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OBJECTIVE: Determining the concentration of prestin in human blood, cerebrospinal fluid (CSF), and perilymph (PL), and evaluating its suitability as a clinical biomarker for sensori-neural hearing loss (SNHL). STUDY DESIGN: Human blood, CSF, and PL samples were intraoperatively collected from 42 patients with tumors of the internal auditory canal or with intracochlear tumors undergoing translabyrinthine or middle fossa tumor removal. Prestin concentration was measured using enzyme-linked immunosorbent assay and linear regression analyses were performed to investigate its associations with audiological as well as vestibular test results. SETTING: Tertiary referral center. RESULTS: The median prestin concentration in blood samples of the 42 study participants (26 women, mean ± standard deviation age, 52.7 ± 12.5 years) was 1.32 (interquartile range, IQR, 0.71-1.99) ng/mL. CSF prestin levels were significantly higher with 4.73 (IQR, 2.45-14.03) ng/mL (P = .005). With 84.74 (IQR, 38.95-122.00) ng/mL, PL prestin concentration was significantly higher compared to blood (P = .01) and CSF (P = .03) levels. Linear regression analyses showed significant associations of CSF prestin concentration with preoperative hearing levels (pure-tone average and word recognition; P = .008, R2 = 0.1894; P = .03, R2 = 0.1857), but no correlations with blood or PL levels. CONCLUSION AND RELEVANCE: This study's findings highlight the volatile nature of prestin levels and provide the first insights into this potential biomarker's concentrations in body fluids apart from blood. Future investigations should comprehensively assess human prestin levels with different etiologies of SNHL, prestin's natural homeostasis and systemic circulation, and its temporal dynamics after cochlear trauma. Finally, clinically approved detection kits for prestin are urgently required prior to considering a potential translational implementation of this diagnostic technique.
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To develop microbiologically safe nanofibrous materials, it is crucial to understand their interactions with microbial cells. Current research indicates that the morphology of nanofibers, particularly the diameter of the fibers, may play a significant role in biofilm formation and retention. However, it has not yet been determined how the fiber diameter of poly-ε-caprolactone (PCL), one of the most widely used biopolymers, affects these microbial interactions. In this study, two nanofibrous materials electrospun from PCL (PCL45 and PCL80) with different fiber diameter and characteristic distance δ between fibers were compared in terms of their ability to support or inhibit bacterial biofilm formation and retain bacterial cells. Strains of Escherichia coli (ATCC 25922 and ATCC 8739) and Staphylococcus aureus (ATCC 25923 and ATCC 6538) were used as model bacteria. Biofilm formation rate and retention varied significantly between the E. coli and S. aureus strains (p < 0.05) for the tested nanomaterials. In general, PCL showed a lower tendency to be colonized by the tested bacteria compared to the control material (polystyrene). Fiber diameter did not influence the biofilm formation rate of S. aureus strains and E. coli 25922 (p > 0.05), but it did significantly impact the biofilm formation rate of E. coli 8739 and biofilm morphology formed by all of the tested bacterial strains. In PCL45, thick uniform biofilm layers were formed preferably on the surface, while in PCL80 smaller clusters formed preferably inside the structure. Further, fiber diameter significantly influenced the retention of bacterial cells of all the tested strains (p < 0.001). PCL45, with thin fibers (average fiber diameter of 376 nm), retained up to 7 log (CFU mL-1) of staphylococcal cells (100% retention). The overall results indicate PCL45's potential for further research and highlight the nanofibers' morphology influence on bacterial interactions and differences in bacterial strains' behavior in the presence of nanomaterials.
