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1.
Phys Rev Lett ; 125(26): 265701, 2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-33449743

RESUMO

We study the dynamics of vortices in a two-dimensional, nonequilibrium system, described by the compact Kardar-Parisi-Zhang equation, after a sudden quench across the critical region. Our exact numerical solution of the phase-ordering kinetics shows that the unique interplay between nonequilibrium and the variable degree of spatial anisotropy leads to different critical regimes. We provide an analytical expression for the vortex evolution, based on scaling arguments, which is in agreement with the numerical results, and confirms the form of the interaction potential between vortices in this system.

2.
Phys Rev Lett ; 125(9): 095301, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32915606

RESUMO

The Kibble-Zurek mechanism constitutes one of the most fascinating and universal phenomena in the physics of critical systems. It describes the formation of domains and the spontaneous nucleation of topological defects when a system is driven across a phase transition exhibiting spontaneous symmetry breaking. While a characteristic dependence of the defect density on the speed at which the transition is crossed was observed in a vast range of equilibrium condensed matter systems, its extension to intrinsically driven dissipative systems is a matter of ongoing research. In this Letter, we numerically confirm the Kibble-Zurek mechanism in a paradigmatic family of driven dissipative quantum systems, namely exciton-polaritons in microcavities. Our findings show how the concepts of universality and critical dynamics extend to driven dissipative systems that do not conserve energy or particle number nor satisfy a detailed balance condition.

3.
J Antimicrob Chemother ; 74(10): 2979-2983, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31335959

RESUMO

BACKGROUND: The pharmacokinetics (PK) of antibiotics change during sepsis and continuous renal replacement therapies in critically ill patients. Limited evidence exists on the use of the oXiris® high-adsorbent membrane. OBJECTIVES: To develop a PK/pharmacodynamic (PD) model for meropenem in critically ill sepsis patients undergoing continuous venovenous haemodiafiltration (CVVHDF) with the oXiris® membrane, and to design an optimal dosing regimen assessed according to the PTA. METHODS: A prospective, open-label, observational PK trial was performed (EUDRACT 2011-005902-30). We conducted PK studies (plasma and ultrafiltrate) for at least 24 h after concomitant administration of CVVHDF and meropenem 1 g q8h. We constructed a PK model using the non-linear mixed-effects approach (NONMEM 7.3). We evaluated the suitability of different dosage regimens using Monte Carlo simulations and calculated the PTA as the percentage of subjects achieving a given percentage of time above the MIC (fT>MIC). RESULTS: The PK of meropenem was best captured by a two-open-compartment model with zero-order input kinetics and first-order elimination. Extracorporeal CL was 7.78 L/h [relative standard error (RSE) 16.45 L/h] and central compartment V (Vc) was 24.9 L (RSE 13.73 L). Simulations showed that, for susceptible Pseudomonas aeruginosa isolates (EUCAST MIC ≤2 mg/L) and attainment of 100%fT>MIC, 500 mg q8h given as extended (EI) or continuous infusion (CI) would be sufficient. For a target of 100%fT>4×MIC, CI of 3000 mg q24h or 2000 mg q8h administered as EI or CI would be required. CONCLUSIONS: We have constructed a PK model of meropenem in sepsis patients undergoing CVVHDF using the oXiris® membrane. This tool will support physicians when calculating the optimal initial dose.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Meropeném/administração & dosagem , Meropeném/farmacocinética , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia de Substituição Renal Contínua/métodos , Estado Terminal , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-Idade , Método de Monte Carlo , Estudos Prospectivos , Pseudomonas aeruginosa/efeitos dos fármacos , Sepse/tratamento farmacológico
4.
Phys Rev Lett ; 121(9): 095302, 2018 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-30230863

RESUMO

We study the phase ordering of parametrically and incoherently driven microcavity polaritons after an infinitely rapid quench across the critical region. We confirm that the system, despite its driven-dissipative nature, satisfies the dynamical scaling hypothesis for both driving schemes by exhibiting self-similar patterns for the two-point correlator at late times of the phase ordering. We show that polaritons are characterized by the dynamical critical exponent z≈2 with topological defects playing a fundamental role in the dynamics, giving logarithmic corrections both to the power-law decay of the number of vortices and to the associated growth of the characteristic length scale.

