Development and validation of an HPLC-DAD method for the quantification of cannabigerol, cannabidiol, cannabinol and cannabichromene in human plasma and mouse matrices.

Cannabigerol, cannabidiol, cannabinol and cannabichromene are non-psychoactive phytocannabinoids, highly present in Cannabis sativa, for which numerous therapeutical applications have been described. However, additional pre-clinical and clinical data, including toxicopharmacokinetic and pharmacodynamic studies, remain required to support their use in clinical practice and new therapeutic applications. To support these studies, a new high performance liquid chromatography technique (HPLC) with diode-array detection (DAD) was developed and validated to quantify these cannabinoids in human plasma and mouse matrices. Sample extraction was accomplished by protein precipitation and double liquid-liquid extraction. Simvastatin and perampanel were used as internal standards in human and mouse matrices, respectively. Chromatographic separation was achieved in 16 min on an InfinityLab Poroshell® 120 C18 column (4.6 mm × 100 mm, 2.7 µm) at 40 °C. A mobile phase composed of water/acetonitrile was pumped with a gradient elution program at 1.0 mL min-1. The technique revealed linearity in the defined concentration ranges with a determination coefficient of over 0.99. Intra and inter-day accuracy and precision values ranged from -14.83 to 13.97% and 1.08 to 13.74%, respectively. Sample stability was assessed to ensure that handling and storage conditions did not compromise analyte concentrations in different matrices. Carry-over was absent and recoveries were over 77.31%. This technique was successfully applied for the therapeutic monitoring of cannabidiol and preliminary pre-clinical studies with cannabigerol and cannabidiol. All samples were within calibration ranges, with the exception of cannabigerol after intraperitoneal administration. This is the first HPLC-DAD technique that simultaneously quantifies cannabinoids in these biological matrices, supporting future pre-clinical and clinical investigations.

"Lipopolysaccharide-induced animal models for neuroinflammation - An overview."

Neuroinflammation is a pathological mechanism contributing to neurodegenerative diseases. For in-depth studies of neuroinflammation, several animal models reported reproducing behavioral dysfunctions and cellular pathological mechanisms induced by brain inflammation. One of the most popular models of neuroinflammation is the one generated by lipopolysaccharide exposure. Despite its importance, the reported results using this model show high heterogeneity, making it difficult to analyze and compare the outcomes between studies. Therefore, the current review aims to summarize the different experimental paradigms used to reproduce neuroinflammation by lipopolysaccharide exposure and its respective outcomes, helping to choose the model that better suits each specific research aim.

Intranasal irbesartan reverts cognitive decline and activates the PI3K/AKT pathway in an LPS-induced neuroinflammation mice model.

BACKGROUND: New strategies are urgently needed to manage and delay the development of Alzheimer's disease (AD). Neuroinflammation is a significant contributor to cognitive decline in neurodegenerative diseases, including AD. Angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) protect hypertensive patients against AD, but the cellular and molecular mechanisms underlying these effects remain unknown. In light of this, the protective effects of three ARBs and three ACEIs against neuroinflammation and cognitive decline were investigated through comprehensive pharmacologicalin vitro/in vivoscreening. METHODS: BV-2 microglia cells were exposed tolipopolysaccharide (LPS) and treated with ARBs and ACEIs to provide initial insights into the anti-inflammatory properties of the drugs. Subsequently, irbesartan was selected, and its efficacy was evaluated inC57/BL6 male miceintranasally administered with irbesartan and injected with LPS. Long-term memory and depressive-like behavior were evaluated; dendritic spines were measured as well as neuroinflammation, neurodegeneration and cognitive decline biomarkers. RESULTS: Irbesartan mitigated memory loss and depressive-like behavior in mice treated with LPS, probably because itincreased spine density, ameliorated synapsis dysfunction and activated the PI3K/AKT pathway. Irbesartan elevated the levels of hippocampalsuperoxide dismutase2 andglutathione peroxidaseandsuppressed LPS-induced astrogliosis. CONCLUSIONS: Overall, this study provides compelling evidence that multiple intranasal administrations of irbesartan can effectively prevent LPS-induced cognitive decline by activating pathways involved in neuroprotection and anti-inflammatory events. These findings underscore the potential of irbesartan as a preventive strategy against the development of AD and other neurodegenerative conditions associated with neuroinflammation.

Intranasal administration of sertraline ensures sustained brain delivery and antidepressant effect in a mouse model of depression.

