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Biomedical subjects

A Bara

Publications and source records attributed to A Bara.

At least 19 recordsLinked to original sources
PubMed2006

Oral xanthines as maintenance treatment for asthma in children.

BACKGROUND: Xanthines have been used in the treatment of asthma as a bronchodilator, though they may also have anti-inflammatory effects. The current role of xanthines in the long-term treatment of childhood asthma needs to be reassessed. OBJECTIVES: To determine the efficacy of xanthines (e.g. theophylline) in the maintenance treatment of paediatric asthma. SEARCH STRATEGY: A search of the Cochrane Airways Group Specialised Register was undertaken with predefined search terms. Searches are current to May 2005. SELECTION CRITERIA: Randomised controlled trials,lasting at least four weeks comparing a xanthine with placebo, regular short-acting beta-agonist (SABA), inhaled corticosteroids (ICS), cromoglycate (SCG), ketotifen (KET) or leukotriene antagonist, in children with diagnosed with chronic asthma between 18 months and 18 years old. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected each study for inclusion in the review and extracted data. Primary outcome was percentage of symptom-free days. MAIN RESULTS: Thirty-four studies (2734 participants) of adequate quality were included. Xanthine versus placebo (17 studies): The proportion of symptom free days was larger with xanthine compared with placebo (7.97% [95% CI 3.41, 12.53]). Rescue medication usage was lower with xanthine, with no significant difference in symptom scores or hospitalisations. FEV1 , and PEF were better with xanthine. Xanthine was associated with non - specific side-effects. Data from behavioural scores were inconclusive. Xanthine versus ICS (four studies) : Exacerbations were less frequent with ICS, but no significant difference on lung function was observed. Individual studies reported significant improvements in symptom measures in favour of steroids, and one study reported a difference in growth rate in favour of xanthine. No difference was observed for study withdrawal or tremor. Xanthine was associated with more frequent headache and nausea. Xanthine versus regular SABA (10 studies): No significant difference in symptoms, rescue medication usage and spirometry. Individual studies reported improvement in PEF with beta-agonist. Beta-agonist treatment led to fewer hospitalisations and headaches. Xanthine was associated with less tremor. Xanthine versus SCG (six studies ): No significant difference in symptoms, exacerbations and rescue medication. Sodium cromoglycate was associated with fewer gastro-intestinal side-effects than xanthine. Xanthine versus KET (one study): No statistical tests of significance between xanthine and ketotifen were reported. Xanthine + ICS versus placebo + same dose ICS (three studies) : Results were conflicting due to clinical/methodological differences, and could not be aggregated. AUTHORS' CONCLUSIONS: Xanthines as first-line preventer alleviate symptoms and reduce requirement for rescue medication in children with mild to moderate asthma. When compared with ICS they were less effective in preventing exacerbations. Xanthines had similar efficacy as single preventative agent compared with regular SABA and SCG. Evidence on AEs (adverse effects) was equivocal: there was evidence for increased AEs overall, but no evidence that any specific AE (including effects on behaviour and attention) occurred more frequently than with placebo. There is insufficient evidence from available studies to make firm conclusions about the effectiveness of xanthines as add-on preventative treatment to ICS, and there are no published paediatric studies comparing xanthines with alternatives in this role. Our data suggest that xanthines are only suitable as first-line preventative asthma therapy in children when ICS are not available. They may have a role as add-on therapy in more severe asthma not controlled by ICS, but further studies are needed to examine this, and to define the risk-benefit ratio compared with other agents.

Aminophylline↗
PubMed2005

Anticholinergic drugs for wheeze in children under the age of two years.

