Resveratrol improves cognitive function in severely burned rats by inhibiting hippocampal NF-κB/JNK pathway / 细胞与分子免疫学杂志

Objective To investigate the protective effect of resveratrol (RSV) on improving cognitive function in severely burned rats and its possible mechanism. Methods 18 male SD rats aged 18-20 months were randomly divided into 3 groups: control group, model group and RSV group, with 6 rats in each group. After successful modeling, the rats in RSV group were gavaged once daily with RSV (20 mg/kg). Meanwhile, the rats in control group and model group were gavaged once daily with an equal volume of sodium chloride solution. After 4 weeks, the cognitive function of all rats was estimated by Step-down Test. The concentration of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) protein in serum of rats were detected by ELISA. The expression of IL-6, TNF-α mRNA and protein were estimated by real-time PCR and Western blotting. The apoptosis of hippocampal neurons was tested by terminal deoxynuclectidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL). The expression of nuclear transcription factor-κB (NF-κB)/c-Jun N-terminal kinase (JNK) pathway-related proteins in hippocampus were assessed by Western blotting. Results Compared with the rats in model group, rats in RSV group exhibited improved cognitive function. Consistently, the rats in RSV group had a reduced concentration of TNF-α and IL-6 in serum, decreased mRNA and protein expressions of TNF-α and IL-6 in hippocampus, and decreased apoptosis rate and relative expression of p-NF-κB p65/NF-κB p65 and p-JNK/JNK in hippocampal neurons. Conclusion RSV alleviates inflammatory response and hippocampal neuronal apoptosis by inhibiting NF-κB/JNK pathway, thereby improving cognitive function in severely burned rats.

Bacopa monnieri: historical aspects to promising pharmacological actions for the treatment on central nervous system diseases / Bacopa monnieri: aspectos históricos de las acciones farmacológicas prometedoras para el tratamiento de enfermedades del sistema nervioso central

Bacopa monnieri(L.) Wettst. (Plantaginaceae), also known as Brahmi, has been used to improve cognitive processes and intellectual functions that are related to the preservation of memory. The objective of this research is to review the ethnobotanical applications, phytochemical composition, toxicity and activity of B. monnieri in the central nervous system. It reviewed articles on B. monnieri using Google Scholar, SciELO, Science Direct, Lilacs, Medline, and PubMed. Saponins are the main compounds in extracts of B. monnieri. Pharmacological studies showed that B. monnieri improves learning and memory and presents biological effects against Alzheimer's disease, Parkinson's disease, epilepsy, and schizophrenia. No preclinical acute toxicity was reported. However, gastrointestinal side effects were reported in some healthy elderly individuals. Most studies with B. monnieri have been preclinical evaluations of cellular mechanisms in the central nervous system and further translational clinical research needs to be performed to evaluate the safety and efficacy of the plant.

Bacopa monnieri (L.) Wettst. (Plantaginaceae), también conocida como Brahmi, se ha utilizado para mejorar los procesos cognitivos y las funciones intelectuales que están relacionadas con la preservación de la memoria. El objetivo de esta investigación es revisar las aplicaciones etnobotánicas, composición fitoquímica, toxicidad y actividad de B. monnieri en el sistema nervioso central. Se revisaron artículos sobre B. monnieri utilizando Google Scholar, SciELO, Science Direct, Lilacs, Medline y PubMed. Las saponinas son los principales compuestos de los extractos de B. monnieri. Los estudios farmacológicos mostraron que B. monnieri mejora el aprendizaje y la memoria y presenta efectos biológicos contra la enfermedad de Alzheimer, la enfermedad de Parkinson, la epilepsia y la esquizofrenia. No se informó toxicidad aguda preclínica. Sin embargo, se informaron efectos secundarios gastrointestinales en algunos ancianos sanos. La mayoría de los estudios con B. monnieri han sido evaluaciones preclínicas de los mecanismos celulares en el sistema nervioso central y es necesario realizar más investigaciones clínicas traslacionales para evaluar la seguridad y eficacia de la planta.

Intrauterine and postnatal exposure to tobacco and wood smoke on hypothalamic development and cognition: an integrative review of the literature / Exposición intrauterina y postnatal al humo de tabaco y de leña en el desarrollo hipotalámico y la cognición: una revisión integrativa de la literatura

SUMMARY: Exposure to air pollution and its pollutants has been associated with important effects on human health since the first years of life, thus it has been seen that exposure to tobacco smoke and wood smoke is directly related to cardiovascular and pulmonary diseases, respiratory and cancers. However, exposure to air pollution during fetal development and its effects on brain structure and function during early childhood and adolescence have been little studied. In this review we have analyzed the literature on prenatal exposure to tobacco and wood smoke and its relationship with hypothalamic development and cognition in the first years of life.The molecular, morphological and physiological aspects of the relationship between pre- and postnatal exposure to tobacco and wood smoke with neural developmental, cognitive and behavioral problems during early childhood and adolescence have not yet been fully clarified. The information available in the scientific literature based on antecedents obtained from epidemiological studies has been negatively affected by confounding variables and great methodological challenges that make it impossible to affirm an exact causal relationship with certainty.

