Hiperconectados: las niñas, los niños y los adolescentes en las redes sociales. El fenómeno de TikTok / Hyperconnected: children and adolescents on social media. The TikTok phenomenon

Las plataformas digitales de comunicación en red revolucionaron el modo de comunicarnos, informarnos y entretenernos; impactaron principalmente en las nuevas generaciones. La pandemia incrementó los patrones de consumo en todas las edades y sus consecuencias: sedentarismo; obesidad; alteraciones del sueño, psicológicas, cognitivas, de la memoria/atención, del rendimiento académico; comportamientos problemáticos y riesgos de ciberacoso. La actividad de las nuevas generaciones en TikTok ­una plataforma donde pueden crear, visualizar, compartir videos y retos virales­ tiene impacto en su comportamiento. Sus publicaciones generan aprobaciones, comentarios y seguidores; esto estimula el circuito dopaminérgico de recompensa, que es la base de los comportamientos adictivos. El pediatra debe conocer estas conductas para recomendar buenas prácticas de uso. Esta revisión narrativa, basada en bibliografía de PubMed Central, SciELO, recomendaciones nacionales e internacionales, tiene como objetivo informar y actualizar a los profesionales sobre la plataforma, sus características y sus recomendaciones de uso seguro.

Network communication digital platforms have revolutionized the way we communicate, get information, and entertain ourselves; they have had a major impact on the new generations. The pandemic has increased consumption patterns at all ages and its consequences: a sedentary lifestyle, obesity, sleep, psychological, cognitive, memory/attention, and academic performance disorders, problematic behaviors, and risks of cyberbullying. The activity of the new generations on TikTok ­a platform that allows them to create, view, share videos and viral challenges­ has affected their behavior. Their posts lead to likes, comments, and followers; this stimulates the dopaminergic reward system, which is the basis of addictive behaviors. Pediatricians should be aware of these behaviors in order to recommend good practices. The objective of this narrative review, based on the bibliography from PubMed Central, SciELO, national and international recommendations, is to provide information and an update to health care providers on TikTok, its characteristics, and the recommendations for safe use.

Paradigma manicomial e proibicionismo como operadores da guerra de raças no Brasil / Asylum paradigm and prohibitionism operating the racial war in Brazil / Paradigma asilar y prohibicionismo como operadores de la guerra racial en Brasil

Este artigo relaciona o paradigma manicomial, relativo à assistência psiquiátrica, à compreensão e ao manejo do campo da saúde mental, ao paradigma proibicionista, referente ao porte, uso e à circulação de drogas, como duas séries de políticas e práticas sociais que operam a guerra de raças que está na base do Estado brasileiro. Com isso, propomos uma investigação arqueogenealógica acerca do emaranhado de condições de emergência das práticas e objetos de saber-poder mobilizados por esses dois paradigmas, atentando ao caráter político das verdades que as sustentam. Dedicamo-nos especialmente ao período entre o final do século XIX e o começo do XX ao interrogar as dinâmicas de forças que constituem as práticas sociais e seus efeitos de subjetivação, produzidos pela sujeição de corpos por meio de uma diversidade de mecanismos morais, disciplinares, eugênicos, higienistas e biopolíticos que articulam os anseios de modernização e produtividade do Estado brasileiro à gestão dos problemas de saúde e segurança do país, colocando a pobreza, o vício e a doença como desdobramento da sua constituição racial. Concluímos, por fim, que o conflito de raças aparece como fundo intrínseco que se atualiza no cerne e a partir dos campos problemáticos da saúde mental e das drogas, colocando como saída dos impasses sociais e políticos eliminar ou pelo menos diluir, via miscigenação ou submissão para integração, o elemento físico e cultural do negro do Brasil.(AU)

This article puts in relation the asylum paradigm, associated to psychiatric care, to the understanding and management of the mental health field, to the prohibitionist paradigm, that refers to the possession, use and circulation of drugs, as two series of social policies and practices that operate racial war that is in the base of the Brazilian State. So on, we propose an archeogenealogical investigation about the emergency conditions of the practices and objects of knowledge-power organized by these two paradigms, paying attention to the political character of the truths that support them. Looking especially at the period between the end of the 19th century and the beginning of the 20th, we questioned the dynamics of forces that constitute social practices and their effects of subjectivation, produced by the subjection of bodies through moral, disciplinary, eugenic, hygienist and biopolitics mechanisms that articulate the modernization and productivity aspirations of the Brazilian State to the management of the country's health and safety problems, understanding poverty, addiction and disease as consequences of its racial constitution. We conclude that the conflict of races is an intrinsic background that is updated at the heart of the problematic fields of mental health and drugs. Considering this, the solution for social and political impasses is the elimination or at least dilution, through miscegenation or submission for integration, of the physical and cultural element of black people in Brazil.(AU)

Este artículo relaciona el paradigma asilar de atención psiquiátrica, comprensión y manejo del campo de la salud mental, con el paradigma prohibicionista, referente a al uso y circulación de drogas, como dos series de políticas y prácticas sociales que operan la guerra racial que está en el fundamento del Estado brasileño. Así, proponemos una investigación arqueogenealógica sobre las condiciones de emergencia de prácticas y objetos de saber-poder movilizados por estos dos paradigmas, prestando atención al carácter político de las verdades que los sustentan. Nos dedicamos especialmente al período entre finales del siglo XIX y principios del XX buscando la dinámica de fuerzas que constituyen a las prácticas sociales y sus efectos de subjetivación, producidos por la sujeción de los cuerpos a través de una diversidad de mecanismos morales, disciplinarios, eugenésicos, higienistas y biopolíticos que articulan las aspiraciones de modernización y productividad del Estado brasileño a la gestión de los problemas de salud y seguridad del país, comprendiendo la pobreza, la adicción y la enfermedad como resultado de su constitución racial. Finalmente, concluimos que el conflicto racial aparece como un trasfondo intrínseco que se actualiza en el cerne y desde los campos problemáticos de la salud mental y de las drogas, tomando como soluciones a los impasses sociales y políticos nacionales, la eliminación o al menos la dilución, a través del mestizaje o de la sumisión para fines de integración, del elemento físico y cultural del negro en Brasil.(AU)

