Purpose: Various protein contents such as enzymes, growth factors, and structural components are responsible for biological activities in organs. We have created a map of vitreous proteins and developed a proteome analysis of human vitreous samples to understand the underlying molecular mechanism and to provide clues to new therapeutic approaches in eyes with proliferative diabetic retinopathy (PDR). Methods: Vitreous and serum samples were obtained from subjects with idiopathic macular hole (MH, 26 cases) and PDR (33 cases). The expressed proteins in the samples were separated by two-dimensional (2-D) polyacrylamide gel electrophoresis. Protein spots were visualized by silver staining, and their expression patterns were analyzed. Some protein spots of concern were excised from the 2-D gels, digested in situ with trypsin, and analyzed by mass spectrometry. Results: More than 400 spots were detected on 2-D gels of MH cases, of which 78 spots were successfully analyzed. The spots corresponded to peptide fragments of 18 proteins, including pigment epithelium-derived factor, prostaglandin-D2 synthase, and interphotoreceptor retinoidbinding protein. These were not identified in the corresponding serum samples. These proteins were also expressed in PDR samples, with no distinct tendency to increase or decrease compared with the MH samples. More than 600 spots were detected on 2-D gels of PDR cases, of which 141 spots were successfully analyzed. The spots corresponded to peptide fragments of 38 proteins. Enolase and catalase were identified among four detected spots. Neither was found in MH vitreous or in PDR serum samples. Conclusion: A map of protein expression was made in human vitreous from eyes with MH and PDR. In the PDR eyes, the increased protein expression observed was due to barrier dysfunction and/or production in the eye. Proteome analysis was useful in systematic screening of various protein expression in human Hyperglycemia induces many abnormal changes, which are observed as diabetic retinopathy, in vascular and retinal cells in eyes with diabetes mellitus. The breakdown of the bloodretina barrier and new vessel formation are caused by hyperglycemia. In these processes, many hyperglycemia-induced biochemical changes occur, which cause vascular dysfunction. According to previous reports, various factors, including many kinds of proteins, are involved in the pathological processes of diabetic retinopathy. A breakdown of the bloodretina barrier is caused by an intraocular increase of vascular endothelial growth factor (VEGF) 1 (1-7), interleukin-6, angiotensin II, and many other cytokines and/or growth factors. New vessel formation is a very complex multistep process and is regulated by many proteins including cytokines and/or growth factors. In addition to the factors mentioned, basic fibroblast growth factor (bFGF) (8, 9), insulin-like growth factor-1 (4), hepatocyte growth factor (HGF) (6, 7), and others are known to be involved during the destructive processes of endogenous ocular tissue. Changes in the...

ObjectiveThe fact that population with type 2 diabetes mellitus and bodyweight of patients are increasing but diabetes care is improving makes it important to explore the up-to-date rates of achieving treatment targets and prevalence of complications. We investigated the prevalence of microvascular/macrovascular complications and rates of achieving treatment targets through a large-scale multicenter-based cohort.Research design and methodsA cross-sectional nationwide survey was performed on 9956 subjects with type 2 diabetes mellitus who consecutively attended primary care clinics. The prevalence of nephropathy, retinopathy, neuropathy, and macrovascular complications and rates of achieving targets of glycated hemoglobin (HbA1c) <7.0%, blood pressure <130/80 mm Hg, and lipids of low-density/high-density lipoprotein cholesterol <3.1/≥1.0 mmol/L and non-high-density lipoprotein cholesterol <3.8 mmol/L were investigated.ResultsThe rates of achieving targets for HbA1c, blood pressure, and lipids were 52.9%, 46.8% and 65.5%, respectively. The prevalence of microvascular complications was ∼28% each, 6.4% of which had all microvascular complications, while that of macrovascular complications was 12.6%. With an increasing duration of diabetes, the rate of achieving target HbA1c decreased and the prevalence of each complication increased despite increased use of diabetes medication. The prevalence of each complication decreased according to the number achieving the 3 treatment targets and was lower in subjects without macrovascular complications than those with. Adjustments for considerable covariates exhibited that each complication was closely inter-related, and the achievement of each target was significantly associated with being free of each complication.ConclusionsAlmost half of the subjects examined did not meet the recommended targets. The risk of each complication was significantly affected by 1 on-target treatment (inversely) and the concomitance of another complication (directly). Total diabetes care including one-by-one management of modifiable risk factors and complications may be important for high-quality care. The future studies including more subjects and clinics with precise complication status are needed.