The pursuit of more potent and efficacious antidepressant therapies is of utmost significance. Herein, the intranasal (IN) route was investigated for sertraline brain delivery, encompassing a comparative pharmacokinetic study after a single-dose administration to mice by IN, intravenous (IV) (4.87 mg/kg) and oral (10 mg/kg) routes, and an efficacy/toxicity study to explore the therapeutic effect in mice subjected to the unpredictable chronic mild stress (UCMS) protocol. Neurotransmitters and melatonin were quantified in prefrontal cortex and plasma, respectively. A different drug biodistribution behavior was unveiled for a CNS-acting drug administered by means of the IN route. For the first time, IN administration of sertraline exhibited heightened systemic exposure (bioavailability = 166 %), and a sustained drug release into the brain, in opposition to IV and oral routes, avoiding drug fluctuation. The lower lung exposition (given by normalized area under the curve) observed after IN instillation envisions the reduction of sertraline pulmonary side effects and similarly other peripheral side effects. IN sertraline treatment displayed significant efficacy in ameliorating anhedonia after one week of administration while the 14-day IN treatment regimen translated into decreased immobility time and increased swimming time in the forced swimming test, suggesting an improvement of the depressive-like behavior displayed by the animal depressive-model. Remarkably, these effects were absent with oral sertraline, despite the higher used dose. Noteworthy neurotransmitter alterations were observed, with IN sertraline markedly reducing adrenaline in the prefrontal cortex, while serotonin and melatonin increased following both administration routes. With its sustained brain delivery and serotonin- and melatonin-enhancing potential, the innovative strategy of IN sertraline holds the potential not only to effectively address depressive symptoms but also to mitigate challenges inherent to classic treatments.

Under the umbrella of depression and Alzheimer's disease physiopathology: Can cannabinoids be a dual-pleiotropic therapy?

Depression and Alzheimer´s disease (AD) are two disorders highly prevalent worldwide. Depression affects more than 300 million people worldwide while AD affects 60-80% of the 55 million cases of dementia. Both diseases are affected by aging with high prevalence in elderly and share not only the main brain affected areas but also several physiopathological mechanisms. Depression disease is already ascribed as a risk factor to the development of AD. Despite the wide diversity of pharmacological treatments currently available in clinical practice for depression management, they remain associated to a slow recovery process and to treatment-resistant depression. On the other hand, AD treatment is essentially based in symptomatology relieve. Thus, the need for new multi-target treatments arises. Herein, we discuss the current state-of-art regarding the contribution of the endocannabinoid system (ECS) in synaptic transmission processes, synapses plasticity and neurogenesis and consequently the use of exogenous cannabinoids in the treatment of depression and on delaying the progression of AD. Besides the well-known imbalance of neurotransmitter levels, including serotonin, noradrenaline, dopamine and glutamate, recent scientific evidence highlights aberrant spine density, neuroinflammation, dysregulation of neurotrophic factor levels and formation of amyloid beta (Aß) peptides, as the main physiopathological mechanisms compromised in depression and AD. The contribution of the ECS in these mechanisms is herein specified as well as the pleiotropic effects of phytocannabinoids. At the end, it became evident that Cannabinol, Cannabidiol, Cannabigerol, Cannabidivarin and Cannabichromene may act in novel therapeutic targets, presenting high potential in the pharmacotherapy of both diseases.

Saúde do adolescente: análise de indicadores de alimentação, atividade física e estilo de vida em países sul-americanos / Adolescent health: analysis of indicators of diet, physical activity, and lifestyle in South American countries

Introdução. A adolescência representa uma importante etapa do ciclo de vida, apresentando a maior taxa de crescimento físico e expansão psicológica após a primeira infância. A adoção de práticas pouco saudáveis na adolescência, incluindo sedentarismo, baixo nível de atividade física e consumo excessivo de alimentos com alto teor de gorduras e açúcares, é associada ao aumento da ocorrência de sobrepeso e obesidade. O consumo de bebidas alcoólicas e o uso de produtos do tabaco são considerados hábitos de risco entre jovens, especialmente porque há tendência de ocorrência concomitante de vários comportamentos de risco. Objetivo. O presente estudo propõe uma análise comparativa de associações entre características de estilo de vida e estado nutricional em amostra representativa de adolescentes de países da América do Sul, a partir dos inquéritos aplicados ao longo dos últimos anos. Metodologia. Trata-se de investigação com delineamento observacional transversal, conduzida a partir de análise de dados secundários em nível individual, incluindo comportamento alimentar, nível de atividade física, consumo de bebidas alcoólicas, uso de produtos do tabaco, relações parentais e bullying, disponibilizados por meio de bases de dados públicas para Argentina, Bolívia, Brasil, Chile, Paraguai, Suriname e Uruguai. Os dados foram analisados por meio de modelos de regressão, utilizando comando survey no software estatístico Stata com aplicação de ponderação para expansão da representatividade da amostra em nível populacional, adotando-se significância estatística de 5% (p≤0,05). Resultados. Adolescentes argentinos e brasileiros apresentaram maior frequência de baixo consumo hortaliças (61,69% e 59,23% dos adolescentes, respectivamente). Os adolescentes do Suriname (33,54%) e do Chile (30,83%) declararam maior frequência no consumo regular de refrigerantes. Registrou-se alta proporção de adolescentes sul-americanos fisicamente inativos (62,75%), considerando-se nível de atividade física recomendada 180 minutos por semana para faixa etária. Por fim, identificou-se associação entre consumo de bebida alcoólica, uso de outros produtos do tabaco e idade do início do tabagismo com presença de excesso de peso entre adolescentes na América do Sul. Conclusão. Os resultados do presente estudo sugerem potencial associação entre excesso de peso dos adolescentes sul-americanos em relação ao baixo consumo de frutas, verduras e legumes, alta frequência de inatividade física e adoção de comportamentos de risco (uso de produtos do tabaco e consumo de bebidas alcoólicas).

