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1.
Ann Lab Med ; 42(2): 178-187, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34635611

RESUMO

Background: Urine tissue inhibitor of metalloproteinases-2/insulin-like growth factor-binding protein 7 (TIMP-2/IGFBP7) (NephroCheck, Ortho Clinical Diagnostics, Raritan, NJ, USA) is a US Food and Drug Administration-approved biomarker for risk assessment of acute kidney injury (AKI) in critically ill adult patients in intensive care units; however, its clinical impact in the emergency department (ED) remains unproven. We evaluated the utility of NephroCheck for predicting AKI development and short-term mortality in the ED. Methods: This was a prospective, observational, five-center international study. We consecutively enrolled ED patients admitted with ≥30% risk of AKI development (assessed by ED physician: ED score) or acute diseases. Serum creatinine was tested on ED arrival (T0), day 1, and day 2 (T48); urine for NephroCheck was collected at T0 and T48. We performed ROC curve and reclassification analyses. Results: Among the 529 patients enrolled (213 females; median age, 65 years), AKI developed in 59 (11.2%) patients. The T0 NephroCheck value was higher in the AKI group than in the non-AKI group (median 0.77 vs. 0.29 (ng/m)2/1,000, P=0.001), and better predicted AKI development than the ED score (area under the curve [AUC], 0.64 vs. 0.53; P=0.04). In reclassification analyses, adding NephroCheck to the ED score improved the prediction of AKI development (P<0.05). The T0 NephroCheck value predicted 30-day mortality (AUC, 0.68; P<0.001). Conclusions: NephroCheck can predict both AKI development and short-term mortality in at-risk ED patients. NephroCheck would be a useful biomarker for early ruling-in or ruling-out of AKI in the ED.


Assuntos
Injúria Renal Aguda , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/urina , Inibidor Tecidual de Metaloproteinase-2 , Doença Aguda , Injúria Renal Aguda/diagnóstico , Idoso , Biomarcadores , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Estudos Prospectivos , Inibidor Tecidual de Metaloproteinase-2/urina , Estados Unidos
2.
Sci Rep ; 11(1): 19675, 2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34608231

RESUMO

Kidney function is affected in COVID-19, while kidney itself modulates the immune response. Here, hypothesize if COVID-19 urine biomarkers level can assess immune activation vs. clinical trajectory. Considering the kidney's critical role in modulating the immune response, we sought to analyze activation markers in patients with pre-existing dysfunction. This was a cross-sectional study of 68 patients. Blood and urine were collected within 48 h of hospital admission (H1), followed by 96 h (H2), seven days (H3), and up to 25 days (H4) from admission. Serum level ferritin, procalcitonin, IL-6 assessed immune activation overall, while the response to viral burden was gauged with serum level of spike protein and αspike IgM and IgG. 39 markers correlated highly between urine and blood. Age and race, and to a lesser extend gender, differentiated several urine markers. The burden of pre-existing conditions correlated with urine DCN, CAIX and PTN, but inversely with IL-5 or MCP-4. Higher urinary IL-12 and lower CAIX, CCL23, IL-15, IL-18, MCP-1, MCP-3, MUC-16, PD-L1, TNFRS12A, and TNFRS21 signified non-survivors. APACHE correlated with urine TNFRS12, PGF, CAIX, DCN, CXCL6, and EGF. Admission urine LAG-3 and IL-2 predicted death. Pre-existing kidney disease had a unique pattern of urinary inflammatory markers. Acute kidney injury was associated, and to a certain degree, predicted by IFNg, TWEAK, MMP7, and MUC-16. Remdesavir had a more profound effect on the urine biomarkers than steroids. Urinary biomarkers correlated with clinical status, kidney function, markers of the immune system activation, and probability of demise in COVID-19.


Assuntos
Injúria Renal Aguda/patologia , Biomarcadores/urina , COVID-19/imunologia , Insuficiência Renal Crônica/patologia , Injúria Renal Aguda/complicações , Adulto , Idoso , Antígenos CD/urina , Biomarcadores/sangue , Antígeno Ca-125/urina , COVID-19/mortalidade , COVID-19/patologia , COVID-19/virologia , Quimiocinas CC/sangue , Estudos Transversais , Feminino , Humanos , Interleucina-12/urina , Interleucina-6/sangue , Masculino , Proteínas de Membrana/urina , Pessoa de Meia-Idade , Pró-Calcitonina/sangue , Insuficiência Renal Crônica/complicações , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/metabolismo , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/sangue
3.
J Med Microbiol ; 70(10)2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34596013

