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1.
Int J Med Microbiol ; 315: 151625, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38824713

RESUMO

OBJECTIVES: We report a case of bacteremia with pyelonephritis in an adult male with an underlying disease caused by α-hemolytic streptococci. α-Hemolytic streptococci were isolated from blood, but it was challenging to identify its species. This study aimed to characterize the causative bacterium SP4011 and to elucidate its species. METHODS: The whole-genome sequence and biochemical characteristics of SP4011 were determined. Based on the genome sequence, phylogenetic analysis was performed with standard strains of each species of α-hemolytic streptococci. Digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) values were calculated. RESULTS: SP4011 showed optochin susceptibility and bile solubility, but did not react with pneumococcal omni antiserum. Phylogenetic analysis of the whole-genome sequence showed that SP4011 clustered with S. pneumoniae and S. pseodopneumoniae and was most closely related to S. pseodopneumoniae. Genomic analysis revealed that ANI and dDDH values between SP4011 and S. pseodopneumoniae were 94.0 % and 56.0 %, respectively, and between SP4011 and S. pneumoniae were 93.3 % and 52.2 %, respectively. Biochemical characteristics also showed differences between SP4011 and S. pseodopneumoniae and between SP4011 and S. pneumoniae. These results indicate that SP4011 is a novel species. CONCLUSION: Our findings indicate that SP4011 is a novel species of the genus Streptococcus. SP4011 has biochemical characteristics similar to S. pneumoniae, making it challenging to differentiate and requiring careful clinical diagnosis. This isolate was proposed to be a novel species, Streptococcus parapneumoniae sp. nov. The strain type is SP4011T (= JCM 36068T = KCTC 21228T).


Assuntos
Bacteriemia , Filogenia , Pielonefrite , Infecções Estreptocócicas , Streptococcus , Humanos , Masculino , Infecções Estreptocócicas/microbiologia , Bacteriemia/microbiologia , Streptococcus/genética , Streptococcus/isolamento & purificação , Streptococcus/classificação , Pielonefrite/microbiologia , Genoma Bacteriano , DNA Bacteriano/genética , Sequenciamento Completo do Genoma , Antibacterianos/farmacologia , Hibridização de Ácido Nucleico , Técnicas de Tipagem Bacteriana , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade
2.
Clin Exp Nephrol ; 28(7): 608-616, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38400935

RESUMO

Since February, 2023, the omicron variant has accounted for essentially all new coronavirus infections in Japan. If future infections involve mutant strains with the same level of infectivity and virulence as omicron, the government's basic policy will be to prevent the spread of infection, without compromising socioeconomic activities. Objectives include protecting pregnant women and elderly persons, and focusing on citizens requiring hospitalization and those at risk of serious illness, without imposing new social restrictions. Although the government tries to raise public awareness through education, most people affected by COVID-19 stay at home, and by the time patients become aware of the seriousness of their disease, it has often reached moderate or higher severity. In this review, we discuss why this situation persists even though the disease seems to have become milder with the shift from the delta variant to omicron. We also propose a pathophysiological method to determine the risk of severe illness. This assessment can be made at home in the early stages of COVID-19 infection, using urine analysis. Applicability of this method to drug discovery and development is also discussed.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , COVID-19/epidemiologia , Medição de Risco , Oxigênio , Fatores de Risco , Urinálise
3.
BMC Nephrol ; 25(1): 275, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39192178

RESUMO

BACKGROUND: Cystinosis is a lysosomal storage disorder characterized by an autosomal recessive phenotype. Intermediate cystinosis, which progresses slowly and causes renal failure, accounts for approximately 5% of all cystinosis cases. Patients with intermediate cystinosis may not exhibit the typical symptoms of cystinosis, such as Fanconi syndrome and ocular symptoms. Because of its diverse clinical presentation and rarity, intermediate cystinosis can be difficult to diagnose. Additionally, few patients can tolerate cystine-depleting drugs, such as cysteamine, because of their complicated administration schedules and side effects. We report a case of intermediate cystinosis that was treated with cysteamine for 10 years. CASE PRESENTATION: Urinary abnormalities were first diagnosed when the patient was 3 years of age during a health examination specifically for 3-year-old children, which is unique to Japan. Cystinosis was diagnosed when the patient was 12 years of age. Cysteamine therapy was initiated and regular cystine concentration measurements were performed. Although proteinuria persisted, the patient's renal function progressed slowly. Two renal biopsies were performed, and multinucleated podocytes and cystine crystals without focal segmental glomerulosclerosis lesions were observed in the biopsy specimens. The patient's renal function remained stable. CONCLUSIONS: This case of intermediate cystinosis was treated with cysteamine over the course of 10 years. Intermediate cystinosis requires an appropriate diagnosis and long-term treatment.


