Assessment on the influence of TLR4 and DNA repair genes in laryngeal cancer susceptibility: a selective examination in a Romanian case control study

Background: Tumor characterization through the study of molecular biology has become an invaluable tool in understanding cancer development and evolution due to its relationship with chromosomal mutations, alterations or aberrations. The purpose of this study was to investigate the involvement of genes such as TLR-4 and DNA repair pathways (XRCC1 and XPD) in laryngeal cancer susceptibility in a Romanian population. Method: We performed a case-control study on 157 laryngeal cancer patients and 101 healthy controls. Genetic testing was carried out using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism. Results: We identified the Gln allele of the XPDLys751Gln polymorphism as an individual risk factor in laryngeal cancer development (Gln vs Lys, adjusted OR=1.65, 95%CI=1.13–2.40, P=0.008). Subjects with the mutant homozygote variant (Gln/Gln) had a two fold increase in cancer risk (adjusted OR=2.18, 95%CI=1.06–4.47, p=0.028) when compared to the reference wild type genotype (Lys/Lys). Stratification by sex and age, identified males under 62 years as the most susceptible group with an almost three fold risk (adjusted OR=2.94, 95%CI=1.31–6.59, p=0.007) for the dominant model (Lys/Gln+Gln/Gln). No associations were found for TLR-4Thr399Ile, XRCC1Arg194Trp and XRCC1Arg399Gln. Conclusion: The results of the study show that the XPDLys751Gln polymorphism may be among other independent risk factors for developing laryngeal cancer where as TLR-4Thr399Ile, XRCC1Arg194Trp and XRCC1 Arg399Gln show no such association. However, we consider the relative small number of the subjects selected for this analyses a possible limitation towards the real influence the obtain results may pertain in laryngeal cancer evolution

Effects of Ototoxic Drugs on Corti’s Explants: Experimental Study

Introduction: Hearing loss represents one of the most frequent human disabilities. Hair cells, the primary sound receptors located in the inner ear are extremely sensitive, but also very fragile. Thedestruction of these cells in humans or in any other mammal is not followed by replacement, and therefore a permanent hearing loss results. Material and Methods: Neonatal mousse CD1 (P0-6) were sacrificed according to the legal standards and ethics. After manual dissection of the cochleae, the entire spiral ganglion was dissected from the modiolus. The explants were treated with gentamicin, followed by incubation for 48 hours at 37°C. Normal and damaged outer hair cells (OHC) or inner hair cells (IHC) were then counted toallow for statistical comparisons between groups. Results: A total of 20,100 outer hair cells from 64 cochleae and 4 groups were analyzed. At 3 mM of gentamicin the hair cells were almost complete damaged. The main type’s alteration in the damaged outer or inner hair cells was absence of hair. The mean difference between the damaged or not damaged OHC/IHC was statistically significant (p<0.001). Discussion: In our study we did not observe more damage in the basal cochlear turn when compared to the second turn. No statistically significant difference was found between the first cochlear turn of subjects on these groups, and turns 2 and 3, respectively. Conclusion: Progressive doses of gentamicin cause increased numbers of damaged outer and inner hair cells with absence of hair (the most frequent finding)

Vertigo Associated with Otosclerosis and Stapes Surgery—A Narrative Review

Otosclerosis is a pathological condition affecting the temporal bone, and is characterized by remodelling of the labyrinthine bone tissue through a dynamic process of osteolysis and osteogenesis. This condition progressively leads to hearing loss, tinnitus, and vertigo. Stapedotomy, a surgical procedure involving the removal of the stapes superstructure and its replacement with a prosthesis, is the treatment of choice to improve hearing in individuals with otosclerosis. However, vestibular dysfunction is a significant complication associated with this procedure, which can occur intraoperatively or postoperatively, ranging from the immediate postoperative period to weeks, months, or even years after surgery. This paper aims to provide a comprehensive review of the most important causes of vertigo associated with otosclerosis and stapes surgery with the goal of minimizing the incidence of this complication. Understanding the underlying factors contributing to vertigo in this context is crucial for the prevention and effective management of vertigo in patients undergoing stapedotomy

Biopolymer Lipid Hybrid Microcarrier for Transmembrane Inner Ear Delivery of Dexamethasone

