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1.
Medicine (Baltimore) ; 100(40): e27463, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34622873

RESUMO

ABSTRACT: Accurate neurological prognostication is of the utmost importance to avoid futile treatments in patients treated with targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA). This study aimed to investigate the prognostic value of serum neutrophil gelatinase-associated lipocalin (NGAL) by comparing with neuron-specific enolase (NSE), which is currently recommended by international guidelines in patients treated with TTM after OHCA.The study included 85 comatose adult patients with OHCA who underwent TTM between May 2018 and December 2020. Serum NGAL and NSE were measured at 24-hour intervals until 72 hours after return of spontaneous circulation (ROSC). The primary outcome was their prognostic performance for poor neurological outcome at 3 months after OHCA.Forty-nine patients (57.6%) had a poor neurological outcome; NGAL levels at all time points measured were significantly higher in these patients than in those with a good outcome (P < .01). NGAL showed lower maximal sensitivity (95% confidence interval [CI]) under a false-positive rate of 0% for the primary outcome compared with NSE (18.2% [95% CI 8.2-32.7] vs 66.7% [95% CI 50.5-80.4]). The combination of NGAL with NSE at 48 h showed the highest sensitivity (69.1% [95% CI 52.9-82.4]) and had the highest area under the curve (0.91 [95% CI 0.81-0.96]) for a poor outcome. The prognostic performance of NGAL alone was inadequate at all time points. However, NGAL combined with NSE at 24 and 28 hours after ROSC showed improved sensitivity compared to NGAL alone.NGAL should be considered a supplementary biomarker in combination with NSE for prognostication in patients with OHCA treated with TTM.


Assuntos
Hipotermia Induzida/métodos , Lipocalina-2/sangue , Parada Cardíaca Extra-Hospitalar/sangue , Parada Cardíaca Extra-Hospitalar/terapia , Fosfopiruvato Hidratase/sangue , Adulto , Fatores Etários , Idoso , Biomarcadores , Coma/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/complicações , Parada Cardíaca Extra-Hospitalar/mortalidade , Prognóstico , Estudos Prospectivos , Fatores Sexuais
2.
Sci Rep ; 11(1): 14630, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34272435

RESUMO

Leptospirosis can cause a high mortality rate, especially in severe cases. This multicenter cross-sectional study aimed to examine both host and pathogen factors that might contribute to the disease severity. A total of 217 leptospirosis patients were recruited and divided into two groups of non-severe and severe. Severe leptospirosis was defined by a modified sequential organ failure assessment (mSOFA) score of more than two or needed for mechanical ventilation support or had pulmonary hemorrhage or death. We found that leptospiremia, plasma neutrophil gelatinase-associated lipocalin (pNGAL), and interleukin 6 (IL-6) at the first day of enrollment (day 1) and microscopic agglutination test (MAT) titer at 7 days after enrollment (days 7) were significantly higher in the severe group than in the non-severe group. After adjustment for age, gender, and the days of fever, there were statistically significant associations of baseline leptospiremia level (OR 1.70, 95% CI 1.23-2.34, p = 0.001), pNGAL (OR 9.46, 95% CI 4.20-21.33, p < 0.001), and IL-6 (OR 2.82, 95% CI 1.96-4.07, p < 0.001) with the severity. In conclusion, a high leptospiremia, pNGAL, and IL-6 level at baseline were associated with severe leptospirosis.


Assuntos
Bacteriemia/sangue , Bacteriemia/imunologia , Imunidade , Leptospira , Leptospirose/sangue , Leptospirose/imunologia , Adulto , Biomarcadores/sangue , Estudos Transversais , DNA Bacteriano , Feminino , Interações Hospedeiro-Patógeno , Humanos , Interleucina-6/sangue , Lipocalina-2/sangue , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Tailândia
3.
J Surg Res ; 266: 222-229, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34023578

RESUMO

INTRODUCTION: Trauma is the leading cause of death among young people. These patients have a high incidence of kidney injury, which independently increases the risk of mortality. As valproic acid (VPA) treatment has been shown to improve survival in animal models of lethal trauma, we hypothesized that it would also attenuate the degree of acute kidney injury. METHODS: We analyzed data from two separate experiments where swine were subjected to lethal insults.  Model 1: hemorrhage (50% blood volume hemorrhage followed by 72-h damage control resuscitation). Model 2: polytrauma (traumatic brain injury, 40% blood volume hemorrhage, femur fracture, rectus crush and grade V liver laceration). Animals were resuscitated with normal saline (NS) +/- VPA 150 mg/kg after a 1-h shock phase in both models (n = 5-6/group). Serum samples were analyzed for creatinine (Cr) using colorimetry on a Liasys 330 chemistry analyzer. Proteomic analysis was performed on kidney tissue sampled at the time of necropsy. RESULTS: VPA treatment significantly (P < 0.05) improved survival in both models. (Model 1: 80% vs 20%; Model 2: 83% vs. 17%). Model 1 (Hemorrhage alone): Cr increased from a baseline of 1.2 to 3.0 in NS control animals (P < 0.0001) 8 h after hemorrhage, whereas it rose only to 2.1 in VPA treated animals (P = 0.004). Model 2 (Polytrauma): Cr levels increased from baseline of 1.3 to 2.5 mg/dL (P = 0.01) in NS control animals 4 h after injury but rose to only 1.8 in VPA treated animals (P = 0.02). Proteomic analysis of kidney tissue identified metabolic pathways were most affected by VPA treatment. CONCLUSIONS: A single dose of VPA (150 mg/kg) offers significant protection against acute kidney injury in swine models of polytrauma and hemorrhagic shock.


