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1.
J Psychiatr Res ; 175: 343-349, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38761516

RESUMEN

Mixed features presentation in bipolar disorder (BD) represents the most severe form of the disease. BD may lead to cognitive and functional deterioration, a process known as neuroprogression, which appears to be exacerbated by increased serum levels of CCL11, a neuroprogression-related cytokine. Metabolic syndrome (MetS) is highly prevalent in BD, and it is known that the presence of MetS may increase inflammation, which may contribute to increased CCL11 levels, and consequently impact on the severity of the disorder. What is not known is whether the MetS mediates the association between CCL11 levels and the presence of mood episodes with mixed features in BD. Therefore, the aim of this study was to investigate the mediating effect of MetS on the relationship between CCL11 levels and the presence of mood episodes with mixed features in BD, in a population-based study. This is a cross-sectional study that included 184 young adults, 92 with BD and 92 populational controls, matched by sex and age. BD diagnosis was assessed using the Mini International Neuropsychiatric Interview - PLUS. Mood episodes with mixed features was defined according to DSM-IV and DSM-5 criteria. MetS was defined according to the National Cholesterol Education Program (NCEP/ATP III). Substance use was assessed through the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). CCL11 serum levels were analyzed using the multiplex analysis method Luminex 200™ system. The mediation model was tested using the MedMod module of the JAMOVI 2.4.8 software. Mediation analysis indicated a trend towards significance of MetS mediating the association between CCL11 and the presence of a mood episode with mixed features in BD (p = 0.065). Individuals with BD presenting with a mood episode with mixed features and MetS may have accelerated neuroprogression due to the influence of MetS on CCL11 levels, therefore, assessing for MetS occurrence in this population and implementing early interventions to prevent its development may be effective ways of delaying cognitive impairments related to this cytokine.

2.
J Ethn Subst Abuse ; : 1-15, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38437060

RESUMEN

University students frequently resort to psychostimulants to enhance their physical and mental performance and manage academic pressures. However, these substances can lead to dependence and other undesired symptoms, and little empirical data are available for relevant stakeholders, raising significant concerns in health care. Therefore, this study aims to characterize neurostimulant use among university students in Rio Grande do Sul, Brazil. We collected from 880 students' data using anonymous self-administration. The questionnaire included consumption patterns of caffeine, nicotine, ecstasy, methamphetamine, "merla" (coca base), methylphenidate, cocaine, crack, and ketamine. Additionally, participants shared information on demographic and socioeconomic factors. Use of at least one neurostimulant was reported by89.2% of the participants. Among nonusers, the most frequently cited reason was "previous information about harmful effects of these drugs." Caffeine, followed by nicotine, ecstasy, and methylphenidate were the most consumed substances, with main reasons being "improving academic performance" and "recreation." Women more often consumed caffeine (72.7%), while other psychostimulants were more consumed by men (42.2%) and individuals of other genders (0.5%). Students who consumed other substances had higher family incomes than that of families of caffeine users. In addition, 60.4% of caffeine users resided with family members, whereas 63.3% of users of other substances did not. Our findings can offer essential data on the reasons and symptoms associated with the use of neurostimulants among university students. This information could aid in raising awareness among students, universities, and health-care agencies about this often-neglected subject.

3.
J Affect Disord ; 327: 230-235, 2023 04 14.
Artículo en Inglés | MEDLINE | ID: mdl-36736792

RESUMEN

OBJECTIVE: The current study assesses whether the association between diagnosis of Bipolar Disorder (BD) in mothers and emotional and behavioral problems (EBP) in their offspring is mediated by a disruption in the offspring's biological rhythms. METHODS: A probabilistic sample of 492 public school children (ages 7-8, 48 % female) were assessed for biological rhythms disruption and EBP using the Biological Rhythms Interview for Assessment in Neuropsychiatry for Kids and the Strengths and Difficulties Questionnaire, respectively. Mothers' mental health (BD = 64) was evaluated using a standardized clinical interview. A mediation analysis was conducted to assess the effect of the mother's diagnosis of BD on the EBP of their offspring in relation to the offspring's biological rhythms disruptions. RESULTS: When compared to offspring of mothers without BD, offspring of mothers with BD showed greater difficulty in maintaining biological rhythms and higher prevalence of EBP. Using the presence of EBP as the outcome, 75 % of the effect of mother's BD diagnosis was mediated by offspring's biological rhythms disruption. CONCLUSIONS: Biological rhythms disruption in children fully mediates the effect of the mother's diagnosis of BD on the child's EBP. These data encourage the development of further studies to find effective strategies to prevent and treat biological rhythms disruption in offspring of mothers with BD.


