Introduction: Diabetic kidney disease (DKD) is a common cause of chronic kidney disease with around 25-40% of patients with diabetes being affected. The course of DKD is variable, and estimated glomerular filtration rate (eGFR) and albuminuria, the currently used clinical markers, are not able to accurately predict the individual disease trajectory, in particular in early stages of the disease. The aim of this study was to assess the association of urine levels of selected protein biomarkers with the progression of DKD at an early stage of disease.
View Article and Find Full Text PDFBACKGROUNDIn type 1 diabetes (T1D), impaired insulin sensitivity may contribute to the development of diabetic kidney disease (DKD) through alterations in kidney oxidative metabolism.METHODSYoung adults with T1D (n = 30) and healthy controls (HCs) (n = 20) underwent hyperinsulinemic-euglycemic clamp studies, MRI, 11C-acetate PET, kidney biopsies, single-cell RNA-Seq, and spatial metabolomics to assess this relationship.RESULTSParticipants with T1D had significantly higher glomerular basement membrane (GBM) thickness compared with HCs.
View Article and Find Full Text PDFUnderlying molecular mechanisms of the kidney protective effects of sodium glucose co-transporter 2 (SGLT2) inhibitors are not fully elucidated. Therefore, we studied the association between urinary epidermal growth factor (uEGF), a mitogenic factor involved in kidney repair, and kidney outcomes in patients with type 2 diabetes (T2D). The underlying molecular mechanisms of the SGLT2 inhibitor canagliflozin on EGF using single-cell RNA sequencing from kidney tissue were examined.
View Article and Find Full Text PDFCongenital portosystemic shunts (CPSS) are rare developmental anomalies resulting in diversion of portal flow to the systemic circulation. These shunts allow intestinal blood to reach the systemic circulation directly, and if persistent or large, may lead to long-term complications. CPSS can have a variety of clinical presentations that depend on the substrate that is bypassing hepatic metabolism or the degree of hypoperfusion of the liver.
View Article and Find Full Text PDFThe molecular mechanisms of sodium-glucose cotransporter-2 (SGLT2) inhibitors (SGLT2i) remain incompletely understood. Single-cell RNA sequencing and morphometric data were collected from research kidney biopsies donated by young persons with type 2 diabetes (T2D), aged 12 to 21 years, and healthy controls (HCs). Participants with T2D were obese and had higher estimated glomerular filtration rates and mesangial and glomerular volumes than HCs.
View Article and Find Full Text PDFHyperfiltration is a state of high glomerular filtration rate (GFR) observed in early diabetes that damages glomeruli, resulting in an iterative process of increasing filtration load on fewer and fewer remaining functional glomeruli. To delineate underlying cellular mechanisms of damage associated with hyperfiltration, transcriptional profiles of kidney biopsies from Pima Indians with type 2 diabetes with or without early-stage diabetic kidney disease were grouped into two hyperfiltration categories based on annual iothalamate GFR measurements. Twenty-six participants with a peak GFR measurement within two years of biopsy were categorized as the hyperfiltration group, and 26 in whom biopsy preceded peak GFR by over two years were considered pre-hyperfiltration.
View Article and Find Full Text PDFBackground: Pulmonary nodules that are deep within lung parenchyma and/or small in size can be challenging to localize for biopsy. This study describes current trends in performance of image-guided localization techniques for pulmonary nodules in pediatric patients.
Methods: A retrospective review was performed on patients < 21 years of age undergoing localization of pulmonary nodules at 15 institutions.
Introduction: Many children with gastric feeding intolerance require postpyloric tube feeding via a gastrojejunal (GJ) tube. Placement or positioning of these tubes is typically a procedure with a low dose of radiation. Although the risk of developing cancer from radiation exposure owing to computed tomography scans is well-documented in children, the risk of cumulative radiation exposure owing to frequent GJ tube replacement often goes unnoticed in the clinical decision-making process.
View Article and Find Full Text PDFInt J Pediatr Otorhinolaryngol
November 2020
Retropharyngeal abscess (RPA) in children is a serious deep neck space infection that rarely is complicated by extension into the mediastinum. RPA with mediastinal abscess requires prompt surgical management, generally via external or transoral approach. We present the case of a 3-year-old boy with RPA with mediastinal extension who was managed with a unique multidisciplinary surgical approach with otolaryngology and interventional radiology.
View Article and Find Full Text PDFPatients <12 months with favorable biology, metastatic neuroblastoma have >90% overall survival following treatment with chemotherapy and surgery. We report two infants with favorable biology, stage 4 neuroblastoma with refractory disease after standard intermediate-risk chemotherapy and additional retrieval chemotherapy. One patient was treated with six additional cycles of isotretinoin and the other observed.
View Article and Find Full Text PDFObjective: The clinical course of juvenile dermatomyositis (JDMS) is unpredictable. MRI is used to determine muscle biopsy site and to monitor disease activity. It is unknown whether soft-tissue features on MRI obtained at diagnosis correlate with clinical outcome.
View Article and Find Full Text PDFBackground: The medial patellofemoral ligament (MPFL), a chief medial restraint preventing lateral patellar dislocation, often is reconstructed in children with recurrent dislocation. The femoral MPFL attachment can be difficult to delineate at surgery. Therefore, the origin of the medial collateral ligament (MCL) frequently is used to approximate the reattachment site.
View Article and Find Full Text PDFLeukotrienes are implicated in the pathogenesis of diverse, inflammation-driven diseases. Metabolic inactivation of leukotriene signaling is an innate response to resolve inflammation, yet little is known of mechanisms regulating disposition of leukotrienes in peripheral tissues afflicted in common inflammatory diseases. We studied leukotriene hydroxylases (CYP4F gene products) in human skin, a common target of inflammation and adverse drug reactions.
View Article and Find Full Text PDFHuman epidermal keratinocytes express subsets of cytochromes P450 (P450) (CYP gene products) that are strongly up-regulated, not regulated, or down-regulated by differentiation-specific factors. We investigated how drug exposure affects epidermal expression of CYP1-4 genes, which encode many drug-metabolizing P450s. Real-time polymerase chain reaction (PCR) assays measured CYP1-4 mRNA levels in epidermal keratinocytes differentiated in vitro in the presence of drug or vehicle for 6 days.
View Article and Find Full Text PDFEpoxyeicosatrienoic acids produced by mouse CYP2B19 have been implicated in mechanisms regulating epidermal cornification (Ladd, P.A., Du, L.
View Article and Find Full Text PDFCYP2B19 is an arachidonic acid monooxygenase highly expressed in the outer, differentiated cell layers of mouse epidermis. We aimed to establish whether CYP2B19 is the source of epidermal epoxyeicosatrienoic acids (EETs), which are implicated in mechanisms regulating epidermal cornification. We show that primary cultures of mouse epidermal keratinocytes expressed native CYP2B19, as determined by mass spectrometry.
View Article and Find Full Text PDFThe cytochrome P450 CYP2B19 is a keratinocyte-specific arachidonic acid epoxygenase expressed in the granular cell layer of mouse epidermis. In cultured keratinocytes, CYP2B19 mRNAs are up-regulated coordinately with those of profilaggrin, another granular cell-specific marker. We investigated effects of the CYP2B19 metabolites 11,12- and 14,15-epoxyeicosatrienoic acids (EETs) on keratinocyte transglutaminase activities and cornified cell envelope formation.
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