Assuntos
Cisteamina , Eliminadores de Cistina , Cistinose , Humanos , Cisteamina/uso terapêutico , Cistinose/tratamento farmacológico , Cistinose/complicações , Eliminadores de Cistina/uso terapêutico , Masculino , Criança , Feminino , Resultado do Tratamento , Pré-Escolar
4.
Clin Exp Nephrol ; 25(7): 685-699, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33835326

RESUMO

Complex molecular cell dynamics in acute kidney injury and its heterogeneous etiologies in patient populations in clinical settings have revealed the potential advantages and disadvantages of emerging novel damage biomarkers. Imaging techniques have been developed over the past decade to further our understanding about diseased organs, including the kidneys. Understanding the compositional, structural, and functional changes in damaged kidneys via several imaging modalities would enable a more comprehensive analysis of acute kidney injury, including its risks, diagnosis, and prognosis. This review summarizes recent imaging studies for acute kidney injury and discusses their potential utility in clinical settings.


Assuntos
Injúria Renal Aguda/diagnóstico por imagem , Injúria Renal Aguda/etiologia , Humanos , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Ultrassonografia
5.
J Infect Chemother ; 27(7): 1043-1050, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33865699

RESUMO

INTRODUCTION: Most of the currently used prognostic models for COVID-19 are based on Western cohorts, but it is unknown whether any are applicable to patients with COVID-19 in Japan. METHODS: This retrospective cohort study included 160 patients with COVID-19 who were admitted to the National Center for Global Health and Medicine between January 26, 2020 and July 25, 2020. We searched PubMed for prognostic models for COVID-19. The predicted outcome was initiation of respiratory support or death. Performance of the candidate models was evaluated according to discrimination and calibration. We recalibrated the intercept of each model with our data. We also updated each model by adding ß2-microglobulin (ß2MG) to the model and recalculating the intercept and the coefficient of ß2MG. RESULTS: Mean patient age was 49.8 years, 68% were male, 88.7% were Japanese. The study outcomes occurred in 15 patients, including two deaths. Two-hundred sixty-nine papers were screened, and four candidate prognostic models were assessed. The model of Bartoletti et al. had the highest area under receiver operating characteristic curve (AUC) (0.88; 95% confidence interval 0.81-0.96). All four models overestimated the probability of occurrence of the outcome. None of the four models showed statistically significant improvement in AUCs by adding ß2MG. CONCLUSIONS: Our results suggest that the existing prediction models for COVID-19 overestimate the probability of occurrence of unfavorable outcomes in a Japanese cohort. When applying a prediction model to a different cohort, it is desirable to evaluate its performance according to the prevalent health situation in that region.


Assuntos
COVID-19 , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , SARS-CoV-2
6.
Blood Purif ; 50(1): 129-131, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32526746

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19) is a global health threat. It is a respiratory disease, and acute kidney injury (AKI) is rare; however, if a patient develops severe AKI, renal replacement therapy (RRT) should be considered. Recently, we had a critically ill COVID-19 patient who developed severe AKI and needed continuous RRT (CRRT). To avoid the potential risk of infection from CRRT effluents, we measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genetic material in the effluents by qRT-PCR, and low copy numbers of the viral genome were detected. Due to unstable hemodynamic status in critically ill patients, CRRT should be the first choice for severe AKI in COVID-19 patients. We suggest prevention of clinical infection and control during administration of RRT in the acute phase of COVID-19 patients with AKI or multiple organ failure.


