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1.
Br J Haematol ; 200(3): 353-357, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36198407

RESUMO

Intravenous Anti-Rhesus-D immunoglobulin (Anti-D) is a first-line treatment option for immune thrombocytopenia in non-splenectomised and RhD-positive patients. In this report, we retrospectively review our experience with intramuscular (IM) Anti-D treatment in 74 adult patients between 1990 and 2018. We found that 73% of patients showed a response; almost all of them had complete responses (68.9%), and 26% achieved complete responses sustained at least 6 months after treatment discontinuation. [Correction added on 02 December 2022, after first online publication: In the preceding sentence, '(68.89%)' has been corrected to '(68.9%)' in this version.] No significant side effects were observed with no cases of acute haemolysis or anaemia reported. We conclude from this study that IM Anti-D is an effective and safe treatment for immune thrombocytopenia.


Assuntos
Púrpura Trombocitopênica Idiopática , Trombocitopenia , Adulto , Humanos , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Estudos Retrospectivos , Imunoglobulina rho(D) , Trombocitopenia/tratamento farmacológico
2.
Curr Issues Mol Biol ; 44(5): 2089-2106, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35678670

RESUMO

Subtilisin proteases, found in all organisms, are enzymes important in the post-translational steps of protein processing. In Leishmania major and L. donovani, this enzyme has been described as essential to their survival; however, few compounds that target subtilisin have been investigated for their potential as an antileishmanial drug. In this study, we first show, by electron microscopy and flow cytometry, that subtilisin has broad localization throughout the cytoplasm and membrane of the parasite in the promastigote form with foci in the flagellar pocket. Through in silico analysis, the similarity between subtilisin of different Leishmania species and that of humans were determined, and based on molecular docking, we evaluated the interaction capacity of a serine protease inhibitor against both life cycle forms of Leishmania. The selected inhibitor, known as PF-429242, has already been used against the dengue virus, arenaviruses, and the hepatitis C virus. Moreover, it proved to have antilipogenic activity in a mouse model and caused hypolipidemia in human cells in vitro. Here, PF-429242 significantly inhibited the growth of L. amazonensis promastigotes of four different strains (IC50 values = 3.07 ± 0.20; 0.83 ± 0.12; 2.02 ± 0.27 and 5.83 ± 1.2 µM against LTB0016, PH8, Josefa and LV78 strains) whilst having low toxicity in the host macrophages (CC50 = 170.30 µM). We detected by flow cytometry that there is a greater expression of subtilisin in the amastigote form; however, PF-429242 had a low effect against this intracellular form with an IC50 of >100 µM for intracellular amastigotes, as well as against axenic amastigotes (94.12 ± 2.8 µM for the LV78 strain). In conclusion, even though PF-429242 does not affect the intracellular forms, this drug will serve as a tool to explore pharmacological and potentially leishmanicidal targets.

3.
Parasitology ; 147(14): 1792-1800, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32958098

RESUMO

Vitamin D has been reported to activate macrophage microbicidal mechanisms by inducing the production of antimicrobial peptides and nitric oxide (NO), but conversely has been shown to contribute to a greater susceptibility to Leishmania amazonensis infection in mice. Thus, this study aimed to evaluate the role of vitamin D during intracellular infection with L. amazonensis by examining its effect on macrophage oxidative mechanisms and parasite survival in vitro. Vitamins D2 and D3 significantly inhibited promastigote and amastigote growth in vitro. Vitamin D3 was not able to induce NO and reactive oxygen species (ROS) production in uninfected macrophages or macrophages infected with L. amazonensis. In addition, vitamin D3 in combination with interferon (IFN)-γ did not enhance amastigote killing and in fact, significantly reduced NO and ROS production when compared with the effect of IFN-γ alone. In this study, we demonstrated that vitamin D directly reduces parasite growth in infected macrophages (approximately 50-60% at 50 µm) but this effect is independent of the activation of macrophage oxidative mechanisms. These findings will contribute to a better understanding of the role of vitamin D in cutaneous leishmaniasis.


