Isostructural Series of Ni(II), Pd(II), Pt(II), and Au(III) Azido Complexes with a N

An isoelectronic and isostructural series of cyclometalated azido complexes [M(N3)(dpb)] with M = Ni(II), Pd(II), Pt(II), and Au(III) based on the N^C^N pincer ligand 1,3-di(2-pyridyl)phenide (dpb) was characterized by X-ray diffraction analysis and investigated for reactivity in the iClick reaction with a wide range of internal and terminal alkynes by using 1H and 19F NMR spectroscopy. Reaction rate constants were found to increase with greater charge density in the order Ni(II) > Pd(II) > Pt(II) > Au(III). Terminal alkynes R-C≡C-R' with strongly electron-withdrawing groups R and R' exhibited faster kinetics than those with electron-donating substituents in the order CF3 > ketone > ester > H > phenyl ≫ amide, while R = CH3 resulted in complete loss of reactivity. Four symmetrical triazolato complexes [M(triazolatoCOOCH3,COOCH3)(dpb)] with M = Ni(II), Pd(II), Pt(II), and Au(III) as well as four nonsymmetrically substituted triazolato complexes [Pt(triazolatoR,R')(dpb)] originating from terminal and internal alkynes were shown by X-ray crystal structure analysis to exclusively feature N2-coordination of the five-membered ring ligand. However, the Pt(II) triazolato complexes exist as a mixture of N1- and N2-coordinated species in solution. Torsion angles between the mean planes of the N^C^N pincer and the triazolato ligand increase from a nearly coplanar to a perpendicular arrangement when going from Au(III)/Pt(II)/Pd(II) to Ni(II), while different substituents R and R' on the alkyne have no influence on the torsion angle and were rationalized by DFT calculations. Finally, a carbohydrate derivative obtained by glucuronic acid conjugation to methyl propiolate demonstrates the facile biofunctionalization of metal complexes via the iClick reaction.

Hearing thresholds at high frequency in patients with cystic fibrosis: a systematic review.

INTRODUCTION: High-frequency audiometry may contribute to the early detection of hearing loss caused by ototoxic medications. Many ototoxic drugs are widely used in the treatment of patients with cystic fibrosis. Early detection of hearing loss should allow known harmful drugs to be identified before the damage affects speech frequencies. The damage caused by ototoxicity is irreversible, resulting in important social and psychological consequences. In children, hearing loss, even when restricted to high frequencies, can affect the development of language. OBJECTIVE: To investigate the efficacy and effectiveness of hearing monitoring through high-frequency audiometry in pediatric patients with cystic fibrosis. METHODS: Electronic databases PubMed, MedLine, Web of Science and LILACS were searched, from January to November 2015. The selected studies included those in which high-frequency audiometry was performed in patients with cystic fibrosis, undergoing treatment with ototoxic drugs and published in Portuguese, English and Spanish. The GRADE system was chosen for the evaluation of the methodological quality of the articles. RESULTS: During the search process carried out from January 2015 to November 2015, 512 publications were identified, of which 250 were found in PubMed, 118 in MedLine, 142 in Web of Science and 2 in LILACS. Of these, nine articles were selected. CONCLUSION: The incidence of hearing loss was identified at high frequencies in cystic fibrosis patients without hearing complaints. It is assumed that high-frequency audiometry can be an early diagnostic method to be recommended for hearing investigation of patients at risk of ototoxicity.

High frequency hearing thresholds and product distortion otoacoustic emissions in cystic fibrosis patients.

