Sex-specific inflammatory markers of risk and presence of depression in adolescents.

BACKGROUND: Associations between inflammatory markers and depression are reported among adults; however, less is known in adolescent depression in particular whether these associations are sex-specific. We aimed to identify inflammatory markers of increased risk and presence of depression in adolescence and their association with severity of depressive symptoms in the entire cohort and separately in boys and girls. METHODS: We measured serum cytokines using a Meso Scale Discovery electrochemiluminescence V-PLEX assay in a cohort of 150 adolescents stratified for risk/presence of depression. Risk group and sex-specific differences in inflammatory markers were assessed with 2-way mixed ANOVA, and sex-moderated associations between inflammatory markers and the severity of depressive symptoms were assessed with moderated multiple hierarchical regression analyses. RESULTS: We found a significant interaction between biological sex and the risk group, where boys showed higher interleukin (IL)-2 levels among the depressed group compared with the low-risk group. The severity of depressive symptoms was associated with elevated levels of IL-2 in boys, and of IL-6 in girls. There was a significant moderating effect of sex on the relationship between IL-2 and the severity of depressive symptoms but not for IL-6. LIMITATIONS: The cross-sectional design means that we cannot be certain about the direction of the associations. CONCLUSIONS: Our findings suggest sex-specific associations between inflammatory markers and the development of adolescent depression, where IL-2 may increase risk for depression and severity of depressive symptoms in boys, but not in girls. However, IL-6 may increase risk for more severe depressive symptoms in girls.

Alterações comportamentais na pandemia de COVID-19, sobrepeso e obesidade de escolares Quilombolas / Behaviors changing during the COVID-19 pandemic and overweight and obese Quilombola schoolchildren's

O estudo descreveu as alterações comportamentais durante a pandemia de COVID-19 e sua asso-ciação com o sobrepeso e obesidade atual de crianças e adolescentes. Participaram do estudo 1.004 crianças e adolescentes de comunidades rurais em áreas de remanescentes de quilombos de Feira de Santana, Bahia (50,3% meninos; Idade: 9,04 ± 1,52 anos). Desfechos: sobrepeso e obesidade, com base nos valores de Índice de Massa Corporal para idade e sexo, avaliados nos pontos de corte da In-ternational Obesity Taskforce. Alterações comportamentais (apetite, sono, psicológicas, sociais) foram avaliadas por meio de questionário preenchido pelos pais. A análise de dados incluiu estatística des-critiva, bivariada e regressão de Poisson múltipla, com estimador robusto de variância, para estimar Razões de Prevalência (RP) e Intervalos de 95% de Confiança (IC95%). A significância estatística foi fixada em valores de p<0,05. Covariáveis: idade, sexo, infecção por COVID-19 e insegurança ali-mentar. Após o período pandêmico, 24% dos participantes estavam com excesso de peso (sobrepeso = 15,5%; obesidade: 8,5%). As principais alterações comportamentais ocorreram no apetite (comer muito mais do que o habitual = 45,6%) e no sono (ir dormir e acordar mais tarde do que o habitual, em 74% e 62,2%, respectivamente). Comer mais que o habitual foi fator associado ao sobrepeso (RP = 1,63; IC95%: 1,14 - 2,32) e à obesidade (RP = 2,00; IC95%:1,22 - 2,25) entre os participantes, após ajuste por sexo, idade, infecção por COVID-19 e insegurança alimentar. As prevalências de sobrepe-so e obesidade subsequentes ao período pandêmico se associaram às alterações comportamentais no apetite ocorridas durante a pandemia entre escolares Quilombolas