5.
Eur J Neurol ; 25(3): 434-e30, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29266596

RESUMO

Deep brain stimulation (DBS) is an established therapy for appropriately selected patients with movement disorders and neuropsychiatric conditions. Although the exact mechanisms and biology of DBS are not fully understood, it is a safe and well-tolerated therapy for many refractory cases of neuropsychiatric disease. Increasingly, DBS has been explored in other conditions with encouraging results. In this paper, available data is reviewed and new DBS targets, challenges and future directions in neurological disorders are explored. A detailed search of the medical literature discussing the potential use of DBS for neurological disorders excluding accepted indications was conducted. All reports were analyzed individually for content and redundant articles were excluded by examining individual abstracts. The level of evidence for each indication was summarized. Multiple studies report promising preliminary data regarding the safety and efficacy of DBS for a variety of neurological indications including chronic pain, tinnitus, epilepsy, Tourette syndrome, Huntington's disease, tardive dyskinesia and Alzheimer's disease. The initial results of DBS studies for diverse neurological disorders are encouraging but larger, controlled, prospective, homogeneous clinical trials are necessary to establish long-term safety and effectiveness. The field of neuromodulation continues to evolve and advances in DBS technology, stereotactic techniques, neuroimaging and DBS programming capabilities are shaping the present and future of DBS research and use in practice.


Assuntos
Estimulação Encefálica Profunda , Doenças do Sistema Nervoso/terapia , Medicina Baseada em Evidências , Humanos
6.
Food Microbiol ; 69: 143-150, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28941895

RESUMO

Tiger nuts' milk beverages are highly perishable products. For this reason, the interest of food industry for their commercialization makes necessary the application of preservation treatments to prolong their shelf-life. In the current study, the effect of ultra-high pressure homogenization (UHPH) on the microbiological and sensory qualities of tiger nuts' milk beverage was evaluated. Characteristics of UHPH-treated products (at 200 and 300 MPa, with inlet temperature of 40 °C) were compared with those of raw (RP) and conventionally homogenized-pasteurized (H-P) beverages, after treatment and during cold storage at 4 °C. Microbiological quality of beverages was studied by enumerating total counts, psychrotrophic bacteria, lactobacilli, enterobacteria, molds and yeasts, and mesophilic spores. Evolution of color and sensory characteristics of beverages were also determined. Microbiological shelf-life of the tiger nuts' milk beverages was extended from 3 to 25, 30 and 57 days by applying H-P and UHPH treatments at 200 and 300 MPa, respectively. Color of beverages was the only attribute that differentiated UHPH samples from the others, with greater luminosity and whiteness. Hence, UHPH treatments showed to be an alternative to the conventional H-P for obtaining tiger nuts' milk beverages with an improved microbiological shelf-life and good sensorial characteristics.


Assuntos
Bactérias/isolamento & purificação , Bebidas/microbiologia , Manipulação de Alimentos/métodos , Nozes/química , Bactérias/classificação , Bactérias/genética , Cor , Manipulação de Alimentos/instrumentação , Humanos , Pasteurização , Pressão , Paladar/imunologia , Temperatura
7.
Ecotoxicol Environ Saf ; 166: 48-55, 2018 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-30245293

RESUMO

Nitrate pollution has emerged as a problem of great importance because in recent years, the levels of nitrate in soil and groundwater have increased, mainly through anthropogenic activities, such as the use of fertilizers in agriculture, domestic wastewater and septic tanks, industrial waste and deforestation. In animals, nitrate reduction to nitrite (NO2) and nitric oxide (NO) promote the formation of methemoglobin in the blood and the generation of highly reactive intermediates that induce oxidative stress in target organs. Exposition to nitrates has been associated with methemoglobinemia, reproductive toxicity, metabolic and endocrine alterations and cancer. This study analyzed acute intoxication with sodium nitrate (NaNO3) in male Wistar rats, aged 12-16 weeks. Four groups with n = 10 rats each were formed: group 1 was the control, and group 2, group 3 and group 4 were treated for 10 days with intragastric doses of 19, 66 and 150 mg/kg/d NaNO3, respectively. Hematological, metabolic and histological biomarkers in the liver were analyzed. The results showed high percentages of methemoglobin, an increase in NO2 in the plasma and an accumulation in the liver. Moreover, there were high counts of white blood cells and platelets in all treated groups. Additionally, there was an increase in the spleen weight in group 4. High levels of glucose, triglycerides, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were observed and were significantly increased in groups 3 and 4. For oxidative stress biomarkers, there were increases in Thiobarbituric Acid Reactive Substances (TBARS), total GSH and SOD activity, mainly in group 4. Changes in mitochondrial activity were not significant. Histopathological analyses of the liver showed inflammation, infiltration of mononuclear cells, steatosis, ischemia and necrosis, and these findings were more evident at high doses of NaNO3 in which high of S-nitrosylation were found. In conclusion, NaNO3 was reduced to NO2, thereby inducing methemoglobinemia, whereas other reactive species generated oxidative stress, causing hematological and metabolic alterations and injury to the liver.


