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BACKGROUND: Proteinuria is broadly classified into glomerular and tubular proteinuria. Urinary beta-2-microglobulin (ß2-MG) is known as a marker for detecting tubulointerstitial diseases. However, tubulointerstitial damage can also lead to an increase in urinary ß2-MG level in some patients with glomerular diseases. This study aimed to determine the ratio of urinary ß2-MG to total protein (TP) concentration in patients with both isolated tubulointerstitial and glomerular disease. METHODS: This multicenter, retrospective study included children with Dent disease or lupus nephritis in five facilities. Their urinary ß2-MG levels were > 1000 µg/L. Urinary ß2-MG and TP concentrations were obtained, and the ratio of urinary ß2-MG to TP concentration (µg/mg) was calculated. The Mann-Whitney U test was performed to compare this ratio between these children. The optimal cutoff value of the ratio for considering the presence of glomerular disease was obtained from the receiver operating characteristic (ROC) curve. RESULTS: We obtained information on 23 children with Dent disease and 14 children with lupus nephritis. The median ratios of urinary ß2-MG to TP concentrations in children with Dent disease and lupus nephritis were 84.85 and 1.59, respectively. The ROC curve yielded the optimal cutoff value of this ratio for distinguishing between these diseases, and the cutoff value was found to be 22.3. CONCLUSION: In children with tubulointerstitial diseases, the urinary ß2-MG concentration may be approximately 8.5% of the TP concentration. The possibility of presenting with glomerular disease should be considered in patients with a ratio of urinary ß2-MG to TP concentration of < 22.3 (µg/mg).
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Enfermedad de Dent , Nefritis Lúpica , Nefritis Intersticial , Humanos , Niño , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/orina , Estudios Retrospectivos , Nefritis Intersticial/diagnóstico , Proteinuria/diagnóstico , Microglobulina beta-2/orina , Biomarcadores/orinaRESUMEN
Mycophenolate mofetil is effective for the treatment of pediatric idiopathic nephrotic syndrome (INS). The dosage of mycophenolate mofetil is adjusted according to the serum concentration of mycophenolic acid (MPA). Kidney function or cyclosporine (CsA) concentrations affect serum MPA levels. However, few studies have focused on the association between serum concentrations of MPA and albumin. This retrospective observational study aimed to evaluate the relationship between the serum concentrations of MPA and albumin in INS children. Subjects were children with INS who underwent the therapeutic drug monitoring of CsA and MPA. We obtained the serum albumin (sAlb) concentration, estimated glomerular filtration rate (eGFR), age, and MPA and CsA areas under concentration-time curves from 0 to 12 h (AUC0-12). Multiple linear regression analysis and generalized estimating equations were performed to predict values for MPA AUC0-12. We obtained information for 51 INS children with 261 MPA AUC0-12 measurements. The standardized regression coefficients of sAlb, eGFR, CsA AUC0-12, and age were 0.54, - 0.21, - 0.07, and 0.04, respectively. Furthermore, MPA AUC0-12 levels positively correlated with sAlb concentrations (p < 0.001) and were inversely correlated with eGFR values (p = 0.005) but not with CsA AUC0-12 (p = 0.24) and age (p = 0.65).Conclusion: Serum albumin concentration was strongly associated with total MPA concentration compared with kidney function or CsA values. Although patients with INS may have a low serum concentration of total MPA in the presence of low sAlb concentration, close attention should be paid to the interpretation of the low MPA values. What is Known: ⢠The dosage of mycophenolate mofetil is adjusted according to the serum concentration of total mycophenolic acid. ⢠Kidney function, cyclosporin concentrations, or serum albumin concentrations influence serum mycophenolic acid levels. What is New: ⢠Serum albumin concentration is more strongly associated with total mycophenolic acid concentration than kidney function or cyclosporin values. ⢠In children with nephrotic syndrome, the total mycophenolic acid concentration may not increase in the presence of severe hypoalbuminemia.
