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Primary study on the assay of superficial hydroxyl group content upon the solid polyvinyl alcohol.

Polyvinyl alcohol is a multipurpose polymer, and there is abundant hydroxyl group on its surface. In this article, we first time attempted to assay the superficial hydroxyl group content on the solid polyvinyl alcohol (PVA-1799) with a degree of polymerization over 1700 and a degree of alcoholysis over 99.0%. The assay was carried out by two different titration systems. The results show: (1) the order of magnitude of superficial hydroxyl group content on its solid surface was about 3.8E-5 mol/cm2 by acylation system with single functional group reagent (acetic anhydride); while (2) the order of magnitude of superficial hydroxyl group content was about 1.4E-7 mol/cm2 by esterification system with bi-functional group reagent (Toluence 2,4-DiIsocyanate, TDI). The results would be useful to provide a quantitative reference when -OH on the solid PVA surface is intended to be utilized for surface modification for some application. Moreover, the results and their difference also offer us the knowledge of the surface modification efficiency.

Acylation↗

Sustained-release oral delivery of theophylline by use of polyvinyl alcohol and polyvinyl alcohol-methyl acrylate polymers.

Crystalline polyvinyl alcohol (PVA) polymer and low-crystallinity polyvinyl alcohol-methyl acrylate copolymer (PVA-MA) were examined as sustained-release tablet excipients with theophylline as a model drug. By blending of different proportions of the crystalline polymer and the low-crystallinity copolymer, it was possible to affect the release characteristics of the tablets. Tablets made with crystalline PVA provided instant release of theophylline in vitro. Tablets made with a larger proportion of PVA-MA relative to PVA provided a very prolonged release profile in vitro. A formulation containing PVA-MA:PVA:theophylline in a ratio of 1:9:10 provided sustained-release profiles in vitro and in vivo in dogs. The dissolution release profile of this PVA-blend tablet formulation in vitro agreed extremely well with the percentage of bioavailable dose absorbed over time in vivo. The formulation provided a plateau of levels in plasma over 16 h. The oral bioavailability of theophylline from this formulation in dogs was approximately 80% and was equivalent to that obtained after administration of Theo-Dur, a marketed extended-release theophylline tablet from Key Pharmaceuticals.

Absorption↗

[Experimental canine hepatic artery embolization with polyvinyl alcohol microspheres].

Polyvinyl alcohol microsphere impregnated with barium sulfate was found to be a good embolizing agent in regard to shape, suspension and distribution in the arteries. Different-phase hepatic artery embolization with microspheres (50 approximately 100 microns, 100 approximately 300 microns) was performed in 20 dogs to evaluate the angiographic and histopathologic changes and hepatic function alterations. Permanent occlusion of the peripheral arterioles was observed on follow-up angiograms one week to six months after embolization. Shrinkage of the embolized segment and focal infarct of the liver were noticed in nearly half of the specimens both grossly and microscopically. The shape and structure of the microspheres were seen unchanged on different-phase specimens, and microspheres as small as 50 microns could reach the corresponding small peripheral arterioles. The liver function alterations were comparable with gelfoam embolization. This study suggested that permanent embolization of small arterioles was possible with such microspheres.

Animals↗

Review of the oral toxicity of polyvinyl alcohol (PVA).

Polyvinyl alcohols (PVA) (CAS no. 9002-89-5) are synthetic polymers used in a wide range of industrial, commercial, medical and food applications. The purpose of this review, this critical evaluation of the available information on PVA, is to support the safety of PVA as a coating agent for pharmaceutical and dietary supplement products. All the available information on PVA gleaned from a comprehensive search of the scientific literature were critically evaluated. Orally administered PVA is relatively harmless. The safety of PVA is based on the following: (1) the acute oral toxicity of PVA is very low, with LD(50)s in the range of 15-20 g/kg; (2) orally administered PVA is very poorly absorbed from the gastrointestinal tract; (3) PVA does not accumulate in the body when administered orally; (4) PVA is not mutagenic or clastogenic; and (5) NOAELs of orally administered PVA in male and female rats were 5000 mg/kg body weight/day in the 90-day dietary study and 5000 mg/kg body weight/day in the two-generation reproduction study, which was the highest dose tested. A critical evaluation of the existing information on PVA supports its safety for use as a coating agent for pharmaceutical and dietary supplement products.

Administration, Oral↗

The gene pvaB encodes oxidized polyvinyl alcohol hydrolase of Pseudomonas sp. strain VM15C and forms an operon with the polyvinyl alcohol dehydrogenase gene pvaA.