Introduction. Adolescence is an important stage in the life cycle, with the highest rate of physical growth and psychological expansion after early childhood. The adoption of unhealthy practices in adolescence, including a sedentary lifestyle, low levels of physical activity and excessive consumption of foods high in fats and sugars, is associated with an increase in the occurrence of overweight and obesity. Alcohol consumption and use of tobacco are considered risk behaviors among youngsters, especially due to trends in occurrence of multiple risk behaviors. Objective. The present study proposes a comparative analysis of association among lifestyle characteristics and nutritional status in representative sample of adolescents in South American countries, through surveys conducted during the last years. Methods. The study presents cross-sectional observational design based on the analysis of secondary data at the individual level, including food consumption patterns, physical activity levels, alcohol consumption, use of tobacco products, parental relationships, and bullying, from datasets publicly available for Argentina, Bolivia, Brazil, Chile, Paraguay, Suriname, and Uruguay. The data were analyzed through regression models, using a survey command in the Stata statistical software with the application of sample weight for expansion of sample representativeness at the population level, adopting a statistical significance of 5% (p≤0.05). Results. Argentinian and Brazilian adolescents presented higher frequency of low consumption of vegetables (61.69% and 59.23% of adolescents, respectively). The adolescents from Suriname (33.54%) and Chile (30.83%) reported higher regular consumption of carbonated soft drinks. There was high proportion of South American adolescents who were physically inactive (62.75%), considering the recommendation of physical activity level 180 minutes per week in the age bracket. Finally, there was association among alcohol consumption, tobacco use, and age of tobacco use initiation in relation to overweight among South American adolescents. Conclusion. The results of the present study suggest potential association of excess body weight among South American adolescents in relation to low consumption of fruits and vegetables, high frequency of physical inactivity, and adoption of risk behaviors (use of tobacco and consumption of alcoholic beverages).

Endogenous GDNF Is Unable to Halt Dopaminergic Injury Triggered by Microglial Activation.

Overactivation of microglial cells seems to play a crucial role in the degeneration of dopaminergic neurons occurring in Parkinson's disease. We have previously demonstrated that glial cell line-derived neurotrophic factor (GDNF) present in astrocytes secretome modulates microglial responses induced by an inflammatory insult. Therefore, astrocyte-derived soluble factors may include relevant molecular players of therapeutic interest in the control of excessive neuroinflammatory responses. However, in vivo, the control of neuroinflammation is more complex as it depends on the interaction between different types of cells other than microglia and astrocytes. Whether neurons may interfere in the astrocyte-microglia crosstalk, affecting the control of microglial reactivity exerted by astrocytes, is unclear. Therefore, the present work aimed to disclose if the control of microglial responses mediated by astrocyte-derived factors, including GDNF, could be affected by the crosstalk with neurons, impacting GDNF's ability to protect dopaminergic neurons exposed to a pro-inflammatory environment. Also, we aimed to disclose if the protection of dopaminergic neurons by GDNF involves the modulation of microglial cells. Our results show that the neuroprotective effect of GDNF was mediated, at least in part, by a direct action on microglial cells through the GDNF family receptor α-1. However, this protective effect seems to be impaired by other mediators released in response to the neuron-astrocyte crosstalk since neuron-astrocyte secretome, in contrast to astrocytes secretome, was unable to protect dopaminergic neurons from the injury triggered by lipopolysaccharide-activated microglia. Supplementation with exogenous GDNF was needed to afford protection of dopaminergic neurons exposed to the inflammatory environment. In conclusion, our results revealed that dopaminergic protective effects promoted by GDNF involve the control of microglial reactivity. However, endogenous GDNF is insufficient to confer dopaminergic neuron protection against an inflammatory insult. This reinforces the importance of further developing new therapeutic strategies aiming at providing GDNF or enhancing its expression in the brain regions affected by Parkinson's disease.

