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Biomedical subjects

A Bewtra

Publications and source records attributed to A Bewtra.

14 recordsLinked to original sources
PubMed1999

IL-1 receptor-type expression in relation to atopy.

BACKGROUND: IL-1 has 2 receptors, type I (IL-1RI) and type II (IL-1RII), which have 2 forms each, membrane (m) and soluble (s). When IL-1 binds to mIL-1RI, the active receptor, an inflammatory response is initiated, which does not occur when IL-1 binds to mIL-1RII, the decoy receptor. Both sIL-1RI and sIL-1RII function as IL-1-mopping mechanisms. We hypothesized that the ratio of active (mIL-1RI) to inactive (mIL-1RII, sIL-1RI, and sIL-1RII) receptors is important in determining the amount of inflammation produced in allergic reactions. OBJECTIVE: Our aim was to compare the concentrations of mIL-1RI and mIL-1RII on cultured PBLs and sIL-1RI, sIL-1RII, and IL-1beta in sera and supernatants of cultured PBMCs from atopic and nonatopic subjects. METHODS: The membrane receptors, soluble receptors, and IL-1beta concentrations were measured by ELISA with specific mAbs. RESULTS: Although there was no difference in the level of serum IL-1beta between the 2 groups, PBMCs from atopic persons spontaneously secreted higher levels of IL-1beta than those from nonatopic donors (P < .05). PBLs from atopic subjects compared with those from nonatopic individuals expressed higher mIL-1RI (P < .0001) and mIL-1RII (P < .05). Levels of both the soluble receptors from both serum (P < .0001) and PBMCs (P < .05) of nonatopic donors were higher than those found in atopic donors. CONCLUSION: This augmentation of mIL-1RI concomitant with a reduction in soluble receptors may be an important contributory factor to the inflammation that occurs with allergen exposure.

Adult↗
PubMed1996

Effects of montelukast (MK-0476), a new potent cysteinyl leukotriene (LTD4) receptor antagonist, in patients with chronic asthma.

BACKGROUND: Cysteinyl leukotrienes mediate signs and symptoms of asthma. In a double-blind, placebo-controlled, crossover study, a new potent and specific cysteinyl leukotriene (LTD4) receptor antagonist, montelukast (MK-0476), was evaluated for tolerability and clinical efficacy in patients with chronic asthma (receiving and not receiving inhaled corticosteroids). METHODS: Twenty-nine nonsmoking patients with asthma (15 treated concomitantly with inhaled corticosteroids) with FEV1 percent predicted values between 50% to 80% received MK-0476, 200 mg, or placebo three times daily for 10 1/3 days (31 doses) in a random, crossover manner, after a 2-week, open, baseline period. Comparisons in FEV1 (mean percent change from baseline after the first and last dose), mean daily daytime asthma and nocturnal awakening scores, and mean daily beta-agonist use were made between treatment periods. RESULTS: Montelukast, compared with placebo, caused improvements in FEV1 (mean percentage point difference of the percentage change from baseline) 3 and 4 hours after dosing on day 1 (hour 3, 9.0%; 95% confidence interval [CI] 0.53, 18.72; hour four, 10.9%; 95% CI -0.25, 20.20) and day 11 (hour 3, 14.0%; 95% CI 0.76, 31.43; hour 4, 13.4%; 95% CI 1.24, 28.83). Reductions were observed in mean daily beta-agonist use (1.0 puff/day [95% CI -1.61, -0.26]), mean daytime symptom scores, and nocturnal awakenings over the 10 1/3 day treatment period. There were no important differences between the groups receiving and those not receiving inhaled corticosteroids. Montelukast was well tolerated with no serious clinical adverse events reported. CONCLUSIONS: In this study Montelukast, 200 mg, administered three times daily for 10 1/3 days, compared with placebo, was generally well tolerated and resulted in significant improvement in chronic asthma, irrespective of the presence of inhaled corticosteroids.

Acetates↗
PubMed1990

Effect of inhaled furosemide on the bronchial response to methacholine and cold-air hyperventilation challenges.

Inhaled furosemide has been recently demonstrated to inhibit the bronchoconstrictive effects of exercise, ultrasonically nebulized distilled water, and antigen challenge. The presumed mechanism of action of these challenges is through mast cell degranulation. We report on the effect of inhaled furosemide on cold-air hyperventilation challenge (CAHC) and methacholine challenge. We studied 10 subjects with mild to moderate asthma in a double-blind, placebo-controlled, crossover study. Inhaled furosemide did not affect FEV1 in the hour after inhalation, and there was no significant difference between placebo or furosemide on the dose of methacholine causing a 20% fall in FEV1. Our results demonstrated inhaled furosemide significantly attenuated the bronchoconstrictive effect at 6 and 9 minutes after CAHC (p less than 0.05 and 0.029, respectively) when furosemide was compared to placebo and approached significance at 12 and 15 minutes after CAHC (p = 0.052 and 0.56, respectively). Inhaled furosemide attenuates CAHC but does not effect methacholine-induced bronchoconstriction.

