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1.
J Zoo Wildl Med ; 52(1): 241-252, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33827182

RESUMO

Native to Southeast Asia, the Sunda pangolin (Manis javanica) is critically endangered largely because of poorly regulated wildlife trade, consumptive practices, and use in traditional Chinese medicine. Efforts to rescue and rehabilitate animals confiscated from the illegal trade are complicated by a general lack of knowledge surrounding the normal health and disease processes unique to the species. To provide clinical reference intervals for normal health states of Sunda pangolins, biochemical parameters were determined from rescued individuals in Vietnam that had undergone a 14-day observation period and met a set of criteria for release back into the wild. Blood samples were collected from 42 apparently healthy Sunda pangolins while anesthetized or awake. Packed cell volume (PCV) and total solids (TS) were determined manually, and serum biochemistry values were determined in-house with a benchtop analyzer. Additional biochemical and mineral parameters not included in the primary panel were determined from a subset of 10 pangolins through an external diagnostic laboratory. Overall reference intervals were calculated for PCV and TS (n = 29) and for standard serum biochemistry parameters (n = 42). Females and males demonstrated significant variation with respect to body mass, potassium (K+), and phosphorus, whereas age was a significant source of variation in alkaline phosphatase. Seasonal variation in glucose (GLU), creatinine (CRE), total proteins, sodium, calcium, and K+ was also observed. Comparisons between anesthetized and awake pangolins demonstrated significant variation in GLU, CRE, and K+. The parameters determined in this study can serve as a clinical reference for ex situ Sunda pangolin conservation efforts. In the context of wildlife rehabilitation, serial bloodwork allows for continued monitoring of patient health and should inform decision making regarding release readiness and timing.


Assuntos
Minerais/sangue , /sangue , Criação de Animais Domésticos , Animais , Animais Selvagens , Glicemia , Nitrogênio da Ureia Sanguínea , Creatina/sangue , Espécies em Perigo de Extinção , Enzimas/sangue , Feminino , Hematócrito , Masculino , Valores de Referência , Vietnã
2.
Life Sci ; 275: 119362, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33741414

RESUMO

Chronic kidney disease (CKD) is defined by decreased glomerular filtration rate (GFR) or increased albumin excretion leading to renal injury. However, exercise training is an important non-pharmacological intervention that ameliorates and protects against Diabetes Mellitus, cardiovascular disease, and CKD. AIM: Our aim was to evaluate the capability of resistance exercise training (RET) to improve CKD outcomes and the contribution of the renal and muscular Akt/mTOR signaling pathway for RET beneficial effects on a CKD model. MAIN METHODS: Male Wistar rats were subjected to RET, followed for 10 weeks, and randomly divided into 5 groups: Sham: Sham-operated; sedentary and nephrectomy (5/6Nx) (SNS); exercising post-5/6Nx (SNE); exercising pre-5/6Nx (ENS); exercising pre- and post-5/6Nx (ENE). The systolic blood pressure (BP) was measured. Creatinine, proteinuria, and blood urea nitrogen (BUN) were evaluated. After euthanasia Renal and muscular Akt/mTOR signaling pathways were analyzed. KEY FINDING: Our study showed that the SNS presented renal injury, hypertension, weight and muscular mass loss and a higher mortality rate. SNS group also decreased renal IL-10 and increased TNF-alfa and TGF-Beta. Renal AKT, mTOR, and rpS6 pathway were increased, PTEN was decreased on SNS. And muscular Akt and mTOR were decreased on SNS. SIGNIFICANCE: The RET before and after the 5/6Nx ameliorates all these parameters mentioned above, suggesting that RET is a good non-pharmacological approach to diminish complications frequently found in CKD. We also suggest that the AKT-m-TOR pathway can play an important role in these beneficial outcomes of RET on the CKD animal model.


Assuntos
Insuficiência Renal Crônica/terapia , Treinamento de Resistência , Animais , Creatina/análogos & derivados , Creatina/sangue , Creatina/urina , Modelos Animais de Doenças , Masculino , Nefrectomia , Ratos , Ratos Wistar
3.
PLoS One ; 15(10): e0239266, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33035213

RESUMO

The prediction of the liver failure (LF) and its proper diagnosis would lead to a reduction in the complications of the disease and prevents the progress of the disease. To improve the treatment of LF patients and reduce the cost of treatment, we build a machine learning model to forecast whether a patient would deteriorate after admission to the hospital. First, a total of 348 LF patients were included from May 2011 to March 2018 retrospectively in this study. Then, 15 key clinical indicators are selected as the input of the machine learning algorithm. Finally, machine learning and the Model for End-Stage Liver Disease (MELD) are used to forecast the LF deterioration. The area under the receiver operating characteristic (AUC) of MELD, GLMs, CART, SVM and NNET with 10 fold-cross validation was 0.670, 0.554, 0.794, 0.853 and 0.912 respectively. Additionally, the accuracy of MELD, GLMs, CART, SVM and NNET was 0.669, 0.456, 0.794, 0.853 and 0.912. The predictive performance of the developed machine model execept the GLMs exceeds the classic MELD model. The machine learning method could support the physicians to trigger the initiation of timely treatment for the LD patients.


