Eugenol and its liposome-based nano carrier reduce anxiety by inhibiting glyoxylase-1 expression in mice / Eugenol e seu nanocarreador à base de lipossoma reduzem a ansiedade ao inibir a expressão de glioxalase 1 em camundongos

Abstract The most common form of psycho-social dysfunction is anxiety with depression being related closely without any age bar. They are present with combined state of sadness, confusion, stress, fear etc. Glyoxalase system contains enzyme named glyoxalase 1 (GLO1).It is a metabolic pathway which detoxifies alpha-oxo-aldehydes, particularly methylglyoxal (MG). Methylglyoxal is mainly made by the breakdown of the glycolytic intermediates, glyceraldehyde-3-phosphates and dihydroxyacetone phosphate. Glyoxylase-1 expression is also related with anxiety behavior. A casual role or GLO-1 in anxiety behavior by using viral vectors for over expression in the anterior cingulate cortex was found and it was found that local GLO-1 over expression increased anxiety behavior. The present study deals with the molecular mechanism of protective activity of eugenol against anxiolytic disorder. A pre-clinical animal study was performed on 42 BALB/c mice. Animals were given stress through conventional restrain model. The mRNA expression of GLO-1 was analyzed by real time RT-PCR. Moreover, the GLO-1 protein expression was also examined by immunohistochemistry in whole brain and mean density was calculated. The mRNA and protein expressions were found to be increased in animals given anxiety as compared to the normal control. Whereas, the expressions were decreased in the animals treated with eugenol and its liposome-based nanocarriers in a dose dependent manner. However, the results were better in animals treated with nanocarriers as compared to the compound alone. It is concluded that the eugenol and its liposome-based nanocarriers exert anxiolytic activity by down-regulating GLO-1 protein expression in mice.

Resumo A forma mais comum de disfunção psicossocial é a ansiedade intimamente relacionada com a depressão, sem qualquer barreira de idade. Elas estão presentes em um estado combinado de tristeza, confusão, estresse, medo etc. O sistema de glioxalase contém uma enzima chamada glioxalase 1 (GLO1). É uma via metabólica que desintoxica alfa-oxo-aldeídos, particularmente metilglioxal (MG). O metilglioxal é produzido principalmente pela quebra dos intermediários glicolíticos, gliceraldeído-3-fosfatos e fosfato de diidroxiacetona. A expressão da glioxalase 1 também está relacionada ao comportamento de ansiedade. Um papel casual ou GLO1 no comportamento de ansiedade usando vetores virais para superexpressão no córtex cingulado anterior foi encontrado e descobriu-se que a superexpressão local de GLO1 aumentava o comportamento de ansiedade. O presente estudo trata do mecanismo molecular da atividade protetora do eugenol contra o transtorno ansiolítico. Um estudo pré-clínico em animais foi realizado em 42 camundongos BALB / c. Os animais foram submetidos ao estresse por meio do modelo de contenção convencional. A expressão de mRNA de GLO1 foi analisada por RT-PCR em tempo real. Além disso, a expressão da proteína GLO1 também foi examinada por imuno-histoquímica em todo o cérebro e a densidade média foi calculada. Verificou-se que as expressões de mRNA e proteínas estavam aumentadas em animais que receberam ansiedade em comparação com o controle normal. Considerando que as expressões foram diminuídas nos animais tratados com eugenol e seus nanocarreadores baseados em lipossomas de forma dependente da dose. No entanto, os resultados foram melhores em animais tratados com nanocarreadores em comparação com o composto sozinho. Conclui-se que o eugenol e seus nanocarreadores baseados em lipossomas exercem atividade ansiolítica por regulação negativa da expressão da proteína GLO1 em camundongos.

Eugenol and its liposome-based nano carrier reduce anxiety by inhibiting glyoxylase-1 expression in mice / Eugenol e seu nanocarreador à base de lipossoma reduzem a ansiedade ao inibir a expressão de glioxalase 1 em camundongos

The most common form of psycho-social dysfunction is anxiety with depression being related closely without any age bar. They are present with combined state of sadness, confusion, stress, fear etc. Glyoxalase system contains enzyme named glyoxalase 1 (GLO1).It is a metabolic pathway which detoxifies alpha-oxo-aldehydes, particularly methylglyoxal (MG). Methylglyoxal is mainly made by the breakdown of the glycolytic intermediates, glyceraldehyde-3-phosphates and dihydroxyacetone phosphate. Glyoxylase-1 expression is also related with anxiety behavior. A casual role or GLO-1 in anxiety behavior by using viral vectors for over expression in the anterior cingulate cortex was found and it was found that local GLO-1 over expression increased anxiety behavior. The present study deals with the molecular mechanism of protective activity of eugenol against anxiolytic disorder. A pre-clinical animal study was performed on 42 BALB/c mice. Animals were given stress through conventional restrain model. The mRNA expression of GLO-1 was analyzed by real time RT-PCR. Moreover, the GLO-1 protein expression was also examined by immunohistochemistry in whole brain and mean density was calculated. The mRNA and protein expressions were found to be increased in animals given anxiety as compared to the normal control. Whereas, the expressions were decreased in the animals treated with eugenol and its liposome-based nanocarriers in a dose dependent manner. However, the results were better in animals treated with nanocarriers as compared to the compound alone. It is concluded that the eugenol and its liposome-based nanocarriers exert anxiolytic activity by down-regulating GLO-1 protein expression in mice.

