Anatomical landmarks for cochlear implantation in ossified cochleas.

PURPOSE: In this study, we aimed to introduce the facial nerve as a new anatomical landmark which can be used in ossified cochleas during cochlear implantation. We also set out to define a safe line to preserve the internal auditory canal (IAC) while drilling the basal turn of the cochlea. METHODS: Thirty patients who had temporal computed tomography (CT) were studied. The distances from the facial nerve and the round window to the IAC, carotid artery, and jugular bulb were measured in the reformatted CT images. We have created a line in the direction of the stapedial tendon from the round window to the IAC and called it ROWIAC (Round window-IAC) line. We have investigated whether this line intersects the IAC and measured the distances from this line to the IAC. RESULTS: Fifty-four temporal CT scans were included to the study. The mean distances from the facial nerve to the IAC, carotid artery, and jugular bulb were 8.8 ± 0.9, 15.0 ± 2.0, and 12.2 ± 2.9 mm, respectively. The mean distances from the round window to these structures were 3.8 ± 0.7, 9.4 ± 2.2, and 8.3 ± 2.9 mm, respectively. ROWIAC line did not intersect the IAC in any of the patients. The mean distance between this line and the IAC was 0.8 ± 0.4 mm. CONCLUSION: We propose that facial nerve and ROWIAC line can be used as potential landmarks during cochlear implantation in ossified cochleas to protect the adjacent neurovascular structures.

Air Injection and Transillumination in Phonosurgery: A Novel Technique.

OBJECTIVES/HYPOTHESIS: The goal of this study was to introduce two novel techniques in phonomicrosurgery, air injection (AIR), and transillumination (TI), to improve the diagnosis and surgical excision of pathological tissue in vocal folds during suspension laryngoscopy while preserving the healthy tissue as much as possible. STUDY DESIGN: Prospective clinical case series. METHODS: Thirty-four patients with benign vocal cord lesions who underwent phonomicrosurgery between January 2016 and May 2017 were evaluated. Pre- and intraoperative recordings were evaluated by three experienced laryngologists. Stroboscopic video images taken during the preoperative diagnosis and interoperative video recordings made before and after AIR and TI were performed were reviewed and compared. During the preoperative evaluation, the surgeons declared their surgical plans and noted changes while observing the intraoperative evaluation during AIR and TI. RESULTS: Sixty-eight vocal folds were evaluated. The initial diagnosis was found to be consistent with the final diagnosis in only 10 patients (29.4%). The diagnoses of 29 vocal folds (42.6%) and the surgical plans changed after AIR and TI. In six cases, submucosal bands, additional morphological structures in the vicinity of the primary pathology, were observed; these could only be visualized with AIR and TI. AIR and TI revealed new pathologies in four vocal folds that were noted to be normal in the preoperative evaluation. CONCLUSION: AIR and TI are useful and promising techniques to identify undiagnosed lesions in vocal folds and to increase the success of minimally invasive phonosurgery.

A novel muscle for electroneurography in peripheral facial palsy: occipitalis.

Electroneurography (ENoG) is one of the most objective tests in grading the damage and prediction of prognosis in peripheral facial palsy (PFP). We aimed to determine temporal changes of ENoG recorded over occipitalis muscle in acute idiopathic PFP. Consecutive 21 patients with unilateral acute idiopathic PFP and age- and sex-matched 15 healthy volunteers were included in the study. Nasal and occipital ENoG values were recorded once in the control group and the same procedure was repeated daily between the second and eight days of the disorder in the PFP group. Occipital ENoG value began to increase on the third day while nasal ENoG value was still within the normal range (27.04 vs 7.69 %, p = 0.0001). In the fourth, fifth and sixth days, occipital ENoG value was significantly high compared to nasal ENoG value (p = 0.0001 for each day) whereas nasal and occipital ENoG values were very similar in the seventh and eighth days (p = 0.181 and p = 0.584, respectively). Our study presents further support for technical possibility of occipital ENoG which may reflect the degree of fiber degeneration earlier than the nasalis muscle in PFP.

Selenoprotein W controls epidermal growth factor receptor surface expression, activation and degradation via receptor ubiquitination.

