response to substance P and methacholine in subjects with and without allergic rhinitis. 245 27

Fertilized oocytes of the inbred genotypes AKR (AK), C57BL/6 (B6), DBA/2 (D2), and CBA (CB) and the hybrid genotypes F1 (female AK X male B6) and F1 (female B6 X male AK) were collected by flushing the oviducts of female mice every 2 h from 2 until 26 h post coitum. Developmental stages of the embryos and DNA content of the pronuclei were estimated by morphological criteria and cytofluorometric measurement of the pronuclei (ethidium bromide-stained DNA), respectively. In all genotypes, S-phase started about 4 h post conception (h.p.c.). The duration of S-phase amounted to 5.9 h (F1 [female B6 X male AK]), 6.4 h (AK), 8.5 h (B6), 9.4 h (F1 [female AK X male B6]), 9.8 h (D2), and 11.4 h (CB). In each of the reciprocal F1 hybrids, the length of S-phase differed from the maternal genotype (p less than 0.01) and resembled closely the paternal genotype (p greater than 0.25). Cleavage from one-cell stage to two-cell stage occurred between 16 and 21 h.p.c.
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PMID:Paternal influence on timing of pronuclear DNA synthesis in naturally ovulated and fertilized mouse eggs. 340 33

The aldehyde dehydrogenase I (ALDH I) gene codes for a mitochondrial enzyme which plays a major role in hepatic alcohol detoxication. It has been related to alcohol flushing in Orientals bearing the atypical ALDH I2 gene. The variant protein results from a lysine for glutamate substitution at position 487 (G-->A change in exon 12). A procedure for ALDH I2 detection consisting in a differentiation between the 'atypical' allele and the 'wild' allele has been improved through PCR and subsequent MboII digestion. Blood samples collected on anticoagulant or directly absorbed on blotting paper were used for DNA amplification in the presence of two specific oligonucleotidic primers, each one able to incorporate a restriction site in the amplimer. After MboII digestion, PCR products were separated by polyacrylamide gel electrophoresis and then visualized with ethidium bromide. This technique permits a rapid and non-radioactive detection of atypical ALDH I2 on a PCR product without the use of allele specific oligonucleotides. It was applied to the study of ALDH I2 allele frequency in random population samples of three ethnic groups: Caucasians, Orientals and African blacks.
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PMID:The frequency of the mitochondrial aldehyde dehydrogenase I2 (atypical) allele in Caucasian, Oriental and African black populations determined by the restriction profile of PCR-amplified DNA. 747 12

Perfluorooctyl bromide is an oxygen-carrying perfluorocarbon presently under development as an artificial blood substitute (Oxygent HT). Intravenous (i.v.) Oxygent HT elicits a mild side-effect profile in man characterized by early onset headache and nausea and delayed onset fever. Early onset flushing has also been observed. Species of Artiodactyla are sensitive to particulate injections and demonstrate a transient pulmonary hypertensive response thought to be associated with the large number of pulmonary intravascular macrophages found in these species. Because of this sensitivity, we chose the swine as a model for further investigations. In anesthetized and conscious swine, i.v. Oxygent HT transiently increased mean pulmonary artery pressure (mPAP) and caused flushing. Both effects peaked at 30 min post injection and were resolved by 2 hrs. Plasma thromboxane B2 (TxB) increased in response to Oxygent HT. Oxygent HT-induced changes in mPAP, flush, and plasma TxB were blocked by aspirin and ibuprofen. Dexamethasone and SQ 29,548 (thromboxane receptor antagonist) blocked the mPAP increase. In conscious swine, Oxygent HT caused a febrile response which was blocked by ibuprofen or dexamethasone. Thus, both early- and late-onset effects of Oxygent HT in swine are blocked by interference with the arachidonic acid cascade. These findings suggest that the 2-phase "flu-like" syndrome induced by Oxygent HT is secondary to the release of products of the arachidonic acid cascade and may be effectively prophylaxed in man with corticosteroids or long plasma half-life cyclooxygenase inhibitors.
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PMID:Characterization and mechanism of side-effects of Oxygent HT (highly concentrated fluorocarbon emulsion) in swine. 784 64

