Aß dissociation by pectolinarin may counteract against Aß-induced synaptic dysfunction and memory impairment.

Alzheimer's disease (AD) is a degenerative brain disorder characterised by various neurological symptoms, including memory impairment and mood disorders, associated with the abnormal accumulation of amyloid b(Aß) and tau proteins in the brain. There is still no definitive treatment available for AD, and the Aß antibody drugs, which are expected to be approved by the FDA, have many limitations. Therefore, there is an urgent need to develop low-molecular-weight therapeutic agents for the management of AD. In this study, we investigated whether pectolinarin, a flavonoid, regulates Aß aggregation and Aß-induced toxicity. Pectolinarin demonstrated concentration-dependent inhibition of Aß aggregation and had the ability to break down pre-formed Aß aggregates, thereby reducing their neurotoxicity. Furthermore, pectolinarin suppressed Aß aggregates-induced reduction in long-term potentiation (LTP) in the hippocampus. Oral administration of pectolinarin in experimental animals inhibited memory impairment and LTP deficits induced by Aß injection in the hippocampus. These results indicate that pectolinarin may reduce toxic Aß species and Aß-induced memory impairments and synaptic dysfunction.

Physicochemically Constructed Unidirectional Aluminum Bismuth Gallium Zinc Oxide Film for Enhanced Nematic Liquid Crystal System Using a Brush-Coating Method.

We propose a convenient brush coating method for liquid crystal (LC) alignment. This method enables film deposition and an alignment layer treatment process simultaneously. Aluminum bismuth gallium zinc oxide (AlBiGaZnO) is used as the alignment layer. After the curing process, a unidirectional AlBiGaZnO film is formed; its surface morphology and chemical composition were verified using scanning electron microscopy and X-ray photoelectron spectroscopy. This oriented structure of the surface was produced by shear-stress which originated from brush movement. That structure induced a surface anisotropic characteristic and resulted in a uniform LC alignment. The uniform and homogeneous LC alignment state on the film was confirmed using polarized optical microscopy and pre-tilt angle analysis. The brush coated AlBiGaZnO film exhibited excellent thermal budget for advanced LC system. The film exhibited enhanced electro-optical performance with a low operating voltage. These results demonstrate the potential of LC alignment technology via the brush coating method.

Long-Term Effects of Hearing Aid Use on Auditory Spectral Discrimination and Temporal Envelope Sensitivity and Speech Perception in Noise.

BACKGROUND: The aims of this study were to evaluate the long-term effects of hearing-aid use on auditory spectral discrimination, temporal envelope sensitivity, and speech perception ability and to determine whether hearing performance changes with the duration of hearing-aid use. METHODS: The study included 13 elderly participants (64.15 ± 9.87 years) who had used hearing-aids for 12 months in everyday life. We compared the auditory performance without hearing-aids at the time of pre-fitting with the auditory performance with hearing-aids at 1 month and 12 months after fitting. Three different psychoacoustic measurements were made at their most comfortable levels to exclude the effect of amplification: (1) spectral-ripple discrimination, (2) temporal modulation detection, and (3) speech recognition in white noise. RESULTS: Repeated-measures analysis of variance demonstrated that the duration of hearing-aid use significantly affected spectral-ripple discrimination thresholds and 100 Hz temporal modulation detection threshold (P < .05). Post hoc tests revealed that the improvements in spectral discrimination in the early post-fitting stage (1 month) did not seem to increase over the period of hearing-aid use, whereas the temporal envelope sensitivity improved continuously over time (up to 12 months). CONCLUSION: These results imply that hearing-aid users adapt to hearing-aid processing for spectral discrimination immediately, whereas they need time to adapt to hearing-aid processing for temporal envelope sensitivity. Alternatively, long-term hearing-aid use could induce positive plastic changes exclusively in terms of temporal envelope sensitivity.

The Relation of Sound Level Tolerance to Tinnitus Ears in Human.