RESUMEN: La exposición a la contaminación del aire se ha asociado con importantes efectos en la salud humana desde los primeros años de vida. Estudios han demostrado con certeza que la exposición al humo de tabaco y humo de leña está directamente relacionada con enfermedades cardiovasculares, pulmonares, respiratorias y cánceres. Sin embargo, la exposición a la contaminación del aire durante el desarrollo fetal y sus efectos a posteriori sobre la estructura y función del cerebro durante la primera infancia y la adolescencia son aún desconocidos. En esta revisión analizamos la literatura sobre la exposición prenatal al tabaco y al humo de leña y su relación con el desarrollo hipotalámico y la cognición en los primeros años de vida. Los aspectos moleculares, morfológicos y fisiológicos de la asociación entre la exposición pre y postnatal al humo de tabaco o al humo de leña con problemas del desarrollo neurológico normal, cognitivos y de comportamiento durante la primera infancia y la adolescencia aún no se han aclarado completamente. La información disponible en la literatura científica basada en antecedentes obtenidos de estudios epidemiológicos ha sido afectada negativamente por variables de confusión y grandes desafíos metodológicos que hacen imposible afirmar una relación directa y causal exacta con certeza.

Anestesia general en infantes: consideraciones neurobiológicas y neuropsicológicas / General anesthesia in infants: neurobiological and neuropsychological concerns

Resumen La anestesia general es una herramienta imprescindible para el proceso quirúrgico, ya que disminuye el dolor, reduce la ansiedad y genera inconsciencia. Sin ella, las cirugías serían dolorosas, riesgosas y emocionalmente traumáticas. La reciente emisión de una alerta sobre el uso de fármacos anestésicos en niños menores de 3 años por parte de la Food and Drug Administration (FDA) de los Estados Unidos generó controversia en torno a sus posibles efectos negativos. En este artículo se abordan los principales hitos del desarrollo neurobiológico del niño y se revisan las posibles consecuencias neuropsicológicas del uso de anestesia general en esta población. La mayoría de los reportes que abordan este tema son de tipo retrospectivo y arrojan resultados controversiales por sus inherentes dificultades metodológicas. Sin embargo, el estudio prospectivo sobre seguridad del uso de anestesia general en niños de la Clínica Mayo (MASK, Mayo Anesthesia Safety in Kids), junto con otros estudios a gran escala, han confirmado algunos datos obtenidos en los estudios experimentales que dieron sustento a la alerta emitida por la FDA. Así, las evidencias hasta ahora publicadas sugieren que el uso de anestesia general es seguro para el desarrollo cognitivo general del niño, aunque evidencian también alteraciones focalizadas en procesos cognitivos específicos que deben ser consideradas por el médico y la familia ante un procedimiento quirúrgico-anestésico.

Abstract General anesthetics are crucial drugs for surgical interventions, which are indicated to induce analgesia, diminish pain, and reduce anxiety in order to facilitate invasive procedures. In pediatric patients, benefits of general anesthetics also include abolishment of motility. Besides their probed benefits on surgery, the recent warning of the Food and Drug Administration (FDA) on the use of general anesthetics in children yielded a controversy on their potential neurotoxic effects. In this review, the main facts of the cerebral development are studied, and the available evidence concerning the use of general anesthesia on the neuropsychological development of children is analyzed. Most of the studies found were uncontrolled retrospective cohorts for which conclusions are difficult to obtain. However, a few group of controlled studies, including the Mayo Anesthesia Safety in Kids study (MASK), have partially supported the FDA warning. Cumulated evidence appears to support the safety use of general anesthetics, but no conclusive data supporting that it may induce massive effects on the cognitive development of exposed children has been reported. Important evidence suggests that specific cognitive functions may result altered under long-term expositions. Such data must be considered for those involved in anesthetic procedures.

Circulación de información sobre medicamentos y otras sustancias para aumentar el rendimiento cognitivo: un estudio de un blog brasileño (2015-2017) / Circulation of information on drugs and other substances to increase cognitive performance: a study of a Brazilian blog (2015-2017)

RESUMEN Al observar los procesos de (bio)medicalización y farmacologización de la sociedad, este artículo aborda los medicamentos que han sido utilizados por individuos sanos para aumentar sus dimensiones cognitivas, como el estado de alerta, la memoria y la concentración. Las llamadas "drogas inteligentes" o "drogas nootrópicas" se han extendido entre los jóvenes a través de Internet. La circulación de información sobre tales drogas se analiza desde un blog brasileño llamado Cérebro Turbinado, sobre el que se realizó una investigación documental basada en el material publicado en el blog entre 2015 y 2017, de acceso público. La investigación adopta marcos teóricos y metodológicos de las ciencias sociales, junto a una perspectiva antropológica. Los resultados muestran que el blog actúa como un medio para la difusión del conocimiento biomédico entre el público lego y muestra la producción de nuevas formas de subjetividad al revelar los significados que se atribuyen a tales sustancias en los procesos de socialización.