Assuntos
Antiparasitários/farmacologia , Colecalciferol/farmacologia , Ergocalciferóis/farmacologia , Leishmania mexicana/efeitos dos fármacos , Vitaminas/farmacologia , Leishmaniose Cutânea/metabolismo , Leishmaniose Cutânea/parasitologia , Macrófagos/metabolismo , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo
4.
Stroke ; 49(10): 2495-2503, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30355106

RESUMO

Background and Purpose- Poststroke, neuronal excitability is tonically reduced in peri-infarct tissue via inhibitory influences of extrasynaptic GABAA receptors. We hypothesized that GABAA α5 blockade by the competitive antagonist S44819 enhances postischemic neurological recovery, brain remodeling, and neuroplasticity. Methods- In an explorative study followed by a confirmation study, male C57Bl6/j mice were exposed to transient intraluminal middle cerebral artery occlusion. Starting 72 hours poststroke, vehicle or S44819 (3 or 10 mg/kg, BID) was delivered orally for 28 days. Neurological recovery, perilesional tissue remodeling, and contralesional pyramidal tract plasticity were evaluated for 42 days, that is, 14 days after completion of S44819 delivery. Results- S44819, delivered at 10 but not 3 mg/kg, persistently improved motor coordination and spatial memory in both studies. Striatal atrophy was reduced by 10 mg/kg S44819 at 42 days post-treatment onset, and neuronal long-term survival in the peri-infarct striatum was increased. Delayed neuroprotection was associated with reduced peri-infarct astrogliosis, increased peri-infarct brain capillary density, and increased neural precursor cell proliferation and differentiation in proximity to the ipsilesional subventricular zone. Contralesional pyramidal tract plasticity, evaluated by anterograde tract tracing at the level of the red nucleus, was not influenced by S44819. Concentrations of neurotrophic (brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor) and angiogenic (vascular endothelial growth factor and basic fibroblast growth factor) growth factors were elevated by 10 mg/kg S44819 in peri-infarct but not contralesional brain tissue. Conclusions- Our data demonstrate that S44819 enhances neurological recovery and peri-infarct brain remodeling in the postacute stroke phase.


Assuntos
Benzodiazepinas/farmacologia , Antagonistas GABAérgicos/farmacologia , Oxazóis/farmacologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neuroproteção/efeitos dos fármacos , Receptores de GABA-A/efeitos dos fármacos , Receptores de GABA-A/metabolismo , Acidente Vascular Cerebral/fisiopatologia
5.
J Biol Inorg Chem ; 22(6): 929-939, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28597089

RESUMO

In our previous work, we demonstrated the promising in vitro effect of VOSalophen, a vanadium complex with a stilbene derivative, against Leishmania amazonensis. Its antileishmanial activity has been associated with oxidative stress in L. amazonensis promastigotes and L. amazonensis-infected macrophages. In the present study, the mechanism involved in the death of parasites after treatment with VOSalophen, as well as in vivo effect in the murine model cutaneous leishmaniasis, has been investigated. Promastigotes of L. amazonensis treated with VOSalophen presented apoptotic cells features, such as cell volume decrease, phosphatidylserine externalization, and DNA fragmentation. An increase in autophagic vacuoles formation in treated promastigotes was also observed, showing that autophagy also may be involved in the death of these parasites. In intracellular amastigotes, DNA fragmentation was observed after treatment with VOSalophen, but this effect was not observed in host cells, highlighting the selective effect of this vanadium complex. In addition, VOSalophen showed activity in the murine model of cutaneous leishmaniasis, without hepatic and renal damages. The outcome described here points out that VOSalophen had promising antileishmanial properties and these data also contribute to the understanding of the mechanisms involved in the death of protozoa induced by metal complexes.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/patologia , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Estilbenos/química , Vanádio/química , Animais , Fragmentação do DNA/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Leishmaniose Cutânea/genética , Camundongos , Camundongos Endogâmicos BALB C , Compostos Organometálicos/uso terapêutico
6.
Int J Food Sci Nutr ; 66(4): 439-44, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25835042

