Background: Polymorphisms in genes linked to the innate and adaptive immune response may be involved in inflammatory bowel disease pathogenesis. Our aim was to investigate associations among ...IL1B‐511, IL1B‐31, IL1RN, TNFA‐307, TLR‐2, TLR‐4, IL2‐330, NOD2 G908R, NOD2 L1007fsinsC polymorphisms and both Crohn's disease (CD) and ulcerative colitis (UC) in a Brazilian population.
Methods: We studied 43 patients with CD, 42 with UC, and 541 blood donors. Polymorphisms were evaluated by PCR, PCR‐CTPP, or PCR‐RFLP. Data were analyzed in multivariate models adjusting for confounding factors.
Results: IL1RN VNTR (P = 0.00, odds ratio OR = 2.43, 95% confidence interval CI = 1.50–3.90), as well as TNFA‐307 polymorphic allele (P = 0.05, OR = 1.70, 95% CI = 1.00–2.94) were associated with UC. Both NOD2 mutations (G908R, P = 0.02, OR = 6.83, 95% CI = 1.62–25.45, and L1007fsinsC, P = 0.00, OR = 20.00, 95% CI = 3.21–124.69) were associated with CD.
Conclusions: Our analyses showed positive associations between proinflammatory polymorphisms at IL1RN and TNFA‐307 loci and UC, as well as polymorphisms in the NOD2 gene and CD. These results highlight the importance of different genetic profiles associated with CD and UC.
(Inflamm Bowel Dis 2008)
Abstract
Background
Multiple studies in the past years have supported the idea that microglial cells play a crucial role in the pathophysiology of Alzheimer’s disease (AD) and that their response ...might be quite heterogeneous. However, whether these cells react differently to Amyloid‐β (Aβ) and Tau pathology, as well as, the molecular mechanisms and distinct pathways underlying these responses remains elusive. In this work, we aimed to investigate the response of microglia to Aβ and Tau fibrils, which are being recognized as one of their most toxic forms. We hypothesize that microglia will present a unique response for Aβ and Tau fibrils.
Method
Transcriptomic analysis of mice primary microglial cultures exposed to Aβ or Tau fibrils (5µM, 12‐24hs) was performed. Differentially expressed genes (DEGs) between control and Aβ or Tau fibrils were identified using the DESeq2 method. Functional enrichment (FEA), semantic similarities and protein‐protein interaction networks were conducted. Differences were statistically significant with FDR‐adjusted p‐value < 0.05 and logFC > 1.
Results
Compared to controls, microglia exposed to Aβ fibrils presented 917 DEGs, while the ones exposed to Tau fibrils presented 672 DEGs, of which, only 275 were shared. In contrast, the FEA indicated that more than 69% (736 BP, 50 MF and 32 CC) of the enriched terms were shared between Aβ and Tau. Among the not shared terms, the semantic similarities analysis identified 16 clusters specific for each treatment: Aβ clusters included “regulation of lipids, carbohydrate and ATP metabolic process”, “response to starvation” and “autophagy”, while Tau clusters included “regulation of transmembrane transport of ions”, “gliogenesis” and “neural cells proliferation”.
Conclusion
This work corroborates the idea that microglia react differently to Aβ or Tau pathology but reveals that this response might not be unique as we hypothesized. Although different at the gene level, a big portion of the microglial response to Aβ and Tau converged to the same mechanisms. Despite that, there is still a smaller quantity of adaptations that are specific, such as substrates handling for Aβ and ions transport for Tau. Further validation of these unique phenotypes is being conducted in additional Aβ and Tau pathology models.