Dexamethasone is one of the most often used corticosteroid drugs for sensorineural hearing loss treatment, and is used either by intratympanic injection or through systemic delivery. In this study, a biopolymer lipid hybrid microcarrier was investigated for enhanced local drug delivery and sustained release at the round window membrane level of the middle ear for the treatment of sensorineural hearing loss (SNHL). Dexamethasone-loaded and dexamethasone-free microparticles were prepared using biopolymers (polysaccharide and protein, pectin and bovine serum albumin, respectively) combined with lipid components (phosphatidylcholine and Dimethyldioctadecylammonium bromide) in order to obtain a biopolymer&ndash;liposome hybrid system, with a complex structure combining to enhance performance in terms of physical and chemical stability. The structure of the microparticles was evaluated by FTIR, XRD, thermal analysis, optical microscopy, and scanning electron microscopy (SEM). The encapsulation efficiency determination and the in vitro Dexamethasone release study were performed using UV-Vis spectroscopy. The high value of encapsulation efficiency and the results of the release study indicated six days of sustained release, encouraging us to evaluate the in vitro cytotoxicity of Dexamethasone-loaded microparticles and their influence on the cytotoxicity induced by Cisplatin on auditory HEI-OC1 cells. The results show that the new particles are able to protect the inner ear sensory cells

The Effect of Pluronic-Coated Gold Nanoparticles in Hearing Preservation Following Cochlear Implantation-Pilot Study

Introduction: During cochlear implantation, electrode insertion can cause cochlear damage, inflammation, and apoptosis, which can affect the residual hearing. Nanoparticles are increasingly studied as a way to increase the availability of inner ear protective factors. We studied the effect on rats of Pluronic-coated gold nanoparticles (Plu-AuNPs) containing dexamethasone, which were applied locally in the rat’s middle ear following the implant procedure. Methods: Seven rats were used in the study. The right ear served as a model for the Dex-Plu-AuNP group. Following the intracochlear dummy electrode insertion through the round window, Dex-Plu-AuNPs were placed in the round window niche. In the right ear, following the same insertion procedure, free dexamethasone (Dex) was placed in the same manner. Auditory brainstem response thresholds (click stimulus, pure tones at 8 kHz, 16 kHz, 24 kHz, and 32 kHz) were measured before and one week after the procedure. A two-tailed T-test was used for the variables. Statistical significance was set as p p = 0.048, t-test). For the other frequencies, statistical analysis showed no significant differences between the mean threshold shifts of the two cohorts. Conclusions: The local application of Plu-AuNPs containing dexamethasone following cochlear implantation may better protect the residual hearing than dexamethasone alone, but a larger sample size is needed to reach a possible statistical significance. Dex-Plu-AuNPs do not seem to cause ototoxicity and may be used as a carrier for other agents. In a clinical setting, Dex-Plu-AuNPs may have the effect of protecting lower frequencies in patients with partial deafness who are candidates for electric acoustic stimulation (EAS). If we consider this tendency, Dex-Plu-AuNPs may also be beneficial for patients with Ménière’s disease

Current Concepts and Future Trends in Increasing the Benefits of Cochlear Implantation: A Narrative Review

Hearing loss is the most common neurosensory disorder, and with the constant increase in etiological factors, combined with early detection protocols, numbers will continue to rise. Cochlear implantation has become the gold standard for patients with severe hearing loss, and interest has shifted from implantation principles to the preservation of residual hearing following the procedure itself. As the audiological criteria for cochlear implant eligibility have expanded to include patients with good residual hearing, more attention is focused on complementary development of otoprotective agents, electrode design, and surgical approaches. The focus of this review is current aspects of preserving residual hearing through a summary of recent trends regarding surgical and pharmacological fundamentals. Subsequently, the assessment of new pharmacological options, novel bioactive molecules (neurotrophins, growth factors, etc.), nanoparticles, stem cells, and gene therapy are discussed

Obstructing Sleep Apnea in Children with Genetic Disorders—A Special Need for Early Multidisciplinary Diagnosis and Treatment

Background—Children with genetic disorders have multiple anatomical and physiological conditions that predispose them to obstructive sleep apnea syndrome (OSAS). They should have priority access to polysomnography (PSG) before establishing their therapeutic protocol. We analyzed the prevalence and the severity of OSAS in a particular group of children with genetic disorders and strengthened their need for a multidisciplinary diagnosis and adapted management. Methods—The retrospective analysis included children with genetic impairments and sleep disturbances that were referred for polysomnography. We collected respiratory parameters from sleep studies: apnea–hypopnea index (AHI), SatO2 nadir, end-tidal CO2, and transcutaneous CO2. Subsequent management included non-invasive ventilation (NIV) or otorhinolaryngological (ENT) surgery of the upper airway. Results—We identified 108 patients with neuromuscular disorders or multiple congenital anomalies. OSAS was present in 87 patients (80.5%), 3 of whom received CPAP, 32 needed another form of NIV during sleep, and 15 patients were referred for ENT surgery. The post-therapeutic follow-up PSG parameters confirmed the success of the treatment. Conclusions—The upper airway obstruction diagnostics and management for children with complex genetic diseases need a multidisciplinary approach. Early detection and treatment of sleep-disordered breathing in children with genetic disorders is a priority for improving their quality of life