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1.
Adv Exp Med Biol ; 1232: 25-31, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31893390

RESUMO

Hypoxic ischemic encephalopathy (HIE) leads to significant mortality and morbidity, and therapeutic hypothermia (TH) has become a standard of care following HIE. After TH, the body temperature is brought back to 37 °C. Early electroencephalography (EEG) is a reliable outcome biomarker following HIE. We hypothesized that changes in cerebral oxidative metabolism, measured as Δ[oxCCO], in relation to changes in brain tissue oxygenation (measured as Δ[HbD]) during rewarming will correlate with injury severity as evidenced on amplitude integrated EEG/EEG at initial presentation. Broadband near-infrared spectroscopy (NIRS) and systemic data were collected during rewarming from 14 infants following HIE over a mean period of 12.5 h. All infants were monitored with video EEG telemetry using a standard neonatal montage. aEEG and EEG background was classified into mild, moderate and severely abnormal groups based on the background pattern. Two infants had mild, 6 infants had moderate and another 6 infants had severe abnormality at presentation. The relationship between [oxCCO] and [HbD] was evaluated between two groups of infants with abnormal electrical activity (mild vs moderate to severe). A significant difference was noted between the groups in the relationship between [oxCCO] and [HbD] (as r2) (p = 0.02). This result indicates that the mitochondrial injury and deranged oxidative metabolism persists in the moderate to severely abnormal group during rewarming.


Assuntos
Eletroencefalografia , Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Biomarcadores/análise , Encéfalo/metabolismo , Humanos , Hipóxia-Isquemia Encefálica/diagnóstico , Lactente , Recém-Nascido , Reaquecimento
2.
Br J Radiol ; 93(1105): 20190562, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31603347

RESUMO

OBJECTIVE: Patients with diabetes mellitus, diabetic nephropathy (DN) and healthy donor were analyzed to test whether the early DN patients can be detected using both blood oxygenation level dependent (BOLD) and diffusion tensor imaging. METHODS: This study was approved by the Ethics Committee of our hospital. MR images were acquired on a 3.0-Tesla MR system (Discovery MR750, General Electric, Milwaukee, WI). 30 diabetic patients were divided into NAU (normal to mildly increased albuminuria, N = 15) and MAU (moderately increased albuminuria, N = 15) group based on the absence or presence of microalbuminuria. 15 controls with sex- and age-matched were enrolled in the study. Prior to MRI scan, all participants were instructed to collect their fresh morning urine samples for quantitative measurement of urinary microalbumin and urinary creatinine. Then, the estimations of serum creatinine, serum uric acid, HbAlc and fasting plasma glucose as well as fundus examinations were performed in all subjects. Then, the values of albumin-creatinine ratio (ACR) and estimated glomerular filtration rate were also calculated. All subjects underwent renal diffusion tensor imaging (DTI) and BOLD acquisition after fasting for 4 h. Regions of interest were placed in renal medulla and cortex for evaluating apparent diffusion coefficient (ADC), fractional anisotropy (FA) and R2* values by two experienced radiologists. The consistency between the two observations was estimated using intragroup correlation coefficients. To test differences in ADC, FA and R2* values across the three groups, the data were analyzed using separate one-way ANOVAs. Post-hoc pair wise comparisons were then performed using t-test. To investigate the clinical relevance of imaging parameters in both regions across the three groups, the correlations of values of the ACR/estimated glomerular filtration rate and of the ADC/FA/R2* were calculated. RESULTS: There was a high level of consistency of those ADC, FA and R2* values across the three groups on both renal cortex and medulla measured by the two doctors. The FA value of medulla in MAU group was lower than that in control (p < 0.01). The R2* value of medulla in the NAU group was higher than that in the control (p < 0.01), and the R2* value of medulla in the MAU group was lower than that in the control (p = 0.009) . Moreover, the current study revealed a decreasing trend in FA values of the renal medulla from the control group to NAU and MAU groups. Finally, a weak negatively correlation between medullary R2* and ACR was found in current study. CONCLUSION: Medullary R2* value might be a new more sensitive predictor of early DN. Meanwhile, BOLD imaging detected the medullary hypoxia at the simply diabetic stage, while DTI didn't identify the medullary directional diffusion changes at this stage. Based on our assumption mentioned above, it's presumable that BOLD imaging may be more sensitive for assessment of the early renal function changes than DTI. These imaging techniques are more accurate and practical than conventional tests. ADVANCES IN KNOWLEDGE: Non-invasive MRI was used to detect renal function changes at early DN stage.


