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1.
Molecules ; 26(11)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200394

RESUMO

Zinc is an effective anti-inflammatory and antioxidant trace element. The aim of this study was to analyse the protective effect of zinc and zinc-prolactin systems as additives of preservation solutions in the prevention of nephron damage caused during ischemia. The study used a model for storing isolated porcine kidneys in Biolasol®. The solution was modified with the addition of Zn at a dose of 1 µg/L and Zn: 1 µg/L with prolactin (PRL): 0.1 µg/L. After 2 h and 48 h of storage, the levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, sodium, potassium, creatinine and total protein were determined. Zinc added to the Biolasol® composition at a dose of 1 µg/L showed minor effectiveness in the protection of nephrons. In turn, Zn2+ added to Biolasol + PRL (PRL: 0.1 µg/L) acted as a prolactin inhibitor. We do not recommend the addition of Zn(II) (1 µg/L) and Zn(II) (1 µg/L) + PRL (0.1 µg/L) to the Biolasol solution.


Assuntos
Isquemia/metabolismo , Rim/metabolismo , Prolactina/metabolismo , Zinco/metabolismo , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Creatinina/metabolismo , Criopreservação/métodos , L-Lactato Desidrogenase/metabolismo , Preservação de Órgãos/métodos , Perfusão/métodos , Potássio/metabolismo , Sódio/metabolismo , Suínos
2.
Int Immunopharmacol ; 96: 107794, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34162156

RESUMO

To explore the characteristics of COVID-19 infection related kidney injury, we retrospectively collected cases of COVID-19 patients with definite clinical outcomes (discharge or death) and relevant laboratory results from Jan 3 to Mar 30, 2020 in Tongji hospital, Wuhan, China. 1509 patients were included, 1393 cases with normal baseline serum creatinine, and 116 cases with elevated baseline serum creatinine (EBSC). On admission, the prevalence of elevated serum creatinine, elevated blood urea nitrogen (BUN) and estimated glomerular filtration (eGFR) under 60 ml/min/1.73 m2 were 7.7%, 6.6% and 7.2%, respectively. The incidence of in-hospital death in the patients with EBSC was 7.8%, which was significantly higher than those with normal serum creatinine (1.2%). Inflammatory, immunological, and organ damage indices were relatively higher in the EBSC group, in which lymphocytes, albumin, and hemoglobin were significantly lower. Kaplan-Meier analysis revealed age above 65 years, males, comorbidities (especially for cardiovascular disease and tumor patients), lymphocyte count < 1.5 × 109/L, leukocyte count > 10 × 109/L, EBSC, eGFR < 60 ml/min/1.73 m2 were associated with in-hospital death. Multivariate Cox proportional hazard regression confirmed that EBSC (HR: 2.643, 95% CI: 1.111-6.285, P = 0.028), eGFR < 60 ml/min/1.73 m2 (HR: 3.889, 95% CI: 1.634-9.257, P = 0.002), were independent risk factors after adjusting for age, sex, any comorbidity, leukocyte and lymphocyte count. Therefore, the prevalence of kidney injury in patients with COVID-19 was high and associated with in-hospital mortality. Early detection and effective intervention of kidney injury may reduce COVID-19 deaths.


Assuntos
Injúria Renal Aguda/mortalidade , COVID-19/complicações , SARS-CoV-2/fisiologia , Idoso , Doenças Cardiovasculares/complicações , China , Comorbidade , Creatinina/sangue , Creatinina/metabolismo , Feminino , Mortalidade Hospitalar , Humanos , Inflamação/patologia , Leucócitos/patologia , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Prognóstico , Estudos Retrospectivos , Fatores de Risco
3.
Nutrients ; 13(5)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34067957

RESUMO

Creatine is a broadly used dietary supplement that has been extensively studied for its benefit on the musculoskeletal system. Yet, there is limited knowledge regarding the metabolic regulation of creatine in cells beyond the muscle. New insights concerning various regulatory functions for creatine in other physiological systems are developing. Here, we highlight the latest advances in understanding creatine regulation of T cell antitumor immunity, a topic that has previously gained little attention in the creatine research field. Creatine has been identified as an important metabolic regulator conserving bioenergy to power CD8 T cell antitumor reactivity in a tumor microenvironment; creatine supplementation has been shown to enhance antitumor T cell immunity in multiple preclinical mouse tumor models and, importantly, to synergize with other cancer immunotherapy modalities, such as the PD-1/PD-L1 blockade therapy, to improve antitumor efficacy. The potential application of creatine supplementation for cancer immunotherapy and the relevant considerations are discussed.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Creatinina/metabolismo , Imunoterapia , Neoplasias/terapia , Animais , Linfócitos T CD8-Positivos/metabolismo , Creatinina/uso terapêutico , Humanos , Imunoterapia/métodos , Neoplasias/imunologia
4.
Eur Rev Med Pharmacol Sci ; 25(8): 3377-3385, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33928626