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Biopelículas , Escherichia coli , Nanofibras , Poliésteres , Staphylococcus aureus , Biopelículas/efectos de los fármacos , Poliésteres/química , Poliésteres/farmacología , Nanofibras/química , Staphylococcus aureus/fisiología , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/fisiología , Escherichia coli/efectos de los fármacosRESUMEN
The use of electrospun polymeric biodegradable materials for medical applications is becoming increasingly widespread. One of the most important parameters regarding the functionality of nanofiber scaffolds during implantation and the subsequent regeneration of damaged tissues concerns their stability and degradation behavior, both of which are influenced by a wide range of factors (the properties of the polymer and the polymer solution, the technological processing approach, the sterilization method, etc.). This study monitored the degradation of nanofibrous materials fabricated from degradable polyesters as a result of the sterilization method applied (ethylene oxide and gamma irradiation) and the solvent system used to prepare the spun polymer solution. Aliphatic polyesters PCL and PLCL were chosen for this study and selected with respect to the applicability and handling in the surgical setting of these nanofibrous materials for vascular bandaging. The results revealed that the choice of solvent system exerts a significant impact on degradation during sterilization, especially at higher gamma irradiation values. The subsequent enzyme-catalyzed degradation of the materials following sterilization indicated that the choice of the sterilization method influenced the degradation behavior of the materials. Whereas wave-like degradation was evident concerning ethylene oxide sterilization, no such behavior was observed following gamma-irradiation sterilization. With concern for some of the tested materials, the results also indicated the potential for influencing the development of degradation within the bulk versus degradation from the surface of the material. Both the sterilization method and the choice of the spinning solvent system were found to impact degradation, which was observed to be most accelerated in the case of PLCL (L-lactide-co-caprolactone copolymer) electrospun from organic acids and subsequently sterilized using gamma irradiation. Since we planned to use these materials in cardiovascular applications, it was decided that their hemocompatibility would also be tested. The results of these tests revealed that changes in the structures of the materials initiated by sterilization may exert thrombogenic and anticoagulant impacts. Moreover, the microscopic analysis suggested that the solvent system used in the preparation of the materials potentially affects the behavior of erythrocytes; however, no indication of the occurrence of hemolysis was detected.
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BACKGROUND: The current requirement is to establish the preoperative diagnosis accurately as possible and to achieve an adequate extent of surgery. The aim of this study was to define the preoperative clinical and molecular genetic risks of malignancy in indeterminate thyroid nodules (Bethesda III and IV) and to determine their impact on the surgical strategy. METHODS: Prospectively retrospective analysis of 287 patients provided the basis of preoperative laboratory examination, sonographic stratification of malignancy risks and cytological findings. Molecular tests focused on pathogenic variants of genes associated with thyroid oncogenesis in cytologically indeterminate nodules (Bethesda III and IV). The evaluation included clinical risk factors: positive family history, radiation exposure and growth in size and/or number of nodules. RESULTS: Preoperative FNAB detected 52 cytologically indeterminate nodules (28.7%) out of 181 patients. Postoperative histopathological examination revealed malignancy in 12 cases (23.7%) and there was no significant difference between Bethesda III and IV categories (P=0.517). Clinical risk factors for malignancy were found in 32 patients (61.5%) and the presence of at least one of them resulted in a clearly higher incidence of malignancy than their absence (31.3% vs. 10.0%, respectively). Pathogenic variants of genes were detected in 12/49 patients in Bethesda III and IV, and in 4 cases (33.3%) thyroid carcinoma was revealed. The rate of malignancies was substantially higher in patients with pathogenic variants than in those without (33.3% vs. 16.2%, respectively). CONCLUSIONS: Our experience implies that molecular genetic testing is one of several decision factors. We will continue to monitor and enlarge our patient cohort to obtain long-term follow-up data.
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The development of an ideal vascular prosthesis represents an important challenge in terms of the treatment of cardiovascular diseases with respect to which new materials are being considered that have produced promising results following testing in animal models. This study focuses on nanofibrous polycaprolactone-based grafts assessed by means of histological techniques 10 days and 6 months following suturing as a replacement for the rat aorta. A novel stereological approach for the assessment of cellular distribution within the graft thickness was developed. The cellularization of the thickness of the graft was found to be homogeneous after 10 days and to have changed after 6 months, at which time the majority of cells was discovered in the inner layer where the regeneration of the vessel wall was found to have occurred. Six months following implantation, the endothelialization of the graft lumen was complete, and no vasa vasorum were found to be present. Newly formed tissue resembling native elastic arteries with concentric layers composed of smooth muscle cells, collagen, and elastin was found in the implanted polycaprolactone-based grafts. Moreover, the inner layer of the graft was seen to have developed structural similarities to the regular aortic wall. The grafts appeared to be well tolerated, and no severe adverse reaction was recorded with the exception of one case of cartilaginous metaplasia close to the junctional suture.