Encapsulated Escitalopram and Paroxetine Intranasal Co-Administration: In Vitro/In Vivo Evaluation.

Depression is a common mental disorder. Its treatment with selective serotonin reuptake inhibitors (SSRIs) is effective only in a fraction of patients, and pharmacoresistance is increasing steadily. Intranasal (IN) drug delivery to the brain stands out as a promising strategy to improve current therapeutic approaches by operating as a shuttle to overcome the blood-brain barrier. This work aimed to simultaneously administer escitalopram and paroxetine by IN route to mice. For this purpose, three nanostructured lipid carriers (NLC1, NLC2, and BorNLC) and one nanoemulsion (NE) were tested for drug loading. After their characterization, investigation of their impact on nasal cell viability and SSRI permeability assays were performed, using a human nasal RPMI 2650 cell line in air-liquid interface. In vitro assays demonstrated that NLCs, including borneol (BorNLC), significantly increased escitalopram permeability (p < 0.01) and paroxetine recovery values (p < 0.05) in relation to the other formulations and non-encapsulated drugs. IN and intravenous (IV) pharmacokinetic studies performed in vivo with a single dose of 2.38 mg/kg demonstrated similar results for escitalopram brain-to-plasma ratios. IN administrations delayed escitalopram peak concentrations in the brain for 15-60 min and no direct nose-to-brain delivery was detected. However, encapsulation with BorNLC considerably decreased escitalopram exposure in the lungs (124 µg min/g) compared with free escitalopram by IN (168 µg min/g) and IV (321 µg min/g) routes. Surprisingly, BorNLC IN instillation increased concentration levels of paroxetine in the brain by five times and accelerated brain drug delivery. Once again, lung exposure was considerably lower with BorNLC (AUCt = 0.433 µg min/g) than that with IV administration (AUCt = 1.01 µg min/g) and non-encapsulated IN formulation (AUCt = 2.82 µg min/g). Direct nose-to-brain delivery was observed for paroxetine IN administration with a direct transport percentage (DTP) of 56.9%. If encapsulated, it increases to 74.2%. These results clearly emphasize that nose-to-brain delivery and lung exposure depend on the formulation and on the characteristics of the drug under investigation. NLCs seem to be an advantageous strategy for nose-to-brain delivery of lipophilic molecules, since they reduce systemic and lung exposure, thereby decreasing adverse effects. For hydrophilic compounds, NLCs are particularly important to decrease lung exposure after IN administration.

Pharmacology of lacosamide: From its molecular mechanisms and pharmacokinetics to future therapeutic applications.

Epilepsy is one of the most common brain disorders, affecting more than 50 million people worldwide. Although its treatment is currently symptomatic, the last generation of anti-seizure drugs is characterized by better pharmacokinetic profiles, efficacy, tolerability and safety. Lacosamide is a third-generation anti-seizure drug that stands out due to its good efficacy and safety profile. It is used with effectiveness in the treatment of partial-onset seizures with or without secondary generalization, primary generalized tonic-clonic seizures and off-label in status epilepticus. Despite scarcely performed until today, therapeutic drug monitoring of lacosamide is proving to be advantageous by allowing the control of inter and intra-individual variability and promoting a successful personalized therapy, particularly in special populations. Herein, the pharmacology, pharmacokinetics, and clinical data of lacosamide were reviewed, giving special emphasis to the latest molecular investigations underlying its mechanism of action and therapeutic applications in pathologies besides epilepsy. In addition, the pharmacokinetic characteristics of lacosamide were updated, as well as current literature concerning the high pharmacokinetic variability observed in special patient populations and that must be considered during treatment individualization.

Is intranasal administration an opportunity for direct brain delivery of lacosamide?

