Origins of Isolated Tubule Microperfusion Methodology

Physiology ◽  
1988 ◽  
Vol 3 (4) ◽  
pp. 176-180
Author(s):  
Maurice B. Burg
Keyword(s):  
Renal Function ◽  
Analytical Methods ◽  
Renal Tubule ◽  
National Institutes Of Health ◽  
Electrolyte Metabolism ◽  
Basic Technology ◽  
Isolated Renal Tubule ◽  
Single Tubules

Understanding of renal function has been facilitated by the technique of perfusion of isolated renal tubule segments in vitro. The basic technology originated in the Laboratory of Kidney and Electrolyte Metabolism of the National Institutes of Health in the early 1960s and then was expanded to apply a variety of analytical methods to single tubules.

scholarly journals The inhibition of parathyroid-hormone actions on gluconeogenesis and phosphate transport by 3-mercaptopicolinate in rabbit renal proximal tubules

1986 ◽  
Vol 233 (1) ◽  
pp. 271-273
Author(s):  
N Yanagawa ◽  
O D Jo
Keyword(s):  
Parathyroid Hormone ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Renal Tubule ◽  
Phosphate Transport ◽  
Proximal Tubules ◽  
Transport Rate ◽  
Renal Proximal Tubules ◽  
Straight Tubules ◽  
Isolated Renal Tubule

By using a glucose microassay and the technique for isolated renal-tubule perfusion in vitro, the addition of 3-mercaptopicolinate, a gluconeogenesis inhibitor which inhibits phosphoenolpyruvate carboxykinase specifically, was found to abolish the effects of parathyroid hormone on gluconeogenesis and phosphate-transport rate in isolated rabbit renal proximal straight tubules, suggesting that these parathyroid-hormone actions may share some unknown, yet 3-mercaptopicolinate-inhibitable, intracellular processes.

Microphysiological systems: What it takes for community adoption

2021 ◽  
pp. 153537022110088
Author(s):  
Passley Hargrove-Grimes ◽  
Lucie A Low ◽  
Danilo A Tagle
Keyword(s):  
Rare Diseases ◽  
Development Process ◽  
Emerging Technology ◽  
National Institutes Of Health ◽  
Drug Development Process ◽  
Microphysiological Systems ◽  
Pediatric Populations ◽  
Neural Disorders ◽  
Future Path

Microphysiological systems (MPS) are promising in vitro tools which could substantially improve the drug development process, particularly for underserved patient populations such as those with rare diseases, neural disorders, and diseases impacting pediatric populations. Currently, one of the major goals of the National Institutes of Health MPS program, led by the National Center for Advancing Translational Sciences (NCATS), is to demonstrate the utility of this emerging technology and help support the path to community adoption. However, community adoption of MPS technology has been hindered by a variety of factors including biological and technological challenges in device creation, issues with validation and standardization of MPS technology, and potential complications related to commercialization. In this brief Minireview, we offer an NCATS perspective on what current barriers exist to MPS adoption and provide an outlook on the future path to adoption of these in vitro tools.

Abstract 17071: Cell Communication Inference in Macrophages

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Nika Taghdiri ◽  
Kevin R King ◽  
David Calcagno ◽  
Zhenxing Fu ◽  
Kenneth Huang ◽  
...  
Keyword(s):  
Image Analysis ◽  
Analytical Methods ◽  
Cell Injury ◽  
Diffusion Mechanism ◽  
Cell Communication ◽  
In Vivo Studies ◽  
Cell Dynamics ◽  
Calcium Indicator

Introduction: Tissue macrophages play diverse roles in the cardiovascular system during health and disease. They have diverse functions within tissues, but our understanding of their dynamics is limited because most macrophage characterization assays are destructive and have low temporal resolution. We asked whether these cells are dynamic and interconnected. Methods: Here, we describe experimental and analytical methods for measuring cell dynamics and inferring communication between cells in vitro and in vivo. We created a mouse (Csf1r-Cre x GCaMP5) expressing the Cre-inducible genetically encoded calcium indicator GCaMP5 under the regulation of the innate immune promoter, Csf1r, to non-destructively quantify high-frequency cell dynamics and differentiated them in culture using m-CSF. We developed custom image analysis routines and parameterization strategies for classifying calcium responses. Results: Our studies revealed that calcium reporter BMDMs display minimal fluctuations at baseline but exhibit a dynamic response to immunogenic DNA sensing. DNA-induced isolated cell injury and death, which precipitated cell communication that spread with a velocity of [9μm/s], consistent with an extracellular diffusion mechanism. We developed quantitative image analysis methods that corrected for random calcium fluctuations and identified statistically significant areas of correlated calcium changes suggestive of communication. An analytical pipeline enabled quantification of calcium spike dynamics and correlations of dynamic calcium profiles of single cell sharing a local microenvironment. This resulted in an “improbable synchrony” metric that allowed localization of communication in time and space. We adapted the pipeline for in vivo studies and tested them in a dorsal window chamber model using intravital microscopy. At 2Hz sampling frequency, we identified 27 potential communication events as they responded to complex microenvironmental cues in vivo. Conclusion: The experimental and analytical methods for inferring cell communication provide a new quantitative toolkit for investigating known as-yet undiscovered cell communication pathways.