Assuntos
Falência Hepática/fisiopatologia , Aprendizado de Máquina , Área Sob a Curva , Bilirrubina/sangue , Creatina/sangue , Feminino , Humanos , Coeficiente Internacional Normatizado , Masculino , Curva ROC , Fatores de Risco
4.
J Endourol ; 34(8): 882-886, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32668987

RESUMO

Background: Ureteral stone disease may be an emergent condition if the appropriate management is not performed in a timely manner. As the coronavirus disease 2019 (COVID-19) continues to spread globally, isolation and restriction orders taken by the governments have become the cores to control the pandemic. In this study, we, therefore, aimed to investigate the ureteral stone presentations in a high-volume university hospital during the COVID-19 restriction order period. Materials and Methods: The data of 149 patients who were hospitalized due to ureteral stone both during the COVID-19 pandemic restriction period and the corresponding period (non-COVID-19) of the previous year were collected and analyzed retrospectively. Unpaired Student's t-test was used to compare continuous variables. The categorical data were assessed using Chi-square and Fisher's exact tests. Results: Of 149 patients, 35 were hospitalized in the COVID-19 restrictions period. While the mean age and the stone characteristics of the two groups did not differ significantly, serum creatinine levels (1.9 ± 1.85 vs 1.15 ± 0.64) and the white blood cell counts (12.45 ± 6.54 vs 8.21 ± 4.15) at hospital admission were significantly higher in the COVID-19 restrictions group (p = 0.034 and p = 0.005, respectively). According to the priority classification recommendations of the European Urology Guidelines Office Rapid Reaction Group for urolithiasis applicable during the COVID-19 pandemic, a significant difference was observed between the two periods (X2 = 9.907, p = 0.019). In particular, the rate of emergency cases was found more than threefold in the COVID-19 period. Although there was no significant difference in terms of the grade of hydronephrosis at hospital admission between the two groups, the rates of grade 3 and 4 hydronephrosis were higher in the COVID-period group (1.8- and 3.3-fold, respectively). Conclusion: The rate of complicated ureteral stone disease significantly increased during the COVID-19 restrictions period. Urologists should prioritize the patients most in need of urgent care during COVID-19-like biosocial crisis.


Assuntos
Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Urolitíase/epidemiologia , Adulto , Betacoronavirus , Creatina/sangue , Serviço Hospitalar de Emergência , Feminino , Hospitalização , Humanos , Hidronefrose/sangue , Hidronefrose/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Admissão do Paciente , Estudos Retrospectivos , Risco , Turquia/epidemiologia , Cálculos Ureterais/epidemiologia , Urolitíase/sangue
5.
PLoS One ; 15(6): e0233925, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32530952

RESUMO

It is important to calculate the drug removal by hemodialysis (HD) for drug dosing regimens in HD patients. However, there are limited and inconsistent information about the dialyzability of drugs by HD. Therefore, the aim of our study is to evaluate drug removal by utilizing a rat model of HD (HD rat) and to extrapolate this result to the drug removal rate in HD patients. HD rats received bilateral nephrectomy and HD for 2 h. The dialysis removal of 6 drugs was evaluated in HD rats. Dialysis efficiency, plasma protein binding rate (PBR) and distribution volume (Vd) of drugs were also measured. Furthermore, we examined the correlation between the dialyzability of drug in HD rats and humans and constructed the prediction formula of the drug dialyzability in HD patients. The clearance of urea and creatinine and normalized dialysis dose in HD rats were 0.83 ± 0.07 mL/min, 0.70 ± 0.08 mL/min, and 0.13 ± 0.06, respectively. The drug dialyzability in HD rats was similar to reported clinical data except for doripenem. A higher correlation was observed between drug dialyzability in reported clinical data and HD rats which were adjusted for PBR (r2 = 0.936; p < 0.001) compared to unadjusted (r2 = 0.812; p = 0.009). Therefore, we constructed the prediction formula of the drug dialyzability in HD patients by utilizing the HD rat model and PBR. This study is useful for evaluating the dialyzability of high-risk drugs in a clinical setting and might provide appropriate preclinical dialyzability data for new drug.


Assuntos
Preparações Farmacêuticas/sangue , Diálise Renal/métodos , Eliminação Renal , Animais , Creatina/sangue , Humanos , Masculino , Taxa de Depuração Metabólica , Modelos Animais , Farmacocinética , Ratos , Ratos Wistar , Ureia/sangue
6.
Drug Discov Ther ; 14(2): 84-88, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32378650

RESUMO

Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. A number of new therapies have been developed based on the pathogenic factors of diabetic nephropathy such as intensive glycemic control, precise hypertension control, lifestyle modifications including exercise and an energy-restricted diet, and numerous novel agents. The utilization of traditional Chinese medicine for patients with diabetic nephropathy has also received increasing attention due to its wide availability, weak side-effects, and proven therapeutic mechanisms and benefits. In this paper, we report the case of patients with diabetic nephropathy, stage 2 or 3. Kangen-karyu extract (7.5 g/day) was administered three times per day for 6 months. The estimated glomerular filtration rate was increased at the 6-month follow-up. The serum creatinine level decreased following administration. At that time, somatic and subjective symptoms had partially disappeared. Here, we present evidence that Kangen-karyu exerts a renoprotective effect against the development of diabetic nephropathy.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Idoso , Creatina/sangue , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/fisiopatologia , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Hemoglobina A Glicada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
7.
Ann Rheum Dis ; 79(4): 499-506, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32079570

