Vasoactive Components of Dialysis Solution

2008 ◽  
Vol 28 (3) ◽  
pp. 283-295 ◽  
Author(s):  
El Rasheid Zakaria ◽  
Anuj A. Patel ◽  
Na Li ◽  
Paul J. Matheson ◽  
Richard N. Garrison
Keyword(s):  
Vascular Reactivity ◽  
Molecular Mechanisms ◽  
Degradation Products ◽  
Low Ph ◽  
Dialysis Solution ◽  
Parallel Increase ◽  
Baxter Healthcare ◽  
Chronic Infusion ◽  
Low Glucose ◽  
Osmotic Solute

Background Conventional peritoneal dialysis (PD) solutions elicit vasodilation, which is implicated in the variable rate of solute transport during the dwell. The components causing such vasoactivity are still controversial. This study was conducted to define the vasoactive components of conventional and new PD solutions. Methods Three visceral peritoneal microvascular levels were visualized by intravital video microscopy of the terminal ileum of anesthetized rats. Anesthesia-free decerebrate conscious rats served as control. Microvascular diameter and blood flow by Doppler measurements were conducted after topical peritoneal exposure to 4 clinical PD solutions and 6 prepared solutions designed to isolate potential vasoactive components of the PD solution. Results All clinically available PD solutions produced a rapid and generalized vasodilation at all intestinal microvascular levels, regardless of the osmotic solute. The pattern and magnitude of this dilation was not affected by anesthesia but was determined by arteriolar size, the osmotic solute, and the solution's buffer anion system. The greatest dilation occurred in the small precapillary arterioles and was elicited by conventional PD solution and heat re-sterilized solution containing low glucose degradation products (GDPs). Hypertonic mannitol solutions produced a dilation that was approximately 50% less than the dilation obtained with glucose solutions with identical osmolarity and buffer. Increasing a solution's osmolarity did not produce a parallel increase in the magnitude of dilation, suggesting a nonlinear relationship between the two variables. Lactate dissolved in an isotonic solution was completely non-vasoactive unless the solution's H+ concentration was increased. At low pH, isotonic lactate produced a rapid but transient vasodilation. This vascular reactivity was similar in magnitude and pattern to that obtained with the isotonic 7.5% icodextrin solution (Extraneal; Baxter Healthcare, Deerfield, Illinois, USA). Conclusions ( 1 ) Hyperosmolarity is the major vasoactive component of PD solution. ( 2 ) Hyperosmolarity and active intracellular glucose uptake account together for approximately 75% of PD solution-induced dilation, whereas GDPs contribute to approximately 25%. ( 3 ) Lactate is vasoactive only at low pH (high [H+]). ( 4 ) The magnitude of PD solution-mediated vasodilation is partially dependent on the nature of the osmotic solute, the GDP contents, and the [H+], which determine the vasoactivity of the lactate-buffer anion system. Studies are required to define the molecular mechanisms of PD-induced vasodilation and to determine the vasoactive properties of these solutions after chronic infusion.

Evidence for Less Irritation to the Peritoneal Membrane in Rats Dialyzed with Solutions Low in Glucose Degradation Products

2004 ◽  
Vol 24 (1) ◽  
pp. 48-57 ◽  
Author(s):  
Katarzyna Wieczorowska–Tobis ◽  
Renata Brelinska ◽  
Janusz Witowski ◽  
Jutta Passlick–Deetjen ◽  
Thomas P. Schaub ◽  
...  
Keyword(s):  
Structural Integrity ◽  
Degradation Products ◽  
Low Ph ◽  
Vascular Density ◽  
Peritoneal Membrane ◽  
Single Chamber ◽  
Neutral Ph ◽  
Glucose Degradation Products ◽  
Chronic Infusion ◽  
New Generation