Assuntos
Nefropatias Diabéticas/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Anisotropia , Biomarcadores/análise , Imagem de Tensor de Difusão , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Testes de Função Renal , Masculino , Pessoa de Meia-Idade
3.
Chemosphere ; 238: 124616, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31466003

RESUMO

The Alagados Reservoir (Southern Brazil) is used as water supply, and since 2002 there have been reports with a presence of cyanobacterial blooms and cyanotoxins. In order to assess the water quality and the ecological integrity of the reservoir, we evaluated biochemical, genotoxic and osmoregulatory biomarkers in the freshwater cichlid fish (Geophagus brasiliensis) that were exposed to PSTs. The fish were sampled in the Alagados Reservoir in February 2016 (Summer) and were divided in three groups: 1) Reservoir group (RES): fish were collected immediately after sampling; 2) Depuration group (DEP): fish were submitted to the depuration experiment for 90 days in the laboratory; and 3) Reproduction group (REP): fish were kept in the laboratory until the fertilization and the chemical analyses were performed on the offspring (F1 generation). In the RES and DEP the blood, brain, muscle, liver and gills were collected for biochemical, genotoxic and osmoregulatory biomarkers analysis. Our results showed that the fish from the Alagados Reservoir (RES) presented oxidative stress and DNA damage; and after 90 days (DEP), the antioxidant system and DNA damage were recovered. Although PSTs were considered a risk to the ecological integrity of this water body; PSTs concentrations were not found in the tissues of the F1 generation. In addition, the biomarkers used were useful tools to evaluate the effects of environment contamination. Therefore, it is necessary to develop new technologies and monitoring programs in order to reduce cyanobaterial blooms, cyanotoxins and human activities that cause the contamination in aquatic environments.


Assuntos
Biomarcadores/análise , Ciclídeos/metabolismo , Dano ao DNA/efeitos dos fármacos , Alimentos Marinhos/análise , Toxinas Biológicas/análise , Poluentes Químicos da Água/análise , Animais , Ciclídeos/crescimento & desenvolvimento , Monitoramento Ambiental , Humanos , Toxinas Biológicas/toxicidade , Poluentes Químicos da Água/toxicidade
4.
Biochem Med (Zagreb) ; 30(1): 010501, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31839719

RESUMO

The current scenario of in vitro and in vivo diagnostics can be summarized using the "silo metaphor", where laboratory medicine, pathology and radiology are three conceptually separated diagnostic disciplines, which will increasingly share many comparable features. The substantial progresses in our understanding of biochemical-biological interplays that characterize many human diseases, coupled with extraordinary technical advances, are now generating important multidisciplinary convergences, leading the way to a new frontier, called integrated diagnostics. This new discipline, which is currently defined as convergence of imaging, pathology and laboratory tests with advanced information technology, has an enormous potential for revolutionizing diagnosis and therapeutic management of human diseases, including those causing the largest number of worldwide deaths (i.e. cardiovascular disease, cancer and infectious diseases). However, some important drawbacks should be overcome, mostly represented by insufficient information technology infrastructures, costs and enormous volume of different information that will be integrated and delivered. To overcome these hurdles, some specific strategies should be defined and implemented, such as planning major integration of exiting information systems or developing innovative ones, combining bioinformatics and imaging informatics, using health technology assessment for assessing cost and benefits, providing interpretative comments in integrated reports, developing and using expert systems and neural networks, overcoming cultural and political boundaries for generating multidisciplinary teams and integrated diagnostic algorithms.


Assuntos
Doenças Cardiovasculares/diagnóstico , Neoplasias/diagnóstico , Sepse/diagnóstico , Biomarcadores/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Subunidade beta da Proteína Ligante de Cálcio S100/metabolismo , Tomografia , Troponina/análise
5.
Medicine (Baltimore) ; 98(52): e18465, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876730

RESUMO

This study aimed to investigate the correlation of long noncoding RNA zinc finger antisense 1 (lncRNA ZFAS1) expression with disease risk, disease severity and inflammatory cytokines levels in lumbar disc degeneration (LDD) patients.83 LDD patients underwent surgery and 28 traumatized, non-LDD patients underwent lumbar disc surgery (controls) were consecutively enrolled in this case-control study. Lumbar disc tissue was obtained during surgery and herniated nucleus pulposus (HNP) was isolated to detect lncRNA ZFAS1 expression and inflammatory cytokines mRNA levels by RT-qPCR, and determine protein levels of inflammatory cytokines by western blot.HNP lncRNA ZFAS1 expression in LDD patients was up-regulated compared with controls (P < .001), and receiver operating characteristic (ROC) curve showed lncRNA ZFAS1 expression disclosed a good predictive value for LDD risk with area under curve (AUC) 0.753 (95% CI 0.646-0.859). And after adjustment by age, gender and body mass index (BMI), lncRNA ZFAS1 (P = .017) remained to be an independent predictive factor for higher LDD risk. In addition, lncRNA ZFAS1 expression was positively associated with Modified Pfirrmann Grade (P = .015). As to inflammatory cytokines, lncRNA ZFAS1 expression was observed to be positively correlated with TNF-α (P = .002), IL-1ß (P = .007) and IL-6 (P = .015) mRNAs expressions while reversely associated with IL-10 mRNA level (P = .014); and lncRNA ZFAS1 expression was also positively correlated with protein levels of TNF-α (P = .038) and IL-6 (P = .027) while reversely associated with IL-10 protein expression (P = .039).lncRNA ZFAS1 expression associates with increased risk, elevated disease severity and higher inflammatory cytokines levels in LDD patients.


Assuntos
Citocinas/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Deslocamento do Disco Intervertebral/metabolismo , Disco Intervertebral/metabolismo , Vértebras Lombares , RNA Antissenso/metabolismo , RNA Longo não Codificante/metabolismo , Adulto , Biomarcadores/análise , Western Blotting , Estudos de Casos e Controles , Citocinas/análise , Feminino , Humanos , Interleucina-10/análise , Interleucina-10/metabolismo , Interleucina-1beta/análise , Interleucina-1beta/metabolismo , Interleucina-6/análise , Interleucina-6/metabolismo , Disco Intervertebral/química , Masculino , Pessoa de Meia-Idade , RNA Longo não Codificante/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/metabolismo
7.
Medicine (Baltimore) ; 98(50): e18322, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852121

RESUMO

BACKGROUND: Drug induced liver injury (DILI) is an increasing cause of acute liver injury especially with increasing need for pharmacotherapy of widening comorbidities amongst our ever-aging population. Uncertainty however remains regarding both acceptable and widely agreeable diagnostic algorithms as well a clear understanding of mechanistic insights that most accurately underpins it. In this review, we have explored the potential role of emerging novel markers of DILI and how they could possibly be integrated into clinical care of patients. METHODS: We explored PUBMED and all other relevant databases for scientific studies that explored potential utility of novel biomarkers of DILI, and subsequently carried out a narrative synthesis of this data. As this is a narrative review with no recourse to patient identifiable information, no ethics committee's approval was sought or required. RESULTS: Novel biomarkers such as microRNA-122 (miR-122) profiles, high mobility group box-1 (HMGB1), glutamate dehydrogenase (GLDH), and cytokeratin-18 (K-18), amongst others do have the potential for reducing diagnostic uncertainties associated with DILI. CONCLUSION: With the increasing validation of some of the novel liver biomarkers such as K-18, mir-122, HMGB-1, and GLDH, there is the potential for improvement in the diagnostic uncertainty commonly associated with cases of DILI.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Glutamato Desidrogenase/análise , Proteína HMGB1/análise , Queratina-18/análise , MicroRNAs/análise , Medição de Risco/métodos , Biomarcadores/análise , Humanos
8.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(5): 731-736, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31762246

RESUMO

OBJECTIVE: To develop a method for detecting nicotine and cotinine in hair by hydrophilic interaction chromatography tandem mass spectrometry. METHODS: Hair samples were hydrolyzed in sodium hydroxide solution before extraction with dichloromethane. The samples were blown to dry with nitrogen and dissolved with mobile phase. The filtrate of the samples was injected into a chromatographic-mass spectrometry system for analysis. The separation was performed by a hydrophilic column, with which methanol-0.1% ammonia was used as the mobile phase. The quantitative detection of Nicotine and Cortinine was carried out with electron spray ionization-triple quadrupole mass spectrometry. The established method was used for detecting nicotine and cotinine in 602 hair samples of pregnant women and 31 hair and urine samples of volunteers. RESULTS: A standard curve was drawn for the established method of hydrophilic liquid chromatography tandem mass spectrometry. Good linearity was obtained for detecting nicotine and cotinine in the range of 0.030-100.000 µg/L, with a detection limit (MDL) of 0.007 6 µg/g and 0.004 4 µg/g, respectively. The inter-day and intra-day precisions reached a level of less than 10%. The recoveries of the spiked samples ranged from 81.0% to 102.0%. About 0.020-0.260 µg/g nicotine and 0.004 8-0.069 0 µg/g cotinine were detected in the pregnant women without exposure to secondhand smoking (SHS), compared with 0.029-0.350 µg/g nicotine and 0.005 6-0.085 0 µg/g cotinine in those exposed to SHS. Nicotine and cotinine were also found in the hair and urine samples of volunteers, which were correlated with smoking (P < 0.05). A dose-response relationship were found between smoking and hair nicotine. CONCLUSIONS: The proposed method is accurate and sensitive for detecting nicotine and cotinine in hair samples. Hair nicotine can be a specific biomarker for assessing exposure to tobacco smoking.


