The Otoprotective Effect of Ear Cryotherapy: Systematic Review and Future Perspectives.

This systematic review investigates ear cooling and cryotherapy in the prevention and treatment of inner ear damage and disease, within the context of animal models and clinical studies. A literature search was carried out in the databases Pubmed and Cochrane Library. Ten studies were identified concerning the otoprotective properties of cryotherapy. Nine of these were rodent in vivo studies (mice, rats, gerbils, guinea pigs). One study involved human subjects and investigated cryotherapy in idiopathic sensorineural hearing loss. The studies were heterogeneous in their goals, methods, and the models used. Disorder models included ischemia and noise damage, ototoxicity (cisplatin and aminoglycoside), and CI-electrode insertion. All ten studies demonstrated significant cryotherapeutic otoprotection for their respective endpoints. No study revealed or expressly investigated otodestructive effects. While limited in number, all of the studies within the scope of the review demonstrated some degree of cryotherapeutic, otoprotective effect. These promising results support the conducting of further work to explore and refine the clinical applicability and impact of cryotherpeutics in otolaryngology.

Effects of auditory rehabilitation with cochlear implant on tinnitus prevalence and distress, health-related quality of life, subjective hearing and psychological comorbidities: Comparative analysis of patients with asymmetric hearing loss (AHL), double-sided (bilateral) deafness (DSD), and single-sided (unilateral) deafness (SSD).

Introduction: Auditory rehabilitation with a cochlear implant (CI), in many cases, positively impacts tinnitus. However, it is unclear if the tinnitus-related benefit of CI is equal for patients with various indications for CI. Therefore, this study aimed to determine differences in tinnitus prevalence and distress, health-related quality of life, subjective hearing, perceived stress, and psychological comorbidities between patients diagnosed with asymmetric hearing loss (AHL), single-sided (unilateral) deafness (SSD), and double-sided (bilateral) deafness (DSD) before and six months after cochlear implantation. Methods: One hundred-one CI candidates were included in this prospective study (39 AHL patients, 23 DSD patients, and 39 SSD patients). The patients completed questionnaires measuring tinnitus distress, health-related quality of life, subjective hearing, perceived stress, and psychological comorbidities before and 6 months after CI. Results: The prevalence of tinnitus in the entire cohort (80.2% before CI) decreased 6 months after CI to 71.3%. The DSD group had the lowest tinnitus prevalence at both time points. The degree of tinnitus-induced distress decreased significantly in all three groups after CI. Differences in quality of life, subjective hearing, and psychological comorbidities between the groups at the study onset disappeared after CI. Significant correlations existed between anxiety, depression, and tinnitus distress in AHL and SSD but not in DSD patients before and after CI. Discussion: Our results demonstrate significant differences between the three groups of CI candidates, which might affect the implantation outcome. These differences suggest a need for personalized psychological counseling during the auditory rehabilitation process, focusing on anxiety and depressive symptoms for SSD and AHL patients.

Therapy-Resistant Atypical Downbeat Nystagmus with Vertigo Confined to Specific Head-Hanging Positions: Mapping to the Gravity Vector on a Multi-Axis Turntable.

Downbeat nystagmus (DBN) observed in head-hanging positions, may be of central or peripheral origin. Central DBN in head-hanging positions is mostly due to a disorder of the vestibulo-cerebellum, whereas peripheral DBN is usually attributed to canalolithiasis of an anterior semicircular canal. Here, we describe an atypical case of a patient who, after head trauma, experienced severe and stereotypic vertigo attacks after being placed in various head-hanging positions. Vertigo lasted 10-15 s and was always associated with a robust DBN. The provocation of transient vertigo and DBN, which both showed no decrease upon repetition of maneuvers, depended on the yaw orientation relative to the trunk and the angle of backward pitch. On a motorized, multi-axis turntable, we identified the two-dimensional Helmholtz coordinates of head positions at which vertigo and DBN occurred (y-axis: horizontal, space-fixed; z-axis: vertical, and head-fixed; x-axis: torsional, head-fixed, and unchanged). This two-dimensional area of DBN-associated head positions did not change when whole-body rotations took different paths (e.g., by forwarding pitch) or were executed with different velocities. Moreover, the intensity of DBN was also independent of whole-body rotation paths and velocities. So far, therapeutic approaches with repeated liberation maneuvers and cranial vibrations were not successful. We speculate that vertigo and DBN in this patient are due to macular damage, possibly an unstable otolithic membrane that, in specific orientations relative to gravity, slips into a position causing paroxysmal stimulation or inhibition of macular hair cells.