ABSTRACT By observing the processes of (bio)medicalization and pharmaceuticalization of society, this article addresses drugs that have been used by healthy individuals to increase cognitive dimensions such as alertness, memory, and concentration. The use of so-called "smart drugs" or "nootropics" has spread among young people, aided by the internet. The circulation of information about such drugs are analyzed using a Brazilian blog called "Cérebro Turbinado," through publications available for public access between 2015 and 2017. The study adopts theoretical and methodological frameworks of the social sciences, including an anthropological perspective. Documental research was conducted on the internet, specifically with scientific dissemination materials and the material available from the aforementioned blog. The results show that the blog acts as a medium for spreading biomedical knowledge among the lay public and indicates the production of new forms of subjectivity by revealing the meanings attributed to these substances in socialization processes.

Polifarmácia e cognição em pacientes com idade avançada / Polypharmacy and cognition in elderly patients

Objetivo: Avaliar a prevalência da polifarmácia e da prescrição de medicações inapropriadas, bem como suas associações com a capacidade cognitiva e funcional do idoso. Métodos: Estudo observacional transversal, no qual foram analisadas as medicações prescritas em 141 prontuários para pacientes acima de 50 anos, em associação com testes que quantificaram a capacidade funcional e cognitiva deles. Resultados: Observou-se média de 4,41 medicamentos por paciente, sendo que 0,41 deles foram considerados inapropriado, segundo o critério de Beers. Verificou-se também relação estatisticamente significativa quanto ao número de medicações e testes que mediam a capacidade funcional e cognitiva dos idosos. Conclusão: O aumento da polifarmácia e da prescrição de medicações potencialmente inadequadas acarretou significativa piora da capacidade cognitiva e funcional do idoso

Objective: To evaluate the prevalence of polypharmacy and of the prescription of inappropriate medications, as well as their associations with the cognitive and functional capacity of the elderly. Methods: Cross-sectional observational study which analyzed the drugs prescribed in 141 medical records for patients over 50 years of age, associated with tests that quantified their functional and cognitive capacity. Results: An average of 4.41 medications per patient was observed, and 0.41 were considered inappropriate according to the Beers criteria. There was also a statistically significant relation regarding the number of medications and tests that measure the functional and cognitive capacity of the elderly. Conclusion: The increase in polypharmacy and in the prescription of potentially inappropriate medications led to a significant impairment of the cognitive and functional capacity of the elderly

The effect of bispectral index monitoring on cognitive performance following sedation for outpatient colonoscopy: a randomized controlled trial

ABSTRACT BACKGROUND: Bispectral index (BIS) monitoring can positively affect cognitive performance through decreasing the use of sedative agents. We aimed to evaluate the effect of BIS monitoring on early cognitive performance among patients undergoing sedation for colonoscopy. DESIGN AND SETTING: Randomized, controlled trial in a university hospital. METHODS: 100 patients were randomized into two groups. In the monitored group (n = 50), the depth of anesthesia was monitored using the BIS, and BIS scores were maintained between 60 and 80. In the usual care group (n = 50), BIS monitoring was not performed. To determine the patients' baseline cognitive performance levels, the mini-mental state examination (MMSE), Trieger dot test (TDT) and clock drawing test (CDT) were used. The patients' post-procedure cognitive performance levels were determined when they were classified as ready for discharge. RESULTS: The total volume (mg) of propofol used [median (range) IQR] in the sedation procedure was lower in the monitored group [100 (50-200) 100-140] than in the usual care group [150 (75-200) 100-200] (P < 0.001). The discharge scores [mean (SD)] using MMSE and CDT were higher in the monitored group [26 (3) and 3 (1), respectively] than in the usual care group [23 (3) and 2 (1), respectively] (P = 0.002 and P = 0.002, respectively). The discharge scores using TDT [mean (SD)] were lower in the monitored group [11 (7)] than in the usual care group [15 (11)] (P = 0.033). CONCLUSION: BIS monitoring among sedated patients was associated with lower propofol use and smaller decline in cognitive performance. CLINICAL TRIAL REGISTRATION: This trial was registered in the Australian New Zealand Clinical Trial Registry (ACTRN12617000134325).

