Charged Polymers as Osmotic Agents for Peritoneal Dialysis

1985 ◽  
Vol 55 ◽  
Author(s):  
Zbylut J. Twardowski ◽  
Karl D. Nolph ◽  
Ramesh Khanna ◽  
Hannelore Hain ◽  
Harold Moore ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Peritoneal Dialysis ◽  
Colloid Osmotic Pressure ◽  
Small Molecular Weight ◽  
Plasma Substitutes ◽  
Chemically Modified ◽  
Charged Polymers ◽  
Gelatin Derivative ◽  
Osmotic Agents

ABSTRACTA sustained ultrafiltration during long-dwell peritoneal dialysis exchanges cannot be achieved with rapidly absorbable small molecular weight substances such as commonly used glucose. Uncharged polymeric substances are absorbed slower, but yield insufficient osmotic driving force because osmolality is inversely proportional to the molecular weight.Charged polymers induce colloid osmotic pressure not only because of the molecules themselves, but also by ions kept in the peritoneal cavity by opposite charges of polymers. In anin vitromodel of peritoneal dialysis, a sustained ultrafiltration has been achieved with several synthetic polymers including polyacrylate, dextran sulfate and polyethylenimine. However, these polymers were locally toxic to the peritoneal membrane when tested in rats and rabbits.Chemically modified gelatin derivatives, such as polygelin, exypolygelatin, and succinylated gelatin are widely used in Europe as plasma substitutes. They are metabolized and have proven to be systemically non-toxic. These gelatin derivative solutions were tested in rat models of peritoneal dialysis. Up to 10% solutions achieved sustained ultrafiltration at the rate proportional to the concentration and no untoward systemic or local effects on the peritoneum were observed. Absorption of gelatin molecules ranged from 40–60% of the infused amounts. The results of the studies indicate that gelatin derivitives have potential for clinical use as osmotic agents in long-dwell peritoneal dialysis exchanges if the absorption rates in humans are markedly lower than in rats.

Polymers as Osmotic Agents for Peritoneal Dialysis

1984 ◽  
Vol 4 (2_suppl) ◽  
pp. 125-131 ◽  
Author(s):  
Zbylut J. Twardowski ◽  
Harold L. Moore ◽  
Terry J. McGary ◽  
Mira Poskuta ◽  
Charalambos Stathakis ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Peritoneal Membrane ◽  
Small Molecular Weight ◽  
Plasma Substitutes ◽  
Dialysis Solution ◽  
Osmotic Agent ◽  
Peritoneal Dialysis Solution ◽  
Solute Absorption ◽  
Osmotic Agents ◽  
Dialysis Solutions

A sustained ultrafiltration during long-dwell peritoneal dialysis exchanges cannot be obtained with rapidly absorbable small molecular weight osmotic agents. Slowly absorbable synthetic poly ions tested on rats and rabbits yielded high and sustained ultrafiltration, but were toxic. Gelatin solutions were not toxic in acute rat studies and produced sustained ultrafiltration but were difficult to work with because of gelation. A review of the literature on the properties of gelatin derivatives, used as plasma substitutes, led us to believe that they may be also useful as osmotic agents in the peritoneal dialysis solutions. In the peritoneal dialysis system, hydrostatic pressure in the blood compartment cannot be readily manipulated. Therefore, traditionally a solute (osmotic agent) is added to the peritoneal dialysis solution to create an osmotic driving force. During the process of ultrafiltration (Figure I), the rate of ultrafiltration decreases with time due to dilution by ultrafiltrate and absorption of the osmotic agent. Thus, ultrafiltration will eventually cease after the dialysis solution is infused. The bigger the molecule of the osmotic agent, the longer ultrafiltration lasts because solute absorption through the peritoneal membrane is slower. Thus, to achieve sustained ultrafiltration, an osmotic agent with a bigger molecule would be more advantageous than the smaller one at comparable osmotic gradients.