RESUMO

Introduction. Pseudomonas aeruginosa produces quorum sensing signalling molecules including 2-alkyl-4-quinolones (AQs), which regulate virulence factor production in the cystic fibrosis (CF) airways.Hypothesis/Gap statement. Culture can lead to condition-dependent artefacts which may limit the potential insights and applications of AQs as minimally-invasive biomarkers of bacterial load.Aim. We aimed to use culture-independent methods to explore the correlations between AQ levels and live P. aeruginosa load in adults with CF.Methodology. Seventy-five sputum samples at clinical stability and 48 paired sputum samples obtained at the beginning and end of IV antibiotics for a pulmonary exacerbation in adults with CF were processed using a viable cell separation technique followed by quantitative P. aeruginosa polymerase chain reaction (qPCR). Live P. aeruginosa qPCR load was compared with the concentrations of three AQs (HHQ, NHQ and HQNO) detected in sputum, plasma and urine.Results. At clinical stability and the beginning of IV antibiotics for pulmonary exacerbation, HHQ, NHQ and HQNO measured in sputum, plasma and urine were consistently positively correlated with live P. aeruginosa qPCR load in sputum, compared to culture. Following systemic antibiotics live P. aeruginosa qPCR load decreased significantly (P<0.001) and was correlated with a reduction in plasma NHQ (plasma: r=0.463, P=0.003).Conclusion. In adults with CF, AQ concentrations correlated more strongly with live P. aeruginosa bacterial load measured by qPCR compared to traditional culture. Prospective studies are required to assess the potential of systemic AQs as biomarkers of P. aeruginosa bacterial burden.


Assuntos
4-Quinolonas/isolamento & purificação , Fibrose Cística/complicações , Infecções por Pseudomonas/complicações , Pseudomonas aeruginosa/isolamento & purificação , Percepção de Quorum , 4-Quinolonas/sangue , 4-Quinolonas/urina , Adolescente , Adulto , Carga Bacteriana , Biomarcadores , Fibrose Cística/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Pseudomonas/microbiologia , Reação em Cadeia da Polimerase em Tempo Real , Escarro/química , Adulto Jovem
4.
Tidsskr Nor Laegeforen ; 1412021 09 28.
Artigo em Inglês, Norueguês | MEDLINE | ID: mdl-34597008

RESUMO

BACKGROUND: Trimethylaminuria is a rare disorder characterised by foul odour from bodily fluids and breath. The condition is caused by a homozygous mutation in the FMO3 (flavin monooxygenase 3) gene coding for the enzyme that converts TMA (trimethylamine) to trimethylamine N-oxide. The result is elevated levels of secreted trimethylamine, which has a strong odour. The condition is likely to affect mental, emotional and social health. The diagnosis is reached by testing of free TMA (trimethylamine) and percentage N-oxidation in urine samples or by genetic testing. CASE PRESENTATION: A man in his fifties had from childhood occasionally been told that his breath resembled rotten fish. He had searched for a diagnosis on the internet and was referred to testing for trimethylaminuria, and the diagnosis was confirmed. INTERPRETATION: Urine test samples with high levels of free TMA and subnormal percentage of trimethylamine N-oxide revealed the diagnosis of trimethylaminuria. There is no causal treatment. Patients are advised to avoid choline-rich foods and take hygienic measures.


Assuntos
Erros Inatos do Metabolismo , Oxigenases , Animais , Criança , Peixes , Humanos , Masculino , Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo/genética , Metilaminas/urina , Mutação , Oxigenases/genética
5.
Sci Rep ; 11(1): 19193, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34584117

RESUMO

Outside of the ongoing COVID-19 pandemic, tuberculosis is the leading cause of infectious disease mortality globally. Currently, there is no commercially available point-of-care diagnostic that is rapid, inexpensive, and highly sensitive for the diagnosis of active tuberculosis disease. Here we describe the development and optimization of a novel, highly sensitive prototype bioelectronic tuberculosis antigen (BETA) assay to detect tuberculosis-specific antigen, CFP10, in small-volume serum and urine samples. In this proof-of-concept study we evaluated the performance of the BETA assay using clinical specimens collected from presumptive tuberculosis patients from three independent cohorts. Circulating CFP10 antigen was detected in ALL serum (n = 19) and urine (n = 3) samples from bacteriologically confirmed tuberculosis patients who were untreated or had less than one week of treatment at time of serum collection, successfully identifying all culture positive tuberculosis patients. No CFP10 antigen was detected in serum (n = 7) or urine (n = 6) samples from individuals who were determined to be negative for tuberculosis disease. Additionally, antigen quantification using the BETA assay of paired serum samples collected from tuberculosis patients (n = 8) both before and after treatment initiation, indicate consistently declining within-person levels of CFP10 antigen during treatment. This novel, low-cost assay demonstrates potential as a rapid, non-sputum-based, point-of-care tool for the diagnosis of tuberculosis disease.