BACKGROUND: Wheeze in infancy and early childhood is common and appears to be increasing though the magnitude of any increase is unclear. Most wheezing episodes in infancy are precipitated by respiratory viral infections. Treatment of very young children with wheeze remains controversial. Anti-cholinergics are often prescribed but practice varies widely and the efficacy of this form of therapy remains the subject for debate. OBJECTIVES: Wheeze in infancy and early childhood is common and appears to be increasing. Most wheezing episodes in infancy are a result of viral infection. Bronchodilator medications such as beta2-agonists and anti-cholinergic agents are often used to relieve symptoms, but patterns of use vary. The objective of this review was to assess the effects of anti-cholinergic therapy in the treatment of wheezing infants. This is a second update of this review. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register of trials and the reference lists of articles. We contacted researchers in the field and industry sources. Searches were current as of June 2004. SELECTION CRITERIA: Randomised trials that compared anti-cholinergic therapy with placebo or beta2-agonists in wheezing children under two years of age. Children with acute bronchiolitis and chronic lung disease were excluded. DATA COLLECTION AND ANALYSIS: Eligibility for inclusion and quality of trials were assessed independently by two reviewers. MAIN RESULTS: Six trials involving 321 infants in three different settings were included. Compared with beta2-agonist alone, the combination of ipratropium bromide and beta2-agonist was associated with a reduced need for additional treatment, but no difference was seen in treatment response, respiratory rate or oxygen saturation improvement in the emergency department. There was no significant difference in length of hospital stay between ipratropium bromide and placebo; or between ipratropium bromide and beta2-agonist combined compared with beta2-agonist alone. However, combined ipratropium bromide and beta2-agonist compared to placebo showed significantly improved clinical scores at 24 hours. Parents preferred ipratropium bromide over nebulised water or placebo for relief of their children's symptoms at home. A further updated search conducted in June 2004 did not yield any new studies. AUTHORS' CONCLUSIONS: There is not enough evidence to support the uncritical use of anti-cholinergic therapy for wheezing infants, although parents using it at home were able to identify benefits.

Adrenergic Antagonists↗
PubMed2004

Azathioprine as an oral corticosteroid sparing agent for asthma.

BACKGROUND: For the majority of chronic asthmatics, symptoms are best controlled by using inhaled steroids. However, for a small group of asthmatics, symptoms can only be controlled by high doses of oral steroids. Continuous use of oral steroid is associated with severe side-effects, but it has been suggested that azathioprine, an immunosuppressive anti-metabolite, often used to reduce the immune response in chronic active hepatitis and severe rheumatoid arthritis, could be useful as an oral steroid sparing agent. There is a need to systematically evaluate the evidence regarding its use to reduce or eliminate oral corticosteroid usage. OBJECTIVES: The objective of this review is to assess the efficacy of adding azathioprine in patients with stable asthma who are dependent on oral corticosteroids with the intention of eventually minimizing or eliminating the use of these steroids. SEARCH STRATEGY: Searches of the Cochrane Airways Group asthma and wheeze trials register were undertaken with predefined search terms. Searches were current as of February 2003 SELECTION CRITERIA: Only studies with a randomised placebo-controlled design met the inclusion criteria for the review. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed studies for suitability for inclusion in the review. Data were extracted and entered into RevMan 4.2.2. MAIN RESULTS: Two small trials recruiting 23 participants met the inclusion criteria for the review. Participants may have been suffering from comorbid lung disease. No data on oral steroid consumption were reported. No significant differences were observed in the studies for FEV(1), FVC, PaO(2) and symptoms. One study reported a statistically significant difference in SGaw, but the clinical importance of this is uncertain. Due to concerns over the small sample sizes and methodological shortcomings in terms of inadequate washout in one study, and methods used in outcome assessment for both studies, the findings of the studies are not generalisable to the issue of steroid tapering. REVIEWER'S CONCLUSIONS: Currently there is a clear lack of evidence to support the use of azathioprine in the treatment of chronic asthma as a steroid sparing-agent. Large, long-term studies with pre-defined steroid reducing protocols are required before recommendations for clinical practice can be made.

