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Several respiratory infections are frequently induced by pathogenic microorganisms in lung epithelial lining fluid (ELF) and alveolar macrophages (AM). Then, two studies concerning designs of antimicrobial therapy systems of respiratory infections were carried out; one was the distribution mechanisms of three macrolide and ketolide antibiotics, clarithromycin (CAM), azithromycin (AZM) and telithromycin (TEL) in plasma, ELF and AM, and the other was the efficient drug delivery to AM by pulmonary administration of fluoroquinolone antibiotic, a ciprofloxacin (CPFX) incorporated into liposomes (CPFX-liposome). In the first study, the areas under drug concentration-time curves (AUCs) in ELF following oral administration of three macrolide and ketolide antibiotics to rats were significantly higher than AUCs in plasma, furthermore AUCs in AM significantly higher than AUCs in ELF. The high distribution of these antibiotics to the respiratory infection site is due to the transport from blood to ELF via MDR1 in lung epithelial cells as well as the uptake by AM. These antibiotics were taken up by AM via active transport system and the trapping in organelles. In the second study, drug delivery efficacy of CPFX-liposome to AM was particle size-dependent over the 100-1000 nm and then become constant at over 1000 nm by pulmonary aerosolization to rats. This result indicates that the most effective size is 1000 nm. Furthermore, the drug delivery efficacy of mannosylated CPFX-liposome (particle size: 1000 nm) was highly delivered to AM and antibacterial effects were significantly higher than those of unmodified CPFX-liposome. This review provides useful findings for microbial therapy systems of respiratory infections.

The traditional Oriental medicine and health supplement have been empirically practiced but most of them have not come through objective examination to prove their efficacy. From pharmacological aspect, we have been investigating the medical benefits of traditional Oriental medicines and health supplements as curatives and their varied actions and mechanisms. The study on airway inflammation has shown that even a Kampo preparation, Bakumondo-to, has anti-inflammatory, anti-allergic, immunomodulatory, secretory-modulating and metabolic regulatory actions. The base of all its actions is founded on the restoration of normal molecular and cellular functions through DNA transcriptional regulation. In other previous studies, we showed that a health supplement, royal jelly (RJ) has weak estrogenic activity. RJ competes with 17β-estradiol for binding to the human estrogen receptors α and β, though it is much weaker than diethylstilbestrol in binding affinity. Treatment of MCF-7 cells with RJ enhances proliferation, and concomitant treatment with tamoxifen blocked this effect. A reporter gene assay showed that RJ enhanced transcription of the luciferase gene through the estrogen-responsive element in MCF-7 cells. Furthermore, subcutaneous injection of RJ restored the expression of vascular endothelial growth factor gene in the uteri of ovariectomized rats. We suggest that the diverse pharmacological functions of RJ can be ascribed, in part, to its estrogenic effects. We hypothesize that polyherbal medicines and health supplements, which have multiple actions, may be better than Western medicine of single component to treat various diseases including 'Mibyou' (presymptomatic disease). Our findings provide us with a new idea on the nature of disorder and disease-state development which involve complicated mechanisms and will contribute to novel principles to prevent diseases and establish new treatment. Adoption of means of translational research should provide objective background for efficacy and stimulate broader application and usage of traditional medicines and health supplements as curatives of Mibyou.

Sandalwood oil is widely used in aromatherapy for alleviating various symptoms. Santalol, a major component of sandalwood oil, has been reported to have central nervous system depressant effects such as sedation. In the present study, we investigated the effect of santalol on the sleep-wake cycle in sleep-disturbed rats. When inhaled at a concentration of 5 X 10(-2) ppm, santalol caused a significant decrease in total waking time and an increase in total non-rapid eye movement (NREM) sleep time. In order to clarify the mechanism of action, olfactory hypofunction was caused in rats by intranasal application of 5% zinc sulfate solution, and thereafter the effects of inhalation of fragrances were evaluated. In this study, it was found that the impairment of the olfactory system showed no significant effect on the changes in sleep parameters induced by santalol. This result suggests that santalol may act via the circulatory system rather than the olfactory system. That is, santalol is thought to be absorbed into the blood through the respiratory mucosa, and then exert its action. From these results, it is concluded that santalol may be useful in patients having difficulty maintaining sleep without being affected by individual differences in perfume-related preference.

Objective and Methods: To assess the clinical significance of CA19-9 in patients with interstitial pneumonia showing pathological nonspecific interstitial pneumonia (NSIP) pattern (IP/NSIP groups), we measured the levels of serum (n = 14) and bronchoalveolar lavage fluid (BALF, n = 10) CA19-9 in IP/NSIP groups., Result: The serum levels of CA19-9 did not correlate with the serum levels of LDH, of KL-6, or of SP-D or with the intensity of chest Ga-67 scintigraphy. There were no significant differences between the serum CA19-9 levels before therapy and those after therapy in improving patients. The levels of CA19-9 in fibrotic NSIP groups (serum:n = 7, 138.3 + /- 79.6 U/ml BALF: n = 5, 845.8 + /- 334.2 U/ml) were significantly higher than those in cellular NSIP groups (serum: n = 7, 12.8 +/-2.1 U/ml, BALF: n = 5, 40.8 +/- 16.2 U/ml). Immunohistochemical stains of CA19-9 showed the strong positivity in the bronchiolar epitheliums located in severe fibrotic lesions and the mucus within the lumens of microscopic honeycomb. The serum levels of CA19-9 were increased in both worsening patients., Conclusion: We speculated that the serum levels of CA19-9 may reflect the progression of lung fibrosis but not the disease activity in IP-NSIP groups.

Airway hypersecretion is a characteristic feature of chronic bronchitis and influences progression and prognosis of the disease, but the underlying mechanism remains uncertain. The increase in intraluminal viscid mucus may lead to disturbance of airway mucociliary clearance and deterioration of obstructive impairment of pulmonary function. Airway surface fluid is composed of mucous glucoprotein released from submucosal glands and goblet cells and water from airway epithelial cells, and the secretory function can be regulated by autonomic nervous system and a variety of chemical mediators and cytokines. Although several drugs may alter secretory responses and physicochemical properties of the sputum, it seems important to select mucoregulating drugs after understanding the mechanisms of hypersecretion and impaired mucociliary transport under individual conditions.