Background Acidic pH and the presence of glucose degradation products (GDP) are believed to compromise the biocompatibility of peritoneal dialysis fluids (PDF). The present study examines the effects of long-term exposure to GDP and low pH by comparing conventional PDF and a new, neutral pH, low GDP solution. Methods All experiments were performed using a chronic infusion model of dialysis in nonuremic rats. The animals were treated for 6 weeks with 2 daily injections of 4.25% glucose-containing PDF. The following PDF were tested: CAPD3 (single-chamber bag, low pH, high GDP), CAPD3 pH 7.4 (single-chamber bag, neutral pH, high GDP), CAPD3-Balance (double-chamber bag, neutral pH, low GDP). All test solutions were obtained from Fresenius Medical Care, Bad Homburg, Germany. Results After 6 weeks of exposure, peritoneal permeability to water, urea, creatinine, glucose, and sodium, assessed by peritoneal equilibration test, was similar in all groups. However, compared to other PDF, dialysis with CAPD3-Balance was associated with reduced concentrations of protein and hyaluronan in the dialysate, decreased peritoneal eosinophilia, and reduced dialysate levels of chemokines CCL2/MCP-1 and CCL5/RANTES. Morphologic changes in the peritoneal membrane of CAPD3-Balance-treated animals were much less pronounced and included reduced vascular density, preservation of the mesothelial monolayer and intercellular junction, and no reduplication of the submesothelial basement membrane. Conclusions A new generation of PDF with physiologic pH and low GDP level produce less irritation to the peritoneal membrane and better preserve its structural integrity. This effect seems to be related predominantly to minimized GDP concentrations.

Comparison between Bicarbonate/Lactate and Standard Lactate Dialysis Solution in Peritoneal Transport and Ultrafiltration: A Prospective, Crossover Single-Dwell Study

2008 ◽  
Vol 28 (1) ◽  
pp. 35-43 ◽  
Author(s):  
Wei Fang ◽  
Robert Mullan ◽  
Hemal Shah ◽  
Salim Mujais ◽  
Joanne M. Bargman ◽  
...  
Keyword(s):  
Detailed Knowledge ◽  
Comparative Physiology ◽  
Inclusion Criteria ◽  
Solution Ph ◽  
Peritoneal Transport ◽  
Dialysis Solution ◽  
Baxter Healthcare ◽  
Low Glucose ◽  
Conventional Solution

Objective It has been proposed that biocompatible bicarbonate/lactate based (Bic/Lac), physiologic-pH peritoneal dialysis (PD) solutions will be beneficial in long-term PD. However, we do not yet have detailed knowledge concerning the comparative physiology of buffer transport for these new solutions and their impact on underlying peritoneal transport of solutes and ultrafiltration (UF). The purpose of this study was to investigate the profile of buffer handling and peritoneal membrane transport characteristics during a single dwell of the new Bic/Lac-based versus standard lactate-based (Lac) PD solution. Methods In this prospective crossover study, we compared a 25 mmol/L bicarbonate/15 mmol/L lactate buffered, physiologic pH, low glucose degradation product (GDP) solution (Physioneal; Baxter Healthcare, McGaw Park, Illinois, USA) with a standard lactate buffered, acidic pH, conventional solution (Dianeal; Baxter). 18 patients underwent two peritoneal equilibration tests (PETs) with 2.5% Dianeal and 2.5% Physioneal separated by 1 week. Buffer transport, mass transfer area coefficients (MTACs), solute transport, and UF were determined for the two PETs. All bags were weighed by a nurse before instillation and after drainage to assess the net UF in each dwell. Results 18 patients that met the inclusion criteria were enrolled in this study. Whereas intraperitoneal pH remained constant at 7.52 ± 0.11 throughout the dwell with the Bic/Lac solution, pH was still in the acidic range with the Lac solution after 1 hour (7.29 ± 0.13, p < 0.001); this difference disappeared after the second hour of dwell. The MTACs for creatinine (10.68 ± 3.66 vs 10.73 ± 2.96 mL/minute/ 1.73 m2, p > 0.05) and urea (27.94 ± 10.50 vs 27.62 ± 6.95 mL/min/1.73 m2, p > 0.05), for Bic/Lac versus Lac respectively, did not differ between these two solutions; transport of glucose and other solutes was also similar. However, after a 4-hour dwell with Bic/Lac solution, net UF was significantly lower than that observed with Lac solution (274.2 ± 223.3 mL vs 366.1 ± 217.3 mL, p = 0.026). Conclusions Compared to standard Lac-based solution, Bic/Lac based, pH neutral, low-GDP solution avoids intra-peritoneal acidity. Peritoneal mass transport kinetics are similar for small solutes. Net UF is significantly lower with Bic/Lac solution; the mechanism for this is unclear.