Epidermal growth factor (EGF) receptor (EGFR) is the founding member of the ErbB family of growth factor receptors that modulate a complex network of intracellular signaling pathways controlling growth, proliferation, differentiation, and motility. Selenoprotein W (SEPW1) is a highly conserved, diet-regulated 9kDa thioredoxin-like protein required for normal cell cycle progression. We report here that SEPW1 is required for EGF-induced EGFR activation and that it functions by suppressing EGFR ubiquitination and receptor degradation. SEPW1 depletion inhibited EGF-dependent cell cycle entry in breast and prostate epithelial cells. In prostate cells, SEPW1 depletion decreased EGFR auto-phosphorylation, while SEPW1 overexpression increased EGFR auto-phosphorylation. SEPW1 depletion increased the rate of EGFR degradation, which decreased total and surface EGFR and suppressed EGF-dependent EGFR endocytosis, EGFR dimer formation, and activation of EGF-dependent pathways. EGFR ubiquitination was increased in SEPW1-depleted cells--in agreement with the increased rate of EGFR degradation, and suggests that SEPW1 suppresses EGFR ubiquitination. Ubiquitination-directed lysozomal degradation controls post-translational EGFR expression and is dysregulated in many cancers. Thus, suppression of EGFR ubiquitination by SEPW1 may be related to the putative increase in cancer risk associated with high selenium intakes. Knowledge of the mechanisms underlying SEPW1's regulation of EGFR ubiquitination may reveal new opportunities for nutritional cancer prevention or cancer drug development.

Assessment of cricopharyngeal muscle aging with apoptotic markers.

OBJECTIVES: The aims of this study were to evaluate histochemical markers of apoptosis in the cricopharyngeus muscle, which is the gatekeeper of the pharyngoesophageal region during the swallowing process; to investigate the effects of primary aging on this muscle; and to determine whether a relationship exists with gastroesophageal reflux disease. MATERIALS AND METHODS: The study included 30 fresh cadavers with a time of death of 12 hours or less obtained from the Turkish Ministry of Justice Forensic Medicine Unit. All cadavers were dissected with routine postmortem skin incisions to extract specimens from the cricopharyngeus muscle and the esophagocardiac junction mucosa. Muscle degeneration and primary aging were demonstrated by immunodetection of Bax, Bcl-2, and Caspase-3 proteins as markers of the apoptosis. Esophageal specimens were examined for the presence of reflux esophagitis. RESULTS: The mean age was 41.5 (14-74) years, and the study included 18 male and 9 female cadavers. Three of them were excluded because of fixation artifacts. The mean Bax, Bcl-2, and Caspase scores showed no statistically significant relationship with age (P = 0.94). The right and left sides of the muscle were investigated separately, and the Bax scores of the right side of the cricopharyngeus muscle showed a statistically significant decrease with age (P = 0.026), whereas the Bax and Bcl-2 scores were increased with age (P = 0.035 and 0.049, respectively) on the left side. Evaluation of the 23 esophagus specimens revealed 10 cases of esophagitis. No relationship was found between the mean of each apoptotic marker and esophagitis. CONCLUSIONS: It is histopathologically not possible to demonstrate muscle death due to either primary aging or reflux. This might be attributable to the defensive capability of this unique muscle to maintain the feeding process.

Effect of anti-adhesive barrier use on laryngotracheal movement after total thyroidectomy: an electrophysiological study.

Impairment of laryngotracheal movement is a possible complication after total thyroidectomy. Here, we aimed to investigate the frequency and extent of impairment of laryngotracheal movement after total thyroidectomy and the effect of anti-adhesive barrier hyaluronic acid-carboxymethylcellulose membrane positioning between strap muscles and laryngotracheal complex on deglutition. The study design is prospective clinical study. Istanbul Training and Research Hospital, Laboratory of Electrophysiology, Istanbul Training and Research Hospital. The patients who underwent total thyroidectomy were selected and dichotomized according to use of seprafilm. Each group consisted of 8 female patients. All patients were assessed clinically and electrophysiologically in the pre/postop period. Electrophysiological investigations included cricopharyngeal muscle (CPM) electromyography (EMG), submental EMG, single bolus analysis [foreburst, reburst, swallowing (pause) patterns], laryngotracheal movement analysis and results were compared between two groups. CPM EMG was normal in both groups. Duration of submental muscle activity during dry and 15 cc water swallowing was similar between two groups (P = 0.751). Pause duration was shorter in group with seprafilm (P < 0.01). Dysphagia limit was 15 cc in both groups. The fore/rebound bursts duration, the time of laryngeal elevation, closure and suspension were similar (P = 0.954). We concluded that use of seprafilm between larynx and strap muscles during total thyroidectomy does not have any adverse effects on swallowing. Anti-adhesive barrier can be used safely during thyroid surgery.

