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1.
Artigo em Inglês | MEDLINE | ID: mdl-38922396

RESUMO

PURPOSE: To verify the ability of pretreatment [18F]FDG PET/CT and T1-weighed dynamic contrast-enhanced MRI to predict pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients. METHODS: This retrospective study includes patients with BC of no special type submitted to baseline [18F]FDG PET/CT, NAC and surgery. [18F]FDG PET-based features reflecting intensity and heterogeneity of tracer uptake were extracted from the primary BC and suspicious axillary lymph nodes (ALN), for comparative analysis related to NAC response (pCR vs. non-pCR). Multivariate logistic regression was performed for response prediction combining the breast tumor-extracted PET-based features and clinicopathological features. A subanalysis was performed in a patients' subsample by adding breast tumor-extracted first-order MRI-based features to the multivariate logistic regression. RESULTS: A total of 170 tumors from 168 patients were included. pCR was observed in 60/170 tumors (20/107 luminal B-like, 25/45 triple-negative and 15/18 HER2-enriched surrogate molecular subtypes). Higher intensity and higher heterogeneity of [18F]FDG uptake in the primary BC were associated with NAC response in HER2-negative tumors (immunohistochemistry score 0, 1 + or 2 + non-amplified by in situ hybridization). Also, higher intensity of tracer uptake was observed in ALN in the pCR group among HER2-negative tumors. No [18F]FDG PET-based features were associated with pCR in the other subgroup analyses. A subsample of 103 tumors was also submitted to extraction of MRI-based features. When combined with clinicopathological features, neither [18F]FDG PET nor MRI-based features had additional value for pCR prediction. The only significant predictors were estrogen receptor status, HER2 expression and grade. CONCLUSION: Pretreatment [18F]FDG PET-based features from primary BC and ALN are not associated with response to NAC, except in HER2-negative tumors. As compared with pathological features, no breast tumor-extracted PET or MRI-based feature improved response prediction.

2.
Biometals ; 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39160443

RESUMO

Studies have shown that deficiencies in magnesium, selenium, and zinc in individuals with obesity compromise the endogenous antioxidant defense system. This study aimed to evaluate the impact of mineral deficiency on enzymatic antioxidant defense in women with obesity. The study involved 63 women with obesity (BMI ≥ 35 kg/m2) and 77 eutrophic women (BMI between 18.5 and 24.9 kg/m2). Variables such as fasting glucose, glycated hemoglobin, fasting insulin, and serum lipids were analyzed. Insulin resistance was measured using the homeostasis assessment model (HOMA-IR) and beta cell function using the homeostasis assessment model (HOMA-ß). Dietary intake of energy, macronutrients (including magnesium, zinc, and selenium), and plasma, erythrocyte, and urinary concentrations of these minerals were measured and analyzed. Serum cortisol, plasma leptin, plasma thiobarbituric acid reactive substances, and the activity of erythrocyte superoxide dismutase (SOD), erythrocyte glutathione peroxidase (GPX), and erythrocyte catalase were also analyzed. Women with obesity had reduced plasma and erythrocyte concentrations and greater urinary excretion of all minerals compared to normal weight women (p < 0.05). There was a positive association between erythrocyte concentrations of zinc and selenium and the activity of the GPX and SOD enzymes in erythrocytes in women with obesity (p < 0.05), in addition to a positive association between serum insulin and the enzyme GPX, which is dependent on dietary selenium (p < 0.05). Individuals with obesity are deficient in magnesium, selenium, and zinc, which appears to impair the antioxidant defense system and contribute to important metabolic disorders such as oxidative stress in these patients.