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BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) comprises the triad of chronic rhinosinusitis with nasal polyps, asthma and intolerance to NSAIDs. Dupilumab treatment, targeting the interleukin-4 (IL-4) receptor α, significantly reduces polyp burden as well as asthma symptoms. Here we aimed to investigate the effect of dupilumab on aspirin intolerance, burden of disease and nasal cytokine profiles in patients with N-ERD. METHODS: In this open-label trial, adult patients with confirmed N-ERD were treated with dupilumab for 6â months. Clinical parameters (e.g. total polyp scores, quality of life questionnaires, smell test, spirometry), oral aspirin provocation testing and blood, nasal and urine sampling were monitored at regular intervals for up to 6â months after starting dupilumab therapy. RESULTS: Of the 31 patients included in the study, 30 completed both aspirin provocation tests. After 6â months of treatment with dupilumab, 23% of patients (n=7 of 30) developed complete aspirin tolerance and an additional 33% of patients (n=10 of 30) tolerated higher doses. Polyp burden was significantly reduced (total polyp score: -2.68±1.84, p<0.001), while pulmonary symptoms (asthma control test: +2.34±3.67, p<0.001) and olfactory performance improved (University of Pennsylvania Smell Identification Test: +11.16±9.54, p<0.001) in all patients after therapy. Patients with increased aspirin tolerance showed a significant decrease in urinary leukotriene E4 levels and their improvement in clinical parameters was associated with a reduction of eotaxin-1, C-C motif chemokine ligand 17, IL-5, IL-17A and IL-6. CONCLUSION: In this study, 57% of N-ERD patients tolerated higher doses of aspirin under dupilumab therapy.
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Asma , Pólipos Nasales , Trastornos Respiratorios , Rinitis , Adulto , Humanos , Aspirina/efectos adversos , Calidad de Vida , Antiinflamatorios no Esteroideos/efectos adversos , Pólipos Nasales/tratamiento farmacológico , Pólipos Nasales/complicaciones , Trastornos Respiratorios/complicaciones , Asma/tratamiento farmacológico , Enfermedad Crónica , Rinitis/tratamiento farmacológico , Rinitis/complicacionesRESUMEN
Active wound dressings are attracting extensive attention in soft tissue repair and regeneration, including bacteria-infected skin wound healing. As the wide use of antibiotics leads to drug resistance we present here a new concept of wound dressings based on the polycaprolactone nanofiber scaffold (NANO) releasing second generation lipophosphonoxin (LPPO) as antibacterial agent. Firstly, we demonstrated in vitro that LPPO released from NANO exerted antibacterial activity while not impairing proliferation/differentiation of fibroblasts and keratinocytes. Secondly, using a mouse model we showed that NANO loaded with LPPO significantly reduced the Staphylococcus aureus counts in infected wounds as evaluated 7 days post-surgery. Furthermore, the rate of degradation and subsequent LPPO release in infected wounds was also facilitated by lytic enzymes secreted by inoculated bacteria. Finally, LPPO displayed negligible to no systemic absorption. In conclusion, the composite antibacterial NANO-LPPO-based dressing reduces the bacterial load and promotes skin repair, with the potential to treat wounds in clinical settings.
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Antibacterianos/administración & dosificación , Vendajes , Nanofibras , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus , Cicatrización de Heridas/efectos de los fármacos , Infección de Heridas/tratamiento farmacológico , Animales , Antibacterianos/uso terapéutico , Modelos Animales de Enfermedad , RatonesRESUMEN
BACKGROUND/AIM: Anastomotic leakage is a feared complication in colorectal surgery. Postoperative peritoneal adhesions can also cause life-threatening conditions. Nanofibrous materials showed their pro-healing properties in various studies. The aim of the study was to evaluate the impact of double-layered nanofibrous materials on anastomotic healing and peritoneal adhesions formation. MATERIALS AND METHODS: Two versions of double-layered materials from polycaprolactone and polyvinyl alcohol were applied on defective anastomosis on the small intestine of healthy pigs. The control group remained with uncovered defect. Tissue specimens were subjected to histological analysis and adhesion scoring after 3 weeks of observation. RESULTS: The wound healing was inferior in the experimental groups, however, no anastomotic leakage was observed and the applied material always kept covering the defect. The extent of adhesions was larger in the experimental groups. CONCLUSION: Nanofibrous materials may prevent anastomotic leakage but delay healing.