Cognitive functions in children with congenital adrenal hyperplasia

ABSTRACT Objective There is controversy regarding cognitive function in patients with congenital adrenal hyperplasia (CAH). This study is aimed at the assessment of cognitive functions in children with CAH, and their relation to hydrocortisone (HC) therapy and testosterone levels. Subjects and methods Thirty children with CAH due to 21 hydroxylase deficiency were compared with twenty age- and sex-matched healthy controls. HC daily and cumulative doses were calculated, the socioeconomic standard was assessed, and free testosterone was measured. Cognitive function assessment was performed using the Wechsler Intelligence Scale - Revised for Children and Adults (WISC), the Benton Visual Retention Test, and the Wisconsin Card Sorting Test (WCST). Results The mean age (SD) of patients was 10.22 (3.17) years [11 males (36.7%), 19 females (63.3%)]. Mean (SD) HC dose was 15.78 (4.36) mg/m 2 /day. Mean (SD) cumulative HC dose 44,689. 9 (26,892.02) mg. Patients had significantly lower scores in all domains of the WISC test, performed significantly worse in some components of the Benton Visual Retention Test, as well as in the Wisconsin Card Sorting Test. There was no significant difference in cognitive performance when patients were subdivided according to daily HC dose (< 10, 10 - 15, > 15 mg/m 2 /day). A positive correlation existed between cumulative HC dose and worse results of the Benton test. No correlation existed between free testosterone and any of the three tests. Conclusion Patients with CAH are at risk of some cognitive impairment. Hydrocortisone therapy may be implicated. This study highlights the need to assess cognitive functions in CAH.

The effect of vitamin D on cognitive functions in young female patients: a prospective controlled study using the Montreal Cognitive Assessment / O efeito da vitamina D nas funções cognitivas em pacientes jovens do sexo feminino: um estudo prospectivo controlado usando a avaliação cognitiva de Montreal

ABSTRACT Aim: Our aim was to determine whether there is a relationship between vitamin D [25(OH)D] and cognitive functioning in women with low 25(OH)D levels. Methods: Ninety female patients, 25-45 years of age, who attended our outpatient clinic and had 25(OH)D levels < 30 ng/mL, were included. The Montreal Cognitive Assessment (MoCA) scale was used to determine cognitive functioning; the scale is divided into seven subgroups. Patients were divided into three subgroups according to their 25(OH)D levels. After a three-month period of 25(OH) D replacement, the patients underwent a re-evaluation using the MoCA scale. Results: The total MoCA score before treatment was significantly different from the score after treatment (p < 0.05). Language and delayed recall functions were significantly different before and after treatment (p < 0.05). Conclusion: Vitamin D levels were related to cognitive functioning in our study group.

RESUMO Objetivo: Nosso objetivo foi determinar se existe uma relação entre a vitamina D [25(OH)D] e o funcionamento cognitivo em mulheres com baixos níveis de 25(OH)D. Métodos: Noventa pacientes do sexo feminino (25-45 anos de idade) que se apresentaram ao nosso ambulatório e tinham níveis de 25(OH)D <30 ng/mL foram incluídas. A escala de avaliação cognitiva de Montreal (MoCA) foi usada para determinar o funcionamento cognitivo; a escala é dividida em sete subgrupos. As pacientes foram divididas em três subgrupos de acordo com seus níveis de 25(OH)D. Após um período de três meses de reposição de 25(OH)D, as pacientes foram submetidas a uma reavaliação de acordo com a escala MoCA. Resultados: O escore total da MoCA antes do tratamento foi significativamente diferente do escore após o tratamento (p <0,05). As funções de idioma e recordação atrasada foram mais significativamente diferentes entre antes e depois do tratamento (p <0,05). Conclusão: O nível de vitamina D foi relacionado ao funcionamento cognitivo em nosso grupo de estudo.

Hypericum perforatum chronic treatment affects cognitive parameters and brain neurotrophic factor levels

Objective: To evaluate the effects of Hypericum perforatum (hypericum) on cognitive behavior and neurotrophic factor levels in the brain of male and female rats. Methods: Male and female Wistar rats were treated with hypericum or water during 28 days by gavage. The animals were then subjected to the open-field test, novel object recognition and step-down inhibitory avoidance test. Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell-line derived neurotrophic factor (GDNF) levels were evaluated in the hippocampus and frontal cortex. Results: Hypericum impaired the acquisition of short- and long-term aversive memory in male rats, evaluated in the inhibitory avoidance test. Female rats had no immediate memory acquisition and decreased short-term memory acquisition in the inhibitory avoidance test. Hypericum also decreased the recognition index of male rats in the object recognition test. Female rats did not recognize the new object in either the short-term or the long-term memory tasks. Hypericum decreased BDNF in the hippocampus of male and female rats. Hypericum also decreased NGF in the hippocampus of female rats. Conclusions: The long-term administration of hypericum appears to cause significant cognitive impairment in rats, possibly through a reduction in the levels of neurotrophic factors. This effect was more expressive in females than in males.

