Echinodorus macrophyllus: Acute toxicological evaluation of hydroxycinnamoyl derivatives from SF1 subfractions.

ETHNOPHARMACOLOGICAL RELEVANCE: Echinodorus macrophyllus (Kunth.) Micheli (Alismataceae), known as chapéu-de-couro in Brazil, is popularly used to treat inflammatory diseases. We have previously demonstrated a significant reduction in the acute inflammation for the aqueous extract of E. macrophyllus (AEEm) and its ethanolic fraction (Fr20) and described that hydroxycinnamoyl derivatives present in SF1 (Fr20 subfraction) showed higher anti-inflammatory properties by mechanisms that include a reduction of TNF-α, IL-1ß, CKCL1/KC, LTB4, and PGE2 levels in exudate. AIM OF THE STUDY: This work describes the acute toxicological effect of SF1 subfraction on SW mice treated orally for five days in the air pouch model by evaluating the hematological and biochemical determinations on the blood samples; the relative organ weight and its histopathological analysis; the liver genotoxicity assessment and the activity of liver enzymes from xenobiotic metabolism. MATERIALS AND METHODS: Fr20 was earlier fractionated on the Sephadex LH-20 column, yielding mainly four subfractions, including SF1. The SF1 toxicity was evaluated in mice challenged with carrageenan on the air pouch inflammation model and orally treated for five days. The body weight was monitored daily, and the organs were weighed after the euthanasia. Hematological and biochemical determinations were carried out using specific commercial kits and following the protocols provided by the manufacturers. The organs were fixed, sectioned, processed for hematoxylin and eosin staining, and analyzed by light microscopy. Genotoxicity assessment was performed by the alkaline single-cell gel electrophoresis. Livers were processed for ethoxyresorufin-O-deethylase (EROD) and Glutathione S-transferase (GST) assays. RESULTS: SF1 exhibited low toxicity, as no significant discrepancy was observed in the relative weight of the body organs of mice. Moreover, the daily treatment with SF1 did not alter the number and percentage of red blood cells or hemoglobin concentration in the blood. The treatment with SF1 did not affect the creatinine concentration, but the 25 mg/kg dose reduced the plasma urea level and uric acid, suggesting its use in treating acute renal failure. The parameters analyzed did not present biochemical alterations indicative of liver disease. Regarding serum triglyceride and cholesterol levels, a significant decrease was detected in both parameters in mice treated with SF1. In addition, the histopathological analysis showed that inflammatory focus in the livers seemed more relevant in the control groups than in those treated. There were no significant changes in the renal or splenic tissues of animals treated with SF1. Treatment with SF1 also does not have a genotoxic effect on liver cells. CONCLUSION: Treatment with SF1 showed no toxicity in mice at doses equivalent to those recommended for humans, which provides evidence of the safety of the therapeutic use of this subfraction.

Crossed aphasia in a left-handed patient with non-fluent variant of primary progressive aphasia with left asymmetric brain SPECT.

Primary progressive aphasia is a clinical syndrome caused by neurodegeneration of areas and neural networks involved in language, usually in the left hemisphere. The term "crossed aphasia" denotes an acquired language dysfunction caused by a lesion in the ipsilateral hemisphere to the dominant hand. Objective: To describe a case of crossed aphasia in a 60-year-old left-handed patient with a non-fluent variant of primary progressive aphasia diagnosis (age of onset=52), evidenced by a left asymmetry on brain SPECT scan. Methods: Clinical and family history, the Edinburgh Handedness Inventory, Measurement of Functional Activities in Older Adults in the Community, the "Mini-Mental State Examination", the Trail Making Test, the Tower of London, and the Neuropsychological assessment for dementia, and neuroimaging studies were carried out. Results: Neuropsychological assessment showed severe cognitive impairment, especially regarding language. The magnetic resonance imaging showed important signs of cortico-subcortical atrophy, with predominance in the frontal and temporal lobes. The single-photon emission computed tomography scan showed moderate to severe hypoperfusion in the left cerebral hemisphere, including the hippocampus. Conclusion: We described a clinical case of crossed aphasia in a left-handed woman with a non-fluent variant of primary progressive aphasia with asymmetry on brain SPECT, mainly on the left, followed up for seven years.

A afasia progressiva primária é uma síndrome clínica causada por uma neurodegeneração de áreas e redes neurais envolvidas na linguagem, geralmente no hemisfério esquerdo. O termo "afasia cruzada" denota uma disfunção adquirida de linguagem causada por uma lesão no hemisfério ipsilateral da mão dominante. Objetivo: Relatamos um caso de afasia cruzada em uma paciente de 60 anos, canhota, com um quadro clínico de afasia progressiva primária variante não fluente (idade de início=52), evidenciada por assimetria no SPECT cerebral à esquerda. Métodos: Foram realizados para o diagnóstico do caso: história clínica e familiar, o Inventário de Dominância de Edinburgh, a Escala de Atividades Funcionais de Pfeffer, o Miniexame do Estado Mental, o Teste das Trilhas, o Teste da Torre de Londres, a Avaliação Neuropsicológica Adequada às Demências e exames de neuroimagem. Resultados: A avaliação neuropsicológica mostrou comprometimento cognitivo severo, principalmente sobre a linguagem; a ressonância magnética do crânio mostrou sinais de involução córtico-subcortical, com predominância nos lobos frontal e temporal e a cintilografia cerebral por emissão de fóton único mostrou hipoperfusão moderada a severa no hemisfério cerebral esquerdo, incluindo o hipocampo. Conclusão: Registramos um caso clínico de afasia cruzada em uma paciente canhota com afasia progressiva primária variante não fluente com assimetria no SPECT cerebral, principalmente à esquerda, seguida há sete anos.

