Transforming growth factor (TGF)-β has been associated with podocyte injury; we have examined its effect on podocyte bioenergetics. We studied transformed mouse podocytes, exposed to TGF-β1, using a ...label-free assay system, Seahorse XF24, which measures oxygen consumption rates (OCR) and extracellular acidification rates (ECAR). Both basal OCR and ATP generation-coupled OCR were significantly higher in podocytes exposed to 0.3-10 ng/ml of TGF-β1 for 24, 48, and 72 h. TGF-β1 (3 ng/ml) increased oxidative capacity 75%, and 96% relative to control after 48 and 72 h, respectively. ATP content was increased 19% and 30% relative to control after a 48- and 72-h exposure, respectively. Under conditions of maximal mitochondrial function, TGF-β1 increased palmitate-driven OCR by 49%. Thus, TGF-β1 increases mitochondrial oxygen consumption and ATP generation in the presence of diverse energy substrates. TGF-β1 did not increase cell number or mitochondrial DNA copy number but did increase mitochondrial membrane potential (MMP), which could explain the OCR increase. Reactive oxygen species (ROS) increased by 32% after TGF-β1 exposure for 48 h. TGF-β activated the mammalian target of rapamycin (mTOR) pathway, and rapamycin reduced the TGF-β1-stimulated increases in OCR, ECAR, ATP generation, cellular metabolic activity, and protein generation. Our data suggest that TGF-β1, acting, in part, via mTOR, increases mitochondrial MMP and OCR, resulting in increased ROS generation and that this may contribute to podocyte injury.
Alport syndrome (AS) is a progressive hereditary renal disease that is characterized by sensorineural hearing loss and ocular abnormalities. It is divided into three modes of inheritance, namely, ...X-linked Alport syndrome (XLAS), autosomal recessive AS (ARAS), and autosomal dominant AS (ADAS). XLAS is caused by pathogenic variants in
COL4A5
, while ADAS and ARAS are caused by those in
COL4A3
/
COL4A4
. Diagnosis is conventionally made pathologically, but recent advances in comprehensive genetic analysis have enabled genetic testing to be performed for the diagnosis of AS as first-line diagnosis. Because of these advances, substantial information about the genetics of AS has been obtained and the genetic background of this disease has been revealed, including genotype–phenotype correlations and mechanisms of onset in some male XLAS cases that lead to milder phenotypes of late-onset end-stage renal disease (ESRD). There is currently no radical therapy for AS and treatment is only performed to delay progression to ESRD using nephron-protective drugs. Angiotensin-converting enzyme inhibitors can remarkably delay the development of ESRD. Recently, some new drugs for this disease have entered clinical trials or been developed in laboratories. In this article, we review the diagnostic strategy, genotype–phenotype correlation, mechanisms of onset of milder phenotypes, and treatment of AS, among others.
Herein, we report the case of an adolescent patient with nephrotic-range proteinuria and hypoproteinemia caused by tiopronin. The patient was a 13-year-old adolescent girl who had been diagnosed with ...cystinuria at the age of 9-years. Initial treatment comprised urinary alkalization and tiopronin. Urinalysis showed 3+ proteinuria 43 months after the initiation of tiopronin treatment. Proteinuria was accompanied by 2.2 g/dL of hypoalbuminemia, hyperlipidemia, and high adiponectin levels. Considering the adverse effects of tiopronin, it was immediately withdrawn. Ten days after withdrawal of the drug, proteinuria and hypoproteinemia had completely resolved, and steroid therapy was therefore not required. These findings are consistent with those of nephrotic syndrome secondary to medication in our patient. Tiopronin, which is a common treatment for cystinuria, may cause nephrotic-range proteinuria and hypoproteinemia. Therefore, periodic urine analyses and patient follow-ups are warranted during tiopronin therapy for cystinuria.
•A fully non-contact medical radar-based vital sign monitoring system was developed for neonatal monitoring at an NICU.•An advanced signal processing algorithm to estimate respiration and cardiac ...peaks in time-series were proposed and implemented in the system.•The proposed system introduces a novel approach for NICU monitoring.