Delayed cell cycle progression in selenoprotein W-depleted cells is regulated by a mitogen-activated protein kinase kinase 4-p38/c-Jun NH2-terminal kinase-p53 pathway.

Selenoprotein W (SEPW1) is a ubiquitous, highly conserved thioredoxin-like protein whose depletion causes a transient p53- and p21(Cip1)-dependent G(1)-phase cell cycle arrest in breast and prostate epithelial cells. SEPW1 depletion increases phosphorylation of Ser-33 in p53, which is associated with decreased p53 ubiquitination and stabilization of p53. We report here that delayed cell cycle progression, Ser-33 phosphorylation, and p53 nuclear accumulation from SEPW1 depletion require mitogen-activated protein kinase kinase 4 (MKK4). Silencing MKK4 rescued G(1) arrest, Ser-33 phosphorylation, and nuclear accumulation of p53 induced by SEPW1 depletion, but silencing MKK3, MKK6, or MKK7 did not. SEPW1 silencing did not change the phosphorylation state of MKK4 but increased total MKK4 protein. Silencing p38γ, p38δ, or JNK2 partially rescued G(1) arrest from SEPW1 silencing, suggesting they signal downstream from MKK4. These results imply that SEPW1 silencing increases MKK4, which activates p38γ, p38δ, and JNK2 to phosphorylate p53 on Ser-33 and cause a transient G(1) arrest.

The effects of corticosteroid on tissue lactoferrin in patients with nasal polyposis.

BACKGROUND: Although, lactoferrin (LF) is the second most important antimicrobial and anti-inflammatory peptide after lysozyme in upper respiratory tract, little is known about its role in chronic rhinosinusitis (CRS). Recent studies pronounced that LF levels were significantly reduced in CRS with nasal polyposis (NP) compared with other subgroups. However, effects of systemic corticosteroid (CS) treatment, which is currently the main NP treatment modality, and subsequent surgical intervention on LF levels are still not known. This study was designed to evaluate the effects of CS treatment and surgical intervention on LF levels in patients with NP. METHODS: Patients with inflammatory NP who were scheduled to undergo CS treatment and a control group were included in this study. LF levels were determined from mucosal samples taken from both groups, before and after CS treatment, and also 1 month after surgical intervention. RESULTS: Twenty-seven patients with NP and 14 patients who underwent septoplasty were included in the study. Tissue LF levels were significantly lower in the NP group compared with the control group (p = 0.014). Tissue LF levels did not change significantly in NP patients after CS treatment. However, a significant reduction in tissue LF was detected 1 month after endoscopic sinus surgery. CONCLUSION: Tissue LF concentrations significantly decreased in patients with NP. CS treatment had no effect on tissue LF levels, whereas postendoscopic sinus surgery, tissue LF levels were getting lower because there was also a reduction in inflammatory load (whether from reduction in mucosa surface area or resolution of disease).

Cricopharyngeal muscle electromyography findings in patients with gastroesophageal reflux disease.

OBJECTIVE: To analyze the grade of reflux and the behavior of the cricopharyngeal muscle (CPM) in patients with gastroesophageal reflux (GER) by means of electromyographic (EMG) analysis of CPM. STUDY DESIGN: Prospective clinical study. SETTING: Istanbul Training and Research Hospital. SUBJECT AND METHODS: Motor unit potential (MUP) recordings and kinesiological recordings of CPM were performed using a concentric needle electrode during dry material swallowing and 3-, 5-, and 10-mL water swallowing. Twenty-four patients with GER were compared with 21 healthy volunteers. RESULTS: GER was mild in 15 patients and moderate-to-severe in 9 patients. MUP recordings were normal in both groups during the preswallowing/postswallowing periods. Kinesiological investigations revealed that the number of patients who did not show a preswallow EMG burst had a positive correlation with the severity of reflux and the amount of liquid swallowed. Rebound bursts were observed in the patient and the control groups. Duration of preswallow and rebound bursts was similar in all groups. Duration of swallowing was shorter in mild GER patients compared with healthy volunteers and moderate-to-severe GER patients. Piecemeal deglutition during 10-mL liquid swallowing was higher in moderate-to-severe GER patients. We also found a positive correlation between the number of swallows and the severity of reflux. CONCLUSION: Needle EMG of the upper esophageal sphincter was normal in GER patients. Kinesiological evaluations showed increased piecemeal deglutition and number of swallows that correlated positively with the severity of GER.

