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1.
Pulm Med ; 2021: 4496488, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721903

RESUMO

When managing coronavirus disease 2019 (COVID-19) patients, radiological imaging complements clinical evaluation and laboratory parameters. We aimed to assess the sensitivity of chest radiography findings in detecting COVID-19, describe those findings, and assess the association of positive chest radiography findings with clinical and laboratory findings. A multicentre, cross-sectional study was conducted involving all primary health care corporation-registered patients (2485 patients) enrolled over a 1-month period during the peak of the 2020 pandemic wave in Qatar. These patients had reverse transcription-polymerase chain reaction-confirmed COVID-19 and underwent chest radiography within 72 hours of the swab test. A positive result on reverse transcription-polymerase chain reaction was the gold standard for diagnosing COVID-19. The sensitivity of chest radiography was calculated. The airspace opacities were mostly distributed in the peripheral and lower lung zones, and most of the patients had bilateral involvement. Pleural effusion was detected in some cases. The risk of having positive chest X-ray findings increased with age, Southeast Asian nationality, fever, or a history of fever and diarrhoea. Patients with cardiac disease, obesity, hypertension, diabetes, and chronic kidney disease were at a higher risk of having positive chest X-ray findings. There was a statistically significant increase in the mean serum albumin, white blood cell count, neutrophil count, and serum C-reactive protein, hepatic enzymes, and total bilirubin with an increase in the radiographic severity score.


Assuntos
COVID-19/diagnóstico , Pulmão/diagnóstico por imagem , Adolescente , Adulto , Fatores Etários , Idoso , Bilirrubina/sangue , Proteína C-Reativa/análise , COVID-19/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Febre , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Doenças não Transmissíveis , Pandemias , Derrame Pleural/diagnóstico por imagem , Atenção Primária à Saúde , Catar/epidemiologia , Fatores Raciais , Estudos Retrospectivos , Sensibilidade e Especificidade , Albumina Sérica , Raios X , Adulto Jovem
2.
PLoS One ; 16(10): e0258127, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34618852

RESUMO

Population risks for neonatal hyperbilirubinaemia (NH) vary. Knowledge of local risks permits interventions that may reduce the proportion becoming severe. Between January 2015 and May 2016, in a resource-limited setting on the Thailand-Myanmar border, neonates from 28 weeks' gestation were enrolled into a prospective birth cohort. Each neonate had total serum bilirubin measurements: scheduled (24, 48, 72 and 144 hours of life) and clinically indicated; and weekly follow up until 1 month of age. Risk factors for developing NH were evaluated using Cox proportional hazard mixed model. Of 1710 neonates, 22% (376) developed NH (83% preterm, 19% term). All neonates born <35 weeks, four in five born 35-37 weeks, and three in twenty born ≥38 weeks had NH, giving an overall incidence of 249 per 1000 livebirths [95%CI 225, 403]. Mortality from acute bilirubin encephalopathy was 10% (2/20) amongst the 5.3% (20/376) who reached the severe NH threshold. One-quarter (26.3%) of NH occurred within 24 hours. NH onset varied with gestational age: at a median [IQR] 24 hours [24, 30] for neonates born 37 weeks or prematurely vs 59 hours [48, 84] for neonates born ≥38 weeks. Risk factors for NH in the first week of life independent of gestational age were: neonatal G6PD deficiency, birth bruising, Sgaw Karen ethnicity, primigravidae, pre-eclampsia, and prolonged rupture of membranes. The genetic impact of G6PD deficiency on NH was partially interpreted by using the florescent spot test and further genotyping work is in progress. The risk of NH in Sgaw Karen refugees may be overlooked internationally as they are most likely regarded as Burmese in countries of resettlement. Given high levels of pathological jaundice in the first 24 hours and overall high NH burden, guidelines changes were implemented including preventive PT for all neonates <35 weeks and for those 35-37 weeks with risk factors.


Assuntos
Bilirrubina/sangue , Deficiência de Glucosefosfato Desidrogenase/sangue , Hiperbilirrubinemia Neonatal/sangue , Kernicterus/sangue , Estudos de Coortes , Estudos Epidemiológicos , Grupos Étnicos/genética , Feminino , Genótipo , Deficiência de Glucosefosfato Desidrogenase/complicações , Deficiência de Glucosefosfato Desidrogenase/genética , Deficiência de Glucosefosfato Desidrogenase/mortalidade , Humanos , Hiperbilirrubinemia Neonatal/genética , Hiperbilirrubinemia Neonatal/mortalidade , Hiperbilirrubinemia Neonatal/patologia , Recém-Nascido , Kernicterus/complicações , Kernicterus/genética , Kernicterus/mortalidade , Masculino , Mianmar/epidemiologia , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/mortalidade , Gravidez , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Tailândia/epidemiologia
3.
Pediatrics ; 148(5)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34716218