RESUMO

OBJECTIVES: The differential diagnosis of seronegative rheumatoid arthritis (negRA) and psoriasis arthritis (PsA) is often difficult due to the similarity of symptoms and the unavailability of reliable clinical markers. Since chronic inflammation induces major changes in the serum metabolome and lipidome, we tested whether differences in serum metabolites and lipids could aid in improving the differential diagnosis of these diseases. METHODS: Sera from negRA and PsA patients with established diagnosis were collected to build a biomarker-discovery cohort and a blinded validation cohort. Samples were analysed by proton nuclear magnetic resonance. Metabolite concentrations were calculated from the spectra and used to select the variables to build a multivariate diagnostic model. RESULTS: Univariate analysis demonstrated differences in serological concentrations of amino acids: alanine, threonine, leucine, phenylalanine and valine; organic compounds: acetate, creatine, lactate and choline; and lipid ratios L3/L1, L5/L1 and L6/L1, but yielded area under the curve (AUC) values lower than 70%, indicating poor specificity and sensitivity. A multivariate diagnostic model that included age, gender, the concentrations of alanine, succinate and creatine phosphate and the lipid ratios L2/L1, L5/L1 and L6/L1 improved the sensitivity and specificity of the diagnosis with an AUC of 84.5%. Using this biomarker model, 71% of patients from a blinded validation cohort were correctly classified. CONCLUSIONS: PsA and negRA have distinct serum metabolomic and lipidomic signatures that can be used as biomarkers to discriminate between them. After validation in larger multiethnic cohorts this diagnostic model may become a valuable tool for a definite diagnosis of negRA or PsA patients.


Assuntos
Artrite Psoriásica/sangue , Artrite Reumatoide/sangue , Acetatos/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina/sangue , Aminoácidos/sangue , Artrite Psoriásica/diagnóstico , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/imunologia , Colina/sangue , Creatina/sangue , Diagnóstico Diferencial , Feminino , Humanos , Ácido Láctico/sangue , Lipidômica , Lipídeos/sangue , Masculino , Metaboloma , Metabolômica , Pessoa de Meia-Idade , Fosfocreatina/sangue , Espectroscopia de Prótons por Ressonância Magnética , Ácido Succínico/sangue
8.
Nefrología (Madrid) ; 40(1): 65-73, ene.-feb. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-198956

RESUMO

INTRODUCCIÓN: En la actualidad, existen pocos datos sobre la evolución de la función renal en pacientes con hipertensión arterial (HTA) resistente y enfermedad renal crónica (ERC), así como de la influencia de diferentes tipos de tratamiento en dicha progresión. OBJETIVO: Evaluar la progresión de la ERC en pacientes con ERC e HTA resistente tratados mediante 2 estrategias terapéuticas diferentes: tratamiento con espironolactona vs. furosemida. MÉTODOS: Incluimos a 30 pacientes (21 H, 9M) con una edad media de 66,3 ± 9,1 años, FGe 55,8 ± 16,5 ml/min/1,73 m2, PAS 162,8 ± 8,2 y PAD 90,2 ± 6,2 mmHg: 15 tratados con espironolactona y 15 con furosemida, seguidos durante un tiempo medio de 32 meses (28-41). RESULTADOS: El descenso medio anual del FGe fue de -2,8 ± 5,4 ml/min/1,73 m2. En el grupo de espironolactona fue de -2,1 ± 4,8ml/min/1,73 m2 y en el de furosemida -3,2 ± 5,6 ml/min/1,73 m2, p < 0,01. En los pacientes con espironolactona la PAS disminuyó 23 ± 9 mmHg vs. 16 ± 3mmHg en el grupo de furosemida (p < 0,01). La PAD se redujo 10 ± 8 mmHg y 6 ± 2 mmHg, respectivamente (p < 0,01). El tratamiento con espironolactona redujo la albuminuria de una mediana de 210 (121-385) mg/g a 65 (45-120) mg/g al final del seguimiento, p < 0,01. En el grupo de furosemida la albuminuria no descendió. La progresión más lenta en la enfermedad renal se asoció con una menor PAS (p = 0,04), mayor FGe basal (p = 0,01), menor albuminuria (p = 0,01), no tener diabetes mellitus (p = 0,01) y recibir tratamiento con espironolactona (p = 0,02). El tratamiento con espironolactona (OR 2,13; IC 1,89-2,29) y la menor albuminuria (OR 0,98; IC 0,97-0,99) mantienen su poder predictivo independiente en un modelo multivariante. CONCLUSIONES: El tratamiento con espironolactona reduce más la presión arterial y la albuminuria en pacientes con HTA resistente comparado con la furosemida y esto se asocia con una progresión más lenta de la ERC a largo plazo


