Klinik und Poliklinik für Hals-, Nasen- und Ohrenkrankheiten, plastische und ästhetische Operationen
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Sonstige beteiligte Institutionen
Objective: To evaluate the safety and effectiveness of round window (RW), oval window (OW), CliP and Bell couplers for use with an active middle ear implant. Methods: This is a multicenter, long-term, prospective trial with consecutive enrollment, involving 6 university hospitals in Germany. Bone conduction, air conduction, implant-aided warble-tone thresholds and Freiburger monosyllable word recognition scores were compared with unaided preimplantation results in 28 moderate-to-profound hearing-impaired patients after 12 months of follow-up. All patients had previously undergone failed reconstruction surgeries (up to 5 or more). In a subset of patients, additional speech tests at 12 months postoperatively were used to compare the aided with the unaided condition after implantation with the processor switched off. An established quality-of-life questionnaire for hearing aids was used to determine patient satisfaction. Results: Postoperative bone conduction remained stable. Mean functional gain for all couplers was 37 dB HL (RW = 42 dB, OW = 35 dB, Bell = 38 dB, CliP = 27 dB). The mean postoperative Freiburger monosyllable score was 71% at 65 dB SPL. The postimplantation mean SRT<sub>50</sub> (speech reception in quiet for 50% understanding of words in sentences) improved on average by 23 dB over unaided testing and signal-to-noise ratios also improved in all patients. The International Outcome Inventory for Hearing Aids (IOI-HA)quality-of-life questionnaire was scored very positively by all patients. Conclusion: A significant improvement was seen with all couplers, and patients were satisfied with the device at 12 months postoperatively. These results demonstrate that an active implant is an advantage in achieving good hearing benefit in patients with prior failed reconstruction surgery.
Background
Tumor hypoxia is a known risk factor for reduced response to radiotherapy. The evaluation of noninvasive methods for the detection of hypoxia is therefore of interest. Osteopontin (OPN) has been discussed as an endogenous hypoxia biomarker. It is overexpressed in many cancers and is involved in tumor progression and metastasis.
Methods
To examine the influence of hypoxia and irradiation on osteopontin expression we used different cell lines (head and neck cancer (Cal27 and FaDu) and glioblastoma multiforme (U251 and U87)). Cells were treated with hypoxia for 24 h and were then irradiated with doses of 2 and 8 Gy. Osteopontin expression was analyzed on mRNA level by quantitative real-time RT-PCR (qPCR) and on protein level by western blot. Cell culture supernatants were evaluated for secreted OPN by ELISA.
Results
Hypoxia caused an increase in osteopontin protein expression in all cell lines. In Cal27 a corresponding increase in OPN mRNA expression was observed. In contrast the other cell lines showed a reduced mRNA expression under hypoxic conditions. After irradiation OPN mRNA expression raised slightly in FaDu and U87 cells while it was reduced in U251 and stable in Cal27 cells under normoxia. The combined treatment (hypoxia and irradiation) led to a slight increase of OPN mRNA after 2 Gy in U251 (24 h) and in U87 (24 and 48 h) cell lines falling back to base line after 8 Gy. This effect was not seen in Cal27 or in FaDu cells. Secreted OPN was detected only in the two glioblastoma cell lines with reduced protein levels under hypoxic conditions. Again the combined treatment resulted in a minor increase in OPN secretion 48 hours after irradiation with 8 Gy.
Conclusion
Osteopontin expression is strongly modulated by hypoxia and only to a minor extent by irradiation. Intracellular OPN homeostasis seems to vary considerably between cell lines. This may explain the partly conflicting results concerning response prediction and prognosis in the clinical setting.
Tinnitus is the perception of a phantom sound that affects between 10 and 15% of the general population. Despite this considerable prevalence, treatments for tinnitus are presently lacking. Tinnitus exhibits a diverse array of recognized risk factors and extreme clinical heterogeneity. Furthermore, it can involve an unknown number of auditory and non-auditory networks and molecular pathways. This complex combination has hampered advancements in the field. The identification of specific genetic factors has been at the forefront of several research investigations in the past decade. Nine studies have examined genes in a case-control association approach. Recently, a genome-wide association study has highlighted several potentially significant pathways that are implicated in tinnitus. Two twin studies have calculated a moderate heritability for tinnitus and disclosed a greater concordance rate in monozygotic twins compared to dizygotic twins. Despite the more recent data alluding to genetic factors in tinnitus, a strong association with any specific genetic locus is lacking and a genetic study with sufficient statistical power has yet to be designed. Future research endeavors must overcome the many inherent limitations in previous study designs. This review summarizes the previously embarked upon tinnitus genetic investigations and summarizes the hurdles that have been encountered. The identification of candidate genes responsible for tinnitus may afford gene based diagnostic approaches, effective therapy development, and personalized therapeutic intervention.