Administration, Inhalation↗
PubMed2003

Colchicine as an oral corticosteroid sparing agent for asthma.

BACKGROUND: Oral corticosteroids are used as a treatment for asthma, but they are often associated with serious side effects. Colchicine is an anti-inflammatory, immuno modulating agent, which could potentially have a beneficial effect in the treatment of asthma as well as act as a steroid-sparing agent. OBJECTIVES: To determine the effectiveness of colchicine as an oral corticosteroid sparing agent for in the treatment of chronic asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register (November 2002), SIGLE (1980 to 2001) and reference lists of potential articles. We also contacted researchers in the field. SELECTION CRITERIA: Randomised controlled trials investigating the addition of colchicine compared to placebo in stable steroid dependent asthmatics. DATA COLLECTION AND ANALYSIS: No trials were found that met the inclusion criteria. MAIN RESULTS: We were unable to perform any meta-analyses. Two small studies have assessed the efficacy of colchicine subsequent to inhaled steroid withdrawal and as a tapering agent in inhaled steroids. Both studies failed to detect a significant difference between colchicine and placebo. REVIEWER'S CONCLUSIONS: No relevant trials have been published, so there is no evidence to indicate that colchicine is beneficial or otherwise in the management of steroid-dependent asthmatic patients. There is a need for well designed randomised controlled trials to be performed.

Adrenal Cortex Hormones↗
PubMed2003

Chloroquine as a steroid sparing agent for asthma.

BACKGROUND: For the majority of chronic asthmatics, symptoms are best controlled using inhaled steroids, but for a small group of asthma sufferers, symptoms cannot be controlled using inhaled steroids and instead continuous use of high dosage oral steroids (corticosteroids) are required. However, using high dosage oral steroids for long periods is associated with severe side effects. Steroid-sparing treatments have been sought and one of these is chloroquine. Chloroquine is an anti-inflammatory agent, also used in the treatment of malarial infection and as a second-line therapy in the treatment of rheumatoid arthritis, sarcoidosis and systemic lupus erythematosus. All these diseases are associated with immunologic abnormalities hence the speculation that chloroquine might be used to control severe, poorly controlled bronchial asthma. There is a need to systematically evaluate the evidence regarding its use to reduce or eliminate oral corticosteroid use in asthma. OBJECTIVES: The object of this review was to assess the efficacy of adding chloroquine to oral corticosteroids in patients with chronic asthma who are dependent on oral corticosteroids with the intention of minimising or eventually eliminating the use of these oral steroids. SEARCH STRATEGY: Searches of the Cochrane Airways Group asthma and wheeze trials register were undertaken with predefined search terms in February 2003. SELECTION CRITERIA: Only studies with a randomised placebo-controlled design met the inclusion criteria for the review. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed studies for suitable in the review. Data were extracted and entered into RevMan 4.2.2 MAIN RESULTS: One small study was included in the review. No significant findings were reported. REVIEWER'S CONCLUSIONS: There is insufficient evidence to support the use of chloroquine as an oral steroid-sparing agent in chronic asthma. Further trials should optimise oral steroid dosage before addition of the steroid-sparing agent.

Adrenal Cortex Hormones↗
PubMed2002

Short acting beta agonists for recurrent wheeze in children under 2 years of age.