Assuntos
Testes Diagnósticos de Rotina/métodos , Fragmentos de Peptídeos , Tuberculose/diagnóstico , Antígenos de Bactérias/sangue , Antígenos de Bactérias/isolamento & purificação , Antígenos de Bactérias/urina , Mycobacterium tuberculosis/imunologia , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/isolamento & purificação , Fragmentos de Peptídeos/urina , Sensibilidade e Especificidade , Tuberculose Pulmonar/diagnóstico
6.
BMC Nephrol ; 22(1): 323, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34579670

RESUMO

BACKGROUND: This is a case report of an asymptomatic SARS-CoV-2 infection associated with new-onset nephrotic syndrome in a pediatric patient. This is the third case of new-onset nephrotic syndrome in children associated with SARS-CoV-2 infection, but is the first case report describing a new-onset nephrotic syndrome presentation in a patient who had asymptomatic COVID-19 infection. CASE PRESENTATION: This is a case of a previously healthy 5 year old female who presented with new-onset nephrotic syndrome in the setting of an asymptomatic COVID-19 infection. She presented with progressive edema, and laboratory findings were significant for proteinuria and hypercholesterolemia. She was treated with albumin, diuretics, and corticosteroid therapy, and achieved clinical remission of her nephrotic syndrome within 3 weeks of treatment. Though she was at risk of hypercoagulability due to her COVID-19 infection and nephrotic syndrome, she was not treated with anticoagulation, and did not develop any thrombotic events. CONCLUSIONS: Our case report indicates that SARS-CoV-2 infection could be a trigger for nephrotic syndrome, even in the absence of overt COVID-19 symptoms.


Assuntos
Infecções Assintomáticas , COVID-19 , Síndrome Nefrótica , Administração dos Cuidados ao Paciente/métodos , Indução de Remissão/métodos , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/fisiopatologia , Pré-Escolar , Edema/diagnóstico , Edema/etiologia , Feminino , Humanos , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/etiologia , Síndrome Nefrótica/sangue , Síndrome Nefrótica/etiologia , Síndrome Nefrótica/terapia , Síndrome Nefrótica/urina , Proteinúria/diagnóstico , Proteinúria/etiologia , SARS-CoV-2/isolamento & purificação , Resultado do Tratamento
7.
J Assoc Physicians India ; 69(6): 11-12, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34472785

RESUMO

BACKGROUND: The development of diabetic nephropathy demands an early detection aiming to decrease the incidence of end stage renal incidence. Podocyte injury is an essential element in the diabetic renal disease occurrence and progression. We attempted to identify podocyte markers in the urine of patients with and without overt diabetic nephropathy, in comparison with controls to diagnose early podocyte injury. METHODS: The study included Type 2 Diabetic individuals with 45 of them having normoalbuminuria, 40 patients with microalbuminuria and 40 of them with macroalbuminuria (based on the albumin-creatinine ratio - ACR) and 45 non diabetic healthy controls from a medical college hospital from South India. Urinary podocin quantification was done among all these patients and compared among the different groups of study, along with other parameters. RESULTS: The fasting blood sugar, post prandial sugar, glycosylated haemoglobin, triglyceride levels and the duration of diabetes along with systolic and diastolic blood pressure, body mass index, all seemed to be strong risk factors for the diabetic kidney disease progression showing a significant correlation with microalbumin, glomerular filtration rate and urine albumin-creatinine ratio. Podocin was excreted in the urine at higher concentrations among patients with ACR less than 30, ACR 30-299 and ACR more than 300 compared to healthy controls respectively (p < 0.001). The glomerular filtration rate showed significant negative correlation with the levels of podocin excreted in urine whereas urinary podocin positively correlated with the fasting blood sugar, post prandial sugar, glycosylated haemoglobin, triglyceride levels and the duration of diabetes along with systolic and diastolic blood pressure, body mass index, microalbumin and urine albumin-creatinine ratio. CONCLUSION: The urinary podocin can serve as an early marker for diabetic nephropathy as well as a marker of disease progression and severity among the patients with Type 2 Diabetes. The standard risk factors have to be identified early and controlled inorder to slow down the progression of diabetic kidney disease.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Proteínas de Membrana , Albuminúria/etiologia , Biomarcadores , Creatinina , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/epidemiologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Rim , Proteínas de Membrana/urina , Prognóstico , Fatores de Risco
8.
Eur J Endocrinol ; 185(5): 729-741, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34524979