BACKGROUND: The aim of this study was to evaluate the relationship between sound level tolerance and tinnitus in humans. METHODS: We compared the loudness discomfort levels at 500 and 3000 Hz pure tones in 33 subjects with bilateral tinnitus and 33 subjects with unilateral tinnitus with normal and symmetric hearing thresholds and those of age- and sex-matched control subjects. RESULTS: Both the tinnitus ears (108.18 ± 10.22 dB HL and 103.03 ± 11.04 dB HL) and non-tinnitus ears (108.94 ± 12.61 dB HL and 104.24 ± 11.60 dB HL) in the unilateral tinnitus subjects showed significantly lower loudness discomfort levels at 500 and 3000 Hz than the control ears (115.91 ± 6.78 dB HL and 111.52 ± 8.88 dB HL, P < .008; α=0.05/6=0.008), whereas there was no difference in the loudness discomfort levels of the tinnitus ears of the bilateral tinnitus subjects (111.52 ± 10.42 dB HL or 106.36 ± 11.34 dB HL) and the control ears. CONCLUSION: These results support the hypothesis that the reduced loudness discomfort levels in tinnitus subjects with normal and symmetric hearing thresholds are associated with a hidden injury to the cochlea that induces the development of tinnitus, especially on one side. Whether tinnitus is perceived unilaterally or bilaterally depends on the status of the auditory system, which may be reflected in the sound level tolerance and loudness discomfort levels.

Systematic review and practical guidance on the use of topical calcipotriol and topical calcipotriol with betamethasone dipropionate as long-term therapy for mild-to-moderate plaque psoriasis.

While many patients with psoriasis are candidates for topical agents, long-term treatment effects are unclear. This systematic review evaluated global findings from clinical trials and real-world studies of topical calcipotriol and the two-compound formulation of calcipotriol and betamethasone dipropionate for mild-to-moderate plaque psoriasis (including scalp psoriasis). PubMed, Embase and MEDLINE were searched for relevant English-language publications along with Chinese, Japanese, Korean and Latin American publication databases. Identified articles were screened by title and abstract against predefined inclusion/exclusion criteria. A narrative synthesis of key efficacy and safety findings from the full papers of selected publications was developed. Thirty-seven relevant papers were identified (25 English, 11 Chinese and one Japanese-language study) including 28 randomized controlled trials. While there was significant heterogeneity in study length, treatment intensity and clinical measures, following a critical review of the published data combined with expert opinion, the following clinical practice recommendations were agreed in order to assist healthcare providers: in adults, long-term treatment with calcipotriol/betamethasone dipropionate is well tolerated and efficacious for up to 1 year on an 'as needed' basis, and for up to 16 weeks on a fixed-treatment regimen. Calcipotriol is also well tolerated and efficacious when used long term (up to 52 weeks) 'as needed' and for up to 20 weeks on a fixed-treatment regimen. Used on an 'as needed' basis for up to 1 year, the safety and efficacy profile of fixed-dose combination calcipotriol/betamethasone dipropionate is more favorable than calcipotriol alone; regular consultation between patients and their dermatologist/primary care physician is required to review psoriasis symptoms and adjust treatment accordingly; a specific treatment goal should be agreed on initiation of topical agent(s) to determine when long-term treatment can begin or if a regimen change is warranted; and application frequency during the continued treatment phase should consider the patients' treatment expectations and goals.

Akt and calcium-permeable AMPA receptor are involved in the effect of pinoresinol on amyloid ß-induced synaptic plasticity and memory deficits.

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders characterized by memory deficits. Although no drug has given promising results, synaptic dysfunction-modulating agents might be considered potential candidates for alleviating this disorder. Pinoresinol, a lignan found in Forsythia suspensa, is a memory-enhancing agent with excitatory synaptic activation. In the present study, we tested whether pinoresinol reduces learning and memory and excitatory synaptic deficits in an amyloid ß (Aß)-induced AD-like mouse model. Pinoresinol enhanced hippocampal long-term potentiation (LTP) through calcium-permeable AMPA receptor, which was mediated by Akt activation. Moreover, pinoresinol ameliorated LTP deficits in amyloid ß (Aß)-treated hippocampal slices via Akt signaling. Oral administration of pinoresinol ameliorated Aß-induced memory deficits without sensory dysfunction. Moreover, AD-like pathology, including neuroinflammation and synaptic deficit, were ameliorated by pinoresinol administration. Collectively, pinoresinol may be a good candidate for AD therapy by modulating synaptic functions.