INTRODUCTION: Actualy, there are few data about glomerular filtration rate (eGFR) drop in patients with resistant hypertension and how diferent therapies can modify chronic kidney disease progression (CKD). OBJECTIVE: To evaluate CKD progression in patients with resistant hypertension undergoing 2 diferent therapies: treatment with spironolactone or furosemide. METHODS: We included 30 patients (21 M, 9 W) with a mean age of 66.3 ± 9.1 years, eGFR 55.8 ± 16.5 ml/min/1.73 m2, SBP 162.8 ± 8.2 and DBP 90.2 ± 6.2 mmHg: 15 patients received spironolactone and 15 furosemide and we followed up them a median of 32 months (28-41). RESULTS: The mean annual eGFR decrease was -2.8 ± 5.4 ml/min/1.73 m2. In spironolactone group was -2.1 ± 4.8 ml/min/1.73 m2 and in furosemide group was -3.2 ± 5.6 ml/min/1.73 m2, P < 0.01. In patients received spironolactone, SBP decreased 23 ± 9 mmHg and in furosemide group decreased 16 ± 3 mmHg, P<.01. DBP decreased 10 ± 8 mmHg and 6 ± 2mmHg, respectively (P<.01). Treatment with spironolactone reduced albuminuria from a serum albumin/creatine ratio of 210 (121-385) mg/g to 65 (45-120) mg/g at the end of follow-up, P<.01. There were no significant changes in the albumin/creatinine ratio in the furosemide group. The slower drop in kidney function was associated with lower SBP (P=.04), higher GFR (P=.01), lower albuminuria (P=.01), not diabetes mellitus (P=.01) and treatment with spironolactone (P=.02). Treatment with spironolactone (OR 2.13, IC 1.89-2.29) and lower albuminuria (OR 0.98, CI 0.97-0.99) maintain their independent predictive power in a multivariate model. CONCLUSION: Treatment with spironolactone is more effective reducing BP and albuminuria in patients with resistant hypertension compared with furosemide and it is associated with a slower progression of CKD in the long term follow up


Assuntos
Humanos , Masculino , Feminino , Idoso , Hipertensão/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Insuficiência Renal Crônica/fisiopatologia , Espironolactona/uso terapêutico , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico , Albuminúria/tratamento farmacológico , Pressão Arterial/efeitos dos fármacos , Creatina/sangue , Creatinina/sangue , Progressão da Doença , Diuréticos/uso terapêutico , Taxa de Filtração Glomerular/fisiologia , Hipertensão/fisiopatologia , Ensaios Clínicos Controlados não Aleatórios como Assunto , Estudos Prospectivos , Insuficiência Renal Crônica/sangue , Albumina Sérica Humana
9.
Hum Exp Toxicol ; 39(4): 402-410, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31957486

RESUMO

OBJECTIVE: The objective of this article is to study the correlation between neutrophil gelatinase-associated lipocalin (NGAL) and soluble CD14 subtype (presepsin) on the severity and prognosis evaluation of acute paraquat poisoning (APP) patients. MATERIALS AND METHODS: We studied 120 APP patients who were divided into three groups: light (28 cases), moderate (52 cases), and heavy poisoning (40 cases) groups. Twenty healthy volunteers were enrolled as controls. RESULTS: Acute kidney injury (AKI) occurred in 86 APP patients (71.7%, 86 of 120). In AKI group, urine NGAL was elevated 3 h after treatment, serum NGAL was elevated 24 h after treatment, and serum creatine (SCr) was elevated 2 days after treatment, which were all significantly higher than non-AKI group. Compared with control group, there were significant differences in presepsin and acute physiology and chronic health status (APACHE) II score of different poisoning groups. There were significant differences in detection indices 24 h, 3 days, and 7 days after treatment among different poisoning groups. There was a positive correlation between urine NGAL and serum paraquat concentration, urine NGAL, and AKI morbidity (r 1 = 0.974, r 2 = 0.766, p < 0.001), suggesting higher urine NGAL level indicated higher AKI morbidity. Receiver operating characteristic curves analysis suggested serum presepsin level and urine NGAL level had higher sensitivity and specificity than APACHE II score when predicting 28-day mortality of APP patients. CONCLUSION: Serum and urine NGAL level is elevated earlier than SCr, which is important for the early diagnosis of APP. Serum presepsin and urine NGAL levels can be used as markers to diagnose the severity of AKI and predict the mortality of APP patients.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Lipocalina-2 , Receptores de Lipopolissacarídeos/sangue , Paraquat/envenenamento , Fragmentos de Peptídeos/sangue , APACHE , Lesão Renal Aguda/sangue , Lesão Renal Aguda/urina , Adolescente , Adulto , Estudos de Casos e Controles , Creatina/sangue , Relação Dose-Resposta a Droga , Humanos , Lipocalina-2/sangue , Lipocalina-2/urina , Pessoa de Meia-Idade , Paraquat/sangue , Prognóstico , Fatores de Tempo , Adulto Jovem
10.
J Environ Sci Health B ; 55(3): 273-282, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31744381

RESUMO

A sudden increase in serum creatinine after paraquat intoxication has been reported in several clinical studies. However, this dramatic change of creatinine may be possibly due to an interconversion of creatine-creatinine in relation to paraquat toxicity. In order to investigate the creatine-creatinine relationship, a liquid chromatography tandem mass spectrometry in combination with electrospray ionization was developed and validated for simultaneous determination of creatine and creatinine in the serum. The chromatographic separation was achieved on a Gemini® C6-Phenyl column with a gradient elution consisting of 0.1% formic acid in ultrapure water and methanol as the mobile phase. The method yielded suitable levels of specificity and selectivity, and calibration curves of creatine and creatinine in serum were linear over the concentration range of 0.5-200 µg mL-1. The limit of quantification of both compounds was 0.5 µg mL-1, and the method was accurate within the recovery range of 96.23-102.75%, indicating the robustness of the method. The method was successfully applied to toxicological samples from paraquat-intoxicated patients, and the concentrations of creatine and creatinine were quantified. High creatine concentrations in serum samples were observed which may lead to high serum creatinine despite normal kidney function as creatine is converted to creatinine in proportion to its concentration.