The aim of the study was to describe behaviors changes during COVID-19 pandemic and its association with subsequent overweight and obesity among Quilombola schoolchildren. Participants in this study were 1,004 children and adolescents from rural communities in the Quilombo areas of Feira de Santana, Bahia (50.3% boys; Age: 9.04 ± 1.52 years). The outcomes were overweight and obesity prevalence based on age-and-sex Body Mass Index values, evaluated according to the International Obesity Task Force cut-offs. Behavior changes (appetite, sleep, psychological, and social) were measured by a proxy report questionnaire. The analysis included descriptive statistics and multiple Poisson regression models, using robust variance to estimate Prevalence Ratio (PR) and 95% Confidence Intervals (95%CI). Co-variables: age, sex, COV-ID-19 infection, and food insecurity. The results presented 24% of overweight subsequent to the pandemic period (overweight without obesity = 15.5%; obesity = 8.5%). Main behavior changes occurred in diet (eating more than usual = 45.6%) and sleep (time to go to bed/time to wake up later than usual, among 74% and 62.2% of participants, respectively). Eating mor than usual was associated to overweight without obesity (PR = 1.63; 95%CI: 1.14 - 2.32) and obesity (PR = 2.00; 95%CI: 1.22 - 2.25), when adjusted by sex, age, COVID-19 infection, and food insecurity. Being overweight and obese subsequent to the COV-ID-19 pandemic was associated with behavior changes in the appetite during the pandemic period among Quilombola schoolchildren

Sleep disturbances, circadian activity, and nocturnal light exposure characterize high risk for and current depression in adolescence.

STUDY OBJECTIVES: Major depressive disorder (MDD) in adolescence is associated with irregularities in circadian rhythms and sleep. The characterization of such impairment may be critical to design effective interventions to prevent development of depression among adolescents. This study aimed to examine self-reported and actimetry-based circadian rhythms and sleep-wake behavior associated with current MDD and high risk (HR) for MDD among adolescents. METHODS: Ninety-six adolescents who took part in the IDEA-RiSCo study were recruited using an empirically developed depression-risk stratification method: 26 classified as low risk (LR), 31 as HR, and 39 as a current depressive episode (MDD). We collected self-report data on insomnia, chronotype, sleep schedule, sleep hygiene as well as objective data on sleep, rest-activity, and light exposure rhythms using actimetry for 10 days. RESULTS: Adolescents with MDD exhibited more severe insomnia, shorter sleep duration, higher social jetlag (SJL), lower relative amplitude (RA) of activity, and higher exposure to artificial light at night (ALAN) compared with the other groups. They also presented poorer sleep hygiene compared with the LR group. The HR group also showed higher insomnia, lower RA, higher exposure to ALAN, and higher SJL compared with the LR group. CONCLUSIONS: HR adolescents shared sleep and rhythm alterations with the MDD group, which may constitute early signs of depression, suggesting that preventive strategies targeting sleep should be examined in future studies. Furthermore, we highlight that actimetry-based parameters of motor activity (particularly RA) and light exposure are promising constructs to be explored as tools for assessment of depression in adolescence.

Handling missing data in rest-activity time series measured by actimetry.

A handling procedure of off-wrist episodes in actimetry time series of motor activity is presented using two records (regular vs. irregular sleep-wake cycle and daytime activity) of 14 consecutive days sampled in 1-minute epochs. We generated single missing value (NA) intervals of 1 h, 2 h, 4 h, 6 h, 12 h, and 24 h as well as random NA episodes following probabilistic rules to simulate real-life off-wrist episodes. Then, we replaced these episodes with "zeroes" (i.e., the default of immobility records), mean or median of the remaining 13 days corresponding to the missing bins. Single missing episodes of up to 12 h resulted in less than 5% variation from the original values. The irregular series showed higher variability in acrophase, MESOR, L5, M10 and RA compared to the regular series. Random missing allocation simulating real-life off-wrist episodes resulted in significant changes in most parameters, and the imputation of zeroes significantly increased the variance; however, replacing NA with mean or median resulted in patterns similar to those of NA. We recommend replacing 'zeroes' with NA whenever possible, given the risk of inflating invariance using zeroes. If the parameters cannot be computed in the presence of NA, we recommend using the weekly mean of corresponding timepoints.

Effects of sildenafil and tadalafil on skin flap viability.

