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1.
medRxiv ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38645167

RESUMO

Apart from ancestry, personal or environmental covariates may contribute to differences in polygenic score (PGS) performance. We analyzed effects of covariate stratification and interaction on body mass index (BMI) PGS (PGSBMI) across four cohorts of European (N=491,111) and African (N=21,612) ancestry. Stratifying on binary covariates and quintiles for continuous covariates, 18/62 covariates had significant and replicable R2 differences among strata. Covariates with the largest differences included age, sex, blood lipids, physical activity, and alcohol consumption, with R2 being nearly double between best and worst performing quintiles for certain covariates. 28 covariates had significant PGSBMI-covariate interaction effects, modifying PGSBMI effects by nearly 20% per standard deviation change. We observed overlap between covariates that had significant R2 differences among strata and interaction effects - across all covariates, their main effects on BMI were correlated with their maximum R2 differences and interaction effects (0.56 and 0.58, respectively), suggesting high-PGSBMI individuals have highest R2 and increase in PGS effect. Using quantile regression, we show the effect of PGSBMI increases as BMI itself increases, and that these differences in effects are directly related to differences in R2 when stratifying by different covariates. Given significant and replicable evidence for context-specific PGSBMI performance and effects, we investigated ways to increase model performance taking into account non-linear effects. Machine learning models (neural networks) increased relative model R2 (mean 23%) across datasets. Finally, creating PGSBMI directly from GxAge GWAS effects increased relative R2 by 7.8%. These results demonstrate that certain covariates, especially those most associated with BMI, significantly affect both PGSBMI performance and effects across diverse cohorts and ancestries, and we provide avenues to improve model performance that consider these effects.

2.
Blood ; 142(15): 1297-1311, 2023 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-37339580

RESUMO

Anaplastic large cell lymphoma (ALCL), a subgroup of mature T-cell neoplasms with an aggressive clinical course, is characterized by elevated expression of CD30 and anaplastic cytology. To achieve a comprehensive understanding of the molecular characteristics of ALCL pathology and to identify therapeutic vulnerabilities, we applied genome-wide CRISPR library screenings to both anaplastic lymphoma kinase positive (ALK+) and primary cutaneous (pC) ALK- ALCLs and identified an unexpected role of the interleukin-1R (IL-1R) inflammatory pathway in supporting the viability of pC ALK- ALCL. Importantly, this pathway is activated by IL-1α in an autocrine manner, which is essential for the induction and maintenance of protumorigenic inflammatory responses in pC-ALCL cell lines and primary cases. Hyperactivation of the IL-1R pathway is promoted by the A20 loss-of-function mutation in the pC-ALCL lines we analyze and is regulated by the nonproteolytic protein ubiquitination network. Furthermore, the IL-1R pathway promotes JAK-STAT3 signaling activation in ALCLs lacking STAT3 gain-of-function mutation or ALK translocation and enhances the sensitivity of JAK inhibitors in these tumors in vitro and in vivo. Finally, the JAK2/IRAK1 dual inhibitor, pacritinib, exhibited strong activities against pC ALK- ALCL, where the IL-1R pathway is hyperactivated in the cell line and xenograft mouse model. Thus, our studies revealed critical insights into the essential roles of the IL-1R pathway in pC-ALCL and provided opportunities for developing novel therapeutic strategies.


Assuntos
Linfoma Anaplásico de Células Grandes , Linfoma Anaplásico Cutâneo Primário de Células Grandes , Neoplasias Cutâneas , Humanos , Animais , Camundongos , Linfoma Anaplásico de Células Grandes/tratamento farmacológico , Linfoma Anaplásico de Células Grandes/genética , Linfoma Anaplásico de Células Grandes/patologia , Receptores Proteína Tirosina Quinases/genética , Quinase do Linfoma Anaplásico/genética , Interleucinas/metabolismo
3.
Front Microbiol ; 12: 769965, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777323