3.
J Comput Assist Tomogr ; 48(1): 92-97, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37551150

RESUMO

OBJECTIVE: The aim of the study is to quantify observer agreement in the magnetic resonance imaging (MRI) classification of inflammatory or fibrotic interstitial lung disease (ILD). METHODS: Our study is a preliminary analysis of a larger prospective cohort. The MRI images of 18 patients with ILD (13 females; mean age, 65 years) were acquired in a 1.5 T scanner and included axial fat-saturated T2-weighted (T2-WI, n = 18) and coronal fat-saturated T1-weighted images before and 1, 3, 5, and 10 minutes after gadolinium administration (n = 16). The MRI studies were evaluated with 2 different methods: a qualitative evaluation (visual assessment and measurement of few regions of interest; evaluations were performed independently by 5 radiologists and 3 times by 1 radiologist) and a segmentation-based analysis with software extraction of signal intensity values (evaluations were performed independently by 2 radiologists and twice by 1 radiologist). Interstitial lung disease was classified as inflammatory or fibrotic, based on previously described imaging criteria. RESULTS: Regarding the qualitative evaluation, intraobserver agreement was excellent (κ = 0.92, P < 0.05) for T2-WI and fair (κ = 0.29, P < 0.05) for T1 dynamic study, while interobserver agreement was moderate (κ = 0.56, P < 0.05) and poor (κ = 0.11, P = 0.18), respectively. In contrast, upon segmentation-based analysis, intraobserver and interobserver agreement were excellent for T2-WI (κ = 0.886, P < 0.001; κ = 1.00, P < 0.001; respectively); for T1-WI, intraobserver agreement was excellent (κ = 0.87, P < 0.05) and interobserver agreement was good (κ = 0.75, P < 0.05). CONCLUSIONS: Segmentation-based MRI analysis is more reproducible than a qualitative evaluation with visual assessment and measurement of few regions of interest.


Assuntos
Doenças Pulmonares Intersticiais , Imageamento por Ressonância Magnética , Feminino , Humanos , Idoso , Estudos Prospectivos , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Variações Dependentes do Observador
4.
Curr Microbiol ; 81(7): 176, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38755426

RESUMO

Antimicrobial resistance (AMR) presents a global challenge as microorganisms evolve to withstand the effects of antibiotics. In addition, the improper use of antibiotics significantly contributes to the AMR acceleration. Essential oils have garnered attention for their antimicrobial potential. Indeed, essential oils extracted from plants contain compounds that exhibit antibacterial activity, including against resistant microorganisms. Hence, this study aimed to evaluate the antimicrobial and antibiofilm activity of the essential oil (EO) extracted from Lippia grata and its combination with ampicillin against Staphylococcus aureus strains (ATCC 25923, ATCC 700698, and JKD6008). The plant material (leaves) was gathered in Mossoro, RN, and the EO was obtained using the hydrodistillation method with the Clevenger apparatus. The antimicrobial activity of the EO was assessed through minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Antibiofilm activity was evaluated by measuring biomass using crystal violet (CV) staining, viable cell counting, and analysis of preformed biofilms. In addition, the synergistic effects of the EO in combination with ampicillin were examined by scanning electron and confocal microscopy. The EO displayed a MIC value of 2.5 mg/mL against all tested S. aureus strains and an MBC only against S. aureus JKD6008 at 2.5 mg/mL. L. grata EO caused complete biofilm inhibition at concentrations ranging from 10 to 0.312 mg/mL against S. aureus ATCC 25923 and 10 to 1.25 mg/mL against S. aureus ATCC 700698 and S. aureus JKD6008. In the viable cell quantification assay, there was a reduction in CFU ranging from 1.0 to 8.0 logs. The combination of EO with ampicillin exhibited a synergistic effect against all strains. Moreover, the combination showed a significantly inhibiting biofilm formation and eradicating preformed biofilms. Furthermore, the EO and ampicillin (individually and in combination) altered the cellular morphology of S. aureus cells. Regarding the mechanism, the results revealed that L. grata EO increased membrane permeability and caused significant membrane damage. Concerning the synergy mechanism, the results revealed that the combination of EO and ampicillin increases membrane permeability and causes considerable membrane damage, further inhibiting bacteria synergistically. The findings obtained here suggest that L. grata EO in combination with ampicillin could be a viable treatment option against S. aureus infections, including MRSA strain.


Assuntos
Ampicilina , Antibacterianos , Biofilmes , Sinergismo Farmacológico , Lippia , Testes de Sensibilidade Microbiana , Óleos Voláteis , Staphylococcus aureus , Biofilmes/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia , Ampicilina/farmacologia , Antibacterianos/farmacologia , Óleos Voláteis/farmacologia , Lippia/química , Extratos Vegetais/farmacologia , Folhas de Planta/química
5.
Proc Natl Acad Sci U S A ; 118(3)2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33431672