Impaired Cardiovascular Parameters in Resistance Training Practitioners Who Take Ergogenic Aids.

BACKGROUND: Although there are studies on blood pressure (BP) and autonomic cardiac control (ACC) impairments caused by ergogenic aids, research has scarcely addressed this analysis during sleep. This study analyzed BP and ACC during sleep and wake periods in three groups of resistance training (RT) practitioners: ergogenic aid non-users, thermogenic supplement (TS) self-users, and anabolic-androgenic steroid (AAS) self-users. METHODS: RT practitioners were selected for the Control Group (CG; n = 15), TS self-users Group (TSG; n = 15), and AAS self-users Group (AASG; n = 15). All individuals underwent cardiovascular Holter monitoring (BP, ACC) during sleep and wake periods. RESULTS: The maximum systolic BP (SBP) during sleep was higher in AASG (p < 0.01) than CG (p < 0.001). CG had lower mean diastolic BP (DBP) than TSG (p < 0.01) and lower mean SBP (p = 0.009) than the other groups. Additionally, CG had higher values (p < 0.01) than TSG and AASG for SDNN and pNN50 during sleep. HF, LF, and LF/HF ratio values during sleep were statistically different in CG (p < 0.001) from the other groups. CONCLUSIONS: Our findings demonstrate that high doses of TS and AAS can impair cardiovascular parameters during sleep in RT practitioners who take ergogenic aids.

Crossed aphasia in a left-handed patient with non-fluent variant of primary progressive aphasia with left asymmetric brain SPECT / Afasia cruzada em paciente canhota com afasia progressiva primária variante não fluente com SPECT cerebral assimétrico à esquerda

ABSTRACT Primary progressive aphasia is a clinical syndrome caused by neurodegeneration of areas and neural networks involved in language, usually in the left hemisphere. The term "crossed aphasia" denotes an acquired language dysfunction caused by a lesion in the ipsilateral hemisphere to the dominant hand. Objective: To describe a case of crossed aphasia in a 60-year-old left-handed patient with a non-fluent variant of primary progressive aphasia diagnosis (age of onset=52), evidenced by a left asymmetry on brain SPECT scan. Methods: Clinical and family history, the Edinburgh Handedness Inventory, Measurement of Functional Activities in Older Adults in the Community, the "Mini-Mental State Examination", the Trail Making Test, the Tower of London, and the Neuropsychological assessment for dementia, and neuroimaging studies were carried out. Results: Neuropsychological assessment showed severe cognitive impairment, especially regarding language. The magnetic resonance imaging showed important signs of cortico-subcortical atrophy, with predominance in the frontal and temporal lobes. The single-photon emission computed tomography scan showed moderate to severe hypoperfusion in the left cerebral hemisphere, including the hippocampus. Conclusion: We described a clinical case of crossed aphasia in a left-handed woman with a non-fluent variant of primary progressive aphasia with asymmetry on brain SPECT, mainly on the left, followed up for seven years.

RESUMO A afasia progressiva primária é uma síndrome clínica causada por uma neurodegeneração de áreas e redes neurais envolvidas na linguagem, geralmente no hemisfério esquerdo. O termo "afasia cruzada" denota uma disfunção adquirida de linguagem causada por uma lesão no hemisfério ipsilateral da mão dominante. Objetivo: Relatamos um caso de afasia cruzada em uma paciente de 60 anos, canhota, com um quadro clínico de afasia progressiva primária variante não fluente (idade de início=52), evidenciada por assimetria no SPECT cerebral à esquerda. Métodos: Foram realizados para o diagnóstico do caso: história clínica e familiar, o Inventário de Dominância de Edinburgh, a Escala de Atividades Funcionais de Pfeffer, o Miniexame do Estado Mental, o Teste das Trilhas, o Teste da Torre de Londres, a Avaliação Neuropsicológica Adequada às Demências e exames de neuroimagem. Resultados: A avaliação neuropsicológica mostrou comprometimento cognitivo severo, principalmente sobre a linguagem; a ressonância magnética do crânio mostrou sinais de involução córtico-subcortical, com predominância nos lobos frontal e temporal e a cintilografia cerebral por emissão de fóton único mostrou hipoperfusão moderada a severa no hemisfério cerebral esquerdo, incluindo o hipocampo. Conclusão: Registramos um caso clínico de afasia cruzada em uma paciente canhota com afasia progressiva primária variante não fluente com assimetria no SPECT cerebral, principalmente à esquerda, seguida há sete anos.

Interaction between Benzo[a]anthracene 7,2-dione 7-oxime (BZA) and calf thymus dsDNA using electroanalytical genosensor.