Assuntos
Poluentes Ambientais/toxicidade , Fígado/efeitos dos fármacos , Nitratos/toxicidade , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Biomarcadores/metabolismo , Glucose/metabolismo , L-Lactato Desidrogenase/metabolismo , Fígado/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Triglicerídeos/metabolismo
8.
Nat Commun ; 15(1): 221, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38177096

RESUMO

Lymphedema (LD) is characterized by the accumulation of interstitial fluid, lipids and inflammatory cell infiltrate in the limb. Here, we find that LD tissues from women who developed LD after breast cancer exhibit an inflamed gene expression profile. Lipidomic analysis reveals decrease in specialized pro-resolving mediators (SPM) generated by the 15-lipoxygenase (15-LO) in LD. In mice, the loss of SPM is associated with an increase in apoptotic regulatory T (Treg) cell number. In addition, the selective depletion of 15-LO in the lymphatic endothelium induces an aggravation of LD that can be rescued by Treg cell adoptive transfer or ALOX15-expressing lentivector injections. Mechanistically, exogenous injections of the pro-resolving cytokine IFN-ß restores both 15-LO expression and Treg cell number in a mouse model of LD. These results provide evidence that lymphatic 15-LO may represent a therapeutic target for LD by serving as a mediator of Treg cell populations to resolve inflammation.


Assuntos
Araquidonato 15-Lipoxigenase , Linfedema , Humanos , Camundongos , Feminino , Animais , Araquidonato 15-Lipoxigenase/genética , Araquidonato 15-Lipoxigenase/metabolismo , Inflamação/metabolismo , Citocinas/metabolismo , Linfócitos T Reguladores/metabolismo
9.
Clin Genet ; 81(5): 470-8, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-21477109

RESUMO

Dyskeratosis congenita (DC) is a telomere biology disorder characterized by a mucocutaneous triad, aplastic anemia, and predisposition to cancer. Mutations in a narrow segment of TINF2 exon 6 have been recognized to cause often-severe DC that is either sporadic or autosomal dominant. We describe three children with very early presentations of DC, including one with the severe variant known as Revesz syndrome. Although most TINF2 mutations reported to date are missense changes, each of our patients carried a novel heterozygous nonsense or frameshift mutation, revealing a new 5' boundary to the affected gene segment in patients with DC. Examination of patient-derived lymphoblastoid cell lines revealed stable expression of the predicted truncated TIN2 proteins. In co-immunoprecipitation assays, the ability of a truncation mutant to interact with TRF1 was severely impaired, whereas the ability of the most common DC-associated mutant was much less affected. This suggests that the disruption of TIN2-TRF1 interaction may contribute to the severe clinical phenotype observed in the context of the TIN2 truncation mutation, but is unlikely to be the primary cause of telomere shortening associated with the more prevalent TIN2 missense mutations. Telomere flow-fluorescent in situ hybridization (FISH) analysis of one pedigree showed the dramatic effect a de novo nonsense TINF2 mutation had on telomere length in early development. These cases underscore the severe manifestations of truncating TINF2 mutations.


