The Purinergic System as a Target for the Development of Treatments for Bipolar Disorder.

The neurobiological and neurochemical mechanisms underlying the pathophysiology of bipolar disorder are complex and not yet fully understood. From circadian disruption to neuroinflammation, many pathways and signaling molecules are important contributors to bipolar disorder development, some specific to a disease subtype or a cycling episode. Pharmacological agents for bipolar disorder have shown only partial efficacy, including mood stabilizers and antipsychotics. The purinergic hypothesis for bipolar disorder emerges in this scenario as a promising target for further research and drug development, given its role in neurotransmission and neuroinflammation that results in behavioral and mood regulation. Here, we review the basic concepts of purinergic signaling in the central nervous system and its contribution to bipolar disorder pathophysiology. Allopurinol and novel P2X7 receptor antagonists are promising candidates for treating bipolar disorder. We further explore currently available pharmacotherapies and the emerging new purinergic targets for drug development in bipolar disorder.

Stabilization and operational selectivity alteration of Lipozyme 435 by its coating with polyethyleneimine: Comparison of the biocatalyst performance in the synthesis of xylose fatty esters.

Differently modified Lipozyme 435 (L435) (immobilized lipase B from Candida antarctica) preparations were used as biocatalysts in the esterification reaction to synthesize sugar fatty acid esters (SFAEs) from xylose (acyl acceptor) and lauric/palmitic acids (acyl donors) in methyl ethyl ketone (MEK) solvent. The L435 treatment with polyethyleneimine (PEI) (2; 25; and 750 KDa) prevented the enzyme leakage in the crude sugar ester reaction product. The 2 KDa PEI coating of this enzyme preparation produced the highest enzyme stability in MEK, buffer solutions (pHs 5 and 7), and methanol aqueous phosphate buffer at pH 7. Using an excess of the acyl donor (1:5 xylose: fatty acid molar ratio), high xylose conversions (70-84%) were obtained after 24 h-reaction using both, non-modified and PEI (2 KDa) coated L435, but the PEI treated biocatalyst afforded a higher xylose modification degree. After 5 reuse cycles with the L435 coated with PEI 2 KDa, the xylose conversions only decreased 10%, while with the non-treated biocatalyst they decreased by 37%. The formation of SFAEs was confirmed by mass spectrometry, which showed the presence of xylose mono-, di-, and triesters. They exhibited emulsion capacities close to that of a commercial sucrose monolaurate.

Four challenges when conducting bibliometric reviews and how to deal with them.

The evidence base in environmental sciences is increasing steadily. Environmental researchers have been challenged to handle massive volumes of data to support more comprehensive studies, assess the current status of science, and move research towards future progress. Bibliometrics can provide important insights into the research directions by providing summarized information for several end users. Here, we present an in-depth discussion on the use of bibliometric indicators to evaluate research outputs through four case studies comprising disciplines in environmental sciences. We discuss four big challenges researchers may face when conducting bibliometric reviews and how to deal with them. We also address some primary questions researchers may answer with bibliometric mapping, drawing lessons from the case studies. Lastly, we clarify some misuses of review concepts and suggest methodological principles of systematic reviews and maps to improve the overall quality of bibliometric studies.

Lipozyme 435-Mediated Synthesis of Xylose Oleate in Methyl Ethyl Ketone.

In this paper, we have performed the Lipozyme 435-catalyzed synthesis of xylose oleate in methyl ethyl ketone (MEK) from xylose and oleic acid. The effects of substrates' molar ratios, reaction temperature, reaction time on esterification rates, and Lipozyme 435 reuse were studied. Results showed that an excess of oleic acid (xylose: oleic acid molar ratio of 1:5) significantly favored the reaction, yielding 98% of xylose conversion and 31% oleic acid conversion after 24 h-reaction (mainly to xylose mono- and dioleate, as confirmed by mass spectrometry). The highest Lipozyme 435 activities occurred between 55 and 70 °C. The predicted Ping Pong Bi Bi kinetic model fitted very well to the experimental data and there was no evidence of inhibitions in the range assessed. The reaction product was purified and presented an emulsion capacity close to that of a commercial sugar ester detergent. Finally, the repeated use of Lipozyme 435 showed a reduction in the reaction yields (by 48 and 19% in the xylose and oleic acid conversions, respectively), after ten 12 h-cycles.

Reviewing research on the synthesis of CALB-catalyzed sugar esters incorporating systematic mapping principles.