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Trasplante de Riñón , Síndrome Nefrótico , Área Bajo la Curva , Atención , Niño , Ciclosporina/uso terapéutico , Humanos , Inmunosupresores/uso terapéutico , Ácido Micofenólico/uso terapéutico , Síndrome Nefrótico/tratamiento farmacológico , Estudios Retrospectivos , Albúmina SéricaRESUMEN
BACKGROUND: Some pediatric patients on maintenance dialysis may need end-of-life care in the future because of being excluded from the indication of kidney transplantation and experiencing difficulty in continuation of their dialysis. This study aimed to thoroughly elucidate mortality outcomes of children on maintenance dialysis including the cause of death and clinical background of exclusion from indication of transplantation. PATIENTS AND METHODS: This single-center retrospective study enrolled 53 children who received kidney transplantation (5) or maintenance peritoneal dialysis (PD, 48) as initial renal replacement therapy (RRT). We examined the selected RRT modalities, mortality outcomes, clinical backgrounds of cause of death, and risk factors of excluding from future the indication of transplantation. RESULTS: Nine (17%) of all 53 patients, all receiving PD (9/48, 19%), were finally excluded from next RRT indication-7 were excluded due to severe extrarenal complications that indicated high risk for transplantation and 2 were excluded due to severe psychomotor retardation and at the guardians' discretion. Patients who were excluded from the indication had a younger age at PD induction and higher proportion of cerebral and cardiac complications or psychomotor retardation than patients who were included in the indication. Of the nine patients, seven died; of which, one patient died due to fatal progression of extrarenal complications and six died due to infectious or noninfectious dialysis-related complications. CONCLUSION: Patients with severe extrarenal complications or psychomotor retardation tend to be excluded from the indication of transplantation. Their condition becomes fatal because of the complications of long-term dialysis and progression in extrarenal complications.
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Fallo Renal Crónico , Trasplante de Riñón , Diálisis Peritoneal , Niño , Humanos , Trasplante de Riñón/efectos adversos , Diálisis Peritoneal/efectos adversos , Diálisis Renal/efectos adversos , Estudios RetrospectivosRESUMEN
BACKGROUND: Serum adiponectin circulates in three multimeric isoforms: high-molecular-weight (HMW), middle-molecular-weight (MMW), and low-molecular-weight (LMW) isoforms. Potential change in the circulating adiponectin levels in patients with nephrotic syndrome (NS) remain unknown. This study aimed to assess the levels of total adiponectin and the distribution of its isoforms in pediatric patients with NS. METHODS: We sequentially measured total adiponectin and each adiponectin isoform levels at the onset of NS, initial remission, and during the remission period of the disease in 31 NS patients. We also calculated the ratios of HMW (%HMW), MMW (%MMW), and LMW (%LMW) to total adiponectin incuding 51 control subjects. RESULTS: The median of total serum adiponectin levels in patients were 36.7, 36.7, and 20.2 µg/mL at the onset, at initial remission, and during the remission period of NS, respectively. These values were significantly higher than those in control subjects. The median values of %HMW, %MMW, and %LMW values were 56.9/27.0/14.1 at the onset, 62.0/21.8/13.4 at the initial remission, and 58.1/21.7/17.5 at during the remission period of NS, respectively. Compared with control subjects, %HMW at initial remission and %MMW at the onset were high, and the %LMW values at the onset and at initial remission were low. CONCLUSIONS: In patients with NS, total serum adiponectin levels increase at the onset of the disease, and the ratio of adiponectin isoforms changes during the course of the disease. Further studies are needed to delineate the mechanisms between proteinuria and adiponectin isoforms change.