RESUMO

Background: Herbivorous insects are one of the main biological threats to crops. One such group of insects, stink bugs, do not eat large amounts of tissue when feeding on soybean, but are damaging to the quality of the seed yield as they feed on green developing seeds leading to poorly marketable harvests. In addition to causing physical damage during sucking-feeding activities, the insects can also transmit microbial pathogens, leading to even greater yield loss. Conducting surveys of the insect intestinal microbiome can help identify possible pathogens, as well as detail what healthy stink bug digestive systems have in common. Methods: We used the conserved V4 region of the 16S rRNA gene to characterize the bacterial microbiome of the red-banded stink bug Piezodorus guildinii collected in Brazil and the United States, as well as the neotropical brown stink bug Euschistus heros collected in Brazil. Results: After quality filtering of the data, 192 samples were kept for analyses: 117 samples from P. guildinii covering three sites in Brazil and four sites in the United States, and 75 samples for E. heros covering 10 sites in Brazil. The most interesting observations were that the diversity and abundance of some bacterial families were different in the different ecoregions of Brazil and the United States. Conclusion: Some families, such as Acetobacteraceae, Bacillaceae, Moraxellaceae, Enterobacteriaceae, and Rhodocyclaceae, may be related to the better adaptation in some localities in providing nutrients, break down cellulose, detoxify phytochemicals, and degrade organic compounds, which makes it difficult to control these species.

4.
J Pediatr ; 236: 86-94.e6, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34019883

RESUMO

OBJECTIVE: To identify systolic blood pressure (SBP) percentile trajectories in children and to describe the early-life risk factors and cardiometabolic correlates of those trajectories. STUDY DESIGN: Using age-, sex-, and height-specific SBP percentiles based on the American Academy of Pediatrics reference, we examined SBP trajectories using latent class mixed models from ages 3 to 8 years (n = 844) from the Growing Up in Singapore Towards healthy Outcomes-study, a Singaporean mother-offspring cohort study. We analyzed associations between SBP trajectories and early-life risk factors using multinomial logistic regression and differences across trajectories in cardiometabolic outcomes using multiple linear regression. RESULTS: Children were classified into 1 of 4 SBP percentile trajectories: "low increasing" (15%), "high stable" (47%), "high decreasing" (20%), and "low stable" (18%). Maternal hypertension during early pregnancy was a predictor of the "high stable" and "low increasing" SBP trajectories. Rapid child weight gain in the first 2 years of life was only associated with the "high stable" trajectory. Compared with children in the "low stable" trajectory, children in the "high stable" SBP trajectory had greater body mass index z scores, sum of skinfold thicknesses, waist circumference from ages 3 to 8 years, and abdominal adipose tissue (milliliters) at 4.5 years (adjusted mean difference [95% CI]: superficial and deep subcutaneous abdominal adipose tissue: 115.2 [48.1-182.3] and 85.5 [35.2-135.8]). Their fat mass (kilograms) (1.3 [0.6-2.0]), triglyceride levels (mmol/L) (0.10 [0.02-0.18]), and homeostasis model assessment of insulin resistance (0.28 [0.11 0.46]) at age 6 years were also greater but not their arterial thickness and stiffness. CONCLUSIONS: Reducing maternal blood pressure during pregnancy and infant weight gain in the first 2 years of life might help to prevent the development of high SBP.


Assuntos
Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/epidemiologia , Fatores Etários , Glicemia/metabolismo , Índice de Massa Corporal , Doenças Cardiovasculares/diagnóstico , Criança , Pré-Escolar , Colesterol/sangue , Feminino , Humanos , Lactente , Modelos Logísticos , Masculino , Fatores de Risco , Singapura , Circunferência da Cintura
5.
Front Neurol ; 12: 643576, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33868149

RESUMO

Objectives: Through a systematic review and meta-analysis of the literature we aimed to compare the levels of BDNF, NGF, NT-3, NT-4, and GDNF between human term and preterm infants, and investigate factors implicated in the variability of effect size estimates. Methods: The analysis was performed in three online databases, MEDLINE Complete, PsycINFO, and CINAHL. A random effects model was used to calculate the standardized mean difference (SMD) of neurotrophic factor levels in preterm infants vs. term within a 95% confidence interval (CI). To explore sources of heterogeneity meta-regression models were implemented. Results: Sixteen studies were included in this meta-analysis. A combined sample of 1,379 preterm and 1,286 term newborns were evaluated. We identified significant lower BDNF (SMD = -0.32; 95% CI: -0.59, -0.06; p = 0.014) and NT-3 (SMD = -0.31; 95% CI: -0.52, -0.09; p = 0.004) levels in preterm compared to term infants. No significant difference was observed in NGF and NT-4 levels between groups. Given that only two effect sizes were generated for GDNF levels, no meta-analytical model was performed. Meta-regression models revealed sample type (placental tissue, cerebrospinal fluid, peripheral blood, and umbilical cord blood) as a significant moderator of heterogeneity for BDNF meta-analysis. No significant associations were found for gestational week, birth weight, and clinical comorbidity of newborns with effect sizes. Conclusions: Our findings indicated that lower BDNF and NT-3 levels may be associated with preterm birth. Future studies with larger samples sizes should investigate neurodevelopmental manifestations resulting from neurotrophic factor dysregulation among preterm infants.