In the present study, the objective was to evaluate in situ interaction between Benzo[a]anthracene 7,2-dione 7-oxime (BZA) and calf thymus dsDNA (ct-dsDNA) using electroanalytical genosensor. Analytical techniques based on Ultraviolet/Visible (UV-Vis) spectroscopy and electroanalytical were used to investigate the interaction processes in solution and immobilized on carbon screen-printed electrodes modified with electrochemical mediator Meldola blue. In addition, was possible to evaluate the degree of damage caused to the genetic material by the analyte through of toxicity estimate (S%). The interaction evaluated by genosensor showed processes of intercalation, degradation, and breaks of the double strand of ct-dsDNA, suggesting that the interaction simulates highly toxic (values varying from 0.6 to 0.8 µA in 48 h of interaction), such as 8-oxoguanine (+0.48 V), which is a by-product of guanine oxidation. Furthermore, monitoring A (+1.10 V) after 1 h showed an S% value between 50 and 90%, indicative of high toxicity, and monitoring G (+0.85 V), which showed S>90%, indicated no toxicity after 10 min. Overall, the electroanalytical genosensor developed in a miniaturized system displayed good reproducibility and stability over time being a quick alternative for assesses the degree of toxicity between toxic xenobiotics and biologically electroactive molecules, such as DNA.

Echinodorus macrophyllus: Hydroxycinnamoyl derivatives reduces neutrophil migration through modulation of cytokines, chemokines, and prostaglandin in the air-pouch model.

ETHNOPHARMACOLOGICAL RELEVANCE: In Brazil, Echinodorus macrophyllus (Alismataceae), popularly known as chapéu-de-couro, is used to treat inflammatory diseases. Previous studies have shown a significant decrease in the acute inflammation for the aqueous extract of E. macrophyllus (AEEm) and its ethanolic fraction (Fr20). AIM OF THE STUDY: This work fractionated Fr20, identified the fraction and substances responsible for the in vivo anti-inflammatory property, and demonstrated important immunomodulatory mechanisms of action. MATERIALS AND METHODS: Fr20 was fractionated using Sephadex LH-20, and the most active fraction was chromatographically analyzed (HPLC-DAD and UPLC-ESI-TOF-MS). Leukotriene B4, Prostaglandin E2, and cytokines were determined by the enzyme-linked immunosorbent assay and in vivo acute inflammation by the air pouch model. RESULTS: The subfractions SF1, SF3, and mainly the SF4 decreased NO levels (p < 0.05). SF3 and SF4 showed high DPPH scavenger activity. SF1 was more effective than SF4 in reducing vasodilation, redness, and leukocyte migration into the 4-h air pouch. SF1 inhibited 90.5% (100 mg/kg) and SF4 54.0% (50 mg/kg), mainly affecting the number of neutrophils. SF1 and SF4 reduced the protein level in the exudate. SF1 was also more effective in inhibiting neutrophil migration in a transwell assay (46.3%) and reduced (86.1%) the Leukotriene B4 level in the exudate. After five days of treatment, some SF1 anti-inflammatory mechanisms were evaluated in the air pouch's 24 h exudate and tissue. Despite the high level of inflammation of the control group in this condition, SF1 confirmed the decrease in the protein level and neutrophils migration into the pouch. It decreased the number of bone marrow cells, indicating a systemic effect of SF1. SF1 also decreased TNF-α (87%), IL-1ß (77%), CKCL1/KC (71.3%), and PGE2 (97.8%) and increased IL-10 (74.1%) levels in the air pouch exudate. Phytochemical analysis of SF1 indicates mainly hydroxycinnamoyl derivatives. CONCLUSION: Hydroxycinnamoyl derivatives present in SF1 are related to the crucial anti-inflammatory mechanisms of E. macrophyllus, decreasing the levels of TNF-α, IL-1ß, CKCL1/KC, LTB4, and PGE2 on the exudate. These results explain the reduction of vasodilatation, erythema, and neutrophil migration into the air pouch model, confirming this plant's anti-inflammatory potential.

Bilateral hearing loss as an initial presentation of Creutzfeldt-Jakob disease / Perda auditiva bilateral como uma apresentação inicial da doença de creutzfeldt-jakob

ABSTRACT. We reported a case of a 61-year-old male patient with anacusis, cerebellar syndrome, myoclonus, and frontal signs. The brain magnetic resonance imaging showed bilateral striated hyperintensity of the fluid-attenuated inversion recovery and restricted diffusion in the diffusion-weighted imaging and hypointense areas corresponding to the apparent diffusion coefficient in the cerebral cortex. The autopsy revealed positive immunohistochemistry for the PrPSc protein. Creutzfeldt-Jakob disease presenting with hearing loss is unusual.

RESUMO. Relatamos o caso de um paciente do sexo masculino, 61 anos, com anacusia, síndrome cerebelar, mioclonia e sinais frontais. A ressonância magnética cerebral mostrou hiperintensidade estriada bilateral do fluid-attenuated inversion recovery (FLAIR) e difusão restrita no diffusion-weighted imaging (DWI) e áreas hipointensas correspondendo ao coeficiente de difusão aparente no córtex cerebral. A autópsia revelou imuno-histoquímica positiva para a proteína PrPSc. A doença de Creutzfeldt-Jakob que se apresenta com perda auditiva é incomum.

Impact of COVID-19 pandemic on the sleep quality of medical professionals in Brazil.