INTRODUCTION: The treatment of patients with cystic fibrosis involves the use of ototoxic drugs, mainly aminoglycoside antibiotics. Due to the use of these drugs, fibrocystic patients are at risk of developing hearing loss. OBJECTIVE: To evaluate the hearing of patients with cystic fibrosis by High Frequency Audiometry and Distortion Product Otoacoustic Emissions. METHODS: Cross-sectional study. The study group consisted of 39 patients (7-20 years of age) with cystic fibrosis and a control group of 36 individuals in the same age group without otologic complaints, with normal audiometric thresholds and type A tympanometric curves. High Frequency Audiometry and Distortion Product Otoacoustic Emissions tests were conducted. RESULTS: The study group had significantly higher thresholds at 250, 1000, 8000, 9000, 10,000, 12,500, and 16,000Hz (p=0.004) as well as higher prevalence of otoacoustic emission alterations at 1000 and 6000Hz (p=0.001), with significantly lower amplitudes at 1000, 1400, and 6000Hz. There was a significant association between alterations in hearing thresholds in High Frequency Audiometry with the number of courses of aminoglycosides administered (p=0.005). Eighty-three percent of patients who completed more than ten courses of aminoglycosides had hearing loss in High Frequency Audiometry. CONCLUSION: A significant number of patients with cystic fibrosis who received repeated courses of aminoglycosides showed alterations in High Frequency Audiometry and Distortion Product Otoacoustic Emissions. The implementation of ten or more aminoglycoside cycles was associated with alterations in High Frequency Audiometry.

Hearing thresholds at high frequency in patients with cystic fibrosis: a systematic review / Limiares auditivos em altas frequências em pacientes com fibrose cística: revisão sistemática

Abstract Introduction: High-frequency audiometry may contribute to the early detection of hearing loss caused by ototoxic medications. Many ototoxic drugs are widely used in the treatment of patients with cystic fibrosis. Early detection of hearing loss should allow known harmful drugs to be identified before the damage affects speech frequencies. The damage caused by ototoxicity is irreversible, resulting in important social and psychological consequences. In children, hearing loss, even when restricted to high frequencies, can affect the development of language. Objective: To investigate the efficacy and effectiveness of hearing monitoring through high-frequency audiometry in pediatric patients with cystic fibrosis. Methods: Electronic databases PubMed, MedLine, Web of Science and LILACS were searched, from January to November 2015. The selected studies included those in which high-frequency audiometry was performed in patients with cystic fibrosis, undergoing treatment with ototoxic drugs and published in Portuguese, English and Spanish. The GRADE system was chosen for the evaluation of the methodological quality of the articles. Results: During the search process carried out from January 2015 to November 2015, 512 publications were identified, of which 250 were found in PubMed, 118 in MedLine, 142 in Web of Science and 2 in LILACS. Of these, nine articles were selected. Conclusion: The incidence of hearing loss was identified at high frequencies in cystic fibrosis patients without hearing complaints. It is assumed that high-frequency audiometry can be an early diagnostic method to be recommended for hearing investigation of patients at risk of ototoxicity.

Resumo Introdução: A audiometria de altas frequências pode contribuir para a detecção precoce de alterações auditivas causadas por medicações ototóxicas. No tratamento dos pacientes com fibrose cística, existem muitos fármacos ototóxicos amplamente utilizados. A detecção precoce de alterações auditivas deve permitir que sejam identificadas antes que o dano atinja as frequências da fala. A lesão causada pela ototoxicidade é irreversível, traz importantes consequências sociais e psicológicas. Nas crianças, a perda auditiva, mesmo restrita às altas frequências, pode afetar o desenvolvimento da linguagem. Objetivo: Investigar a eficácia e a efetividade do monitoramento da audição por meio da audiometria de altas frequências em pacientes pediátricos com fibrose cística. Método: Foram consultadas as bases de dados eletrônicas PubMed, Medline, Web of Science e Lilacs, de janeiro a novembro de 2015. Foram selecionados os estudos em que foi feita audiometria de altas frequências em pacientes com fibrose cística em tratamento com medicamentos ototóxicos e publicados em português, inglês e espanhol. Para a avaliação da qualidade metodológica dos artigos optou-se pelo uso do sistema Grade. Resultados: No processo de busca feito de janeiro de 2015 a novembro de 2015 foram encontradas 512 publicações, 250 na PubMed, 118 na Medline, 142 na Web of Science e dois na Lilacs. Desses, foram selecionados nove artigos. Conclusão: Identificou-se a ocorrência de perda auditiva em altas frequências em pacientes com fibrose cística sem queixas auditivas. Admite-se que audiometria em altas frequências possa ser um método de diagnóstico precoce a ser recomendado para investigação auditiva de pacientes em risco de ototoxicidade.

