光2+2環化付加反応を利用した複素環化合物への炭素鎖導入法の開発

金沢大学薬学部研究課題/領域番号:58771584, 研究期間(年度):1983出典：研究課題「光2+2環化付加反応を利用した複素環化合物への炭素鎖導入法の開発」課題番号58771584（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-58771584/）を加工して作

Lemon Polyphenols Suppress Diet-induced Obesity by Up-Regulation of mRNA Levels of the Enzymes Involved in β-Oxidation in Mouse White Adipose Tissue

The aim of this study was to investigate the effect of dietary lemon polyphenols on high-fat diet-induced obesity in mice, and on the regulation of the expression of the genes involved in lipid metabolism to elucidate the mechanisms. Mice were divided into three groups and fed either a low fat diet (LF) or a high fat diet (HF) or a high fat diet supplemented with 0.5% w/w lemon polyphenols (LP) extracted from lemon peel for 12 weeks. Body weight gain, fat pad accumulation, the development of hyperlipidemia, hyperglycemia, and insulin resistance were significantly suppressed by lemon polyphenols. Supplementation with lemon polyphenols also significantly up-regulated the mRNA level of the peroxisome proliferator activated receptor-α (PPARα) compared to the LF and HF groups in the liver. Furthermore, the mRNA level of acyl-CoA oxidase (ACO) was up-regulated in the LP group compared to the LF group, but not HF group in the liver, and was also significantly increased in the epididymal white adipose tissue. Thus, feeding with lemon polyphenols suppressed body weight gain and body fat accumulation by increasing peroxisomal β-oxidation through up-regulation of the mRNA level of ACO in the liver and white adipose tissue, which was likely mediated via up-regulation of the mRNA levels of PPARα

Efficacy of combined photodynamic therapy and sub-Tenon’s capsule injection of triamcinolone acetonide for age-related macular degeneration

Purpose : To evaluate the efficacy of combined photodynamic therapy (PDT) and sub-Tenon’s capsule injection of triamcinolone acetonide (TA) for the treatment of choroidal neovascularization (CNV) in age-related macular degeneration (AMD) at 1-year follow-up. Methods : A total of 117 eyes with subfoveal CNV caused by AMD were included. Sixty-eight eyes were treated with combined PDT and sub-tenon injection of 20 mg TA and compared with a control group of 49 eyes treated with PDT alone. All patients completed 1 year follow-up. The main outcome measures were best-corrected visual acuity (BCVA) and retreatment frequency. Results : There were no significant differences in age, sex, VA, lesion type, and greatest linear dimension between the two groups at baseline. BCVA analysis showed statistically no significant differences between the two groups. The PDT+TA group required a lower mean number of treatments (1.38 versus 1.67, P=0.032). Conclusion : Our study confirms that sub-Tenon’s capsule injection of TA with PDT significantly reduces the retreatment frequency of PDT

Quantification of Modified Tyrosines in Healthy and Diabetic Human Urine using Liquid Chromatography/Tandem Mass Spectrometry

The quantification of urinary oxidized tyrosines, dityrosine (DiY), nitrotyrosine (NY), bromotyrosine (BrY), and dibromotyrosine (DiBrY), was accomplished by quadruple liquid chromatography-tandem mass spectrometry (LC/MS/MS). The sample was partially purified by solid phase extraction, and was then applied to the LC/MS/MS using multiple-reaction monitoring (MRM) methods. The analysis for the DiY quantification was done first. The residual samples were further butylated with n-butanol/HCl, and the other modified tyrosines were then quantified with isotopic dilution methods. MRM peaks of the modified tyrosines (DiY, NY, BrY, and DiBrY) from human urine were measured and the elution times coincided with the authentic and isotopic standards. The amounts of modified tyrosines in healthy human urine (n = 23) were 8.8 ± 0.6 (DiY), 1.4 ± 0.4 (NY), 3.8 ± 0.3 (BrY), and 0.7 ± 0.1 (DiBrY) µmol/mol of creatinine, respectively. A comparison of the modified tyrosines with urinary 8-oxo-deoxyguanosine, pentosidine, and Nε-(hexanoyl)lysine was also performed. Almost all products, except for NY, showed good correlations with each other. The amounts of the modified tyrosines (NY, BrY, and DiBrY) in the diabetic urine were higher than those in the urine from healthy people

Reactions of 6-metheoxy-3-azabicyclo[4.2.0]octan-2-one and its 7-substituted derivatives

金沢大学大学院自然科学研究科生理活性物質科学金沢大学薬学

Efficacy of intravitreal bevacizumab (AvastinTM) for short-term treatment of diabetic macular edema

Purpose : To report the efficacy of intravitreal injections of bevacizumab for diabetic macular edema (DME) in the short-term. Design : Retrospective, noncomparative, interventional case series.Methods : Medical records of 20 eyes of 19 patients who underwent intravitreal injections of bevacizumab for persistent diabetic macular edema were reviewed retrospectively. All eyes received intravitreal injections of bevacizumab (1.25 mg/ 0.05 ml). The clinical course of best-corrected visual acuity (BCVA) using a logarithm of the minimum angle of resolution chart, and averaged foveal retinal thickness using an optical coherence tomography (OCT) were monitored for up to four weeks after the injection. Results : BCVA at one week improved by two lines or more in six eyes (30%) and in nine eyes (45%) at four weeks. However, no significant improvement in the mean BCVA from baseline was observed at one week (P>0.05) and four weeks (P>0.05). Mean retinal thicknesses (RT) were 411±170μm at baseline, 349±102μm at one week after the injection (P0.05). One week after the injection, significant regression of macular edema was seen. However, recurrence occurred at four weeks. No complications such as severe vision loss, endophthalmitis, or systemic events developed. Conclusion : No changes in BCVA and RT were observed in the short-term observation after the intravitreal injection of bevacizumab for DME