RESUMO

OBJECTIVE: The aim of the study was to find factors associated with the mortality of admission to the intensive care unit (ICU) in patients with COVID-19. MATERIALS AND METHODS: Retrospective observational study with a database of 1987 patients with COVID-19 who had attended the emergency department of a private hospital network between February 2020 and April 2020 were analyzed. Clinical variables and some laboratory parameters were studied. The Charlson and Elixhauser comorbidity indices were calculated. The dependent variables were mortality and admission to the ICU. A descriptive and correlational analysis was performed. Logistic regression models and Kaplan-Meier survival curves were established. RESULTS: Positive correlations were observed between age, creatinine, and D-dimer levels, as well as with the scores obtained with the Charlson and Elixhauser indices. Differences in the levels of these parameters were also observed when analyzing variables such as mortality, sex or admission to the ICU. Mortality was associated with high creatinine and D-dimer levels and advanced age. Survival curves indicated longer survival in patients not admitted to the ICU, admitted to the hospital during the week, and in those with lower creatinine and D-dimer levels. CONCLUSIONS: Mortality in Spanish patients with COVID-19 admitted to private hospitals was associated with high creatinine and D-dimer levels and advanced age. Longer survival was obtained on weekdays. This study provides valuable information on the management and nursing care of these patients in order to optimize resources in pandemic situations.


Assuntos
COVID-19/fisiopatologia , Creatinina/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Mortalidade Hospitalar , Unidades de Terapia Intensiva/estatística & dados numéricos , Plantão Médico/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , COVID-19/metabolismo , COVID-19/mortalidade , Comorbidade , Estado Terminal , Serviço Hospitalar de Emergência , Feminino , Hospitalização , Hospitais Privados , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2 , Espanha , Fatores de Tempo
5.
Nutrients ; 13(3)2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33800983

RESUMO

Hericium erinaceus (H. erinaceus) is widely studied as a medicinal and edible fungus. Recent studies have shown that H. erinaceus has protective effects for diseases, such as inflammatory bowel disease and cancer, which are related to gut microbiota. To investigate the benefits of H. erinaceus intake on gut microbiota and blood indices in adulthood, we recruited 13 healthy adults to consume H. erinaceus powder as a dietary supplement. Blood changes due to H. erinaceus consumption were determined by routine hematological examination and characterized by serum biochemical markers. Microbiota composition was profiled by 16S ribosomal RNA gene sequencing. Results showed that daily H. erinaceus supplementation increased the alpha diversity within the gut microbiota community, upregulated the relative abundance of some short-chain fatty acid (SCFA) producing bacteria (Kineothrix alysoides, Gemmiger formicilis, Fusicatenibacter saccharivorans, Eubacterium rectale, Faecalibacterium prausnitzii), and downregulated some pathobionts (Streptococcus thermophilus, Bacteroides caccae, Romboutsia timonensis). Changes within the gut microbiota were correlated with blood chemical indices including alkaline phosphatase (ALP), low-density lipoprotein (LDL), uric acid (UA), and creatinine (CREA). Thus, we found that the gut microbiota alterations may be part of physiological adaptations to a seven-day H. erinaceus supplementation, potentially influencing beneficial health effects.


Assuntos
Biomarcadores/sangue , Alimentos Fortificados , Microbioma Gastrointestinal/efeitos dos fármacos , Hericium , Adulto , Fosfatase Alcalina/metabolismo , Bactérias/classificação , Bactérias/genética , Creatinina/metabolismo , Ácidos Graxos Voláteis , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Gota/prevenção & controle , Humanos , Doenças Inflamatórias Intestinais/prevenção & controle , Cálculos Renais/prevenção & controle , Lipoproteínas LDL , Masculino , Projetos Piloto , RNA Ribossômico 16S/genética , Ácido Úrico
6.
Life Sci ; 277: 119506, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33865881

RESUMO

Diclofenac, one of the most commonly used non-steroidal anti-inflammatory drugs, leads to severe adverse effects on the kidneys. The aim of the present study was to investigate the potential pretreatment effect of phosphodiesterase (1, 3 & 5) inhibitors on diclofenac-induced acute renal failure in rats. Rats orally received pentoxifylline (100 mg/kg), vinpocetine (20 mg/kg), cilostazol (50 mg/kg), or sildenafil (5 mg/kg) once per day for 6 consecutive days. Diclofenac (15 mg/kg) was injected on day-4, -5 and -6 in all groups except normal control group. The used phosphodiesterase inhibitors significantly reduced the diclofenac-induced elevation in the serum levels of blood urea nitrogen, creatinine and cystatin C. Moreover, the renal tissue contents of tumor necrosis factor (TNF)-α, nuclear factor (NF)-κB as well as the protein expression of toll-like receptor (TLR) 4 and high mobility group box (HMGB) 1 were markedly reduced by the used phosphodiesterase inhibitors, as compared to the diclofenac control. This was reflected on the marked improvement in histopathological changes induced by diclofenac. Sildenafil showed the best protection regarding TNF-α and NF-κB, while cilostazol showed the best results regarding TLR4, HMGB1 and histopathological examination. This study revealed the good protective effect of these phosphodiesterase inhibitors against diclofenac-induced acute renal failure.