Vascular complication is one of the causes of skin flap healing failure. Sildenafil and tadalafil, a type-5 phosphodiesterase inhibitor, can improve flap viability, however, the action mechanisms involved in this process are still unclear. To assess the effects of orally administered sildenafil and tadalafil on the healing kinetics and skin flap viability, sixty-two Wistar rats were divided into three groups: control (n = 22), sildenafil (n = 20), and tadalafil (n = 20). The solutions were administered orally (dose: 10 mg/kg) immediately after the surgical procedure and then every 24 h. At postoperative days 7 and 14, the skin flap samples were collected, submitted to histological processing and evaluated under optical microscopy. In experimental groups (sildenafil and tadalafil), we found an increased vascularization (p < 0.05) on the 7th and 14th day associated with the ulcer size decrease on the 14th day, although it was not significant. There was a higher influx of neutrophils and a decrease of mononuclear population on the 7th day (p < 0.05). On the 14th day, these differences were observed only in the tadalafil group (p < 0.05). This study suggested positive results with the use of sildenafil and tadalafil as adjuvant drugs in skin flap viability.

Cortisol and development of depression in adolescence and young adulthood - a systematic review and meta-analysis.

INTRODUCTION: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the development of major depressive disorder (MDD) in adulthood. Less work has focused on the role of the HPA axis in depression in adolescence and young adulthood globally. The aim of this study was to conduct a systematic review and meta-analysis of worldwide research investigating the relationship between cortisol, a measure of HPA axis activity, and MDD in adolescence and young adulthood. METHOD: We searched MEDLINE, PsycINFO, Cochrane Database of Systematic Reviews, Web of Science, Lilacs, African Journals Online, and Global Health for studies which examined the relationship between cortisol and MDD in global youth (10-24 years old). RESULTS: Twenty-six studies were included in the systematic review and 14 were eligible for the meta-analysis, but only one study included young adults in their sample. Results from the meta-analysis demonstrated that elevated morning, but not evening, cortisol levels was prospectively associated with later MDD development in adolescence and young adulthood. However, morning cortisol levels did not significantly differ between healthy controls and individuals with MDD in cross-sectional studies. Afternoon cortisol and cortisol stress response also did not differ between adolescents with MDD and healthy controls. Qualitative synthesis of the three studies examining nocturnal cortisol showed higher nocturnal cortisol was both longitudinally and cross-sectionally associated with MDD in adolescence. CONCLUSION: Our findings suggest elevated morning cortisol precedes depression in adolescence. Despite this, we did not find any differences in other cortisol measures in association with MDD in cross-sectional studies. Taken together, these findings suggest that elevated morning and nocturnal cortisol are risk factors for depression in adolescence rather than a biomarker of existing MDD. This supports a role for the hyperactivity of the HPA axis in the development of MDD in adolescence. Most of the studies were from high-income-countries (HICs) and thus further work would need to be conducted in low- and middle-income countries (LMICs) to understand if our findings are generalisable also to these populations.

Síndrome de Cornelia de Lange: análise de uma série de 33 pacientes em um centro de referência / Cornelia de Lange syndrome: analysis of a series of 33 patients in an excellence center

Introdução: A Síndrome de Cornelia de Lange (CdLS) (OMIM: 122470) é uma doença genética rara com quadro clínico e fenótipo variáveis, compreendendo um grupo de doenças denominado coesinopatias. Entre suas principais características: deficiência intelectual (DI), baixa estatura, doença do refluxo gastroesofágico (DRGE), hipertricose, dismorfismos faciais e anomalias em membros superiores. O diagnóstico pode ser dificultado nos quadros atenuados. O objetivo do estudo foi determinar os principais achados clínicos e moleculares em uma série de pacientes com o diagnóstico clínico de CdLS.Métodos: Foram avaliados 33 pacientes com diagnóstico clínico e/ou molecular de CdLS (18 sexo feminino e 15 masculino) com idades entre 1 mês e 43 anos. Aplicou-se um escore clínico visando a categorização dos pacientes baseado em Kline et al. (2018). Esta ferramenta utiliza sinais clínicos para determinar as formas clássicas (n: 23), não clássicas (n: 6) e os casos que, apesar de não se enquadrarem nestas categoriais, também deveriam ser testados molecularmente para a síndrome (n: 4).Resultados: Atraso do desenvolvimento/DI, distúrbios de comportamento, déficit de crescimento e DRGE foram as comorbidades mais prevalentes. Entre as dismorfias: sinofris, micrognatia, narinas antevertidas e comissura labial desviada para baixo. Os achados moleculares nos pacientes submetidos ao sequenciamento completo do exoma revelaram 6 variantes em NIPBL (46%), 2 variantes em SMC1A (15%), 1 variante em SMC3, 1 variante em HDAC8, 1 variante em AHDC1 e 2 resultados negativos.Conclusões: Os dados obtidos revelaram uma grande heterogeneidade de apresentação da síndrome. A utilização de escores clínicos podem auxiliar no diagnóstico de CdLS.