Lacosamide is well-known as an effective and safe anticonvulsant drug. Nevertheless, there is also evidence of anti-epileptogenic, neuroprotective and antinociceptive properties of lacosamide. It is currently available as oral and intravenous (IV) formulations, and its brain concentrations and therapeutic effects depend on its passage across the blood-brain barrier (BBB). Therefore, to circumvent the restrictive BBB, we herein evaluated the intranasal (IN) administration of lacosamide. Nasal thermoreversible gels were screened in vitro for their influence on the viability of human nasal septum (RPMI 2650) and lung adenocarcinoma (Calu-3) cells. According to the Alamar Blue test, the in situ gel composed of Pluronic F-127 (22.5%, w/v) and Carbopol 974P (0.2%, w/v) did not affect cell viability, which remained higher than 85%, within the concentration range of lacosamide. The in situ gel was intranasally administered to healthy male CD-1 mice (8.33 mg/kg) to describe the pharmacokinetic profiles of lacosamide in plasma, brain, lung and kidney and compare them with those obtained after IV administration of the same dose. Accordingly, IN administration allowed a fast (tmax in plasma: 5 min) and complete systemic absorption of lacosamide (absolute bioavailability: 120.46%). Interestingly, IN lacosamide demonstrated higher exposure (given by the AUCt) in the brain (425.44 µg.min/mL versus 274.49 µg.min/mL), but lower exposure in kidneys (357.56 µg.min/mL versus 762.61 µg.min/mL), in comparison to IV administration. These findings, together with the tmax in brain of 15 min, a drug targeting efficiency (DTE) of 128.67% and a direct transport percentage of 22.28%, evidence that part of lacosamide reaches the brain directly after nasal administration, even though penetration into the brain from the systemic circulation seems to be the major determinant of brain exposure. Importantly, lacosamide concentrations found in lungs following IN administration were considerably higher than those observed after IV injection, until 30 min post-dosing (p < 0.05). Nevertheless, attained drug concentrations were lower than those tested in vitro in the Calu-3 cell line (1-100 µM), indicating that adverse effects are unlikely to occur in vivo. Hence, it seems that the proposed IN route has potential to be a suitable and valuable strategy for the brain delivery of lacosamide in emergency conditions and for the chronic treatment of epilepsy and other neurological diseases.

Repairing blood-CNS barriers: Future therapeutic approaches for neuropsychiatric disorders.

Central nervous system (CNS) drug development faces significant difficulties that translate into high rates of failure and lack of innovation. The pathophysiology of neurological and psychiatric disorders often results in the breakdown of blood-CNS barriers, disturbing the CNS microenvironment and worsening disease progression. Therefore, restoring the integrity of blood-CNS barriers may have a beneficial influence in several CNS disorders and improve treatment outcomes. In this review, pathways that may be modulated to protect blood-CNS barriers from neuroinflammatory and oxidative insults are featured. First, the participation of the brain endothelium and glial cells in disruption processes is discussed. Then, the relevance of regulatory systems is analysed, specifically the hypothalamic-pituitary axis, the renin-angiotensin system, sleep and circadian rhythms, and glutamate neurotransmission. Lastly, compounds of endogenous and exogenous origin that are known to mediate the repair of blood-CNS barriers are presented. We believe that enhancing the protection of blood-CNS barriers is a promising therapeutic strategy to pursue in the future.

Cystic fibrosis: Physiopathology and the latest pharmacological treatments.

Cystic fibrosis (CF) is a lethal autosomal recessive genetic disease, caused by a mutation in the cystic fibrosis transmembrane conductance regulator gene (CFTR), which primarily affects the lungs and digestive system. This gene encodes the CFTR protein, a distinctive membrane transporter of the ATP-binding cassette (ABC) superfamily. It functions as a chloride channel, allowing the balance and transport of chloride through the apical membrane of epithelial cells. Due to its ubiquitous location, mutations in the CFTR gene trigger multiple changes in ion transport and metabolic pathways, affecting various organs, as it will be herein explained. Pulmonary impairment is the most characteristic comorbidity of CF and respiratory failure is the main cause of death. This review presents the importance of an early diagnosis of CF to establish, as soon as possible, a primary therapy for symptomatic prevention and relief. It also mentions new therapeutic approaches that include CFTR modulators. They are correctors and/or potentiators of the deficient CFTR channel. In an attempt to overcome the disadvantages of CFTR modulators, the application of biotechnology techniques is addressed, such as gene therapy, gene editing, RNA therapy and therapeutic microRNAs. The potential of the intranasal administration route is another presented aspect.

Compassion fatigue among nurses working on an adult emergency and urgent care unit. / Fadiga por compaixão em enfermeiros de urgência e emergência hospitalar de adultos.

OBJECTIVE: to assess compassion fatigue levels among nurses and its variation according socio-demographic and professional characteristics. METHOD: quantitative, descriptive and cross-sectional study, with 87 nurses from an emergency and urgent care unit for adults from a university hospital. A socio-demographic and professional questionnaire, along with the Professional Quality of Life Scale 5 were used. Data analysis was performed using descriptive and inferential statistics. RESULTS: compassion satisfaction presents the highest means, followed by burnout and secondary traumatic stress. Among the participants, 51% presented a high level of compassion satisfaction, 54% a high level of burnout, and 59% a high level of secondary traumatic stress. Older participants presented higher score of compassion satisfaction, and younger nurses, women, nurses having less job experience and nurses without leisure activities showed higher means of secondary traumatic stress. CONCLUSION: we found compassion fatigue, expressed in the large percentage of nurses with high levels of burnout and secondary traumatic stress. Fatigue is related to individual factors such as age, gender, job experience and leisure activities. Doing research and understanding this phenomenon allow the development of health promotion strategies at work.