RESUMO

OBJECTIVES: We aimed to reassess the relationship between phototherapy and cancer in an extended version of a previous cohort and to replicate a report from Quebec of increased cancer risk after phototherapy beginning at age 4 years. METHODS: This cohort study included 139 100 children born at ≥35 weeks' gestation from 1995 to 2017, followed through March 16, 2019, in Kaiser Permanente Northern California hospitals who had a qualifying bilirubin level from -3 mg/dL to +4.9 mg/dL from the American Academy of Pediatrics phototherapy threshold; an additional 40 780 children and 5 years of follow-up from our previous report. The exposure was inpatient phototherapy (yes or no), and the outcomes were various types of childhood cancer. We used Cox proportional hazard models, controlling for propensity-score quintiles, and allowed for time-dependent exposure effects to assess for the risk of cancer after a latent period. RESULTS: Over a mean (SD) follow-up of 8.2 (5.7) years, the crude incidence of cancer per 100 000 person-years was 25.1 among those exposed to phototherapy and 19.2 among those not exposed (233 cases of cancer). After propensity adjustment, phototherapy was not associated with any cancer (hazard ratio [HR]: 1.13, 95% confidence interval [CI]: 0.83-1.54), hematopoietic cancer (HR: 1.17, 95% CI: 0.74-1.83), or solid tumors (HR: 1.01, 95% CI: 0.65-1.58). We also found no association with cancer diagnoses at age ≥4 years. CONCLUSIONS: We did not confirm previous, concerning associations between phototherapy and adjusted risk of any cancer, nonlymphocytic leukemia, or brain and/or central nervous systems tumors in later childhood.


Assuntos
Neoplasias/etiologia , Fototerapia/efeitos adversos , Bilirrubina/sangue , California/epidemiologia , Criança , Pré-Escolar , Métodos Epidemiológicos , Feminino , Humanos , Incidência , Masculino , Resultados Negativos , Neoplasias/epidemiologia , Fatores de Tempo
4.
Sci Rep ; 11(1): 17988, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34504135

RESUMO

Type C hepatic encephalopathy (HE) is a neuropsychiatric disease caused by chronic liver disease. Management of type C HE remains an important challenge because treatment options are limited. Both the antibiotic rifaximin and probiotics have been reported to reduce the symptoms of HE, but longitudinal studies assessing their effects on brain metabolism are lacking and the molecular mechanisms underpinning their effects are not fully understood. Therefore, we evaluated in detail the effects of these different treatments on the neurometabolic changes associated with type C HE using a multimodal approach including ultra-high field in vivo 1H MRS. We analyzed longitudinally the effect of rifaximin alone or in combination with the probiotic Vivomixx on the brain metabolic profile in the hippocampus and cerebellum of bile duct ligated (BDL) rats, an established model of type C HE. Overall, while rifaximin alone appeared to induce no significant effect on the neurometabolic profile of BDL rats, its association with the probiotic resulted in more attenuated neurometabolic alterations in BDL rats followed longitudinally (i.e. a smaller increase in Gln and milder decrease in Glu and Cr levels). Given that both rifaximin and some probiotics are used in the treatment of HE, the implications of these findings may be clinically relevant.


Assuntos
Antibacterianos/uso terapêutico , Cerebelo/metabolismo , Encefalopatia Hepática/dietoterapia , Encefalopatia Hepática/tratamento farmacológico , Hipocampo/metabolismo , Metaboloma/efeitos dos fármacos , Probióticos/uso terapêutico , Rifaximina/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Animais , Bilirrubina/sangue , Modelos Animais de Doenças , Encefalopatia Hepática/sangue , Estudos Longitudinais , Masculino , Espectroscopia de Prótons por Ressonância Magnética/métodos , Ratos , Ratos Wistar , Resultado do Tratamento
6.
Pan Afr Med J ; 39: 60, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422183

RESUMO

Introduction: exchange blood transfusion (EBT) is a form of massive transfusion useful in rapidly reducing serum bilirubin levels, but serum bilirubin levels frequently rebound within hours of completing the procedure, due to equilibration of extravascular bilirubin as well as on-going hemolysis. The study was carried out to determine the pattern of reduction in serum bilirubin levels following EBT among neonates with severe hyperbilirubinemia, as well as the factors contributing to this pattern, so as to establish evidence-based expectations following EBT. Methods: a retrospective descriptive study covering a two-year period in a Nigerian tertiary hospital. Details of the EBT procedures, including serial serum bilirubin levels, were obtained from the hospital records of all newborn babies who had double volume EBT done for severe hyperbilirubinaemia during the study period. Data was analyzed using the statistical software SPSS version 21.0. Results: the mean total serum bilirubin (TSB) before EBT in the 36 babies was 17.9 ± 6.3 mg/dl. The mean percentage decrease in TSB immediately following EBT was 44.3 ± 10.2%. Six hours after EBT, TSB levels had increased from the immediate post-EBT values by an average of 57.5 ± 32.2%. Twenty-four hours after the procedure, TSB values in most (87.1%) cases were still higher than the immediate post-EBT values, but lower than the pre-EBT values. Post-EBT anemia was recorded among 33.3% of the babies. Conclusion: EBT is effective in rapidly reducing serum bilirubin levels and preventing acute bilirubin encephalopathy in neonates with severe hyperbilirubinemia, despite the rebound increase that occurs in TSB values after the procedure.