Objectives:
Despite recent advancements in diagnostic tools, the genomic landscape of hereditary hearing loss remains largely uncharacterized. One strategy to understand genome-wide aberrations includes the analysis of copy number variation that can be mapped using SNP-microarray technology. A growing collection of literature has begun to uncover the importance of copy number variation in hereditary hearing loss. This pilot study underpins a larger effort that involves the stage-wise analysis of hearing loss patients, many of whom have advanced to high-throughput sequencing analysis.
Data description:
Our data originate from the Infinium HumanOmni1-Quad v1.0 SNP-microarrays (Illumina) that provide useful markers for genome-wide association studies and copy number variation analysis. This dataset comprises a cohort of 108 individuals (99 with hearing loss, 9 normal hearing family members) for the purpose of understanding the genetic contribution of copy number variations to hereditary hearing loss. These anonymized SNP-microarray data have been uploaded to the NCBI Gene Expression Omnibus and are intended to benefit other investigators interested in aggregating platform-matched array patient datasets or as part of a supporting reference tool for other laboratories to better understand recurring copy number variations in other genetic disorders.
Causal therapies for the auditory-pathway and inner-ear diseases are still not yet available for clinical application. Regenerative medicine approaches are discussed and examined as possible therapy options. Neural stem cells could play a role in the regeneration of the auditory pathway. In recent years, neural stem and progenitor cells have been identified in the cochlear nucleus, the second nucleus of the auditory pathway. The current investigation aimed to analyze cell maturation concerning cellular calcium activity. Cochlear nuclei from PND9 CD rats were microscopically dissected and propagated as neurospheres in free-floating cultures in stem-cell medium (Neurobasal, B27, GlutaMAX, EGF, bFGF). After 30 days, the dissociation and plating of these cells took place under withdrawal of the growth factors and the addition of retinoic acid, which induces neural cell differentiation. Calcium imaging analysis with BAPTA-1/Oregon Green was carried out at different times during the differentiation phase. In addition, the influence of different voltage-dependent calcium channels was analyzed through the targeted application of inhibitors of the L-, N-, R- and T-type calcium channels. For this purpose, comparative examinations were performed on CN NSCs, and primary CN neurons. As the cells differentiated, a significant increase in spontaneous neuronal calcium activity was demonstrated. In the differentiation stage, specific frequencies of the spontaneous calcium oscillations were measured in different regions of the individual cells. Initially, the highest frequency of spontaneous calcium oscillations was ascertainable in the maturing somata. Over time, these were overtaken by calcium oscillations in the axons and dendrites. Additionally, in the area of the growth cones, an increasing activity was determined. By inhibiting voltage-dependent calcium channels, their expression and function in the differentiation process were confirmed. A comparable pattern of maturation of these channels was found in CN NSCs and primary CN neurons. The present results show that neural stem cells of the rat cochlear nucleus differentiated not only morphologically but also functionally. Spontaneous calcium activities are of great relevance in terms of neurogenesis and integration into existing neuronal structures. These functional aspects of neurogenesis within the auditory pathway could serve as future targets for the exogenous control of neuronal regeneration.
This study aimed to discover expert opinion on the surgical techniques and materials most likely to achieve maximum postoperative residual hearing preservation in cochlear implant (CI) surgery and to determine how these opinions have changed since 2010. A previously published questionnaire used in a study published in 2010 was adapted and expanded. The questionnaire was distributed to an international group of experienced CI surgeons. Present results were compared, via descriptive statistics, to those from the 2010 survey. Eighteen surgeons completed the questionnaire. Respondents clearly favored the following: round window insertion, slow array insertion, and the peri- and postoperative use of systematic antibiotics. Insertion depth was regarded as important, and electrode arrays less likely to induce trauma were preferred. The usefulness of dedicated soft-surgery training was also recognized. A lack of agreement was found on whether the middle ear cavity should be flushed with a non-aminoglycoside antibiotic solution or whether a sheath or insertion tube should be used to avoid contaminating the array with blood or bone dust. In conclusion, this paper demonstrates how beliefs about CI soft surgery have changed since 2010 and shows areas of current consensus and disagreement.