Uso não prescrito de metilfenidato e desempenho acadêmico de estudantes de medicina / Non-prescribed use of methylphenidate and academic performance of medical students / El uso no prescrito de metilfenidato y el rendimiento académico de estudiantes de medicina

O metilfenidato é um fármaco indicado no tratamento do transtorno de déficit de atenção e hiperatividade (TDAH) e da narcolepsia. Atua no sistema nervoso central inibindo a recaptação de dopamina e noradrenalina, o que provoca um efeito psicoestimulante. Estudos anteriores demonstraram um aumento no consumo da droga por indivíduos saudáveis que buscam aprimoramento cognitivo. O objetivo deste estudo foi investigar a relação entre o uso não prescrito de metilfenidato e o desempenho acadêmico de estudantes de medicina de uma universidade do sul de Santa Catarina. Trata-se de uma pesquisa descritiva de caráter quantitativo. Participaram da pesquisa 243 acadêmicos do segundo ao oitavo semestre do curso de medicina; os dados foram coletados por meio de um questionário e analisados com ajuda do software SPSS versão 21.0. A prevalência de uso não prescrito do metilfenidato foi de 2,9%, enquanto 17,3% dos pesquisados afirmaram já ter utilizado o medicamento alguma vez na vida. As motivações para consumo mais citadas foram melhorar o desempenho cognitivo (10%) e ficar acordado por mais tempo (4,1%), e a forma de obtenção mais comum foi por meio de amigos (56,5%). O psicoestimulante não apresentou efeitos de aprimoramento cognitivo, uma vez que participantes que nunca utilizaram o fármaco apresentaram um desempenho acadêmico superior (8,80) se comparados àqueles que usam (7,92) ou já usaram (8,01). Os resultados corroboram a hipótese de efeito relacionado a sensações de bem-estar em pessoas saudáveis, o que torna preocupante a injustificada exposição aos efeitos adversos da droga. Ressalta-se a necessidade de ações que visem à promoção de saúde mental aos universitários.(AU)

Methylphenidate is a drug indicated for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It acts on the central nervous system by inhibiting dopamine and norepinephrine reuptake, causing a psychostimulant effect. Previous studies have shown an increase in drug use by healthy individuals seeking cognitive enhancement. This study aimed to investigate the relationship between non-prescribed methylphenidate use and academic performance of medical students of a university in southern Santa Catarina. It is quantitative descriptive study. A total of 243 students from the second to the eighth semester of the medicine school participated in the research; data were collected by using a questionnaire and analyzed with the software SPSS Version 21.0. The prevalence of non-prescribed methylphenidate use was 2.9% and 17.3% of respondents said they had used the drug once in their lifetime. The most cited motivations for consumption were improving cognitive performance (10%) and staying awake longer (4.1%), with the most common way of obtention being through friends (56.5%). The psychostimulant had no cognitive enhancement effects since participants who never used the drug had a higher academic performance (8.80) compared with those who use (7.92) or have used it (8.01). The results corroborate the hypothesis of an effect related to feelings of well-being in healthy people, thus making the unjustified exposure to the adverse effects of the drug concerning. We emphasize the need for actions aimed at promoting mental health to university students.(AU)

El metilfenidato es un medicamento indicado para el tratamiento del trastorno por déficit de atención e hiperactividad (TDAH) y de la narcolepsia. Actúa sobre el sistema nervioso central al inhibir la reabsorción de dopamina y norepinefrina, causando un efecto psicoestimulante. Estudios anteriores han demostrado un aumento del consumo de este medicamento por personas sanas que buscan una mejora cognitiva. El objetivo de este estudio fue investigar la relación entre el uso no prescrito de metilfenidato y el rendimiento académico de los estudiantes de medicina de una universidad en el sur de Santa Catarina (Brasil). Se trató de una investigación cuantitativa descriptiva. Participaron en la investigación 243 estudiantes del segundo al octavo semestre del curso de medicina; los datos se recolectaron mediante un cuestionario y se analizaron con la ayuda del software SPSS, versión 21.0. La prevalencia del uso no prescrito de metilfenidato fue del 2,9%, y el 17,3% de los encuestados dijeron que habían usado el medicamento en algún momento de sus vidas. Las motivaciones de consumo más citadas fueron: mejorar el rendimiento cognitivo (10%) y permanecer despierto por más tiempo (4,1%), y la forma más común de obtenerlo fue con los amigos (56,5%). El psicoestimulante no tuvo ningún efecto de mejora cognitiva, ya que los participantes que nunca lo usaron tuvieron un rendimiento académico superior (8,80) en comparación con aquellos que lo usan (7,92) o lo han usado (8,01). Los resultados corroboraron la hipótesis de un efecto relacionado con los sentimientos de bienestar en personas sanas, lo que provoca una exposición injustificada a los efectos adversos de este fármaco. Se enfatiza la necesidad de acciones dirigidas a promover la salud mental de los estudiantes universitarios.(AU)

Polyaspartic acid grafted dopamine polymer chelated Fe 3+ for magnetic resonance imaging visual photothermal therapy agent / 生物医学工程学杂志

This study aims to explore the potential of polyaspartic acid grafted dopamine copolymer (PAsp- g-DA) chelated Fe 3+ for magnetic resonance imaging (MRI) visual photothermal therapy. Polyaspartic acid grafted copolymer of covalently grafted dopamine and polyethylene glycol (PAsp- g-DA/PEG) was obtained by the ammonolysis reaction of poly succinimide (PSI), and then chelated with Fe 3+ in aqueous solution. The relaxivity in vitro, magnetic resonance imaging enhancement in vivo and photothermal conversion effect at 808 nm were investigated. The results showed that polymeric iron coordination had good near-infrared absorption and photothermal conversion properties, good magnetic resonance enhancement effect, and good longitudinal relaxation efficiency under different magnetic field intensities. In summary, this study provides a new magnetic resonance visual photothermal therapeutic agent and a new research idea for the research in related fields.