BACKGROUND: Wheeze is a common symptom in infancy and is a common cause for both primary care consultations and hospital admission. Beta2-adrenoceptor agonists (b2-agonists) are the most frequently used as bronchodilator but their efficacy is questionable. OBJECTIVES: To determine the effectiveness of b2-agonist for the treatment of infants with recurrent and persistent wheeze. SEARCH STRATEGY: Relevant trials were identified using the Cochrane Airways Group database (CENTRAL), Medline and Pubmed. The database search used the following terms: Wheeze or asthma and Infant or Child and Short acting beta-agonist or Salbutamol (variants), Albuterol, Terbutaline (variants), Orciprenaline, Fenoterol SELECTION CRITERIA: Randomised controlled trials comparing the effect of b2-agonist against placebo in children under 2 years of age who had had two or more previous episodes of wheeze, not related to another form of chronic lung disease. DATA COLLECTION AND ANALYSIS: Eight studies met the criteria for inclusion in this meta-analysis. The studies investigated patients in three settings: at home (3 studies), in hospital (2 studies) and in the pulmonary function laboratory (3 studies). The main outcome measure was change in respiratory rate except for community based studies where symptom scores were used. MAIN RESULTS: The studies were markedly heterogeneous and between study comparisons were limited. Improvement in respiratory rate, symptom score and oxygen saturation were noted in one study in the emergency department following two salbutamol nebulisers but this had no impact on hospital admission. There was a reduction in bronchial reactivity following salbutamol. There was no significant benefit from taking regular inhaled salbutamol on symptom scores recorded at home. REVIEWER'S CONCLUSIONS: There is no clear benefit of using b2-agonists in the management of recurrent wheeze in the first two years of life although there is conflicting evidence. At present, further studies should only be performed if the patient group can be clearly defined and there is a suitable outcome parameter capable of measuring a response.

Adrenergic beta-Agonists↗
PubMed2002

Dapsone as an oral corticosteroid sparing agent for asthma.

BACKGROUND: Oral corticosteroids are used as a treatment for asthma, however they are often associated with serious side effects. Dapsone is a sulfone with anti-inflammatory properties, therefore it may have a beneficial effect in the treatment of asthma and act as a corticosteroid-sparing agent. OBJECTIVES: The objective of this review is to assess the safety and efficacy of adding dapsone to oral corticosteroids in adults with stable asthma who are dependent on oral corticosteroids with the intention of eventually minimizing or eliminating the use of these steroids. SEARCH STRATEGY: The Cochrane Airways group trials register and reference lists of potential articles were searched. SELECTION CRITERIA: Randomised controlled trials investigating the addition of dapsone compared to placebo in stable corticosteroid dependent asthmatics. DATA COLLECTION AND ANALYSIS: No trials were found that met the selection criteria. MAIN RESULTS: No meta-analyses could be performed. REVIEWER'S CONCLUSIONS: No randomised controlled trials have been published, so there is no reliable evidence to show whether dapsone is beneficial or otherwise in the management of steroid-dependent asthmatic patients. There is a need for well designed randomised controlled trials to be performed. These must be carried out double-blind, since oral corticosteroid reduction requires a judgement on the part of the physician, who may be open to bias if the treatment allocation is known.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Humidity control for chronic asthma.

BACKGROUND: Humidity control measures in the home environment of patients with asthma have been recommended, however there is no consensus about the usefulness of these measures. OBJECTIVES: To study the effect of dehumidification of the home environment on asthma control. SEARCH STRATEGY: A search of the clinical trials registers of the Cochrane Collaboration and Cochrane Airways Group using search terms for asthma and [humid* OR water vapour OR water vapor* OR water-vapour* OR water-vapor*]. SELECTION CRITERIA: Randomized controlled trials on the use of humidity control measures in the home environment of patients with asthma were evaluated for inclusion. Only one trial could be included. DATA COLLECTION AND ANALYSIS: Data was extracted using a predesigned data extraction form. No data was available for entering into RevMan for analysis. MAIN RESULTS: The included trial using mechanical ventilation with or without high efficiency vacuum cleaners did not show any clinical benefit to asthma patients. There was a decline in the house dust mite count and the antigen level. This open trial had a low sample size. REVIEWER'S CONCLUSIONS: There is a need for studying the health benefits of dehumidification by a double blind randomized controlled trial with adequate sample size measuring clinical outcomes in patients of asthma.

Asthma↗
PubMed2000

Holding chambers versus nebulisers for beta-agonist treatment of acute asthma.

