Relationship and factors responsible for regulating fasting and post‐challenge plasma glucose levels in the early stage development of type 2 diabetes mellitus

Aims/Introduction

Elevation of 2-h plasma glucose (2-h PG) levels keeps step with fasting plasma glucose (FPG) levels elevation, but some individuals show dominant elevation of 2-h PG and others FPG. We analyzed dependent and independent relationships between 2-h PG and FPG, and investigated the factors regulating 2-h PG and FPG.

Materials and Methods

In 1,657 Japanese participants who underwent a 75-g oral glucose tolerance test at the initial examination for a medical check-up, we carried out simple linear regression analysis between 2-h PG and FPG levels on the three patterns of independent variables. We divided the participants into two subgroups: the 2-h PG-side group and the FPG-side from the regression line, and examined the relationships between 2-h PG-FPG and factors responsible for elevation of plasma glucose levels.

Results

There was a significant positive correlation between 2-h PG and FPG levels. The regression line of both 2-h PG and FPG as independent variables was in accordance with the regression line of 2-h PG as an independent variable and FPG as a dependent variable. In 2-h PG-side group, age was the independent factor affecting 2-h PG in addition to insulinogenic index and insulin sensitivity index (ISI composite). In the FPG-side group, triglyceride was the independent factor affecting FPG in addition to insulinogenic index and ISI composite.

Conclusions

Two-hour PG was an independent predictor of FPG. In addition to the importance of decreased insulin secretion and insulin sensitivity, age was the strong factor to elevate 2-h PG levels in the 2-h PG-side group and triglyceride was the strong factor to elevate FPG levels in the FPG-side group in the early stage of development of type 2 diabetes.     

Nonsurgical orthodontic treatment of a hypodivergent adult patient with bilateral posterior scissors bite and excessive overjet

This report illustrates successful nonsurgical orthodontic treatment of a hypodivergent adult patient with bilateral posterior scissors bite (Brodie bite) and excessive overjet. A 26-year-old woman primarily reported maxillary incisor protrusion. She was diagnosed with Class ll division 1 malocclusion with skeletal Class I, short face, low mandibular plane angle and bilateral posterior scissors bite. A lingual arch with anterior bite block and posterior miniscrews with preadjusted edgewise appliances were used to improve the bilateral scissors bite. After achieving molar occlusion, the maxillary first premolars were extracted, and six miniscrews were used to improve the anterior-posterior and vertical discrepancies. After active treatment for 56 months, the convex facial profile with excessively protruded lips was improved and good interdigitation with ideal incisor relationship was achieved. Additionally, the irregular movements of the incisal path and the bilateral condyles during lateral excursion were improved. At 13 months of retention, a satisfactory facial profile, occlusion, and jaw movements were maintained. The treatment results suggest that miniscrews and fixed bite blocks were effective and efficient to facilitate correction of the bilateral scissors bite, excessive overjet, and vertical relationship correction in this nonsurgical orthodontic treatment.     