Continuous monitoring of vital signs plays a pivotal role in neonatal intensive care units (NICUs). In this paper, we present a system for monitoring fully non-contact medical radar-based vital signs to measure the respiratory rate (RR), heart rate (HR), I:E ratio, and heart rate variability (HRV). In addition, we evaluated its performance in a physiological laboratory and examined its adaptability in an NICU.
A non-contact medical radar-based vital sign monitoring system that includes 24 GHz radar installed in an incubator was developed. To enable reliable monitoring, an advanced signal processing algorithm (i.e., a nonlinear filter to separate respiration and heartbeat signals from the output of radar), template matching to extract cardiac peaks, and an adaptive peak detection algorithm to estimate cardiac peaks in time-series were proposed and implemented in the system. Nine healthy subjects comprising five males and four females (24 ± 5 years) participated in the laboratory test. To evaluate the adaptability of the system in an NICU setting, we tested it with three hospitalized infants, including two neonates.
The results indicate strong agreement in healthy subjects between the non-contact system and reference contact devices for RR, HR, and inter-beat interval (IBI) measurement, with correlation coefficients of 0.83, 0.96, and 0.94, respectively. As anticipated, the template matching and adaptive peak detection algorithms outperformed the conventional approach. These showed a more accurate IBI close to the reference Bland–Altman analysis (proposed: bias of -3 ms, and 95% limits of agreement ranging from -73 to 67 ms; conventional: bias of -11 ms, and 95% limits of agreement ranging from -229 to 207 ms). Moreover, in the NICU clinical setting, the IBI correlation coefficient and 95% limit of agreement in the conventional method are 0.31 and 91 ms. The corresponding values obtained using the proposed method are 0.93 and 21 ms.
The proposed system introduces a novel approach for NICU monitoring using a non-contact medical radar sensor. The signal processing method combining cardiac peak extraction algorithm with the adaptive peak detection algorithm shows high adaptability in detecting IBI the time series in various application settings.
Bioenergetic characterization of mouse podocytes Abe, Yoshifusa; Sakairi, Toru; Kajiyama, Hiroshi ...
American Journal of Physiology: Cell Physiology,
08/2010, Letnik:
299, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Mitochondrial dysfunction contributes to podocyte injury, but normal podocyte bioenergetics have not been characterized. We measured oxygen consumption rates (OCR) and extracellular acidification ...rates (ECAR), using a transformed mouse podocyte cell line and the Seahorse Bioscience XF24 Extracellular Flux Analyzer. Basal OCR and ECAR were 55.2 +/- 9.9 pmol/min and 3.1 +/- 1.9 milli-pH units/min, respectively. The complex V inhibitor oligomycin reduced OCR to approximately 45% of baseline rates, indicating that approximately 55% of cellular oxygen consumption was coupled to ATP synthesis. Rotenone, a complex I inhibitor, reduced OCR to approximately 25% of the baseline rates, suggesting that mitochondrial respiration accounted for approximately 75% of the total cellular respiration. Thus approximately 75% of mitochondrial respiration was coupled to ATP synthesis and approximately 25% was accounted for by proton leak. Carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), which uncouples electron transport from ATP generation, increased OCR and ECAR to approximately 360% and 840% of control levels. FCCP plus rotenone reduced ATP content by 60%, the glycolysis inhibitor 2-deoxyglucose reduced ATP by 35%, and 2-deoxyglucose in combination with FCCP or rotenone reduced ATP by >85%. The lactate dehydrogenase inhibitor oxamate and 2-deoxyglucose did not reduce ECAR, and 2-deoxyglucose had no effect on OCR, although 2-deoxyglucose reduced ATP content by 25%. Mitochondrial uncoupling induced by FCCP was associated with increased OCR with certain substrates, including lactate, glucose, pyruvate, and palmitate. Replication of these experiments in primary mouse podocytes yielded similar data. We conclude that mitochondria play the primary role in maintaining podocyte energy homeostasis, while glycolysis makes a lesser contribution.
