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1.
Rev Assoc Med Bras (1992) ; 66Suppl 2(Suppl 2): 112-117, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32965368

RESUMO

OBJECTIVE: We aimed to present a review of renal changes in patients with COVID-19. METHODS: We performed a systematic review of the literature to identify original articles regarding clinical, laboratory, and anatomopathological kidney changes in patients infected with SARS-CoV-2 published until May 7, 2020. The search was carried out across PubMed, Scopus, and Embase using the keywords "COVID-19", "coronavirus", "SARS-CoV-2", "kidney injury" and "kidney disease". Fifteen studies presented clinical and laboratory renal changes in patients with COVID-19, and three addressed anatomopathological changes. DISCUSSION: Acute kidney injury (AKI) was a relevant finding in patients with COVID-19. There were also significant changes in laboratory tests that indicated kidney injury, such as increased serum creatinine and blood urea nitrogen (BUN), proteinuria, and hematuria. The presence of laboratory abnormalities and AKI were significant in severely ill patients. There was a considerable prevalence of AKI among groups of patients who died of COVID-19. Histopathological analysis of the kidney tissue of patients infected with SARS-CoV-2 suggested that the virus may directly affect the kidneys. CONCLUSION: Although COVID-19 affects mainly the lungs, it can also impact the kidneys. Increased serum creatinine and BUN, hematuria, proteinuria, and AKI were frequent findings in patients with severe COVID-19 and were related to an increased mortality rate. Further studies focusing on renal changes and their implications for the clinical condition of patients infected with the novel coronavirus are needed.


Assuntos
Lesão Renal Aguda/etiologia , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Lesão Renal Aguda/fisiopatologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/urina , Creatinina/sangue , Hematúria/etiologia , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/metabolismo , Pneumonia Viral/urina , Proteinúria/etiologia , Urina/química
2.
ACS Nano ; 14(9): 11787-11798, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32830949

RESUMO

The COVID-19 pandemic has become a major worldwide crisis. Although respiratory symptoms are a key feature of the disease, many people who are hospitalized with COVID-19 also suffer acute kidney injury, a condition that exacerbates patient mortality and may have to be treated through renal replacement therapy. Much of the focus on hospital capacity during the pandemic has centered on the availability of ventilators. However, supplies for dialysis treatment, including dialysate, have also run dangerously low in hospitals at the epicenter of the pandemic. Therefore, there is an urgent need to develop materials that can efficiently and rapidly regenerate dialysate, removing toxins and restoring electrolyte concentrations so that this vital resource remains readily available. In this work, Ti3C2Tx, a two-dimensional transition-metal carbide (MXene) that is known to efficiently adsorb urea, was used to remove creatinine and uric acid from an aqueous solution and dialysate, with a maximum adsorption capacity of 45.7 and 17.0 mg/g, respectively. We systematically analyzed and modeled the adsorption kinetics, isotherms, and thermodynamics, thus determining the rate-limiting step and adsorption mechanism. A fixed-bed column loaded with Ti3C2Tx was designed to further evaluate the adsorption performance under continuous fluid-flow conditions, mirroring conditions of continuous renal replacement therapy modalities. The maximum capacity and 50% breakthrough volume were calculated to further approach the practical application of Ti3C2Tx for removal of uremic toxins. Our findings suggest that Ti3C2Tx has the potential to be used as an efficient sorbent for the regeneration of dialysate, allowing for accelerated dialysate regeneration by removing filtered toxins and leading to more portable dialysis devices.


Assuntos
Creatinina/química , Soluções para Diálise/química , Titânio/química , Toxinas Biológicas/química , Adsorção , Humanos , Diálise Renal/métodos , Urina/química
3.
Intensive Care Med ; 46(7): 1339-1348, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32533197