Single-centre experience and practical considerations of the benefit of a second cochlear implant in bilaterally deaf adults.

PURPOSE: Bilateral cochlear implant (CI) implantation is increasingly used in the auditory rehabilitation of bilaterally deafened adults. However, after successful unilateral implantation, objective patient counselling is essential. METHODS: We investigated the extra benefit of a second CI in adults in terms of health-related quality of life, tinnitus, stress, anxiety, depression, quality of hearing, and speech recognition. Hearing ability was assessed by using the Freiburg monosyllable speech discrimination test (FB MS) and the Oldenburg sentence test with azimuth variations. In a prospective patient cohort, we administered validated questionnaires before a CI, after a first CI and after a second CI implantation. RESULTS: The study included 29 patients, made up of nine women and 20 men. The median time between the first and the second implantation was 23 months. The mean total NCIQ score and TQ before a CI improved significantly after both implantations. Stress, anxiety, and depression were stable over time and were not significantly affected by CI implantations. Speech recognition with noise significantly improved after the first and again after the second CI. Correlation analysis showed a strong connection between auditory performance and HRQoL. CONCLUSION: We demonstrated that a unilateral CI benefitted many fields and that the second sequential CI leads again to additional improvement. Bilateral CI implantation should, therefore, be the standard form of auditory rehabilitation in deafened adults.

Comparison of sheep and human middle-ear ossicles: anatomy and inertial properties.

The sheep middle ear has been used in training to prepare physicians to perform surgeries and to test new ways of surgical access. This study aimed to (1) collect anatomical data and inertial properties of the sheep middle-ear ossicles and (2) explore effects of these features on sound transmission, in comparison to those of the human. Characteristic dimensions and inertial properties of the middle-ear ossicles of White-Alpine sheep (n = 11) were measured from high-resolution micro-CT data, and were assessed in comparison with the corresponding values of the human middle ear. The sheep middle-ear ossicles differed from those of human in several ways: anteroinferior orientation of the malleus handle, relatively small size of the incus with a relatively short distance to the lenticular process, a large area of the articular surfaces at the incudostapedial joint, and a relatively small moment of inertia along the anterior-posterior axis. Analysis in this study suggests that structure and orientation of the middle-ear ossicles in the sheep are conducive to an increase in the hinge-like ossicular-lever-action around the anterior-posterior axis. Considering the substantial anatomical differences, outcomes of middle-ear surgeries would presumably be difficult to assess from experiments using the sheep middle ear.

Binaural Hearing Rehabilitation Improves Speech Perception, Quality of Life, Tinnitus Distress, and Psychological Comorbidities.

