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Billions of neurons are interconnected in the central nervous system (CNS). Identification of specific neuronal circuit is indispensable for understanding the relationship between structure and function in the CNS. The midbrain dopamine (DA) neuron system consists of the retrorubral area (A8), the substantia nigra (SN; A9) and the ventral tegmental area (VTA; A10). We hypothesized that genetic methods using cell-type-specific promoters may offer the possibility to express tracer molecules in DA neurons to facilitate neuronal tracing. To address this, we used the 2.5 kb rat tyrosine hydroxylase (TH) promoter in adenovirus or adeno-associated virus (AAV) to express tracers specifically in DA neurons. We found that stereotaxic injection of TH promoter containing adenoviral construct resulted in cell-type-specific transgene expression in the noradrenaline (NA) neurons of the locus coeruleus (LC). However, it caused a significant toxicity to DA neurons in the SN. In contrast, stereotaxic injection of TH promoter containing AAV to the SN resulted in cell-type-specific transgene expression in DA neurons with no detectable toxicity. Taken together, our results demonstrate that it is possible to selectively trace DA neuronal circuits in rodent brains using the TH promoter in the context of AAV.Gene Therapy (2009) 16, 437–440; doi:10.1038/gt.2008.148; published online 18 September 2008 [ABSTRACT FROM AUTHOR]

This review will cover two main areas of acid-base balance, both of which are attended with much misconception and misunderstanding. One is the external balance of acids and alkali; the other is the contribution of bone buffering in acute and chronic metabolic acidosis. [ABSTRACT FROM AUTHOR]

Summary: Numerous studies support the idea that neuromuscular blockade facilitates facemask ventilation after induction of anaesthesia. Although improved airway patency or pulmonary compliance and a resolution of laryngospasm have been suggested as possible causes, the exact mechanism remains unclear. We aimed to assess whether neuromuscular blockade improves facemask ventilation and to clarify whether this phenomenon is associated with the vocal cord angle. This prospective observational study included patients aged between 20 and 65 years scheduled for elective surgery under general anaesthesia. After induction of anaesthesia, patients' lungs were ventilated with pressure‐controlled ventilation using a facemask. During facemask ventilation, a flexible bronchoscope was inserted through a self‐sealing diaphragm at the elbow connector attached to the facemask and breathing circuit and positioned to allow a continuous view of the vocal cords. The mean tidal volume and vocal cord angle were measured before and after administration of neuromuscular blocking drugs. Of 108 patients, 100 completed the study. Mean (SD) tidal volume ((11.0 (3.9) ml.kg‐1 vs. 13.6 (2.6) ml.kg‐1; p < 0.001) and mean (SD) vocal cord angle (17° (10°) vs. 26° (5°); p < 0.001) increased significantly after neuromuscular blockade. The proportional increase in mean tidal volume after neuromuscular blockade was positively correlated with vocal cord angle (Spearman's ρ = 0.803; p < 0.001). In conclusion, neuromuscular blockade facilitated facemask ventilation, and the improvement was correlated with further opening of the vocal cords. [ABSTRACT FROM AUTHOR]

The continuous-cooling transformation behaviour of Ti-45.5 at.% Al-0.05 at.% B alloy was quantitatively measured using a real-time resistivity-temperature-time measurement apparatus operating under a high vacuum. The addition of a small amount of B does not significantly alter the α-γ-phase equilibria but significantly raises the α-γ lamellar start temperature of Ti-45.5 at.% Al alloy at most cooling rates. Furthermore, it markedly increases the critical cooling rate for the ordering reaction. The effect of B addition, which greatly stabilizes the lamellar structure up to a fast cooling rate, is to accelerate the lamellar formation kinetics; the lamellar spacing was nevertheless distinctively larger in a B-doped alloy. This is because lamellae in B-doped alloy nucleate heterogeneously on titanium borides at the grain boundary; the borides are effective nucleation sites particularly since local Ti depletion can occur near the interface of the growing titanium borides during cooling. In the absence of B addition, the lamellar structure starts to form only at temperatures below T0, suggesting that a large undercooling is required for the nucleation of lamellae even at the grain boundaries. On the other hand, the B addition greatly retards the kinetics of the α-to-α2 ordering reaction by markedly increasing its critical cooling rate without a large change in the ordering temperature. This is believed to be due to its tendency to segregate strongly to the antiphase boundaries. [ABSTRACT FROM AUTHOR]

