Streaming potential kidney

BACKGROUND: Carbapenem-induced neurotoxicity is an unusual side effect, with seizure being the most commonly reported symptom. Among the carbapenems, imipenem-cilastin is classically associated with the most severe neurotoxicity side effects. Carbapenem is mainly excreted by the kidney and its half-life is significantly increased in patients with chronic kidney disease (CKD). Therefore, dose adjustment is necessary in such patients. Ertapenem-associated neurotoxicity is increasingly being reported in CKD patients, but rarely seen in patients with recommended dose adjustment...

BACKGROUND AND OBJECTIVES: Adsorption of uremic solutes to activated carbon provides a potential means to limit dialysate volumes required for new dialysis systems. The ability of activated carbon to take up uremic solutes has, however, not been adequately assessed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Graded volumes of waste dialysate collected from clinical hemodialysis treatments were passed through activated carbon blocks. Metabolomic analysis assessed the adsorption by activated carbon of a wide range of uremic solutes...

AIMS: Glomerular damage indicated by proteinuria is a main symptom in diabetic nephropathy. Mineralocorticoid receptor (MR) antagonists (MRAs) are beneficial irrespective of aldosterone availability. Thus, we hypothesized an alternatively activated MR to promote glomerular damage in proteinuric diabetic nephropathy. Specifically, we aimed first to demonstrate the presence of steroid hormones serving as alternative MR targets in type II diabetic patients with proteinuric kidney disease, second whether MR selectivity was modified, third to characterize MR and glucocorticoid receptor (GR) expression and activity in glomerular cell types exposed to eu- and hyperglycemic conditions, fourth to characterize the pro-fibrotic potential of primary human renal mesangial cells (HRMC) upon stimulation with aldosterone and cortisol, and fifth to specify the involvement of the MR and/or GR in pro-fibrotic signaling...

Inherited kidney diseases (IKDs) are a large group of disorders affecting different nephron segments, many of which progress towards kidney failure due to the absence of curative therapies. With the current advances in genetic testing, the understanding of the molecular basis and pathophysiology of these disorders is increasing and reveals new potential therapeutic targets. RNA has revolutionized the world of molecular therapy and RNA-based therapeutics have started to emerge in the kidney field. To apply these therapies for inherited kidney disorders, several aspects require attention...

Biosynthesized silver nanoparticles have a wide range of biological activities and using nanoparticles as one of the novel approaches in cancer therapy. In this present research work, the anti-cancer efficacy of Cucumis melo fruit extract and its silver nanoparticles was explored. Wistar rats were divided into six groups and hepatic cancer was induced with 0.01% DEN (diethylnitrosamine) through drinking water for 16 weeks. Cyclophosphamide was given as the standard drug at the dose of 50 mg/kg body weight. Hematological parameters showed a decrease in the levels of hemoglobin (Hb), packed cell volume (PCV), red blood cells (RBC), mean corpuscular volume (MCV), mean corpuscular Hb (MCH), mean corpuscular Hb concentration (MCHC), and platelets (PLTS) levels except white blood cell (WBC) in DEN-induced cancer animals...

Background: Pragmatic trials inform clinical decision with better generalizability and can bridge different streams of medicine. This study collated the expectations regarding pragmatic trial design of integrative medicine (IM) for diabetes and kidney diseases among patients and physicians. Dissonance between users' perspective and existing pragmatic trial design was identified. The association between risk of bias and pragmatism of study design was assessed. Method: A 10-group semi-structured focus group interview series [21 patients, 14 conventional medicine (ConM) and 15 Chinese medicine (CM) physicians] were purposively sampled from private and public clinics in Hong Kong...

Propionic aciduria (PA) is caused by deficiency of the mitochondrial enzyme propionyl-CoA carboxylase (PCC). Due to inefficient propionate catabolism patients are endangered by life-threatening ketoacidotic crisis. Protein and amino acid restriction are major therapeutic pillars. However, long-term complications like neurological deterioration and cardiac abnormalities cannot be prevented. Chronic kidney disease (CKD), which is a well-known characteristic of methylmalonic aciduria two enzymatic steps downstream from PCC, has been recognized as a novel late-onset complication in PA...

Umbelliferone (UMB; 7-hydroxycoumarin) is a natural compound that exhibited a diversity of pharmacological activities. Its protective effects against various ischemia/reperfusion (IR) injuries, including heart, kidney, and testis, have been observed. However, their effect on hepatic IR is still not investigated yet. Here, this study was conducted to examine the potential protective role of UMB during the early phase of hepatic IR injury via targeting Keap-1/Nrf-2/ARE and its closely related signaling pathway, TLR4/NF-κB-p65...

BACKGROUND: Diabetic nephropathy (DN) is the major complication of diabetes mellitus, and leading cause of end-stage renal disease. The underlying molecular mechanism of DN is not yet completely clear. The aim of this study was to analyze a DN microarray dataset using weighted gene co-expression network analysis (WGCNA) algorithm for better understanding of DN pathogenesis and exploring key genes in the disease progression. METHODS: The identified differentially expressed genes (DEGs) in DN dataset GSE47183 were introduced to WGCNA algorithm to construct co-expression modules...

BACKGROUND: The Apolipoprotein 1 (APOL1) protein is a product of the human APOL1 gene located on chromosome 22q13.1 and performs functions including lipid transport and metabolism, programmed cell death, autophagy and innate immunity against intracellular pathogens. It is unique among its gene family in its possession of a signal peptide that confers on it the ability for export out of the cell and into the blood stream. The aim of this review is to explore the genetic epidemiology and biology of the APOL1 gene, describe its association with different renal and extra-renal disorders and highlight the timelines of the discoveries of the various associations...

