Análise da contribuição do inflamassoma na heterogeneidade clínica de pacientes com doença falciforme

In spite of having a molecular basis, Sickle cell disease (SCD) is an inflammatory state with abnormal cell activation. Physiopathological factors are not completely understood, but it is known that interleukins plays an important role in inflammation. Inflammasome complex is an innate immune pathway involved in the production of active IL-1β and IL-18. The participation of this complex in sickle cell disease is still not clear. Polymorphisms of inflammasome are simple amino acid substitution that can lead to a loss or gain of function and may be associated with clinical manifestations. NLRP3 is the most studied and well-known inflammasome, associated especially to auto-inflammatory diseases. Aim: To analyze the contribution of inflammasome to the clinical heterogeneity of SCD. To this, the association of inflammasome gene polymorphisms and a functional in vitro study were performed. Methods: In the association study 161 patients were included. Retrospective data were collected to fill clinical and laboratorial information. Patients were classified in two different groups: mild (0-1) or severe (> 2 organ damage). DNA samples were collected from 88 patients and 73 were used from a biorepository (BR- 116). Minor allelic frequency and literature information were used to choose 10 SNPs. Real-time PCR technique with allele and specific probes was used in TaqMan® assays (Applied Biosystms, Thermo Fisher Scientific). To functional study (n=7), PBMC and monocytes from healthy patients and controls were challenged with LPS and / or ATP, with subsequent IL-1β dosage by the ELISA method. All volunteers received a free and informed consent form. Multivariate analysis were performed by the software R Studio 3.5.3 (www.r-project.org), SNP association package. Mann-Whitney test was applied to group comparison. Results: The gain-offunction polymorphism rs16944 has resulted in a significant protection factor for SCD severity. The loss of function variant in the IL18 gene (rs1834481) was associated to high count of monocytes and leucocytes. In the functional test, patients with SCD tend to have less inflammasome activation when compared to controls. Conclusion: The promoter variant -511 C>T in IL1β resulted significantly associated to mild presentation in SCD patients (padj=0.001). PBM analysis showed that SCD cells seems to be less prone to activate inflammasome than HD.Introdução: A doença falcifome (DF) é causada por uma simples mudança de base (adenina por timina, c.20A>T) no gene da cadeia da ß-globina, com produção de hemoglobina S. Os principais mecanismos fisiopatológicos da DF envolvem anemia hemolítica e eventos vaso-oclusivos. Apesar da patogênese comum, os pacientes com DF apresentam quadros clínicos variados e diferentes graus de gravidade. A inflamação é uma caraterística frequente e vários padrões moleculares associados ao dano (DAMPs), como a própria hemoglobina falciforme, podem ativar o complexo inflamassoma com consequente produção das citocinas pró-inflamatórias IL-1ß e IL- 18. Variantes genéticas nos componentes do inflamassoma foram previamente associadas a manifestações clínicas que também ocorrem nos pacientes com DF. Portanto, levantamos a hipótese de que o inflamassoma possa contribuir na patogênese da DF e explicar, pelo menos em parte, a heterogeneidade clínica da doença. Objetivos: Avaliar a distribuição de polimorfismos nos principais genes do inflamassoma de acordo com a gravidade da DF e analisar a ativação do complexo em monócitos e PBMC dos pacientes. Material e métodos: Foram analisadas 10 variantes gênicas funcionais nos principais componentes do inflamassoma em uma coorte de 161 pacientes com DF (SS/Sβ) através de ensaios alelo-especificos e qPCR. A distribuição dos polimorfismos foi avaliada através de análise multivariada, de acordo com a gravidade da DF e de dados clínicos e laboratoriais. A ativação do inflamassoma em monócitos e PBMC isolados de sangue periférico foi comparada entre pacientes (n=10) e controles (n=9), através de dosagem de IL1-β pelo método de ELISA. Resultados: O polimorfismo ganho-de função rs16944 no gene IL1β resultou em um fator protetor para gravidade da DF. A variante perda-de-função no gene IL18 (rs1834481) associou-se com valores mais altos de monócitos e leucócitos. No teste funcional, pacientes com AF tendem a ativar menos o inflamassoma quando comparados aos controles. Conclusão: O polimorfismo da IL1β (-511C>T) pode contribuir na heterogeneidade clínica da DF, além de que, quando comparados a controles normais, os monócitos e PBMC desses pacientes tendem a produzir menos IL1β.Dados abertos - Sucupira - Teses e dissertações (2019