Assuntos
Bilirrubina/sangue , Transfusão Total/métodos , Hiperbilirrubinemia Neonatal/terapia , Feminino , Humanos , Recém-Nascido , Masculino , Nigéria , Estudos Retrospectivos , Índice de Gravidade de Doença , Centros de Atenção Terciária , Fatores de Tempo , Resultado do Tratamento
7.
PLoS One ; 16(8): e0255230, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34351969

RESUMO

BACKGROUND: Hyperbilirubinemia is a devastating complication in patients admitted to an intensive care unit (ICU). The sequential organ failure assessment (SOFA) score classifies hyperbilirubinemia without further detailed analyses for bilirubin increase above 12 mg/dL. We evaluated whether the level of bilirubin increase in patients with extreme hyperbilirubinemia (total bilirubin ≥ 12 mg/dL) affects and also helps estimate mortality or recovery. METHODS: A retrospective cohort analysis comprising 427 patients with extreme hyperbilirubinemia admitted to the ICU of Samsung Medical Center, Seoul, Korea between 2011 and 2015 was conducted. Extreme hyperbilirubinemia was classified into four grades: grade 1 (12-14.9 mg/dL), grade 2 (15-19.9 mg/dL), grade 3 (20-29.9 mg/dL), and grade 4 (≥ 30 mg/dL). These grades were then assessed for their association with hospital mortality and recovery from hyperbilirubinemia to SOFA grade (point) 2 or below (total bilirubin < 6 mg/dL). The influences of various factors, some of which caused extreme hyperbilirubinemia, while others induced bilirubin recovery, were assessed. RESULTS: A total of 427 patients (mean age: 59.8 years, male: 67.0%) were evaluated, and the hospital mortality for these patients was very high (76.1%). Extreme hyperbilirubinemia was observed in 111 (grade 1, 26.0%), 99 (grade 2, 23.2%), 131 (grade3, 30.7%), and 86 (grade 4, 20.1%) patients with mortality rates of 62.2%, 71.7%, 81.7%, and 90.7%, respectively (p < 0.001). The peak bilirubin value correlated with the mortality (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.04-1.15, p < 0.001). Compared to those with grade 1 extreme hyperbilirubinemia, the mortality rate gradually increased as the grade increased (OR [95% CI]: 1.92 [0.70-5.28], 3.55 [1.33-9.48], and 12.47 [3.07-50.59] for grades 2, 3 and 4, respectively). The main causes of extreme hyperbilirubinemia were infection including sepsis and hypoxic hepatitis. The recovery from hyperbilirubinemia was observed in 110 (25.8%) patients. Mortality was lower for those who recovered from hyperbilirubinemia than for those who did not (29.1% vs. 92.4%, p < 0.001). The favorable factors of bilirubin recovery were albumin and ursodeoxycholic acid (UDCA). CONCLUSIONS: This study determined that the level of extreme hyperbilirubinemia is an important prognostic factor in critically ill patients. We expect the results of this study to help predict the clinical course of and determine the optimal treatment for extreme hyperbilirubinemia.


Assuntos
Bilirrubina/sangue , Estado Terminal , Hiperbilirrubinemia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Sobreviventes , Adulto Jovem
8.
Pediatrics ; 148(3)2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34376530

RESUMO

BACKGROUND AND OBJECTIVES: The neonatal hereditary spherocytosis (HS) index, defined as the mean corpuscular hemoglobin concentration divided by the mean corpuscular volume, has been proposed as a screening tool for HS in neonates. In a population of mostly white infants, an HS Index >0.36 was 97% sensitive and >99% specific. We evaluated the utility of the HS Index among a more racially and ethnically diverse population and determined if its discrimination varies with total serum bilirubin (TSB) levels. METHODS: Infants born at ≥35 weeks' gestation at 15 Kaiser Permanente Northern California hospitals from 1995 to 2015 were eligible (N = 670 272). Erythrocyte indices from the first complete blood count drawn at ≤7 days and TSB levels drawn at ≤30 days were obtained. Diagnoses of HS were confirmed via chart review. RESULTS: HS was confirmed in 79 infants, 1.2 per 10 000. HS was more common among infants of white and "other" race or ethnicity and among those with higher peak TSB levels. The area under the receiver operating characteristic curve for the HS Index was 0.84 (95% confidence interval 0.78-0.90). Likelihood ratios ranged from 10.1 for an HS Index ≥0.380 to 0.1 for an HS Index <0.310. Dichotomized at 0.36, the HS Index was 56% sensitive and 93% specific. Discrimination of the HS Index appeared best among infants with TSB levels <10 mg/dL. CONCLUSIONS: The HS Index, when obtained from a CBC drawn within the first week after birth, had only modest ability to alter the probability of HS.


