Sleep disorders in Down syndrome: a systematic review / Distúrbios do sono na síndrome de Down: revisão sistemática

ABSTRACT Background: Sleep disorders are commonly observed in children with Down syndrome (DS) and can lead to significant behavioral and cognitive morbidities in these individuals. Objective: To perform a systematic review evaluating sleep disorders in individuals with DS. Methods: Search strategies were based on combinations of keywords: "Down syndrome"; "trisomy 21"; "sleep disorders"; "dyssomnias"; "sleep apnea"; "obstructive"; "sleeplessness"; "insomnia"; "parasomnias"; and "excessive daytime sleepiness". PubMed and Science Direct were used. Only original studies and retrospective reviews in English published between January 2011 and March 2021 were included. Results: 52 articles were included, most of them involving children and adolescents under 18 years of age. The main sleep disorder associated with DS was obstructive sleep apnea (OSA). Some studies reported the presence of cognitive dysfunction in patients with DS and sleep-disordered breathing, and few have been found about parasomnia, insomnia, and daytime sleepiness in these patients. Movement disorders and unusual postures during sleep may be related to disordered sleep breathing in DS. The main treatment options for OSA are continuous positive airway pressure therapy (CPAP), surgery, and weight control. Computational modeling associated with MRI has been used to plan surgical interventions in these patients. Conclusions: Individuals with DS are at high risk of developing sleep-related breathing disorders. The main sleep disorder associated with DS was OSA. The presence of sleep-disordered breathing contributes to a worsening of cognitive function in patients with DS.

RESUMO Antecedentes: Os distúrbios do sono são comumente observados em crianças com síndrome de Down (SD) e podem levar a morbidades comportamentais e cognitivas significativas nesses indivíduos. Objetivo: Realizar uma revisão sistemática para avaliar os distúrbios do sono em indivíduos com SD. Métodos: As estratégias de busca foram baseadas em combinações de palavras-chave: "Síndrome de Down"; "trissomia 21"; "distúrbios do sono"; "dissonias"; "apneia do sono"; "obstrutivo"; "insônia"; "insônia"; "parassonias" e "sonolência diurna excessiva". PubMed e Science Direct foram usados. Apenas estudos originais e revisão retrospectiva de prontuários escritos em inglês e publicados de janeiro de 2011 a março de 2021 foram incluídos. Resultados: Foram selecionados 52 artigos, a maioria com crianças e adolescentes menores de 18 anos. O principal distúrbio do sono associado à SD foi a apneia obstrutiva do sono (AOS). Alguns estudos relatam a presença de disfunção cognitiva em pacientes com SD e distúrbios respiratórios do sono, e poucos foram encontrados sobre parassonia, insônia e sonolência diurna nesses pacientes. Distúrbios do movimento e posturas incomuns durante o sono podem estar relacionados ao distúrbio respiratório do sono na SD. As principais opções de tratamento para AOS são pressão positiva contínua nas vias aéreas (CPAP), abordagem cirúrgica e controle de peso. A modelagem computacional associada à ressonância magnética tem sido usada para planejar intervenções cirúrgicas nesses pacientes. Conclusões: Indivíduos com SD apresentam alto risco de desenvolver distúrbios respiratórios relacionados ao sono. O principal distúrbio do sono associado à SD foi a AOS. A presença de distúrbios respiratórios do sono contribui para a piora das funções cognitivas em pacientes com SD.

Sleep disorders in Down syndrome: a systematic review.

BACKGROUND: Sleep disorders are commonly observed in children with Down syndrome (DS) and can lead to significant behavioral and cognitive morbidities in these individuals. OBJECTIVE: To perform a systematic review evaluating sleep disorders in individuals with DS. METHODS: Search strategies were based on combinations of keywords: "Down syndrome"; "trisomy 21"; "sleep disorders"; "dyssomnias"; "sleep apnea"; "obstructive"; "sleeplessness"; "insomnia"; "parasomnias"; and "excessive daytime sleepiness". PubMed and Science Direct were used. Only original studies and retrospective reviews in English published between January 2011 and March 2021 were included. RESULTS: 52 articles were included, most of them involving children and adolescents under 18 years of age. The main sleep disorder associated with DS was obstructive sleep apnea (OSA). Some studies reported the presence of cognitive dysfunction in patients with DS and sleep-disordered breathing, and few have been found about parasomnia, insomnia, and daytime sleepiness in these patients. Movement disorders and unusual postures during sleep may be related to disordered sleep breathing in DS. The main treatment options for OSA are continuous positive airway pressure therapy (CPAP), surgery, and weight control. Computational modeling associated with MRI has been used to plan surgical interventions in these patients. CONCLUSIONS: Individuals with DS are at high risk of developing sleep-related breathing disorders. The main sleep disorder associated with DS was OSA. The presence of sleep-disordered breathing contributes to a worsening of cognitive function in patients with DS.

