Dietary Intake of Polyunsaturated Fatty Acids and Diabetic Nephropathy: Cohort Analysis of the Tsugaru Study.

BACKGROUND/AIM: Diabetic nephropathy (DN) is the leading cause of end-stage renal failure and its incidence continues to increase. To decrease this, a countermeasure from an early stage is required. This is a DN stage 2 observation study that analyzed the results of a concurrent dietary survey in the Tsugaru study and discussed the relationship between dietary intake of n-3 fatty acid and DN. PATIENTS AND METHODS: Patients with stage 2 DN and aged 20 years or older in the Tsugaru region of Aomori Prefecture were enrolled. We examined the association between urinary albumin excretion (UAE) at enrollment and 36 months later and n-3PUFA intake obtained from a dietary survey. RESULTS: Of the 317 subjects at enrollment, 234 were followed for 36 months, of whom 123 were able to complete the dietary survey. After 36 months of follow-up of these 123 subjects, 28 were in remission and 18 had progressed. Correlations between UAE at 36 months and each of the parameters were examined and UAE at enrollment showed a positive correlation (r=0.4224, p<0.001); correlations between eicosapentaenoic acid (EPA)/arachidonic acid (AA), EPA+docosahexaenoic acid/AA, and n-6/n-3 and UAE at 36 months were weak. As shown by multiple regression analysis, the factor influencing UAE after 36 months was UAE at enrollment. CONCLUSION: Concerning the relationship between fatty acid intake balance and UAE, the previously reported renoprotective effect of n-3 fatty acids could not be demonstrated.

Prevalence of potential candidates for electric-acoustic stimulation implant in a hearing-impaired population.

OBJECTIVE: To estimate the prevalence of potential electric-acoustic stimulation (EAS) implant candidates in a hearing-impaired population through a review of auditory examinations. METHODS: In total, 7356 patients underwent audiometric examination in our department between 2011 and 2014. The prevalence of patients meeting the audiometric criteria for EAS and standard cochlear implant (CI) was assessed. RESULTS: The percentage of EAS implant candidates meeting the pure-tone audiometric criteria was 0.71% (n=34) among the hearing-impaired individuals (n=4758) examined in our department, whereas 2.52% (n=120) met the criteria for standard CI. Among the 34 EAS implant candidates, 2 individuals (5.83%) received EAS implant surgery after approval of the EAS device in Japan. CONCLUSIONS: There was a lower prevalence of EAS implant candidates than standard CI candidates. Nevertheless, healthcare professionals should carefully examine the audiograms of patients with high frequency hearing loss with regard to meeting the indication criteria for EAS implant. This will enable patients to gain access to adequate information relating to further examinations and treatment options.

Sulforaphane, a natural component of broccoli, inhibits vestibular schwannoma growth in vitro and in vivo.

Vestibular schwannoma (VS) is an intracranial tumor that causes significant morbidity, including hearing loss, tinnitus, dizziness, and possibly even death from brainstem compression. However, FDA-approved pharmacologic treatments for VS do not exist. Sulforaphane (SFN) is a naturally occurring isothiocyanate found in cruciferous vegetables, such as broccoli, with potent chemoprotective effects in several cell types. Our objective was to determine whether SFN is effective against VS in vitro and in vivo. Human primary VS cells, HEI-193 schwannoma cells, and SC4 Nf2-/- Schwann cells were used to investigate the inhibitory effects of SFN in vitro. Cell proliferation was assessed by bromodeoxyuridine (BrdU) incorporation, and cell viability and metabolic activity was calculated by MTT assay. Apoptosis was measured by flow cytometry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and Western blot for cleaved caspases. A mouse model with a murine schwannoma allograft was also used to examine the antitumor activity of SFN. SFN exhibited significant antiproliferative activity in schwannoma cells in vitro, via the inhibition of HDAC activity and the activation of ERK. SFN treatment induced apoptosis and cell cycle arrest at the G2/M phase. SFN also significantly inhibited schwannoma growth in vivo. Our preclinical studies motivate a future prospective clinical study of SFN for the treatment of VS.

Atomic-scale disproportionation in amorphous silicon monoxide.

Solid silicon monoxide is an amorphous material which has been commercialized for many functional applications. However, the amorphous structure of silicon monoxide is a long-standing question because of the uncommon valence state of silicon in the oxide. It has been deduced that amorphous silicon monoxide undergoes an unusual disproportionation by forming silicon- and silicon-dioxide-like regions. Nevertheless, the direct experimental observation is still missing. Here we report the amorphous structure characterized by angstrom-beam electron diffraction, supplemented by synchrotron X-ray scattering and computer simulations. In addition to the theoretically predicted amorphous silicon and silicon-dioxide clusters, suboxide-type tetrahedral coordinates are detected by angstrom-beam electron diffraction at silicon/silicon-dioxide interfaces, which provides compelling experimental evidence on the atomic-scale disproportionation of amorphous silicon monoxide. Eventually we develop a heterostructure model of the disproportionated silicon monoxide which well explains the distinctive structure and properties of the amorphous material.

Preclinical validation of anti-nuclear factor-kappa B therapy to inhibit human vestibular schwannoma growth.