RESUMO

Acute kidney injury (AKI) has been reported in up to 25% of critically-ill patients with SARS-CoV-2 infection, especially in those with underlying comorbidities. AKI is associated with high mortality rates in this setting, especially when renal replacement therapy is required. Several studies have highlighted changes in urinary sediment, including proteinuria and hematuria, and evidence of urinary SARS-CoV-2 excretion, suggesting the presence of a renal reservoir for the virus. The pathophysiology of COVID-19 associated AKI could be related to unspecific mechanisms but also to COVID-specific mechanisms such as direct cellular injury resulting from viral entry through the receptor (ACE2) which is highly expressed in the kidney, an imbalanced renin-angotensin-aldosteron system, pro-inflammatory cytokines elicited by the viral infection and thrombotic events. Non-specific mechanisms include haemodynamic alterations, right heart failure, high levels of PEEP in patients requiring mechanical ventilation, hypovolemia, administration of nephrotoxic drugs and nosocomial sepsis. To date, there is no specific treatment for COVID-19 induced AKI. A number of investigational agents are being explored for antiviral/immunomodulatory treatment of COVID-19 and their impact on AKI is still unknown. Indications, timing and modalities of renal replacement therapy currently rely on non-specific data focusing on patients with sepsis. Further studies focusing on AKI in COVID-19 patients are urgently warranted in order to predict the risk of AKI, to identify the exact mechanisms of renal injury and to suggest targeted interventions.


Assuntos
Lesão Renal Aguda/virologia , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Sistema Renina-Angiotensina/fisiologia , Lesão Renal Aguda/tratamento farmacológico , Lesão Renal Aguda/fisiopatologia , Lesão Renal Aguda/terapia , Betacoronavirus/fisiologia , Transtornos da Coagulação Sanguínea/virologia , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/urina , Creatinina/sangue , Estado Terminal , Hematúria/etiologia , Humanos , Rim/fisiopatologia , Rim/virologia , Pandemias , Pneumonia Viral/metabolismo , Pneumonia Viral/urina , Proteinúria/etiologia , Urinálise , Urina/química , Urina/virologia
4.
J Vis Exp ; (159)2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32449741

RESUMO

Duchenne muscular dystrophy (DMD), a progressive and fatal muscle disease, is caused by mutations in the DMD gene that result in the absence of dystrophin protein. To date, we have completed an investigator-initiated first-in-human study at the National Center of Neurology and Psychiatry based on the systemic injection of the morpholino oligonucleotides which are prone to exon-53 skipping. For the effective treatment of DMD, in vitro testing with myoblasts derived from DMD patients to screen drugs and assess patient eligibility before undertaking clinical trials is thought to be essential. Very recently, we reported a new MYOD1-converted urine-derived cell (UDC) treated with the histone methyltransferase inhibitor (3-deazaneplanocin A hydrochloride), as a cellular model of DMD. The new autologous UDC might show phenocopy of the disease-specific phenotypes of DMD, leading to the application of precision medicine in a variety of muscle-related diseases. In this article, we describe a detailed protocol for efficient modelling of DMD muscle cells using MYOD1-converted UDCs along with reverse transcriptase polymerase chain reaction (RT-PCR), Western blotting, and immunocytochemistry to evaluate the restoration of dystrophin mRNA and protein levels after exon skipping.


Assuntos
Células Cultivadas/química , Éxons/genética , Fibras Musculares Esqueléticas/metabolismo , Distrofia Muscular de Duchenne/genética , Urina/química , Humanos , Transfecção
5.
Am J Gastroenterol ; 115(6): 906-915, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32433273

RESUMO

INTRODUCTION: The low FODMAP diet (LFD) reduces symptoms and bifidobacteria in irritable bowel syndrome (IBS). ß-galactooligosaccharides (B-GOS) may reduce the symptoms and increase bifidobacteria in IBS. We investigated whether B-GOS supplementation alongside the LFD improves IBS symptoms while preventing the decline in bifidobacteria. METHODS: We performed a randomized, placebo-controlled, 3-arm trial of 69 Rome III adult patients with IBS from secondary care in the United Kingdom. Patients were randomized to a sham diet with placebo supplement (control) or LFD supplemented with either placebo (LFD) or 1.4 g/d B-GOS (LFD/B-GOS) for 4 weeks. Gastrointestinal symptoms, fecal microbiota (fluorescent in situ hybridization and 16S rRNA sequencing), fecal short-chain fatty acids (gas-liquid chromatography) and pH (probe), and urine metabolites (H NMR) were analyzed. RESULTS: At 4 weeks, adequate symptom relief was higher in the LFD/B-GOS group (16/24, 67%) than in the control group (7/23, 30%) (odds ratio 4.6, 95% confidence interval: 1.3-15.6; P = 0.015); Bifidobacterium concentrations (log10 cells/g dry weight) were not different between LFD and LFD/B-GOS but were lower in the LFD/B-GOS (9.49 [0.73]) than in the control (9.77 [0.41], P = 0.018). A proportion of Actinobacteria was lower in LFD (1.9%, P = 0.003) and LFD/B-GOS (1.8%, P < 0.001) groups than in the control group (4.2%). Fecal butyrate was lower in the LFD (387.3, P = 0.028) and LFD/B-GOS (346.0, P = 0.007) groups than in the control group (609.2). DISCUSSION: The LFD combined with B-GOS prebiotic produced a greater symptom response than the sham diet plus placebo, but addition of 1.4 g/d B-GOS did not prevent the reduction of bifidobacteria. The LFD reduces fecal Actinobacteria and butyrate thus strict long-term use should not be advised.