RESUMO

Context: 17α-Hydroxylase/17,20-lyase deficiency (17OHD) caused by mutations in the CYP17A1 gene is a rare form of congenital adrenal hyperplasia typically characterised by cortisol deficiency, mineralocorticoid excess and sex steroid deficiency. Objective: To examine the phenotypic spectrum of 17OHD by clinical and biochemical assessment and corresponding in silico and in vitro functional analysis. Design: Case series. Patients and results: We assessed eight patients with 17OHD, including four with extreme 17OHD phenotypes: two siblings presented with failure to thrive in early infancy and two with isolated sex steroid deficiency and normal cortisol reserve. Diagnosis was established by mass spectrometry-based urinary steroid profiling and confirmed by genetic CYP17A1 analysis, revealing homozygous and compound heterozygous sequence variants. We found novel (p.Gly111Val, p.Ala398Glu, p.Ile371Thr) and previously described sequence variants (p.Pro409Leu, p.Arg347His, p.Gly436Arg, p.Phe53/54del, p.Tyr60IlefsLys88X). In vitro functional studies employing an overexpression system in HEK293 cells showed that 17,20-lyase activity was invariably decreased while mutant 17α-hydroxylase activity retained up to 14% of WT activity in the two patients with intact cortisol reserve. A ratio of urinary corticosterone over cortisol metabolites reflective of 17α-hydroxylase activity correlated well with clinical phenotype severity. Conclusion: Our findings illustrate the broad phenotypic spectrum of 17OHD. Isolated sex steroid deficiency with normal stimulated cortisol has not been reported before. Attenuation of 17α-hydroxylase activity is readily detected by urinary steroid profiling and predicts phenotype severity. Significance statement: Here we report, supported by careful phenotyping, genotyping and functional analysis, a prismatic case series of patients with congenital adrenal hyperplasia due to 17α-hydroxylase (CYP17A1) deficiency (17OHD). These range in severity from the abolition of function, presenting in early infancy, and unusually mild with isolated sex steroid deficiency but normal ACTH-stimulated cortisol in adult patients. These findings will guide improved diagnostic detection of CYP17A1 deficiency.


Assuntos
Esteroide 17-alfa-Hidroxilase/genética , Adolescente , Hiperplasia Suprarrenal Congênita/genética , Amenorreia/genética , Simulação por Computador , Corticosterona/urina , Insuficiência de Crescimento/enzimologia , Insuficiência de Crescimento/genética , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Hormônios Esteroides Gonadais/deficiência , Ginecomastia/etiologia , Ginecomastia/genética , Células HEK293 , Humanos , Hidrocortisona/deficiência , Lactente , Recém-Nascido , Masculino , Mineralocorticoides/metabolismo , Mutação/genética , Fenótipo , Esteroides/urina , Adulto Jovem
9.
Int J Mol Sci ; 22(18)2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34576312

RESUMO

Ehlers-Danlos syndromes (EDS) are an inherited heterogeneous group of connective tissue disorders characterized by an abnormal collagen synthesis affecting skin, ligaments, joints, blood vessels, and other organs. It is one of the oldest known causes of bruising and bleeding, and it was described first by Hippocrates in 400 BC. In the last years, multiple gene variants involved in the pathogenesis of specific EDS subtypes have been identified; moreover, new clinical diagnostic criteria have been established. New classification models have also been studied in order to differentiate overlapping conditions. Moreover, EDS shares many characteristics with other similar disorders. Although distinguishing between these seemingly identical conditions is difficult, it is essential in ensuring proper patient care. Currently, there are many genetic and molecular studies underway to clarify the etiology of some variants of EDS. However, the genetic basis of the hypermobile type of EDS (hEDS) is still unknown. In this review, we focused on the study of two of the most common forms of EDS-classic and hypermobile-by trying to identify possible biomarkers that could be of great help to confirm patients' diagnosis and their follow up.


