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1.
Cell ; 163(2): 367-80, 2015 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-26411289

RESUMEN

Intestinal Th17 cells are induced and accumulate in response to colonization with a subgroup of intestinal microbes such as segmented filamentous bacteria (SFB) and certain extracellular pathogens. Here, we show that adhesion of microbes to intestinal epithelial cells (ECs) is a critical cue for Th17 induction. Upon monocolonization of germ-free mice or rats with SFB indigenous to mice (M-SFB) or rats (R-SFB), M-SFB and R-SFB showed host-specific adhesion to small intestinal ECs, accompanied by host-specific induction of Th17 cells. Citrobacter rodentium and Escherichia coli O157 triggered similar Th17 responses, whereas adhesion-defective mutants of these microbes failed to do so. Moreover, a mixture of 20 bacterial strains, which were selected and isolated from fecal samples of a patient with ulcerative colitis on the basis of their ability to cause a robust induction of Th17 cells in the mouse colon, also exhibited EC-adhesive characteristics.


Asunto(s)
Adhesión Bacteriana , Citrobacter rodentium/fisiología , Infecciones por Enterobacteriaceae/inmunología , Infecciones por Escherichia coli/inmunología , Escherichia coli O157/fisiología , Mucosa Intestinal/inmunología , Células Th17/inmunología , Animales , Infecciones Bacterianas/inmunología , Células Epiteliales/inmunología , Células Epiteliales/microbiología , Células Epiteliales/ultraestructura , Heces/microbiología , Humanos , Inmunoglobulina A/inmunología , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos , Microscopía Electrónica de Rastreo , Ratas , Ratas Endogámicas F344 , Especificidad de la Especie
2.
Clin Exp Nephrol ; 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38734869

RESUMEN

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are major genetic polycystic kidney diseases that can progress to end-stage kidney disease (ESKD). Longitudinal data on the clinical characteristics associated with clinical outcomes in polycystic kidney disease (PKD), including the development of ESKD and cardiovascular disease (CVD) are lacking in Japan. To address this unmet need the authors are establishing a novel, web-based, Nationwide Cohort Registry Study-the Japanese Registry of PKD (JRP). METHODS: The JRP is a prospective cohort study for ADPKD (aim to recruit n = 1000 patients), and both a retrospective and prospective study for ARPKD (aim to recruit n = 100). In the prospective registry, patients will be followed-up for 10 years every 6 months and 12 months for patients with ADPKD and ARPKD, respectively. Data collection will be recorded on Research Electronic Data Capture (REDCap) starting on April 1, 2024, with recruitment ending on March 31, 2029. (jRCT 1030230618). RESULTS: Data to be collected include: baseline data, demographics, diagnostic and genetic information, radiological and laboratory findings, and therapeutic interventions. During follow-up, clinical events such as development of ESKD, hospitalization, occurrence of extra kidney complications including CVD events, and death will be recorded, as well as patient-reported health-related quality of life for patients with ADPKD. CONCLUSIONS: The JRP is the first nationwide registry study for patients with ADPKD and ARPKD in Japan, providing researchers with opportunities to advance knowledge and treatments for ADPKD and ARPKD, and to inform disease management and future clinical practice.

3.
Clin Exp Nephrol ; 27(10): 809-818, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37368094

RESUMEN

BACKGROUND: Clinical practice guidelines recommend antihypertensive and tolvaptan therapies for patients with autosomal dominant polycystic kidney disease (ADPKD) in Japan. However, tolvaptan therapy may pose an economic burden. The Japanese Ministry of Health, Labour and Welfare supports patients with intractable diseases. This study aimed to confirm the impact of the intractable disease system in Japan on the clinical treatment of ADPKD. METHODS: We analyzed the data of 3768 patients with ADPKD having a medical subsidy certificate from the Japanese Ministry of Health, Labour and Welfare in 2015-2016. The following quality indicators were use: the adherence rate to the 2014 clinical practice guideline for polycystic kidney disease (prescription rates of antihypertensive agents and tolvaptan in this cohort) and the number of Japanese patients with ADPKD nationwide started on renal replacement therapy in 2014 and 2020. RESULTS: Compared with new applications from 2015 to 2016, the prescription rates of antihypertensives and tolvaptan for the indicated patients at the 2017 renewal application increased by 2.0% (odds ratio = 1.41, p = 0.008) and 47.4% (odds ratio = 10.1, p > 0.001), respectively. These quality indicators improved with antihypertensive treatment, especially in patients with chronic kidney disease stages 1-2 (odds ratio = 1.79, p = 0.013) and in those aged < 50 years (odds ratio = 1.70, p = 0.003). The number of patients with ADPKD who were started on renal replacement therapy in Japan decreased from 999 in 2014 to 884 in 2020 in the nationwide database (odds ratio = 0.83, p < 0.001). CONCLUSIONS: The Japanese public intractable disease support system contributes to improvement of ADPKD treatment.