Asunto(s)
Trastorno Bipolar , Problema de Conducta , Niño , Humanos , Femenino , Masculino , Madres , Emociones , Periodicidad
4.
Microorganisms ; 11(1)2023 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-36677517

RESUMEN

Leishmaniasis is a neglected tropical disease, affecting more than 350 million people globally. However, there is currently no vaccine available against human leishmaniasis, and current treatment is hampered by high cost, side-effects, and painful administration routes. It has become a United Nations goal to end leishmaniasis epidemics by 2030, and multitarget drug strategy emerges as a promising alternative. Among the multitarget compounds, flavonoids are a renowned class of natural products, and a structurally diverse library can be prepared through organic synthesis, which can be tested for biological effectiveness. In this study, we synthesised 17 flavonoid analogues using a scalable, easy-to-reproduce, and inexpensive method. All synthesised compounds presented an impressive inhibition capacity against rCPB2.8, rCPB3, and rH84Y enzymes, which are highly expressed in the amastigote stage, the target form of the parasite. Compounds 3c, f12a, and f12b were found to be effective against all isoforms. Furthermore, their intermolecular interactions were also investigated through a molecular modelling study. These compounds were highly potent against the parasite and demonstrated low cytotoxic action against mammalian cells. These results are pioneering, representing an advance in the investigation of the mechanisms behind the antileishmanial action of flavonoid derivatives. Moreover, compounds have been shown to be promising leads for the design of other cysteine protease inhibitors for the treatment of leishmaniasis diseases.

5.
J Psychiatr Res ; 158: 255-260, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36621181

RESUMEN

This study aims to compare the serum cytokine levels between controls, individuals with a current depressive episode (CDE) with childhood trauma and individuals with CDE without childhood trauma. This is a cross-sectional with paired sample nested in a population-based study. For the purposes of the current study, subjects who had psychotic symptoms, generalized anxiety disorder, and who refused to perform blood collection were excluded. Subsequently, only individuals who had a current depressive episode were selected (n = 76). Another 76 subjects were randomly paired by sex and age, constituting a population control group. The measurements of serum cytokine levels were performed using the multiplex analysis method. In the group with a CDE, when compared to the population control group, the following cytokines were high: IL-1ß, IL-2, IL-4, IL-6, IL-17A, IFN-γ and TNF-α (p < 0.05). On the other hand, there was a decrease in the levels of cytokines IL-10 (p = 0.027) and IL12p70 (p = 0.001). Bonferroni test demonstrates that there is no statistically significant difference in serum cytokine levels between subjects with a CDE, with and without trauma (p > 0.05). In a multivariable logistic regression, adjusting for socioeconomic status, tobacco, alcohol and illicit drugs abuse/dependence, and use of psychiatric medication, we found that cytokines serum levels remained associated with CDE even when adjusted for these potential confounders. Our findings demonstrate that monitoring cytokine levels and immune function may be beneficial in preventing the development of a CDE. However, future research is necessary to investigate the impact of trauma on the relationship between inflammation and CDE.


Asunto(s)
Experiencias Adversas de la Infancia , Trastornos Psicóticos , Humanos , Niño , Estudios Transversales , Citocinas , Factor de Necrosis Tumoral alfa , Biomarcadores
6.
Cell Mol Neurobiol ; 43(1): 357-366, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35128618

RESUMEN

The CACNA1C gene encodes the pore-forming alpha-1c subunit of L-type voltage-gated calcium channels. The calcium influx through these channels regulates the transcription of the brain-derived neurotrophic factor (BDNF). Polymorphisms in this gene have been consistently associated with psychiatric disorders, and alterations in BDNF levels are a possible biological mechanism to explain such associations. Here, we sought to investigate the effect of the CACNA1C rs1006737 and rs4765913 polymorphisms and their haplotypes on serum BDNF concentration. We further aim to investigate the regulatory function of these SNPs and the ones linked to them. The study enrolled 641 young adults (362 women and 279 men) in a cross-sectional population-based survey. Linear regression was used to test the effects of polymorphisms and haplotypes on BDNF levels adjusted for potential confounders. Moreover, regulatory putative functional roles were assessed using in silico approach. BDNF levels were not associated with CACNA1C polymorphisms/haplotype in the total sample. When the sample was stratified by sex, checking the effect of polymorphisms on men and women separately, the A-allele of rs4765913 was associated with lower BDNF levels in women compared with the TT genotype (p = 0.010). The AA (rs1006737-rs4765913) haplotype was associated with BDNF levels in opposite directions regarding sex, with lower levels of BDNF in women (p = 0.040) compared to those without this haplotype, while with higher levels in men (p = 0.027). These findings were supported by the presence of regulatory marks only on the male fetal brain. Our results suggest that the BDNF levels regulation may be a potential mechanism underpinning the association between CACNA1C and psychiatric disorders, with a differential role in women and men.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Predisposición Genética a la Enfermedad , Adulto Joven , Humanos , Masculino , Femenino , Factor Neurotrófico Derivado del Encéfalo/genética , Estudios Transversales , Canales de Calcio Tipo L/genética , Polimorfismo de Nucleótido Simple/genética
7.
Mol Neurobiol ; 60(3): 1659-1674, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36547848