Eugenia piauhiensis Vellaff. essential oil and γ-elemene its major constituent exhibit antileishmanial activity, promoting cell membrane damage and in vitro immunomodulation.

Leishmaniasis is considered as one of the most Neglected Tropical Diseases (NTDs) in the world, caused by protozoan parasites of the genus Leishmania. Treatment of leishmaniasis by chemotherapy remains a challenge because of limited efficacy, toxic side effects, and drug resistance. The search for new therapeutic agents from natural sources has been a constant for the treatment of diseases such as leishmaniasis. The objective of this study was to evaluate the biological activity of Eugenia piauhiensis Vellaff. essential oil (EpEO) and its major constituent γ-elemene on promastigote and amastigote forms of Leishmania (Leishmania) amazonensis, its cytotoxicity, and possible mechanisms of action. EpEO was more active (IC50 6.43 ± 0.18 µg/mL) against promastigotes than γ-elemene [9.82 ± 0.15 µg/mL (48.05 ± 0.73 µM)] and the reference drug miltefosine [IC50 17.25 ± 0.26 µg/mL (42.32 ± 0.64 µM)]. EpEO and γ-elemene exhibited low cytotoxicity against J774.A1 macrophages, with CC50 225.8 ± 3.57 µg/mL and 213.21 ± 3.3 µg/mL (1043 ± 16.15 µM), respectively. Additionally, EpEO and γ-elemene present direct activity against the parasite, decreasing plasma membrane integrity. EpEO and γ-elemene also proved to be even more active against intracellular amastigotes of the parasite [IC50 4.59 ± 0.07 µg/mL and 8.06 ± 0.12 µg/mL (39.44 ± 0.59 µM)], respectively), presenting indirect effects through macrophage activity modulation. Anti-amastigote activity was associated with increased TNF-α, IL-12, NO, and ROS levels. In conclusion, our results suggest EpEO and γ-elemene as promising candidates for new drug development against leishmaniasis.

Methyl gallate: Selective antileishmanial activity correlates with host-cell directed effects.

Leishmaniasis is a widespread tropical infection caused by different species of Leishmania protozoa. Many of the available drugs against the disease are toxic and in certain cases parasite drug resistance is developed. The discovery of drugs for the treatment of leishmaniasis is a pressing concern. In the present work, we describe in vitro studies of the phenolic compound methyl gallate (MG) against Leishmania (Leishmania) amazonensis and its possible mechanisms of action. The in vitro activity of MG was assayed against L. amazonensis (promastigotes, axenic amastigotes, and intramacrophagic amastigotes). Cytotoxicity tests were performed with J774A.1 macrophages and THP-1 cell derived macrophages. To evaluate mechanisms of action, we analyzed cellular TNF-α, IL-12, IFN-γ, IL-10, IL-6, NO, ROS levels, arginase activity, and structural mechanisms (phagocytic and lysosomal activities) involving macrophage activation. Meglumine antimoniate and amphotericin B were used as reference drugs. It was observed that MG effectively inhibited the growth of both promastigote (IC50 5.71 µM) and amastigote-like forms (EC50 5.39 µM), with much higher selectivity indexes than the reference drugs, being more benign towards J774A.1 macrophages than meglumine antimoniate and amphotericin B, at 1631- and 70.92-fold respectively, with respect to the promastigote form. Additionally, MG proved to be even more active against intracellular amastigotes of the parasite (EC50 4.24 µM). Our results showed that antileishmania activity was associated with increased TNF-α, IL-12, NO and ROS levels, as well as decreased IL-6 and decreased arginase activity. In addition, MG induced increased phagocytic capability, and lysosomal volume in macrophages; structural parameters of microbicidal activity. Taken together, our results suggest that MG may be a promising candidate for new drug development against leishmaniasis.