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Immobilization of a lysine-terminated heparin to polyvinyl alcohol.

Lysine terminated heparin, prepared by the nitrous acid partial depolymerization and reductive amination of heparin, failed to increase the active heparin content of a heparin-polyvinyl alcohol (heparin-PVA) hydrogel relative to the unmodified commercial heparin. The depolymerization of heparin resulted in a loss of biological activity which outweighed the increase in the terminal amine groups (produced by reductive amination), that were used for glutaraldehyde immobilization to the PVA. The loss in anti-thrombin activity (thrombin time or chromogenic substrate) paralleled the increase in anhydromannose end groups due to depolymerization making it necessary to optimize the loss of activity against the increase in terminal amine groups after amination. For example, depolymerization at a high sodium nitrite concentration (81 g/l) at pH4 and 25 degrees C for 20 min, resulted in a loss of 22-40% of the biological activity but achieved an anhydromannose content of 600 nmoles/mg (approximately 7 cleavage sites/molecule). After the anhydromannose groups were reductively aminated by lysine, the anhydromannose content was reduced to 190 nmol/mg indicating a terminal lysine content of 410 nmol/mg. This resulted in an increase in heparin content of the final hydrogel by 53% on mass terms. However, given the reduction in biological activity, it was not surprising that the modified heparin-PVA hydrogel coated on a polyethylene tube was no better than the hydrogel with unmodified heparin in inactivating thrombin in a flow circuit. These results point out the need for care in interpreting heparin immobilization results and for new strategies to increase the active heparin content of this hydrogel.

Gels↗

Stedim 6 and Clearflex, two new multilayer materials for infusion containers. Comparative study of their compatibility with five drugs versus glass flasks and polyvinyl chloride bags.

Stedim 6 and Clearflex, two new polyethylene-lined materials for infusion bags, were studied for their compatibility with disodium clodronate, chlorpromazine and maprotiline hydrochlorides, diazepam, and clorazepate dipotassium salt, comparatively with borosilicate glass flasks and polyvinyl chloride bags. Diazepam, the only drug to exhibit a marked sorption in PVC bags (the loss reached 25% of the initial concentration after a contact duration of 72 h), showed lower sorption in Stedim 6 bags (loss about 11% under the same conditions) and none in Clearflex bags. No significant difference was observed between the infusion solutions used as vehicles of the drugs (5% dextrose and 0.9% sodium chloride isotonic solutions). The results are discussed in terms of lipophilicity of the drugs and crystallinity of the polymers.

Adsorption↗

Hepatocyte culture utilizing porous polyvinyl formal resin maintains long-term stable albumin secretion activity.

To investigate the effects of culture conditions on the maintenance of metabolic functions of cultured hepatocytes, long-term hepatocyte culture lasting 20 days was performed under two different culture conditions, i.e. stationary cultures utilizing porous polymer (polyvinyl formal (PVF) resin) as a substratum and conventional monolayer dish cultures without PVF. Metabolic activities specific to hepatocytes were evaluated in terms of ammonia metabolism, urea synthesis, and albumin secretion. Concerning ammonia metabolic and urea synthetic activities, no significant differences in maintenance of these activities were found between the two culture conditions, and these activities rapidly decreased with the elapse of the culture period, especially during the early stage of the experiments. However, after day 10, these activities in the stationary cultures were maintained at a slightly more favorable level than in the monolayer cultures. On the other hand, compared with ammonia metabolism and urea synthesis, stable and well-maintained albumin secretion of hepatocytes (60% of the activity in day 1) was exhibited in the stationary culture experiments, despite that this particular activity under the monolayer culture condition gradually reduced to a very low level (5.7% of that on day 1) at the end of the culture. From the morphological observations, hepatocytes immobilized in the PVF resin revealed individual spherical shapes without forming multicellular aggregation, and it was suggested that this characteristic structure contributed to good albumin secretion of hepatocytes. In conclusion, the advantages of the hepatocyte culture technique utilizing PVF resin over the conventional dish culture in maintaining some representative metabolic function specific to hepatocytes were clarified.

