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Biomedical subjects

A K Bewtra

Publications and source records attributed to A K Bewtra.

At least 37 records · Page 2Linked to original sources
PubMed1991

Attenuation of antigen-induced bronchoconstriction in guinea pigs by a new xanthine derivative (HWA448).

We examined the effect of a new xanthine derivative, HWA448, on antigen-induced bronchoconstriction in actively sensitized guinea pigs. Guinea pigs were sensitized by intraperitoneal injection of bovine serum albumin (BSA) on two occasions, separated by 10 days. Two weeks after the second injection, the animal was placed in a two-chambered whole body plethysmograph and specific airway resistance (SRaw) was monitored for 10 min after an aerosol inhalation of BSA. HWA448 prevented the increase in SRaw after challenge (at 5 and 20 mg/kg i.p.). Aminophylline also prevented the increase in SRaw at 20 mg/kg, but not at a 5-mg/kg dose. The concentration of HWA448, which produced 50% relaxation of the tracheal rings constricted with 0.1 mM of histamine, was 49.9 microM as compared with 18.2 microM in aminophylline. HWA448 has a protective effect on antigen-induced bronchoconstriction in guinea pigs and may be a useful agent in the therapy of bronchial asthma.

Aminophylline↗
PubMed1991

Terfenadine effect on the bronchoconstriction, dermal response, and leukopenia induced by platelet-activating factor.

We have investigated the protective effect of oral terfenadine, a H1 antagonist, on the dermal and pulmonary response, and changes of circulating WBCs to injected and inhaled platelet activating factor. Nine men with mild asthma participated in a double-blind, crossover study using terfenadine, 120 mg, or placebo. Three hours after administration of study drug, pulmonary function was measured, and a PAF challenge was performed. Skin test to histamine and PAF was performed prior to study drug, and 2.5 hours after drug. Circulating WBC count was determined prior to PAF inhalation and during the PAF challenge. There was a significant improvement in pulmonary function on terfenadine. Terfenadine significantly inhibited the wheal and flare response to histamine and the flare response to injected PAF. Terfenadine did not have an effect on the change in circulating WBC count or the change in pulmonary function to inhaled PAF. These results suggest a limited role for endogenous histamine for the effects of PAF.

Asthma↗
PubMed1991

Variations in chemotaxis and chemokinesis of neutrophils of different densities from patients with allergic rhinitis.

We investigated chemotaxis and chemokinesis of neutrophils of different densities from normals and subjects with allergic rhinitis (AR). The chemotaxis of neutrophils with lower density was significantly increased compared with neutrophils with higher density in AR using fMLP (P less than .01) or PAF (P less than .05). In normal subjects, however, there was no significant difference in neutrophil chemotaxis of the two fractions. No significant difference was found in neutrophil chemokinesis of the two fractions from AR or normals. These results indicate that neutrophils with lower density from AR possess greater affinity to fMLP or PAF as compared with neutrophils with higher density and this may be relevant to the pathophysiology of AR.

Cell Movement↗
PubMed1990

Heterogeneity in chemotaxis of neutrophils with different densities.

We investigated N-formyl-Methionyl-Leucyl-Phenylalanine (fMLP)-induced chemotaxis of neutrophils with different densities. FMLP-induced (10(-8)M) chemotaxis of neutrophils with lower density were significantly reduced when compared to neutrophils with higher density (p less than 0.05). These findings imply a relationship between the neutrophil density and chemotaxis.

Adult↗
PubMed1990

Persistence of increased nonspecific bronchial reactivity in allergic children and adolescents.