Assuntos
Bifidobacterium/genética , Dieta com Restrição de Carboidratos/métodos , Galactose/uso terapêutico , Microbioma Gastrointestinal/genética , Síndrome do Intestino Irritável/terapia , Oligossacarídeos/uso terapêutico , Prebióticos , Adulto , Terapia Combinada , Dietoterapia/métodos , Fezes/química , Feminino , Fermentação , Humanos , Hibridização in Situ Fluorescente , Síndrome do Intestino Irritável/metabolismo , Síndrome do Intestino Irritável/microbiologia , Síndrome do Intestino Irritável/fisiopatologia , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S , Resultado do Tratamento , Urina/química , Adulto Jovem
6.
Sci Total Environ ; 733: 139313, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32446074

RESUMO

For sanitation systems aiming at recycling nutrients, separately collecting urine at source is desirable as urine contains most of the nutrients in wastewater. However, reducing the volume of the collected urine and recovering majority of its nutrients is necessary, as this improves the transportability and the end-application of urine-based fertilisers. In this study, we present an innovative method, alkaline dehydration, for treating fresh human urine into a nutrient-rich dry solid. Our aim was to investigate whether fresh urine (pH < 7) added to five different alkaline media (pH > 11) could be dehydrated at elevated temperatures (50 and 60 °C) with minimal loss of urea, urine's principal nitrogen compound. We found that it was possible to concentrate urine 48 times, yielding dry end-products with high fertiliser value: approximately, 10% N, 1% P, and 4% K. We monitored the physicochemical properties and the composition of various dehydration media to provide useful insights into their suitability for dehydrating urine. We demonstrated that it is possible to recover >90% nitrogen when treating fresh urine by alkaline dehydration by inhibiting the enzymatic hydrolysis of urea at elevated pH and minimising the chemical hydrolysis of urea with high urine dehydration rates.


Assuntos
Desidratação , Fertilizantes/análise , Humanos , Nitrogênio/análise , Temperatura , Urina/química , Águas Residuárias
7.
Clin Chem Lab Med ; 58(7): 1121-1124, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: covidwho-52616

RESUMO

Background Among patients with coronavirus disease 2019 (COVID-19), the cases of a significant proportion of patients are severe. A viral nucleic acid test is used for the diagnosis of COVID-19, and some hematological indicators have been used in the auxiliary diagnosis and identification of the severity of COVID-19. Regarding body fluid samples, except for being used for nucleic acid testing, the relationship between COVID-19 and routine body fluid parameters is not known. Our aim was to investigate the value of urine biochemical parameters in the prediction of the severity of COVID-19. Methods A total of 119 patients with COVID-19 were enrolled at Renmin Hospital of Wuhan University. According to the severity of COVID-19, the patients were divided into three groups (moderate 67, severe 42 and critical 10), and 45 healthy persons were enrolled in the same period as healthy controls. The relationship between the results of urine biochemical parameters and the severity of COVID-19 was analyzed. Results The positive rates of urine occult blood (BLOOD) and proteinuria (PRO) were higher in COVID-19 patients than in healthy controls (p < 0.05); the urine specific gravity (SG) value was lower in patients than in healthy controls (p < 0.05), and the urine potential of hydrogen (pH) value was higher in patients than in healthy controls (p < 0.01). The positive rates of urine glucose (GLU-U) and PRO in the severe and critical groups were higher than those in the moderate group (p < 0.01 and p < 0.05, respectively); other biochemical parameters of urine were not associated with the severity of COVID-19. Conclusions Some urine biochemical parameters are different between patients with severe acute respiratory syndrome (SARS)-CoV-2 and healthy controls, and GLU-U and PRO may be helpful for the differentiation of COVID-19 severity.