Assuntos
Cotinina/análise , Cabelo/química , Nicotina/análise , Biomarcadores/análise , Cromatografia Líquida , Feminino , Humanos , Interações Hidrofóbicas e Hidrofílicas , Gravidez , Espectrometria de Massas em Tandem , Poluição por Fumaça de Tabaco
9.
Isr Med Assoc J ; 21(11): 747-751, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31713364

RESUMO

BACKGROUND: The frequency of increased high-sensitivity C-reactive protein (hs-CRP) and the time course of evolution of their levels in patients with acute idiopathic pericarditis (AIP) are not well established. OBJECTIVES: To assess the time course of evolution of hs-CRP levels and the possible clinical significance of maximal hs-CRP levels in patients with AIP. METHODS: We retrospectively reviewed the medical files of 241 patients admitted to the hospital with a diagnosis of AIP between March 2006 and March 2017. Data on demographics, time of symptom onset, laboratory and imaging findings, and outcome were collected. RESULTS: Data on serum hs-CRP levels were available for 225 patients (age 18-89 years, 181 men). Fever, pleural effusion, and age were independently associated with hs-CRP levels. Major cardiac complications (MCC) (death, cardiac tamponade, cardiogenic shock, large pericardial effusion, ventricular tachycardia, pericardiocentesis, or pericardiectomy) were more common in patients with hs-CRP levels above the median compared to those below (21.2% vs. 4.5%, respectively, P < 0.001). Hs-CRP levels were independently associated with MCC (odds ratio [OR] 1.071, 95% confidence interval [95%CI] 1.016-1.130, P = 0.011). Hs-CRP levels were elevated in 76.0%, 92.3% and 96.0% of the patients tested <6 hours, 7-12 hours, and >12 hours of symptom onset, respectively (P = 0.003). The frequency of elevated hs-CRP among patients tested > 24 hours was 98.1%. CONCLUSIONS: Hs-CRP levels rise rapidly among patients with AIP. Maximal hs-CRP levels are associated with MCC. A normal hs-CRP level is rare among patients tested > 24 hours of symptom onset.


Assuntos
Proteína C-Reativa/análise , Pericardite/sangue , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Feminino , Humanos , Israel , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
10.
Z Gastroenterol ; 57(11): 1298-1303, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31739375

RESUMO

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) can involve different organs and is diagnosed by a combination of clinicopathological features, including storiform fibrosclerosis infiltrated by numerous IgG4-positive plasma cells that frequently forms tumor-like lesions with or without associated obliterative phlebitis. Involvement of the stomach is rare and can occur as part of a multiorgan involvement of IgG4-RD or as isolated gastric involvement. CASE REPORT: We report 2 female patients with therapy-refractory gastric ulcers associated with gastric wall thickening and lymphadenopathy that were highly suggestive of gastric cancer or lymphoma. Biopsies failed to confirm a diagnosis, and IgG4-RD was diagnosed only after surgical resection in both patients. The previous literature on gastric IgG4-RD is summarized and shows different characteristics in patients with multiorgan IgG4-RD and isolated gastric IgG4-RD. As reported for autoimmune pancreatitis type 1, patients with multiorgan IgG4-RD are mainly elderly men with frequently elevated serum IgG4 concentrations. In contrast, isolated gastric IgG4-RD predominantly affects female patients with normal serum IgG4 levels. Surgical resection is commonly performed due to the clinical suspicion of malignancy and the absence of findings indicative of IgG4-RD on biopsy. Today, diagnosis is confirmed histopathologically only after resection. CONCLUSION: IgG4-RD should be taken into account when gastric malignancy is suspected endoscopically or radiologically and biopsies fail to confirm the presence of a malignancy (especially subepithelial tumors or refractory gastric ulcers). Serum IgG4 concentrations are insufficient to confirm localized gastric IgG4-RD. Diagnostic workups need to be improved to avoid unnecessary surgical resections with the attendant potential morbidity and mortality.