An overview of portuguese wordnets

Semantic relations between words are key to building systems that aim to understand and manipulate language. For En- glish, the “de facto” standard for representing this kind of knowledge is Princeton’s WordNet. Here, we describe the wordnet-like resources currently available for Portuguese: their origins, methods of creation, sizes, and usage restrictions. We start tackling the problem of comparing them, but only in quantitative terms. Finally, we sketch ideas for potential collaboration between some of the projects.(undefined

Improvement in wall motion after pindolol : a mechanism for the preservation of left ventricular function in coronary artery disease

1. In order to evaluate the mechanism by which beta blockers with intrinsic sympathomimetic activity preserve left ventricular systolic function at rest, 46 patients with coronary artery disease were studied by right and left heart catheterization and left ventriculography. Patients were studied using a double-blind, randomized protocol before and after a single intravenous dose of 3 mg propranolol (N = 22) or 0.5 mg pindolol (N = 24). 2. Mean right atrial pressure increased similarly after both drugs. Mean pulmonary artery pressure, left ventricular end-diastolic pressure, mean aortic pressure, and peripheral vascular resistance did not change significantly after either drug. Cardiac index (before: 3.0 ± 0. 7 (mean± SEM); after: 2.8 ± 0.2 I min·l m·2) and heart rate (before: 78 ± 15; after: 72 ± 12 bpm) decreased only after propranolol administration. 3. Ejection fraction decreased only after propranolol (48 ± 16 to 41 ± 15%). Improvement in segmental wall motion abnormalities was noted (23 of 47 segments) only after pindolol. The total left ventricular wall motion score improved after pindolol and worsened after propranolol (P < 0.05). In patients with impaired left ventricular function, pindolol administration resulted in improved resting ejection fraction. 4. Thus, the acute hemodynamic consequences of pindolol administration differ from those of propranolol owing to the preservation of left ventricular systolic function which seems to be related to the intrinsic sympathomimetic effect of pindolol on areas of reversible wall motion abnormality

A IMPORTÂNCIA DO PREPARO PRÉVIO ODONTOLÓGICO NA CONDIÇÃO BUCAL DE PACIENTES COM CÂNCER DE CABEÇA E PESCOÇO E O IMPACTO DA PANDEMIA DE COVID-19 NOS AGRAVOS TECIDUAIS

O câncer de cabeça e pescoço (CCP) compreende o grupo de neoplasias malignas que acometem a cavidade oral, faringe, laringe, cavidade nasal, seios paranasais e glândulas salivares (Kawashita et al., 2020). A radioterapia é uma das terapias locais mais eficazes utilizadas, porém, ela afeta, negativamente, os tecidos saudáveis da região irradiada, provocando complicações bucais (Lopes, 2020)

Familial occurrence of cervical artery dissection - coincidence or sign of familial predisposition?

Background and Purpose: The etiology of spontaneous cervical artery dissection (CeAD) is poorly understood in most patients. Mild cervical trauma preceding the dissection event is a common finding, but many CeAD occur spontaneously. It is likely that genetic factors may increase the risk for CeAD. However, familial cases are excedingly rare. Familial clustering of CeAD may be accidental or associated with genetic or environmental risk factors shared between affected relatives. In this explorative study, we aim to show that specific risk factors for familial CeAD exist. Methods: Age of onset, sex, affected artery and number of recurrent CeAD were documented for familial patients and compared with published findings from patients with sporadic CeAD. Concordance of age, sex and dissected artery within the families was analyzed by correlation analysis and by analysis of variance or Kruskal-Wallis testing. Results: The study sample consisted of 9 new patients with a family history of CeAD enrolled in the Neurology Department of the University of Heidelberg or referred to Heidelberg from other centers. The study sample also included published findings from another 23 patients, in total 32 patients. The mean age of the patients with familial CeAD at their first dissections was 38.4 +/- 13.3 years. Twenty (62.5%) patients were female and 12 patients (37.5%) suffered multiple dissections. Four patients (12.5%) presented with recurrent dissections after >1 year. Patients with a familial history of CeAD were younger (p = 0.023) and presented more often with multiple dissections (p = 0.024) and recurrent dissections (p = 0.018). Age at the first event(correlation analysis p = 0.026; analysis of variance p = 0.029) and site of the dissection (correlation analysis p = 0.032; Kruskal-Wallis test p = 0.018) differed between the families, and there was no concordance of gender of affected family members (correlation analysis p = 0.500; Kruskal-Wallis test p = 0.211). Conclusions: The high prevalence of multiple dissection events and of long-term (>1 year) recurrent dissections in patients with a familial history of CeAD indicates that a specific predisposition for familial CeAD exists. Since age of onset and affected vessel differ between families, the risk profile for familial CeAD is heterogeneous. A large-scale (whole exome) sequencing analysis of 14 patients from 7 of the analyzed families is currently being performed in order to identify causative genetic variants

