RESUMO
Tuberculostatic drugs are the most common drug groups with global hepatotoxicity. Awareness of potentially severe hepatotoxic reactions is vital, as hepatic impairment can be a devastating and often fatal condition. The treatment problems that may arise, within this class of medicines, are mainly of two types: adverse reactions (collateral, toxic or hypersensitive reactions) and the initial or acquired resistance of Mycobacterium tuberculosis to one or more antituberculosis drugs. Prevention of adverse reactions, increase treatment adherence and success rates, providing better control of tuberculosis (TB). In this regard, obtaining new drugs with low toxicity and high tuberculostatic potential is essential. Thus, in this work, we have designed or synthesized new derivatives of isoniazid (INH), such as new Isonicotinoylhydrazone (INH-a, INH-b and INH-c). These derivatives demonstrated good biocompatibility, antimicrobial property similar to that of parent isoniazid and last but not least, a significantly improved Pharmacotoxicological profile compared to that of isoniazid.
Assuntos
Antituberculosos , Hidrazonas , Isoniazida/análogos & derivados , Animais , Antituberculosos/farmacologia , Antituberculosos/toxicidade , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Hidrazonas/farmacologia , Hidrazonas/toxicidade , Isoniazida/farmacologia , Isoniazida/toxicidade , Dose Letal Mediana , Masculino , Camundongos , Mycobacterium tuberculosis/efeitos dos fármacos , Testes de Toxicidade Aguda , Testes de Toxicidade CrônicaRESUMO
OBJECTIVES: The present pilot study was performed to evaluate the HPA axis and ANS activity by measuring salivary cortisol and α-amylase diurnal trajectory and production, respectively, in mild or moderate-to-severe (MS) OSA-affected, but otherwise healthy, children. Moreover, a correlative analysis was performed between the salivary biomarker concentrations and the PSG variables characterizing the OSA severity. METHODS: We studied 27 consecutive OSA patients (13 mild OSA; 14 MS OSA) and seven healthy children who were enrolled as controls by collecting salivary samples and measuring cortisol and α-amylase levels using enzyme-linked bioassays. RESULTS: Compared with controls, both mild and MS OSA children showed: (1) increased salivary cortisol diurnal production, (2) maintenance of the physiological circadian activity of the HPA axis, and (3) no changes in α-amylase diurnal trajectory and production. In addition, morning salivary cortisol concentrations was negatively associated with the disease severity in the MS OSA group. CONCLUSIONS: OSA is associated with dysregulation of the HPA axis activity in children, the latter potentially underlying some of the adverse consequences of the disease.