6.
Epidemiol Infect ; 149: e94, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33845928

RESUMO

The global outbreak of coronavirus disease 2019 (COVID-19) is greatly threatening the public health in the world. We reconstructed global transmissions and potential demographic expansions of severe acute respiratory syndrome coronavirus 2 based on genomic information. We found that intercontinental transmissions were rare in January and early February but drastically increased since late February. After world-wide implements of travel restrictions, the transmission frequencies decreased to a low level in April. We identified a total of 88 potential demographic expansions over the world based on the star-radiative networks and 75 of them were found in Europe and North America. The expansion numbers peaked in March and quickly dropped since April. These findings are highly concordant with epidemic reports and modelling results and highlight the significance of quarantine validity on the global spread of COVID-19. Our analyses indicate that the travel restrictions and social distancing measures are effective in containing the spread of COVID-19.


Assuntos
COVID-19/epidemiologia , Genoma Viral , Política Pública , SARS-CoV-2/genética , Viagem , África/epidemiologia , Ásia/epidemiologia , Austrália/epidemiologia , COVID-19/transmissão , COVID-19/virologia , Controle de Doenças Transmissíveis , Europa (Continente)/epidemiologia , Genômica , Humanos , Internacionalidade , América do Norte/epidemiologia , Filogenia , Distanciamento Físico , América do Sul/epidemiologia
7.
Rev. bras. pesqui. méd. biol ; Braz. j. med. biol. res;54(2): e10099, 2021. tab
Artigo em Inglês | LILACS, Coleciona SUS | ID: biblio-1142582

RESUMO

The objective of this study was to analyze the infection rate and drug resistance of Ureaplasma urealyticum (UU) and Mycoplasma hominis (MH) in the genitourinary tract of Chinese patients. From December 2018 to June 2019, vaginal secretion or urinary secretion of outpatients in our hospital were selected for culture and drug sensitivity analysis of Ureaplasma urealyticum and Mycoplasma hominis. In 4082 Chinese samples, 1567 Mycoplasma were detected, a detection rate of 38.39%, among which 1366 cases were UU single positive, accounting for 33.47%, 15 cases were MH single positive, accounting for 0.36%, 186 cases were UU and MH mixed positive, accounting for 4.56%. The most affected age groups were 21-30 years and 31-40 years, accounting for 19.09 and 15.05%, respectively. The results of drug sensitivity showed that doxycycline, minocycline, josamycin, clarithromycin, and roxithromycin were more sensitive to mycoplasma infection. The distribution of Ureaplasma urealyticum and Mycoplasma hominis in the human genitourinary system and their sensitivity to antibiotics is different for sex and age groups.


Assuntos
Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Ureaplasma urealyticum/efeitos dos fármacos , Infecções por Ureaplasma/microbiologia , Mycoplasma hominis/efeitos dos fármacos , Testes de Sensibilidade Microbiana , China , Ureaplasma urealyticum/isolamento & purificação , Mycoplasma hominis/isolamento & purificação , Povo Asiático , Antibacterianos/farmacologia
8.
Medicine (Baltimore) ; 99(49): e23489, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33285754