Assuntos
Injúria Renal Aguda/metabolismo , Inibidores de Fosfodiesterase/farmacologia , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/patologia , Animais , Nitrogênio da Ureia Sanguínea , Cilostazol/farmacologia , Creatinina/metabolismo , Diclofenaco/efeitos adversos , Diclofenaco/farmacologia , Rim/patologia , Masculino , NF-kappa B/metabolismo , Pentoxifilina/farmacologia , Inibidores de Fosfodiesterase/metabolismo , Diester Fosfórico Hidrolases/metabolismo , Ratos , Ratos Wistar , Citrato de Sildenafila/farmacologia , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Alcaloides de Vinca/farmacologia
7.
Medicine (Baltimore) ; 100(14): e25411, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33832138

RESUMO

ABSTRACT: This study is to investigate the role of neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC) and creatinine in the diagnosis of acute kidney injury (AKI) secondary to liver cirrhosis.A total of 825 patients (including 540 liver cirrhosis patients and 285 healthy controls) were enrolled. Liver cirrhosis patients were further subdivided into AKI secondary to liver cirrhosis group (AKI group, 210 patients) and simple liver cirrhosis group (LC group, 330 patients). Serum NGAL/urine NGAL (sNGAL/uNGAL), and serum creatinine (sCr) levels as well as estimated glomerular filtration rates were measured. The diagnostic performances of these indicators in AKI secondary to liver cirrhosis were evaluated.The levels of sNGAL, uNGAL, CysC and sCr in the AKI group were significantly higher than those of LC and healthy control groups. However, the eGFR and c-aGFR of AKI group were significantly lower. With the progression of AKI (AKI-S1→AKI-S2→AKI-S3), the levels of sNGAL, uNGAL, CysC and sCr increased gradually, while the levels of c-aGFR and eGFR decreased gradually. The sNGAL, uNGAL and CysC were positively correlated with sCr (r = 0.638, 0.635, and 0.650), but negatively correlated with c-aGFR (r = -0.617, -0.606 and -0.655). However, eGFR had a negative correlation with sCr (r = -0.711), but a positive correlation with c-aGFR (r = 0.736). ROC curve analysis showed that the area under the curve for uNGAL was the largest (0.976), followed by sNGAL (0.967). The diagnostic efficacy of uNGAL and sNGAL in AKI group were 0.907 and 0.870, and the risk degrees were OR = 54.524 and 5.115, respectively.NGAL might perform better than sCr and CysC in the diagnosis of AKI secondary to liver cirrhosis, while uNGAL might be a better indicator than sNGAL in AKI diagnosis.


Assuntos
Injúria Renal Aguda/diagnóstico , Creatinina/metabolismo , Cistatina C/metabolismo , Lipocalina-2/metabolismo , Cirrose Hepática/complicações , Injúria Renal Aguda/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Estudos de Casos e Controles , Feminino , Taxa de Filtração Glomerular , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Curva ROC , Sensibilidade e Especificidade
8.
PLoS One ; 16(4): e0249346, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33861750

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a serious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and in severe cases associated with acute respiratory distress syndrome (ARDS). OBJECTIVE: To describe the clinical characteristics of patients with ARDS-COVID-19. MATERIALS AND METHODS: This study involved 197 male Egyptian participants, among them111 COVID-19 patients presented with ARDS, 60 COVID-19 patients presented with non-ARDS, and 26 Non-COVID-19 patients. We reported the analysis results of clinical and laboratory information, including blood routine tests, blood biochemistry parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine and C-reactive protein (CRP)], thrombotic activity (D-dimer) and serum ferritin and lactate dehydrogenase (LDH). RESULTS: The levels of hemoglobin, AST, creatinine, monocyte count, monocyte %, RBC count, TLC, and platelet count were not significantly different among the groups. The lymphopenia and increased CRP, ALT, D-dimer, ferritin, and LDH were observed in patients with ARDS-COVID-19. CONCLUSION: COVID-19 patients with ARDS presented with lymphopenia, increased thrombotic activity, increased CRP, LDH, and ferritin levels. The results revealed that CRP, D-dimer, LDH levels, and lymphopenia have a significant association with the COVID-19 severity and can be used as biomarkers to predict the disease severity.


Assuntos
COVID-19/diagnóstico , COVID-19/epidemiologia , Síndrome do Desconforto Respiratório/virologia , Adulto , Idoso , Alanina Transaminase/sangue , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/sangue , Aspartato Aminotransferases/metabolismo , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , COVID-19/sangue , COVID-19/virologia , Creatinina/sangue , Creatinina/metabolismo , Egito/epidemiologia , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Hospitalização , Humanos , L-Lactato Desidrogenase/sangue , L-Lactato Desidrogenase/metabolismo , Contagem de Leucócitos , Contagem de Linfócitos , Linfopenia/sangue , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Síndrome do Desconforto Respiratório/sangue , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/epidemiologia , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
9.
Molecules ; 26(7)2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33800652

RESUMO

In Thailand, people in the highland communities whose occupational exposure to pesticides used the root of Litsea martabanica as a detoxifying agent. However, the scientific data to support the traditional use of this plant are insufficient. This study aimed to evaluate the antioxidant activity and anti-pesticide potential of L. martabanica root extract. Antioxidant properties were investigated by 2,2'-diphenyl-1-picrylhydrazyl (DPPH) assay, superoxide radicals scavenging assay, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay, ferric reducing antioxidant power (FRAP), and total phenolic content determination. In all assays, L. martabanica extracts and their fractions exhibited high antioxidant activities differently. The water extract is traditionally used as a detoxifying agent. Therefore, it was chosen for in vivo experiments. The rats received the extract in a way that mimics the traditional methods of tribal communities followed by chlorpyrifos for 16 days. The results showed that acetylcholinesterase activity decreases in pesticide-exposed rats. Treatment with the extract caused increasing acetylcholinesterase activity in the rats. Therefore, L. martabanica extract may potentially be used as a detoxifying agent, especially for the chlorpyrifos pesticide. The antioxidant properties of L. martabanica may provide a beneficial effect by protecting liver cells from damage caused by free radicals. Histopathology results revealed no liver cell necrosis and showed the regeneration of liver cells in the treatment group. L. martabanica extract did not cause changes in behavior, liver weight, hematological and biochemical profiles of the rats.


