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1.
Diabetes Res Clin Pract ; 167: 108351, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32711001

RESUMO

AIMS: Coronavirus disease (COVID-19), also referred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is instigated by a novel coronavirus. The disease was initially reported in Wuhan, China, in December 2019. Diabetes is a risk factor associated with adverse outcomes. Herein, our objective was to investigate the characteristics of laboratory findings of type 2 diabetes mellitus (T2DM) patients infected with SARS-CoV-2. METHODS: This was a retrospective study and included 80 T2DM patients of Jinling Hospital from 2010 to 2020, as well as 76 COVID-19 patients without T2DM and 55 COVID-19 patients with T2DM who were treated at Huoshen hill Hospital from February 11 to March 18, 2020. We then compared the differences in laboratory test results between the three groups. RESULTS: The levels of lymphocytes, uric acid (UA), and globulin in the T2DM group were significantly higher. In contrast, C-reactive protein (CRP), creatinine, and lactic dehydrogenase (LDH)levels were lower than those in the COVID-19 (p < 0.05) and COVID-19 + T2DM groups (p < 0.05). No considerable difference was observed regarding the levels of alanine aminotransferase (ALT), white blood cell (WBC), aspartate aminotransferase (AST), globulin, and blood urea nitrogen (BUN) in the three groups (p > 0.05). CONCLUSION: T2DM patients infected with SARS-CoV-2 showed decreased levels of body mass index (BMI), lymphocytes, UA, and albumin, and increased CRP levels. The decreased BMI, UA, and albumin levels may be associated with oxidative stress response and nutritional consumption. The decreased lymphocyte counts and increased CRP levels may be related to the infection.


Assuntos
Infecções por Coronavirus/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Pneumonia Viral/metabolismo , Idoso , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Betacoronavirus , Nitrogênio da Ureia Sanguínea , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Comorbidade , Infecções por Coronavirus/complicações , Creatinina/metabolismo , Diabetes Mellitus Tipo 2/complicações , Feminino , Globulinas/metabolismo , Humanos , L-Lactato Desidrogenase/metabolismo , Contagem de Linfócitos , Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica/metabolismo , Ácido Úrico/metabolismo
2.
Medicina (Kaunas) ; 56(7)2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32708858

RESUMO

The evolving pandemic of Coronavirus Disease 2019 has posed a substantial health risk worldwide. However, there is a paucity of data regarding the clinical course and the therapeutic management of patients with chronic kidney disease and COVID-19 infection. To date, most evidence has come from renal transplantation, with about 45 patients reported thus far, and the current data from the ERA-EDTA (ERACODA) registry for transplanted patients and patients on Renal Replacement Therapy (RRT); as for those with glomerular diseases, data are lacking. Herein, we report the case of a 62-year-old patient with severe membranoproliferative glomerulonephritis who had been receiving a high burden of immunosuppression until four months before the COVID-19 infection. He developed severe disease with acute respiratory failure requiring mechanical ventilation. After treatment with hydroxychloroquine and azithromycin, despite his low chances, he gradually recovered and survived. To the best of our knowledge, this is one of the few reported patients with glomerulonephritis who had COVID-19 Besides our single case with glomerulonephritis early during the disease outbreak, the very low prevalence of COVID-19 infection in the country's transplant recipients (0.038%) and dialysis patients (0.24%) reflects the impact of the rapid implementation of social distancing rules as well as of preventive measures for disease control in the hospitals and dialysis units in our country.


Assuntos
Infecções por Coronavirus/complicações , Crioglobulinemia/complicações , Glomerulonefrite Membranoproliferativa/complicações , Pneumonia Viral/complicações , Insuficiência Respiratória/etiologia , Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Betacoronavirus , Ceftriaxona/uso terapêutico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Creatinina/metabolismo , Crioglobulinemia/imunologia , Ciclofosfamida , Inibidores Enzimáticos/uso terapêutico , Glomerulonefrite Membranoproliferativa/tratamento farmacológico , Glomerulonefrite Membranoproliferativa/imunologia , Glomerulonefrite Membranoproliferativa/metabolismo , Glucocorticoides/uso terapêutico , Grécia , Humanos , Hidroxicloroquina/uso terapêutico , Hospedeiro Imunocomprometido , Fatores Imunológicos/uso terapêutico , Falência Renal Crônica/terapia , Transplante de Rim , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/imunologia , Pulmão/diagnóstico por imagem , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Diálise Renal , Respiração Artificial , Insuficiência Respiratória/terapia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rituximab/uso terapêutico , Tomografia Computadorizada por Raios X
3.
JCI Insight ; 5(14)2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32559180