Experimental study of dopamine ameliorating the inflammatory damage of olfactory bulb in mice with allergic rhinitis / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the effects of dopamine on olfactory function and inflammatory injury of olfactory bulb in mice with allergic rhinitis (AR). Methods: AR mouse model was established by using ovalbumin (OVA), and the mice were divided into two groups: olfactory dysfunction (OD) group and without OD group through buried food pellet test (BFPT). The OD mice were randomly divided into 2 groups, and OVA combined with dopamine (3, 6, 9 and 12 days, respectively) or OVA combined with an equal amount of PBS (the same treatment time) was administered nasally. The olfactory function of mice was evaluated by BFPT. The number of eosinophils and goblet cells in the nasal mucosa were detected by HE and PAS staining. Western blotting, immunohistochemistry or immunofluorescence were used to detect the expression of olfactory marker protein (OMP) in olfactory epithelium, the important rate-limiting enzyme tyrosine hydroxylase (TH) of dopamine, and the marker proteins glial fibrillary acidic protein (GFAP) and CD11b of glial cell in the olfactory bulb. TUNEL staining was used to detect the damage of the olfactory bulb. SPSS 26.0 software was used for statistical analysis. Results: AR mice with OD had AR pathological characteristics. Compared with AR mice without OD, the expression of OMP in olfactory epithelium of AR mice with OD was reduced (F=26.09, P<0.05), the expression of GFAP and CD11b in the olfactory bulb was increased (F value was 38.95 and 71.71, respectively, both P<0.05), and the expression of TH in the olfactory bulb was decreased (F=77.00, P<0.05). Nasal administration of dopamine could shorten the time of food globule detection in mice to a certain extent, down-regulate the expression of GFAP and CD11b in the olfactory bulb (F value was 6.55 and 46.11, respectively, both P<0.05), and reduce the number of apoptotic cells in the olfactory bulb (F=25.64, P<0.05). But dopamine had no significant effect on the number of eosinophils and goblet cells in nasal mucosa (F value was 36.26 and 19.38, respectively, both P>0.05), and had no significant effect on the expression of OMP in the olfactory epithelium (F=55.27, P>0.05). Conclusion: Dopamine can improve olfactory function in mice with AR to a certain extent, possibly because of inhibiting the activation of glial cells in olfactory bulb and reducing the apoptotic injury of olfactory bulb cells.

Trends of vasopressor use in intensive care units in Colombia / Tendencias de consumo de vasopresores en unidades de cuidados intensivos de Colombia

Abstract Introduction Vasopressors are essential in the management of various types of shock. Objective To establish the trend of vasopressors use in the intensive care units (ICU) in a population of patients affiliated with the Colombian Health System, 2010-2017. Methods Observational trial using a population database of patients hospitalized in eleven ICUs in various cities in Colombia. The drugs dispensed to hospitalized patients over 18 years old, from January 2010 until December 2017 were considered. A review and analysis of the vasopressors dispensed per month was conducted, taking into account sociodemographic and pharmacological variables (vasopressor used and daily doses defined per 100/beds/day (DBD). Results 81,348 dispensations of vasopressors, equivalent to 26,414 treatments in 19,186 patients receiving care in 11 hospitals from 7 cities were reviewed. The mean age of patients was 66.3±18.1 years and 52.6 % were males. Of the total number of treatments recorded, 17,658 (66.8 %) were with just one vasopressor. Norepinephrine was the most frequently prescribed drug (75.9 % of the prescriptions dispensed; 60.5 DBD), followed by adrenaline (26.6 %; 41.6 DBD), dopamine (19.4%), dobutamine (16.0 %), vasopressin (8.5 %) and phenylephrine (0.9 %). The use of norepinephrine increased from 2010 to 2017 (+6.19 DBD), whilst the use of other drugs decreased, particularly the use of adrenaline (-60.6 DBD) and dopamine (-10.8 DBD). Conclusions Norepinephrine is the most widely used vasopressor showing a growing trend in terms of its use during the study period, which is supported by evidence in favor of its effectiveness and safety in patients with shock.

Resumen Introducción Los fármacos vasopresores son fundamentales en el manejo de los diferentes tipos de choque. Objetivo Determinar la tendencia de utilización de fármacos vasopresores en unidades de cuidados intensivos (UCI) en una población de pacientes afiliados al Sistema de Salud de Colombia, 2010-2017. Métodos Estudio observacional, a partir de una base de datos poblacional con pacientes hospitalizados en once UCI de diferentes ciudades de Colombia. Se obtuvieron las dispensaciones de pacientes mayores de 18 años hospitalizados desde enero de 2010 hasta diciembre de 2017. Se hizo revisión y análisis de la dispensación mensual de vasopresores. Se consideraron variables sociodemográficas y farmacológicas (medicamento vasopresor usado y dosis diarias definidas por 100 camas/día [DCD]). Resultados Se revisaron 81.348 dispensaciones de vasopresores, equivalentes a 26.414 terapias en 19.186 pacientes atendidos en 11 hospitales de 7 ciudades, cuya edad promedio fue 66,3±18,1 años y el 52,6 % eran hombres. Del total de terapias registradas, 17.658 (66,8 %) fueron con un solo vasopresor. La norepinefrina fue el más comúnmente prescrito (75,9 % de las dispensaciones; 60,5 DCD), seguido por adrenalina (26,6 %; 41,6 DCD), dopamina (19,4 %), dobutamina (16,0 %), vasopresina (8,5 %) y fenilefrina (0,9 %). El uso de norepinefrina se incrementó de 2010 a 2017 (+6,19 DCD), mientras que el de otros fármacos disminuyó, especialmente adrenalina (-60,6 DCD) y dopamina (-10,8 DCD). Conclusiones La norepinefrina es el fármaco vasopresor más utilizado y el que ha demostrado una tendencia de uso incremental durante el periodo de estudio, lo cual está respaldado por evidencia a favor de su efectividad y seguridad en pacientes con choque.