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Adiponectina/sangre , Síndrome Nefrótico/sangre , Síndrome Nefrótico/tratamiento farmacológico , Antiinflamatorios/uso terapéutico , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Peso Molecular , Prednisolona/uso terapéutico , Isoformas de Proteínas/sangre , Inducción de RemisiónRESUMEN
BACKGROUND: Only a few studies have investigated epidemiological and clinicopathological information regarding pediatric and adolescent and young adult (AYA) patients with renal disease. The purpose of this study was to clarify the differences and relationship of clinicopathological findings between pediatric and AYA patients using the Japan Renal Biopsy Registry (J-RBR). METHODS: This cross-sectional study analyzed data from patients registered in the J-RBR between 2007 and 2017. Clinicopathological findings at diagnosis were analyzed for 3,463 pediatric (age < 15 years) and 6,532 AYA (age 15-30 years) patients. RESULTS: Although chronic nephritic syndrome was the most common clinical diagnosis at age > 5 years, nephrotic syndrome was the most frequent diagnosis at age < 4 years. The most common pathological diagnosis as classified by pathogenesis in pediatric patients was primary glomerular disease (except IgA nephropathy), whereas IgA nephropathy was increased in AYA patients. Mesangial proliferative glomerulonephritis was the most common pathological diagnosis as classified by histopathology in both pediatric and AYA patients. Minor glomerular abnormalities were the most frequent histopathologic diagnoses of nephrotic syndrome in childhood, but their frequency decreased with age. CONCLUSION: To the best of our knowledge, this is the first report of clinicopathological features of pediatric and AYA patients in a large nationwide registry of renal biopsy. There were differences of clinical, pathological and histopathologic findings between pediatric and AYA patients.
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Glomerulonefritis por IGA/epidemiología , Glomerulonefritis Membranoproliferativa/epidemiología , Síndrome Nefrótico/epidemiología , Adolescente , Adulto , Distribución por Edad , Biopsia , Niño , Preescolar , Estudios Transversales , Femenino , Tasa de Filtración Glomerular , Glomerulonefritis por IGA/patología , Glomerulonefritis Membranoproliferativa/patología , Humanos , Lactante , Japón/epidemiología , Glomérulos Renales/patología , Masculino , Síndrome Nefrótico/patología , Proteinuria/epidemiología , Proteinuria/patología , Sistema de Registros , Adulto JovenRESUMEN
BACKGROUND: Developmental programming of chronic kidney disease (CKD) in young adults is linked to preterm birth and intrauterine growth restriction (IUGR). Which confers a higher risk of progression to chronic kidney damage in children with very low birth weight (VLBW; born weighing < 1500 g): prematurity or IUGR? METHODS: This is a national historical cohort study of children with VLBW cared for in perinatal medical centers in Japan. Predictive factors included three latent variables (prematurity, IUGR, stress during neonatal period) and eight observed variables (gestational age, birth weight Z-score, maternal age, duration of treatment with antibiotics and diuretics, maternal smoking, late-onset circulatory collapse, kidney dysfunction) during the perinatal period. The primary endpoint was estimated glomerular filtration rate (eGFR) at age ≥ 3 years. A structural equation model was used to examine the pathologic constitution. RESULTS: The 446 children with VLBW included 253 boys and 193 girls, of mean age 5.8 ± 2.6 years and mean eGFR 111.7 ml/min/1.73 m2 at last encounter. Pathway analyses showed intrauterine malnutrition (ß = 0.85) contributed more to chronic kidney damage than stress during the neonatal period (ß = - 0.19) and prematurity (ß = 0.12), and kidney dysfunction and late-onset circulatory collapse were important observed variables in stress during the neonatal period. CONCLUSIONS: IUGR was more harmful to future kidneys of VLBW neonates. Neonatal kidney dysfunction and late-onset circulatory collapse were important risk factors for subsequent CKD development. This emphasizes the need for obstetricians to monitor for fetal growth restriction and neonatologists to minimize neonatal stress to prevent CKD in later life.