Assuntos
Biomarcadores/urina , Infecções por Coronavirus/urina , Pneumonia Viral/urina , Urina/química , Idoso , Betacoronavirus/metabolismo , Betacoronavirus/patogenicidade , Coronavirus/metabolismo , Coronavirus/patogenicidade , Infecções por Coronavirus/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/metabolismo , Índice de Gravidade de Doença
8.
Clin Chem Lab Med ; 58(7): 1121-1124, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32286242

RESUMO

Background Among patients with coronavirus disease 2019 (COVID-19), the cases of a significant proportion of patients are severe. A viral nucleic acid test is used for the diagnosis of COVID-19, and some hematological indicators have been used in the auxiliary diagnosis and identification of the severity of COVID-19. Regarding body fluid samples, except for being used for nucleic acid testing, the relationship between COVID-19 and routine body fluid parameters is not known. Our aim was to investigate the value of urine biochemical parameters in the prediction of the severity of COVID-19. Methods A total of 119 patients with COVID-19 were enrolled at Renmin Hospital of Wuhan University. According to the severity of COVID-19, the patients were divided into three groups (moderate 67, severe 42 and critical 10), and 45 healthy persons were enrolled in the same period as healthy controls. The relationship between the results of urine biochemical parameters and the severity of COVID-19 was analyzed. Results The positive rates of urine occult blood (BLOOD) and proteinuria (PRO) were higher in COVID-19 patients than in healthy controls (p < 0.05); the urine specific gravity (SG) value was lower in patients than in healthy controls (p < 0.05), and the urine potential of hydrogen (pH) value was higher in patients than in healthy controls (p < 0.01). The positive rates of urine glucose (GLU-U) and PRO in the severe and critical groups were higher than those in the moderate group (p < 0.01 and p < 0.05, respectively); other biochemical parameters of urine were not associated with the severity of COVID-19. Conclusions Some urine biochemical parameters are different between patients with severe acute respiratory syndrome (SARS)-CoV-2 and healthy controls, and GLU-U and PRO may be helpful for the differentiation of COVID-19 severity.


Assuntos
Biomarcadores/urina , Infecções por Coronavirus/urina , Pneumonia Viral/urina , Urina/química , Idoso , Betacoronavirus/metabolismo , Betacoronavirus/patogenicidade , Coronavirus/metabolismo , Coronavirus/patogenicidade , Infecções por Coronavirus/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/metabolismo , Índice de Gravidade de Doença
9.
PLoS Negl Trop Dis ; 14(4): e0008246, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32324742

RESUMO

The development of an accurate protein-based antigen detection assay for diagnosis of active visceral leishmaniasis (VL) would represent a major clinical advance. VL is a serious and fatal disease caused by the parasites Leishmania infantum and Leishmania donovani. The gold standard confirmatory diagnostic test for VL is the demonstration of parasites or their DNA from aspirates from spleen, lymph node, and bone marrow or from blood buffy coats. Here we describe the production and use of monoclonal antibodies (mAbs) for the development of a sensitive and specific antigen detection capture ELISA for VL diagnosis. This test simultaneously detects six leishmania protein biomarkers that we have previously described (Li-isd1, Li-txn1, Li-ntf2, Ld-mao1, Ld-ppi1 and Ld-mad1). The initial clinical validation of this new mAb-based multiplexed capture ELISA showed a sensitivity of ≥93%. The test was negative with 35 urine samples from healthy control subjects as well as with 30 patients with confirmed non-VL tropical diseases (cutaneous leishmaniasis, n = 6; Chagas disease, n = 6; schistosomiasis, n = 6; and tuberculosis, n = 12). These results strongly support the possible utility of this mAb-based multiplexed capture ELISA as a promising diagnostic test for active VL as well as for monitoring the treatment efficacy of this disease. The test is ready for upscaling and validation for clinical use.


Assuntos
Anticorpos Monoclonais/imunologia , Antígenos de Protozoários/urina , Leishmania donovani/química , Leishmania infantum/química , Leishmaniose Visceral/diagnóstico , Urinálise/métodos , Urina/química , Adolescente , Adulto , Idoso , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Biomarcadores/urina , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Adulto Jovem
10.
J Vet Sci ; 21(2): e23, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32233131