RESUMO

The aim of this study was to investigate the phenolic composition of a natural food colourant (G8000™) as well as its effects on plasma markers after 28-day consumption by healthy individuals at a dietary dose (70 g). Parameters of total cholesterol and its fractions, triglycerides and plasma enzymes biomarkers of muscle injury were measured. Major compounds identified in G8000™ by ESI-MS showed the presence of anthocyanins, organic acids, phenolic acids as well as monosaccharides. HDL levels significantly increased from 43 ± 10.2 mg/dL to 95 ± 16.9 mg/dL. LDL levels significantly decreased from 110 ± 40.9 mg/dL to 69 ± 39 mg/dL (p < 0.001). No significant statistical differences (p > 0.05) were observed for total cholesterol, triglycerides and VLDL. After the intake, plasma enzyme CK-MB decreased from 20 ± 12.1 U/L to 10 ± 1.9 U/L while LDH levels increased from 275 ± 124.4 U/L to 317 ± 114.7 U/L (p < 0.005). No significant differences were observed for CK levels. Taken together, dietary intake of natural colourant G8000™ was able to exert beneficial effects on atherosclerosis biomarkers.


Assuntos
HDL-Colesterol/sangue , LDL-Colesterol/sangue , Corantes de Alimentos/farmacologia , Extratos Vegetais/sangue , Extratos Vegetais/farmacologia , Vitis , Adulto , Biomarcadores/sangue , Feminino , Corantes de Alimentos/metabolismo , Humanos , Masculino , Fenóis/sangue , Fenóis/farmacologia , Triglicerídeos/sangue , Adulto Jovem
7.
Biometals ; 27(1): 183-94, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24442571

RESUMO

Synthesis, characterization, DFT studies and biological assays of new gold(I) and gold(III) complexes of benzimidazole are reported. Molecular and structural characterizations of the compounds were based on elemental (C, H and N) and thermal (TG-DTA) analyses, and FT-IR and UV-Visible spectroscopic measurements. The structures of complexes were proposed based DFT calculations. The benzimidazole compounds (Lig1 and Lig2) and the gold complexes were tested against three Leishmania species related to cutaneous manifestations of leishmaniasis. The free benzimidazole compounds showed no leishmanicidal activity. On the other hand, the gold(I and III) complexes have shown to possess significant activity against Leishmania in both stages of parasite, and the gold(III) complex with Lig2 exhibited expressive leishmanicidal activity with IC50 values below 5.7 µM. Also, the gold complexes showed high leishmania selectivity. The gold(I) complex with Lig1, for example, is almost 50 times more toxic for the parasite than for macrophages. Besides the leishmanicidal activity, all complexes exhibited toxic effect against SK-Mel 103 and Balb/c 3T3, cancer cells.


Assuntos
Antiprotozoários/farmacologia , Benzimidazóis/química , Leishmania/efeitos dos fármacos , Compostos Organoáuricos/síntese química , Compostos Organoáuricos/farmacologia , Células 3T3 , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antiprotozoários/síntese química , Antiprotozoários/química , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Compostos Organoáuricos/química , Teoria Quântica , Relação Estrutura-Atividade
8.
Aust Fam Physician ; 43(1): 36-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24563892

RESUMO

A case study A previously healthy woman, aged 37 years, presented with a 4-week history of pruritic periungual rash and subungual pain. Physical examination revealed scaly, fissured, erythematous plaques around her fingernails (Figure 1). Underneath the acrylic artificial nails that she had been wearing for 6 weeks, onycholysis and nail bed hyperkeratosis were evident. Oral terbinafine and amorolfine nail polish were prescribed by the general practitioner but had no clinical benefit.


Assuntos
Acrilatos/efeitos adversos , Dermatite Alérgica de Contato/diagnóstico , Exantema/etiologia , Unhas , Adulto , Anti-Inflamatórios/uso terapêutico , Betametasona/análogos & derivados , Betametasona/uso terapêutico , Cosméticos/efeitos adversos , Dermatite Alérgica de Contato/tratamento farmacológico , Dermatite Alérgica de Contato/etiologia , Diagnóstico Diferencial , Feminino , Humanos , Onicomicose/diagnóstico , Testes do Emplastro , Psoríase/diagnóstico
9.
Neotrop Entomol ; 53(1): 101-109, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37878204

RESUMO

The present study describes the immature stages of Opoptera syme (Hübner, [1821]) using SEM and Micro-CT to generate 2D and 3D models to study the morphology and chaetotaxy, and present information on the natural history, behavior, and population biology. In laboratory, eggs were laid singly, and the isolated larvae passed through six to seven instars. Host plant in the study site is unknown, but larvae are known to feed on bamboos; in laboratory, larvae accepted the ornamental bamboo Bambusa textilis McClure, 1940. Adults are diurnal and univoltine, flying from December to April (the austral summer). The present study adds information to the biology and natural history of Brassolini, an iconic and still poorly known tribe of Neotropical butterflies.


