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  • 1
    Online Resource
    Online Resource
    S. Karger AG ; 2012
    In:  Neurodegenerative Diseases Vol. 10, No. 1-4 ( 2012), p. 253-256
    In: Neurodegenerative Diseases, S. Karger AG, Vol. 10, No. 1-4 ( 2012), p. 253-256
    Abstract: 〈 i 〉 Background: 〈 /i 〉 White matter changes (WMC) and microbleeds (MBs) are common in the elderly and in patients with Alzheimer’s disease (AD). 〈 i 〉 Objective: 〈 /i 〉 To describe the prevalence, anatomical distribution and longitudinal changes of WMC and MBs in normal aging subjects compared to AD patients and to describe current evidence of their effects on the clinical course of AD. 〈 i 〉 Methods: 〈 /i 〉 Short literature review. 〈 i 〉 Results: 〈 /i 〉 WMC and MBs are more frequent and progress more rapidly in AD patients than in cognitively normal elderly. New MBs occur in up to one quarter of AD cases without any therapeutic intervention. WMC and MBs influence the clinical course of AD. 〈 i 〉 Conclusion: 〈 /i 〉 WMC and MBs might represent treatment targets in clinical trials on AD.
    Type of Medium: Online Resource
    ISSN: 1660-2854 , 1660-2862
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2012
    detail.hit.zdb_id: 2126858-7
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  • 2
    In: Neurodegenerative Diseases, S. Karger AG, Vol. 10, No. 1-4 ( 2012), p. 135-137
    Abstract: 〈 i 〉 Background: 〈 /i 〉 Physical activity and cardiorespiratory fitness relate to better cognitive performance. Little is known about the effects of fitness on structural brain abnormalities in the elderly. 〈 i 〉 Objective: 〈 /i 〉 Assess the association between maximal oxygen consumption (VO 〈 sub 〉 2 〈 /sub 〉 max), white matter lesion (WML) volume and brain parenchymal fraction (BPF) in a large cohort of community-dwelling elderly individuals. 〈 i 〉 Methods: 〈 /i 〉 The study population consisted of 715 participants of the Austrian Stroke Prevention Study who underwent brain MRI with semi-automated measurement of WML volume (cm 〈 sup 〉 3 〈 /sup 〉 ) and automated assessment of BPF (%) by the use of SIENAX. A maximal exercise stress test was done on a bicycle ergometer. VO 〈 sub 〉 2 〈 /sub 〉 max was calculated based on maximum and resting heart rate. 〈 i 〉 Results: 〈 /i 〉 After adjustment for possible confounders, VO 〈 sub 〉 2 〈 /sub 〉 max was independently associated with WML volume (β = –0.10; p = 0.02); no significant relationship existed with silent cerebral infarcts and BPF. Associations between VO 〈 sub 〉 2 〈 /sub 〉 max and WML load were only significant in men, but not in women. 〈 i 〉 Conclusion: 〈 /i 〉 Our findings may have important preventive implications because WMLs are known to be a major determinant of cognitive decline and disability in old age.
    Type of Medium: Online Resource
    ISSN: 1660-2854 , 1660-2862
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2012
    detail.hit.zdb_id: 2126858-7
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  • 3
    In: Neurodegenerative Diseases, S. Karger AG, Vol. 7, No. 1-3 ( 2010), p. 122-126
    Abstract: 〈 i 〉 Background: 〈 /i 〉 Diagnostic criteria separating vascular dementia from other dementias, particularly Alzheimer’s disease (AD) neglect the real world in which most AD cases present with at least some vascular brain lesions. Most importantly, vascular lesions, even if subtle, exert significant effects on the patients’ cognitive functioning if they coexist with AD pathology. 〈 i 〉 Objectives: 〈 /i 〉 To emphasize the need for an integrative dementia concept in which the vascular component represents an important end point in trial planning and a possibility for disease modification along the whole spectrum of combined vascular and primary degenerative pathology. 〈 i 〉 Methods: 〈 /i 〉 Review of the literature on possible surrogate markers to study the contribution of vascular brain damage in dementia. 〈 i 〉 Results: 〈 /i 〉 The longitudinal change in volume of white matter lesions is the best elaborated putative surrogate marker for the study of the vascular component in dementia. Validation of the role of lacunes and microbleeds as surrogate end points is poor. Loss of brain volume is an important adjunct outcome measure even though the vascular origin of atrophy remains uncertain. 〈 i 〉 Conclusions: 〈 /i 〉 A focus on pure vascular dementia distracts from the importance of vascular factors in dementia. Consideration of the vascular component in future clinical trials will improve our pathophysiological understanding and provide options for treatment.