RESUMEN

Extracellular ATP can be a danger signal, but its role in striatal circuits afflicted in Parkinson's disease (PD) is unclear and was now investigated. ATP was particularly released at high stimulation intensities from purified striatal nerve terminals of mice, which were endowed with different ATP-P2 receptors (P2R), although P2R antagonists did not alter corticostriatal transmission or plasticity. Instead, ATP was extracellularly catabolized into adenosine through CD73 to activate adenosine A2A receptors (A2AR) modulating corticostriatal long-term potentiation (LTP) in mice. In the presymptomatic phase of a 6-hydroxydopamine rat model of PD, ATP release from striatal nerve terminals was increased and was responsible for a greater impact of CD73 and A2AR on corticostriatal LTP. These observations identify increased ATP release and ATP-derived formation of extracellular adenosine bolstering A2AR activation as a key pathway responsible for abnormal synaptic plasticity in circuits involved in the onset of PD motor symptoms. The translation of these findings to humans prompts extending the use of A2AR antagonists from only co-adjuvants of motor control in Parkinsonian patients to neuroprotective drugs delaying the onset of motor symptoms.


Asunto(s)
Adenosina , Enfermedad de Parkinson , Ratas , Humanos , Ratones , Animales , Adenosina/metabolismo , Adenosina Trifosfato/metabolismo , Potenciación a Largo Plazo , Plasticidad Neuronal
8.
Eur Arch Psychiatry Clin Neurosci ; 273(1): 41-50, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36181558

RESUMEN

The influence of temperament traits on bipolar disorder (BD) has been investigated. Both temperament traits and BD are partially genetically determined and seem to be influenced by variations in the CACNA1C gene. These variations presented a significant interactive effect with biological sex, although studies that evaluate this relationship are scarce. Here, we assessed the mediation effect of temperament traits on the relationship between two polymorphisms in the CACNA1C gene (rs1006737 and rs4765913) and BD according to sex. This is a cross-sectional study consisting of 878 Caucasian individuals (508 women and 370 men), aged 18-35, enrolled in a population-based study in the city of Pelotas, Southern Brazil. BD diagnosis was evaluated using the clinical interview MINI 5.0, and temperament traits were assessed via the application of the Affective and Emotional Composite Temperament Scale (AFECTS). Mediation models were tested using the modeling tool PROCESS (version 3.3) for SPSS. Bootstrapping-enhanced mediation analyses in women indicated that traits anger (39%) and caution (27%) mediated the association between the rs4765913 SNP and BD, while traits volition (29%), anger (35%), and caution (29%) mediated the association between the AA haplotype (rs1006737-rs4765913) and the BD. No effect was encountered for cisgender men. Our model revealed that paths from CACNA1C SNPs to BD are mediated by specific temperament traits in women, reinforcing the definition of temperament traits as endophenotypes.


Asunto(s)
Trastorno Bipolar , Femenino , Humanos , Masculino , Trastorno Bipolar/psicología , Canales de Calcio Tipo L/genética , Estudios Transversales , Emociones , Polimorfismo de Nucleótido Simple , Temperamento , Adolescente , Adulto Joven , Adulto
9.
J Neurochem ; 161(2): 173-186, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35157328

RESUMEN

Severe traumatic brain injury (TBI) is associated with high rates of mortality and long-term disability linked to neurochemical abnormalities. Although purine derivatives play important roles in TBI pathogenesis in preclinical models, little is known about potential changes in purine levels and their implications in human TBI. We assessed cerebrospinal fluid (CSF) levels of purines in severe TBI patients as potential biomarkers that predict mortality and long-term dysfunction. This was a cross-sectional study performed in 17 severe TBI patients (Glasgow Coma Scale <8) and 51 controls. Two to 4 h after admission to ICU, patients were submitted to ventricular drainage and CSF collection for quantification of adenine and guanine purine derivatives by HPLC. TBI patients' survival was followed up to 3 days from admission. A neurofunctional assessment was performed through the modified Rankin Scale (mRS) 2 years after ICU admission. Purine levels were compared between control and TBI patients, and between surviving and non-surviving patients. Relative to controls, TBI patients presented increased CSF levels of GDP, guanosine, adenosine, inosine, hypoxanthine, and xanthine. Further, GTP, GDP, IMP, and xanthine levels were different between surviving and non-surviving patients. Among the purines, guanosine was associated with improved mRS (p = 0.042; r = -0.506). Remarkably, GTP displayed predictive value (AUC = 0.841, p = 0.024) for discriminating survival versus non-survival patients up to 3 days from admission. These results support TBI-specific purine signatures, suggesting GTP as a promising biomarker of mortality and guanosine as an indicator of long-term functional disability.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Biomarcadores/líquido cefalorraquídeo , Lesiones Traumáticas del Encéfalo/diagnóstico , Estudios Transversales , Escala de Coma de Glasgow , Guanosina , Guanosina Trifosfato , Humanos , Purinas , Xantina
10.
Dement Neuropsychol ; 14(3): 283-289, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32973981