Assuntos
Disceratose Congênita/genética , Mutação , Proteínas de Ligação a Telômeros/genética , Sequência de Aminoácidos , Substituição de Aminoácidos , Sequência de Bases , Linhagem Celular , Pré-Escolar , Disceratose Congênita/diagnóstico , Disceratose Congênita/metabolismo , Evolução Fatal , Feminino , Expressão Gênica , Ordem dos Genes , Humanos , Lactente , Masculino , Dados de Sequência Molecular , Fenótipo , Ligação Proteica , Encurtamento do Telômero , Proteínas de Ligação a Telômeros/metabolismo , Proteína 1 de Ligação a Repetições Teloméricas/metabolismo
10.
J Dairy Sci ; 95(9): 4796-4803, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22916883

RESUMO

The objective of this study was to investigate the influence of conventional and ultra-high-pressure homogenization on interactions between proteins within drained rennet curds. The effect of fat content of milk (0.0, 1.8, or 3.6%) and homogenization treatment on dissociation of proteins by different chemical agents was thus studied. Increasing the fat content of raw milk increased levels of unbound whey proteins and calcium-bonded caseins in curds; in contrast, hydrophobic interactions and hydrogen bonds were inhibited. Both homogenization treatments triggered the incorporation of unbound whey proteins in the curd, and of caseins through ionic bonds involving calcium salts. Conventional homogenization-pasteurization enhanced interactions between caseins through hydrogen bonds and hydrophobic interactions. In contrast, ultra-high-pressure homogenization impaired hydrogen bonding, led to the incorporation of both whey proteins and caseins through hydrophobic interactions and increased the amount of unbound caseins. Thus, both homogenization treatments provoked changes in the protein interactions within rennet curds; however, the nature of the changes depended on the homogenization conditions.


Assuntos
Quimosina/metabolismo , Gorduras/análise , Proteínas do Leite/metabolismo , Leite/química , Pasteurização/métodos , Animais , Bovinos , Ligação de Hidrogênio , Leite/metabolismo , Proteínas do Leite/análise , Pressão , Proteínas do Soro do Leite
11.
Fish Physiol Biochem ; 38(2): 441-54, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21671023

RESUMO

Common snook (Centropomus undecimalis) is one of the most important marine species under commercial exploitation in the Gulf of Mexico; for this reason, interest in developing its culture is a priority. However, larviculture remains as the main bottleneck for massive production. In this sense, our objective was to determine the changes of digestive enzymes activities using biochemical and electrophoretic techniques during 36 days of Common snook larviculture fed with live preys (microalgae, rotifers, and Artemia). During larviculture, all digestive enzymatic activities were detected with low values since yolk absorption, 2 days after hatching (dah) onwards. However, the maximum values for alkaline protease (6,500 U mg protein(-1)), trypsin (0.053 mU × 10(-3) mg protein(-1)), and Leucine aminopeptidase (1.4 × 10(-3) mU mg protein(-1)) were detected at 12 dah; for chymotrypsin at 25 dah (3.8 × 10(-3) mU mg protein(-1)), for carboxypeptidase A (280 mU mg protein(-1)) and lipase at 36 dah (480 U mg protein(-1)), for α-amylase at 7 dah (1.5 U mg protein(-1)), for acid phosphatases at 34 dah (5.5 U mg protein(-1)), and finally for alkaline phosphatase at 25 dah (70 U mg protein(-1)). The alkaline protease zymogram showed two active bands, the first (26.3 kDa) at 25 dah onwards, and the second (51.6 kDa) at 36 dah. The acid protease zymogram showed two bands (RF = 0.32 and 0.51, respectively) at 34 dah. The digestive enzymatic ontogeny of C. undecimalis is very similar to other strictly marine carnivorous fish, and we suggest that weaning process should be started at 34 dah.


Assuntos
Digestão , Hidrolases/metabolismo , Perciformes/metabolismo , Animais , Larva/enzimologia , Larva/crescimento & desenvolvimento , Perciformes/crescimento & desenvolvimento
12.
Hipertens Riesgo Vasc ; 39(2): 69-78, 2022.
Artigo em Espanhol | MEDLINE | ID: mdl-35331672