Results of submacular surgery to remove diabetic submacular hard exudates

Purpose : To evaluate outcomes of submacular surgery to remove massive submacular hard exudates with diabetic macular edema. Design : Retrospective, noncomparative, interventional consecutive case series. Participants : Fifty-six eyes of 40 patients with massive submacular hard exudates with diabetic macular edema. Intervention : Submacular surgery was performed to remove massive submacular hard exudates. Main Outcome Measures : Preoperative and postoperative visual acuities and clinical findings. All patients were followed for more than 1 year postoperatively. Results : The macular hard exudates underlying the fovea almost disappeared, and macular edema remarkably reduced following surgery. Visual acuities ranged from 0.01 to 0.3 before surgery, and from 0.04 to 1.0 after surgery. Visual acuity improved by two lines or more in 45 eyes (80.4%), remained unchanged in 8 eyes (14.3%) and worsened in 3 eyes (5.3%). Visual acuity improved to 0.3 or more in 24 eyes (42.9%). Better postoperative visual acuity (0.3 or better) was related to hemoglobin A1C (HbA1C) and the size of hard exudates. Conclusions : Results showed the efficacy of submacular surgery to remove massive hard exudates with diabetic macular edema, and outcomes were satisfactory

Diagnostic imaging in patients with retinitis pigmentosa

Retinitis pigmentosa (RP) is a progressive inherited retinal disease, and patients with RP have reduced visual function caused by a degeneration of the photoreceptors and retinal pigment epithelium (RPE). At the end stage of RP, the degeneration of the photoreceptors in the fovea reduces central vision, and RP is one of the main causes of acquired blindness in developed countries. Therefore, morphological and functional assessments of the photoreceptors in the macula area can be useful in estimating the residual retinal function in RP patients. Optical coherence tomography (OCT) is a wellestablished method of examining the retinal architecture in situ. The photoreceptor inner/outer segment (IS/OS) junction is observed as a distinct, highly reflective line by OCT. The presence of the IS/OS junction in the OCT images is essential for normal visual function. Fundus autofluorescence (FAF) results from the accumulation of lipofuscin in the RPE cells and has been used to investigate RPE and retinal function. More than one-half of RP patients have an abnormally high density parafoveal FAF ring (AF ring). The AF ring represents the border between functional and dysfunctional retina. In this review, we shall summarize recent progress on diagnostic imaging in eyes with RP

Wound sealing-related complications of 25-gauge vitrectomy in proliferative diabetic retinopathy versus simple macular pathology

Purpose : To compare the incidence of wound sealing-related complications of 25-gauge transconjunctival sutureless vitrectomy (25-G TSV) for proliferative diabetic retinopathy (PDR) versus non-diabetic simple macular pathology (SMP). Methods : A retrospective comparative study was conducted on 377 eyes that underwent 25-G TSV for PDR (n=189 eyes) or non-diabetic SMP (n=188 eyes). Both groups were compared retrospectively and followed for at least 1 month (range 1-6 months). Main outcome measure was the incidence of postoperative wound sealing-related complications in both groups. Results : We found a statistically significant lower incidence of wound sealing-related complications on the 1st postoperative day in the PDR than SMP group (P-value 0.05). The incidence were as follows : 9% vs 18% for hypotony, 0% vs 2% for choroidal detachment, 0% vs 2% for external leakage and 1% vs 8% for conjunctival bleb formation, for the PDR and SMP groups respectively. This was associated with a significantly higher postoperative inflammation and IOP in PDR group. The day 1 higher postoperative IOP and inflammation were correlated with the presence of PDR pathology. Conclusion : The higher postoperative inflammation and IOP following vitrectomy in diabetic eyes, especially when combined with endolaser photocoagulation, makes such eyes less susceptible to wound sealing-related complications following sutureless vitrectomy

Detection of Nε-(hexanoyl)lysine in the tropomyosin 1 protein in N-methyl-N'-nitro-N-nitrosoguanidine-induced rat gastric cancer cells

Nε-(Hexanoyl)lysine, formed by the reaction of lysine with n-6 lipid hydroperoxide, is a lipid peroxidation marker during the initial stage of oxidative stress. The aim of the present study is to indentify Nε-(hexanoyl)lysine-modified proteins in neoplastic transformed gastric mucosal cells by N-methyl-N'-nitro-N-nitrosoguanidine, and to compare the levels of these proteins between gastric mucosal cells and normal gastric cells. Much greater fluorescence of 2-[6-(4'-hydroxy)phenoxyl-3H-xanthen-3-on-9-yl]benzoic acid, an index of the intracellular levels of reactive oxygen species, was observed for gastric mucosal cells compared to normal gastric cells. Nε-(Hexanoyl)lysine-modified proteins were detected by SDS-PAGE or two-dimensional electrophoresis and Western blotting using anti-Nε-(hexanoyl)lysine polyclonal antibody, and a protein band of between 30–40 kDa was clearly increased in gastric mucosal cells compared to normal gastric cells. Two Nε-(hexanoyl)lysine-modified protein spots in gastric mucosal cells were identified as the tropomyosin 1 protein by mass spectrometry using a MASCOT search. The existence of Nε-(hexanoyl)lysine modification in tropomyosin 1 was confirmed by Western blotting of SDS-PAGE-separated or two-dimensional electrophoresis-separated proteins as well as by the immunoprecipitation with anti-tropomyosin 1 antibody. These data indicate that Nε-(hexanoyl)lysine modification of tropomyosin 1 may be related to neoplastic transformation by N-methyl-N'-nitro-N-nitrosoguanidine in gastric epithelial cells