Respiratory rate (RR) is known to be a more accurate predictor of clinical deterioration than other vital signs. However, there were few respiration measurement devices certified as medical devices ...that could be used in daily clinical settings. Therefore, using a bult‐in microcontroller (72×57×12 mm) instead of a personal computer, we developed a portable stand‐alone respiration measurement device with minimum workload in computing that can be used for non‐contact measurement in 30 s using a Doppler radar. In this study, the problems of respiration measurement using a Doppler radar, such as miscounting of respiratory peaks were clarified, and proposed device with respiratory peaks miscount prevention algorithm achieved high accuracy RR measurement. Clinical testing was conducted on pediatric outpatients of Children's Medical Center, Showa University Koto Toyosu Hospital. The measurement accuracy of the system was confirmed to be comparable to the respiration measurement accuracy of stationary certified medical devices used in hospital, such as capnometers and the chest wall impedance method used in bedside monitors.
IntroductionRenin-angiotensin system (RAS) plays a key role in various types of cardiovascular disease and many kinds of RAS inhibitors have been developed. The effect of discontinuation of RAS ...inhibitors on clinical outcomes is still controversial. This study aims to evaluate the effects of discontinuing RAS inhibitor medication on the clinical outcomes of patients continuously taking these agents.Methods and analysisThis article presents a systematic review protocol described in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. We will include randomised controlled trials in which the effects of RAS inhibitor withdrawal were evaluated. Initially, four authors will search for eligible studies in MEDLINE, EMBASE, the Cochrane Database Trial Register, European trial registry and ClinicalTrials.gov. Abstracts and full-text screenings will be performed by the four authors with data extraction performed by each author independently. We will include patients taking RAS inhibitors—including ACE inhibitor, angiotensin receptor blocker and angiotensin receptor neprilysin inhibitor and exclude the patients undergoing renal replacement therapy (RRT), adolescents (under 18 years of age) and patients with acute infectious diseases. Our search will be performed on 1 May 2023. Studies in which the patients discontinued RAS inhibitors due to any reason will be included. Patients who continuously took RAS inhibitors under conditions in which the intervention group discontinued these agents will be considered eligible as the comparison group. Death (any cause), Death (cardiovascular disease (CVD)) and CVD events will be set as primary outcomes. Secondary outcomes will be set as RRT, acute kidney injury, renal function (analysis of the change in estimated glomerular filtration rate), hyperkalaemia, proteinuria and blood pressure.Ethics and disseminationResearch ethics approval was not required in this study due to it being a systematic review, and any data belonging to individuals cannot be identified. The results of this study will be disseminated through peer-reviewed journals and conferences.Trial registration numberPROSPERO CRD42022300777.
The patient in this study was a healthy 9-month-old infant who was admitted to our hospital with fever. He had a 5-days's history of fever prior to admission and experienced movement restrictions of ...the right hip the day before he was referred to our hospital.Blood tests revealed leukocytosis (2,4850/μL) and elevated serum C-reactive protein levels (6.43mg/dL). T2-weighted magnetic resonance images of the lower limb showed a high signal intensity in the distal aspect of the right tibia. Methicillin-sensitive Staphylococcus aureus was isolated on blood culture. After a confirmed diagnosis of a right tibial osteomyelitis, the patient was treated with intravenous cefazolin (100mg/kg/day) and oral cephalexin (100mg/kg/day) for 57 days. In our patient, the fever preceded local symptoms such as abnormal posture, impaired movements, and redness and swelling of the right ankle joint, which should be helpful for early detection of tibial osteomyelitis. Specifically, in Japan, there are few reported cases of infants with tibial osteomyelitis. However, in some of these cases, fever occurs as the presenting symptom, without local symptoms at onset. Therefore, repeated and detailed systemic examinations are essential to avoid overlooking osteomyelitis in children.
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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