Assuntos
Antídotos/farmacologia , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Clorpirifos/toxicidade , Inseticidas/toxicidade , Litsea/química , Acetilcolinesterase/metabolismo , Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Antídotos/isolamento & purificação , Antioxidantes/isolamento & purificação , Aspartato Aminotransferases/metabolismo , Benzotiazóis/antagonistas & inibidores , Benzotiazóis/química , Bilirrubina/metabolismo , Compostos de Bifenilo/antagonistas & inibidores , Compostos de Bifenilo/química , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Clorpirifos/antagonistas & inibidores , Creatinina/metabolismo , Inseticidas/antagonistas & inibidores , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Fitoterapia/métodos , Picratos/antagonistas & inibidores , Picratos/química , Extratos Vegetais/química , Raízes de Plantas/química , Ratos , Ratos Sprague-Dawley , Ácidos Sulfônicos/antagonistas & inibidores , Ácidos Sulfônicos/química
10.
Am J Kidney Dis ; 78(3): 340-349.e1, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33775708

RESUMO

RATIONALE & OBJECTIVE: An early change in proteinuria is considered a reasonably likely surrogate end point in immunoglobulin A nephropathy (IgAN) and can be used as a basis for accelerated approval of therapies, with verification in a postmarketing confirmatory trial. Glomerular filtration rate (GFR) slope is a recently validated surrogate end point for chronic kidney disease progression and may be considered as the end point used for verification. We undertook a meta-analysis of clinical trials in IgAN to compare treatment effects on change in proteinuria versus change in estimated GFR (eGFR) slope. STUDY DESIGN: Individual patient-level meta-analysis. SETTING & STUDY POPULATIONS: Individual data of 1,037 patients from 12 randomized trials. SELECTION CRITERIA FOR STUDIES: Randomized trials of IgAN with proteinuria measurements at baseline and 6 (range, 2.5-14) months and at least a further 1 year of follow-up for the clinical outcome. ANALYTICAL APPROACH: For each trial, we estimated the treatment effects on proteinuria and on the eGFR slope, computed as the total slope starting at baseline or the chronic slope starting 3 months after randomization. We used a Bayesian mixed-effects analysis to relate the treatment effects on proteinuria to effects on GFR slope across these studies and developed a prediction model for the treatment effect on the GFR slope based on the effect on proteinuria. RESULTS: Across all studies, treatment effects on proteinuria accurately predicted treatment effects on the total slope at 3 years (median R2 = 0.88; 95% Bayesian credible interval [BCI], 0.06-1) and on the chronic slope (R2 = 0.98; 95% BCI, 0.29-1). For future trials, an observed treatment effect of approximately 30% reduction in proteinuria would confer probabilities of at least 90% for nonzero treatment benefits on the total and chronic slopes of eGFR. We obtained similar results for proteinuria at 9 and 12 months and total slope at 2 years. LIMITATIONS: Study population restricted to 12 trials of small sample size, leading to wide BCIs. There was heterogeneity among trials with respect to study design and interventions. CONCLUSIONS: These results provide new evidence supporting that early reduction in proteinuria can be used as a surrogate end point for studies of chronic kidney disease progression in IgAN.


Assuntos
Creatinina/metabolismo , Gerenciamento Clínico , Taxa de Filtração Glomerular/fisiologia , Glomerulonefrite por IGA/urina , Teorema de Bayes , Progressão da Doença , Glomerulonefrite por IGA/fisiopatologia , Glomerulonefrite por IGA/terapia , Humanos , Projetos de Pesquisa , Urinálise
11.
JAMA Netw Open ; 4(3): e211095, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33688965