Importance: A strategy that prioritizes individuals for SARS-CoV-2 vaccination according to their risk of SARS-CoV-2-related mortality would help minimize deaths during vaccine rollout. Objective: To develop a model that estimates the risk of SARS-CoV-2-related mortality among all enrollees of the US Department of Veterans Affairs (VA) health care system. Design, Setting, and Participants: This prognostic study used data from 7 635 064 individuals enrolled in the VA health care system as of May 21, 2020, to develop and internally validate a logistic regression model (COVIDVax) that predicted SARS-CoV-2-related death (n = 2422) during the observation period (May 21 to November 2, 2020) using baseline characteristics known to be associated with SARS-CoV-2-related mortality, extracted from the VA electronic health records (EHRs)...

Diabetes Mellitus (DM) is an endocrine disease, which is the 3rd leading cause of death in humans; additionally, it is one of the major key concerns over the globe. The high levels of glucose in the blood stream are as well characterized by hyperglycaemia leading to serious damage to the heart, blood vessels, kidney, eyes, and nerves. The best treatment of DM is still not available; many scientists worldwide are trying hard to seek out suitable treatment of DM. Though numerous synthetic drugs are developed for the treatment of diabetes but their utility has been hampered because of several side effects and poor efficacy...

Microscopy imaging experiments generate vast amounts of data, and there is a high demand for smart acquisition and analysis methods. This is especially true for transmission electron microscopy (TEM) where terabytes of data are produced if imaging a full sample at high resolution, and analysis can take several hours. One way to tackle this issue is to collect a continuous stream of low resolution images whilst moving the sample under the microscope, and thereafter use this data to find the parts of the sample deemed most valuable for high-resolution imaging...

The encapsulation of nanoparticles within microparticles designed for specific delivery to the colon is a relevant strategy to avoid premature degradation or release of nanoparticles during their passage through the stomach and upper gastrointestinal tract (GIT), allowing the targeted delivery of chemotherapeutics to the colon after oral administration. Here, we designed an oral multiparticulate system to achieve targeted release in the colon. In this sense, chitosan nanoparticles (CS NPs) encapsulated with 5-fluorouracil (5-FU) and incorporated into retrograded starch and pectin (RS/P) microparticles were developed and their in vivo distribution along the mouse GIT after oral administration was monitored using multispectral optical imaging...

The high GFR in vertebrates obligates large energy expenditure. Homer Smith's teleologic argument that this high GFR was needed to excrete water as vertebrates evolved in dilute seas is outdated. The GFR is proportional to the metabolic rate among vertebrate species and higher in warm-blooded mammals and birds than in cold-blooded fish, amphibians, and reptiles. The kidney clearance of some solutes is raised above the GFR by tubular secretion, and we presume secretion evolved to eliminate particularly toxic compounds...

Hepsin, a transmembrane serine protease abundant in renal endothelial cells, is a promising therapeutic target against several cancers, particularly prostate cancer. It is involved in the release and polymerization of uromodulin in the urine, which plays a role in kidney stone formation. In this work, we design new potential hepsin inhibitors for high activity, improved specificity towards hepsin, and promising ADMET properties. The ligands were developed in silico through a novel hierarchical pipeline. This pipeline explicitly accounts for off-target binding to the related serine proteases matriptase and HGFA (human hepatocyte growth factor activator)...

Understanding to what extent stem cell potential is a cell-intrinsic property or an emergent behavior coming from global tissue dynamics and geometry is a key outstanding question of systems and stem cell biology. Here, we propose a theory of stem cell dynamics as a stochastic competition for access to a spatially localized niche, giving rise to a stochastic conveyor-belt model. Cell divisions produce a steady cellular stream which advects cells away from the niche, while random rearrangements enable cells away from the niche to be favorably repositioned...

Canonical epithelial sodium channels (ENaCs) are heterotrimers formed by α, β, and γ ENaC subunits in vertebrates and belong to the Degenerin/ENaC family of proteins. Proteins from this family form mechanosensitive channels throughout the animal kingdom. Activity of canonical ENaC is regulated by shear force (SF) mediating Na+ absorption in the kidney and vascular tone of arteries. Expression analysis suggests that non-canonical ENaC, formed by single or only two subunits, exist in certain tissues, but it is unknown if these channels respond to SF...

BACKGROUND & AIMS: Parenteral nutrition (PN) is a valuable and life-saving treatment for patients with intestinal failure. While its use is increasing, it has been demonstrated to be a risk factor for intravenous catheter-related blood stream infection (CRBSI) - a significant, serious and potentially fatal complication of PN use. CRBSI can have serious secondary consequences for patients, though, there is a paucity of literature describing these. The aim of this study is to audit the incidence of, and evaluate the consequences of, complications associated with CRBSI...

Autosomal dominant polycystic kidney (ADPKD) is a common genetic disorder characterized by the presence of numerous fluid-filled cysts that lead to a progressive decline in renal function. Cystic tissues and primary cyst epithelial cells obtained from discarded human ADPKD kidneys provide unique biomaterials for the investigation of cellular mechanisms involved in cyst growth and changes in the microenvironment adjacent to the cysts. ADPKD cells have been used to develop straightforward in vitro cell model assays to study events down-stream of the mutant proteins in carefully controlled experimental conditions, test specific hypotheses, and evaluate the cellular response to potential therapeutic drugs...