Clinical efficacy of inhaled corticosteroids in COPD

The use of inhaled corticosteroids in asthma is regarded as first-line therapy. But the efficacy of inhaled corticosteroids in the treatment of chronic obstructive pulmonary disease (COPD) remains controversial. However data from some large studies provide the evidence that regular treatment with inhaled glucocorticosteroids is appropriate for symptomatic COPD patients with an FEVi<50% predicted and repeated exacerbations. In these studies glucocorticosteroids combined with a long-acting beta-agonist was more effective than the individual components. However, additional studies are needed to clarify the effects of inhaled corticosteroids on mortality and to define their long-term adverse effects.     

Neural adjustment in the activation of the lower leg muscles through daily physical exercises in community-based elderly persons

Reflecting the rapidly aging population, community-based interventions in the form of physical exercise have been introduced to promote the health of elderly persons. Many investigation studies have focused on muscle strength in the lower leg as a potent indicator of the effect of physical exercises. The objective of this study was to assess the effect of long-term daily exercises on neural command in lower leg muscle activations. Twenty-six community-based elderly persons (13 men and 13 women; 69.8 +/- 0.5 years old) participated in this study. Daily exercise was comprised of walking for more than 30 min, stretching, muscle strengthening and balance exercise, and was continued for three months. Muscle strength and surface electromyography of the tibia anterior, rectus femoris, and biceps femoris were measured in maximum isometric voluntary contraction both before and after the intervention. The mean frequency of the firing of motor units was calculated based on fast Fourier transformation of the electromyography. As the results of the intervention, muscle strength increased significantly only in biceps femoris, whereas the mean frequency of motor units decreased significantly in every muscle, indicating that motor unit firing in lower frequency efficiently induces the same or greater strength compared with before the intervention. Thus, synchronization of motor units compensates for the lower frequency of motor unit firing to maintain muscular strength. In conclusion, long-term physical exercises in the elderly can modulate the neural adjustment of lower leg muscles to promote efficient output of muscle strength.     

Salivary duct carcinoma in the mandible: a case report

Salivary duct carcinoma (SDC) is a distinctive and aggressive neoplasm. The most frequent site of origin is the parotid gland, followed by the submandibular gland. SDC originating in the minor salivary glands, particularly in the ectopic glands within the mandible, is extremely rare. We describe a 62-year-old man with SDC in the mandible, who presented with a painless lump in the right submandibular region (later identified as lymph node metastasis) and ipsilateral mental nerve palsy. Histologic examination after ablative surgery revealed SDC originating in the mandible and cervical nodal metastases spreading to levels I-III. The patient remains alive 59 months after presentation as a result of postoperative full-dose irradiation and regular intensive chemotherapy using TXT, 5-FU, and CDDP. However, the patient has local recurrence and distant metastases to the lung and brain. In this report, we also discuss the specific diagnostic criteria and developmental theories of intraosseous salivary gland tumors.     

Intrinsic function of S100A8/A9 complex as an anti-inflammatory protein in liver injury induced by lipopolysaccharide in rats

BACKGROUND: We hypothesized that the S100A8/A9 complex is effective in the suppression of acute inflammatory changes. METHODS: To clarify such a functional role of the S100A8/A9 complex in acute inflammatory disorder, the complex purified from human leukocytes (approx. 1 mg) was intraperitoneally injected into rats 1.0 or 3.5 h after an injection of lipopolysaccharide (LPS). RESULTS: The serum concentrations of interleukin-6 (IL-6) and nitric oxide (NOx) were significantly decreased in the treated rats. Conversely, when anti-S100A8/A9 complex IgG was injected into the tail blood vessel of a rat 1.0 h after the injection of LPS, the serum concentration of IL-6 increased slightly, indicating that the antibody immunoregulatorily blocked the activity of the complex as an anti-inflammatory protein in vivo. In addition, the S100A8/A9 complex bound non-specifically with interleukin-1beta (IL-1beta), IL-6 and TNF-alpha in vitro, suggesting that the complex could bind with these cytokines in vivo. A large number of endogenous S100A8/A9 complex-positive cells that accumulated in the inflamed region in the liver 6 h after the injection of LPS were microscopically observed, while apparent inflammatory changes were not found microscopically in other organs, such as the kidney, lung and spleen. In rats treated with the S100A8/A9 complex, neither acute inflammatory changes nor S100A8/A9 complex-positive cells were also observed microscopically in the liver tissue. CONCLUSIONS: These findings suggest that the S100A8/A9 complex indirectly suppresses the overproduction of NOx from activated neutrophils and/or macrophages by neutralizing the activity of pro-inflammatory cytokines. Thus, the S100A8/A9 complex may play an important role in the suppression of acute inflammation by modulating the vital activity of pro-inflammatory cytokines in vivo.     

Niemann-Pick C1-like 1 overexpression facilitates ezetimibe-sensitive cholesterol and beta-sitosterol uptake in CaCo-2 cells

Previous in vivo studies including those with knockout mice suggested that Niemann-Pick C1-like 1 (NPC1L1) plays an essential role in the intestinal absorption of cholesterol. To characterize the mechanism of cholesterol uptake mediated by NPC1L1, an in vitro system reflecting the function of this transporter needs to be established. In the present study, we constructed NPC1L1 overexpressing CaCo-2 cells as an in vitro model and characterized the transport properties of NPC1L1. Immunohistochemical staining revealed that CaCo-2 cells express NPC1L1 on the apical membrane. It was also demonstrated that the uptakes of both cholesterol and beta-sitosterol are increased by NPC1L1 overexpression. In addition, the uptake of cholesterol was increased in a dose-dependent manner by an increase in the content of taurocholate in micelles, whereas micellar phosphatidylcholine showed a negative correlation with cholesterol uptake. Furthermore, it was confirmed that sterol uptake increased by NPC1L1 overexpression was inhibited by ezetimibe. We could thus establish an in vitro intestinal model to study the mechanism of NPC1L1-dependent sterol uptake and to screen drug candidates whose target is NPC1L1.