Spontaneous Infection Caused by Streptococcus agalactiae in KK-Ay Mice.

During 2006 through 2012, spontaneous group B Streptococcus infections were reported in 22 female KK-Ay mice, an animal model of type 2 diabetes. The affected mice were 5 to 27 wk old, and the cases involved various body sites, including cases of submandibular, caudal, and lumbar abscesses (n =18) or led to torticollis (n = 2), hydrocephalus (n = 1), or moribund clinical signs (n = 1). At necropsy, the mouse with hydrocephalus also demonstrated retained exudate in the uterus, and the moribund mouse showed renal inflammation. Streptococcus agalactiae was isolated in pure culture from all except 2 cases: the facial abscess also yielded Klebsiella pneumoniae, and the uterine exudate was coinfected with Staphylococcus aureus. In addition, S. agalactiae was isolated from the oral cavity and feces of normal KK-Ay mice. S. agalactiae potentially can cause a clinically significant spontaneous infection in a mouse model of diabetes.

Antimicrobial resistance in Campylobacter coli and Campylobacter jejuni in cynomolgus monkeys (Macaca fascicularis) and eradication regimens.

BACKGROUND: Campylobacter spp. are zoonotic pathogens, however, knowledge about their presence and antimicrobial resistance in nonhuman primates is limited. Our animal facility purchased cynomolgus monkeys (Macaca fascicularis) from various Asian countries: China, Cambodia, Indonesia, the Philippines, and Vietnam. METHODS: Colonization by Campylobacter spp. was investigated in 238 of the monkeys from 2009 to 2012 and antimicrobial susceptibility testing was carried out for these isolates. Furthermore, we eradicated these pathogens from these monkeys. RESULTS: Campylobacter spp. were isolated from 47 monkeys from three specific countries: China, Cambodia, and Indonesia, with respective isolation rates of 15%, 36%, and 67%. Two monkeys, which were each infected with Campylobacter jejuni and Campylobacter coli, showed clinical symptoms of diarrhea and bloody feces. In total, 41 isolates of C. coli and 17 isolates of C. jejuni were detected. Antimicrobial susceptibility varied: in the monkeys from China, erythromycin (ERY)-, tetracycline (TET)-, and ciprofloxacin-resistant C. coli, in the monkeys from Cambodia, amoxicillin-intermediate, TET- and ciprofloxacin-resistant C. coli and amoxicillin- and ciprofloxacin-resistant C. jejuni, and in the monkeys from Indonesia, ciprofloxacin-resistant C. coli and TET- and ciprofloxacin-resistant C. jejuni were common (>75%). Multiresistant isolates of C. coli were found in monkeys from all countries and multiresistant isolates of C. jejuni were found in monkeys from Indonesia. The eradication rate with azithromycin was comparable to that with gentamicin (GEN) by oral administration, and was higher than those with amoxicillin-clavulanic acid (AMC) and chloramphenicol (CHL). CONCLUSION: From the perspective of zoonosis, we should acknowledge multiresistant Campylobacter spp. isolated from the monkeys as a serious warning.

Efficacy on the risk of vertebral fracture with administration of once-weekly 17.5 mg risedronate in Japanese patients of established osteoporosis with prevalent vertebral fractures: a 156-week longitudinal observational study in daily practice.