Albumins↗

A new polyvinyl chloride coil with improved performance for blood warming.

A new polyvinyl chloride (PVC) coil has been tested. The thinner walls give a better heat transfer so that an output temperature of 32.7 degrees occurs at 150 ml/min under test. This is higher than any PVC coil previously tested. Suggestions are made about methods of further improving the performance.

Blood Transfusion↗

Polyvinyl alcohol--gelatin patches of salicylic acid: preparation, characterization and drug release studies.

Polyvinyl alcohol-gelatin patches were developed and salicylic acid was incorporated at different stages of preparation of the patches. The patches were characterized by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), differential scanning calorimetry, tensile strength test, and scanning electron microscopy. The release patterns of the drug from the patches were also studied. The FTIR spectra of the blank patch indicated complete esterification of the free carboxylic groups of gelatin. The XRD studies indicated a crystalline form of the drug entrapped in the patches. Release of the drug from the patches followed Higuchian/Fickian kinetics indicating a diffusion-controlled release process.

Absorption↗

Managing milk leakage in breastfeeding women: a clinical trial evaluating a polyvinyl chloride device versus disposable nursing pads.

The object of this clinical trial was to evaluate the effectiveness and to investigate possible problems associated with the use of a polyvinyl chloride (PVC) device ("blis") compared to a disposable nursing pad, for controlling milk leakage among nursing mothers. Seventy-one women completed the single blind, paired comparison, randomized trial. Among the 28 women having a strong early preference, 21 opted for the PVC device (p = 0.01). Of the 37 women experiencing excessive milk leakage who preferred one of the devices, 24 preferred the PVC device (p = 0.05). There was no evidence that one device caused more problems or feeding complications than the other. This study is important in alleviating anxiety about device safety while promoting breastfeeding in mothers fearful of leaking at inopportune times.

Adolescent↗

Vaginal absorption of polyvinyl alcohol in Fischer 344 rats.

Polyvinyl alcohol (PVA) is a polymer with a wide range of molecular weights and uses. Recently, low molecular weight formulations of PVA have been used as components of contraceptive products designed for intravaginal administration in human females. Previous studies in animals have determined that little or no absorption of PVA occurs from the gastrointestinal (GI) tract. However, there is some concern that PVA of lower molecular weights might be absorbed across membranes of the reproductive tract. Consequently, this work has investigated the absorption of low molecular weight PVA across biological membranes of the reproductive and GI tracts of Fischer 344 rats. Oral administration of ten consecutive daily doses of 14C PVA resulted in little apparent absorption of the dose from the GI tract. In contrast, intravaginal administration of 14C PVA resulted in increasing concentrations of PVA-derived radioactivity in major tissues following one, three or ten daily doses of the estimated human dose of 3 mg/kg. PVA-derived radioactivity was concentrated mainly in the liver, reaching a peak greater than 1750 ng equivalents/g tissue 24 hours following ten daily doses. Over 300 ng equivalents/g tissue were still present in the liver 30 days following the last dose.

Absorption↗

Evaluation of an immunoisolation membrane formed by incorporating a polyvinyl alcohol hydrogel within a microporous filter support.

An immunoisolation membrane formed by incorporating a high water content polyvinyl alcohol (PVA) hydrogel into a microporous polyether sulfone (PES) filter has been investigated in this study. The PVA hydrogel is formed in situ within the filter pores via glutaraldehyde (GA) crosslinking under acidic conditions. The tortuous nature of the microporous filter pores securely anchors the embedded hydrogel to provide excellent structural integrity. The high void fraction of the PES filter support (>80%) and high water content of the PVA hydrogel (>85% water by weight) allow excellent solute transport rates, while an appropriate level of glutaraldehyde crosslinking supplies the required molecular size selectivity. In vitro permeability measurements made with solutes covering a wide range of molecular sizes demonstrate high transport rates for small nutrient molecules with rapidly diminishing permeabilities above a molecular weight of approximately 1,000 Dalton. Implantation experiments show that the membrane properties are not deleteriously affected by prolonged in vivo exposure or common sterilization techniques. Thus, this hybrid hydrogel/filter membrane system offers a promising approach to the immunoisolation of implanted cells.