Assuntos
Síndrome de Ehlers-Danlos/diagnóstico , Biomarcadores/sangue , Biomarcadores/metabolismo , Biomarcadores/urina , Tecido Conjuntivo/metabolismo , Tecido Conjuntivo/patologia , Síndrome de Ehlers-Danlos/genética , Síndrome de Ehlers-Danlos/metabolismo , Predisposição Genética para Doença , Humanos
11.
An Pediatr (Engl Ed) ; 95(3): 139-146, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34507648

RESUMO

INTRODUCTION: Aggressive parenteral nutrition with delivery of high amino acid and energy doses is used to improve growth and neurodevelopmental outcomes in very low birth weight (VLBW) preterm infants. Recent findings, however, suggest that this approach may cause electrolyte imbalances. The aim of our study was to compare the prevalence of hypercalcaemia, hypophosphataemia, and hypokalaemia in 2 groups of preterm infants that received parenteral nutrition with different amounts of amino acids and to analyse perinatal and nutritional variables associated with the development of electrolyte imbalances. METHODS: We conducted a retrospective observational study comparing 2 groups of preterm infants born before 33 weeks' gestation with birth weights of less than 1500 g managed with parenteral nutrition. One of the groups received less than 3 g/kg/day of amino acids and the other received 3 g/kg//day of amino acids or more. We analysed the prevalence of electrolyte imbalances and possible associations with aggressive parenteral nutrition, adjusting for potential confounders. RESULTS: We studied 114 infants: 60 given less than 3 g/kg/day of amino acids (low-intake group) and 54 given at least 3 g/kg/day (high-intake group). The prevalence of electrolyte imbalances was similar in both groups. The prevalence of hypercalcaemia was 1.67% in the low-intake group and 1.85% in the high-intake group (P > .99), the prevalence of severe hypophosphataemia 11.7% vs 9.3%, and the prevalence of hypokalaemia 15.0% vs 11.1% (P > .99). A calcium to phosphorus ratio greater than 1.05 had a protective effect against hypophosphataemia (P = .007). CONCLUSIONS: We did not find an association between hypercalcaemia, hypophosphataemia, and hypokalaemia and the amino acid dose delivered by PN in the high-intake group of preterm infants.


Assuntos
Recém-Nascido Prematuro , Nutrição Parenteral/efeitos adversos , Eletrólitos/sangue , Eletrólitos/urina , Feminino , Humanos , Hipercalcemia/sangue , Hipercalcemia/epidemiologia , Hipofosfatemia/epidemiologia , Incidência , Lactente , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Gravidez , Síndrome da Realimentação , Estudos Retrospectivos
12.
Int Heart J ; 62(5): 1057-1061, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34544990

RESUMO

Tolvaptan, a vasopressin type-2 receptor antagonist, is utilized to ameliorate fluid retention following cardiac surgery. However, the optimal timing of tolvaptan administration considering novel biomarkers remains unknown. We prospectively included patients who underwent cardiac surgery between 2016 and 2020. We measured perioperative trends of free water reabsorption mediators including plasma arginine vasopressin and urine aquaporin-2. A total of 20 patients (68 [60, 75] years old, 18 men) were included. Urine volume decreased gradually after the initial 3 hours following cardiac surgery. The plasma arginine vasopressin level increased significantly with a peak at postoperative 6 hours, whereas the urine aquaporin-2 level increased later with a delayed peak at postoperative 12 hours. As a result, urine aquaporin-2 relative to the plasma arginine vasopressin level, which represents the activity of the collecting ducts and indicates predicted responses to tolvaptan, was a minimum at postoperative 6 hours. Tolvaptan administration immediately after cardiac surgery might not be recommended given the transient refractoriness to tolvaptan probably due to the stunning of kidney collecting ducts.


Assuntos
Aquaporina 2/urina , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Insuficiência Cardíaca/tratamento farmacológico , Rim/efeitos dos fármacos , Vasopressinas/sangue , Idoso , Antagonistas dos Receptores de Hormônios Antidiuréticos/administração & dosagem , Antagonistas dos Receptores de Hormônios Antidiuréticos/uso terapêutico , Arginina Vasopressina/sangue , Biomarcadores/sangue , Biomarcadores/urina , Líquidos Corporais/efeitos dos fármacos , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Humanos , Rim/metabolismo , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios/normas , Cuidados Pós-Operatórios/estatística & dados numéricos , Estudos Prospectivos , Tolvaptan/administração & dosagem , Tolvaptan/uso terapêutico
13.
Investig Clin Urol ; 62(5): 500-519, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34488250

RESUMO

Molecular markers detected in urine may improve our understanding of the evolution of bladder cancer (BCa) and its micro- and macroenvironment. Detection of such markers will identify disease earlier, allow stratification of patients according to risk, and improve prognostication and prediction of outcomes, thereby facilitating targeted therapy. However, current guidelines have yet to embrace such markers for routine management of BCa, and most research studies have focused on urine-based tumor markers. In this review, we summarize known urinary biomarkers for BCa and highlight newly identified molecules. We then discuss the challenges that must be overcome to incorporate these markers into clinical care.