RESUMEN

Schizophrenia and common mental disorders are noteworthy social and economic concern worldwide. Epidemiologic studies on the impact of specific mental disorders in emerging countries are scarce. OBJECTIVES: We aimed to characterize the demographic, social, and economic burden of schizophrenia and common mental disorders patients in the health system in Brazil. METHODS: Data on these conditions in Brazil between 2008 and 2019 were collected through the website of the Departamento de Informática do Sistema Único de Saúde (Information Technology Department of the Unified Health System - DATASUS) maintained by the Brazilian Ministry of Health. Mean annual hospital admissions were 154,009.67, and cumulative incidence of 77.44 admissions per 100,000 inhabitants. RESULTS: Average annual hospital expenses were US$ 67,216,056.04, with an average admission cost of US$ 432.58. The most affected age groups were older adults albeit younger individuals showed a trend towards increase of occurrences in recent years. There were a higher number of admissions in men compared to women. CONCLUSIONS: We consider the results obtained important to assist in evaluating and guiding public policies regarding the prevention and treatment in health systems.


A esquizofrenia e os transtornos mentais comuns são uma preocupação social e econômica notável em todo o mundo. Estudos epidemiológicos sobre o impacto de transtornos mentais específicos em países emergentes são escassos. OBJETIVOS: Nosso objetivo foi caracterizar a carga demográfica, social e econômica de pacientes com esquizofrenia e transtornos mentais comuns no sistema de saúde no Brasil. MÉTODOS: Os dados sobre essas condições no Brasil entre 2008 e 2019 foram coletados por meio do site do Departamento de Informática do Sistema Único de Saúde (DATASUS), mantido pelo Ministério da Saúde do Brasil. As internações hospitalares anuais médias foram de 154.009,67, e a incidência acumulada de 77,44 internações por 100.000 habitantes. RESULTADOS: As despesas hospitalares médias anuais foram de US$ 67.216.056,04, com um custo médio de internação de US$ 432,58. As faixas etárias mais afetadas foram os adultos mais velhos, embora os mais jovens tenham demonstrado tendência a aumento de ocorrências nos últimos anos. Houve um número maior de admissões entre os homens em comparação às mulheres. CONCLUSÕES: Consideramos importantes os resultados obtidos para auxiliar na avaliação e orientação de políticas públicas de prevenção e tratamento nos sistemas de saúde.

11.
Dement. neuropsychol ; 14(3): 283-289, July-Sept. 2020. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1133642

RESUMEN

ABSTRACT. Schizophrenia and common mental disorders are noteworthy social and economic concern worldwide. Epidemiologic studies on the impact of specific mental disorders in emerging countries are scarce. Objectives: We aimed to characterize the demographic, social, and economic burden of schizophrenia and common mental disorders patients in the health system in Brazil. Methods: Data on these conditions in Brazil between 2008 and 2019 were collected through the website of the Departamento de Informática do Sistema Único de Saúde (Information Technology Department of the Unified Health System - DATASUS) maintained by the Brazilian Ministry of Health. Mean annual hospital admissions were 154,009.67, and cumulative incidence of 77.44 admissions per 100,000 inhabitants. Results: Average annual hospital expenses were US$ 67,216,056.04, with an average admission cost of US$ 432.58. The most affected age groups were older adults albeit younger individuals showed a trend towards increase of occurrences in recent years. There were a higher number of admissions in men compared to women. Conclusions: We consider the results obtained important to assist in evaluating and guiding public policies regarding the prevention and treatment in health systems.