Selenoprotein W depletion induces a p53- and p21-dependent delay in cell cycle progression in RWPE-1 prostate epithelial cells.

The anticancer activity of selenium (Se) has been demonstrated in myriad animal and in vitro studies, yet the mechanisms remain obscure. The main form of Se in animal tissues is selenocysteine in selenoproteins, but the relative importance of selenoproteins versus smaller Se compounds in cancer protection is unresolved. Selenoprotein W (SEPW1) is a highly conserved protein ubiquitously expressed in animals, bacteria, and archaea. SEPW1 depletion causes a delay in cell cycle progression at the G1/S transition of the cell cycle in breast and prostate epithelial cells. Tumor suppressor protein p53 is a master regulator of cell cycle progression and is the most frequently mutated gene in human cancers. p53 was increased in SEPW1 silenced cells and was inversely correlated with SEPW1 mRNA in cell lines with altered SEPW1 expression. Silencing SEPW1 decreased ubiquitination of p53 and increased p53 half-life. SEPW1 silencing increased p21(Cip1/WAF1/CDKN1A), while p27 (Kip1/CDKN1B) levels were unaffected. G1-phase arrest from SEPW1 knockdown was abolished by silencing p53 or p21. Cell cycle arrest from SEPW1 silencing was not associated with activation of ATM or phosphorylation of Ser-15 in p53, suggesting the DNA damage response pathway was not involved. Silencing GPX1 had no effect on cell cycle, suggesting that G1-phase arrest from SEPW1 silencing was not due to loss of antioxidant protection. More research is required to identify the function of SEPW1 and how it affects stability of p53.

Determining the most suitable costal cartilage level for rhinoplasty: an experimental study.

OBJECTIVE: The aim of this study was to compare the biomechanical properties of septal cartilage (SC) and costal cartilage (CC) grafts harvested from different ribs and to find at which level CC has characteristics closest to SC. STUDY DESIGN: Experimental cadaver study. SETTING: Istanbul Training and Research Hospital. MATERIAL AND METHOD: Cartilage grafts were harvested from the 6th, 7th, and 8th ribs and the SC of 10 fresh cadavers. Shaped cartilage grafts were subjected to a bending test. Results were measured, and the force-deflection curve was plotted. Flexural strength (σ(f)) and flexural modulus of elasticity (E(f)) were determined. Fractured surfaces were evaluated by scanning electron microscopy (SEM). RESULTS: According to F(max), it was determined that ribs 6, 7, and 8 have significantly more durability compared with the SC (Ps = .030, .004, and .001). With regard to deflection, there was no significant difference between the SC and the 6th and 7th ribs and between the 6th and 7th ribs (Ps = 1.000, .088, and .306), while a significant difference was found between the SC and the 8th rib (P = .001). According to σ(f), no differences were seen between the 6th and 7th rib (P = .782), while difference was detected between the 6th and 8th and the 7th and 8th ribs (p = .001). Similar trends were established in E(f) values as in σ(f.) These results were confirmed by SEM images. CONCLUSION: The 7th CC can be used as autograft because it shows similar properties to SC. However, the 6th CC is preferred if more flexibility is desired, and the 8th CC is preferred where more strength is needed.

Nasal septal packing: which one?

The aim of this study was to investigate the effects of four different types of nasal packs on pain, nasal fullness and postoperative bleeding following septoplasty. Prospective randomised double blind study was conducted. The study group included 119 patients who underwent endonasal septoplasty under general anaesthesia. Four types of nasal packing materials were utilized: (1) Merocel standard 8-cm nasal dressing without airway, (2) Doyle Combo splint (DCS), (3) Merocel in a glove finger and (4) Vaseline gauze. All packs were removed at the 48th hour (±3 h) after the surgery. Three different variables were investigated following the surgical procedure: (1) pain, (2) nasal fullness and (3) bleeding after removal of the nasal packing material. DCS produced the greatest pain at the first and sixth postoperative hours. At the first postoperative day, the greatest pain score was reported for Merocel in the glove finger and the least for Merocel. The pain scores during the removal of the nasal packings were highest for Merocel and lowest for Merocel in the glove finger. DCS had the lowest nasal fullness score. Bleeding ratio was highest for Merocel, followed by Vaseline gauze, DCS and Merocel in the glove finger. Many different commercially available packing materials are presently used, each with inherent advantages and disadvantages. We evaluated the pain, nasal fullness and bleeding potential of four nasal packing materials and determined that Merocel had the highest pain potential during removal and the highest rate of bleeding following removal.