Asunto(s)
Riñón Poliquístico Autosómico Dominante , Humanos , Tolvaptán/uso terapéutico , Riñón Poliquístico Autosómico Dominante/diagnóstico , Riñón Poliquístico Autosómico Dominante/tratamiento farmacológico , Antagonistas de los Receptores de Hormonas Antidiuréticas/uso terapéutico , Japón/epidemiología , Antihipertensivos/uso terapéutico , Sistema de Registros
4.
Clin Exp Nephrol ; 26(9): 898-908, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35556186

RESUMEN

BACKGROUND: The prognosis of lupus nephritis (LN) has improved following the introduction of effective immunosuppressive therapy and progress in supportive care. This study examined recent renal and patient prognosis for adults with LN in Japan. METHODS: We conducted a nationwide retrospective cohort study of LN patients who received a renal biopsy between 2007 and 2012 that were registered in the Japan Renal Biopsy Registry. Of 623 registered adults with LN from 25 institutions and their affiliated or community hospitals, 489 were eligible for this study. RESULTS: The median age at renal biopsy was 39 years, and 82.2% of patients were female. Renal biopsies were performed in 348 patients with new-onset LN, 106 with relapse LN, and 35 with refractory LN. The distribution of ISN/RPS 2003 Classes was as follows: I 1.6%; II 5.3%; III (± V) 27.0%; IV (± V) 47.0%; V 18.4%; VI 0.6%. During the median observation period of 63.8 months, 36 patients (7.3%) reached a doubling of serum creatinine or end-stage kidney disease (ESKD), and 28 patients (5.7%) died. The 5 year renal and patient survival rates were 93.9% and 94.7%, respectively. Multivariate analysis revealed body mass index (BMI) and estimated glomerular filtration rate (eGFR) were independent risk factors for a doubling of serum creatinine in ESKD. Age and eGFR were independent risk factors for death. CONCLUSION: Recent prognosis for adults with LN are relatively good in Japan. Risk factors for impaired renal function are BMI and eGFR at renal biopsy, while age and eGFR are risk factors for death.


Asunto(s)
Fallo Renal Crónico , Nefritis Lúpica , Adulto , Biopsia/efectos adversos , Creatinina , Femenino , Humanos , Japón/epidemiología , Riñón , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/etiología , Fallo Renal Crónico/patología , Nefritis Lúpica/tratamiento farmacológico , Masculino , Pronóstico , Estudios Retrospectivos
5.
J Ind Microbiol Biotechnol ; 49(3)2022 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-34878143

RESUMEN

Cell-bound ß-glycosidases of basidiomycetous yeasts show promise as biocatalysts in galactooligosaccharide (GOS) production. Using degenerated primers designed from Hamamotoa singularis (Hs) bglA gene, we newly identified three genes that encode cell-bound ß-glycosidase from Sirobasidium magnum (Sm), Rhodotorula minuta (Rm), and Sterigmatomyces elviae (Se). These three genes, also named bglA, encoded family 1 glycosyl hydrolases with molecular masses of 67‒77 kDa. The BglA enzymes were approximately 44% identical to the Hs-BglA enzyme and possessed a unique domain at the N-terminus comprising 110 or 210 amino acids. The Sm-, Rm-, and Se-BglA enzymes as well as the Hs-BglA enzyme were successfully produced by recombinant Aspergillus oryzae, and all enzymes were entirely secreted to the supernatants. Furthermore, addition of some nonionic detergents (e.g. 0.4% [v/v] Triton-X) increased the production, especially of the Hs- or Se-BglA enzyme. Out of the BglA enzymes, the Se-BglA enzyme showed remarkable thermostability (∼70°C). Additionally, the Sm- and Se-BglA enzymes had better GOS yields, so there was less residual lactose than in others. Accordingly, the basidiomycetous BglA enzymes produced by recombinant A. oryzae would be applicable to GOS production, and the Se-BglA enzyme appeared to be the most promising enzyme for industrial uses.