RESUMO

BACKGROUND: The effects of sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists on major adverse cardiovascular events (MACE) in type 2 diabetic subgroups defined by race, ethnicity, and region are unestablished. METHODS: We searched PubMed and Embase for related randomized controlled trials. We conducted random-effects meta-analysis, stratified by drug class, on MACE in various subgroups defined by 3 factors of interest (ie, race, ethnicity, and region) to estimate pooled hazard ratio (HR) and 95% confidence interval. Random-effects meta-regression was conducted to evaluate the differences between 2 drug classes. RESULTS: We included 11 randomized controlled trials for pooled analysis. Compared with placebo, SGLT2is and GLP-1 RAs significantly reduced the risk of MACE (HR ranged from 0.76 to 0.93) in most diabetic subgroups defined by 3 factors of interest. The 2 drug classes did not significantly reduced this risk in the Black race group (HR 0.92, 95% confidence interval 0.70-1.20). The effect of the 2 drug classes on MACE was not significantly different in all diabetic subgroups of interest (P-value for subgroup differences ranged from .101 to .971). CONCLUSIONS: SGLT2is and glucagon-like peptide 1 receptor agonists can significantly reduce the risk of MACE in most type 2 diabetic subgroups defined by race, ethnicity, and region, whereas they fail to do it in Black individuals.


Assuntos
Doenças Cardiovasculares/etnologia , Diabetes Mellitus Tipo 2/etnologia , Etnicidade/estatística & dados numéricos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/uso terapêutico , Grupos Raciais/estatística & dados numéricos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Adulto , Sudeste Asiático/epidemiologia , População Negra/estatística & dados numéricos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Sistema Cardiovascular/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , América do Norte/epidemiologia , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , América do Sul/epidemiologia
9.
Braz J Med Biol Res ; 54(2): e10099, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33263642

RESUMO

The objective of this study was to analyze the infection rate and drug resistance of Ureaplasma urealyticum (UU) and Mycoplasma hominis (MH) in the genitourinary tract of Chinese patients. From December 2018 to June 2019, vaginal secretion or urinary secretion of outpatients in our hospital were selected for culture and drug sensitivity analysis of Ureaplasma urealyticum and Mycoplasma hominis. In 4082 Chinese samples, 1567 Mycoplasma were detected, a detection rate of 38.39%, among which 1366 cases were UU single positive, accounting for 33.47%, 15 cases were MH single positive, accounting for 0.36%, 186 cases were UU and MH mixed positive, accounting for 4.56%. The most affected age groups were 21-30 years and 31-40 years, accounting for 19.09 and 15.05%, respectively. The results of drug sensitivity showed that doxycycline, minocycline, josamycin, clarithromycin, and roxithromycin were more sensitive to mycoplasma infection. The distribution of Ureaplasma urealyticum and Mycoplasma hominis in the human genitourinary system and their sensitivity to antibiotics is different for sex and age groups.


Assuntos
Mycoplasma hominis/efeitos dos fármacos , Infecções por Ureaplasma/microbiologia , Ureaplasma urealyticum/efeitos dos fármacos , Adulto , Antibacterianos/farmacologia , Povo Asiático , China , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Mycoplasma hominis/isolamento & purificação , Ureaplasma urealyticum/isolamento & purificação , Adulto Jovem
10.
Braz J Med Biol Res ; 53(11): e9551, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33053115

RESUMO

The objective of this study was to investigate the effect of Mycobacterium vaccae on Jagged 1 and gamma delta T17 (γδT17) cells in asthmatic mice. An asthma mouse model was established through immunization with ovalbumin (OVA). Gamma-secretase inhibitor (DAPT) was used to block the Notch signaling pathway. M. vaccae was used to treat asthma, and related indicators were measured. Blocking Notch signaling inhibited the production of γδT17 cells and secretion of cytokine interleukin (IL)-17, which was accompanied by a decrease in Jagged1 mRNA and protein expression in the treated asthma group compared with the untreated asthma group. Similarly, treatment with M. vaccae inhibited Jagged1 expression and γδT17 cell production, which was associated with decreased airway inflammation and reactivity. The Notch signaling pathway may play a role in the pathogenesis of asthma through the induction of Jagged1 receptor. On the other hand, the inhibitory effect of M. vaccae on Jagged1 receptor in γδT17 cells could be used for the prevention and treatment of asthma.