RESUMO

BACKGROUNDReprogramming of host metabolism supports viral pathogenesis by fueling viral proliferation, by providing, for example, free amino acids and fatty acids as building blocks.METHODSTo investigate metabolic effects of SARS-CoV-2 infection, we evaluated serum metabolites of patients with COVID-19 (n = 33; diagnosed by nucleic acid testing), as compared with COVID-19-negative controls (n = 16).RESULTSTargeted and untargeted metabolomics analyses identified altered tryptophan metabolism into the kynurenine pathway, which regulates inflammation and immunity. Indeed, these changes in tryptophan metabolism correlated with interleukin-6 (IL-6) levels. Widespread dysregulation of nitrogen metabolism was also seen in infected patients, with altered levels of most amino acids, along with increased markers of oxidant stress (e.g., methionine sulfoxide, cystine), proteolysis, and renal dysfunction (e.g., creatine, creatinine, polyamines). Increased circulating levels of glucose and free fatty acids were also observed, consistent with altered carbon homeostasis. Interestingly, metabolite levels in these pathways correlated with clinical laboratory markers of inflammation (i.e., IL-6 and C-reactive protein) and renal function (i.e., blood urea nitrogen).CONCLUSIONIn conclusion, this initial observational study identified amino acid and fatty acid metabolism as correlates of COVID-19, providing mechanistic insights, potential markers of clinical severity, and potential therapeutic targets.FUNDINGBoettcher Foundation Webb-Waring Biomedical Research Award; National Institute of General and Medical Sciences, NIH; and National Heart, Lung, and Blood Institute, NIH.


Assuntos
Infecções por Coronavirus/metabolismo , Ácidos Graxos/metabolismo , Interleucina-6/metabolismo , Cinurenina/metabolismo , Estresse Oxidativo , Pneumonia Viral/metabolismo , Insuficiência Renal/metabolismo , Adulto , Idoso , Aminoácidos/metabolismo , Betacoronavirus , Glicemia/metabolismo , Estudos de Casos e Controles , Creatina/metabolismo , Creatinina/metabolismo , Cistina , Ácidos Graxos não Esterificados/metabolismo , Feminino , Humanos , Masculino , Metaboloma , Metabolômica , Metionina/análogos & derivados , Pessoa de Meia-Idade , Pandemias , Poliaminas/metabolismo , Proteólise , Triptofano/metabolismo
4.
Toxicon ; 184: 152-157, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32531289

RESUMO

Aflatoxicosis is one of the threats that cause severe mortalities in fish farms. The dietary functional additives are a friendly approach attributed to beneficial effects on aquatic animals. The study aimed at evaluating the impact of Spirulina platensis (SP) on the biochemical indices and antioxidative function of Nile tilapia (Oreochromis niloticus) intoxicated with aflatoxin B1 (AFB1). A control diet and 3 test diets were enriched with 0% SP/0 mg AFB1/kg (control), 1% SP (SP), 2.5 mg AFB1/kg diet (AFB1), and 1% SP+2.5 mg AFB1/kg diet (SP/AFB1). The diets were supplied to three aquaria for each group twice daily at the rate of 2.5% for 30 days. The blood alanine transaminase (ALT), alkaline phosphatase (ALP), and aspartate transaminase (AST) were significantly increased by AFB1 toxicity with regards to fish fed the control and SP diets (P < 0.05). The inclusion of SP in the diet of tilapia intoxicated with AFB1 lowered the levels of ALT, AST, and ALP in comparison to fish contaminated with AFB1 without SP (P < 0.05). The total blood protein and albumin were decreased in fish contaminated with AFB1 (P < 0.05); however, the dietary SP resulted in improving the blood protein and albumin with similar levels with the control and SP diets. The urea and creatinine were increased in tilapia fed AFB1 diet without SP (P < 0.05); however, the inclusion of SP reduced the levels of urea and creatinine with similar levels with the control and SP diets. The antioxidative capacity of Nile tilapia fed SP and contaminated with AFB1 is expressed by superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) concentration. The activities of SOD and GSH were decreased by AFB1 (P < 0.05); however, dietary SP increased the SOD and GSH in fish fed AFB1. On the other hand, the concentration of MDA was increased in tilapia fed AFB1 (P < 0.05); however, SP decreased the level of MDA in fish fed AFB1. In conclusion, the application of SP in the aquafeed seems to be an innovative approach to relieve the toxic influences of AFB1 on aquatic animals.


Assuntos
Aflatoxina B1/toxicidade , Ciclídeos/fisiologia , Venenos/toxicidade , Spirulina/fisiologia , Alanina Transaminase/metabolismo , Ração Animal , Animais , Antioxidantes/metabolismo , Aspartato Aminotransferases/metabolismo , Catalase/metabolismo , Creatinina/metabolismo , Dieta , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Malondialdeído/metabolismo , Estresse Oxidativo , Superóxido Dismutase/metabolismo
5.
Life Sci ; 256: 117901, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32504759

RESUMO

AIMS: Cyclophosphamide (CTX) is an effective anti-tumor and immunosuppressive agent, but it induces nephrotoxicity in clinical applications. The present study aimed to evaluate the protective effect of pyrroloquinoline quinone (PQQ) on CTX-induced nephrotoxicity. MAIN METHODS: We injected male ICR mice with CTX (80 mg/kg/day), and determined nephrotoxicity indices, MDA and antioxidant defenses, inflammatory cytokines, and the levels of main proteins in the Nrf2-HO-1 and NLRP3 signaling pathways. KEY FINDINGS: PQQ has significantly decreased the serum levels of creatinine and urea compared to Model group. When treated with PQQ, MDA, IL-1ß, IL-6, and TNF-α levels have decreased, and SOD, GSH-Px, and CAT activity have increased in the kidney tissues of CTX-induced mice. PQQ activated the Nrf2-mediated signaling pathway, as indicated by the increased expression of Nrf2, HO-1, GCLM, and NQO1. Moreover, PQQ inhibited the NLRP3 inflammatory pathway, as indicated by the reduced expression of NLRP3, ASC, and Caspase-1. SIGNIFICANCE: Our results suggest that PQQ protects against CTX-induced nephrotoxicity, probably by activating the Nrf2-mediated antioxidant pathway and inhibiting the NLRP3 inflammatory pathway.