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Enfermedades del Prematuro , Recién Nacido de muy Bajo Peso , Nacimiento Prematuro , Insuficiencia Renal Crónica , Peso al Nacer , Niño , Preescolar , Estudios de Cohortes , Femenino , Retardo del Crecimiento Fetal/epidemiología , Edad Gestacional , Humanos , Recién Nacido , Japón , Masculino , Embarazo , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/etiología , Factores de RiesgoRESUMEN
Renal tubular dysgenesis (RTD) is the absence or poor development of the renal proximal tubules caused by gene mutations in the renin-angiotensin system. Although RTD has been considered fatal, improving neonatal intensive care management has enhanced survival outcomes. However, little has been reported on the survival of extremely preterm infants. This study reports the survival of an extremely preterm infant with RTD and discusses the appropriate management of RTD by reviewing the literature. A female infant weighing 953 g was delivered at 27 weeks' gestation by Cesarean section because of oligohydramnios. She exhibited severe persistent pulmonary hypertension, severe systemic hypotension, and renal dysfunction shortly after birth. Respiratory management was successfully undertaken using nitric oxide inhalation and high-frequency oscillatory ventilation. Desmopressin was effective in maintaining her blood pressure and urinary output. She was diagnosed with RTD based on genetic testing, which revealed a compound heterozygous mutation in the angiotensin-converting enzyme gene in exon 18 (c.2689delC; p.Pro897fs) and exon 20 (c.3095dupT; p.Leu1032fs). At 2 years, she started receiving oral fludrocortisone for treating persistently high serum creatinine levels, which was attributed to nephrogenic diabetes insipidus caused by RTD. Subsequently, her urine output decreased, and renal function was successfully maintained. Currently, there is no established treatment for RTD. Considering cases reported to date, treatment with vasopressin and fludrocortisone appears to be most effective for survival and maintenance of renal function in patients with RTD. This study presents the successful management of RTD using this strategy in an extremely preterm infant.
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Recien Nacido Prematuro/fisiología , Túbulos Renales Proximales/anomalías , Anomalías Urogenitales/terapia , Secuencia de Bases , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Túbulos Renales Proximales/enzimología , Peptidil-Dipeptidasa A/genética , Análisis de Supervivencia , Anomalías Urogenitales/enzimología , Anomalías Urogenitales/genéticaRESUMEN
Mutations in the TTC21B gene have been identified in patients with nephronophthisis and were recently found in some patients with focal segmental glomerulosclerosis. We herein report a Japanese boy with end-stage renal disease due to medullary polycystic kidney disease and primary focal segmental glomerulosclerosis. Next-generation sequencing detected a new compound heterozygous missense mutation in the TTC21B gene. His renal pathological findings and gene mutations have not been previously reported in patients with ciliopathy. For children with severe renal dysfunction, mutations in the TTC21B gene cause both ciliopathy characterized by bilateral polycystic kidney disease and primary focal segmental glomerulosclerosis.
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Glomeruloesclerosis Focal y Segmentaria/complicaciones , Glomeruloesclerosis Focal y Segmentaria/genética , Fallo Renal Crónico/etiología , Fallo Renal Crónico/cirugía , Proteínas Asociadas a Microtúbulos/genética , Enfermedades Renales Poliquísticas/complicaciones , Enfermedades Renales Poliquísticas/genética , Adolescente , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Japón , Masculino , Mutación MissenseRESUMEN
Eculizumab, a humanized monoclonal antibody to complement C5, is a therapeutic drug for atypical hemolytic-uremic syndrome (aHUS) that inhibits the terminal pathway of complement. Patients on eculizumab therapy may become more susceptible to infection with capsule-forming bacteria, including meningococci. Therefore, meningococcal vaccination is required for patients who are on eculizumab therapy. However, the means to prevent meningococcal infection in infants who cannot be vaccinated with the available meningococcal vaccine have not yet been established internationally. In two infants with aHUS at 4-5 months after birth, prophylactic oral amoxicillin was administered, and meningococcal infection was not detected during the period between the initiation of eculizumab therapy and the administration of meningococcal vaccine. Neither adverse events related to amoxicillin nor thrombotic microangiopathy occurred during the treatment. Thus, oral administration of amoxicillin may be effective for preventing meningococcal infection under treatment with eculizumab in infants who have not received meningococcal vaccination.