Use of the cell quota and chlorophyll content for normalization of cylindropermopsin produced by two Cylindrospermopsis raciborskii strains grown under different light intensities

The production of cylindrospermopsin (CYN) by Cylindrospermopsis raciborskii (Woloszynska) Seenaya and Subba Raju (Cyanobacteria) was already shown to be changed by variations in light intensities. Influences of light intensity on CYN production by two different C. raciborskii strains (CYP011K and CYP030A) were studied in batch culture conditions. The strains were grown under photon light intensities from 40 to 348 μmol photons m-2 s-1. The growth rates were measured by exponential regression of cell number variation along the time. The concentration of chlorophyll-a (Chl-a) was measured by spectrophotometric methods and the CYN concentration was measured by high-performance liquid chromatographic methods. Data from these CYN analyses were evaluated as cell quota (ng CYN 10-6 cells) or as the relative proportion between toxin concentration and chlorophyll-a concentration (CYN Chl-a-1). The CYP011K showed higher growth rates than the CYP030A strains. According to the cell quota results, the production of CYN by these two strains of C. raciborskii is not affected by the intensity of the surrounding light during growth. However, analysis of the relative proportion of CYN Chl-a-1 led to different interpretations, as a negative relation between light intensity and CYN production

Degradation of multiple peptides by microcystin-degrader Paucibacter toxinivorans (2C20).

Since conventional drinking water treatments applied in different countries are inefficient at eliminating potentially toxic cyanobacterial peptides, a number of bacteria have been studied as an alternative to biological filters for the removal of microcystins (MCs). Here, we evaluated the degradation of not only MCs variants (-LR/DM-LR/-RR/-LF/-YR), but also non-MCs peptides (anabaenopeptins A/B, aerucyclamides A/D) by Paucibactertoxinivorans over 7 days. We also evaluated the degradation rate of MC-LR in a peptide mix, with all peptides tested, and in the presence of M. aeruginosa crude extract. Furthermore, biodegradation was assessed for non-cyanobacterial peptides with different chemical structures, such as cyclosporin A, (Glu1)-fibrinopeptide-B, leucine-enkephalin, and oxytocin. When cyanopeptides were individually added, P. toxinivorans degraded them (99%) over 7 days, except for MC-LR and -RR, which decreased by about 85 and 90%, respectively. The degradation rate of MC-LR decreased in the peptide mix compared to an individual compound, however, in the presence of the Microcystis extract, it was degraded considerably faster (3 days). It was noted that biodegradation rates decreased in the mix for all MCs while non-MCs peptides were immediately degraded. UPLC–QTOF–MS/MS allowed us to identify two linear biodegradation products for MC-LR and MC-YR, and one for MC-LF. Furthermore, P. toxinivorans demonstrated complete degradation of non-cyanobacterial peptides, with the exception of oxytocin, where around 50% remained after 7 days. Thus, although P. toxinivorans was previously identified as a MC-degrader, it also degrades a wide range of peptides under a range of conditions, which could be optimized as a potential biological tool for water treatment

Polydextrose: Physiological Function, And Effects On Health

Polydextrose (PDX) is a non-digestible oligosaccharide used widely across most sectors of the food industry. It is a randomly linked glucose oligomer containing small amounts of sorbitol and citric acid. The random bonds in PDX prevent mammalian digestive enzymes from readily hydrolyzing the molecule and it has a reported energy value of 1 kcal/g. These properties have led to the acceptance in many countries that PDX provides similar physiological effects as other dietary fibers and has shown prebiotic potential. Dietary intervention with prebiotics has been shown to selectively stimulate the growth and/or activity of one or a limited number of intestinal bacteria associated with several physiological benefits on health. Therefore, the objective of this review was a survey of the literature on the effect of supplementation with PDX in health, and to list the benefits for maintaining health and/or reducing the development of diseases.8