Asunto(s)
Aspergillus oryzae , Glicósido Hidrolasas , Aspergillus oryzae/metabolismo , Lactosa/metabolismo , Oligosacáridos , beta-Glucosidasa/metabolismo
6.
Clin Exp Nephrol ; 24(4): 307-313, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31845065

RESUMEN

BACKGROUND: Hyperuricemia is a known risk factor for end-stage renal disease. Although xanthine oxidase (XO) inhibitors are expected to protect the kidney function, evidence to this end is insufficient at present. METHODS: This study was a multi-center, open-labeled, randomized study conducted in Mie Prefecture in Japan. Patients were included if they were between 20 and 80 years old and had a serum uric acid (sUA) level ≥ 7.0 mg/dl with or without gout, estimated glomerular filtration rate (eGFR) of 15-60 ml/min/1.73 m2, and urinary protein creatinine ratio (uPCR) of 0.15-3.5 g/gCr. Patients were randomly assigned to a Topiroxostat or Febuxostat group, and the treatment target for the sUA level was < 6.0 mg/dl. The primary outcome was the change in the uPCR after 24 weeks. RESULTS: The change in the median uPCR after 24 weeks was not statistically significant after treatment in the Topiroxostat or Febuxostat group (0.05 g/gCr and - 0.04 g/gCr, respectively). However, the sUA levels decreased significantly in both groups (Topiroxostat group: 8.6 ± 1.1 at baseline to 6.0 ± 1.1 mg/dl at 24 weeks, Febuxostat group: 8.4 ± 1.1 mg/dl at baseline to 5.9 ± 1.3 mg/dl at 24 weeks). No significant change in the eGFR after 24 weeks was noted in either the Topiroxostat or Febuxostat group (- 0.04 ± 4.59 ml/min/1.73 m2 and 0.31 ± 4.70 ml/min/1.73 m2, respectively). CONCLUSIONS: In this study, XO inhibitors did not significantly reduce the uPCR in chronic kidney disease stage 3 and 4 patients with hyperuricemia.


Asunto(s)
Febuxostat/uso terapéutico , Hiperuricemia/tratamiento farmacológico , Nitrilos/uso terapéutico , Piridinas/uso terapéutico , Insuficiencia Renal Crónica/complicaciones , Xantina Oxidasa/antagonistas & inhibidores , Anciano , Creatinina/orina , Febuxostat/farmacología , Femenino , Humanos , Hiperuricemia/complicaciones , Masculino , Persona de Mediana Edad , Nitrilos/farmacología , Piridinas/farmacología , Insuficiencia Renal Crónica/orina
8.
Clin Exp Nephrol ; 24(5): 389-401, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32189101

RESUMEN

BACKGROUND: Practice patterns and bleeding complications of percutaneous native kidney biopsy (PNKB) have not recently been investigated and the Japanese Society of Nephrology performed a nationwide questionnaire survey in 2018. METHODS: The survey consisted of nine sections about PNKB: (1) general indications; (2) indications for high-risk patients; (3) informed consent; (4) pre-biopsy evaluation; (5) procedures; (6) sedation; (7) post-biopsy hemostasis, bed rest, and examinations; (8) bleeding complications; and (9) specimen processing. A supplementary survey examined bleeding requiring transcatheter arterial embolization (TAE). RESULTS: Overall, 220 directors of facilities (nephrology facility [NF], 168; pediatric nephrology facility [PF], 52) completed the survey. Indications, procedures, and monitoring protocols varied across facilities. Median lengths of hospital stay were 5 days in NFs and 6 days in PFs. Gauge 14, 16, 18 needles were used in 5%, 56%, 33% in NFs and 0%, 63%, 64% in PFs. Mean limits of needle passes were 5 in NFs and 4 in PFs. The bed rest period was 16-24 h in 60% of NFs and 65% of PFs. Based on 17,342 PNKBs, incidence rates of macroscopic hematuria, erythrocyte transfusion, and TAE were 3.1% (NF, 2.8%; PF, 6.2%), 0.7% (NF, 0.8%; PF, 0%), and 0.2% (NF, 0.2%; PF, 0.06%), respectively. Forty-six percent of facilities processed specimens all for light microscopy, immunofluorescence, and electron microscopy, and 21% processed for light microscopy only. Timing of bleeding requiring TAE varied among PNKB cases. CONCLUSION: Wide variations in practice patterns of PNKB existed among facilities, while PNKBs were performed as safely as previously reported.