RESUMO

The link between synaptic plasticity and reorganization of brain activity in health and disease remains a scientific challenge. We examined this question in Parkinson's disease (PD) where functional up-regulation of postsynaptic D2 receptors has been documented while its significance at the neural activity level has never been identified. We investigated cortico-subcortical plasticity in PD using the oculomotor system as a model to study reorganization of dopaminergic networks. This model is ideal because this system reorganizes due to frontal-to-parietal shifts in blood oxygen level-dependent (BOLD) activity. We tested the prediction that functional activation plasticity is associated with postsynaptic dopaminergic modifications by combining positron emission tomography/functional magnetic resonance imaging to investigate striatal postsynaptic reorganization of dopamine D2 receptors (using 11C-raclopride) and neural activation in PD. We used covariance (connectivity) statistics at molecular and functional levels to probe striato-cortical reorganization in PD in on/off medication states to show that functional and molecular forms of reorganization are related. D2 binding across regions defined by prosaccades showed increased molecular connectivity between both caudate/putamen and hyperactive parietal eye fields in PD in contrast with frontal eye fields in controls, in line with the shift model. Concerning antisaccades, parietal-striatal connectivity dominated in again in PD, unlike frontal regions. Concerning molecular-BOLD covariance, a striking sign reversal was observed: PD patients showed negative frontal-putamen functional-molecular associations, consistent with the reorganization shift, in contrast with the positive correlations observed in controls. Follow-up analysis in off-medication PD patients confirmed the negative BOLD-molecular correlation. These results provide a link among BOLD responses, striato-cortical synaptic reorganization, and neural plasticity in PD.


Assuntos
Núcleo Caudado/metabolismo , Lobo Frontal/metabolismo , Plasticidade Neuronal , Lobo Parietal/metabolismo , Doença de Parkinson/metabolismo , Putamen/metabolismo , Receptores de Dopamina D2/metabolismo , Idoso , Mapeamento Encefálico , Estudos de Casos e Controles , Núcleo Caudado/diagnóstico por imagem , Núcleo Caudado/efeitos dos fármacos , Núcleo Caudado/patologia , Dopamina/metabolismo , Antagonistas de Dopamina/uso terapêutico , Feminino , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Oxigênio/sangue , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/efeitos dos fármacos , Lobo Parietal/patologia , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/patologia , Tomografia por Emissão de Pósitrons , Putamen/diagnóstico por imagem , Putamen/efeitos dos fármacos , Putamen/patologia , Racloprida/uso terapêutico , Movimentos Sacádicos/fisiologia , Sinapses/efeitos dos fármacos , Sinapses/metabolismo , Sinapses/patologia
6.
Chem Biodivers ; 21(2): e202301840, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38088493

RESUMO

Resistance to antimicrobial drugs has been considered a public health problem. Likewise, the increasing resistance of cancer cells to drugs currently used in therapy has also become a problem. Therefore, the research and development of synthetic peptides bring a new perspective on the emergence of new drugs for treating this resistance since bioinformatics provides a means to optimize these molecules and save time and costs in research. Peptides have several mechanisms of action, such as forming pores on the cell membrane and inhibiting protein synthesis. Some studies report the use of antimicrobial peptides with the potential for action against cancer cells, suggesting a repositioning of antimicrobial peptides to fight back cancer resistance. There is an alteration in the microenvironment, making its net charge negative for the survival and growth of cancer cells. The changes in glycoproteins favor the membrane to have a more negative charge, favoring the interaction between the cells and the peptide, thus making possible the repositioning of these antimicrobial peptides against cancer. Here, we will discuss the mechanism of action, targets and effects of peptides, comparison between microbial and cancer cells, and proteomic changes caused by the interaction of peptides and cells.


Assuntos
Anti-Infecciosos , Neoplasias , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Antimicrobianos , Reposicionamento de Medicamentos , Proteômica , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Neoplasias/tratamento farmacológico
7.
Mol Cell ; 57(6): 1124-1132, 2015 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-25752575

RESUMO

The Mec1/Tel1 kinases (human ATR/ATM) play numerous roles in the DNA replication stress response. Despite the multi-functionality of these kinases, studies of their in vivo action have mostly relied on a few well-established substrates. Here we employed a combined genetic-phosphoproteomic approach to monitor Mec1/Tel1 signaling in a systematic, unbiased, and quantitative manner. Unexpectedly, we find that Mec1 is highly active during normal DNA replication, at levels comparable or higher than Mec1's activation state induced by replication stress. This "replication-correlated" mode of Mec1 action requires the 9-1-1 clamp and the Dna2 lagging-strand factor and is distinguishable from Mec1's action in activating the downstream kinase Rad53. We propose that Mec1/ATR performs key functions during ongoing DNA synthesis that are distinct from their canonical checkpoint role during replication stress.