Assuntos
Mycobacterium , Transdução de Sinais , Animais , Proteína Jagged-1 , Camundongos , Ovalbumina , Receptores Notch
11.
Rev. bras. pesqui. méd. biol ; Braz. j. med. biol. res;53(11): e9551, 2020. graf
Artigo em Inglês | LILACS, Coleciona SUS | ID: biblio-1132485

RESUMO

The objective of this study was to investigate the effect of Mycobacterium vaccae on Jagged 1 and gamma delta T17 (γδT17) cells in asthmatic mice. An asthma mouse model was established through immunization with ovalbumin (OVA). Gamma-secretase inhibitor (DAPT) was used to block the Notch signaling pathway. M. vaccae was used to treat asthma, and related indicators were measured. Blocking Notch signaling inhibited the production of γδT17 cells and secretion of cytokine interleukin (IL)-17, which was accompanied by a decrease in Jagged1 mRNA and protein expression in the treated asthma group compared with the untreated asthma group. Similarly, treatment with M. vaccae inhibited Jagged1 expression and γδT17 cell production, which was associated with decreased airway inflammation and reactivity. The Notch signaling pathway may play a role in the pathogenesis of asthma through the induction of Jagged1 receptor. On the other hand, the inhibitory effect of M. vaccae on Jagged1 receptor in γδT17 cells could be used for the prevention and treatment of asthma.


Assuntos
Animais , Coelhos , Transdução de Sinais , Mycobacterium , Ovalbumina , Receptores Notch , Proteína Jagged-1
12.
J Agric Food Chem ; 67(42): 11769-11777, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31575115

RESUMO

The inhibitory effect of brazilin against α-synuclein (α-syn) fibrillogenesis, disruption effect against mature fibrils, and the following cytotoxicity were examined by systematical biochemical, biophysical, cellular biological, and molecular simulation experiments. It is found that brazilin inhibited α-syn fibrillogenesis and disrupted the performed fibrils with a concentration-dependent manner. Moreover, cellular experimental data showed that brazilin effectively reduced the cytotoxicity induced by α-syn aggregates. Finally, molecular dynamics simulations were performed to explore the interactions between brazilin and α-syn pentamer. It is found that brazilin directly interacts with α-syn pentamer, and the hydrophobic interactions are favorable for brazilin binding with the α-syn pentamer, while the electrostatic part provides adverse effects. Three binding regions were identified to inhibit α-syn fibrillogenesis or disrupt the preformed aggregates. Furthermore, six important residues (i.e., G51, V52, A53, E61, V66, and K80) of α-syn were also identified. We expected that brazilin is an effective agent against α-syn fibrillogenesis and associated cytotoxicity.


Assuntos
Amiloide/química , Benzopiranos/química , Substâncias Protetoras/química , alfa-Sinucleína/química , Motivos de Aminoácidos , Amiloide/metabolismo , Amiloide/toxicidade , Animais , Benzopiranos/metabolismo , Linhagem Celular , Interações Hidrofóbicas e Hidrofílicas , Simulação de Dinâmica Molecular , Células PC12 , Agregados Proteicos , Ligação Proteica , Ratos , alfa-Sinucleína/metabolismo , alfa-Sinucleína/toxicidade
13.
PLoS One ; 14(7): e0220031, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31339922

RESUMO

The sugarcane borer moth, Diatraea saccharalis, is one of the most important pests of sugarcane and maize crops in the Western Hemisphere. The pest is widespread throughout South and Central America, the Caribbean region and the southern United States. One of the most intriguing features of D. saccharalis population dynamics is the high rate of range expansion reported in recent years. To shed light on the history of colonization of D. saccharalis, we investigated the genetic structure and diversity in American populations using single nucleotide polymorphism (SNPs) markers throughout the genome and sequences of the mitochondrial gene cytochrome oxidase (COI). Our primary goal was to propose possible dispersal routes from the putative center of origin that can explain the spatial pattern of genetic diversity. Our findings showed a clear correspondence between genetic structure and the geographical distributions of this pest insect on the American continents. The clustering analyses indicated three distinct groups: one composed of Brazilian populations, a second group composed of populations from El Salvador, Mexico, Texas and Louisiana and a third group composed of the Florida population. The predicted time of divergence predates the agriculture expansion period, but the pattern of distribution of haplotype diversity suggests that human-mediated movement was most likely the factor responsible for the widespread distribution in the Americas. The study of the early history of D. saccharalis promotes a better understanding of range expansion, the history of invasion, and demographic patterns of pest populations in the Americas.


