DRUG TOXICITY AS A RESULT OF INTERFERENCE WITH PHYSIOLOGICAL CONTROL MECHANISMS

1965 ◽  
Vol 123 (1) ◽  
pp. 42-54 ◽  
Author(s):  
James R. Gillette
Keyword(s):  
Drug Toxicity ◽  
Control Mechanisms ◽  
Physiological Control

Control of Thrombin Mediated Cleavage of Protein S

1986 ◽  
Vol 56 (02) ◽  
pp. 151-154 ◽  
Author(s):  
Christina A Mitchell ◽  
Lena Hau ◽  
Hatem H Salem
Keyword(s):  
Anticoagulant Activity ◽  
Activated Protein C ◽  
Surface Protein ◽  
Protein S ◽  
Intact Protein ◽  
Control Mechanisms ◽  
Physiological Control ◽  
Endothelial Cell Surface ◽  
Thrombin Cleavage ◽  
Cofactor Activity

SummaryThrombin has been shown to cleave the vitamin K dependent cofactor protein S with subsequent loss of its cofactor activity. This study examines the control mechanisms for thrombin cleavage of protein S.The anticoagulant activity of activated protein C (APC) is enhanced fourteen fold by the addition of protein S. Thrombin cleaved protein S is seven fold less efficient than the native protein, and this loss of activity is due to reduced affinity of cleaved protein S for APC or the lipid surface compared to the intact protein.In the absence of Ca++, protein S is very sensitive to minimal concentrations of thrombin. As little as 1.5 nM thrombin results in complete cleavage of 20 nM protein S in 10 min and loss of cofactor activity. Ca++, in concentrations greater than 0.5 mM, will inhibit this cleavage and in the presence of physiological Ca++ concentrations, no cleavage of protein S could be demonstrated in spite of high concentrations of thrombin (up to 1 μM) and prolonged incubations (up to two hours). The endothelial surface protein thrombomodulin is very efficient in inhibiting the cleavage of protein S by thrombin suggesting that any thrombin formed on the endothelial cell surface is unlikely to cleave protein S, thus allowing the intact protein to act as a cofactor to APC.We conclude that the inhibitory effects of Ca++ and thrombomodulin on thrombin mediated cleavage of protein S imply that this event, by itself, is unlikely to represent a physiological control of the activity of protein S.

Detection of interactions between myogenic and TGF mechanisms using nonlinear analysis

1994 ◽  
Vol 267 (1) ◽  
pp. F160-F173 ◽  
Author(s):  
K. H. Chon ◽  
Y. M. Chen ◽  
V. Z. Marmarelis ◽  
D. J. Marsh ◽  
N. H. Holstein-Rathlou
Keyword(s):  
Nonlinear Approximation ◽  
Nonlinear Modeling ◽  
Tubuloglomerular Feedback ◽  
Control Mechanisms ◽  
Physiological Control ◽  
Renal Autoregulation ◽  
Wiener Kernels ◽  
Highly Nonlinear ◽  
Single Nephron ◽  
Kidney Blood Flow

Previous studies using linear techniques have provided valuable insights into the dynamic characteristics of whole kidney autoregulation and have led to the general conclusion that the myogenic mechanism and tubuloglomerular feedback (TGF) are highly nonlinear control mechanisms. To explore further the dynamic nature of these nonlinear autoregulatory mechanisms, we introduce the technique of nonlinear modeling using Volterra-Wiener kernels. In the past several years, use of Volterra-Wiener kernels for nonlinear approximation has been most notably applied to neurophysiology. Recent advances in algorithms for computation of the kernels have made this technique more attractive for the study of the dynamics of nonlinear physiological systems, such as the system mediating renal autoregulation. In this study, the general theory and requirements for using this technique are discussed. The feasibility of using the technique on whole kidney pressure and flow data is examined, and a basis for using the Volterra-Wiener kernels to detect interactions between physiological control mechanisms is established. As a result of this method, we have identified the presence of interactions between the oscillating components of the myogenic and the TGF mechanisms at the level of the whole kidney blood flow in normotensive rats. An interaction between these oscillatory components had previously been demonstrated only at the single-nephron level.

Fluid management: An update for perioperative practitioners

2021 ◽  
pp. 175045892096417
Author(s):  
Christopher Wood
Keyword(s):  
Fluid Balance ◽  
Fluid Management ◽  
Postoperative Nausea And Vomiting ◽  
Perioperative Period ◽  
Adverse Outcomes ◽  
Intravenous Fluid ◽  
Team Approach ◽  
Control Mechanisms ◽  
Physiological Control ◽  
Comprehensive Overview