Assuntos
Ciclofosfamida/efeitos adversos , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Cofator PQQ/uso terapêutico , Transdução de Sinais , Animais , Antioxidantes/metabolismo , Nitrogênio da Ureia Sanguínea , Peso Corporal/efeitos dos fármacos , Creatinina/metabolismo , Citocinas/metabolismo , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Rim/efeitos dos fármacos , Rim/enzimologia , Rim/patologia , Masculino , Malondialdeído/metabolismo , Camundongos Endogâmicos ICR , Modelos Biológicos , Tamanho do Órgão/efeitos dos fármacos , Cofator PQQ/química , Cofator PQQ/farmacologia
7.
Am Heart J ; 223: 23-33, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32135338

RESUMO

BACKGROUND: Randomized clinical trials demonstrated the efficacy and safety of apixaban in preventing stroke in patients with atrial fibrillation (AF). However, data on patients with low creatinine clearance (CCr), especially CCr 15-29 mL/min, are limited. METHODS: The J-ELD AF Registry is a large-scale, multicenter prospective observational study of Japanese nonvalvular AF patients aged ≥75 years taking on-label dose (standard dose of 5 mg bid or reduced dose of 2.5 mg bid) of apixaban. The entire cohort (3,015 patients from 110 institutions) was divided into 3 CCr subgroups: CCr ≥50 mL/min (n = 1,165, 38.6%), CCr 30-49 mL/min (n = 1,395, 46.3%), and CCr 15-29 mL/min (n = 455, 15.1%). RESULTS: The event incidence rates (/100 person-years) were 1.76, 1.39, and 1.67 for stroke or systemic embolism (log rank P = .762); 1.39, 1.93, and 3.13 for bleeding requiring hospitalization (log rank P = .159); 1.75, 2.76, and 7.87 for total deaths (log rank P < .001); and 0.46, 0.84, and 2.62 for cardiovascular deaths (log rank P < .001), respectively. After adjusting for confounders by Cox regression analysis, CCr 15-29 was an independent risk for total death and cardiovascular death but not for stroke or systemic embolism, or bleeding requiring hospitalization. CONCLUSIONS: The incidence of events in each CCr value group was comparable for stroke or systemic embolism and bleeding requiring hospitalization, and significantly higher for total deaths and cardiovascular deaths only in the CCr 15- to 29-mL/min group, in Japanese nonvalvular AF patients aged ≥75 years.


Assuntos
Fibrilação Atrial/metabolismo , Creatinina/metabolismo , Inibidores do Fator Xa/uso terapêutico , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Embolia/epidemiologia , Feminino , Hemorragia/epidemiologia , Humanos , Masculino , Estudos Prospectivos , Sistema de Registros , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Resultado do Tratamento
8.
Life Sci ; 248: 117464, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32097667

RESUMO

AIMS: The present study was carried out to investigate the influences of Selenium/Zinc-Enriched probiotics (SeZnP) on growth performance, serum enzyme activity, antioxidant capability, inflammatory factors and gene expression associated with Wistar rats inflated under high ambient thermal-stress. MAIN METHODS: Sixty male rates with six-weeks of age were randomly allocated into five groups (12 per group) and fed basal diet (Control), basal diet supplemented with probiotics (P), Zinc-Enriched probiotics (ZnP, 100 mg/L), Selenium-Enriched Probiotics (SeP, 0.3 mg/L) and Selenium/Zinc-Enriched probiotics (SeZnP, 0.3 mg + 100 mg/L). The experiment lasted 30 days. Blood and Tissues samples were taken to investigate serum enzyme activity, antioxidants capability and inflammatory factors by using of commercial kits and antioxidant, heat shock and inflammatory related molecules expressions were determined by qRT-PCR. KEY FINDINGS: Data analysis revealed that thermal stress significantly increased the level of Aspartate-aminotransferase, Alanine-aminotransferase, Lactate-dehydrogenase, Creatine-kinase, blood urea nitrogen, Creatinine and Alkaline phosphatase compared to P, ZnP, SeP or SeZnP groups (P < 0.01). However, supplementation of ZnP, SeP, and SeZnP significantly enhanced glutathione content, glutathione-peroxidase & superoxide-dismutase activity, and decreased malondialdehyde content (P < 0.05). Moreover, the concentration of IL-2, IL-6 and IL-8 were significantly increased while IL-10 was significantly decreased (P < 0.05). Furthermore, the expression of GPx1 and SOD1 genes were significantly increased, but COX-2, iNOS, HSP70 and 90 mRNA levels were significantly decreased (P < 0.05). Finally, the highest influence of the mentioned parameters was observed in SeZnP supplemented group. SIGNIFICANCE: Our study suggests that SeZnP supplementation serves as possible and best nutritive than ZnP or SeP for Wistar rats raising under high ambient temperature.