Assuntos
Doença Relacionada a Imunoglobulina G4/diagnóstico , Imunoglobulina G/sangue , Plasmócitos/imunologia , Idoso , Biomarcadores/análise , Diagnóstico Diferencial , Feminino , Humanos , Doença Relacionada a Imunoglobulina G4/imunologia , Doença Relacionada a Imunoglobulina G4/cirurgia , Linfadenopatia/etiologia , Neoplasias Gástricas/diagnóstico
11.
Biochemistry (Mosc) ; 84(11): 1346-1358, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31760922

RESUMO

Neprilysin (NEP) is a zinc-dependent metalloproteinase that exists in organisms in both transmembrane and soluble forms. NEP substrates are involved in regulating the cardiovascular and nervous systems. In this review, we discuss some of the biochemical characteristics and physiological functions of this enzyme with special emphasis on the use of NEP as a therapeutic target. The history and various physiological aspects of applying NEP inhibitors for treating heart failure and attempts to increase NEP activity when treating Alzheimer's disease using gene and cell therapies are described. Another important issue discussed is the role of NEP as a potential marker for predicting the risk of cardiovascular disease complications. The diagnostic and prognostic performance of soluble NEP in various types of heart failure is analyzed and presented. We also discuss the methods and approaches for measuring NEP activity for prognosis and diagnosis, as well as a possible new role of natriuretic peptides (NEP substrates) in cardiovascular diagnostics.


Assuntos
Doença de Alzheimer/diagnóstico , Neprilisina/metabolismo , Doença de Alzheimer/tratamento farmacológico , Biomarcadores/análise , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Neprilisina/análise , Neprilisina/antagonistas & inibidores , Inibidores de Proteases/uso terapêutico , Sistema Renina-Angiotensina , Yin-Yang
12.
Rev Med Suisse ; 15(671): 2082-2086, 2019 Nov 13.
Artigo em Francês | MEDLINE | ID: mdl-31742938

RESUMO

Chronic obstructive pulmonary disease (COPD) is a heterogeneous group of chronic respiratory diseases which phenotyping is less codified as for asthma yet as essential. The phenotype helps to better understand the evolution of the disease, punctuated by exacerbations and favors a better targeting for treatments and clinical work-up. The latest studies, mostly based on the ECLIPSE and SPIROMICS cohorts, highlight the importance of the search for eosinophilia and the complete assessment of cardiovascular comorbidities. This article will discuss the role of lung function, exacerbations, biomarkers, and comorbidities in COPD phenotyping.


Assuntos
Fenótipo , Doença Pulmonar Obstrutiva Crônica , Biomarcadores/análise , Humanos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia
13.
Georgian Med News ; (294): 98-103, 2019 Sep.
Artigo em Russo | MEDLINE | ID: mdl-31687958

RESUMO

The article reveals the modern aspects of IPF pathogenesis in with an emphasis on the main proposed prognostic biomarkers. IPF remains the leader among diseases with unknown etiology, the diagnosis and management of which are not very successful, despite the obvious progress in molecular medicine. There is presented analysis of the significance of IPF potential biomarkers and their concentrations in the blood and bronchoalveolar lavage fluids (BAL): endothelin-1, CC-chemokine ligand 18, interleukin-1, surfactant protein SP-D in the review. The role of their changing levels in the blood and BAL for assessing the course of the IPF and its prognosis, as well as the prevailing importance of the polymorphism of the genes encoding them, is shown. Obviously, the progressive accumulation of fibroblast-myofibroblast cells in the lungs IPF patients worsens the prognosis of disease, forms its own environment with a set of cytokines, growth factors, collagen, fibronectin in the extracellular matrix of fibrous lungs. The insufficient amount of studies in the face of the rarity of the disease leaves a lot of controversial issues for solution in the future. Obviously, to assess the prognosis of IPF mortality, it is necessary to include a very large number of patients, to extend the observation period, which increases their cost and reduces the opportunities and desire of pharmaceutical companies to participate in these studies.