Active lifestyle enhances protein expression profile in subjects with Lewy body pathology / O estilo de vida ativo melhora o perfil de expressão de proteínas em indivíduos com a patologia de corpos de lewy

ABSTRACT. Clinical trials of the effects of physical activity have reported improvements in symptoms and quality of life in patients with Parkinson's disease (PD). Additionally, morphological brain changes after exercising were reported in PD animal models. However, these lifestyle-related changes were not evaluated in postmortem brain tissue. Objective: We aimed to evaluate, by immunohistochemistry, astrocytes, tyrosine hydroxylase (TH) and structural proteins expression (neurofilaments and microtubules — MAP2) changes in postmortem brain samples of individuals with Lewy body pathology. Methods: Braak PD stage≥III samples, classified by neuropathology analysis, from The Biobank for Aging Studies were classified into active (n=12) and non-active (n=12) groups, according to physical activity lifestyle, and paired by age, sex and Braak staging. Substantia nigra and basal ganglia were evaluated. Results: Groups were not different in terms of age or gender and had similar PD neuropathological burden (p=1.00). We observed higher TH expression in the active group in the substantia nigra and the basal ganglia (p=0.04). Astrocytes was greater in the non-active subjects in the midbrain (p=0.03) and basal ganglia (p=0.0004). MAP2 levels were higher for non-active participants in the basal ganglia (p=0.003) and similar between groups in the substantia nigra (p=0.46). Neurofilament levels for non-active participants were higher in the substantia nigra (p=0.006) but not in the basal ganglia (p=0.24). Conclusion: Active lifestyle seems to promote positive effects on brain by maintaining dopamine synthesis and structural protein expression in the nigrostriatal system and decrease astrogliosis in subjects with the same PD neuropathology burden.

RESUMO. Estudos dos efeitos da atividade física relataram melhora nos sintomas e na qualidade de vida de pacientes com doença de Parkinson (DP). Além disso, alterações morfológicas do cérebro após o exercício físico foram relatadas em modelos animais da DP. No entanto, essas mudanças relacionadas ao estilo de vida não foram avaliadas em tecido cerebral post-mortem. Objetivo: Avaliar a expressão de astrócitos, tirosina hidroxilase (TH) e a expressão de proteínas estruturais (neurofilamentos e microtúbulos — MAP2) por imuno-histoquímica, em amostras cerebrais post-mortem de indivíduos com corpos de Lewy. Métodos: Amostras com estágio de Braak para DP≥III, classificação neuropatológica, fornecidas pelo biobanco de estudos do envelhecimento foram classificadas em grupos ativos (n=12) e não ativos (n=12), de acordo com o estilo de vida (atividade física), e pareados por idade, sexo e estadiamento de Braak. Analisou-se a substância negra e gânglios da base. Resultados: Idade, sexo e classificação para DP foram semelhantes (p=1,00). Observou-se maior expressão de TH no grupo ativo (p=0,04). Amostras de não ativos revelaram maior expressão de astrócitos no mesencéfalo (p=0,03) e nos gânglios da base (p=0,0004); MAP2 nos gânglios da base (p=0,003); os níveis de neurofilamentos foram maiores na substância negra (p=0,006). Conclusão: O estilo de vida ativo parece promover efeitos positivos no cérebro, mantendo a síntese de dopamina e a expressão estrutural de proteínas no sistema nigrostriatal e com diminuição da ativação de astrócitos em indivíduos com a mesma classificação neuropatológica para a DP.

Dopamina e comportamento alimentar: polimorfismos em receptores dopaminérgicos e fenótipos relacionados à obesidade / Dopamine and eating behavior: dopaminergic receptor polymorphisms and obesity related phenotypes

Dentre os sistemas neurais responsáveis pela ingestão dos alimentos, destaca-se a via dopaminérgica mesolímbica que, através da liberação de dopamina nos núcleos de accumbens, desperta prazer e motivação para recompensas químicas e naturais. Esta via de recompensa age através dos receptores dopaminérgicos transmembranares, que variam de DRD1 a DRD5. Desta forma, considerando os efeitos prazerosos despertados pela ingestão alimentar, é plausível que variações genéticas em genes do sistema dopaminérgico possam ter um papel na arquitetura genética da obesidade. Este estudo tem como objetivo realizar uma revisão narrativa da literatura sobre a influência de variantes genéticas nos receptores dopaminérgicos em fenótipos relacionados com a obesidade. Em conjunto, os principais achados desta revisão indicaram que os genes codificadores dos receptores DRD2 e DRD4 possam ser os mais relevantes no contexto da obesidade e fenótipos relacionados. No entanto, a obesidade é uma doença complexa e multifatorial e novos estudos são ainda necessários para uma melhor compreensão do impacto da dopamina nos desfechos relacionado à obesidade. É importante também destacar que esses efeitos podem ser específicos para subgrupos de pacientes e que outros fatores, além das variantes genéticas, devem ser considerados. (AU)