RESUMO

The identification of biomarkers that distinguish diseased from healthy individuals is of great interest in human and veterinary fields. In this research area, a metabolomic approach and its related statistical analyses can be useful for biomarker determination and allow non-invasive discrimination of healthy volunteers from breast cancer patients. In this study, we focused on the most common canine neoplasm, mammary gland tumor, and herein, we describe a simple method using ultra-high-performance liquid chromatography to determine the levels of tyrosine and its metabolites (epinephrine, 3,4-dihydroxy-L-phenylalanine, 3,4-dihydroxyphenylacetic acid, and vanillylmandelic acid), tryptophan and its metabolites (5-hydroxyindolacetic acid, indoxyl sulfate, serotonin, and kynurenic acid) in canine mammary cancer urine samples. Our results indicated significantly increased concentrations of three tryptophan metabolites, 5-hydroxyindolacetic acid (p < 0.001), serotonin, indoxyl sulfate (p < 0.01), and kynurenic acid (p < 0.05), and 2 tyrosine metabolites, 3,4-dihydroxy-L-phenylalanine (p < 0.001), and epinephrine (p < 0.05) in urine samples from the mammary gland tumor group compared to concentrations in urine samples from the healthy group. The results indicate that select urinary tyrosine and tryptophan metabolites may be useful as non-invasive diagnostic markers as well as in developing a therapeutic strategy for canine mammary gland tumors.


Assuntos
Cromatografia Líquida de Alta Pressão/veterinária , Doenças do Cão/urina , Neoplasias Mamárias Animais/urina , Tirosina/urina , Animais , Biomarcadores/urina , Cromatografia Líquida de Alta Pressão/métodos , Cães , Feminino , Tirosina/metabolismo , Urina/química
11.
Arch. argent. pediatr ; 118(2): e178-e182, abr. 2020. tab, ilus
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1100431

RESUMO

La enfermedad de jarabe de arce es una entidad autosómica recesiva producida por un error congénito en el metabolismo de tres aminoácidos esenciales de cadena ramificada: valina, leucina e isoleucina. La forma neonatal de esta enfermedad se manifiesta por un cuadro de compromiso neurológico grave y progresivo, asociado a un olor peculiar de la orina, consecuencia de la eliminación del exceso de estos aminoácidos. Este olor a azúcar quemada remeda a la melaza obtenida de los arces, lo que da nombre a esta enfermedad. El mejor método para eliminar estos tóxicos es la hemodiafiltración, pero, en los centros en los que esta práctica no es posible, la diálisis peritoneal constituye una alternativa.Se presenta a un recién nacido con leucinosis, con compromiso grave del sistema nervioso central, en quien la diálisis peritoneal fue de utilidad para superar la descompensación metabólica.


Maple syrup disease is an autosomal recessive entity caused by a congenital error in the metabolism of three essential branched-chain amino acids: valine, leucine and isoleucine. The neonatal form of this disease is expressed by a severe and progressive neurological compromise, associated with a peculiar smell of urine, a consequence of the elimination of the excess of these amino acids. This smell of burnt sugar mimics the molasses obtained from maples, which gives its name to this disease. The best method to eliminate these toxins is hemodiafiltration, but in centers where this practice is not possible, peritoneal dialysis is an alternative.We present a newborn with leukinosis with severe central nervous system involvement in whom peritoneal dialysis was useful to overcome metabolic decompensation.


Assuntos
Humanos , Masculino , Recém-Nascido , Diálise Peritoneal , Doença da Urina de Xarope de Bordo/diagnóstico , Urina/química , Perda de Peso , Doença da Urina de Xarope de Bordo/terapia
12.
Physiol Rev ; 100(4): 1621-1705, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32191559

RESUMO

The urothelium, which lines the renal pelvis, ureters, urinary bladder, and proximal urethra, forms a high-resistance but adaptable barrier that surveils its mechanochemical environment and communicates changes to underlying tissues including afferent nerve fibers and the smooth muscle. The goal of this review is to summarize new insights into urothelial biology and function that have occurred in the past decade. After familiarizing the reader with key aspects of urothelial histology, we describe new insights into urothelial development and regeneration. This is followed by an extended discussion of urothelial barrier function, including information about the roles of the glycocalyx, ion and water transport, tight junctions, and the cellular and tissue shape changes and other adaptations that accompany expansion and contraction of the lower urinary tract. We also explore evidence that the urothelium can alter the water and solute composition of urine during normal physiology and in response to overdistension. We complete the review by providing an overview of our current knowledge about the urothelial environment, discussing the sensor and transducer functions of the urothelium, exploring the role of circadian rhythms in urothelial gene expression, and describing novel research tools that are likely to further advance our understanding of urothelial biology.