Assuntos
Injúria Renal Aguda/prevenção & controle , Hemorragia/complicações , Inibidores de Histona Desacetilases/uso terapêutico , Traumatismo Múltiplo/complicações , Ácido Valproico/uso terapêutico , Injúria Renal Aguda/sangue , Injúria Renal Aguda/etiologia , Animais , Creatinina/sangue , Avaliação Pré-Clínica de Medicamentos , Hemorragia/sangue , Hemorragia/mortalidade , Inibidores de Histona Desacetilases/farmacologia , Rim/efeitos dos fármacos , Rim/metabolismo , Lipocalina-2/sangue , Traumatismo Múltiplo/sangue , Traumatismo Múltiplo/mortalidade , Proteoma/efeitos dos fármacos , Suínos , Ácido Valproico/farmacologia
4.
Breast Dis ; 40(S1): S115-S117, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34057126

RESUMO

OBJECTIVES: Breast cancer is the most prevalent carcinoma found in Indonesian women, and its incidence remains high worldwide. Lipocalin 2 has been linked with the progression of breast cancer. Matrix metalloproteinase 9 (MMP9) is an enzyme that has an important role in angiogenesis. We investigated the relationship between lipocalin 2 and MMP9 and the ability of lipocalin 2 for predicting MMP9 levels in female patients with breast cancer. METHOD: A total of 55 female patients with breast cancer were enrolled in this cross-sectional study. Lipocalin 2 and MMP9 were measured by enzyme-linked immunosorbent assay. RESULTS: Lipocalin 2 was significantly correlated with MMP9 levels (r = 0.756, p < 0.001). Lipocalin 2 levels could describe the MMP9 levels (𝛽 = 0.76, p < 0.001, R2 = 56.9%). CONCLUSION: Higher lipocalin 2 levels in female patients with breast cancer indicate higher MMP9 levels. Lipocalin 2 can be used to predict MMP9 levels.


Assuntos
Neoplasias da Mama/sangue , Lipocalina-2/sangue , Metaloproteinase 9 da Matriz/sangue , Adulto , Neoplasias da Mama/diagnóstico , Congressos como Assunto , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade
5.
BMC Psychiatry ; 21(1): 272, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34039300

RESUMO

BACKGROUND: Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disease that is characterized by its clinical heterogeneity and complex pathophysiology. This complexity comes from the diversity of pathophysiological factors that have been proposed to be involved in the natural history of the disorder. Many theories on OCD pathology support inflammation as a pathophysiological factor, although studies are not consistent on the presence of a pro-inflammatory state among OCD patients. However, some pre-clinical animal studies suggest lipocalin-2 (LCN2), an analogous form of the acute-phase pro-inflammatory protein neutrophil gelatinase-associated lipocalin (NGAL), may be involved in in the regulation of the stress response, which is thought to be disrupted in OCD. METHODS: Twenty-one OCD patients and 19 healthy subjects participated in this exploratory study. Levels of NGAL were assessed in the peripherous blood of all participants. Severity of disease was assessed using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). RESULTS: OCD patients exhibited significantly higher levels of NGAL when compared to healthy control subjects. No correlation was found between elevated levels of NGAL and severity of symptoms. CONCLUSIONS: This is the first study to report elevated levels of NGAL among OCD patients, adding evidence for a possible role of immune dysregulation in the pathophysiology of OCD.


Assuntos
Lipocalina-2/sangue , Transtorno Obsessivo-Compulsivo , Humanos
6.
Curr Med Sci ; 41(2): 323-328, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33877549

RESUMO

Neutrophilic airway inflammation is one of the features of severe asthma. Neutrophil gelatinase-associated lipocalin (NGAL), or lipocalin-2, is a glycoprotein associated with neutrophilic inflammation and can be detected in blood. Recently, blood NGAL levels have been reported to be elevated in chronic obstructive pulmonary disease. However, the clinical significance of serum NGAL levels in patients with asthma has not been elucidated. The aim of this study was to explore the association between serum NGAL level and clinical parameters in patients with asthma. Sixty-one non-smoking people with stable asthma were enrolled in this study. All patients underwent blood collection and pulmonary function tests. The associations between serum NGAL levels and clinical parameters were analyzed retrospectively. Serum NGAL levels in patients with asthma and obstructive ventilatory defect were higher than those in patients with asthma without obstructive ventilatory defect (76.4±51.4 ng/mL vs. 39.3±27.4 ng/mL, P=0.0019). Serum NGAL levels were correlated with forced expired flow at 50% of vital capacity %predicted and forced expired flow at 75% of vital capacity %predicted (r=-0.3373, P=0.0078 and r=-0.2900, P=0.0234, respectively). Results of a multiple regression analysis demonstrated that serum NGAL level was independently associated with obstructive ventilatory defect. Serum NGAL levels were elevated in patients with asthma and obstructive ventilatory defect. NGAL may be involved in airway remodeling possibly mediated by neutrophilic inflammation in asthma.