Assuntos
Biomarcadores/sangue , Líquido da Lavagem Broncoalveolar/química , Fibrose Pulmonar Idiopática/diagnóstico , Pulmão/metabolismo , Biomarcadores/análise , Quimiocinas CC , Endotelina-1 , Humanos , Fibrose Pulmonar Idiopática/sangue , Fibrose Pulmonar Idiopática/mortalidade , Interleucina-1 , Pulmão/fisiopatologia , Prognóstico , Proteína D Associada a Surfactante Pulmonar/análise , Proteína D Associada a Surfactante Pulmonar/sangue , Surfactantes Pulmonares/análise , Surfactantes Pulmonares/sangue
14.
Endocrinol. diabetes nutr. (Ed. impr.) ; 66(9): 571-578, nov. 2019. tab, graf
Artigo em Inglês | IBECS | ID: ibc-184380

RESUMO

Introduction: Psychological and neuroendocrine alterations are typical characteristics in anorexia nervosa patients. The role of adipokines and cytokines as mediators of body systems' adaptations to the patients' abnormal eating behavior is not well understood. The duration of disease seems to be a determinant of nutritional status and associated hormone changes. We aimed to assess whether alterations in adipokines, cytokines and cortisol do already exist in patients with a recent disease onset by means of a case-control study. Methods: Forty-one adolescent female patients on their first-episode and diagnosed with anorexia nervosa, were matched by age and socioeconomic status (SES) (1:1) with healthy girls. Leptin, soluble leptin receptor (sOB-R), adiponectin, cortisol, and the cytokines IL-1β, IL-2, IL-6 and TNF-alfa were examined. Results: The results showed reduced leptin and increased sOB-R and cortisol levels in AN patients. Adiponectin was also increased but opposite to the previous biomarkers did not correlate with BMI Z-score. Serum TNF-alfa and IL-2 showed significantly lower and higher values, respectively, in the AN patients than in the controls. Cortisol showed the strongest correlation with sOB-R (r = 0.436; P = 0.005). Conclusions: Our study confirms previous findings on adipokine and cortisol alterations in AN patients, while overall cytokine results did not show a clear disruption in AN patients with short disease duration. The results highlight the need to disentangle the role of the sOB-R in the interactions between leptin and cortisol secretion


Introducción: Las alteraciones psicológicas y neuroendocrinas son típicas de las pacientes con anorexia nerviosa (AN). El papel de las adipoquinas y citocinas como mediadores de la adaptación del organismo al comportamiento alimentario alterado no es bien conocido. La duración de la enfermedad parece ser un determinante del estado nutricional y de los cambios hormonales asociados. Nuestro objetivo ha sido establecer si existen alteraciones de adipoquinas, citocinas y cortisol en pacientes con un comienzo reciente de la enfermedad en un estudio caso-control. Métodos: Cuarenta y una chicas adolescentes diagnosticadas de AN en su primer episodio fueron emparejadas por edad y estado socioeconómico (1:1) con adolescentes sanas. Se midieron la leptina, el receptor soluble de leptina, la adiponectina, el cortisol y las citocinas IL-1β, IL-2, IL-6 y TNF-alfa. Resultados: Las pacientes con AN mostraron niveles reducidos de leptina y elevados de receptor de leptina y cortisol. La adiponectina también se observó elevada pero, al contrario que los otros marcadores, no correlacionó con el Z-score del índice de masa corporal. Las pacientes mostraron valores de TNF-alfa e IL-2 menores y mayores, respectivamente, que las controles. El cortisol y el receptor de leptina mostraron la correlación más fuerte de todas las observadas (r = 0,436; p = 0,005). Conclusiones: Se confirman los resultados previos de adipoquinas y cortisol en pacientes con AN. Sin embargo, los resultados globales de citocinas no muestran una alteración clara en pacientes con corta duración de la enfermedad. Los resultados apuntan la necesidad de desentrañar el papel del receptor soluble de leptina en las interacciones entre leptina y cortisol


Assuntos
Humanos , Feminino , Adolescente , Anorexia/diagnóstico , Anorexia/fisiopatologia , Análise Química do Sangue , Biomarcadores/análise , Leptina/sangue , Hidrocortisona/sangue , Citocinas/sangue , Estudos de Casos e Controles , Antropometria
15.
Clin Exp Rheumatol ; 37 Suppl 120(5): 73-87, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31621570