Assuntos
COVID-19/epidemiologia , Neoplasias da Bexiga Urinária/urina , Biomarcadores Tumorais/urina , Humanos , Kit de Reagentes para Diagnóstico , Neoplasias da Bexiga Urinária/diagnóstico
14.
Nat Commun ; 12(1): 5671, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34580290

RESUMO

Primary cilia are microtubule based sensory organelles important for receiving and processing cellular signals. Recent studies have shown that cilia also release extracellular vesicles (EVs). Because EVs have been shown to exert various physiological functions, these findings have the potential to alter our understanding of how primary cilia regulate specific signalling pathways. So far the focus has been on lgEVs budding directly from the ciliary membrane. An association between cilia and MVB-derived smEVs has not yet been described. We show that ciliary mutant mammalian cells demonstrate increased secretion of small EVs (smEVs) and a change in EV composition. Characterisation of smEV cargo identified signalling molecules that are differentially loaded upon ciliary dysfunction. Furthermore, we show that these smEVs are biologically active and modulate the WNT response in recipient cells. These results provide us with insights into smEV-dependent ciliary signalling mechanisms which might underly ciliopathy disease pathogenesis.


Assuntos
Síndrome de Bardet-Biedl/patologia , Proteínas de Transporte/metabolismo , Cílios/patologia , Vesículas Extracelulares/metabolismo , Animais , Síndrome de Bardet-Biedl/urina , Proteínas de Transporte/genética , Cílios/metabolismo , Células Epiteliais , Técnicas de Inativação de Genes , Células HEK293 , Humanos , Rim/citologia , Rim/patologia , Camundongos , Cultura Primária de Células , Via de Sinalização Wnt
15.
J Chromatogr A ; 1653: 462422, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34348207

RESUMO

Gastric carcinoma is one of the most common and deadly forms of cancer. Early detection is critical for successful treatment of gastric cancer, and examination of BAs in urine may provide a critical diagnostic tool for identifying gastric cancer at stages when it can still be cured. Bile acids (BAs) are a crucial toxic factor correlated with the injury of gastric mucosa and as such, quantifying the amount of BA in patient's urine could provide a new means to quickly and non-invasively identify the presence of gastric cancer in the early stages. Here, a covalent organic framework (COF) material synthesized on the basis of 1,3,5-tris(4-nitrophenyl)benzene (TAPB) and pyromellitic dianhydride (PMDA) was used as stationary phase for SPE column that was coupled to LC-MS/MS for quantitative analysis of eight BAs in human urine, including cholic acid (CA), deoxycholic acid (DCA), glycochenodeoxycholic acid (GCDCA), glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), lithocholic acid (LCA), hyodeoxycholic acid (HDCA), and chenodeoxycholic acid (CDCA). The enrichment effect of synthesized COF material was better than commercial SPE and HLB column. The sensitivity can increase 9.37- to 54.30- fold (calculated by the ratio of peak area between before and after enrichment). The probable mechanism is due to the great porosity and the similar polarity with BAs of the COF material. By compared with previous literatures, our method had the minimum limit of detection, which achieved 46.40, 25.75, 47.40, 47.37, 30.42, and 33.92 pg /mL, respectively, for GCA, GCDCA, CA, CDCA, HDCA and DCA after enrichment. These eight BAs also accomplished excellent linearity from 0.34 to 10,000 ng/mL. This material was successfully applied in the measurements of these six BAs in human urine from 76 gastric cancer patients and 32 healthy people. Compared to healthy people, levels of CA, CDCA, DCA, and HDCA were significantly elevated and levels of GCDCA were depressed, respectively, in gastric cancer patients. Our work suggests that these acids may act as potential biomarkers for gastric cancer and our framework provides a method for "non-invasive" diagnosis of gastric cancer.


Assuntos
Ácidos e Sais Biliares , Cromatografia Líquida , Neoplasias Gástricas , Espectrometria de Massas em Tandem , Ácidos e Sais Biliares/urina , Humanos , Neoplasias Gástricas/urina , Urinálise
16.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34360940

RESUMO

With iron at its core, the tetrapyrrole heme ring is a cardinal prosthetic group made up of many proteins that participate in a wide array of cellular functions and metabolism. Once released, due to its pro-oxidant properties, free heme in sufficient amounts can result in injurious effects to the kidney and other organs. Heme oxygenase-1 (HO-1) has evolved to promptly attend to such injurious potential by facilitating degradation of heme into equimolar amounts of carbon monoxide, iron, and biliverdin. HO-1 induction is a beneficial response to tissue injury in diverse animal models of diseases, including those that affect the kidney. These protective attributes are mainly due to: (i) prompt degradation of heme leading to restraining potential hazardous effects of free heme, and (ii) generation of byproducts that along with induction of ferritin have proven beneficial in a number of pathological conditions. This review will focus on describing clinical aspects of some of the conditions with the unifying end-result of increased heme burden and will discuss the molecular mechanisms that ensue to protect the kidneys.