Asunto(s)
Biopsia/efectos adversos , Embolización Terapéutica/estadística & datos numéricos , Instituciones de Salud/estadística & datos numéricos , Riñón/patología , Hemorragia Posoperatoria/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia/instrumentación , Biopsia/métodos , Niño , Preescolar , Transfusión de Eritrocitos/estadística & datos numéricos , Femenino , Hematuria/etiología , Humanos , Lactante , Recién Nacido , Consentimiento Informado/estadística & datos numéricos , Japón , Tiempo de Internación/estadística & datos numéricos , Masculino , Microscopía Electrónica/estadística & datos numéricos , Persona de Mediana Edad , Agujas/estadística & datos numéricos , Nefrología/estadística & datos numéricos , Política Organizacional , Selección de Paciente , Pediatría/estadística & datos numéricos , Hemorragia Posoperatoria/etiología , Cuidados Preoperatorios , Encuestas y Cuestionarios , Adulto Joven
9.
Artículo en Japonés | MEDLINE | ID: mdl-32963140

RESUMEN

It is important to optimize the exposure dose when conducting interventional radiology, but optimization is difficult for medical centers to achieve independently. In 2005, we administered a questionnaire on the measurement of dose rates and awareness of exposure reduction when performing percutaneous coronary intervention. Ten years later, we conducted a follow-up survey of the same 31 centers to determine the current situation and identify trends. The results of the survey showed that the mean fluoroscopy dose rate decreased to 55% of the 2005 value, from 28.2 to 15.6 mGy/min, and the mean radiography dose rate decreased to 71% of the 2005 value, from 4.2 to 3.0 mGy/s. Dose rates for both fluoroscopy and radiography decreased by 84% of facilities. The results also indicated greater cooperation by physicians compared to 10 years ago. In particular, there was a considerable increase in the exchange of ideas with physicians regarding exposure, suggesting a stronger level of interest in exposure. The overall score for questionnaire items was 33% higher than that in the previous survey. These results show that in the past 10 years, awareness of exposure reduction has improved, and dose optimization has been a major factor in the downward trend in dose rates in radiography and fluoroscopy.


Asunto(s)
Intervención Coronaria Percutánea , Radiografía Intervencional , Angiografía Coronaria , Fluoroscopía , Estudios de Seguimiento , Dosis de Radiación , Encuestas y Cuestionarios , Rayos X
11.
Clin Exp Hypertens ; 41(1): 92-99, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-29584458

RESUMEN

BACKGROUND: Intradialytic hypertension (HTN), which is one of the poor prognostic markers in patients undergoing hemodialysis, may be associated with sympathetic overactivity. The L/N-type calcium channel blocker, cilnidipine, has been reported to suppress sympathetic nerves activity in vivo. Therefore, we hypothesized that cilnidipine could attenuate intradialytic systolic blood pressure (SBP) elevation. METHODS: Fifty-one patients on chronic hemodialysis who had intradialytic-HTN (SBP elevation ≥10 mmHg during hemodialysis) and no fluid overload were prospectively randomized into two groups: control and cilnidipine groups. Cilnidipine group patients took cilnidipine (10 mg/day) for 12 weeks. The primary endpoint was the change in the intradialytic SBP elevation before and after the 12-week intervention. RESULTS: Before the intervention, no differences were observed in age, sex or pre-dialytic SBP (148.5 ± 12.9 vs. 148.3 ± 19.3 mmHg) between the two groups. Intradialytic SBP elevation was unchanged in the control group. Cilnidipine significantly lowered the post-dialytic SBP with an attenuation of the intradialytic SBP elevation from 12.0 ± 15.4 mmHg to 4.8 ± 10.1 mmHg. However, the observed difference in the intradialytic SBP elevation by cilnidipine did not reach statistical significance (group×time interaction effect p = 0.25). Cathecolamine levels were unaffected by the intervention in both groups. CONCLUSION: Cilnidipine lowers both the pre- and post-dialytic SBP and might attenuate intradialytic SBP elevation. Therefore, cilnidipine may be effective in lowering SBP during HD in patients with intradialytic-HTN.