Efeitos da carga anticolinérgica cognitiva em idosos ­ uma revisão integrativa / Effect of anticholinergic cognitive burden in the elderly ­ an integrative review

Idosos são mais susceptíveis aos efeitos adversos cognitivos de fármacos com atividade anticolinérgica. Isso se deve a fatores associados à velhice, como comprometimento da atividade colinérgica central, aumento da permeabilidade da barreira hematoencefálica, redução do metabolismo hepático e da excreção renal e polifarmácia. A escala de Carga Anticolinérgica Cognitiva (ACB) foi elaborada com o intuito de reduzir a ocorrência eventos adversos cognitivos à farmacoterapia, como declínio cognitivo, demência e delírio. O objetivo desta revisão integrativa foi reunir achados obtidos em estudos clínicos sobre a associação entre alterações cognitivas e ACB por meio da escala. A busca nas bases MEDLINE/PubMed e BVS-Bireme gerou 11 artigos completos em inglês. Sete são longitudinais, três transversais e um observacional. Oito foram conduzidos nos Estados Unidos. Nove de 10 evidenciaram a relação entre ACB e déficit cognitivo. O MMSE foi o teste de avaliação cognitiva mais usado. As evidências mostram a importância da revisão da farmacoterapia de todo paciente com déficit cognitivo ou delírio. Deve-se evitar assumir que o declínio cognitivo é demência até as possíveis causas farmacológicas tenham sido descartadas. (AU)

Elderly people are more susceptible to cognitive adverse effects of medications with anticholinergic activity. This is due to factors associated with aging, such as decline in central cholinergic activity, increase in blood-brain barrier permeability, decline in hepatic and renal metabolism and polypharmacy. The Anticholinergic Cognitive Burden (ACB) scale was developed reduce the risk for developing adverse cognitive outcomes such as cognitive impairment, dementia and delirium. The purpose of this integrative review is to bring together findings from clinical studies on the association between cognitive impairment and ACB scale. The search in MEDLINE/PubMed and BVS-Medicine bases generated 11 full articles in English. Seven were longitudinal, three transversal and one observational. Eight of them were conducted in the United States. Nine of 10 showed the relationship between the ACB and cognitive impairment due to at least one moderate or severe anticholinergic medication or due to concomitant use of multiple medications. MMSE was the most commonly cognitive assessment. Evidence shows the importance of the review of pharmacotherapy of all patients with cognitive impairment or delirium. It is important not to assume that cognitive decline is dementia until pharmacologic causes have been excluded. (AU)

Tryptophan overloading activates brain regions involved with cognition, mood and anxiety

ABSTRACT Tryptophan is the only precursor of serotonin and mediates serotonergic activity in the brain. Previous studies have shown that the administration of tryptophan or tryptophan depletion significantly alters cognition, mood and anxiety. Nevertheless, the neurobiological alterations that follow these changes have not yet been fully investigated. The aim of this study was to verify the effects of a tryptophan-enriched diet on immunoreactivity to Fos-protein in the rat brain. Sixteen male Wistar rats were distributed into two groups that either received standard chow diet or a tryptophan-enriched diet for a period of thirty days. On the morning of the 31st day, animals were euthanized and subsequently analyzed for Fos-immunoreactivity (Fos-ir) in the dorsal and median raphe nuclei and in regions that receive serotonin innervation from these two brain areas. Treatment with a tryptophan-enriched diet increased Fos-ir in the prefrontal cortex, nucleus accumbens, paraventricular hypothalamus, arcuate and ventromedial hypothalamus, dorsolateral and dorsomedial periaqueductal grey and dorsal and median raphe nucleus. These observations suggest that the physiological and behavioral alterations that follow the administration of tryptophan are associated with the activation of brain regions that regulate cognition and mood/anxiety-related responses.

Hyperbaric Oxygen Pretreatment Improves Cognition and Reduces Hippocampal Damage Via p38 Mitogen-Activated Protein Kinase in a Rat Model

PURPOSE: To investigate the effects of hyperbaric oxygen (HBO) pretreatment on cognitive decline and neuronal damage in an Alzheimer’s disease (AD) rat model. MATERIALS AND METHODS: Rats were divided into three groups: normal saline (NS), AD, and HBO+AD. In the AD group, amyloid β peptide (Aβ)₁₋₄₀ was injected into the hippocampal CA1 region of the brain. NS rats received NS injection. In the HBO+AD group, rats received 5 days of daily HBO therapy following Aβ₁₋₄₀ injection. Learning and memory capabilities were examined using the Morris water maze task. Neuronal damage and astrocyte activation were evaluated by hematoxylin-eosin staining and immunohistochemistry, respectively. Dendritic spine density was determined by Golgi-Cox staining. Tumor necrosis factor-α, interleukin-1β, and interleukin-10 production was assessed by enzyme-linked immunosorbent assay. Neuron apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling. Protein expression was examined by western blotting. RESULTS: Learning and memory dysfunction was ameliorated in the HBO+AD group, as shown by significantly lower swimming distances and escape latency, compared to the AD group. Lower rates of neuronal damage, astrocyte activation, dendritic spine loss, and hippocampal neuron apoptosis were seen in the HBO+AD than in the AD group. A lower rate of hippocampal p38 mitogen-activated protein kinase (MAPK) phosphorylation was observed in the HBO+AD than in the AD group. CONCLUSION: HBO pretreatment improves cognition and reduces hippocampal damage via p38 MAPK in AD rats.