A 5.7 kbp SphI fragment containing the polyvinyl alcohol (PVA) dehydrogenase gene pvaA and its 1.9 kbp 5'-flanking region was cloned from the PVA-degrading bacterium Pseudomonas sp. VM15C. The pvaB gene, encoding oxidized PVA hydrolase, was found in the region upstream of pvaA. Sequence data and expression studies indicated that pvaA and B constitute an operon in the order pvaBA. The pvaB gene encoded a protein of 379 amino acid residues (40610 Da), and a lipoprotein signal sequence and the lipase consensus sequence, Gly-X-Ser-X-Gly, characteristic of the active-site serine region in serine hydrolases, were detected in the deduced amino acid sequence. The pvaB product with the pvaA product constituted an enzyme system for the cleavage of PVA molecules. The pvaA product introduced beta-diketone groups into the PVA molecule, and the pvaB product hydrolysed these beta-diketone groups in oxidized PVA. The pvaB product also hydrolysed 4,6-nonanedione at a low rate, but not acetylacetone or 5-nonanone. It was completely inhibited by PMSF and was concluded to be a serine hydrolase. There were no proteins showing high similarity to the pvaB product in the databases, but minor similarity to a number of serine hydrolases including polyhydroxyalkanoate depolymerases was apparent.

Alcohol Oxidoreductases↗

Histopathological follow-up study of 66 cerebral arteriovenous malformations after therapeutic embolization with polyvinyl alcohol.

Embolization with polyvinyl alcohol (PVA) is an accepted method of rendering complex arteriovenous malformations (AVM's) more amenable to surgery, but its effects on human vascular tissues have not been adequately documented. The authors reviewed the histopathology of 66 intracranial AVM's resected 1 to 76 days after embolization with PVA. The mean age of the patients was 36 years, and their AVM's were located in the cerebral hemispheres (92%), the cerebellum (6%), or the corpus callosum (2%). In 79% of cases, at least one vessel contained PVA particles; in most cases, the vessel was filled with sharp, angular PVA particles in a serpiginous pattern. Polyvinyl alcohol particles indented the endothelium in 69% of cases but were rarely found subendothelially. Clotted blood and fibroblasts were present among the particles, and abundant intraluminal mononuclear and polymorphonuclear inflammatory cells were found in all vessels containing PVA particles. Foreign-body giant cells appeared 2 to 14 days after embolization in the majority of cases. Patchy mural angionecrosis and necrotizing vasculitis were found in 39% of the cases. Recanalized lumina were seen in 18% of PVA-embolized vessels. Foreign materials resembling cotton fibers and other particulate substances, which were probably contaminants of the contrast solution or the embolic material, were found in 65% of the cases. These findings suggest a specific chain of events in the interaction between PVA and vessel wall components and may explain some important sequelae of embolization therapy.

Adolescent↗

[Therapeutic embolization with polyvinyl alcohol (Ivalon). Clinical experiences].

Polyvinyl alcohol is rigid foam used in pressed or unpressed form for the purpose of embolisation. It is suitable for both micro-embolisation in the vascular periphery and for central vascular occlusion. Polyvinyl alcohol will result in permanent vascular occlusion. Basing on the experience collected with 71 embolizations, the article reports on the technique applied and on the results obtained with craniofacial, thoracic, abdominal, pelvic and peripheral embolisation.

Adolescent↗

NTP Toxicology and Carcinogenesis Studies of Polyvinyl Alcohol (CAS No.9002-89-5) in Female B6C3F1 Mice (Intravaginal Studies).

