Growth Velocity and Nutritional Status in Children Exposed to Zika Virus during Pregnancy from Amazonas Cohort, Brazil.

The high incidence of Zika virus (ZIKV) infection in the period of 2015-2016 in Brazil may have affected linear height growth velocity (GV) in children exposed in utero to ZIKV. This study describes the growth velocity and nutritional status based on the World Organization (WHO) standards of children exposed to ZIKV during pregnancy and followed up in a tertiary unit, a reference for tropical and infectious diseases in the Amazon. Seventy-one children born between March 2016 and June 2018 were monitored for anthropometric indices: z-score for body mass index (BMI/A); weight (W/A); height (H/A) and head circumference (HC/A); and growth velocity. The mean age at the last assessment was 21.1 months (SD ± 8.93). Four children had congenital microcephaly and severe neurological impairment. The other 67 were non-microcephalic children (60 normocephalic and 7 macrocephalic); of these; 24.2% (16 children) had neurological alterations, and 28.8% (19 children) had altered neuropsychomotor development. Seventeen (24.2%) children had inadequate GV (low growth velocity). The frequencies of low growth among microcephalic and non-microcephalic patients are 25% (1 of 4 children) and 23.9% (16 of 67 children); respectively. Most children had normal BMI/A values during follow-up. Microcephalic patients showed low H/A and HC/A throughout the follow-up, with a significant reduction in the HC/A z-score. Non-microcephalic individuals are within the regular ranges for H/A; HC/A; and W/A, except for the H/A score for boys. This study showed low growth velocity in children with and without microcephaly, highlighting the need for continuous evaluation of all children born to mothers exposed to ZIKV during pregnancy.

Neurological Findings in Children without Congenital Microcephaly Exposed to Zika Virus in Utero: A Case Series Study.

The Zika virus can induce a disruptive sequence in the fetal brain and is manifested mainly by microcephaly. Knowledge gaps still exist as to whether the virus can cause minor disorders that are perceived later on during the first years of life in children who are exposed but are asymptomatic at birth. In this case series, we describe the outcomes related to neurodevelopment through the neurological assessment of 26 non-microcephalic children who had intrauterine exposure to Zika virus. Children were submitted for neurological examinations and Bayley Scales-III (cognition, language, and motor performance). The majority (65.4%) obtained satisfactory performance in neurodevelopment. The most impaired domain was language, with 30.7% impairment. Severe neurological disorders occurred in five children (19.2%) and these were spastic hemiparesis, epilepsy associated with congenital macrocephaly (Zika and human immunodeficiency virus), two cases of autism (one exposed to Zika and Toxoplasma gondii) and progressive sensorineural hearing loss (GJB2 mutation). We concluded that non-microcephalic children with intrauterine exposure to Zika virus, in their majority, had achieved satisfactory performance in all neurodevelopmental domains. One third of the cases had some impairment, but the predominant group had mild alterations, with low occurrence of moderate to severe disorders, similar to other studies in Brazil.

Anxiolytic and antidepressant-like effects of Annona coriacea (Mart.) and caffeic acid in mice.

This research evaluated the anxiolytic and antidepressant-like effects of a hydroethanolic extract from the leaves of Annona coriacea (EHFAC) and caffeic acid (CA). Mice were intraperitoneally treated with saline, EHFAC (1, 10, 20 mg/kg) or CA (0.15 mg/kg) and subject to the elevated plus-maze, open field, rota-rod, forced swimming and reserpine-induced akinesia tests. Pro-convulsant and anticholinergic effects were also evaluated. EHFAC presented anxiolytic-like effect on the elevated plus-maze, which was partially reversed by flumazenil. A similar effect was observed with CA. In the forced swimming test, EHFAC and CA reduced the immobility time of mice; such effect was potentiated when EHFAC or CA were associated with imipramine, bupropion and fluoxetine. The antidepressant-like effect was reinforced as EHFAC partially reversed the reserpine-induced akinesia. In addition, a pre-treatment with EHFAC and CA did not decrease the latency to 1st seizure of animals that received a sub-convulsive dose of PTZ, nor reduced the intensity of oxotremorine-induced tremors. Taken together, the results indicate that EHFAC and CA have anxiolytic and antidepressant-like effects, which involve important neurotransmitter systems, such as GABAergic and monoaminergic ones, being devoid of side effects, commonly associated with classical psychotropic drugs.