OBJECTIVES: To determine and compare the benefit of binaural hearing rehabilitation via cochlear implantation (CI) on speech perception, assessment of auditory abilities, tinnitus distress, health-related quality of life (HRQoL) and psychological comorbidities in patients suffering from asymmetric hearing loss (AHL) as well as bilaterally-deafened and sequentially bilaterally-implanted patients. METHODS: 53 patients were implanted between 2011 and 2016. 24 AHL patients were implanted unilaterally, using a hearing aid on the other side. 29 bilaterally-deafened patients were sequentially implanted bilaterally. Speech perception, subjective hearing quality, HRQoL, tinnitus distress, anxiety, depressiveness, perceived stress level and coping abilities were evaluated before implantation, as well as 6 and 24 months postoperatively. RESULTS: Before CI, AHL and bilaterally-deaf patients showed significant differences regarding assessment of auditory abilities, speech discrimination, tinnitus distress and HRQoL. 24 months after CI both groups significantly improved in those scales. We could not find a significant difference between the groups after 2 years. Tinnitus distress significantly decreased 6 and 24 months postoperatively in both groups. CONCLUSIONS: This study demonstrates the long-term benefit of binaural hearing rehabilitation in AHL and bilaterally-deaf patients not only regarding speech perception but also HRQoL, tinnitus distress and subjective hearing quality. Bilaterally-deafened patients present lower scores preoperatively, but they did not differ from AHL patients 2 years after CI. Up to now, this is the first study evaluating the outcome of CI in AHL patients compared to bilaterally-implanted patients and demonstrating the benefit of binaural hearing rehabilitation in these specific groups.

Phosphorus recovery from process waste water made by the hydrothermal carbonisation of spent coffee grounds.

This study investigates the recovery of phosphorus from the process water obtained through hydrothermal carbonisation (HTC) of a 'wet' biomass waste, namely spent coffee grounds. HTC was shown to liberate more than 82% of the total phosphorus in the grounds in the form of dissolved ortho-phosphate. Nanofiltration was used to concentrate the inorganic nutrients of the HTC process water, achieving a mass concentration factor of 3.9 times. The natural stoichiometry of phosphorus, magnesium and ammoniacal nitrogen in the nanofiltration retentate was favourable for struvite precipitation. 92.8% of aqueous phosphorus was recovered as struvite through simple pH adjustment, yielding a total phosphorus recovery of 75% from the feedstock spent coffee grounds.

A Meta-Analysis of Survival Outcomes Following Reoperation in Recurrent Glioblastoma: Time to Consider the Timing of Reoperation.

Background: Glioblastoma multiforme (GBM) inevitably recurs, but no standard regimen has been established for recurrent patients. Reoperation at recurrence alleviates mass effects, and the survival benefit has been reported in many studies. However, in most studies, the effect of reoperation timing on survival benefit was ignored. The aim of this meta-analysis was to investigate whether reoperation provided similar survival benefits in recurrent GBM patients when it was analyzed as a fixed or time-dependent covariate. Methods: A systematic literature search of PubMed, EMBASE, and Cochrane databases was performed to identify original articles that evaluated the associations between reoperation and prognosis in recurrent GBM patients. Results: Twenty-one articles involving 8,630 patients were included. When reoperation was considered as a fixed covariate, it was associated with better overall survival (OS) and post-progression survival (PPS) (OS: HR = 0.66, 95% CI 0.61-0.71, p < 0.001, I 2 = 0%; PPS: HR = 0.70, 95% CI 0.57-0.88, p < 0.01, I 2 = 70.2%). However, such a survival benefit was not observed when reoperation was considered as a time-dependent covariate (OS: HR = 2.19, 95% CI 1.47-3.27, p < 0.001; PPS: HR = 0.95, 95% CI 0.82-1.10, p = 0.51, I 2 = 0%). The estimate bias caused by ignoring the time-dependent nature of reoperation was further demonstrated by the re-analysis of survival data in three included studies. Conclusions: The timing of reoperation may have an impact on the survival outcome in recurrent GBM patients, and survival benefits of reoperation in recurrent GBM may be overestimated when analyzed as fixed covariates. Proper analysis methodology should be used in future work to confirm the clinical benefits of reoperation.

Distorted sound perception and subjective benefit after stapedotomy - a prospective single-centre study.

