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Neuropeptide Y Attenuates Stress‐Induced Bone Loss Through Suppression of Noradrenaline Circuits 下载免费PDF全文
PA Baldock S Lin L Zhang T Karl Y Shi F Driessler A Zengin B Hörmer NJ Lee IPL Wong EJD Lin RF Enriquez B Stehrer MJ During E Yulyaningsih S Zolotukhin ST Ruohonen E Savontaus A Sainsbury H Herzog 《Journal of bone and mineral research》2014,29(10):2238-2249
Chronic stress and depression have adverse consequences on many organ systems, including the skeleton, but the mechanisms underlying stress‐induced bone loss remain unclear. Here we demonstrate that neuropeptide Y (NPY), centrally and peripherally, plays a critical role in protecting against stress‐induced bone loss. Mice lacking the anxiolytic factor NPY exhibit more anxious behavior and elevated corticosterone levels. Additionally, following a 6‐week restraint, or cold‐stress protocol, Npy‐null mice exhibit three‐fold greater bone loss compared to wild‐type mice, owing to suppression of osteoblast activity. This stress‐protective NPY pathway acts specifically through Y2 receptors. Centrally, Y2 receptors suppress corticotropin‐releasing factor expression and inhibit activation of noradrenergic neurons in the paraventricular nucleus. In the periphery, they act to control noradrenaline release from sympathetic neurons. Specific deletion of arcuate Y2 receptors recapitulates the Npy‐null stress response, coincident with elevated serum noradrenaline. Importantly, specific reintroduction of NPY solely in noradrenergic neurons of otherwise Npy‐null mice blocks the increase in circulating noradrenaline and the stress‐induced bone loss. Thus, NPY protects against excessive stress‐induced bone loss, through Y2 receptor‐mediated modulation of central and peripheral noradrenergic neurons. © 2014 American Society for Bone and Mineral Research. 相似文献
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B. H. Sullivan Jr. COL. MC U. S. ARMY Nelson S. Irey LT. COL. MC U. S. ARMY Vincent J. Pileggi ST LT. MSC U. S. ARMY Richard I. Crone COL. MC U. S. ARMY John R. Gibson LT. COL. MC U. S. ARMY 《Digestive diseases and sciences》1957,2(4):210-223
Summary 1. Twenty-two patients with infectious mononucleosis were studied by liver biopsy and paper electrophoresis of the serum proteins. The findings were compared with a similar group of 30 patients with infectious hepatitis.2. The essential histologic features of infectious mononucleosis were the presence in the hepatic sinusoids and portal tracts of chronic inflammatory cells resembling small lymphocytes, with essentially no parenchymal cell damage. Admixed with this lymphocytic infiltrate, but in relatively minimal numbers, were a few plasma cells and polymorphonuclear leukocytes. In addition, in infectious mononucleosis there were, with rare exceptions, no lipochrome-containing Kupffer cells. Thus, in the majority of cases, the histologic picture was distinct from that seen in infectious hepatitis. Only in comparing a few of the more severe infectious mononucleosis cases with subsiding infectious hepatitis cases was there any tendency for the two pictures to merge, and the distinction on histologic grounds between the two entities could be made in the great majority of cases.3. The most commonly seen abnormalities in the paper electrophoretic patterns of sera obtained from patients with infectious mononucleosis were decreased albumin, increased gamma globulin, not infrequent but variable changes in alpha2 globulin, and the presence of abnormal proteins migrating with mobilities intermediate to alpha2 and beta, and beta and gamma globulins. The abnormalities observed in infectious hepatitis were similar to those of infectious mononucleosis, except that in hepatitis alpha2 globulin was decreased more consistently, gamma globulin increased less frequently, and beta globulin, which was normal in practically all the cases of infectious mononucleosis, was increased in a considerable number of cases.4. Treatment of patients with infectious mononucleosis need not include prolonged bed rest and restriction of activity in an effort to avoid the development of chronic liver disease. 相似文献
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F Haque ST Fazal SA Ahmad SZ Abbas S Naseem 《Journal of Medical Imaging and Radiation Oncology》2006,50(1):63-65
Primary osteogenic sarcoma of the skull is an exceedingly rare condition. An adult male patient is described, who had a painless swelling in the right forehead that had rapidly enlarged in the previous 6 months. Radiological investigations showed a large destructive mass lesion involving the right side of the frontal bone with extension into the frontal sinus, causing marked extradural compression of brain parenchyma. Histopathological examination confirmed the lesion to be primary osteogenic sarcoma. 相似文献
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Expression of differential nitric oxide synthase isoforms in human normal gastric mucosa and gastric cancer tissue 总被引:10,自引:2,他引:10
The present study investigated the expression and distribution of three
isoforms of nitric oxide synthase (NOS) in different anatomical regions of
the human stomach and in gastric neoplastic tissues by immunohistochemistry
using specific antibodies. Intracellular localization of individual
isoenzymes of NOS was detected in normal gastric mucosa. Gastric cancer
tissues had a marked reduction of all three NOS isoforms expression. The
expression of the endothelial NOS, neuronal NOS and inducible NOS in the
tumor tissue was significantly lower than in normal gastric mucosa (P =
0.01, P = 0.02, P < 0.01, respectively). In the tumor tissue the
expression of inducible NOS was significantly lower than the expression of
both constitutive forms of NOS (P < 0.01). There was a tendency to
higher expression of both constitutive forms of NOS in earlier stages T2 of
the tumor compared to advanced T4 tumor. In contrast, the expression of
inducible NOS was higher than in the advanced T4 tumor than in the earlier
stages T2 of the tumor. The mapping of the expression of endothelial NOS,
neuronal NOS and inducible NOS in human stomach showed higher expression of
NOS isoforms in the distal third than in the proximal third of the stomach
(P = 0.03, P = 0.04, P = 0.01, respectively). We conclude that there is
greater expression of NOS in the stomach corpus and in antrum than in the
proximal third of the normal human stomach mirroring the anatomical
predilection of common pathological changes in this part of the human
stomach. Furthermore, there was loss of the expression of individual
isoenzymes in gastric neoplasms.
相似文献
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目的 探讨血管新生指标CD34、CD31、vWF、Ⅳ型胶原纤维及层粘连蛋白在肝细胞肝癌(HCC)中的表达及意义 ,同时比较上述几种血管新生因子与增殖细胞核抗原 (PCNA)、病理指标及预后的相关性 ,以便筛选出有效的临床预后指标。方法 采用免疫组化方法 ,对 5 3例肝细胞肝癌的标本进行CD31、CD34、vWF、Ⅳ型胶原纤维及层粘连蛋白的染色、计数 ,并用检测数据与患者的临床资料进行统计分析。结果 统计染色的血管面积后发现 ,CD34与多种临床病理指标无相关性 ;CD31与肝内门静脉浸润相关 ;vWF与肿瘤的TNM分期及肝内门静脉浸润呈正相关 ;CollⅣ与肝内门静脉浸润呈正相关、与术后生存期呈负相关 ;Lam与肝硬化及术中出血量呈负相关、与术后生存期呈正相关。PCNA与肿瘤TNM分期有关。结论 在HCC中 ,CollⅣ、vWF、及CD31为肝细胞肝癌的有效血管新生及预后指标 ;Lam则与肝硬化及术中出血相关 ;PCNA指数肿瘤分期有关 ;CD34不能用作血管新生或预后指标 相似文献
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