Assuntos
Contagem de Células Sanguíneas , Triagem Neonatal , Esferocitose Hereditária/diagnóstico , Bilirrubina/sangue , Índices de Eritrócitos , Feminino , Humanos , Recém-Nascido , Funções Verossimilhança , Masculino , Sensibilidade e Especificidade , Esferocitose Hereditária/sangue
9.
Front Immunol ; 12: 606146, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34354697

RESUMO

In search for novel biomarkers to assess graft quality, we investigated whether defined candidate genes are predictive for outcome after liver transplantation (LT). Zero-hour liver biopsies were obtained from 88 livers. Gene expression of selected candidate markers was analyzed and correlated with clinical parameters as well as short and long-term outcomes post LT. Whereas both, the calculated Eurotransplant Donor-Risk-Index and the donor body mass index, had either a poor or no predictive value concerning serum levels indicative for liver function (ALT, AST, GGT, bilirubin) after 6 months, chronological donor age was weakly predictive for serum bilirubin (AUC=0.67). In contrast, the major histcompatibility complex class I related chain A (MICA) mRNA expression demonstrated a high predictive value for serum liver function parameters revealing an inverse correlation (e.g. for ALT: 3 months p=0.0332; 6 months p=0.007, 12 months 0.0256, 24 months p=0.0098, 36 months, p=0.0153) and proved significant also in a multivariate regression model. Importantly, high expression of MICA mRNA revealed to be associated with prolonged graft survival (p=0.024; log rank test) after 10 years of observation, whereas low expression was associated with the occurrence of death in patients with transplant related mortality (p=0.031). Given the observed correlation with short and long-term graft function, we suggest MICA as a biomarker for pre-transplant graft evaluation.


Assuntos
Biomarcadores/metabolismo , Rejeição de Enxerto/diagnóstico , Antígenos de Histocompatibilidade Classe I/metabolismo , Transplante de Fígado , Fígado/metabolismo , Fatores Etários , Bilirrubina/sangue , Feminino , Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Análise de Sobrevida
10.
Biomed Pharmacother ; 138: 111509, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34311524

RESUMO

The effect of hyper-mineral waters on human health has long been debated. This pilot study evaluated the influence of San Martino® water (Sardinia, Italy), on clinical and biological parameters, following the treatment of 10 hospitalized patients. Crenotherapy consisted of 1-2 L of the water daily for 10 days. A complete blood count, serum electrolytes, liver and kidney function tests, fasting lipid profile and plasma glucose, and abdominal ultrasound imaging were assessed before and at the end of treatment. In addition, body weight, dyspeptic symptoms, bowel movements, diuresis, uricuria and blood pressure were evaluated daily. According to its physico-chemical properties, the water is hyper-mineral (TDS 2808 mg/L) with a high content of bicarbonate and iron. At the end of the study, diuresis increased by 60% (850 vs 1295 ml/24 h, P = 0.009) and uricuria by 41% (362 vs 490 mg/24 h, P = 0.022) respectively, whereas plasma uric acid level decreased by 7% (4.7 vs 4.3 mg/dL, P = 0.043). Compared to the basal values, serum gamma-glutamyl transferase, alkaline phosphatase and total bilirubin levels, showed a reduction of 65% (31 vs 18 U/L, P = 0.022), 15% (96 vs 90 U/L, P = 0.041), and 11% (0.53 vs 0.45 g/dL, P = 0.041), respectively. Bowel movements improved in 62.5% of patients with constipation, and 80% of dyspeptic patients experienced symptoms relief. Compliance to the treatment reached 100%. Mild differences were observed in body weight and blood pressure, although not in ultrasound imaging during crenotherapy. These findings suggest that the San Martino® hyper-mineral water may have some benefits to human health. Additional studies with a larger-sized cohort and for a longer period are needed to confirm these preliminary results.