Structural Studies of Fibrinolysis by Electron and Light Microscopy

1999 ◽  
Vol 82 (08) ◽  
pp. 277-282 ◽  
Author(s):  
Yuri Veklich ◽  
Jean-Philippe Collet ◽  
Charles Francis ◽  
John W. Weisel
Keyword(s):  
Electron Microscopy ◽  
Light Microscopy ◽  
Plasminogen Activator ◽  
Structural Changes ◽  
Molecular Mechanisms ◽  
Degradation Products ◽  
Molecular Model ◽  
Three Dimensional ◽  
Tissue Type ◽  
Type Plasminogen Activator

IntroductionMuch is known about the fibrinolytic system that converts fibrin-bound plasminogen to the active protease, plasmin, using plasminogen activators, such as tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator. Plasmin then cleaves fibrin at specific sites and generates soluble fragments, many of which have been characterized, providing the basis for a molecular model of the polypeptide chain degradation.1-3 Soluble degradation products of fibrin have also been characterized by transmission electron microscopy, yielding a model for their structure.4 Moreover, high resolution, three-dimensional structures of certain fibrinogen fragments has provided a wealth of information that may be useful in understanding how various proteins bind to fibrin and the overall process of fibrinolysis (Doolittle, this volume).5,6 Both the rate of fibrinolysis and the structures of soluble derivatives are determined in part by the fibrin network structure itself. Furthermore, the activation of plasminogen by t-PA is accelerated by the conversion of fibrinogen to fibrin, and this reaction is also affected by the structure of the fibrin. For example, clots made of thin fibers have a decreased rate of conversion of plasminogen to plasmin by t-PA, and they generally are lysed more slowly than clots composed of thick fibers.7-9 Under other conditions, however, clots made of thin fibers may be lysed more rapidly.10 In addition, fibrin clots composed of abnormally thin fibers formed from certain dysfibrinogens display decreased plasminogen binding and a lower rate of fibrinolysis.11-13 Therefore, our increasing knowledge of various dysfibrinogenemias will aid our understanding of mechanisms of fibrinolysis (Matsuda, this volume).14,15 To account for these diverse observations and more fully understand the molecular basis of fibrinolysis, more knowledge of the physical changes in the fibrin matrix that precede solubilization is required. In this report, we summarize recent experiments utilizing transmission and scanning electron microscopy and confocal light microscopy to provide information about the structural changes occurring in polymerized fibrin during fibrinolysis. Many of the results of these experiments were unexpected and suggest some aspects of potential molecular mechanisms of fibrinolysis, which will also be described here.

scholarly journals Frequency-dependent interactions determine outcome of competition between two breast cancer cell lines

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Audrey R. Freischel ◽  
Mehdi Damaghi ◽  
Jessica J. Cunningham ◽  
Arig Ibrahim-Hashim ◽  
Robert J. Gillies ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Critical Density ◽  
Low Ph ◽  
Breast Cancer Cell Lines ◽  
Frequency Dependent ◽  
Density Dependent ◽  
Low Glucose ◽  
Competition Assays ◽  
Mcf 7

AbstractTumors are highly dynamic ecosystems in which diverse cancer cell subpopulations compete for space and resources. These complex, often non-linear interactions govern continuous spatial and temporal changes in the size and phenotypic properties of these subpopulations. Because intra-tumoral blood flow is often chaotic, competition for resources may be a critical selection factor in progression and prognosis. Here, we quantify resource competition using 3D spheroid cultures with MDA-MB-231 and MCF-7 breast cancer cells. We hypothesized that MCF-7 cells, which primarily rely on efficient aerobic glucose metabolism, would dominate the population under normal pH and low glucose conditions; and MDA-MB-231 cells, which exhibit high levels of glycolytic metabolism, would dominate under low pH and high glucose conditions. In spheroids with single populations, MCF-7 cells exhibited equal or superior intrinsic growth rates (density-independent measure of success) and carrying capacities (density-dependent measure of success) when compared to MDA-MB-231 cells under all pH and nutrient conditions. Despite these advantages, when grown together, MCF-7 cells do not always outcompete MDA-MB-231 cells. MDA-MB-231 cells outcompete MCF-7 cells in low glucose conditions and coexistence is achieved in low pH conditions. Under all conditions, MDA-MB-231 has a stronger competitive effect (frequency-dependent interaction) on MCF-7 cells than vice-versa. This, and the inability of growth rate or carrying capacity when grown individually to predict the outcome of competition, suggests a reliance on frequency-dependent interactions and the need for competition assays. We frame these results in a game-theoretic (frequency-dependent) model of cancer cell interactions and conclude that competition assays can demonstrate critical density-independent, density-dependent and frequency-dependent interactions that likely contribute to in vivo outcomes.