RESUMO. A esquizofrenia e os transtornos mentais comuns são uma preocupação social e econômica notável em todo o mundo. Estudos epidemiológicos sobre o impacto de transtornos mentais específicos em países emergentes são escassos. Objetivos: Nosso objetivo foi caracterizar a carga demográfica, social e econômica de pacientes com esquizofrenia e transtornos mentais comuns no sistema de saúde no Brasil. Métodos: Os dados sobre essas condições no Brasil entre 2008 e 2019 foram coletados por meio do site do Departamento de Informática do Sistema Único de Saúde (DATASUS), mantido pelo Ministério da Saúde do Brasil. As internações hospitalares anuais médias foram de 154.009,67, e a incidência acumulada de 77,44 internações por 100.000 habitantes. Resultados: As despesas hospitalares médias anuais foram de US$ 67.216.056,04, com um custo médio de internação de US$ 432,58. As faixas etárias mais afetadas foram os adultos mais velhos, embora os mais jovens tenham demonstrado tendência a aumento de ocorrências nos últimos anos. Houve um número maior de admissões entre os homens em comparação às mulheres. Conclusões: Consideramos importantes os resultados obtidos para auxiliar na avaliação e orientação de políticas públicas de prevenção e tratamento nos sistemas de saúde.


Asunto(s)
Humanos , Salud Mental , Ansiedad , Trastorno Bipolar , Trastornos del Humor , Depresión
12.
Psychoneuroendocrinology ; 116: 104671, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32422464

RESUMEN

Early life stressors, such as childhood trauma, have been associated to alterations in immune response that can last until adulthood. In this context, interleukin 1ß (IL-1ß) emerges as a pro-inflammatory cytokine with a pivotal role. Also, considering the temperament differences in stress susceptibility, and even immune dysfunction, studies investigating the complex interaction between these factors are scarce. Thus, the aim of the present study was to evaluate the moderating role of temperament traits in the relationship between childhood trauma and serum IL-1ß levels. This cross-sectional study consisted of 325 individuals, men and women, aged 18-35, enrolled from a population-based study in the city of Pelotas, Southern Brazil. Our main results indicate that higher serum levels of IL-1ß were associated with trauma severity (p < 0.01), and the variance of anger could explain 29% of IL-1ß increase in individuals who suffered severe trauma (p < 0.05). The effect of anger was considerably stronger in men than in women (46% and 25%, respectively). Moreover, the variance of sensitivity also explained 15% of IL-1ß increase (p < 0.05) as well as the variance of volition explained 11% of IL-1ß decrease (p < 0.05) in individuals who suffered severe trauma in the general population. Our results indicate that emotional individual differences can moderate the impact of childhood trauma on low-grade inflammation in young adults.


Asunto(s)
Experiencias Adversas de la Infancia , Ira/fisiología , Inmunidad Innata/inmunología , Inflamación/inmunología , Interleucina-1beta/sangre , Trauma Psicológico/inmunología , Trauma Psicológico/fisiopatología , Temperamento/fisiología , Adolescente , Adulto , Estudios Transversales , Femenino , Humanos , Individualidad , Inflamación/sangre , Masculino , Trauma Psicológico/sangre , Índice de Severidad de la Enfermedad , Factores Sexuales , Adulto Joven
13.
Clin Rehabil ; 34(1): 91-98, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31603002

RESUMEN

OBJECTIVE: This study aims to compare the effect of intradialytic aerobic exercise with blood flow restriction, without blood flow restriction (conventional) and no exercise (control) on muscle strength and walking endurance among chronic kidney disease patients. DESIGN: Open label and parallel group randomized controlled trial. SUBJECTS: Adult patients with chronic kidney disease on hemodialysis. INTERVENTION: A 12-week intradialytic training with or without blood flow restriction compared with a control group. MAIN MEASURES: Strength and walking endurance were measured using thoracolumbar dynamometry and a 6-minute walk test, respectively, before and after training. RESULTS: A total of 66 patients were randomized into three groups: blood flow restriction group (n = 22), conventional exercise group (n = 22) and control group (n = 22). There were seven dropouts, and 59 patients were included in the analysis. There was a significant increase in the 6-minute walking distance in the blood flow restriction group (from 412.7 (115.9) to 483.0 (131.0) m, P = 0.007) in comparison with the conventional exercise group (from 426.79 (115.00) to 433.2 (120.42) m, not significant) and the control group (from 428.4 (108.1) to 417.3 (100.2) m, not significant). The change in the walking distance over time was significantly different among groups (intervention group/time, P = 0.02). The simple effects test found a significant time effect only in the blood flow restriction group. There was no significant difference in strength change between the groups. CONCLUSION: Among chronic kidney disease patients, intradialytic exercise of low/moderate intensity with blood flow restriction was more effective in improving walking endurance than conventional exercise or no exercise.