Assuntos
Antioxidantes/administração & dosagem , Suplementos Nutricionais , Regulação da Expressão Gênica/efeitos dos fármacos , Resposta ao Choque Térmico/efeitos dos fármacos , Probióticos/administração & dosagem , Selênio/administração & dosagem , Zinco/administração & dosagem , Alanina Transaminase/genética , Alanina Transaminase/metabolismo , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Animais , Aspartato Aminotransferases/genética , Aspartato Aminotransferases/metabolismo , Nitrogênio da Ureia Sanguínea , Creatina Quinase/genética , Creatina Quinase/metabolismo , Creatinina/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Resposta ao Choque Térmico/genética , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo , Masculino , Malondialdeído/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Wistar , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
9.
Diabetes Res Clin Pract ; 161: 108079, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32057963

RESUMO

AIMS: To investigate the agreement of glomerular filtration rate (GFR) determination between 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA) plasma clearance (GFREDTA) and 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) plasma clearance (GFRDTPA), the Gates 99mTc-DTPA renographic method (GFRGates) and the serum creatinine Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI, GFRSCr) in patients with type 2 diabetes mellitus (T2DM). METHODS: Ninety-nine T2DM patients underwent GFR determinations simultaneously with 51Cr-EDTA and 99mTc-DTPA (using the slope-intercept technique and the Brochner-Mortensen correction) and also with GFRGates and GFRSCr. RESULTS: In the comparison between GFREDTA versus GFRDTPA, GFRGates and GFRSCr, the Bland-Altman statistic provided 0.0 ± 13.2, 17.4* ± 28.8 and -5.9* ± 30.1 (*p < 0.001 for the difference from 0). Lin's concordance correlation coefficient showed substantial (0.976), poor (0.737) and poor (0.872) agreement, respectively. The proportion of the index results within the 30% and 10% of GFREDTA measurements were 95% and 74% for GFRDTPA, 53% and 19% for GFRGates, and 83% and 26% for GFRSCr, respectively. CONCLUSION: In T2DM patients, a clinically acceptable agreement is demonstrated between 51Cr-EDTA and 99mTc-DTPA plasma clearance for GFR measurements, suggesting conditional interchangeability between those compounds. Both the CKD-EPI prediction equation and the Gates' renographic method cannot assess GFR reliably, the latter appearing less unfailing than the former.


Assuntos
Creatinina/metabolismo , Diabetes Mellitus Tipo 2/sangue , Taxa de Filtração Glomerular/fisiologia , Insuficiência Renal Crônica/sangue , Pentetato de Tecnécio Tc 99m/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Renografia por Radioisótopo , Insuficiência Renal Crônica/diagnóstico , Adulto Jovem
10.
PLoS Med ; 17(2): e1003050, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32109242

RESUMO

BACKGROUND: In studies including the general population, the presence of non-malignant monoclonal gammopathy (MG) can be causally associated with kidney damage and shorter survival. We assessed whether the presence of an MG is associated with a higher risk of kidney failure or death in individuals with chronic kidney disease (CKD). METHODS AND FINDINGS: Data were used from 3 prospective cohorts of individuals with CKD (not on dialysis or with a kidney transplant): (1) Renal Impairment in Secondary Care (RIISC, Queen Elizabeth Hospital and Heartlands Hospital, Birmingham, UK, N = 878), (2) Salford Kidney Study (SKS, Salford Royal Hospital, Salford, UK, N = 861), and (3) Renal Risk in Derby (RRID, Derby, UK, N = 1,739). Participants were excluded if they had multiple myeloma or any other B cell lymphoproliferative disorder with end-organ damage. Median age was 71.0 years, 50.6% were male, median estimated glomerular filtration rate was 42.3 ml/min/1.73 m2, and median urine albumin-to-creatinine ratio was 3.4 mg/mmol. All non-malignant MG was identified in the baseline serum of participants of RIISC. Further, light chain MG (LC-MG) was identified and studied in participants of RIISC, SKS, and RRID. Participants were followed up for kidney failure (defined as the initiation of dialysis or kidney transplantation) and death. Associations with the risk of kidney failure were estimated by competing-risks regression (handling death as a competing risk), and associations with death were estimated by Cox proportional hazards regression. In total, 102 (11.6%) of the 878 RIISC participants had an MG. During a median follow-up time of 74.0 months, there were 327 kidney failure events and 202 deaths. The presence of MG was not associated with risk of kidney failure (univariable subhazard ratio [SHR] 0.97 [95% CI 0.68 to 1.38], P = 0.85; multivariable SHR 1.16 [95% CI 0.80 to 1.69], P = 0.43), and although there was a higher risk of death in univariable analysis (hazard ratio [HR] 2.13 [95% CI 1.49 to 3.02], P < 0.001), this was not significant in multivariable analysis (HR 1.37 [95% CI 0.93 to 2.00], P = 0.11). Fifty-five (1.6%) of the 3,478 participants from all 3 studies had LC-MG. During a median follow-up time of 62.5 months, 564 of the 3,478 participants progressed to kidney failure, and 803 died. LC-MG was not associated with risk of kidney failure (univariable SHR 1.07 [95% CI 0.58 to 1.96], P = 0.82; multivariable SHR 1.42 [95% CI 0.78 to 2.57], P = 0.26). There was a higher risk of death in those with LC-MG in the univariable model (HR 2.51 [95% CI 1.59 to 3.96], P < 0.001), but not in the multivariable model (HR 1.49 [95% CI 0.93 to 2.39], P = 0.10). An important limitation of this work was that only LC-MG, rather than any MG, could be identified in participants from SKS and RRID. CONCLUSIONS: The prevalence of MG was higher in this CKD cohort than that reported in the general population. However, the presence of an MG was not independently associated with a significantly higher risk of kidney failure or, unlike in the general population, risk of death.