Administration, Inhalation↗
PubMed1988

The development of a sensitive and specific radioreceptor assay for leukotriene B4.

To establish a simple and sensitive quantitation of leukotriene B4 (LTB4), we developed a radioreceptor assay (RRA) using a highly specific [3H]leukotriene B4[( 3H]LTB4) binding to a guinea pig spleen homogenate. The assay detected LTB4 levels as low as 0.12 pmol per tube. Fifty percent inhibition of bound [3H]LTB4 was obtained by 2.5 nM of unlabeled LTB4. [3H]LTB4 competition studies indicated that 20-hydroxy-LTB4 was 8 times, 6-trans-LTB4 was 640 times and 20-carboxy-LTB4 was 1000 times less effective than LTB4. The peptide leukotrienes C4, D4 and E4 showed no effect on [3H]LTB4 binding. Recovery rates averaged 97% after ethanol extraction and evaporation of known amounts of LTB4. The intra-assay coefficients of variation for three samples were 2.4%, 7.2% and 8.4%, respectively. This assay was validated by measuring LTB4 released from human granulocytes stimulated with calcium ionophore A23187. The LTB4 level was maximal at 10 min (156.8 +/- 36.2 pmol/3 x 10(6) cells) and decreased rapidly after 15 min. This radioreceptor assay for leukotriene B4 is highly sensitive and is comparable to the reported sensitivity by radioimmunoassay. The method is simpler and less expensive than other methods such as high pressure liquid chromatography and is suitable for routine measurement of leukotriene B4.

Animals↗
PubMed1986

Segregation analysis of bronchial response to methacholine inhalation challenge in families with and without asthma.

A segregation analysis was performed on the bronchial response to a standardized methacholine inhalation challenge obtained from members of 83 families that were part of a Natural History of Asthma study population. Each bronchial response was expressed as the area under the best fitting parabolic dose-response curve. Standard methods of statistical analysis demonstrated that age, sex, and recent respiratory infection had a significant effect on the bronchial response to methacholine inhalation. Segregation analysis indicated that, although a familial component exists in the transmission of bronchial response to methacholine, the bimodal distribution of the bronchial response is not due to segregation at a single autosomal locus.

Asthma↗
PubMed1985

The effect of age on methacholine response.

Bronchial reactivity to inhaled methacholine exists in subjects with asthma but may occur in subjects with allergic rhinitis, chronic lung diseases, and during respiratory infections. In the absence of these factors, we found that age also has a significant effect on the methacholine response. One hundred forty-eight subjects, 5 to 76 years of age, were studied as normal control subjects in a natural history of asthma study. The methacholine response was measured by standard techniques. The analysis demonstrated that age had a significant effect on the methacholine response. In addition to known factors influencing the results of methacholine inhalation, young and older subjects may exhibit bronchial responses that may falsely suggest hyperreactive airway disease.

Adolescent↗
PubMed1985

Pertussis booster vaccination and immediate hypersensitivity.

Twelve non-atopic and 27 atopic preschool children were studied to determine the effect of pertussis booster vaccination on cutaneous histamine sensitivity and IgE antibody response to the naturally-occurring ragweed aeroallergen. Prick tests of histamine and ragweed extract, as well as ragweed-RAST, were performed prior to, and after, their booster injections. Ragweed skin tests and RAST were not repeated until 2 weeks after the end of ragweed pollination. None of the parameters changed significantly in either group regardless of the type of immunization administered.

Antibody Formation↗
PubMed1985

Tissue distribution and functional correlation of [3H]leukotriene C4 and [3H]leukotriene D4 binding sites in guinea-pig uterus and lung preparations.