Asunto(s)
Terapia por Ejercicio/métodos , Diálisis Renal , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/terapia , Caminata/fisiología , Adulto , Anciano , Constricción , Tolerancia al Ejercicio/fisiología , Femenino , Humanos , Extremidad Inferior/irrigación sanguínea , Masculino , Persona de Mediana Edad , Fuerza Muscular/fisiología , Estado Nutricional , Torniquetes
14.
Brain Behav Immun Health ; 2: 100034, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38377429

RESUMEN

Mental disorders (MDs) are highly prevalent and potentially debilitating complex disorders which causes remain elusive. Looking into deeper aspects of etiology or pathophysiology underlying these diseases would be highly beneficial, as the scarce knowledge in mechanistic and molecular pathways certainly represents an important limitation. Association between MDs and inflammation/neuroinflammation has been widely discussed and accepted by many, as high levels of pro-inflammatory cytokines were reported in patients with several MDs, such as schizophrenia (SCZ), bipolar disorder (BD) and major depression disorder (MDD), among others. Correlation of pro-inflammatory markers with symptoms intensity was also reported. However, the mechanisms underlying the inflammatory dysfunctions observed in MDs are not fully understood yet. In this context, microglial dysfunction has recently emerged as a possible pivotal player, as during the neuroinflammatory response, microglia can be over-activated, and excessive production of pro-inflammatory cytokines, which can modify the kynurenine and glutamate signaling, is reported. Moreover, microglial activation also results in increased astrocyte activity and consequent glutamate release, which are both toxic to the Central Nervous System (CNS). Also, as a result of increased microglial activation in MDs, products of the kynurenine pathway were shown to be changed, influencing then the dopaminergic, serotonergic, and glutamatergic signaling pathways. Therefore, in the present review, we aim to discuss how neuroinflammation impacts on glutamate and kynurenine signaling pathways, and how they can consequently influence the monoaminergic signaling. The consequent association with MDs main symptoms is also discussed. As such, this work aims to contribute to the field by providing insights into these alternative pathways and by shedding light on potential targets that could improve the strategies for pharmacological intervention and/or treatment protocols to combat the main pharmacologically unmatched symptoms of MDs, as the SCZ.

15.
Cien Saude Colet ; 24(7): 2593-2599, 2019 Jul 22.
Artículo en Portugués, Inglés | MEDLINE | ID: mdl-31340276

RESUMEN

This study assessed job satisfaction and work overload among doctors, nurses, psychologists, and nursing technicians working in community mental health services and conducted a comparison between nurses and other healthcare professionals. Using convenience sampling, a cross-sectional study was conducted with 61 healthcare professionals working in psychosocial care centers in a municipality located in the South Region of Brazil. Data was collected using a sociodemographic questionnaire, work impact assessment scale (Impacto - Br), and mental health professional satisfaction scale (Satis - Br). Data analysis was performed using the statistical software package SPSS 21.0. The average overall work overload score of nurses was 2.92 ± 0.42 and the average overall job satisfaction score was 3.38 ± 0.51. The level of satisfaction of nurses with the quality of services provided was lower than that of other professionals (3.36 ± 0.77 compared to 3.78 ± 0.56, respectively; p = 0.04). The factor that had the greatest negative influence on work overload among nurses was feeling physically tired (2.99 ± 0.92), while the factor that had the greatest positive influence on job satisfaction was good working relationships (4.06 ± 0.65).


Avaliar a satisfação profissional e a sobrecarga de trabalho dos enfermeiros atuantes em serviços de saúde mental e realizar uma comparação em relação aos demais profissionais do serviço. Estudo transversal, com amostragem por critério de conveniência, realizado em 2016 com 61 profissionais da área de saúde mental dos Centros de atenção psicossocial de um município localizado no extremo sul do Brasil. Para coleta de dados foi aplicado um questionário sociodemográfico e as Escalas de avaliação do impacto do trabalho (Impacto-Br) e de satisfação da equipe (Satis-Br). A análise dos dados foi realizada através do programa SPSS 21.0.O nível de sobrecarga global dos enfermeiros foi de 2,92 ± 0,42 e de satisfação global de 3,38 ± 0,51. Quando avaliado os escores na escala Satis-Br, houve uma diminuição estatisticamente significativa nos níveis de satisfação dos enfermeiros (3,36 ± 0,77) em relação aos demais profissionais atuantes no serviço (3,78 ± 0,56) no escore qualidade dos serviços oferecido (p = 0,04). O fator que promoveu maior nível de sobrecarga de trabalho entre os enfermeiros estão relacionados ao sentimento de se sentir fisicamente cansado (2,99 ± 0,92). Já o fator que promoveu maior satisfação profissional está relacionado ao bom relacionamento com a equipe (4,06 ± 0,65).