Surgical management of lateral neck abscesses in children: a retrospective analysis of 100 cases
(2023)
Cervical abscesses are relatively common infections in pediatric patients. There is an ongoing debate about the necessity and time point of surgical drainage. The identification of a focus of infection might play an important role in facilitating a therapeutic decision. In a retrospective study, 100 pediatric patients aged 1–18 years who underwent incision and drainage of a lateral cervical abscess at our institution were analyzed. Patients were divided into two groups based on whether a focus of infection could be identified or not. Data collection included patient characteristics, microbiological results, antibiotic regimen, and clinical course. A focus of infection was found in 29% (29/100) of the patients, most frequently in the tonsils. A causative microorganism was found in 75% (75/100) of all patients, with Staphylococcus aureus and Streptococcus pyogenes being the most common pathogens. All patients received an empiric antibiotic therapy in addition to surgery. Antibiotic medication was changed in 31% in both groups (9/29 with a focus of infection and 22/71 without a focus of infection) during therapy. Children without an identified focus of infection generally were younger and had more comorbidities reducing immune response while also showing differences in the pathogens involved. There were no complications associated to surgery or antibiotic therapy in any of the patients involved.
Conclusion: Children with an identified focus of infection show several differences compared to those with isolated lateral abscesses, especially regarding the microorganisms involved. But the focus of infection seems not to have an impact on patient’s outcome.
What is Known:
• Neck abscesses are a relatively common disease in the pediatric population and may cause serious complications.
• Therapy in general consists of intravenous antibiotics with or without surgery.
What is New:
• The focus identification has no impact on patient’s outcome.
• Children with an identified focus of infection show several differences compared to those with isolated lateral abscesses, especially regarding their medical history, age, and the microorganisms involved.
This study aimed to evaluate the feasibility and accuracy of electromagnetic navigation at the lateral skull base in combination with flat panel volume computed tomography (fpVCT) datasets. A mastoidectomy and a posterior tympanotomy were performed on 10 samples of fresh frozen temporal bones. For registration, four self-drilling titanium screws were applied as fiducial markers. Multi-slice computed tomography (MSCT; 600 µm), conventional flat panel volume computed tomography (fpVCT; 466 µm), micro-fpVCT (197 µm) and secondary reconstructed fpVCT (100 µM) scans were performed and data were loaded into the navigation system. The resulting fiducial registration error (FRE) was analysed, and control of the navigation accuracy was performed. The registration process was very quick and reliable with the screws as fiducials. Compared to using the MSCT data, the micro-fpVCT data led to significantly lower FRE values, whereas conventional fpVCT and secondary reconstructed fpVCT data had no advantage in terms of accuracy. For all imaging modalities, there was no relevant visual deviation when targeting defined anatomical points with a navigation probe. fpVCT data are very well suited for electromagnetic navigation at the lateral skull base. The use of titanium screws as fiducial markers turned out to be ideal for comparing different imaging methods. A further evaluation of this approach by a clinical trial is required.
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.
Introduction
Cochlear implants known to provide support in individuals with bilateral hearing loss may also be of great benefit for individuals with unilateral hearing loss. This case report demonstrates the positive effects of cochlear implantation on speech understanding in noise conditions in patients with unilateral hearing loss and normal hearing on the contralateral side. To the best of our knowledge, the data presented here are from the first few cases to receive a cochlear implant for unilateral hearing loss.
Case presentation
Four Caucasian German men, two aged 48 and the others aged 51 and 57 years old, with post-lingual unilateral hearing loss and normal hearing on the contralateral side were implanted with a cochlear implant. All our patients were members of the German army. Before and after implantation, they were given a battery of speech tests in different hearing conditions to assess the effect of unilateral cochlear implantation on speech understanding in noise conditions. Test results showed that all patients benefited from unilateral cochlear implantation, particularly in terms of speech understanding in noise conditions.