Assuntos
Borboletas , Lepidópteros , Animais , Borboletas/anatomia & histologia , Brasil , Larva/anatomia & histologia , Estações do Ano , Biologia
10.
Chem Biol Drug Des ; 103(5): e14535, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38772877

RESUMO

Despite efforts, available alternatives for the treatment of leishmaniasis are still scarce. In this work we tested a class of 15 quinolinylhydrazone analogues and presented data that support the use of the most active compound in cutaneous leishmaniasis caused by Leishmania amazonensis. In general, the compounds showed activity at low concentrations for both parasitic forms (5.33-37.04 µM to promastigotes, and 14.31-61.98 µM to amastigotes). In addition, the best compound (MHZ15) is highly selective for the parasite. Biochemical studies indicate that the treatment of promastigotes with MHZ15 leads the loss of mitochondrial potential and increase in ROS levels as the primary effects, which triggers accumulation of lipid droplets, loss of plasma membrane integrity and apoptosis hallmarks, including DNA fragmentation and phosphatidylserine exposure. These effects were similar in the intracellular form of the parasite. However, in this parasitic form there is no change in plasma membrane integrity in the observed treatment time, which can be attributed to metabolic differences and the resilience of the amastigote. Also, ultrastructural changes such as vacuolization suggesting autophagy were observed. The in vivo effectiveness of MHZ15 in the experimental model of cutaneous leishmaniasis was carried out in mice of the BALB/c strain infected with L. amazonensis. The treatment by intralesional route showed that MHZ15 acted with great efficiency with significantly reduction in the parasite load in the injured paws and draining lymph nodes, without clinical signs of distress or compromise of animal welfare. In vivo toxicity was also evaluated and null alterations in the levels of hepatic enzymes aspartate aminotransferase, and alanine aminotransferase was observed. The data presented herein demonstrates that MHZ15 exhibits a range of favorable characteristics conducive to the development of an antileishmanial agent.


Assuntos
Apoptose , Hidrazonas , Leishmaniose Cutânea , Camundongos Endogâmicos BALB C , Mitocôndrias , Animais , Apoptose/efeitos dos fármacos , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Hidrazonas/farmacologia , Hidrazonas/química , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/parasitologia , Antiprotozoários/farmacologia , Antiprotozoários/química , Antiprotozoários/uso terapêutico , Leishmania/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Feminino , Leishmania mexicana/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos
11.
Plant Dis ; 97(6): 780-788, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30722600

RESUMO

Interest in rational use and reuse of water has increased in recent years, especially in forest nurseries. However, before water can be reused in nurseries, it must be properly treated to eradicate plant pathogens to reduce risks of pathogen dispersal and losses to disease. In the present study, the efficacy of irrigation water treatment by ultrafiltration and conventional physical-chemical treatment was studied to eliminate Botrytis cinerea, Cylindrocladium candelabrum, Ralstonia solanacearum, and Xanthomonas axonopodis, the pathogens most commonly found in Brazilian forest nurseries. Ultrafiltration eradicated over 99% of R. solanacearum, X. axonopodis, and B. cinerea and 100% of C. candelabrum. The few remaining cells or conidia of R. solanacearum and B. cinerea did not induce disease in irrigated rooted cuttings. Flocculation and fast sand filtration used in physical-chemical treatment completely eliminated C. candelabrum but the other pathogens were only removed after chlorination of the filtered water. Both forms of treatment are viable, practical, and safe methods for plant pathogen removal from irrigation water.