Rigorous evidence reviews must follow specific guidelines designed to improve transparency, reproducibility, and to minimize biases to which traditional reviews are susceptible. While evidence synthesis methods, such as systematic reviews and maps, have been used in several research fields, the majority of reviews published in the realm of chemical engineering are nonsystematic. In this study, we incorporated principles of systematic mapping to conduct a literature review covering research on the synthesis of sugar fatty acid esters (SFAE) with Candida antarctica lipase B (CALB). Our results showed that the simple monosaccharides were the most cited sugars among studies we conducted. The direct use of renewable raw materials and frequently available resources to produce alternative sugar esters (SE) was scarcely reported in our data set. We found that free fatty acids (FFA) were the most commonly cited acyl donors amongst all publications, with lauric, oleic, and palmitic acids accounting for ∼43% of the occurrences. Tertiary alcohols (ter-butyl alcohol (T-but) and 2-methyl-2-butanol (2M2B)) and ionic liquids were the most used solvents to synthesize SE. The co-occurence analysis of keywords involving solvent terms showed that most of the papers evaluated different solvents as reaction media (mostly in the form of a bisolvent system), also investigating the impact of their choice on sugar ester productivities. Given the potential of reviews informing us of research decisions, this article reveals trends and spaces across CALB-catalyzed SE synthesis research, in addition to introducing a new methodological perspective for developing reviews in the field of chemical engineering.

P2Y2 receptor activation promotes esophageal cancer cells proliferation via ERK1/2 pathway.

Esophageal cancer is a prominent worldwide illness that is divided into two main subtypes: esophageal squamous cell carcinoma and esophageal adenocarcinoma. Mortality rates are alarming, and the understanding of the mechanisms involved in esophageal cancer development, becomes essential. Purinergic signaling is related to many diseases and among these various types of tumors. Here we studied the effects of the P2Y2 receptor activation in different types of esophageal cancer. Esophageal tissue samples of healthy controls were used for P2Y2R expression quantification. Two human esophageal cancer cell lines Kyse-450 (squamous cell carcinoma) and OE-33 (adenocarcinoma) were used to perform in vitro analysis of cell proliferation, migration, adhesion, and the signaling pathways involved in P2Y2R activation. Data showed that P2Y2R was expressed in biopsies of patients with ESCC and adenocarcinoma, as well as in the two human esophageal cancer cell lines studied. The RT-qPCR analysis demonstrated that OE-33 cells have higher P2RY2 expression than Kyse-450 squamous cell line. Results showed that P2Y2R activation, induced by ATP or UTP, promoted esophageal cancer cells proliferation and colony formation. P2Y2R blockage with the selective antagonist, AR-C 118925XX, led to decreased proliferation, colony formation and adhesion. Treatments with ATP or UTP activated ERK 1/2 pathway in ESCC and ECA cells. The P2Y2R antagonism did not alter the migration of esophageal cancer cells. Interestingly, the esophageal cancer cell lines presented a distinct profile of nucleotide hydrolysis activity. The modulation of P2Y2 receptors may be a promising target for esophageal cancer treatment.

Effects of single-dose antipurinergic therapy on behavioral and molecular alterations in the valproic acid-induced animal model of autism.

Autism spectrum disorder (ASD) is characterized by deficits in communication and social interaction, restricted interests, and stereotyped behavior. Environmental factors, such as prenatal exposure to valproic acid (VPA), may contribute to the increased risk of ASD. Since disturbed functioning of the purinergic signaling system has been associated with the onset of ASD and used as a potential therapeutic target for ASD in both clinical and preclinical studies, we analyzed the effects of suramin, a non-selective purinergic antagonist, on behavioral, molecular and immunological in an animal model of autism induced by prenatal exposure to VPA. Treatment with suramin (20 mg/kg, intraperitoneal) restored sociability in the three-chamber apparatus and decreased anxiety measured by elevated plus maze apparatus, but had no impact on decreased reciprocal social interactions or higher nociceptive threshold in VPA rats. Suramin treatment did not affect VPA-induced upregulation of P2X4 and P2Y2 receptor expression in the hippocampus, and P2X4 receptor expression in the medial prefrontal cortex, but normalized an increased level of interleukin 6 (IL-6). Our results suggest an important role of purinergic signaling modulation in behavioral, molecular, and immunological aberrations described in VPA model, and indicate that the purinergic signaling system might be a potential target for pharmacotherapy in preclinical studies of ASD.

Midbrain Dopaminergic Neurons Differentiated from Human-Induced Pluripotent Stem Cells.

The work with midbrain dopaminergic neurons (mDAN) differentiation might seem to be hard. There are about 40 different published protocols for mDAN differentiation, which are eventually modified according to the respective laboratory. In many cases, protocols are not fully described, failing to provide essential tips for researchers starting in the field. Considering that commercial kits produce low mDAN percentages (20-50%), we chose to follow a mix of four main protocols based on Kriks and colleagues' protocol, from which the resulting mDAN were engrafted with success in three different animal models of Parkinson's disease. We present a differential step-by-step methodology for generating mDAN directly from human-induced pluripotent stem cells cultured with E8 medium on Geltrex, without culture on primary mouse embryonic fibroblasts prior to mDAN differentiation, and subsequent exposure of neurons to rock inhibitor during passages for improving cell viability. The protocol described here allows obtaining mDAN with phenotypical and functional characteristics suitable for in vitro modeling, cell transplantation, and drug screening.