The effects of memantine on recovery, cognitive functions, and pain after propofol anesthesia / Efeitos da memantina sobre a recuperação, funções cognitivas e dor após a anestesia com propofol

Abstract Objectives: Postoperative cognitive dysfunction refers to the problems associated with thought and memory that are often experienced after major surgery. The aim of this study is to evaluate the effects of intraperitoneally administered memantine on recovery, cognitive functions, and pain after propofol anesthesia. Methods: The study was conducted in Gazi University Animal Research Laboratory, Ankara, Turkey in January 2012. Twenty-four adult female Wistar Albino rats weighing 170-270 g were educated for 300 s in the radial arm maze (RAM) over three days. Group P was administered 150 mg kg−1 of intraperitoneal (IP) propofol; Group M was given 1 mg kg−1 of IP memantine; and Group MP was given 1 mg kg−1 of IP memantine before being administered 150 mg kg−1 of IP propofol. The control group received only IP saline. RAM and hot plate values were obtained after recovery from the groups that received propofol anesthesia and 30 min after the administration of drugs in other two groups. Results: The duration of recovery for Group MP was significantly shorter than Group P (p < 0.001), and the number of entries and exits in the RAM by Group MP was significantly higher during the first hour when compared to Group P (p < 0.0001). Hot plate values, on the other hand, were found to be significantly increased in all groups when compared to the control values, aside from Group C (p < 0.0001). Conclusion: In this study, memantine provided shorter recovery times, better cognitive functions, and reduced postoperative pain. From this study, we find that memantine has beneficial effects on recovery, cognitive functions, and pain after propofol anesthesia.

Resumo Objetivos: A disfunção cognitiva no pós-operatório refere-se a problemas associados ao pensamento e à memória que são frequentemente manifestados após uma cirurgia de grande porte. O objetivo deste estudo foi avaliar os efeitos da memantina administrada por via intraperitoneal sobre a recuperação, as funções cognitivas e a dor após a anestesia com propofol. Métodos: O estudo foi feito no Laboratório de Pesquisa com Animais da Universidade de Gazi, Ankara, Turquia, em janeiro de 2012. Vinte e quatro ratos albinos do sexo feminino, adultos, da linhagem Wistar, com 170-270 g, foram treinados durante 300 segundos no labirinto radial de oito braços (LRB) durante três dias. O Grupo P recebeu 150 mg/kg−1 de propofol por via intraperitoneal (IP), o Grupo H recebeu 1 mg/kg−1 de memantina IP e o Grupo MP recebeu 1 mg/kg−1 de memantina IP antes da administração de 150 mg/kg−1 de propofol (IP). O grupo controle recebeu apenas solução salina IP. Os valores do LRB e da placa quente foram obtidos após a recuperação dos grupos que receberam propofol e 30 minutos após a administração dos fármacos nos outros dois grupos. Resultados: O tempo de recuperação do Grupo MP foi significativamente menor do que o do Grupo P (p < 0,001) e o número de entradas e saídas do LRB do Grupo MP foi significativamente maior durante a primeira hora, em comparação com o Grupo P (p < 0,0001). Os valores da placa quente, por outro lado, foram significativamente maiores em todos os grupos, em comparação com os valores do grupo controle, exceto pelo Grupo C (p < 0,0001). Conclusão: No presente estudo, memantina proporcionou tempos mais curtos de recuperação, funções cognitivas melhores e reduziu a dor no pós-operatório. A partir deste estudo, descobrimos que a memantina tem efeitos benéficos sobre a recuperação, as funções cognitivas e a dor após anestesia com propofol.

The effect of sugammadex on postoperative cognitive function and recovery / O efeito de sugamadex sobre a função cognitiva e recuperação no pós-operatório