Asunto(s)
Personal de Salud/psicología , Satisfacción en el Trabajo , Servicios de Salud Mental/organización & administración , Enfermeras y Enfermeros/psicología , Adulto , Anciano , Brasil , Estudios Transversales , Fatiga/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Carga de Trabajo/psicología , Adulto Joven
16.
Ciênc. Saúde Colet. (Impr.) ; 24(7): 2593-2599, jul. 2019. tab
Artículo en Portugués | LILACS | ID: biblio-1011832

RESUMEN

Resumo Avaliar a satisfação profissional e a sobrecarga de trabalho dos enfermeiros atuantes em serviços de saúde mental e realizar uma comparação em relação aos demais profissionais do serviço. Estudo transversal, com amostragem por critério de conveniência, realizado em 2016 com 61 profissionais da área de saúde mental dos Centros de atenção psicossocial de um município localizado no extremo sul do Brasil. Para coleta de dados foi aplicado um questionário sociodemográfico e as Escalas de avaliação do impacto do trabalho (Impacto-Br) e de satisfação da equipe (Satis-Br). A análise dos dados foi realizada através do programa SPSS 21.0.O nível de sobrecarga global dos enfermeiros foi de 2,92 ± 0,42 e de satisfação global de 3,38 ± 0,51. Quando avaliado os escores na escala Satis-Br, houve uma diminuição estatisticamente significativa nos níveis de satisfação dos enfermeiros (3,36 ± 0,77) em relação aos demais profissionais atuantes no serviço (3,78 ± 0,56) no escore qualidade dos serviços oferecido (p = 0,04). O fator que promoveu maior nível de sobrecarga de trabalho entre os enfermeiros estão relacionados ao sentimento de se sentir fisicamente cansado (2,99 ± 0,92). Já o fator que promoveu maior satisfação profissional está relacionado ao bom relacionamento com a equipe (4,06 ± 0,65).


Abstract This study assessed job satisfaction and work overload among doctors, nurses, psychologists, and nursing technicians working in community mental health services and conducted a comparison between nurses and other healthcare professionals. Using convenience sampling, a cross-sectional study was conducted with 61 healthcare professionals working in psychosocial care centers in a municipality located in the South Region of Brazil. Data was collected using a sociodemographic questionnaire, work impact assessment scale (Impacto - Br), and mental health professional satisfaction scale (Satis - Br). Data analysis was performed using the statistical software package SPSS 21.0. The average overall work overload score of nurses was 2.92 ± 0.42 and the average overall job satisfaction score was 3.38 ± 0.51. The level of satisfaction of nurses with the quality of services provided was lower than that of other professionals (3.36 ± 0.77 compared to 3.78 ± 0.56, respectively; p = 0.04). The factor that had the greatest negative influence on work overload among nurses was feeling physically tired (2.99 ± 0.92), while the factor that had the greatest positive influence on job satisfaction was good working relationships (4.06 ± 0.65).


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Anciano , Adulto Joven , Personal de Salud/psicología , Satisfacción en el Trabajo , Servicios de Salud Mental/organización & administración , Enfermeras y Enfermeros/psicología , Brasil , Estudios Transversales , Encuestas y Cuestionarios , Carga de Trabajo/psicología , Fatiga/epidemiología , Persona de Mediana Edad
17.
Psychiatry Res ; 273: 685-689, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-31207853

RESUMEN

OBJECTIVE: The aim of this study was to assess if cytokines levels (IL-6 and IL-10) are related to major depressive disorder (MDD) and bipolar disorder (BD), in a population-based study. METHODS: This was a cross-sectional study population-based, involving 1037 people aged 18-35. MDD, BD, anxiety and suicide risk were assessed using the Mini International Neuropsychiatric Interview. Serum IL-6 and IL-10 were measured by ELISA using a commercial kit. RESULTS: The total sample comprised 1034 young adults, being 14.4% with MDD and 13.7% with BD. MDD and BD groups showed significantly higher serum IL-6 levels (p ≤ 0.001) and IL-10 levels (p ≤ 0.001) when compared to healthy control group. No correlation was found between serum IL-6 and IL-10 levels in health control group (p = 0.830; r = -0.008), non-suicide risk (p = 0.337; r = 0.032) and non-anxiety disorder (p = 0.375; r = 0.031). Covariance analysis showed that mood disorders alone, increase both interleukin levels (IL-6, p = 0.019; and IL-10, p = 0.026), whilst the interaction of mood disorders and suicide risk or anxiety disorders did not. CONCLUSION: Our results suggest that inflammatory dysregulation may be involved in the physiopathology of mood disorders and serum IL-6 and IL-10 levels are putative biomarkers for these disorders.


