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Melatonin reduces oxidative stress and improves vascular function in pulmonary hypertensive newborn sheep
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Flavio Torres Alejandro González‐Candia Camilo Montt Germán Ebensperger Magdalena Chubretovic María Serón‐Ferré Roberto V. Reyes Aníbal J. Llanos Emilio A. Herrera 《Journal of pineal research》2015,58(3):362-373
Pulmonary hypertension of the newborn (PHN) constitutes a critical condition with severe cardiovascular and neurological consequences. One of its main causes is hypoxia during gestation, and thus, it is a public health concern in populations living above 2500 m. Although some mechanisms are recognized, the pathophysiological facts that lead to PHN are not fully understood, which explains the lack of an effective treatment. Oxidative stress is one of the proposed mechanisms inducing pulmonary vascular dysfunction and PHN. Therefore, we assessed whether melatonin, a potent antioxidant, improves pulmonary vascular function. Twelve newborn sheep were gestated, born, and raised at 3600 meters. At 3 days old, lambs were catheterized and daily cardiovascular measurements were recorded. Lambs were divided into two groups, one received daily vehicle as control and another received daily melatonin (1 mg/kg/d), for 8 days. At 11 days old, lung tissue and small pulmonary arteries (SPA) were collected. Melatonin decreased pulmonary pressure and resistance for the first 3 days of treatment. Further, melatonin significantly improved the vasodilator function of SPA, enhancing the endothelial‐ and muscular‐dependent pathways. This was associated with an enhanced nitric oxide‐dependent and nitric oxide independent vasodilator components and with increased nitric oxide bioavailability in lung tissue. Further, melatonin reduced the pulmonary oxidative stress markers and increased enzymatic and nonenzymatic antioxidant capacity. Finally, these effects were associated with an increase of lumen diameter and a mild decrease in the wall of the pulmonary arteries. These outcomes support the use of melatonin as an adjuvant in the treatment for PHN. 相似文献
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Miguel A. Sanz Pau Montesinos Haesook T. Kim Guillermo J. Ruiz-Argüelles María S. Undurraga María R. Uriarte Lem Martínez Rafael H. Jacomo Homero Gutiérrez-Aguirre Raul A. M. Melo Rosane Bittencourt Ricardo Pasquini Katia Pagnano Evandro M. Fagundes Edo Vellenga Alexandra Holowiecka Ana J. González-Huerta Pascual Fernández Javier De la Serna Salut Brunet Elena De Lisa José González-Campos José M. Ribera Isabel Krsnik Arnold Ganser Nancy Berliner Raul C. Ribeiro Francesco Lo-Coco Bob L?wenberg Eduardo M. Rego 《Annals of hematology》2015,94(8):1347-1356
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Age-related bone loss has been associated with high levels of marrow adipogenesis. Estrogens (E2) are known to regulate the differentiation of marrow precursors into osteoblasts, however, their role in bone marrow adipogenesis
remain unknown. E2 regulate adipocyte differentiation in subcutaneous and visceral fat through interaction with other nuclear receptors. This
interaction has not been assessed in bone marrow adipocytes in vivo. In this study, we compared two groups of animals, young
and old, after either oophorectomy (OVX) or oophorectomy plus E2 (OVX + E2) replacement. We found that absence of E2 was associated with higher levels of PPARγ and lower levels of Sirt1 most significantly in the old group. In addition, old
mice responded better to E2 replacement in terms of reducing adipogenesis and PPARγ expression as well as increasing levels of Sirt1 expression. Our
findings represent a new understanding of the role of E2 in age-related bone loss, which could be mediated through the regulation of Sirt1 expression within the bone marrow. In addition,
this evidence suggests that old individuals may show a better response to E2 administration in terms of reverting the high levels of marrow fat seen in age-related bone loss. 相似文献
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Microanatomy and surgical approaches to the infratemporal fossa: an anaglyphic three-dimensional stereoscopic printing study. 总被引:2,自引:0,他引:2