scholarly journals The cross-bridge cycle and skeletal muscle fatigue

2008 ◽  
Vol 104 (2) ◽  
pp. 551-558 ◽  
Author(s):  
Robert H. Fitts
Keyword(s):  
Peak Power ◽  
Molecular Mechanisms ◽  
Fiber Type ◽  
Low Ph ◽  
Forward Rate ◽  
Maximal Velocity ◽  
Functional Changes ◽  
Cross Bridge ◽  
The Cross

The functional correlates of fatigue observed in both animals and humans during exercise include a decline in peak force (P0), maximal velocity, and peak power. Establishing the extent to which these deleterious functional changes result from direct effects on the myofilaments is facilitated through understanding the molecular mechanisms of the cross-bridge cycle. With actin-myosin binding, the cross-bridge transitions from a weakly bound low-force state to a strongly bound high-force state. Low pH reduces the number of high-force cross bridges in fast fibers, and the force per cross bridge in both fast and slow fibers. The former is thought to involve a direct inhibition of the forward rate constant for transition to the strong cross-bridge state. In contrast, inorganic phosphate (Pi) is thought to reduce P0 by accelerating the reversal of this step. Both H+ and Pi decrease myofibrillar Ca2+ sensitivity. This effect is particularly important as the amplitude of the Ca2+ transient falls with fatigue. The inhibitory effects of low pH and high Pi on P0 are reduced as temperature increases from 10 to 30°C. However, the H+-induced depression of peak power in the slow fiber type, and Pi inhibition of myofibrillar Ca2+ sensitivity in slow and fast fibers, are greater at high compared with low temperature. Thus the depressive effects of H+ and Pi at in vivo temperatures cannot easily be predicted from data collected below 25° C. In vitro, reactive oxygen species reduce myofibrillar Ca2+ sensitivity; however, the importance of this mechanism during in vivo exercise is unknown.

Development of Toxic Degradation Products during Heat Sterilization of Glucose-Containing Fluids for Peritoneal Dialysis: Influence of Time and Temperature

1995 ◽  
Vol 15 (1) ◽  
pp. 26-32 ◽  
Author(s):  
Per Kjellstrand ◽  
Evi Martinson ◽  
Anders Wieslander ◽  
Björn Holmquist
Keyword(s):  
Peritoneal Dialysis ◽  
Glucose Solution ◽  
Degradation Products ◽  
General Pattern ◽  
Low Ph ◽  
Uv Absorbance ◽  
Influence Of Temperature ◽  
In Vitro Systems

Objective Fluids for peritoneal dialysis (PD) cause cytotoxic reactions in many different in vitro systems. The low pH, the high osmolality of the fluids, and the glucose degradation products formed during heat sterilization have been considered responsible. In the present study, we investigate the influence of temperature and time during heat sterilization of PD fluids and glucose solutions on glucose degradation and cytotoxicity of the solutions. Design Ampoules containing PD-fluid or glucose solution were heated in an oil bath to predetermined F o values (combinations of time and temperature giving equal energy/bacteriallethality). Cytotoxicity of the solutions was measured as groWth inhibition of cultured L-929 fibroblasts. Glucose degradation was measured as UV absorbance at 228 and 284 nm. Results The same general pattern was seen in both PD fluid and glucose solution. Cytotoxicity decreased from 90% to 15% when the sterilization temperature was increased from 115° to 140°C and concomitantly the length of time shortened in order to maintain equal bacteriallethality. Under the same conditions, degradation products, measured as UV absorbance at 284 nm, decreased from 0.2 to 0.02. Conclusion To minimizethe development of cytotoxic breakdown products, high temperatures over short periods of time should be used to heat-sterilize PD fluids. Even as small an increase as 5°C at around 120°C will improve the quality of the solutions.