RESUMO

Statement of the Spanish Interdisciplinary Vascular Prevention Committee on the updated European Guidelines on Cardiovascular Disease Prevention. We present the Spanish adaptation of the 2021 European Guidelines on Cardiovascular Disease (CVD) prevention in clinical practice. The current guidelines besides the individual approach greatly emphasize on the importance of population level approaches to the prevention of cardiovascular diseases. Systematic global CVD risk assessment is recommended in individuals with any major vascular risk factor. Regarding LDL-Cholesterol, blood pressure, and glycemic control in patients with diabetes mellitus, goals and targets remain as recommended in previous guidelines. However, it is proposed a new, stepwise approach (Step 1 and 2) to treatment intensification as a tool to help physicians and patients pursue these targets in a way that fits patient profile. After Step 1, considering proceeding to the intensified goals of Step 2 is mandatory, and this intensification will be based on 10-year CVD risk, lifetime CVD risk and treatment benefit, comorbidities and patient preferences. The updated SCORE algorithm-SCORE2, SCORE-OP- is recommended in these guidelines, which estimates an individual's 10-year risk of fatal and non-fatal CVD events (myocardial infarction, stroke) in healthy men and women aged 40-89 years. Another new and important recommendation is the use of different categories of risk according different age groups (< 50, 50-69 ≥ 70 years). Different flow charts of CVD risk and risk factor treatment in apparently healthy persons, in patients with established atherosclerotic CVD, and in diabetic patients are recommended. Patients with chronic kidney disease are considered high risk or very high-risk patients according to the levels of glomerular filtration rate and albumin-to-creatinine ratio. New lifestyle recommendations adapted to the ones published by the Spanish Ministry of Health as well as recommendations focused on the management of lipids, blood pressure, diabetes and chronic renal failure are included.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus , Pressão Sanguínea , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Feminino , Humanos , Estilo de Vida , Masculino , Fatores de Risco
13.
J Dermatolog Treat ; 32(2): 180-187, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31696747

RESUMO

BACKGROUND: Infliximab (IFX) trough concentrations (Cmin) have been linked to treatment efficacy in psoriatic patients. Inter-individual IFX Cmin variability and factors influencing IFX pharmacokinetics could explain differences in treatment response. OBJECTIVE: To evaluate the association between IFX Cmin and clinical outcomes in psoriatic patients. METHODS: Prospective study of 33 patients with moderate to severe psoriasis receiving IFX at Bellvitge University Hospital, between October 2013 and November 2016. IFX Cmin and antibodies toward infliximab (ATI) were measured. RESULTS: We collected 155 IFX Cmin and ATI values (mean age, 46 (14) years; 11 (33.3%) women). Mean IFX Cmin was 2.5 (2.4) mg/L and ATIs were detected in six patients, resulting in undetectable IFX Cmin. IFX Cmin was significantly associated with ATI and body mass index (BMI) (ß -2.51, 95% CI -3.56 to -1.4 and ß -0.05, 95% CI -0.09 to -0.01). PASI score and PASI 90/100 response were significantly associated with IFX Cmin (IRR 0.80, 95% CI 0.70 to 0.92; OR 1.79, 95% CI 1.18 to 2.71 and OR 1.79, 95% CI 1.14 to 2.81). CONCLUSION: IFX Cmin significantly influences PASI 90/100 response rates. IFX Cmin wa significantly associated with ATI and BMI. The observed inter-individual variability in IFX Cmin supports the need for IFX drug monitoring.


Assuntos
Fármacos Dermatológicos/uso terapêutico , Infliximab/uso terapêutico , Psoríase/tratamento farmacológico , Adulto , Índice de Massa Corporal , Fármacos Dermatológicos/farmacocinética , Feminino , Meia-Vida , Humanos , Infliximab/farmacocinética , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Psoríase/patologia , Índice de Gravidade de Doença
14.
Actas Urol Esp (Engl Ed) ; 44(3): 187-195, 2020 Apr.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31843220