Introduction: Cornelia de Lange syndrome (CdLS) (OMIM: 122470) is a rare genetic disease with variable clinical presentation and phenotype, part of a group of disorders termed cohesinopathies. Intellectual disability, growth retardation, gastroesophageal reflux disease, hypertrichosis, facial dysmorphisms, and anomalies of the upper limbs are the most common clinical characteristics. Diagnosis may be difficult, especially in attenuated presentations. The aim of this study was to determine the main clinical and molecular findings in a series of patients with clinical diagnosis of CdLS.Methods: Thirty-three patients with typical clinical and/or molecular diagnosis of CdLS (18 female and 15 male) aged between 1 month and 43 years were evaluated. A clinical score was applied to categorize patients. This tool uses clinical signs to determine the classic (n: 23) and nonclassic (n: 6) forms, in addition to a category to suggest which cases should be molecularly tested for the syndrome (n: 4).Results: Developmental delay/intellectual disability, behavioral disorders, growth retardation, and gastroesophageal reflux disease were the most prevalent comorbidities. Dysmorphic features included synophrys micrognathia, anteverted nostrils, and labial commissure turning downwards. Molecular findings in those who underwent whole exome sequencing revealed 6 variants in NIPBL (46%), 2 variants in SMC1A (15%), 1 variant in SMC3, 1 variant in HDAC8, 1 variant in AHDC1, and 2 negative results.Conclusions: The data revealed a great heterogeneity in the presentation of the syndrome. The use of clinical scores can help in the diagnosis of CdLS.

Exploring the role of immune pathways in the risk and development of depression in adolescence: Research protocol of the IDEA-FLAME study.

Extensive research suggests a role for the innate immune system in the pathogenesis of depression, but most of the studies are conducted in adult populations, in high-income countries and mainly focus on the study of inflammatory proteins alone, which provides only a limited understanding of the immune pathways involved in the development of depression. The IDEA-FLAME study aims to identify immune phenotypes underlying increased risk of developing depression in adolescence in a middle-income country. To this end, we will perform deep-immunophenotyping of peripheral blood mononuclear cells and RNA genome-wide gene expression analyses in a longitudinal cohort of Brazilian adolescents stratified for depression risk. The project will involve the 3-year follow-up of an already recruited cohort of 150 Brazilian adolescents selected for risk/presence of depression on the basis of a composite risk score we developed using sociodemographic characteristics (50 adolescents with low-risk and 50 with high-risk of developing depression, and 50 adolescents with a current major depressive disorder). We will 1) test whether the risk group classification at baseline is associated with differences in immune cell frequency, phenotype and functional status, 2) test whether baseline immune markers (cytokines and immune cell markers) are associated with severity of depression at 3-year follow-up, and 3) identify changes in gene expression of immune pathways over the 3-year follow-up in adolescents with increased risk and presence of depression. Because of the exploratory nature of the study, the findings would need to be replicated in a separate and larger sample. Ultimately, this research will contribute to elucidating key immune therapeutic targets and inform the development of interventions to prevent onset of depression among adolescents.