Assuntos
Distribuição Animal , Evolução Molecular , Lepidópteros/genética , Filogenia , Agricultura , Animais , Código de Barras de DNA Taxonômico , Ecossistema , Lepidópteros/classificação , América do Norte , Polimorfismo de Nucleotídeo Único , América do Sul
14.
Blood ; 134(2): 171-185, 2019 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-31151983

RESUMO

The success of programmed cell death protein 1 (PD-1)/PD-L1-based immunotherapy highlights the critical role played by PD-L1 in cancer progression and reveals an urgent need to develop new approaches to attenuate PD-L1 function by gaining insight into how its expression is controlled. Anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALK+ ALCL) expresses a high level of PD-L1 as a result of the constitutive activation of multiple oncogenic signaling pathways downstream of ALK activity, making it an excellent model in which to define the signaling processes responsible for PD-L1 upregulation in tumor cells. Here, using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 library screening, we sought a comprehensive understanding of the molecular effectors required for PD-L1 regulation in ALK+ ALCL. Indeed, we determined that PD-L1 induction is dependent on the nucleophosmin-ALK oncoprotein activation of STAT3, as well as a signalosome containing GRB2/SOS1, which activates the MEK-ERK and PI3K-AKT signaling pathways. These signaling networks, through STAT3 and the GRB2/SOS1, ultimately induce PD-L1 expression through the action of transcription factors IRF4 and BATF3 on the enhancer region of the PD-L1 gene. IRF4 and BATF3 are essential for PD-L1 upregulation, and IRF4 expression is correlated with PD-L1 levels in primary ALK+ ALCL tissues. Targeting this oncogenic signaling pathway in ALK+ ALCL largely inhibited the ability of PD-L1-mediated tumor immune escape when cocultured with PD-1-positive T cells and natural killer cells. Thus, our identification of this previously unrecognized regulatory hub not only accelerates our understanding of the molecular circuitry that drives tumor immune escape but also provides novel opportunities to improve immunotherapeutic intervention strategies.


Assuntos
Antígeno B7-H1/biossíntese , Regulação Neoplásica da Expressão Gênica/fisiologia , Linfoma Anaplásico de Células Grandes/metabolismo , Transdução de Sinais/fisiologia , Quinase do Linfoma Anaplásico/genética , Quinase do Linfoma Anaplásico/metabolismo , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Humanos , Linfoma Anaplásico de Células Grandes/genética , Regulação para Cima
15.
Acta Cir Bras ; 34(5): e201900504, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31166460

RESUMO

PURPOSE: To establish a new rat model, the pathogenesis of which is closer to the clinical occurrence of chronic obstructive jaundice with liver fibrosis. METHODS: 90 SD rats were randomly divided into 3 groups. Group A common bile duct ligation, group B common bile duct injection compont and group C injection saline. The serum of three groups was extracted, and the liver function was detected by ELISA. HE staining, Masson staining and immunohistochemistry were used to detect liver pathology. RESULTS: Group B showed a fluctuant development of jaundice, obstructive degree reached a peak at 2 weeks, and decreased from 3 weeks. HA, LA and PCIII were significantly higher than control group. 3 weeks after surgery, liver tissue fibrosis occurred in group B, and a wide range of fiber spacing was formed at 5 weeks. Immunohistochemistry showed that hepatic stellate cells were more active than the control group. CONCLUSION: Intra-biliary injection of Compont gel is different from the classic obstructive jaundice animal model caused by classic bile duct ligation, which can provide an ideal rat model of chronic obstructive jaundice with liver fibrosis.


Assuntos
Ductos Biliares/efeitos dos fármacos , Modelos Animais de Doenças , Géis/administração & dosagem , Icterícia Obstrutiva/induzido quimicamente , Cirrose Hepática/induzido quimicamente , Fosfatase Alcalina/sangue , Animais , Aspartato Aminotransferases/sangue , Compostos Azo , Ductos Biliares/patologia , Bilirrubina/análise , Ensaio de Imunoadsorção Enzimática , Amarelo de Eosina-(YS) , Feminino , Imuno-Histoquímica , Injeções , Icterícia Obstrutiva/patologia , Cirrose Hepática/patologia , Verde de Metila , Distribuição Aleatória , Ratos Sprague-Dawley , Valores de Referência , Reprodutibilidade dos Testes , Albumina Sérica/análise , Fatores de Tempo , gama-Glutamiltransferase/sangue
16.
Acta cir. bras. ; 34(5): e201900504, June 3, 2019. tab, graf, ilus
Artigo em Inglês | VETINDEX | ID: vti-23233