Polyvinyl alcohol is produced primarily for use in textile sizing, adhesives, polymerization aids, and paper coatings. It is also used in surgical drapes, towels, and gauze sponges; protective gloves; cosmetic formulations; topical ophthalmic preparations; plastic sponge implants for reconstructive surgery; and intravaginal contraceptive foam and film. In addition, polyvinyl alcohol is used with magnesium sulfate to dilate the cervix of women prior to induction of labor. It is estimated that hundreds of thousands of women in the United States use an intravaginal product containing polyvinyl alcohol each year. The Food and Drug Administration nominated low-viscosity polyvinyl alcohol for a 2-year study because of concern about the lack of information about the long-term toxic and carcinogenic effects by the intravaginal route. Female B6C3F1 mice received polyvinyl alcohol (approximately 99% pure) in deionized water by intravaginal administration for 30 days or 2 years. 30-DAY STUDY IN MICE: Three groups of 50 female B6C3F1 mice were used in this intravaginal study. The vehicle control group received only 20 &mgr;L of a deionized water vehicle. The other two groups each received 20 &mgr;L of 25% polyvinyl alcohol in deionized water. Animals in one dose group were returned to their cages after dosing; animals in the other dose group were restrained in a vertical nose-down position in restraint bags for several minutes after dosing. Animals were dosed daily for 30 consecutive days. All mice survived to the end of the study. The final mean body weights and body weight gains of dosed mice were similar to those of the vehicle control group. Abnormalities noted in the vaginal area after dosing included vaginal plugs, secretions, and swelling. These vaginal changes were minimal to mild and occurred in vehicle controls as well as in dosed mice. Restraint of mice after dosing appeared to eliminate vaginal secretions but increased both the incidence of vaginal irritation and the severity of vaginal opening swelling. At necropsy, mildly enlarged uterine horns were observed in 10 vehicle control mice, three 25% mice, and seven 25% (restrained) mice. No chemical-related lesions were observed. 2-YEAR STUDY IN MICE: Three groups of 100 female B6C3F1 mice were used in this intravaginal study: an untreated control group, a vehicle control group receiving 20 &mgr;L deionized water vehicle only, and a dosed group receiving 20 &mgr;L 25%% polyvinyl alcohol in deionized water. Animals were dosed 5 days per week, excluding holidays, for 104 to 105 weeks. Survival, Body Weights, and Clinical Findings: Survival of dosed mice was similar to that of the two control groups. The final mean body weight of vehicle control mice was less than that of the untreated control group. The mean body weights of the dosed mice were less than those of the untreated controls from week 17 until the end of the study. The only clinical finding was vaginal irritation, observed in six mice in the vehicle control group and 11 mice in the dosed group. Pathology Findings: No neoplasms or nonneoplastic lesions related to chemical treatment were observed. The incidences of reproductive tract nonneoplastic lesions in the dosed group did not differ significantly from those in the vehicle control group; similarly, the incidences of reproductive tract nonneoplastic lesions in the vehicle control group did not differ significantly from those in the untreated control group. CONCLUSIONS: Under the conditions of this 2-year study, there was no evidence of carcinogenic activity of polyvinyl alcohol (molecular weight approximately 24,000) in female B6C3F1 mice administered 20 &mgr;L of a 25%% solution intravaginally. There were no neoplasms or nonneoplastic lesions considered related to treatment with polyvinyl alcohol. Synonyms: Ethenol homopolymer, PVA Trade names: Akwa Tears, Alcotex, Alvyl, Aracet, Cipoviol, Covol, Elvanol, Ethenol, Gelvatol, Gohsenol, Ivalon, Kuralon, Kurare, Lemol, Liquifilm, Mowiol, Polydesis, Polysizer, Polyvinol, Polyviol, Poval, Resistoflex, Rhodoviol, Sno, Poval, Resistoflex, Rhodoviol, Sno Tears, Solvar, Sumitex, Vibatex, Vinacol, Vinalak, Vinarol, Vinarole, Vinavilol, Vinol, Vinylon

Journal Article↗

Biochemical and molecular characterization of a periplasmic hydrolase for oxidized polyvinyl alcohol from Sphingomonas sp. strain 113P3.

Oxidized polyvinyl alcohol hydrolase (OPH) and polyvinyl alcohol dehydrogenase were found to be constitutively present in the periplasm of Sphingomonas sp. strain 113P3 (formerly Pseudomonas sp. 113P3). The OPH was purified to homogeneity with a yield of 40 % and a 5.9-fold increase in specific activity. The enzyme was a homodimer consisting of 35 kDa subunits. Its activity was inhibited by PMSF, Hg(2+) and Zn(2+). The enzyme hydrolysed oxidized polyvinyl alcohol (oxidized PVA) and p-nitrophenyl acetate (PNPA), but did not hydrolyse any of the mono- or diketones tested. K(m) and V(max) values for oxidized PVA and PNPA were 0.2 and 0.3 mM, and 0.1 and 3.4 micromol min(-1) mg(-1), respectively. The gene for OPH was cloned and sequenced. Sequencing analysis revealed that the open reading frame consisted of 1095 bp, corresponding to a protein of 364 amino acids residues, encoding a signal peptide and a mature protein of 34 and 330 amino acids residues, respectively. The presence of a serine-hydrolase motif (a lipase box; Gly-X-Ser-X-Gly) strongly suggested that the enzyme belongs to the serine-hydrolase family. The protein exhibited homology with OPH of the Pseudomonas sp. strain VM15C (63 % identity) and the polyhydroxybutyrate depolymerases from Mesorhizobium loti, Rhizobium sp. and Sinorhizobium meliloti (29-32 % identity). The oph gene was expressed in Escherichia coli under the control of the lac promoter. The recombinant protein had the same molecular mass and N-terminal amino acid sequence as the purified OPH from strain 113P3.