Asunto(s)
Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/uso terapéutico , Dihidropiridinas/uso terapéutico , Hipertensión/tratamiento farmacológico , Anciano , Canales de Calcio Tipo L , Canales de Calcio Tipo N , Catecolaminas/sangre , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Masculino , Estudios Prospectivos , Diálisis Renal , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/terapia , Sistema Nervioso Simpático/fisiopatología , Sístole
12.
Int Heart J ; 60(5): 1211-1218, 2019 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-31484857

RESUMEN

Extra- and/or intracorporeal renal replacement therapy can improve the cardiorenal hemodynamics in patients with advanced heart failure (HF) refractory to medical therapy and renal failure. Here, we report the case of a 51-year-old woman with inotrope-dependent end-stage HF and chronic renal failure due to anthracycline-induced cardiomyopathy, in whom the induction of hemodiafiltration and subsequent chronic peritoneal dialysis (PD) provided a dramatic improvement of her cardiac hemodynamics from restrictive to almost normal physiology assessed by echocardiography and cardiac catheterization. The patient returned to office work with New York Heart Association functional class I-II symptoms for at least 3 years with continuous ambulatory PD after hospital discharge.


Asunto(s)
Síndrome Cardiorrenal/terapia , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/diagnóstico por imagen , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Diálisis Peritoneal/métodos , Antraciclinas/efectos adversos , Antraciclinas/uso terapéutico , Biopsia con Aguja , Síndrome Cardiorrenal/diagnóstico por imagen , Enfermedad Crónica , Progresión de la Enfermedad , Ecocardiografía Doppler/métodos , Electrocardiografía/métodos , Femenino , Insuficiencia Cardíaca/terapia , Hemodiafiltración/métodos , Hemodinámica/fisiología , Humanos , Inmunohistoquímica , Fallo Renal Crónico/diagnóstico , Persona de Mediana Edad , Pronóstico , Reinserción al Trabajo , Resultado del Tratamiento
13.
BMC Microbiol ; 18(1): 209, 2018 12 12.
Artículo en Inglés | MEDLINE | ID: mdl-30541439

RESUMEN

BACKGROUND: The importance of the gut microbiota at the early stage of life and their longitudinal effect on host health have recently been well investigated. In particular, Bifidobacterium longum subsp. longum, a common component of infant gut microbiota, appears in the gut shortly after birth and can be detected there throughout an individual's lifespan. However, it remains unclear whether this species colonizes in the gut over the long term from early infancy. Here, we investigated the long-term colonization of B. longum subsp. longum by comparing the genotypes of isolates obtained at different time points from individual subjects. Strains were isolated over time from the feces of 12 subjects followed from early infancy (the first six months of life) up to childhood (approximately six years of age). We also considered whether the strains were transmitted from their mothers' perinatal samples (prenatal feces and postnatal breast milk). RESULTS: Intra-species diversity of B. longum subsp. longum was observed in some subjects' fecal samples collected in early infancy and childhood, as well as in the prenatal fecal samples of their mothers. Among the highlighted strains, several were confirmed to colonize and persist in single individuals from as early as 90 days of age for more than six years; these were classified as long-term colonizers. One of the long-term colonizers was also detected from the corresponding mother's postnatal breast milk. Quantitative polymerase chain reaction data suggested that these long-term colonizers persisted in the subjects' gut despite the existence of the other predominant species of Bifidobacterium. CONCLUSIONS: Our results showed that several strains belonging to B. longum subsp. longum colonized in the human gut from early infancy through more than six years, confirming the existence of long-term colonizers from this period. Moreover, the results suggested that these strains persisted in the subjects' gut while co-existing with the other predominant bifidobacterial species. Our findings also suggested the importance of microbial-strain colonization in early infancy relative to their succession and showed the possibility that probiotics targeting infants might have longitudinal effects. TRIAL REGISTRATION: TRN: ISRCTN25216339 . Date of registration: 11/03/2016. Prospectively registered.