Effects of the Hyptis martiusii Benth. leaf essential oil and 1,8-cineole (eucalyptol) on the central nervous system of mice.

The aim of this study was to characterize the central effects of the Hyptis martiusii leaf essential oil (OEHM) and 1,8-cineole (eucalyptol) using behavioral animal models. Gas chromatography coupled to mass spectrometry (GC/MS) was used to characterize the chemical compounds present in the OEHM. For the behavioral tests, female Swiss mice treated with the OEHM (25, 50, 100 and 200 mg/kg, i.p.) and 1,8-cineole (50 mg/kg, i.p.) were used and subjected to the following tests: open field, elevated cross maze, rotarod, sodium pentobarbital- or ethyl ether-induced sleep time, pentylenetetrazol-induced convulsions, haloperidol-induced catalepsy, and ketamine-induced hyperkinesia. GC/MS analysis identified 20 constituents with the majority of them being monoterpenes and sesquiterpenes, with eucalyptol (1,8-cineol), the major sample compound (25.93%), standing out. The results showed the OEHM (25, 50 100 and 200 mg/kg, i.p.) and its major compound (50 mg/kg, i.p.) reduced animal motility in the open field test, increased pentobarbital- and ethyl ether-induced sleep time, as well as death latency in the pentylenetetrazole-induced convulsion model. However, the tested compounds were devoid of anxiolytic-like and myorelaxant activity. In addition, the OEHM (100 and 200 mg/kg, i.p.) and 1,8-cineole (50 mg/kg, i.p.) potentiated haloperidol-induced catalepsy and reduced ketamine-induced hyperkinesia. Taken together, the results suggest the OEHM has important hypnotic-sedative and antipsychotic-like effects, which appear to be due to the monoterpene 1,8-cineole, the major compound identified in the essential oil.

Phytochemical Analysis and Central Effects of Annona Muricata Linnaeus: Possible Involvement of the Gabaergic and Monoaminergic Systems.

Annona muricata Linnaeus (Annonaceae), popularly known as graviola, is used in folk medicine as both sedative and anticonvulsant. This study correlates the neurochemical profile with the behavioral effects of the hydroalcoholic extract from the leaves of Annona muricata (HLEAM) in mice, proposing to elucidate their mechanism of action on the central nervous system. Flavonoids and phenolic compounds were identified and quantified by High Performance Liquid Chromatography (HPLC) method. The acute toxicity (median lethal dose - LD50) was determined by probitos method using the percentage of mortality based on the Hippocratic screen. HLEAM (25, 50 and 100 mg/kg) was tested, intraperitoneally (i.p.), in models of sedation, anxiety, motor coordination, and seizures. The endogenous levels of dopamine, norepinephrine and DOPAC were assayed by reverse-phase HPLC with electrochemical detection. The HPLC analysis of the extract revealed the presence of flavonoids (quercetin, isoquercitrin, quercitrin, rutin, and kaempferol) and phenolics acids (gallic, chlorogenic, ellagic and caffeic acids). The LD50 was 1091.7 mg/kg and Hippocratic screening indicated central nervous system depressant effect. HLEAM presented sedative effects at doses of 25, 50, and 100 mg/kg, as well as anxiolytic and anticonvulsant effects at a dose of 100 mg/kg. In addition, these effects were partially reversed by flumazenil. The monoamines analysis by HPLC showed that HLEAM decreased the level of norepinefrine and dopamine in the mouse brain striatum. Thus, the results indicate a possible interaction of HLEAM with the GABAergic and monoaminergic systems, adding medicinal value to the popular use of the plant for the treatment of behavioral and neurological disorders.

Antiparasitic Activity and Essential Oil Chemical Analysis of the Piper Tuberculatum Jacq Fruit.