Currently, the only available evidence for the efficacy of once-weekly 17.5 mg risedronate in preventing vertebral fractures was obtained in a 48-week study in Japan. We performed a 156-week prospective, longitudinal, observational study to determine the efficacy of the 17.5 mg risedronate in preventing vertebral fractures. We included Japanese patients with established osteoporosis who were older than 50 years and had radiographically confirmed vertebral fractures. The primary endpoint was the incidence of vertebral fractures every 24 weeks, with the final interval spanning 36 weeks. We also calculated the change in bone mineral density of the lumbar spine (L2-4 BMD) and urinary N-telopeptide of type I collagen (u-NTX), and assessed the incidence of adverse drug reactions and the drug adherence rate. Data from 241 patients were available for analysis of vertebral fracture prevention. The incidence rate of vertebral fractures decreased in a time-dependent manner (P = 0.0006; Poisson regression analysis). The risk ratio (fracture incidence per 100 person-years in the final 36 weeks versus that in the first 24 weeks) was 0.21 (95 % confidence interval 0.08-0.55). Compared to baseline values, L2-4 BMD increased by 6.41 % at 156 weeks, while u-NTX decreased by 36 % at 24 weeks and was maintained thereafter (P < 0.0001). The incidence rate of adverse drug reactions was 9.18 %. Drug adherence rates assessed every 4 weeks were over 90 %. Our results indicate that 156 weeks of treatment with once-weekly 17.5 mg risedronate effectively reduced the risk of vertebral fracture in Japanese patients with established osteoporosis older than 50 years.

Single-Crystal-Like Organic Thin-Film Transistors Fabricated from Dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]thiophene (DNTT) Precursor-Polystyrene Blends.

High-mobility short-channel organic thin-film transistors fabricated using a dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]-thio--phene (DNTT) precursor (5,14-N--phenylmaleimide DNTT, endo-isomer-rich fraction) and polystyrene (PS) blends are reported. The DNTT grains are "single-crystal"-like and the field-effect mobility of the devices ranges up to 4.7 cm(2) V(-1) s(-1). The PS layer functions as a hydrophobic passivation layer on the Si/SiO2 substrate.

Soluble organic semiconductor precursor with specific phase separation for high-performance printed organic transistors.

A soluble precursor of dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]thiophene (DNTT) is developed for high-performance printed organic thin-film transistors (OTFTs). The DNTT precursor enables excellent thin-film formation and can induce specific phase separations when blended with inert polymers. The DNTT OTFTs processed from the precursor/polymer blend exhibit field-effect mobilities of up to 1.1 cm(2) V(-1) s(-1) and excellent durability against air exposure and thermal stress.

Effect of azilsartan versus candesartan on morning blood pressure surges in Japanese patients with essential hypertension.

Morning blood pressure (BP) surge is reported as a risk factor for cardiovascular events and end-organ damage independent of the 24-h BP level. Controlling morning BP surge is therefore important to help prevent onset of cardiovascular disease. We compared the efficacy of azilsartan and candesartan in controlling morning systolic BP (SBP) surges by analyzing relevant ambulatory BP monitoring data in patients with/without baseline BP surges. As part of a 16-week randomized, double-blind study of azilsartan (20-40 mg once daily) and candesartan (8-12 mg once daily) in Japanese patients with essential hypertension, an exploratory analysis was carried out using ambulatory BP monitoring at baseline and week 14. The effects of study drugs on morning BP surges, including sleep trough surge (early morning SBP minus the lowest night-time SBP) and prewaking surge (early morning SBP minus SBP before awakening), were evaluated. Patients with sleep trough surge of at least 35 mmHg were defined by the presence of a morning BP surge (the 'surge group'). Sleep trough surge and prewaking surge data were available at both baseline and week 14 in 548 patients, 147 of whom (azilsartan 76; candesartan 71) had a baseline morning BP surge. In surge group patients, azilsartan significantly reduced both the sleep trough surge and the prewaking surge at week 14 compared with candesartan (least squares means of the between-group differences -5.8 mmHg, P=0.0395; and -5.7 mmHg, P=0.0228, respectively). Once-daily azilsartan improved sleep trough surge and prewaking surge to a greater extent than candesartan in Japanese patients with grade I-II essential hypertension.

Effect of azilsartan versus candesartan on nocturnal blood pressure variation in Japanese patients with essential hypertension.