Abstract Background and objective: Sugammadex is the first selective relaxant binding agent. When compared with neostigmine, following sugammadex administration patients wake earlier and have shorter recovery times. In this study, we hypothesized that fast and clear awakening in patients undergoing general anesthesia has positive effects on cognitive functions in the early period after operation. Methods: Approved by the local ethical committee, 128 patients were enrolled in this randomized, prospective, controlled, double-blind study. Patients were allocated to either Sugammadex group (Group S) or the Neostigmine group (Group N). The primary outcome of the study was early postoperative cognitive recovery as measured by the Montreal Cognitive Assessment (MoCA) and Mini Mental State Examination (MMSE). After baseline assessment 12-24 h before the operation. After the operation, when the Modified Aldrete Recovery Score was ≥9 the MMSE and 1 h later the MoCA tests were repeated. Results: Although there was a reduction in MoCA and MMSE scores in both Group S and Group N between preoperative and postoperative scores, there was no statistically significant difference in the slopes (p > 0.05). The time to reach TOF 0.9 was 2.19 min in Group S and 6.47 min in Group N (p < 0.0001). Recovery time was 8.26 min in Group S and 16.93 min in Group N (p < 0.0001). Conclusion: We showed that the surgical procedure and/or accompanying anesthetic procedure may cause a temporary or permanent regression in cognitive function in the early postoperative period. However, better cognitive performance could not be proved in the Sugammadex compared to the Neostigmine.

Resumo Justificativa e objetivo: Sugamadex é o primeiro agente de ligação relaxante seletivo. Após a administração de sugamadex, os tempos de despertar e de recuperação dos pacientes são menores, em comparação com neostigmina. Neste estudo, a hipótese foi que um despertar mais rápido e claro dos pacientes submetidos à anestesia geral tem efeitos positivos sobre as funções cognitivas no pós-operatório imediato. Métodos: Após a aprovação do Comitê de Ética local, 128 pacientes foram incluídos neste estudo prospectivo, randômico, controlado e duplo-cego. Os pacientes foram designados para o grupo sugamadex (Grupo S) ou grupo neostigmina (Grupo N). O desfecho primário do estudo foi a recuperação cognitiva no pós-operatório imediato, de acordo com a mensuração da Avaliação de Montreal da Função Cognitiva (MoCA) e com o Mini Exame do Estado Mental (MMSE), após a avaliação inicial 12-24 h antes da operação. Após a operação, quando o escore de recuperação de Aldrete modificado era ≥ 9, o teste MMSE e, uma hora depois, o teste MoCA foram repetidos. Resultados: Embora tenha havido uma redução nos escores de MoCA e MMSE tanto no Grupo S quanto no Grupo N, entre os escores pré- e pós-operatório não houve diferença estatisticamente significativa nas reduções (p > 0,05). O tempo para atingir TOF 0,9 foi de 2,19 min no Grupo S e de 6,47 min no Grupo N (p < 0,0001). O tempo de recuperação foi de 8,26 min no Grupo S e de 16,93 min no Grupo N (p < 0,0001) Conclusão: Mostramos que o procedimento cirúrgico e/ou procedimento anestésico de acompanhamento pode causar uma regressão temporária ou permanente da função cognitiva no pós-operatório imediato. No entanto, um desempenho cognitivo melhor não pode ser provado no grupo sugamadex em comparação com o grupo neostigmina.

Cannabinoids in neurology – Brazilian Academy of Neurology / Canabinoides e seu uso em neurologia – Academia Brasileira de Neurologia

O uso do canabidiol em algumas condições neurológicas foi liberado pelo Conselho Regional de Medicina de São Paulo e pela Agência Nacional de Vigilância Sanitária (ANVISA). Especialistas em nome da Academia Brasileira de Neurologia prepararam uma posição crítica sobre o uso do canabidiol e outros derivados da cannabis em doenças neurológicas.

The use of cannabidiol in some neurological conditions was allowed by Conselho Regional de Medicina de São Paulo and by Agência Nacional de Vigilância Sanitária (ANVISA). Specialists on behalf of Academia Brasileira de Neurologia prepared a critical statement about use of cannabidiol and other cannabis derivatives in neurological diseases.

Effects of galantamine and galantamine combined with nimodipine on cognitive speed and quality of life in mixed dementia: a 24-week, randomized, placebo-controlled exploratory trial (the REMIX study) / Efeitos da galantamina e da galantamina combinada à nimodipina sobre a velocidade de processamento cognitivo e qualidade de vida na demência mista: ensaio clínico exploratório, randomizado e controlado com placebo (estudo REMIX)

The effects of galantamine (GAL) on quality of life (QoL) and cognitive speed, as well its effects combined with nimodipine (NIM) in Alzheimer disease (AD) with cerebrovascular disease (mixed dementia), have not been explored. Method : Double-blind, placebo-controlled, multicenter Brazilian trial, studying the effects of GAL/NIM vs. GAL/placebo (PLA) in mild to moderate mixed dementia. Patients were randomized to receive GAL/NIM or GAL/PLA for 24 weeks. Primary efficacy measures were changes on a computerized neuropsychological battery (CNTB) and QoL Scale in Alzheimer's Disease (QoL-AD) from baseline to week 24. Results : Twenty-one patients received at least one drug dose (9 GAL/NIM and 12 GAL/PLA). Groups were matched for age, sex, education, cognitive and QoL scores at baseline. No significant differences were observed between groups on primary or secondary measures. QoL and cognitive performance showed significant improvement (p<0.05) from baseline when all GAL-treated patients were analyzed. Adverse events were predominantly mild to moderate. Conclusion : GAL treatment improved QoL in mixed dementia, in addition to its previously known cognitive benefits. The combination GAL/NIM was not advantageous. However, the small sample size precludes any definitive conclusions. Trial registered at ClinicalTrials.gov: NCT00814658 .