The Identifying Depression Early in Adolescence Risk Stratified Cohort (IDEA-RiSCo): Rationale, Methods, and Baseline Characteristics.

Background: The characterization of adolescents at high risk for developing depression has traditionally relied on the presence or absence of single risk factors. More recently, the use of composite risk scores combining information from multiple variables has gained attention in prognostic research in the field of mental health. We previously developed a sociodemographic composite score to estimate the individual level probability of depression occurrence in adolescence, the Identifying Depression Early in Adolescence Risk Score (IDEA-RS). Objectives: In this report, we present the rationale, methods, and baseline characteristics of the Identifying Depression Early in Adolescence Risk Stratified Cohort (IDEA-RiSCo), a study designed for in-depth examination of multiple neurobiological, psychological, and environmental measures associated with the risk of developing and with the presence of depression in adolescence, with a focus on immune/inflammatory and neuroimaging markers. Methods: Using the IDEA-RS as a tool for risk stratification, we recruited a new sample of adolescents enriched for low (LR) and high (HR) depression risk, as well as a group of adolescents with a currently untreated major depressive episode (MDD). Methods for phenotypic, peripheral biological samples, and neuroimaging assessments are described, as well as baseline clinical characteristics of the IDEA-RiSCo sample. Results: A total of 7,720 adolescents aged 14-16 years were screened in public state schools in Porto Alegre, Brazil. We were able to identify individuals at low and high risk for developing depression in adolescence: in each group, 50 participants (25 boys, 25 girls) were included and successfully completed the detailed phenotypic assessment with ascertainment of risk/MDD status, blood and saliva collections, and magnetic resonance imaging (MRI) scans. Across a variety of measures of psychopathology and exposure to negative events, there was a clear pattern in which either the MDD group or both the HR and the MDD groups exhibited worse indicators in comparison to the LR group. Conclusion: The use of an empirically-derived composite score to stratify risk for developing depression represents a promising strategy to establish a risk-enriched cohort that will contribute to the understanding of the neurobiological correlates of risk and onset of depression in adolescence.

Fonoterapia intensiva em paciente com fissura de palato submucosa - relato de caso / Intensive speech therapy in a patient with submucosal cleft palate - case report / Fonoterapia intensiva en um paciente con fisura palatina submoucosa - reporte de caso

Introdução: A fissura de palato submucosa é uma malformação craniofacial, que pode ocasionar alterações de fala, e a fonoterapia intensiva é uma possibilidade de tratamento. Objetivo: relatar o caso de uma paciente com fissura submucosa de palato sintomática não operada que participou de um programa de fonoterapia intensiva para reabilitação de fala, descrever os processos terapêuticos e comparar a produção da fala antes e depois da terapia. Metodologia: o programa de fonoterapia intensiva foi realizado com uma paciente do gênero feminino de 13 anos de idade, com fissura submucosa de palato sintomática, não operada; e constituiu de três sessões diárias de terapia fonoaudiológica durante um período de 4 semanas, resultando em um total de 60 sessões de terapia. Antes da primeira sessão, e após a última, foi realizada avaliação clínica da fala e instrumental da função velofaríngea. Resultados: sistematização do fechamento velofaríngeo, melhora na inteligibilidade de fala, correção das articulações compensatórias, da fraca pressão intraoral e hipernasalidade em fala dirigida. Conclusão: o programa de fonoterapia intensiva proporcionou resultados positivos em período curto na reabilitação da fala da paciente.

Introduction: Submucosal cleft palate is a craniofacial malformation that can cause speech disorders and intensive speech therapy is an alternative treatment. Objective: report the case of a patient with submucous cleft who participated in an intensive speech therapy program, describe the therapeutic processes and compare speech production before and after therapy. Methods: the intensive therapy program was conducted with a 13-year-old female patient with submucosal cleft and consisted of three daily speech therapy sessions over a period of 4 weeks, resulting in 60 therapy sessions. Before the first session and after the last session, clinical and instrumental assessments of velopharyngeal function were performed. Results: systematization of velopharyngeal closure, improvement of speech intelligibility, elimination of compensatory articulations, weak intraoral pressure and hypernasal resonance in monitored speech. Conclusion: The intensive speech therapy program provided positive short-term results in speech rehabilitation of a patient with submucosal cleft.

