Pharmacokinetics of Beclomethasone Dipropionate in an Hydrofluoroalkane-134a Propellant System in Japanese Children with Bronchial Asthma

ABSTRACTBackgroundHydrofluoroalkane-134a (HFA) has been shown to be a safe replacement for chlorofluorocarbons (CFCs) as a pharmaceutical propellant, with the advantage that it has no ozone-depleting potential. This is the first report of the pharmacokinetics of beclomethasone dipropionate (BDP) delivered from a pressurized solution formulation using an HFA propellant system (HFA-BDP) in Japanese children with bronchial asthma.MethodsPlasma concentrations of beclomethasone 17-monopropionate (17-BMP), a major metabolite of BDP, following an inhaled dose of HFA-BDP (200 μg as four inhalations from 50 μg/actuation) in five Japanese children with bronchial asthma were quantified and analyzed by a non-compartmental analysis to obtain pharmacokinetic parameters.ResultsThe area under the concentration-time curve from time zero to the last quantifiable time (AUC0-t) was 1659 ± 850 pg • h/mL (arithmetic mean ± standard deviation (SD)), the maximum concentration observed (Cmax) was 825 ± 453 pg/mL and the apparent elimination half-life (t1/2) was 2.1 ± 0.7 hours. The time to reach Cmax (Tmax) was 0.5 hours in all patients. No special relationship was observed between these parameters and age or body weight. These parameters were compared with the previously reported parameters of American children with bronchial asthma. The Japanese/American ratio of the geometric means of each parameter was 1.36 for AUC0-t, 1.04 for Cmax and 1.4 for t1/2. The median of Tmax was 0.5 hours in American patients as well as Japanese patients.ConclusionsThe pharmacokinetics of HFA-BDP in Japanese children with bronchial asthma are reported for the first time and a similarity to those in American children is suggested

Pressure-Induced Antiferromagnetic Bulk Superconductor EuFe2_2As2_2

We present the magnetic and superconducting phase diagram of EuFe$_2$As$_2$ for $B \parallel c$ and $B \parallel ab$. The antiferromagnetic phase of the Eu$^{2+}$ moments is completely enclosed in the superconducting phase. The upper critical field vs. temperature curves exhibit strong concave curvatures, which can be explained by the Jaccarino-Peter compensation effect due to the antiferromagnetic exchange interaction between the Eu$^{2+}$ moments and conduction electrons.Comment: submitted to the proceedings of the M2S-IX Toky

Prevention of pin tract infection with titanium-copper alloys

金沢大学医薬保健研究域医学系The most frequent complication in external fixation is pin tract infection. To reduce the incidence of implant-associated infection, many published reports have looked at preventing bacterial adhesion by treating the pin surface. This study aimed to evaluate the antibacterial activity of a Titanium-Copper (Ti-Cu) alloy on implant infection, and to determine the potential use of the Ti-Cu alloy as a biomaterial. Two forms of Ti-Cu alloys were synthesized: one with 1% Cu and the other with 5% Cu. For analyzing infectious behavior, the implants were exposed to Staphylococcus aureus and Escherichia coli. The reaction of pathogens to the Ti-Cu alloys was compared with their reaction to stainless steel and pure titanium as controls. Both Ti-Cu alloys evidently inhibited colonization by both bacteria. Conversely, cytocompatibility studies were performed using fibroblasts and colony formation on the metals was assessed by counting the number of colonies. Ti-1% Cu alloy showed no difference in the number of colonies compared with the control. External fixator pins made of Ti-Cu alloys were evaluated in a rabbit model. The tissue-implant interactions were analyzed for the presence of infection, inflammatory changes and osteoid-formation. Ti-1% Cu alloy significantly inhibited inflammation and infection, and had excellent osteoid-formation. Copper blood levels were measured before surgery and at 14 days postoperatively. Preoperative and postoperative blood copper values were not statistically different. Overall, it was concluded that Ti-Cu alloys have antimicrobial activity and substantially reduce the incidence of pin tract infection. Ti-1% Cu alloy shows particular promise as a biomaterial. © 2009 Wiley Periodicals, Inc

Comparison of muscle quality and functional capacity between Japanese and Brazilian older individuals

Muscle quality is well-known to decrease with aging and is a risk factor for metabolic abnormalities. However, there is a lack of information on race-associated differences in muscle quality and other neuromuscular features related to functional performance. This study aimed to compare muscle quality, function, and morphological characteristics in Japanese and Brazilian older individuals. Eighty-four participants aged 65–87 years were enrolled in the study (42 Japanese: 23 men, 19 women, mean age 70.4 years; 42 Brazilians: 23 men, 19 women, mean age 70.8 years). Echo intensity (EI) and muscle thickness (MT) of the quadriceps femoris were measured using B-mode ultrasonography. A stepwise multiple linear regression analysis with EI as a dependent variable revealed that MT was a significant variable for Japanese participants (R2 = 0.424, P = 0.001), while MT and subcutaneous adipose tissue (SCAT) thickness were significant variables for Brazilian participants (R2 = 0.490, P = 0.001). A second stepwise multiple linear regression analysis was performed after excluding MT and SCAT thickness from the independent variables. Sex and age for Japanese participants (R2 = 0.381, P = 0.001) and lean body mass and body mass index for Brazilian participants (R2 = 0.385, P = 0.001) were identified as significant independent variables. The present results suggest that MT is closely correlated with muscle quality in Japanese and Brazilian older individuals. Increases in muscle size may induce decreases in intramuscular adipose tissue and/or connective tissues, which are beneficial for reducing the risks of metabolic impairments in Japanese and Brazilian older individuals