BACKGROUND: In acute asthma inhaled beta-agonists are often administered to relieve bronchospasm by wet nebulisation, but some have argued that metered-dose inhalers with a holding chamber (spacer) can be equally effective. In the community setting nebulisers are more expensive, require a power source and need regular maintenance. OBJECTIVES: There is controversy as to whether wet nebulisers are better than metered dose inhalers with holding chambers to deliver beta2-agonist medications for acute asthma. Comparisons of hospital and home use are also of interest. The objective of this review was to assess the effects of holding chambers compared to nebulisers for the delivery of beta2-agonists for acute asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and the Cochrane Controlled Trials Register. SELECTION CRITERIA: Randomised trials in adults and children (from two years of age) with asthma, where holding chamber beta2-agonist delivery was compared with wet nebulisation. DATA COLLECTION AND ANALYSIS: One reviewer applied study inclusion criteria and extracted the data. Trial quality was assessed independently by two reviewers. Missing data were obtained from the authors or estimated. MAIN RESULTS: This review analysed 686 children and 375 adults included in 16 trials. Method of delivery of beta2-agonist did not appear to affect hospital admission rates. In adults, the odds ratio of holding chamber versus nebuliser was 1.12, 95% confidence interval 0.45 to 2.76. The odds ratio for children was 0.91, 95% confidence interval 0.4 to 2.1. Children's length of stay in the emergency department was significantly shorter when the holding chamber was used, with a weighted mean difference of -0.62 hours, 95% confidence interval -0.84 to -0.40 hours. Adults' length of stay in the emergency department was similar for the two delivery methods. Peak flow and forced expiratory volume were also similar for the two delivery methods. Pulse rate was lower for holding chamber in children, weighted mean difference -8.3% baseline, 95% confidence interval -11.5 to -5.0,. REVIEWER'S CONCLUSIONS: Metered-dose inhalers with holding chamber produced outcomes that were at least equivalent to nebuliser delivery. Holding chambers may have some advantages compared to nebulisers for children with acute asthma.

Acute Disease↗
PubMed2000

Long-acting beta2-agonists for chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation which is only partially reversible. Long acting beta2-agonists, effective in the management of asthma,are also recommended for COPD management so it is important to establish whether these drugs are effective in reducing COPD symptoms in view of the potential side effect and cost burden. OBJECTIVES: To determine the effectiveness of long acting beta2-adrenoceptor agonists in improving lung function and quality of life and reducing dyspnoea in patients with COPD. SEARCH STRATEGY: A search was carried out using the Cochrane Airways Group register. Bibliographies of identified RCTs were searched for additional relevant RCTs. Authors of identified RCTs were contacted for other published and unpublished studies. In addition, unpublished studies were also obtained from the pharmaceutical companies that manufacture long acting beta2- adrenoceptor agonists. SELECTION CRITERIA: All randomised controlled trials over four weeks in duration comparing treatment with long-acting beta2-adrenoceptor agonists (salmeterol and formoterol) with placebo in patients with stable non-reversible COPD. Outcome measures included forced expiratory volume in one second (FEV1), peak expiratory flow rate (PEFR), symptom scores, six minute walk distance, quality of life scores, Borg scores for dyspnoea and rescue bronchodilator use. DATA COLLECTION AND ANALYSIS: Data extraction and study quality assessment was performed independently by two reviewers. Where further or missing data were required, authors of studies were contacted. MAIN RESULTS: Thirty three abstracts were identified as potentially relevant. Of these, four randomised controlled trials (RCTs) were included in this review. Two were parallel group studies of 16 week duration and two were cross-over studies with four week treatment arms. All four RCTs assessed the efficacy of salmeterol in COPD. In a 16 week study of salmeterol 50 mcg and 100 mcg twice daily treatment, a significant increase in FEV1 was seen in both treatment groups. The weighted mean difference (WMD) for the increase in FEV1 for the 50 mcg group was 0.10 litre (95% CI: 0.05;0. 15) and in the 100 mcg group the WMD was 0.12 litre (95% CI: 0.06; 0. 17 ). In the two cross-over studies of four weeks treatment, salmeterol 50 mcg twice daily treatment did not show significant increases in FEV1 (WMD = 0.04 litre, 95% CI: -0.06; 0.15). Similarly, morning and night time PEFR was not significantly improved with salmeterol treatment. In a 16 week study, disease-specific quality of life, measured using the St. George's Respiratory Questionnaire (SGRQ), showed a significant improvement after 50 mcg twice daily, but not after 100 mcg twice daily. This improvement exceeded the threshold for a clinically significant change with this questionnaire. General health status, as measured by the Medical Outcomes Short Form 36, did not improve in any of the eight components with either salmeterol dose. No significant difference was demonstrated in the mean change from baseline in the six minute walk distance (WMD = 1.9 metres, 95% CI: -15.4;19.3). Breathlessness was reduced in one study in patients receiving salmeterol 50 mcg twice daily group. Significantly more patients in this group had Borg scores for breathlessness less than three (a score of three indicating moderate dyspnoea) compared to the placebo treated group (Peto Odds Ratio = 0.60, 95% CI: 0.40; 0.88). Neither dose of salmeterol influenced the incidence of COPD exacerbations, (50 mcg: Peto Odds Ratio = 0.74, 95% CI: 0.47, 1.15) and (100 mcg: Peto Odds Ratio = 0.98, 95% CI: 0.64, 1.52). REVIEWER'S CONCLUSIONS: Treatment of patients with COPD with long acting beta2-agonists produces only small increases in FEV1. In one study, a dose of salmeterol 50 mcg twice daily produced a reduction in breathlessness and a clinically significant improvement in quality of life. (ABSTRACT TRUNCATED)