A forma mais comum de disfunção psicossocial é a ansiedade intimamente relacionada com a depressão, sem qualquer barreira de idade. Elas estão presentes em um estado combinado de tristeza, confusão, estresse, medo etc. O sistema de glioxalase contém uma enzima chamada glioxalase 1 (GLO1). É uma via metabólica que desintoxica alfa-oxo-aldeídos, particularmente metilglioxal (MG). O metilglioxal é produzido principalmente pela quebra dos intermediários glicolíticos, gliceraldeído-3-fosfatos e fosfato de diidroxiacetona. A expressão da glioxalase 1 também está relacionada ao comportamento de ansiedade. Um papel casual ou GLO1 no comportamento de ansiedade usando vetores virais para superexpressão no córtex cingulado anterior foi encontrado e descobriu-se que a superexpressão local de GLO1 aumentava o comportamento de ansiedade. O presente estudo trata do mecanismo molecular da atividade protetora do eugenol contra o transtorno ansiolítico. Um estudo pré-clínico em animais foi realizado em 42 camundongos BALB / c. Os animais foram submetidos ao estresse por meio do modelo de contenção convencional. A expressão de mRNA de GLO1 foi analisada por RT-PCR em tempo real. Além disso, a expressão da proteína GLO1 também foi examinada por imuno-histoquímica em todo o cérebro e a densidade média foi calculada. Verificou-se que as expressões de mRNA e proteínas estavam aumentadas em animais que receberam ansiedade em comparação com o controle normal. Considerando que as expressões foram diminuídas nos animais tratados com eugenol e seus nanocarreadores baseados em lipossomas de forma dependente da dose. No entanto, os resultados foram melhores em animais tratados com nanocarreadores em comparação com o composto sozinho. Conclui-se que o eugenol e seus nanocarreadores baseados em lipossomas exercem atividade ansiolítica por regulação negativa da expressão da proteína GLO1 em camundongos.

Inhalation of Cananga odorata essential oil relieves anxiety behaviors in autism-like rats via regulation of serotonin and dopamine metabolism / 中西医结合学报

OBJECTIVE@#Anxiety is one of the most common symptoms associated with autistic spectrum disorder. The essential oil of Cananga odorata (Lam.) Hook. f. & Thomson, usually known as ylang-ylang oil (YYO), is often used in aromatherapy as a mood-regulating agent, sedative, or hypotensive agent. In the present study, the effects and mechanisms of YYO in alleviating anxiety, social and cognitive behaviors in autism-like rats were investigated.@*METHODS@#The prenatal valproic acid (VPA) model was used to induce autism-like behaviors in offspring rats. The effectiveness of prenatal sodium valproate treatment (600 mg/kg) on offspring was shown by postnatal growth observation, and negative geotaxis, olfactory discrimination and Morris water maze (MWM) tests. Then three treatment groups were formed with varying exposure to atomized YYO to explore the effects of YYO on the anxiety, social and cognitive behaviors of the autistic-like offspring through the elevated plus-maze test, three-chamber social test, and MWM test. Finally, the monoamine neurotransmitters, including serotonin, dopamine and their metabolites, in the hippocampus and prefrontal cortex (PFC) of the rats were measured using a high-performance liquid chromatography.@*RESULTS@#Offspring of VPA exposure rats showed autism-like behaviors. In the VPA offspring, medium-dose YYO exposure significantly elevated the time and entries into the open arms in the elevated plus-maze test, while low-dose YYO exposure significantly enhanced the social interaction time with the stranger rat in session 1 of the three-chamber social test. VPA offspring treated with YYO exposure used less time to reach the platform in the navigation test of the MWM test. YYO exposure significantly elevated the metabolism of serotonin and dopamine in the PFC of VPA offspring.@*CONCLUSION@#YYO exposure showed the effects in alleviating anxiety and improving cognitive and social abilities in the offspring of VPA exposure rats. The role of YYO was related to the regulation of the metabolism of serotonin and dopamine. Please cite this article as: Zhang N, Wang ST, Yao L. Inhalation of Cananga odorata essential oil relieves anxiety behaviors in autism-like rats via regulation of serotonin and dopamine metabolism. J Integr Med. 2023; 21(2): 205-214.

Plantas com ação no sistema nervoso central que constam na relação nacional de plantas medicinais de interesse ao sus (RENISUS) / Plants acting on the central nervous system: review plantas com ação no sistema nervoso central que constam na relação nacional de plantas medicinais de interesse ao sus (RENISUS) / Plantas con acción sobre el sistema nervioso central incluidas en la lista nacional de plantas medicinales de interés para sus (RENISUS)

A depressão é uma doença grave que atinge a população em geral, estudos epidemiológicos estimam que a prevalência da depressão ao longo da vida no Brasil está em torno de 15,5%. Os fatores que desencadeiam o aparecimento da depressão incluem fatores sociais, psicológicos, biológicos e também fatores externos específicos como eventos estressantes, solidão, consumo de álcool e drogas, doenças crônicas e dar á luz (depressão pós-parto). O objetivo da presente pesquisa consistiu em realizar uma revisão bibliográfica sobre as principais plantas medicinais com ação antidepressiva. A ansiedade vem se tornando um dos principais problemas da atualidade, sendo intensificada pela pandemia causada pelo coronavírus, onde constatou-se que durante o pico da pandemia onde os casos confirmados de COVID-19 no Brasil ascenderam de 45.757 para 330.890, e as mortes, de 2.906 para 21.048, o sentimento de tristeza/depressão atingiu 40% dos adultos brasileiros. Os sintomas de depressão podem ser amenizados quando a disponibilidade sináptica de monoaminas são aumentadas, e esse aumento pode ocorrer através da diminuição da metabolização desses neurotransmissores. Neste sentido, busca-se através da farmacoterapia a utilização de antidepressivos que disponibilizem as monoaminas na fenda sináptica. A escolha do fármaco é feita com base nos sintomas da depressão e na boa resposta a uma determinada classe de antidepressivos. Em fevereiro de 2009 o Ministério da saúde lançou a Relação Nacional de Plantas Medicinais de Interesse ao SUS (RENISUS), contendo 71 espécies vegetais que são distribuídas de forma in natura nas unidades básicas de saúde (UBS). Destas, somente três espécies apresentam efeito antidepressivo e ansiolítico comprovados na literatura sendo Matricharia chamomilla, Erytrinum mulungu e a Passiflora incarnata que também fazem parte da RENISUS. Além destas, outras espécies como a Melissa officinalis, Lippia alba, Valeriana officinalis e Piper methysticum são utilizadas pela população para tratar ansiedade, insônia e depressão, sugerindo desta forma que estas espécies sejam incluídas na RENISUS.

