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T Yamagata,
T Hirano,
H Sugiura,
S Yanagisawa,
T Ichikawa,
K Ueshima,
K Akamatsu, M Nakanishi,
K Matsunaga,
Y Minakata,
M Ichinose
[show abstract]
[hide abstract]
ABSTRACT: Regular use of long-acting bronchodilators is recommended for symptomatic COPD patients. A transdermal type of beta 2-agonist, tulobuterol, was recently developed. This agent shows the pharmacokinetic property of a sustained serum concentration for 24h. However, little has been reported about the bronchodilatory properties of this agent.
The aim of the present study was to compare the bronchodilatory action of transdermal beta 2-agonist tulobuterol with that of inhaled long-acting beta 2-agonist salmeterol.
An open-label, randomized crossover study was performed. Eleven patients with stable COPD were enrolled in the study. Tulobuterol (2mg/day) or salmeterol (50 microg, twice daily) was administered in a randomized, crossover manner. Forced expiratory volume in 1s (FEV1), forced vital capacity (FVC) and inspiratory capacity (IC) were measured before administration, every 2h from 12 to 24h, and at 36 h after the initial administration.
Transdermal beta 2-agonist tulobuterol showed an improvement in FEV1, FVC and IC after dosing compared with those at baseline. Salmeterol also improved all parameters of FEV1, FVC and IC, and showed a greater improvement compared with the transdermal beta 2-agonist tulobuterol (p<0.05). The values of the area under the curve (AUC) of FEV1, FVC and IC during the administration of tulobuterol were 2.98+/-1.05, 1.81+/-0.98, 0.75+/-0.85 L h, respectively, and during the administration of salmeterol they were 6.39+/-1.12, 6.61+/-1.34, 4.28+/-0.91 L h, respectively.
The transdermal beta 2-agonist tulobuterol showed bronchodilatory action for at least 24h by once daily administration. However, its bronchodilatory potency was about three times less than that of the inhaled beta 2-agonist salmeterol.
Pulmonary Pharmacology & Therapeutics 02/2008; 21(1):160-5. · 2.80 Impact Factor
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K Akamatsu,
T Yamagata,
T Takahashi,
K Miura,
S Maeda,
Y Yamagata,
T Ichikawa,
S Yanagisawa,
K Ueshima,
T Hirano, M Nakanishi,
K Matsunaga,
Y Minakata,
M Ichinose
[show abstract]
[hide abstract]
ABSTRACT: A combination of bronchodilators may be effective in the treatment of chronic obstructive pulmonary disease (COPD). We examined the effect of adding a long-acting anti-cholinergic agent (tiotropium) to a transdermal-type beta(2)-agonist (tulobuterol) on dyspnea as well as pulmonary function.
In a multicentre, randomized, parallel design study, 60 COPD patients treated with the transdermal beta(2)-agonist tulobuterol were divided into a tiotropium added group (Tulo+Tio group, n=40) or transdermal beta(2)-agonist tulobuterol alone group (Tulo group, n=20), and then treated for 4 weeks after a 2 week run-in period. Pulmonary function and a dyspnea (Medical Research Council (MRC)) scale were assessed before and after the treatment. Daily peak expiratory flow (PEF) monitoring was also performed.
After 4 weeks, the Tulo+Tio group showed a significant increase in pulmonary function compared with the Tulo group; DeltaFVC (0.31+/-0.06 L vs. 0.06+/-0.05 L, p< 0.01), DeltaFEV(1) (0.15+/-0.03 L vs. -0.02+/-0.02 L, p<0.0001), and DeltaPEF (41.0+/-5.1 L/min vs. 0.5+/-3.5 L/min, p<0.0001). The MRC dyspnea scale was also significantly improved in Tulo+Tio, but not in Tulo group.
These results suggest that tiotropium caused a significant improvement in both pulmonary function and dyspnea in COPD patients already treated with the transdermal beta(2)-agonist tulobuterol.
Pulmonary Pharmacology & Therapeutics 02/2007; 20(6):701-7. · 2.80 Impact Factor
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T Ichikawa,
K Matsunaga,
Y Minakata,
S Yanagisawa,
K Ueshima,
K Akamatsu,
T Hirano, M Nakanishi,
H Sugiura,
T Yamagata,
M Ichinose
[show abstract]
[hide abstract]
ABSTRACT: Exhaled breath condensate (EBC) is thought to contain substances of the lower airway epithelial lining fluid (ELF) aerosolized by turbulent flow. However, contamination by saliva may affect the EBC when collected orally.
The purpose of this study was to compare the cytokine expression levels in EBC with those in saliva, and to clarify the influence of saliva on cytokine measurements of EBC.
EBC and saliva samples were obtained from 10 adult subjects with stable asthma. To estimate differences in the contents of substances between EBC and saliva, the total protein concentration of each sample was measured. Further, we also measured the total protein concentration of ELF obtained from another patient group with suspected lung cancer using a micro sampling probe during bronchoscopic examination and roughly estimated the dilution of EBC by comparing the total protein concentration of EBC and ELF from those two patient groups. The cytokine expression levels of EBC and saliva from asthmatic group were assessed by a cytokine protein array.