RESUMO

Importance: Acute kidney injury (AKI) occurs in up to half of patients hospitalized with coronavirus disease 2019 (COVID-19). The longitudinal effects of COVID-19-associated AKI on kidney function remain unknown. Objective: To compare the rate of change in estimated glomerular filtration rate (eGFR) after hospital discharge between patients with and without COVID-19 who experienced in-hospital AKI. Design, Setting, and Participants: A retrospective cohort study was conducted at 5 hospitals in Connecticut and Rhode Island from March 10 to August 31, 2020. Patients who were tested for COVID-19 and developed AKI were screened, and those who survived past discharge, did not require dialysis within 3 days of discharge, and had at least 1 outpatient creatinine level measurement following discharge were included. Exposures: Diagnosis of COVID-19. Main Outcomes and Measures: Mixed-effects models were used to assess the association between COVID-19-associated AKI and eGFR slope after discharge. The secondary outcome was the time to AKI recovery for the subgroup of patients whose kidney function had not returned to the baseline level by discharge. Results: A total of 182 patients with COVID-19-associated AKI and 1430 patients with AKI not associated with COVID-19 were included. The population included 813 women (50.4%); median age was 69.7 years (interquartile range, 58.9-78.9 years). Patients with COVID-19-associated AKI were more likely to be Black (73 [40.1%] vs 225 [15.7%]) or Hispanic (40 [22%] vs 126 [8.8%]) and had fewer comorbidities than those without COVID-19 but similar rates of preexisting chronic kidney disease and hypertension. Patients with COVID-19-associated AKI had a greater decrease in eGFR in the unadjusted model (-11.3; 95% CI, -22.1 to -0.4 mL/min/1.73 m2/y; P = .04) and after adjusting for baseline comorbidities (-12.4; 95% CI, -23.7 to -1.2 mL/min/1.73 m2/y; P = .03). In the fully adjusted model controlling for comorbidities, peak creatinine level, and in-hospital dialysis requirement, the eGFR slope difference persisted (-14.0; 95% CI, -25.1 to -2.9 mL/min/1.73 m2/y; P = .01). In the subgroup of patients who had not achieved AKI recovery by discharge (n = 319), COVID-19-associated AKI was associated with decreased kidney recovery during outpatient follow-up (adjusted hazard ratio, 0.57; 95% CI, 0.35-0.92). Conclusions and Relevance: In this cohort study of US patients who experienced in-hospital AKI, COVID-19-associated AKI was associated with a greater rate of eGFR decrease after discharge compared with AKI in patients without COVID-19, independent of underlying comorbidities or AKI severity. This eGFR trajectory may reinforce the importance of monitoring kidney function after AKI and studying interventions to limit kidney disease after COVID-19-associated AKI.


Assuntos
Injúria Renal Aguda/metabolismo , COVID-19/metabolismo , Creatinina/metabolismo , Injúria Renal Aguda/complicações , Injúria Renal Aguda/epidemiologia , Afro-Americanos , Idoso , Idoso de 80 Anos ou mais , COVID-19/complicações , COVID-19/epidemiologia , Estudos de Coortes , Comorbidade , Feminino , Seguimentos , Taxa de Filtração Glomerular , Hispano-Americanos , Humanos , Hipertensão/epidemiologia , Testes de Função Renal , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Modelos de Riscos Proporcionais , Insuficiência Renal Crônica/epidemiologia , Estudos Retrospectivos , SARS-CoV-2 , Estados Unidos/epidemiologia
12.
Medicine (Baltimore) ; 100(12): e25096, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761672

RESUMO

BACKGROUND: Diabetic nephropathy (DN) is the most common microvascular complication of diabetes. Its clinical manifestation is proteinuria, and it is a common cause of renal failure. At present, angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor antagonists are often used to treat early DN, and they have good curative effect. On this basis, the treatment of early DN with the combination of astragalus injection is becoming more and more widespread. Therefore, the purpose of this study is to prove the efficacy and safety of astragalus injection combined with Western medicine in the treatment of early DN, and to provide reference value for clinical practice in the future. METHODS: English databases (PubMed, Embase, Web of Science, the Cochrane Library) and Chinese databases (China National Knowledge Infrastructur, Wanfang, VP Information Chinese Journal Service Platform, China Biology Medicine disc) will be searched by computer. From the establishment of the database to February 2021, a randomized controlled trial of astragalus injection combined with Western medicine in the treatment of early DN will be conducted. Two researchers independently evaluate the quality of the included study and extract the data. Included literature is analyzed by Meta with RevMan5.3 software. RESULTS: In this study, the efficacy and safety of astragalus injection combined with Western medicine in the treatment of early DN are evaluated by serological indexes such as Urinary albumin excretion rates (UAER), serum creatinine and blood urea nitrogen, as well as the adverse reactions of drugs. CONCLUSION: This study will provide reliable evidence-based evidence for astragalus injection combined with Western medicine for the treatment of early DN. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/A9JGP.


Assuntos
Antagonistas de Receptores de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Astrágalo (Planta) , Nefropatias Diabéticas/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Nitrogênio da Ureia Sanguínea , Creatinina/metabolismo , Nefropatias Diabéticas/sangue , Quimioterapia Combinada , Humanos , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Albumina Sérica/metabolismo , Revisões Sistemáticas como Assunto , Resultado do Tratamento
13.
J Vis Exp ; (169)2021 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-33749673

RESUMO

Orthotopic liver transplantation (OLT) in rats is a tried and proven animal model used for preoperative, intraoperative, and postoperative studies, including ischemia-reperfusion injury (IRI) of extrahepatic organs. This model requires numerous experiments and devices. The duration of anhepatic phase is closely related to the time to develop IRI after transplantation. In this experiment, we used hemodynamic changes to induce extrahepatic organ damage in rats and determined the maximum tolerance time. The time until the most severe organ injury varied for different organs. This method can easily be replicated and can also be used to study IRI of the extrahepatic organs after liver transplantation.