RESUMO

INTRODUCTION: Gleason score biopsy undergrading (GSBU) can have an impact on the management and prognosis of patients with prostate cancer. We analyze the possible impact of time and other clinical and analytical factors in the appearance of GSBU in our series. PATIENTS AND METHOD: Ambispective, multicenter study of 1955 patients with localized prostate cancer undergoing radical prostatectomy between 2005 and 2018. Descriptive statistics and hypothesis testing are reported by univariate and multivariate analyses. RESULTS: Mean age 63.69 (44-80) years, median PSA 8.70 ng / ml (1.23-99). GSBU was observed in 34.7% of the entire cohort. In 72.8% of the cases, the GSBU occurred in one consecutive Gleason score, with the progression from 3 + 3 to 3 + 4 being the most frequent (289 patients, 47.6%). Performing radical prostatectomy 90-180 days before or after the biopsy does not have an impact on its undergrading in any of the groups. In the univariate and multivariate analysis, the presence of tumor or pathological rectal examination in both lobes, the tumor load ≥50% of cylinders and a DPSA ≥0.20, showed independent discriminative capacity to select patients who presented GSBU. CONCLUSIONS: The time from biopsy to radical prostatectomy did not show impact on GSBU. The number of affected cylinders, bilateral tumor and DPSA are easily accessible parameters that can help us select patients with greater probability of presenting GSBU.


Assuntos
Próstata/patologia , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Prospectivos , Prostatectomia/métodos , Estudos Retrospectivos , Fatores de Tempo , Tempo para o Tratamento
15.
Folia Microbiol (Praha) ; 53(5): 423-6, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19085077

RESUMO

No significant difference (p > 0.05) was observed in the specific aminopeptidase activity (SAA) developed by Pseudomonas fluorescens, P. putida and Flavobacterium odoratum either growing at pH 5.0-6.5 or at 7 and 12 degrees C. Nevertheless, a significant difference was found when comparing the SAA of these organisms. The SAA of F. odoratum was lower than those of pseudomonads. The 4-nitroaniline test is reliable to estimate the G(-) load of fresh food products.


Assuntos
Aminopeptidases/metabolismo , Compostos de Anilina/metabolismo , Flavobacterium/enzimologia , Pseudomonas fluorescens/enzimologia , Pseudomonas putida/enzimologia , Proteínas de Bactérias/metabolismo , Técnicas Bacteriológicas , Meios de Cultura , Flavobacterium/crescimento & desenvolvimento , Concentração de Íons de Hidrogênio , Pseudomonas fluorescens/crescimento & desenvolvimento , Pseudomonas putida/crescimento & desenvolvimento , Temperatura
16.
J Clin Invest ; 105(10): 1465-72, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10811854

RESUMO

Transgenic mice expressing the BV8S2 chain, which is specific for the myelin basic protein determinant Ac1-11, possess a naturally induced set of regulatory T cells directed against BV8S2. Further activation of anti-BV8S2 T cells in male mice with recombinant BV8S2 protein can inhibit IFN-gamma release by Ac1-11-specific T cells through a cytokine-driven mechanism and prevent induction of experimental autoimmune encephalomyelitis (EAE). In contrast, naive female mice possess fewer anti-BV8S2-reactive T cells, and treatment with BV8S2 delayed but did not prevent EAE. We here demonstrate that combining T-cell receptor (TCR) vaccination with supplemental estrus doses of estrogen potentiated IL-10 production by anti-BV8S2-reactive T cells and induced Ac1-11-specific T cells to produce IL-10 and TGF-beta. This combined treatment resulted in full protection against EAE, which was not observed with either therapy alone. These findings imply that supplemental estrogen can enhance the efficacy of TCR-based immunotherapy for autoimmune diseases that predominate in females.


Assuntos
Encefalomielite Autoimune Experimental/terapia , Estradiol/administração & dosagem , Receptores de Antígenos de Linfócitos T/administração & dosagem , Animais , Sinergismo Farmacológico , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/prevenção & controle , Feminino , Imunoterapia , Masculino , Camundongos , Camundongos Transgênicos , Proteína Básica da Mielina/genética , Proteína Básica da Mielina/imunologia , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/imunologia , Caracteres Sexuais , Vacinação
17.
Clin Oncol (R Coll Radiol) ; 19(2): 154-61, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17355113

RESUMO

Since the discovery of nuclear factor-kappa B (NF-kappaB) in 1986, many studies have been conducted showing the link between the NF-kappaB signalling pathway and control of the inflammatory response. Today it is well known that control of the inflammatory response and apoptosis is closely related to the activation of NF-kappaB. Three NF-kappaB activation pathways exist. The first (the classical pathway) is normally triggered in response to microbial and viral infections or exposure to pro-inflammatory cytokines that activate the tripartite IKK complex, leading to phosphorylation-induced IkappaB degradation and depends mainly on IKKbeta activity. The second (the alternative pathway), leads to selective activation of p52:RelB dimers by inducing the processing of the NF-kappaB2/p100 precursor protein, which mostly occurs as a heterodimer with RelB in the cytoplasm. This pathway is triggered by certain members of the tumour necrosis factor cytokine family, through selective activation of IKKalpha homodimers by the upstream kinase NIK. The third pathway is named CK2 and is IKK independent. NF-kappaB acts through the transcription of anti-apoptotic proteins, leading to increased proliferation of cells and tumour growth. It is also known that some drugs act directly in the inhibition of NF-kappaB, thus producing regulation of apoptosis; some examples are aspirin and corticosteroids. Here we review the role of NF-kappaB in the control of apoptosis, its link to oncogenesis, the evidence of several studies that show that NF-kappaB activation is closely related to different cancers, and finally the potential target of NF-kappaB as cancer therapy.


Assuntos
Apoptose , Núcleo Celular/metabolismo , NF-kappa B/metabolismo , Neoplasias/metabolismo , Humanos , NF-kappa B/genética , Neoplasias/genética , Transdução de Sinais , Transcrição Gênica
18.
J Dairy Sci ; 90(1): 13-23, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17183071

RESUMO

The effects of single- or 2-stage ultra-high pressure homogenization (UHPH; 100 to 330 MPa) at an inlet temperature of 30 degrees C on the cheese-making properties of bovine milk were investigated. Effects were compared with those from raw, heat-pasteurized (72 degrees C for 15 s), and conventional homogenized-pasteurized (15 + 3 MPa, 72 degrees C for 15 s) treatments. Rennet coagulation time, rate of curd firming, curd firmness, wet yield, and moisture content of curds were assessed. Results of particle size and distribution of milk, whey composition, and gel microstructure observed by confocal laser scanning microscopy were analyzed to understand the effect of UHPH. Single-stage UHPH at 200 and 300 MPa enhanced rennet coagulation properties. However, these properties were negatively affected by the use of the UHPH secondary stage. Increasing the pressure led to higher yields and moisture content of curds. The improvement in the cheese-making properties of milk by UHPH could be explained by changes to the protein-fat structures due to the combined effect of heat and homogenization.


Assuntos
Queijo , Manipulação de Alimentos/métodos , Leite/química , Pressão , Animais , Quimosina/química , Concentração de Íons de Hidrogênio , Proteínas do Leite/química , Nitrogênio/análise , Tamanho da Partícula , Temperatura , Fatores de Tempo , Água/análise , Proteínas do Soro do Leite
19.
Cancer Res ; 61(3): 1196-206, 2001 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-11221851

RESUMO

After therapeutic hormone deprivation, prostate cancer (CaP) cells often develop androgen-independent growth through not-well-defined mechanisms. The presence of neuroendocrine (NE) cells is often greater in prostate carcinoma than in normal prostate, and the frequency of NE cells correlates with tumor malignancy, loss of androgen sensitivity, increase of autocrine-paracrine activity, and poor prognosis. In some CaPs, neuropeptides have been previously implicated as growth factors. Peptidylglycine alpha-amidating monooxygenase (PAM) is the enzyme producing alpha-amidated bioactive peptides from their inactive glycine-extended precursors. In the present work, we demonstrate that androgen-independent PC-3 and DU145 cell lines, derived from human CaP, express PAM in vitro and in xenografts implanted in athymic nude mice, indicating that they are able to produce alpha-amidated peptides. Contrarily, barely detectable levels of PAM were found in the androgen-sensitive LNCaP cell line. We also show that whereas PC-3 and DU145 cells produce and secrete adrenomedullin (AM), a multifunctional amidated peptide, no expression was found in LNCaP cells. We further demonstrate that AM acts as a growth factor for DU145 cells, which suggests the existence of an autocrine loop mechanism that could potentially drive neoplastic growth. PAM mRNA levels were found to be 3-fold higher in prostate adenocarcinomas compared with that of human benign prostate hyperplasia (BPH) as demonstrated by real-time quantitative reverse transcription-PCR. The analysis of AM message expression in BPH and CaP (Gleason's score, 6-9) shows a clear distinction between benign and CaP. The expression was detected only in adenocarcinomas tissues with a marked increase in samples with a high Gleason's score. Immunocytochemically, AM was localized in the carcinomatous epithelial compartment. NE phenotype, assessed after the immunocytochemical localization of neuron-specific enolase (NSE), was found in both the epithelial and the stromal compartments of cancers; in BPH, only some spare basal cells were NSE-labeled. Cancer progression could be accelerated by peptides secreted by a population of cells capable of inducing androgen-independent tumoral growth via autocrine-paracrine mechanisms.