Conclusions
Unilateral cochlear implantation might be a successful treatment method for patients with unilateral hearing loss not benefiting from alternative treatment options. The results of this case report open up the field of cochlear implantation for expanded criteria and new areas of research.
Due to the wide variety of benign and malignant salivary gland tumors, classification and malignant behavior determination based on histomorphological criteria can be difficult and sometimes impossible. Spectroscopical procedures can acquire molecular biological information without destroying the tissue within the measurement processes. Since several tissue preparation procedures exist, our study investigated the impact of these preparations on the chemical composition of healthy and tumorous salivary gland tissue by Fourier-transform infrared (FTIR) microspectroscopy. Sequential tissue cross-sections were prepared from native, formalin-fixed and formalin-fixed paraffin-embedded (FFPE) tissue and analyzed. The FFPE cross-sections were dewaxed and remeasured. By using principal component analysis (PCA) combined with a discriminant analysis (DA), robust models for the distinction of sample preparations were built individually for each parotid tissue type. As a result, the PCA-DA model evaluation showed a high similarity between native and formalin-fixed tissues based on their chemical composition. Thus, formalin-fixed tissues are highly representative of the native samples and facilitate a transfer from scientific laboratory analysis into the clinical routine due to their robust nature. Furthermore, the dewaxing of the cross-sections entails the loss of molecular information. Our study successfully demonstrated how FTIR microspectroscopy can be used as a powerful tool within existing clinical workflows.
Automated analysis of the inner ear anatomy in radiological data instead of time-consuming manual assessment is a worthwhile goal that could facilitate preoperative planning and clinical research. We propose a framework encompassing joint semantic segmentation of the inner ear and anatomical landmark detection of helicotrema, oval and round window. A fully automated pipeline with a single, dual-headed volumetric 3D U-Net was implemented, trained and evaluated using manually labeled in-house datasets from cadaveric specimen (N = 43) and clinical practice (N = 9). The model robustness was further evaluated on three independent open-source datasets (N = 23 + 7 + 17 scans) consisting of cadaveric specimen scans. For the in-house datasets, Dice scores of 0.97 and 0.94, intersection-over-union scores of 0.94 and 0.89 and average Hausdorf distances of 0.065 and 0.14 voxel units were achieved. The landmark localization task was performed automatically with an average localization error of 3.3 and 5.2 voxel units. A robust, albeit reduced performance could be
attained for the catalogue of three open-source datasets. Results of the ablation studies with 43 mono-parametric variations of the basal architecture and training protocol provided task-optimal parameters for both categories. Ablation studies against single-task variants of the basal architecture showed a clear performance beneft of coupling landmark localization with segmentation and a dataset-dependent performance impact on segmentation ability.
Background: The benefit of hearing rehabilitation is often measured using audiological tests or subjective questionnaires/interviews. It is important to consider both aspects in order to evaluate the overall benefits. Currently, there is no standardized method for reporting combined audiological and patient reported subjective outcome measures in clinical practice. Therefore, this study focuses on showing the patient’s audiological, as well as subjective outcomes in one graph using data from an existing study. Method: The present paper illustrated a graph presenting data on four quadrants with audiological and subjective findings. These quadrants represented speech comprehension in quiet (unaided vs. aided) as WRS% at 65 dB SPL, speech recognition in noise (unaided vs. aided) as SRT dB SNR, sound field threshold (unaided vs. aided) as PTA\(_4\) in dB HL, wearing time and patient satisfaction questionnaire results. Results: As an example, the HEARRING graph in this paper represented audiological and subjective datasets on a single patient level or a cohort of patients for an active bone conduction hearing implant solution. The graph offered the option to follow the user’s performance in time. Conclusion: The HEARRING graph allowed representation of a combination of audiological measures with patient reported outcomes in one single graph, indicating the overall benefit of the intervention. In addition, the correlation and consistency between some results (e.g., aided threshold and aided WRS) can be better visualized. Those users who lacked performance benefits on one or more parameters and called for further insight could be visually identified.