RESUMO

Purpose: To establish a new rat model, the pathogenesis of which is closer to the clinical occurrence of chronic obstructive jaundice with liver fibrosis. Methods: 90 SD rats were randomly divided into 3 groups. Group A common bile duct ligation, group B common bile duct injection compont and group C injection saline. The serum of three groups was extracted, and the liver function was detected by ELISA. HE staining, Masson staining and immunohistochemistry were used to detect liver pathology. Results: Group B showed a fluctuant development of jaundice, obstructive degree reached a peak at 2 weeks, and decreased from 3 weeks. HA, LA and PCIII were significantly higher than control group. 3 weeks after surgery, liver tissue fibrosis occurred in group B, and a wide range of fiber spacing was formed at 5 weeks. Immunohistochemistry showed that hepatic stellate cells were more active than the control group. Conclusion: Intra-biliary injection of Compont gel is different from the classic obstructive jaundice animal model caused by classic bile duct ligation, which can provide an ideal rat model of chronic obstructive jaundice with liver fibrosis.(AU)


Assuntos
Animais , Feminino , Ratos , Icterícia Obstrutiva , Fibrose , Hepatopatias , Ducto Colédoco/efeitos dos fármacos , China , Modelos Animais de Doenças
17.
Environ Pollut ; 251: 609-618, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31108294

RESUMO

While infants are developing, they are easily affected by toxic chemicals existing in their environments, such as semi-volatile organic compounds (SVOCs): phthalates, polycyclic aromatic hydrocarbons (PAHs), polybrominated diphenyl ethers (PBDEs), and organophosphate esters (OPEs). However, the specific living environment of infants, including increased plastic products and foam floor mats, may increase the presence of these chemicals. In this study, 68 air, dust, and window film samples were collected from homes, with 3- to 6-month-old infant occupants, to analyze phthalates, PAHs, PBDEs, and OPEs. High detection rates and concentrations suggest that these SVOCs are widespread in infant environments and are associated with cooking methods, smoking habits, the period of time after decoration, and room floors. The partitioning behavior of SVOCs indicates that the logarithms of the dust/gas-phase air partition coefficient (logKD) and the window film/gas-phase air partition coefficient (logKF) in homes are not at an equilibrium state when the logarithm of the octanol/air partition coefficient (logKOA) is less than 8 or greater than 11. Considering the 3 exposure routes, ingestion and dermal absorption have become the main routes of infant exposure to phthalates and OPEs, and ingestion and inhalation have become the dominant routes of exposure to PAHs and PBDEs. The total carcinogenic risk of SVOCs, which have carcinogenic toxicities, via ingestion and dermal absorption for infants in homes exceeds the acceptable value, suggesting that the current levels of these SVOCs in homes might pose a risk to infant health.


Assuntos
Poluição do Ar em Ambientes Fechados/análise , Poeira/análise , Exposição por Inalação/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Compostos Orgânicos Voláteis/análise , China , Éteres Difenil Halogenados/análise , Habitação/normas , Humanos , Lactente , Organofosfatos/análise , Ácidos Ftálicos/análise
18.
Rev. bras. anestesiol ; Rev. bras. anestesiol;69(2): 211-213, Mar.-Apr. 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1003395

RESUMO

Abstract We presented a 39-year-old female patient with life-threatening hypoxemia after tricuspid valve replacement because of Ebstein's anomaly. And the severe cyanosis is due to bioprosthetic valve stenosis and atrial septal defect. Anesthetic management of a patient with severe obstructive prosthetic valve dysfunction can be challenging. Similar considerations should be given to patients with Ebstein's anomaly to maintain the pressure equalized between the right and left atrial. Transesophageal echocardiography and cerebral oxygen saturation provided real time information in perioperative care.


Resumo Apresentamos o caso de uma paciente de 39 anos, com hipoxemia em risco de vida após a substituição da valva tricúspide devido à anomalia de Ebstein e cianose grave devido à estenose de valva bioprotética e comunicação interatrial. O manejo anestésico de um paciente com disfunção obstrutiva grave de prótese valvar pode ser um desafio. Os pacientes com anomalia de Ebstein também precisam de atenção especial para manter a pressão equalizada entre o átrio direito e o esquerdo. A ecocardiografia transesofágica e a saturação cerebral de oxigênio forneceram informações em tempo real nos cuidados perioperatórios.