Assuntos
Replicação do DNA , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteômica/métodos , Proteínas Proto-Oncogênicas c-ets/metabolismo , Proteínas Repressoras/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Quinase do Ponto de Checagem 2/genética , Quinase do Ponto de Checagem 2/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Fosfoproteínas/análise , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Fosforilação , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas c-ets/genética , Proteínas Repressoras/genética , Proteínas de Saccharomyces cerevisiae/genética , Transdução de Sinais , Variante 6 da Proteína do Fator de Translocação ETS
8.
An Acad Bras Cienc ; 95(suppl 1): e20220945, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37466541

RESUMO

The studying material were recently collected with Malaise traps in Northeastern Brazil, and the authors found a new species of Amydrostylus, which represents the second known species of this endemic genus from the open/dry biomes of Brazil. The discovery results will provide more new diagnosis for the genus and allow a better knowledge of the male terminalia morphology, leading to a new interpretation of some of its structures. Male and female specimens are described and illustrated here.


Assuntos
Dípteros , Animais , Feminino , Masculino , Brasil , Ecossistema
9.
J Digit Imaging ; 36(4): 1864-1876, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37059891

RESUMO

The objective is to assess the performance of seven semiautomatic and two fully automatic segmentation methods on [18F]FDG PET/CT lymphoma images and evaluate their influence on tumor quantification. All lymphoma lesions identified in 65 whole-body [18F]FDG PET/CT staging images were segmented by two experienced observers using manual and semiautomatic methods. Semiautomatic segmentation using absolute and relative thresholds, k-means and Bayesian clustering, and a self-adaptive configuration (SAC) of k-means and Bayesian was applied. Three state-of-the-art deep learning-based segmentations methods using a 3D U-Net architecture were also applied. One was semiautomatic and two were fully automatic, of which one is publicly available. Dice coefficient (DC) measured segmentation overlap, considering manual segmentation the ground truth. Lymphoma lesions were characterized by 31 features. Intraclass correlation coefficient (ICC) assessed features agreement between different segmentation methods. Nine hundred twenty [18F]FDG-avid lesions were identified. The SAC Bayesian method achieved the highest median intra-observer DC (0.87). Inter-observers' DC was higher for SAC Bayesian than manual segmentation (0.94 vs 0.84, p < 0.001). Semiautomatic deep learning-based median DC was promising (0.83 (Obs1), 0.79 (Obs2)). Threshold-based methods and publicly available 3D U-Net gave poorer results (0.56 ≤ DC ≤ 0.68). Maximum, mean, and peak standardized uptake values, metabolic tumor volume, and total lesion glycolysis showed excellent agreement (ICC ≥ 0.92) between manual and SAC Bayesian segmentation methods. The SAC Bayesian classifier is more reproducible and produces similar lesion features compared to manual segmentation, giving the best concordant results of all other methods. Deep learning-based segmentation can achieve overall good segmentation results but failed in few patients impacting patients' clinical evaluation.


Assuntos
Aprendizado Profundo , Linfoma , Neoplasias , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18/metabolismo , Teorema de Bayes , Linfoma/diagnóstico por imagem
10.
J Biol Chem ; 296: 100533, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33713703

RESUMO

Saccharomyces cerevisiae exhibits gene expression homeostasis, which is defined as the buffering of transcription levels against changes in DNA copy number during the S phase of the cell cycle. It has been suggested that S. cerevisiae employs an active mechanism to maintain gene expression homeostasis through Rtt109-Asf1-dependent acetylation of histone H3 on lysine 56 (H3K56). Here, we show that gene expression homeostasis can be achieved independently of H3K56 acetylation by Tos4 (Target of Swi6-4). Using Nanostring technology, we establish that Tos4-dependent gene expression homeostasis depends on its forkhead-associated (FHA) domain, which is a phosphopeptide recognition domain required to bind histone deacetylases (HDACs). We demonstrate that the mechanism of Tos4-dependent gene expression homeostasis requires its interaction with the Rpd3L HDAC complex. However, this is independent of Rpd3's well-established roles in both histone deacetylation and controlling the DNA replication timing program, as established by deep sequencing of Fluorescence-Activated Cell Sorted (FACS) S and G2 phase populations. Overall, our data reveals that Tos4 mediates gene expression homeostasis through its FHA domain-dependent interaction with the Rpd3L complex, which is independent of H3K56ac.