BACKGROUND: Abnormal variations in night-time hypertension such as "non-dipping" type (< 10% decrease in nocturnal systolic blood pressure [SBP] from daytime SBP) are a risk factor for cardiovascular events independent of 24-h BP. METHODS: As part of a randomized, double-blind study of azilsartan (20-40 mg once daily) and candesartan (8-12 mg once daily) in Japanese patients with essential hypertension, an exploratory analysis was performed using ambulatory BP monitoring (ABPM) at baseline and Week 14. Effects of study drugs on nocturnal BP variations according to patients' nocturnal SBP dipping status were evaluated. RESULTS: ABPM data were available for 273 patients treated with azilsartan and 275 with candesartan. In the dipping group (≥ 10% decrease from daytime SBP), azilsartan produced a greater reduction from baseline in daytime than in night-time SBP (- 14.1 and - 10.9 mmHg, respectively), and the change in daytime SBP was significantly greater with azilsartan than with candesartan (p = 0.0077). In the non-dipping group, azilsartan produced a greater reduction from baseline in night-time than in daytime SBP (- 20.2 and - 9.9 mmHg, respectively), and reductions in both night-time SBP (p = 0.02) and daytime SBP (p = 0.0042) were significantly greater with azilsartan than with candesartan. CONCLUSIONS: Once-daily azilsartan improved non-dipping night-time SBP to a greater extent than candesartan in Japanese patients with grade I-II essential hypertension.

Comparison of the efficacy and safety of azilsartan with that of candesartan cilexetil in Japanese patients with grade I-II essential hypertension: a randomized, double-blind clinical study.

Azilsartan is a novel angiotensin receptor blocker being developed for hypertension treatment. This 16-week, multicenter, randomized, double-blind study compared the efficacy and safety of azilsartan (20-40 mg once daily by forced titration) and its ability to provide 24-h blood pressure (BP) control, with that of candesartan cilexetil (candesartan; 8-12 mg once daily by forced titration) in 622 Japanese patients with grade I-II essential hypertension. Efficacy was evaluated by clinic-measured sitting BP, and by ambulatory BP monitoring (ABPM) at week 14. Participants (mean age: 57 years, 61% males) had a mean baseline sitting BP of 159.8/100.4 mm Hg. The mean change from baseline in sitting diastolic BP at week 16 (primary endpoint) was -12.4 mm Hg in the azilsartan group and -9.8 mm Hg in the candesartan group, demonstrating a statistically significant greater reduction with azilsartan vs. candesartan (difference: -2.6 mm Hg, 95% confidence interval (CI): -4.08 to -1.22 mm Hg, P=0.0003). The week 16 (secondary endpoint) mean change from baseline in sitting systolic BP was -21.8 mm Hg and -17.5 mm Hg, respectively, a significant decrease with azilsartan vs. candesartan (difference: -4.4 mm Hg, 95% CI: -6.53 to -2.20 mm Hg, P<0.0001). On ABPM, the week 14 mean changes from baseline in diastolic and systolic BP were also significantly greater with azilsartan over a 24-h period, and during the daytime, night-time and early morning. Safety and tolerability were similar among the two groups. These data demonstrate that once-daily azilsartan provides a more potent 24-h sustained antihypertensive effect than that of candesartan but with equivalent safety.

Gestational changes in production of NO and expression of NOS mRNA isoforms in the rat placenta.

To monitor changes in NO production over time in the fetal placenta of rats, we used electron paramagnetic resonance spectroscopy with the Fe-N-(dithiocarboxy) sarcosine (Fe-DTCS) complex as an NO-trapping reagent. The expression of nitric oxide synthase (NOS) isoforms was examined in parallel using quantitative RT-PCR. NO production was first detected on day 13.5 of gestation. NO levels reached a peak on day 15.5, then decreased significantly during the last few days of gestation. The pattern of expression of NOS II mRNA was in good agreement with changes in NO levels, whereas NOS III mRNA expression did not change markedly during gestation. Thus, it appears that NO levels in the placenta are NOS II-dependent and differ at different gestational stages.