Assuntos
Transplante de Fígado , Traumatismo por Reperfusão/fisiopatologia , Alanina Transaminase/metabolismo , Amilases/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Creatinina/metabolismo , Modelos Animais de Doenças , Hemodinâmica , Ligadura , Fígado/patologia , Fígado/fisiopatologia , Masculino , Especificidade de Órgãos , Ratos Sprague-Dawley
14.
Oxid Med Cell Longev ; 2021: 8841726, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33628387

RESUMO

Doxorubicin is a drug that belongs to the anthracycline antibiotics. Nephrotoxicity is one of the serious side effects of doxorubicin treatment. Crocin, which is one of the most bioactive components of saffron, has antioxidant, anti-inflammatory, and antitumor effects. The current study was aimed at investigating the possible protective effects of crocin against doxorubicin-induced nephrotoxicity to elucidate the underlying mechanism of this effect. The study included four groups, six rats in each group: normal control, crocin control, doxorubicin, and crocin/doxorubicin. Doxorubicin and crocin/doxorubicin groups received intraperitoneal injections of doxorubicin (3.5 mg/kg twice weekly for 3 weeks). Rats in the crocin control group and the crocin/doxorubicin group were treated with intraperitoneal injections of crocin (100 mg/kg body weight per day) for 3 weeks. Biomarkers of kidney function and oxidative stress as well as the abundance of mRNA for nuclear factor-κß and inducible nitric oxide synthase were evaluated. In addition, the abundance of cyclooxygenase 2 and tumor necrosis factor α immunoreactivity was evaluated. Crocin treatment had renoprotective effects manifested by significant improvement in kidney function as well as a reduction in the abundance of biomarkers of oxidative stress markers and inflammatory mediators. In conclusion, crocin has a protective effect against doxorubicin-induced nephrotoxicity in rats by serving as an antioxidant and attenuating the expression of NF-κB, iNOS, COX2, and TNFα.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Carotenoides/uso terapêutico , Doxorrubicina/efeitos adversos , Nefropatias/induzido quimicamente , Nefropatias/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Biomarcadores/metabolismo , Carotenoides/farmacologia , Creatinina/metabolismo , Ciclo-Oxigenase 2/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Rim/fisiopatologia , Nefropatias/fisiopatologia , Masculino , NF-kappa B/genética , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
15.
Int J Mol Sci ; 22(3)2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33573145

RESUMO

Renal ischemia and reperfusion (I/R) injury is the most common cause of acute kidney injury (AKI). Pathogenesis of postischemic AKI involves hemodynamic changes, oxidative stress, inflammation process, calcium ion overloading, apoptosis and necrosis. Up to date, therapeutic approaches to treat AKI are extremely limited. Thus, the aim of this study was to evaluate the effects of hyperbaric oxygen (HBO) preconditioning on citoprotective enzyme, heme oxygenase-1 (HO-1), pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins expression, in postischemic AKI induced in normotensive Wistar and spontaneously hypertensive rats (SHR). The animals were randomly divided into six experimental groups: SHAM-operated Wistar rats (W-SHAM), Wistar rats with induced postischemic AKI (W-AKI) and Wistar group with HBO preconditioning before AKI induction (W-AKI + HBO). On the other hand, SHR rats were also divided into same three groups: SHR-SHAM, SHR-AKI and SHR-AKI + HBO. We demonstrated that HBO preconditioning upregulated HO-1 and anti-apoptotic Bcl-2 protein expression, in both Wistar and SH rats. In addition, HBO preconditioning improved glomerular filtration rate, supporting by significant increase in creatinine, urea and phosphate clearances in both rat strains. Considering our results, we can also say that even in hypertensive conditions, we can expect protective effects of HBO preconditioning in experimental model of AKI.


Assuntos
Injúria Renal Aguda/prevenção & controle , Heme Oxigenase (Desciclizante)/metabolismo , Oxigenação Hiperbárica/métodos , Hipertensão/complicações , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/patologia , Injúria Renal Aguda/urina , Animais , Creatinina/metabolismo , Creatinina/urina , Modelos Animais de Doenças , Humanos , Hipertensão/fisiopatologia , Hipertensão/terapia , Rim/irrigação sanguínea , Rim/patologia , Rim/fisiopatologia , Masculino , Oxigênio/administração & dosagem , Fosfatos/metabolismo , Fosfatos/urina , Ratos , Ratos Endogâmicos SHR , Ratos Wistar , Eliminação Renal/fisiologia , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/urina , Regulação para Cima , Ureia/metabolismo , Ureia/urina
16.
Molecules ; 26(3)2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33525350

RESUMO

Plant hormones are small regulatory molecules that exert pharmacological actions in mammalian cells such as anti-oxidative and pro-metabolic effects. Kinetin belongs to the group of plant hormones cytokinin and has been associated with modulatory functions in mammalian cells. The mammalian adenosine receptor (A2a-R) is known to modulate multiple physiological responses in animal cells. Here, we describe that kinetin binds to the adenosine receptor (A2a-R) through the Asn253 residue in an adenosine dependent manner. To harness the beneficial effects of kinetin for future human use, we assess its acute toxicity by analyzing different biochemical and histological markers in rats. Kinetin at a dose below 1 mg/kg had no adverse effects on the serum level of glucose or on the activity of serum alanine transaminase (ALT) or aspartate aminotransferase (AST) enzymes in the kinetin treated rats. Whereas, creatinine levels increased after a kinetin treatment at a dose of 0.5 mg/kg. Furthermore, 5 mg/kg treated kinetin rats showed normal renal corpuscles, but a mild degeneration was observed in the renal glomeruli and renal tubules, as well as few degenerated hepatocytes were also observed in the liver. Kinetin doses below 5 mg/kg did not show any localized toxicity in the liver and kidney tissues. In addition to unraveling the binding interaction between kinetin and A2a-R, our findings suggest safe dose limits for the future use of kinetin as a therapeutic and modulatory agent against various pathophysiological conditions.


