The Role of Apelin on the Alleviative Effect of Angiotensin Receptor Blocker in Unilateral Ureteral Obstruction-Induced Renal Fibrosis

Background: Apelin is a selective endogenous ligand of the APJ receptor, which genetically has closest identity to the angiotensin II type 1 receptor (AT-1). The effects of the apelin/APJ system on renal fibrosis still remain unclear. Methods: We examined the effects of the apelin/APJ system on renal fibrosis during AT-1 blockade in a mouse unilateral ureteral obstruction (UUO) model. Results: We obtained the following results: (1) At UUO day 7, mRNA expressions of apelin/APJ and phosphorylations of Akt/endothelial nitric oxide synthase (eNOS) in the UUO kidney were increased compared to those in the nonobstructed kidney. (2) AT-1 blockade by the treatment with losartan resulted in a further increase of apelin mRNA as well as phosphorylations of Akt/eNOS proteins, and this was accompanied by alleviated renal interstitial fibrosis, decreased myofibroblast accumulation, and a decreased number of interstitial macrophages. (3) Blockade of the APJ receptor by the treatment with F13A during losartan administration completely abrogated the effects of losartan in the activation of the Akt/eNOS pathway and the amelioration of renal fibrosis. (4) Inhibition of NOS by the treatment with L-NAME also resulted in a further increase in renal fibrosis compared to the control group. Conclusion: These results suggest that increased nitric oxide production through the apelin/APJ/Akt/eNOS pathway may, at least in part, contribute to the alleviative effect of losartan in UUO-induced renal fibrosis

Magnetic Flux-Based Nondestructive Evaluation Technologies for Assessing Corrosion Damage in External and Internal Post-Tensioned Tendons: Development Efforts and Evaluation Results

DTFH61-14-D-00011This report presents research work related to developing and evaluating magnetic flux-based nondestructive evaluation (NDE) technologies for detecting corrosion damage in external and internal post-tensioned (PT) tendons. For the external tendons, two types of magnetic main flux method (MMFM) systems\u2014a solenoid type and a permanent magnet type\u2014 were developed and validated in the laboratory and in the field. The solenoid-type MMFM system was the most accurate NDE method. Its lowest damage detection limit would be 0.4-percent section loss for the point measurement method and 1.0-percent section loss for the scan measurement method. The permanent-type MMFM system is suitable for locating potential problem areas containing more than 3.0-percent section loss in external PT tendons. It has more versatile applications in the field because of its simpler hardware and speedy operation. Ideally, both MMFM systems can be employed in sequence during the field investigations: the permanent magnet type identifies potentially problematic areas by quickly scanning all suspected tendons, followed by the point measurements in the suspicious areas with the solenoid type. A return flux method prototype was developed for the internal tendons. It reached the immediate goal of detecting relatively small section losses hidden in internal tendons in laboratory environments and proved its concept successfully. It could detect a section loss larger than 15.3-percent in internal mockup tendons surrounded by vertical rebars at 6.0-inch or wider spacing when the clear concrete cover was less than 7.5 inches for metal ducts and 6.5 inches for polyethylene ducts. Without interference from the vertical rebars, as little as 9.0-percent section loss could be identified at the 6.0-inch cover. However, poor results were obtained in the anchorage zone in the box girder specimen. It is recommended that the present prototype be further improved to make it a field-deployable NDE system

Micro-CT image analysis of fracture callus at day 14 in B6 and <i>DAP12</i>^{<i>–/–</i>} mice.

<p>(A) Representative axial images of fracture callus in B6 and <i>DAP12</i>^{<i>–/–</i>} mice. Dense trabecular structure and deteriorated cortical shell formation on the surface in <i>DAP12</i>^{<i>–/–</i>} mice compared with B6 mice. (B) Structural parameter analysis of fracture callus of B6 and <i>DAP12</i>^{<i>–/–</i>} mice. Trabecular thickness was significantly larger in <i>DAP12</i>^{<i>–/–</i>} mice than in B6 mice, and the percentage of new cortical shell area was significantly lower in <i>DAP12</i>^{<i>–/–</i>} mice. There were no significant differences in TV, BV/TV, Tb.N or Tb.Sp. *<i>p</i><0.05.</p

Immunostaining using an anti-F4/80 antibody.

<p>(A) Representative images of fracture hematoma at day 3. Scale bar = 200 μm. <i>DAP12</i>^{<i>–/–</i>} mice showed less fluorescence from F4/80-positive cells in fracture hematoma. (B) Quantitative analysis of F4/80-positive cells. The number of F4/80-positive cells was significantly decreased in <i>DAP12</i>^{<i>–/–</i>} mice than in B6 mice. *<i>p</i><0.05.</p

mRNA expression of osteogenic, chondrogenic and proinflammatory genes.

<p>(A) Expression levels of <i>Col1a1</i>, <i>Col2a1</i>, and <i>Col10a1</i> in the fracture callus. <i>DAP12</i>^{<i>–/–</i>} mice demonstrated a delayed increase in <i>Col1a1</i> gene expression. <i>DAP12</i>^{<i>–/–</i>} mice showed significantly lower expression of <i>Col1a1</i> at day 7 and significantly higher expression at day 14. In <i>DAP12</i>^{<i>–/–</i>} mice, the expression of <i>Col2a1</i> and <i>Col10a1</i> was significantly lower at day 5 and significantly higher at day 14. <i>DAP12</i>^{<i>–/–</i>} mice showed delayed decreases in <i>Col2a1</i> and <i>Col10a1</i> gene expression. (B) Expression levels of <i>Tnf</i>, <i>Il1b</i>, and <i>Il6</i> in fracture hematomas. The expression of <i>Tnf</i> was significantly lower in <i>DAP12</i>^{<i>–/–</i>} mice at days 3 and 5. There were no significant differences in the expression of <i>Il1b</i> or <i>Il6</i>. *<i>p</i><0.05, **<i>p</i><0.01, ***<i>p</i><0.001.</p

The Left Superior Longitudinal Fasciculus within the Primary Sensory Area of Inferior Parietal Lobe Plays a Role in Dysgraphia of Kana Omission within Sentences

Functional neurological changes after surgery combined with diffusion tensor imaging (DTI) tractography can directly provide evidence of anatomical localization of brain function. Using these techniques, a patient with dysgraphia before surgery was analyzed at our hospital in 2011. The patient showed omission of kana within sentences before surgery, which improved after surgery. The brain tumor was relatively small and was located within the primary sensory area (S1) of the inferior parietal lobe (IPL). DTI tractography before surgery revealed compression of the branch of the superior longitudinal fasciculus (SLF) by the brain tumor. These results suggest that the left SLF within the S1 of IPL plays a role in the development of dysgraphia of kana omission within sentences