Endothelium-derived relaxing factor in regulation of basal cardiopulmonary and renal function

1991 ◽  
Vol 261 (2) ◽  
pp. R323-R328 ◽  
Author(s):  
M. A. Perrella ◽  
F. L. Hildebrand ◽  
K. B. Margulies ◽  
J. C. Burnett
Keyword(s):  
Renal Function ◽  
Competitive Inhibitor ◽  
Vehicle Group ◽  
Relaxing Factor ◽  
Anesthetized Dogs ◽  
Endothelium Derived Relaxing Factor ◽  
Renal Vascular ◽  
Renal Responses

The endothelium has emerged as an important modulator of vascular tone by producing both vasodilating and vasoconstricting substances. In vitro studies have demonstrated that endothelial cells produce endothelium-derived relaxing factor (EDRF), which promotes vasodilation via the stimulation of intracellular guanosine 3',5'-cyclic monophosphate (cGMP). However, the role of EDRF in the basal regulation of cardiopulmonary and renal function is not well defined. The present study was therefore designed to assess the function of EDRF by studying two groups of normal anesthetized dogs, of which one received a competitive inhibitor to EDRF generation, NG-monomethyl-L-arginine (L-NMMA; 50 micrograms.kg-1.min-1 iv), and the other received a vehicle. The L-NMMA infusion produced no significant increase in mean arterial pressure but marked increases in systemic, pulmonary, and renal vascular resistances compared with the vehicle group. Although renal blood flow decreased with L-NMMA, no changes were observed in glomerular filtration rate or sodium excretion. Associated with the cardiopulmonary and renal responses with L-NMMA was a modest increase in plasma endothelin (7.9 +/- 1.3 to 10.2 +/- 1.8 pg/ml, P less than 0.05), an endothelium-derived vasoconstrictor. No alteration was observed in plasma or urinary cGMP with EDRF inhibition. These cardiopulmonary and renal responses with L-NMMA may be attributed not only to EDRF inhibition but to an imbalance between endothelium-derived relaxing and contracting factors.

scholarly journals Pharmacokinetics of lamivudine in human immunodeficiency virus-infected patients with renal dysfunction.

1996 ◽  
Vol 40 (6) ◽  
pp. 1514-1519 ◽  
Author(s):  
A E Heald ◽  
P H Hsyu ◽  
G J Yuen ◽  
P Robinson ◽  
P Mydlow ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Renal Function ◽  
Renal Impairment ◽  
Normal Renal Function ◽  
Severe Renal Impairment ◽  
Moderate Renal Impairment ◽  
Pharmacokinetic Parameters ◽  
Geometric Means ◽  
Immunodeficiency Virus

The purpose of this study was to determine the safety and pharmacokinetics of lamivudine (3TC), a nucleoside analog that has shown potent in vitro and recent in vivo activity against human immunodeficiency virus. Sixteen human immunodeficiency virus-infected patients, six with normal renal function (creatinine clearance [CLCR], > or = 60 ml/min), four with moderate renal impairment (CLCR, 10 to 40 ml/min), and six with severe renal impairment (CLCR, < 10 ml/min), were enrolled in the study. After an overnight fast, patients were administered 300 mg of 3TC orally. Blood was obtained before 3TC administration and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, and 48 h afterward. Timed urine collections were performed for patients able to produce urine. Serum and urine were assayed for 3TC by reverse-phase high-performance liquid chromatography with UV detection. Pharmacokinetic parameters were calculated by using standard noncompartmental techniques. The peak concentration of 3TC increased with decreasing renal function; geometric means were 2,524, 3,538, and 5,684 ng/ml for patients with normal renal function, moderate renal impairment, and severe renal impairment, respectively. The terminal half-life also increased with decreasing renal function; geometric means were 11.5, 14.1, and 20.7 h for patients with normal renal function, moderate renal impairment, and severe renal impairment, respectively. Both oral and renal clearances were linearly correlated with CLCR. A 300-mg dose of 3TC was well tolerated by all three patient groups. The pharmacokinetics of 3TC is profoundly affected by impaired renal function. Dosage adjustment, by either dose reduction or lengthening of the dosing interval, is warranted.

Long-Term Treatment with Pivmecillinam in Patients with Recurrent Bacteriuria

1982 ◽  
Vol 10 (3) ◽  
pp. 179-182
Author(s):  
B Bresky ◽  
K Lincoln
Keyword(s):  
Escherichia Coli ◽  
Adverse Effect ◽  
Renal Function ◽  
Term Treatment ◽  
The Body ◽  
End Of Treatment ◽  
Long Term Treatment ◽  
Tract Infections

Thirty out-patients with chronic recurrent urinary tract infections, who had failed to respond to 10 days treatment with either pivmecillinam and/or amoxycillin, received a 3-month course of pivmecillinam at a dose of 200 mg, three times daily. Twenty-seven patients had bacteriuria due to Enterobacteriaceae, mainly Escherichia coli, sensitive to mecillinam in vitro. Pivmecillinam eradicated all the initial urinary pathogens. Reinfections occurred during treatment in three patients, who remained asymptomatic. Four subjects complained of gastro-intestinal side-effects, and therapy was withdrawn in three instances. Another three patients described unusual adverse events towards the end of the course of treatment, described as an odd sensation in the body and a desire for salt. The sensation disappeared a few days after the end of treatment. Treatment with pivmecillinam had no adverse effect on haematopoietic, hepatic or renal function.

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