Tensile characteristics of costal and septal cartilages used as graft materials.

OBJECTIVES: To determine the biomechanical characteristics of septal cartilage (SC) and costal cartilage (CC) taken from fresh cadavers using tensile testing and to establish CC graft material of a suitable thickness (ie, with tensile characteristics closest to those of SC). METHODS: Grafts of varying thickness were harvested from the central part of the seventh-rib CC and SC of 18 fresh cadavers. Tensile testing was performed with a 0.5-kilonewton load calibrated at 7 mm/min. The results were shown as a force-elongation curve. RESULTS: No significant difference according to tensile force was observed between the SC group and the 1.0-mm and 1.5-mm CC groups (P = .09 and P = .32, respectively). However, a significant difference was observed between the SC group and the 2.0-mm CC group (P = .04). Although the strength value of the CC group was 5.03 MPa, the modulus of elasticity was 1.33 MPa. In the SC group, the strength value was 12.42, but the modulus of elasticity was 1.39 MPa. The strength value of the SC group was higher than that of the CC group (P = .001), but the modulus of elasticity value of the CC group was higher than that of the SC group (P = .001). CONCLUSIONS: From the standpoint of tensile testing for preparing columellar struts, 1.0-mm and 1.5-mm CC have similar characteristics to SC and thus can be used instead of it. However, it is important to determine the thickness of CC by considering the expected characteristics of the established material and the forces that affect the area in the nose where the graft will be placed.

Delayed cell cycle progression from SEPW1 depletion is p53- and p21-dependent in MCF-7 breast cancer cells.

Selenium (Se) is an essential redox-active trace element with close connections to cancer. Most of Se's biological functions have been attributed to the antioxidant properties of Se-containing proteins. However, the relative contribution of selenoproteins and small Se compounds in cancer protection is still a matter of debate. The tumor suppressor p53 is the most frequently mutated gene in human cancer and is often referred to as the "guardian of the genome". In response to genomic stresses, p53 causes cell cycle arrest to allow time for genomic damage to be repaired before cell division or induces apoptosis to eliminate irreparably damaged cells. Selenoprotein W (SEPW1) is a highly conserved small thioredoxin-like protein required for cell cycle progression. The present work shows that SEPW1 facilitates the G1 to S-phase transition by down-regulating expression of the cyclin-dependent kinase inhibitor p21. SEPW1 controls p21 by modulating levels of the p53 transcription factor, and this is associated with changes in phosphorylation of Ser-33 in p53. More work is needed to identify the mechanism by which SEPW1 regulates phosphorylation of Ser-33 and the kinase or phosphatase enzymes involved.

Histopathological characteristics of sulcus vocalis.

OBJECTIVE: To describe the frequency of sulcus vocalis in a population and to establish its histopathological properties. STUDY DESIGN: A cadaver study. SETTING: Istanbul Training and Research Hospital and Ministry of Justice National Forensic Institute. SUBJECTS AND METHODS: One hundred (21 women, 79 men) fresh cadaver larynges were examined. Two hundred vocal folds were coronally sectioned and examined by light microscopy. Sulcus types, depths, degree of fibrosis in Reinke space, basement membrane thickness, and perisulcus degeneration were determined. RESULTS: Sulcus vocalis was found in 39 of 100 cases (39%), with a male preponderance of 41.8% compared with women at 28.6%. Twenty-one (54%) cases had unilateral and 18 (46%) cases had bilateral sulcus. Among 200 vocal folds, 57 had sulcus (28%). A total of 21 sulcus cases were type 1 (37%), 18 were type 2 (31.5%), and the remaining 18 cases were type 3 (31.5%). Of the 39 (30.7%) sulcus cases, 12 were confirmed by histopathological examination, although they looked morphologically normal following macroscopic evaluation. Vocal ligament involvement was found in 14 cases with type 2 (78%) and in 15 cases with type 3 sulcus (83%). CONCLUSION: Sulcus vocalis is a common pathology in the population and can be observed at all ages. The accuracy of diagnosis seems to depend on the measurement of the sulcus depth and the histological characteristics. For this reason, tools and strategies should be established in living subjects for effective management of this challenging disorder.