Assuntos
Falência Renal Crônica/epidemiologia , Gamopatia Monoclonal de Significância Indeterminada/epidemiologia , Mortalidade , Insuficiência Renal Crônica/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Albuminúria , Estudos de Coortes , Comorbidade , Creatinina/metabolismo , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Cadeias Leves de Imunoglobulina , Falência Renal Crônica/metabolismo , Falência Renal Crônica/terapia , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/metabolismo , Paraproteinemias/epidemiologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Diálise Renal , Insuficiência Renal Crônica/metabolismo , Reino Unido/epidemiologia
11.
Ann Biol Clin (Paris) ; 78(1): 93-107, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32108587

RESUMO

The measurement performance of 13 biochemistry parameters (CEA, CA 19-9, amylase, lipase, sodium, potassium, chloride, creatinine, glucose, protein, albumin, LDH, triglycerides) was tested in a panel of biological fluids other than blood and urine (peritoneal, pleural, pancreatic fluids ...). Our protocol, based on a risk analysis, allowed us to justify our choices and compare the performance obtained with those of the serum or plasma matrix already validated. Thus, the coefficients of variation obtained in body fluids are comparable. The assessment of accuracy (spiking and dilution tests) shows the absence of bias, which is consistent with the absence of matrix effect. The linearity studied by dilution tests shows that the upper limits of the measurement interval communicated by the supplier are applicable to body fluids. The absence of contamination and stability have been also confirmed. All analytes are stable for 3 days at room temperature, 7 days between 2 and 8̊C, and 6 months at -20̊C; except LDH and lipase. For most analytes, at least one interference (hemolysis, icterus, lipemia) was found. Finally, a bibliographical study, confronted with the experience of prescribers, led us to define optimal thresholds to help interpret patients' results. In conclusion, this work has allowed us to validate analytical methods for body fluids testing after relying on their comparability to the blood matrix. We have also been able to adapt our practices and finally be accredited according to the standard NF IN ISO 15189.


Assuntos
Biomarcadores/análise , Líquidos Corporais/química , Técnicas de Laboratório Clínico , Albuminas/análise , Albuminas/metabolismo , Amilases/análise , Amilases/metabolismo , Biomarcadores/metabolismo , Líquidos Corporais/metabolismo , Antígeno CA-19-9/análise , Antígeno CA-19-9/metabolismo , Antígeno Carcinoembrionário/análise , Antígeno Carcinoembrionário/metabolismo , Cloretos/análise , Cloretos/metabolismo , Técnicas de Laboratório Clínico/métodos , Técnicas de Laboratório Clínico/normas , Creatinina/análise , Creatinina/metabolismo , Glucose/análise , Glucose/metabolismo , Humanos , L-Lactato Desidrogenase/análise , L-Lactato Desidrogenase/metabolismo , Lipase/análise , Lipase/metabolismo , Potássio/análise , Potássio/metabolismo , Proteínas/análise , Proteínas/metabolismo , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Sódio/análise , Sódio/metabolismo , Temperatura , Triglicerídeos/análise , Triglicerídeos/metabolismo
12.
Anticancer Res ; 40(1): 299-304, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892580

RESUMO

BACKGROUND/AIM: To clarify whether renal dysfunction affects the incidence of adverse events associated with oxaliplatin, the present study was designed to investigate the relationship between creatinine clearance (Ccr) and the incidence of oxaliplatin-related adverse events. PATIENTS AND METHODS: A total of 287 CRC patients who received the first cycle of oxaliplatin-based chemotherapy were eligible. Adverse events, including nausea, vomiting, neutropenia and thrombocytopenia, were graded, and the relationship between Ccr and the incidence of adverse events was examined using multivariable logistic regression analysis. RESULTS: A multivariable analysis indicated that the incidence of grade ≥2 nausea increased, while the incidence of other adverse events tended to be higher, as the Ccr decreased. Particularly, renal dysfunction (Ccr <60 ml/min) was a significant risk factor for grade ≥2 nausea (p=0.042). CONCLUSION: Care should be taken to avoid adverse events associated with oxaliplatin in patients with renal dysfunction.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Rim/fisiopatologia , Oxaliplatina/efeitos adversos , Oxaliplatina/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Creatinina/metabolismo , Feminino , Humanos , Incidência , Rim/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Fatores de Risco , Adulto Jovem
13.
Cell Death Dis ; 11(1): 73, 2020 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996668