    Type of Medium: Online Resource
    ISSN: 1660-2854 , 1660-2862
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2010
    detail.hit.zdb_id: 2126858-7
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  • 4
    Online Resource
    Online Resource
    S. Karger AG ; 2002
    In:  Cerebrovascular Diseases Vol. 13, No. Suppl. 2 ( 2002), p. 16-20
    In: Cerebrovascular Diseases, S. Karger AG, Vol. 13, No. Suppl. 2 ( 2002), p. 16-20
    Abstract: A 3-year follow-up of 273 participants (mean age 60 years) of the Austrian Stroke Prevention Study provides first information on the rate, clinical predictors and cognitive consequences of MRI white matter lesions (WML) in elderly individuals without neuropsychiatric disease. Lesion progression was found in 17.9% of individuals over a time period of 3 years. Diastolic blood pressure and early confluent or confluent white matter hyperintensities at baseline were the only significant predictors of white matter hyperintensity progression. Genetic association studies in the setting of the Austrian Stroke Prevention Study provide first evidence for genetic susceptibility factors for progression of WML. We observed associations with the paraoxonase Leu→Met 54 polymorphism and with the M235T polymorphism of the angiotensinogen gene. Lesion progression had no influence on the course of neuropsychologic test performance over the observational period, but the statistical power of this analysis was low.
    Type of Medium: Online Resource
    ISSN: 1015-9770 , 1421-9786
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2002
    detail.hit.zdb_id: 1482069-9
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  • 5
    In: Cellular Physiology and Biochemistry, S. Karger AG, Vol. 44, No. 4 ( 2017), p. 1411-1424
    Abstract: Background/ Aims: This study was performed to reveal signaling pathways exploited by pigment epithelium-derived factor (PEDF) derived from retinal (glial) Müller cells to protect retinal ganglion cells (RGCs) from cell death. Methods: The survival of RGCs was determined in the presence of conditioned culture media (MCM) from or in co-cultures with Müller cells. The significance of PEDF-induced STAT3 activation was evaluated in viability assays and using Western blotting analyses and siRNA-transfected cells. Results: Secreted mediators of Müller cells increased survival of RGCs under normoxia or hypoxia to a similar degree as of PEDF- or IL-6-exposed cells. PEDF and MCM induced an increased STAT3 activation in RGCs and R28 cells, and neutralization of PEDF in MCM attenuated STAT3 activation. Inhibition of STAT3 reduced PEDF-promoted survival of RGCs. Similar to IL-6, PEDF induced STAT3 activation, acting in a dose-dependent manner via the PEDF receptor (PEDF-R) encoded by the PNPLA2 gene. Ablation of PEDF-R attenuated MCM-induced STAT3 activation and compromised the viability of PEDF-exposed R28 cells. Conclusions: Müller cells are an important source of PEDF, which promotes RGC survival through STAT3 activation and, at least in part, via PEDF-R. Enhancing the secretory function of Müller cells may be useful to promote RGC survival in retinal neurodegenerative diseases.
    Type of Medium: Online Resource
    ISSN: 1015-8987 , 1421-9778
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2017
    detail.hit.zdb_id: 1482056-0
    SSG: 12
    SSG: 15,3
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  • 6
    In: Obesity Facts, S. Karger AG, Vol. 11, No. 2 ( 2018), p. 93-108
    Abstract: 〈 b 〉 〈 i 〉 Objective: 〈 /i 〉 〈 /b 〉 We aimed to determine the effect of human 〈 i 〉 SH2B1 〈 /i 〉 variants on leptin and insulin signaling, major regulators of energy homeostasis, on the RNA level. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We analyzed the expression of infrequent alleles of seven 〈 i 〉 SH2B1 〈 /i 〉 variants (Arg67Cys, Lys150Arg, Thr175Ala, Thr343Met, Thr484Ala, Ser616Pro and Pro689Leu) in response to insulin or leptin cell stimulation. Two of these were identified in own mutation screens, the others were predicted to be deleterious or to serve as controls. The variants were analyzed in a homologous system of mouse hypothalamic cells. Changes in expression of downstream genes were measured. Student’s t-test for independent samples was applied and effect sizes using Cohen’s d were calculated. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 In 34 of 54 analyzed genes involved in leptin (JAK/STAT or AKT) signaling, variants nominally changed expression. The expression of three genes was considerably increased (p values ≤ 0.001: 〈 i 〉 Gbp2b 〈 /i 〉 (67Cys; d = 25.11), 〈 i 〉 Irf9 〈 /i 〉 (689Leu; d = 44.65) and 〈 i 〉 Isg15 〈 /i 〉 (150Arg; d = 20.35)). Of 32 analyzed genes in the insulin signaling pathway, the expression of 10 genes nominally changed (p ≤ 0.05), three resulted in p values ≤ 0.01 ( 〈 i 〉 Cap1 〈 /i 〉 (150Arg; d = 7.48), 〈 i 〉 Mapk1 〈 /i 〉 (343Met; d = –6.80) and 〈 i 〉 Sorbs1 〈 /i 〉 (689Leu; d = 7.82)). 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 The increased expression of genes in leptin (JAK/STAT or AKT) signaling implies that the main mode of action for human 〈 i 〉 SH2B1 〈 /i 〉 mutations might affect leptin signaling rather than insulin signaling.