Assuntos
Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , COVID-19/complicações , COVID-19/terapia , Terapia de Substituição Renal Contínua , Terapia de Substituição Renal Contínua/métodos , Humanos , Intubação Intratraqueal , Masculino , Respiração Artificial , SARS-CoV-2/isolamento & purificação
7.
J Clin Apher ; 36(3): 313-321, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33325084

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of direct hemoperfusion using a polymyxin B-immobilized polystyrene column (PMX-DHP) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive pneumonia patients. METHODS: This study was a case series conducted at a designated infectious diseases hospital. Twelve SARS-CoV-2-positive patients with partial pressure of arterial oxygen/percentage of inspired oxygen (P/F) ratio < 300 were treated with PMX-DHP on two consecutive days each during hospitalization. We defined day 1 as the first day when PMX-DHP was performed. PMX-DHP efficacy was assessed on days 7 and 14 after the first treatment based on eight categories. Subsequently, improvement in P/F ratio and urinary biomarkers on days 4 and 8, malfunctions, and ventilator and extracorporeal membrane oxygenation avoidance rates were also evaluated. RESULTS: On day 14 after the first treatment, disease severity decreased in 58.3% of the patients. P/F ratio increased while urine ß2-microglobulin decreased on days 4 and 8. Cytokine measurement pre- and post-PMX-DHP revealed decreased levels of interleukin-6 and the factors involved in vascular endothelial injury, including vascular endothelial growth factor. Twenty-two PMX-DHPs were performed, of which seven and five PMX-DHPs led to increased inlet pressure and membrane coagulation, respectively. When the membranes coagulated, the circuitry needed to be reconfigured. Circuit problems were usually observed when D-dimer and fibrin degradation product levels were high before PMX-DHP. CONCLUSIONS: Future studies are expected to determine the therapeutic effect of PMX-DHP on COVID-19. Because of the relatively high risk of circuit coagulation, coagulation capacity should be assessed beforehand.


Assuntos
COVID-19/terapia , Hemoperfusão/instrumentação , Hemoperfusão/métodos , Polimixina B/química , Poliestirenos/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Artérias/metabolismo , Biomarcadores/urina , Gasometria , Citocinas/sangue , Endotélio Vascular/metabolismo , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/metabolismo , Respiração Artificial , Estudos Retrospectivos , Risco , Microglobulina beta-2/urina
8.
Am J Physiol Renal Physiol ; 318(3): F647-F659, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31984788

RESUMO

CD148 is a transmembrane protein tyrosine phosphatase (PTP) that is expressed in the renal vasculature, including the glomerulus. Previous studies have shown that CD148 plays a role in the negative regulation of growth factor signals (including epidermal growth factor and vascular endothelial growth factor), suppressing cell proliferation and transformation. However, the role of CD148 in kidney disease remains unknown. Here, we generated an agonistic anti-CD148 antibody and evaluated its effects in murine diabetic nephropathy (DN). Monoclonal antibodies (mAbs) against the mouse CD148 ectodomain sequence were generated by immunizing CD148 knockout (CD148KO) mice. The mAbs that increased CD148 activity were selected by biological (proliferation) and biochemical (PTP activity) assays. The mAb (18E1) that showed strong agonistic activity was injected (10 mg/kg ip) in streptozotocin-induced wild-type and CD148KO diabetic mice for 6 wk, and the renal phenotype was then assessed. The effects of 18E1 mAb in podocyte growth factor signals were also assessed in culture. Compared with control IgG, 18E1 mAb significantly decreased albuminuria and mesangial expansion without altering hyperglycemia and blood pressure in wild-type diabetic mice. Immunohistochemical evaluation showed that 18E1 mAb significantly prevented the reduction of podocyte number and nephrin expression and decreased glomerular fibronectin expression and renal macrophage infiltration. The 18E1 mAb showed no effects in CD148KO diabetic mice. Furthermore, we demonstrated that 18E1 mAb reduces podocyte epidermal growth factor receptor signals in culture and in diabetic mice. These findings suggest that agonistic anti-CD148 mAb attenuates DN in mice, in part by reducing epidermal growth factor receptor signals in podocytes. This antibody may be used for the treatment of early DN.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Nefropatias Diabéticas/terapia , Albuminúria , Animais , Linhagem Celular , Diabetes Mellitus Experimental/complicações , Receptores ErbB/agonistas , Receptores ErbB/genética , Receptores ErbB/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Imunoglobulina G/uso terapêutico , Camundongos , Camundongos Knockout , Proteínas Tirosina Fosfatases Classe 3 Semelhantes a Receptores/genética , Proteínas Tirosina Fosfatases Classe 3 Semelhantes a Receptores/imunologia , Proteínas Tirosina Fosfatases Classe 3 Semelhantes a Receptores/metabolismo , Transdução de Sinais
9.
Emerg Infect Dis ; 26(11): 2758-2761, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32730734