RESUMO

Our preliminary work has revealed that vitamin D receptor (VDR) activation is protective against cisplatin induced acute kidney injury (AKI). Ferroptosis was recently reported to be involved in AKI. Here in this study, we investigated the internal relation between ferroptosis and the protective effect of VDR in cisplatin induced AKI. By using ferroptosis inhibitor ferrostatin-1 and measurement of ferroptotic cell death phenotype in both in vivo and in vitro cisplatin induced AKI model, we observed the decreased blood urea nitrogen, creatinine, and tissue injury by ferrostatin-1, hence validated the essential involvement of ferroptosis in cisplatin induced AKI. VDR agonist paricalcitol could both functionally and histologically attenuate cisplatin induced AKI by decreasing lipid peroxidation (featured phenotype of ferroptosis), biomarker 4-hydroxynonenal (4HNE), and malondialdehyde (MDA), while reversing glutathione peroxidase 4 (GPX4, key regulator of ferroptosis) downregulation. VDR knockout mouse exhibited much more ferroptotic cell death and worsen kidney injury than wild type mice. And VDR deficiency remarkably decreased the expression of GPX4 under cisplatin stress in both in vivo and in vitro, further luciferase reporter gene assay showed that GPX4 were target gene of transcription factor VDR. In addition, in vitro study showed that GPX4 inhibition by siRNA largely abolished the protective effect of paricalcitol against cisplatin induced tubular cell injury. Besides, pretreatment of paricalcitol could also alleviated Erastin (an inducer of ferroptosis) induced cell death in HK-2 cell. These data suggested that ferroptosis plays an important role in cisplatin induced AKI. VDR activation can protect against cisplatin induced renal injury by inhibiting ferroptosis partly via trans-regulation of GPX4.


Assuntos
Lesão Renal Aguda/metabolismo , Antineoplásicos/toxicidade , Cisplatino/toxicidade , Ferroptose/genética , Mitocôndrias/metabolismo , Receptores de Calcitriol/metabolismo , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/enzimologia , Lesão Renal Aguda/genética , Aldeídos/metabolismo , Animais , Morte Celular/genética , Linhagem Celular , Creatinina/metabolismo , Cicloexilaminas/farmacologia , Ergocalciferóis/farmacologia , Ferroptose/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia Eletrônica de Transmissão e Varredura , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/ultraestrutura , Fenilenodiaminas/farmacologia , Piperazinas/metabolismo , RNA Interferente Pequeno , Receptores de Calcitriol/agonistas , Receptores de Calcitriol/genética
14.
Sci Rep ; 10(1): 1241, 2020 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-31988325

RESUMO

Modified creatinine (Cr) index, calculated by age, sex, pre-dialysis serum Cr concentration, and Kt/V for urea, is an indicator of skeletal muscle mass in hemodialysis (HD) patients. It remains unknown whether the modified Cr index predicts infection-related mortality in this population. We investigated the association between the modified Cr index and infection-related mortality. A total of 3046 patients registered in the Q-Cohort Study, a multicenter, observational study of HD patients, were analyzed. Associations between sex-specific quartiles (Q1-Q4) of the modified Cr index and the risk for infection-related mortality were analyzed by Cox proportional hazard model. During a median follow-up of 8.8 years, 387 patients died of infection. The estimated risk for infection-related mortality was significantly higher in the lower quartiles (Q1, Q2, and Q3) than in the highest quartile (Q4) as the reference group (hazard ratios and 95% confidence intervals [CI]: Q1, 2.89 [1.70-5.06], Q2, 2.76 [1.72-4.62], and Q3, 1.79 [1.12-2.99]). The hazard ratio (95% CI) for a 1 mg/kg/day decrease in the modified Cr index was 1.18 (1.09-1.27, P < 0.01) for infection-related mortality. In conclusion, a lower modified Cr index is associated with an increased risk for long-term infection-related mortality in the HD population.


Assuntos
Creatinina/sangue , Infecções/mortalidade , Diálise Renal/mortalidade , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Estudos de Coortes , Creatinina/metabolismo , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Medição de Risco , Fatores de Risco , Resultado do Tratamento
15.
Ann Neurol ; 87(4): 547-555, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31957062

RESUMO

OBJECTIVE: To determine the clinical and molecular features in patients with amyotrophic lateral sclerosis 4 (ALS4) due to mutations in the senataxin (SETX) gene and to develop tools for evaluating SETX variants. METHODS: Our study involved 32 patients, including 31 with mutation in SETX at c.1166 T>C (p.Leu389Ser) and 1 with mutation at c.1153 G>A (p.Glu385Lys). Clinical characterization of the patients included neurological examination, blood tests, magnetic resonance imaging (MRI), and dual-energy x-ray absorptiometry (DEXA). Fibroblasts and motor neurons were obtained to model the disease and characterize the molecular alteration in senataxin function. RESULTS: We report key clinical features of ALS4. Laboratory analysis showed alteration of serum creatine kinase and creatinine in the Leu389Ser ALS4 cohort. MRI showed increased muscle fat fraction in the lower extremities, which correlates with disease duration (thigh fat fraction R2 = 0.35, p = 0.01; lower leg fat fraction R2 = 0.49, p < 0.01). DEXA measurements showed lower extremities are more affected than upper extremities (average fat z scores of 2.1 and 0.6, respectively). A cellular assay for SETX function confirmed that like the Leu389Ser mutation, the Glu385Lys variant leads to a decrease in R loops, likely from a gain of function. INTERPRETATION: We identified clinical laboratory and radiological features of ALS4, and hence they should be monitored for disease progression. The molecular characterization of R-loop levels in patient-derived cells provides insight into the disease pathology and assays to evaluate the pathogenicity of candidate mutations in the SETX gene. ANN NEUROL 2020;87:547-555.