The role of small molecular weight compounds to increase vacuolation induced by VacA toxin in vitro

2010 ◽  
Vol 24 (5) ◽  
pp. 1373-1378 ◽  
Author(s):  
Juan Sun ◽  
Yan Wu ◽  
Zhuang Su ◽  
Zhifang Liu ◽  
Bingzhong Su ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Small Molecular Weight

Complexing of Low Mr-Weight Human Urokinase In Rat Serum And Its Degradation Into Fragments Of Very Small Molecular Weight In Vivo But Not In Vitro

1981 ◽  
Author(s):  
Ph Schneider ◽  
M Ruegg ◽  
F Bachmann
Keyword(s):  
Molecular Weight ◽  
Inferior Vena ◽  
Vena Cava ◽  
Albino Rats ◽  
Small Molecular Weight ◽  
Rat Serum ◽  
Blood Samples ◽  
Sds Page

Highly purified lew molecular weight urokinase (LMR-UK), moving on SDS-PAGE (reduced and nan-reduced) as a single band of 32 kdalton, was labelled with 125I by the chlora- mine-T method. 106 cpn of this 125I-LMr-UK (94% TCA preci- pitable) were injected into the inferior vena cava of la- par atomized albino rats, which were maintained at 37°C. Blood samples were collected by cardiac puncture 5, 30 and 90 min respectively after the injection. Serun, obtained from these samples, was fractionated on a Sephadex G-100 column, calibrated with proteins of known Mr. Radioactivity was measured in the collected fractions.In the 5 min sample, the radioactivity was distributed in 2 peaks, corresponding to 32 kdalton and to < 70 kdalton respectively. In the 30 min sample, the distribution was characterized by a diminution of the 32 kdalton peak and the appearance of a third peak corresponding to a Mr of < 4 kdalton. In the 90 min sample, the LMr-UK peak had disappeared almost completely. About 40% of the 125I-activity was present in a skewed high Mr peak with a broad maximum in the 85-100 kdalton region; ≥ 60% of the 125I-activity was recovered in late fractions corresponding to < 4 kdalton. In control experiments, pooled rat serum was incubated in vitro with 125I-LMr-UK for 5, 30 and 90 min respectively and samples were fractionated on the same column. The radioactivity distribution shewed only the 32 and > 70 kdalton peaks, but no < 4 kdalton peak.These results suggest that LMr-UK is complexed to a carrier protein, both in vivo and in vitro, but that it is degraded into small fragments in vivo only. Attempts to characterize the nature of these complexes are in progress.

On-Line Hemodiafiltration with Pre- and Postdilution: A Comparison of Efficacy

1997 ◽  
Vol 20 (2) ◽  
pp. 81-90 ◽  
Author(s):  
P. Ahrenholz ◽  
R.E. Winkler ◽  
W. Ramlow ◽  
M. Tiess ◽  
W. Müller
Keyword(s):  
Molecular Weight ◽  
Theoretical Description ◽  
Convective Transport ◽  
Small Molecular Weight ◽  
Dialysate Flow ◽  
Significant Difference ◽  
On Line ◽  
The Impact

Since the introduction of on-line substituate preparation, high substituate rates (Qs) in pre- and postdilution for hemodiafiltration (HDF) procedures can be realized. During postdilution HDF (POD-HDF) and additional convective removal is possible, but in vivo Qs is limited to approx. 1/3Qb (bloodflow). With predilution HDF (PRD-HDF) higher Qs and therefore high convective transport rates by ultrafiltration can be reached. On the other hand the blood concentration is diminished by predilution. Further decrease of the diffusive transport is caused by reduced dialysate flow Qd due to separation of the substituate from the dialysate (Fresenius 4008 On-Line HDF, Gambro AK100 Ultra). The theoretical description of the combined diffusive-convective transport is limited to 1-dimensional models and small UF-rates. Therefore for practical and theoretical purposes the assessment of the efficacy of on-line PRD-HDF and POD-HDF in different molecular weight ranges is desirable. By means of in vitro experiments the effective clearances Keff of hemodialysis (HD, dialyzer: Fresenius F60) for urea, creatinine, vitamin B12 and inulin were compared with measured and theoretical Keff of POD- and PRD-HDF. The theoretical expectation is confirmed that Keff for small molecular weight substances decreases slightly with PRD-HDF and increases for larger molecules. In the case of POD-HDF Keff for small molecular weight substances increases slightly and strongly for larger molecules. In vivo experiments were performed to measure the real substance removal from patient's blood and to figure out the impact of dialysate flow (collection of the used dialysate during the 1. treatment hour and concentration measurements for urea, creatinine, phosphate, ß2-MG). The results show that the substraction of Qs from Qd reduces Keff for urea, creatinine and phosphate but not for ß2-MG. PRD-HDF with Qd = 500 ml/min is significantly less effective for small molecules than HD. There is no significant difference of Keff for urea, creatinine, phosphate during HD and PRD-HDF with Qd = 800 ml/min, but a significant increase of 10-15% for POD-HDF Keff for ß2-MG increases by 75% for PRD-HDF and 95% for POD-HDF compared with HD (Qd = 500 ml/min).