RESUMO

We report detection of severe acute respiratory syndrome coronavirus 2 RNA in hemodialysis effluent from a patient in Japan with coronavirus disease and prolonged inflammation. Healthcare workers should observe strict standard and contact precautions and use appropriate personal protective equipment when handling hemodialysis circuitry from patients with diagnosed coronavirus disease.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Infecção Hospitalar/virologia , Rins Artificiais/virologia , Pneumonia Viral/diagnóstico , Diálise Renal/instrumentação , Idoso , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Infecções por Coronavirus/virologia , Contaminação de Equipamentos , Humanos , Japão , Falência Renal Crônica/terapia , Falência Renal Crônica/virologia , Masculino , Pandemias , Pneumonia Viral/virologia , SARS-CoV-2
10.
Clin Exp Nephrol ; 24(5): 458-464, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31984460

RESUMO

BACKGROUND: Serum anion gap (AG) has recently been proven to represent a biomarker for predicting prognosis in patients with end-stage renal disease (ESRD). However, whether change in AG (ΔAG) at the time of starting hemodialysis predicts mortality after starting hemodialysis in elderly patients with ESRD remains unknown. METHODS: This retrospective cohort investigated the association between ΔAG and mortality after starting hemodialysis in the elderly. The cohort comprised patients ≥ 75 years old who started hemodialysis for ESRD at National Center for Global Health and Medicine between 2010 and 2017 and at Yokosuka Kyosai Hospital between 2007 and 2011. Patients were stratified into three groups (G1-3) based on ΔAG, calculated according to the equation: ΔAG = sodium - (chloride + bicarbonate) - 12. The primary outcome was death within 1 year of starting hemodialysis. Data were analyzed using Cox proportional hazard models with adjustments for baseline characteristics. RESULTS: We enrolled 254 patients (59% male). Median ΔAG was 2.6 (G1: > 3, n = 111; G2: 0-3, n = 103; G3: < 0, n = 40). The primary outcome was observed in 43 patients. Hazard ratios (HRs) were significantly higher for G1 and G3 than for G2 (G1: HR 2.47, 95% confidence interval 1.13-5.37; G3: HR 3.86, 95% confidence interval 1.62-9.16). Adjusted HRs (aHRs) were significantly higher for G1 and G3 than for G2 (G1: aHR 3.06, 95% confidence interval 1.23-7.62; G3: aHR 3.12, 95% confidence interval 1.10-8.78). CONCLUSIONS: A J-curve phenomenon is evident between ΔAG and early mortality after starting hemodialysis in the elderly.


Assuntos
Equilíbrio Ácido-Base , Falência Renal Crônica/mortalidade , Falência Renal Crônica/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Cloretos/sangue , Feminino , Humanos , Hiperfosfatemia/epidemiologia , Japão/epidemiologia , Estimativa de Kaplan-Meier , Falência Renal Crônica/terapia , Masculino , Limitação da Mobilidade , Prognóstico , Modelos de Riscos Proporcionais , Diálise Renal , Estudos Retrospectivos , Fatores de Risco
11.
Clin Exp Nephrol ; 24(11): 1077-1083, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32748309

RESUMO

BACKGROUND: Delirium is an independent predictor of death in patients undergoing dialysis for end-stage renal disease (ESRD). However, it is unknown whether delirium during hospitalization at the start of hemodialysis (HD) in elderly populations is associated with early mortality. METHODS: We conducted a retrospective cohort study to investigate the association between delirium and early mortality in the elderly after starting HD. The cohort consisted of patients ≥ 75 years who started dialysis for ESRD at the National Center for Global Health and Medicine from 2010 to 2017 and at Yokosuka Kyosai Hospital from 2007 to 2011. Delirium was defined as patients who showed new symptoms of transient confused thinking and reduced awareness of their environment and were prescribed antipsychotic medications. The primary outcome was death within 1 year. Data were analyzed using Cox proportional hazard models with adjustments for baseline characteristics. A multinomial logistic regression was used to identify the determinants of patients developing delirium. RESULTS: We enrolled 259 patients (males, 60%); 33 patients were diagnosed with delirium. The primary outcome was observed in 19 patients with delirium (58%) and 24 patients without delirium (11%) (p < 0.01). Delirium was independently associated with all-cause mortality within 1 year after starting HD (hazard ratio 7.82, 95% confidence interval 4.26-14.3; adjusted hazard ratio 7.16, 95% confidence interval 3.49-14.7). Delirium was positively correlated with "cognitive impairment" as well as "the use of steroids." CONCLUSION: Delirium is independently associated with early mortality in the elderly after starting HD.