Adrenergic beta-Agonists↗
PubMed2000

Anti-cholinergic drugs for wheeze in children under the age of two years.

BACKGROUND: Wheeze in infancy and early childhood is common and appears to be increasing though the magnitude of any increase is unclear. Most wheezing episodes in infancy are precipitated by respiratory viral infections. Treatment of very young children with wheeze remains controversial. Anti-cholinergics are often prescribed but practice varies widely and the efficacy of this form of therapy remains the subject for debate. OBJECTIVES: Wheeze in infancy and early childhood is common and appears to be increasing. Most wheezing episodes in infancy are a result of viral infection. Bronchodilator medications such as beta2-agonists and anti-cholinergic agents are often used to relieve symptoms, but patterns of use vary. The objective of this review was to assess the effects of anti-cholinergic therapy in the treatment of wheezing infants. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and the reference lists of articles. We contacted researchers in the field and industry sources. SELECTION CRITERIA: Randomised trials that compared anti-cholinergic therapy with placebo or beta2-agonists in wheezing children under two years of age. Children with acute bronchiolitis and chronic lung disease were excluded. DATA COLLECTION AND ANALYSIS: Eligibility for inclusion and quality of trials were assessed independently by two reviewers. MAIN RESULTS: Six trials involving 321 infants in three different settings were included. Compared with beta2-agonist alone, the combination of ipratropium bromide and beta2-agonist was associated with a reduced need for additional treatment, but no difference was seen in treatment response, respiratory rate or oxygen saturation improvement in the emergency department. There was no significant difference in length of hospital stay between ipratropium bromide and placebo; or between ipratropium bromide and beta2-agonist combined compared with beta2-agonist alone. However, combined ipratropium bromide and beta2-agonist compared to placebo showed significantly improved clinical scores at 24 hours. Parents preferred ipratropium bromide over nebulised water or placebo for relief of their children's symptoms at home. REVIEWER'S CONCLUSIONS: There is not enough evidence to support the uncritical use of anti-cholinergic therapy for wheezing infants, although parents using it at home were able to identify benefits.