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Anticuerpos Monoclonales Humanizados/efectos adversos , Síndrome Hemolítico Urémico Atípico/tratamiento farmacológico , Inactivadores del Complemento/efectos adversos , Infecciones Meningocócicas/prevención & control , Administración Oral , Amoxicilina/administración & dosificación , Amoxicilina/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Inactivadores del Complemento/administración & dosificación , Inactivadores del Complemento/uso terapéutico , Humanos , Lactante , Infusiones Intravenosas , Masculino , Infecciones Meningocócicas/inducido químicamente , Infecciones Meningocócicas/tratamiento farmacológico , Infecciones Meningocócicas/microbiología , Vacunas Meningococicas/administración & dosificación , Vacunas Meningococicas/normas , Neisseria meningitidis/efectos de los fármacos , Neisseria meningitidis/aislamiento & purificación , Resultado del TratamientoRESUMEN
Many studies have demonstrated that oxidative stress plays an important role in several ailments including neurodegenerative diseases and cerebral ischemic injury. Previously we synthesized some carbazole compounds that have anti-oxidant ability in vitro. In this present study, we found that one of these 22 carbazole compounds, compound 13 (3-ethoxy-1-hydroxy-8- methoxy-2-methylcarbazole-5-carbaldehyde), had the ability to protect neuro2a cells from hydrogen peroxide-induced cell death. It is well known that neurite loss is one of the cardinal features of neuronal injury. Our present study revealed that compound 13 had the ability to induce neurite outgrowth through the PI3K/Akt signaling pathway in neuro2a cells. These findings suggest that compound 13 might exert a neurotrophic effect and thus be a useful therapy for the treatment of brain injury.
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Carbazoles/farmacología , Peróxido de Hidrógeno/farmacología , Proyección Neuronal/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/fisiología , Animales , Carbazoles/química , Diferenciación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Estructura Molecular , Transducción de Señal/efectos de los fármacosRESUMEN
Large-dose cyclic tidal peritoneal dialysis (TPD) is an original prescription of TPD involving frequent infusion and drainage of the dialysate to increase weekly urea clearance normalized to total body water (Kt/Vurea ) and fluid removal. This study aimed to evaluate the efficiency of solute clearance and fluid removal achieved with large-dose cyclic TPD compared to that achieved with nightly peritoneal dialysis (NPD). Seventeen patients with end-stage renal disease, for whom maintenance PD was changed from NPD to large-dose cyclic TPD, were enrolled. Their median age at administration of PD was 4.9 years. Kt/Vurea and fluid removal were compared between large-dose cyclic TPD and NPD. The median peritoneal Kt/Vurea achieved with NPD and large-dose cyclic TPD was 1.5 and 2.7, respectively. The median peritoneal Kt/Vurea per hour with large-dose cyclic TPD was significantly higher than that with NPD (P = 0.0003). Among nine patients who used dialysates with the same glucose concentration for both NPD and large-dose cyclic TPD, nightly fluid removal amount per hour with large-dose cyclic TPD was significantly higher than that with NPD (P = 0.0039). Large-dose cyclic TPD is a useful prescription of PD for increasing Kt/Vurea and fluid removal.
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Soluciones para Diálisis , Fallo Renal Crónico/terapia , Diálisis Peritoneal/métodos , Urea/metabolismo , Niño , Preescolar , Femenino , Glucosa/metabolismo , Humanos , Lactante , Masculino , Estudios Retrospectivos , Factores de TiempoRESUMEN
To determine the optimal method of evaluating kidney function in patients with thyroid dysfunction, this study compared the estimated glomerular filtration rate derived from serum creatinine, cystatin C, or ß2-microglobulin with inulin or creatinine clearance in two pediatric patients, one with hypothyroidism and the other with hyperthyroidism. It was observed that the kidney function decreased in a hypothyroid child and enhanced in a hyperthyroid child, with their kidney function becoming normalized by treatment with drugs, which normalized their thyroid function. Kidney function cannot be accurately evaluated using cystatin C-based or ß2-microglobulin-based estimated glomerular filtration rate in patients with thyroid dysfunction, as these tests overestimated glomerular filtration rate in a patient with hypothyroidism and underestimated glomerular filtration rate in a patient with hyperthyroidism, perhaps through a metabolic rate-mediated mechanism. In both our patients, 24-h urinary creatinine secretion was identical before and after treatment, suggesting that creatinine production is not altered in patients with thyroid dysfunction. Therefore, kidney function in patients with thyroid dysfunction should be evaluated using creatinine-based estimated glomerular filtration rate.