Amyloid-β oligomers (AβOs) toxicity causes mitochondrial dysfunction, leading to synaptic failure in Alzheimer’s disease (AD). Considering presynaptic high energy demand and tight Ca
2+
regulation, ...impairment of mitochondrial function can lead to deteriorated neural activity and cell death. In this study, an AD mouse model induced by ICV (intracerebroventricular) injection of AβOs was used to investigate the toxicity of AβOs on presynaptic function. As a therapeutic approach, GUO (guanosine) was given by oral route to evaluate the neuroprotective effects on this AD model. Following 24 h and 48 h from the model induction, behavioral tasks and biochemical analyses were performed, respectively. AβOs impaired object recognition (OR) short-term memory and reduced glutamate uptake and oxidation in the hippocampus. Moreover, AβOs decreased spare respiratory capacity, reduced ATP levels, impaired Ca
2+
handling, and caused mitochondrial swelling in hippocampal synaptosomes. Guanosine crossed the BBB, recovered OR short-term memory, reestablished glutamate uptake, recovered mitochondrial Ca
2+
homeostasis, and partially prevented mitochondrial swelling. Therefore, this endogenous purine presented a neuroprotective effect on presynaptic mitochondria and should be considered for further studies in AD models.
RESUMO O sofrimento psíquico do estudante universitário, particularmente do estudante de Medicina, é conhecido e tem sido motivo de preocupação. O Núcleo de Apoio Psicopedagógico ao Estudante da ...Faculdade de Medicina (Napem) da Universidade Federal de Minas Gerais tem como função acolher o estudante que demanda ajuda espontaneamente. O objetivo deste trabalho foi analisar os motivos da busca por atendimento descritos pelos próprios estudantes ao preencherem a ficha de inscrição no Napem. Foram catalogadas 273 fichas, que representam o total de inscrições de novos estudantes em dois anos da última década. Para preservar a identidade dos estudantes, os anos analisados não foram identificados. Desse grupo, 235 eram estudantes de Medicina, 28 de Fonoaudiologia, 4 do curso superior de Tecnologia em Radiologia e 6 eram estudantes de outros cursos. A metodologia utilizada para análise dos dados foi qualitativa, com análise de conteúdo, e o teste do qui-quadrado foi empregado para a comparação de frequências. Os motivos descritos pelos estudantes foram alocados em cinco categorias estabelecidas pelos pesquisadores – distúrbios do humor, problemas pessoais, características de personalidade, questões acadêmicas e outros. Os resultados mostraram que os distúrbios do humor foram os mais frequentemente relatados (44,3%), seguidos por características de personalidade (26,4%) e por problemas pessoais (13,9%). As questões acadêmicas foram as que apresentaram menor frequência (5,5%). O desejo de morrer foi descrito por 17 (6,2%) estudantes. Quando os estudantes de Medicina foram comparados aos dos demais cursos, não foi observada diferença estatisticamente significativa entre as categorias (p = 0,21), sendo também observado o predomínio de motivos alocados na categoria distúrbios do humor (41,7%). Entretanto, quando considerados separadamente os dois períodos analisados, a frequência de distúrbios do humor nos alunos do curso de Medicina foi significativamente maior (p = 0,0005) entre os inscritos no segundo ano, comparados aos inscritos no primeiro ano do estudo. Deve ser ressaltado, ainda, que quase 50% do total de estudantes que se inscreveu no segundo ano analisado neste estudo cursavam os períodos iniciais, resultado significativamente maior (p = 0,002) quando comparado ao dos inscritos no primeiro ano do estudo. Embora reconhecendo as limitações referentes à análise da demanda preliminar de atendimento formulada pelo aluno ao procurar ajuda, particularmente quando expressa de forma escrita, acredita-se que os resultados deste estudo possam contribuir para a organização dos serviços de apoio psíquico e servir de alerta para essa questão. Pela magnitude do problema, fica evidente a necessidade da existência de espaços de acolhimento para os estudantes e de atuação precoce no início do curso, com atividades que possam recebê-los e escutá-los quando do ingresso na faculdade, como, por exemplo, os programas de tutoria.