Animals↗

Stability of intravenous famotidine stored in polyvinyl chloride syringes.

The stability of intravenous famotidine in dextrose 5% injection (D5W), NaCl 0.9% injection (NS), and sterile water for injection stored in polyvinyl chloride (PVC) syringes at 4 degrees C for 14 days was studied. The concentration of famotidine samples was determined at time 0, 7 days, and 14 days by reverse-phase high-performance liquid chromatography. Samples were inspected for visual changes and tested for changes in pH. Results of the HPLC analysis indicated that the famotidine samples remained within 94-100 percent and 99-103 percent of the time 0 concentrations at 7 and 14 days, respectively. Repeated measures analysis of variance demonstrated a significant time effect on famotidine concentration as concentrations changed over time (p less than 0.01). This change was small in magnitude, however, and concentrations decreased at 7 days and increased at 14 days. Famotidine is stable at a concentration of 2 mg/mL in D5W, NS, and sterile water for injection stored in PVC syringes at 4 degrees C for 14 days.

Chromatography, High Pressure Liquid↗

Stability of famotidine in polyvinyl chloride minibags and polypropylene syringes and compatibility of famotidine with selected drugs.

OBJECTIVE: (1) to determine the stability of famotidine 200 micrograms/mL in admixtures with dextrose 5% injection (D5W) and NaCl 0.9% injection (NS) in polyvinyl chloride (PVC) minibags and polypropylene syringes, at room temperature (22 degrees C), protected and unprotected from light for 15 days; and (2) to evaluate the visual compatibility of famotidine with 34 selected drugs for four hours at room temperature. DESIGN: Concentration of famotidine samples was determined on day 0 and again on days 3, 6, 9, 12, and 15 by a stability-indicating HPLC. Inspection for visual and pH changes was also performed at these time intervals. RESULTS: More than 95 percent of the day 0 famotidine concentration remained in all samples over the 15-day study period. During this period, all samples remained clear and colorless and no change in absorbance at 450 and 540 nm was observed. The pH of the samples also remained unchanged. Famotidine 2000 micrograms/mL was found to be compatible with 33 selected drugs; only furosemide was found to be incompatible. A white precipitate was observed when an equal volume of famotidine 2000 micrograms/mL in NS was mixed with furosemide 3000 micrograms/mL in D5W. The concentration of famotidine in the supernatant gradually decreased during the 4-hour study period. At 0.5, 1.0, 2.0, and 4.0 hours after mixture of famotidine with furosemide, famotidine concentrations were 97.5, 23.6, 21.7, and 17.2 percent of the initial famotidine concentration, respectively. CONCLUSIONS: Our results show that famotidine 200 micrograms/mL was stable in admixture with D5W and NS in PVC minibags and polypropylene syringes when these solutions were stored at room temperature, protected and unprotected from light for 15 days. Famotidine 2000 micrograms/mL in NS was compatible with 33 of the drugs, and was incompatible with furosemide.

Analysis of Variance↗

Rapid loss of fentanyl citrate admixed with fluorouracil in polyvinyl chloride containers.

