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)

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

Fresh cod fillets (Gadus morhua) were sprayed with a 10% acetate buffer (pH 5.6), packed with an industrial gas-flushing packaging machine under modified atmospheres (50% CO2--45% O2--5% N2, 2 cm3/1 g gas/product ratio) and stored at 7 degrees C for 12 days. Control cod fillets were directly packed and stored under the same conditions. A reduction of the aerobic plate counts was observed immediately after the cod fillets had been sprayed. During storage under modified atmospheres, there was complete inhibition of H2S-producing bacteria and Enterobacteriaceae in the treated cod fillets. Production of total volatile bases and trimethylamine (TMA) was inhibited in treated fillets for 10 days' storage under modified atmospheres. Inhibition of TMA production can be attributed to growth inhibition of H2S-producing bacteria, inhibition of the trimethylamine oxide (TMAO)-dependent metabolism of TMAO-reducing bacteria and the stable pH during storage. The shelf-life, at 7 degrees C, of treated cod fillets, based on cooked flavour score, was almost 12 days, ca 8 days more than shelf-life of the control fillets.
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PMID:Shelf-life extension of cod fillets with an acetate buffer spray prior to packaging under modified atmospheres. 1079 51

A novel method is reported for quantifying protein adsorption to naked silica tubings and for assessing the efficacy of polymers added to the background electrolyte as dynamic wall modifiers. It consisted 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 was then affected by electrophoretically driving sodium dodecyl sulphate micelles into the capillary from the cathodic reservoir: the peak of eluted material is quantified by using a dual laser beam instrument able to read the fluorescein isothiocyanate-derivatized myoglobin at 520 nm and the internal standard (sulphorodamine) at 630 nm. Four polymers have been assessed as potential quenchers of interaction of proteins with the silica wall: hydroxypropylmethylcellulose (HPMC, Mr = 1000000), hydroxyethylcellulose (HEC, Mr = 27000), poly(vinyl alcohol) (PVA, Mr = 49000) and short-chain poly(dimethylacrylamide) [poly(DMA)] (average Mr ca. 150000). HPMC, poly(DMA) and PVA were effective in the 0.005 to 0.02% (w/v) range, whereas HEC was active in the 0.1 to 0.8% concentration range. All polymers, however, except for poly(DMA), exhibited a rather poor performance in suppressing protein interactions with the siliceous surface, and could inhibit adsorption only by, at most, 50% (contrary to oligoamines which can quench such interactions by >90%). It is hypothesized that dynamically adsorbed polymers leave ample regions of the capillary inner surface unmasked, thus allowing strong interactions of proteins with the silica wall. This is also confirmed by the modest reduction of electroendoosmotic flow upon polymer adsorption, as compared with an untreated silica surface. Although poly(DMA) can inhibit protein adsorption by as much as 85%, its hydrophobic nature could in turn provide more adsorption sites for less hydrophilic proteins than myoglobin.
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PMID:Quantitative studies on the adsorption of proteins to the bare silica wall in capillary electrophoresis. II. Effects of adsorbed, neutral polymers on quenching the interaction. 1081 68

Hypertension is an important risk factor for erectile dysfunction (ED). Consequently, there is a high coincidence between hypertension and ED. Oral sildenafil (Viagra) is an effective treatment for ED in patients with treated or untreated hypertension. The most common adverse events of sildenafil (headache, flushing, hypotension) result from its moderate vasodilating properties. The concomitant use of sildenafil and organic nitrates is contraindicated because it may lead to a potentiation of the decreases in blood pressure and thus cause life-threatening hypotension. In contrast, the concomitant use of sildenafil and different classes of antihypertensive agents (beta-blockers, alpha-blockers, diuretics, ACE inhibitors, calcium antagonists) may lead to additive but not to potentiating blood pressure decreases. Thus, this combination is unlikely to cause clinically significant hypotension or an increased incidence of adverse events. Sildenafil is an effective and well-tolerated treatment for ED in patients taking concomitant antihypertensive medication, including those on multidrug regimens.
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PMID:[Interaction between sildenafil and antihypertensive drugs: what is evidence-based?]. 1159 59