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Fuga Anastomótica , Nanofibras , Anastomosis Quirúrgica/efectos adversos , Fuga Anastomótica/etiología , Fuga Anastomótica/patología , Fuga Anastomótica/prevención & control , Animales , Colon/patología , Porcinos , Adherencias Tisulares/prevención & control , Cicatrización de HeridasRESUMEN
Anastomotic leakage is a severe complication in gastrointestinal surgery. It is often a reason for reoperation together with intestinal passage blockage due to formation of peritoneal adhesions. Different materials as local prevention of these complications have been studied, none of which are nowadays routinely used in clinical practice. Nanofabrics created proved to promote healing with their structure similar to extracellular matrix. We decided to study their impact on anastomotic healing and formation of peritoneal adhesions. We performed an experiment on 24 piglets. We constructed 3 hand sutured end-to-end anastomoses on the small intestine of each pig. We covered the anastomoses with a sheet of polycaprolactone nanomaterial in the first experimental group, with a sheet of copolymer of polylactic acid with polycaprolactone in the second one and no fortifying material was used in the Control group. The animals were sacrificed after 3 weeks of observation. Clinical, biochemical and macroscopic signs of anastomotic leakage or intestinal obstruction were monitored, the quality of the scar tissue was assessed histologically, and a newly developed scoring system was employed to evaluate the presence of adhesions. The material is easy to manipulate with. There was no mortality or major morbidity in our groups. No statistical difference was found inbetween the groups in the matter of level of peritoneal adhesions or the quality of the anastomoses. We created a new adhesion scoring system. The material appears to be safe however needs to be studied further to prove its' positive effects.
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Fuga Anastomótica/prevención & control , Duodeno/cirugía , Nanofibras/uso terapéutico , Enfermedades Peritoneales/prevención & control , Andamios del Tejido , Anastomosis Quirúrgica , Animales , Modelos Animales de Enfermedad , Femenino , Masculino , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Nanofibras/ultraestructura , Enfermedades Peritoneales/etiología , Poliésteres , Distribución Aleatoria , Porcinos , Adherencias Tisulares/etiología , Adherencias Tisulares/prevención & control , Cicatrización de HeridasRESUMEN
Nanotechnologies allow the production of yarns containing nanofibres for use in composites, membranes and biomedical materials. Composite yarns with a conventional thread core for mechanical strength and a nanofibrous envelope for functionality, e.g. biological, catalytic, have many advantages. Until now, the production of such yarns has been technologically difficult. Here, we show an approach to composite yarn production whereby a plume of nanofibers generated by high throughput AC needleless and collectorless electrospinning is wound around a classic thread. In the resulting yarn, nanofibres can form up to 80% of its weight. Our yarn production speed was 10 m/min; testing showed this can be increased to 60 m/min. After the yarn was embedded into knitwear, scanning electron microscope images revealed an intact nanofibrous envelope of the composite yarn. Our results indicate that this production method could lead to the widespread production and use of composite nanofibrous yarns on an industrial scale.
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The study involved the electrospinning of the copolymer poly(L-lactide-co-ε-caprolactone) (PLCL) into tubular grafts. The subsequent material characterization, including micro-computed tomography analysis, revealed a level of porosity of around 70%, with pore sizes of 9.34 ± 0.19 µm and fiber diameters of 5.58 ± 0.10 µm. Unlike fibrous polycaprolactone, the electrospun PLCL copolymer promoted fibroblast and endothelial cell adhesion and proliferation in vitro. Moreover, the regeneration of the vessel wall was detected following implantation and, after six months, the endothelialization of the lumen and the infiltration of arranged smooth muscle cells producing collagen was observed. However, the degradation rate was found to be accelerated in the rabbit animal model. The study was conducted under conditions that reflected the clinical requirements-the prostheses were sutured in the end-to-side fashion and the long-term end point of prosthesis healing was assessed. The regeneration of the vessel wall in terms of endothelialization, smooth cell infiltration and the presence of collagen fibers was observed after six months in vivo. A part of the grafts failed due to the rapid degradation rate of the PLCL copolymer.