Assuntos
Balneologia , Defecação , Diurese , Intestinos/fisiopatologia , Rim/fisiopatologia , Águas Minerais/uso terapêutico , Fosfatase Alcalina/sangue , Bilirrubina/sangue , Biomarcadores/sangue , Biomarcadores/urina , Feminino , Humanos , Pacientes Internados , Itália , Masculino , Projetos Piloto , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento , Ácido Úrico/sangue , Ácido Úrico/urina , gama-Glutamiltransferase/sangue
11.
Int Heart J ; 62(4): 829-836, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34276023

RESUMO

Liver dysfunction is one of the most recognized complications in patients with acute heart failure (HF) and therefore a liver function score may be useful for risk-stratification in those patients. Recently, the albumin-bilirubin (ALBI) score was developed as a new model to assess liver function in liver disease. We explored the association between the ALBI score at admission and in-hospital mortality in patients with acute HF.We enrolled 262 patients (median age, 86 years, 137 males) who were admitted to our hospital for treatment of acute HF. The following data were recorded: vital signs, laboratory data including B-type natriuretic peptide (BNP) level, echocardiographic data at admission, demographic and clinical characteristics, and treatment and prognostic information. The Get With the Guidelines-Heart Failure (GWTG-HF) risk score was calculated as an established risk model for each patient. The primary outcome was all-cause in-hospital mortality.During hospitalization, 37 patients (14.1%) died. The in-hospital mortality rate was significantly higher in patients with ALBI scores > -2.25 compared with patients with ALBI scores ≤ -2.25 (21.1% versus 4.5%, respectively; P = 0.0001). Multivariate analysis revealed that the GWTG-HF score (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.08-1.25, P < 0.0001), BNP level (OR 1.0007, 95% CI 1.0003-1.001, P = 0.0003) and ALBI score (OR 6.0, 95% CI 1.8-19.6, P = 0.0017) were independently associated with in-hospital mortality.Our results indicated that the ALBI score was independently associated with in-hospital mortality in patients hospitalized for acute HF.


Assuntos
Bilirrubina/sangue , Insuficiência Cardíaca/mortalidade , Albumina Sérica , Idoso , Idoso de 80 Anos ou mais , Ecocardiografia , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico por imagem , Mortalidade Hospitalar , Humanos , Japão/epidemiologia , Masculino , Estudos Retrospectivos
12.
Methods Mol Biol ; 2342: 695-707, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34272713

RESUMO

New molecular entities (NMEs) are evaluated using a rigorous set of in vitro and in vivo studies to assess their safety and suitability for testing in humans. Regulatory health authorities require that therapeutic and supratherapeutic doses be administered, by the intended route of administration, to two nonclinical species prior to human testing. The purpose of these studies is to identify potential target organ toxicity and to determine if the effects are reversible. Liver is a potential site for toxicity caused by orally administered NMEs due to high exposure during first pass after oral administration. A range of clinical chemistry analytes are routinely measured in both nonclinical and clinical studies to evaluate and monitor for hepatotoxicity. While bilirubin itself circulates within a wide range of concentrations in many animal species and humans, without causing adverse effects and possibly providing benefits, bilirubin is one of the few readily monitored circulating biomarkers that can provide insight into liver function. Therefore, any changes in plasma or urine bilirubin levels must be carefully evaluated. Changes in bilirubin may occur as a result of adaptive nontoxic changes or severe toxicity. Examples of adaptive nontoxic changes in liver function, which may elevate direct (conjugated) and/or indirect (unconjugated) bilirubin above baseline levels, include reversible inhibition of UGT1A1-mediated bilirubin metabolism and OATP1B1-, OATP1B3-, or MRP2-mediated transport. Alternatively, hepatocellular necrosis, hypoalbuminuria, or cholestasis may also lead to elevation of bilirubin; in some cases, these effects may be irreversible.This chapter aims to demonstrate application of enzyme kinetic principles in understanding the risk of bilirubin elevation through inhibition of multiple processes-involving both enzymes and transporters. In the sections that follow, we first provide a brief summary of bilirubin formation and disposition. Two case examples are then provided to illustrate the enzyme kinetic studies needed for risk assessment and for identifying the mechanisms of bilirubin elevation. Caveats of methods and data interpretation are discussed in these case studies. The data presented in this chapter is unpublished at the time of compilation of this book. It has been incorporated in this chapter to provide a sense of complexities in enzyme kinetics to the reader.


Assuntos
Bilirrubina/análise , Glucuronosiltransferase/metabolismo , Transportador 1 de Ânion Orgânico Específico do Fígado/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Bibliotecas de Moléculas Pequenas/administração & dosagem , Animais , Bilirrubina/sangue , Bilirrubina/urina , Cães , Desenvolvimento de Medicamentos , Humanos , Concentração Inibidora 50 , Cinética , Ratos , Bibliotecas de Moléculas Pequenas/efeitos adversos
13.
Sci Rep ; 11(1): 14474, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34262065