Development of a bioreactor system for cytotoxic evaluation of pharmacological compounds in living cells using NMR spectroscopy.

INTRODUCTION: The evaluation of drug's cytotoxicity is a crucial step in the development of new pharmacological compounds. 31P NMR can be a tool for toxicological screening, as it enables the study of drugs' cytotoxicity and their effect on cell energy metabolism in a real-time, in a non- invasive and non-destructive way. This paper details a step-by-step protocol to implement a bioreactor system able to maintain cell viability during NMR acquisitions, at high cell densities and for several hours, enabling toxicological evaluation of pharmacological compounds in living cells. METHOD: HeLa cells were immobilized in agarose gel threads and continuously perfused with oxygenated medium inside a 5 mm NMR tube. Signals corresponding to intracellular high-energy phosphorous compounds were continuously monitored by 31P NMR to assess cell energy levels, intracellular pH and intracellular free Mg2+ concentrations ([Mg2+]f) under control and in the presence of two different cytotoxic drugs, calix-NH2 or 5-fluorouracil (5-FU). RESULTS: The bioreactor system was effective in maintaining cell energy levels as well as intracellular pH and [Mg2+]f along time, with a good 31P NMR signal to noise ratio. Calix-NH2 and 5-FU decreased cell energy levels by 35% and 39%, respectively, with a negligible increase in intracellular [Mg2+]f, and without affecting intracellular pH. DISCUSSION: The immobilization and perfusion system here detailed, along with 31P NMR, is useful in toxicological evaluation of new pharmacological compounds, enabling the continuous assessment of drugs' effect on energy levels, intracellular pH and [Mg2+]f in intact cells, for several hours without compromising cell viability.

Fadiga por compaixão em enfermeiros de urgência e emergência hospitalar de adultos / Compassion fatigue among nurses working on an adult emergency and urgent care unit / Fatiga por compasión en enfermeros de un servicio hospitalario de urgencias y emergencias de adultos

Objetivo avaliar o nível de fadiga por compaixão em enfermeiros e sua associação em função de características sociodemográficas/profissionais. Método estudo quantitativo, descritivo e transversal, com 87 enfermeiros de um serviço de urgência e emergência de adultos, de um hospital universitário. Aplicaram-se um questionário sociodemográfico/profissional e a escala Professional Quality of Life Scale 5 . Para a análise dos dados, recorreu-se à estatística descritiva e inferencial. Resultados verificou-se que a satisfação por compaixão apresenta as médias mais elevadas, seguida do burnout e do estresse traumático secundário. Encontraram-se no nível elevado 51% dos enfermeiros na satisfação por compaixão, 54% no burnout e 59% no estresse traumático secundário. Os participantes com mais idade apresentaram médias superiores de satisfação por compaixão, enquanto os do sexo feminino, mais novos, com menos tempo de experiência profissional e que não tinham atividades de lazer evidenciaram média superior de estresse traumático secundário. Conclusão existe fadiga por compaixão expressa na grande percentagem de enfermeiros com elevados níveis de burnout e de estresse traumático secundário. A fadiga depende de fatores individuais como idade, sexo, experiência profissional e atividades de lazer. A pesquisa e a compreensão desse fenômeno permitem o desenvolvimento de estratégias de promoção de saúde no trabalho.

Objective to assess compassion fatigue levels among nurses and its variation according socio-demographic and professional characteristics. Method quantitative, descriptive and cross-sectional study, with 87 nurses from an emergency and urgent care unit for adults from a university hospital. A socio-demographic and professional questionnaire, along with the Professional Quality of Life Scale 5 were used. Data analysis was performed using descriptive and inferential statistics. Results compassion satisfaction presents the highest means, followed by burnout and secondary traumatic stress. Among the participants, 51% presented a high level of compassion satisfaction, 54% a high level of burnout, and 59% a high level of secondary traumatic stress. Older participants presented higher score of compassion satisfaction, and younger nurses, women, nurses having less job experience and nurses without leisure activities showed higher means of secondary traumatic stress. Conclusion we found compassion fatigue, expressed in the large percentage of nurses with high levels of burnout and secondary traumatic stress. Fatigue is related to individual factors such as age, gender, job experience and leisure activities. Doing research and understanding this phenomenon allow the development of health promotion strategies at work.