Assuntos
Obstrução das Vias Respiratórias/sangue , Asma/sangue , Lipocalina-2/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Adulto Jovem
7.
Am J Med Sci ; 361(6): 736-743, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33892917

RESUMO

BACKGROUND: Acute kidney injury (AKI) is increasingly being seen in patients with acute coronary syndromes (ACS) and it is associated with higher short-term and long-term morbidity and mortality. Therefore, it is of paramount importance to identify those ACS patients at risk for the development of AKI. The objective of this study was to evaluate two different plasma biomarkers calprotectin and neutrophil gelatinase-associated lipocalin (NGAL) in early detecting the development of AKI in ACS patients. METHODS: 172 ACS patients admitted to the Coronary Care Unit in Yantai Yuhuangding Hospital were prospectively enrolled. Their blood samples were obtained on admission and subjected to enzyme-linked immunosorbent assay to determine the levels of novel biomarkers. The clinical data and biomarkers were recorded and analyzed. RESULTS: In this study, 23 (13.4%) patients had a diagnosis of AKI. Statistical analysis demonstrated that in ACS patients with AKI, the following two biomarkers were significantly higher than these without AKI: plasma calprotectin (5942.26 ± 1955.88 ng/mL vs. 3210.29 ± 1833.60 ng/mL, p < 0.001) and plasma NGAL (164.91 ± 43.63 ng/mL vs. 122.48 ± 27.33 ng/mL, p < 0.001). Plasma calprotectin and NGAL could discriminate the development of AKI respectively with an area under the ROC curve (AUC) of 0.864 and 0.850. A combination of the two plasma biomarkers calprotectin and NGAL could early discriminate AKI in ACS patients with an AUC of 0.898. CONCLUSIONS: This study demonstrated a promising panel of plasma calprotectin and NGAL as early diagnostic biomarkers for AKI in ACS patients.


Assuntos
Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico por imagem , Injúria Renal Aguda/sangue , Injúria Renal Aguda/diagnóstico por imagem , Complexo Antígeno L1 Leucocitário/sangue , Lipocalina-2/sangue , Síndrome Coronariana Aguda/epidemiologia , Injúria Renal Aguda/epidemiologia , Idoso , Biomarcadores/sangue , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
8.
Ann Hematol ; 100(6): 1401-1409, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33796899

RESUMO

Sickle cell nephropathy (SCN) develops via altered hemodynamics and acute kidney injury, but conventional screening tests remain normal until advanced stages. Early diagnostic biomarkers are needed so that preventive measures can be taken. This study evaluates the role of neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker of SCN in steady state and vaso-occlusive crisis (VOC). In this case-control study, 74 sickle cell disease (SCD) patients (37 in steady state and 37 in VOC) and 53 control subjects had hematological and biochemical measurements including plasma and urine NGAL. Univariate and logistic regression analyses were used to find the associations between variables. The receiver operating characteristic (ROC) curve was used to determine the diagnostic performance characteristics of plasma and urine NGAL for detection of VOC. Plasma and urine NGAL, urine microalbumin:creatinine ratio, and urine protein:creatinine ratio were significantly higher in VOC. Microalbuminuria was present in 17.1% steady state and 32.0% VOC patients. Microalbuminuria showed significant correlations with age, plasma NGAL, WBC, and hemolytic parameters. Area under the ROC curve for plasma NGAL was 0.69 (95%CI = 0.567-0.813; p = 0.006) and 0.86 (95%CI = 0.756-0.954; p < 0.001) for urine NGAL. Urine NGAL cut-off value of 12.0 ng/mL had 95% sensitivity and 65% specificity. These results confirm the presence of nephropathy during VOC and suggest that plasma and urine NGAL would be useful in the identification of SCN. Urine NGAL should be used as the screening biomarker, and patients with VOC and urine NGAL > 12.0 ng/mL should be selected for aggressive management to prevent progression of renal damage.


Assuntos
Injúria Renal Aguda/sangue , Anemia Falciforme/sangue , Lipocalina-2/sangue , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/urina , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/urina , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Feminino , Humanos , Lipocalina-2/urina , Masculino , Curva ROC
9.
Nat Commun ; 12(1): 2057, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33824339

RESUMO

Lipocalin 2 (LCN2) was recently identified as an endogenous ligand of the type 4 melanocortin receptor (MC4R), a critical regulator of appetite. However, it remains unknown if this molecule influences appetite during cancer cachexia, a devastating clinical entity characterized by decreased nutrition and progressive wasting. We demonstrate that LCN2 is robustly upregulated in murine models of pancreatic cancer, its expression is associated with reduced food consumption, and Lcn2 deletion is protective from cachexia-anorexia. Consistent with LCN2's proposed MC4R-dependent role in cancer-induced anorexia, pharmacologic MC4R antagonism mitigates cachexia-anorexia, while restoration of Lcn2 expression in the bone marrow is sufficient in restoring the anorexia feature of cachexia. Finally, we observe that LCN2 levels correlate with fat and lean mass wasting and is associated with increased mortality in patients with pancreatic cancer. Taken together, these findings implicate LCN2 as a pathologic mediator of appetite suppression during pancreatic cancer cachexia.