An interprofessional team approach is required to achieve optimum fluid balance for patients during the perioperative period. Incorrect management of fluid assessment and monitoring is associated with adverse outcomes. The scientific understanding of perioperative fluid balance has improved over recent years leading to changes in clinical practice with regard to volume and choice of intravenous fluid. It is important that perioperative practitioners have an understanding of intravenous fluid, fluid compartmentalisation, fluid mechanics and intravascular fluid control mechanisms. Optimum fluid status not only shortens hospital stay but also reduces the incidence of postoperative nausea and vomiting and complication profiles. This article aims to provide perioperative practitioners with a comprehensive overview of fluid management. It will cover important issues surrounding physiological control of fluid balance, choice of intravenous fluid therapy, methods to monitor intravascular volume and factors which influence delivery.

scholarly journals Protease-Activated Receptors: Contribution to Physiology and Disease

2004 ◽  
Vol 84 (2) ◽  
pp. 579-621 ◽  
Author(s):  
VALERIA S. OSSOVSKAYA ◽  
NIGEL W. BUNNETT
Keyword(s):  
Protease Inhibitors ◽  
Serine Proteases ◽  
Inflammatory Cells ◽  
Coagulation Factors ◽  
Control Mechanisms ◽  
Physiological Control ◽  
Protease Activated Receptors ◽  
Future Challenges ◽  
Tethered Ligand ◽  
Selective Agonists

Ossovskaya, Valeria S., and Nigel W. Bunnett. Protease-Activated Receptors: Contribution to Physiology and Disease. Physiol Rev 84: 579–621, 2004; 10.1152/physrev.00028.2003.—Proteases acting at the surface of cells generate and destroy receptor agonists and activate and inactivate receptors, thereby making a vitally important contribution to signal transduction. Certain serine proteases that derive from the circulation (e.g., coagulation factors), inflammatory cells (e.g., mast cell and neutrophil proteases), and from multiple other sources (e.g., epithelial cells, neurons, bacteria, fungi) can cleave protease-activated receptors (PARs), a family of four G protein-coupled receptors. Cleavage within the extracellular amino terminus exposes a tethered ligand domain, which binds to and activates the receptors to initiate multiple signaling cascades. Despite this irreversible mechanism of activation, signaling by PARs is efficiently terminated by receptor desensitization (receptor phosphorylation and uncoupling from G proteins) and downregulation (receptor degradation by cell-surface and lysosomal proteases). Protease signaling in tissues depends on the generation and release of proteases, availability of cofactors, presence of protease inhibitors, and activation and inactivation of PARs. Many proteases that activate PARs are produced during tissue damage, and PARs make important contributions to tissue responses to injury, including hemostasis, repair, cell survival, inflammation, and pain. Drugs that mimic or interfere with these processes are attractive therapies: selective agonists of PARs may facilitatehealing, repair, and protection, whereas protease inhibitors and PAR antagonists can impede exacerbated inflammation and pain. Major future challenges will be to understand the role of proteases and PARs in physiological control mechanisms and human diseases and to develop selective agonists and antagonists that can be used to probe function and treat disease.

Physiological control of pituitary hormone secretory-burst mass, frequency, and waveform: a statistical formulation and analysis

2003 ◽  
Vol 285 (3) ◽  
pp. R664-R673 ◽  
Author(s):  
Daniel M. Keenan ◽  
Ferdinand Roelfsema ◽  
Nienke Biermasz ◽  
Johannes D. Veldhuis
Keyword(s):  
Hormone Secretion ◽  
Primary Data ◽  
Slow Phase ◽  
Pituitary Hormone ◽  
Control Mechanisms ◽  
Physiological Control ◽  
Elimination Kinetics ◽  
Burst Frequency ◽  
Statistical Solution ◽  
Tsh Secretion

The present study investigates the time-varying control of pituitary hormone secretion over the day and night (D/N). To this end, we implemented an analytical platform designed to reconstruct simultaneously 1) basal (nonpulsatile) secretion, 2) single or dual secretory-burst waveforms, 3) random effects on burst amplitude, 4) stochastic pulse-renewal properties, 5) biexponential elimination kinetics, and 6) experimental uncertainty. The statistical solution is conditioned on a priori pulse-onset times, which are estimated in the first stage. Primary data composed of thyrotropin (TSH) concentrations were monitored over 24 h in 27 healthy adults. According to statistical criteria, 21/27 profiles favored a dual compared with single secretory-burst waveform. An objectively defined waveform change point (D/N boundary) emerged at 2046 (±23 min), after which 1) the mass of TSH released per burst increases by 2.1-fold ( P < 0.001), 2) TSH secretory-burst frequency rises by 1.2-fold ( P < 0.001), 3) the latency to maximal TSH secretion within a burst decreases by 67% ( P < 0.001), 4) variability in secretory-burst shape diminishes by 50% ( P < 0.001), and 5) basal TSH secretion declines by 17% ( P < 0.002). In contrast, the regularity of successive burst times and the slow-phase half-life are stable. In conclusion, nycthemeral mechanisms govern TSH secretory-burst mass, frequency, waveform, and variability but not evidently TSH elimination kinetics or the pulse-timing process. Further studies will be required to assess the generality of the foregoing distinctive control mechanisms in other hypothalamo-pituitary axes.

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