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Zinc oxide nanoparticles (ZnO-NPs) are commonly used for industrial applications. Consequently, there is increasing exposure of humans to them. The in vitro analysis of cytotoxicity and genotoxicity is commonly performed under standard cell culture conditions. Thus, the question arises of how the results of genotoxicity and cytotoxicity experiments would alter if human plasma was used instead of cell culture medium containing of fetal calf serum (FCS). Human mesenchymal stem cells (hMSCs) were cultured in human plasma and exposed to ZnO-NPs. A cultivation in expansion medium made of DMEM consisting 10% FCS (DMEM-EM) served as control. Genotoxic and cytotoxic effects were evaluated with the comet and MTT assay, respectively. hMSC differentiation capacity and ZnO-NP disposition were evaluated by histology and transmission electron microscopy (TEM). The protein concentration and the amount of soluble Zn2+ were measured. The cultivation of hMSCs in plasma leads to an attenuation of genotoxic and cytotoxic effects of ZnO-NPs compared to control. The differentiation capacity of hMSCs was not altered. The TEM showed ZnO-NP persistence in cytoplasm in both groups. The concentrations of protein and Zn2+ were higher in plasma than in DMEM-EM. In conclusion, the cultivation of hMSCs in plasma compared to DMEM-EM leads to an attenuation of cytotoxicity and genotoxicity in vitro.
Locoregional recurrence is a major reason for therapy failure after surgical resection of head and neck squamous cell carcinoma (HNSCC). The physiological process of postoperative wound healing could potentially support the proliferation of remaining tumor cells. The aim of this study was to evaluate the influence of wound fluid (WF) on the cell cycle distribution and a potential induction of epithelial-mesenchymal transition (EMT). To verify this hypothesis, we incubated FaDu and HLaC78 cells with postoperative WF from patients after neck dissection. Cell viability in dependence of WF concentration and cisplatin was measured by flow cytometry. Cell cycle analysis was performed by flow cytometry and EMT-marker expression by rtPCR. WF showed high concentrations of interleukin (IL)-6, IL-8, IL-10, CCL2, MCP-1, EGF, angiogenin, and leptin. The cultivation of tumor cells with WF resulted in a significant increase in cell proliferation without affecting the cell cycle. In addition, there was a significant enhancement of the mesenchymal markers Snail 2 and vimentin, while the expression of the epithelial marker E-cadherin was significantly decreased. After cisplatin treatment, tumor cells incubated with WF showed a significantly higher resistance compared with the control group. The effect of cisplatin-resistance was dependent on the WF concentration. In summary, proinflammatory cytokines are predominantly found in WF. Furthermore, the results suggest that EMT can be induced by WF, which could be a possible mechanism for cisplatin resistance.
Compliance und Therapieversagen bei nCPAP-Therapie zur Therapie des obstruktiven Schlafapnoesyndroms
(2009)
Das Ziel der vorliegenden Studie war die Erhebung der Ursachen für ein Therapieversagen der nCPAP-Therapie. Der Therapieerfolg bei Vorliegen eines obstruktiven Schlafapnoesyndroms wird im Wesentlichen durch den individuellen Leidensdruck und die Nebenwirkungen der nCPAP-Therapie beeinflusst. Patienten mit einer milderen Form des obstruktiven Schlafapnoesyndroms haben einen geringeren Nutzen von der nCPAP-Therapie als Patienten mit einem höheren Leidensdruck. Die Schwere der Krankheit zeigt sich z. B. in einem höheren RDI und einer schlechteren Sauerstoffsättigung vor Therapie. Es zeigte sich ein Trend, dass die Therapieversager bei besseren Ausgangswerten eine geringere Verbesserung unter der Therapie als die ausreichend Therapierten erfuhren. Die Therapieversager profitierten objektiv und subjektiv weniger von der Therapie, so dass sie weniger bereit waren, Nebenwirkungen zu akzeptieren und diese als störender bewerteten. Sie klagten vermehrt über lokale Probleme durch die Maske. Die maximal tolerierten Beatmungsdrücke lagen unter denen der ausreichend Therapierten. Die Verbesserung der Tagesmüdigkeit war bei den Therapieversagern signifikant schlechter. Sie erfuhren seltener eine Steige-rung der Lebensfreude und verzeichneten häufiger eine Zunahme sozialer Probleme. So empfinden sie die Therapie als störenden Einschnitt in ihre Le-bensführung und nicht als Hilfe. Durch diese Unzufriedenheit brechen sie die Therapie ab oder greifen zu Hilfsmitteln, wie z. B. der Rampenfunktion, einem Luftbefeuchter oder Alternativtherapien wie Nasenpflaster oder Protrusions-schienen. Letztendlich wurde diese Unzufriedenheit der Therapieversager in der signifi-kant schlechteren Bewertung von Maske, Gerät und nCPAP-Therapie insge-samt deutlich. Obwohl viele Autoren ähnlicher Studien davon ausgehen, dass keine höhe-ren Erfolgsquoten mehr zu erzielen sind, muss eine weitere Minimierung der Nebenwirkungen, wie z. B. durch eine intensive individuelle Betreuung mit Beobachtung und Behebung der Nebenwirkungen und Verwendung von Hilfsmitteln das Ziel sein. Davon profitieren sowohl die ausreichend Therapierten als auch die Therapieversager.