Assuntos
Cinetina/farmacologia , Cinetina/toxicidade , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/toxicidade , Animais , Antioxidantes/fisiologia , Antioxidantes/toxicidade , Biomarcadores/metabolismo , Creatinina/metabolismo , Citocininas/metabolismo , Glucose/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/metabolismo , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Reguladores de Crescimento de Plantas/farmacologia , Reguladores de Crescimento de Plantas/toxicidade , Ratos , Receptores Purinérgicos P1/metabolismo
17.
Arch. med. deporte ; 38(201): 48-53, ene.-feb. 2021. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-201644

RESUMO

La creatina es un suplemento deportivo con una elevada evidencia científica sobre sus efectos en el rendimiento y con resultados emergentes en la salud, incluida la de deportistas vegetarianos y adultos mayores. El tipo de creatina y las dosis efectivas, han sido bien estudiadas presentando resultados consistentes. Sin embargo, no son muchos los estudios que han evaluado el momento de la ingesta en cuanto a su interacción con los efectos de la creatina. El objetivo de esta revisión, es analizar la diferente literatura científica existente sobre los protocolos de suplementación con creatina y su interacción con el momento de la ingesta, con el fin de evaluar si existe un efecto mayor de la dosis ergogénica considerada efectiva de creatina cuando esta es ingerida antes, después del entrenamiento o en otro momento del día. Los resultados de este trabajo presentaron diferentes tipos de protocolos y dosis en la suplementación con creatina, a pesar de ser diversos los protocolos mostrados en la literatura, el más efectivo constó de un consumo de 0,3 g/kg/d durante cinco días, seguido de un consumo de 0,03 g/kg/d consiguiendo de esta forma, una mayor reserva de PCr en el músculo esquelético. Los estudios mostraron mayores beneficios cuando la ingesta de creatina se realizó en los momentos cercanos al entreno debido al mayor flujo sanguíneo, apuntando los estudios a mejoras significativas en un consumo post-entreno, debido a que la creatina puede aumentar la formación de glucógeno en el músculo y aumentar la sensibilidad a la insulina


Creatine is a sports supplement with high scientific evidence on its effects on performance and with emerging health's results, including for vegetarian athletes and older adults. The creatine type and effective doses have been well studied, presenting consistent results. However, not many studies have evaluated the ingestion timing in terms of its interaction with the creatine effects. The aim of this review is to analyze the different existing scientific literature on creatine supplementation protocols and their interaction with the timing of ingestion, in order to assess whether there is a greater effect of the ergogenic dose of creatine considered effective when It is ingested before, post workout or at another time of the day. The results of this work presented different types of protocols and doses in creatine supplementation, despite being diverse the protocols shown in the literature, the most effective consisted of a consumption of 0.3 g/kg/d for five days, followed by a consumption of 0.03 g/kg/d, thus achieving a greater reserve of PCr in skeletal muscle. Studies showed greater benefits when creatine intake was carried out in the moments close to workout due to greater blood flow, the studies pointing to significant improvements in post-workout consumption, since creatine can increase the rate of glycogen uptake in muscle and increase insulin sensitivity


Assuntos
Humanos , Desempenho Atlético/fisiologia , Creatinina/administração & dosagem , Suplementos Nutricionais , Creatinina/metabolismo , Substâncias para Melhoria do Desempenho/administração & dosagem , Fatores Etários , Fatores de Tempo , Músculo Esquelético/fisiologia , Força Muscular/fisiologia
18.
Protein Pept Lett ; 28(7): 781-787, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33504292

RESUMO

BACKGROUND: Brazilian flora is rich in plants with medicinal properties, which though popular, has contributed to the development of a range of phytotherapic products that use plants to treat and cure diseases. However, studies that use Brazilian plants in the treatment of metabolic disorders are still scarce in the literature. OBJECTIVE: The aim of this study was to analyze the effect of hepatotoxicity Lafoensia pacari on the metabolism of mice with obesity induced by a high-fat diet and to verify the phytochemical difference between the Lafoensia pacari bark of the trunk, leaves, and branches. METHODS: The plant material was collected from April to May in the municipality of Bonito de Minas, MG, Brazil. Qualitative tests for the presence of secondary metabolite classes were performed for leaves, branches and bark of the trunk. Through histological analysis, we evaluated hepatocytes and cell lesions in the liver. RESULTS: The comparative phytochemical analysis of the plant did not reveal alterations between the different plant parts. The phytochemical test showed that is preferable to use the leaves to make the extract to be applied, aiming to reduce the plant aggression. After treatment, greater changes were observed in the animals that received the high-fat diet and the hydroethanolic extract; the levels of AST, ALT, albumin and creatinine that were increased, thus demonstrating a possible toxicity. There were no significant differences in body weight. In the histological analysis, the animals without plant treatment displayed decreased liver weight and reduction in the inflammatory infiltrate. CONCLUSION: We conclude that Lafoensia pacari should be better evaluated for oral consumption and may cause liver damage.