Assuntos
Urotélio/crescimento & desenvolvimento , Animais , Fenômenos Biomecânicos , Ritmo Circadiano , Humanos , Urina/química , Urina/fisiologia , Urotélio/citologia , Urotélio/metabolismo
13.
Int J Occup Environ Med ; 11(2): 85-94, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32218556

RESUMO

BACKGROUND: For many years, several studies drew attention to the possible nephrotoxic effects of silica and distinct renal dysfunction involving glomerular and renal tubules in workers exposed to silica. OBJECTIVE: To determine the early signs of subclinical nephrotoxic effects among some Egyptian workers exposed to silica in the pottery industry. METHODS: This study was carried out in El-Fawakhir handicraft pottery area, in Greater Cairo, Egypt. The studied population included 29 non-smoking male workers occupationally exposed to silica in addition to 35 non-smoking administrative male subjects who represented the comparison group in the study. Measured urinary parameters were concentrations of total protein (TP), microalbumin (Malb), activities of alkaline phosphatase (ALP), γ-glutamyl transferase (γ-GT), lactate dehydrogenase (LDH), kidney injury molecule-1 (KIM-1), and silicon (Si). RESULTS: Silica-exposed workers showed significantly (p<0.05) increased levels of urinary TP, Malb, ALP, γ-GT, LDH, and KIM-1 compared with the comparison group. Among the silicaexposed group, increased urinary Si levels were positively and significantly correlated (Spearman's ρ>0.60, p<0.001 for all variables) with the elevated urinary proteins (including KIM-1) and enzymes levels. All measured urinary parameters were positively and significantly correlated (ρ>0.75, p<0.001 for all variables) with the duration of work among exposed subjects. No significant correlation was observed between the measured variables and the age of workers. CONCLUSION: There is associated subclinical glomerular and tubular affection among silica exposed workers, which is related to the duration and intensity of exposure.


Assuntos
Nefropatias/induzido quimicamente , Nefropatias/fisiopatologia , Rim/efeitos dos fármacos , Exposição Ocupacional/efeitos adversos , Insuficiência Renal/induzido quimicamente , Dióxido de Silício/toxicidade , Adulto , Estudos de Casos e Controles , Egito , Humanos , Indústrias , Glomérulos Renais/efeitos dos fármacos , Túbulos Renais Proximais/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Proteinúria , Dióxido de Silício/urina , Urina/química
14.
PLoS One ; 15(3): e0230072, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32182259

RESUMO

In the urinary metabolomics for finding biomarkers in urine, owing to high concentrations of urea, for chromatography-based metabolomic analysis, urea needed to be degraded by urease. This urease pretreatment has been the key step of sample preparation for standard urinary metabolomics until today even for mass spectrometry-based analysis. The urease pretreatment involving incubation of urine with urease contradicts the concept of metabolome sampling, which should immediately arrest metabolic reactions to prevent alterations of a metabolite profile. Nonetheless, the impact of urease pretreatment has not been clearly elucidated yet. We found that activities of urease and endogenous urinary enzymes and metabolite contaminants from the urease preparations introduce artefacts into metabolite profiles, thus leading to misinterpretation.


Assuntos
Biomarcadores/urina , Metaboloma , Metabolômica/métodos , Manejo de Espécimes/métodos , Urease/metabolismo , Urinálise/métodos , Urina/química , Adulto , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Urinálise/normas
15.
Nat Commun ; 11(1): 561, 2020 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-32047148

RESUMO

Parabens are preservatives widely used in consumer products including cosmetics and food. Whether low-dose paraben exposure may cause adverse health effects has been discussed controversially in recent years. Here we investigate the effect of prenatal paraben exposure on childhood overweight by combining epidemiological data from a mother-child cohort with experimental approaches. Mothers reporting the use of paraben-containing cosmetic products have elevated urinary paraben concentrations. For butyl paraben (BuP) a positive association is observed to overweight within the first eight years of life with a stronger trend in girls. Consistently, maternal BuP exposure of mice induces a higher food intake and weight gain in female offspring. The effect is accompanied by an epigenetic modification in the neuronal Pro-opiomelanocortin (POMC) enhancer 1 leading to a reduced hypothalamic POMC expression. Here we report that maternal paraben exposure may contribute to childhood overweight development by altered POMC-mediated neuronal appetite regulation.