RESUMO

Osteoarthritis (OA) is a disease of the whole joint, including synovium, bone and cartilage. OA is a slow degenerative and very heterogeneous disease, with both varying levels of disease activity and progression. Biomarkers are urgently needed to assist drug developers in selecting and developing the projects with the highest chance of success. Biomarkers for enrichment of clinical studies, early efficacy as well as other diagnostic tools are needed. Osteoporosis and OA have many similarities. In osteoporosis an armamentarium of treatments are now available with high clinical efficacy and well-described effects on biomarkers. Possibly, lessons learned from the osteoporosis field in the use of biomarkers may be applied in the OA field, from both technical and scientific perspectives. To help guide the way, the FDA has recently published the BEST guidelines, to facilitate obtaining a common vocabulary to assist biomarker researchers. In the current review, we will review the biomarkers of OA, with emphasis on bone, cartilage and synovial biomarkers, and draw clear perspectives to the use of biomarkers for drug development and clinical practice in the osteoporosis field.


Assuntos
Biomarcadores/análise , Cartilagem Articular , Osteoartrite , Biomarcadores/metabolismo , Cartilagem Articular/metabolismo , Humanos , Osteoartrite/metabolismo , Osteoporose/metabolismo , Membrana Sinovial
16.
Cancer Immunol Immunother ; 68(11): 1733-1745, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31598757

RESUMO

Tumors and their surrounding area represent spatially organized "ecosystems", where tumor cells and the immune contextures of the different compartments are in a dynamic interplay, with potential clinical impact. Here, we aimed to investigate the prognostic significance of peritumoral tertiary lymphoid structures (TLS) either alone or jointly with the intratumoral densities and spatial distribution of CD8 + and CD163 + cells in breast cancer (BCa) patients. TLS were identified peritumorally, within the area distancing up to 5 mm from the infiltrative tumor border, counted and further characterized as adjacent or distal, in formalin-fixed, paraffin-embedded tumor tissue samples from a cohort of 167 patients, with histologically confirmed invasive ductal BCa. TLS and tumor-infiltrating immune cells were determined by H&E and immunohistochemistry. Clinical follow-up was available for 112 of these patients. Patients with peritumoral TLS exhibited worse disease-free survival (DFS) and overall survival (OS) as compared to patients lacking TLS. Moreover, the density of peritumoral TLS was found to be crucial for prognosis, since patients with abundant TLS exhibited the worst DFS and OS. By combining the density of adjacent TLS (aTLS) with our recently published intratumoral signatures based on the differential distribution of CD8 + and CD163 + in the tumor center and invasive margin, we created two improved immune signatures with superior prognostic strength and higher patient population coverage. Our observations strengthen the notion for the fundamental role of the dynamic interplay between the immune cells within the tumor microenvironment (center/invasive margin) and the tumor surrounding area (peritumoral TLS) on the clinical outcome of BCa patients.


Assuntos
Biomarcadores/análise , Neoplasias da Mama/imunologia , Linfócitos do Interstício Tumoral/imunologia , Estruturas Linfoides Terciárias/imunologia , Microambiente Tumoral/imunologia , Neoplasias da Mama/patologia , Feminino , Seguimentos , Humanos , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida , Estruturas Linfoides Terciárias/patologia
17.
Results Probl Cell Differ ; 68: 321-353, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31598863

RESUMO

When shifting research focus from model to non-model species, many differences in the working approach should be taken into account and usually methodological modifications are required because of the lack of genetics/genomics and developmental information for the vast majority of organisms. This lack of data accounts for the largely incomplete understanding of how the two components-genes and developmental programs-are intermingled in the process of evolution. A deeper level of knowledge was reached for a few model animals, making it possible to understand some of the processes that guide developmental changes during evolutionary time. However, it is often difficult to transfer the obtained information to other, even closely related, animals. In this chapter, we present and discuss some examples, such as the choice of molecular markers to be used to characterize differentiation and developmental processes. The chosen examples pertain to the study of germline in molluscs, reptiles, and other non-model animals.


Assuntos
Biomarcadores/metabolismo , Diferenciação Celular , Células Germinativas/citologia , Células Germinativas/metabolismo , Moluscos/citologia , Répteis , Animais , Biomarcadores/análise , Répteis/embriologia
18.
Lakartidningen ; 1162019 Oct 08.
Artigo em Sueco | MEDLINE | ID: mdl-31593290

RESUMO

Due to a low level of understanding of mechanisms involved in spontaneous preterm delivery there is a lack of reliable biomarkers. Existing biomarkers have a low positive predictive value but a high negative predictive value. Use of tests with high negative predictive value will reduce unnecessary interventions and hospitalization of women with threatening preterm delivery. When given to the right pregnant women, antenatal corticosteroid treatment are still the most important obstetrical intervention and reduces both neonatal mortality and short- and long-term morbidity.Several ongoing national Swedish multicenter studies may increase the understanding of the roles of cervical length, preeclampsia screening and magnesium sulfate dosage in the context of preterm delivery in a Nordic setting. Major development has been achieved in prediction and prevention of preterm preeclampsia at the cost of a 10% screen positive rate.