OBJECTIVE: To evaluate the quality of perceived sound after stapedotomy over a 1-year follow-up period focussing on incidence of dysacusis, particularly distorted sound perception (DSP). DSP was assessed by (i) determination of the frequencies and hearing level that such perceptions are elicited by pure tones (pure-tone-evoked distorted sound perception, PTE-DSP), a novel psychoacoustic measurement introduced in this paper, and (ii) assessment of patient-reported occurrence of DSP using the Amsterdam Post Operative Sound Evaluation (APOSE) questionnaire (APOSE-DSP). DESIGN: Prospective study. STUDY SAMPLE: Patients (n = 23) with otosclerosis undergoing stapedotomy. RESULTS: An air-bone gap of <20 dB was achieved in 100% of the patients. Three weeks postoperatively, 48% of the patients reported measured PTE-DSP and 39% of the patients experienced APOSE-DSP. The PTE-DSP significantly decreased during the 1-year follow-up period (p = 0.03). Postoperatively, APOSE-DSP was associated with a smaller benefit (improvement in air conduction; p = 0.03), yet, a lower bone conduction pure-tone average was associated with PTE-DSP (p = 0.006). CONCLUSIONS: DSP after stapedotomy is associated with a smaller benefit 3 months after stapedotomy. DSP commonly occur after stapedotomy, but decrease over time. This is important information to be included in patient counselling before stapedotomy.

Recurrent unilateral peripheral facial palsy in a patient with an enlarged styloid process.

BACKGROUND: Recurrent peripheral facial paresis is a rare symptom that may be caused by multiple pathologic conditions. METHODS: We report a case of recurrent peripheral facial palsies caused by an ipsilateral enlarged styloid process. A surgical excision of the process was performed. RESULTS: The treatment was well tolerated. Postoperatively, no further recurrent paresis was observed. CONCLUSION: To the best of our knowledge, this is the first case study of an enlarged styloid process with facial paresis. A detailed workup, including imaging, should be performed in cases with recurrent facial paresis and/or cases with a history of trauma and facial paresis and, of course, to exclude a neoplastic etiology.

Proof of Concept for an Intracochlear Acoustic Receiver for Use in Acute Large Animal Experiments.

(1) Background: The measurement of intracochlear sound pressure (ICSP) is relevant to obtain better understanding of the biomechanics of hearing. The goal of this work was a proof of concept of a partially implantable intracochlear acoustic receiver (ICAR) fulfilling all requirements for acute ICSP measurements in a large animal. The ICAR was designed not only to be used in chronic animal experiments but also as a microphone for totally implantable cochlear implants (TICI). (2) Methods: The ICAR concept was based on a commercial MEMS condenser microphone customized with a protective diaphragm that provided a seal and optimized geometry for accessing the cochlea. The ICAR was validated under laboratory conditions and using in-vivo experiments in sheep. (3) Results: For the first time acute ICSP measurements were successfully performed in a live specimen that is representative of the anatomy and physiology of the human. Data obtained are in agreement with published data from cadavers. The surgeons reported high levels of ease of use and satisfaction with the system design. (4) Conclusions: Our results confirm that the developed ICAR can be used to measure ICSP in acute experiments. The next generation of the ICAR will be used in chronic sheep experiments and in TICI.

Sheep as a large animal ear model: Middle-ear ossicular velocities and intracochlear sound pressure.

Animals are frequently used for the development and testing of new hearing devices. Dimensions of the middle ear and cochlea differ significantly between humans and commonly used animals, such as rodents or cats. The sheep cochlea is anatomically more like the human cochlea in size and number of turns. This study investigated the middle-ear ossicular velocities and intracochlear sound pressure (ICSP) in sheep temporal bones, with the aim of characterizing the sheep as an experimental model for implantable hearing devices. Measurements were made on fresh sheep temporal bones. Velocity responses of the middle ear ossicles at the umbo, long process of the incus and stapes footplate were measured in the frequency range of 0.25-8 kHz using a laser Doppler vibrometer system. Results were normalized by the corresponding sound pressure level in the external ear canal (PEC). Sequentially, ICSPs at the scala vestibuli and tympani were then recorded with custom MEMS-based hydrophones, while presenting identical acoustic stimuli. The sheep middle ear transmitted most effectively around 4.8 kHz, with a maximum stapes velocity of 0.2 mm/s/Pa. At the same frequency, the ICSP measurements in the scala vestibuli and tympani showed the maximum gain relative to the PEC (24 dB and 5 dB, respectively). The greatest pressure difference across the cochlear partition occurred between 4 and 6 kHz. A comparison between the results of this study and human reference data showed middle-ear resonance and best cochlear sensitivity at higher frequencies in sheep. In summary, sheep can be an appropriate large animal model for research and development of implantable hearing devices.