Assuntos
Cromatografia Líquida/métodos , Creatina/sangue , Creatinina/sangue , Paraquat/envenenamento , Espectrometria de Massas em Tandem/métodos , Calibragem , Estudos de Coortes , Humanos , Limite de Detecção , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray/métodos
11.
Res Sports Med ; 28(1): 147-154, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30028191

RESUMO

Exhaustive exercise induces various disturbances of homeostasis, with impaired bioenergetics often associated with strenuous muscular work. However, no study so far validated serum biomarkers of creatine metabolism vs. traditional markers of exhaustive exercise and fatigue. Here, we investigated how well changes in serum guanidinoacetic acid (GAA), creatine and creatinine correlate with responses in blood lactate, creatine kinase, interleukin-6 and cortisol in 11 young active men (age 23.2 ± 3.7 years; VO2max 49.5 ± 5.4 ml/kg/min) exposed to exhaustive exercise. All participants were subjected to running at individual running speed at anaerobic threshold until exhaustion, with venous blood drawn at baseline and during an exercise session at 5-min intervals. Running-to-exhaustion markedly affected serum GAA and creatine levels, with circulating GAA increased for 5.3 ± 8.5%(95% CI, -0.4 to 11.0), and serum creatine elevated by 33.9 ± 21.8% (95% CI, 19.3 to 48.6) compared to baseline levels (P ≤ 0.05). In addition, moderate-to-strong positive linear correlations were found between exhaustive exercise-induced changes in serum cortisol and GAA levels (r = 0.79; P = 0.03), and cortisol and creatine concentrations (r = 0.81; P = 0.03). This suggests a link between cortisol and heavy exercise-induced impaired bioenergetics, with future studies needed to evaluate a cause-and-effect interconnection between cortisol and GAA-creatine axis.


Assuntos
Creatina/sangue , Creatinina/sangue , Exercício Físico/fisiologia , Fadiga Muscular , Resistência Física , Biomarcadores/sangue , Humanos , Masculino , Corrida/fisiologia , Adulto Jovem
12.
J Nutr ; 150(3): 443-449, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31687740

RESUMO

BACKGROUND: Arginine:glycine amidinotransferase, necessary for the conversion of arginine (Arg) to guanidinoacetic acid (GAA), is expressed mainly in kidney and pancreas. The methylation of GAA to creatine (Cre) primarily occurs in the liver. The role of the gut in Cre homeostasis has not been characterized. OBJECTIVE: We aimed to quantify the contribution of kidney, pancreas, and gut as sources of GAA for Cre synthesis. METHODS: Sow-reared, feed-deprived Yucatan miniature piglets (17-21 d old) were randomly assigned to acute intravenous treatments (expressed in µmol/kg/min) of: 1) Arg (4.8) + methionine (1.4) (Arg/Met), 2) Cre (0.6) with Arg/Met (Cre/Arg/Met), 3) citrulline (4.8) + methionine (1.4) (Cit/Met), or 4) alanine (6.2) (Ala). Suckling piglets were also studied. RESULTS: Renal GAA release was higher during Cit/Met compared with all other treatments (53-360% higher; P < 0.01), suggesting that Cit is a better precursor than Arg for renal GAA synthesis. Kidneys contributed higher (P < 0.01) proportions of the total GAA with Cit/Met (89%) and Arg/Met (68%) treatments compared with pancreas and gut. In the suckling pigs, kidneys contributed 88% of the GAA, with the remainder released by pancreas. None of the treatments resulted in a net flux of Cre across the kidney or pancreas. In the gut, Arg/Met and Cre/Arg/Met, but not Cit/Met, resulted in a net release of Cre. Cre/Arg/Met resulted in a higher net GAA release from the gut (P < 0.0001) and pancreas (P < 0.001) (68% of total GAA produced) compared with all other treatments (<19% from both organs), perhaps because GAA not needed for creatine synthesis was subsequently released. CONCLUSIONS: Cit is a better precursor than Arg for renal GAA synthesis, and kidney is the major source of GAA for Cre synthesis in neonatal piglets, but the gut also has the capacity to synthesize GAA and Cre when Arg and Met are available.