Assuntos
Humanos , Feminino , Adulto , Estenose da Valva Tricúspide/cirurgia , Cianose/etiologia , Anomalia de Ebstein/cirurgia , Anestésicos/administração & dosagem , Bioprótese/efeitos adversos , Índice de Gravidade de Doença , Próteses Valvulares Cardíacas/efeitos adversos , Ecocardiografia Transesofagiana/métodos , Assistência Perioperatória/métodos , Implante de Prótese de Valva Cardíaca/métodos , Comunicação Interatrial/cirurgia , Hipóxia/etiologia
19.
Food Res Int ; 116: 538-547, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30716978

RESUMO

Novel structured lipids (SLs) enriched with medium-and long-chain triacylglycerols (MLCTs) were synthesized to combine the benefits of both arachidonic acid and medium-chain fatty acids; however, they are susceptible to oxidative degradation. In this work, the influences of the partial replacement of whey protein isolate (WPI) as the primary wall material by prebiotic carbohydrates, such as maltodextrin (MD) and inulin (IN) as the secondary wall materials on the physicochemical characteristics and oxidative stability of the spray-dried MLCTs-rich SLs microcapsules were investigated. The highest values of viscosity and zeta-potential were achieved by the WPI/IN (1:1) emulsions. Size distributions of all the emulsions were mono modal and became bimodal after microencapsulation process. The microcapsules prepared with WPI/IN (1:1) had the lowest lightness and the highest yellowness values. The partial replacement treatments increased the solubility and reduced the moisture content of the produced microcapsules. The partial replacement of WPI by IN significantly enhanced the encapsulation efficiency (89.10 ±â€¯1.03%), wettability properties (205 ±â€¯10.61 S), and decreased the incidence of surface oil on the microcapsules. The free oil content was noted as 5.73 ±â€¯0.05, 3.83 ±â€¯0.01, and 2.40 ±â€¯0.03% for the microcapsules produced using WPI, WPI/MD (1:1), and WPI/IN (1:1), respectively. Larger microcapsules and fairer flowing properties were achieved in the powders produced with only WPI. The partial replacement of WPI by IN provided the best oxidative stability of the microencapsulated MLCTs-rich SLs. The results revealed that MD and IN with WPI together, particularly IN proved to be a good substitute secondary wall material for spray-dried MLCTs-rich SLs, therefore suggesting its usefulness in functional food applications.


Assuntos
Cápsulas/química , Dessecação/métodos , Lipídeos/química , Triglicerídeos/química , Proteínas do Soro do Leite/química , Ácidos Araquidônicos , Carboidratos , Fenômenos Químicos , Emulsões/química , Alimento Funcional , Inulina , Proteínas do Leite/química , Oxirredução , Tamanho da Partícula , Polissacarídeos , Pós , Prebióticos , Viscosidade , Proteínas do Soro do Leite/isolamento & purificação
20.
Braz J Anesthesiol ; 69(2): 211-213, 2019.
Artigo em Português | MEDLINE | ID: mdl-30446210

RESUMO

We presented a 39-year-old female patient with life-threatening hypoxemia after tricuspid valve replacement because of Ebstein's anomaly. And the severe cyanosis is due to bioprosthetic valve stenosis and atrial septal defect. Anesthetic management of a patient with severe obstructive prosthetic valve dysfunction can be challenging. Similar considerations should be given to patients with Ebstein's anomaly to maintain the pressure equalized between the right and left atrial. Transesophageal echocardiography and cerebral oxygen saturation provided real time information in perioperative care.


Assuntos
Anestésicos/administração & dosagem , Cianose/etiologia , Anomalia de Ebstein/cirurgia , Estenose da Valva Tricúspide/cirurgia , Adulto , Bioprótese/efeitos adversos , Ecocardiografia Transesofagiana/métodos , Feminino , Comunicação Interatrial/cirurgia , Próteses Valvulares Cardíacas/efeitos adversos , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Hipóxia/etiologia , Assistência Perioperatória/métodos , Índice de Gravidade de Doença
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