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Prótesis Vascular , Arterias Carótidas/patología , Poliésteres/química , Injerto Vascular , Células 3T3 , Animales , Aorta/patología , Adhesión Celular , Colágeno/metabolismo , Perros , Células Endoteliales , Fibroblastos/citología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Imagenología Tridimensional , Ratones , Miocitos del Músculo Liso/citología , Polímeros/química , Porosidad , Conejos , Ratas , Regeneración , Porcinos , Ingeniería de Tejidos/métodos , Andamios del Tejido , Microtomografía por Rayos XRESUMEN
Quantification of the structure and composition of biomaterials using micro-CT requires image segmentation due to the low contrast and overlapping radioopacity of biological materials. The amount of bias introduced by segmentation procedures is generally unknown. We aim to develop software that generates three-dimensional models of fibrous and porous structures with known volumes, surfaces, lengths, and object counts in fibrous materials and to provide a software tool that calibrates quantitative micro-CT assessments. Virtual image stacks were generated using the newly developed software TeIGen, enabling the simulation of micro-CT scans of unconnected tubes, connected tubes, and porosities. A realistic noise generator was incorporated. Forty image stacks were evaluated using micro-CT, and the error between the true known and estimated data was quantified. Starting with geometric primitives, the error of the numerical estimation of surfaces and volumes was eliminated, thereby enabling the quantification of volumes and surfaces of colliding objects. Analysis of the sensitivity of the thresholding upon parameters of generated testing image sets revealed the effects of decreasing resolution and increasing noise on the accuracy of the micro-CT quantification. The size of the error increased with decreasing resolution when the voxel size exceeded 1/10 of the typical object size, which simulated the effect of the smallest details that could still be reliably quantified. Open-source software for calibrating quantitative micro-CT assessments by producing and saving virtually generated image data sets with known morphometric data was made freely available to researchers involved in morphometry of three-dimensional fibrillar and porous structures in micro-CT scans.
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In the present work, we developed a novel needleless emulsion electrospinning technique that improves the production rate of the core/shell production process. The nanofibres are based on poly-ε-caprolactone (PCL) as a continuous phase combined with a droplet phase based on Pluronic F-68 (PF-68). The PCL-PF-68 nanofibres show a time-regulated release of active molecules. Needleless emulsion electrospinning was used to encapsulate a diverse set of compounds to the core phase [i.e. 5-(4,6-dichlorotriazinyl) aminofluorescein -PF-68, horseradish peroxidase, Tetramethylrhodamine-dextran, insulin growth factor-I, transforming growth factor-ß and basic fibroblast growth factor]. In addition, the PF-68 facilitates the preservation of the bioactivity of delivered proteins. The system's potential was highlighted by an improvement in the metabolic activity and proliferation of mesenchymal stem cells. The developed system has the potential to deliver susceptible molecules in tissue-engineering applications.
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Emulsiones/química , Proteínas/administración & dosificación , Ingeniería de Tejidos/métodos , Animales , Materiales Biocompatibles/farmacología , Colágeno Tipo II/metabolismo , Dextranos/química , Peroxidasa de Rábano Silvestre/metabolismo , Péptidos y Proteínas de Señalización Intercelular/farmacología , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Nanofibras/química , Nanofibras/ultraestructura , Agujas , Poloxámero/química , Poliésteres/química , Rodaminas/química , Porcinos , Porcinos Enanos , Andamios del Tejido/químicaRESUMEN
Herein, we describe a simple spinneret setup for needleless coaxial electrospinning that exceeds the limited production capacity of current approaches. The proposed weir spinneret enables coaxial electrospinning from free liquid surface. This approach leads to the formation of coaxial nanofibers with higher and uniform shell/core ratio, which results in the possibility of better tuning of the degradation rate. The throughput and quality increase favor the broader application of coaxial nanofibers from weir spinnerets as systems for controlled drug delivery in regenerative medicine and tissue engineering.
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Sistemas de Liberación de Medicamentos , Nanofibras , Tecnología Farmacéutica/métodos , Preparaciones de Acción Retardada , Humanos , Medicina Regenerativa/métodos , Ingeniería de Tejidos/métodosRESUMEN
It has been shown that glucocorticoids reduce the hearing threshold shifts associated with cochlear implantation. Previous studies evaluated the administration of glucocorticoids immediately before surgery or the repeated pre- or perioperative systemic application of glucocorticoids. The aim of this study was to evaluate the effects of a sustained release dexamethasone hydrogel in hearing preservation cochlear implantation. To address this issue, a guinea pig model of cochlear implantation was used. 30 normal hearing pigmented guinea pigs were randomized into a group receiving a single dose of a dexamethasone/poloxamer407 hydrogel one day prior to surgery, a second group receiving the hydrogel seven days prior to surgery and a control group. A silicone cochlear implant electrode designed for the use in guinea pigs was inserted to a depth of 5 mm through a cochleostomy. Compound action potentials of the auditory nerve (frequency range 0.5-32 kHz) were measured preoperatively, directly postoperatively and on postoperative days 3, 7, 14, 21 and 28. Following the last audiometry, temporal bones were harvested and histologically evaluated. Dexamethasone hydrogel application one day prior to surgery resulted in significantly reduced hearing threshold shifts at low, middle and high frequencies measured at postoperative day 28 (p < 0.05). Application of the hydrogel seven days prior to surgery did not show such an effect. Dexamethasone application one day prior to surgery resulted in increased outer hair cell counts in the cochlear apex and in reduced spiral ganglion cell counts in the basal and middle turn of the cochlea, a finding that was associated with a higher rate of electrode translocation in this group. In this study, we were able to demonstrate functional benefits of a single preoperative intratympanic application of a sustained release dexamethasone hydrogel in a guinea pig model of cochlear implantation.