Restoration of E-cadherin expression by selective Cox-2 inhibition and the clinical relevance of the epithelial-to-mesenchymal transition in head and neck squamous cell carcinoma

BACKGROUND: The epithelial-to-mesenchymal transition (EMT) accompanied by the downregulation of E-cadherin has been thought to promote metastasis. Cyclooxygenase-2 (Cox-2) is presumed to contribute to cancer progression through its multifaceted function, and recently its inverse relationship with E-cadherin was suggested. The aim of the present study was to investigate whether selective Cox-2 inhibitors restore the expression of E-cadherin in head and neck squamous cell carcinoma (HNSCC) cells, and to examine the possible correlations of the expression levels of EMT-related molecules with clinicopathological factors in HNSCC. METHODS: We used quantitative real-time PCR to examine the effects of three selective Cox-2 inhibitors, i.e., celecoxib, NS-398, and SC-791 on the gene expressions of E-cadherin (CDH-1) and its transcriptional repressors (SIP1, Snail, Twist) in the human HNSCC cell lines HSC-2 and HSC-4. To evaluate the changes in E-cadherin expression on the cell surface, we used a flowcytometer and immunofluorescent staining in addition to Western blotting. We evaluated and statistically analyzed the clinicopathological factors and mRNA expressions of Cox-2, CDH-1 and its repressors in surgical specimens of 40 patients with tongue squamous cell carcinoma (TSCC). RESULTS: The selective Cox-2 inhibitors upregulated the E-cadherin expression on the cell surface of the HNSCC cells through the downregulation of its transcriptional repressors. The extent of this effect depended on the baseline expression levels of both E-cadherin and Cox-2 in each cell line. A univariate analysis showed that higher Cox-2 mRNA expression (p = 0.037), lower CDH-1 mRNA expression (p = 0.020), and advanced T-classification (p = 0.036) were significantly correlated with lymph node metastasis in TSCC. A multivariate logistic regression revealed that lower CDH-1 mRNA expression was the independent risk factor affecting lymph node metastasis (p = 0.041). CONCLUSIONS: These findings suggest that the appropriately selective administration of certain Cox-2 inhibitors may have an anti-metastatic effect through suppression of the EMT by restoring E-cadherin expression. In addition, the downregulation of CDH-1 resulting from the EMT may be closely involved in lymph node metastasis in TSCC

Changes in Pediatric Patient Trends in Eating and Swallowing Disorders: A Comparison between the First and Fifth Year after Establishment of the Special Needs Dental Center

A Special Needs Dental Center （hereafter referred to as the Center） was established at Showa University Dental Hospital in April 2012 to treat patients who need special care. In cooperation with the Division of Dentistry for Persons with Disabilities, the Division of Hygiene and Oral Health is mainly engaged in the treatment of patients with eating and swallowing disorders. It has been five years since the establishment of the Center. The present study was aimed to establish an effective medical support method through a comparative study of changes in patient trends. A total of 65 patients who visited the Center from April 2017 to March 2018 were examined and their statistics were compared with those of 60 previously reported patients who initially visited the Center for medical examination in 2012. In 2012, many visits occurred during the nursing period; however, in 2017, the number of patients who visited after the weaning period increased. Other noted trends were increased diversity in primary disease, more patient referrals, fewer patients with severe swallowing dysfunction, and more patients with oral dysfunction. The necessity of eating and swallowing practice is thought to increase when lifestyle and oral environment change. The treatment of eating and swallowing disorders is important in the dental profession. Due to the introduction of insurance coverage in Japan in 2018 for developmental insufficiency of oral function, more pediatric patients with eating and swallowing disorders will likely be treated in the future

Clinical Statistics for Dysphagia Patients ≦ 18 Years of Age in the Center of Special Needs Dentistry, April 2012-March 2013

In April 2012, the Center of Special Needs Dentistry (SND) was established at Showa University Dental Hospital to provide function training for children with eating and swallowing disorders. A statistical clinical assessment was performed on new patients ≤18 years of age who visited the Center over a 1-year period (April 2012–March 2013) to assess the conditions present at the initial visit. In all, 60 patients (29 boys, 31 girls, mean (± SD) age 4.2±4.1 years, range 0-18 years of age) were included in the study. Most patients were <1 year of age (32%) and most came from one of four cities in the Johnan area (Shinagawa City, Meguro City, Ota City and Setagaya City). The most common primary diseases at the initial visit were cerebral palsy and cleft lip and palate. The third largest patient group was of healthy children with oral function problem. Over 60% of patients attended the Center of SND because of an eating-related complaint. More than 50% of patients were obtaining nutrients via oral intake; the remaining patients were obtaining nutrients via non-oral or a combination of oral and non-oral intake. Because of the young age of the patients and the fact that most were from neighboring areas, it can be inferred that effective community health care is being provided. It is necessary for the Center of SND to continue to provide professional treatment for dysphagia and to contribute to community medicine