Depression is a serious disease that affects the general population, epidemiological studies estimate that the prevalence of depression throughout life in Brazil is around 15.5%. The factors that trigger the onset of depression include social, psychological, biological and also specific external factors such as stressful events, loneliness, alcohol and drug consumption, chronic diseases and giving birth (postpartum depression). The objective of the present research was to carry out a literature review on the main medicinal plants with antidepressant action. Anxiety has become one of the main problems of today, being intensified by the pandemic caused by the coronavirus, where it was found that during the peak of the pandemic where confirmed cases of COVID-19 in Brazil rose from 45,757 to 330,890, and deaths, from 2,906 to 21,048, the feeling of sadness/depression reached 40% of Brazilian adults. Symptoms of depression can be alleviated when synaptic availability of monoamines is increased, and this increase can occur through decreased metabolization of these neurotransmitters. In this sense, the use of antidepressants that make monoamines available in the synaptic cleft is sought through pharmacotherapy. The choice of drug is based on symptoms of depression and good response to a particular class of antidepressants. In February 2009, the Ministry of Health launched the National List of Medicinal Plants of Interest to the SUS (RENISUS), containing 71 plant species that are distributed in natura form in basic health units (UBS). Of these, only three species have antidepressant and anxiolytic effects proven in the literature, being Matricharia chamomilla, Erytrinum mulungu and Passiflora incarnata, which are also part of RENISUS. In addition to these, other species such as Melissa officinalis, Lippia alba, Valeriana officinalis and Piper methysticum are used by the population to treat anxiety, insomnia and depression, thus suggesting that these species are included in RENISUS.

Los estudios epidemiológicos estiman que la prevalencia de la depresión a lo largo de la vida en Brasil es de alrededor del 15,5%. Los factores que desencadenan la aparición de la depresión son sociales, psicológicos, biológicos y también factores externos específicos, como los acontecimientos estresantes, la soledad, el consumo de alcohol y drogas, las enfermedades crónicas y el parto (depresión posparto). El objetivo de esta investigación fue realizar una revisión bibliográfica sobre las principales plantas medicinales con acción antidepresiva. La ansiedad se ha convertido en uno de los principales problemas de la actualidad, intensificándose por la pandemia causada por el coronavirus, donde se encontró que durante el pico de la pandemia donde los casos confirmados de COVID-19 en Brasil aumentaron de 45.757 a 330.890, y las muertes, de 2.906 a 21.048, el sentimiento de tristeza/depresión alcanzó el 40% de los adultos brasileños. Los síntomas de la depresión pueden aliviarse cuando se aumenta la disponibilidad sináptica de las monoaminas, y este aumento puede producirse mediante una disminución de la metabolización de estos neurotransmisores. En este sentido, se busca a través de la farmacoterapia el uso de antidepresivos que hagan disponibles las monoaminas en la hendidura sináptica. La elección del fármaco se hace en función de los síntomas de la depresión y de la buena respuesta a una clase concreta de antidepresivos. En febrero de 2009, el Ministerio de Salud lanzó la Lista Nacional de Plantas Medicinales de Interés para el SUS (RENISUS), que contiene 71 especies de plantas que se distribuyen in natura en unidades básicas de salud (UBS). De ellas, sólo tres especies tienen efectos antidepresivos y ansiolíticos probados en la literatura: Matricharia chamomilla, Erytrinum mulungu y Passiflora incarnata, que también forman parte del RENISUS. Además de éstas, otras especies como Melissa officinalis, Lippia alba, Valeriana officinalis y Piper methysticum son utilizadas por la población para tratar la ansiedad, el insomnio y la depresión, lo que sugiere que estas especies se incluyan en el RENISUS.

Acupuncture attenuates comorbid anxiety- and depressive-like behaviors of atopic dermatitis through modulating neuroadaptation in the brain reward circuit in mice