Asunto(s)
Bifidobacterium longum/crecimiento & desarrollo , Bifidobacterium longum/aislamiento & purificación , Microbioma Gastrointestinal , Intestinos/microbiología , Adulto , Bifidobacterium longum/clasificación , Bifidobacterium longum/genética , Niño , Preescolar , Heces/microbiología , Femenino , Humanos , Lactante , Masculino , Leche Humana/microbiología , Madres , Filogenia
14.
Circ J ; 82(2): 586-595, 2018 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-29093429

RESUMEN

BACKGROUND: The aim of this study was to assess the echocardiographic characteristics of chronic hemodialysis (HD) patients with end-stage renal disease (ESRD) in a multicenter prospective cohort study.Methods and Results:Three hundred and fifteen patients with ESRD (67.9±10.6 years, 47.6% male) on chronic HD for ≥1 year were examined on transthoracic echocardiography, including Doppler-derived aortic valve area (AVA) measurement. Only 11.5% and 3.4% of all patients had normal left ventricular (LV) geometry and normal LV filling pattern, respectively. The majority of patients had aortic and mitral valvular calcification, and approximately 50% of all 315 patients had aortic valve narrowing with AVA <2.0 cm2. Patients were divided into 3 groups according to AVA index tertile: group 1, highest tertile; group 2, middle tertile; and group 3, lowest tertile. Group 3 was older, had a greater cardiothoracic ratio on chest X-ray, higher plasma brain natriuretic peptide and total LV afterload, and lower stroke volume index than the other 2 groups. Age and intact parathyroid hormone (PTH) level were independently associated with low AVA index. CONCLUSIONS: Patients with ESRD on chronic HD have a high prevalence of cardiac structural and functional abnormalities including calcified aortic sclerosis. High age and PTH were associated with aortic valve narrowing in these patients.


Asunto(s)
Ecocardiografía/métodos , Cardiopatías Congénitas/diagnóstico por imagen , Fallo Renal Crónico/complicaciones , Diálisis Renal , Anciano , Estenosis de la Válvula Aórtica , Calcinosis , Humanos , Persona de Mediana Edad , Válvula Mitral/patología , Hormona Paratiroidea/sangre , Estudios Prospectivos , Factores de Riesgo , Función Ventricular Izquierda
15.
Artif Organs ; 42(6): E90-E101, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29473183

RESUMEN

In vitro biocompatibility assessments that consider physiologically appropriate conditions of cell exposure to peritoneal dialysis fluids (PDFs) are still awaited. In this study, we found that fragmentation of Golgi apparatus occurred in a pH-dependent manner within 30-min exposure to five distinct commercially available PDFs, which showed no marked difference in their effects on cell viability in the conventional MTT assay. Fluorescence microscopy analysis of labeling antibody against cis-Golgi protein GM130 indicated that the stacked cisternal structure was maintained in the perinuclear area of both M199 culture medium and a neutral-pH PDF groups. However, this specific structure became partially disassembled over time even in a neutral-pH PDF, and fragmentation was markedly enhanced in cells exposed to neutralized-pH PDFs in correspondence with their intracellular pH; moreover, in acidic PDFs, Golgi staining was diffuse and scattered in the entire cytoplasm and showed partial aggregation. The Golgi fragmentation markedly observed with the neutralized PDFs could be reversed by replacing either the media with a neutral-pH medium or a mixture of PDF and PD effluent (PDF) in a gradient manner mimicking clinical conditions. Furthermore, although weaker than pH effect, notable effects of other PDF-related factors were also observed after 30-min exposure to pH-adjusted PDFs. Lastly, the results of studies conducted using MAPK/SAPK inhibitors indicated that the mechanism underlying the Golgi fragmentation described here differs from that associated with the fragmentation that occurs at the G2/M checkpoint in the cell cycle. We conclude that Golgi fragmentation is suitable for rapid biocompatibility assessment of PDF not only because of its strong pH dependence but also because the fragmentation is recognizably affected by PDF constituents.