Assuntos
Apetite , Caquexia/complicações , Lipocalina-2/metabolismo , Neoplasias Pancreáticas/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anorexia/sangue , Anorexia/complicações , Barreira Hematoencefálica/patologia , Medula Óssea/patologia , Caquexia/sangue , Linhagem Celular Tumoral , Modelos Animais de Doenças , Comportamento Alimentar , Feminino , Deleção de Genes , Humanos , Lipocalina-2/sangue , Masculino , Camundongos Knockout , Pessoa de Meia-Idade , Modelos Biológicos , Músculos/patologia , Neutrófilos/patologia , Tamanho do Órgão , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/genética , Receptor Tipo 4 de Melanocortina/agonistas , Receptor Tipo 4 de Melanocortina/metabolismo , Regulação para Cima
10.
Nutrients ; 13(3)2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33806669

RESUMO

Implementing permissive dehydration (DEH) during short-term heat acclimation (HA) may accelerate adaptations to the heat. However, HA with DEH may augment risk for acute kidney injury (AKI). This study investigated the effect of HA with permissive DEH on time-trial performance and markers of AKI. Fourteen moderately trained men (age and VO2max = 25 ± 0.5 yr and 51.6 ± 1.8 mL.kg-1.min-1) were randomly assigned to DEH or euhydration (EUH). Time-trial performance and VO2max were assessed in a temperate environment before and after 7 d of HA. Heat acclimation consisted of 90 min of cycling in an environmental chamber (40 °C, 35% RH). Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) were assessed pre- and post-exercise on day 1 and day 7 of HA. Following HA, VO2max did not change in either group (p = 0.099); however, time-trial performance significantly improved (3%, p < 0.01) with no difference between groups (p = 0.485). Compared to pre-exercise, NGAL was not significantly different following day 1 and 7 of HA (p = 0.113) with no difference between groups (p = 0.667). There was a significant increase in KIM-1 following day 1 and 7 of HA (p = 0.002) with no difference between groups (p = 0.307). Heat acclimation paired with permissive DEH does not amplify improvements in VO2max or time-trial performance in a temperate environment versus EUH and does not increase markers of AKI.


Assuntos
Aclimatação/fisiologia , Injúria Renal Aguda/etiologia , Desidratação/fisiopatologia , Exercício Físico/fisiologia , Temperatura Alta/efeitos adversos , Adulto , Ciclismo/fisiologia , Biomarcadores/sangue , Desidratação/complicações , Teste de Esforço , Receptor Celular 1 do Vírus da Hepatite A/sangue , Humanos , Lipocalina-2/sangue , Masculino , Consumo de Oxigênio , Termotolerância
11.
Nutr Metab Cardiovasc Dis ; 31(6): 1822-1831, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-33853719

RESUMO

BACKGROUND AND AIMS: Several susceptibility gene variants predisposing to nonalcoholic fatty liver disease (NAFLD) have been identified in chronic kidney disease (CKD). Evidence supports that 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13) rs72613567 plays a role in NAFLD development by affecting lipid homeostasis. Since lipid droplets may accumulate in the kidneys and contribute to renal injury, we investigated the association between the HSD17B13 rs72613567 variant and markers of renal function/injury in NAFLD. METHODS AND RESULTS: We measured estimated glomerular filtration rate (eGFR), urinary/serum neutrophil gelatinase-associated lipocalin (NGAL), and urinary albumin-to-creatinine ratio (u-ACR) in individuals with biopsy-proven NAFLD. Multivariable regression analyses were undertaken to examine the associations between the HSD17B13 rs72613567 variant and markers of renal function/injury. Individuals were stratified by HSD17B13 rs72613567 genotypes into -/-, A/- and A/A groups. HSD17B13 rs72613567 genotypes were not significantly associated with eGFR and urinary/serum NGAL levels. Conversely, the prevalence of abnormal albuminuria in the A/- + A/A group was lower than in the -/- group (4.92% vs. 19.35%, p = 0.001). Additionally, the mean u-ACR levels were lower among carriers of the A/- or A/A genotypes with coexisting hypertension or diabetes, than among those with the -/- genotype. The risk of abnormal albuminuria (adjusted-odds ratio 0.16, p = 0.001) remained significantly lower in the A/- + A/A group after adjustment for established renal risk factors and histologic severity of NAFLD. CONCLUSION: HSD17B13 rs72613567: A allele is associated with a lower risk of having abnormal albuminuria, but not with lower eGFR or urinary/serum NGAL levels, in patients with biopsy-proven NAFLD.