Atopic dermatitis (AD) is highly comorbid with negative emotions such as anxiety and depression. Although acupuncture has demonstrated efficacy in AD, its influence on comorbid anxiety and depression remains unclear. We sought to explore the impact and mechanisms of action of acupuncture on comorbid anxiety and depression of AD. AD-like skin lesions were induced by the topical application of MC903 to the mouse cheek. Acupuncture was performed at Gok-Ji (LI11) acupoints. AD-like phenotypes were quantified by lesion scores, scratching behavior, and histopathological changes. The effects of acupuncture on comorbid anxiety and depression-like behaviors were assessed using the elevated plus-maze (EPM), open-field tests (OFT), and tail-suspension test (TST). In addition, biochemical changes in the brain reward regions were investigated by immunoblotting for the expression of tyrosine hydroxylase (TH), dopamine D1 receptor (D1R), phospho-dopamine and cAMP-regulated phosphoprotein-32 kDa (pDARPP-32), phospho-cAMP response element binding protein (pCREB), ΔFosB, and brain-derived neurotrophic factor (BDNF) in the nucleus accumbens, dorsolateral striatum, and ventral tegmental area. Acupuncture effectively improved the chronic itching and robust AD-like skin lesions with epidermal thickening. Additionally, it considerably reduced comorbid anxiety- and depression-like symptoms, as indicated by more time spent in the open arms of the EPM and in the center of the open field and less time spent immobile in the TST. Higher pCREB, ΔFosB, BDNF, and pDARPP-32 levels, and reduced TH and D1R protein expression in the brain reward regions of AD mice were reversed by acupuncture treatment. The beneficial effects of acupuncture on clinical symptoms (scratching behavior) and comorbid psychological distress in AD strongly correlated with dorsal striatal ΔFosB levels. Collectively, these data indicate that acupuncture had a significant, positive impact on comorbid anxiety- and depression-like behaviors by modulating neuroadaptation in the brain reward circuit in mice with AD, providing a novel perspective for the non-pharmacological management of psychiatric comorbidities of AD.

Hepatopatía inflamatoria asintomática asociada a uso de mirtazapina: reporte de caso / Asymptomatic inflammatory liver disease associated with mirtazapine use: case report

Resumen La mirtazapina es un antidepresivo atípico con características complejas, que incluye actividad agonista/antagonista en una amplia variedad de receptores que produce efectos terapéuticos en la ansiedad, depresión y el sueño. Sin embargo, se han reportado casos de lesión hepática inducida por antidepresivos con ausencia de sintomatología, bajo la forma de variantes hepatocelular, colestásica y mixta. Este es el caso de una paciente que de carácter incidental presenta cambios en la analítica hepática tras el uso de mirtazapina a partir del cual se hace una breve revisión de la evidencia encontrada hasta el momento.

Mirtazapine is an atypical antidepressant with complex characteristics, including agonist/antagonist activity at a wide variety of receptors that produces therapeutic effects on anxiety, depression and sleep disorder. However, cases of antidepressant-induced liver injury with no symptoms have been reported, in the form of hepatocellular, cholestatic, and mixed variants. This is the case of a patient who incidentally presents changes in liver analysis after the use of mirtazapine, from which a brief review of the evidence found so far is made.

Citrus limon (L.) Burm f. Essential Oil Has Anxiolytic and Sedative Properties by Modulating GABAA-Receptors

Abstract The high prevalence of anxiety disorders associated with pharmacotherapy side effects have motivated the search for new pharmacological agents. Species from Citrus genus, such as Citrus limon (sicilian lemon), have been used in folk medicine as a potential therapy to minimize emotional disorders. In order to searching for new effective treatments with fewer side effects, the present study evaluated the anxiolytic mechanism of action and the hypnotic-sedative activity from the Citrus limon fruit's peels essential oil (CLEO). Adults male Swiss mice were submitted to barbiturate-induced sleep test; elevated plus-maze (EPM) and light-dark box (LDB) (evaluation of the mechanism of action); rotarod; and catalepsy tests. CLEO oral treatment decreased latency and increased the sleep total time; moreover it induced in animals an increased the number of entries and percentage of time spent into open arms of the EPM; an increased the number of transitions and the percentage of time into light compartment in the LDB; which were only antagonized by flumazenil pretreatment, with no injury at motor function. Thus, results suggest that CLEO treatment induced an anxiolytic behavior suggestively modulated by the benzodiazepine binding site of the GABAA receptor or by an increase of GABAergic neurotransmission, without cause impairment in the motor coordination.

An easy and reliable way to prevent electrocardiographic deteriorations of patients undergoing off-pump coronary artery bypass surgery: preoperative anxiolytic treatment

Abstract Objective: To investigate the effects of preoperative anxiety relieving on electrophysiological changes in patients undergoing off-pump coronary artery bypass surgery. Methods: A total of 61 patients at ASA III risk group in the age range of 18-65 years were enrolled in the present study. Patients were randomly divided into two groups. Group S (Sedation group) was administered 0.04 mg/kg lorazepam per os (PO) twice before the operation. Group C (control group) was not administered with any anxiolytic premedication. State Trait Anxiety Inventory (STAI-I) and Beck Anxiety Inventory (BAI) were used to evaluate the level of anxiety. Electrocardiography (ECG), pulse oximeter and standard monitoring were performed for each patient. QT and P dispersions in each derivation of all ECGs were calculated. Results: Preoperative STAI-I scores were significantly lower in sedation group compared to the controls. Mean values of QT dispersion measured before induction, at the 1st minute of induction, 30th second of intubation and 4th minute of intubation in sedation group were significantly reduced compared to controls (P=0.024; P=0.027; P=0.001; P=0.033, respectively). The mean values of P dispersion measured before induction, at the 3rd minute of induction, 30th second of intubation and 4th minute of intubation in sedation group were significantly reduced compared to controls (P=0.001; P=0.020; P=0.023; P=0.005, respectively). Conclusion: Elevated anxiety levels in patients undergoing coronary bypass surgery have a negative effect through prolonged QT and P-wave dispersion times. Anxiolytic treatment before surgery may be useful to prevent ventricular and atrial arrhythmias and associated complications through decreasing the QT and P-wave dispersion duration.

Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test

Objective: Cannabidiol (CBD), one of the non-psychotomimetic compounds of Cannabis sativa, causes anxiolytic-like effects in animals, with typical bell-shaped dose-response curves. No study, however, has investigated whether increasing doses of this drug would also cause similar curves in humans. The objective of this study was to compare the acute effects of different doses of CBD and placebo in healthy volunteers performing a simulated public speaking test (SPST), a well-tested anxiety-inducing method. Method: A total of 57 healthy male subjects were allocated to receive oral CBD at doses of 150 mg (n=15), 300 mg (n=15), 600 mg (n=12) or placebo (n=15) in a double-blind procedure. During the SPST, subjective ratings on the Visual Analogue Mood Scale (VAMS) and physiological measures (systolic and diastolic blood pressure, heart rate) were obtained at six different time points. Results: Compared to placebo, pretreatment with 300 mg of CBD significantly reduced anxiety during the speech. No significant differences in VAMS scores were observed between groups receiving CBD 150 mg, 600 mg and placebo. Conclusion: Our findings confirm the anxiolytic-like properties of CBD and are consonant with results of animal studies describing bell-shaped dose-response curves. Optimal therapeutic doses of CBD should be rigorously determined so that research findings can be adequately translated into clinical practice.

Evaluación del efecto sedativo del Midazolam con y sin Ketamina, por vía subcutánea, en pacientes dentales pediátricos / Evaluation of the Sedative Effect of Midazolam with and Without Ketamine, by Subcutaneous Via in Pediatric Dental Patients

Resumen El miedo y la ansiedad de los niños por el tratamiento dental pueden conducir a dificultades en el manejo de la conducta por parte del profesional, lo cual puede ser una barrera para el éxito del tratamiento dental. Los niños no cooperadores pueden necesitar recibir tratamiento dental bajo sedación, la que se indica cuando la guía de comportamiento no farmacológico no tiene éxito. Existen ensayos controlados aleatorios que comparan diferentes protocolos sedantes para procedimientos dentales; sin embargo, la evidencia de superioridad de una forma sobre otra es débil. El objetivo del presente estudio es evaluar el efecto sedativo de Midazolam por vía subcutánea, con y sin ketamina, en procedimientos odontológicos realizados en pacientes pediátricos no cooperadores. Se llevó a cabo un ensayo clínico aleatorizado, cruzado, con cegamiento simple, en 13 niños (10 del género masculino y 3 del femenino) de 19 a 48 meses de edad, ASA I y comportamiento Frankl I. Los dos métodos se aplicaron en el mismo paciente, y el orden de los mismos fue asignado aleatoriamente, para las dos citas de tratamiento. En cada sesión se evaluaron: el comportamiento general del paciente, los movimientos corporales y el llanto, por medio de la escala de Houpt modificada. Además, se monitorearon la frecuencia cardíaca y la saturación de oxígeno por medio de un oxímetro de pulso.

Abstract Children's fear and anxiety about dental treatment can lead to difficulties in the behavior management by the practitioner, which can be a barrier to successful dental treatment. Non cooperative children may need dental treatment under sedation, which is indicated when the non-pharmacological behavioral guidance is unsuccessful. There are randomized controlled trials comparing different sedative protocols for dental procedures; however, evidence of superiority from one form over another is weak. The aim of the present study was to evaluate the sedative effect of midazolam subcutaneously, with and without ketamine, on dental procedures performed in non-cooperative pediatric patients. A randomized, crossover clinical trial with single blinding was performed in 13 children (10 males and 3 females) from 19 to 48 months of age, ASA I and Frankl I behavior. The two methods were applied in the same patient, and the order of the same was assigned randomly, for the two treatment appointments. In each session were evaluated the patient's general behavior, body movements and crying through the modified Houpt scale. In addition, heart rate and oxygen saturation were monitored by means of a pulse oximeter.

Long-term effects of ayahuasca in patients with recurrent depression: a 5-year qualitative follow-up

Background Ayahuasca is a botanical hallucinogenic preparation traditionally used by indigenous populations of Northwestern Amazonian countries for ritual and therapeutic purposes. It is rich in β-carboline alkaloids and N,N-dimethyltryptamine (DMT). Preclinical, observational, and experimental studies suggest that ayahuasca and its alkaloids have anxiolytic and antidepressive effects. We recently reported in an open-label trial that ayahuasca administration was associated with significant decreases in depression symptoms for 2-3 weeks after the experimental session in 17 patients with treatment-resistant major depressive disorder. Objectives To investigate if the experiment had any long-lasting effects on patients Methods Eight patients were interviewed 4 to 7 years after ayahuasca intake. Results Our results suggest that ayahuasca was well tolerated and that symptom reductions were limited to a few weeks. Importantly, most patients believed that the experience was among the most important of their lives, even 4-7 years later. Discussion To the best of our knowledge, this is the first long-term follow-up of a clinical sample that participated in an ayahuasca trial. Further studies with different and repeated dosing should be designed to further explore the antidepressive and anxiolytic effects of ayahuasca.

La controversia científico-técnica sobre las benzodiacepinas en profesionales de la salud pública de Uruguay / A controvérsia científico-técnica sobre as benzodiazepinas entre profissionais de saúde pública do Uruguai / The scientific-technical controversy over benzodiazepines among public health professionals in Uruguay

Resumen La controversia científico-técnica internacional sobre las benzodiacepinas, intensa durante los años ochenta y noventa, cuestionó su lugar en la práctica clínica, por su potencialidad adictiva, y por el abuso que médicos y pacientes parecerían realizar. Este artículo presenta resultados de una investigación que tuvo como objetivo analizar el papel de dicha controversia en las prácticas médica, psiquiátrica y psicológica en los servicios de salud pública uruguayos. Se utilizó metodología cualitativa y se combinó relevamiento de artículos académicos nacionales (1960-2012), entrevistas en profundidad a 45 profesionales y dos grupos de discusión. Se efectuó análisis de contenido desde cuatro ejes: ansiedad en la clínica, prescripción, relación tratamientos farmacológicos con no farmacológicos y valoración de benzodiacepinas. Se obtuvo un panorama diacrónico de la controversia académica y se identificó una valoración condicional de estos medicamentos realizada por los profesionales que supone: reconocimiento de atributos positivos y negativos de las benzodiacepinas, uso mesurado, médicos y pacientes vigilantes de sus propios comportamientos. Se concluye que la controversia se plantea en términos individuales, lo que obstaculiza una discusión global de las dimensiones políticas y colectivas implicadas.