    Type of Medium: Online Resource
    ISSN: 1662-4025 , 1662-4033
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2018
    detail.hit.zdb_id: 2455819-9
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  • 7
    In: Cellular Physiology and Biochemistry, S. Karger AG, Vol. 40, No. 3-4 ( 2016), p. 431-442
    Abstract: Background: Cardiotoxicity is the major side effect of doxorubicin. As mechanisms that are involved in cardiotoxicity are ambiguous, new methods for attenuating cardiotoxicity are needed. Recent studies have shown that bisphosphonates can decrease oxidative stress. Therefore, the objective of this study was to evaluate the effect of pamidronate on preventing acute doxorubicin-induced cardiotoxicity. Methods: Sixty-four male Wistar rats were allocated into four groups: the control group (C), the pamidronate group (P), the doxorubicin group (D) and the doxorubicin/pamidronate group (DP). The rats in the P and DP groups received pamidronate injections (3 mg/kg, IP). After 24 hours, the rats in the D and DP groups received doxorubicin injections (20 mg/kg, IP). Forty-eight hours after doxorubicin injection, the rats were killed. Echocardiography, isolated heart study and biochemical analysis were performed. Results: Doxorubicin-induced acute cardiotoxicity showed increased matrix metalloproteinases (MMP)-2 activation, oxidative damage and induced alterations in myocardial energetic metabolism. Pamidronate did not inhibit MMP-2 activation but attenuated oxidative stress and improved myocardial energetic metabolism. Regarding cardiac function, the DP group exhibited a decrease in the left ventricular ejection fraction in the echocardiography and a decrease in +dP/dt in the isolated heart study compared with other groups. The same DP group presented serum hypocalcaemia. Conclusions: Despite its ability to reduce oxidative stress and improve energy metabolism in the heart, pamidronate worsened systolic function in rats treated with doxorubicin, and therefore we cannot recommend its use in conjunction with anthracycline chemotherapy.
    Type of Medium: Online Resource
    ISSN: 1015-8987 , 1421-9778
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2016
    detail.hit.zdb_id: 1482056-0
    SSG: 12
    SSG: 15,3
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  • 8
    In: Dermatology, S. Karger AG, Vol. 239, No. 3 ( 2023), p. 379-386
    Abstract: 〈 b 〉 〈 i 〉 Background and Objectives: 〈 /i 〉 〈 /b 〉 Benign skin tumors are the most common skin findings and contribute to the major reasons for consulting a dermatologist. However, the frequency of benign skin tumors concerning different body areas and their relationship with sun-related behavior have not been sufficiently characterized. We aimed to improve knowledge about the anatomic distribution of the most frequently occurring benign skin tumors among a healthy predominant elderly population. Furthermore, we investigated associations with sun-related habits. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 In total, 100 participants, 37 men, and 63 women (mean age: 67.2 years; range: 46–86 years) were enrolled in the Graz Study on Health and Aging (GSHA) cohort. Full body images were investigated for melanocytic nevi, seborrheic keratoses, hemangiomas, dermatofibromas, and lentigines. Information on the phenotypic trait, sun exposure, use of sun-protective measures, and history of sunburns was collected in a questionnaire. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Common melanocytic nevi were the most frequently encountered skin lesions. Male sex was associated with multiple common nevi on the abdomen and the presence of atypical nevi. High sun exposure in central European latitudes during adolescence was positively associated with multiple common nevi on the total body. Multiple common nevi and atypical nevi on the back correlated with frequent use of sunscreens with SPF during young adulthood and adolescence, respectively. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Our study adds new knowledge about the most frequently occurring benign skin tumors, considering all visible body areas. This research may serve as a reference basis for following epidemiological studies.