Assuntos
Delírio/mortalidade , Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/epidemiologia , Feminino , Hospitalização , Humanos , Japão/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Modelos de Riscos Proporcionais , Diálise Renal , Estudos Retrospectivos , Esteroides/uso terapêutico
12.
Magn Reson Med ; 80(6): 2655-2669, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29845659

RESUMO

PURPOSE: Renal fibrosis is a hallmark of progressive renal disease; however, current clinical tests are insufficient for assessing renal fibrosis. Here we evaluated the utility of quantitative magnetization transfer MRI in detecting renal fibrosis in a murine model of progressive diabetic nephropathy (DN). METHODS: The db/db eNOS-/- mice, a well-recognized model of progressive DN, and normal wild-type mice were imaged at 7T. The quantitative magnetization transfer data were collected in coronal plane using a 2D magnetization transfer prepared spoiled gradient echo sequence with a Gaussian-shaped presaturation pulse. Parameters were derived using a two-pool fitting model. A normal range of cortical pool size ratio (PSR) was defined as Mean±2SD of wild-type kidneys (N = 20). The cortical regions whose PSR values exceeded this threshold (threshold PSR) were assessed. The correlations between the PSR-based and histological (collagen IV or picrosirius red stain) fibrosis measurements were evaluated. RESULTS: Compared with wild-type mice, moderate increases in mean PSR values and scattered clusters of high PSR region were observed in cortex of DN mouse kidneys. Abnormally high PSR regions (% area) that were detected by the threshold PSR were significantly increased in renal cortexes of DN mice. These regions progressively increased on aging and highly correlated with histological fibrosis measures, while the mean PSR values correlated much less. CONCLUSION: Renal fibrosis in DN can be assessed by the quantitative magnetization transfer MRI and threshold analysis. This technique may be used as a novel imaging biomarker for DN and other renal diseases.


Assuntos
Nefropatias Diabéticas/diagnóstico por imagem , Fibrose/diagnóstico por imagem , Rim/diagnóstico por imagem , Imageamento por Ressonância Magnética , Animais , Interpretação de Imagem Assistida por Computador/métodos , Rim/patologia , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo III/metabolismo , Distribuição Normal , Reprodutibilidade dos Testes
13.
Kidney Int ; 89(2): 374-85, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26535996

RESUMO

Elucidation of acute kidney diseases and disorders (AKD), including acute kidney injury (AKI), is important to prevent their progression to chronic kidney disease. Current animal AKI models are often too severe for use in evaluating human AKI. Therefore, new animal models of mild kidney injury are needed. Here a new clinically relevant animal model using multiple low doses of cisplatin (CP) was used to evaluate AKD. When 10 mg/kg CP was administered intraperitoneally once weekly for three times to L-type fatty acid-binding protein (L-FABP) transgenic mice, moderate renal interstitial fibrosis and tubule dilatation occurred, accompanied by brush-border loss. Urinary L-FABP, a promising biomarker of AKI, changed more drastically than blood urea nitrogen or creatinine. Preventing fibrosis in organs was also studied. Oral administration of a recently reported selective semicarbazide-sensitive amine oxidase inhibitor, PXS-4728A, for 1 week attenuated kidney injury and interstitial fibrosis compared with vehicle. Inhibition of renal lipid accumulation in semicarbazide-sensitive amine oxidase inhibitor-treated mice, together with reduced oxidative stress and L-FABP suppression in proximal tubules, suggested an antifibrotic effect of semicarbazide-sensitive amine oxidase inhibition in this CP-AKD model, a representative onco-nephrology. Thus, semicarbazide-sensitive amine oxidase inhibitors may be promising candidates for the prevention of chronic kidney disease in patients using CP to treat malignancy.