Introducción: el fissura palatina submucosa es una malformación craneofacial, por esta razón puede causar trastornos del habla y la terapia intensiva del habla es un tratamiento alternativo. Objetivo: relatar el caso de una paciente con fisura palatina submucosa que participó en un programa intensivo de terapia fonoaudiológica para la rehabilitación del habla, describir los procesos terapéuticos y comparar la producción del habla antes y después de la terapia. Metodos: el programa de cuidados intensivos se llevó a cabo con una paciente del género femenino de 13 años de edad con fisura palatina submoucosa y consistió en tres sesiones diarias de terapia fonoaudiológica durante un período de 4 semanas, lo que resultó en un total de 60 sesiones de terapia. Antes de la primera sesión y después de la última, se realizó una evaluación clínica e instrumental de la función velofaríngea. Resultados: sistematización del cierre velofaríngeo, mejor inteligibilidad del habla, eliminación de las articulaciones compensatorias, de la presión intraoral débil y de la resonancia hipernasal en el habla dirigida. Conclusión: el programa de cuidados intensivos proporcionó resultados positivos en un corto período de tiempo en la rehabilitación del habla de una paciente con fisura submucosa.

Gestação e papilomavírus humano (HPV): vias de transmissão e complicações / Gestation and human papillomavirus (HPV): transmission routes and complications

Introdução: Dentre as doenças que acometem as gestantes, temos a infecção pelo papilomavírus humano (HPV). A principal via de transmissão do HPV é o contato sexual. Há, entretanto, crescentes evidências de que a infecção pelo HPV é adquirida por meio de vias não sexuais, como a transmissão vertical. A complicação mais temida é a papilomatose juvenil nos recém-nascidos (RNs). Objetivo: Avaliar as vias de transmissão do HPV em gestantes e as possíveis complicações dessa infecção para o RN. Metodologia: Pesquisa realizada nas bases de dados: Lilacs, PubMed, Embase e Cochrane Library. Descritores: gravidez, Papillomaviridae, Papillomavírus humano, transmissão e condiloma acuminado. O critério de escolha foi selecionar artigos que tivessem como enfoque a gestação e a infecção pelo HPV. Resultados e discussão: A transmissão não sexual do HPV ocorre de diversas formas, como contato com pele e mucosas, autoinoculação, fômites ou no período perinatal. A transmissão perinatal pode ocorrer no canal do parto, na cesariana por infecção ascendente, transmissão na fertilização de espermatozoides ou transplacentária, além da amamentação. A infecção traz complicações como parto precoce, aborto e papilomatose juvenil. Conclusão: Embora o mecanismo clássico da contaminação seja a passagem no canal de parto, outras vias de transmissão podem ocorrer desde o período pré, peri e pós-natal. Não está estabelecido se o HPV detectado ao nascimento causa infecção persistente ou transitória. Por isso, as gestantes devem ser orientadas quanto as diferentes vias de transmissão e sobre as possíveis complicações nos RNs.

L-carnitine Prevents Oxidative Stress in the Brains of Rats Subjected to a Chemically Induced Chronic Model of MSUD.

