The kynurenine pathway in Alzheimer’s disease: a meta-analysis of central and peripheral levels

Objective: Changes in the kynurenine pathway are recognized in psychiatric disorders, but their role in Alzheimer’s disease (AD) is less clear. We aimed to conduct a systematic review and meta-analysis to determine whether tryptophan and kynurenine pathway metabolites are altered in AD. Methods: We performed a systematic review and random-effects meta-analyses. Inclusion criteria were studies that compared AD and cognitively normal (CN) groups and assessed tryptophan or kynurenine pathway metabolites in cerebrospinal fluid or peripheral blood. Results: Twenty-two studies with a total of 1,356 participants (664 with AD and 692 CN individuals) were included. Tryptophan was decreased only in peripheral blood. The kynurenine-to-tryptophan ratio was only increased in peripheral blood of the AD group. 3-Hydroxykynurenine was decreased only in cerebrospinal fluid and showed higher variability in the CN group than the AD group. Kynurenic acid was increased in cerebrospinal fluid and decreased in peripheral blood. Finally, there were no changes in kynurenine and quinolinic acid between the groups. Conclusions: Our results suggested a shift toward the kynurenine pathway in both the brain and in the periphery, as well as a shift towards increased kynurenic acid production in the brain but decreased production in peripheral blood. In addition, our analysis indicated dissociation between the central and peripheral levels, as well as between plasma and serum for some of these metabolites. Finally, changes in the kynurenine pathway are suggested to be a core component of AD. More studies are warranted to verify and consolidate our results

Qualidade de vida relacionada à saúde de adolescentes no Rio Grande Do SuL, BRASIL

Este estudo descritivo, de corte transversal, verificou a QVRS percebida por 376 alunos de 14 a 16 anos estratificados por idade, sexo e rede de ensino, de Gravataí, RS, Brasil, através do Kidscreen-52. Os dados demonstraram que aqueles que se encontravam insatisfeitos com a sua QVRS se enquadraram no 2º quartil (1%), isto é, abaixo dos 50% da amostra; 42% se enquadraram no 3o quartil e 57% no quarto, apontando percepção muito satisfatória de QVRS. Constatou-se uma tendência de as meninas apresentarem escores superiores aos meninos nestas três últimas dimensões. Concluiuse que a amostra investigada possui percepção muito satisfatória de QVRS.UY-MoUC

Treatment implications of predominant polarity and the polarity index: a comprehensive review.

Background: Bipolar disorder (BD) is a serious and recurring condition that affects approximately 2.4% of the global population. About half of BD sufferers have an illness course characterized by either a manic or a depressive predominance. This predominant polarity in BD may be differentially associated with several clinical correlates. The concept of a polarity index (PI) has been recently proposed as an index of the antimanic versus antidepressive efficacy of various maintenance treatments for BD. Notwithstanding its potential clinical utility, predominant polarity was not included in the DSM-5 as a BD course specifier. Methods: Here we searched computerized databases for original clinical studies on the role of predominant polarity for selection of and response to pharmacological treatments for BD. Furthermore, we systematically searched the Pubmed database for maintenance randomized controlled trials (RCTs) for BD to determine the PI of the various pharmacological agents for BD. Results: We found support from naturalistic studies that bipolar patients with a predominantly depressive polarity are more likely to be treated with an antidepressive stabilization package, while BD patients with a manic-predominant polarity are more frequently treated with an antimanic stabilization package. Furthermore, predominantly manic BD patients received therapeutic regimens with a higher mean PI. The calculated PI varied from 0.4 (for lamotrigine) to 12.1 (for aripiprazole). Conclusions: This review supports the clinical relevance of predominant polarity as a course specifier for BD. Future studies should investigate the role of baseline, predominant polarity as an outcome predictor of BD maintenance RCTs. Keywords

Efeitos da pregabalina sobre alterações comportamentais induzidas pela cetamina em ratos

Objective: The aim of this study is to investigate the effects of pregabalin on the behavior of rats under the influence of ketamine, an NMDA receptor antagonist that mimics the symptoms of schizophrenia. Methods: Rats were injected with saline or 25 mg/kg ketamine intraperitoneally. After that, behavior modifications were investigated by the evaluation of stereotypy and hyperlocomotion, after treating rats with pregabalin (at doses of 30 mg/kg or 100 mg/kg) or placebo (saline solution). Results: The administration of pregabalin reduced ketamine-induced hyperlocomotion. However, neither doses of pregabalin had a significant effect on ketamine-induced stereotypy. Conclusion: This is the first study to investigate the effects of pregabalin using an animal model of psychosis. Furthermore, our results indicate that behavioral changes induced by ketamine in rats can be reversed with the use of pregabalin, suggesting its potential to treat psychotic symptoms.Objetivo: O presente estudo tem como objetivo investigar os efeitos da pregabalina sobre as alterações comportamentais em ratos induzidas pela cetamina, um antagonista do receptor glutamatérgico NMDA, utilizado em modelos animais de psicose. Métodos:\ud Ratos receberam injeção com solução salina ou cetamina, na dose de 25 mg/kg, com posterior avaliação das alterações comportamentais induzidas, através da avaliação da estereotipia e hiperlocomoção, depois destes ratos terem sido tratados com pregabalina (30 mg/kg ou 100 mg/kg) ou placebo. Resultados: A administração de pregabalina reduziu a hiperlocomoção nos ratos sob o efeito da cetamina. No entanto, nenhuma das doses de pregabalina teve efeito significativo sobre a estereotipia induzida pela cetamina. Conclusão:\ud Este é o primeiro estudo que investiga os efeitos da pregabalina em um modelo animal de psicose. Nossos resultados indicam que alterações comportamentais induzidas pela cetamina em ratos podem ser revertidas após uso da pregabalina, o que sugere um possível potencial desta no tratamento de sintomas psicóticos.CNPqINCTFMRP-USPUNES

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality