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1.
Nature ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009005

RESUMO

Transmission spectroscopy has been a workhorse technique over the past two decades to constrain the physical and chemical properties of exoplanet atmospheres 1-5. One of its classical key assumptions is that the portion of the atmosphere it probes - the terminator region - is homogeneous. Several works in the past decade, however, have put this into question for highly irradiated, hot (Teq ≳ 1000 K) gas giant exoplanets both empirically 6-10 and via 3-dimensional modelling 11-17. While models predict clear differences between the evening (day-to-night) and morning (night-to-day) terminators, direct morning/evening transmission spectra in a wide wavelength range has not been reported for an exoplanet to date. Under the assumption of precise and accurate orbital parameters on WASP-39 b, here we report the detection of inhomogeneous terminators on the exoplanet WASP-39 b, which allows us to retrieve its morning and evening transmission spectra in the near-infrared (2 - 5 µm) using JWST. We observe larger transit depths in the evening which are, on average, 405±88 ppm larger than the morning ones, also having qualitatively larger features than the morning spectrum. The spectra are best explained by models in which the evening terminator is hotter than the morning terminator by 177 - 57 + 65 K with both terminators having C/O ratios consistent with solar. General circulation models (GCMs) predict temperature differences broadly consistent with the above value and point towards a cloudy morning terminator and a clearer evening terminator.

2.
Cir Esp (Engl Ed) ; 102(6): 300-306, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38342139

RESUMO

AIM: Accurate diagnosis of complicated appendicitis is of importance to ensure that patients receive early and effective treatment, minimizing the risk of postoperative complications to promote successful recovery. Biochemical markers are a promising tool to identify complicated appendicitis. We aimed to evaluate the potential role of novel parameters related with neutrophil activation, known as "Extended Inflammation Parameters" (EIP), included in blood cell count reported by Sysmex XN-Series analyzers, compared to other canonical biomarkers in identifying complicated appendicitis. METHOD: Prospective observational study including patients with confirmed diagnosis of acute appendicitis. C-reactive protein (CRP), procalcitonin, cell blood count, including white blood cell (WBC), absolute neutrophil (ANC) and immature granulocyte (IG) count and EIP (neutrophil reactivity [NEUT-RI] and granularity intensity [NEUT-GI]) were analyzed before surgery. Their accuracy to diagnose complicated appendicitis was tested in an ROC curve analysis. RESULTS: Our population study included 119 patients, and appendicitis was complicated in 58 (48.7%). NLR, CRP and procalcitonin levels, ANC and IG count and NEUT-RI and NEUT-GI were higher in patients with complicated appendicitis. Regarding accuracy for complicated appendicitis, CRP was the biomarker with the highest performance (ROC AUC: 0.829), with an optimal cutoff of 73.1 mg/L (sensitivity: 63.8%, specificity: 88.5%). NEUT-RI and NEUT-GI achieved both significant but poor accuracy, with ROC AUC of 0.606 and 0.637, respectively. CONCLUSIONS: Novel laboratory tests reported by Sysmex XN-Series analyzers have poor accuracy for identifying complicated appendicitis. In this study, CRP was the biomarker with the highest performance and may be useful as predictor of the severity of acute appendicitis.


Assuntos
Apendicite , Biomarcadores , Proteína C-Reativa , Ativação de Neutrófilo , Pró-Calcitonina , Apendicite/sangue , Apendicite/diagnóstico , Apendicite/cirurgia , Humanos , Estudos Prospectivos , Feminino , Masculino , Adulto , Proteína C-Reativa/análise , Pessoa de Meia-Idade , Biomarcadores/sangue , Pró-Calcitonina/sangue , Doença Aguda , Contagem de Leucócitos/métodos , Contagem de Leucócitos/instrumentação , Testes Hematológicos/métodos , Testes Hematológicos/instrumentação , Curva ROC , Idoso , Neutrófilos , Inflamação/sangue
3.
Nature ; 626(8001): 979-983, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38232945

RESUMO

The recent inference of sulfur dioxide (SO2) in the atmosphere of the hot (approximately 1,100 K), Saturn-mass exoplanet WASP-39b from near-infrared JWST observations1-3 suggests that photochemistry is a key process in high-temperature exoplanet atmospheres4. This is because of the low (<1 ppb) abundance of SO2 under thermochemical equilibrium compared with that produced from the photochemistry of H2O and H2S (1-10 ppm)4-9. However, the SO2 inference was made from a single, small molecular feature in the transmission spectrum of WASP-39b at 4.05 µm and, therefore, the detection of other SO2 absorption bands at different wavelengths is needed to better constrain the SO2 abundance. Here we report the detection of SO2 spectral features at 7.7 and 8.5 µm in the 5-12-µm transmission spectrum of WASP-39b measured by the JWST Mid-Infrared Instrument (MIRI) Low Resolution Spectrometer (LRS)10. Our observations suggest an abundance of SO2 of 0.5-25 ppm (1σ range), consistent with previous findings4. As well as SO2, we find broad water-vapour absorption features, as well as an unexplained decrease in the transit depth at wavelengths longer than 10 µm. Fitting the spectrum with a grid of atmospheric forward models, we derive an atmospheric heavy-element content (metallicity) for WASP-39b of approximately 7.1-8.0 times solar and demonstrate that photochemistry shapes the spectra of WASP-39b across a broad wavelength range.

4.
Nature ; 620(7973): 292-298, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37257843

RESUMO

Close-in giant exoplanets with temperatures greater than 2,000 K ('ultra-hot Jupiters') have been the subject of extensive efforts to determine their atmospheric properties using thermal emission measurements from the Hubble Space Telescope (HST) and Spitzer Space Telescope1-3. However, previous studies have yielded inconsistent results because the small sizes of the spectral features and the limited information content of the data resulted in high sensitivity to the varying assumptions made in the treatment of instrument systematics and the atmospheric retrieval analysis3-12. Here we present a dayside thermal emission spectrum of the ultra-hot Jupiter WASP-18b obtained with the NIRISS13 instrument on the JWST. The data span 0.85 to 2.85 µm in wavelength at an average resolving power of 400 and exhibit minimal systematics. The spectrum shows three water emission features (at >6σ confidence) and evidence for optical opacity, possibly attributable to H-, TiO and VO (combined significance of 3.8σ). Models that fit the data require a thermal inversion, molecular dissociation as predicted by chemical equilibrium, a solar heavy-element abundance ('metallicity', [Formula: see text] times solar) and a carbon-to-oxygen (C/O) ratio less than unity. The data also yield a dayside brightness temperature map, which shows a peak in temperature near the substellar point that decreases steeply and symmetrically with longitude towards the terminators.

5.
Nature ; 617(7961): 483-487, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37100917

RESUMO

Photochemistry is a fundamental process of planetary atmospheres that regulates the atmospheric composition and stability1. However, no unambiguous photochemical products have been detected in exoplanet atmospheres so far. Recent observations from the JWST Transiting Exoplanet Community Early Release Science Program2,3 found a spectral absorption feature at 4.05 µm arising from sulfur dioxide (SO2) in the atmosphere of WASP-39b. WASP-39b is a 1.27-Jupiter-radii, Saturn-mass (0.28 MJ) gas giant exoplanet orbiting a Sun-like star with an equilibrium temperature of around 1,100 K (ref. 4). The most plausible way of generating SO2 in such an atmosphere is through photochemical processes5,6. Here we show that the SO2 distribution computed by a suite of photochemical models robustly explains the 4.05-µm spectral feature identified by JWST transmission observations7 with NIRSpec PRISM (2.7σ)8 and G395H (4.5σ)9. SO2 is produced by successive oxidation of sulfur radicals freed when hydrogen sulfide (H2S) is destroyed. The sensitivity of the SO2 feature to the enrichment of the atmosphere by heavy elements (metallicity) suggests that it can be used as a tracer of atmospheric properties, with WASP-39b exhibiting an inferred metallicity of about 10× solar. We further point out that SO2 also shows observable features at ultraviolet and thermal infrared wavelengths not available from the existing observations.

6.
Nature ; 614(7949): 670-675, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36623550

RESUMO

The Saturn-mass exoplanet WASP-39b has been the subject of extensive efforts to determine its atmospheric properties using transmission spectroscopy1-4. However, these efforts have been hampered by modelling degeneracies between composition and cloud properties that are caused by limited data quality5-9. Here we present the transmission spectrum of WASP-39b obtained using the Single-Object Slitless Spectroscopy (SOSS) mode of the Near Infrared Imager and Slitless Spectrograph (NIRISS) instrument on the JWST. This spectrum spans 0.6-2.8 µm in wavelength and shows several water-absorption bands, the potassium resonance doublet and signatures of clouds. The precision and broad wavelength coverage of NIRISS/SOSS allows us to break model degeneracies between cloud properties and the atmospheric composition of WASP-39b, favouring a heavy-element enhancement ('metallicity') of about 10-30 times the solar value, a sub-solar carbon-to-oxygen (C/O) ratio and a solar-to-super-solar potassium-to-oxygen (K/O) ratio. The observations are also best explained by wavelength-dependent, non-grey clouds with inhomogeneous coverageof the planet's terminator.

7.
Nature ; 614(7949): 664-669, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36623549

RESUMO

Measuring the abundances of carbon and oxygen in exoplanet atmospheres is considered a crucial avenue for unlocking the formation and evolution of exoplanetary systems1,2. Access to the chemical inventory of an exoplanet requires high-precision observations, often inferred from individual molecular detections with low-resolution space-based3-5 and high-resolution ground-based6-8 facilities. Here we report the medium-resolution (R ≈ 600) transmission spectrum of an exoplanet atmosphere between 3 and 5 µm covering several absorption features for the Saturn-mass exoplanet WASP-39b (ref. 9), obtained with the Near Infrared Spectrograph (NIRSpec) G395H grating of JWST. Our observations achieve 1.46 times photon precision, providing an average transit depth uncertainty of 221 ppm per spectroscopic bin, and present minimal impacts from systematic effects. We detect significant absorption from CO2 (28.5σ) and H2O (21.5σ), and identify SO2 as the source of absorption at 4.1 µm (4.8σ). Best-fit atmospheric models range between 3 and 10 times solar metallicity, with sub-solar to solar C/O ratios. These results, including the detection of SO2, underscore the importance of characterizing the chemistry in exoplanet atmospheres and showcase NIRSpec G395H as an excellent mode for time-series observations over this critical wavelength range10.

8.
Nature ; 614(7949): 653-658, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36623551

RESUMO

Measuring the metallicity and carbon-to-oxygen (C/O) ratio in exoplanet atmospheres is a fundamental step towards constraining the dominant chemical processes at work and, if in equilibrium, revealing planet formation histories. Transmission spectroscopy (for example, refs. 1,2) provides the necessary means by constraining the abundances of oxygen- and carbon-bearing species; however, this requires broad wavelength coverage, moderate spectral resolution and high precision, which, together, are not achievable with previous observatories. Now that JWST has commenced science operations, we are able to observe exoplanets at previously uncharted wavelengths and spectral resolutions. Here we report time-series observations of the transiting exoplanet WASP-39b using JWST's Near InfraRed Camera (NIRCam). The long-wavelength spectroscopic and short-wavelength photometric light curves span 2.0-4.0 micrometres, exhibit minimal systematics and reveal well defined molecular absorption features in the planet's spectrum. Specifically, we detect gaseous water in the atmosphere and place an upper limit on the abundance of methane. The otherwise prominent carbon dioxide feature at 2.8 micrometres is largely masked by water. The best-fit chemical equilibrium models favour an atmospheric metallicity of 1-100-times solar (that is, an enrichment of elements heavier than helium relative to the Sun) and a substellar C/O ratio. The inferred high metallicity and low C/O ratio may indicate significant accretion of solid materials during planet formation (for example, refs. 3,4,) or disequilibrium processes in the upper atmosphere (for example, refs. 5,6).

10.
Eur J Clin Invest ; 51(5): e13511, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33569769

RESUMO

BACKGROUND: Early identification of patients at high risk of progression to severe COVID-19 constituted an unsolved challenge. Although growing evidence demonstrates a direct association between endotheliitis and severe COVID-19, the role of endothelial damage biomarkers has been scarcely studied. We investigated the relationship between circulating mid-regional proadrenomedullin (MR-proADM) levels, a biomarker of endothelial dysfunction, and prognosis of SARS-CoV-2-infected patients. METHODS: Prospective observational study enrolling adult patients with confirmed COVID-19. On admission to emergency department, a blood sample was drawn for laboratory test analysis. Primary and secondary endpoints were 28-day all-cause mortality and severe COVID-19 progression. Area under the curve (AUC) and multivariate regression analysis were employed to assess the association of the biomarker with the established endpoints. RESULTS: A total of 99 patients were enrolled. During hospitalization, 25 (25.3%) cases progressed to severe disease and the 28-day mortality rate was of 14.1%. MR-proADM showed the highest AUC to predict 28-day mortality (0.905; [CI] 95%: 0.829-0.955; P < .001) and progression to severe disease (0.829; [CI] 95%: 0.740-0.897; P < .001), respectively. MR-proADM plasma levels above optimal cut-off (1.01 nmol/L) showed the strongest independent association with 28-day mortality risk (hazard ratio [HR]: 10.470, 95% CI: 2.066-53.049; P < .005) and with progression to severe disease (HR: 6.803, 95% CI: 1.458-31.750; P = .015). CONCLUSION: Mid-regional proadrenomedullin was the biomarker with highest performance for prognosis of death and progression to severe disease in COVID-19 patients and represents a promising predictor for both outcomes, which might constitute a potential tool in the assessment of prognosis in early stages of this disease.


Assuntos
Adrenomedulina/sangue , COVID-19/sangue , Endotélio Vascular/metabolismo , Inflamação/sangue , Mortalidade , Fragmentos de Peptídeos/sangue , Precursores de Proteínas/sangue , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , COVID-19/mortalidade , Causas de Morte , Progressão da Doença , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Respiração Artificial/estatística & dados numéricos , SARS-CoV-2 , Índice de Gravidade de Doença
11.
Adv Lab Med ; 2(2): 287-295, 2021 May.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-37363327

RESUMO

Objectives: Paracetamol intoxication is one of the causes of elevated procalcitonin concentrations unrelated to infection. We report a case series of two patients intoxicated with paracetamol whose laboratory data revealed a significant elevation of serum procalcitonin concentrations without clinical, radiological and/or biological evidence of infection. The underlying mechanism by which paracetamol triggers an increase in procalcitonin concentrations is still unclear. Case presentation: We report two cases of paracetamol intoxication. Both patients were admitted to the Emergency Department (ED) and subsequently transferred to the Intensive Care Unit (ICU). The patients exhibited elevated procalcitonin levels during the first hours of admission without clinical and/or microbiological evidence of infection that could explain such increase. Notably, only Case 1 developed liver injury, with alterations in alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin and esterified bilirubin concentrations, which were not observed in Case 2. Conclusions: The two patients showed elevated procalcitonin concentrations resulting from paracetamol intoxication, although only a patient exhibited signs of liver injury. These findings suggest that increased procalcitonin levels induced by a paracetamol overdose cannot be fully explained by hepatocyte injury alone, but other mechanisms involving other organs and tissues may also be associated. In any case, although this mechanism is not well understood, it is important to be aware of this limitation when using procalcitonin as a biomarker of infection in patients intoxicated with paracetamol.

13.
Am Nat ; 195(5): 876-885, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32364781

RESUMO

When the strength or nature of a host-parasite interaction changes over the host life cycle, the consequences of parasitism can depend on host population age structure. Avian brood parasites reduce hosts' breeding success, and host age may play a role in this interaction if younger hosts are more likely parasitized and/or less able to defend themselves. We analyzed whether the age of female magpie (Pica pica) hosts is associated with parasite attack or their ability to reject foreign eggs. We recorded parasitism and model egg rejection of known-age individuals over their lifetime and established whether the likelihood of parasitism or egg rejection changed with age or longevity. Parasitism probability did not change with female age, and there was a trend toward longer-lived females being less likely to be parasitized. However, model egg rejection probability increased with age for each individual female, and longer-lived females were more prone to reject model eggs. Most females in the population were young, and the majority of them accepted model eggs, suggesting that brood parasites exploiting younger host individuals are benefitting from a lower defense level of their hosts. Our results stress that the intensity of selection by brood parasites may be mediated by the age structure of host populations, a to-date neglected aspect in brood parasite-host research.


Assuntos
Interações Hospedeiro-Parasita , Comportamento de Nidação , Reprodução , Aves Canoras/fisiologia , Fatores Etários , Animais , Óvulo , Rejeição em Psicologia
14.
Ups J Med Sci ; 125(1): 19-29, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31809668

RESUMO

Background: An antibody panel is needed to definitively differentiate between adenocarcinoma (AC) and squamous cell carcinoma (SCC) in order to meet more stringent requirements for the histologic classification of lung cancers. Staining of desmosomal plaque-related proteins may be useful in the diagnosis of lung SCC.Materials and methods: We compared the usefulness of six conventional (CK5/6, p40, p63, CK7, TTF1, and Napsin A) and three novel (PKP1, KRT15, and DSG3) markers to distinguish between lung SCC and AC in 85 small biopsy specimens (41 ACs and 44 SCCs). Correlations were examined between expression of the markers and patients' histologic and clinical data.Results: The specificity for SCC of membrane staining for PKP1, KRT15, and DSG3 was 97.4%, 94.6%, and 100%, respectively, and it was 100% when the markers were used together and in combination with the conventional markers (AUCs of 0.7619 for Panel 1 SCC, 0.7375 for Panel 2 SCC, 0.8552 for Panel 1 AC, and 0.8088 for Panel 2 AC). In a stepwise multivariate logistic regression model, the combination of CK5/6, p63, and PKP1 in membrane was the optimal panel to differentiate between SCC and AC, with a percentage correct classification of 96.2% overall (94.6% of ACs and 97.6% of SCCs). PKP1 and DSG3 are related to the prognosis.Conclusions: PKP1, KRT15, and DSG3 are highly specific for SCC, but they were more useful to differentiate between SCC and AC when used together and in combination with conventional markers. PKP1 and DSG3 expressions may have prognostic value.


Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Desmossomos/metabolismo , Neoplasias Pulmonares/diagnóstico , Adenocarcinoma/metabolismo , Carcinoma de Células Escamosas/metabolismo , Desmogleína 3/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Queratina-15/metabolismo , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Placofilinas/metabolismo , Prognóstico , Sensibilidade e Especificidade
15.
Nat Commun ; 10(1): 3109, 2019 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-31337752

RESUMO

Biological responses to climate change have been widely documented across taxa and regions, but it remains unclear whether species are maintaining a good match between phenotype and environment, i.e. whether observed trait changes are adaptive. Here we reviewed 10,090 abstracts and extracted data from 71 studies reported in 58 relevant publications, to assess quantitatively whether phenotypic trait changes associated with climate change are adaptive in animals. A meta-analysis focussing on birds, the taxon best represented in our dataset, suggests that global warming has not systematically affected morphological traits, but has advanced phenological traits. We demonstrate that these advances are adaptive for some species, but imperfect as evidenced by the observed consistent selection for earlier timing. Application of a theoretical model indicates that the evolutionary load imposed by incomplete adaptive responses to ongoing climate change may already be threatening the persistence of species.


Assuntos
Aclimatação/fisiologia , Aves/fisiologia , Mudança Climática , Fenótipo , Animais , Seleção Genética/fisiologia , Fatores de Tempo
16.
Proc Natl Acad Sci U S A ; 116(20): 9723-9728, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31036661

RESUMO

The radii and orbital periods of 4,000+ confirmed/candidate exoplanets have been precisely measured by the Kepler mission. The radii show a bimodal distribution, with two peaks corresponding to smaller planets (likely rocky) and larger intermediate-size planets, respectively. While only the masses of the planets orbiting the brightest stars can be determined by ground-based spectroscopic observations, these observations allow calculation of their average densities placing constraints on the bulk compositions and internal structures. However, an important question about the composition of planets ranging from 2 to 4 Earth radii (R⊕) still remains. They may either have a rocky core enveloped in a H2-He gaseous envelope (gas dwarfs) or contain a significant amount of multicomponent, H2O-dominated ices/fluids (water worlds). Planets in the mass range of 10-15 M⊕, if half-ice and half-rock by mass, have radii of 2.5 R⊕, which exactly match the second peak of the exoplanet radius bimodal distribution. Any planet in the 2- to 4-R⊕ range requires a gas envelope of at most a few mass percentage points, regardless of the core composition. To resolve the ambiguity of internal compositions, we use a growth model and conduct Monte Carlo simulations to demonstrate that many intermediate-size planets are "water worlds."

17.
P R Health Sci J ; 37(4): 208-212, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30548056

RESUMO

OBJECTIVE: Obesity, almost all around the world, has been described by the medical authorities as the most common pediatric illness in children and youngsters. The purpose of this study is to explore, describe, and analyze the experiences of obese adolescents on being obese and trying to reach a healthy weight. DESIGN AND METHODS: A convenience sample of eight obese adolescents from 15 to 17 years old of both genders from three high schools of the educational region of San Juan, Puerto Rico was obtained. A phenomenological multiple-case study was conducted using a semi structured interview. RESULTS: The experience of trying to reach a healthy weight is difficult because it requires a lot of physical effort to do exercises and physical activities, they lack the support of parents and trainers, and because of the availability of food with low nutritional value in their environment. Participants also pointed out that it is difficult due to the negative feelings that adolescents experience while performing the activities to lose weight. CONCLUSION: The goal to reach a healthy weight is difficult. It is recommended that agencies that work with overweight and obesity problems provide people with the knowledge, strategies, alternatives, and needed activities from a biopsychosocial perspective to help adolescents with this health condition to be successful in reaching and keeping a healthy weight.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Obesidade Infantil/terapia , Apoio Social , Redução de Peso/fisiologia , Adolescente , Peso Corporal/fisiologia , Currículo , Exercício Físico/fisiologia , Exercício Físico/psicologia , Feminino , Humanos , Entrevistas como Assunto , Masculino , Obesidade Infantil/psicologia , Porto Rico , Instituições Acadêmicas
18.
Biomédica (Bogotá) ; 38(4): 456-462, oct.-dic. 2018. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-983954

RESUMO

El síndrome hemofagocítico es una condición clínica e histológica grave, secundaria a diferentes procesos. La glomerulonefritis colapsante es una podocitopatía proliferativa, generalmente de pronóstico desfavorable para la función renal. Se presenta un caso en el que las dos condiciones aparecieron asociadas, lo cual es una forma infrecuente de presentación del linfoma hepatoesplénico de células T. Se discute, asimismo, el papel de los marcadores de desdiferenciación podocitaria en esta glomerulopatía, y se revisan la fisiopatología y el tratamiento.


The hemophagocytic syndrome is a serious clinical-histological entity secondary to different diseases. Collapsing glomerulonephritis is a proliferative podocytopathy that usually has an unfavorable renal prognosis. We present a case in which both entities were associated, which is an infrequent form of hepatosplenic T-cell lymphoma. In addition, we review the role of the markers of podocyte dedifferentiation in this glomerulopathy and its pathophysiology and treatment.