Maple syrup urine disease (MSUD), or branched-chain α-keto aciduria, is an inherited disorder that is caused by a deficiency in branched-chain α-keto acid dehydrogenase complex (BCKAD) activity. Blockade of this pathway leads to the accumulation of the branched-chain amino acids (BCAAs), leucine, isoleucine, and valine, and their respective ketoacids in tissues. The main clinical symptoms presented by MSUD patients include ketoacidosis, hypoglycemia, opisthotonos, poor feeding, apnea, ataxia, convulsions, coma, psychomotor delay, and mental retardation. Although increasing evidence indicates that oxidative stress is involved in the pathophysiology of this disease, the mechanisms of the brain damage caused by this disorder remain poorly understood. In the present study, we investigated the effect of BCAAs on some oxidative stress parameters and evaluated the efficacy of L-carnitine (L-car), an efficient antioxidant that may be involved in the reduction of oxidative damage observed in some inherited neurometabolic diseases, against these possible pro-oxidant effects of a chronic MSUD model in the cerebral cortex and cerebellum of rats. Our results showed that chronic BCAA administration was able to promote both lipid and protein oxidation, impair brain antioxidant defenses, and increase reactive species production, particularly in the cerebral cortex, and that L-car was able to prevent these effects. Taken together, the present data indicate that chronic BCAA administration significantly increased oxidative damage in the brains of rats subjected to a chronic model of MSUD and that L-car may be an efficient antioxidant in this disorder.

New quinoline derivatives demonstrate a promising antimalarial activity against Plasmodium falciparum in vitro and Plasmodium berghei in vivo.

Malaria continues to be an important public health problem in the world. Nowadays, the widespread parasite resistance to many drugs used in antimalarial therapy has made the effective treatment of cases and control of the disease a constant challenge. Therefore, the discovery of new molecules with good antimalarial activity and tolerance to human use can be really important in the further treatment of the disease. In this study we have investigated the antiplasmodial activity of 10 synthetic compounds derived from quinoline, five of them combined to sulfonamide and five to the hydrazine or hydrazide group. The compounds were evaluated according to their cytotoxicity against HepG2 and HeLa cell lines, their antimalarial activity against CQ-sensitive and CQ-resistant Plasmodium falciparum strains and, finally, their schizonticide blood action in mice infected with Plasmodium berghei NK65. The compounds exhibited no cytotoxic action in HepG2 and HeLa cell lines when tested up to a concentration of 100 µg/mL. In addition, the hydrazine or hydrazide derivative compounds were less cytotoxic against cell lines and more active against CQ-sensitive and CQ-resistant P. falciparum strains, showing high SI (>1000 when SI was calculated using the CC50 from the 3D7 strain as reference). When tested in vivo, the hydrazine derivative 1f compound showed activity against the development of blood parasites similar to that observed with CQ, the reference drug. Interestingly, the 1f compound demonstrated the best LipE value (4.84) among all those tested in vivo. Considering the in vitro and in vivo activities of the compounds studied here and the LipE values, we believe the 1f compound to be the most promising molecule for further studies in antimalarial chemotherapy.

Neonatal hyperglycemia induces oxidative stress in the rat brain: the role of pentose phosphate pathway enzymes and NADPH oxidase.

Recently, the consequences of diabetes on the central nervous system (CNS) have received great attention. However, the mechanisms by which hyperglycemia affects the central nervous system remain poorly understood. In addition, recent studies have shown that hyperglycemia induces oxidative damage in the adult rat brain. In this regard, no study has assessed oxidative stress as a possible mechanism that affects the brain normal function in neonatal hyperglycemic rats. Thus, the present study aimed to investigate whether neonatal hyperglycemia elicits oxidative stress in the brain of neonate rats subjected to a streptozotocin-induced neonatal hyperglycemia model (5-day-old rats). The activities of glucose-6-phosphate-dehydrogenase (G6PD), 6-phosphogluconate-dehydrogenase (6-PGD), NADPH oxidase (Nox), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx), the production of superoxide anion, the thiobarbituric acid-reactive substances (TBA-RS), and the protein carbonyl content were measured. Neonatal hyperglycemic rats presented increased activities of G6PD, 6PGD, and Nox, which altogether may be responsible for the enhanced production of superoxide radical anion that was observed. The enhanced antioxidant enzyme activities (SOD, CAT, and GSHPx) that were observed in neonatal hyperglycemic rats, which may be caused by a rebound effect of oxidative stress, were not able to hinder the observed lipid peroxidation (TBA-RS) and protein damage in the brain. Consequently, these results suggest that oxidative stress could represent a mechanism that explains the harmful effects of neonatal hyperglycemia on the CNS.