Pharmacology and Safety of SB-497115-GR, an Orally Active Small Molecular Weight TPO Receptor Agonist, in Chimpanzees, Rats and Dogs.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2063-2063 ◽  
Author(s):  
Teresa Sellers ◽  
Timothy Hart ◽  
Michael Semanik ◽  
Krishna Murthy
Keyword(s):  
Molecular Weight ◽  
Clinical Trials ◽  
Receptor Agonist ◽  
Fold Increase ◽  
Distinct Species ◽  
In Vivo Studies ◽  
Small Molecular Weight ◽  
Platelet Counts

Abstract SB 497115-GR is a small molecular weight Tpo receptor (TpoR) agonist that has properties similar to thrombopoietin (TPO), primarily inducing proliferation and differentiation of megakaryocytes from bone marrow progenitor cells. SB-497115-GR is being developed for the treatment of thrombocytopenias, such as immune thrombocytopenic purpura. In vitro and in vivo studies have demonstrated that SB-497115-GR has very distinct species specificity. SB-497115 or other molecules in this class induced dose dependent STAT activation in platelets from humans and chimpanzees but not in platelets from laboratory animal species commonly used in drug safety studies. In order to demonstrate in vivo activity of SB-497115-GR, a single dose and 5 daily dose pharmacology and safety study in chimpanzees was conducted. To support initiation of clinical trials, a comprehensive package of toxicology studies was conducted including studies up to 14 days duration in rats and dogs. All procedures involving the care and use of animals in these studies were reviewed and approved by the appropriate Institutional Animal Care and Use Committees. Female chimpanzees (1–3/group) were administered vehicle or SB-497115-GR at doses of 0.1 to 10 mg/kg/day by oral gavage. For toxicology studies, SB-497115-GR was administered orally to rats (10/sex/group) by gavage at doses of 3 to 40 mg/kg/day and to dogs (3/sex/group) by capsule at doses of 3 to 30 mg/kg/day for 14 days. SB-497115-GR was well tolerated in chimpanzees, rats and dogs at all doses tested. In chimpanzees, no treatment related increases in platelet counts were observed after administration of single doses of up to 10 mg/kg or 5 daily doses of up to 3 mg/kg/day. However, following 5 daily doses of 10 mg/kg/day SB-497115-GR, there was a 1.3- to 2.4-fold increase in circulating platelet counts in 3 chimpanzees. A similar change in reticulated platelet counts was observed preceding this increase. In contrast, there was no effect of treatment for up to 14 days on platelet counts in rats or dogs. In conclusion, SB-497115-GR, an orally bioavailable small molecular weight agonist of the TpoR, has been shown to increase platelet counts in chimpanzees. These in vivo data confirm the in vitro data demonstrating the unique species-specific effects of this novel Tpo receptor agonist on platelets and were predictive of a pharmacodynamic effect currently being observed in human clinical trials.

Fate of receptor-bound human chorionic gonadotrophin in pseudopregnant rat ovaries perfused in vitro

1985 ◽  
Vol 109 (1) ◽  
pp. 115-121
Author(s):  
Hannu Rajaniemi ◽  
Jan Sogn ◽  
Paul Holmes ◽  
Björn Källfelt ◽  
Per Olof Janson
Keyword(s):  
Molecular Weight ◽  
Histological Examination ◽  
Gel Filtration ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Cell Periphery ◽  
Small Molecular Weight ◽  
Immunohistochemical Studies

Abstract. Pseudopregnant rats were injected with [125I] hCG, anaesthesized 1 h later and after cannulation of the aorta the ovaries were isolated and perfused with Gey & Gey buffer containing 0.2% BSA. The release of radioactivity was monitored for 2 h and analyzed by gel filtration. Five to ten per cent of the radioactivity was released within 2 h and represented small molecular weight peptides and iodotyrosine and [125I]hCG. Analysis of the ovarian radioactivity prior to and after perfusion revealed that virtually all hCG was receptor-bound. Loading the medium with unlabelled hCG displaced [125I]hCG from the receptor but did not enhance its degradation. Histological examination showed that the ovarian tissues were still intact after the 2 h perfusion. Immunohistochemical studies revealed a localization of the hCG at the cell periphery both prior to and after perfusion. These results provide evidence showing that the rate of internalization of receptor-hCG complexes in rat luteal cells is slow in vivo.