RESUMO

We investigated the impact on survival of modified albumin-bilirubin (mALBI) grade versus Child-Pugh classification in patients with hepatocellular carcinoma (HCC) who received lenvatinib. A total of 524 patients with HCC who received lenvatinib were included. Univariate analysis showed that mALBI grade 2b/3 and Child-Pugh class B/C were significantly associated with survival [hazard ratio (HR), 2.471; 95% confidence interval (CI), 1.944-3.141 and HR, 2.178; 95%CI, 1.591-2.982]. In patients with a Child-Pugh score of 5, multivariate analysis showed that mALBI grade 2b/3 was independently associated with survival (HR, 1.814; 95%CI, 1.083-3.037). Conversely, among patients with mALBI grade 1/2a, there was no difference in survival between those with a Child-Pugh class of 5 or 6 (p = 0.735). Time-dependent receiver operating characteristic analysis showed that the ALBI score predicted survival better than the Child-Pugh score. The optimal cut-off value of the ALBI score for predicting survival was nearly the same as the value separating mALBI grades 2a and 2b. In conclusion, the mALBI grade was a better predictor of survival than the Child-Pugh classification in patients with unresectable HCC who received lenvatinib therapy.


Assuntos
Bilirrubina/sangue , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Albumina Sérica Humana/análise , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Compostos de Fenilureia/efeitos adversos , Quinolinas/efeitos adversos , Curva ROC , Taxa de Sobrevida
14.
Front Immunol ; 12: 682400, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276670

RESUMO

Background: Systemic lupus erythematosus (SLE) affects many organs and systems of the human organism, at present, its specific pathogenesis is not completely clear, but inflammation is considered to be an important factor involved in the pathogenesis and progression of SLE. Gamma-glutamyl transpeptidase (GGT) and total bilirubin (TBIL) have different effects on inflammation: GGT has pro-inflammatory effects, on the contrary, TBIL has anti-inflammatory effects. Study has found that GGT and TBIL play opposite roles in metabolic diseases. However, the roles of them in SLE are unknown. Meanwhile, the relationship between GGT and SLE also remains unexplored. Method: We recruited 341 SLE patients and 332 healthy individuals in Liaocheng People's Hospital from August 2018 to May 2019. We diagnosed SLE using 2019 revised American College of Rheumatology (ACR) SLE criteria, and modeled the study outcomes using logistic regression to explore the respective relationship between GGT, TBIL and SLE. We also analyzed the interaction of GGT and TBIL in the progression of SLE. Results: We found that the levels of CRP, IL-6 and TNF-α in the aggravated group were significantly higher than those in the unaggravated group, the levels of C3 and C4 in the aggravated group were significantly lower than those in the unaggravated group. According to Spearman correlation analysis, GGT is proportional to CRP (rs=0.417) and IL-6 (rs=0.412), inversely proportional to C3 (rs=-0.177) and C4 (rs=0.-132). TBIL was inversely proportional to CRP (rs=-0.328) and TNF(rs=-0.360), and positively proportional to C3 (rs=0.174) and C4 (rs=0.172). In the fully adjusted model, compared to the lowest quartile, the highest quartile of GGT exhibited a positive association with the risk of SLE aggravation (OR=2.99, 95% CI: 1.42-6.31, P<0.001). At the same time, compared to the highest quartile, the quartile lowest of TBIL exhibited a positive association with the risk of SLE aggravation (OR=2.66, 95% CI: 1.27-5.59, P<0.001) in the fully adjusted model. Through interaction analysis, we found that women with high GGT levels had an increased risk of SLE aggravation when they had a low level of TBIL (OR=3.68, 95% CI: 1.51-9.01, for women with Q1 TBIL and Q4 GGT compared to women with Q2-Q4 TBIL and Q1-Q3 GGT, P for interaction <0.001), the combined AUC value (AUCCOMBINED=0.711) of high GGT level and TBIL were higher than their respective values (AUCGGT=0.612, AUCTBIL=0.614). Conclusion: We found that the effects of GGT and TBIL in the progression of SLE are opposite. High GGT level might be a risk factor for SLE aggravation, as GGT levels increased, so did the risk of SLE aggravation. At the same time, we found that low TBIL level might be a risk factor for SLE aggravation. Moreover, high GGT level and low TBIL level had a subadditive effect on the increased risk of SLE aggravation.


Assuntos
Bilirrubina/sangue , Biomarcadores , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , gama-Glutamiltransferase/sangue , Adulto , Estudos de Casos e Controles , China , Citocinas/metabolismo , Progressão da Doença , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Índice de Gravidade de Doença , Fatores Sexuais
15.
Biomed Pharmacother ; 140: 111732, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34130201