Effect of green tea extract on bonding durability of an etch-and-rinse adhesive system to caries-affected dentin

Objective Green tea extract has been advocated as a matrix metalloproteinase (MMP) inhibitor; however, its effect on bond durability to caries-affected dentin has never been reported. Thus, the aim of this in vitro study was to evaluate the effect of two MMP inhibitors (2% chlorhexidine and 2% green tea extract), applied after acid etching, on bond durability of an etch-and-rinse adhesive system to caries-affected dentin. Material and Methods Occlusal enamel was removed from third molars to expose the dentin surface, and the molars were submitted to a caries induction protocol for 15 days. After removal of infected dentin, specimens were conditioned with 37% phosphoric acid (15 seconds) and randomly divided into three groups, according to the type of dentin pretreatment (n=10): NT: no treatment; GT: 2% green tea extract; CLX: 2% chlorhexidine. The etch-and-rinse adhesive system (Adper™ Single Bond 2, 3M ESPE, St. Paul, MN, USA) was applied according to the manufacturer's instructions, and composite resin restorations were built on the dentin. After 24 hours, at 37°C, the resin-tooth blocks were sectioned perpendicularly to the adhesive interface in the form of sticks (0.8 mm2 of adhesive area) and randomly subdivided into two groups according to when they were to be submitted to microtensile bond strength (μTBS) testing: immediately or 6 months after storage in distilled water. Data were reported in MPa and submitted to two-way ANOVA for completely randomized blocks, followed by Tukey’s test (α=0.05). Results After 24 hours, there was no significant difference in the μTBS of the groups. After 6 months, the GT group had significantly higher μTBS values. Conclusion It was concluded that the application of 2% green tea extract was able to increase bond durability of the etch-and-rinse system to dentin. Neither the application of chlorhexidine nor non-treatment (NT - control) had any effect on bond strength after water storage

Prophylactic treatment of vestibular migraine

Introduction: Vestibular migraine (VM) is now accepted as a common cause of episodic vertigo. Treatment of VM involves two situations: the vestibular symptom attacks and the period between attacks. For the latter, some prophylaxis methods can be used. The current recommendation is to use the same prophylactic drugs used for migraines, including beta-blockers, antidepressants and anticonvulsants. The recent diagnostic definition of vestibular migraine makes the number of studies on its treatment scarce. Objective: To evaluate the efficacy of prophylactic treatment used in patients from a VM outpatient clinic. Methods: Review of medical records from patients with VM according to the criteria of the Barany Society/International Headache Society of 2012 criteria. The drugs used in the treatment and treatment response obtained through the visual analog scale (VAS) for dizziness and headache were assessed. The pre and post-treatment VAS scores were compared (the improvement was evaluated together and individually, per drug used). Associations with clinical subgroups of patients were also assessed. Results: Of the 88 assessed records, 47 were eligible. We included patients that met the diagnostic criteria for VM and excluded those whose medical records were illegible and those of patients with other disorders causing dizziness and/or headache that did not meet the 2012 criteria for VM. 80.9% of the patients showed improvement with prophylaxis (p < 0.001). Amitriptyline, Flunarizine, Propranolol and Topiramate improved vestibular symptoms (p < 0.001) and headache (p < 0.015). The four drugs were effective in a statistically significant manner. There was a positive statistical association between the time of vestibular symptoms and clinical improvement. There was no additional benefit in hypertensive patients who used antihypertensive drugs as prophylaxis or depressed patients who used antidepressants in relation to other prophylactic drugs. Drug association did not show statistically significant results in relation to the use of a single drug. Conclusions: Prophylactic medications used to treat VM improve the symptoms of this disease, but there is no statistically significant difference between the responses of prophylactic drugs. The time of vestibular symptom seems to increase the benefit with prophylactic treatment. (C) 2016 Associacao Brasileira de Otorrinolaringologia e Cirurgia Cervico-Facial. Published by Elsevier Editora Ltda.Univ Fed Sao Paulo UNIFESP, Dept Otorrinolaringol & Cirurgia Cabeca & Pescoco, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, Dept Otorrinolaringol & Cirurgia Cabeca & Pescoco, Sao Paulo, SP, BrazilWeb of Scienc