OBJECTIVE: To study the physical compatibility and chemical stability of fluorouracil 1 and 16 mg/mL with fentanyl citrate 12.5 micrograms/mL in dextrose 5% and in sodium chloride 0.9% injection. DESIGN: Test solutions of the drugs in dextrose 5% injection and in sodium chloride 0.9% injection were prepared in triplicate and stored at -20, 4, 23, and 32 degrees C. Samples were removed immediately and at various times over 7 days and stored at -70 degrees C until analyzed. Physical compatibility was assessed visually and by measuring turbidity with a color-correcting turbidimeter; particle content was measured with a light-obscuration particle sizer and counter. Chemical stability was determined by measuring the concentration of each drug in the test solutions in duplicate with stability-indicating HPLC. RESULTS: Fentanyl citrate was rapidly lost when admixed with fluorouracil in polyvinyl chloride (PVC) containers, losing about 25% in the first 15 minutes and about 50% in the first hour. The loss of fentanyl citrate was so rapid that accurate time zero determinations were not possible. The extent of fentanyl loss increased with time and occurred more rapidly at the higher temperatures (i.e., 23, 32 degrees C). Losses of 70% or more occurred in all samples within 24 hours. Fentanyl underwent rapid sorption to the containers at the high pH (9.0-9.5) of the fluorouracil admixtures. Adjusting the pH of a fentanyl citrate solution (containing no fluorouracil) in PVC containers to pH 9 with sodium hydroxide also resulted in rapid sorption loss. Fentanyl citrate sorption did not occur when admixtures were prepared in polyethylene containers. Fluorouracil remained stable for at least 7 days at all temperatures. There were no visual or subvisual changes in turbidity or particle content in any of the test solutions at any time. CONCLUSIONS: When admixed with fluorouracil 1 and 16 mg/mL in dextrose 5% injection and sodium chloride 0.9% injection, fentanyl citrate 12.5 micrograms/mL underwent rapid and extensive loss due to sorption to the PVC containers, making the combination unacceptable within minutes of mixing. The sorption results from the alkaline pH of the admixture and, presumably, could occur from the admixture of fentanyl citrate with any sufficiently alkaline drug.

Analgesics, Opioid↗

Stability of fosphenytoin sodium with intravenous solutions in glass bottles, polyvinyl chloride bags, and polypropylene syringes.

OBJECTIVE: To determine the stability of fosphenytoin sodium admixtures with NaCl 0.9% injection and dextrose 5% (D5W) injection when stored in glass or polyvinyl chloride (PVC) containers, to evaluate the compatibility of fosphenytoin with 11 other intravenous solutions, and to determine the stability of fosphenytoin repackaged in polypropylene syringes. METHODS: Dilutions of fosphenytoin sodium 1, 8, and 20 mg phenytoin sodium equivalents (PE)/mL were prepared in NaCl 0.9%, D5W, and 11 other intravenous fluids. Aliquots of each solution in NaCL 0.9% or D5W were transferred to three glass bottles for storage at 25 degrees C and 21 PVC bags for storage at 25, 4, or -20 degrees C. Aliquots of each admixture with the other intravenous fluids were transferred to three PVC bags and stored at 25 degrees C for 7 days. In addition, 63 syringes were filled with fosphenytoin sodium 50 mg PE/mL (undiluted) and stored at 25, 4, or -20 degrees C. Samples of each solution from the three containers were analyzed for visual compatibility, pH, and fosphenytoin concentration initially and at 0.5, 1, 2, 3, 7, 14, and 30 days during storage at 25 and 4 degrees C and at 1, 7, 14, and 30 days during storage at -20 degrees C. Following removal of containers from the freezer, additional samples were obtained after 7 days at 4 or 25 degrees C, and 7 days at 25 degrees C, and then 7 days at -20 degrees C. RESULTS: No visible precipitation or change in color or clarity was observed in any of the fosphenytoin solutions during the study. The concentration of fosphenytoin at each sampling time remained within 97-104% of initial concentration, regardless of container, concentration, intravenous admixture, or storage temperature. CONCLUSIONS: Fosphenytoin sodium, either undiluted in polypropylene syringes or diluted with NaCl 0.9% or D5W in PVC bags, remains stable for at least 30 days at room temperature, under refrigeration, or frozen. After removal from the freezer, fosphenytoin can be thawed, kept at 4 or 25 degrees C for 7 days, and then returned to the freezer for another 7 days. Admixtures of fosphenytoin sodium in various other intravenous fluids are stable for at least 7 days at room temperature.