Nonspecific bronchial reactivity (BR) is commonly associated with asthma. It can be found, however, in subjects with allergic rhinitis. Studies have not been done looking at changes in nonspecific BR in allergic children over time. Therefore, we report on our longitudinal study of BR in allergic children and adolescents. The reported subjects are part of a larger ongoing study in a selected population of families with asthma and of twins. Initiated in 1972, the subjects reported in this study are subjects who have had at least one follow-up visit through 1989 and did not have asthma, but had allergic histories at either their initial visit or follow-up visits. Subjects completed a questionnaire, had skin tests, determination of a serum IgE level, and a determination of nonspecific BR with a methacholine challenge. Subjects were 6 years of age or older or 21 years of age or younger at initial visit. Subjects from families with asthma (N = 76; mean age, 12.09 years; +/- 4.6 SD) and twins (N = 36; mean age, 11.81 years; +/- 3.81 SD) were followed longitudinally, and their age at follow-up visits was not restricted. In this study we observed that, of 106 subjects, 66% initially demonstrated nonspecific BR. At their first and second follow-up visits, 70.4% and 61.3% demonstrated persistence of their BR. These data demonstrate that allergic children and adolescents have increased nonspecific BR. There was not a significant loss of BR over time in the studied subjects.

Adolescent↗
PubMed1990

Alpha- and beta-adrenergic-receptor systems in bronchial asthma and in subjects without asthma: reduced mononuclear cell beta-receptors in bronchial asthma.

We assessed the adrenergic-receptor system in individuals with bronchial hyperreactivity, beta-Adrenergic receptors on mononuclear cell membranes, alpha-adrenergic receptors on platelet membranes, and the cAMP response in these cell types to different stimuli, including platelet-activating factor (PAF), were determined. Studies were assessed in 10 subjects with mild asthma, six methacholine-sensitive subjects without asthma, and 10 normal subjects. The density and affinity of beta-receptors and alpha-receptors were determined by Scatchard analysis. Our findings were that (1) subjects with asthma had a significantly lower density of beta-receptors compared to normal subjects, (2) subjects with asthma had a significantly lower cAMP response to isoproterenol stimulation compared to the two other groups, (3) in subjects without asthma. PAF decreased the basal cAMP level and significantly inhibited the response to isoproterenol stimulation, (4) there was no difference in density and affinity of platelet alpha-receptors or in platelet cAMP responses to stimulation by alpha-agonists among these three groups, and (5) neither cAMP response or beta-receptor density on mononuclear cells were significantly correlated with pulmonary-function tests (FEV/FVC times 100), sensitivity to methacholine, or cold-air inhalation. These results suggest that patients with asthma may have a lower isoproterenol cAMP response and decreased density of beta-adrenergic receptors on mononuclear cells in the absence of beta-agonist therapy. It is speculated that release of PAF and other mediators secondary to allergen exposure, even in the absence of overt attacks of asthma, may inhibit the response to endogenous or exogenous beta-adrenergic agonists.

Adolescent↗
PubMed1990

Fibronectin levels in plasma after platelet-activating factor inhalation.

We evaluated fibronectin levels in plasma and blood leukocyte counts after platelet-activating factor-acether (PAF) inhalation to examine whether PAF may cause pulmonary vascular injury. PAF inhalation challenges were performed on 5 normal subjects and 5 atopic asthmatics. Fibronectin levels in plasma were significantly increased at 5 min (342.5 +/- 36.9 micrograms/ml) after PAF challenge as compared with the baseline values of 277.1 +/- 33.0 micrograms/ml (p less than 0.024). Total white blood cell and neutrophil counts were significantly decreased 5 min after PAF inhalation (WBC from 5,360 +/- 460 to 4,260 +/- 380/mm3, p less than 0.028; neutrophils from 3,113 +/- 441 to 2,214 +/- 344/mm3, p less than 0.043). Our study shows that plasma fibronectin levels transiently increase and that peripheral total WBC counts decrease after PAF inhalation. Elevated fibronectin levels may provide evidence of pulmonary vascular injury due to neutrophils which might be primed and recruited to pulmonary circulation by PAF.

Administration, Inhalation↗
PubMed1990

Elevation of neutrophil chemotactic activity in the human serum and the decreased number of neutrophils after platelet-activating factor inhalation.

We previously reported a significant decrease in neutrophils at 5 min and an increased number of neutrophils at 15 min after PAF-acether inhalation. To investigate the mechanism, we measured the neutrophil chemotactic activity of the sera. Neutrophil chemotactic activity (NCA) of the serum at 5 min was greater than at baseline (p less than 0.01) or at 15 min (p less than 0.05). Furthermore, we investigated the correlation between the change in NCA and decreased number of neutrophils. A significant correlation was found between these two at 5 min (r = 0.751, p less than 0.05). These data suggest that an elevation of NCA may play an important role in the decrease of circulating neutrophils after PAF-acether inhalation.