scholarly journals The Anti-Inflammatory and Antioxidant Properties of n-3 PUFAs: Their Role in Cardiovascular Protection

Biomedicines ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 306 ◽  
Author(s):  
Francesca Oppedisano ◽  
Roberta Macrì ◽  
Micaela Gliozzi ◽  
Vincenzo Musolino ◽  
Cristina Carresi ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Vascular Reactivity ◽  
Molecular Mechanisms ◽  
Antioxidant Properties ◽  
Cardiac Cells ◽  
Membrane Phospholipids ◽  
Mitochondrial Functions ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Polyunsaturated fatty acids (n-3 PUFAs) are long-chain polyunsaturated fatty acids with 18, 20 or 22 carbon atoms, which have been found able to counteract cardiovascular diseases. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in particular, have been found to produce both vaso- and cardio-protective response via modulation of membrane phospholipids thereby improving cardiac mitochondrial functions and energy production. However, antioxidant properties of n-3 PUFAs, along with their anti-inflammatory effect in both blood vessels and cardiac cells, seem to exert beneficial effects in cardiovascular impairment. In fact, dietary supplementation with n-3 PUFAs has been demonstrated to reduce oxidative stress-related mitochondrial dysfunction and endothelial cell apoptosis, an effect occurring via an increased activity of endogenous antioxidant enzymes. On the other hand, n-3 PUFAs have been shown to counteract the release of pro-inflammatory cytokines in both vascular tissues and in the myocardium, thereby restoring vascular reactivity and myocardial performance. Here we summarize the molecular mechanisms underlying the anti-oxidant and anti-inflammatory effect of n-3 PUFAs in vascular and cardiac tissues and their implication in the prevention and treatment of cardiovascular disease.

scholarly journals “NEPP” Peritoneal Dialysis Regimen has Beneficial Effects on Plasma Cel and 3-DG, but not Pentosidine, CML, and MGO

2012 ◽  
Vol 32 (1) ◽  
pp. 45-54 ◽  
Author(s):  
Caatje Y. le Poole ◽  
Frans J. van Ittersum ◽  
Rob M. Valentijn ◽  
Tom Teerlink ◽  
Bengt Lindholm ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Plasma Levels ◽  
Plasma Proteins ◽  
Degradation Products ◽  
Beneficial Effects ◽  
Glycation End Products ◽  
Low Load ◽  
Carboxymethyl Lysine ◽  
Low Glucose ◽  
Acid Exchange

BackgroundStandard peritoneal dialysis (PD) solutions contain high levels of glucose and glucose degradation products (GDPs), both contributing to the formation of advanced glycation end products (AGEs). We studied the contribution to plasma GDP and AGE levels of 2 PD regimens that differ in glucose and GDP loads: high load [standard PD (sPD) using 4 glucose-lactate exchanges] and low load [1 amino acid exchange, 1 icodextrin exchange, and 2 glucose-bicarbonate/lactate exchanges (“NEPP”)].MethodsIn a prospective crossover study (2 periods of 24 weeks), new continuous ambulatory PD patients were randomized to NEPP-sPD ( n = 23) or to sPD-NEPP ( n = 27).ResultsAfter the start of PD, absolute increases were observed in plasma levels of 3-deoxyglucosone (3-DG, 220.4 nmol/L, p < 0.0001) and in Nε-(carboxymethyl) lysine (CML) in plasma proteins (0.02 μmol/L CML per 1 mol/L lysine, p < 0.0001). During the first 6 weeks, 3-DG tended to increase more with sPD treatment (p = 0.08), and CML, with NEPP treatment (p = 0.002). In both groups, Nε-(carboxyethyl)lysine (CEL) in plasma proteins declined significantly with the start of PD. Treatment with NEPP resulted in higher levels of methylglyoxal (MGO) and lower levels of 3-DG and CEL. Pentosidine in the albumin fraction tended to increase less during NEPP treatment.ConclusionsA low glucose and GDP PD regimen (NEPP) resulted in plasma levels of 3-DG and CEL that were lower than those with a glucose-based sPD regimen. Starting PD with NEPP was associated with a steeper increase in CML, and continuing treatment with NEPP resulted in higher MGO levels.

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