Human MYO15A is located on chromosome 17p11.2, has 66 exons and encodes unconventional myosin XVA. Recessive mutations of MYO15A are associated with profound, nonsyndromic hearing loss DFNB3 in humans, and deafness and circling behavior in shaker 2 mice. In the inner ear, this motor protein is necessary for the development of hair cell stereocilia, which are actin-filled projections on the apical surface and the site of mechanotransduction of sound. The longest isoform of myosin XVA has 3,530 amino acid residues. Two isoform classes of MYO15A are distinguished by the presence or absence of 1,203 residues preceding the motor domain encoded by alternatively-spliced exon 2. It is not known whether this large N-terminal extension of myosin XVA is functionally necessary for hearing. We ascertained approximately 600 consanguineous families segregating hereditary hearing loss as a recessive trait and found evidence of linkage of markers at the DFNB3 locus to hearing loss in 38 of these families ascertained in Pakistan (n=30), India (n=6), and Turkey (n=2). In this study, we describe 16 novel recessive mutations of MYO15A associated with severe to profound hearing loss segregating in 20 of these DFNB3-linked families. Importantly, two homozygous mutant alleles-c.3313G>T (p.E1105X) and c.3334delG (p.G1112fsX1124) of MYO15A-located in exon 2 are associated with severe to profound hearing loss segregating in two families. These data demonstrate that isoform 1, containing the large N-terminal extension, is also necessary for normal hearing.
The functional resemblance between kidney proximal tubular and inner ear epithelial cells which has often been pointed out in the literature led us to hypothesize that nephrotoxic agents that cause renal tubular injury might also impair the function of inner ear cells. As one of the most toxic environmental nephrotoxic agents is cadmium, we aimed to study its effects on hearing experimentally in rats. In this study, increased blood and renal cortical cadmium levels were associated with high cadmium accumulation in ear ossicles and labyrinth in rats exposed to cadmium. The changes in auditory brainstem response (ABR) and otoacoustic emission in 2-month-old male rats exposed to drinking water containing 5 and 15 ppm CdCl2 for 30 days showed that cadmium-induced nephrotoxicity was associated with signs of defective hearing at a concentration of 15 ppm CdCl2 but that 5 ppm CdCl2 caused hearing loss without affecting kidney function. The mean latency of ABR wave 1, which indicates the function of the cochlea, was 1.335 +/- 0.31 ms in the control group and 1.641 +/- 0.052 and 1.74 +/- 0.88 ms in the rats subjected to 5 and 15 ppm CdCl2, respectively (p < 0.001). In the cadmium-treated groups short interpeak wave I-III latencies (p < 0.01) indicated cochlear dysfunction and this was also supported by the distortion product otoacoustic emission results (p < 0.001). Non-significant changes in wave III and V latencies were accepted as evidence of unaltered function of the other parts of the auditory system. These results suggest that hair cells are more sensitive to cadmium than kidney tubule cells and that the cochlear component of hearing is more vulnerable to cadmium toxicity than other parts of the auditory system.
Cadmium, which has adverse effects on many physiological systems, is an important environmental pollutant. Our previous experimental study showed that cadmium also has a dose-dependent deleterious effect on the auditory system in rats. Because zinc reverses cadmium cytotoxicity in many systems, we investigated the possible preventive effect of a zinc-enriched diet given isochronally on cadmium-induced hearing loss in rats. Fifty-four male rats were divided into three equal groups. Control rats were fed normal rat food and tap water, whereas the cadmium group was subjected to 15 ppm cadmium-containing water as CdCl2. The third group received 15 ppm CdCl2 and food enriched with 200 ppm zinc as ZnSO4 for 30 d. On d 30, eight animals from each group were used for the measurement of kidney functions. In the remaining animals, hearing functions were measured by auditory brainstem response and distortion product otoacoustic emission. Blood cadmium increased from 1.87+/-1.69 to 6.08+/-2.62 microg/dL and elevated cadmium contents of ear ossicles and kidney cortex were associated with a decreased glomerular filtration rate in rats subjected to high cadmium. A zinc-enriched diet obviously reduced cadmium accumulation in the kidney and prevented the nephrotoxicity. Our data indicated that cadmium-induced ototoxicity seems to be partially zinc preventable and zinc addition to diet without altering cadmium content in ear ossicles may help to prevent cadmium-induced hearing loss.
Background and Aim: Accelerated weight gain after (adeno)tonsillectomy has been reported in a number of studies. Whether (adeno)tonsillectomy is also a risk factor for development of overweight is unknown. We investigated serum leptin and plasma ghrelin levels before and 1 year after (adeno)tonsillectomy operation in children. Materials and Methods: We studied 31 patients and 29 age- and sex-matched healthy control children. Auxologic evaluation and biochemical investigations were performed before surgery and 1 year later. Results: One year after surgery, height SDS (p = 0.001) and weight SDS (p = 0.004) were significantly increased in both groups. No changes in BMI SDS (p = 0.105) were observed. Preoperative leptin levels were significantly higher in patients than controls (p < 0.001). IGF-1, IGFBP-3, HOMA-IR and ghrelin values were not significantly different between the groups. One year after surgery, IGF-1 (p = 0.001) and IGFBP-3 (p = 0.001) were significantly increased, while ghrelin (p < 0.001) was significantly decreased. Postoperative leptin levels of patients were also significantly higher than preoperative values (p = 0.036). Conclusion: Significantly higher leptin levels in patients compared to control both before and 1 year after an obstruction-relieving surgery suggested that higher levels might be due to leptin resistance in these patients. Based on our findings we recommend measurement of leptin levels longitudinally for at least 5 years after adenotonsillectomy.
Our objective is to examine the effects of using nasal packing or transseptal suture in septoplasty in young patients, specifically on the polysomnographic parameters in the post-operative period. A total of 43 patients who had undergone septoplasty surgery after a diagnosis of septum deviation were included in the study. Packing was inserted in 23 patients, and transseptal suture was performed in the other 20 patients. A polysomnography test was performed on the patients on the first day after surgery and during the post-operative period. A post-operative increase was found in the apnea-hypopnea index (AHI) within both the packing and suture groups. The AHI increase in the packing group was statistically significant (p < 0.05). In the post-operative period, the fall in average oxygen desaturation in the packing group was significantly higher compared to suture group (p < 0.001). In addition, the arousal index was significantly higher in the packing group (p < 0.05). The use of nasal packing in young patients after septoplasty surgery reduced the quality of life after surgery and had negative effects on respiration during sleep. The finding that nasal packing caused obstructive sleep apnea syndrome even in young patients leads us to hypothesise that the effect of the packing on comorbid patients' respiratory function during sleep would be even more severe.
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