Risk assessment of endocrine disrupting phthalates and hormonal alterations in children and adolescents.

Risk assessment and hormone evaluation were carried out for di(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP), endocrine disrupting chemicals (EDCs), in 302 Korean children (n = 223) and adolescents (n = 79) (< age 19). Urinary and serum concentrations of DEHP, MEHP (mono(2-ethylhexyl) phthalate), DBP, MBP (monobutyl phthalate), and PA (phthalic acid, a common final metabolite of phthalates) were detected in children and adolescents. Daily exposure levels were estimated to be 16.45 ± 36.50 µg/kg b.w./day for DEHP, which is one-third of the tolerable daily intake (TDI) value (50 µg/kg b.w./day), but 14 out of 302 participants had a hazard index (HI = intake/TDI) value >1. The mean daily exposure level of DBP was 1.23 ± 1.45 µg/kg b.w./day, which is one-eighth of the TDI value (10 µg/kg b.w./day), but 1 out of 302 participants had a HI value > 1. Positive correlations were observed between serum DBP or MEHP, and serum estradiol (E2) and/or luteinizing hormone (LH) in prepubescent children. In addition, serum MBP levels were found to be negatively correlated with serum triiodothyronine (T3) or thyroxine (T4) in male participants, and serum DEHP levels with serum thyroid stimulating hormone (TSH) in female adolescents. Low-density lipoprotein (LDL) levels were positively correlated with serum PA levels in children and adolescents. DEHP, DBP or its metabolites may be associated with altered hormone levels in children and adolescents. Data suggest that exposure levels of DEHP and DBP in Korean children need to be reduced to levels below TDI to protect them from EDC-mediated toxicities. Abbreviations: DBP: dibutyl phthalate; DEHP: di(2-ethylhexyl) phthalate; E2: estradiol; EDC: endocrine disrupting chemical; EFSA: European Food Safety Authority; FSH: follicle stimulating hormone; HDL: high density lipoprotein; HI: hazard index; LDL: low density lipoprotein; LH: luteinizing hormone; MEHP: mono(2-ethylhexyl) phthalate; MBP: monobutyl phthalate; PA: phthalic acid; PPAR: peroxisome proliferator-activated receptor gamma; PVC: polyvinyl chloride; T3: triiodothyronine; T4: thyroxine; TDI: tolerable daily intake; TG: triglyceride; TSH: thyroid stimulating hormone; UPLC/MS/MS: Ultra Performance Liquid Chromatography/Tandem Mass Spectrometry; WWF: World Wildlife Fund.

Synthesis, biodistribution and antitumor activity of hematoporphyrin-platinum(II) conjugates.

A new series of platinum(II) complexes of pegylated hematoporphyrin derivatives with controlled hydrophobic/hydrophilic balance were synthesized by introducing different kinds of poly(ethylene glycol) and amine ligands to the porphyrin ring. The antitumor activity of the porphyrin-platinum(II) conjugates was assayed in vitro and in vivo against leukemia L1210 cell line and various human tumor cell lines. The present complexes exhibited high antitumor activity and improved water solubility as well as considerable lipophilicity. In particular, complex 16 showed not only higher in vivo activity (T/C%=258) than cisplatin (T/C%=184) and carboplatin (T/C%=168), but also excellent solubility in water and organic solvent. The antitumor activity of complex 20 was superior to that of carboplatin against all human tumor cell lines tested. Moreover, some amphiphilic complexes (7 and 12) exhibited elevated tumor-localizing effect (tumor/muscle ratio>2).