INTRODUCTION: Coronavirus pandemic began in China in 2019 (COVID-19), causing not only public health problems but also great psychological distress, especially for physicians involved in coping with the virus or those of the risk group in social isolation, and this represents a challenge for the psychological resilience in the world population. Studies showed that health professionals had psychological symptoms such as depression, anxiety, insomnia, stress, among others. OBJECTIVES: To investigate the quality of sleep and the prevalence rate of sleeping disorders among physicians during COVID-19 pandemic, and identify the psychological and social factors associated with the condition. METHODS: A cross-sectional study of an online questionnaire was applied for physicians in Brazil. Among the 332 participants included, 227 were women. Sociodemographic assessment was used in the questionnaire, as well as the scale of impact on the events of modifications caused by COVID-19, assessment on sleep quality (PSQI), presence and severity of insomnia (ISI), depressive symptoms (PHQ-9), and anxiety (GAD-7). RESULTS: Most physicians (65.6%) had changes in sleep. Poor sleep quality was reported by 73.1%, depressive symptoms were present in 75.8%, and anxiety in 73.4%. CONCLUSION: Our study found that more than 70% of the physicians assessed had impaired sleep quality, characterizing insomnia symptoms during COVID-19 outbreak. Related factors included an environment of isolation, concerns about COVID-19 outbreak and symptoms of anxiety and depression. Special interventions are needed to promote health professionals' mental well-being and implement changes in this scenario.

Impact of COVID-19 pandemic on the sleep quality of medical professionals in Brazil / Impacto da pandemia COVID-19 na qualidade do sono dos médicos no Brasil

ABSTRACT Introduction: Coronavirus pandemic began in China in 2019 (COVID-19), causing not only public health problems but also great psychological distress, especially for physicians involved in coping with the virus or those of the risk group in social isolation, and this represents a challenge for the psychological resilience in the world population. Studies showed that health professionals had psychological symptoms such as depression, anxiety, insomnia, stress, among others. Objectives: To investigate the quality of sleep and the prevalence rate of sleeping disorders among physicians during COVID-19 pandemic, and identify the psychological and social factors associated with the condition. Methods: A cross-sectional study of an online questionnaire was applied for physicians in Brazil. Among the 332 participants included, 227 were women. Sociodemographic assessment was used in the questionnaire, as well as the scale of impact on the events of modifications caused by COVID-19, assessment on sleep quality (PSQI), presence and severity of insomnia (ISI), depressive symptoms (PHQ-9), and anxiety (GAD-7). Results: Most physicians (65.6%) had changes in sleep. Poor sleep quality was reported by 73.1%, depressive symptoms were present in 75.8%, and anxiety in 73.4%. Conclusion: Our study found that more than 70% of the physicians assessed had impaired sleep quality, characterizing insomnia symptoms during COVID-19 outbreak. Related factors included an environment of isolation, concerns about COVID-19 outbreak and symptoms of anxiety and depression. Special interventions are needed to promote health professionals' mental well-being and implement changes in this scenario.

RESUMO Introdução: A pandemia de coronavírus iniciada na China em 2019 (COVID-19) não só causou problemas de saúde pública mas também trouxe grande sofrimento psíquico, principalmente aos médicos envolvidos no enfrentamento da doença ou àqueles do grupo de risco em isolamento social, e representa um desafio para a resiliência psicológica da população mundial. Estudos mostram que profissionais de saúde apresentaram sintomas psicológicos como depressão, ansiedade, insônia, estresse, entre outros. Objetivos: Investigar a qualidade do sono e a taxa de prevalência de transtornos do sono entre os médicos durante a pandemia do COVID-19, e identificar os fatores psicológicos e sociais associados ao quadro. Métodos: Estudo transversal com aplicação de questionário on-line a médicos do Brasil e inclusão de 332 participantes, dos quais 227 eram mulheres. Foram utilizados questionários com avaliação sociodemográfica, escala de impacto a eventos com modificações causadas pelo COVID-19, avaliação da qualidade do sono (PSQI), presença e gravidade da insônia (IGI), sintomas depressivos (PHQ-9) e ansiedade (TAG-7). Resultados: A maioria dos médicos (65,6%) apresentou alterações no sono, sendo a má qualidade do sono reportada por 73,1%. Sintomas depressivos estiveram presentes em 75,8%, e ansiedade em 73,4%. Conclusão: Nosso estudo constatou que mais de 70% dos médicos avaliados apresentavam comprometimento da qualidade do sono, caracterizando sintomas de insônia durante o surto de COVID-19. Os fatores relacionados incluíram ambiente de isolamento, preocupações com o surto de COVID-19 e sintomas de ansiedade e depressão. Intervenções especiais são necessárias para promover o bem-estar mental dos profissionais de saúde e implementar mudanças nesse cenário.

Bilateral hearing loss as an initial presentation of Creutzfeldt-Jakob disease.

We reported a case of a 61-year-old male patient with anacusis, cerebellar syndrome, myoclonus, and frontal signs. The brain magnetic resonance imaging showed bilateral striated hyperintensity of the fluid-attenuated inversion recovery and restricted diffusion in the diffusion-weighted imaging and hypointense areas corresponding to the apparent diffusion coefficient in the cerebral cortex. The autopsy revealed positive immunohistochemistry for the PrPSc protein. Creutzfeldt-Jakob disease presenting with hearing loss is unusual.

