Incidência de hipersedação e síndrome de abstinência submetidos ao uso de sedoanalgésicos em hospitais brasileiros / Incidence of hypersedation and withdrawal syndrome submitted to the use of sedoanalgesics in brazilian hospitals

A unidade de terapia intensiva (UTI) é um ambiente muito propício à ocorrência de eventos adversos a medicamentos, tanto pelo estado crítico dos pacientes internados quanto pela polimedicação e frequentes modificações na farmacoterapia, o que tende a prejudicar a evolução clínica do paciente. Em UTIs pediátricas, a questão adquire aspectos diferenciados devido a imaturidade do organismo dos pacientes, o que o torna mais suscetível a efeitos prejudiciais de fármacos, além de promover farmacocinética diferenciada. Nos casos em que é necessário o uso de sedoanalgésicos, sobretudo para o emprego de suporte ventilatório, lida-se com os riscos de sedação profunda, síndrome de abstinência, além de aumento do tempo de internação e sequelas de longo prazo. Nesse contexto, o presente artigo se propõe a discutir, através de uma revisão bibliográfica, a ocorrência de hipersedação e síndrome de abstinência em pacientes pediátricos, internados em UTIs de hospitais brasileiros

Neurobehavioral and Antioxidant Effects of Ethanolic Extract of Yellow Propolis

Propolis is a resin produced by bees from raw material collected from plants, salivary secretions, and beeswax. New therapeutic properties for the Central Nervous System have emerged. We explored the neurobehavioral and antioxidant effects of an ethanolic extract of yellow propolis (EEYP) rich in triterpenoids, primarily lupeol and β-amyrin. Male Wistar rats, 3 months old, were intraperitoneally treated with Tween 5% (control), EEYP (1, 3, 10, and 30 mg/kg), or diazepam, fluoxetine, and caffeine (positive controls) 30 min before the assays. Animals were submitted to open field, elevated plus maze, forced swimming, and inhibitory avoidance tests. After behavioral tasks, blood samples were collected through intracardiac pathway, to evaluate the oxidative balance. The results obtained in the open field and in the elevated plus maze assay showed spontaneous locomotion preserved and anxiolytic-like activity. In the forced swimming test, EEYP demonstrated antidepressant-like activity. In the inhibitory avoidance test, EEYP showed mnemonic activity at 30 mg/kg. In the evaluation of oxidative biochemistry, the extract reduced the production of nitric oxide and malondialdehyde without changing level of total antioxidant, catalase, and superoxide dismutase, induced by behavioral stress. Our results highlight that EEYP emerges as a promising anxiolytic, antidepressant, mnemonic, and antioxidant natural product

Acidente vascular encefálico isquêmico na exposição crônica ao etanol: estudo pré-clínico da comorbidade e da resposta a minociclina