RESUMO

Nerol, a monoterpene is evident to possess diverse biological activities, including antioxidant, anti-microbial, anti-spasmodic, anthelmintic, and anti-arrhythmias. This study aims to evaluate its hepatoprotective effect against paracetamol-induced liver toxicity in a rat model. Five groups of rats (n = 7) were orally treated (once daily) with 0.05% tween 80 dissolved in 0.9% NaCl solution (vehicle), paracetamol 640 mg/kg (negative control), 50 mg/kg silymarin (positive control), or nerol (50 and 100 mg/kg) for 14 days, followed by the hepatotoxicity induction using paracetamol (PCM). The blood samples and livers of the animals were collected and subjected to biochemical and microscopical analysis. The histological findings suggest that paracetamol caused lymphocyte infiltration and marked necrosis, whereas maintenance of the normal hepatic structural was observed in group pre-treated with silymarin and nerol. The rats pre-treated with nerol significantly and dose-dependently reduced the hepatotoxic markers in animals. Nerol at 100 mg/kg significantly reversed the paracetamol-induced altered situations, including the liver enzymes, plasma proteins, antioxidant enzymes and serum bilirubin, lipid peroxidation (LPO) and cholesterol [e.g., total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c)] levels in animals. Taken together, nerol exerted significant hepatoprotective activity in rats in a dose-dependent manner. PCM-induced toxicity and nerol induced hepatoprotective effects based on expression of inflammatory and apoptosis factors will be future line of work for establishing the precise mechanism of action of nerol in Wistar albino rats.


Assuntos
Acetaminofen , Monoterpenos Acíclicos/uso terapêutico , Analgésicos não Narcóticos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Monoterpenos Acíclicos/farmacologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Catalase/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/patologia , Globulinas/análise , Glutationa/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Substâncias Protetoras/farmacologia , Ratos Sprague-Dawley , Ratos Wistar , Albumina Sérica/análise , Superóxido Dismutase/sangue , gama-Glutamiltransferase/sangue
16.
Commun Biol ; 4(1): 731, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34127764

RESUMO

Human serum albumin (HSA) constitutes the primary transporter of fatty acids, bilirubin, and other plasma compounds. The binding, transport, and release of its cargos strongly depend on albumin conformation, which is affected by bound ligands induced by physiological and pathological conditions. HSA is both highly oxidized and heavily loaded with fatty acids and bilirubin in chronic liver disease. By employing small-angle X-ray scattering we show that HSA from the plasma of chronic liver disease patients undergoes a distinct opening compared to healthy donors. The extent of HSA opening correlates with clinically relevant variables, such as the model of end-stage liver disease score, bilirubin, and fatty acid levels. Although the mild oxidation of HSA in vitro does not alter overall structure, the alteration of patients' HSA correlates with its redox state. This study connects clinical data with structural visualization of albumin dynamicity in solution and underlines the functional importance of albumin's inherent flexibility.


Assuntos
Hepatopatias/metabolismo , Albumina Sérica/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Bilirrubina/sangue , Estudos de Casos e Controles , Doença Hepática Terminal/metabolismo , Ácidos Graxos/sangue , Humanos , Hepatopatias/sangue , Masculino , Pessoa de Meia-Idade , Oxirredução , Estrutura Terciária de Proteína , Adulto Jovem
17.
Medicine (Baltimore) ; 100(24): e26265, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34128857

RESUMO

ABSTRACT: Although evidence for the application of an albumin-bilirubin (ALBI) grading system to assess liver function in hepatocellular carcinoma (HCC) is available, less is known whether it can be applied to determine the prognosis of single HCC with different tumor sizes. This study aimed to address this gap.Here, we enrolled patients who underwent hepatectomy due to single HCC from 2010 to 2014. Analyses were performed to test the potential of the ALBI grading system to monitor the long-term survival of single HCC subjects with varying tumor sizes.A total of 265 participants were recruited. The overall survival (OS) among patients whose tumors were ≤7 cm was remarkably higher than those whose tumors were >7 cm. The Cox proportional hazards regression model identified the tumor differentiation grade, ALBI grade, and maximum tumor size as key determinants of OS. The ALBI grade could stratify the patients who had a single tumor ≤7 cm into 2 distinct groups with different prognoses. The OS between ALBI grades 1 and 2 was comparable for patients who had a single tumor >7 cm.We showed that the ALBI grading system can predict disease outcomes in patients with a single HCC with a tumor size ≤7 cm. However, the ALBI grade may not predict the prognosis of patients with a single tumor >7 cm.


Assuntos
Bilirrubina/sangue , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Gradação de Tumores/mortalidade , Albumina Sérica/análise , Adulto , Idoso , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/cirurgia , Feminino , Hepatectomia/mortalidade , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos
18.
Medicine (Baltimore) ; 100(22): e26180, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087882

RESUMO

BACKGROUND: Heart failure (HF) is one of the common and critical disease, and often accompanied by increased level of serum bilirubin, but the role of an indicator of bilirubin to monitor the prognosis of patients with heart failure is still unclear, so we implemented the study to systematically evaluate the predictive value of bilirubin in HF. METHODS: A comprehensive search and systematic review will be conducted on electronic databases such as Medline, Cochrane Library, Embase, Web of Science, Cochrane Clinical Trials Database of study on the relationship between bilirubin and prognosis of HF patients. Review Manager software (version 5.3.5) and STATA 14 software (version 14.0) will be used for data analysis and synthesis. RESULTS: The results will systematically and comprehensively reveal the evidence on the predictive value of bilirubin in HF. CONCLUSION: The study will display the effect of bilirubin level on the prognosis of patients with heart failure, and help clinicians to pay more attention to the level of bilirubin in patients with HF, and can take certain treatment measures as earlier as possible. INPLASY REGISTRATION NUMBER: INPLASY202140116.