12.
Aquac Int ; : 1-18, 2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37361878

RESUMO

The way the media portrays aquaculture-related events can influence how this industry is perceived by the public and affect its success. Since media are an important source of public information, media content analysis has been carried out in several regions of the world. This study aimed to determine which aspects of aquaculture were more exposed and how they were discussed by regional media in the Madeira archipelago, an oceanic group of Portuguese islands. Analysis of aquaculture's media coverage in the two most-read regional newspapers of Madeira was carried out over a 5-year period (2017 to 2021). For each news article, the assessment focused on the geographic scope, the main topics covered, the stakeholders with access to the debate, and the general tone of the article (risk/benefit framework). A total of 297 articles were analyzed. Results indicate the occurrence of trigger events that contributed to a shift in the amount of news published and in the way media framed aquaculture. In general, political and economic issues dominated the coverage, whereas social, environmental, scientific, and landscape matters received less media attention. The voice of the government was predominant throughout the 5 years in analysis and aquaculture was generally framed with a balanced tone, slightly more negative. Open and transparent communication between the stakeholders and the media is fundamental for the sustainable development of the aquaculture industry.

13.
Foods ; 12(17)2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37685163

RESUMO

Araçá is a Brazilian native fruit belonging to the Myrtaceae family. Although some studies already prove its health benefits, it is still necessary to explore the phenolic compounds in all its parts separately. This study aimed to investigate the free, esterified, glycosylated, and insoluble phenolics in two morphotypes of araçá, red and yellow, evaluating peel, pulp, and seed separately, using liquid chromatography coupled to mass spectrometry (LC-ESI-QqQ-MS/MS). Fourteen phenolics and five anthocyanins were quantified in both morphotypes. The peels presented the highest contents, followed by the pulp and seeds. Red araçá stood out over the yellow one only in the phenolic fractions resulting from the peel, with the yellow araçá being superior in the phenolic fractions of the pulp and seed. The highest antioxidant capacities were detected for the pulp-esterified phenolics (498.3 µmol g-1) and peel-free phenolics (446.7 µmol g-1) of yellow araçá. Principal component analysis (PCA) indicated specific markers to differentiate the samples. All parts of the araçá proved to be a rich source of phenolic compounds, in different fractions, mainly in the peel. This information will be beneficial to stimulate the consumption of native fruits and their possible use in the development of new products.

14.
Cad Saude Publica ; 39(3): e00131022, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37098973

RESUMO

This study aimed to analyze the multiple characteristics of the decentralization of the Brazilian National Food and Nutritional Security System (SISAN) in a period before the institutional dismantling. Data from the 26 Brazilian states were collected in two public information systems, referring to the years 2017/2018. An exploratory and descriptive study was performed using a hierarchical cluster analysis, based on an analysis model with multiple characteristics of the system decentralization. The results indicated the formation of three clusters, showing the similarity among states with greater intersectoral and participatory character, better relationship with municipalities, and allocation of resources. On the other hand, states with less intersectoral and participatory character, linked to the low allocation of resources, execution of food security actions, and municipal support were clustered. These clusters composed mainly of North and Northeastern states, with a lower Gross Domestic Product, average Human Development Index, and a higher occurrence of food insecurity, expressed characteristics that may be related to greater obstacles in the system decentralization process. This information can help in the decision-making about the SISAN in a more equitable manner, supporting the actors involved in its maintenance and defense, at a time when the country presents an austere political and economic situation, marked by the progressive worsening of food insecurity.


Assuntos
Abastecimento de Alimentos , Alimentos , Humanos , Brasil/epidemiologia , Política
15.
Nutrients ; 15(21)2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37960164

RESUMO

BACKGROUND: Traditional methods for assessing individual energy consumption often involve lengthy and intricate procedures. This study aims to introduce an Energy Consumption Estimation Scale, utilizing Item Response Theory (IRT) for adolescents aged 18-19 years. METHODS: This psychometric investigation applies IRT to 93 items extracted from a validated food frequency questionnaire. The study encompasses a representative sample of 2515 adolescents from the São Luís birth cohort in Brazil. The latent trait, energy intake, is derived using IRT and subsequently validated through hierarchical multiple linear regression modeling. Significance was established at p < 0.05. RESULTS: A Samejima's model was successfully fitted (CFI and TLI > 0.9 and RMSEA < 0.08), effectively capturing variations across all energy consumption levels. Factors associated with the latent trait demonstrate consistent behavioral patterns. Adolescents with higher energy intake exhibited increased consumption of dairy products, artificially sweetened beverages, and seasonal fruits and vegetables. CONCLUSIONS: The proposed Energy Consumption Estimation Scale demonstrates a reliable measurement of energy intake and serves as a practical and concise alternative for assessing energy consumption among adolescents. These findings suggest the potential for adapting similar models for different age groups and incorporating diverse food items based on the obtained results.