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Microglial activation has been suggested to play important roles in various neurodegenerative diseases by phagocytosis and producing various factors such as nitric oxide (NO), proinflammatory cytokines. Excessive production of NO, as a consequence of increased inducible nitric oxide synthase (iNOS) in microglia, contributes to the neurodegeneration. During a search for compounds that regulate endoplasmic reticulum (ER) stress, a dibenzoylmethane derivative, 2,2'-dimethoxydibenzoylmethane (DBM 14-26) was identified as a novel neuroprotective agent (Takano et al., Am. J. Physiol. Cell Physiol. 293, C1884-1894, 2007). We previously reported in cultured astrocytes that DBM 14-26 protected hydrogen peroxide-induced cell death and inhibited lipopolysaccharide (LPS)-induced NO production (Takano et al., J. Neurosci. Res. 89, 955-965, 2011). In the present study, we assessed the effects of DBM 14-26 on microglia using the mouse cell line BV-2 and found that DBM 14-26 inhibited LPS-induced iNOS expression and NO production also in microglia. DBM 14-26 also suppressed LPS-induced IL-1ß expression. Conditioned medium of BV-2 cells stimulated by LPS significantly decreased cell viability of neuron (human neuroblastoma SH-SY5Y cells) compared with the absence of LPS. Conditioned medium of BV-2 cells stimulated by LPS in the presence of DBM 14-26 did not significantly decreased cell viability of neuron. These results indicate that microglial activation by LPS causes neuronal cell death and DBM 14-26 protect neuron through the inhibition of microglial activation. Functional regulation of microglia by DBM 14-26 could be a therapeutic candidate for the treatment of neurodegenerative diseases.
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Astrocitos/efectos de los fármacos , Chalconas/farmacología , Microglía/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo II/efectos de los fármacos , Animales , Astrocitos/metabolismo , Línea Celular , Citocinas/metabolismo , Lipopolisacáridos/farmacología , Microglía/metabolismo , Fármacos Neuroprotectores/farmacología , Óxido Nítrico Sintasa de Tipo II/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
The short D4Z4 repeat on chromosome 4q35 is a confirmatory genetic cause of facioscapulohumeral muscular dystrophy (FSHD), which presents with no renal complications. We herein report a five-year-old girl previously diagnosed with Coat's-like retinopathy, deafness, and mental retardation, who was found to have early-onset, severe FSHD. Despite the absence of muscle weakness, a Southern blot analysis showed a short D4Z4 repeat on chromosome 4q35. She presented with steroid-resistant nephrotic syndrome, and her renal histopathological findings were severe glomerular endothelial injury, which is a new complication associated with this genetic abnormality. Screening of renal complications may be necessary for FSHD patients. This patient requires close follow-up for her muscle symptoms.
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Cromosomas Humanos Par 4/genética , Endotelio Vascular/patología , Glomérulos Renales/patología , Distrofia Muscular Facioescapulohumeral/patología , Southern Blotting , Preescolar , Femenino , HumanosRESUMEN
Although carbapenem is the recommended for urinary tract infection (UTI) caused by extended-spectrum beta-lactamase (ESBL)-producing organisms, non-carbapenems have been reported to be effective for adult patients with UTI caused by ESBL-producing organisms. The purpose of this study was to evaluate the efficacy of non-carbapenems for pediatric patients with UTI due to ESBL-producing Escherichia coli (E. coli) based on the microbiologic and clinical outcomes. Fifteen children, who were treated for first febrile UTI caused by ESBL-producing E. coli were enrolled in this study. Antimicrobial susceptibilities and ESBL production were determined according to the Clinical and Laboratory Standards Institute guidelines. To detect CTX-M genes, polymerase chain reaction was performed with specific primers for blaCTX-M detection. Of the 15 enrolled patients, 10 (66.7%) were boys and 5 (33.3%) were girls, with a median age of four months. VUR was detected in six patients (40%). For detection of blaCTX-M by PCR, CTX-M-3, CTX-M-8, CTX-M-14, and CTX-M-15 were detected in five, one, eight, and one patient, respectively. Overall, 14 of the 15 isolates (93.3%) were susceptible for fosfomycin (FOM), and all isolates were susceptible for cefmetazole (CMZ), flomoxef (FMOX), and imipenem/cilastatin (IPM/CS). Of the 15 patients, 12 (80%) clinically improved without the use of carbapenems. In conclusion, even if isolates of ESBL-producing E. coli are multidrug resistant based on MIC assessment, clinical susceptibility to non-carbapenems, such as CMZ, FMOX, and FOM, is possible. Accordingly, carbapenems may not be required all the time for treatment of pediatric UTI in clinical practice.