With the increase of neglected diseases such as leishmaniasis and Chagas disease, there was a need for the search for new therapeutic alternatives that reduce the harm caused by medicine available for treatment. Thus, this study was performed to investigate the antiparasitic activity of the essential oil from the fruits of Piper tuberculatum Jacq, against lines of Leishmania braziliensis (MHOM/CO/88/UA301), Leishmania infantum (MHOM/ES/92/BCN83) and Trypanosoma cruzi (LC-B5 clone). Before running protocols, an analysis of the chemical composition of essential oil was conducted, which presented monoterpenes and sesquiterpenes. As major constituents, ß-pinene and α-pinene were identified. Regarding to antiparasitic activity, the essential oil had an EC50 values of 133.97 µg/mL and 143.59 µg/mL against variations promastigotes of L. infantum and L. braziliensis, respectively. As for trypanocidal activity, the oil showed EC50 value of 140.31 µg/mL against epimastigote form of T. cruzi. Moreover, it showed moderate cytotoxicity in fibroblasts with LC50 value of 204.71 µg/mL. The observed effect may be related to the presence of terpenes contained in the essential oil, since it has its antiparasitic activity proven in the literature.

Avaliação da atividade moduladora e citotóxica do óleo essencial das folhas de Hyptis martiusii Benth / Evaluación de la actividad moduladora y citotóxica del aceite esencial de las hojas de Hyptis martiusii Benth / Assessment of Modulatory and Cytotoxic Activity of the Essential Oil in Hyptis Martiusii Benth Leaves

Resumo Introdução: a espécie Hyptis martiusii Benth, comumente chamada de "cidrera del campo", têm múltiplas propriedades biológicas, como ser inseticida, antifúngica e anti-inflamatória. O objetivo deste estudo foi investigar a atividade moduladora do óleo essencial das folhas frescas de Hyptis martiusii em associação com diferentes antibióticos contra as bactérias Staphylococcus aureus, Escherichia coli e Pseudomonas aeruginosa, e avaliar a atividade citotóxica da espécie. Materiais e métodos: o estudo utilizou a concentração inibitória mínima (CIM) como uma forma de avaliar a modulação com uma inoculação de 100 microlitros de cada estirpe bacteriana. As provas de citotoxicidade se realizaram mediante cultivo in vitro de células do tecido conectivo de camundongo (fibroblastos de mamíferos). Resultados: a pesquisa demonstrou que o óleo essencial das folhas de Hyptis martiusii Benth (OEHM) apresenta sinergismo só em associação com os antibióticos gentamicina e imipenem contra as bactérias Pseudomonas aeruginosa e Escherichia coli. No entanto, apresenta antagonismo em associação com amicacina, gentamicina e imipenem contra as três bactérias estudadas. Para além da ciprofloxacina não demonstrou resultados relevantes. Em relação com a atividade citotóxica, a concentração letal média (LC50) expôs um valor de 263,12 [ig/ml. Conclusão: finalmente, revelou-se que a H. martiusii apresenta atividade citotóxica sinérgica contra as bactérias avaliadas.

Resumen Introducción: la especie Hyptis martiusii Benth, comúnmente llamada "cidreira do campo", tiene múltiples propiedades biológicas, como ser insecticida, antifúngica y antiinflamatoria. El objetivo de este estudio fue investigar la actividad moduladora del aceite esencial de las hojas frescas de Hyptis martiusii en asociación con diferentes antibióticos contra las bacterias Staphylococcus aureus, Escherichia coli y Pseudomonas aeruginosa, y evaluar la actividad citotóxica de la especie. Materiales y métodos: el estudio utilizó la concentración mínima inhibitoria (CMI) como una forma de evaluar la modulación con una inoculación de 100 microlitros de cada cepa bacteriana. Las pruebas de citotoxicidad se realizaron mediante cultivo in vitro de células de tejido conectivo de ratón (fibroblastos de mamíferos). Resultados: la investigación demostró que el aceite esencial de las hojas de Hyptis martiusii Benth (OEHM) presenta sinergismo solo en asociación con los antibióticos gentamicina e imipenem contra las bacterias Pseudomonas aeruginosa y Escherichia coli. Sin embargo, presenta antagonismo en asociación con amikacina, gentamicina e imipenem contra las tres bacterias estudiadas. Además de la ciprofloxacina, no demostró resultados relevantes. En relación con la actividad citotóxica, la concentración letal media (CL50) exhibió un valor de 263,12 [ig/ml. Conclusión: finalmente, se reveló que la H. martiusii presenta actividad citotóxica sinérgica contra las bacterias evaluadas.