Asthma↗
PubMed1998

[Clinical analysis of pneumonia treated at the hospital].

104 cases of pneumonia, treated in Department of Pulmonary Diseases of Military Medical Academy in the years 1995-1997, were analysed. Patients were divided into two groups. In the first group were 58 patients which had acute symptoms of pneumonia and the treatment was started in our department without any treatment before. In the second group were 45 patients which had acute symptoms two or three weeks before admission to hospital. In this period these patients received one or more antibiotics. The bacteriological findings and the periods of the treatment were analysed in these both groups.

Acute Disease↗
PubMed1997

[The influence of multiple histamine inhalation on nonspecific airway hyperresponsiveness to histamine in patients with bronchial asthma].

The study was performed in 19 patients with stable mild/moderate asthma aged from 16 to 66. Nonspecific airway hyperresponsiveness (AH) to histamine was measured according to Cockcroft's et al. method and expresses as PC20H in mg/ml. The study was controlled by inhalation of PBS. The histamine or PBS challenges were performed three times at 45 min. intervals on the third day in case when the stability of AH on two preceding days was observed. The geometric means of PC20H (xg PC20H) during the consecutive three days did not change. They were 0.97, 0.92, 0.87 mg/ml (p > 0.05) respectively. Three times histamine challenges performed on the same day induced the decrease of AH (xg PC20H increased from 1.48 to 6.55 mg/ml) in 5 patients. In 4 other subjects the increase of AH was observed (xg PC20H decreased from 1.14 to 0.20 mg/ml). In 10 subjects the three times histamine challenges performed on the same day had no influence on AH to histamine.

Administration, Inhalation↗
PubMed1997

[An increase of nonspecific airway hyperreactivity after repeated challenge with subthreshold doses of allergen in asthma patients].

The study was performed in 11 patients suffering from stable mild and moderate atopic asthma. Bronchial allergen challenges were performed according to Chai et al method. Airway hyperreactivity-AH (PC20H in mg/ml) was determined in each study day before subthreshold allergen inhalation dose, meaning the dose which did not induce asthmatic responses. Then FEV1 was measured in 2, 5, 15, 30 i 60 min. after allergen provocation throughout 4 to 9 consecutive days. A significant increase of PC20H was observed in 8 patients (xg PC20H in whole group decreased from 0.93 to 0.35 mg/ml after allergen challenges). The authors conclude that allergen inhalation challenge without asthmatic bronchial responses can cause an increase AH.

Adult↗
PubMed1995

Specificity of different organic nitrates to elicit NO formation in rabbit vascular tissues and organs in vivo.