Assuntos
Regulação Fúngica da Expressão Gênica , Histona Acetiltransferases/metabolismo , Histonas/metabolismo , Homeostase , Lisina/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Acetilação , Histona Acetiltransferases/genética , Histonas/genética , Lisina/genética , Processamento de Proteína Pós-Traducional , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento , Proteínas de Saccharomyces cerevisiae/genética
11.
J Urban Health ; 99(3): 519-532, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35467327

RESUMO

Climate variations cause public health problems, but the literature is still scarce on studies involving health interventions against climate-sensitive diseases. The objective of this review was to identify health interventions for the prevention of such diseases. We conducted a scoping review using the JBI Methodology. Six large research databases were searched (PubMed, Scopus, Web of Science, Lilacs, Embase, and Cochrane). The following inclusion criterion was used: studies addressing health interventions to prevent climate-sensitive diseases or consequences of climate on people's health. The exclusion criteria consisted of thesis, dissertations, conference proceedings, studies with unclear information/methodology, and studies not addressing climate-related health interventions. No language or date restrictions were applied. Of 733 studies identified and screened by title and abstract, 55 studies underwent full-text screening, yielding 13 studies for review. The health interventions identified were classified into three levels of management. The macro level included the use of epidemiological models, renewable energy, and policies sensitive to climate change. The meso level comprised interventions such as the creation of environmental suitability maps, urban greening, chemoprophylaxis, water security plans, and sanitation projects, among other measures. Some interventions are at the intersection, such as educational campaigns and the modification of artificial larvae sites. Finally, the micro level contained interventions such as the inspection of window screens and the use of light-colored clothing and repellents. The health interventions at the macro, meso, and micro levels and the intersection may serve as a basis for public managers to implement appropriate interventions against climate-sensitive diseases.


Assuntos
Mudança Climática , Saúde Pública , Humanos
12.
BMC Vet Res ; 18(1): 449, 2022 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-36564739

RESUMO

BACKGROUND: Cryptosporidium is the most common protozoan that can infect a wide variety of animals, including mammals and birds. Fecal samples of six saffron finches, Sicalis flaveola, from a commercial establishment were screened for the presence of Cryptosporidium by the modified Ziehl-Neelsen technique and nested PCR of the 18S rRNA gene followed by sequencing of the amplified fragments. RESULTS: The species Cryptosporidium galli was identified in all six saffron fiches, in addition to Cryptosporidium andersoni in one of the birds, indicating a mixed infection. Only two birds had feathers that were ruffled and dirty with feces. Concomitant infection with Isospora spp. was observed in all birds. CONCLUSIONS: Saffron finches are a possible host of C. andersoni and this is the first report of this species in a captive bird and the third report of parasitism by C. galli in Sicalis flaveola.


Assuntos
Crocus , Criptosporidiose , Cryptosporidium , Tentilhões , Passeriformes , Animais , Cryptosporidium/genética , Crocus/genética , Filogenia , Fezes , DNA de Protozoário/genética , Mamíferos/genética
13.
Oral Dis ; 28(6): 1705-1714, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33825326

RESUMO

OBJECTIVES: To verify the presence of Streptococcus mutans (S. mutans) in atherosclerotic plaque (AP) using techniques with different sensitivities, correlating with histological changes in plaque and immunoexpression of inflammatory markers. MATERIALS AND METHODS: Thirteen AP samples were subjected to real-time polymerase chain reaction (qRT-PCR), histopathological analyses, histochemical analysis by Giemsa staining (GS), and immunohistochemical analysis for S. mutans, IL-1ß, and TNF-α (streptavidin-biotin-peroxidase method). Ten necropsy samples of healthy vessels were used as controls. RESULTS: All AP samples showed histopathological characteristics of severe atherosclerosis and were positive for S. mutans (100.0%) in qRT-PCR and immunohistochemical analyses. GS showed that Streptococcus sp. colonized the lipid-rich core regions and fibrous tissue, while the control group was negative for Streptococcus sp. IL-1ß and TNF-α were expressed in 100% and 92.3% of the AP tested, respectively. The control samples were positive for S. mutans in qRT-PCR analysis, but negative for S. mutans, IL-1ß, and TNF-α in immunohistochemical analyses. CONCLUSION: The detection of S. mutans in AP and the visualization of Streptococcus sp. suggested a possible association between S. mutans and atherosclerosis. The results obtained from the control samples suggested the presence of DNA fragments or innocuous bacteria that were not associated with tissue alteration. However, future studies are necessary to provide more information.