Administration, Inhalation↗
PubMed1990

Density distribution and density conversion of neutrophils in allergic subjects.

We investigated the density distribution of neutrophils in peripheral blood of allergic subjects. We divided neutrophils into four groups: fraction 1 (density greater than 1.085), fraction 2 (1.081 less than density less than or equal to 1.085), fraction 3 (1.077 less than density less than or equal to 1.081) and fraction 4 (density less than or equal to 1.077). The percentage of neutrophils in fraction 2 in allergic rhinitis (AR) subjects or asthmatics was lower than that in normals (p less than 0.01). The percentage of neutrophils in fraction 3 and fraction 4 from AR or asthmatics was greater than that in normals (fraction 3, p less than 0.01; fraction 4, p less than 0.05). In neutrophils from AR subjects (fraction 3), chemotaxis to N-formyl-methionyl-leucyl-phenylalanine or platelet-activating factor (PAF) was enhanced compared to fraction 2. PAF (10(-7) M) changed the density of neutrophils (p less than 0.01), which were inhibited by WEB 2086 (p less than 0.05). Furthermore, granulocyte-macrophage colony-stimulating factor changed the density of neutrophils (p less than 0.01). These findings suggest that biological agents may activate neutrophils and convert their density resulting in neutrophils with lower density in allergic subjects.

Asthma↗
PubMed1990

The presence of airway reactivity before the development of asthma.

Exaggerated airway reactivity is an essential component of the current asthmatic. It is not clear, however, if airway reactivity is genetically determined or acquired. To examine the possibility that increased bronchial reactivity exists prior to the development of asthma, we report on 20 subjects who were studied before and after the onset of clinical asthma. Subjects were part of a larger on-going study of the Natural History of Asthma. Thirteen subjects indicated by their answers to the National Heart, Lung, and Blood Institute respiratory questionnaire that they were not asthmatic at their initial visit. Seven subjects had pulmonary symptoms on their initial visit, but had not been diagnosed as asthmatic. Bronchial reactivity was assessed using a standardized methacholine challenge. For the 20 subjects, there was a mean interval of 3.5 yr between the initial visit and the diagnosis of asthma. Ten of 13 nonasthmatic subjects had moderate or strongly positive responses (208 breath units or less) to methacholine prior to onset of asthma. These 13 subjects were compared to age- and sex-matched controls, from both asthmatic and nonasthmatic families, who had not become asthmatic. There was a difference in bronchial responses at the initial visit between the 13 study subjects and their control subjects from nonasthmatic families, but not between the subjects and their controls from asthmatic families. Five of 7 subjects with pulmonary symptoms had responses of 100 breath units or less. Overall, 19 of 20 subjects had strongly positive responses to methacholine after the diagnosis of asthma was established. The results show that enhanced airway reactivity usually precedes the development of asthma, which could support a genetic basis for it.

Adolescent↗
PubMed1990

Association of MS Pi phenotype with airway hyperresponsiveness.

Asthmatic families (AFs) and normal families (NFs) were studied to determine the relationship between bronchial hyperresponsiveness and alpha 1-antitrypsin protease inhibitor phenotype. We studied IgE levels, skin test scores, and methacholine sensitivity. In both the AF and NF groups, the subjects with the MS phenotype had significantly greater methacholine-induced bronchial hyperresponsiveness sensitivity than the MM and MZ subjects. These findings suggest that the S allele may be associated with bronchial hyperresponsiveness.

Adolescent↗
PubMed1990

Effect of PAF-acether inhalation on nonspecific bronchial reactivity and adrenergic response in normal and asthmatic subjects.