Among the neural systems responsible for food ingestion, the mesolimbic dopaminergic pathway stands out by eliciting pleasure and motivation for chemical and natural rewards through the release of dopamine in the nucleus accumbens. This reward pathway is regulated by transmembrane dopaminergic receptors, which range from DRD1 to DRD5. Thus, considering the pleasurable effects aroused by food intake, it is plausible that genetic variations in genes of the dopaminergic system may have a role in the genetic architecture of obesity. This study aims to conduct a narrative review of the literature on the influence of genetic variants of dopaminergic receptors on obesity-related phenotypes. Taken together, the main findings of this review indicated that the genes encoding the DRD2 and DRD4 receptors may be the most relevant in the context of obesity and related phenotypes. However, obesity is a complex and multifactorial disease and new studies are still being conducted to better understand the impact of dopamine on obesity-related outcomes. It is also important to note that these effects can be specific to subgroups of patients and that other factors, in addition to genetic variants, must be considered. (AU)

Comparative assessment of effect of malt with different bud length on prolactin in hyperprolactinemia rat

Malt is the mature fruit of Hordeum vulgare L. after germination and drying and has been applied for treatment female abnormal galactorrhea. Previous studies have showed total alkaloids in malt have anti-HPRL effect. However, total alkaloids of malt change with the growth cycle, and the specified levels of total alkaloids in different bud length of malt have not been decided. To determine the definitive level of total alkaloids in different buds of malt and the most suitable bud length for clinical application by comparing effects on hyperprolactinemia rat. During the budding of malt, the content of total alkaloids first increased and then decreased, and it peaked at a bud length of 0.75 cm. Treated the HPRL model rats with different buds of malt, the PRL level was decreased, the number of PRLpositive cells and the mRNA expression level in the pituitary were significantly declined, and the number of dopamine D1 and D2 receptors in the hypothalamus was increased. The above changes were most significant in 0.75 cm bud. These results suggest that in terms of the content of effective substance and the effects on HPRL model rats, a malt bud length of 0.75 cm is optimal for clinical application.

Heterogeneous expression of DOPA decarboxylase to improve the production of dopamine in Escherichia coli / 生物工程学报

Dopamine is the precursor of a variety of natural antioxidant compounds. In the body, dopamine acts as a neurotransmitter that regulates a variety of physiological functions of the central nervous system. Thus, dopamine is used for the clinical treatment of various types of shock. Dopamine could be produced by engineered microbes, but with low efficiency. In this study, DOPA decarboxylase gene from Sus scrofa (Ssddc) was cloned into plasmids with different copy numbers, and transformed into a previously developed L-DOPA producing strain Escherichia coli T004. The resulted strain was capable of producing dopamine from glucose directly. To further improve the production of dopamine, a sequence-based homology alignment mining (SHAM) strategy was applied to screen more efficient DOPA decarboxylases, and five DOPA decarboxylase genes were selected from 100 candidates. In shake-flask fermentation, the DOPA decarboxylase gene from Homo sapiens (Hsddc) showed the highest dopamine production (3.33 g/L), while the DOPA decarboxylase gene from Drosophila Melanogaster (Dmddc) showed the least residual L-DOPA concentration (0.02 g/L). In 5 L fed-batch fermentations, production of dopamine by the two engineered strains reached 13.3 g/L and 16.2 g/L, respectively. The residual concentrations of L-DOPA were 0.45 g/L and 0.23 g/L, respectively. Finally, the Ssddc and Dmddc genes were integrated into the genome of E. coli T004 to obtain genetically stable dopamine-producing strains. In 5 L fed-batch fermentation, 17.7 g/L of dopamine was produced, which records the highest titer reported to date.

Altered dopamine metabolism and its role in pathogenesis of Parkinson's disease / 生理学报

Parkinson's disease (PD), one of the most frequent neurodegenerative disorders, is characterized by the selective loss of dopaminergic neurons in the substantia nigra (SN). Genetic vulnerability, aging, environmental insults are believed to contribute to the pathogenesis of PD. However, the cellular and molecular mechanism of dopaminergic neurons degeneration remains incompletely understood. Dopamine (DA) metabolism is a cardinal physiological process in dopaminergic neurons, which is closely related to the loss of dopaminergic neurons in the SN. DA metabolism takes part in several pathological processes of PD neurodegeneration, such as iron metabolism disturbance, α-synuclein mis-folding, endoplasmic reticulum stress, protein degradation dysfunction, neuroinflammatory response, etc. In this review, we will describe altered DA metabolism and its contributions to PD pathogenesis.

Effect of electroacupuncture preconditioning on the contents of dopamine and 5-hydroxytryptamine in lateral hypothalamus area and cerebellar fastigial nucleus of rats with myocardial ischemia-reperfusion injury / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) preconditioning at heart meridian acupoints on the contents of dopamine (DA) and 5-hydroxytryptamine (5-HT) in lateral hypothalamus area (LHA) and cerebellar fastigial nucleus (FN) in the rats with acute myocardial ischemia-reperfusion injury (MIRI), and explore the role and mechanism of LHA and FN in the effect of EA at heart meridian acupoints against acute MIRI.@*METHODS@#Sixty SD rats were randomly divided into a sham-operation group, a model group, an EA heart meridian group and an EA lung meridian group, 12 rats in each group, as well as an LHA plus heart meridian group (damage of bilateral LHA) and an FN plus heart meridian group (damage of bilateral FN), 6 rats in each one. Three days after nucleus destruction, EA was applied to "Shenmen" (HT 7) and "Tongli" (HT 5) in the EA heart meridian group, the LHA plus heart meridian group and the FN plus heart meridian group and EA was applied to "Taiyuan" (LU 9) and "Lieque" (LU 7) in the EA lung meridian group, with 1 V in stimulating voltage and 2 Hz in frequency, lasting 20 minutes each time, once a day, for consecutively 7 days before model replication. Except in the sham-operation group, MIRI rat models were duplicated by ligation of the left anterior descending branch of the coronary artery in the rest groups. Using Power lab physiological recorder, ST segment displacement value was recorded before modeling, 30 min after ligation and 120 min after reperfusion separately. The high performance liquid chromatography-electrochemical detection and analysis system was adopted to determine the contents of DA and 5-HT in LHA and FN dialysate after rat modeling in each group.@*RESULTS@#In comparison of ST segment displacement value 30 min after ligation and 120 min after reperfusion among groups, the value in the model group was higher than that in the sham-operation group (@*CONCLUSION@#EA preconditioning at heart meridian acupoints can effectively alleviate myocardial injury in acute MIRI rats, during which, DA and 5-HT in LHA and FN may be the important material basis.