Chromatography, High Pressure Liquid↗

Ultrastructural immunocytochemistry of particulate fractions using polyvinyl chloride microculture wells.

A method is described for immunoelectron microscopy of particulate subcellular fractions using polyvinyl chloride (soft) microculture wells as mechanical supports and reaction vessels. Appropriate quantities of particles are centrifuged onto the well bottoms, fixed and permeabilized if necessary, then labeled by standard procedures, fixed in glutaraldehyde and tannic acid, and prepared for thin section electron microscopy. The centrifugation, the fixations, and the embedment in Epon are discussed in detail.

Animals↗

Localization of xanthine oxidoreductase activity using the tissue protectant polyvinyl alcohol and final electron acceptor Tetranitro BT.

We have detected xanthine oxidoreductase activity in unfixed cryostat sections of rat and chicken liver, rat duodenum, and bovine mammary gland using the tissue protectant polyvinyl alcohol, the electron carrier 1-methoxyphenazine methosulfate, the final electron acceptor Tetranitro BT, and hypoxanthine as a substrate. Enzyme activity was localized in rat duodenum at lateral membranes and brush borders of enterocytes and in goblet cells and mucus. Hepatocytes in pericentral areas and especially sinusoidal cells showed high activity in rat liver. Xanthine oxidoreductase was also detected in epithelial cells and milk lipid globules of lactating bovine mammary gland, which is known to contain large quantities of the oxidase form of the enzyme. Chicken liver, which contains an inconvertible dehydrogenase form, also showed high activity in sinusoidal cells. Therefore, we conclude that the tetrazolium reaction demonstrates both the dehydrogenase and the oxidase form of xanthine oxidoreductase. Control activity, in the absence of hypoxanthine or in the presence of the competitive inhibitor allopurinol, was low in all tissues studied. Addition of O2 or NAD to the incubation medium did not change the specific reaction in bovine mammary gland or chicken liver, implying that the dehydrogenase and the oxidase form are not dependent on their natural electron acceptors in this tetrazolium salt reaction. We conclude that the present light microscopic method gives specific and precise localization of xanthine oxidoreductase activity in situ.

Allopurinol↗

A quantitative histochemical study of xanthine oxidase activity in rat liver using the cerium capture method in the presence of polyvinyl alcohol.

A recently developed histochemical technique to demonstrate xanthine oxidase activity in milk globules of bovine mammary gland and in epithelial cells of rat small intestine using cerium ions and a semipermeable membrane was slightly modified. The semipermeable membrane method was replaced by the addition of 10% (w/v) polyvinyl alcohol to the incubation medium. This technically more simple procedure enabled detection of xanthine oxidase activity in unfixed cryostat sections of rat liver. Both methods gave qualitatively and quantitatively similar results. Activity was found in sinusoidal cells and in liver parenchymal cells, with 50% higher activity in pericentral than in periportal areas. The specificity of the reaction was proven by the generation of only small amounts of final reaction product on incubation either in the absence of the substrates hypoxanthine or oxygen or in the presence of hypoxanthine and allopurinol. Allopurinol is a specific inhibitor of xanthine oxidase activity. The amount of final reaction product, as measured cytophotometrically in rat liver, increased linearly with incubation time (15-90 min) and with section thickness (up to 12 microns). By varying the hypoxanthine concentrations, a Km value of 0.05 mM was found. Addition of dithiothreitol to the incubation medium reduced the amount of final reaction product by 85%, which was caused by conversion of reversible xanthine oxidase into xanthine dehydrogenase. This histochemical method can be used for quantitative analysis of in situ xanthine oxidase activity.

Animals↗

Leaching of diethylhexyl phthalate from polyvinyl chloride materials into etoposide intravenous solutions.