A MEMS Condenser Microphone-Based Intracochlear Acoustic Receiver.

GOAL: Intracochlear sound pressure (ICSP) measurements are limited by the small dimensions of the human inner ear and the requirements imposed by the liquid medium. A robust intracochlear acoustic receiver (ICAR) for repeated use with a simple data acquisition system that provides the required high sensitivity and small dimensions does not yet exist. The work described in this report aims to fill this gap and presents a new microelectromechanical systems (MEMS) condenser microphone (CMIC)-based ICAR concept suitable for ICSP measurements in human temporal bones. METHODS: The ICAR head consisted of a passive protective diaphragm (PD) sealing the MEMS CMIC against the liquid medium, enabling insertion into the inner ear. The components of the MEMS CMIC-based ICAR were expressed by a lumped element model (LEM) and compared to the performance of successfully fabricated ICARs. RESULTS: Good agreement was achieved between the LEM and the measurements with different sizes of the PD. The ICSP measurements in a human cadaver temporal bone yielded data in agreement with the literature. CONCLUSION: Our results confirm that the presented MEMS CMIC-based ICAR is a promising technology for measuring ICSP in human temporal bones in the audible frequency range. SIGNIFICANCE: A sensor for evaluation of the biomechanical hearing process by quantification of ICSP is presented. The concept has potential as an acoustic receiver in totally implantable cochlear implants.

Efficacy of Surgery and Further Treatment of Progressive Glioblastoma.

BACKGROUND: Treatment options for patients with glioblastoma at progression have remained controversial, and selection criteria for the appropriate type of intervention remain poorly defined. The objectives were to determine which factors favor the decision for second surgery and which factors are associated with overall survival (OS) and to evaluate the National Institutes of Health (NIH) recurrent glioblastoma scale. The scale includes tumor involvement of eloquent brain regions, functional status, and tumor volume. METHODS: A retrospective single-center analysis of patients with newly diagnosed glioblastoma undergoing initial surgery between January 2007 and December 2011 was performed. Patients were separated into two groups: those with versus those without second resection surgery at disease progression. OS was compared using the multiple logistic regression model, Cox proportional hazard regression, and Kaplan-Meier survival analysis. RESULTS: The data of 98 patients were statistically analyzed. Among the patients, 58 had initial surgery only (age 61.27 years; median OS [mOS] 14.81 months) and 40 underwent second surgery at disease progression (age 55 years; mOS 18.86 months). Age was the only predictor for repeated surgery (P = 0.012; odds ratio 0.94). At the time of tumor progression, administration of alkylating chemotherapy (P = 0.004; hazard ratio [HR] 0.24) or bevacizumab (P = 0.001; HR 0.23) was associated with longer OS. Reoperation was associated with a lower HR (P = 0.134; HR 0.66). The NIH recurrent glioblastoma scale showed statistically significant improvement of prognosis prediction with the addition of age. CONCLUSIONS: Surgery of progressive glioblastoma and postoperative treatment at the time of progression is associated with improved OS in some patients. The addition of age may improve survival prediction of the NIH recurrent glioblastoma scale.

Hydrocephalus after resection and adjuvant radiochemotherapy in patients with glioblastoma.