1. In the present study we assessed the formation of nitric oxide (NO) from classical and thiol-containing organic nitrates in vascular tissues and organs of anaesthetized rabbits, and established a relationship between the relaxant response elicited by nitroglycerin (NTG) and NO formation in the rabbit isolated aorta. Furthermore, the effect of isolated cytochrome P450 on NO formation from organic nitrates was investigated. 2. Rabbits received diethyldithiocarbamate (DETC; 200 mg kg-1 initial bolus i.p. and 200 mg kg-1 during 20 min, i.v.) and either saline, or one of the following organic nitrates: nitroglycerin (NTG, 0.5 mg kg-1), isosorbide dinitrate (ISDN), N-(3-nitratopivaloyl)-L-cysteine ethylester (SPM 3672), S-carboxyethyl-N-(3-nitratopivaloyl)-L-cysteine ethylester (SPM 5185), at 10 mg kg-1 each. After 20 min the animals were killed, blood vessels and organs were removed, and subsequently analyzed for spin-trapped NO by cryogenic electron spin resonance (e.s.r.) spectroscopy. 3. In the saline-treated control group, NO remained below the detection limit in all vessels and organs. In contrast, all of the nitrates tested elicited measurable NO formation, which was higher in organs (liver, kidney, heart, lung, spleen) (up to 4.8 nmol g-1 20 min-1) than in blood vessels (vena cava, mesenteric bed, femoral artery, aorta) (up to 0.7 nmol g-1 20 min-1). Classical organic nitrates (NTG, ISDN) formed NO preferentially in the mesenteric bed and the vena cava, while the SPM compounds elicited comparable NO formation in veins and arteries. 4. Using a similar spin trapping technique, NO formation was assessed in vitro in phenylephrine-precontracted rabbit aortic rings. The maximal relaxation elicited by a first exposure (10 min) to NTG (0.3 to 10 microM) was positively correlated (r = 0.8) with the net increase (NTG minus basal) of NO spin-trapped during a second exposure to the same concentration of NTG in the presence of DETC. 5. Cytochrome P450 purified from rabbit liver enhanced NO formation in a NADPH-dependent fashion from NTG, but not from the other nitrates, as assessed by activation of purified soluble guanylyl cyclase. 6. We conclude that the vessel selective action of different organic nitrates in vivo reflects differences in vascular NO formation. Thus, efficient preload reduction by classical organic nitrates can be accounted for by higher NO formation in venous capacitance as compared to arterial conductance and resistance vessels. In contrast, NO is released from cysteine-containing nitrates (SPMs) to a similar extent in arteries and veins, presumably independently of an organic nitrate-specific biotransformation. Limited tissue bioavailability of NTG and ISDN might account for low NO formation in the aorta, while true differences in biotransformation seem to account for differences in NO formation in the other vascular tissues.

Animals↗
PubMed1994

Pyrrolidine dithiocarbamate selectively prevents the expression of the inducible nitric oxide synthase in the rat aorta.

Exposure of rat aortic rings without endothelium to interleukin-1 beta for 5 h significantly attenuated the contractions due to phenylephrine and increased the tissue content of guanosine 3',5'-cyclic monophosphate (cyclic GMP) due to the induction of nitric oxide synthase. The presence of pyrrolidine dithiocarbamate, a specific inhibitor of nuclear transcription factor kappa B activation, during the exposure of the rings to interleukin-1 beta prevented these responses to interleukin-1 beta. Rat aortic rings which had been incubated for 5 h with interleukin-1 beta in the absence and presence of pyrrolidine dithiocarbamate prior to the organ chamber experiment had a similar concentration-dependent relaxation curve for acetylcholine in rings with endothelium, and for 3-morpholino-sydnonimine (SIN-1) in rings without. Pyrrolidine dithiocarbamate applied acutely did not alter the tone elicited by phenylephrine in rings with or without endothelium and had no effect on the subsequent relaxation induced by acetylcholine in rings with endothelium or by SIN-1 in rings without endothelium. These observations suggest that pyrrolidine dithiocarbamate prevents the interleukin-1 beta-mediated expression of the inducible nitric oxide synthase without affecting the activity of the constitutive enzyme in the rat aorta.

Acetylcholine↗
PubMed1993

Contractility of the tail artery in rats treated with bezafibrate and fed atherogenic diet.

Bezafibrate, a potent hypolipidemic agent, was studied as potentially preventive in the atherosclerosis-associated vascular hyperresponsiveness to alpha-adrenoceptors agonists in rats. Contractile responses to norepinephrine (NE) were determined in isolated tail arteries of rats fed an atherogenic or a standard diet. Atherogenic diet was biochemically confirmed to induce hypercholesterolemia. Used for 1 month, atherogenic diet increased pressor responses to NE in physiologic salt solution (PSS) and Ca(2+)-free PSS. When bezafibrate (100 mg/kg orally, p.o.) was administered simultaneously with atherogenic diet for 1 month, the effect was inhibited, but bezafibrate administered from day 15 of our experiment had no effect on vasoconstrictor responses to NE. Bezafibrate prevented changes in contractile responses of rat tail artery in the early stages of atherogenesis.

Administration, Oral↗