Abstract Introduction: The species Hyptis martiusii Benth. commonly called "cidreira do campo" has multiple biological properties, such as antifungal, anti-inflammatory, and insecticide. The aim of this study was to investigate the modulating activity of the essential oil of the fresh leaves of Hyptis martiusii in association with different antibiotics against the bacteria Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, as also the cytotoxic activity of this species. Materials and methods: The study used the MIC (minimum inhibitory concentration) as a way of assessing the modulation using an inoculation of 100 microliters of each bacterial strain. The cytotoxicity tests were conducted using in vitro culture of mouse connective tissue cells (fibroblasts of mammals). Results: The research demonstrated that the essential oil from leaves of Hyptis martiusii Benth (OEHM) presented synergism only when associated with the antibiotics gentamicin and imipenem against the bacteria Pseudomonas aeruginosa and Escherichia coli. However, it presented antagonism in association with amikacin, gentamicin and imipenem against the three studied bacteria. In addition to the ciprofloxacin showed no relevant results. In relation to the cytotoxic activity the lethal concentration (LC50) exhibited a value of 263.12 [ig/ml. Conclusion: Ultimately it was established, that H. Martiusii presents a synergistic cytotoxic activity against the evaluated bacteria.

Modulação in vitro da atividade antibiótica pelo óleo essencial dos frutos de Piper tuberculatum Jacq / Modulación in vitro de la actividad antibiótica por el aceite esencial de frutos de Piper tuberculatum Jacq / In vitro modulation of the antibiotic activity of essential oil from fruits of Piper tuberculatum Jacq

Introdução: Piper tuberculatum Jacq., popularmente conhecida como pimenta-longaou pimenta-d'Arda, é utilizada empiricamente no tratamento de doenças respiratórias (asma, bronquite e tosse) e digestivas (dores abdominais e diarreias). Na literatura é descrita com importantes atividades anti-inflamatória, antimicrobiana, antileucêmico e anti-helmíntica. Objetivos: avaliar a atividade moduladora do óleo essencial dos frutos de P. tuberculatum (OEPT) em associação com diferentes antibióticos frente à Staphylococcus aureus, Escherichia coli e Pseudomona aeruginosa. Metodos: Os frutos (frescos) de P. tuberculatum foram coletados em Barbalha/CE e submetidos à hidrodestilação em aparelho tipo Clevenger para ser extraído o óleo essencial, após a extração o óleo essencial foi tratado com sulfato de sódio anidro para eliminação da umidade residual. A avaliação da atividade antibacteriana e modulação (em resistência bacteriana) frente às cepas de S. aureus (SA358), E. coli (EC27) e P. aeruginosa (PA03) foram determinadas pelo método de microdiluição para identificar a concentração inibitória mínima (CIM), realizada em triplicata. CIM de ≤ 256 µg/mL foi considerado clinicamente relevante. Resultados: a atividade antibacteriana do OEPT exibiu um CIM de ≥ 1024 µg/mL contra as cepas de bactérias de padrão resistente a múltiplas drogas. Na avaliação da atividade moduladora, o OEPT antagonizou o efeito da amicacina contra E. coli e S. aureus, mas teve efeito sinérgico contra P. aeruginosa. Combinado com a getamicina o óleo exibiu antagonismo frente a E. coli, no entanto não apresentou resultado relevante contra S. aureas e P. aeruginosa. A associação do OEPT com o antibiótico imipenem resultou efeito mais relevante, apresentando sinergismo para todas as bactérias avaliadas, por outro lado, em associação com ciprofloxacino não apresentou efeito significante em relação ao controle. Conclusão: O OEPT apresentou uma melhor atividade quando associado ao imipenem frente todas as bactérias avaliadas, mostrando ser uma possível alternativa no desenvolvimento de novos fármacos com atividade antibacteriana advindos de produtos fitoterápicos(AU)