Assuntos
Heme/metabolismo , Hemoglobinúria/metabolismo , Nefropatias/metabolismo , Rabdomiólise/metabolismo , Animais , Ferritinas/metabolismo , Heme/urina , Heme Oxigenase-1/metabolismo , Hemoglobinúria/patologia , Humanos , Nefropatias/patologia , Rabdomiólise/patologia
17.
Nutrients ; 13(8)2021 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-34445043

RESUMO

Postmenopausal women are at higher risk of developing cardiovascular diseases due to changes in lipid profile and body fat, among others. The aim of this study was to evaluate the association of urinary tartaric acid, a biomarker of wine consumption, with anthropometric (weight, waist circumference, body mass index (BMI), and waist-to-height ratio), blood pressure, and biochemical variables (blood glucose and lipid profile) that may be affected during the menopausal transition. This sub-study of the PREDIMED (Prevención con Dieta Mediterránea) trial included a sample of 230 women aged 60-80 years with high cardiovascular risk at baseline. Urine samples were diluted and filtered, and tartaric acid was analyzed by liquid chromatography coupled to electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Correlations between tartaric acid and the study variables were adjusted for age, education level, smoking status, physical activity, BMI, cholesterol-lowering, antihypertensive, and insulin treatment, total energy intake, and consumption of fruits, vegetables, and raisins. A strong association was observed between wine consumption and urinary tartaric acid (0.01 µg/mg (95% confidence interval (CI): 0.01, 0.01), p-value < 0.001). Total and low-density lipoprotein (LDL) cholesterol were inversely correlated with urinary tartaric acid (-3.13 µg/mg (-5.54, -0.71), p-value = 0.016 and -3.03 µg/mg (-5.62, -0.42), p-value = 0.027, respectively), whereas other biochemical and anthropometric variables were unrelated. The results suggest that wine consumption may have a positive effect on cardiovascular health in postmenopausal women, underpinning its nutraceutical properties.


Assuntos
Consumo de Bebidas Alcoólicas/urina , LDL-Colesterol/sangue , Colesterol/sangue , Tartaratos/urina , Vinho , Idoso , Idoso de 80 Anos ou mais , Antropometria , Biomarcadores/sangue , Biomarcadores/urina , Doenças Cardiovasculares/prevenção & controle , Estudos Transversais , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
Ann Clin Lab Sci ; 51(4): 503-511, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34452888

RESUMO

OBJECTIVE: To compare the e!cacy and functional outcomes of dl-3-n-Butylphthalide (NBP) and human urinary kallidinogenase (HUK) on ischemic stroke patients and to determine their effects on serum tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factor (VEGF). METHODS: A prospective study was conducted on 57 ischemic stroke patients. Functional outcomes were assessed by the National Institute Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), and the activities of daily living score (ADL), whereas TNF-α and VEGF expressions were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: TNF-α was significantly down-regulated in the NBP group and upregulated in the control group two weeks after treatment (p=0.017 and p=0.047, respectively). A significant difference in VEGF expressions was observed between the two groups (330.25±120.64 vs. 437.15±137.68, p=0.041) two weeks after treatment. Both groups showed significant improvement in NIHSS and ADL scores three months after treatment (p<0.001), with the NBP group exhibiting improvement in NIHSS scores as early as two weeks after treatment (p=0.008). The three-month NIHSS scores of the two groups were significantly lower than those of the control group (p=0.010 and p=0.008, respectively). Both the NBP and HUK groups showed a significant decline in mRS scores two weeks and three months after treatment (p<0.05). CONCLUSIONS: Both treatments are effective and can significantly promote recovery in stroke patients. Additionally, both options have similar effects in promoting long-term recovery, with NBP exerting a greater impact on serum VEGF and TNF-α expressions.