Resumo A controvérsia científico-técnica internacional sobre as benzodiazepinas, intensa durante os anos 1980 e 1990, questionou seu lugar na prática clínica devido a sua potencialidade aditiva e pelo abuso que médicos e pacientes pareciam realizar. Este artigo apresenta resultados de uma pesquisa que teve como objetivo analisar o papel dessa controvérsia nas práticas médica, psiquiátrica e psicológica nos serviços de saúde pública do Uruguai. Utilizou-se metodologia qualitativa e combinou-se um levantamento de artigos acadêmicos nacionais (1960-2012), entrevistas em profundidade com 45 profissionais e dois grupos de discussão. Realizou-se análise de conteúdo a partir de quatro eixos: ansiedade na clínica, prescripção, relação entre tratamentos farmacológicos e não farmacológicos e avaliação das benzodiacepinas. Obteve-se um panorama diacrônico da controvérsia acadêmica e identificou-se uma avaliação condicional desses medicamentos realizada pelos profissionais, que supõe: reconhecimento de atributos positivos e negativos das benzodiazepinas, uso controlado, médicos e pacientes vigilantes de seus próprios comportamentos. Conclui-se que a controvérsia é levantada em termos individuais, o que obstaculiza uma discussão global das dimensões políticas e coletivas implicadas.

Abstract The international technoscientific controversy on benzodiazepines, especially intense during the 1980s and 1990s, questioned the place of benzodiazepines in clinical practice because of its addictive potentiality and the abuse of physicians and patients. This article presents some results from a research that aimed to analyze the role of benzodiazepine controversy in medical, psychiatric and psychological practices in Uruguayan public health services. This research methodology was qualitative, combining a review of national academic articles (1960-2012), in-depth interviews with 45 professionals and two discussion groups. Content analysis was carried out using four axes: anxiety in clinic practice, prescription, relationship between pharmacologic and non-pharmacologic treatment, and benzodiazepines valoration. We obtained a diachronic pictures of the academic controversy and we identified a conditional assessment of these medicines made by the professionals. This assessment implies: the recognition of positive and negative attributes of benzodiazepines, a controlled use of benzodazepines, and professionals and patients that must watch their own behaviors. We conclude that the controversy is presented mainly in individual terms, and this prevents a global discussion on the political and collective dimensions involved.

Efeito da ingestão de ômega-3 sobre a ansiedade em estudantes universitários / The effect of ingest of omega-3 on anxiety in university students

Introdução: A ansiedade pode ser observada por meio de alterações psicológicas, podendo ocorrer manifestações de medo e do sentimento de insegurança. Os estudantes universitários correspondem a um grupo de risco para o desenvolvimento da ansiedade, pois o mercado de trabalho atual exige um profissional que, além da capacidade técnica da área em que estuda, também tenha habilidade cognitiva, técnica especializada e comportamental. O estudo teve como objetivo analisar o efeito da ingestão de ômega-3 sobre a ocorrência e intensidade da sensação subjetiva de ansiedade em estudantes da Universidade Potiguar. Método: Participaram do estudo 20 estudantes do curso de Nutrição, dos gêneros masculino e feminino, com idade média de 25±3 anos. Os participantes foram distribuídos aleatoriamente entre o grupo experimental e controle. Os alunos do grupo experimental receberam 1000 mg de ômega-3 na forma de cápsula em dose única. A ansiedade foi induzida pelo Teste de Simulação de Falar em Público. Para mensurar a ocorrência e intensidade da sensação de ansiedade foi utilizado o Inventário de Ansiedade Traço ­ Estado (IDATE-T e E). Para a análise estatística foi utilizado o software IBM SPSS® v. 22.0 para Microsoft Windows®. Resultados: No momento da indução da ansiedade, os estudantes do grupo experimental apresentaram média no escore do IDATE-E de 60,1±3,4 pontos. Os escores do IDATE-E mantiveram-se entre as categorias de média e alta ansiedade no decorrer do experimento, sugerindo que a quantidade do ácido graxo ofertada não provocou efeito ansiolítico. Conclusões: O ômega-3 não representa um tratamento alternativo para a ansiedade.(AU)

Introduction: The anxiety can be observed through of psychological changes, may occur manifestations of fear and sense of insecurity. The university students represent a risk group for the development of anxiety because the current labor market requires a professional who, in addition to the technical capacity of the area that studies, also have cognitive, specialized, and behavioral abilities. The study aimed to analyze the effect of omega-3 intake on the occurrence and intensity of the subjective feeling of anxiety in students at the Universidade Potiguar. Methods: The study included 20 undergraduate students of nutrition male and female, mean age of 25±3 years old. Participants were distributed randomly between the experimental and control groups, whose experimental group received 1000 mg of ômega-3 in capsule form as a single dose. Anxiety was induced speaking simulation test in public. For measuring the occurrence and intensity of sensation of anxiety was used Inventário de Ansiedade Traço ­ Estado (IDATE-T e E). For the statistical analysis software IBM SPSS® v.22.0 for Microsoft Windows® was used. Results: In the results, it was possible to observe na increase in the IDATE-E score once the numbers were maintained above the anxiety group during the test (average=60.1±3.4 points), suggesting that the fatty acid did not have an anxiolytics effect on the psychological parameter that alters anxiety. Conclusions: Thus, the supplied amount of omega-3 showed no effect in the treatment of anxiety.(AU)