Summary: Food allergy is a major public health problem. Studies have shown that long‐term interactions between activated leucocyte cell adhesion molecule (ALCAM/CD166) on the surface of antigen‐presenting cells, and CD6, a co‐stimulatory molecule, influence immune responses. However, there are currently no studies on the functions of ALCAM in food allergy. Therefore, we aimed to identify the functions of ALCAM in ovalbumin (OVA)‐induced food allergy using ALCAM‐deficient mice. Wild‐type (WT) and ALCAM‐deficient (ALCAM–/–) mice were sensitized intraperitoneally and with orally fed OVA. The mice were killed, and parameters related to food allergy and T helper type 2 (Th2) immune responses were analysed. ALCAM serum levels increased and mRNA expression decreased in OVA‐challenged WT mice. Serum immunoglobulin (Ig)E levels, Th2 cytokine mRNA and histological injuries were higher in OVA‐challenged WT mice than in control mice, and these were attenuated in ALCAM–/– mice. T cell proliferation of total cells, CD3+CD4+ T cells and activated T cells in immune tissues were diminished in OVA‐challenged ALCAM–/– mice. Proliferation of co‐cultured T cells and dendritic cells (DCs) was decreased by the anti‐CD6 antibody. In addition, WT mice sensitized by adoptive transfer of OVA‐pulsed ALCAM–/– BM‐derived DCs showed reduced immune responses. Lastly, serum ALCAM levels were higher in children with food allergy than in control subjects. In this study, serum levels of ALCAM were elevated in food allergy‐induced WT mice and children with food allergy. Moreover, immune responses and T cell activation were attenuated in OVA‐challenged ALCAM–/– mice. These results indicate that ALCAM regulates food allergy by affecting T cell activation. [ABSTRACT FROM AUTHOR]

Objective The Korean Cosmetic Act regulates the use of functional cosmetics) by the law. Four functional cosmetic groups, whitening, anti-wrinkle, UV protection and combination of whitening and anti-wrinkle, were categorized according to the Korean Cosmetic Act and Functional Cosmetics Codex. In this study, high-performance liquid chromatography ( HPLC) coupled with photodiode array detection ( DAD) was employed for the simultaneous detection of arbutin (and its decomposition product, hydroquinone), niacinamide, ascorbyl glucoside, ethyl ascorbyl ether and adenosine in functional cosmetic products such as creams, emulsions and lotions. Methods Separation by HPLC- DAD was conducted using a C18 column with a gradient elution of 5 m m KH2 PO4 buffer (containing 0.1% phosphoric acid) and methanol (containing 0.1% phosphoric acid). The wavelengths for the detection of arbutin, hydroquinone, niacinamide, adenosine, ascorbyl glucoside and ethyl ascorbyl ether were 283, 289, 261, 257, 238 and 245 nm, respectively. Results This method exhibited good linearity ( R2 ≥ 0.999), precision (expressed as relative standard deviation ( RSD) < 2%) and mean recoveries (89.42-104.89%). The results obtained by monitoring 100 market samples showed that the detected levels of the tested materials are within the acceptable authorized concentration. Conclusion The method developed herein is simple and can be used for market survey and quality control of functional cosmetics. [ABSTRACT FROM AUTHOR]

Background Clusterin is a sensitive cellular biosensor of oxidative stress and has been studied as a biomarker for inflammation-associated diseases. Clusterin levels in childhood asthma have not been evaluated. Objectives (1) To evaluate sputum clusterin levels in children with asthma compared to a control group. (2) To assess the relationships between sputum clusterin levels and airway inflammation, pulmonary function, and bronchial hyperresponsiveness. Methods This study included 170 children aged 5-18 years with stable asthma ( n = 91), asthma exacerbation ( n = 29), or no asthma (healthy controls; n = 50). Induced sputum, pulmonary function, and methacholine challenge tests were performed. Stable asthma was classified into two groups according to the severity. Clusterin levels in sputum were measured using an enzyme-linked immunosorbent assay. Results Children with stable asthma had a higher clusterin level than healthy controls [4540 (3872-5651) pg/mL vs. 3857 (1054-4369) pg/mL, P < 0.001]. The clusterin level was also more elevated in eosinophil-dominant sputum than in non-eosinophilic sputum in stable asthma [5094 (4243-6257) pg/mL vs. 4110 (1871-4839) pg/mL, P = 0.0017]. Clusterin levels were associated with asthma severity. Paradoxically, clusterin levels were lower during asthma exacerbation than in stable asthma [1838 (350-4790] pg/mL vs. 4540 (3872-5651) pg/mL, P < 0.001]. Clusterin levels were strongly correlated with the methacholine concentration that caused a 20% decrease in the forced expiratory volume in 1 s ( r = −0.617, P < 0.001); there was no significant correlation between clusterin levels and other pulmonary function parameters. Conclusions and Clinical Relevance Clusterin levels were altered in children with stable asthma and asthma exacerbation because of its antioxidant and anti-inflammatory effects. Clusterin may be a marker that reflects airway inflammation and severity of symptoms, and it can be used in the assessment and management of childhood asthma. [ABSTRACT FROM AUTHOR]