Assuntos
17-Hidroxiesteroide Desidrogenases/genética , Albuminúria/genética , Taxa de Filtração Glomerular , Rim/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/genética , Polimorfismo de Nucleotídeo Único , Adulto , Albuminúria/diagnóstico , Albuminúria/epidemiologia , Albuminúria/fisiopatologia , Biópsia , China/epidemiologia , Estudos Transversais , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Rim/metabolismo , Lipocalina-2/sangue , Lipocalina-2/urina , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Fenótipo , Prevalência , Medição de Risco , Fatores de Risco , Adulto Jovem
12.
J Cancer Res Ther ; 17(1): 198-203, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33723155

RESUMO

Introduction: Neutrophil gelatinase-associated lipocalin (NGAL) has been reported to be unregulated in many cancers and to suppress tumor suppressor genes like p53 leading to cell proliferation. Studies to report its relationship with carcinoma cervix (Ca Cx) are still scant. Materials and Methods: Serum NGAL levels were analyzed in 30 patients of histopathologically proven locally advanced Ca Cx at the time of diagnosis and 3 weeks after standard chemoradiation by enzyme-linked immunosorbent assay. These patients underwent either brachytherapy or supplementary external beam radiotherapy (EBRT) depending on the response of treatment. The results were analyzed statistically by applying Student's paired t-test. Results: No statistically significant difference (P > 0.05) was observed in patients of Ca Cx before and after treatment or when compared stage wise, histopathological grade wise, or response wise. But the levels were found to increase when duration of treatment was ≥8 weeks (P = 0.040) and to decrease significantly when duration of treatment was <8 weeks (P = 0.0052). The NGAL levels also increased significantly after treatment in patients who received EBRT and supplementary radiotherapy (P = 0.019) while the pre- and post-treatment difference in NGAL levels was not statistically significant in patients who received EBRT + intracavitary brachytherapy (P > 0.05). Conclusion: As the duration as well as modality of treatment is quite important in Ca Cx, shorter duration associated with better results and lower NGAL levels, NGAL might prove to be a useful biomarker although further studies are needed to support the claim.


Assuntos
Adenocarcinoma/patologia , Biomarcadores Tumorais/sangue , Quimiorradioterapia/métodos , Lipocalina-2/sangue , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/sangue , Adenocarcinoma/metabolismo , Adenocarcinoma/terapia , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/terapia
13.
Diab Vasc Dis Res ; 18(2): 14791641211002470, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33775157

RESUMO

BACKGROUND: Tissue inhibitor of metalloproteinase-1 (TIMP-1) has been suggested as a marker for abnormal regulation of tissue remodelling in type 1 diabetes. Metalloproteinase-9 (MMP-9) has been associated with matrix turnover, and Neutrophil gelatinase associated lipocalin (NGAL) is a marker of tubular injury in diabetic nephropathy. The aim was to analyse these biomarkers to unmask early diabetic complications. METHODS: Thirty-three type 1 diabetes patients, aged 20-35 years, and disease duration 20 ± 5.3 years were included. Along with clinical examination, neurophysiological measurements, routine biochemistry, plasma concentrations of TIMP-1, MMP-9 and NGAL were determined with immunoenzymatic techniques. RESULTS: TIMP-1 correlated with abnormal unilateral and bilateral vibratory sense foot perception (r = -0.49 and r = -0.51, respectively), foot neuropathy impairment assessment score (NIA; r = -0.55), neuropathy symptom assessment score (r = 0.42), microalbuminuria (r = 0.50) and eGFR (r = -0.45). MMP-9 correlated with impaired foot NIA (r = 0.51). Multiple regression analysis showed an association for TIMP-1 (p = 0.004) with impaired neurophysiological examinations and renal dysfunction along with NGAL (p = 0.016 and p = 0.015 respectively). CONCLUSIONS: This study suggests that plasma levels of TIMP-1, MMP-9 and NGAL may serve as useful biomarkers in unravelling subclinical neuropathy and nephropathy in type 1 diabetes.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Nefropatias Diabéticas/sangue , Neuropatias Diabéticas/sangue , Inibidor Tecidual de Metaloproteinase-1/sangue , Adulto , Biomarcadores/sangue , Estudos Transversais , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/etiologia , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/etiologia , Diagnóstico Precoce , Feminino , Humanos , Lipocalina-2/sangue , Masculino , Metaloproteinase 9 da Matriz/sangue , Valor Preditivo dos Testes , Adulto Jovem
14.
Sci Rep ; 11(1): 6799, 2021 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-33762606

RESUMO

Chronic Lung Allograft Dysfunction (CLAD), manifesting as Bronchiolitis Obliterans Syndrome (BOS) or Restrictive Allograft Syndrome (RAS), is the main reason for adverse long-term outcome after Lung Transplantation (LTX). Until now, no specific biomarkers exist to differentiate between CLAD phenotypes. Therefore, we sought to find suitable cytokines to distinguish between BOS, RAS and Azithromycin Responsive Allograft Dysfunction (ARAD); and reveal potential similarities or differences to end-stage fibrotic diseases. We observed significantly increased Lipocalin-2 serum concentrations in RAS compared to BOS patients. In addition, in RAS patients immunohistochemistry revealed Lipocalin-2 expression in bronchial epithelium and alveolar walls. Patients with ARAD showed significantly lower Activin-A serum concentrations compared to Stable-LTX and BOS patients. Further, increased serum concentrations of Lipocalin-2 and Activin-A were predictors of worse freedom-from-CLAD in Stable-LTX patients. These biomarkers serve as promising serum biomarkers for CLAD prediction and seem suitable for implementation in clinical practice.