Assuntos
Esclerose Amiotrófica Lateral/metabolismo , DNA Helicases/metabolismo , Enzimas Multifuncionais/metabolismo , RNA Helicases/metabolismo , Absorciometria de Fóton , Tecido Adiposo/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Esclerose Amiotrófica Lateral/diagnóstico por imagem , Esclerose Amiotrófica Lateral/genética , Esclerose Amiotrófica Lateral/fisiopatologia , Western Blotting , Creatina Quinase/metabolismo , Creatinina/metabolismo , DNA Helicases/genética , Eletromiografia , Feminino , Fibroblastos , Humanos , Células-Tronco Pluripotentes Induzidas , Lactente , Extremidade Inferior/diagnóstico por imagem , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Enzimas Multifuncionais/genética , Músculo Esquelético/diagnóstico por imagem , Mutação , Condução Nervosa , Estruturas R-Loop/genética , RNA Helicases/genética , RNA Mensageiro , Extremidade Superior/diagnóstico por imagem , Adulto Jovem
16.
Am J Kidney Dis ; 75(1): 21-29, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31303349

RESUMO

RATIONALE & OBJECTIVE: Angiotensin-converting enzyme (ACE) inhibitors are beneficial in heart failure with reduced ejection fraction (HFrEF). We sought to describe longitudinal trends in estimated glomerular filtration rate (eGFR) in HFrEF and how ACE-inhibitor therapy influences these changes. STUDY DESIGN: Post hoc analysis of trial data. SETTINGS & PARTICIPANTS: Symptomatic (Treatment Trial, n=2,423) and asymptomatic (Prevention Trial, n=4,094) patients from the Studies of Left Ventricular Dysfunction (SOLVD). EXPOSURE: Enalapril versus placebo. OUTCOMES: Early and long-term eGFR slope (ie, within and after the first 6 weeks) and 4 kidney end points: (1) serum creatinine level increase by≥0.3mg/dL, (2)>30% eGFR decline, (3)>40% eGFR decline, and (4) incident eGFR<30mL/min/1.73m2. ANALYTICAL APPROACH: Shared parameter models, multivariable Cox regression models. RESULTS: Baseline mean eGFR was lower in the Treatment Trial than in the Prevention Trial, 69.5±19.8 (SD) versus 76.2±18.6mL/min/1.73m2. Following randomization, an early eGFR decline occurred in the enalapril group; however, slopes during the median 3-year follow-up were not statistically different by randomization arm in either the Treatment Trial (-0.84 in enalapril vs-1.36mL/min/1.73m2 per year in placebo; P=0.08) or Prevention Trial (-1.27 in enalapril vs-1.36mL/min/1.73m2 per year in placebo; P=0.7). Random assignment to enalapril treatment increased the risk for all 4 outcomes in the Treatment Trial in the first 6-week period (HRs were 1.48 [95% CI, 1.10-1.99] for creatinine increase by≥0.3mg/dL; 1.38 [95% CI, 0.98-1.94] for eGFR decline> 30%; 2.60 [95% CI, 1.30-5.21] for eGFR decline> 40%; and 4.71 [95% CI, 1.78-12.50] for eGFR<30mL/min/1.73m2), but after the first year was not significantly associated with increased risk. A similar albeit less pronounced pattern was observed in the Prevention Trial, with risks present only in the early period. LIMITATIONS: Creatinine results were not blinded, making it possible that ACE-inhibitor/placebo dosing was influenced by creatinine level. CONCLUSION: Kidney function decline is slow in HFrEF. Although random assignment to enalapril treatment results in a statistically increased risk for kidney surrogates, the risk is limited to the early phase and late eGFR slopes and risks are not different by randomly assigned group.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Creatinina/metabolismo , Enalapril/uso terapêutico , Taxa de Filtração Glomerular , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Renal Crônica/epidemiologia , Volume Sistólico , Idoso , Doenças Assintomáticas , Feminino , Insuficiência Cardíaca/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Análise Multivariada , Modelos de Riscos Proporcionais , Insuficiência Renal Crônica/metabolismo
17.
J Forensic Sci ; 65(1): 128-133, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31365136

RESUMO

Urea, uric acid, and creatinine have been demonstrated to be relatively stable in postmortem blood (BL), thus being useful for diagnostic purposes. However, no studies have explored their levels in BL, vitreous humor (VH), and synovial fluid (SF) concurrently. Therefore, we measured and compared their levels in these fluids. We also determined the effects of various factors on their levels. The results indicated that BL urea, uric acid, and creatinine levels were significantly higher than VH and SF levels. VH and SF urea levels and SF creatinine levels had a strong correlation with BL urea and creatinine levels, respectively. BL creatinine levels were higher in men than in women. BL and SF creatinine levels were negatively correlated with age. SF uric acid and BL, VH, and SF creatinine levels exhibited a positive correlation with weight. Only VH creatinine levels were positively correlated with body mass index. None of urea, uric acid, and creatinine levels were correlated with postmortem interval.