Bronchial hyperreactivity, although recognized as a hallmark of asthma, is not totally understood. Mast cell-derived mediators, including histamine, have been shown to cause immediate bronchoconstriction, but until recently, no single mediator has been shown to induce prolonged changes in airway reactivity. Recent reports indicate PAF-acether (PAF) can induce increased nonspecific bronchial reactivity in normal subjects but not in asthmatics. We sought to elucidate the role of PAF in airway hyperreactivity by comparing the effect of inhaled PAF on methacholine and isoproterenol airway responsiveness in six nonasthmatic and six asthmatic subjects. Neither nonspecific airway reactivity nor isoproterenol responsiveness was changed following PAF inhalation in the nonasthmatic subjects in the six days following PAF. Asthmatics had increased airway responsiveness to methacholine at two hours post-PAF, which did not persist. Responsiveness to isoproterenol did not change in the asthmatic subjects. Additional evaluation of the role of PAF in causing changes in airway reactivity is warranted.

Adult↗
PubMed1990

A controlled, double-blind study of the effect of quazolast on nasal challenge with ragweed antigen.

Quazolast is a potent mediator release inhibitor as determined by in vitro and in vivo testing. A placebo-controlled, double-blind, two-way crossover study compared the safety and efficacy of Quazolast, 400 mg bid orally, with placebo in 23 subjects with ragweed (RW) allergy, out of season. Subjects were assigned to two 7-day treatments in a random sequence with an 8-day washout. Subjects were challenged on days 1 and 7 of each trial with serial dilutions (10, 100, 1000, 1350, and 2700 PNU/0.135 mL) of RW, using metered pump spray bottles, (two sprays delivered 0.135 mL), preceded by saline control. Efficacy evaluation consisted of nasal flow rates measured by rhinomanometry, sneeze counts, nasal itchiness scores, and weight of nasal secretions during challenges. During Quazolast treatment, subjects had significantly lower (P less than .05) mean percent decreases in nasal flow rate at 1350 and 2700 PNU. Nasal itchiness scores were significantly lower (P less than .05) during Quazolast treatment than at placebo at 1000, 1350, and 2700 PNU. Although sneeze counts were lower during treatment with Quazolast than with placebo, the results did not reach statistical significance. No significant improvement was seen in the weight of nasal secretions. Adverse experiences, clinical laboratory results, and physical examinations were unremarkable, posttreatment. Quazolast was superior to placebo in protecting against nasal congestion and nasal itchiness after ragweed nasal challenge.

Adult↗
PubMed1989

Comparison of ultrasonically nebulized distilled water and cold-air hyperventilation challenges in asthmatic patients.

Cold-air hyperventilation (CAHC) and ultrasonically nebulized distilled water (UNDW) challenges were compared in 11 asthmatic patients who were moderately sensitive to methacholine. The challenges were performed on two separate days within one week of each other. Baseline FEV1 on each test day was greater than 70 percent of predicted. Ten of 11 subjects' FEV1 decreased at least 15 percent, and nine of 11 decreased at least 20 percent during the UNDW. Ten of 11 subjects' FEV1 decreased at least 10 percent, and eight of 11 decreased at least 15 percent during the CAHC. Using a Spearman rank coefficient, the results of the CAHC and UNDW were compared; the best correlation between the various CAHC and UNDW measurements equaled only 0.51. The correlation between UNDW and CAHC suggests that the mechanism of action of each challenge may be different.

Adult↗
PubMed1989

Effect of platelet-activating factor inhalation on nonspecific bronchial reactivity in man.

Bronchial hyperactivity is a recognized hallmark of asthma, characterized by an exaggerated bronchial response to numerous mediators, including histamine. It is also well recognized that bronchial hyperresponsiveness is increased following allergen exposure, although no particular mediator has been shown to induce this response. The recent observation that PAF can induce increased nonspecific bronchial reactivity in normal subjects emphasizes its importance as an inflammatory mediator. In this report we sought to further elucidate the role of PAF in airway hyperreactivity by comparing the effect of PAF on methacholine-induced airway responsiveness in six non-asthmatic subjects. Nonspecific airway responsiveness was not significantly increased following PAF inhalation at 6 hours nor was it increased at 1, 2, 7, or 14 days. Further elucidation of the potential role of PAF in explaining changes in airway reactivity is necessary.

Adult↗