Assuntos
Azitromicina/efeitos adversos , Biomarcadores/sangue , Transplante de Pulmão/efeitos adversos , Disfunção Primária do Enxerto/etiologia , Ativinas/sangue , Adulto , Idoso , Azitromicina/uso terapêutico , Brônquios/metabolismo , Bronquiolite Obliterante/etiologia , Citocinas/sangue , Feminino , Humanos , Lipocalina-2/sangue , Masculino , Metaloproteinase 9 da Matriz/sangue , Pessoa de Meia-Idade , Fenótipo , Transplante Homólogo/efeitos adversos
15.
Zhongguo Fei Ai Za Zhi ; 24(2): 108-111, 2021 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-33626852

RESUMO

BACKGROUND: Lung cancer is the highest incidence of cancer in the world, which seriously threatens human health. Early diagnosis and treatment of lung cancer is particularly important for the survival of lung cancer patients. Serum tumor markers have been widely used as an important method for early diagnosis of tumor. However, there are few early diagnostic markers for lung cancer. Therefore, the aim of this study was to investigate the expression level of Lipocalin-2 and its clinical significance in serum of patients with lung cancer. METHODS: The serum levels of Lipocalin-2 in 60 lung cancer patients and 63 healthy people were detected by enzyme-linked immunosorbent assay (ELISA), and the relationship between the expression level of Lipocalin-2 and the clinical characteristics of lung cancer was analyzed. RESULTS: The expression level of Lipocalin-2 in peripheral blood serum of patients with lung cancer was significantly higher than that of healthy people, and the difference was statistically significant (P<0.001). The expression of Lipocalin-2 in patients with lung cancer was related to the differentiation, stage and lymph node metastasis of pathological tissues, and the difference was statistically significant (P<0.05). The expression level of Lipocalin-2 in serum of patients with poorly differentiated lung cancer was higher than that of patients with well differentiated lung cancer; the expression level of Lipocalin-2 in serum of patients with lymph node metastasis was higher than that of patients without lymph node metastasis; the expression level of Lipocalin-2 in patients with clinical stage III + IV lung cancer was significantly higher than that of patients with clinical stage I + II lung cancer, and the differences were statistically significant (P<0.05). CONCLUSIONS: Lipocalin-2 is highly expressed in serum of patients with lung cancer, which is related to pathological differentiation, stage and lymph node metastasis. It is expected to become a potential new tumor marker for clinical diagnosis of lung cancer.


Assuntos
Lipocalina-2/sangue , Neoplasias Pulmonares/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Lipocalina-2/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias
16.
Arch Pathol Lab Med ; 145(3): 320-326, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33635951

RESUMO

CONTEXT.­: Delayed recognition of acute kidney injury (AKI) results in poor outcomes in military and civilian burn-trauma care. Poor predictive ability of urine output (UOP) and creatinine contribute to the delayed recognition of AKI. OBJECTIVE.­: To determine the impact of point-of-care (POC) AKI biomarker enhanced by machine learning (ML) algorithms in burn-injured and trauma patients. DESIGN.­: We conducted a 2-phased study to develop and validate a novel POC device for measuring neutrophil gelatinase-associated lipocalin (NGAL) and creatinine from blood samples. In phase I, 40 remnant plasma samples were used to evaluate the analytic performance of the POC device. Next, phase II enrolled 125 adults with either burns that were 20% or greater of total body surface area or nonburn trauma with suspicion of AKI for clinical validation. We applied an automated ML approach to develop models predicting AKI, using a combination of NGAL, creatinine, and/or UOP as features. RESULTS.­: Point-of-care NGAL (mean [SD] bias: 9.8 [38.5] ng/mL, P = .10) and creatinine results (mean [SD] bias: 0.28 [0.30] mg/dL, P = .18) were comparable to the reference method. NGAL was an independent predictor of AKI (odds ratio, 1.6; 95% CI, 0.08-5.20; P = .01). The optimal ML model achieved an accuracy, sensitivity, and specificity of 96%, 92.3%, and 97.7%, respectively, with NGAL, creatinine, and UOP as features. Area under the receiver operator curve was 0.96. CONCLUSIONS.­: Point-of-care NGAL testing is feasible and produces results comparable to reference methods. Machine learning enhanced the predictive performance of AKI biomarkers including NGAL and was superior to the current techniques.