Effect of electroacupuncture on serum melatonin and dopamine in aged insomnia / 中国针灸

OBJECTIVE@#To observe the clinical effect of electroacupuncture (EA) on aged insomnia, and explore its possible mechanism.@*METHODS@#A total of 60 patients with aged insomnia were randomly divided into an EA group (30 cases) and a sham EA group (30 cases, 1 case dropped off). The patients in the EA group were treated with acupuncture at Baihui (GV 20), Yintang (GV 29), Shenmen (HT 7), Sanyinjiao (SP 6), Xinshu (BL 15) and Shenshu (BL 23), and EA was used at Baihui (GV 20) and Yintang (GV 29), with intermittent wave, 2 Hz in frequency. In the sham EA group, the acupoints and the EA connection acupoints were the same as those in the EA group, 2-3 mm in depth, but no current was connected. The intervention was given 30 min each time, once every other day, 3 times a week for 4 weeks in the both groups. Before and after treatment, the Pittsburgh sleep quality index (PSQI) and Montreal cognitive assessment (MoCA) scale were used to assess sleep quality and cognitive function, and serum melatonin (MT) and dopamine (DA) levels were detected.@*RESULTS@#After treatment, the total score and sub-item scores of PSQI in the EA group were lower than those before treatment (@*CONCLUSION@#Electroacupuncture can improve sleep quality and cognitive function in aged insomnia patients, and its mechanism may be related to regulating serum MT and DA levels.

Evolución clínica de niños con shock séptico refractario a fluidos tratados con dopamina o adrenalina. Estudio retrospectivo en un servicio de emergencias pediátrico de Argentina / Clinical outcome of children with fluid-refractory septic shock treated with dopamine or epinephrine. A retrospective study at a pediatric emergency department in Argentina

RESUMEN Objetivo: Analizar la evolución clínica de niños con shock séptico refractario a volumen tratados inicialmente con dopamina o adrenalina. Métodos: Estudio de cohorte retrospectivo con ámbito en un servicio de urgencias pediátrico de un hospital de tercer nivel. Población: niños ingresados con shock séptico refractario a volumen. Se comparó la evolución clínica entre 2 grupos: Grupo Dopamina y Grupo Adrenalina. Las variables de interés fueron: uso de ventilación mecánica invasiva, días de inotrópicos, estancia hospitalaria, estancia en cuidados intensivos y mortalidad. Para variables numéricas y categóricas utilizamos medidas de tendencia central y para comparación las pruebas de U Mann Whitney y χ2 test. Resultados: Incluimos 118 pacientes. El 58,5% recibió dopamina y 41,5% adrenalina. El uso de ventilación mecánica invasiva fue 38,8% para adrenalina versus 40,6% para dopamina (p = 0,84) con una mediana de 4 días para adrenalina y 5,5 para dopamina (p = 0,104). La mediana para días de inotrópicos fue de 2 días para ambos grupos (p = 0,714). La mediana de estancia hospitalaria fue de 11 para adrenalina y 13 para dopamina (p = 0,554) y de estancia en cuidados intensivos se registró una mediana de 4 días (0 - 81 días) siendo igual en ambos grupos (p = 0,748). La mortalidad fue de 5% para el Grupo Adrenalina versus 9% para el Grupo Dopamina (p = 0,64). Conclusiones: En nuestro centro, no observamos diferencias en uso de ventilación mecánica invasiva y tiempo de inotrópicos, estancia hospitalaria y cuidados intensivos y mortalidad entre niños ingresados al servicio de urgencias pediátrico con diagnóstico de shock séptico refractario a volumen tratados inicialmente con dopamina o adrenalina.

Abstract Objective: To analyze the clinical outcome of children with fluid-refractory septic shock initially treated with dopamine or epinephrine. Methods: A retrospective cohort study was conducted at a pediatric emergency department of a tertiary hospital. Population: children admitted because of fluid-refractory septic shock. Clinical outcome was compared between two groups: Dopamine and Epinephrine. Variables evaluated were use of invasive mechanical ventilation, days of inotropic therapy, length of hospital stay, intensive care stay, and mortality. For numerical and categorical variables, we used measures of central tendency. They were compared by the Mann-Whitney U-test and the (2 test. Results: We included 118 patients. A total of 58.5% received dopamine and 41.5% received epinephrine. The rate of invasive mechanical ventilation was 38.8% for epinephrine versus 40.6% for dopamine (p = 0.84), with a median of 4 days for the Epinephrine Group and 5.5 for the Dopamine Group (p = 0.104). Median time of inotropic therapy was 2 days for both groups (p = 0.714). Median hospital stay was 11 and 13 days for the Epinephrine and Dopamine groups, respectively (p = 0.554), and median stay in intensive care was 4 days (0 - 81 days) in both groups (p = 0.748). Mortality was 5% for the Epinephrine Group versus 9% for the Dopamine Group (p = 0.64). Conclusions: At our center, no differences in use of invasive mechanical ventilation, time of inotropic therapy, length of hospital stay, length of intensive care unit stay, or mortality were observed in children admitted to the pediatric emergency department with a diagnosis of fluid-refractory septic shock initially treated with dopamine versus epinephrine.