The mean total protein concentrations in EBC, saliva and ELF were 4.6 microg/ml, 2,398 microg/ml and 14,111 microg/ml, respectively. The dilution of EBC could be estimated as 1:3000. Forty cytokines were analyzed by a cytokine protein array and each cytokine expression level of EBC was found to be different from that of saliva. Corrected by the total protein concentration, all cytokine expression levels of EBC were significantly higher than those of saliva.
These results suggest that the salivary influence on the cytokine assessment in EBC may be negligible.
Analytical Chemistry Insights 02/2007; 2:85-92.
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T Hirano,
T Yamagata,
M Gohda,
Y Yamagata,
T Ichikawa,
S Yanagisawa,
K Ueshima,
K Akamatsu, M Nakanishi,
K Matsunaga,
Y Minakata,
M Ichinose
[show abstract]
[hide abstract]
ABSTRACT: Reactive nitrogen species (RNS) are thought to be one of the important factors in the pathogenesis of chronic obstructive pulmonary disease (COPD). A study was undertaken to examine the effects of theophylline and fluticasone propionate (FP) on RNS production in subjects with COPD.
Sixteen COPD subjects participated in the study. Theophylline (400 mg/day orally) or FP (400 mug/day inhalation) were administered for 4 weeks in a randomised crossover manner with a washout period of 4 weeks. Induced sputum was collected at the beginning and end of each treatment period. 3-nitrotyrosine (3-NT), which is a footprint of RNS, was quantified by high performance liquid chromatography with an electrochemical detection method as well as by immunohistochemical staining.
Theophylline significantly reduced the level of 3-NT in the sputum supernatant as well as the number of 3-NT positive cells (both p<0.01). FP also reduced 3-NT formation, but the effect was smaller than that of theophylline. Theophylline also significantly reduced the neutrophil cell counts in the sputum (p<0.01), while FP treatment had no effect on the number of inflammatory cells in the sputum, except eosinophils.
Theophylline reduces nitrative stress and neutrophil infiltration in COPD airways to a larger extent than inhaled corticosteroid.
Thorax 10/2006; 61(9):761-6. · 6.84 Impact Factor
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Thorax 11/2005; 60(10):882. · 6.84 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: It is well known that there are various adverse effects during chemotherapy for cancer treatment. A taste disorder is also seen in 35-70% of patients. It has been reported that a zinc deficiency is associated with the development of these alterations in taste sensation. The purpose of this pilot study was to determine whether the zinc including infusion had the effect on taste disorder in patients with lung cancer. Taste disorder was evaluated as the increase in electrical taste thresholds using an electrogustometer. The plasma zinc concentration was also measured. Although there was no significant correlation, the increase in taste thresholds was detected in many patients who had a low zinc concentration even before receiving chemotherapy. Moreover, after 2 weeks of chemotherapy, almost all patients who did not have a zinc containing infusion showed development of taste disorder (5/5, 100% at chorda tympani area; 4/5, 80% at glossopharyngeal area), whereas no development of taste disorder was observed in those patients receiving a zinc containing infusion. These results suggest the possibility that the administration of zinc during chemotherapy could be a useful supportive therapy for preventing taste disorder and to help maintain a better quality of life.
Journal of experimental & clinical cancer research: CR 01/2004; 22(4):557-63. · 1.50 Impact Factor
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K. Akamatsu,
T. Yamagata,
T. Takahashi,
K. Miura,
S. Maeda,
Y. Yamagata,
T. Ichikawa,
S. Yanagisawa,
K. Ueshima,
T. Hirano, M. Nakanishi,
K. Matsunaga,
Y. Minakata,
M. Ichinose
[show abstract]
[hide abstract]
ABSTRACT: BackgroundA combination of bronchodilators may be effective in the treatment of chronic obstructive pulmonary disease (COPD). We examined the effect of adding a long-acting anti-cholinergic agent (tiotropium) to a transdermal-type β2-agonist (tulobuterol) on dyspnea as well as pulmonary function.MethodsIn a multicentre, randomized, parallel design study, 60 COPD patients treated with the transdermal β2-agonist tulobuterol were divided into a tiotropium added group (Tulo+Tio group, n=40) or transdermal β2-agonist tulobuterol alone group (Tulo group, n=20), and then treated for 4 weeks after a 2 week run-in period. Pulmonary function and a dyspnea (Medical Research Council (MRC)) scale were assessed before and after the treatment. Daily peak expiratory flow (PEF) monitoring was also performed.ResultsAfter 4 weeks, the Tulo+Tio group showed a significant increase in pulmonary function compared with the Tulo group; ΔFVC (0.31±0.06 L vs. 0.06±0.05 L, p< 0.01), ΔFEV1 (0.15±0.03 L vs. −0.02±0.02 L, p<0.0001), and ΔPEF (41.0±5.1 L/min vs. 0.5±3.5 L/min, p<0.0001). The MRC dyspnea scale was also significantly improved in Tulo+Tio, but not in Tulo group.ConclusionThese results suggest that tiotropium caused a significant improvement in both pulmonary function and dyspnea in COPD patients already treated with the transdermal β2-agonist tulobuterol.
Pulmonary Pharmacology & Therapeutics.