Screening for symptoms of anxiety and depression in patients admitted to a university hospital with acute coronary syndrome / Rastreio de sintomas ansiosos e depressivos em pacientes com síndrome coronariana aguda internados em um hospital universitário

Abstract Objective: To investigate the prevalence of anxiety and depression in patients admitted for acute coronary syndrome to a university hospital and to examine associations with use of psychotropic drugs. Methods: Ninety-one patients who had had an acute coronary event were enrolled on this cross-sectional prevalence study. Characteristics of the study population and the prevalence rates of depression and anxiety in the sample were assessed using the Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS) psychiatric consultation protocol, which includes clinical and sociodemographic data, and the Hospital Anxiety and Depression Scale (HADS). Results: The prevalence of symptoms of anxiety was 48.4% (44 patients) and the prevalence of depressive symptoms was 26.4% (24 patients). Of these, 19 patients (20.9% of the whole sample) had scores indicative of both types of symptoms concomitantly. Considering the whole sample, just 17 patients (18.7%) were receiving treatment for anxiety or depression with benzodiazepines and/or antidepressants. Conclusions: Anxiety and depression are disorders that are more prevalent among patients with acute coronary syndrome than in the general population, but they are generally under-diagnosed and under-treated. Patients with anxiety and depression simultaneously had higher scores on the HADS for anxiety and depression and therefore require more intensive care.

Resumo Objetivo: Investigar a prevalência de ansiedade e depressão em pacientes com síndrome coronariana aguda internados em um hospital universitário e examinar sua associação com o uso de drogas psicotrópicas. Métodos: Noventa e um pacientes que sofreram evento coronariano agudo foram incluídos nesse estudo transversal de prevalência. O protocolo de interconsulta psiquiátrica do Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), com os dados clínicos e sociodemográficos, e a Escala Hospitalar de Ansiedade e Depressão (HADS) foram utilizados para avaliar as características da população estudada e a prevalência de depressão e ansiedade nessa amostra. Resultados: A prevalência de sintomas ansiosos foi de 48,4% (44 pacientes), e a de sintomas depressivos, de 26,4% (24 pacientes). Desses, 19 (20,9% do total da amostra) pontuaram para os dois sintomas concomitantemente. Considerando a amostra como um todo, apenas 17 pacientes (18,7%) estavam recebendo tratamento para ansiedade ou depressão com benzodiazepínicos e/ou antidepressivos. Conclusão: Ansiedade e depressão são transtornos mais prevalentes em pacientes com síndrome coronariana aguda do que na população geral, mas geralmente são subdiagnosticados e subtratados. Os pacientes com presença simultânea de ansiedade e depressão apresentam escores mais altos na escala HADS para ansiedade e depressão e necessitam, portanto, de um controle mais intensivo.

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.

Pacientes que usan Cannabis sativa sp. con fines medicinales en Cuidados Paliativos, Hospital Gustavo Fricke: resultados de una encuesta local / Patients that use medical cannabis sativa for palliative care in the Hospital Gustavo Fricke: results from a local survey

El uso de Cannabis sativa sp.* de forma medicinal en pacientes con cáncer se ha utilizado como estrategia terapéutica para el alivio sintomático multimodal y mejoría en la calidad de vida. Dentro de los reportes descritos, la planta y sus derivados son utilizados por sus efectos analgésicos, antieméticos, orexígenos y ansiolíticos. Estos efectos son atribuibles a la manipulación exógena del sistema endocannabinoide mediante los compuestos biológicamente activos de la planta. Realizamos un estudio descriptivo a nivel local a través de una encuesta a los pacientes ingresados al programa de Cuidados Paliativos del Hospital Gustavo Fricke, para documentar el uso de cannabis de forma medicinal en pacientes oncológicos. De un total de 22 pacientes encuestados, 17 la utilizaban para manejo del dolor y 11 de ellos contestaron que el alivio era "mucho". Los pacientes refieren además utilizarla para el manejo de la ansiedad, sueño y apetito. La vía de administración más utilizada era la digestiva (n=18). Siete pacientes reportaron efectos adversos, y fue la vía inhalatoria la que presentó mayor cantidad de ellos (4/7). El más frecuente fue la psicoactividad (n=2). De los pacientes encuestados, ninguno utilizaba cannabis bajo indicación médica ni conocía los compuestos presentes en el preparado vegetal utilizado. Es llamativa la falta de indicación o asesoría médica con respecto a su uso y la utilización de preparados no-estandarizados cuya eficacia y seguridad no está demostrada. Palabras clave:

Cannabis sativa sp. is frequently used in patients with cancer as a therapeutic strategy for multimodal symptomatic relief and to improve quality of life. Previous reports describe its analgesic, antiemetic, orexigenic, and anxiolytic effects. These effects are attributable to the exogenous manipulation of the endocannabinoid system with biologically active components present in the cannabis plant. We conducted a local descriptive study, in which patients from the Palliative Care Program from Gustavo Fricke Hospital were surveyed to document the use of cannabis for medicinal purposes in oncological patients. From a total of 22 patients surveyed, 17 used it for pain relief and 11 reported that relief it provided was "a lot". Patients also referred using it to manage anxiety, sleep, and appetite. The most frequent form of administration was via oral (n = 18). Seven patients reported adverse effects, with inhalation being the administration route with most adverse events (4/7). The most frequent side effect was psychoactivity (n = 2). Of the patients surveyed, none of them used cannabis under medical prescription, and none knew the components present in the preparation. The lack of medical prescription and assessment in regards to cannabis use and the employment of non-standardized preparations, for which efficacy and safety has yet not been demonstrated, is alarming.