To study the interaction of human pathogens with their host target structures, human tissue models based on primary cells are considered suitable. Complex tissue models of the human airways have been used as infection models for various viral and bacterial pathogens. The Gram-negative bacterium Bordetella pertussis is of relevant clinical interest since whooping cough has developed into a resurgent infectious disease. In the present study, we created three-dimensional tissue models of the human ciliated nasal and tracheo-bronchial mucosa. We compared the innate immune response of these models towards the B. pertussis virulence factor adenylate cyclase toxin (CyaA) and its enzymatically inactive but fully pore-forming toxoid CyaA-AC\(^-\). Applying molecular biological, histological, and microbiological assays, we found that 1 µg/ml CyaA elevated the intracellular cAMP level but did not disturb the epithelial barrier integrity of nasal and tracheo-bronchial airway mucosa tissue models. Interestingly, CyaA significantly increased interleukin 6, interleukin 8, and human beta defensin 2 secretion in nasal tissue models, whereas tracheo-bronchial tissue models were not significantly affected compared to the controls. Subsequently, we investigated the interaction of B. pertussis with both differentiated primary nasal and tracheo-bronchial tissue models and demonstrated bacterial adherence and invasion without observing host cell type-specific significant differences. Even though the nasal and the tracheo-bronchial mucosa appear similar from a histological perspective, they are differentially susceptible to B. pertussis CyaA in vitro. Our finding that nasal tissue models showed an increased innate immune response towards the B. pertussis virulence factor CyaA compared to tracheo-bronchial tissue models may reflect the key role of the nasal airway mucosa as the first line of defense against airborne pathogens.
Purpose
In cancer of unknown primary (CUP), positron emission tomography/computed tomography (PET/CT) with the glucose analog [\(^{18}\)F]FDG represents the standard imaging approach for localization of the malignant primary. Frequently, however, [\(^{18}\)F]FDG PET/CT cannot precisely distinguish between small occult tumors and chronic inflammation, especially in Waldeyer’s tonsillar ring. To improve the accuracy for detecting primary tumors in the Waldeyer’s tonsillar ring, the novel PET tracer [\(^{68}\)Ga]Ga-FAPI-4 for specific imaging of fibroblast activation protein (FAP) expression was used as a more specific target for cancer imaging.
Methods
Eight patients with suspicion of a malignant tumor in Waldeyer’s tonsillar ring or a CUP syndrome were examined. PET/CT scans with [\(^{18}\)F]-FDG and [\(^{68}\)Ga]Ga-FAPI-4 were performed for pre-operative tumor localization. After surgical resection, histopathological and immunohistochemical results were compared to PET/CT findings.
Results
Histopathology revealed a palatine or lingual tonsil carcinoma in all patients. In case of lymph node metastases smaller than 7 mm in size, the [\(^{18}\)F]FDG PET/CT detection rate of cervical lymph node metastases was higher than that of [\(^{68}\)Ga]FAPI PET/CT, while both tracers identified the primary tumors in all eight cases. The size of the primary and the lymph node metastases was directly correlated to the respective FAP expression, as detected by immunohistochemistry. The mean SUVmax for the primary tumors was 21.29 ± 7.97 for \(^{18}\)F-FDG and 16.06 ± 6.29 for \(^{68}\)Ga-FAPI, respectively (p = 0.2). The mean SUVmax for the healthy contralateral tonsils was 8.38 ± 2.45 for [\(^{18}\)F]FDG and 3.55 ± 0.47 for [\(^{68}\)Ga]FAPI (p < 0.001). The SUVmax ratio of [68Ga]FAPI was significantly different from [\(^{18}\)F] FDG (p = 0.03). Mean TBRmax for the [\(^{68}\)Ga]Ga-FAPI-4 tracer was markedly higher in comparison to [\(^{18}\)F]FDG (10.90 vs. 4.11).
Conclusion
Non-invasive imaging of FAP expression by [\(^{68}\)Ga]FAPI PET/CT resulted in a better visual detection of the malignant primary in CUP, as compared to [\(^{18}\)F]FDG imaging. However, the detection rate of lymph node metastases was inferior, presumably due to low FAP expression in small metastases. Nevertheless, by offering a detection method for primary tumors with the potential of lower false positive rates and thus avoiding biopsies, patients with CUP syndrome may benefit from [\(^{68}\)Ga]FAPI PET/CT imaging.