Assuntos
Creatina/biossíntese , Glicina/análogos & derivados , Mucosa Intestinal/metabolismo , Rim/metabolismo , Fígado/metabolismo , Pâncreas/metabolismo , Aminoácidos/metabolismo , Animais , Creatina/sangue , Feminino , Glicina/sangue , Glicina/metabolismo , Metilação , Suínos , Porco Miniatura
13.
Am J Kidney Dis ; 75(2): 195-203, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31563467

RESUMO

RATIONALE & OBJECTIVE: Although a declining body mass index (BMI) is associated with higher mortality in patients on hemodialysis, BMI cannot distinguish lean body mass from fat mass. It remains unclear whether changes over time in lean body mass are associated with mortality. We examined the prognostic significance of changes in the modified creatinine index, a proxy for lean body mass. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Outpatients (n=349; mean age, 67.4 years; 60% men) undergoing maintenance hemodialysis 3 times a week at a treatment center. PREDICTOR: Modified creatinine index and BMI trajectories over a 1-year period. OUTCOMES: All-cause mortality. ANALYTICAL APPROACH: We calculated the percentage of change in modified creatinine index and BMI over a 1-year period. Patients were categorized according to change in modified creatinine index/BMI: no decline (≥0%) or decline (<0%). Kaplan-Meier and Cox proportional hazard analyses were performed to examine whether modified creatinine index and BMI trajectories were associated with mortality. RESULTS: During follow-up (median, 1,157 days), 79 patients died. Decreasing modified creatinine index (HR, 1.31; 95% CI, 1.11-1.54) and BMI (HR, 1.25; 95% CI, 1.01-1.54) over time, measured as continuous variables and expressed per 1-standard deviation decrease, were independently associated with higher risk for all-cause mortality. The decline in modified creatinine index/no decline in BMI group (HR, 2.14; 95% CI, 1.04-4.45) and the decline in modified creatinine index/decline in BMI group (HR, 3.05; 95% CI, 1.58-5.90) had higher rates of mortality compared to the no decline in modified creatinine index/decline in BMI group. LIMITATIONS: The absence of a direct measure of lean body and fat mass and limited generalizability to non-Japanese hemodialysis populations. CONCLUSIONS: The modified creatinine index trajectory is independently associated with mortality and provides additional prognostic information to the BMI trajectory in patients on hemodialysis.


Assuntos
Índice de Massa Corporal , Creatina/sangue , Falência Renal Crônica/terapia , Pacientes Ambulatoriais , Diálise Renal/mortalidade , Idoso , Biomarcadores/sangue , Causas de Morte/tendências , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Falência Renal Crônica/sangue , Falência Renal Crônica/mortalidade , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Fatores de Tempo
14.
J Coll Physicians Surg Pak ; 29(12): 1159-1164, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31839087

RESUMO

OBJECTIVE: To evaluate abdominal volume index (AVI), body roundness index (BRI), body adiposity index (BAI), a body shape index (ABSI) and conicity index (C-Index) for differences in subjects with or without metabolic syndrome, diabetes, nephropathy, and dyslipidemia; and secondly, to evaluate the diagnostic performance through measuring area under curve (AUC) by ROC curve analysis for new and conventional obesity measures in diagnosing metabolic syndrome. STUDY DESIGN: Cross-sectional analytical study. PLACE AND DURATION OF STUDY: PNS Hafeez Hospital, Islamabad, from January 2016 to December 2018. METHODOLOGY: Baseline anthropometric measures including BMI, WHpR, WHtR, AVI, BRI, BAI, ABSI and C-Index were measured for 232 subjects along with measurement of various biochemical parameters. Differences among subjects with and without metabolic syndrome, diabetes, nephropathy, and groups based upon insulin resistance were noted. ROC curve analysis was utilised to measure AUC for all anthropometric measures for diagnosing metabolic syndrome. RESULTS: Pearson's correlation between obesity measures and lipid indices suggested highest correlation for AVI for most lipid indices followed by WHpR and WHtR. Mean AUC for obesity measures were greater than 0.80 for WHtR and AVI, followed by other parameters. The least AUC i.e. 0.320, was observed for ABSI. The differences between various anthropometric measures for groups based upon metabolic syndrome, diabetes, nephropathy, and insulin resistance remain variable indicating that each anthropometric index may depict a different aspect of the metabolic risk. CONCLUSION: WHtR and AVI showed the highest AUC to diagnose metabolic syndrome and were better associated with metabolic diseases.


Assuntos
Dislipidemias/etiologia , Nefropatias/etiologia , Síndrome Metabólica/etiologia , Obesidade Abdominal/complicações , Antropometria/métodos , Índice de Massa Corporal , Creatina/sangue , Estudos Transversais , Dislipidemias/sangue , Dislipidemias/diagnóstico , Feminino , Humanos , Resistência à Insulina , Nefropatias/sangue , Nefropatias/diagnóstico , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Obesidade Abdominal/sangue , Obesidade Abdominal/diagnóstico , Prognóstico , Fatores de Risco
15.
Ecotoxicol Environ Saf ; 186: 109752, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31605954

RESUMO

Tilapias are cultured globally and are rising in acceptance as the most important freshwater aquaculture species. Monitoring of serum biomarkers is a promising tool in aquaculture to screen the health status as they are virtuous indicators of extreme stress and organ dysfunction in fish. The present study examined the serum biomarkers of oxytetracycline (OTC)-dosed Nile tilapia Oreochromis niloticus at 0, 80 and 800 mg/kg biomass/day, i.e., 0X, 1X, and 10X the approved dose (X = 80 mg OTC/kg biomass/day) for 10 consecutive days. The fish biomass and levels of serum glucose, aspartate aminotransferase, alanine aminotransferase, creatinine and C-reactive protein (CRP) were determined at scheduled intervals. A significant dose-dependent reduction in fish biomass during the OTC-dosing (5.84%) and post-OTC dosing (8.16%) periods was observed. All the serum biomarkers of Nile tilapia increased significantly on day 10 OTC-dosing. Though their levels reduced significantly, normalcy was not achieved even after 42 days of cessation of OTC-dosing, except CRP. The CRP reached the normal level on day 25 post-OTC dosing in the 1X group. The results, thus, demonstrated that the oral OTC-dosing influences the physiological state of apparently healthy Nile tilapia in a dose-dependent manner. These changes were, however, reversible upon discontinuation of OTC-dosing. The set of data observed on growth reduction and elevated serum biomarker levels even after 42 days of cessation of OTC-dosing, thus, raises questions on the utility of oral OTC-dosing.