Asociación entre el sistema de recompensa del cerebro y elección de comida en adultos mayores y de mediana edad / Association between the reward system and food choice in middle-aged and older adults

Resumen Introducción. Todos los días las personas toman diferentes decisiones relacionadas con su elección de alimentos, lo que a su vez determina sus hábitos alimenticios. El sistema de recompensa del cerebro (SRC) permite asociar ciertas situaciones con una sensación de placer, lo que influye en la posterior elección de alimentos. Objetivo. Describir cómo influye el SRC en el proceso de elección de comida en adultos de mediana edad y en adultos mayores autosuficientes. Materiales y métodos. Se realizó una búsqueda de la literatura en PubMed y SciELO. Se buscaron artículos escritos en inglés y español y publicados entre 1996 y 2018 utilizando los siguientes términos (en ambos idiomas): "elección de la comida", "sistema de recompensa", "nutrición", "adulto", "adulto mayor", "estado nutricional" y "envejecimiento". Resultados. 50 artículos cumplieron con los criterios de inclusión. Solo 1 estudio estaba escrito en español; 22 fueron realizados en adultos mayores y el resto en adultos entre 20 y 40 años. Conclusiones. Teniendo en cuenta el escaso número de estudios sobre la conducta alimentaria en general, y en particular sobre la elección de comida en adultos mayores y de mediana edad, es necesario realizar más estudios en Latinoamérica sobre los procesos que subyacen al SRC y su relación con la elección de comida, y cómo estos cambian con la edad para predecir posibles conductas alimentarias e implementar intervenciones efectivas, pues una dieta saludable es esencial para un envejecimiento saludable.

Abstract Introduction: Every day, people make different decisions regarding the food they choose, which in turn determine their eating habits. The reward system (RS) allows associating certain situations to pleasure, which influences subsequent food choices. Objective: To describe how the RS influences the selection of foods in middle-aged and self-reliant older adults. Materials and methods: A literature search was conducted in PubMed and SciELO. Articles written in English and Spanish and published between 1996 and 2018 were included in the search; the following search terms (in both languages) were used: "food choice", "reward system", "nutrition", "adult", "elderly", "nutritional status" and "aging". Results: 50 articles met the inclusion criteria. Only 1 study was written in Spanish; 22 were conducted on older adults and the rest on adults between 20 and 40 years old. Conclusions: Studies on eating behavior in general and on food choice in older and middle-aged adults in particular, are scarce. Therefore, further research in the Latin-America is needed to analyze the processes underlying the RS and its relationship to food choice, and how these processes change as people age in order to predict possible eating behaviors and implement effective interventions, since a healthy diet is essential for healthy aging.

Angina de Ludwig complicada con shock séptico / Ludwig´s angina complicated with septic shock

Introduction: Ludwig's angina is one of the soft tissue infections of the neck and tongue floor with the most admissions to intensive care units (ICU) due to its compromise of the airway and complications from septic shock. The incidence is higher in the adult population, and with the use of the latest generation antibiotics, its incidence has decreased. One of the most frequent causes is the presence of an odontogenic focus such as abscesses, mainly in the second and third molars. Objective: To describe a clinical case, admitted to the hospital ICU, highlighting the comprehensive management and adequate antibiotic therapy. Main data of the case: 24-year-old female patient, a native of Latacunga, went to the emergency service of the Hospital del Sur de Quito for a fever of 10 days of evolution and taking the general condition with signs of shock, and intense pain in the tongue, with edema, and impaired phonation. For initial management, intravenous tramal, IV hydrocortisone, and a broad spectrum antibiotic with piperacillin with tazobactam 4 grams IV every 6 hours, and IV metronidazole every 8 hours. Conclusions: Ludwig's angina is a pathology that usually involves young patients, whose evolution is rapid and its inadequate management leads to death, associated with obstructive respiratory failure and severe sepsis, which requires a timely diagnosis.

Introducción: La angina de Ludwig constituye una de las infecciones de los tejidos blandos del cuello y piso de la lengua con más ingresos en las unidades de cuidados intensivos (UCI) por su compromiso de la vía aérea y complicaciones por shock séptico. La incidencia es mayor en la población adulta, y con el uso de los antibióticos de última generación, su incidencia ha disminuido. Una de las causas más frecuentes es la presencia de un foco odontogénico como los abscesos, principalmente en el segundo y el tercer molar. Objetivo: Describir un caso clínico, internado en la UCI del hospital, destacando el manejo integral y la terapia antibiótica adecuada. Datos principales del caso: paciente femenina de 24 años, natural de Latacunga, acude al servicio de emergencias del Hospital del sur de Quito por fiebre de 10 días de evolución y toma del estado general con signos de shock, y dolor intenso en lengua, con edema, y deterioro de la fonación. Para el abordaje inicial se administra tramadol por vía intravenosa (IV), hidrocortisona IV y antibiótico de amplio espectro con piperacilina con tazobactam 4 gramos IV cada 6 horas, y metronidazol IV cada 8 horas. Conclusiones: la angina de Ludwig es una afección que habitualmente involucra pacientes jóvenes, cuya evolución es rápida y su inadecuado abordaje conlleva a la muerte, asociado con insuficiencia respiratoria obstructiva y sepsis grave, por lo que requiere un diagnóstico oportuno

Therapeutic Effect of a Novel Chimeric Molecule Targeting Both Somatostatin and Dopamine Receptors on Growth Hormone-Secreting Pituitary Adenomas