Factors influencing the outcome of idiopathic sudden sensorineural hearing loss treated with hyperbaric oxygen therapy.

Idiopathic sudden sensorineural hearing loss (ISSNHL) is an otologic emergency with an incidence of about 5-20 per 100,000 of the population per year. There is no universally accepted standard protocol for the treatment of patients with ISSNHL. Hyperbaric oxygen therapy (HBOT), was first reported to improve the outcome following acute inner ear disorders during the late 1960s by both French and German authors. The increase in perilymph oxygenation produced by HBOT provides logical basis for the use of this treatment modality in ISSNHL. We reviewed the records of 97 cases that received HBOT for SSNHL to identify the factors that may affect the treatment outcomes. The effects of age, gender, affected ear, status of the contralateral ear, symptoms associated with hearing loss, presence of a cardiovascular disease, dyslipidemia, history of diabetes mellitus, seasonal factor, smoking, degree of hearing loss, audiogram type, medical treatments provided prior to HBOT, onset time, and number of HBOT sessions were evaluated. The mean hearing gain in all cases after the HBOT was 29.5 dB. The gains were statistically significant in the following cases: early onset of HBOT (p = 0.016), higher number of HBOT sessions (p < 0.01), steroid usage (p = 0.009), low frequency-ascending and total audiogram configuration (p < 0.01) and profound hearing loss (p = 0.011). The success rate was significantly lower in cases with high frequency-descending audiogram configuration (p < 0.001). The most important factor affected the prognosis favorably was found as steroid therapy. This retrospective study and our clinical experience suggest that HBOT has beneficial effects when administered in the early phase of the disease together with steroids. HBOT is a safe practice when used properly by an experienced hyperbaric team. In the treatment of ISSNHL, 20 sessions of HBOT at 2.5 ATA can be tolerated well besides some minor side effects. HBOT should be considered for the cases especially with total or profound hearing loss.

Regulation of redox signaling by selenoproteins.

The unique chemistry of oxygen has been both a resource and threat for life on Earth for at least the last 2.4 billion years. Reduction of oxygen to water allows extraction of more metabolic energy from organic fuels than is possible through anaerobic glycolysis. On the other hand, partially reduced oxygen can react indiscriminately with biomolecules to cause genetic damage, disease, and even death. Organisms in all three superkingdoms of life have developed elaborate mechanisms to protect against such oxidative damage and to exploit reactive oxygen species as sensors and signals in myriad processes. The sulfur amino acids, cysteine and methionine, are the main targets of reactive oxygen species in proteins. Oxidative modifications to cysteine and methionine can have profound effects on a protein's activity, structure, stability, and subcellular localization. Non-reversible oxidative modifications (oxidative damage) may contribute to molecular, cellular, and organismal aging and serve as signals for repair, removal, or programmed cell death. Reversible oxidation events can function as transient signals of physiological status, extracellular environment, nutrient availability, metabolic state, cell cycle phase, immune function, or sensory stimuli. Because of its chemical similarity to sulfur and stronger nucleophilicity and acidity, selenium is an extremely efficient catalyst of reactions between sulfur and oxygen. Most of the biological activity of selenium is due to selenoproteins containing selenocysteine, the 21st genetically encoded protein amino acid. The most abundant selenoproteins in mammals are the glutathione peroxidases (five to six genes) that reduce hydrogen peroxide and lipid hydroperoxides at the expense of glutathione and serve to limit the strength and duration of reactive oxygen signals. Thioredoxin reductases (three genes) use nicotinamide adenine dinucleotide phosphate to reduce oxidized thioredoxin and its homologs, which regulate a plethora of redox signaling events. Methionine sulfoxide reductase B1 reduces methionine sulfoxide back to methionine using thioredoxin as a reductant. Several selenoproteins in the endoplasmic reticulum are involved in the regulation of protein disulfide formation and unfolded protein response signaling, although their precise biological activities have not been determined. The most widely distributed selenoprotein family in Nature is represented by the highly conserved thioredoxin-like selenoprotein W and its homologs that have not yet been assigned specific biological functions. Recent evidence suggests selenoprotein W and the six other small thioredoxin-like mammalian selenoproteins may serve to transduce hydrogen peroxide signals into regulatory disulfide bonds in specific target proteins.