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Implantación Coclear/métodos , Dexametasona/administración & dosificación , Células Ciliadas Auditivas Externas/patología , Hidrogeles/química , Esteroides/administración & dosificación , Potenciales de Acción , Administración Tópica , Animales , Audiometría , Umbral Auditivo/efectos de los fármacos , Cóclea/fisiopatología , Implantes Cocleares , Preparaciones de Acción Retardada , Electrodos , Potenciales Evocados Auditivos del Tronco Encefálico/efectos de los fármacos , Glucocorticoides/administración & dosificación , Cobayas , Pérdida Auditiva/fisiopatología , Pruebas Auditivas , Ganglio Espiral de la Cóclea/fisiopatologíaRESUMEN
CONCLUSION: The intraoperative application of glucocorticoid-loaded hydrogels seems to cause a reduction in neutrophil infiltration. No beneficial effect on hearing thresholds was detected. OBJECTIVES: To evaluate the application of dexamethasone- and triamcinolone acetonide-loaded hydrogels for effects on hearing preservation and foreign body reaction in a guinea pig model for cochlear implantation (CI). METHODS: A total of 48 guinea pigs (n = 12 per group) were implanted with a single channel electrode and intraoperatively treated with 50 µl of a 20% w/v poloxamer 407 hydrogel loaded with 6% dexamethasone or 30% triamcinolone acetonide, a control hydrogel, or physiological saline. Click- and tone burst-evoked compound action potential thresholds were determined preoperatively and directly postoperatively as well as on days 3, 7, 14, 21, and 28. At the end of the experiment, temporal bones were prepared for histological evaluation by a grinding/polishing technique with the electrode in situ. Three ears per treatment group were serially sectioned and evaluated for histological alterations. RESULTS: The intratympanic application of glucocorticoid-loaded hydrogels did not improve the preservation of residual hearing in this cochlear implant model. The foreign body reaction to the electrode appeared reduced in the glucocorticoid-treated animals. No correlation was found between the histologically described trauma to the inner ear and the resulting hearing threshold shifts.
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Implantación Coclear , Reacción a Cuerpo Extraño/prevención & control , Glucocorticoides/administración & dosificación , Audición/efectos de los fármacos , Hidrogeles , Cuidados Intraoperatorios , Potenciales de Acción , Animales , Cóclea/efectos de los fármacos , Cóclea/patología , Cóclea/cirugía , Implantes Cocleares/efectos adversos , Dexametasona/administración & dosificación , Modelos Animales de Enfermedad , Potenciales Evocados Auditivos del Tronco Encefálico , Femenino , Reacción a Cuerpo Extraño/etiología , Reacción a Cuerpo Extraño/patología , Cobayas , Masculino , Infiltración Neutrófila , Triamcinolona Acetonida/administración & dosificaciónRESUMEN
OBJECTIVES/HYPOTHESIS: To evaluate the selective glucocorticoid receptor agonist (SEGRA) compound A, a potential novel therapeutic for inner ear disorders, for ototoxic effects. STUDY DESIGN: Laboratory animal study. METHODS: Experimental guinea pigs were grouped as follows: Systemic application of compound A (1.5 mg/kg and 4.5 mg/kg; n = 6/group) and intratympanic application of compound A (1 mM and 10 mM; n = 6/group). Contralateral ears in topically treated animals served as controls. Hearing thresholds were determined by auditory brainstem response before and directly after the application of compound A, as well as on days 3, 7, 14, 21, and 28. At the end of the experiments, temporal bones were harvested for histological evaluation. RESULTS: Systemic administration of compound A (1.5 mg/kg and 4.5 mg/kg) did not cause hearing threshold shifts, whereas the intratympanic injection (1 mM and 10 mM) resulted in a hearing loss. Histological analysis of the middle and inner ears after topical compound A application showed alterations in the tympanic membranes, the auditory ossicles, and the round window membranes, whereas spiral ganglion cells and hair cells were not affected. CONCLUSION: SEGRAs such as compound A could provide novel therapeutic options for the treatment of inner ear disorders and reduce metabolic side effects. Whereas the intratympanic application of compound A resulted in a hearing loss, the systemic application of compound A merits evaluation for otoprotective effects in trauma models.
