Adrenomedullin regenerates alveoli and vasculature in elastase-induced pulmonary emphysema in mice

RATIONALE: Adrenomedullin, a potent vasodilator peptide, regulates cell growth and survival. However, whether adrenomedullin contributes to lung regeneration remains unknown. OBJECTIVES: To investigate whether adrenomedullin influences the kinetics of bone marrow cells, and whether adrenomedullin promotes regeneration of alveoli and vasculature and thereby improves lung structure and function in elastase-induced emphysema in mice. METHODS: Adrenomedullin or vehicle was randomly administered to C57BL/6 mice for 5 days. We counted the numbers of mononuclear cells and stem cell antigen-1-positive cells in circulating blood. After intratracheal injection of elastase or saline, mice were randomized to receive continuous infusion of adrenomedullin or vehicle for 14 days. Functional and histologic analyses were performed 28 days after treatment. RESULTS: Twenty-eight days after elastase injection, destruction of the alveolar walls was observed. However, adrenomedullin infusion significantly inhibited the increase in lung volume, static lung compliance, and mean linear intercept in mice given elastase. Adrenomedullin increased the numbers of mononuclear cells and stem cell antigen-1-positive cells in circulating blood. Adrenomedullin significantly increased the number of bone marrow-derived cells incorporated into the elastase-treated lung. Some of these cells were positive for cytokeratin or von Willebrand factor. Infusion of adrenomedullin after the establishment of emphysema also had beneficial effects on lung structure and function. In vitro, addition of adrenomedullin attenuates elastase-induced cell death in alveolar epithelial cells and endothelial cells. CONCLUSIONS: Adrenomedullin improved elastase-induced emphysema at least in part through mobilization of bone marrow cells and the direct protective effects on alveolar epithelial cells and endothelial cells.     

Splenectomy-reduced hepatic injury induced by ischemia/reperfusion in the rat

Abstract: In the present study, we investigated the role of the spleen in experimental hepatic ischemia/reperfusion in the rat. After a 90-min period of ischemia in the left and middle hepatic lobes, the ischemia was released and the liver was reperfused for up to 24 h. Plasma alanine aminotransferase reached a peak 3 h after the onset of reperfusion, and gradually decreased thereafter. A histological examination revealed evidence of hepatocellular necrosis and degeneration, especially 24 h after the onset of reperfusion. In addition, there was a noticeable accumulation of polymorphonuclear cells in the liver following ischemia/reperfusion. A splenectomy performed just prior to ischemia/reperfusion reduced both biochemical and histological hepatocellular injury. The number of polymorphonuclear cells in the liver following ischemia/reperfusion was significantly reduced in rats subjected to splenectomy, suggesting that the increase in polymorphonuclear cells may contribute to liver injury. The number of mononuclear cells also increased in the marginal zones of the spleen following ischemia/reperfusion, and appeared to be derived from the splenic monocyte/macrophage population, based on immunohistochemical studies. The spleen plays an important role in the pathogenesis of hepatic ischemia/reperfusion injury and the splenic monocyte/macrophage population contributes to liver damage.     

Maturation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes by Soluble Factors from Human Mesenchymal Stem Cells

1. Download high-res image (220KB)
2. Download full-size image

     

Sonographic findings in two cases of lymphangioma of the mesocolon in adults

Lymphangioma of the mesocolon is very rare. We report two cases of surgically resected and histologically proven mesocolic lymphangioma in adults. In both cases, ultrasound revealed a large cystic mass with multiple thin septa in the lower abdomen. A peculiar finding was the large craniocaudal sliding movement of the mass synchronized with the patient's respiration, which was a clue to the diagnosis of mesenteric lymphangioma. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 46 :78–81, 2018;     

Evidence for a putatively new angiotensin II-generating enzyme in the vascular wall

An inhibitor of angiotensin I (ANG I) converting enzyme, SA446, reduced the response to ANG I of blood vessels isolated from dogs and monkeys, but did not abolish the response even at high concentrations. The residual action of ANG I in the presence of high concentrations of SA446 could be abolished by (Sar1, Ala8)-ANG II. Vascular strips and crude extracts of vessels and lungs possessed the enzymic activity generating ANG II from ANG I, or hippuric acid from hippuryl-histidyl-leucine (HHL). The HHL-hydrolysing activity of the crude extracts was completely inhibited by SA446 (10(-7) mol/l) and/or Na2-EDTA (10(-3) mol/l). However, the octapeptide generation was not abolished despite the combined treatment with SA446 (5 X 10(-4) mol/l) and Na2-EDTA (5 x 10(-3) mol/l). The residual activity forming ANG II was inhibited by chymostatin and soybean trypsin inhibitor, which however did not affect the HHL-hydrolysis. Combined treatment with SA446 (10(-5) mol/l) and chymostatin (2.5 X 10(-5) mol/l) abolished the vascular action of ANG I but did not alter the action of ANG II. These results strongly suggest that besides the ANG I converting enzyme, another enzyme which generates ANG II is present in vascular tissues and lungs, and may play an important role in the local generation of ANG II, which possibly regulates the regional vascular tone.