Introduction: Since 1996, the preferred approach for positioning the active middle-ear implant Vibrant Soundbridge© is a mastoidectomy and a posterior tympanotomy. With this device, placement of the floating mass transducer (FMT) on the long incus process is the standard method for treatment of mild-to-severe sensorineural hearing loss in the case of normal middle-ear anatomy. The aim of this study was to determine the vibrational effectiveness of FMT placement at the short incus process. Materials and Methods: An extended antrotomy and a posterior tympanotomy were performed in 5 fresh human temporal bones. As a control for normal middle-ear function, the tympanic membrane was stimulated acoustically and the vibration of the stapes footplate and the round-window (RW) membrane were (sequentially) measured by laser Doppler vibrometry. Vibration responses for coupling of an FMT to the long incus process (standard coupling) were compared to those for coupling to the short incus process. Results: Apart from narrow frequency bands near 3 and 9 kHz for the stapes footplate and RW membrane, respectively, the velocity responses presented no significant differences between standard coupling of the FMT and coupling to the short incus process. Conclusion: Coupling the FMT to the short incus process may be a viable alternative in cases where the surgical approach is limited to an extended antrotomy. A reliable technique for attachment to the short incus process has yet to be developed.
Background:
According to only a handful of historical sources, Osmunda regalis, the royal fern, has been used already in the middle age as an anti-cancer remedy. To examine this ancient cancer cure, an ethanolic extract of the roots was prepared and analysed in vitro on its effectiveness against head and neck cancer cell lines.
Methods:
Proliferation inhibition was measured with the MTT assay. Invasion inhibition was tested in a spheroid-based 3-D migration assay on different extracellular matrix surfaces. Corresponding changes in gene expression were analysed by qRT-PCR array. Induction of apoptosis was measured by fluorescence activated cell sorting (FACS) with the Annexin V binding method. The plant extract was analysed by preliminary phytochemical tests, liquid chromatography/mass spectroscopy (LC-MS) and thin layer chromatography (TLC). Anti-angiogenetic activity was determined by the tube formation assay.
Results:
O. regalis extract revealed a growth inhibiting effect on the head and neck carcinoma cell lines HLaC78 and FaDu. The toxic effect seems to be partially modulated by p-glycoprotein, as the MDR-1 expressing HLaC79-Tax cells were less sensitive. O. regalis extract inhibited the invasion of cell lines on diverse extracellular matrix substrates significantly. Especially the dispersion of the highly motile cell line HlaC78 on laminin was almost completely abrogated. Motility inhibition on laminin was accompanied by differential gene regulation of a variety of genes involved in cell adhesion and metastasis. Furthermore, O. regalis extract triggered apoptosis in HNSCC cell lines and inhibited tube formation of endothelial cells. Preliminary phytochemical analysis proved the presence of tannins, glycosides, steroids and saponins. Liquid chromatography/mass spectroscopy (LC-MS) revealed a major peak of an unknown substance with a molecular mass of 864.15 Da, comprising about 50% of the total extract. Thin layer chromatography identified ferulic acid to be present in the extract.
Conclusion:
The presented results justify the use of royal fern extracts as an anti-cancer remedy in history and imply a further analysis of ingredients.
Background: Zinc oxide nanoparticles (ZnO NPs) are among the most frequently applied nanomaterials in consumer products. Evidence exists regarding the cytotoxic effects of ZnO NPs in mammalian cells; however, knowledge about the potential genotoxicity of ZnO NPs is rare, and results presented in the current literature are inconsistent. Objectives: The aim of this review is to summarize the existing data regarding the DNA damage that ZnO NPs induce, and focus on the possible molecular mechanisms underlying genotoxic events. Methods: Electronic literature databases were systematically searched for studies that report on the genotoxicity of ZnO NPs. Results: Several methods and different endpoints demonstrate the genotoxic potential of ZnO NPs. Most publications describe in vitro assessments of the oxidative DNA damage triggered by dissoluted Zn2+ ions. Most genotoxicological investigations of ZnO NPs address acute exposure situations. Conclusion: Existing evidence indicates that ZnO NPs possibly have the potential to damage DNA. However, there is a lack of long-term exposure experiments that clarify the intracellular bioaccumulation of ZnO NPs and the possible mechanisms of DNA repair and cell survival.
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.