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  • 1
    In: Experimental Biology and Medicine, SAGE Publications, Vol. 228, No. 5 ( 2003-05), p. 517-524
    Abstract: Increasing evidence supports the notion that reduction of cellular expression and activity of antioxidant proteins and the resulting increase of oxidative stress are fundamental causes in the aging processes and neurodegenerative diseases. In the present study, we evaluated, in the brains of young and aged rats, the gene expression profiles of two inducible proteins critically involved in the cellular defense against endogenous or exogenous oxidants: heme oxygenase-1 (HO-1) and manganese superoxide dismutase-2 (SOD-2). SOD-2 is an essential antioxidant and HO-1 has been reported to be very active in regulating cellular redox homeostasis. Deregulation of these enzymes has been extensively reported to play a crucial role in the pathogenesis of neurodegenerative disorders. To measure the regional distribution of HO-1 and SOD-2 transcript levels in the rat brain, we have developed a real time quantitative reverse transcription-polymerase chain reaction protocol. Although these two genes presented a highly dissimilar range of expression, with SOD-2 〉 HO-1, both transcripts were highly expressed in the cerebellum and the hippocampus, showing in a different scale a strikingly parallel distribution gradient. To further investigate the regional brain expression of these mRNAs, we performed in situ hybridization using specific riboprobes. In situ hybridization results showed that both transcripts were highly concentrated in the hippocampus, the cerebellum and some specific regions of the brain cortex. We have also quantified, by reverse transcription-polymerase chain reaction, the brain expression of HO-1 and SOD-2 mRNAs in middle aged (12 months) and aged (28 months) rats. We found that the hippocampus of aged rats presents a significant down regulation of SOD2 mRNA expression and a parallel upregulation of HO-1 mRNA compared with young (6 months) and middle-aged rats. Furthermore, in the cerebellum of the aged rats, we detected a parallel significant upregulation of both HO-1 and SOD-2 transcripts. These regional age-dependent differences may help to explain the increased susceptibility to oxidative damage in these two brain areas during aging.
    Type of Medium: Online Resource
    ISSN: 1535-3702 , 1535-3699
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2003
    detail.hit.zdb_id: 2020856-X
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  • 2
    In: Therapeutic Advances in Medical Oncology, SAGE Publications, Vol. 14 ( 2022-01), p. 175883592210939-
    Abstract: Myxofibrosarcoma (MFS) is a common entity of adult soft tissue sarcomas (STS) characterized by a predilection of the extremities and a high local recurrence rate. Originally classified as a myxoid variant of malignant fibrous histiocytoma, this musculoskeletal tumor has been recognized since 2002 as a distinct histotype showing a spectrum of malignant fibroblastic lesions with myxoid stroma, pleomorphism and curvilinear vessels. Currently, the molecular pathogenesis of MFS is still poorly understood and its genomic profile exhibits a complex karyotype with a number of aberrations including amplifications, deletions and loss of function. The diagnosis is challenging due to the unavailability of specific immunohistochemical markers and is based on the analysis of cytomorphologic features. The mainstay of treatment for localized disease is represented by surgical resection, with (neo)-adjuvant radio- and chemotherapy. In the metastatic setting, chemotherapy represents the backbone of treatments, however its role is still controversial and the outcome is very poor. Recent advent of genomic profiling, targeted therapies and larger enrollment of patients in translational and clinical studies, have improved the understanding of biological behavior and clinical outcome of such a disease. This review will provide an overview of current diagnostic pitfalls and clinical management of MFS. Finally, a look at future directions will be discussed.
    Type of Medium: Online Resource
    ISSN: 1758-8359 , 1758-8359
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
    detail.hit.zdb_id: 2503443-1
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  • 3
    In: Therapeutic Advances in Respiratory Disease, SAGE Publications, Vol. 15 ( 2021-01), p. 175346662110093-
    Abstract: Severe eosinophilic asthma is frequently associated to chronic rhinosinusitis and nasal polyposis (CRSwNP) that contribute to poor asthma control. Mepolizumab is an anti-IL-5 monoclonal antibody, approved for the treatment of severe eosinophilic asthma. A limited number of studies have assessed the efficacy of mepolizumab on CRSwNP in severe asthmatics. We aim to evaluate the efficacy of mepolizumab on sino-nasal symptoms, polyp growth and asthma control in severe eosinophilic asthma patients with CRSwNP in real life. Methods: In this study 44 severe eosinophilic asthma patients with CRSwNP were treated with mepolizumab (100 mg q4w) for 1 year. The following outcomes were assessed before (T0), after 6 (T6) and 12 months (T12) of treatment: sino/nasal outcome test (SNOT-22), Total Endoscopic Nasal Polyp Score (TENPS), %FEV1 (FEV1/FEV1 predicted) and Asthma control test (ACT). Blood eosinophil count, exhaled nitric oxide (FENO) and prednisone intake were measured. In a subgroup of patients, nasal cytology was performed before (T0), after 6 (T6) and after 12 months (T12) of treatment with mepolizumab. Results: We reported a significant reduction of SNOT-22 [from 51.5 ± 21.2 at baseline (T0) to 31.70 ± 17.36 at T6 and 29.7 ± 21.5 at T12 (T0–T12 p  〈  0.001)] and a decrease of TENPS (from 2.88 ± 3.07 to 1.70 ± 2.37 and 1.77 ± 2.56 at T0, T6 and T12, respectively, T0–T12 p = 0.99). A significant improvement of %FEV 1 , ACT and a decrease in blood eosinophils and mean prednisone intake were also reported. No statistically significant decreasing trend was measured for FENO. Nasal cytology findings suggest a significant reduction of eosinophil percentage following mepolizumab treatment (from 16.8 ± 7.2% to 3.6 ± 6.2% and 0.8 ± 2.4% at T0, T6 and T12 respectively, T0 to T12: p  〈  0.001). Conclusions: Mepolizumab improves sino-nasal and asthma symptoms and reduces polyp growth in patients with severe eosinophilic asthma and concomitant CRSwNP in real life. The reviews of this paper are available via the supplemental material section.
    Type of Medium: Online Resource
    ISSN: 1753-4666 , 1753-4666
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
    detail.hit.zdb_id: 2387506-9
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