BACKGROUND: Acromegaly is a rare disease primarily caused by growth hormone (GH)-secreting pituitary adenomas, and its treatment is costly. Moreover, some patients are unresponsive to treatment. Hence, there are increasing efforts to develop new drugs with improved effectiveness for this disease. BIM23B065 is a novel chimeric molecule that acts on both somatostatin and dopamine receptors. This study aimed to investigate the effects of BIM23B065 compared with those of a somatostatin receptor analog and a dopamine agonist.METHODS: The effects of BIM23B065 on the proliferation, GH and insulin-like growth factor-1 (IGF-1) levels, and extracellular signal-regulated kinase (ERK) 1/2 and cyclic AMP response element binding (CREB) phosphorylation of GH3 cells were investigated with MTS assay, enzyme-linked immunosorbent assay, and Western blotting, respectively. The dosage and treatment duration of BIM23B065 were tested in animal models of GH-secreting pituitary adenoma. The effect of BIM23B065 (3 mg/kg/day) on changes in IGF-1 levels before and after treatment was further investigated.RESULTS: In vitro, BIM23B065 treatment decreased GH release in the culture media and downregulated ERK 1/2 and CREB phosphorylation to 22% and 26%, respectively. In vivo, IGF-1 expression decreased to 50 % after 4 weeks of treatment with BIM23B065 using an osmotic pump implant. Moreover, magnetic resonance imaging results showed that the tumor size decreased significantly following treatment with BIM23B065 for 4 weeks.CONCLUSION: The novel chimeric molecule was effective in decreasing IGF-1 and GH levels and may serve as an effective therapeutic agent for acromegaly.

Effect of benzo(a)pyrene on dopaminergic neurons and α-synuclein in brain and its mechanism involved / 北京大学学报(医学版)

OBJECTIVE@#To analyze the effect of benzopyrene on the decrease of dopaminergic neurons, and the increase and aggregation of α-synuclein, which are the pathological features of Parkinson's disease, and to explore its possible mechanisms.@*METHODS@#Eight-month-old transgenic mice with human SNCA gene were randomly divided into a BaP-exposed group and a control group. BaP and solvent corn oil were injected intraperitoneally to BaP-exposed group and control group respectively, once a day for 60 days. The motor dysfunction of mice was tested by rotarod test. The effects of BaP on the decrease of dopaminergic neurons and increase and aggregation of α-synuclein were observed by immunohistochemistry and Western blot experiments respectively, and the expression of related mRNA was detected by quantitative real-time PCR (qRT-PCR). Twenty genes were tested in the study, mainly related to neurotransmitter transporter (2 genes), neurotransmitter receptor function (10 genes), cellular autophagy (5 genes), and α-synuclein aggregation and degradation (3 genes).@*RESULTS@#After BaP exposure, the movement time of the mice in the rotarod test was significantly reduced (P<0.05). The substantia nigra dopami-nergic neurons in the mice were significantly reduced, which was 62% of the control group (P<0.05), and the expression of α-synuclein in the midbrain increased, which was 1.36 times that of the control group (P<0.05). After BaP exposure, mRNA expressions of 14 genes in the midbrain of the mice were significantly down-regulated (P<0.05). Alpha-synuclein degradation and cell autophagy (5 genes), neuron transporters (2 genes), and neurotransmitter receptor functions (5 genes) were involved. The expression of one gene, Synphilin-1, was significantly up-regulated (P<0.01), which was related to α-synuclein aggregation.@*CONCLUSION@#BaP exposure not only inhibited function of neurotransmitter receptor and dopamine transporter, but also interfered cell autophagy, thereby hindering the degradation of α-synuclein, which could lead to decrease of dopaminergic neurons in substantia nigra and increase and aggregation of α-synuclein in midbrain, as the significant pathology of Parkinson's disease. Therefore, BaP exposure may increase the risk of Parkinson's disease.

Chronic stress increases dopamine levels in hippocampal dentate gyrus and impairs spatial learning and memory in rats / 生理学报

The objective of this study was to elucidate the effect of chronic stress (CS) on dopamine (DA) level and synaptic efficiency in the hippocampal dentate gyrus (DG) during spatial learning and memory. Sprague Dawley (SD) male rats were randomly divided into control group and CS group (n = 10). CS group was treated with chronic mild unpredictable stress, and control group did not receive any treatments. The levels of epinephrine and corticosterone (CORT) in serum were measured by using enzyme-linked immunosorbent assay (ELISA); the spatial learning and memory abilities of rats were measured by Morris water maze (MWM) test. Meanwhile, the amplitude of field excitatory postsynaptic potential (fEPSP) and concentration of DA in the DG region were determined by in vivo electrophysiology, microdialysis and HPLC techniques during MWM test in rats. After that, the DA D1 receptor (D1R) and its key downstream members in DG were examined by immunohistochemistry or Western blot assay. The results showed that the levels of epinephrine and CORT in the serum of the rats in CS group were significantly increased compared with those in the control group (P < 0.05). In CS group rats, the escape latency was significantly prolonged and the number of platform crossing was markedly decreased during MWM test, compared with those in control group (P < 0.05). Furthermore, the amplitude of fEPSP in the DG was not changed during MWM test in CS rats, while it was significantly increased on the 3rd day of MWM test in control group (P < 0.05). Compared with baseline or control group, CS group showed significantly increased DA level from the 1st to 3rd days of MWM test in the DG (P < 0.05). In addition, the protein expression of D1R was markedly up-regulated in the DG in CS group, while the protein expression levels of p-PKA, p-CREB and BDNF were significantly reduced, compared with those in control group. These results suggest that CS may impair spatial learning and memory abilities in rats through the enhancement of the DA levels in the hippocampal DG.