OBJECTIVE: Glioblastomas are the most common primary malignant brain tumors in adults with a poor prognosis. The current study sought to identify risk factors in glioblastoma patients that are closely associated with communicating hydrocephalus. METHODS: We retrospectively analyzed data from 151 patients who were diagnosed with a glioblastoma between 2007 and 2011 and underwent complete surgical resection closely followed by adjuvant radiochemotherapy. RESULTS: We observed a significant tendency toward communicating hydrocephalus in cases of ventricular opening during surgical tumor resection (Fisher's exact test p<0.001) and a noticeable, although not statistically significant, correlation between the onset of communicating hydrocephalus and evidence of leptomeningeal tumor dissemination (Fisher's exact test p=0.067). Additionally, there was a trend toward frontal tumor location and a larger tumor volume in patients with communicating hydrocephalus. The majority of patients suffering from communicating hydrocephalus received a cerebrospinal fluid (CSF) shunt implantation after radiation therapy (63.6%, Fisher's exact test p=0.000). CONCLUSION: We identified the following risk factors associated with the onset of communicating hydrocephalus in glioblastoma patients: ventricular opening during tumor resection and leptomeningeal tumor dissemination. Shunt implantation seems to be safe and effective in these patients.

Appraisal of the Karnofsky Performance Status and proposal of a simple algorithmic system for its evaluation.

BACKGROUND: For over 60 years, the Karnofsky Performance Status (KPS) has proven itself a valuable tool with which to perform measurement of and comparison between the functional statuses of individual patients. In recent decades conditions for patients have changed, and so too has the KPS undergone several adjustments since its initial development. DISCUSSION: The most important works regarding the KPS tend to focus upon a variety of issues, including but not limited to reliability, validity and health-related quality of life. Also discussed is the question of what quantity the KPS may in fact be said to measure. The KPS is increasingly used as a prognostic factor in patient assessment. Thus, questions regarding if and how it affects survival are relevant. SUMMARY: This review honors the original intention of the discoverer and gives an overview of adaptations made in recent years. The proposed algorithm suggests specific updates with the goal of ensuring continued adequacy and expediency in the determination of the KPS.

Stimulation sites in the subthalamic nucleus projected onto a mean 3-D atlas of the thalamus and basal ganglia.

BACKGROUND: In patients with severe forms of Parkinson's disease (PD), deep brain stimulation (DBS) commonly targets the subthalamic nucleus (STN). Recently, the mean 3-D Morel-Atlas of the basal ganglia and the thalamus was introduced. It combines information contained in histological data from ten post-mortem brains. We were interested whether the Morel-Atlas is applicable for the visualization of stimulation sites. METHODS: In a consecutive PD patient series, we documented preoperative MRI planning, intraoperative target adjustment based on electrophysiological and neurological testing, and perioperative CT target reconstruction. The localization of the DBS electrodes and the optimal stimulation sites were projected onto the Morel-Atlas. RESULTS: We included 20 patients (median age 62 years). The active contact had mean coordinates Xlat = ±12.1 mm, Yap = -1.8 mm, Zvert = -3.2 mm. There was a significant difference between the initially planned site and the coordinates of the postoperative active contact site (median 2.2 mm). The stimulation site was, on average, more anterior and more dorsal. The electrode contact used for optimal stimulation was found within the STN of the atlas in 38/40 (95 %) of implantations. CONCLUSIONS: The cluster of stimulation sites in individual patients-as deduced from preoperative MR, intraoperative electrophysiology and neurological testing-showed a high degree of congruence with the atlas. The mean 3D Morel Atlas is thus a useful tool for postoperative target visualization. This represents the first clinical evaluation of the recently created atlas.

Detection of IKKbeta-IKKgamma subcomplexes in monocytic cells and characterization of associated signaling.