Relatamos o caso de um paciente do sexo masculino, 61 anos, com anacusia, síndrome cerebelar, mioclonia e sinais frontais. A ressonância magnética cerebral mostrou hiperintensidade estriada bilateral do fluid-attenuated inversion recovery (FLAIR) e difusão restrita no diffusion-weighted imaging (DWI) e áreas hipointensas correspondendo ao coeficiente de difusão aparente no córtex cerebral. A autópsia revelou imuno-histoquímica positiva para a proteína PrPSc. A doença de Creutzfeldt-Jakob que se apresenta com perda auditiva é incomum.

Comparison between the Mini-Mental State Examination and Montreal Cognitive Assessment as a Cognitive Screening Tool in Patients with Human Immunodeficiency Virus-Associated Neurocognitive Disorders.

INTRODUCTION: The number of human immunodeficiency virus-associated neurocognitive disorders has increased, reaching more than 50% of the cases. However, there are currently no substantial data on the screening methods for this disease. This study aimed to evaluate and compare the Mini-Mental State Examination to the Montreal Cognitive Assessment in human immunodeficiency virus-infected patients. METHODS: This was an observational study comprising 82 human immunodeficiency virus-positive individuals with and without cognitive complaints. RESULTS: Positive correlation (p<0.001) between the Mini-Mental State Examination and the Montreal Cognitive Assessment test scores was observed, but the mean scores revealed that the Mini-Mental State Examination showed worse performance for trails (p<0.001), cube copying (p<0.001), and clock drawing (p<0.001) than the Montreal Cognitive Assessment. CONCLUSIONS: The Mini-Mental State Examination and the Montreal Cognitive Assessment tests should be used concomitantly for the assessment of human immunodeficiency virus-associated neurocognitive disorders, but visuoexecutive and visuospatial dysfunctions are better evaluated using the Montreal Cognitive Assessment test than the Mini-Mental State Examination.

Development of a highly sensitive xanthine oxidase-based biosensor for the determination of antioxidant capacity in Amazonian fruit samples.

The paper describes the development of an amperometric biosensor using Prussian Blue (PB) modified electrodes containing xanthine oxidase (XOD). The enzyme is immobilized by photo-polymerization into an azide-unit pendant water-soluble photopolymer (PVA-AWP). The parameters of the fabrication of the biosensor, XOD:PVA/AWP ratio, crosslinking irradiation time, and XOD charge, were optimized. Operational conditions for electrode preparation were defined as 1:2 ratio of XOD:PVA/AWP; exposure time to neon light of 30  min; pH = 7.5  at room temperature and enzymatic charge of 8 mU per electrode. The biosensors showed stable, fast, simple, selective, cost-effective and sensitive (-2.72E-8  A mol L-1), with a good linear range (1.0-75  µmol L-1), and respectively detection and quantification limits for antioxidants of 2.17, and 7.15  µmol L-1. The applicability of this biosensor was demonstrated by in vitro analysis of gallic acid as standard antioxidant and Amazonian fruits as natural sources.

Comparison between the Mini-Mental State Examination and Montreal Cognitive Assessment as a Cognitive Screening Tool in Patients with Human Immunodeficiency Virus-Associated Neurocognitive Disorders

Abstract INTRODUCTION: The number of human immunodeficiency virus-associated neurocognitive disorders has increased, reaching more than 50% of the cases. However, there are currently no substantial data on the screening methods for this disease. This study aimed to evaluate and compare the Mini-Mental State Examination to the Montreal Cognitive Assessment in human immunodeficiency virus-infected patients. METHODS: This was an observational study comprising 82 human immunodeficiency virus-positive individuals with and without cognitive complaints. RESULTS: Positive correlation (p<0.001) between the Mini-Mental State Examination and the Montreal Cognitive Assessment test scores was observed, but the mean scores revealed that the Mini-Mental State Examination showed worse performance for trails (p<0.001), cube copying (p<0.001), and clock drawing (p<0.001) than the Montreal Cognitive Assessment. CONCLUSIONS: The Mini-Mental State Examination and the Montreal Cognitive Assessment tests should be used concomitantly for the assessment of human immunodeficiency virus-associated neurocognitive disorders, but visuoexecutive and visuospatial dysfunctions are better evaluated using the Montreal Cognitive Assessment test than the Mini-Mental State Examination.

Flavonoid-enriched fraction from Echinodorus macrophyllus aqueous extract exhibits high in-vitro and in-vivo anti-inflammatory activity.

OBJECTIVES: Echinodorus macrophyllus (Kunth) Micheli (Alismataceae) is popularly used as an infusion to treat inflammatory diseases. This work fractionated the aqueous extract of E. macrophyllus (AEEm) to improve its anti-inflammatory effects. METHODS: Aqueous extract of E. macrophyllus was fractionated by Sephadex LH-20 and analysed by HPLC-DAD. Anti-inflammatory action was evaluated, in vivo, by air pouch model (total leucocyte, protein and leukotriene B4 (LTB4 )), and, in vitro, by neutrophil migration (transwell assay) and its Mac1 expression (flow cytometry), and RAW 264.7 nitric oxide (NO) production (Griess reaction). KEY FINDINGS: Fr20 reduced total leucocyte at 2.5 mg/kg (29.7%) while ethanolic extract of E. macrophyllus (EAEm) increased it (94.0%). Fr20 showed higher (P < 0.05) inhibition (89.8%) of LTB4 in exudate than EAEm (75.0%). Fr20 and EAEm decreased exudate protein and inflammatory infiltrate in pouch tissues, in-vitro neutrophil migration, and NO production. Otherwise, Fr40 did not reduce leucocytes and exudate protein (until 50 mg/kg) nor tissue inflammation, and increased in-vitro NO production. The inhibition of neutrophil migration by EAEm, but not Fr20, was dependent on reduced Mac-1 expression. CONCLUSIONS: The fractionation of AEEm provided a more potent anti-inflammatory fraction containing flavonoids (Fr20) that reduces the migration of neutrophils and LTB4 release, probably contributing to its mechanism of action.

Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis.

Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is the second major cause of death by parasites, after malaria. The arsenal of drugs against leishmaniasis is small, and each has a disadvantage in terms of toxicity, efficacy, price, or treatment regimen. Our group has focused on studying new drug candidates as alternatives to current treatments. The pterocarpanquinone LQB-118 was designed and synthesized based on molecular hybridization, and it exhibited antiprotozoal and anti-leukemic cell line activities. Our previous work demonstrated that LQB-118 was an effective treatment for experimental cutaneous leishmaniasis. In this study, we observed that treatment with 10 mg/kg of body weight/day LQB-118 orally inhibited the development of hepatosplenomegaly with a 99% reduction in parasite load. An in vivo toxicological analysis showed no change in the clinical, biochemical, or hematological parameters. Histologically, all of the analyzed organs were normal, with the exception of the liver, where focal points of necrosis with leukocytic infiltration were observed at treatment doses 5 times higher than the therapeutic dose; however, these changes were not accompanied by an increase in transaminases. Our findings indicate that LQB-118 is effective at treating different clinical forms of leishmaniasis and presents no relevant signs of toxicity at therapeutic doses; thus, this framework is demonstrated suitable for developing promising drug candidates for the oral treatment of leishmaniasis.

Depression and anxiety in individuals with amyotrophic lateral sclerosis: a systematic review.

INTRODUCTION: Studies assessing symptoms of depression and anxiety in individuals with amyotrophic lateral sclerosis (ALS) have reported contradictory results. The objective of this systematic review is to identify the prevalence of these mood disorders in the literature. METHODS: We searched the PubMed, HighWire, MEDLINE, SciELO, LILACS and ScienceDirect databases. Literature was selected for review in two stages, according to eligibility criteria. The first stage involved searching databases and checking titles and abstracts. The second step consisted of reading complete articles and excluding those that did not meet the inclusion criteria. The inclusion criteria were articles written in Portuguese, English or Spanish, published in the last five years and involving people with ALS diagnosed according to the El Escorial criteria. RESULTS: The database searches returned a total of 1,135 titles and abstracts and then 1,117 of these were excluded. Eighteen articles were selected for review. The 12-item Amyotrophic Lateral Sclerosis Depression Inventory (ADI-12) was the only instrument designed specifically to assess depression in ALS, but it was only used in three studies. No instruments specifically designed for anxiety in ALS were used. A large number of studies found presence and slight increase of anxiety disorders. There was considerable large variation in the results related to depressive disorders, ranging from moderate depression to an absence of symptoms. CONCLUSIONS: Patients with ALS may exhibit symptoms of depression and anxiety at different levels, but there is a need for studies using specific instruments with larger samples in order to ascertain the prevalence of symptoms in ALS and the factors associated with it.

Depression and anxiety in individuals with amyotrophic lateral sclerosis: a systematic review / Depressão e ansiedade em pessoas com esclerose lateral amiotrófica: uma revisão sistemática

Introduction Studies assessing symptoms of depression and anxiety in individuals with amyotrophic lateral sclerosis (ALS) have reported contradictory results. The objective of this systematic review is to identify the prevalence of these mood disorders in the literature. Methods We searched the PubMed, HighWire, MEDLINE, SciELO, LILACS and ScienceDirect databases. Literature was selected for review in two stages, according to eligibility criteria. The first stage involved searching databases and checking titles and abstracts. The second step consisted of reading complete articles and excluding those that did not meet the inclusion criteria. The inclusion criteria were articles written in Portuguese, English or Spanish, published in the last five years and involving people with ALS diagnosed according to the El Escorial criteria. Results The database searches returned a total of 1,135 titles and abstracts and then 1,117 of these were excluded. Eighteen articles were selected for review. The 12-item Amyotrophic Lateral Sclerosis Depression Inventory (ADI-12) was the only instrument designed specifically to assess depression in ALS, but it was only used in three studies. No instruments specifically designed for anxiety in ALS were used. A large number of studies found presence and slight increase of anxiety disorders. There was considerable large variation in the results related to depressive disorders, ranging from moderate depression to an absence of symptoms. Conclusions Patients with ALS may exhibit symptoms of depression and anxiety at different levels, but there is a need for studies using specific instruments with larger samples in order to ascertain the prevalence of symptoms in ALS and the factors associated with it.