Asunto(s)
Soluciones para Diálisis/efectos adversos , Aparato de Golgi/patología , Diálisis Peritoneal/efectos adversos , Línea Celular , Supervivencia Celular , Soluciones para Diálisis/química , Puntos de Control de la Fase G2 del Ciclo Celular , Aparato de Golgi/ultraestructura , Humanos , Concentración de Iones de Hidrógeno , Puntos de Control de la Fase M del Ciclo Celular , Concentración Osmolar
16.
BMC Nephrol ; 19(1): 162, 2018 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-29973143

RESUMEN

BACKGROUND: While the majority of adult-onset minimal change nephrotic syndrome (MCNS) is a primary or an idiopathic form of disease, it can also occur as a secondary form. Reports on the spontaneous remission of MCNS are rare since the condition is typically treated with corticosteroids. We herein describe the spontaneous remission of adult-onset MCNS in a patient who developed nephrotic syndrome after type B influenza infection. CASE PRESENTATION: A 50-year-old woman experienced fever, cough, malaise, and low back pain, which had persisted for 6 days before she presented to our hospital, and edema of the face and limbs, which had persisted for 5 days before her presentation. She was diagnosed with type B influenza infection and later exhibited an exacerbation of facial edema, decreased urine output, and a high level of proteinuria. She was referred to our department after the diagnosis of nephrotic syndrome. On admission, her proteinuria level was 20.88 g/gCr and her selectivity index value was 0.13. The examination of a kidney biopsy specimen obtained on the fourth day of hospitalization under a light microscope revealed minor abnormalities. An immunofluorescence showed only nonspecific granular IgM deposits in the mesangium. Electron microscopy showed extensive foot process effacement without any immune complex deposits. Based on these findings, the patient was diagnosed with MCNS. After admission, the proteinuria decreased to 0.06 g/gCr with rest and sodium restriction (6 g/day) alone; a complete remission from nephrotic syndrome was observed at approximately 2 weeks after the onset of symptoms. There have been no signs of recurrence of nephrotic syndrome in the one years since. CONCLUSION: We experienced a rare case in which spontaneous remission of MCNS occurred within a short period of 2 weeks after influenza B infection. When patients present with nephrotic syndrome after an infection, it is necessary to consider MCNS in the differential diagnosis, which also includes post-infectious glomerulonephritis and the acute exacerbation of IgA nephropathy.


Asunto(s)
Virus de la Influenza B , Gripe Humana/diagnóstico , Síndrome Nefrótico/diagnóstico , Remisión Espontánea , Femenino , Humanos , Gripe Humana/complicaciones , Persona de Mediana Edad , Síndrome Nefrótico/complicaciones
17.
BMC Nephrol ; 19(1): 363, 2018 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-30558557

RESUMEN

BACKGROUND: Although the renal toxicity of Deferasirox, an oral iron chelator, has been reported to be mild, there have been reports of acute interstitial nephritis or Fanconi syndrome due to this agent. Thin basement membrane disease (TBMD) is a hereditary disease characterized primarily by hematuria, with gross hematuria also observed in about 7% of cases. We herein report a case of TBMD that presented with acute kidney injury and gross hematuria during treatment with Deferasirox. CASE PRESENTATION: The patient was a 63-year-old man who had been diagnosed with myelodysplastic syndrome 6 years ago. He had started taking Deferasirox at 125 mg due to post-transfusion iron overload 6 months ago. Deferasirox was then increased to 1000 mg three months ago. When the serum creatinine level increased, Deferasirox was reduced to 500 mg three weeks before hospitalization. Although the serum creatinine level decreased once, he developed a fever and macroscopic hematuria one week before hospitalization. The serum creatinine level increased again, and Deferasirox was stopped four days before hospitalization. He was admitted for the evaluation of acute kidney injury and gross hematuria. Treatment with temporary hemodialysis was required, and a kidney biopsy was performed on the eighth day of admission. Although there was no major abnormality in the glomeruli, the leakage of red blood cells into the Bowman's space was observed. Erythrocyte cast formation was observed in the tubular lumen, which was associated with acute tubular necrosis. The results of an electron microscopic study were compatible with TBMD. CONCLUSION: Although Deferasirox is known to be nephrotoxic, gross hematuria is relatively rare. When we encounter a case of acute kidney injury with gross hematuria during treatment with Deferasirox, TBMD should be considered as a possible cause of gross hematuria.