Assuntos
Injúria Renal Aguda/prevenção & controle , Alilamina/análogos & derivados , Amina Oxidase (contendo Cobre)/antagonistas & inibidores , Antineoplásicos/efeitos adversos , Benzamidas/uso terapêutico , Cisplatino/efeitos adversos , Actinas/metabolismo , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Alilamina/farmacologia , Alilamina/uso terapêutico , Animais , Benzamidas/farmacologia , Quimiocina CCL2/metabolismo , Avaliação Pré-Clínica de Medicamentos , Proteínas de Ligação a Ácido Graxo/genética , Fibrose , Interleucina-6/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
14.
Anal Chem ; 88(12): 6135-9, 2016 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-27282958

RESUMO

A fluorescence enhanced phenomenon was found within a micrometer-sized liquid droplet, and it was adopted to construct droplet enhanced fluorescence (DEF) for ultrasensitive fluorescence detection. In this paper, an inkjet was utilized to eject perfect spherical droplets to construct a microspherical resonator and to develop a DEF system. It was utilized to implement ultrasensitive fluorescence detection in a liquid specimen with a volume of several microliters. The DEF detection of fluorescent molecules, fluorescein sodium, was used as a model to validate the proposed enhanced fluorescence detection method. A low limit of detection (LOD) for fluorescein sodium of 124 pM was obtained. The sensitive detection of single stranded DNA (ssDNA) was experimentally completed, with a wide range of linearity with a LOD of 312 pM. The proposed mechanism can be used as an ultrasensitive detection technique for analyzing microliters of liquid samples.

15.
Am J Pathol ; 185(7): 1889-98, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25987249

RESUMO

Type 2 diabetes mellitus is a leading health issue worldwide. Among cases of diabetes mellitus nephropathy (DN), the major complication of type 2 diabetes mellitus, the nephrotic phenotype is often intractable to clinical intervention and demonstrates the rapid decline of renal function to end-stage renal disease. We recently identified the gene for glypican-5 (GPC5), a cell-surface heparan sulfate proteoglycan, as conferring susceptibility for acquired nephrotic syndrome and additionally identified an association through a genome-wide association study between a variant in GPC5 and DN of type 2 diabetes mellitus. In vivo and in vitro data showed a progressive increase of GPC5 in type 2 DN along with severity; the excess was derived from glomerular mesangial cells. In this study, diabetic kidney showed that accumulation of fibroblast growth factor (Fgf)2 strikingly induced progressive proteinuria that was avoided in Gpc5 knockdown mice. The efficacy of Gpc5 inhibition was exerted through expression of the Fgf receptors 3 and 4 provoked in the diabetic kidney attributively. Extraglomerular Fgf2 was pathogenic in DN, and the deterrence of Gpc5 effectively inhibited the glomerular accumulation of Fgf2, the subsequent increase of mesangial extracellular matrix, and the podocytes' small GTPase activity. These findings elucidate the pivotal role of GPC5, identified as a susceptible gene in the genome-wide association study, in hyperglycemia-induced glomerulopathy.


Assuntos
Diabetes Mellitus Tipo 2/genética , Nefropatias Diabéticas/etiologia , Glipicanas/metabolismo , Síndrome Nefrótica/etiologia , Adulto , Idoso , Animais , Linhagem Celular , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , Suscetibilidade a Doenças , Feminino , Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/metabolismo , Mesângio Glomerular/patologia , Glipicanas/genética , Humanos , Hiperglicemia/complicações , Hiperglicemia/patologia , Rim/metabolismo , Rim/patologia , Falência Renal Crônica/etiologia , Falência Renal Crônica/patologia , Masculino , Células Mesangiais/metabolismo , Células Mesangiais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Síndrome Nefrótica/patologia , Podócitos/metabolismo , Proteinúria/etiologia , Ratos
16.
J Am Soc Nephrol ; 24(12): 2034-43, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24092928