Introdução Estudos avaliando sintomas depressivos e ansiosos em pessoas com esclerose lateral amiotrófica (ELA) têm apresentado resultados contraditórios. Esta revisão sistemática tem por objetivo identificar a prevalência desses transtornos do humor na literatura. Métodos A pesquisa foi feita nas bases de dados PubMed, HighWire, MEDLINE, SciELO, LILACS e ScienceDirect. A seleção dos estudos foi realizada em duas etapas de acordo com os critérios de elegibilidade. A primeira etapa envolveu pesquisa nas bases de dados e revisão de títulos e resumos. Na segunda etapa houve a leitura dos artigos completos e a exclusão dos que não preenchiam os critérios de inclusão. Os critérios de inclusão eram: publicação nos idiomas português, inglês ou espanhol, nos últimos 5 anos e envolvendo pessoas com ELA conforme o El Escorial. Resultados Um total de 1.135 títulos e resumos foram selecionados, mas 1.117 foram excluídos. Como resultado, 18 artigos foram incluídos na revisão. O Inventário de Depressão da Esclerose Lateral Amiotrófica com 12 itens (ADI-12) foi o único instrumento específico para avaliação da depressão na ELA utilizado, porém em apenas três estudos. Nenhum instrumento específico para ansiedade na ELA foi utilizado. Boa parte dos estudos apontaram presença e ligeiro aumento das desordens de ansiedade. Já para depressão houve grande diversidade de respostas, variando de depressão moderada à ausência de sintomas. Conclusões Pessoas com ELA podem apresentar sintomas depressivos e ansiosos em proporções diferentes, mas há a necessidade de estudos com instrumentos específicos e com amostras mais amplas para que se possa averiguar a prevalência das sintomatologias na ELA e os fatores associados a elas.

Visual reproduction test in normal elderly: influence of schooling and visual task complexity / Teste de reprodução visual em idosos normais: influência da escolaridade e de tarefas visuais complexas

ABSTRACT. Tests of visual reproduction are used to assess visual memory. However, when the test is based on geometrical elements results could be influenced by schooling. Objective: To evaluate the influence of different schooling levels on performance of a visual reproduction task. Methods: A sample of 253 individuals (66 male and 187 female), aged 60 to 92 years were evaluated on a visual reproduction task comprising three geometric pictures of increasing complexity. Each individual was shown a picture for 8 to10 seconds and a drawing of it was then immediately elicited. Four groups were defined according to the following schooling levels: illiterate, 1 to 4 years, 5 to 8 years and over 8 years. Individual performance was measured by summing the items correctly reproduced for the three pictures. Results: A significant difference for age was found between the illiterate and other three schooling groups. The reproduction of picture one was better reproduced than pictures 2 and 3 for all schooling levels (p<0.001). Pictures 2 and 3 did not differ among the schooling levels. Picture reproduction among the schooling levels showed that the group with over 8 years of schooling performed better on pictures 1 and 2 (p<0.001) but not on picture 3. Conclusion: Individuals aged 60 years or older, with 8 years' schooling or less, showed a reduced capacity to reproduce geometric pictures of a high degree of complexity. Clinical evaluations that use geometrical tests could be misinterpreted when not controlled for schooling level.

RESUMO. Teste de reprodução visual é usado para avaliar a memória visual, baseado em elementos geométricos e o resultado deve ser influenciado pela escolaridade. Objetivo: Avaliar os diferentes níveis de escolaridade durante a reprodução de tarefas visuais. Métodos: Uma amostra de 253 indivíduos (66 masculinos e 187 femininos), com idade entre 60 e 92 anos, foi avaliada em uma tarefa de reprodução visual composta por três desenhos geométricos de crescente complexidade. Cada indivíduo foi exposto a cada desenho geométrico de uma vez, e esse desenho foi reproduzido após 10 segundos de observação. Quatro grupos foram designados de acordo com o seguinte nível de escolaridade: analfabeto, 1 a 4 anos, 5 a 8 anos, e acima de 8 anos de escolaridade. A performance dos indivíduos foi medida pelos itens corretamentes reproduzidos. Resultados: Uma significante diferença da idade foi encontrada entre pacientes analfabetos e os outros três grupos de escolaridades diferentes. O desenho 1 foi reproduzido melhor do que os desenhos 2 e 3 em todos os níveis de escolaridade (p<0,001). Os desenhos 2 e 3 não diferiram em nenhum nível de escolaridade. A reprodução de um desenho entre níveis de escolaridade mostrou que o grupo acima de 8 anos de escolaridade realizou melhor nos desenhos 1 e 2 (p<0,001), mas não foi no desenho 3. Conclusão: Indivíduos com idade de 60 anos ou mais com até 8 anos de escolaridade mostrou capacidade diminuída na reprodução de desenhos geométricos de alto grau de complexidade. A avaliação clínica usando testes geométricos poderia ser mal interpretada quando a escolaridade não estiver de acordo com o grau de complexidade do teste.

Visual reproduction test in normal elderly: Influence of schooling and visual task complexity.