Assuntos
Creatinina/metabolismo , Líquido Sinovial/metabolismo , Ureia/metabolismo , Ácido Úrico/metabolismo , Corpo Vítreo/metabolismo , Adolescente , Adulto , Idoso , Peso Corporal , Estudos de Coortes , Feminino , Medicina Legal , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Adulto Jovem
18.
J Forensic Sci ; 65(2): 508-512, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31483499

RESUMO

Vitreous fluid sampling for postmortem chemistry analysis is discouraged in pediatric forensic cases involving head trauma due to the risk of introducing retinal artifacts. Aqueous fluid is physically separated from the posterior chamber of the eye, and therefore, unlikely to produce vitreal artifact when sampled. Analysis of aqueous fluid is therefore proposed as a substitute for vitreous. Vitreous and aqueous fluid was sampled concurrently from 28 pediatric and 55 adult decedents, and sodium (Na), potassium (K), chloride (Cl), urea nitrogen (UN), creatinine (Cr), and glucose (Glc) concentrations were compared. Significant correlation existed between all analytes regardless of age or postmortem interval, and linear regression equations were derived. Aqueous concentrations were generally higher than vitreous for Na, K, and Cr and were marginally lower for Cl, UN, and Glc. Assuming vitreous fluid as a standard for correlating postmortem chemistry to antemortem serum values, aqueous may be a viable substitute for vitreous when expected differences are considered.


Assuntos
Humor Aquoso/metabolismo , Corpo Vítreo/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cloretos/metabolismo , Creatinina/metabolismo , Feminino , Medicina Legal/métodos , Glucose/metabolismo , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Potássio/metabolismo , Sódio/metabolismo , Ureia/metabolismo , Adulto Jovem
19.
Chem Biol Interact ; 315: 108863, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31628940

RESUMO

Gentamicin-induced nephrotoxicity has been well documented, although the causing mechanisms and preventative measures need further investigation. The current study aimed to explore the potential protective impacts of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on gentamicin-induced nephrotoxicity and the potential mechanisms in rats. Rats were randomly divided into four groups as follows: group1: normal control, group 2: received gentamicin only (100 mg/kg intraperitoneally), group 3: concurrently received gentamicin and celecoxib (30 mg/kg, orally) and group 4: received celecoxib. Celecoxib administration decreased gentamicin-induced rise in kidney weight, renal somatic index (RSI), blood urea nitrogen (BUN), serum creatinine (Cr), protein in urine, lactate dehydrogenase (LDH), nitric oxide (NOx), meanwhile, it increased serum albumin, urine Cr level and creatinine clearance (CCr), increased the renal endogenous antioxidant status, revealed by decreased malondialdehyde (MDA) and increased superoxide dismutase (SOD) and reduced glutathione (GSH). Gentamicin-induced elevated nuclear factor kappa B-P65 subunit (NFκB-p65), tumor necrosis factor-alpha (TNF-α) and apoptotic markers (tumor suppressor protein (p53) and caspase-3) protein levels were significantly decreased upon celecoxib treatment. Moreover, celecoxib suppressed renal myeloperoxidase (MPO) activity and posed improvement of histological features. In immunohistochemistry, celecoxib-treated rats showed decreased immunoreactivity against COX-2 in tubular cells and a mild positive immunoreactivity against heat shock protein 70 (HSP70) in renal interstitial cells. These findings propose that celecoxib treatment mitigates renal dysfunction via decreasing renal inflammation, oxidative/nitrosative stress, and apoptosis.


Assuntos
Caspase 3/metabolismo , Celecoxib/farmacologia , Nefropatias/tratamento farmacológico , Rim/efeitos dos fármacos , NF-kappa B/metabolismo , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Nitrogênio da Ureia Sanguínea , Creatinina/metabolismo , Ciclo-Oxigenase 2/metabolismo , Gentamicinas/farmacologia , Glutationa/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Masculino , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Fator de Transcrição RelA/metabolismo
20.
Vet Clin North Am Exot Anim Pract ; 23(1): 47-58, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31759451

RESUMO

Renal disease often remains undetected in living patients. Urinalysis might contribute to the diagnosis of some kinds of renal and metabolic diseases. Blood uric acid concentrations reflect the excretory functional capacity of the renal proximal tubules. In contrast, blood urea concentrations are significantly affected by the bird's hydration status and have been proposed as a useful variable to detect prerenal causes for renal impairment in birds. Measurement of exogenous creatinine excretion shows promising preliminary results to become a useful test for the assessment of renal excretion in birds.


Assuntos
Doenças das Aves/fisiopatologia , Creatinina/análise , Nefropatias/veterinária , Animais , Doenças das Aves/diagnóstico , Aves , Creatinina/metabolismo , Rim/metabolismo , Nefropatias/diagnóstico , Nefropatias/fisiopatologia , Nefrologia , Ureia/análise , Ácido Úrico/análise , Urinálise/veterinária
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