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  • 1.
    Berglin, Cecilia Engmer
    et al.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Otorhinolaryngol, Stockholm, Sweden..
    Pierre, Pernilla Videhult
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar. Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Ekborn, Andreas
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Otorhinolaryngol, Stockholm, Sweden..
    Bramer, Tobias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Edsman, Katarina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Hultcrantz, Malou
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Otorhinolaryngol, Stockholm, Sweden..
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Local treatment of the inner ear: A study of three different polymers aimed for middle ear administration2015Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 135, nr 10, s. 985-994Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Conclusion: A formulation based on sodium hyaluronate (NaHYA) was the most promising candidate vehicle for intra-tympanic drug administration regarding conductive hearing loss, inflammatory reactions, and elimination. Objectives: Recent advances in inner ear research support the idea of using the middle ear cavity for drug administration to target the inner ear. This paper presents rheological and safety assessments of three candidate polymer formulations for intra-tympanic drug administration. Method: The formulations were based on sodium carboxymethyl cellulose (NaCMC), sodium hyaluronate (NaHYA), and poloxamer 407 (POL). Rheological studies were performed with a controlled rate instrument of the couette type. Safety studies were performed in guinea pigs subjected to an intra-tympanic injection of the formulations. Hearing function was explored with ABR before and 1, 2, and 3 weeks after the injection. Elimination of the formulations marked with coal was explored with an endoscopic digital camera 1, 2, and 3 weeks after injection. Middle and inner ear morphology was examined with light microscopy 6 days after injection. Results: The results speak in favor of NaHYA, since it did not cause prolonged hearing threshold elevations. The results of the elimination and morphological investigations support the conclusion of NaHYA being the most promising candidate for intra-tympanic administration.

  • 2.
    Pierre, Pernilla Videhult
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar. Karolinska Inst, Div Audiol, Dept Clin Sci Intervent & Technol, Alfred Nobels Alle 10 Plan 5, SE-14183 Huddinge, Sweden.
    Haglöf, Jakob
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för analytisk farmaceutisk kemi.
    Linder, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Engskog, Mikael K R
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för analytisk farmaceutisk kemi.
    Arvidsson, Torbjörn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för analytisk farmaceutisk kemi.
    Pettersson, Curt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för analytisk farmaceutisk kemi.
    Fransson, Anette E
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Cisplatin-induced metabolome changes in serum: an experimental approach to identify markers for ototoxicity2017Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 137, nr 10, s. 1024-1030Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Ototoxicity from treatment with the anticancer drug cisplatin remains a clinical problem. A wide range of intracellular targets of cisplatin has been found in vivo.

    AIM: To investigate cisplatin-induced change of the serum metabolite profile and its association with ototoxicity.

    MATERIAL AND METHODS: Guinea pigs (n = 14) were treated with cisplatin (8 mg/kg b.w., i.v.) 30 min after administration of the otoprotector candidate sodium thiosulfate (group STS; n = 7) or sodium chloride (group NaCl; n = 7). Ototoxicity was evaluated by ABR (3-30 kHz) before and 4 d after drug treatment, and by assessment of hair cell loss. A blood sample was drawn before and 4 d after drug treatment and the polar metabolome in serum was analyzed using LC-MS.

    RESULTS: Cisplatin-treatment caused significant threshold elevations and outer hair cell (OHC) loss in both groups. The ototoxicity was generally lower in group STS, but a significant difference was reached only at 30 kHz (p = .007). Cisplatin treatment altered the metabolite profile significantly and similarly in both groups. A significant inverse correlation was found between L-acetylcarnitine, N-acetylneuraminic acid, ceramide, and cysteinylserine and high frequency hearing loss in group NaCl. The implication of these correlations should be explored in targeted studies.