Alcohol Oxidoreductases↗

Preparation and thrombogenicity of alkylated polyvinyl alcohol coated tubing.

A polyvinyl alcohol hydrogel (PVA) was reacted with a C18 isocyanate at 80 degrees C in dimethyl formamide (DMF) in order to improve the platelet reactivity of the hydrogel through an influence on albumin adsorption or retention. A C4 isocyanate was used as a control. Surface coverage by XPS appeared to be approximately 100% for both C4 and C18 modified surfaces, although the limited solubility of C18 isocyanate in DMF may have resulted in a nonuniform surface. Relative to PVA or the solvent treated control, octadecylation resulted in increased albumin adsorption (from a single protein solution) and increased retention when the adsorbed albumin was exposed to a fibrinogen solution. However, octadecylation did not obviate the platelet reactivity problem in preliminary studies: systemic platelet counts were reduced by about half over 4 days in a canine AV shunt experiment and the initial rate of platelet destruction for C18-PVA was greater (36%/day) even than for the solvent-treated PVA. Surprisingly in preliminary studies butylation of PVA resulted in little or no thrombocytopenia and did not appear to increase significantly the fractional rate of platelet destruction relative to the shunt only blank. It is presumed that the nonspecific effect of alkylation (independent of chain length) was the dominant contribution to the reduced platelet reactivity. A similar effect of C18-PVA presumably would have been observed had the limited solubility of C18 isocyanate not precluded a uniform surface coverage.

Adsorption↗

A quantitative study of the effects of different grades of polyvinyl alcohol on the activities of certain enzymes in unfixed tissue sections.

Different grades of the colloid stabilizer, polyvinyl alcohol, used for protecting unfixed cryostat sections during cytochemical reactions, may have different effects on enzymatic activity. The influence of three grades of polyvinyl alcohol on the activities of "soluble", membrane-bound and membrane-enclosed enzymes has been investigated in unfixed sections; the activities were measured microdensitometrically. The largest molecular weight polyvinyl alcohol (G18/140, mol. wt. about 90 000) did not retain glucose-6-phosphate dehydrogenase activity in sections of rat liver even when used at the maximum convenient concentration (12%); G04/140 and M05/140 (molecular weights of 15 000 and 25 000 respectively) retained this soluble enzyme if used at concentrations of 30 and 20% respectively. At these concentrations, lactate dehydrogenase activity was apparently decreased when G04/140 and M05/140 were used; this diminished activity has been shown to be due to the need to establish optimal concentrations of reactants for each grade of polyvinyl alcohol and for each reaction. When optimal concentrations of reactants were used, the activities of this enzyme in the presence of each grade of polyvinyl alcohol were identical. The presence of any type of polyvinyl alcohol did not influence the activities of mitochondrial succinate dehydrogenase or of the smooth endoplasmic reticulum enzyme, delta5,3beta-hydroxysteroid dehydrogenase. However, the presence of polyvinyl alcohol improved the state of the section.

3-Hydroxysteroid Dehydrogenases↗

Experimental hybrid islet transplantation: application of polyvinyl alcohol membrane for entrapment of islets.

In this study, we first examined in vitro a polyvinyl alcohol membrane to be used to contain hybrid islet cells, and second we tested a bioartificial pancreas with entrapment of pancreatic islets in polyvinyl alcohol membrane in rats with experimentally induced diabetes. The permeability of the polyvinyl alcohol membrane to different substances was studied in a two-cell chamber system. Glucose, insulin, and nutrients passed through the membrane easily, whereas the passage of immunoglobulin G was completely prevented, indicating that this membrane could be effective in protecting the bioartificial pancreas from immunorejection. Approximately 2,000 islets collected from three Sprague-Dawley rats were enclosed in a mesh-reinforced polyvinyl alcohol tube and transplanted into the peritoneal cavity of six Wistar rats with streptozotocin-induced diabetes. Their nonfasting serum glucose levels were significantly decreased for at least 12 days. Six diabetic rats receiving intraperitoneal transplantation of free islets without the tube showed a slight but significant decrease in nonfasting serum glucose levels for only 3 days. One diabetic rat with transplantation of the bioartificial pancreas had a significant and sustained decrease in nonfasting glucose levels from pretransplanted levels of 440-500 mg/dl to a mean value of 162 +/- 13 mg/dl for over 3 months without immunosuppression. The bioartificial pancreas was then removed, and glucose levels gradually increased to over 500 mg/dl. The results of the present study suggest that a bioartificial pancreas with entrapment of islets in a polyvinyl alcohol membrane could be a promising therapeutic approach to diabetes mellitus.