Asunto(s)
Trastorno Bipolar/sangre , Trastorno Depresivo Mayor/sangre , Interleucina-10/sangre , Interleucina-6/sangre , Trastornos del Humor/sangre , Adolescente , Adulto , Biomarcadores/sangre , Estudios Transversales , Femenino , Humanos , Masculino , Escalas de Valoración Psiquiátrica , Adulto Joven
19.
Br J Pharmacol ; 176(18): 3666-3680, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31220343

RESUMEN

BACKGROUND AND PURPOSE: Parkinson's disease (PD) involves an initial loss of striatal dopamine terminals evolving into degeneration of dopamine neurons in substantia nigra (SN), which can be modelled by 6-hydroxydopamine (6-OHDA) administration. Adenosine A2A receptor blockade attenuates PD features in animal models, but the source of the adenosine causing A2A receptor over-activation is unknown. As ATP is a stress signal, we have tested if extracellular catabolism of adenine nucleotides into adenosine (through ecto-5'-nucleotidase or CD73) leads to A2A receptor over-activation in PD. EXPERIMENTAL APPROACH: Effects of blocking CD73 with α,ß-methylene ADP (AOPCP) were assayed in 6-OHDA-treated rats and dopamine-differentiated neuroblastoma SH-SY5Y cells. KEY RESULTS: 6-OHDA increased ATP release and extracellular conversion into adenosine through CD73 up-regulation in SH-SY5Y cells. Removing extracellular adenosine with adenosine deaminase, blocking CD73 with AOPCP, or blocking A2A receptors with SCH58261 were equi-effective in preventing 6-OHDA-induced damage in SH-SY5Y cells. In vivo striatal exposure to 6-OHDA increased ATP release and extracellular formation of adenosine from adenosine nucleotides and up-regulated CD73 and A2A receptors in striatal synaptosomes. Intracerebroventricular administration of AOPCP phenocopied effects of SCH58261, attenuating 6-OHDA-induced (a) increase of contralateral rotations after apomorphine, (b) reduction of dopamine content in striatum and SN, (c) loss of TH staining in striatum and SN, (d) motor dysfunction in the cylinder test, and (e) short-term memory impairment in the object recognition test. CONCLUSION AND IMPLICATIONS: Our data indicate that increased ATP-derived adenosine formation is responsible for A2A receptor over-activation in PD, suggesting CD73 as a new target to manage PD.


Asunto(s)
5'-Nucleotidasa/metabolismo , Adenosina Trifosfato/metabolismo , Adenosina/metabolismo , Trastornos Parkinsonianos/metabolismo , Receptor de Adenosina A2A/metabolismo , 5'-Nucleotidasa/antagonistas & inhibidores , Antagonistas del Receptor de Adenosina A2/farmacología , Adenosina Difosfato/análogos & derivados , Adenosina Difosfato/farmacología , Animales , Línea Celular Tumoral , Humanos , Masculino , Oxidopamina/farmacología , Pirimidinas/farmacología , Ratas Wistar , Triazoles/farmacología
20.
Epilepsy Res ; 152: 35-41, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30875635

RESUMEN

Generalized seizures trigger excessive neuronal firing that imposes large demands on the brain glucose/lactate availability and utilization, which synchronization requires an integral mitochondrial oxidative capability. We investigated whether a single convulsive crisis affects brain glucose/lactate availability and mitochondrial energy production. Adult male Wistar rats received a single injection of pentylentetrazol (PTZ, 60 mg/kg, i.p.) or saline. The cerebrospinal fluid (CSF) levels of glucose and lactate, mitochondrial respirometry, [14C]-2-deoxy-D-glucose uptake, glycogen content and cell viability in hippocampus were measured. CSF levels of glucose and lactate (mean ± SD) in control animals were 68.08 ± 11.62 mg/dL and 1.17 ± 0.32 mmol/L, respectively. Tonic-clonic seizures increased glucose levels at 10 min (96.25 ± 13.19) peaking at 60 min (113.03 ± 16.34) returning to control levels at 24 h (50.12 ± 12.81), while lactate increased at 10 min (3.23 ± 1.57) but returned to control levels at 360 min after seizures (1.58 ± 0.21). The hippocampal [14C]-2-deoxy-D-glucose uptake, glycogen content, and cell viability decreased up to 60 min after the seizures onset. Also, an uncoupling between mitochondrial oxygen consumption and ATP synthesis via FoF1-ATP synthase was observed at 10 min, 60 min and 24 h after seizures. In summary, after a convulsive seizure glucose and lactate levels immediately rise within the brain, however, considering the acute impact of this metabolic crisis, mitochondria are not able to increase energy production thereby affecting cell viability.


Asunto(s)
Glucosa/líquido cefalorraquídeo , Ácido Láctico/líquido cefalorraquídeo , Mitocondrias/metabolismo , Convulsiones/líquido cefalorraquídeo , Animales , Desoxiglucosa/metabolismo , Modelos Animales de Enfermedad , Transporte de Electrón/efectos de los fármacos , Etanolaminas/toxicidad , Glucógeno/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/ultraestructura , Masculino , Mitocondrias/efectos de los fármacos , Ratas , Ratas Wistar , Convulsiones/inducido químicamente , Factores de Tiempo
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