RESUMO

Accumulating evidence of the beyond-glucose lowering effects of a gut-released hormone, glucagon-like peptide-1 (GLP-1), has been reported in the context of remote organ connections of the cardiovascular system. Specifically, GLP-1 appears to prevent apoptosis, and inhibition of dipeptidyl peptidase-4 (DPP-4), which cleaves GLP-1, is renoprotective in rodent ischemia-reperfusion injury models. Whether this renoprotection involves enhanced GLP-1 signaling is unclear, however, because DPP-4 cleaves other molecules as well. Thus, we investigated whether modulation of GLP-1 signaling attenuates cisplatin (CP)-induced AKI. Mice injected with 15 mg/kg CP had increased BUN and serum creatinine and CP caused remarkable pathologic renal injury, including tubular necrosis. Apoptosis was also detected in the tubular epithelial cells of CP-treated mice using immunoassays for single-stranded DNA and activated caspase-3. Treatment with a DPP-4 inhibitor, alogliptin (AG), significantly reduced CP-induced renal injury and reduced the renal mRNA expression ratios of Bax/Bcl-2 and Bim/Bcl-2. AG treatment increased the blood levels of GLP-1, but reversed the CP-induced increase in the levels of other DPP-4 substrates such as stromal cell-derived factor-1 and neuropeptide Y. Furthermore, the GLP-1 receptor agonist exendin-4 reduced CP-induced renal injury and apoptosis, and suppression of renal GLP-1 receptor expression in vivo by small interfering RNA reversed the renoprotective effects of AG. These data suggest that enhancing GLP-1 signaling ameliorates CP-induced AKI via antiapoptotic effects and that this gut-kidney axis could be a new therapeutic target in AKI.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismo , Cisplatino/toxicidade , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Mucosa Intestinal/metabolismo , Injúria Renal Aguda/tratamento farmacológico , Animais , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Inibidores da Dipeptidil Peptidase IV/farmacologia , Exenatida , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hipoglicemiantes/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Peptídeos/farmacologia , Piperidinas/farmacologia , RNA Interferente Pequeno/farmacologia , Receptores de Glucagon/agonistas , Receptores de Glucagon/genética , Receptores de Glucagon/metabolismo , Traumatismo por Reperfusão/induzido quimicamente , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Uracila/análogos & derivados , Uracila/farmacologia , Peçonhas/farmacologia
17.
CEN Case Rep ; 13(1): 19-25, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37103638

RESUMO

Although mRNA vaccines for COVID-19 are highly beneficial and are recommended for patients with kidney disease, adverse reactions in some patients after vaccination have been problematic. Various vasculitis and renal disorders have been reported after vaccination; however, a causal relationship has not yet been identified. In this report, we describe a case of rapidly progressive glomerulonephritis that developed after SARS-CoV-2 vaccination, in which both anti-glomerular basement membrane (anti-GBM) and myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA) were present. The patient's renal biopsy showed that of the 48 glomeruli in total, four showed global sclerosis and none showed segmental sclerosis. The biopsy showed 11 cellular glomerular crescents and 5 fibrocellular glomerular crescents. Renal function improved with steroids, rituximab, and plasma exchange. Approximately 9 months later, MPO-ANCA was again elevated, and the pulmonary lesions worsened, again requiring multidisciplinary treatment. This case suggests that caution should be exercised in the development of double-positive disease after vaccination, and that long-term observation may be necessary because of the possibility of relapse.


Assuntos
Autoanticorpos , COVID-19 , Glomerulonefrite , Nefrite , Humanos , Anticorpos Anticitoplasma de Neutrófilos , Vacinas contra COVID-19/efeitos adversos , SARS-CoV-2 , Seguimentos , Esclerose/patologia , COVID-19/complicações , Membrana Basal Glomerular/patologia , Nefrite/complicações , Doença Crônica , Peroxidase , Recidiva , Vacinação/efeitos adversos
18.
Clin J Gastroenterol ; 17(4): 711-716, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38589719

RESUMO

The necessity of biliary drainage before pancreaticoduodenectomy remains controversial in cases involving malignant obstructive jaundice; however, the benefits of biliary drainage have been reported in cases with severe hyperbilirubinemia. Herein, we present the case of a 61-year-old man suffering from jaundice due to distal cholangiocarcinoma. In this case, obstructive jaundice was refractory to repeat endoscopic drainage and bilirubin adsorption. Hyperbilirubinemia persisted despite successful implementation of biliary endoscopic sphincterotomy and two rounds of plastic stent placements. Stent occlusion and migration were unlikely and oral cholagogues proved ineffective. Owing to the patient's surgical candidacy and his aversion to nasobiliary drainage due to discomfort, bilirubin adsorption was introduced as an alternative therapeutic intervention. Following repeated adsorption sessions, a gradual decline in serum total bilirubin levels was observed and pancreaticoduodenectomy was scheduled. The patient successfully underwent pancreaticoduodenectomy with portal vein resection and reconstruction and D2 lymph node dissection. After the surgery, the serum bilirubin levels gradually decreased and the patient remained alive, with no recurrence at 26 months postoperatively. Therefore, this case highlights the feasibility and safety of performing pancreaticoduodenectomy in patients with severe, refractory jaundice who have not responded to repeated endoscopic interventions and have partially responded to bilirubin adsorption.


