Impairment of cerebellar long‑term depression and GABAergic transmission in prion protein deficient mice ectopically expressing PrPLP/Dpl

Prion protein (PrPC) knockout mice, named as the “Ngsk” strain (Ngsk Prnp0/0 mice), show late-onset cerebellar Purkinje cell (PC) degeneration because of ectopic overexpression of PrPC-like protein (PrPLP/Dpl). Our previous study indicated that the mutant mice also exhibited alterations in cerebellum-dependent delay eyeblink conditioning, even at a young age (16 weeks of age) when neurological changes had not occurred. Thus, this electrophysiological study was designed to examine the synaptic function of the cerebellar cortex in juvenile Ngsk Prnp0/0 mice. We showed that Ngsk Prnp0/0 mice exhibited normal paired-pulse facilitation but impaired long-term depression of excitatory synaptic transmission at synapses between parallel fibres and PCs. GABAA-mediated inhibitory postsynaptic currents recorded from PCs were also weakened in Ngsk Prnp0/0 mice. Furthermore, we confirmed that Ngsk Prnp0/0 mice (7–8-week-old) exhibited abnormalities in delay eyeblink conditioning. Our findings suggest that these alterations in both excitatory and inhibitory synaptic transmission to PCs caused deficits in delay eyeblink conditioning of Ngsk Prnp0/0 mice. Therefore, the Ngsk Prnp0/0 mouse model can contribute to study underlying mechanisms for impairments of synaptic transmission and neural plasticity, and cognitive deficits in the central nervous system

Vaporized Hydrogen Peroxide and Ozone Gas Synergistically Reduce Prion Infectivity on Stainless Steel Wire

Prions are infectious agents causing prion diseases, which include Creutzfeldt–Jakob disease (CJD) in humans. Several cases have been reported to be transmitted through medical instruments that were used for preclinical CJD patients, raising public health concerns on iatrogenic transmissions of the disease. Since preclinical CJD patients are currently difficult to identify, medical instruments need to be adequately sterilized so as not to transmit the disease. In this study, we investigated the sterilizing activity of two oxidizing agents, ozone gas and vaporized hydrogen peroxide, against prions fixed on stainless steel wires using a mouse bioassay. Mice intracerebrally implanted with prion-contaminated stainless steel wires treated with ozone gas or vaporized hydrogen peroxide developed prion disease later than those implanted with control prion-contaminated stainless steel wires, indicating that ozone gas and vaporized hydrogen peroxide could reduce prion infectivity on wires. Incubation times were further elongated in mice implanted with prion-contaminated stainless steel wires treated with ozone gas-mixed vaporized hydrogen peroxide, indicating that ozone gas mixed with vaporized hydrogen peroxide reduces prions on these wires more potently than ozone gas or vaporized hydrogen peroxide. These results suggest that ozone gas mixed with vaporized hydrogen peroxide might be more useful for prion sterilization than ozone gas or vaporized hydrogen peroxide alone

Pengaruh Dimensi Benda Uji Terhadap Kuat Tekan Beton

Kuat tekan adalah karakteristik mekanik utama dari beton yang dapat diketahui melalui penelitian uji tekan di laboratorium terhadap benda uji. Baik dalam bentuk kubus ataupun silinder dengan ukuran standar: 10cm x 10cm x 10cm dan 15cm x 15cm untuk kubus dan 10cm x 20cm dan 15cm x 30cm untuk silinder. Untuk mendapatkan informasi mengenai kecendrungan harga kuat tekan beton dengan variasi dimensi benda uji, telah dilakukan penelitian-penelitian di laboratoriun untuk mendapatkan komposisi campuran tertentu pada umur beton 28 hari, variasi ukuran benda uji dibuat: 10cm x 10cm x 10cm, 12,5cm x 12,5cm x 12,5cm dan 15cm x 15cm x 15cm untuk kubus dan 10cm x 20cm, 12,5cm x 25cm dan 15cm x 30cm untuk silinder. Dengan jumlah benda uji masing-masing 20 buah untuk setiap ukuran benda uji. Melalui prosedur standar pengujian kuat tekan dan menggunakan formula-formula baku perhitungan tekan rata-rata diperoleh informasi bahwa peningkatan ukuran dimensi benda uji menghasilkan penurunan kuat tekan rata-rata, untuk benda uji kubus dengan ukuran masing-masing: 10cm x 10cm x 10cm, 12,5cm x 12,5cm x 12,5cm dan 15cm x 15cm x 15cm diperoleh kuat tekan rata-rata masing-masing: 32,86MPa, 31,26MPa dan 31,036MPa. Sedangkan untuk silinder dengan kururan 10cm x 20cm, 12,5cm x 25cm dan 15cm x 30cm diperoleh kuat tekan rata-rata masing-masing: 31,47MPa, 30,85MPa dan 30,44MPa

Age-specific serum anti-Müllerian hormone concentration in Japanese women and its usefulness as a predictor of the ovarian response

Purpose: To compare the ovarian response predictive ability of anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), and estradiol (E2) and to determine the age-specific distribution of serum AMH concentrations of Japanese women. Methods: This was a multicenter (four-site), observational, analytic, cross-sectional Japanese study consisting of two parts: Study 1 (the prediction of the ovarian response of 236 participants who were undergoing controlled ovarian stimulation [COS]) and Study 2 (the distribution of the AMH concentration with an assay of 417 healthy women who were aged 20-49 years and who had normal menstrual cycles). Results: The AMH had a significantly higher predictive value for the normal and high responders than FSH and E2 as a stronger correlation between the ovarian response and AMH was observed than for FSH and E2. The serum AMH concentration decreased proportionally with age. Conclusion: The AMH concentration correlated well with the oocyte count in the patients who were undergoing COS for in vitro fertilization and was shown to predict the risk of ovarian hyperstimulation syndrome among these patients