Assuntos
Exposição Materna/efeitos adversos , Sobrepeso/etiologia , Parabenos/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/etiologia , Conservantes Farmacêuticos/efeitos adversos , Animais , Criança , Pré-Escolar , Ingestão de Alimentos , Feminino , Humanos , Hipotálamo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sobrepeso/genética , Sobrepeso/metabolismo , Sobrepeso/fisiopatologia , Parabenos/análise , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Conservantes Farmacêuticos/análise , Pró-Opiomelanocortina/genética , Pró-Opiomelanocortina/metabolismo , Urina/química , Ganho de Peso
16.
Int J Mol Sci ; 21(1)2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31948051

RESUMO

Posttraumatic stress disorder (PTSD) causes mental and somatic diseases. Intermittent hypoxic conditioning (IHC) has cardio-, vaso-, and neuroprotective effects and alleviates experimental PTSD. IHC's ability to alleviate harmful PTSD effects on rat heart, liver, and brain was examined. PTSD was induced by 10-day exposure to cat urine scent (PTSD rats). Some rats were then adapted to 14-day IHC (PTSD+IHC rats), while PTSD and untreated control rats were cage rested. PTSD rats had a higher anxiety index (AI, X-maze test), than control or PTSD+IHC rats. This higher AI was associated with reduced glycogen content and histological signs of metabolic and hypoxic damage and of impaired contractility. The livers of PTSD rats had reduced glycogen content. Liver and blood alanine and aspartate aminotransferase activities of PTSD rats were significantly increased. PTSD rats had increased norepinephrine concentration and decreased monoamine oxidase A activity in cerebral cortex. The PTSD-induced elevation of carbonylated proteins and lipid peroxidation products in these organs reflects oxidative stress, a known cause of organ pathology. IHC alleviated PTSD-induced metabolic and structural injury and reduced oxidative stress. Therefore, IHC is a promising preventive treatment for PTSD-related morphological and functional damage to organs, due, in part, to IHC's reduction of oxidative stress.


Assuntos
Estresse Oxidativo , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/terapia , Alanina Transaminase/metabolismo , Animais , Ansiedade/induzido quimicamente , Ansiedade/fisiopatologia , Aspartato Aminotransferases/metabolismo , Escala de Avaliação Comportamental , Encéfalo/metabolismo , Gatos , Córtex Cerebral/enzimologia , Córtex Cerebral/metabolismo , Modelos Animais de Doenças , Glicogênio/metabolismo , Hipóxia , Fígado/enzimologia , Fígado/metabolismo , Masculino , Aprendizagem em Labirinto , Monoaminoxidase/metabolismo , Miocárdio/citologia , Miocárdio/metabolismo , Miocárdio/patologia , Norepinefrina/metabolismo , Odorantes , Ratos , Ratos Wistar , Transtornos de Estresse Pós-Traumáticos/enzimologia , Transtornos de Estresse Pós-Traumáticos/metabolismo , Urina/química
18.
Sci Rep ; 10(1): 1242, 2020 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-31988353

RESUMO

The aim of this study was to establish a peptidomic profile based on LC-MS/MS and random forest (RF) algorithm to distinguish the urinary peptidomic scenario of type 2 diabetes mellitus (T2DM) patients with different stages of diabetic kidney disease (DKD). Urine from 60 T2DM patients was collected: 22 normal (stage A1), 18 moderately increased (stage A2) and 20 severely increased (stage A3) albuminuria. A total of 1080 naturally occurring peptides were detected, which resulted in the identification of a total of 100 proteins, irrespective of the patients' renal status. The classification accuracy showed that the most severe DKD (A3) presented a distinct urinary peptidomic pattern. Estimates for peptide importance assessed during RF model training included multiple fragments of collagen and alpha-1 antitrypsin, previously associated to DKD. Proteasix tool predicted 48 proteases potentially involved in the generation of the 60 most important peptides identified in the urine of DM patients, including metallopeptidases, cathepsins, and calpains. Collectively, our study lightened some biomarkers possibly involved in the pathogenic mechanisms of DKD, suggesting that peptidomics is a valuable tool for identifying the molecular mechanisms underpinning the disease and thus novel therapeutic targets.