The effect of selenium supplementation on DTH skin responses in healthy North American men.

The trace element selenium (Se) is essential for immune system development and function in animals. However, the exact functions of Se in the human immune system and the achievable health benefits from Se supplementation remain unclear. To test whether an increased intake of dietary Se affects immune function, we conducted a randomized, controlled trial of Se supplementation in healthy free-living men. Forty-two men were administered 300microg of Se a day as high-Se Baker's yeast, or low-Se yeast for 48 weeks. Serum immunoglobulins, differential complete blood counts and lymphocyte sub-populations were measured every 6 weeks. Tests of delayed-type hypersensitivity (DTH) skin responses to mumps, candida, trychophyton, tuberculin-purified protein, and tetanus were performed at baseline and at the end of 48 weeks of treatment. Supplementation increased blood Se concentration by 50%. Surprisingly, consumption of the low-Se yeast induced anergy in DTH skin responses and increased counts of natural killer (NK) cells and T lymphocytes expressing both subunits of the high affinity interleukin-2 receptor (IL2R). DTH skin responses and IL2R+ cells did not change in the high-Se group, suggesting Se supplementation blocked induction of DTH anergy. There were no differences between groups in quality of life indicators, number of days sick, other leukocyte phenotypes, serum immunoglobulins, or complement factors. These results suggest that Se plays a role in immunotolerization, a cell-mediated process involved in many aspects of immune function.

Selenium supplementation does not affect testicular selenium status or semen quality in North American men.

Selenium (Se) is essential for sperm function and male fertility, but high Se intake has been associated with impaired semen quality. We reported previously a decrease in sperm motility in men fed high-Se foods, but we could not rule out the influence of other environmental and dietary factors. We now report on a randomized, controlled study on the potential adverse effects of Se supplementation on semen quality in 42 free-living men administered Se (300 microg/d) as high-Se yeast for 48 weeks. Semen analysis was performed 4 times before treatment began, then twice each week during treatment at 6, 12, 24, 36, and 48 weeks, and then after treatment at 72 and 96 weeks. Blood samples were collected 3 times before treatment and at each subsequent visit. Se concentration increased 61% in blood plasma and 49% in seminal plasma. However, Se supplementation had no effect on sperm Se, serum androgen concentrations, or sperm count, motility, progressive velocity, or morphology. We observed progressive decreases in serum luteinizing hormone, semen volume, and sperm Se in both the high-Se and placebo groups. Moreover, sperm straight-line velocity and percent normal morphology increased in Se-treated and placebo-treated participants. The lack of an increase in sperm Se suggests that testicular Se stores were unaffected, even though the participants' dietary Se intake was tripled and their total body Se approximately doubled by supplementation. These results are consistent with animal studies showing the Se status of testes to be unresponsive to dietary Se intake.

Selenoprotein W modulates control of cell cycle entry.

The present study was conducted to identify targets of selenium (Se) provided to cultured human cells in physiologically relevant doses and forms. Breast and prostate epithelial cells were supplemented with Se provided as 100 nM sodium selenite or high-Se serum and gene expression was profiled with DNA microarrays. Pure sodium selenite affected expression of 560 genes in MCF-10A breast cells, including 60 associated with the cell cycle (p = 2.8 x 10(-16)). Selenoprotein W (SEPW1) was the only selenoprotein messenger RNA (mRNA) increased by both sodium selenite (specific) and high-Se serum (physiologic). SEPW1 small interfering RNA inhibited G1-phase progression and increased G1-phase gene transcripts, while decreasing S-phase and G2/M-phase gene transcripts, indicating the cell cycle was interrupted at the G1/S transition. SEPW1 mRNA levels were maximal during G1-phase, dropped after the G1/S transition and increased again after G2/M-phase. SEPW1-underexpressing prostate cells had increased mRNA for BCL2, which can induce a G1 arrest, and decreased mRNA for RBBP8 and KPNA2, which modulate the Rb/p53 checkpoint pathway. These results suggest that SEPW1 and the G1/S transition are physiological targets of Se in breast and prostate epithelial cells.