A Proteomic Approach for the Diagnosis of ‘Oketsu’ (blood stasis), a Pathophysiologic Concept of Japanese Traditional (Kampo) Medicine

‘Oketsu’ is a pathophysiologic concept in Japanese traditional (Kampo) medicine, primarily denoting blood stasis/stagnant syndrome. Here we have explored plasma protein biomarkers and/or diagnostic algorithms for ‘Oketsu’. Sixteen rheumatoid arthritis (RA) patients were treated with keishibukuryogan (KBG), a representative Kampo medicine for improving ‘Oketsu’. Plasma samples were diagnosed as either having an ‘Oketsu’ (n = 19) or ‘non-Oketsu’ (n = 29) state according to Terasawa's ‘Oketsu’ scoring system. Protein profiles were obtained by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) and hierarchical clustering and decision tree analyses were performed. KBG treatment for 4 or 12 weeks decreased the ‘Oketsu’ scores significantly. SELDI protein profiles gave 266 protein peaks, whose expression was significantly different between the ‘Oketsu’ and ‘non-Oketsu’ states. Hierarchical clustering gave three major clusters (I, II, III). The majority (68.4%) of ‘Oketsu’ samples were clustered into one cluster as the principal component of cluster I. The remaining ‘Oketsu’ profiles constituted a minor component of cluster II and were all derived from patients cured of the ‘Oketsu’ state at 12 weeks. Construction of the decision tree addressed the possibility of developing a diagnostic algorithm for ‘Oketsu’. A reduction in measurement/pre-processing conditions (from 55 to 16) gave a similar outcome in the clustering and decision tree analyses. The present study suggests that the pathophysiologic concept of Kampo medicine ‘Oketsu’ has a physical basis in terms of the profile of blood proteins. It may be possible to establish a set of objective criteria for diagnosing ‘Oketsu’ using a combination of proteomic and bioinformatics-based classification methods

DNA Methylation Profiles of Primary Colorectal Carcinoma and Matched Liver Metastasis

BACKGROUND: The contribution of DNA methylation to the metastatic process in colorectal cancers (CRCs) is unclear. METHODS: We evaluated the methylation status of 13 genes (MINT1, MINT2, MINT31, MLH1, p16, p14, TIMP3, CDH1, CDH13, THBS1, MGMT, HPP1 and ERα) by bisulfite-pyrosequencing in 79 CRCs comprising 36 CRCs without liver metastasis and 43 CRCs with liver metastasis, including 16 paired primary CRCs and liver metastasis. We also performed methylated CpG island amplification microarrays (MCAM) in three paired primary and metastatic cancers. RESULTS: Methylation of p14, TIMP3 and HPP1 in primary CRCs progressively decreased from absence to presence of liver metastasis (13.1% vs. 4.3%; 14.8% vs. 3.7%; 43.9% vs. 35.8%, respectively) (P<.05). When paired primary and metastatic tumors were compared, only MGMT methylation was significantly higher in metastatic cancers (27.4% vs. 13.4%, P = .013), and this difference was due to an increase in methylation density rather than frequency in the majority of cases. MCAM showed an average 7.4% increase in DNA methylated genes in the metastatic samples. The numbers of differentially hypermethylated genes in the liver metastases increased with increasing time between resection of the primary and resection of the liver metastasis. Bisulfite-pyrosequencing validation in 12 paired samples showed that most of these increases were not conserved, and could be explained by differences in methylation density rather than frequency. CONCLUSIONS: Most DNA methylation differences between primary CRCs and matched liver metastasis are due to random variation and an increase in DNA methylation density rather than de-novo inactivation and silencing. Thus, DNA methylation changes occur for the most part before progression to liver metastasis

Efficacy and Safety of Topical Travoprost with Sofzia(R) Preservative for Japanese Glaucoma Patients

The purpose of this study is to evaluate the intraocular pressure (IOP) -lowering effect and safety of topical travoprost with sofziaR and without benzalkonium chloride on Japanese patients with glaucoma. Topical travoprost (0.04%) was used on 39 glaucoma patients with no prior use of topical prostaglandin F2a analogues (Beginning group). The IOP, number of conjunctiva! follicules, degrees of conjunctiva! hyperemia, and degrees of superficial punctate keratitis (SPK, AD-classification) were determined at the beginning of the treatment and after 1 month and 3 months. 37 other patients who were using 0.005% topical latanoprost were switched to 0.04% topical travoprost and analyzed in the same way (Switched group). For the Beginning group, the IOP was significantly decreased after 3 months (p <0.0001). The conjunctiva! follicule score was decreased significantly (p =0.033). Both the SPK area score and density score for the cases with SPK at the baseline decreased significantly (p =0.034 and p =0.024). In the switched group, the IOP was not changed significantly at 3 months after the switch (p =0.118). Both the conjunctiva! follicule and hyperemia score were significantly decreased at 3 month (p =0.0074 and p =0.0047). The SPK area score for the cases with SPK at the time of switch decreased significantly (p =0.013). Travoprost with sofziaR preservative had an equal effect in reducing the IOP as latanoprost. It had low toxicity on the ocular surface of Japanese glaucoma patients