Tests of visual reproduction are used to assess visual memory. However, when the test is based on geometrical elements results could be influenced by schooling. OBJECTIVE: To evaluate the influence of different schooling levels on performance of a visual reproduction task. METHODS: A sample of 253 individuals (66 male and 187 female), aged 60 to 92 years were evaluated on a visual reproduction task comprising three geometric pictures of increasing complexity. Each individual was shown a picture for 8 to 10 seconds and a drawing of it was then immediately elicited. Four groups were defined according to the following schooling levels: illiterate, 1 to 4 years, 5 to 8 years and over 8 years. Individual performance was measured by summing the items correctly reproduced for the three pictures. RESULTS: A significant difference for age was found between the illiterate and other three schooling groups. The reproduction of picture one was better reproduced than pictures 2 and 3 for all schooling levels (p<0.001). Pictures 2 and 3 did not differ among the schooling levels. Picture reproduction among the schooling levels showed that the group with over 8 years of schooling performed better on pictures 1 and 2 (p<0.001) but not on picture 3. CONCLUSION: Individuals aged 60 years or older, with 8 years' schooling or less, showed a reduced capacity to reproduce geometric pictures of a high degree of complexity. Clinical evaluations that use geometrical tests could be misinterpreted when not controlled for schooling level.

Teste de reprodução visual é usado para avaliar a memória visual, baseado em elementos geométricos e o resultado deve ser influenciado pela escolaridade. OBJETIVO: Avaliar os diferentes níveis de escolaridade durante a reprodução de tarefas visuais. MÉTODOS: Uma amostra de 253 indivíduos (66 masculinos e 187 femininos), com idade entre 60 e 92 anos, foi avaliada em uma tarefa de reprodução visual composta por três desenhos geométricos de crescente complexidade. Cada indivíduo foi exposto a cada desenho geométrico de uma vez, e esse desenho foi reproduzido após 10 segundos de observação. Quatro grupos foram designados de acordo com o seguinte nível de escolaridade: analfabeto, 1 a 4 anos, 5 a 8 anos, e acima de 8 anos de escolaridade. A performance dos indivíduos foi medida pelos itens corretamentes reproduzidos. RESULTADOS: Uma significante diferença da idade foi encontrada entre pacientes analfabetos e os outros três grupos de escolaridades diferentes. O desenho 1 foi reproduzido melhor do que os desenhos 2 e 3 em todos os níveis de escolaridade (p<0,001). Os desenhos 2 e 3 não diferiram em nenhum nível de escolaridade. A reprodução de um desenho entre níveis de escolaridade mostrou que o grupo acima de 8 anos de escolaridade realizou melhor nos desenhos 1 e 2 (p<0,001), mas não foi no desenho 3. CONCLUSÃO: Indivíduos com idade de 60 anos ou mais com até 8 anos de escolaridade mostrou capacidade diminuída na reprodução de desenhos geométricos de alto grau de complexidade. A avaliação clínica usando testes geométricos poderia ser mal interpretada quando a escolaridade não estiver de acordo com o grau de complexidade do teste.

Clinicopathologic analysis of progressive non-fluent aphasia and corticobasal degeneration:case report and review / Estudo clínicopatologico de afasia progressiva não-fluente e degeneração córtico-basal: relato de caso e revisão

Objective: To investigate progressive non-fluent aphasia and histopathologically-proven corticobasal degeneration. Methods: We evaluated symptoms, signs, neuropsychological deficits, and radiology data longitudinally, in a patient with autopsy-proven corticobasal degeneration and correlated these observations directly to the neuroanatomic distribution of the disease. Results: At presentation, a specific pattern of cognitive impairment was evident with an extreme extrapyramidal motor abnormality. Follow-up examination revealed persistent impairment of praxis and executive functioning, progressive worsening of language performance, and moderately preserved memory. The motor disorder manifested and worsened as the condition progressed. Many of the residual nerve cells were ballooned and achromatic with eccentric nuclei. Tau-immunoreactive pathology was significantly more prominent in neurons in the frontal and parietal cortices and dentate nuclei than in temporal neocortex, hippocampi and brainstem. Conclusion: The clinical diagnosis of progressive non-fluent aphasia secondary to corticobasal degeneration hinged on a specific pattern of impaired cognition as well as an extrapyramidal motor disorder, reflecting the neuroanatomic distribution of the disease in frontal and anterior temporal cortices and the dentate nuclei.

Objetivo: Investigar o quadro clínico de afasia progressiva não-fluente e confirmação histopatológica de degeneração córtico-basal. Métodos: Foram avaliadas as alterações clínicas, neuropsicológicas e de neuroimagem, durante todo o curso clínico da doença. O diagnóstico de degeneração córtico-basal foi confirmado por estudo histopatológico. Essas observações foram diretamente relacionadas com a distribuição anatômica da doença. Resultados: Foi observada uma forma específica de prejuízo cognitivo associada com importante alteração extrapiramidal. Durante o curso clínico, surgiram apraxia e disfunção executiva, piora progressiva da linguagem e memória moderadamente preservada. As alterações extrapiramidais pioraram progressivamente à rigidez universal e postura distônica. As reações de imunohistoquímica para a proteína tau foram significativamente mais proeminentes nos neurônios residuais de aspecto baloniformes e acromáticos do córtex frontal e parietal e núcleo denteado do cerebelo do que nos do neocórtex temporal, hipocampo e tronco cerebral. Conclusão: O diagnóstico clínico de afasia progressiva não-fluente quando evolui para degeneração córtico-basal deve apresentar uma forma específica de prejuízo cognitivo, incluindo as alterações motoras, refletindo uma distribuição neuroanatômica da doença no córtex frontal e temporal anterior e no núcleo denteado do cerebelo.