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1.
Neuropharmacology ; 107: 339-350, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27040794

RESUMO

Congenital central hypoventilation syndrome (CCHS) is a neurorespiratory disease characterized by life-threatening sleep-related hypoventilation involving an alteration of CO2/H(+) chemosensitivity. Incidental findings have suggested that desogestrel may allow recovery of the ventilatory response to CO2. The effects of desogestrel on resting ventilation have not been reported. This study was designed to test the hypothesis that desogestrel strengthens baseline ventilation by analyzing the ventilation of CCHS patients. Rodent models were used in order to determine the mechanisms involved. Ventilation in CCHS patients was measured with a pneumotachometer. In mice, ventilatory neural activity was recorded from ex vivo medullary-spinal cord preparations, ventilation was measured by plethysmography and c-fos expression was studied in medullary respiratory nuclei. Desogestrel increased baseline respiratory frequency of CCHS patients leading to a decrease in their PETCO2. In medullary spinal-cord preparations or in vivo mice, the metabolite of desogestrel, etonogestrel, induced an increase in respiratory frequency that necessitated the functioning of serotoninergic systems, and modulated GABAA and NMDA ventilatory regulations. c-FOS analysis showed the involvement of medullary respiratory groups of cell including serotoninergic neurons of the raphe pallidus and raphe obscurus nuclei that seem to play a key role. Thus, desogestrel may improve resting ventilation in CCHS patients by a stimulant effect on baseline respiratory frequency. Our data open up clinical perspectives based on the combination of this progestin with serotoninergic drugs to enhance ventilation in CCHS patients.


Assuntos
Desogestrel/uso terapêutico , Hipoventilação/congênito , Ventilação Pulmonar/efeitos dos fármacos , Neurônios Serotoninérgicos/efeitos dos fármacos , Apneia do Sono Tipo Central/tratamento farmacológico , Adulto , Animais , Animais Recém-Nascidos , Desogestrel/farmacologia , Relação Dose-Resposta a Droga , Feminino , Agonistas de Receptores de GABA-A/farmacologia , Humanos , Hipoventilação/tratamento farmacológico , Hipoventilação/fisiopatologia , Masculino , Bulbo/efeitos dos fármacos , Bulbo/fisiologia , Camundongos , Técnicas de Cultura de Órgãos , Ventilação Pulmonar/fisiologia , Neurônios Serotoninérgicos/fisiologia , Apneia do Sono Tipo Central/fisiopatologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/fisiologia , Adulto Jovem
2.
Respir Res ; 16: 80, 2015 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-26122307

RESUMO

BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare genetic disease due to PHOX2B mutations. CCHS patients suffer from many autonomic disorders, dominated clinically by defective ventilatory automatisms. From birth, the life of CCHS patients depends on ventilatory support during sleep, involving a high burden of care. Whether or not this impairs the quality of life of these patients during adulthood remains unknown. METHODS: We applied the medical outcome study short form-36 (SF-36) to 12 CCHS patients aged 15-33 (9 women) at the time of their passage from pediatric to adult care. Scores for the SF-36 dimensions were compared to the age- and gender-matched French reference population after transformation into standardized Z-scores. The SF-36 physical component summary score (PCS) and mental component summary score (MCS) were compared to American reference values. RESULTS: Median Z-scores were significantly different from zero for PF (physical functioning, p = 0.020) and GH (general health perception, p = 0.0342) and for PCS (p = 0.020). The other physical dimensions (RP, role limitation due to physical function; BP, bodily pain) and the mental dimensions (VT, vitality; SF, social functioning; RE, role limitation due to emotional function; MH, mental health) and MCS were not altered. CONCLUSIONS: We conclude that, despite the physical constraints imposed by CCHS and its anxiogenic nature, this disease is associated with an impairment of health-related quality of life in young adults that remains moderate. Whatever the underlying explanations, these results convey hope to parents with a child diagnosed with CCHS and for patients themselves.


Assuntos
Nível de Saúde , Proteínas de Homeodomínio/genética , Hipoventilação/congênito , Mutação/genética , Qualidade de Vida , Apneia do Sono Tipo Central/diagnóstico , Apneia do Sono Tipo Central/genética , Fatores de Transcrição/genética , Adulto , Estudos Transversais , Feminino , Humanos , Hipoventilação/diagnóstico , Hipoventilação/genética , Hipoventilação/psicologia , Masculino , Qualidade de Vida/psicologia , Apneia do Sono Tipo Central/psicologia , Inquéritos e Questionários , Adulto Jovem
3.
Int J Infect Dis ; 29: 37-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25449232

RESUMO

Group A Streptococcus (GAS) is a well-known cause of vulvovaginitis in prepubescent girls, but it is rarely described in adult women. We describe the case of a 64-year-old woman who presented with endometritis revealed by GAS bacteraemia, followed by recurrent vulvovaginitis due to a wild-type strain of GAS. She relapsed twice despite amoxicillin treatment. Her husband was found to be an asymptomatic carrier after GAS was identified in nasal and rectal swabs. She was cured after eradication of carriage in both herself and her husband with amoxicillin and rifampin. When recurrent Streptococcus pyogenes genital infections occur, test and treat the partner.


Assuntos
Parceiros Sexuais , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus pyogenes , Vulvovaginite/diagnóstico , Vulvovaginite/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva , Infecções Estreptocócicas/microbiologia , Vulvovaginite/microbiologia
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