Etoposide intravenous solution is associated with leaching of diethylhexyl phthalate (DEHP) from bags and tubings made from polyvinyl chloride (PVC). Recent evidence suggests that this may be more substantial than previously found. Since DEHP is potentially hepatotoxic and carcinogenic, it is preferable to prepare and administer etoposide bags and tubings made from non-PVC materials.

Antineoplastic Agents, Phytogenic↗

The resting volume and compliance characteristics of the bronchial cuff of left polyvinyl chloride double-lumen endobronchial tubes.

The resting volume of a low-pressure, high-volume cuff is an important factor that determines the cuff compliance, because it is the maximum volume that maintains the low-pressure characteristics of the cuff. Modern polyvinyl chloride (PVC) double-lumen tubes (DLT) are designed with a low-pressure bronchial cuff to minimize the risk of bronchial damage. Maintenance of the low-pressure characteristics of this cuff, however, requires knowledge of how its resting volume and compliance vary between different DLT sizes and brands, and how the compliance changes when the cuff is inflated inside different-sized bronchi. We, therefore, measured the bronchial cuff pressure-volume relationship for each of the adult sizes, 35 Fr, 37 Fr, 39 Fr, and 41 Fr, of the Mallinckrodt, Sheridan, Rusch, and Portex left DLTs. The compliance of each cuff was characterized by: 1) the cuff resting volume, defined as the smallest cuff volume beyond which a 0.5-mL increase in volume resulted in more than 10 mm Hg increase in cuff pressure; and 2) the cuff pressure at 3-mL volume. Measurements were repeated for sizes 35 Fr and 41 Fr left Mallinckrodt DLTs with the bronchial cuff lying inside two canine left main-stem bronchi measuring 11 mm and 13 mm in diameter. The bronchial cuff resting volume ranged from 1.5 to 5.0 mL in different sizes and brands of DLTs, which could be explained by differences in cuff size between different manufacturers and between different DLT sizes of the same manufacturer.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchi↗

Basic fibroblast growth factor released from a platinum coil with a polyvinyl alcohol core enhances cellular proliferation and vascular wall thickness: an in vitro and in vivo study.

OBJECTIVE: We developed a new type of platinum coil that has a polyvinyl alcohol (PVA) core to absorb and release various biologically active materials for the endovascular treatment of intracranial aneurysms. We evaluated its efficacy as an embolic material with basic fibroblast growth factor (bFGF) in an in vitro and in vivo study. METHODS: A small PVA thread was inserted into the central space of the primary coil. This coil was named the PVA-core coil. Ten-millimeter segments of the PVA-core coil were used in this study. PVA-core coils were immersed in a bFGF solution for 1 hour. The PVA-core coil, which absorbed bFGF in the PVA-core, was named the FGF-core coil. Initially, the dose of bFGF released from the PVA core into saline was measured by performing an enzyme-linked immunosorbent assay. In the in vitro study, FGF-core coils, PVA-core coils, and unmodified coils were cultured with fibroblasts (NIH3T3), and then their surfaces were observed with electron microscopy. In the in vivo study, each coil was implanted into a rat common carotid artery. The rats were killed, and the arterial lumen was histologically examined at 14 and 28 days after coil implantation. RESULTS: BFGF was released from the PVA core into saline within 24 hours by performing an enzyme-linked immunosorbent assay. Electron microscopic findings demonstrated remarkable cellular adhesion to the surfaces of the FGF-core coils, but no adhesion to the surfaces of the PVA-core coils and the unmodified coils was found. Histologically, remarkable cell proliferation in the vascular lumen was demonstrated in the common carotid arteries of the FGF-core coil implantation group at the 14th and 28th days. Cellular components proliferated around the implanted coil, and these components mainly stained blue with Masson trichrome. These changes did not occur in the PVA-core coil group and the unmodified coil group. CONCLUSION: We suggest that FGF-core coils may be effective in inducing fibrotic changes inside aneurysms. These coils may be used as an embolic material to cure cerebral aneurysms.

Animals↗