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Potenciales Evocados Auditivos del Tronco Encefálico/efectos de los fármacos , Receptores de Glucocorticoides/antagonistas & inhibidores , Membrana Timpánica/efectos de los fármacos , Membrana Timpánica/patología , Adenina/farmacología , Administración Tópica , Animales , Umbral Auditivo/fisiología , Biopsia con Aguja , Citratos/farmacología , Modelos Animales de Enfermedad , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Femenino , Glucosa/farmacología , Cobayas , Inmunohistoquímica , Inyecciones Intraperitoneales , Masculino , Fosfatos/farmacología , Distribución Aleatoria , Valores de ReferenciaRESUMEN
BACKGROUND: Thyroid cancer includes a broad spectrum of tumours with different prognoses. The global incidence has been increasing in recent years. Variables affecting its etiology are dietary, especially iodine intake and to a lesser extent selenium, environmental, like - ionizing radiation and, increased TSH level. These factors interplay with epigenetic and genetic changes within the cell. This review article presents thyroid cancer epidemiology, describes its main characteristics and the influence of environmental and lifestyle risk factors in the Czech Republic in comparison with other countries. METHODS AND RESULTS: An epidemiological study of Czech patients with malignant thyroid carcinoma was made on the basis of the National Oncologic Registry (NOR) and Czech Statistical Office data summarized on the web portal SVOD. The data were compared with international data from the project GLOBOCAN 2008 Cancer Incidence and Mortality Worldwide. Apart from risk factors, prognostic factors with effect on patient survival were also analyzed. The survey showed that the incidence of thyroid cancer has been steadily growing in the Czech Republic. Since the beginning of the 1980s, it has increased 4 fold. It has a higher incidence than most other European countries but it is ranked with countries with an average and decreasing mortality. Obviously, the improved detection methods do not explain the growing incidence. The highest incidence is found for papillary carcinoma (PTC), now over 80% of cases. For follicular and medullar cancers, the incidence has not increased and for anaplastic carcinoma there is a slight decrease. Women over 40 years of age constitute the highest risk group. CONCLUSIONS: There are a number of reasons for these trends, such as improved diagnostic techniques using ultrasound and FNAB and more radical surgery. There are also dietary/environmental factors (iodine deficiency and to a lesser extent selenium), nitrates, polychlorinated biphenyls, increased ionizing radiation, and prolonged increase in TSH. The prognosis of patients with DTC depends on the age at the time of diagnosis. A favorable prognosis also depends on timely detection.
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Neoplasias de la Tiroides/epidemiología , Adulto , Distribución por Edad , Anciano , República Checa/epidemiología , Exposición a Riesgos Ambientales/efectos adversos , Métodos Epidemiológicos , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Mortalidad/tendencias , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Traumatismos por Radiación/epidemiología , Distribución por Sexo , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/patología , Carga TumoralRESUMEN
AIM: Platelet derivatives serve as an efficient source of natural growth factors. In the current study, α-granules were incorporated into coaxial nanofibers. MATERIALS & METHODS: A nanofiber scaffold containing α-granules was prepared by coaxial electrospinning. The biological potential of the nanofiber scaffold was evaluated in chondrocyte and mesenchymal stem cell cultivation studies. Additionally, the concentration of TGF-ß1 was determined. RESULTS: Microscopy studies showed that intact α-granules were incorporated into the coaxial nanofibers. The cultivation tests showed that the novel scaffold stimulated viability and extracellular matrix production of chondrocytes and mesenchymal stem cells. In addition, the concentration of growth factors necessary for the induction of cell proliferation significantly decreased. CONCLUSION: The system preserved α-granule bioactivity and stimulated cell viability and chondrogenic differentiation of mesenchymal stem cells. Core/shell nanofibers incorporating α-granules are a promising system for tissue engineering, particularly cartilage engineering.