Assuntos
Nascimento Prematuro , Corticosteroides/administração & dosagem , Biomarcadores/análise , Cerclagem Cervical , Medida do Comprimento Cervical , Colo do Útero/anatomia & histologia , Feminino , Fibronectinas/análise , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Sulfato de Magnésio/administração & dosagem , Pessários , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/prevenção & controle , Gravidez , Nascimento Prematuro/diagnóstico , Nascimento Prematuro/prevenção & controle , Nascimento Prematuro/terapia , Cuidado Pré-Natal/métodos , Progesterona/administração & dosagem , Suécia , Tocolíticos/administração & dosagem
19.
J Appl Oral Sci ; 27: e20180476, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31596364

RESUMO

OBJECTIVES: Miniscrew has been frequently used, considering that anchorage control is a critical point in orthodontic treatment, and its failure, the main adverse problem. Using two groups of stable (successful) and unstable (failed) mini-implants, this in vivo study aimed to quantify proinflammatory cytokines IL-1 α, IL-6, IL-17, and TNF-α and osteoclastogenesis marker RANK, RANKL, and OPG in gingival tissue, using the real-time polymerase chain reaction technique. METHODOLOGY: Thirteen patients of both sexes (11-49 years old) under orthodontic treatment were selected, obtaining 11 successful and 7 failed mini-implants. The mini-implants were placed and removed by the same surgeon, in both jaws. The mean time of permanence in the mouth was 29.4 months for successful and 7.6 months for failed mini-implants. At removal time, peri-mini-implant gingival tissue samples were collected and processed for quantification of the proinflammatory cytokines and osteoclastogenesis markers. Nonparametric Wilcoxon rank-sum test considering the clusters and Kruskal-Wallis test were used for statistical analysis (α=0.05). RESULTS: No significant difference (p>0.05) was observed between the groups for either quantification of cytokines or osteoclastogenesis markers, except for IL-6 (p<0.05). CONCLUSIONS: It may be concluded that the expression of IL-1α, IL-17, TNF-α, RANK, RANKL, and OPG in peri-implant gingival tissue were not determinant for mini-implant stability loss, but the higher IL-6 expression could be associated with mini-implant failure.


Assuntos
Citocinas/análise , Implantes Dentários/efeitos adversos , Gengivite/patologia , Procedimentos de Ancoragem Ortodôntica/efeitos adversos , Osteogênese/fisiologia , Peri-Implantite/patologia , Adolescente , Adulto , Perda do Osso Alveolar , Biomarcadores/análise , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoprotegerina/análise , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
20.
DNA Cell Biol ; 38(11): 1223-1232, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31566423

RESUMO

To date, the clinical course of idiopathic membranous nephropathy (iMN) remains unclear and lacks direct and effective diagnostic methods. To better understand the host gene expression changes involved in the iMN process and identify the potential signatures for clinical diagnosis, we performed a whole genome-wide transcriptome profile of peripheral blood cells (PBC) from patients with iMN and healthy controls (HCs). A total of 188 differentially expressed genes (DEGs) were detected in patients with iMN versus HCs. Gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that these DEGs were mainly correlated with protein targeting, ion homeostasis GO terms, and ribosome and phagosome pathways. The top 10 differentially expressed protein-coding genes with >2-fold changes and high expression levels were validated using quantitative real-time PCR, and showed high consistency with the high-throughput sequencing results. HLA-C, S100A8, and FTH1 genes were selected for further validation and showed the most significant difference between the iMN and HC group, indicating that they could be used as potential clinical diagnostic biomarkers. Our results provide novel potential diagnostic signatures for iMN and have important implications for better understanding the pathogenesis of iMN.


Assuntos
Biomarcadores/sangue , Células Sanguíneas/metabolismo , Glomerulonefrite Membranosa , Transcriptoma , Biomarcadores/análise , Estudos de Casos e Controles , Perfilação da Expressão Gênica , Glomerulonefrite Membranosa/sangue , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , RNA/análise , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de RNA
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