Glatiramer acetate, formerly known as copolymer 1, is a mixture of synthetic polypeptides composed of four amino acids. Glatiramer acetate has been shown to be effective in preventing and suppressing experimental autoimmune encephalitis (EAE), the animal model of multiple sclerosis (MS). Therefore it was tested in several clinical studies, where it was found to slow the progression of disability and to reduce the relapse rate and the magnetic resonance imaging (MRI)-defined disease activity and burden in relapsing-remitting MS. As a daily standard dose, 20mg of glatiramer acetate is injected subcutaneously. After injection, glatiramer acetate undergoes rapid degradation to amino acids and shorter peptides; so it is not possible to measure any systemic plasma concentrations or excretion rates. Two major mechanisms have been proposed to explain the effects of glatiramer acetate in EAE and MS: the induction of glatiramer acetate-reactive T helper 2 (Th2)-like regulatory suppressive cells and the interference with T cell activation as an altered peptide ligand. The most common adverse effects were mild injection site reactions (erythema, inflammation and induration). The most remarkable adverse event is the acute and transient immediate postinjection reaction manifested by flushing, chest tightness, palpitations and dyspnoea. Other reported adverse effects are transient chest pain and lymphadenopathy. Antibodies to glatiramer acetate induced during treatment do not interfere with its clinical effects. In several controlled clinical studies, glatiramer acetate has been shown to provide consistent, reproducible clinical benefits in the target population of patients with relapsing-remitting MS. The safety profile and risk-benefit ratio are excellent. Overall, glatiramer acetate is very well tolerated and has an excellent risk-benefit profile in patients with relapsing-remitting MS.
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PMID:Risk-benefit assessment of glatiramer acetate in multiple sclerosis. 1173 54

Alcoholic beverages are causally related to cancer of the oral cavity, pharynx, larynx and esophagus. Ethanol is oxidized to acetaldehyde and then to acetate by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), both of which have genetic polymorphisms. A review of case-control studies of the effects of ALDH2, ADH2 and ADH3 genotypes shows consistently positive associations between inactive heterozygous ALDH2 and the less-active ADH2 genotypes and the risk for esophageal cancer in East Asian heavy drinkers and this enzyme-related vulnerability may extend to light-to-moderate drinkers. Some studies suggest similar associations with the risk for head and neck cancer in moderate-to-heavy-drinking Japanese. An established carcinogen in experimental animals, acetaldehyde can interact with human DNA. ALDH2-associated cancer susceptibility fits into a scenario in which acetaldehyde plays a critical role in the development of human cancer. Alcohol flushing and drinking behavior may partly explain this carcinogenic effect in carriers of less-active ADH2 genotypes. Whether the ADH3 genotype influences head and neck cancer risk in Western nations is controversial. Professional and public education about risky conditions connected to the ALDH2 and ADH2 genotypes and environmental factors is important in a new strategic approach to the prevention of alcohol-related cancers in East Asians. The use of simple tests to identify inactive ALDH2 on the basis of alcohol flushing responses could benefit many people, by helping them to identify their own cancer risks. Such testing could also help clinicians diagnose esophageal cancer earlier, through the use of endoscopic screening in the high-risk population.
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PMID:Genetic polymorphisms of alcohol and aldehyde dehydrogenases and risk for esophageal and head and neck cancers. 1267 87

Elevated blood pressure is a risk factor for a variety of cardiovascular disorders, including coronary heart disease, peripheral vascular disease, cardiac failure and cerebrovascular disease. The prevailing view is that an elevated systolic rather than diastolic blood pressure is the major contributor in mortality and morbidity attributed to cardiovascular disorders. Isolated high systolic blood pressure, especially in the elderly, is a major risk factor and should undoubtedly be a target for drug treatment. In the general population, systolic and diastolic blood pressure are highly correlated, and thus it is difficult to dissociate the effects of these two components of the blood pressure and specifically ascribe cardiovascular risk factors to just elevated systolic blood pressure. Therefore, the goal in therapy of an individual with hypertension must be to reduce elevated systolic and diastolic blood pressure in order to reduce mortality and morbidity. ACE and neutral peptidase inhibitors are a new class of drugs that may be beneficial in the treatment of patients with hypertension and heart failure. They may also be useful in the treatment of diabetic patients with hypertension and/or heart failure. Drugs of this class are dual inhibitors of ACE and neutral endopeptidase, and are capable of affecting vascular tone and fluid balance. They are capable of producing vasodilatation by virtue of inhibiting the production of angiotensin II, degradation of natriuretic peptides and bradykinin. They also appear to promote natriuresis and diuresis by amplifying the actions of natriuretic peptidase and reducing aldosterone effects. In addition, they should also attenuate trophogenic actions of the renin angiotensin system and the sympathetic nervous system. Omapatrilat is one drug that appears to be at the advanced stages of clinical development. This drug has been shown to be quite effective in the treatment of hypertension. Evidence also seems to indicate that treatment with omapatrilat results in a higher tendency towards preventing death and worsening heart failure when compared with treatment with a pure ACE inhibitor in patients with advanced heart failure. Overall safety with omapatrilat appears to be good, but like other ACE inhibitors the incidence of cough is higher when compared with placebo. Other common adverse effects noted are headaches, facial flushing/warm sensation, dizziness, nausea and dyspnoea. Of greater concern is the occurrence of angio-oedema, the true incidence of which remains to be fully established as part of the published medical literature.
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PMID:Dual ACE and neutral endopeptidase inhibitors: novel therapy for patients with cardiovascular disorders. 1501 94