Assuntos
Ingestão de Energia , Edulcorantes , Adolescente , Humanos , Inquéritos e Questionários , Frutas , Verduras
16.
Elife ; 122023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36917493

RESUMO

Aggregates of the tau protein are a well-known hallmark of several neurodegenerative diseases, collectively referred to as tauopathies, including frontal temporal dementia and Alzheimer's disease (AD). Monitoring the transformation process of tau from physiological monomers into pathological oligomers or aggregates in a high-throughput, quantitative manner and in a cellular context is still a major challenge in the field. Identifying molecules able to interfere with those processes is of high therapeutic interest. Here, we developed a series of inter- and intramolecular tau biosensors based on the highly sensitive Nanoluciferase (Nluc) binary technology (NanoBiT) able to monitor the pathological conformational change and self-interaction of tau in living cells. Our repertoire of tau biosensors reliably reports i. molecular proximity of physiological full-length tau at microtubules; ii. changes in tau conformation and self-interaction associated with tau phosphorylation, as well as iii. tau interaction induced by seeds of recombinant tau or from mouse brain lysates of a mouse model of tau pathology. By comparing biosensors comprising different tau forms (i.e. full-length or short fragments, wild-type, or the disease-associated tau(P301L) variant) further insights into the tau transformation process are obtained. Proof-of-concept data for the high-throughput suitability and identification of molecules interfering with the pathological tau transformation processes are presented. This novel repertoire of tau biosensors is aimed to boost the disclosure of molecular mechanisms underlying pathological tau transformation in living cells and to discover new drug candidates for tau-related neurodegenerative diseases.


Assuntos
Doença de Alzheimer , Tauopatias , Camundongos , Animais , Proteínas tau/genética , Proteínas tau/metabolismo , Doença de Alzheimer/metabolismo , Tauopatias/patologia , Microtúbulos/metabolismo , Neurônios/fisiologia , Encéfalo/metabolismo
17.
J Saudi Heart Assoc ; 35(2): 169-176, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37465617

RESUMO

Background: Risk factors for postoperative chylothorax in children who had cardiothoracic procedures are not always clear. Due to complex course in post-operative care, It's always challenging to find the risk factors, and their management. Objective: The aim of our study was to identify the incidence, risk factors and effective treatment approaches for chylothorax after pediatric heart surgery. Methods: Children who had the cardiac surgery and subsequently developed chylothorax were included in the study. The ratio of the experimental group to the control group was 1:2. Decannulations of extracorporeal membrane oxygenation (ECMO) were not included in the analysis of patient outcomes. For each patient, we keep track of their age, weight, gender, syndrome, RACH-1 scoring, fluid balance, bypass time, clamp time, redo operations, open or close heart surgeries, and rhythm difficulties. Care logs were kept for every single therapy that was administered. Primary outcome was chylothorax, with secondary outcomes included time in the intensive care unit (ICU), length of hospital stay (LOS), and death. Results: 5210 surgeries were performed in six years. 96 patients developed the chylothorax with incidence of 1.8%. In chylothorax group, mean weight was 6.7 ± 4.2, while mean age was 11.7 ± 15.2. Clamp time was 74.5 ± 53.5 versus 39.9 ± 13.7. Mean bypass time was 128.34(76.25) versus 84.3 ± 25.1 with an odds ratio 1.02 (Z test 0.0001). Six (6.3%) children with chylothorax had redo cardiac surgeries in the same admission (p-value 0.01) while none in other. Five (5.2%) cases got operated by thoracotomy, three from left side. Mean Chest tube duration was 10±7.8 days versus 3.8±2.4 in control group. (p-value 0.02). chylothorax resolved (mean resolving time = 4 days) in 76 (79.2%) children with monogen formula. Two patients receive midodrine with no significant effect. Four children underwent surgical repair for chylothorax. Conclusion: Bypass time linearly increases incidence of chylothorax. Younger age, low weight, syndromic children, redo operations, non-open-heart surgeries, and arrhythmias also contribute to this. Gender, fluid balance, and RACHS-1 Scoring were not significant. While further research and testing are required for the use of midodrine. However, the low-fat formula of Monogen has proven to be an effective treatment.

