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Antiviral activity of polyacrylic and polymethacrylic acids. I. Mode of action in vitro.

Polyacrylic acid (PAA) and polymethacrylic acid (PMAA) were investigated for their antiviral properties in tissue culture. Compared to other related polyanions, as dextran sulfate, polystyrene sulfonate, polyvinyl sulfate, and polyphloroglucinol phosphate, PAA and PMAA were found to be significantly more antivirally active and less cytotoxic. PMAA added 24 hr prior to virus inoculation inhibited viral growth most efficiently but it was still effective when added 3 hr after infection. Neither a direct irreversible action on the virus nor inhibition of virus penetration into the cell could explain the antiviral activity of PMAA. PMAA inhibited the adsorption of the virus to the host cell and suppressed the one-cycle viral synthesis in tissue cultures inoculated with infectious RNA.

Acrylates

Lymphocytosis induced by polymethacrylic acid. Dose-effect and toxicity.

Intravenous polymethacrylic acid (PMAA) significantly increases the number of lymphocytes in the blood of the rat. The relationship between dose-effect and lymphocytosis is linear. The lethal dose in 30 days of PMAA is 120 mg/kg b.w. and the half-lethal dose 80 mg/kg b.w. The treatment with 40 mg/kg b.w. intravenous PMAA gives no toxic histological changes either in the lymph organs, the liver or the kidneys. Thus, PMAA appears to be, at present, a most suitable agent by which to provoke experimentally, migration of the reserve lymphocytes into the blood.

Acrylic Resins

Mobilization of B and T lymphocytes and haemopoietic stem cells by polymethacrylic acid and dextran sulphate.

The leucocytosis which can be evoked by the polyanions dextran sulphate (DS), polymethacrylic acid (PMAA) and the copolymer of PMAA and styrene (PMAA--STYR) was studied in mice. After intravenous administration of these polyanions peak numbers of leucocytes were found in the peripheral blood 3 hr after injection. All three types of polyanions increased the number of lymphocytes, granulocytes and monocytes. Dose--response studies revealed that the nature of the polyanion determined the degree of leucocyte mobilization. The most potent mobilizer was found to be DS. This polyanion could evoke a six-fold increase of the number of peripheral blood leucocytes. By means of the membrane fluorescence technique it could be demonstrated that optimal doses of DS, PMAA and PMAA--STYR mobilized both B and T lymphocytes. The ratio between the number of B and T cells mobilized was greater for DS than for the other two polyanions. Intravenous injection of DS, PMAA and PMAA--STYR also increased the number of circulating haemopoietic stem cells (CFU-S). The most potent stem cell mobilizer appeared to be PMAA--STYR. This polyanion evoked a twenty-five-fold increase in the number of CFU-S.

Acrylic Resins

Polymethacrylic acid: induction of lymphocytosis and tissue distribution.

Polmethacrylic acid (PMAA) induces up to a three-fold increase in the lymphocyte population of peripheral blood in rats, goats and calves after intravenous administration. Other routes of administration are less effective. A maximum lymphocytosis is achieved after 3 hr with all doses in excess of 30 mg PMAA/kg body weight; over the next few hours the lymphocyte level declines to normal. Granulocytes increase steadily for the first 7 hr before declining. Multiple doses of PMAA 2 hr apart failed to maintain or significantly alter the lymphocytosis. PMAA was labelled with 125I and 14C, and was traced to various sites in the rat. The greatest accumulation of radioactivity was in the spleen, lungs, liver, kidney, adrenals and mesenteric lymph nodes (with 14C-PMAA). The accumulation appeared more specific for spleen and lymph nodes since there was only a small loss of activity following removal of blood by whole body perfusion. This supports previous findings indicating that these two tissues play a major role in the development of lymphocytosis. Accumulation in the bone marrow may be indicative of stem cell mobilization. The results are discussed in terms of the lymphocytosis-inducing mechanism and the site of action of PMAA and the possible clinical application to ECIB therapy is considered.

Acrylic Resins

[Characterization and determination of residual monomer content of implantation materials from polymethacrylic acid methylester].

Cold polymerizates "Kallocryl K" and "Palacos" were characterized by means of physico-chemical methods of examination. The residual monomer content of the polymerizates, which is of major toxicological interest, was also determined quantitatively. It was possible to show that the residual monomer content decreases exponentially as a function of the duration of polymerization. "Palacos" polymerizates had much higher residual monomer contents than "Kallocryl K" polymerizates when the same time of polymerization was used. Also discussed in this paper are possible methods of reducing the residual monomer content prior to implantation of the plastic materials.

Dental Implantation

Effect of antiviral agents in equine abortion virus-infected hamsters.

Equine abortion virus, a member of the herpesvirus group, produces a lethal infection in hamsters. With this system, the protective effect of certain inhibitors of deoxyribonucleic acid viruses, inducers of interferon and exogenous interferon, was evaluated. Of the various agents studied, 9-beta-d-arabinofuranosyladenine markedly suppressed mortality, and 5-iodo-2'-deoxyuridine, distamycin A, and N-ethylisatin beta-thiosemicarbazone were inactive. Of the inducers tested, statolon, ultraviolet-irradiated Newcastle disease virus, and polyriboinosinic:polyribocytidylic acid (poly I:C) were protective, and endotoxin, polyacrylic acid, and polymethacrylic acid did not protect. Administration of exogenous interferon did not afford protection. Statolon and ultraviolet-irradiated Newcastle disease virus induced circulating interferon in hamsters, whereas poly I:C, endotoxin, and polyacrylic acid did not produce interferon. Because of the severity of the disease produced in hamsters by equine abortion virus, lack of protective activity by an agent in this system should not preclude possible efficacy against other members of the herpesvirus group.