A racial difference in the incidence of basal cell carcinoma, sebaceous gland carcinoma, and squamous cell carcinoma can be considered in making a diagnosis.

OBJECTIVELiraglutide (glucagon-like peptide-1 [GLP-1] receptor agonist) and sitagliptin (dipeptidyl peptidase-4 inhibitor) are approved in Japan for treating type 2 diabetes mellitus (T2DM). We compared the efficacy and safety of adding liraglutide or sitagliptin to a sulfonylurea in Japanese T2DM patients.METHODSPatients aged 18 to <80 years with hemoglobin A1c (HbA1c; National Glycohemoglobin Standardization Program [NGSP]) of 6.9–9.4%, body mass index ≤35 kg/m2, and treatment with a sulfonylurea and/or one or two non-sulfonylurea oral antidiabetic drugs for greater than or equal to eight weeks before enrollment were eligible. Patients were randomized in an open-label manner to either 0.9 mg/day liraglutide (n = 50) or 50–100 mg/day sitagliptin (n = 49) and were treated for 24 weeks. Non-sulfonylureas were discontinued before randomization. Patients using other oral antidiabetic drugs started sulfonylurea treatment. The primary endpoint was the change in HbA1c from baseline to Week 24.RESULTSHbA1c decreased in both groups, and the reduction was significantly greater throughout in the liraglutide group except for Week 24 (0.59 ± 0.80 vs. 0.24 ± 0.94%; P = 0.0525). Fasting plasma glucose (FPG) decreased significantly in the liraglutide group compared with the sitagliptin group (−21.15 ± 31.22 vs. +0.46 ± 39.39 mg/dL; P = 0.0014). Homeostasis model assessment of β cell function and C-peptide increased significantly in the liraglutide group but not in the sitagliptin group. Hypoglycemic symptoms and adverse events occurred in four and nine patients, respectively, in the liraglutide group, and in two and five patients, respectively, in the sitagliptin group.CONCLUSIONTreatment with liraglutide or sitagliptin together with a sulfonylurea improved HbA1c in Japanese T2DM patients in primary care. Both drugs were associated with low rates of adverse events and hypoglycemia. The improvement in β cell function probably contributed to the improvement in glycemic control in the liraglutide group.

. Purpose:  Previously, we established a porcine vitreous tissue‐derived hyalocyte cell line (PH5) and investigated the regulation of hyaluronan synthesis in these cells by cytokines. The objective of the current study was to establish human vitreous tissue‐derived cells and to compare their characteristics with those of PH5 cells. Methods:  Human vitreous specimens from two patients were cultured in the presence of 10% foetal bovine serum and immortalized by infection with human papilloma virus 16 genes E6 and E7. We used reverse transcription polymerase chain reaction (RT‐PCR) to analyse and compare the expression profiles for several genes in the human vitreous tissue‐derived cells and PH5 cells. To investigate the regulation of hyaluronan production in response to cytokine stimulation, the expression of hyaluronan synthase isoforms was examined using RT‐PCR, and hyaluronan production was measured using enzyme‐linked immunosorbent assay (ELISA). Results:  Two types of cells, HV64 and HV65, were derived from human vitreous tissue. The HV64 and HV65 cell‐doubling times were 58 hr and 76 hr, respectively. The cells expressed messenger RNA (mRNAs) encoding collagen type I α1 (COL1A1), collagen type II α1 (COL2A1), CD11b, CD14, CD68, CD204 and CD206 but did not express mRNA for glial fibrillary acidic protein (GFAP). Cytokine stimulation did not induce the expression of hyaluronan synthase mRNA or the production of hyaluronan. In contrast, mRNAs for GFAP and hyaluronan synthase‐2 were expressed in the porcine PH5 cells, and treatment with transforming growth factor‐β1 and/or platelet‐derived growth factor‐BB induced the production of hyaluronan in PH5 cells. Conclusion:  The new human vitreous tissue‐derived cells have macrophage‐like characteristics and are different from our previously developed porcine hyalocyte cells. These human vitreous tissue‐derived cells might be useful for studies of human intraocular diseases.