Stroke is the second largest cause of death in the world and the leading in Brazil, with 87% of strokes due to ischemic processes. Chronic ethanol consumption, usually beginning in adolescence, is recognized as an independent risk factor for increased morbidity and mortality by stroke. Although cases combining the two diseases are relatively common, there is no data in animals or clinical models demonstrating the quality or mechanisms of interaction between the two morbidities, nor its impact on therapeutic intervention. Considering the recent studies proposing minocycline as a new therapeutic tool for the treatment of stroke, this study aimed to investigate the interaction between the Chronic Alcoholic Intoxication (CAI) started in adolescence and the stroke in motor cortex of adult rats, and the effects of treatment with minocycline on this interaction, using behavioral, cellular and molecular parameters. Female Wistar rats (35 days-old) were chronically exposed to ethanol (6.5 g/kg/day, 22.5% w/v) or water for 55 days. One day after the end of the CAI focal ischemia was induced in motor cortex with the endothelin-1 (ET-1), followed by seven-day treatment with minocycline or saline. After this period, the animals were assayed with open field and rota rod tests. Immediately, animals were sacrificed and cortex was dissected for evaluation of nitrite and lipid peroxidation levels. In all groups, some animals were perfused and the motor cortex subjected to histological analysis to assess the damage, and immunohistochemical labeling to neuronal death (anti-NeuN), microglial/macrophage (anti-ED1) and astrocytes (anti-GFAP) activation. The ethanol intoxication from puberty to adulthood potentiated the damage caused by stroke, causing major losses in capacity to start and running movements as well as the strength and motor coordination compared to ischemic animals pretreated with water. These manifestations were accompanied by increased neuronal loss, reduced ED-1+ and GFAP+ cells and higher levels of nitrite and lipid peroxidation. Treatment with minocycline was effective in preventing/reverse motor deficits and tissue damage induced by focal ischemia, also inhibiting the increase in oxidative stress markers. The CAI either alone with succeeded by focal ischemia, harmed the outcome of treatment with minocycline. Our results indicate that heavy alcohol intoxication during adolescence exacerbates the motor deficit and tissue damage in animals subjected to focal ischemia. This process appears to be associated with microglia/astroglial activation, but mainly with oxidative stress. It also shows that the previous history of CAI started adolescence interferes significantly in the treatment of cerebral ischemia with minocycline.O acidente vascular encefálico (AVE) é a segunda maior causa de morte no mundo e a principal no Brasil, sendo que 87% dos AVE ocorrem por processos isquêmicos (AVEI). O consumo crônico de etanol, que se inicia geralmente na adolescência, é reconhecido como um fator de risco independente para a elevação da morbidade e mortalidade por AVEI. Apesar de que casos que combinem as duas patologias sejam relativamente frequentes, não há dados disponíveis em modelos animais ou clínicos que demonstrem a qualidade ou mecanismos de interação entre as duas morbidades, e tão pouco suas consequências sobre a intervenção terapêutica. Considerando então os recentes estudos que propõem a minociclina como nova ferramenta terapêutica para o tratamento do AVEI, este estudo teve por objetivo investigar a interação entre a Intoxicação Alcoólica Crônica (IAC) iniciada na adolescência e o AVEI em córtex motor na fase adulta em ratos, e os efeitos do tratamento com minociclina sobre esta interação, usando parâmetros comportamentais, celulares e moleculares. Ratas Wistar (de 35 dias de idade) foram expostas cronicamente a etanol (6,5 g/kg/dia, 22,5% m/v) ou água por 55 dias. Um dia após o fim da IAC, foi induzida isquemia focal no córtex motor com endotelina- 1 (ET-1), seguindo-se sete dias de tratamento com minociclina ou salina. Ao final deste período os animais foram testados em modelos de campo aberto e rota rod. A seguir, os animais foram sacrificados e o córtex dissecado para avaliação dos níveis de nitritos e de peroxidação lipídica. De cada grupo, alguns animais foram perfundidos e o córtex motor submetidos à analise histológica, para avaliação do dano, e histopatológica, para a morte neuronal (anti-NeuN), ativação microglial/macrófagica (Anti-ED1) e astrocitária (anti-GFAP). A intoxicação por etanol a partir da puberdade até a idade adulta potencializou os danos causados pela isquemia, causando grandes perdas na capacidade de iniciar e gerir os movimentos, bem como na coordenação e força motora em comparação aos animais isquêmicos pré-tratados com água. Estas manifestações foram acompanhadas de aumento da perda neuronal, redução do número de células ED1+ e GFAP+ e maiores níveis de nitritos e peroxidação lipídica. O tratamento com minociclina foi eficiente em prevenir/reverter as perdas motoras e danos teciduais induzidos pela isquemia focal, inibindo também a elevação dos marcadores de estresse oxidativo. A IAC tanto isoladamente como sucedida pela isquemia focal, modificaram o desfecho do tratamento com minociclina. Os nossos resultados indicam que a intoxicação com álcool durante a adolescência agrava o déficit motor e danos no tecido em animais sujeitos a isquemia focal no córtex motor. Este processo parece estar associado com a ativação microglial/ astrocitária, mas principalmente com o estresse oxidativo. Mostra ainda que o histórico prévio de IAC iniciado na adolescência interfere significativamente no tratamento da isquemia cerebral com minociclina

Methylmercury plus Ethanol Exposure: How Much Does This Combination Affect Emotionality?

Mercury is a heavy metal found in organic and inorganic forms that represents an important toxicant with impact on human health. Mercury can be released in the environment by natural phenoms (i.e., volcanic eruptions), industrial products, waste, or anthropogenic actions (i.e., mining activity). Evidence has pointed to mercury exposure inducing neurological damages related to emotional disturbance, such as anxiety, depression, and insomnia. The mechanisms that underlie these emotional disorders remain poorly understood, although an important role of glutamatergic pathways, alterations in HPA axis, and disturbance in activity of monoamines have been suggested. Ethanol (EtOH) is a psychoactive substance consumed worldwide that induces emotional alterations that have been strongly investigated, and shares common pathophysiological mechanisms with mercury. Concomitant mercury and EtOH intoxication occur in several regions of the world, specially by communities that consume seafood and fish as the principal product of nutrition (i.e., Amazon region). Such affront appears to be more deleterious in critical periods of life, such as the prenatal and adolescence period. Thus, this review aimed to discuss the cellular and behavioral changes displayed by the mercury plus EtOH exposure during adolescence, focused on emotional disorders, to answer the question of whether mercury plus EtOH exposure intensifies depression, anxiety, and insomnia observed by the toxicants in isolation

Margaritaria nobilis L.F. (Phyllanthaceae): Ethnopharmacology and Application of Computational Tools in the Annotation of Bioactive Molecules