Assuntos
Injúria Renal Aguda/diagnóstico , Biomarcadores/sangue , Queimaduras/complicações , Aprendizado de Máquina , Testes Imediatos , Ferimentos e Lesões/complicações , Injúria Renal Aguda/sangue , Injúria Renal Aguda/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Creatinina/sangue , Feminino , Humanos , Lipocalina-2/sangue , Masculino , Pessoa de Meia-Idade , Militares , Valor Preditivo dos Testes
17.
PLoS One ; 16(2): e0246027, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33544738

RESUMO

OBJECTIVE: Bacterial Infections remains a leading cause of death in the Paediatric Intensive Care Unit (PICU). In this era of rising antimicrobial resistance, new tools are needed to guide antimicrobial use. The aim of this study was to investigate the accuracy of procalcitonin (PCT), neutrophil gelatinase-associated lipocalin (NGAL), resistin, activated partial thromboplastin time (aPTT) waveform and C-reactive protein (CRP) for the diagnosis of serious bacterial infection (SBI) in children on admission to PICU and their use as prognostic indicators. SETTING: A regional PICU in the United Kingdom. PATIENTS: Consecutive PICU admissions between October 2010 and June 2012. MEASUREMENTS: Blood samples were collected daily for biomarker measurement. The primary outcome measure was performance of study biomarkers for diagnosis of SBI on admission to PICU based on clinical, radiological and microbiological criteria. Secondary outcomes included durations of PICU stay and invasive ventilation and 28-day mortality. Patients were followed up to day 28 post-admission. MAIN RESULTS: A total of 657 patients were included in the study. 92 patients (14%) fulfilled criteria for SBI. 28-day mortality was 2.6% (17/657), but 8.7% (8/92) for patients with SBI. The combination of PCT, resistin, plasma NGAL and CRP resulted in the greatest net reclassification improvement compared to CRP alone (0.69, p<0.005) with 10.5% reduction in correct classification of patients with SBI (p 0.52) but a 78% improvement in correct classification of patients without events (p <0.005). A statistical model of prolonged duration of PICU stay found log-transformed maximum values of biomarkers performed better than first recorded biomarkers. The final model included maximum values of CRP, plasma NGAL, lymphocyte and platelet count (AUC 79%, 95% CI 73.7% to 84.2%). Longitudinal profiles of biomarkers showed PCT levels to decrease most rapidly following admission SBI. CONCLUSION: Combinations of biomarkers, including PCT, may improve accurate and timely identification of SBI on admission to PICU.


Assuntos
Infecções Bacterianas/sangue , Infecções Bacterianas/diagnóstico , Proteína C-Reativa/metabolismo , Lipocalina-2/sangue , Pró-Calcitonina/sangue , Biomarcadores/sangue , Criança , Pré-Escolar , Estado Terminal , Diagnóstico Precoce , Feminino , Humanos , Masculino , Tempo de Tromboplastina Parcial , Prognóstico
18.
Vet Surg ; 50(3): 641-649, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33522003

RESUMO

OBJECTIVE: To investigate neutrophil gelatinase-associated lipocalin (NGAL) concentrations in serum and synovial fluid (SF) from horses with joint inflammation. STUDY DESIGN: Experimental studies and retrospective clinical study. SAMPLE POPULATION: Serum and SF samples were available from healthy horses (n = 19), clinical cases, and horses with experimental joint inflammation. Clinical cases included horses with (n = 10) or without (n = 10) septic arthritis. Experimental intra-articular inflammation was induced by lipopolysaccharide (LPS; n = 7, severe inflammation), lidocaine (n = 6, moderate inflammation), or mepivacaine (n = 6, mild inflammation). METHODS: Availability of samples was based on approval from the local ethical committee and from the Danish Animal Experiments Inspectorate. Neutrophil gelatinase-associated lipocalin was measured with a previously validated enzyme-linked immunosorbent assay. Repeated-measurements one- and two-way analysis of variance and correlation analysis were used to analyze NGAL concentrations and white blood cell counts (WBC). RESULTS: After injection of LPS or lidocaine, SF NGAL concentrations increased 343- (P = .0035) and 60-fold (P = .0038) relative to baseline, respectively. Serum NGAL also increased in both groups (P < .05) but to lower concentrations than in SF. Concentrations were higher after injection of lidocaine SF NGAL than after injection of mepivacaine (P < .05) at 6 and 12 hours. Synovial fluid concentrations of NGAL were higher in horses with septic arthritis than in the nonseptic group (P = .0070) and in healthy controls (P = .0071). Concentrations of NGAL correlated with WBC in SF (P < .0001, R2 = 0.49) and in blood (P = .0051, R2 = 0.27). CONCLUSION: Neutrophil gelatinase-associated lipocalin concentrations increased in SF in response to experimentally induced and naturally occurring joint inflammation. Synovial fluid NGAL concentration correlated with WBC and, thus, seems to reflect intensity of joint inflammation. CLINICAL SIGNIFICANCE: Neutrophil gelatinase-associated lipocalin may prove to be a useful biomarker of joint inflammation and infection in horses.