Assuntos
Ração Animal , Antibacterianos/efeitos adversos , Aquicultura/métodos , Ciclídeos/fisiologia , Dieta , Oxitetraciclina/efeitos adversos , Estresse Fisiológico/efeitos dos fármacos , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Biomassa , Glicemia/metabolismo , Proteína C-Reativa/metabolismo , Ciclídeos/sangue , Ciclídeos/crescimento & desenvolvimento , Creatina/sangue , Humanos , Índia , Alimentos Marinhos , Tilápia
16.
Parasit Vectors ; 12(1): 486, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619276

RESUMO

BACKGROUND: In the animal production sector, enteritis is responsible for serious economic losses, and intestinal parasitism is a major stress factor leading to malnutrition and lowered performance and animal production efficiency. The effect of enteric parasites on the gut function of teleost fish, which represent the most ancient bony vertebrates, is far from being understood. The intestinal myxozoan parasite Enteromyxum leei dwells between gut epithelial cells and causes severe enteritis in gilthead sea bream (Sparus aurata), anorexia, cachexia, growth impairment, reduced marketability and increased mortality. METHODS: This study aimed to outline the gut failure in this fish-parasite model using a multifaceted approach and to find and validate non-lethal serum markers of gut barrier dysfunction. Intestinal integrity was studied in parasitized and non-parasitized fish by immunohistochemistry with specific markers for cellular adhesion (E-cadherin) and tight junctions (Tjp1 and Cldn3) and by functional studies of permeability (oral administration of FITC-dextran) and electrophysiology (Ussing chambers). Serum samples from parasitized and non-parasitized fish were analyzed using non-targeted metabolomics and some significantly altered metabolites were selected to be validated using commercial kits. RESULTS: The immunodetection of Tjp1 and Cldn3 was significantly lower in the intestine of parasitized fish, while no strong differences were found in E-cadherin. Parasitized fish showed a significant increase in paracellular uptake measured by FITC-dextran detection in serum. Electrophysiology showed a decrease in transepithelial resistance in infected animals, which showed a diarrheic profile. Serum metabolomics revealed 3702 ions, from which the differential expression of 20 identified compounds significantly separated control from infected groups in multivariate analyses. Of these compounds, serum inosine (decreased) and creatine (increased) were identified as relevant and validated with commercial kits. CONCLUSIONS: The results demonstrate the disruption of tight junctions and the loss of gut barrier function, a metabolomic profile of absorption dysfunction and anorexia, which further outline the pathophysiological effects of E. leei.


Assuntos
Enterite/veterinária , Doenças dos Peixes/parasitologia , Metabolômica , Myxozoa/patogenicidade , Doenças Parasitárias em Animais/parasitologia , Dourada/parasitologia , Animais , Caderinas/metabolismo , Claudina-3/metabolismo , Creatina/sangue , Dextranos/metabolismo , Modelos Animais de Doenças , Eletrofisiologia , Enterite/parasitologia , Ensaio de Imunoadsorção Enzimática , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/metabolismo , Imuno-Histoquímica , Inosina/sangue , Mucosa Intestinal/metabolismo , Intestinos/parasitologia , Intestinos/patologia , Doenças Parasitárias em Animais/patologia , Permeabilidade , Proteína da Zônula de Oclusão-1/metabolismo
17.
Clin Exp Med ; 19(4): 479-486, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31542837

RESUMO

IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. The classic manifestation of IgAN is episodic hematuria and proteinuria. Nephrotic syndrome (NS) is not very common in IgAN, reported to occur in only 5-10% of IgAN patients. However, the clinical and pathological characteristics and long-term outcomes of patients with NS-IgAN at onset remain unknown. A retrospective study was conducted, enrolling 1165 patients with biopsy-proven IgAN from West China Hospital in 2008-2015. Patients with renal biopsy of minimal change disease with mesangial IgA deposits were excluded. The renal endpoint was defined as 50% decrease in eGFR or progressing into end-stage renal disease (ESRD). A total of 1165 patients were enrolled with average age of 34.58, and 171 (14.7%) patients were presented with NS. Comparing NS and non-NS groups, significance differences were shown in hypertension (HTN), 24-h urine protein, serum albumin, serum creatine, eGFR and uric acid. NS group had severe pathological changes such as endocapillary hypercellularity, tubular atrophy or interstitial fibrosis and crescent, but less segmental glomerulosclerosis or adhesion and global sclerosis. During the average follow-up of 44.27 months, 29.8% (51/171) NS patients and 15.8% (157/994) non-NS patients progressed to the renal endpoint. 5-year renal survival rates were 73.1% and 87.8% (P < 0.001) in NS and non-NS groups, respectively. This study demonstrated that IgAN patients with NS had higher serum creatine, lower eGFR, lower uric acid, more acute lesions and poor prognosis. NS was an independent risk factor for progression to the renal endpoint.