Margaritaria nobilis is a shrubby species widely distributed in Brazil from the Amazon to the Atlantic Rainforest. Its bark and fruit are used in the Peruvian Amazon for disinfecting abscesses and as a tonic in pregnancy, respectively, and its leaves are used to treat cancer symptoms. From analyses via UHPLC-MS/MS, we sought to determine the chemical profile of the ethanolic extract of M. nobilis leaves by means of putative analyses supported by computational tools and spectral libraries. Thus, it was possible to annotate 44 compounds, of which 12 are phenolic acid derivatives, 16 are O-glycosylated flavonoids and 16 hydrolysable tannins. Among the flavonoids, although they are known, except for kaempferol, which has already been isolated from this species, the other flavonoids (10, 14, 15, 21, 24–26, 28–30, 33–35, 40 and 41) are being reported for the first time in the genus. Among the hydrolysable tannins, six ellagitannins present the HHDP group (6, 19, 22, 31, 38 and 43), one presents the DHHDP group (5), and four contain oxidatively modified congeners (12, 20, 37 and 39). Through the annotation of these compounds, we hope to contribute to the improved chemosystematics knowledge of the genus. Furthermore, supported by a metric review of the literature, we observed that many of the compounds reported here are congeners of authentically bioactive compounds. Thus, we believe that this work may help in understanding future pharmacological activities

The Role of the Adenosine System on Emotional and Cognitive Disturbances Induced by Ethanol Binge Drinking in the Immature Brain and the Beneficial Effects of Caffeine

Binge drinking intake is the most common pattern of ethanol consumption by adolescents, which elicits emotional disturbances, mainly anxiety and depressive symptoms, as well as cognitive alterations. Ethanol exposure may act on the adenosine neuromodulation system by increasing adenosine levels, consequently increasing the activation of adenosine receptors in the brain. The adenosine modulation system is involved in the control of mood and memory behavior. However, there is a gap in the knowledge about the exact mechanisms related to ethanol exposure’s hazardous effects on the immature brain (i.e., during adolescence) and the role of the adenosine system thereupon. The present review attempts to provide a comprehensive picture of the role of the adenosinergic system on emotional and cognitive disturbances induced by ethanol during adolescence, exploring the potential benefits of caffeine administration in view of its action as a non-selective antagonist of adenosine receptors

“Special K” Drug on Adolescent Rats: Oxidative Damage and Neurobehavioral Impairments

Ketamine is used in clinical practice as an anesthetic that pharmacologically modulates neurotransmission in postsynaptic receptors, such as NMDA receptors. However, widespread recreational use of ketamine in “party drug” worldwide since the 1990s quickly spread to the Asian orient region. Thus, this study aimed at investigating the behavioral and oxidative effects after immediate withdrawal of intermittent administration of ketamine in adolescent female rats. For this, twenty female Wistar rats were randomly divided into two groups: control and ketamine group (n=10/group). Animals received ketamine (10 mg/kg/day) or saline intraperitoneally for three consecutive days. Three hours after the last administration, animals were submitted to open field, elevated plus-maze, forced swim tests, and inhibitory avoidance paradigm. Twenty-four hours after behavioral tests, the blood and hippocampus were collected for the biochemical analyses. Superoxide dismutase, catalase, nitrite, and lipid peroxidation (LPO) were measured in the blood samples. Nitrite and LPO were measured in the hippocampus. The present findings demonstrate that the early hours of ketamine withdrawal induced oxidative biochemistry unbalance in the blood samples, with elevated levels of nitrite and LPO. In addition, we showed for the first time that ketamine withdrawal induced depressive- and anxiety-like profile, as well as short-term memory impairment in adolescent rodents. The neurobehavioral deficits were accompanied by the hippocampal nitrite and LPO-elevated levels

Effects of chronic ethanol (EtOH) administration (6.5 g/kg/day) during adolescence over a period of 55 days (i.e., from the 35th day until the 90th day of life) in the body weight gain of rats.

<p>The results are expressed as mean ± SEM of the body weight with interval of 7 days (n = 10 animals per group). *P<0.05 compared to control group (One-way ANOVA with repeated measures followed by Tukey’s test).</p

Effects of chronic ethanol (EtOH) administration (6.5 g/kg/day) during adolescence on the oxidative stress parameters of Wistar rats.

<p>The results are expressed as mean ± SEM of the: (A) Nitrite concentration per milligram of protein; (B) Malondialdehyde (MDA) concentration per miligrams of protein (n = 5 animals per group). *P<0.05 compared to control group (t-Student test).</p

Schematic representation of the methodology utilized to count cells in the motor cortex area.

<p>Schematic representation of the methodology utilized to count cells in the motor cortex area.</p