Assuntos
Neoplasias dos Ductos Biliares , Bilirrubina , Colangiocarcinoma , Drenagem , Icterícia Obstrutiva , Pancreaticoduodenectomia , Humanos , Masculino , Pancreaticoduodenectomia/métodos , Icterícia Obstrutiva/etiologia , Icterícia Obstrutiva/cirurgia , Pessoa de Meia-Idade , Bilirrubina/sangue , Drenagem/métodos , Colangiocarcinoma/cirurgia , Colangiocarcinoma/complicações , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/complicações , Stents , Adsorção , Cuidados Pré-Operatórios/métodos
19.
Sci Rep ; 14(1): 12550, 2024 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822071

RESUMO

Extracorporeal blood purification with polymyxin B immobilized fiber column direct hemoperfusion (PMX-DHP), is reported to be effective in treating COVID-19 pneumonitis with oxygen demand. This multicenter prospective study evaluated the efficacy and safety of PMX-DHP in oxygen-requiring patients with COVID-19 admitted between September 28, 2020, and March 31, 2022. The primary endpoint was the percentage of clinical improvement 15 days after treatment. The secondary endpoint was the percentage of worsened disease status. Data from the COVID-19 patient registry were used for the synthetic control group. The improvement rate on Day 15 did not differ between PMX-treated patients and controls; however, the deterioration rate was 0.38 times lower in the PMX-treated group, and the death rates on Day 29 were 0 and 11.1% in the PMX-treated and control groups, respectively. The PMX group showed a 0.73 times higher likelihood for reduced intensive care demand, as 16.7% of PMX-treated patients and 22.8% of controls worsened. After treatment blood oxygenation improved, urinary ß2-microglobulin and liver-type fatty acid-binding protein showed significant decreases, and IL-6 decreased once during treatment but did not persist. In this study, PMX treatment effectively prevented the worsening of COVID-19 pathology, accompanied by improved oxygenation. PMX treatment to remove activated cells may effectively improve patient outcomes.


Assuntos
COVID-19 , Hemoperfusão , Polimixina B , Humanos , COVID-19/terapia , Polimixina B/administração & dosagem , Polimixina B/uso terapêutico , Masculino , Feminino , Hemoperfusão/métodos , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , SARS-CoV-2/isolamento & purificação , Resultado do Tratamento , Oxigênio , Oxigenoterapia/métodos , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem
20.
CEN Case Rep ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38727797

RESUMO

Acute kidney injury (AKI) secondary to severe falciparum malaria possesses a high mortality rate; however, a prognostic marker of renal dysfunction has not yet been identified. Thus, we reported a case of a patient with AKI secondary to falciparum malaria who underwent hemodialysis and a renal biopsy due to prolonged renal dysfunction. The male patient, in his 50 s, presented to our hospital with vomiting, diarrhea, fever, and decreased level of consciousness. The Giemsa-stained peripheral blood film revealed approximately 5% parasitemia, and a rapid diagnostic test was positive for Plasmodium falciparum. He was diagnosed with severe falciparum malaria and was started on quinine hydrochloride. Hemodialysis was initiated due to the decreased urine output and fluid retention. Subsequently, he was weaned off hemodialysis. The histopathological analysis of a renal biopsy revealed interstitial fibrosis, tubular atrophy, and chronic inflammatory cell infiltration; thus, malarial nephropathy was diagnosed. Thereafter, his renal function stabilized, and he was discharged from the hospital. The urinary liver-type fatty acid-binding protein (L-FABP) level decreased before renal function improved. Our report highlighted that long-term follow-up is essential for severe AKI secondary to malaria. The urinary L-FABP level may be a useful prognostic indicator of AKI secondary to severe falciparum malaria.

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