High frequency hearing thresholds and product distortion otoacoustic emissions in cystic fibrosis patients, / Limiares auditivos em altas frequências e emissões otoacústicas na fibrose cística

ABSTRACT INTRODUCTION: The treatment of patients with cystic fibrosis involves the use of ototoxic drugs, mainly aminoglycoside antibiotics. Due to the use of these drugs, fibrocystic patients are at risk of developing hearing loss. OBJECTIVE: To evaluate the hearing of patients with cystic fibrosis by High Frequency Audiometry and Distortion Product Otoacoustic Emissions. METHODS: Cross-sectional study. The study group consisted of 39 patients (7-20 years of age) with cystic fibrosis and a control group of 36 individuals in the same age group without otologic complaints, with normal audiometric thresholds and type A tympanometric curves. High Frequency Audiometry and Distortion Product Otoacoustic Emissions tests were conducted. RESULTS: The study group had significantly higher thresholds at 250, 1000, 8000, 9000, 10,000, 12,500, and 16,000 Hz (p = 0.004) as well as higher prevalence of otoacoustic emission alterations at 1000 and 6000 Hz (p = 0.001), with significantly lower amplitudes at 1000, 1400, and 6000 Hz. There was a significant association between alterations in hearing thresholds in High Frequency Audiometry with the number of courses of aminoglycosides administered (p = 0.005). Eighty-three percent of patients who completed more than ten courses of aminoglycosides had hearing loss in High Frequency Audiometry. CONCLUSION: A significant number of patients with cystic fibrosis who received repeated courses of aminoglycosides showed alterations in High Frequency Audiometry and Distortion Product Otoacoustic Emissions. The implementation of ten or more aminoglycoside cycles was associated with alterations in High Frequency Audiometry.

Resumo INTRODUÇÃO: O tratamento dos pacientes com fibrose cística envolve o uso de medicamentos ototóxicos, principalmente de antibióticos aminoglicosídeos. Devido ao uso destes medicamen-tos, os pacientes fibrocísticos apresentam risco de desenvolver perda auditiva. OBJETIVO: Avaliar a audição dos pacientes com fibrose cística pela Audiometria de Altas Frequências (AAF) e Emissões Otoacústicas por Produto de Distorção (EOAPD). MÉTODO: Estudo transversal. O grupo de estudo foi constituído por 39 pacientes com idades entre 7 e 20 anos com fibrose cística e o grupo controle por 36 indivíduos da mesma faixa etária, sem queixas otológicas, com limiares audiométricos normais e curvas timpanométricas tipo A. Foram realizados os exames de audiometria de altas frequências e emissões otoacústicas por produto de distorção. RESULTADOS: O grupo de estudo apresentou limiares significativamente mais elevados em 250; 1000; 8.000; 9.000; 10.000; 12.500 e 16.000 Hz; (p = 0,004) e maior prevalência de alterações nas emissões otoacústicas em 1.000 e 6.000 Hz (p = 0,001); com amplitudes significativamente mais baixas em 1.000; 1.400 e 6.000 Hz. Houve associação significativa entre as alterações dos limiares auditivos na AAF com o número de ciclos de aminoglicosídeos realizados (p = 0,005). Oitenta e três por cento dos pacientes que foram submetidos a mais de 3 ciclos de aminoglicosídeos apresentaram perda auditiva na AAF. CONCLUSÃO: Um número significativo de pacientes com fibrose cística que receberam repetidos ciclos de aminoglicosídeos apresentou alterações na AAF e EOAPD. A realização de 10 ou mais ciclos de aminoglicosídeos esteve associada às alterações na AAF.