Introducción: Piper tuberculatum Jacq. popularmente conocida como pimenta-longa o pimenta-d'Arda, se utiliza empíricamente en el tratamiento de enfermedades respiratorias (asma, bronquitis y tos) y digestivas (dolor abdominal y diarrea). En la literatura es describe con importantes actividades antiinflamatorias, antimicrobianas, antileucémicas y antihelmínticas. Objetivo: evaluar la actividad moduladora de los aceites esenciales de frutos de P. tuberculatum (AEPT) en asociación con diferentes antibióticos contra Staphylococcus aureus, Escherichia coli y Pseudomona aeruginosa. Metodología: los frutos (frescos) de P. tuberculatum fueron recolectados en Barbalha/CE y sometidos a hidrodestilación en un equipo Clevenger, para extraer el aceite essencial (AEPT), el cual, una vez extraído, fue tratado con sulfato de sodio anhidro para eliminar la humedad residual. Se evaluó su actividad antibacteriana contra las cepas de S. aureus (SA358), E. coli (EC27) y P. aeruginosas (PA03). Empleando el método de microdilución se determinó la concentración inhibitoria mínima (CIM), con tres réplicas por cada tratamiento. Un valor de CIM ≤ 256 µg/mL se considera clínicamente relevante. Resultados: la actividad antibacteriana del AEPT exhibió una CIM ≥ 1024 µg/mL contra las cepas estándar de bacterias resistentes a múltiples fármacos. En efecto, la actividad AEPT antagoniza el efecto de amikacina contra E. coli y S. aureus, pero tenía un efecto sinérgico contra P. aeruginosa. Combinado con la getamicina el aceite exhibió antagonismo contra E. coli, sin embargo no presentó resultado relevante ante S. aureus y P. aeruginosa. La asociación de AEPT con el antibiótico imipenem resultó el efecto más relevante, mostrando sinergismo frente a todas las bacterias evaluadas. Por el contrario, en asociación con ciprofloxacina no mostró ningún efecto significativo con respecto al control. Conclusión: el AEPT presentó una mejor actividad cuando se asoció a imipenem, frente todas las bacterias evaluadas, demostrando ser una posible alternativa en el desarrollo de nuevos fármacos con actividad antimicrobiana, a partir de productos herbarios(AU)

Introduction: Piper tuberculatum Jacq., commonly known as pimenta-longa or pimenta-d'Arda, is empirically used to treat respiratory conditions (asthma, bronchitis and coughing) and digestive disorders (abdominal pain and diarrhea). Reference may be found in the literature to outstanding antiinflammatory, antimicrobial, antileukemic and antihelmintic activity. Objective: Evaluate the modulatory activity of essential oils from fruits of P. tuberculatum (AEPT) combined with various antibiotics againstStaphylococcus aureus, Escherichia coli and Pseudomona aeruginosa. Methods: Fresh fruits of P. tuberculatum were collected in Barbalha, CE, and subjected to hydrodistillation in a Clevenger set to extract the essential oil (AEPT). The oil extracted was then treated with anhydrous sodium sulfate to eliminate residual humidity. Antibacterial activity was evaluated against strains of S. aureus (SA358), E. coli (EC27) and P. aeruginosas (PA03). Minimum inhibitory concentration (MIC) was determined by the microdilution method, with three replications for each treatment. A MIC ≤ 256 µg/mL was considered to be clinically relevant. Results: Antibacterial activity of AEPT displayed a MIC of ≥1024 µg/mL against standard strains of multi-drug resistant bacteria. In fact, activity of AEPT antagonized the effect of amikacin against E. coli and S. aureus, but had a synergic effect against P. aeruginosa. Combined with gentamicin, the oil exhibited antagonism against E. coli, but no relevant result was obtained against S. aureus and P. aeruginosa. Combination of AEPT with the antibiotic imipenem had the most relevant effect, displaying synergism against all the bacteria evaluated. However, in combination with ciprofloxacin it did not show any significant effect with respect to the control. Conclusion: AEPT displayed better activity against all the bacteria evaluated when combined with imipenem, proving to be a possible alternative for the development of new herbal drugs with antimicrobial activity(AU)