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Objective: The infratemporal fossa (ITF) is a continuation of the temporal fossa between the internal surface of the zygoma and the external surface of the temporal bone and greater wing of the sphenoid bone that is sitting deep to the ramus of the mandible. The principal structure to understanding its relationships is the lateral pterygoid muscle. Other important structures are the medial pterygoid muscle, the maxillary artery, the pterygoid venous plexus, the otic ganglion, the chorda tympani nerve and the mandibular nerve. In this study, we describe the microsurgical anatomy of the ITF, as viewed by step-by-step anatomical dissection and also through the perspective of three lateral approaches and one anterior surgical approach. Methods: Eight cadaver specimens were dissected. In one side of all specimens, an anatomical dissection was done in which a wide preauricular incision from the neck on the anterior border of the sternoclidomastoid muscle at the level of the cricoid cartilage to the superior temporal line was made. The flap was displaced anteriorly and the structures of the neck were dissected followed by a zygomatic osteotomy and dissection of the ITF structures. On the other side were the surgical approaches to the ITF. The combined infratemporal and posterior fossa approach was done in two specimens, the subtemporal preauricular infratemporal fossa approach in two, the zygomatic approach in two, and the lateral transantral maxillotomy in two. The anatomical dissections were documented on the three-dimensional (3D) anaglyphic method to produce stereoscopic prints. Results: The lateral pterygoid muscle is one of the principal structures to enable understanding of the relationships into the ITF. The tendon of the temporal muscle inserts in the coronoid process at the ITF. The maxillary artery is the terminal branch of the external carotid artery that originates at the neck of the mandible and runs into the parotid gland. In our dissections the maxillary artery was lateral to the buccal, lingual, and inferior alveolar nerves. We found the second part of the maxillary artery superficial to the lateral pterygoid muscle in all specimens The anterior and posterior branches of the deep temporal artery supply the temporal muscle. In two cases we found a middle deep temporal artery. The different approaches that we used provided different views of the same anatomical landmarks and this provides not only safer surgery but also the best choice to approach the ITF according with the pathology extension. Conclusions: The ITF is a complex region on the skull base that is affected by benign and malignant tumors. The study through different routes is helpful to disclose the relationship among the anatomical structures. Although the authors have shown four approaches, there are a variety of approaches and even a combination of these can be used. This type of anatomical knowledge is essential to choosing the best approach to treat lesions in this area. 相似文献
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The present study was designed to examine the effects of a >30kDa fraction of medium conditioned for 2 days by adult rat seminiferoustubules on inhibin secretion by cultured tubules, and on spermatogenesisand fertility of male rats. Inhibin secretion was assayed byadding the >30 kDa fraction to 5 cm segments of adult ratseminiferous tubules and measuring inhibin by radioimmunoassayat 2 day intervals. Fertility was assayed by injecting malerats daily for up to 45 days with the >30 kDa fraction andthen mating them with a proestrus female, or by injecting for15 days and mating them with two female rats. The assay usedto evaluate the in-vivo effect of the >30 kDa fraction onthe testis involved an assessment of frequencies of seminiferoustubule stages scored by transillumination on intact tubules.The addition of the >30 kDa fraction to the adult rat seminiferoustubules cultured for 2 days resulted in an inhibition of inhibinsecretion into the medium. This effect was reversed when thefraction was removed and changed with fresh medium and culturedfor a further 4 days. The >30 kDa fraction administered i.p.to adult male rats resulted in a low fertilization rate comparedto control rats (67%) (P < 0.05). The assessment of frequenciesof seminiferous tubule stages scored by transillumination showedan increased frequency of stage VI and decreased frequency ofstages VII and VIII after treatment. The results of the presentstudy provide additional evidence that local regulation of Sertolicell function is mediated by a >30 kDa component or componentssecreted by adult seminiferous tubules which could arrest spermatogenesis. 相似文献