Comprehensive lipid profiling of bleomycin‐induced lung injury

Drug‐induced lung injury is an adverse effect of drug treatment that can result in respiratory failure. Because lipid profiling could provide cutting‐edge understanding of the pathophysiology of toxicological responses, we performed lipidomic analyses of drug‐induced lung injury. We used a mouse model of bleomycin‐induced lung injury and followed the physiological responses at the acute inflammatory (day 2), inflammatory‐to‐fibrosis (day 7) and fibrosis (day 21) phases. The overall lipid profiles of plasma, lung and bronchoalveolar lavage fluid (BALF) revealed that drastic changes in lipids occurred in the lung and BALF, but not in the plasma, after 7 and 21 days of bleomycin treatment. In the lung, the levels of ether‐type phosphatidylethanolamines decreased, while those of phosphatidylcholines, bismonophosphatidic acids and cholesterol esters increased on days 7 and 21. In BALF, the global lipid levels increased on days 7 and 21, but only those of some lipids, such as phosphatidylglycerols/bismonophosphatidic acids and phosphatidylinositols, increased from day 2. The lung levels of prostaglandins, such as prostaglandin D₂, were elevated on day 2, and those of 5‐ and 15‐lipoxygenase metabolites of docosahexaenoic acid were elevated on day 7. In BALF, the levels of 12‐lipoxygenase metabolites of polyunsaturated fatty acids were elevated on day 7. Our comprehensive lipidomics approach suggested anti‐inflammatory responses in the inflammatory phase, phospholipidosis and anti‐inflammatory responses in the inflammatory‐to‐fibrosis phase, and increased oxidative stress and/or cell phenotypic transitions in the fibrosis phase. Understanding these molecular changes and potential mechanisms will help develop novel drugs to prevent or treat drug‐induced lung injury.     

Progressive Bundling of Fibrillin Microfibrils into Oxytalan Fibers in the Chick Presumptive Dermis

Dorsoventral fibers in the presumptive dermis of the chick limb bud reported first by Hurle's group in 1989 are now revealed as bundles of fibrillin microfibrils (Isokawa et al., 2004). The bundles, which could be called oxytalan fibers at the light microscopic level, are aligned perpendicularly to the overlying ectoderm and form a unique fiber array, originating directly from the basal lamina. This well‐oriented organization is beneficial in examining the process of in vivo bundling of microfibrils into oxytalan fibers. In this study, sections through the presumptive limb dermis were preferentially prepared from chick embryos at Days 4–6 (ED4‐6). Immunohistochemically, fibrillin‐positive dots representing cross‐sectioned surfaces of individual fibers, increased in size from ED4 to 6, but their number per unit area remained constant. Ultrastructurally, a single oxytalan fiber at ED4 consisted of ～15 microfibrils; the latter number increased fourfold from ED4 to 5 and threefold from ED5 to 6. Oxytalan fibers were all closely associated with mesenchymal cell; notably, the fibers at ED5 and 6 were held in a shallow ditch on the cell body or by lamellipodial cytoplasmic protrusion. In the sites of cell–fiber adhesion, microfibrils in the periphery of an oxytalan fiber appeared to adhere directly or by means of short flocculent strands to a nearby cell membrane; the latter showed a thickening of plasmalemma and its undercoat, indicating the presence of adhesive membrane specification. These findings suggest that the bundling of microfibrils is a progressive and closely cell‐associated process. Anat Rec, 2013. © 2012 Wiley Periodicals, Inc.     

FER overexpression is associated with poor postoperative prognosis and cancer-cell survival in non-small cell lung cancer

Here, we show that overexpression of fer tyrosine kinase (FER), a non-receptor tyrosine kinase, predicts poor postoperative outcome and might be involved in cancer-cell survival in non-small cell lung cancer (NSCLC). Systematic screening using in silico analyses and quantitative RT-PCR revealed that FER was overexpressed in about 10% of NSCLC patients. Evaluation of FER expression using immunohistochemistry (IHC) on tissue microarrays was consistent with the mRNA level detected using quantitative RT-PCR. In analyses of 135 NSCLC patients who had undergone potential curative resection, we found that FER overexpression detected using IHC had no association with clinicopathological features such as age, sex, smoking history, histological type, disease stage, T factor, N factor, adjuvant chemotherapy history, or EGFR mutation, but was correlated with poor postoperative survival periods. A multivariate Cox regression analysis showed that this prognostic impact was independent of other clinicopathological features. In functional analyses of FER in vitro, FER exhibited a transforming activity, suggesting that it possesses oncogenic functions. We also found that human lung cancer NCI-H661 cells, which exhibited FER-outlier expression, were led to apoptosis by the knockdown of FER using RNA interference. FER overexpression might serve as a prognostic biomarker and be involved in cancer-cell survival in NSCLC.