18.
PLoS One ; 18(4): e0283941, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37014877

RESUMO

Intracellular accumulation of tau protein is a hallmark of Alzheimer's Disease and Progressive Supranuclear Palsy, as well as other neurodegenerative disorders collectively known as tauopathies. Despite our increasing understanding of the mechanisms leading to the initiation and progression of tau pathology, the field still lacks appropriate disease models to facilitate drug discovery. Here, we established a novel and modulatable seeding-based neuronal model of full-length 4R tau accumulation using humanized mouse cortical neurons and seeds from P301S human tau transgenic animals. The model shows specific and consistent formation of intraneuronal insoluble full-length 4R tau inclusions, which are positive for known markers of tau pathology (AT8, PHF-1, MC-1), and creates seeding competent tau. The formation of new inclusions can be prevented by treatment with tau siRNA, providing a robust internal control for use in qualifying the assessment of potential therapeutic candidates aimed at reducing the intracellular pool of tau. In addition, the experimental set up and data analysis techniques used provide consistent results in larger-scale designs that required multiple rounds of independent experiments, making this is a versatile and valuable cellular model for fundamental and early pre-clinical research of tau-targeted therapies.


Assuntos
Doença de Alzheimer , Tauopatias , Camundongos , Animais , Humanos , Proteínas tau/genética , Proteínas tau/metabolismo , Camundongos Transgênicos , Encéfalo/metabolismo , Tauopatias/metabolismo , Doença de Alzheimer/patologia , Neurônios/metabolismo , Descoberta de Drogas
19.
Clocks Sleep ; 5(4): 581-589, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37873839

RESUMO

There seems to be a consensus that adolescents worldwide are not getting enough sleep. This study aimed to evaluate the psychometric properties of the Epworth Sleepiness Scale (ESS) in adolescents using the item response theory. A psychometric study was conducted with 2206 adolescents aged 18 and 19 years in the city of São Luís, Maranhão, Brazil. The dimensionality of the ESS was assessed by principal component analysis. A Samejima's graded response model (SGRM) was fitted to it. The findings of this study showed a good internal consistency and the unidimensionality of the ESS. Considering the latent trait continuum, we obtained three levels, with anchor items. For the item 'Sitting still in a public place', the adolescents presented a small possibility of dozing in level 1, and a medium and great possibility in level 2. The item 'Sitting around talking to someone' presented small, medium, and great possibilities of dozing in level 3. The ESS with five items showed satisfactory psychometric properties. In addition, the results from the SGRM showed that adolescents with high levels of sleepiness are likely to nod off or sleep sitting up while talking to someone. This study allows us to understand excessive daytime sleepiness in adolescents.

20.
Suicide Life Threat Behav ; 53(6): 1086-1107, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37864416

RESUMO

INTRODUCTION: Suicide is one of the leading causes of death, with a trend for its increase in Brazil in past decades. This study aimed to review the characteristics of suicides in Brazilian postmortem studies. METHODS: Studies investigating suicide deaths in Brazil, and based on autopsy or psychological autopsy were included. Proportions were pooled across studies with the use of random and fixed effects models. RESULTS: 6777 references were retrieved from six databases (searches up to January, 2023), and 45 studies included. In autopsy studies (k = 37, n = 16,231), substance use at toxicological analysis was found in 36.42% of cases (95% CI: 30.05-43.32), previous suicide attempts in 23.92% (95% CI: 6.73-57.78). In psychological autopsy studies (k = 8, n = 139), previous suicide attempts were reported in 28.09% (95% CI: 19.74-38.28), psychiatric conditions/symptoms in 90.67% (95% CI: 67.79-97.82), family history of suicidality in 21.33% (95% CI: 13.5-32.03). Most suicide deaths were reported in males and took place at the victim's home, hanging was the most frequent suicide method. Included studies presented significant limitations in quality assessment. CONCLUSION: Future studies should present more robust methodology, including bigger samples, the use of controls, and validated methodology.


Assuntos
Transtornos Relacionados ao Uso de Substâncias , Tentativa de Suicídio , Masculino , Humanos , Brasil/epidemiologia , Projetos de Pesquisa , Ideação Suicida
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