    Type of Medium: Online Resource
    ISSN: 1018-8665 , 1421-9832
    RVK:
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2023
    detail.hit.zdb_id: 1482189-8
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  • 9
    In: Cerebrovascular Diseases, S. Karger AG, Vol. 32, No. 2 ( 2011), p. 186-193
    Abstract: 〈 i 〉 Background: 〈 /i 〉 The MRI-based mismatch concept has been used to estimate the risk of infarction in ischemic stroke. Based on multiple studies on magnetic resonance perfusion imaging, it seems unlikely that any perfusion parameter threshold will provide a reliable prediction of radiological or clinical outcome for all patients. The goal of our study was to find a minimally biased yet maximally useful perfusion postprocessing protocol which would offer the treating physician a useful estimate of tissue fate. 〈 i 〉 Methods: 〈 /i 〉 One hundred and forty-five acute ischemic stroke patients, admitted within 24 h after stroke to the Charité – University Medicine Hospital in Berlin between March 2008 and November 2009, were included in this study. Using three different software packages (Perfscape/Neuroscape, PMA and Stroketool), maps of mean transit time, cerebral blood flow (CBF) and T 〈 sub 〉 max 〈 /sub 〉 were created. Three different thresholds were applied on each parameter map and subsequent volumes of hypoperfused tissue were calculated. 〈 i 〉 Results: 〈 /i 〉 Overall, the maps and thresholds giving the least amount of overestimation of the final infarct volume were T 〈 sub 〉 max 〈 /sub 〉 8 s in Perfscape/Neuroscape, CBF 20 ml/100 g/min in PMA and CBF 15% (of the highest value on the scale for a given patient) in Stroketool. In patients with persistent vessel occlusion, a CBF map with a restrictive threshold showed volumes of tissue at definite risk of infarction in up to 100% of patients. The additional use of a CBF map with a high threshold enabled identification of patients without penumbras. 〈 i 〉 Conclusions: 〈 /i 〉 No combination of software, map and threshold was able to give a reliable estimate of tissue fate for either all patients or any subgroup of patients. However, in patients with vessel occlusion, combination of a CBF map with a low and a high threshold can enable calculation of the minimum volume of brain tissue that will inevitably be lost if the occlusion persists.
    Type of Medium: Online Resource
    ISSN: 1015-9770 , 1421-9786
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2011
    detail.hit.zdb_id: 1482069-9
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  • 10
    Online Resource
    Online Resource
    S. Karger AG ; 2019
    In:  Audiology and Neurotology Vol. 24, No. 5 ( 2019), p. 253-257
    In: Audiology and Neurotology, S. Karger AG, Vol. 24, No. 5 ( 2019), p. 253-257
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 The most common complaint of patients affected by chemotherapy-induced hearing loss is difficulty understanding speech in noisy environments despite the use of hearing aids. Cochlear dead regions, those areas with damaged or absent inner hair cells and dendrites, may account for this type of hearing loss. However, it is unknown whether this condition is associated with cisplatin agents. 〈 b 〉 〈 i 〉 Objective: 〈 /i 〉 〈 /b 〉 The aim of this study was to determine whether cisplatin is associated with hearing loss and cochlear dead regions. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 This prospective cross-sectional study was conducted in patients participating in routine audiological monitoring during and after chemotherapy treatment. Adults undergoing audiological evaluation who had completed chemotherapy treatment were invited to participate. Patients were divided into 3 groups according to pure tone thresholds. Group 1 patients had thresholds over 70 dB (HL) at 2,000 Hz and higher frequencies. Group 2 patients had thresholds below 70 dB (HL) up to 2,000 Hz. Patients in the control group had normal thresholds at all frequencies. The threshold equalizing noise test (TEN[HL]) was used to identify cochlear dead regions by repeating thresholds in the presence of TEN noise played from a compact disc. The presence of cochlear dead regions was established when the masked threshold was 10 dB or greater above the TEN level and 10 dB or greater above the absolute threshold at any frequency. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Twelve patients were included in study group 1, 10 patients in study group 2, and 7 patients in the control group. Cochlear dead regions were present in all patients with hearing loss and in none of the control group. For groups 1 and 2, mean differences between absolute and masked thresholds were 21 and 16 dB at 500 Hz; 22 and 15 dB at 1,000 Hz; 31 and 17 dB at 2,000 Hz; 32 and 20 dB at 3,000 Hz; and 31 and 21 dB at 4,000 Hz, respectively. Nevertheless, analysis of variance testing with Bonferroni analysis showed a difference between groups 1 and 2 only at 2,000, 3,000, and 4,000 Hz. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 We found unresponsive or dead cochlear regions in patients who had undergone cisplatin chemotherapy even among patients with mild to moderate hearing loss.
    Type of Medium: Online Resource
    ISSN: 1420-3030 , 1421-9700
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2019
    detail.hit.zdb_id: 1481979-X
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