Assuntos
Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/mortalidade , Síndrome Nefrótica/epidemiologia , Adulto , China/epidemiologia , Creatina/sangue , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/urina , Humanos , Masculino , Síndrome Nefrótica/etiologia , Síndrome Nefrótica/mortalidade , Síndrome Nefrótica/urina , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Ácido Úrico/metabolismo , Adulto Jovem
18.
BMJ Case Rep ; 12(8)2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31401569

RESUMO

Granulomatous interstitial nephritis (GIN) is a rare entity identified in <1% of native kidney biopsies. The most frequent aetiology is drug-related, followed by systemic granulomatous conditions. Among drugs implicated in GIN, antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) are the most frequent. We report the case of a 45-year-old white man referred to a nephrology consult due to chronic kidney disease. He had a history of arterial hypertension with 10 years of evolution, hyperuricaemia, medicated with allopurinol and NSAID abuse for at least 20 years. Urine sediment was blunt, without proteinuria. Renal ultrasound was normal. A kidney biopsy revealed well-defined epithelioid granulomas with glomerular wrinkling and collapse. Infectious and systemic conditions were excluded, favouring the hypothesis of drug-induced GIN, probably related to NSAIDs. Kidney biopsy remains the gold standard for the diagnosis of GIN. Facing a patient with renal failure without significant proteinuria or active sediment, one should look for causes of tubulointerstitial injury.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Granuloma/induzido quimicamente , Nefrite Intersticial/induzido quimicamente , Biópsia , Nitrogênio da Ureia Sanguínea , Creatina/sangue , Taxa de Filtração Glomerular , Granuloma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/diagnóstico , Nefrite Intersticial/patologia , Transtornos Relacionados ao Uso de Substâncias/diagnóstico
19.
Clin Biochem ; 73: 77-81, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31386833

RESUMO

OBJECTIVES: HbA1c shows low in patients with hemolysis, whereas glycated albumin (GA) is not affected by hemolysis. Therefore, the GA/HbA1c ratio reflects hemolysis in diabetic patients with hemolysis. Erythrocyte creatine (EC) is an indicator of hemolysis that reflects the mean erythrocyte age. The aim of this study was to examine whether HbA1c adjusted by EC accurately reflected glycemic control in patients with hemolysis. MATERIALS AND METHODS: A total of 238 individuals, consisting of 131 diabetic patients and 107 non-diabetic subjects, and consisting of 42 patients with hemolysis, and 196 subjects without hemolysis were selected for the study. HbA1c expressed in the IFCC units (iA1c) as well as in the NGSP units (A1C) were used. From the fact that EC and the GA/iA1c ratio showed a significant positive correlation, a formula for iA1c adjusted by EC (ECadj-iA1c) was created from a regression equation between EC and the GA/iA1c ratio. RESULTS: Significant correlations were observed between the GA/iA1c ratio and various hemolytic indicators but not between the GA/ECadj-iA1c ratio and those hemolytic indicators. The GA/iA1c ratio in individuals with hemolysis was significantly higher than in individuals without hemolysis, while no significant differences were observed in the GA/ECadj-iA1c ratio between the groups. Further, iA1c concentrations in non-diabetic patients with hemolysis were significantly lower than in the non-diabetic subjects without hemolysis, whereas ECadj-iA1c and GA concentrations showed no significant difference between the two groups. CONCLUSIONS: These results suggested that ECadj-iA1c accurately reflected glycemic control in patients with hemolysis.


Assuntos
Creatina/sangue , Diabetes Mellitus/sangue , Eritrócitos/metabolismo , Hemoglobina A Glicada/metabolismo , Hemólise , Idoso , Diabetes Mellitus/patologia , Eritrócitos/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Albumina Sérica/metabolismo
20.
Sci Rep ; 9(1): 11129, 2019 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-31366905

RESUMO

Vulvar cancer is a rare malignancy with poor prognosis that generally occurs in elderly patients. The individual prognosis is difficult to assess. Serum creatinine levels are frequently elevated in elderly patients. Recent evidence have shown shown that - besides indicating kidney impairment - serum creatinine levels may be used to predict the survival in cancer patients. Several studies observed an association between elevated serum creatinine levels and poor prognosis in patients with solid tumors. In this retrospective cohort study, serum creatinine levels were evaluated in 170 patients with invasive vulvar cancer. Serum creatinine levels were correlated to established clinicopathologic factors. Univariate and multivariate survival analysis were performed. Elevated serum creatinine levels (>1.2 mg/dl) were significantly associated with both poor disease specific and overall survival. Three year overall survival rates were 74.8% and 32.5% for patients with serum creatinine levels of ≤ and >1.2 mg/dl, respectively. In a multivariate survival model, serum creatinine levels were significantly associated with overall survival independent of tumor stage and patients' age. In conclusion, pretherapeutic serum creatinine levels may be useful as an independent prognostic parameter in patients with vulvar cancer.


Assuntos
Creatina/sangue , Neoplasias Vulvares/sangue , Neoplasias Vulvares/patologia , Idoso , Biomarcadores Tumorais/sangue , Feminino , Humanos , Masculino , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
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