Seed amplification assays (SAA) are becoming commonly used in synucleinopathies to detect α-synuclein aggregates. Studies in Parkinson’s disease (PD) and isolated REM-sleep behavior disorder (iRBD) have shown a considerably lower sensitivity in the olfactory epithelium than in CSF or skin. To get an insight into α-synuclein (α-syn) distribution within the nervous system and reasons for low sensitivity, we compared SAA assessment of nasal brushings and skin biopsies in PD (n = 27) and iRBD patients (n = 18) and unaffected controls (n = 30). α-syn misfolding was overall found less commonly in the olfactory epithelium than in the skin, which could be partially explained by the nasal brushing matrix exerting an inhibitory effect on aggregation. Importantly, the α-syn distribution was not uniform: there was a higher deposition of misfolded α-syn across all sampled tissues in the iRBD cohort compared to PD (supporting the notion of RBD as a marker of a more malignant subtype of synucleinopathy) and in a subgroup of PD patients, misfolded α-syn was detectable only in the olfactory epithelium, suggestive of the recently proposed brain-first PD subtype. Assaying α-syn of diverse origins, such as olfactory (part of the central nervous system) and skin (peripheral nervous system), could increase diagnostic accuracy and allow better stratification of patients.
Objective
Growing interest in measuring the cochlear duct length (CDL) has emerged, since it can influence the selection of cochlear implant electrodes. Currently the measurements are performed with ionized radiation imaging. Only a few studies have explored CDL measurements in magnetic resonance imaging (MRI). Therefore, the presented study aims to fill this gap by estimating CDL in MRI and comparing it with multislice computed tomography (CT).
Study Design
Retrospective data analyses of 42 cochleae.
Setting
Tertiary care medical center.
Methods
Diameter (A value) and width (B value) of the cochlea were measured in HOROS software. The CDL and the 2-turn length were determined by the elliptic circular approximation (ECA). In addition, the CDL, the 2-turn length, and the angular length were determined via HOROS software by the multiplanar reconstruction (MPR) method.
Results
CDL values were significantly shorter in MRI by MPR (d = 1.38 mm, P < .001) but not by ECA. Similar 2-turn length measurements were significantly lower in MRI by MPR (d = 1.67 mm) and ECA (d = 1.19 mm, both P < .001). In contrast, angular length was significantly higher in MRI (d = 26.79°, P < .001). When the values were set in relation to the frequencies of the cochlea, no clinically relevant differences were estimated (58 Hz at 28-mm CDL).
Conclusion
In the presented study, CDL was investigated in CT and MRI by using different approaches. Since no clinically relevant differences were found, diagnostics with radiation may be omitted prior to cochlear implantation; thus, a concept of radiation-free cochlear implantation could be established.
Objectives: To assess the subjective and objective performance of the new fine structure processing strategy (FSP) compared to the previous generation coding strategies CIS+ and HDCIS. Methods: Forty-six adults with a minimum of 6 months of cochlear implant experience were included. CIS+, HDCIS and FSP were compared in speech perception tests in noise, pitch scaling and questionnaires. The randomized tests were performed acutely (interval 1) and again after 3 months of FSP experience (interval 3). The subjective evaluation included questionnaire 1 at intervals 1 and 3, and questionnaire 2 at interval 2, 1 month after interval 1. Results: Comparison between FSP and CIS+ showed that FSP performed at least as well as CIS+ in all speech perception tests, and outperformed CIS+ in vowel and monosyllabic word discrimination. Comparison between FSP and HDCIS showed that both performed equally well in all speech perception tests. Pitch scaling showed that FSP performed at least as well as HDCIS. With FSP, sound quality was at least as good and often better than with HDCIS. Conclusions: Results indicate that FSP performs better than CIS+ in vowel and monosyllabic word understanding. Subjective evaluation demonstrates strong user preferences for FSP when listening to speech and music.