Animals↗

Symbiotic utilization of polyvinyl alcohol by mixed cultures.

Polyvinyl alcohol (PVA)-utilizing cultures were obtained from various sources. They were mixed cultures even after cyclical transfer to liquid and plate media with PVA as a sole source of carbon. Component bacteria were isolated from the several mixed cultures, and it was shown that PVA was utilized symbiotically by two bacterial members which could not utilize PVA in each respective pure culture. From a mixed culture, strains VM15, VM15A (Pseudomonas putida) and VM15C (Pseudomonas sp.) were isolated as members essential for PVA utilization. VM15C was the predominant strain in the mixed-culture population and produced PVA-degrading enzyme. The culture supernatant of VM15A enabled VM15C to grow on PVA. VM15A was presumed to supply VM15C with a unique growth stimulant which was distinct from usual growth factors.

Journal Article↗

The wound healing process in surgical patients evaluated by the expanded polytetrafluoroethylene and the polyvinyl alcohol sponge: a comparison with special reference to intrapatient variability.

The aim of this study was to compare two wound healing models in surgical patients with special reference to the intrapatient variability. Two pieces of expanded polytetrafluoroethylene tubing and one perforated silicone tube containing two polyvinyl alcohol sponges were subcutaneously inserted into 28 patients and were removed after 10 (9 to 11) days. The amount of hydroxy-l-proline in two segments of the same piece of expanded polytetrafluoroethylene tubing correlated significantly with each other. Similar results were found for proline. Proline content in each polyvinyl alcohol sponge correlated weakly with each other, whereas no correlation was found between hydroxy-l-proline content in the two polyvinyl alcohol sponges from the same patient. In addition, no correlation was found between leucine in the two adjacent polyvinyl alcohol sponges or between the hydroxy-l-proline/leucine ratio in these same sponges. No concordance could be detected between the averages of hydroxy-l-proline content in the two segments of expanded polytetrafluoroethylene tubing and the hydroxy-l-proline content in the two polyvinyl alcohol sponges from the same person, although an association between the averages of proline in the two pieces of expanded polytetrafluoroethylene tubing and proline content in the two polyvinyl alcohol sponges from the same individual was observed. The measurement error was greater for the polyvinyl alcohol sponges than for the expanded polytetrafluoroethylene tubing implants during the first 10 days after wounding. The expanded polytetrafluoroethylene tubing accumulated 2.5 times more hydroxy-l-proline per length unit than the polyvinyl alcohol sponge. We concluded that the expanded polytetrafluoroethylene implant rather than the polyvinyl alcohol implant is preferred for quantitation of subcutaneous collagen deposition in surgical patients because it accumulates more new tissue and has a lower variability.

Journal Article↗

Application of polyvinyl alcohol hydrogel membrane as anti-adhesive interposition after spinal surgery.

STUDY DESIGN: Three inflammatory and adhesive changes inside the spinal canal were analyzed histopathologically in cats. OBJECTIVE: To investigate the usefulness of a polyvinyl alcohol hydrogel sheet as an interposition over the dura to prevent inflammatory and adhesive reaction after laminectomy. SUMMARY OF BACKGROUND DATA: A major concern after laminectomy is scar tissue formation that may result in extradural compression or make subsequent surgery to the same area difficult and hazardous. METHODS: Wide laminectomy was performed at L5 in 30 adult cats. The dura was covered with a polyvinyl alcohol hydrogel sheet, free fat graft, or without interposition as a control. Animals were killed at 3 or 12 weeks. RESULTS: In the control group, adhesion of the exposed dura was apparent. Thick, fibrous connective tissue was observed between the dura and the paravertebral muscles. In the fat graft group, the dura was separated from the scar tissue by living grafted fat. However, the dura was adherent to the grafted fat and fibroblasts migrated into the interstitial space. In the polyvinyl alcohol hydrogel group, only a thin synovium-like layer was formed around the polyvinyl alcohol hydrogel sheet. CONCLUSIONS: Polyvinyl alcohol hydrogel is made of water and alcohol, and has been shown to be nontoxic to tissues. This is permeable to low molecular weight, but impermeable to large cells such as fibroblasts. Thus, the polyvinyl alcohol hydrogel sheet prevents migration of inflammatory cells and subsequently reduces intraspinal canal scar tissue formation and adhesive reaction. Other beneficial properties are extreme elasticity and low friction, which eliminate mechanical reaction to the spinal cord. The polyvinyl alcohol hydrogel sheet is believed to be useful in eliminating scar tissue formation and does not interfere with the dynamic gliding movement of the spinal cord and nerve roots.

Adipose Tissue↗