Os efeitos da galantamina (GAL) sobre qualidade de vida (QdV) e velocidade de processamento cognitivo, bem como da combinação com nimodipina (NIM) no tratamento da doença de Alzheimer (DA) com doença cerebrovascular (demência mista) ainda não foram investigados. Método : Estudo multicêntrico brasileiro, duplo-cego, controlado com placebo, avaliando os efeitos de GAL/NIM x GAL/placebo (PLA) na demência mista leve a moderada. Pacientes receberam tratamento com GAL/NIM ou GAL/PLA por 24 semanas. Medidas de eficácia primária foram as variações no desempenho em bateria de testes neuropsicológicos computadorizados e na escala QdV-DA ao final do estudo. Resultados : Vinte um pacientes receberam pelo menos uma dose da droga (9 GAL/NIM e 12 GAL/PLA). Os grupos foram emparelhados por idade, sexo, escolaridade, escores cognitivos e de QdV na linha de base. Não foram observadas diferenças significativas entre os dois grupos nas medidas de eficácia primária e secundária. Na avaliação de todos os pacientes que receberam GAL, houve melhora significativa (p<0,05) em QdV-DA e desempenho cognitivo. Os eventos adversos foram predominantemente leves a moderados. Conclusão : O tratamento com GAL proporcionou melhora da QdV na demência mista, além dos benefícios cognitivos previamente conhecidos. A combinação GAL/NIM não foi vantajosa. O reduzido tamanho amostral impede conclusões definitivas. .

Patterns of non-medical use of methylphenidate among 5th and 6th year students in a medical school in southern Brazil / Padrões do uso não médico de metilfenidato em estudantes do 5º e do 6º ano de uma faculdade de medicina do Brasil

Objectives: To evaluate the prevalence of methylphenidate (MPH) use among 5th and 6th year medical students, to discriminate MPH use with and without medical indication, and to correlate MPH use with alcohol intake. Methods: This is a cross-sectional study in which medical students were invited to answer a questionnaire to evaluate academic and socioeconomic status, MPH use patterns, and attitudes towards neuroenhancing drugs. The Alcohol Use Disorders Identification Test (AUDIT) was used to assess alcohol intake; a score ≥ 8 suggests potentially hazardous alcohol use. Results: Fifty-two participants (34.2%) had already used MPH, of which 35 (23.02%) had used it without medical indication. The number of 6th year students who had used MPH was more than twice higher than that of their 5th year counterparts (32.89 vs. 13.15%, respectively; p = 0.004). Also, 43.6% (p = 0.031) of the users of MPH had an AUDIT score ≥ 8; 33.3% (p = 0.029) of non-medical users of MPH had an AUDIT score ≥ 8. Conclusions: In this study, the use of MPH without medical indication was prevalent. Our findings also confirmed the association between non-medical use of MPH and potentially hazardous alcohol use (AU)

Objetivos: Avaliar a prevalência do uso do metilfenidato entre estudantes do 5º e do 6º ano de uma faculdade de medicina, discriminar o uso com ou sem indicação médica e correlacionar o uso de metilfenidato com a ingestão de álcool. Métodos: Este é um estudo transversal, em que os alunos de medicina foram convidados a responder um questionário para avaliação do status socioeconômico e acadêmico, padrões do uso do metilfenidato e atitude em relação a drogas potencializadoras da cognição. Também foi aplicado o questionário The Alcohol Use Disorder Identification Test (AUDIT), que avalia o consumo de bebidas alcoólicas, onde um score ≥ 8 significa ingestão potencialmente perigosa de álcool. Resultados: Cinquenta e dois participantes (34,2%) já haviam usado metilfenidato, sendo que 35 destes (23,02%) haviam usado a substância sem indicação médica. O número de estudantes do 6º ano que fizeram uso não médico de metilfenidato foi mais de duas vezes maior do que o número de estudantes do 5º ano (32,89 versus 13,15%, respectivamente; p = 0,004). Em relação ao AUDIT, 43,6% (p = 0,031) dos usuários de metilfenidato tiveram escores ≥ 8; 33,3% (p = 0,029) dos usuários não médicos de metilfenidato tiveram escores ≥ 8 no AUDIT. Conclusões: Neste estudo, o uso de metilfenidato sem indicação médica foi prevalente. Os achados também evidenciaram a associação entre o uso não médico de metilfenidato e o uso potencialmente perigoso de álcool (AU)