In der vorliegenden Arbeit wurden Gefrierschnitte von 28 Cholesteatomen mit unterschiedlichen Entzündungsgraden immunhistochemisch untersucht. Ziel dieser Studie war es, durch immunologische Färbemethoden eine quantitative und qualitative Bestimmung immunkompetenter Zellen im histologischen Präparat der Cholesteatomperimatrix durchzuführen. Dabei wurde die indirekte Immunperoxidase-Methode angewandt. Als Zelloberflächenmarker dienten dabei CD 25, CD 28, CD 40, CD 40 Ligand, CD 69, B7-1 und B7-2. Die Ergebnisse zeigten eine allgemeine Tendenz zu Zellhäufungen im Bereich der Perimatrix und stützen die These, daß sich die Entzündungsreaktion vorwiegend in der Perimatrix abspielt. Ein weiteres Resultat war, daß aktivierte T-Zellen in Abhängigkeit von der klinischen Aggressivität des Cholesteatoms vermehrt auftreten.
Background
Fabry Disease (FD) is an X-linked hereditary lysosomal storage disorder which leads to a multisystemic intralysosomal accumulation of globotriaosylceramid (Gb3). Besides prominent renal and cardiac organ involvement, patients commonly complain about vestibulocochlear symptoms like high-frequency hearing loss, tinnitus and vertigo. However, comprehensive data especially on vertigo remain scarce. The aim of this study was to examine the prevalence and characteristics of vertigo and hearing loss in patients with FD, depending on renal and cardiac parameters and get hints about the site and the pattern of the lesions.
Methods
Single-center study with 57 FD patients. Every patient underwent an oto-rhino-laryngological examination as well as videonystagmography and vestibular evoked myogenic potentials (VEMPs) and audiological measurements using pure tone audiometry and auditory brainstem response audiometry (ABR). Renal function was measured by eGFR, cardiac impairment was graduated by NYHA class.
Results
More than one out of three patients (35.1%) complained about hearing loss, 54.4% about vertigo and 28.1% about both symptom. In 74% a sensorineural hearing loss of at least 25 dB was found, ABR could exclude any retrocochlear lesion. Caloric testing showed abnormal values in 71.9%, VEMPs were pathological in 68%. A correlation between the side or the shape of hearing loss and pathological vestibular testing could not be revealed.
Conclusions
Hearing loss and vertigo show a high prevalence in FD. While hearing loss seems due to a cochlear lesion, peripheral vestibular as well as central nervous pathologies cause vertigo. Thus, both the site of lesion and the pathophysiological patterns seem to differ.
Background
Fabry disease (FD) is an X-linked recessive hereditary lysosomal storage disorder which results in the accumulation of globotriaosylceramid (Gb3) in tissues of kidney and heart as well as central and peripheral nervous system.
Besides prominent renal and cardiac organ involvement, cochlear symptoms like high-frequency hearing loss and tinnitus are frequently found with yet no comprehensive data available in the literature.
Objective
To examine hearing loss in patients with FD depending on cardiac and renal function.
Material and methods
Single-center study with 68 FD patients enrolled between 2012 and 2016 at the Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery of the University of Würzburg. Every subject underwent an oto-rhino-laryngological examination as well as behavioral, electrophysiological and electroacoustical audiological testing. High-frequency thresholds were evaluated by using a modified PTA\(_{6}\) (0.5, 1, 2, 4, 6, 8) and HF-PTA (6, 8 kHz). Renal function was measured by eGFR, cardiac impairment was graduated by NYHA class.
Results
Sensorineural hearing loss was detected in 58.8% of the cohort, which occurred typically in sudden episodes and affected especially high frequencies. Hearing loss is asymmetric, beginning unilaterally and affecting the contralateral ear later. Tinnitus was reported by 41.2%. Renal and cardiac impairment influenced the severity of hearing loss (p < 0.05).
Conclusions
High frequency hearing loss is a common problem in patients with FD. Although not life-threatening, it can seriously reduce quality of life and should be taken into account in diagnosis and therapy. Optimized extensive hearing assessment including higher frequency thresholds should be used.
Diese Dissertation stellt das Verfahren des Brain Electrical Activity Mappings der späten Vestibulär Evozierten Potentiale (BEAM-VestEP) bei Tinnituspatienten vor im Hinblick auf die therapeutische Wirksamkeit der kompetitiv-kinästhetischen-Interaktionstherapie auf der Basis der Brügger Therapie im „Murnauer Konzept“ und überprüft ihre Evidenz.