Salbutamol inhibits neutropenia, increased airway resistance, and gas exchange abnormalities provoked by platelet-activating factor (PAF) challenge in normal persons. To further explore the intriguing dissociation between spirometric abnormalities and gas exchange defects shown in patients with asthma, we investigated whether the salbutamol-induced improvement in gas exchange disturbances after PAF is the result of bronchodilation by comparing this effect with that of ipratropium bromide. We hypothesized that ipratropium bromide, an anticholinergic agent without vascular effects, should block PAF-induced bronchoconstriction but not interfere with its systemic, neutropenic, and gas exchange effects. We studied eight nonsmokers with mild asthma (26 +/- 2.0 SE yr of age) who, prior to PAF challenge (18 micrograms), inhaled either ipratropium bromide (80 micrograms) or salbutamol (300 micrograms) in a randomized, double-blind, crossover fashion 1 wk apart. Peripheral blood neutrophils, respiratory system resistance (Rrs), arterial blood gases and ventilation-perfusion (VA/Q) inequalities were measured 5, 15, and 45 min after PAF. Compared with pretreatment with salbutamol, ipratropium bromide also blocked the increase of respiratory system resistance (Rrs) but did not prevent facial flushing and neutropenia (p < 0.03) at 5 min nor the decrease of PaO2 (p = 0.08 and 0.05), the increase of AaPO2 (p < 0.02 each), and the deterioration of VA/Q relationships (p < 0.05 each) at 5 and 15 min, respectively. This functional pattern was similar to that observed previously in normal subjects and in nonpremedicated asthmatic patients after PAF, with return to baseline values at 45 min. By contrast, salbutamol blocked PAF-induced increased Rrs, in addition to all the other PAF-induced abnormalities. These findings indicate that, in patients with mild asthma, salbutamol inhibits PAF-induced neutropenia and gas exchange abnormalities by mechanisms involving other than airway smooth muscle narrowing, possibly by acting on both the bronchial and pulmonary circulations.
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PMID:Inhibition of PAF-induced gas exchange defects by beta-adrenergic agonists in mild asthma is not due to bronchodilation. 923 Jul 20

A novel method is reported for quantifying protein adsorption to naked silica tubings and for assessing the efficacy of amino quenchers added to the background electrolyte. It consists of flushing a fluorescently-labelled protein (myoglobin) into a capillary equilibrated in Tris-acetate buffer, pH 5.0, until full saturation of the potential adsorbing sites. Desorption is then affected by driving electrophoretically sodium dodecyl sulphate (SDS) micelles into the capillary from the cathodic reservoir: the peak of eluted material is quantified fluorometrically by using a dual laser beam instrument able to read the fluorescein-isothiocyanate-labelled myoglobin at 520 nm and the internal standard (sulphorodamine) at 630 nm. As potential quenchers, a series of monoamines have been investigated (triethylamine, triethanolamine, ethylamine), followed by diamines (putrescine, cadaverine and hexamethonium bromide) and finally by oligoamines [spermidine, spermine and TEPA (tetraethylenepentamine), i.e., a tri- a tetra- and a pentamine, respectively]. Two values of molarities have been derived: a value at 50% (a kind of a dissociation constant) and a value at 90% inhibition of binding of macromolecules to the silica surface. According to these figures of merit, mono- and diamines are rather poor quenchers of interaction with the wall, since the 50% values are of the order of 50-100 mM and the 90% values reach as high as 560 mM. On the contrary, oligoamines, especially spermine and TEPA, are most effective, since the 50% molarities are in the sub-millimolar range and the 90% values are of the order of ca. 1 mM. Figures of merit have also been derived for different washing procedures. Those most commonly adopted in routine practice, i.e., of washing with either 1 M NaOH or with 1 M HCl, or with both, leave behind traces of proteins still bound to the wall, whereas the SDS micelle electrophoretic desorption seems to be 100% effective.
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PMID:Protein adsorption to the bare silica wall in capillary electrophoresis quantitative study on the chemical composition of the background electrolyte for minimising the phenomenon. 1067 82