  • 3.
    Pierre, Pernilla Videhult
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Johnson, Ann-Christin
    Fridberger, Anders
    Subjective and Clinically Assessed Hearing Loss; A Cross-Sectional Register-Based Study on a Swedish Population Aged 18 through 50 Years2015Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 4Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives Questionnaire studies suggest that hearing is declining among young adults. However, few studies have examined the reliability of hearing questionnaires among young adult subjects. This study examined the associations between pure tone audiometrically assessed (PTA) hearing loss and questionnaire responses in young to middle aged adults. Materials and Methods A cross-sectional study using questionnaire and screening PTA (500 through 6000 Hz) data from 15322 Swedish subjects (62% women) aged 18 through 50 years. PTA hearing loss was defined as a hearing threshold above 20 dB in both ears at one or more frequencies. Data were analysed with chi-square tests, nonlinear regression, binary logistic regression, and the generalized estimating equation (GEE) approach. Results The prevalence of PTA hearing loss was 6.0% in men and 2.9% in women (p < 0.001). Slight hearing impairment was reported by 18.5% of the men and 14.8% of the women (p < 0.001), whereas 0.5% of men and women reported very impaired hearing. Using multivariate GEE modelling, the odds ratio of PTA hearing loss was 30.4 (95% CI, 12.7-72.9) in men and 36.5 (17.2-77.3) in women reporting very impaired hearing. The corresponding figures in those reporting slightly impaired hearing were 7.06 (5.25-9.49) in men and 8.99 (6.38-12.7) in women. These values depended on the sound stimulus frequency (p = 0.001). The area under the ROC curve was 0.904 (0.892-0.915) in men and 0.886 (0.872-0.900) in women. Conclusions Subjective hearing impairment predicted clinically assessed hearing loss, suggesting that there is cause for concern as regards the future development of hearing in young to middle-aged people.

  • 4.
    Pirttilä, Kristian
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Analytisk farmaceutisk kemi.
    Pierre, Pernilla Videhult
    Karolinska Inst, Div Audiol, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Haglöf, Jakob
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Analytisk farmaceutisk kemi.
    Engskog, Mikael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Analytisk farmaceutisk kemi.
    Hedeland, Mikael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Analytisk farmaceutisk kemi.
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Arvidsson, Torbjörn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Analytisk farmaceutisk kemi.
    Pettersson, Curt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Analytisk farmaceutisk kemi.
    An LCMS-based untargeted metabolomics protocol for cochlear perilymph: highlighting metabolic effects of hydrogen gas on the inner ear of noise exposed Guinea pigs2019Inngår i: Metabolomics, ISSN 1573-3882, E-ISSN 1573-3890, Vol. 15, nr 10, artikkel-id 138Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction

    Noise-induced hearing loss (NIHL) is an increasing problem in society and accounts for a third of all cases of acquired hearing loss. NIHL is caused by formation of reactive oxygen species (ROS) in the cochlea causing oxidative stress. Hydrogen gas (H-2) can alleviate the damage caused by oxidative stress and can be easily administered through inhalation.

    Objectives

    To present a protocol for untargeted metabolomics of guinea pig perilymph and investigate the effect of H-2 administration on the perilymph metabolome of noise exposed guinea pigs.

    Methods

    The left ear of guinea pigs were exposed to hazardous impulse noise only (Noise, n = 10), noise and H-2 (Noise + H2, n = 10), only H-2 (H2, n = 4), or untreated (Control, n = 2). Scala tympani perilymph was sampled from the cochlea of both ears. The polar component of the perilymph metabolome was analyzed using a HILIC-UHPLC-Q-TOF-MS-based untargeted metabolomics protocol. Multivariate data analysis (MVDA) was performed separately for the exposed- and unexposed ear.

    Results

    MVDA allowed separation of groups Noise and Noise + H2 in both the exposed and unexposed ear and yielded 15 metabolites with differentiating relative abundances. Seven were found in both exposed and unexposed ear data and included two osmoprotectants. Eight metabolites were unique to the unexposed ear and included a number of short-chain acylcarnitines.

    Conclusions

    A HILIC-UHPLC-Q-TOF-MS-based protocol for untargeted metabolomics of perilymph is presented and shown to be fit-for-purpose. We found a clear difference in the perilymph metabolome of noise exposed guinea pigs with and without H-2 treatment.

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