Assuntos
Linfo-Histiocitose Hemofagocítica , Glomerulonefrite , Antígenos de Diferenciação , Insuficiência Renal , Linfoma , Transtornos Linfoproliferativos
19.
Biosci Rep ; 38(2)2018 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-29599129

RESUMO

The aim of the present study is to analyze the effects of 5-aminoisoquinoline (5-AIQ), a poly(ADP-ribose) polymerase-1 (PARP1) inhibitor, over renal dysfunction and fibrosis during recovery phase of cisplatin (CisPt)-induced acute kidney injury (AKI) in rats. Male Wistar rats were distributed in three groups (n=8 each group): control, CisPt, and CisPt + 5-AIQ. Control and CisPt groups received a subcutaneous injection of either saline or 7 mg/kg CisPt, respectively. CisPt + 5-AIQ group received two intraperitoneal injections of 10 mg/kg 5-AIQ 2 h before and 24 h after CisPt treatment. Thirteen days after the treatment, rats were housed in metabolic cages and 24-h urine collection was made. At day 14, CisPt-treated rats showed increased diuresis, N-acetyl-ß-d-glucosaminidase (NAG) excretion, glucosuria and sodium fractional excretion (NaFE), and decreased creatinine clearance (CrCl). 5-AIQ significantly increased CrCl and decreased NAG excretion, glucosuria, and NaFE. In plasma, CisPt increased sodium, urea, and creatinine concentrations, while 5-AIQ treatment decreased these variables to the levels of control group. 5-AIQ completely prevented the body weight loss evoked by CisPt treatment. CisPt also induced an increased renal expression of PAR polymer, α-smooth muscle actin (α-SMA), transforming growth factor-ß1 (TGF-ß1), and collagen-IV. These variables were decreased in CisPt + 5-AIQ group. Tubular lesions and renal fibrosis were also decreased by 5-AIQ treatment. We conclude that inhibition of PARP1 with 5-AIQ can attenuate long-term nephrotoxic effects associated with the CisPt treatment, preventing renal dysfunction and body weight decrease and ameliorating tubular lesions and collagen deposition.


Assuntos
Injúria Renal Aguda , Cisplatino/efeitos adversos , Isoquinolinas/farmacologia , Rim , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Animais , Cisplatino/farmacologia , Fibrose , Rim/metabolismo , Rim/patologia , Testes de Função Renal , Masculino , Ratos , Ratos Wistar
20.
Oncotarget ; 9(3): 4120-4133, 2018 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-29423109

RESUMO

Immune-checkpoint inhibitors show encouraging results in cancer treatment, but the clinical benefit is limited exclusively to a subset of patients. We analyzed the density and composition of tumor T-cell infiltration in non-small-cell lung carcinoma (NSCLC) in relation to PD-L1 and HLA class I (HLA-I) expression. We found that positive HLA-I expression, independently on PD-L1 status, is the key factor determining the increased density of the immune infiltrate. When both markers were analyzed simultaneously, we identified four phenotypes of HLA-I and PD-L1 co-expression. They demonstrated different patterns of tumor infiltration and clinicopathologic characteristics, including the tumor size and lymphatic spread. All HLA-I+/PD-L1+ tumors had a high degree of intratumoral infiltration with CD8+T-lymphocytes, whereas HLA-I loss was associated with a significantly reduced number of tumor infiltrating T-lymphocytes mostly restrained in the stroma surrounding the tumor nest. HLA-I-negative/PD-L1-positive tumors had bigger size (T) and lower grade of infiltration with CD8+T-cells. It represents a cancer immune escape phenotype that combines two independent mechanisms of immune evasion: loss of HLA-I and upregulation of PD-L1. Using GCH-array analysis of human lung cancer cell lines we found that the loss of heterozygosity (LOH) with complete or partial deletion of HLA-I genes is the principal mechanism of HLA-I alterations. This irreversible defect, which could potentially decrease the clinical efficacy of lung cancer immunotherapy, appears to be underestimated. In conclusion, our results suggest that the analysis of HLA-I is very important for the selection of potential responders to cancer immunotherapy.

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