Background Atopic dermatitis ( AD) and contact dermatitis ( CD) are both T cell-mediated eczematous disorders. Interleukin ( IL)-17, expressed by T helper (Th)17 cells, is involved in recruitment of inflammatory cells into AD and CD skin. Aim In this study, we investigated whether IL-17 regulates immune dysregulation and affects skin barrier in oxazolone ( OXA)-induced AD-like and CD-like disease models in mice, by comparing IL-17 null mutant ( IL-17−/−) vs. wild-type ( WT) mouse strains in the models. Methods IL-17−/− and WT Balb/c mice were used for OXA induction of AD-like and CD-like skin diseases. Ear swelling was measured by a micrometer. Skin biopsies were obtained for RNA isolation and histology. Real-time quantitative PCR analysis was performed to quantify mRNA expression of Th2 cytokines. Skin permeability was measured by a vapometer, and structural changes in the skin were evaluated by electron and confocal microscopy. Results Both OXA-induced AD and CD responses were alleviated in IL-17−/− mice relative to WT, as demonstrated by reductions in ear swelling, inflammatory cell infiltration and levels of Th2 cytokines. These endpoints were used to characterize inflammatory dysregulation in both AD and CD models. Skin-barrier dysfunction, measured by increases in transepidermal water loss and dysfunction of lamellar bodies, and reductions in lipid distribution, were seen in both AD and CD in WT mice. In IL-17−/− mice, however, these responses were significantly diminished. Conclusions The results indicate that the IL-17 gene may play a role in modulating immune dysregulation and affecting skin barrier in OXA-induced AD-like and CD-like skin disease models in the Balb/c mouse. [ABSTRACT FROM AUTHOR]

A newly developed recombinant factor IX (BAX3261) was investigated for prophylactic use in paediatric patients aged <12 years with severe (FIX level <1%) or moderately severe (FIX level 1-2%) haemophilia B. The aim of this prospective clinical trial was to assess the safety, haemostatic efficacy and pharmacokinetic profile of BAX326 in previously treated paediatric patients. BAX326 was administered as prophylaxis twice a week for a period of 6 months, and on demand for treatment of bleeds. Safety was assessed by the occurrence of related AEs, thrombotic events and immunologic assessments. Efficacy was evaluated by annualized bleeding rate (ABR), and by treatment response rating (excellent, good, fair, none). PK was assessed over 72 h. None of the 23 treated paediatric subjects had treatment-related SAEs or AEs. There were no thrombotic events, inhibitory or specific binding antibodies against FIX, rFurin or CHO protein. Twenty-six bleeds (19 non-joint vs. 7 joint bleeds) occurred (mean ABR 2.7 ± 3.14, median 2.0), of which 23 were injury-related. Twenty subjects (87%) did not experience any bleeds of spontaneous aetiology. Haemostatic efficacy of BAX326 was excellent or good for >96% of bleeds (100% of minor, 88.9% of moderate and 100% of major bleeds); the majority (88.5%) resolved after 1-2 infusions. Longer T1/2 and lower IR were observed in younger children (<6 years) compared to those aged 6 to 12 years. BAX326 administered as prophylactic treatment as well as for controlling bleeds is efficacious and safe in paediatric patients aged <12 years with haemophilia B. [ABSTRACT FROM AUTHOR]

BAX326 is a recombinant factor IX (rFIX; nonacog gamma) manufactured without the addition of any materials of human or animal origin, and with two viral inactivation steps (solvent/detergent treatment and 15 nm nanofiltration). The aim of this prospective trial was to investigate the pharmacokinetics, haemostatic efficacy and safety of BAX326 in previously treated patients aged 12-65 years with severe or moderately severe haemophilia B. BAX326 was safe and well tolerated in all 73 treated subjects; adverse events considered related to treatment (2.7% incidence, all non-serious) were transient and mild, and no hypersensitivity reactions, inhibitor formation or thrombotic events were observed. Pharmacokinetic (PK) equivalence ( n = 28) between BAX326 and a licensed rFIX was confirmed in terms of the ratio of geometric mean AUC0-72 h per dose. Twice-weekly prophylaxis [mean duration 6.2 (±0.7) months; 1.8 (±0.1) infusions per week, 49.5 (±4.8) IU kg−1 per infusion] was effective in preventing bleeding episodes, with a significantly lower (79%, P < 0.001) annualized bleed rate (4.2) compared to an on-demand treatment in a historical control group (20.0); 24 of 56 subjects on prophylaxis (43%) did not bleed throughout the study observation period. Of 249 total acute bleeds, 211 (84.7%) were controlled with one to two infusions of BAX326. Haemostatic efficacy at resolution of bleed was rated excellent or good in 96.0% of all treated bleeding episodes. The results of this study indicate that BAX326 is safe and efficacious in treating bleeds and routine prophylaxis in patients aged 12 years and older with haemophilia B. [ABSTRACT FROM AUTHOR]