The IkappaB kinase (IKK) complex is one major step in the regulation of the NF-kappaB/Rel system that is involved in inflammatory and immune responses as well as in proliferation and apoptosis. At present it is not clear whether besides the "classical" IKKalpha-IKKbeta-IKKgamma configuration additional complexes exist in vivo that solely contain IKKbeta and IKKgamma (without IKKalpha). In the current study we were able to demonstrate in monocytic cells that endogenous complexes, which only include IKKbeta as the kinase-active molecule do indeed exist in vivo and that these complexes contain IKKgamma as an additional component. Furthermore, we showed that these IKKbeta-IKKgamma complexes are involved in mainstream NF-kappaB activation cascades because they can be activated by tumor necrosis factor. In contrast, these subcomplexes appear not to participate in NIK-dependent pathways. As a next step we showed that exogenous IKKbeta-IKKgamma complexes can be formed in an intact cell by overexpression and that these artificial complexes fulfill the requirement for participation in regular signaling. Finally, in the absence of IKKalpha we found a retarded proteolysis of IkappaBalpha, but not of IkappaB in, which is associated with a reduced IKK activity. Differential pathways represented by various IKK subcomplexes may open attractive possibilities in treatment of inflammation or cancer allowing specific therapeutic intervention.

Antipsoriatic drug anthralin induces EGF receptor phosphorylation in keratinocytes: requirement for H(2)O(2) generation.

Even though anthralin is a well-established topical therapeutic agent for psoriasis, little is known about its effects and biochemical mechanisms of signal transduction. In contrast to a previous report, we found that anthralin induced time- and concentration-dependent phosphorylation of epidermal growth factor receptor in primary human keratinocytes. Four lines of evidence show that this process is mediated by reactive oxygen species. First, we found that anthralin induces time-dependent generation of H(2)O(2). Second, there is a correlation between a time-dependent increase in anthralin-induced epidermal growth factor receptor phosphorylation and H(2)O(2) generation. Third, the structurally different antioxidants n-propyl gallate and N-acetylcysteine inhibited epidermal growth factor receptor phosphorylation induced by anthralin. Fourth, overexpression of catalase inhibited this process. The epidermal growth factor receptor-specific tyrosine kinase inhibitor PD153035 abrogated anthralin-induced epidermal growth factor receptor phosphorylation and activation of extracellular-regulated kinase 1/2. These findings establish the following sequence of events: (1) H(2)O(2) generation, (2) epidermal growth factor receptor phosphorylation, and (3) extracellular-regulated kinase activation. Our data identify anthralin-induced reactive oxygen species and, more specifically, H(2)O(2) as an important upstream mediator required for ligand-independent epidermal growth factor receptor phosphorylation and downstream signaling.

Vitamin C derivative ascorbyl palmitate promotes ultraviolet-B-induced lipid peroxidation and cytotoxicity in keratinocytes.

Among the preventative and protective strategies against the harmful effects of ultraviolet radiation to the skin is the application of antioxidants. Ascorbic acid has been shown to protect against sunburn, delay the onset of skin tumors, and reduce ultraviolet-B-radiation-induced skin wrinkling. In this work, we sought to determine the antioxidative properties of a lipid-soluble derivative of ascorbic acid, ascorbic acid-6-palmitate. We found that ascorbic acid-6-palmitate reduced cellular levels of reactive oxygen species following ultraviolet B irradiation. Treatment of keratinocytes with ascorbic acid-6-palmitate inhibited ultraviolet-B-mediated activation of epidermal growth factor receptor, extracellular regulated kinases 1 and 2, and p38 kinase because of its ability to prevent reduced glutathione depletion and scavenge hydrogen peroxide. Ascorbic acid-6-palmitate strongly promoted ultraviolet-B-induced lipid peroxidation, c-Jun N-terminal kinase activation, and cytotoxicity, however. End products of lipid peroxidation, such as 4-hydroxy-2-nonenal, have been reported to mediate stress-activated protein kinase activation and cell toxicity in epithelial cells. The lipid component of ascorbic acid-6-palmitate probably contributes to the generation of oxidized lipid metabolites that are toxic to epidermal cells. Our data suggest that, despite its antioxidant properties, ascorbic acid-6-palmitate may intensify skin damage following physiologic doses of ultraviolet radiation.