The determination of methanogenic activity with a pH-stat titration bioassay is evaluated utilising a mathematical model of this system. For given kinetic parameters and experimental conditions the model calculates the development of titrant flow and acetate concentration during experiments. Simulations of experiments under various conditions are compared. They show that the original method inherently causes a strong drift of acetate concentration during the experiments and a misestimation of methanogenic activity. As a solution to these disadvantages the addition of sodium hydroxide to the titrant and a careful control of pH during flushing the reactor with gas prior to the experiment are recommended. In this way a better constancy of acetate concentration and a more accurate determination of methanogenic activity should be achievable. The accuracy of this method is limited by the stability of pH-electrode calibration parameters.
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PMID:Factors affecting constancy of acetate concentration and correct determination of methanogenic activity in pH-stat experiments. 1464 Feb 7

The fixed-dose combination of enalapril 10mg with nitrendipine 20mg combines an ACE inhibitor with a calcium channel antagonist (CCA) and is indicated for the treatment of patients with mild-to-moderate hypertension whose blood pressure (BP) is inadequately controlled with enalapril or nitrendipine monotherapy. In randomised, double-blind clinical trials, enalapril/nitrendipine 10/20 mg/day was significantly more effective than its individual components in reducing diastolic BP (DBP) in patients with mild-to-moderate hypertension inadequately controlled with enalapril 10 mg/day or nitrendipine 20 mg/day. The fixed-dose combination was similar in efficacy at reducing DBP to amlodipine 10 mg/day in patients who failed to achieve BP control with amlodipine 5 mg/day, and to losartan/hydrochlorothiazide 50/12.5 mg/day in patients who received the combinations as first-line therapy. Enalapril/nitrendipine 10/20 mg produced a consistent antihypertensive effect that persisted for the entire 24-hour dosage interval as shown by ambulatory BP monitoring. Enalapril/nitrendipine 10/20 mg was well tolerated in clinical trials where it was administered to patients with mild-to-moderate hypertension for up to 12 weeks. The adverse events were those expected of ACE inhibitors and CCAs and included cough, headache and flushing. Evidence from clinical trials, including a pooled analysis, suggests that the incidence of oedema may be significantly lower with the fixed-dose combination than with CCA monotherapy. In conclusion, enalapril/nitrendipine 10/20 mg is a well tolerated fixed-dose combination of two established antihypertensive agents administered once daily that effectively lowers BP throughout the 24-hour dosage interval. Importantly, the fixed-dose combination may have a lower incidence of oedema than CCA monotherapy. Enalapril/nitrendipine 10/20 mg provides an additional treatment option for patients with mild-to-moderate hypertension for whom combination therapy is appropriate.
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PMID:Fixed-dose combination enalapril/nitrendipine: a review of its use in mild-to-moderate hypertension. 1513 92

All currently available antihypertensive drugs can cause adverse drug reactions. Potential adverse drug reactions should already be taken into account when a new antihypertensive regimen is started. It is furthermore important to ask at follow-up visits specifically about common adverse reactions. The aims of this article are therefore to shortly summarise common and typical adverse drug reactions of antihypertensives. All antihypertensives may cause dizziness, hypotension, allergies, rashes, gastrointestinal complaints and dry mouth. Thiazide diuretics furthermore may cause electrolyte disturbances, dehydration and hyperuricemia, betablockers may cause bronchospasm, bradycardia, cold extremities and sleep disturbances and calcium antagonists may cause flushing, ankle oedema and gingival hyperplasia. Concerning potential lethal adverse drug reactions, it is important to know that ACE inhibitors and angiotensin receptor antagonists are contraindicated in all patients with a history of angioedema. However, angiotensin receptor antagonists are well-suited alternatives for patients with ACE inhibitor-induced cough or hypogeusia. Rare adverse drug reactions are commonly recognised only after drug approval based on spontaneous reporting. This demonstrates the importance of considering medications as potential causes of new complaints and symptoms and to reports such suspected adverse drug reactions to the national pharmacovigilance centres. Only the local or international accumulation of comparable spontaneous reports allows the drug regulation agencies to recognise new and unexpected adverse drug reactions early and to initiate appropriate measures.
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PMID:[Antihypertensives--which adverse drug reactions are clinically relevant?]. 1519 39


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