Objetivo evaluar el nivel de fatiga por compasión de los enfermeros y su asociación con las características sociodemográficas/profesionales. Método se trata de un estudio cuantitativo, descriptivo y transversal, realizado entre 87 enfermeros de un servicio de urgencias y emergencias de adultos de un hospital universitario. Se aplicó un cuestionario sociodemográfico/profesional y la Escala de Calidad de Vida Profesional (ProQOL5). Para el análisis de los datos se utilizaron las estadísticas descriptiva e inferencial. Resultados se comprobó que la satisfacción por compasión alcanza medias elevadas, seguida de burnout y de estrés traumático secundario. En el 51% de los enfermeros se halló satisfacción por compasión, en el 54%, burnout y en el 59%, estrés traumático secundario. Los participantes con más edad presentaban medias superiores de satisfacción por compasión y los del sexo femenino, más jóvenes, con menos tiempo de experiencia profesional y que no participaban de actividades de ocio, evidenciaban una media superior de estrés traumático secundario. Conclusión existe fatiga por compasión expresa en gran porcentaje de los enfermeros con niveles elevados de burnout y de estrés traumático secundario. La fatiga depende de factores individuales como edad, sexo, experiencia profesional y actividades de ocio. La investigación y la comprensión de este fenómeno permiten el desarrollo de estrategias para la promoción de la salud laboral.

Use of an acellular collagen-elastin matrix to support bladder regeneration in a porcine model of peritoneocystoplasty.

INTRODUCTION: Bladder reconstruction without using the intestine remains a challenge to this day despite the development of new biomaterials and cell cultures. Human bladder engineering is merely anecdotic, and mostly in vitro and animal studies have been conducted. MATERIAL AND METHODS: In our study using a porcine model, we performed a bladder augmentation using an autologous parietal peritoneum graft (peritoneocystoplasty) and determined whether the attachment of an acellular collagen-elastin matrix (Group 1) or lack of (Group 2) had better histologic and functional results. Thus far, peritoneocystoplasty has rarely been performed or combined with a biomaterial. RESULTS: After 6 weeks, we observed different degrees of retraction of the new bladder wall in both groups, although the retraction was lower and the histological analysis showed more signs of regeneration (neoangiogenesis and less fibrosis) in Group 1 than when compared with Group 2. No transitional cells were found in the new bladder wall in any of the groups, and no differences were observed in the functional test results. CONCLUSIONS: Performing a peritoneocystoplasty is an easy and safe procedure. The data supports the benefit of an acellular collagen-elastin matrix to reinforce bladder regeneration. However, in our study we observed too much retraction of the new wall and the histologic results were not acceptable to consider it an appropriate cystoplasty technique.

DFT calculations for structural prediction and applications of intercalated lamellar compounds.

The intercalated layered materials are commonly built from structures complex enough to have large unit cells and, because of this, calculations of their electronic structures are very demanding in terms of memory, processing and time. Also, the versatility of these compounds enables the synthesis of a large number of derived materials difficult to characterize. Only in the last two decades, a combination of theoretical methodologies and advances in processing made density-functional theory (DFT) calculations quite interesting as an investigation tool for this family of materials. Since the intercalated layered or lamellar compounds correspond to a large group of important classes of materials and their experimental data were, and are still being, generated, only a small part of the data comes from electronic structure simulations. In this review, we have listed some relevant types of intercalated lamellar materials, the useful methodologies implemented in the standard suit of codes for DFT calculations and examples of the many applications of the calculations to the understanding of physical and chemical properties, to the planning of novel materials with desirable properties, and even to assist the structural characterization, by simulating complex results from nuclear magnetic resonance, vibrational spectroscopy and powder X-ray diffraction. In addition to the properties simulated directly as observables, other quantities such as density of states, partial charges and electronic density difference, provide relevant information about the materials and their behavior under diverse physical and chemical conditions. The combination of the geometric, electronic and vibrational structures also leads to the simulations of thermodynamic potentials, entropy and phase diagrams in the solid state. This significant ensemble of research tools makes DFT calculations very compelling and useful to gain new insights into innovation developments for intercalated lamellar materials.

Role of Neurotrophic Factors in Parkinson's Disease.

Parkinson's disease is an age-associated progressive neurodegenerative disorder that has gained crescent social and economic impact due to the aging of the western society. All current therapies are symptomatic and fail to reverse or halt the progression of dopaminergic neurons loss. The discovery of the capability of neurotrophic factors to protect these neurons lead numerous research groups to focus their efforts in developing therapies aiming at promoting the control of Parkinson´s disease through the delivery of neurotrophic factors to the brain or by boosting their endogenous levels. Both strategies were successful in inducing protection of dopaminergic neurons and motor recovery in preclinical models of the disease. Contrariwise, very limited success was obtained in clinical studies, where glial cell line-derived neurotrophic factor and neurturin were the neurotrophic factors of choice for Parkinson's disease therapy. These drawbacks motivate the development of novel forms of delivery or the modification of the injected molecules aiming at providing a more stable and effective administration with improved diffusion in the target tissue, and without the immune responses observed in the earliest clinical studies. Although promising results were obtained with some of these new approaches performed in experimental models of the disease, they were not yet tested in human studies. In this review, we present the current knowledge on neurotrophic factors and their role in Parkinson's disease, focusing on the strategies that have been developed to increase their levels in target areas of the brain to achieve protection of dopaminergic neurons and motor behaviour recovery.