Modulação in vitro da atividade antibiótica pelo óleo essencial dos frutos de Piper tuberculatum Jacq / In vitro modulation of the antibiotic activity of essential oil from fruits of Piper tuberculatum Jacq

Introdução: Piper tuberculatum Jacq., popularmente conhecida como pimenta-longa ou pimenta-d'Arda, é utilizada empiricamente no tratamento de doenças respiratórias (asma, bronquite e tosse) e digestivas (dores abdominais e diarreias). Na literatura é descrita com importantes atividades anti-inflamatória, antimicrobiana, antileucêmico e anti-helmíntica. Objetivos: avaliar a atividade moduladora do óleo essencial dos frutos de P. tuberculatum (OEPT) em associação com diferentes antibióticos frente à Staphylococcus aureus, Escherichia coli e Pseudomona aeruginosa. Metodos: Os frutos (frescos) de P. tuberculatum foram coletados em Barbalha/CE e submetidos à hidrodestilação em aparelho tipo Clevenger para ser extraído o óleo essencial, após a extração o óleo essencial foi tratado com sulfato de sódio anidro para eliminação da umidade residual. A avaliação da atividade antibacteriana e modulação (em resistência bacteriana) frente às cepas de S. aureus (SA358), E. coli (EC27) e P. aeruginosa (PA03) foram determinadas pelo método de microdiluição para identificar a concentração inibitória mínima (CIM), realizada em triplicata. CIM de ≤ 256 µg/mL foi considerado clinicamente relevante. Resultados: a atividade antibacteriana do OEPT exibiu um CIM de ≥ 1024 µg/mL contra as cepas de bactérias de padrão resistente...(AU)

Introducción: Piper tuberculatum Jacq. popularmente conocida como pimenta-longa o pimenta-d'Arda, se utiliza empíricamente en el tratamiento de enfermedades respiratorias (asma, bronquitis y tos) y digestivas (dolor abdominal y diarrea). En la literatura es describe con importantes actividades antiinflamatorias, antimicrobianas, antileucémicas y antihelmínticas. Objetivo: evaluar la actividad moduladora de los aceites esenciales de frutos de P. tuberculatum (AEPT) en asociación con diferentes antibióticos contra Staphylococcus aureus, Escherichia coli y Pseudomona aeruginosa. Metodología: los frutos (frescos) de P. tuberculatum fueron recolectados en Barbalha/CE y sometidos a hidrodestilación en un equipo Clevenger, para extraer el aceite essencial (AEPT), el cual, una vez extraído, fue tratado con sulfato de sodio anhidro para eliminar la humedad residual. Se evaluó su actividad antibacteriana contra las cepas de S. aureus (SA358), E. coli (EC27) y P. aeruginosas (PA03). Empleando el método de microdilución se determinó la concentración inhibitoria mínima (CIM), con tres réplicas por cada tratamiento. Un valor de CIM ≤ 256 µg/mL se considera clínicamente...(AU)

Introduction: Piper tuberculatum Jacq., commonly known as pimenta-longa or pimenta-d'Arda, is empirically used to treat respiratory conditions (asthma, bronchitis and coughing) and digestive disorders (abdominal pain and diarrhea). Reference may be found in the literature to outstanding antiinflammatory, antimicrobial, antileukemic and antihelmintic activity. Objective: Evaluate the modulatory activity of essential oils from fruits of P. tuberculatum (AEPT) combined with various antibiotics againstStaphylococcus aureus, Escherichia coli and Pseudomona aeruginosa. Methods: Fresh fruits of P. tuberculatum were collected in Barbalha, CE, and subjected to hydrodistillation in a Clevenger set to extract the essential oil (AEPT). The oil extracted was then treated with anhydrous sodium sulfate to eliminate residual humidity. Antibacterial activity was evaluated against strains of S. aureus (SA358), E. coli (EC27) and P. aeruginosas (PA03). Minimum inhibitory concentration (MIC) was determined by the microdilution method, with three replications for each treatment. A MIC ≤ 256 µg/mL was considered to be clinically relevant. Results: Antibacterial activity of AEPT displayed a MIC of ≥1024 µg/mL against standard strains of multi-drug resistant bacteria. In fact, activity of AEPT antagonized the effect of amikacin against...(AU)