scholarly journals In-Vitro Characterization of Nanoparticles and Antiagregation Tests on Brown Seaweed Extracts (Sargassum polycystum) Types of Sellulase Enzyme Hydrolysis

2019 ◽  
Vol 17 (2) ◽  
pp. 164
Author(s):  
Kartiningsih Kartiningsih ◽  
Syamsudin Abdillah ◽  
Partomuan Simanjuntak ◽  
Cyntia Cyntia ◽  
Haryo Haryo
Keyword(s):  
Molecular Weight ◽  
Brown Seaweed ◽  
Spherical Shape ◽  
Enzyme Hydrolysis ◽  
Seaweed Extract ◽  
Small Molecular Weight ◽  
Quality Requirements ◽  
Physical Quality ◽  
Before And After

Brown seaweed contains fucoidan, a large molecular weight sulfate polysaccharide (about 100,000 Da) which has platelet antiagregation activity. This activity is achieved if the fucoidan has a small molecular weight (3900-7600 Da) so this activity can increase by hydrolized with sellulase Enzym. The purpose of this study was to obtain extract nanoparticles that meet physical quality requirements and have a higher platelet antiagregation activity than brown seaweed extract both before and after hydrolysis. Extraction was using kinetic maseration method using 80% ethanol after that using 2% calcium chloride solution. The results were dried and hydrolyzed with cellulase enzyme and nanoparticles were made by ionic gelation method. Nanoparticle characterization results in particle size of 552.8, polydispersity index of 0.569, potential zeta of +53.5 mV, and spherical shape. In-vitro testing results for platelet antiagregation activity showed the percentage of platelet aggregation inhibition of brown seaweed extract with a concentration 500µg / mL is 22.19% and extracts after hydrolysis was 57.94% and nanoparticles extract after hydrolysis was 72.93%. Extract nanoparticles meet physical quality requirements and extracted nanoparticles after hydrolysis have the highest platelet antiagregation activity compared to brown seaweed extract both before and after hydrolysis.

scholarly journals Neuroendocrine Synaptic Vesicles Are Formed In Vitro by Both Clathrin-dependent and Clathrin-independent Pathways

1998 ◽  
Vol 143 (4) ◽  
pp. 947-955 ◽  
Author(s):  
Gongyi Shi ◽  
Victor Faúndez ◽  
Jack Roos ◽  
Esteban C. Dell'Angelica ◽  
Regis B. Kelly
Keyword(s):  
Molecular Weight ◽  
Plasma Membrane ◽  
Synaptic Vesicles ◽  
Brefeldin A ◽  
Adaptor Protein ◽  
Interacting Proteins ◽  
Small Molecular Weight ◽  
Adp Ribosylation Factor ◽  
Dependent Pathway

In the neuroendocrine cell line, PC12, synaptic vesicles can be generated from endosomes by a sorting and vesiculation process that requires the heterotetrameric adaptor protein AP3 and a small molecular weight GTPase of the ADP ribosylation factor (ARF) family. We have now discovered a second pathway that sorts the synaptic vesicle-associated membrane protein (VAMP) into similarly sized vesicles. For this pathway the plasma membrane is the precursor rather than endosomes. Both pathways require cytosol and ATP and are inhibited by GTPγS. The second pathway, however, uses AP2 instead of AP3 and is brefeldin A insensitive. The AP2-dependent pathway is inhibited by depletion of clathrin or by inhibitors of clathrin binding, whereas the AP3 pathway is not. The VAMP-containing, plasma membrane–derived vesicles can be readily separated on sucrose gradients from transferrin (Tf)-containing vesicles generated by incubating Tf-labeled plasma membrane preparations at 37°C. Dynamin- interacting proteins are required for the AP2-mediated vesiculation from the plasma membrane, but not from endosomes. Thus, VAMP is sorted into small vesicles by AP3 and ARF1 at endosomes and by AP2 and clathrin at the plasma membrane.

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