Vestibular schwannomas (VSs), the most common tumors of the cerebellopontine angle, arise from Schwann cells lining the vestibular nerve. Pharmacotherapies against VS are almost non-existent. Although the therapeutic inhibition of inflammatory modulators has been established for other neoplasms, it has not been explored in VS. A bioinformatic network analysis of all genes reported to be differentially expressed in human VS revealed a pro-inflammatory transcription factor nuclear factor-kappa B (NF-κB) as a central molecule in VS pathobiology. Assessed at the transcriptional and translational level, canonical NF-κB complex was aberrantly activated in human VS and derived VS cultures in comparison to control nerves and Schwann cells, respectively. Cultured primary VS cells and VS-derived human cell line HEI-193 were treated with specific NF-κB siRNAs, experimental NF-κB inhibitor BAY11-7082 (BAY11) and clinically relevant NF-κB inhibitor curcumin. Healthy human control Schwann cells from the great auricular nerve were also treated with BAY11 and curcumin to assess toxicity. All three treatments significantly reduced proliferation in primary VS cultures and HEI-193 cells, with siRNA, 5 µM BAY11 and 50 µM curcumin reducing average proliferation (±standard error of mean) to 62.33% ± 10.59%, 14.3 ± 9.7%, and 23.0 ± 20.9% of control primary VS cells, respectively. These treatments also induced substantial cell death. Curcumin, unlike BAY11, also affected primary Schwann cells. This work highlights NF-κB as a key modulator in VS cell proliferation and survival and demonstrates therapeutic efficacy of directly targeting NF-κB in VS.

New series of avenanthramides in oat seed.

Avenanthramides are characteristic constituents of oat seeds. We analyzed the methanol extract of oat seeds by HPLC and detected three compounds 1, 2, and 3 eluted at retention times similar to avenanthramides. The three compounds were purified by column chromatography and HPLC. Spectroscopic analyses of 1, 2, and 3 suggested that they are amides of 4,5-dihydroxyanthranilic acid with caffeic, p-coumaric, and ferulic acids, respectively. Their identities were confirmed by comparing spectra and chromatographic behavior with compounds synthesized from 4,5-dihydroxyanthranilic acid and N-hyrdroxysuccinimide esters of hydroxycinnamic acids. LC-MS/MS analysis with multiple reaction monitoring showed that the amounts of 1, 2, and 3 were 16.5-26.9% of corresponding avenanthamides with 5-hydroxyanthranilic acid. Compounds 1, 2, and 3 showed stronger 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity than the corresponding avenanthramides with 5-hydroxyanthranilic acid, indicating the involvement of 4,5-dihydroxyanthranilic acid moiety in the scavenging of DPPH radicals.

Iodized oil accumulation in hypervascular hepatocellular carcinoma after transcatheter arterial chemoembolization: comparison of imaging findings with CT during hepatic arteriography.

PURPOSE: To compare the degree of tumor enhancement seen on computed tomography (CT) during hepatic arteriography (CT/HA) performed before transcatheter arterial chemoembolization (TACE) versus that determined based on the accumulation of iodized oil seen on CT images obtained after TACE in patients with hypervascular hepatocellular carcinoma (HCC) and evaluate the discrepancy in findings between the two imaging modalities (more or less oil accumulation after TACE compared with enhancement on CT/HA). MATERIALS AND METHODS: CT/HA, TACE, and iodized oil CT after TACE were performed in 69 patients with 83 hypervascular HCCs with use of an interventional CT system. The degree of contrast enhancement of the lesion on CT/HA and the iodized oil accumulation on unenhanced CT after TACE were compared. RESULTS: Among 83 HCCs, the degree of enhancement on CT/HA before TACE corresponded to the iodized oil accumulation on CT in 56 (67.5%). Fifteen of 83 HCCs (18%) showed incomplete or poor accumulation of iodized oil despite good enhancement on CT/HA images. Twelve of 83 HCCs (14.5%) showed moderate or complete accumulation of iodized oil despite poor or no enhancement on CT/HA images. In particular, in two patients with occluded portal veins, iodized oil did not accumulate in the tumor despite good visualization on CT/HA. CONCLUSIONS: Although iodized oil accumulation in hypervascular HCCs correlates with the degree of lesion enhancement on CT/HA in most cases, a discrepancy may occur in a substantial number of cases, which likely affects the prediction of therapeutic effects in hypervascular HCCs.

Beneficial effect of neutrophil elastase inhibitor on anti-Thy1.1 nephritis in rats.

BACKGROUND: Neutrophil elastase, one of the proteinases released by neutrophils, plays an important role at the sites of inflammation and was reported to be involved in the pathogenesis of glomerulonephritis. Sivelestat is a selective neutrophil elastase inhibitor used for acute lung injury associated with systemic inflammatory response syndrome. There have been few reports on the effects of sivelestat on renal disease. METHODS: In male Wistar rats, anti-Thy1.1 nephritis was induced by the injection of anti-Thy1.1 antibody. The rats were divided into four groups: nephritic rats treated with low- (group A) and high-dose sivelestat (group B), those not treated with sivelestat (group C) and control rats (group D). Urine samples were obtained every day during the experiment. The rats were killed on day 6 in order to obtain the blood plasma and kidneys. Measurement of urine protein levels, blood biochemical values and histological examination of the kidneys were carried out. RESULTS: Increased levels of proteinuria were observed in the nephritic rats (groups A, B and C) compared with group D. The proteinuria level was significantly suppressed by sivelestat in groups A and B in a dose-dependent fashion compared with group C. The light microscopy revealed an increased glomerular cell count in group C, which was significantly suppressed in group B. In the electron microscopic study, sivelestat suppressed the fusion of epithelial foot process, especially in group B. CONCLUSION: Neutrophil elastase is suggested to be involved in the development of anti-Thy1.1 nephritis, and the neutrophil elastase inhibitor sivelestat reduces the tissue injury of anti-Thy1.1 nephritis in rats.