Dietary patterns and gestational diabetes mellitus in a low income pregnant women population in Brazila cohort study

Our aim is to verify the association between dietary patterns during early pregnancy and development of gestational diabetes mellitus (GDM) in a low income Brazilian population. A cohort study followed 841 healthy pregnant women from the 15-20th gestational week until delivery. This study was conducted at the Instituto de Medicina Integral Prof. Fernando Figueira, Brazil. 838 pregnant women during the first half of a healthy pregnancy with a monthly family income below US $ 500.00 were selected. 95 (11.3%) pregnant women developed gestational diabetes mellitus. Three dietary patterns from factor analysis were extracted. The traditional pattern was characterized by dairy products, fruits, vegetable and fish. The mixed pattern included fried food, pizza, juice, manioc flour, red meat and candies. The western pattern was characterized by eggs, white bread, cookies, pasta, pizza, fried food, chicken, candies, chocolate, salty snacks and soft drinks. There were no differences among GDM incidence according to these three dietary patterns. This finding remained after adjustment for maternal age, maternal education, body mass index pre-pregnancy and parity. We concluded that eating patterns studied during early pregnancy were not associated to the development of GDM in this sample of Brazilian pregnant women with low income(AU)

Hábitos dietéticos e diabetes mellitus gestacional em uma população de gestantes de baixa renda no Brasil estudo de coorte. Nosso objetivo foi verificar a associação entre o padrão alimentar no começo da gravidez com o desenvolvimento de diabetes mellitus gestacional (DMG) em um grupo populacional de baixa renda no Brasil. Um estudo de coorte seguiu 841 gestantes saudáveis da 15-20 semana gestacional até o parto. Esse estudo foi realizado no Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Brasil. Oitocentas e trinta e oito gestantes no curso da primeira metade da gestação e com uma renda familiar abaixo de US $ 500.00 foram selecionadas. Noventa e cinco gestantes (11.3%) desenvolveram DMG. Três padrões alimentares distintos foram extraídos através da técnica do fator de análise. O padrão alimentar tradicional foi caracterizado pela ingestão de produtos lácteos, frutas, vegetais e peixes. O padrão alimentar misto incluiu frituras, pizza, sucos, farinha de mandioca, carne vermelha e doces. O padrão alimentar ocidental foi caracterizado por ovos, pão branco, biscoitos, massa, pizza, carne de galinha, doces, chocolate, salgadinhos e refrigerantes. Não foi observado diferença na incidência de DMG entre os três padrões alimentares identificados. Esse achado permaneceu inalterado após o ajuste para a idade e nível de educação maternal, assim como para o IMC antes da gravidez e paridade. Em conclusão, o padrão alimentar materno durante o começo da gravi- dez entre gestantes de baixa renda não parece estar associado com o desenvolvimento de DMG(AU)

Surgical Trauma Caused by Different Abdominal Access Routes-Comparison of Open Surgical, Laparoscopic, and NOTES Transgastric Techniques in a Porcine Model.

BACKGROUND: Investigations indicate that natural orifice translumenal endoscopic surgery (NOTES) procedures induce a less pronounced postoperative inflammatory response than open or laparoscopic surgery, inflicting less trauma. In NOTES procedures, no skin incision is performed. We compare the inflammatory response added by the type of incision by measuring C-reactive protein (CRP) and tumors necrosis factor-alfa (TNF-α). METHODS: Twenty-seven pigs were randomized to open surgical, laparoscopic, or transgastric NOTES abdominal access. After completion of the accesses, no surgery was performed. All accesses were left open for 40 minutes followed by closure, animals were survived for 7 days. Blood samples were drawn at the start of the accesses, at 20 and 40 minutes during the procedure, and at postoperative day (POD) 1, 3, and 7. Analyses of CRP and TNF-α were performed. RESULTS: CRP increased in all animals until POD1. This increase was greater in the open group (P = .006). No significant differences in CRP-levels were found at POD 1, 3, or 7. TNF-α showed a peak during the procedure, at 20 and 40 minutes, with normalization at POD1 for 1/3 of the open and laparoscopic animals, but not for the NOTES animals. Due to variations within the groups, no statistical difference was shown between them. At postmortem, 1/3 of the pigs in the laparoscopic and open groups had wound infections, while no NOTES animals showed infections. CONCLUSIONS: This study provides no statistically significant differences in inflammatory response after the different abdominal accesses. However, the lack of a TNF-α-peak in the NOTES group might indicate a less pronounced response, supporting the initial theories.