Assuntos
Aterosclerose , Cárie Dentária , Placa Aterosclerótica , Cárie Dentária/microbiologia , Humanos , Streptococcus mutans/genética , Streptococcus sobrinus , Fator de Necrose Tumoral alfa
14.
An Acad Bras Cienc ; 94(2): e20210715, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35830084

RESUMO

Samanea tubulosa Benth. it has been widely used in traditional medicine to treat inflammatory processes. The present study aimed to investigate the antinociceptive effect and mechanism of action of the fractions obtained from the Samanea tubulosa pods in mice. The antinociceptive activity was evaluated in formalin, capsaicin and glutamate tests and the. The possible mechanisms of action involved in the antinociceptive effect of the hexane and ethyl acetate fraction in the opioid system, also the the K + ATP channels and the L-arigine pathways of nitric oxide were evaluated. The chemical characterization analysis revealed in the hexane fraction the presence of triterpenes such as lupenone and lupeol. In the glutamate test, the hexane and ethyl acetate fractions showed antinociceptive activity at the dose of 12.5 and 25 mg kg-1. The antinociception produced by the hexane and ethyl acetate fractions was significantly reversed by naloxone, indicating that the fractions act through the opioid pathway. Antinociceptive response of the ethyl acetate fraction was blocked by glibenclamide, indicating that this fraction acts via the K + ATP channels activation. It is concluded that the fractions under study exert antinociceptive activity possibly related to the opioid route and through K+ ATP channels activation.


Assuntos
Dor Aguda , Fabaceae , Dor Aguda/tratamento farmacológico , Trifosfato de Adenosina , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Analgésicos Opioides , Animais , Fabaceae/metabolismo , Ácido Glutâmico , Hexanos , Camundongos
15.
Hum Mol Genet ; 28(13): 2174-2188, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30816415

RESUMO

The understanding of the natural history of Alzheimer's disease (AD) and temporal trajectories of in vivo molecular mechanisms requires longitudinal approaches. A behavioral and multimodal imaging study was performed at 4/8/12 and 16 months of age in a triple transgenic mouse model of AD (3xTg-AD). Behavioral assessment included the open field and novel object recognition tests. Molecular characterization evaluated hippocampal levels of amyloid ß (Aß) and hyperphosphorylated tau. Magnetic resonance imaging (MRI) included assessment of hippocampal structural integrity, blood-brain barrier (BBB) permeability and neurospectroscopy to determine levels of the endogenous neuroprotector taurine. Longitudinal brain amyloid accumulation was assessed using 11C Pittsburgh compound B positron emission tomography (PET), and neuroinflammation/microglia activation was investigated using 11C-PK1195. We found altered locomotor activity at months 4/8 and 16 months and recognition memory impairment at all time points. Substantial early reduction of hippocampal volume started at month 4 and progressed over 8/12 and 16 months. Hippocampal taurine levels were significantly decreased in the hippocampus at months 4/8 and 16. No differences were found for amyloid and neuroinflammation with PET, and BBB was disrupted only at month 16. In summary, 3xTg-AD mice showed exploratory and recognition memory impairments, early hippocampal structural loss, increased Aß and hyperphosphorylated tau and decreased levels of taurine. In sum, the 3xTg-AD animal model mimics pathological and neurobehavioral features of AD, with early-onset recognition memory loss and MRI-documented hippocampal damage. The early-onset profile suggests temporal windows and opportunities for therapeutic intervention, targeting endogenous neuroprotectors such as taurine.


Assuntos
Doença de Alzheimer/metabolismo , Hipocampo/metabolismo , Taurina/metabolismo , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/metabolismo , Animais , Biomarcadores , Barreira Hematoencefálica/metabolismo , Modelos Animais de Doenças , Hipocampo/diagnóstico por imagem , Inflamação/genética , Inflamação/metabolismo , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microglia/metabolismo , Imagem Molecular , Imagem Multimodal , Presenilina-1/genética , Proteínas tau/genética , Proteínas tau/metabolismo
16.
Mol Phylogenet Evol ; 160: 107113, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33610648