The level of vitamin D-binding protein (DBP) is increased in the cerebrospinal fluid of patients with Alzheimer's disease (AD), suggesting a relationship with its pathogenesis. In this study, we investigated whether and how DBP is related to AD using several different approaches. A pull-down assay and a surface plasmon resonance binding assay indicated direct interactions between purified DBP and amyloid beta (Aβ), which was confirmed in the brain of AD patients and transgenic AD model mice by immunoprecipitation assay and immunohistochemical double-staining method. Moreover, atomic force microscopic examination revealed that DBP reduced Aβ aggregation in vitro. DBP also prevented Aβ-mediated death in cultured mouse hippocampal HT22 cell line. Finally, DBP decreased Aβ-induced synaptic loss in the hippocampus and rescued memory deficits in mice after injection of Aβ into the lateral ventricle. These results provide converging evidence that DBP attenuates the harmful effects of Aβ by a direct interaction, and suggest that DBP is a promising therapeutic agent for the treatment of AD. [ABSTRACT FROM AUTHOR]

Yu K-H, Hong K-S, Lee B-C, Oh M-S, Cho Y-J, Koo J-S, Park J-M, Bae H-J, Han M-K, Ju Y-S, Kang D-W, Appelros P, Norrving B, Terent A. Comparison of 90-day case-fatality after ischemic stroke between two different stroke outcome registries using propensity score matching analysis. Acta Neurol Scand: 2011: 123: 325-331. © 2010 John Wiley & Sons A/S. It has not been clarified whether the disparity in ischemic stroke outcome between populations is caused by ethnic and geographic differences or by variations in case mix. Propensity score matching (PSM) analysis can overcome some analytical problems but is rarely used in stroke outcome research. This study was to compare the ischemic stroke case-fatality between two PSM cohorts of Sweden and Korea. Prognostic variables related to baseline characteristics and stroke care were included in our PSM model. Then, we selected 7675 Swedish and 1220 Korean patients with ischemic stroke from each stroke registers and performed one-to-one matching based on propensity scores of each patient. After PSM, all measured variables were well balanced in 1163 matched subjects, and the 90-day case-fatality was identical 6.2% (HR 0.997, 95%CI 0.905-1.099) in Sweden and Korea. No difference is found in the 90-day case-fatality in propensity score-matched Swedish and Korean patients with ischemic stroke. [ABSTRACT FROM AUTHOR]

The proper approach to diagnosis and management in patients with a first episode of a calcium-containing kidney stone is controversial, and we have reviewed the literature in a search for objective information. Six large retrospective studies show the "natural cumulative recurrence rate of renal stones" to be 14% at 1 year, 35% at 5 years, and 52% at 10 years. Randomized studies of the use of either thiazides or allopurinol suggest a modest beneficial effect of about 35% over placebo. Considering that the risk of this specific therapy is about 5%, the morbidity associated with renal stones is limited, and relatively less invasive procedures can often replace nephrolithotomy, we conclude that use of specific drug therapy, namely thiazides or allopurinol, is not warranted in patients with a first kidney stone and, therefore, that extensive metabolic evaluation is unnecessary. [ABSTRACT FROM AUTHOR]

The authors report on the fabrication of rubrene organic thin-film transistors (OTFTs) with crystalline and amorphous channels, which were achieved by patterning a rubrene thin film deposited under a specific condition. The deposited film was mostly covered by amorphous rubrene matrix with smooth surface except many crystalline rubrene disks embedded with rough surface. When the channel of OTFT covers some portion of crystalline disks, the OTFT displayed a typical field effect behavior while it showed little drain current with the channel covered with amorphous background. Typical field mobility obtained from OTFT with crystalline disks was 1.23×10-4 cm2/V s with an on/off current ratio of ∼103. [ABSTRACT FROM AUTHOR]

We examine various ZnSe spectra to obtain that which best represents the dielectric response ε of ZnSe. The measured evolution of pseudodielectric function 〈ε〉 data with chemical etching shows that the natural overlayer on ZnSe can be modeled accurately only if we assume that it contains amorphous Se. Hence previous assumptions made in correcting 〈ε〉 mathematically are not correct, and data obtained on stripped samples yield the best representation of ε. © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]