Chinese phytotherapy to reduce stress, anxiety and improve quality of life: randomized controlled trial / Fitoterapia china para reducción de estrés, ansiedad y mejoría de calidad de vida: ensayo clínico randomizado / Fitoterapia chinesa para redução de estresse, ansiedade e melhoria de qualidade de vida: ensaio clínico randomizado

Abstract OBJECTIVE To evaluate the effect of Chinese phytotherapyto reduce stress levels, anxiety and improve quality of life. METHOD double-blind randomized controlled trial with 89 volunteers divided into three groups: control (no intervention), Placebo and Phytotherapy. The study was conducted in 2015 with healthy adults treated at the Integrated and Eastern Therapy Institute,in Sao Paulo, Brazil. Participants were evaluated at baseline and after three weeks with the Stress Symptoms List (SSL), Anxiety Inventory-Trait and State and SF12v2 for quality of life. Intervention groups received a placebo or Gan May Zao formula (GMDZ)flaskwith 50 ml. RESULTS According to ANOVA, there were significant differences (p = 0.025) after treatment of stress (SSL2). And the difference was between control and Phytotherapy groups, according to the Tukey post hoc (p = 0.022). There were no differences in the levels of state-anxiety and physical and mental domains in the SF12v2. CONCLUSION The GMDZ formula reduced stress levels, but more studies are needed with greater sample, with reassessment of dosage and a longer period of treatment to confirm and extend the results. Brazilian Registry of Clinical Trials: RBR-28s4hz.

Resumen OBJETIVO Evaluar el efecto de la fitoterapia china en la reducción de los niveles de estrés, ansiedad y mejoría de calidad de vida. MÉTODO Ensayo clínico aleatorizado, doble ciego, con 89 voluntarios divididos en tres grupos: Control (sin intervención), Placebo y Fitoterapia. Se realizó en 2015, con adultos sanos atendidos en el Instituto de Terapia Integrada y Oriental, São Paulo. Fueron evaluados en el baseline y, después de 3 semanas, por el Listado de Síntomas de Estrés (LSE), Inventario de Ansiedad Rasgo-Estado y el SF12v2 de calidad de vida. Los grupos de intervención recibieron un frasco de 50 ml de placebo o la fórmula GanMai Da Zao (GMDZ). RESULTADOS Según ANOVA, hubo diferencia (p = 0,025) en el post tratamiento de estrés (LSE2). Y la diferencia fue entre los grupos Control y Fitoterapia, de acuerdo con el post hoc de Tukey (p = 0,022). No hubo diferencias en los niveles de ansiedad-estado y dominio físico y mental del SF12V2. CONCLUSIÓN La fórmula GMDZ redujo los niveles de estrés, pero son necesarios más estudios con muestra significativa, con reevaluación de la posología y un período mayor de tratamiento para confirmar y ampliar los resultados. Registro Brasileño de Ensayos Clínicos: RBR-28s4hz.

Resumo OBJETIVO Avaliar o efeito da fitoterapia chinesa na redução de níveis de estresse, ansiedade e melhoria de qualidade de vida. MÉTODO Ensaio clínico randomizado duplo-cego, com 89 voluntários divididos em três grupos: Controle (sem intervenção), Placebo e Fitoterapia. Foi realizado em 2015, com adultos saudáveis atendidos no Instituto de Terapia Integrada e Oriental, São Paulo. Foram avaliados no baseline e, após 3 semanas,pela Lista de Sintomas de Stress (LSS), Inventário de Ansiedade-Traço e Estado e o SF12v2 de qualidade de vida. Os grupos de intervenção receberam um frasco de 50 ml de placebo ou da fórmula Gan Mai Da Zao (GMDZ). RESULTADOS Segundo ANOVA, houve diferença (p=0,025) no pós-tratamento de estresse (LSS2). E a diferença foi entre os grupos Controle e Fitoterapia, de acordo com o post hocde Tukey (p=0,022). Não houve diferenças nos níveis de ansiedade-estado e domínio físico e mental do SF12v2. CONCLUSÃO A fórmula GMDZ reduziu os níveis de estresse, mas são necessários mais estudos com amostra significativa, com reavaliação da posologia e um período maior de tratamento para confirmar e ampliar os resultados. Registro Brasileiro de Ensaios Clínicos: RBR-28s4hz.

Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies

Objective: To conduct a systematic literature review of animal and human studies reporting anxiolytic or antidepressive effects of ayahuasca or some of its isolated alkaloids (dimethyltryptamine, harmine, tetrahydroharmine, and harmaline). Methods: Papers published until 3 April 2015 were retrieved from the PubMed, LILACS and SciELO databases following a comprehensive search strategy and using a predetermined set of criteria for article selection. Results: Five hundred and fourteen studies were identified, of which 21 met the established criteria. Studies in animals have shown anxiolytic and antidepressive effects of ayahuasca, harmine, and harmaline, and experimental studies in humans and mental health assessments of experienced ayahuasca consumers also suggest that ayahuasca is associated with reductions in anxiety and depressive symptoms. A pilot study reported rapid antidepressive effects of a single ayahuasca dose in six patients with recurrent depression. Conclusion: Considering the need for new drugs that produce fewer adverse effects and are more effective in reducing anxiety and depression symptomatology, the described effects of ayahuasca and its alkaloids should be further investigated.