RESUMO

We evaluated the role of Quaternary climatic fluctuations on the demographic history and population structure of amphibian species endemic to the 'campo rupestre' in the Neotropics, evaluating their distributional shifts, demographic changes, and lineage formation from the end of Pleistocene to present. We chose two anurans endemic to the high-elevation 'campo rupestre' in the Espinhaço Range (ER) in northeastern and southeastern Brazil (Bokermannohyla alvarengai and Bokermannohyla oxente), as models to test the role of Quaternary climatic fluctuations over their distribution range in this region. We collected tissue samples throughout their distribution range and used statistical phylogeography to examine processes of divergence and population demography. We generated spatial-temporal reconstructions using Bayesian inference in a coalescent framework in combination with hind-cast projections of species distribution models (SDMs). We also used the results and literature information to test alternative diversification scenarios via approximate Bayesian computation (ABC). Our results show that Quaternary climatic fluctuations influenced the geographic ranges of both species showing population expansion during the last glacial maximum (LGM) and range contraction during interglacial periods, as inferred from selected ABC models and from past projections of SDMs. We recovered Pleistocene diversification for both species occuring in distinctly unique periods for each taxon. An older and range-restricted lineage was recovered in a geographically isolated geological massif, deserving conservation and further taxonomic study. The diversification and distribution of these amphibian species endemic to the Neotropical 'campo rupestre' were influenced by Quaternary climatic fluctuations. The expansion of cold adapted species restricted to higher elevations during glacial periods and their concomitant retraction during interglacial periods may have been crucial for producing patterns of species richness and endemism along elevation gradients in tropical and subtropical domains. Such processes may influence the evolution of the biota distributed in heterogeneous landscapes with varied topography.


Assuntos
Anuros/classificação , Clima , Filogeografia , Animais , Teorema de Bayes , Filogenia
17.
Artigo em Inglês | MEDLINE | ID: mdl-33542085

RESUMO

PURPOSE: The aim of this study was to re-evaluate the differentiation of patients with dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) and Parkinson's disease (PD) using a quantitative analysis of 123I-FP-CIT SPECT scans. METHODS: Thirty-six patients with in vivo 123I-FP-CIT SPECT and neuropathological diagnoses were included. Based on neuropathological criteria, patients were further subclassified into nine AD, eight DLB, ten PD and nine with other diagnoses. An additional 16 healthy controls (HC) scanned with 123I-FP-CIT SPECT were also included. All images were visually assessed as normal versus abnormal uptake by consensus of five nuclear medicine physicians. Bihemispheric mean was calculated for caudate binding potential (CBP), putamen binding potential (PBP) and putamen-to-caudate ratio (PCR). RESULTS: Patients with DLB had significantly lower CBP and PBP than patients with AD and significantly higher PCR than patients with PD. Qualitative visual analysis of the images gave an accuracy of 88% in the evaluation of the status of the nigrostriatal pathway considering all individuals, and 96% considering only the patients with PD, AD and DLB. Quantitative analyses provided a balanced accuracy of 94%, 94% and 100% in binary classifications DLB versus AD, DLB versus PD and PD versus AD, respectively, and an accuracy of 93% in the differentiation among patients with DLB, AD and PD simultaneously. No statistically significant differences were observed between the AD and HC. CONCLUSIONS: This study demonstrates a very high diagnostic accuracy of the quantitative analysis of(123I-FP-CIT SPECT data to differentiate among patients with DLB, PD and AD.

18.
Gastrointest Endosc ; 93(6): 1393-1400, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33220297

RESUMO

BACKGROUND AND AIMS: Radiotherapy may cause hemorrhagic radiation proctopathy (HRP). For conservative treatment of refractory HRP, argon plasma coagulation (APC) is the first-choice therapy. Endorectal formalin instillation (EFI), in turn, is an attractive treatment option because of its satisfactory results, great availability, and low cost. Nevertheless, comparative studies between these procedures are rather scarce. This study aims to make a prospective and randomized comparison of the outcomes in 2 HRP patient groups treated with either APC or EFI. METHODS: Twenty-seven patients (11 women), with a mean age of 67 years (range, 36-83), were randomized to receive either APC (n = 14) or EFI (n = 13). On completion of the treatment, comparisons were made in relation to the baseline for each patient and between groups for endoscopic findings according to the Vienna score and the telangiectasia distribution pattern score (TDP); the impact of radiation proctitis on patients' lives was made according to the modified radiation toxicity score (MRTS) and hemoglobin levels. Number of sessions, duration of therapy, and adverse events were also compared between groups. The endoscopic therapeutic success (ETS) was defined by the absence or only few residual telangiectasias (TDP ≤1) on conclusion. RESULTS: An ETS of 92.8% was achieved in patients treated with APC and 92.3% for those treated with EFI (P > .05); there was an MRTS improvement of 85.7% in APC patients and 69.2% in EFI patients (P > .05). Mild adverse events occurred, respectively, in 23% and 28.5% in the EFI and APC groups (P > .05). CONCLUSIONS: The study showed that APC and EFI have similar efficacy and a high safety profile for HRP treatment. (Clinical trial registration number: 3.120.353.).