Assuntos
Doenças dos Cavalos/metabolismo , Inflamação/veterinária , Artropatias/veterinária , Lipocalina-2/metabolismo , Animais , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Feminino , Doenças dos Cavalos/induzido quimicamente , Cavalos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Artropatias/induzido quimicamente , Artropatias/metabolismo , Lidocaína/efeitos adversos , Lipocalina-2/sangue , Lipocalina-2/líquido cefalorraquidiano , Lipopolissacarídeos/efeitos adversos , Masculino , Mepivacaína/efeitos adversos , Estudos Retrospectivos
19.
Am J Cardiol ; 147: 70-79, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33617811

RESUMO

Prompt treatment may mitigate the adverse effects of congestion in the early phase of heart failure (HF) hospitalization, which may lead to improved outcomes. We analyzed 814 acute HF patients for the relationships between time to first intravenous loop diuretics, changes in biomarkers of congestion and multiorgan dysfunction, and 1-year composite end point of death or HF hospitalization. B-type natriuretic peptide (BNP), high sensitivity cardiac troponin I (hscTnI), urine and serum neutrophil gelatinase-associated lipocalin, and galectin 3 were measured at hospital admission, hospital day 1, 2, 3 and discharge. Time to diuretics was not correlated with the timing of decongestion defined as BNP decrease ≥ 30% compared with admission. Earlier BNP decreases but not time to diuretics were associated with earlier and greater decreases in hscTnI and urine neutrophil gelatinase-associated lipocalin, and lower incidence of the composite end point. After adjustment for confounders, only no BNP decrease at discharge was significantly associated with mortality but not the composite end point (p = 0.006 and p = 0.062, respectively). In conclusion, earlier time to decongestion but not the time to diuretics was associated with better biomarker trajectories. Residual congestion at discharge rather than the timing of decongestion predicted a worse prognosis.


Assuntos
Diuréticos/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Peptídeo Natriurético Encefálico/sangue , Tempo para o Tratamento , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Esquema de Medicação , Feminino , Galectina 3/sangue , Insuficiência Cardíaca/mortalidade , Hospitalização , Humanos , Lipocalina-2/sangue , Lipocalina-2/urina , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Troponina I/sangue
20.
Ren Fail ; 43(1): 168-179, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33459127

RESUMO

The two primary mechanisms by which iodinated contrast media (CM) causes contrast-induced acute kidney injury (CIAKI) are the hemodynamic effect causing intrarenal vasoconstriction and the tubular toxic effect causing acute tubular necrosis. Inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), which degrades prostaglandin E2 (PGE2), promotes tissue repair and regeneration in many organs. PGE2 causes intrarenal arterial vasodilation. In this study, we investigated whether a 15-PGDH inhibitor can act as a candidate for blocking these two major mechanisms of CIAKI. We established a CIAKI mouse model by injecting a 10 gram of iodine per body weight (gI/kg) dose of iodixanol into each mouse tail vein. A 15-PGDH inhibitor (SW033291), PGE1, or PGE2 were administered to compare the renal functional parameters, histologic injury, vasoconstriction, and renal blood flow changes. In addition, human renal proximal tubular epithelial cells were cultured in a CM-treated medium. SW033291, PGE1, or PGE2 were added to compare any changes in cell viability and apoptosis rate. CIAKI mice that received SW033291 had lower serum levels of creatinine, neutrophil gelatinase-associated lipocalin, and kidney injury molecule 1 (p < 0.001); lower histologic injury score and TUNEL positive rates (p < 0.001); and higher medullary arteriolar area (p < 0.05) and renal blood flow (p < 0.001) than CM + vehicle group. In cell culture experiments, Adding SW033291 increased the viability rate (p < 0.05) and decreased the apoptosis rate of the tubular epithelial cells (p < 0.001). This 15-PGDH inhibitor blocks the two primary mechanisms of CIAKI, intrarenal vasoconstriction and tubular cell toxicity, and thus has the potential to be a novel prophylaxis for CIAKI. Abbreviations: 15-PGDH: 15-hydroxyprostaglandin dehydrogenase; AMP: adenosine monophosphate; CIAKI: contrast-induced acute kidney injury; CM: contrast media; EP: prostaglandin E2 receptor; hRPTECs: human-derived renal proximal tubule epithelial cells; KIM-1: kidney injury molecule-1; MTT: 3-(4,5-Dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide; NGAL: neutrophil gelatinase-associated lipocalin; PBS: phosphate-buffered saline; PGE1: prostaglandin E1; PGE2: prostaglandin E2; RBF: renal blood flow; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling; α-SMA: α-Smooth muscle actin.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/prevenção & controle , Meios de Contraste/efeitos adversos , Hidroxiprostaglandina Desidrogenases/antagonistas & inibidores , Piridinas/farmacologia , Tiofenos/farmacologia , Animais , Creatinina/sangue , Feminino , Humanos , Rim/fisiopatologia , Lipocalina-2/sangue , Camundongos , Camundongos Endogâmicos C57BL , Prostaglandinas E/farmacologia , Ácidos Tri-Iodobenzoicos/efeitos adversos
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