Assuntos
Adenocarcinoma/metabolismo , Oxigenases de Função Mista/metabolismo , Complexos Multienzimáticos , Peptídeos/metabolismo , Neoplasias da Próstata/metabolismo , Adenocarcinoma/enzimologia , Adrenomedulina , Animais , Divisão Celular/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Camundongos , Camundongos Nus , Oxigenases de Função Mista/biossíntese , Oxigenases de Função Mista/genética , Proteínas de Neoplasias/metabolismo , Transplante de Neoplasias , Neoplasias Hormônio-Dependentes/enzimologia , Neoplasias Hormônio-Dependentes/metabolismo , Peptídeos/genética , Peptídeos/farmacologia , Fosfopiruvato Hidratase/metabolismo , Hiperplasia Prostática/enzimologia , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/enzimologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transplante Heterólogo , Células Tumorais Cultivadas
20.
J Thromb Haemost ; 14(11): 2158-2168, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27558946

RESUMO

Essentials Pediatric studies on peripherally inserted central catheter (PICC)-related thrombosis are scarce. This study analyzes incidence and risk factors for PICC-related venous thrombosis in children. PICC-related thrombosis is a common, and nearly always, asymptomatic complication. Echo-guided insertion and a catheter to vein ratio < 0.33 may notably decrease this complication. SUMMARY: Background Upper-extremity venous thrombosis is associated with the use of peripherally inserted central catheters (PICCs). Few pediatric studies have focused on this issue. Objectives To determine the incidence and risk factors for PICC-related superficial vein thrombosis (SVT) and deep vein thrombosis (DVT) in children. Patients/methods An observational follow-up cohort study was conducted at a single hospital between June 2012 and June 2015. All patients receiving a PICC were enrolled and followed up, with weekly Doppler ultrasound examination of the catheterized limb until PICC removal. Patient, procedural and follow-up data were analyzed. Results In the study period, 265 PICCs were inserted (median age of patients 6.5 years, interquartile range [IQR] 2.4-13 years; median weight 20 kg, IQR 11-38 kg; 54% males; 67.9% chronically ill), and patients were followed up for a total of 9743 days. The median indwelling time was 21 days (IQR 12-37 days). During follow-up, 88 (33.2% of insertions) PICC-related thromboses (incidence rate [IR] 9.03 per 1000 catheter-days) were diagnosed, 66 (24.9%) as isolated SVT, seven (2.6%) as isolated DVT, and 15 (5.7%) as SVT with associated DVT (IR 6.78, 0.71 and 1.54 per 1000 catheter-days, respectively). Only 9.9% of patients with SVT and 18.2% of those with DVT were symptomatic. The main risk factors for PICC-related SVT and DVT were a catheter/vein ratio of > 0.33 and thrombosis of the catheterized superficial vein, respectively. Conclusions PICC-related thrombosis is a common and nearly always asymptomatic complication in children, the SVT rate being approximately three times higher than the DVT rate. Optimal vein and catheter selection, yielding the lowest possible catheter/vein ratio, may decrease the rate of PICC-related thrombosis.


Assuntos
Cateterismo Venoso Central/efeitos adversos , Cateterismo Periférico/efeitos adversos , Trombose Venosa Profunda de Membros Superiores/epidemiologia , Trombose Venosa/epidemiologia , Adolescente , Cateteres de Demora/efeitos adversos , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Incidência , Masculino , Fatores de Risco , Ultrassonografia Doppler , Trombose Venosa Profunda de Membros Superiores/etiologia , Trombose Venosa/etiologia
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