Assuntos
Nefropatias Diabéticas/diagnóstico , Peptídeos/análise , Peptídeos/urina , Idoso , Algoritmos , Biomarcadores/urina , Cromatografia Líquida/métodos , Biologia Computacional/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteoma/análise , Espectrometria de Massas em Tandem/métodos , Urina/química
19.
Res Vet Sci ; 129: 39-52, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31931262

RESUMO

The objective of this study was to determine urinary metabotypes of dairy cows prior to, during, and after diagnosis of subclinical mastitis (SCM). Twenty controls (CON) and 6 cows with SCM were included in the study. DI/LC-MS/MS was used to measure 186 metabolites in the urine at -8 and - 4 wks prepartum, disease diagnosis, and at +4 and + 8 wks postpartum. Results showed a total of 24 and 27 metabolites that differentiated SCM and CON cows at -8 and - 4 wks, respectively, with 5 top metabolites having an accuracy to predict SCM of 1.0, for both time point. Altered metabolites included several acylcarnitines (ACs), phosphatidylcholines (PCs), amino acids (AAs), and biogenic amines (BAs). During SCM diagnosis week there were a total of 22 metabolites that differentiated the SCM and CON cows including 13 ACs, 5 AAs, hexose, and phosphatidylethanolamine ae C44:3. The top 5 metabolites Symmetric dimethylarginine (SDMA), methylglutarylcarnitine, dodecanoylcarnitine, phosphatidylethanolamine ae C42:1, and phosphatidylethanolamine ae C42:0 showed an AUC of 1.0. Metabolite alterations continued at +4 and + 8 wks postpartum with 13 (9 ACs, 3 glycerophospholipids, and 1 BA) and 28 metabolites (14 ACs, 2 glycerophospholipids, hexose, 8 AAs, and 2 BAs) that differentiated the two groups, respectively. The top 5 most important metabolites, for both time points, showed AUCs of 1.0. Results of this study showed that typical urinary metabotypes preceded SCM event starting from -8 and - 4 wks prepartum. Metabotypes typical of SCM continued to be present during the week of SCM and at +4 and + 8 wks postpartum. These data show that the urine of dairy cows can be used with very high accuracy for screening dairy cows for susceptibility to SCM prior to entering into the dry off period and a potential new pen-side test can help dairy producers and veterinarians to make selective treatments.


Assuntos
Biomarcadores/urina , Mastite Bovina/diagnóstico , Metaboloma , Urina/química , Animais , Infecções Assintomáticas , Bovinos , Cromatografia Líquida/veterinária , Feminino , Espectrometria de Massas em Tandem/veterinária
20.
Toxicology ; 431: 152366, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31926187

RESUMO

Kidney injury is a major adverse effect of cisplatin use. Metabolomics has been used to characterize physiological or pathological conditions through identification of metabolites and characterization of the metabolic pathway. Metabolomics profiling could allow for identification of nephrotoxic mechanisms of cisplatin and identification of biomarkers of cisplatin-induced injury. In this study, we performed metabolomics analysis to characterize key changes in metabolite levels during cisplatin-induced acute kidney injury (AKI) in rats, and screened for sensitive biomarkers for early diagnosis using HPLC-TOF/MS. Rats were intraperitoneally injected with 7.5 mg/kg or 15 mg/kg of cisplatin, or normal saline, and 12 h urine and kidney samples were collected after 72 h. Serum biochemical parameters and kidney histological evaluations showed dose-dependent AKI in response to cisplatin. Metabolomics analysis showed that 37 and 35 endogenous metabolite levels changed in rat urine and kidneys, respectively. Seven key metabolic pathways were disrupted, including the tricarboxylic acid cycle (TCA cycle), phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, glycerophospholipid metabolism, taurine and hypotaurine metabolism, d-glutamine and d-glutamate metabolism, and nicotinate and nicotinamide metabolism. These pathways are involved in energy generation, and amino acid and lipid metabolism, and disruption of these pathways could contribute to oxidative stress injury, inflammation, and cell membrane damage. Furthermore, 11 sensitive metabolites in urine were screened as potential biomarkers of AKI. To validate these biomarkers, we quantified 4 off these biomarkers, and confirmed that levels of these metabolites were altered in urine of rats treated with CDDP.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/metabolismo , Antineoplásicos/toxicidade , Cisplatino/toxicidade , Metabolômica , Animais , Biomarcadores/urina , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Metabolismo dos Lipídeos , Masculino , Espectrometria de Massas , Redes e Vias Metabólicas/efeitos dos fármacos , Controle de Qualidade , Ratos , Ratos Sprague-Dawley , Urina/química
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