Comunicação efetiva entre o Centro Cirúrgico e a Unidade de Terapia Intensiva / Effective communication between surgical center and intensive care unit

Objetivo: construir um instrumento para a comunicação efetiva durante a passagem de plantão entre o Centro Cirúrgico e a Unidade de Terapia Intensiva. Método: relato de experiências, sobre a construção do impresso em quatro fases: brainstorming do grupo; confecção do impresso; teste-piloto; reformulação das informações e finalização do impresso. Resultados: foi elaborado um impresso com informações sobre o pré-operatório (história prévia e antecedentes clínicos e cirúrgicos), intraoperatório (intercorrências, informação transfusional, antibiótico profilático, intubação difícil) e pós-operatório (condição de via aérea, drenos, sondas, curativos, medidas de prevenção de trombose, analgesia e transporte). Conclusão: o impresso proporcionou segurança e facilidade para transferência das informações para a unidade de destino e facilitou o planejamento da assistência de enfermagem sendo bem aceito pelos componentes de ambas as equipes...

Eficácia da tromboprofilaxia não farmacológica em pacientes hospitalizados: estudo caso-controle aninhado / Non-pharmacological thromboprophylaxis efficacy in hospitalized patients: a nested case-control study

Introdução: a trombose venosa adquirida durante hospitalização (TV) é complicação potencialmente fatal, mas prevenível pela tromboprofilaxia primária (TP), que pode ser farmacológica ou não farmacológica (TPNF). A TPNF inclui mobilização precoce do paciente no leito, meias elásticas compressivas graduadas ou compressão pneumática intermitente de membros inferiores. O objetivo deste estudo foi avaliar a eficácia daTPNF em pacientes admitidos em hospital público, ajustando para confundimento por indicação. Material e método: este é um estudo com análise de caso-controle aninhado em coorte do programa de TP do Hospital Naval Marcílio Dias, Rio de Janeiro, entre 1995 e 2001. Os participantes foram pacientes hospitalizados maiores de 18 anos sem anticoagulação ou suspeita de TV à admissão. Casos foram participantes com TV. Cinco controles foram selecionados para cada caso com pareamento por sexo, idade e ano de internação. A medida de desfecho foi a razão de chances (OR) para TV sintomática, diagnosticada objetivamente em participantes submetidos à TPNF comparados a participantes sem TP. Resultados: houve 76 casos entre 21.067 participantes pareados a 379 controles. A OR não ajustada para TV foi de 0,41 (IC 95% 0,22-0,77) e a OR ajustada para confundimento foi de 0,42 (IC 95% 0,19-0,92). A taxa de incidência para TV entre participantes submetidos à TPNF foi de 1,6 por 1.000 internações e entre participantessem TP, 4,0 por 1.000 internações. Conclusão: após ajustes para fatores de confundimento, o risco de TV foi reduzido pela metade com medidas tromboprofiláticas não farmacológicas em relação a pacientes sem tromboprofilaxia.

Introduction: Hospital-acquired venous thrombosis (VT) is a potentially fatal but preventable complication. Thromboprophylaxis may include pharmacological or non-pharmacological strategies (NPTP). NPTP may include early patient ambulation, graduated elastic compressive stockings or compressive pneumatic compression of lower limbs. Our objective was to measure NPTP efficacy in a brazilian public hospital. Material and Method: This is a case-control study nested in a cohort comprising patients admitted to Hospital Naval Marcílio Dias from 1995 to 2001 who participated in the hospital TP program; Participants were over 18 years of age, without anticoagulation or suspected VT at admission. Cases were participants who developed VT during hospital stay. Five controls were matched by age, gender and date of VT to each index case. Outcome was evaluated by OR for VT comparing participants submitted to NPTB to no TP. Results: There were 76 cases matched to 379 controls out of 21,067 participants. Unadjusted OR for VT was 0.41 (95% CI 0.22-0.77) and the adjusted OR for confounding was 0.42 (95% CI 0.19-0.92). VT incidence was 1.6/1000 hospital admissions in participants receiving NFTP and 4.0/1000 hospital admissions in participants with no TP. Conclusion: After adjustment for confounding, venous thrombosis risk was halved by non-pharmacological thromboprophylaxis compared with no thromboprophylaxis.

A indexação de livros: a percepção de catalogadores e usuários de bibliotecas universitárias. Um estudo de observação do contexto sociocognitivo com protocolos verbais / The indexing books: the perception of cataloguers and users of university libraries. An observational study of the socio-cognitive context with verbal protocols

Por que é importante investigar a indexação durante a catalogação? A resposta é que, por meio de tal procedimento, é possível conhecer as realidades de bibliotecários e usuários. A pesquisa apresentada neste livro se destaca por dois motivos: trata-se de um trabalho coletivo, com objetivos, fundamentação teórica e metodológica comuns; adota uma abordagem sociocognitiva que não só evidencia a tarefa de indexação de assuntos na catalogação de livros por catalogadores, como também privilegia e entrelaça as diferentes visões dos usuários do catálogo, discentes, docentes, pesquisadores, bibliotecários de referência e dirigentes de bibliotecas - grupos que fazem parte do contexto sociocognitivo dos catalogadores, pois são usuários dos resultados da tarefa que realizam. Esta é uma obra de referência para os profissionais de biblioteconomia...