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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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Carlos Robles-Medranda Manuel Valero Miguel Puga-Tejada Roberto Oleas Jorge Baquerizo-Burgos Miguel Soria-Alc var Haydee Alvarado-Escobar Hannah Pitanga-Lukashok 《World journal of gastrointestinal endoscopy》2020,12(1):23-32
BACKGROUND Accurate detection of gastric infection by Helicobacter pylori(H.pylori) and premalignant lesions are important for effective provision of treatment,preventing the development of gastric neoplasia.Optical enhancement systems with optical magnification improved the identification of mucosal superficial and vascular patterns in patients with dyspepsia.AIM To evaluate an optical enhancement system with high-definition magnification,for diagnosis of normal gastric mucosa,H.pylori-associated gastritis,and gastric atrophy.METHODS A cross-sectional,nonrandomized study from November 2015 to April 2016 performed in a single-tertiary academic center from Ecuador.Seventy-two consecutive patients with functional dyspepsia according to the Rome III criteria,were tested for H.pylori using a stool antigen test and were assigned to an Hp+group or an Hp-control group.Esophagogastroduodenoscopy with highdefinition optical magnification and digital chromoendoscopy was performed,and patients were classified into 4 groups,in accordance to the microvasculararchitecture pattern of the mucosa.Interobserver and intraobserver agreement among operators were calculated.RESULTS Of the 72 participants,35 were Hp+ and 37 were Hp-.Among 10 patients with normal mucosal histology in biopsy samples,90% had a Type I pattern of microvascular architecture by endoscopy.Among participants with type IIa and type IIb patterns,significantly more were Hp+ than Hp-(32 vs 8),and most(31 out of 40) had histological diagnoses of chronic active gastritis.Two of the three participants with a histological diagnosis of atrophy had a type III microvascular pattern.The type I pattern predicted normal mucosa,type IIa–IIb predicted H.pylori infection,and type III predicted atrophy with sensitivities of 90.0%,91.4%,and 66.7%,respectively.The intraobserver and interobserver agreements had kappa values of 0.91 and 0.89,respectively.CONCLUSION High-definition optical magnification with digital chromoendoscopy is useful for diagnosis of normal gastric mucosa and H.pylori-associated gastritis with high accuracy,but further studies are needed to determine whether endoscopic diagnosis of gastric atrophy is feasible. 相似文献
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A Friend is truly a treasure, in accordance with age and competence’s qualitative changes. The aim of this study was to con?rm the increase in friendship competence and its multifactorial nature in 3- up to 10-year-old children, and to verify gender differences, and parenting in?uences on the concept of friendship. A semi-structured interview was administered in a natural context to 3- to 10-year-old children (N?=?167; Mean?=?7.6 years; SD?=?2.16). According to Selman’s Model, the coding provides ?ve sub-categories: (1) friendship; (2) social perspective taking; (3) emotions understanding; (4) social interaction strategies; and (5) aggressiveness. Three parental style questionnaires were administered to parents. Results point up an increase in social skills according to age. The Friendship Interview turned out to be a reliable tool able to investigate how the concept of friendship is also structured in preschool children. 相似文献
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Marco Maruzzo Umberto Basso Eugenio Borsatti Laura Evangelista Filippo Alongi Orazio Caffo Francesca Maines Sara Galuppo Rocco De Vivo Fable Zustovich Dario Palleschi Andrea Zivi Teodoro Sava Mariella Sorarù Roberto Iacovelli Maurizio Nicodemo Susanne Baier Lucia Fratino Vittorina Zagonel 《Clinical genitourinary cancer》2019,17(1):e187-e194
Background
Radium 223 was introduced for metastatic castration-resistant prostate cancer based on the results of a randomized controlled trial showing risk reduction for death and skeletal events. Our aim was to evaluate the outcome of patients receiving radium 223 in a real-world setting.Patients and Methods
We conducted a multicenter retrospective analysis in the Triveneto region of Italy.Results
One hundred fifty-eight patients received radium 223 in our region. After a median follow-up of 9.5 months, 75 patients died. The median overall survival (OS) was 14.2 months, and the median progression-free survival (PFS) was 6.2 months. Seventy-one (45%) patients achieved progression as best response. Thirty-seven (23%) patients stopped the treatment early because of progression. Eastern Cooperative Oncology Group performance status was prognostic for OS (18.4 vs. 12.3 vs. 7.5 months; 0 vs. 1, P = .0062; 0 vs. 2, P = .0002), whereas previous prostatectomy or docetaxel exposure were not. A neutrophil to lymphocytes ratio ≥ 3 significantly impacted OS (18.1 vs. 9.7 months; P < .001) and slightly impacted PFS (6.6 vs. 5.6 months; P = .05). Patients with a baseline alkaline phosphatase (ALP) value ≥ 220 U/L had worse OS and PFS (24.1 vs. 10.5 months; 7.2 vs. 5.5 months; P < .001). Patients with changes in ALP value achieved better OS (P = .029) and PFS (P = .002). There was no difference according to the line of therapy (0 vs. ≥ 1; P = .490). The main grade 3/4 toxicities were anemia, asthenia, and thrombocytopenia.Conclusion
This large real-world report confirms comparable OS and PFS data when compared with the pivotal study, as well as the predictive role of ALP and neutrophil to lymphocytes ratio. The definition of the optimal position of radium 223 in the treatment of metastatic castration-resistant prostate cancer has still to be defined. 相似文献9.
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Roberto Manfredi Sergio Sabbatani Leonardo Calza 《The Brazilian journal of infectious diseases》2007,11(6):605-609
A patient with HIV infection developed the first episode of AIDS-defining opportunism (severe Candida albicans esophagitis) with an underlying CD4+ lymphocyte count of 1,025 cells/microL. After treatment with a highly active antiretroviral therapy (HAART), taken with insufficient compliance and leaving a residual viral load, our patient suffered from two relapses of esophageal candidiasis, which occurred three months and seven years later, when his CD4+ lymphocyte count was 930 and 439 cells/microL, respectively, and a viral load slightly above 10(4) copies/mL was still present. Also in the HAART era, Candida esophagitis remains one of the most common AIDS-defining diseases, but a presentation with a concurrent CD4+ count above 1,000 cells/microL remains a rare exception, as well as the two isolated, subsequent relapses, occurred with a CD4+ count ranging from 439 to 930 cells/microL, and a residual HIV viremia due to insufficient adherence to the prescribed HAART regimens. Our case report represents the opportunity to revisit the epidemiology and, especially, the pathogenesis of this opportunistic fungal complication in HIV-infected patients and in other subjects at risk, on the ground of an extensive literature review, and to explore possible alternative supporting factors other than the crude absolute CD4+ lymphocyte count, with emphasis on the possible role of a persisting HIV viremia, and other potential contributing factors. Clinicians engaged with immunocompromised patients and subjects with HIV disease, should be aware that a Candida esophagitis may occur and relapse also when the cell-mediated immunity, as measured by a simple CD4+ cell count, do not show relevant abnormalities. 相似文献