Assuntos
Bilirrubina/sangue , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos como Assunto , Gerenciamento de Dados , Feminino , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico
19.
Chem Biodivers ; 18(8): e2100222, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34085382

RESUMO

Yinzhihuang oral liquid (YZH) is a traditional Chinese medicine that has been widely used in Asia to prevent and treat neonatal hyperbilirubinemia, but the published preclinical studies on its anti-hyperbilirubinemia effect are conducted in adult animals, partly due to the lack of preclinical neonatal hyperbilirubinemia animal models. In the present study, we tested six reagents to induce hyperbilirubinemia in neonatal rats, and established two appropriate neonatal hyperbilirubinemia rat models by subcutaneous injection of δ-Aminolevulinic acid (ALA, 200 mg/kg) or novobiocin (NOVO, 200 mg/kg). Oral treatment of YZH (80, 160 and 320 mg/kg) significantly decreased serum conjugated bilirubin levels in ALA-treated neonatal rats and serum unconjugated bilirubin levels in NOVO-treated neonatal rats, respectively. Additionally, pre-treatment of YZH also prevented the increase of serum bilirubin levels in both ALA- and NOVO-treated rats. Mechanistically, YZH significantly up-regulated the mRNA expression of genes involved in hepatic bilirubin disposition (organic anion-transporting polypeptide 1b2, Oatp1b2; multidrug resistance-associated protein 2, Mrp2) and bilirubin conjugation (UDP-glucuronosyltransferase 1a1, Ugt1a1). Additionally, YZH up-regulated the mRNA expression of cytochrome P450 1A1 (Cyp1a1), the target gene of aryl hydrocarbon receptor (AhR), and increased the nuclear protein levels of AhR in livers of neonatal rats. YZH and its two active ingredients, namely baicalin (BCL) and 4'-hydroxyacetophenone (4-HT), up-regulated the mRNA expression of AhR target genes (CYP1A1 and UGT1A1) and increased nuclear protein levels of AhR in HepG2 cells. In conclusion, the present study provides two neonatal hyperbilirubinemia animal models and evaluates the anti-hyperbilirubinemia effect and mechanisms of YZH in neonatal animals.


Assuntos
Medicamentos de Ervas Chinesas/química , Administração Oral , Ácido Aminolevulínico/toxicidade , Animais , Animais Recém-Nascidos , Bilirrubina/sangue , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Células Hep G2 , Humanos , Hiperbilirrubinemia/induzido quimicamente , Hiperbilirrubinemia/tratamento farmacológico , Hiperbilirrubinemia/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Medicina Tradicional Chinesa , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Novobiocina/toxicidade , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Hidrocarboneto Arílico/antagonistas & inibidores , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Regulação para Cima/efeitos dos fármacos
20.
Sci Rep ; 11(1): 11610, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34078983

RESUMO

Following access into the cell, colloidal silver nanoparticles exhibit generalized cytotoxic properties, thus appear as omnipotent microbicidal, but not suitable for systemic use unless are free of toxic effects on host cells. The AgNP-Serum-18 when prepared from silver nitrate, using dextrose as reducing and group-matched homologous serum as a stabilizing agent, selective endocytosis, and oxidative stress-dependent bio-functional damages to the host are mostly eliminated. For their bio-mimicking outer coat, there is the least possibility of internalization into host cells or liberation of excess oxidants in circulation following interaction with erythrocytes or vascular endothelial cells. The presence of infection-specific antibodies in the serum can make such nano-conjugates more selective. A potent antimicrobial action and a wide margin of safety for mammalian cells in comparison with very similar PVA-capped silver nanoparticles have been demonstrated by the in-vitro challenge of such nanoparticles on different microbes, human liver cell-line, and in-vivo study on mice model. This may open up wide-range therapeutic prospects of colloidal nanoparticles.


Assuntos
Antibacterianos/farmacologia , Nanopartículas Metálicas/química , Nitrato de Prata/farmacologia , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Antibacterianos/síntese química , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Coloides , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Nanopartículas Metálicas/ultraestrutura , Camundongos , Testes de Sensibilidade Microbiana , Especificidade de Órgãos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento
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