Assuntos
Fármacos Antiobesidade/toxicidade , Fígado/efeitos dos fármacos , Lythraceae/química , Obesidade/tratamento farmacológico , Extratos Vegetais/toxicidade , Alanina Transaminase/metabolismo , Albuminas/metabolismo , Alcaloides/isolamento & purificação , Alcaloides/toxicidade , Animais , Fármacos Antiobesidade/química , Aspartato Aminotransferases/metabolismo , Peso Corporal/efeitos dos fármacos , Brasil , Creatinina/metabolismo , Dieta Hiperlipídica/efeitos adversos , Flavonoides/isolamento & purificação , Flavonoides/toxicidade , Glutationa Peroxidase/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/patologia , Fenóis/isolamento & purificação , Fenóis/toxicidade , Casca de Planta/química , Extratos Vegetais/química , Folhas de Planta/química , Caules de Planta/química , Metabolismo Secundário , Superóxido Dismutase/metabolismo
19.
Gerontology ; 67(3): 255-266, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33406518

RESUMO

OBJECTIVE: We aim to investigate the clinical characteristics and risk factors for the severe cases of coronavirus disease 2019 (COVID-19) in comparison with the non-severe patients. METHODS: We searched PubMed, EMBASE, Web of Science, and CNKI to collect all relevant studies published before July 26, 2020, and a total of 30 papers were included in this meta-analysis. RESULTS: In the severe COVID-19 patients, 60% (95% CI = 56-64%) were male, 25% (95% CI = 21-29%) were over 65 years old, 34% (95% CI = 24-44%) were obese, and 55% (95% CI = 41-70%) had comorbidities. The most prevalent comorbidities were hypertension (34%, 95% CI = 25-44%), diabetes (20%, 95% CI = 15-25%), and cardiovascular disease (CVD; 12%, 95% CI = 9-16%). The most common blood test abnormalities were elevated C-reactive protein (CRP; 87%, 82-92%), decreased lymphocyte count (68%, 58-77%), and increased lactate dehydrogenase (69%, 95% CI = 57-81%). In addition, abnormal laboratory findings revealing organ dysfunctions were frequently observed in the severe cases, including decrease in albumin (43%, 95% CI = 24-63%) and increase in aspartate aminotransferase (47%, 95% CI = 38-56%), alanine aminotransferase (28%, 95% CI = 16-39%), troponin I/troponin T (TnI/TnT; 29%, 95% CI = 13-45%), and serum Cr (SCr; 10%, 95% CI = 5-15%). CONCLUSION: The male, elderly and obese patients and those with any comorbidities, especially with hypertension, diabetes, and CVD, were more likely to develop into severe cases. But the association between hypertension, diabetes, CVD, and severity of COVID-19 was declined by the increase of age. A significant elevation in cardiac TnI/TnT, the hepatic enzymes, and SCr and the reduction in lymphocytes with elevated CRPs are important markers for the severity. Specific attention should be given to the elderly male and obese patients and those with indications of severe immune injury in combination with bacterial infection and indication of multi-organ dysfunction or damages.


Assuntos
COVID-19/epidemiologia , COVID-19/metabolismo , Distribuição por Idade , Fatores Etários , Idoso , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Proteína C-Reativa/metabolismo , COVID-19/fisiopatologia , Doenças Cardiovasculares/epidemiologia , Comorbidade , Creatinina/metabolismo , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , L-Lactato Desidrogenase/metabolismo , Linfopenia , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Fatores de Risco , SARS-CoV-2 , Distribuição por Sexo , Troponina I/metabolismo , Troponina T/metabolismo
20.
Res Vet Sci ; 135: 36-41, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33422730

RESUMO

The assessment of renal function in birds is difficult because sensitive biomarkers are lacking. Previous studies have demonstrated the feasibility of measuring the exogenous creatinine clearance in pigeons, indicating the potential use of this technique for the assessment of renal function in birds. The aim of the study was to index the exogenous creatinine elimination rate by body surface area, enabling comparison between different species. Exploratory data on common buzzards (Buteo buteo), Eurasian eagle-owls (Bubo bubo), domestic goose (Anser anser domesticus) and racing pigeons (Columba livia) were collected and indexed by body surface area. A sterile creatinine solution was administered at a dose DM = 50 mg kg-1 i.m. into the deep pectoral muscle of 52 clinically healthy birds of the four species with different body masses. The time course of the plasma creatinine concentration was measured and analyzed by a parametric pharmacokinetic Bateman model, followed by indexing the exogenous creatinine clearance (ECC) by body surface area. The exploratory ECC values for birds with a mean body mass ranging from 0.42 kg (pigeon) to 8.2 kg (goose) were between 0.4261 mL min-1 dm-2 (CI 0.3882-0.4672) and 0.8717 mL min-1 dm-2 (CI 0.8091-0.9362). ECC indexed by body surface area turned out to be independent from body mass. Resulting exploratory data covering species with different body masses are comparable with published data from very complex studies of avian renal function.


Assuntos
Aves/classificação , Aves/fisiologia , Superfície Corporal/veterinária , Creatinina/metabolismo , Taxa de Filtração Glomerular/veterinária , Animais , Especificidade da Espécie
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