Assuntos
Benzofuranos/uso terapêutico , Biomarcadores/sangue , Isquemia Encefálica/patologia , AVC Isquêmico/patologia , Calicreínas/administração & dosagem , Fator de Necrose Tumoral alfa/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/sangue , Isquemia Encefálica/terapia , Estudos de Casos e Controles , Feminino , Humanos , AVC Isquêmico/sangue , AVC Isquêmico/terapia , Calicreínas/urina , Masculino , Pessoa de Meia-Idade , Fármacos Neuroprotetores/uso terapêutico , Prognóstico , Adulto Jovem
19.
Nutrients ; 13(8)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34444943

RESUMO

BACKGROUND: Micronutrient malnutrition is a form of undernutrition that causes diseases, and this is mainly due to insufficient intake of nutrients in daily foods. The status of micronutrients for people in Sudan remains scarce, and information is limited. The aim of this study is to highlight the status of micronutrients among women of reproductive age (15-49 years of age) and their children in Sudan. METHODS: This manuscript is a quantitative descriptive study, based on the data from Sudan Micronutrient Survey (SMS); it is part of the second round of the Simple Spatial Survey Method (S3M II) in Sudan (a total of 93,882 households). RESULTS: The level of consumption of vitamin A-rich foods was found to be moderate at 67.36% for reproductive-age women and low at 23.44% for under-five children. Similarly, consumption rate of vitamin B-rich foods among reproductive-age women was 62.13%, and low for children at 11.02%. The consumption of iron-, calcium-, and zinc-rich foods was moderate among women (66.75%, 47.69%, 69.72%, respectively) and very low in children (12.28%, 17.62%, 14.99%, respectively). The iron deficiency prevalence was 47% in non-pregnant women, 58% in pregnant women, and 54% in children. The prevalence of anemia was 30% in non-pregnant women, 37% in pregnant women, and 48% in children. Generally, urinary iodine concentration was inadequate in lactating and non-pregnant women as well as in pregnant women. Most indicators of micronutrients in Sudan for children and women of reproductive age were highly significant. Sudan needs more efforts to create an enabling environment through legislation, policies, and strategies to strengthen the nutrition-sensitive and specific interventions and improving status of micronutrients among women and children, focusing on food fortification, food supplements, and counseling on micronutrients intake for mothers during antenatal and postnatal services as well as raising community awareness.


Assuntos
Desnutrição/epidemiologia , Micronutrientes/deficiência , Estado Nutricional , Adolescente , Adulto , Anemia/epidemiologia , Anemia Ferropriva/epidemiologia , Pré-Escolar , Dieta/métodos , Suplementos Nutricionais , Feminino , Alimentos Fortificados , Humanos , Lactente , Ferro/administração & dosagem , Ferro/sangue , Masculino , Desnutrição/sangue , Desnutrição/urina , Pessoa de Meia-Idade , Gravidez , Reprodução , Sudão/epidemiologia , Inquéritos e Questionários , Vitamina A/administração & dosagem , Vitaminas/administração & dosagem , Vitaminas/sangue , Adulto Jovem , Zinco/administração & dosagem , Zinco/deficiência
20.
J Urol ; 206(4): 806-817, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34384237

RESUMO

PURPOSE: Benign prostatic hyperplasia (BPH) is a histologic diagnosis describing proliferation of smooth muscle and epithelial cells within the prostatic transition zone. The prevalence and severity of lower urinary tract symptoms (LUTS) in aging men are progressive and impact the health and welfare of society. This revised Guideline provides a useful reference on effective evidence-based management of male LUTS/BPH. See the accompanying algorithm for a summary of the procedures detailed in the Guideline (figures 1 and 2[Figure: see text][Figure: see text]). MATERIALS AND METHODS: The Minnesota Evidence Review Team searched Ovid MEDLINE, Embase, Cochrane Library, and AHRQ databases to identify eligible English language studies published between January 2008 and April 2019, then updated through December 2020. Search terms included Medical Subject Headings (MeSH) and keywords for pharmacological therapies, drug classes, and terms related to LUTS or BPH. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]). RESULTS: Nineteen guideline statements pertinent to evaluation, work-up, and medical management were developed. Appropriate levels of evidence and supporting text were created to direct both primary care and urologic providers towards streamlined and suitable practices. CONCLUSIONS: The work up and medical management of BPH requires attention to individual patient characteristics, while also respecting common principles. Clinicians should adhere to recommendations and familiarize themselves with standards of BPH management.


Assuntos
Sintomas do Trato Urinário Inferior/diagnóstico , Hiperplasia Prostática/diagnóstico , Urologia/normas , Suplementos Nutricionais , Humanos , Sintomas do Trato Urinário Inferior/etiologia , Sintomas do Trato Urinário Inferior/terapia , Sintomas do Trato Urinário Inferior/urina , Masculino , Próstata/patologia , Hiperplasia Prostática/complicações , Hiperplasia Prostática/patologia , Hiperplasia Prostática/terapia , Sociedades Médicas/normas , Estados Unidos , Agentes Urológicos/uso terapêutico , Urologia/métodos
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