Asunto(s)
Lesión Renal Aguda/etiología , Deferasirox/efectos adversos , Membrana Basal Glomerular/patología , Hematuria/etiología , Quelantes del Hierro/efectos adversos , Túbulos Renales/patología , Diagnóstico Diferencial , Humanos , Masculino , Persona de Mediana Edad , Necrosis/diagnóstico
18.
BMC Nephrol ; 18(1): 348, 2017 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-29197349

RESUMEN

BACKGROUND: Renal failure due to the infiltration of chronic lymphocytic leukemia (CLL) cells into the tubulointerstitial area of the kidney is uncommon. Furthermore, granulomatous interstitial nephritis (GIN) is a rare histological diagnosis in patients undergoing a renal biopsy. We herein report a case of GIN due to the diffuse infiltration of CLL cells in a patient who developed progressive renal failure. CASE PRESENTATION: The patient was a 55-year-old man who had been diagnosed with CLL 4 years earlier and who had been followed up without treatment. Although his serum creatinine level had remained normal for three and a half years, it started to increase in the six months prior to his presentation. A urinalysis showed mild proteinuria without any hematuria at the time of presentation. A renal biopsy revealed the diffuse infiltration of CLL cells into the tubulointerstitial area with non-caseating epithelioid cell granulomas. Despite cyclophosphamide treatment, his renal function did not improve, and he ultimately required maintenance hemodialysis. CONCLUSION: When progressive renal failure is combined with CLL, GIN due to the direct infiltration of CLL cells should be considered as a differential diagnosis.


Asunto(s)
Leucemia Linfocítica Crónica de Células B/sangre , Leucemia Linfocítica Crónica de Células B/diagnóstico , Nefritis Intersticial/sangre , Nefritis Intersticial/diagnóstico , Humanos , Leucemia Linfocítica Crónica de Células B/complicaciones , Masculino , Persona de Mediana Edad , Nefritis Intersticial/etiología
19.
Appl Environ Microbiol ; 82(19): 5806-14, 2016 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-27451451

RESUMEN

UNLABELLED: Asymptomatic infant carriers of toxigenic Clostridium difficile are suggested to play a role in the transmission of C. difficile infection (CDI) in adults. However, the mode of C. difficile carriage in infants remains to be fully elucidated. We investigated longitudinal changes in carriage rates, counts, and strain types of toxigenic C. difficile in infants. Stools collected from 111 healthy infants in Belgium periodically from birth until the age of 6 months were examined by quantitative PCR targeting 16S rRNA and toxin genes. Toxigenic C. difficile was detected in 18 of 111 infants (16%) in the period up to the age of 6 months. The carriage rate of toxigenic C. difficile remained below 5% until the age of 3 months. The carriage rate increased to 13% 1 week after weaning (average age, 143 days) and reached 16% at the age of 6 months. Counts of toxigenic C. difficile bacteria ranged from 10(4) to 10(8) cells/g of stool. Notably, two infants retained >10(8) cells/g of stool for at least several weeks. Average counts in the 18 infants hovered around 10(7) cells/g of stool from the age of 3 days until the age of 6 months, showing no age-related trend. Genotyping of toxigenic C. difficile isolates from the 18 infants revealed that 11 infants each retained a particular monophyletic strain for at least a month. The genotype most frequently identified was the same as that frequently identified in symptomatic adult CDI patients. Thus, toxigenic C. difficile strains-potential causes of CDI in adults-colonized the infants' intestines. IMPORTANCE: Our study provides longitudinal data on counts and strain types of toxigenic C. difficile in infants. We found that considerable numbers of toxigenic C. difficile bacteria colonized the infants' intestines. The results of strain typing suggest that toxigenic C. difficile carried by healthy infants could be potentially pathogenic to adults. These results and findings are informative not only for ecological studies but also for efforts to prevent or control the spread of CDI in adults.


Asunto(s)
Portador Sano/epidemiología , Clostridioides difficile/fisiología , Genotipo , Toxinas Bacterianas/genética , Bélgica/epidemiología , Portador Sano/microbiología , Clostridioides difficile/clasificación , Clostridioides difficile/genética , Recuento de Colonia Microbiana , Electroforesis Capilar , Heces/microbiología , Femenino , Humanos , Lactante , Recién Nacido , Estudios Longitudinales , Masculino , ARN Ribosómico 16S/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Tiempo
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