To determine the distribution of leukotriene (LT) C4 and LTD4 receptors and functional significance of each receptor, we used [3H]LTC4 and [3H]LTD4 to measure the binding activity in various tissue homogenates and to correlate the relative ability of the LT agonists to inhibit binding with their contractile responses in guinea-pig uterine or lung parenchymal preparations. Guinea-pig brain contained the highest binding activity of 1 to 2 nM [3H] LTC4 followed by small intestine, heart, lung, kidney, uterus, etc., whereas guinea-pig lung had at least 2.7-fold greater [3H] LTD4 binding activity than any other tissues tested. In the brain and uterine homogenates, the rank order of potency for the compounds in competing with [3H]LTC4 for binding sites was LTC4 much greater than LTD4 greater than LTE4 greater than FPL-55712 = arachidonic acid. The in vitro functional study showed that the ability of the LT agonists to produce uterine contraction was in the order of LTC4 greater than LTD4 greater than LTE4, which is compatible with their relative effect for inhibition of uterine or brain [3H]LTC4 binding. In the lung homogenate, either LTC4, LTD4 or LTE4 inhibited effectively [3H]LTD4 binding and the potency order for the [3H]LTD4 competition study was LTD4 greater than LTE4 greater than LTC4 much greater than FPL-55712 greater than arachidonic acid. These LT agonists also produced lung contraction effectively and the difference among their contractile ability was not significant. We conclude that 1) there are distinct functional LTC4 and LTD4 receptors, 2) activation of the LTC4 receptor could account for the uterine contraction due to the LT agonists and 3) the lung contraction induced by LTC4, LTD4 and LTE4 is at least mediated partly by the LTD4 receptor.

Animals↗
PubMed1984

Identification of calcium antagonist receptor binding sites using (3H)nitrendipine in bovine tracheal smooth muscle membranes.

(3H)Nitrendipine binding to the bovine tracheal muscle membrane at 25 degrees C was rapid, saturable (Bmax = 14.8 +/- 3.9 fmol/mg protein) and of high affinity (Kd = 0.15 +/- 0.04 nM). The rank order of Ca2+ antagonists competing for airway (3H)nitrendipine binding was nitrendipine not equal to nisoldipine not equal to nifedipine much greater than verapamil. Cromolyn, however, neither inhibited nor increased the binding.

Animals↗
PubMed1984

Safety of nifedipine in subjects with bronchial asthma and COPD.

This prospective study was undertaken to evaluate the safety of nifedipine, a calcium channel blocking agent, on 60 subjects with asthma, chronic obstructive pulmonary disease (COPD), angina, and normal subjects. All subjects received nifedipine, 20 mg, sublingually. Spirometry was done pre-drug administration and every 20 minutes after for two hours. Parameters measured were forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and forced expiratory flow at 25 percent to 75 percent of total volume (FEF25-75%). Subjects with asthma and COPD were also given nifedipine 20 mg three times daily, orally for two weeks, and tested biweekly during this period. All bronchodilators, beta-blockers, and long acting nitrates were withheld for five half-lives of the drug prior to test day. There was no adverse effect on the pulmonary function. We found a statistically significant improvement (p less than 0.05) in FEV1 after nifedipine. There was no tachyphylaxis at the end of two weeks. Nifedipine is safe in patients with asthma and/or chronic bronchitis.

Adult↗
PubMed1976

The effect of beta adrenergic blockade on bronchial sensitivity to acetyl-beta-methacholine in normal and allergic rhinitis subjects.

The effect of propranolol inhalation on sensitivity to methacholine inhalation was studied in normal and allergic rhinitis subjects to determine whether beta adrenergic blockade alters sensitivity to mediators in nonasthmatic atopic individuals. A partial beta adrenergic blockade is suggested as being instrumental in asthma. Hay fever patients studied showed similar effects and also developed asthma for the first time.

Adolescent↗
PubMed1976

Comparison of the bronchodilating effects of SCH 1000 with isoproterenol in patients with bronchial asthma.

The effect of SCH 1000 and isoproterenol was evaluated in 10 patients with extrinsic asthma. The onset of action for the SCH 1000 dose compared to the baseline response occurred at or before 15 minutes (FEV1 and MEFR). The onset of action for the isoproterenol dose occurred at or before one minute for all three pulmonary function variables. At the 1-, 3-, 6- and 15-minute intervals the response to the isoproterenol dose was significantly greater than the response to the SCH 1000 dose for FEV1, FVC and MEFR. At 30 and 60 minutes, however, the response to SCH 1000 was progressively increasing, whereas the response to isoproterenol was decreasing. The maximum improvement in FEV1 for isoproterenol was 49% at three and six minutes, whereas for SCH 1000 was 28% at 60 minutes. In patients with chronic bronchitis or bronchial asthma SCH 1000 may be considered as a therapeutic alternative to beta-adrenergic bronchodilators and in patients who also have cardiac arrythmias or angina pectoris and are adversely affected by sympathomimetic drugs.

Acetylcholine↗