A solid-phase extraction method based on an ion-exchange retention mechanism has been used for in-line preconcentration of inorganic anions prior to their separation by capillary electrophoresis (CE). A single capillary containing a preconcentration and a separation zone has been used in a commercial CE instrument without instrumental modification. Analyte anions were retained on a preconcentration zone comprising an adsorbed layer of cationic latex particles, while separation was achieved in a separation zone comprising fused silica modified by adsorption of a cationic polymer. Elution of the adsorbed analytes was achieved using an eluotropic gradient formed by a transient isotachophoretic boundary between a fluoride electrolyte and a naphthalenedisulfonate electrolyte. Optimization of the electrolyte concentrations, sample injection times, and back-flushing times allowed the successful separation of sub-ppb levels of inorganic anions using a 100-min injection at 2 bar pressure, introducing over 40 capillary volumes of sample. A method based on a 10-min injection allowed a 100-fold increase in sensitivity over conventional hydrodynamic injection for Br-, I-, NO3-, CrO4(2-), and MoO4(2-) with a total analysis time of 25 min. Detection limits were dependent on the injection time but were in the range 2.2-11.6 ppb for a 10-min injection time. This approach was used to determine NO3- in Antarctic ice cores where the analysis could be performed using a sample volume 100 times less than that used for ion chromatography.
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PMID:On-column ion-exchange preconcentration of inorganic anions in open tubular capillary electrochromatography with elution using transient-isotachophoretic gradients. 3. Implementation and method development. 1203 14

The results of a vertical dipole tracer experiment performed in highly fractured rocks of the Clare Valley, South Australia, are presented. The injection and withdrawal piezometers were both screened over 3 m and were separated by 6 m (midpoint to midpoint). Due to the long screen length, several fracture sets were intersected, some of which do not connect the two piezometers. Dissolved helium and bromide were injected into the dipole flow field for 75 minutes, followed by an additional 510 minutes of flushing. The breakthrough of helium was retarded relative to bromide, as was expected due to the greater aqueous diffusion coefficient of helium. Also, only -25% of the total mass injected of both tracers was recovered. Modeling of the tracer transport was accomplished using an analytical one-dimensional flow and transport model for flow through a fracture with diffusion into the matrix. The assumptions made include: streamlines connecting the injection and withdrawal point can be modeled as a dipole of equal strength, flow along each streamline is one dimensional, and there is a constant Peclet number for each streamline. In contrast to many other field tracer studies performed in fractured rock, the actual travel length between piezometers was not known. Modeling was accomplished by fitting the characteristics of the tracer breakthrough curves (BTCs), such as arrival times of the peak concentration and the center of mass. The important steps were to determine the fracture aperture (240 microm) based on the parameters that influence the rate of matrix diffusion (this controls the arrival time of the peak concentration); estimating the travel distance (11 m) by fitting the time of arrival of the centers of mass of the tracers; and estimating fracture dispersivity (0.5 m) by fitting the times that the inflection points occurred on the front and back limbs of the BTCs. This method works even though there was dilution in the withdrawal well, the amount of which can be estimated by determining the value that the modeled concentrations need to be reduced to fit the data (approximately 50%). The use of two tracers with different diffusion coefficients was not necessary, but it provides important checks in the modeling process because the apparent retardation between the two tracers is evidence of matrix diffusion and the BTCs of both tracers need to be accurately modeled by the best fit parameters.
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PMID:Analysis of a vertical dipole tracer test in highly fractured rock. 1223 67

A preliminary study of a modified microconcentric nebulizer (CEI-100, CETAC) as the sample introduction device of capillary electrophoresis inductively coupled plasma mass spectrometry (CE-ICP-MS) for the determination of monophosphate nucleotides is described. The monophosphate nucleotides studied include adenosine 5'-monophosphate (AMP), guanosine 5'-monophosphate (GMP), uridine 5'-monophosphate (UMP) and inosine 5'-monophosphate (IMP). The species studied were well separated using a 70 cm length x 75 microm id fused silica capillary while the applied voltage was set at -22 kV and a 20 mmol l(-1) ammonium citrate/citric acid buffer (pH 4.0) containing 0.1% m/v cationic polymer (hexadimethrine bromide, Polybrene) was used as the electrophoretic buffer. The electroosmotic flow was reversed by flushing the fused silica capillary with 0.2% m/v Polybrene to accelerate separation. The detection limit of various species studied was in the range of 0.036-0.054 microg P ml(-1), which corresponded to the absolute detection limit of 1.1-1.6 pg P based on the injection volume of 30 nl. We determined the concentrations of nucleotides in two IG-enriched monosodium glutamates purchased from the local market. The recovery was in the range of 100-112% for various species, and the concentrations of IMP and GMP in these samples were in the range of 0.15-0.18% m/m.
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PMID:Determination of monophosphate nucleotides by capillary electrophoresis inductively coupled plasma mass spectrometry. 1243 Jun 3


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