ABSTRACT The psychological distress experienced by university students, particularly medical students, is well-known and has long been a cause for concern. In the School of Medicine of the Universidade Federal de Minas Gerais, the School of Medicine Psychopedagogical Student Support Center (Núcleo de Apoio Psicopedagógico ao Estudante da Faculdade de Medicina - NAPEM) provides care to students who spontaneously seek help. The purpose of this study was to analyze the reasons described when completing the Napem application form by students for their seeking the assistance. A total of 273 students enrolled in the two years studied, which were both in the last decade. To preserve the identity of the students, the years analyzed were not identified. Of this group, 235 were medical students, 28 students of Speech Therapy, four undergraduate students of Technology in Radiology and six were students of other courses. The methodology used for data analysis was qualitative, with content analysis and the frequency comparison was performed using the chi-square test. The reasons to seek care written by the students in the application form were placed in five categories established by the researchers – “mood disorders,” “personal problems,” “personality traits,” “academic issues” and others. The results showed that “mood disorders” were the most frequently reported (44.3%), followed by “personality traits” (26.4%) and “personal problems” (13.9%). The “academic questions” presented the lowest frequency (5.5%). The desire to die was described by 17 (6.2%) students. When the medical students were compared to the students of the other courses, there was no statistically significant difference among the frequencies of the five categories (p = 0.21) with motives allocated in the category “mood disorders” (41.7%) being predominantly observed. However, when considering two studied periods separately, the frequency of the category “mood disorders” for medical students was significantly higher (p = 0.0005) in the second year than in the first year of study. It should be emphasized that almost 50% of the students enrolled in the second year analyzed attended the centre for first two years, a significantly higher result (p = 0.002) when compared to those enrolled in the first year of the study. Even recognizing the limitations regarding the analysis of the student’s preliminary demand for care when seeking help, particularly when expressed in written form, it is believed that the results of this study can contribute to the organization of psychological support services. Due to the magnitude of the problem, there is a clear need to have welcome spaces for the students with activities that can receive them and listen to them when they enter college, such as mentoring programs.
Major depressive disorder (MDD) leads to pervasive changes in the health of afflicted patients. Despite advances in the understanding of MDD and its treatment, profound innovation is needed to ...develop fast-onset antidepressants with higher effectiveness. When acutely administered, the endogenous nucleoside guanosine (GUO) shows fast-onset antidepressant-like effects in several mouse models, including the olfactory bulbectomy (OBX) rodent model. OBX is advocated to possess translational value and be suitable to assess the time course of depressive-like behavior in rodents. This study aimed at investigating the long-term behavioral and neurochemical effects of GUO in a mouse model of depression induced by bilateral bulbectomy (OBX). Mice were submitted to OBX and, after 14 days of recovery, received daily (ip) administration of 7.5 mg/kg GUO or 40 mg/kg imipramine (IMI) for 45 days. GUO and IMI reversed the OBX-induced hyperlocomotion and recognition memory impairment, hippocampal BDNF increase, and redox imbalance (ROS, NO, and GSH levels). GUO also mitigated the OBX-induced hippocampal neuroinflammation (IL-1, IL-6, TNF-α, INF-γ, and IL-10). Brain microPET imaging (
18
FFDG) shows that GUO also prevented the OBX-induced increase in hippocampal FDG metabolism. These results provide additional evidence for GUO antidepressant-like effects, associated with beneficial neurochemical outcomes relevant to counteract depression.
Helicobacter pylori is one of the most common infections worldwide. In most individuals it consists in a lifelong host-pathogen relationship without consequences, but in some subjects it is ...associated with peptic ulcer disease and gastric cancer. Polymorphism in genes that code bacterial virulence factors,
cagA and
vacA, are independently associated with the infection severe outcomes and are geographically diverse. In the last decade, accumulated knowledge allowed to characterize typical
H. pylori strain patterns for all the major human populations; patterns that can be used to study the origin of specific human groups. Thus, the presence or absence of
cagA,
cagA EPIYA genotypes, and
vacA subtypes can be used as tools to study not only the geographic origin of specific human populations, but also to identify markers of historical contact between different ethnicities. We report here a study including a set of native Amazon Amerindians that had supposedly been some, but little, contact with European Brazilian colonizer and/or African slaves. They harbor
H. pylori strains in a mixed pattern with Asian and Iberian Peninsula characteristics. It is possible that this finding represents
H. pylori recombination upon short contact between human groups. Alternatively, it could be due to a founder effect from a small cluster of Asian origin native Americans.
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