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Antibacterianos/uso terapéutico , Carbapenémicos/uso terapéutico , Infecciones por Escherichia coli/tratamiento farmacológico , Escherichia coli , Infecciones Urinarias/tratamiento farmacológico , Preescolar , Infecciones por Escherichia coli/microbiología , Femenino , Fiebre , Humanos , Lactante , Japón/epidemiología , Masculino , Estudios Retrospectivos , Infecciones Urinarias/microbiología , beta-LactamasasRESUMEN
We developed a concise protocol for the synthesis of ellipticine quinone from the appropriate 3-iodoindole-2-carbaldehydes in four steps. The key step is the construction of carbazole-1,4-quinone through tandem Ring-Closing Metathesis (RCM) and dehydrogenation under oxygen atmosphere. Therefore, the ellipticine quinone analogs possessing substitution at the 8- and/or 9-positions were synthesized using this method. In total, 14 compounds were evaluated for antiproliferative activity against HCT-116 and HL-60 cell lines; 9-nitroellipticine quinone was found to have superior activity compared to calothrixin B.
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Antineoplásicos/farmacología , Benzoquinonas/farmacología , Elipticinas/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Benzoquinonas/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Elipticinas/química , Humanos , Estructura Molecular , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
BACKGROUND: The suitable dosage regime of mycophenolate mofetil (MMF) based on the pharmacokinetics of mycophenoric acid (MPA) for pediatric patients with idiopathic nephrotic syndrome (INS) is controversial. The pharmacokinetics of MPA is influenced by renal function, serum albumin concentration, and concomitant medications, especially calcineurin inhibitors. This study analyzed the pharmacokinetics of MPA in clinically stable children with INS receiving cyclosporine (CyA). METHODS: This retrospective study enrolled children with INS receiving MMF (Cellcept®) (30-40 mg/kg/day in two divided doses) combined with CyA (Neoral®) without relapse and renal dysfunction. Pharmacokinetic parameters, including the area under the concentration-time curve (AUC) calculated by the trapezoid method, were calculated from seven serial blood samples. RESULTS: Thirty-two patients (22 males) of median age 11.0 years were included; 32 pharmacokinetic studies were performed. The median MMF dose was 16.2 mg/kg/time or 470.4 mg/m2/time. The median AUC0-12 was 44.3 ng h/mL. AUC0-12 of all patients showed excellent correlations with C2 (r 2 = 0.6405, P < 0.0001), resulting in a regression formula of AUC0-12 = 21.971 + 2.6059 C2. Comparisons of dose/body weight-normalized AUC0-12 values among age groups showed a lower value in the youngest group (≤5 years). CONCLUSION: In children with clinically stable INS receiving CyA, C2 monitoring was the most useful single parameter for estimating MPA pharmacokinetics. Younger children required higher MMF doses.
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Inhibidores de la Calcineurina/administración & dosificación , Ciclosporina/administración & dosificación , Inmunosupresores/administración & dosificación , Inmunosupresores/farmacocinética , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/farmacocinética , Síndrome Nefrótico/tratamiento farmacológico , Adolescente , Factores de Edad , Área Bajo la Curva , Niño , Preescolar , Cálculo de Dosificación de Drogas , Quimioterapia Combinada , Femenino , Humanos , Inmunosupresores/sangre , Masculino , Ácido Micofenólico/sangre , Síndrome Nefrótico/sangre , Síndrome Nefrótico/diagnóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
We herein report a novel mutation in a Japanese family with an X-linked Alport syndrome (AS) mutation in COL4A5. Patient 1 was a 2-year-old Japanese girl. She and her mother (patient 2) had a history of proteinuria and hematuria without renal dysfunction, deafness, or ocular abnormalities. Pathological findings were consistent with AS, and a genetic analysis revealed that both patients had a heterozygous mutation (c.2767G>C) in exon 32. In summary, the identification of mutations and characteristic pathological findings was useful in making a diagnosis of AS. For a close long-term follow-up, the early detection and treatment of women with X-linked AS are important.