Assuntos
Formaldeído , Proctite , Adulto , Idoso , Idoso de 80 Anos ou mais , Coagulação com Plasma de Argônio , Feminino , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Humanos , Pessoa de Meia-Idade , Proctite/etiologia , Proctite/terapia , Estudos Prospectivos , Resultado do Tratamento
19.
Eur Radiol ; 31(5): 3071-3079, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33125562

RESUMO

OBJECTIVES: To compare lesion features extracted from 18F-FDG PET/CT images acquired on analog and digital scanners, on consecutive imaging data from the same subjects. METHODS: Whole-body 18F-FDG PET/CT images from 55 oncological patients were acquired twice after a single 18F-FDG injection, with a digital and an analog PET/CT scanner, alternately. Twenty-nine subjects were examined first on the digital, and 26 first on the analog equipment. Image reconstruction was performed using manufacturer standard clinical protocols and protocols that fulfilled EARL1 specifications. Twenty-five features based on lesion standardized uptake value (SUV) and geometry were assessed. To compare these features, intraclass correlation coefficient (ICC), relative difference (RD), absolute value of RD (|RD|), and repeatability coefficient (RC) were used. RESULTS: In total, 323 18F-FDG avid lesions were identified. High agreement (ICC > 0.75) was obtained for most of the lesion features pulled out from both scanners' imaging data, especially when reconstruction protocols fulfilled EARL1 specifications. For EARL1 reconstruction images, the features frequently used in clinics, SUVmax, SUVpeak, SUVmean, metabolic tumor volume, and total lesion glycolysis, reached an ICC of 0.92, 0.95, 0.87, 0.98, and 0.98, and a median RD (digital-analog) of 3%, 5%, 4%, - 3% and 1%, respectively. Using standard reconstruction protocols, the ICC were 0.84, 0.93, 0.80, 0.98, and 0.98, and the RD were 20%, 11%, 13%, - 7%, and 7%, respectively. CONCLUSION: Under controlled acquisition and reconstruction parameters, most of the features studied can be used for research and clinical work. This is especially important for multicenter studies and patient follow-ups. KEY POINTS: • Using manufacturer standard clinical reconstruction protocols, lesions SUV was significantly higher when using the digital scanner, especially the SUVmax that was approximately 20% higher. • High agreement was obtained for the majority of the lesion features when using reconstruction protocols that fulfilled EARL1 specifications. • Longitudinal patient studies can be performed interchangeably between digital and analog scanners when both fulfill EARL1 specifications.


Assuntos
Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Glicólise , Humanos , Processamento de Imagem Assistida por Computador , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Tomógrafos Computadorizados , Carga Tumoral
20.
Transpl Infect Dis ; 23(4): e13600, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33728731

RESUMO

INTRODUCTION: Hospital do Rim is a high-volume kidney transplant (KT) center located in São Paulo, a city with 12.2 million inhabitants. Over the last 18 years, we performed 11 436 KT, 70% of which from deceased donors. To mitigate the effects of reduction in the number of transplants on the waiting list, sequential measures were implemented when COVID-19 was declared pandemic. METHODS: The first step was to provide SARS-COV-2 RT-PCR testing for all symptomatic employees and patients and the compulsory use of personal protective equipment in the hospital facilities. Living donor KT were postponed, and all deceased donors and recipients were tested before the transplantation. The immunosuppressive protocols were maintained, and telehealth strategies were developed. RESULTS: Among the 1013 employees, there were 214 cases of COVID-19, nine required ward hospitalization, and no deaths occurred. In 26%, the probable source of contamination was occupational. From the first patient diagnosed with COVID-19 in 03/20/2020 till 10/21/2020, 523 deceased KT were performed, a 21% increase compared with 2019, with no confirmed donor-derived SARS-CoV-2 infection. Four patients were transplanted with a positive pretransplant SARS-CoV-2 test, but none of them developed the disease. Overall, of 11 875 KT followed in our center, 674 developed COVID-19. Among the hospitalized, 53% required mechanical ventilation, and 45% required hemodialysis. Their overall mortality rate was 27.5%. CONCLUSION: This experience shows the challenges that transplant centers faced as the pandemic unfolded and illustrates the effectiveness of the sequential measures implemented to provide a safe environment for transplantation.


Assuntos
COVID-19 , Transplante de Rim , Brasil , Humanos , Transplante de Rim/efeitos adversos , Pandemias , SARS-CoV-2
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