Animals

Silicone rubber-hydrogel composites as polymeric biomaterials. II. Hydrophilicity and permeability to water-soluble low-molecular-weight compounds.

The surface and transport properties of water-swollen silicone rubber-hydrogel composites were investigated. Surface wettability of these materials, composed of a polysiloxane matrix and the hydrogel phase consisting of very fine particles of lightly cross-linked poly(2-hydroxyethylmethacrylate), increased markedly with increasing content of the hydrogel phase. For composite materials containing a lightly cross-linked 2-hydroxyethylmethacrylate (HEMA)-methacrylic acid (MAA) copolymer and polymethacrylic acid (PMAA) as the hydrogel phase, permeability to water-soluble organic compounds and drugs were measured. The permeability varied within a broad range depending on the composition and content of the hydrogel phase. High permeation rates could be obtained while still retaining relatively fair mechanical properties. Relationships between the composition of silicone rubber-hydrogel composites, their structure and the permeation coefficients of the individual permeates are discussed.

Biocompatible Materials

[Enzymatic and conformational stability of polymeric complexes of alpha-amylase].

The enzymatic and conformational stability of Bacillus subtilis alpha-amylase and its polymeric complexes in acid media and subsequent renaturation in weakly alkaline media were investigated. The following parameters of alpha-amylase secondary structure were determined from circular dichroism spectra: helical units -25%, beta-structures -9%; beta-turns -13%; disordered conformations -53%. After complexation with polymethacrylic acid (PMAA) the alpha-amylase secondary structure did not change, and the tertiary structure underwent only small local changes. Complexation of alpha-amylase with linear and cross-linked PMAA led to an increase in both enzymatic and conformational stabilities in acid media. Purification of alpha-amylase using a biosorbent resulted in higher acid resistance of the free enzyme and of that in the complex with PMAA. Moreover, the degree of reversibility of the acid inactivation also increased.

Bacillus subtilis

[Effect of film formers and plasticizers on the stability of resistance and disintegration behavior. 4. Pharmaceutical-technological and analytical studies of gastric juice-resistant commercial preparations].

Chemical an physical properties of film coating materials determine stability of enteric coated pharmaceutical dosage forms. About 80% of commercial enteric coated drugs with coatings of celluloseacetate phthalate or polymethacrylic acid ester did not change acid resistance or disintegration time after 2 years, storage at 20 degrees C or 40 degrees C. Disintegration time of 4 drugs which are enteric coated with hydroxypropylmethylcellulose phthalate, decreased more often. Some of these did not fulfill acid resistance requirements of the Ph. Eur., tests which show influence of softeners to stability of enteric coatings have to be extended.

Cellulose

Lymphocytosis in rats treated with polyacids.

Inoculation of rats i.v. with dextran sulfate or polymethacrylic acid causes lymphocytosis. Electron microscopy of sections of cervical lymph nodes in control rats showed active passage of small lymphocytes through the high endothelial cells (HEC) of the post-capillary venules. In treated rats there was no indication of such passage: the HEC were free of small lymphocytes; and in about 25% of the venules apparently stationary lymphocytes, lacking microvilli, were found appressed to the luminal walls of the HEC.

Acrylic Resins

Lymphocytosis induced by polyanions in rats.

More than twenty different polymers, mostly polyanions, were tested in rats for their ability to mobilize lymphocytes into the peripheral blood within 2--3 h. The various polyanions differed in basic structure, in side-chain (size and type), in molecular weight and configuration and in amount and type of anionic charge along the molecule. Neutral polymers and a polycation were also tested for comparison. Some of the polyanions were found to be very effective, others less so and some completely ineffective. Some were also toxic. The basic polymer to which the others were compared was polymethacrylic acid (PMAA), an already recognized mobilizing agent. The best agents were the heparinoids, sulphated polyanions, and the best of these, causing a 3--4-fold increase, were dextran sulphate and polyvinyl sulphuric acid (PVSA). Heparin, although the strongest anticoagulant, was the weakest mobilizer. Some factors that appear capable of modifying mobilization to varying degrees were molecular weight, size and configuration, sulphate content and mode of administration. In the case of PVSA, the smaller molecular weight substance gave a more prolonged lymphocytosis in blood. The high molecular weight substance gave a peak after 2 h, slightly earlier than with PMAA (2--3 h). The administration of protamine chloride to the rat (i.v.) caused an immediate reversal of mobilization, following a course to control values which was essentially identical to the normal decline, only earlier. Dextran sulphate of low molecular weight seems to be the polyanion of choice in subsequent mobilization experiments dealing with determination of the specific mononuclear cell type being mobilized. The single factor that all mobilizing polyanions have in common is a negative molecular charge. It is not yet known exactly how this charge induces the mobilization of mononuclear cells, nor what causes the variability in effectiveness among polyanions.

Acrylamides

[Resistance and disintegration behavior of gastric juice-resistant drug products. 3. Pharmaceutical-technological and analytical studies of gastric juice-resistant commercial preparations].

Enteric coated commercial dosage forms often do not correspond with acid resistance and disintegration requirements of the Ph. Eur. About 15-20% of 181 tested samples disintegrate during acid resistance test or do not disintegrate in buffer solution pH = 6.8. The percentage was extremely high amongst enteric coated pancreatin or cardiac glycosides (about 30%) preparations. Storage conditions and time influence acid resistance and disintegration time. 80% of 34 products coated with celluloseacetate phthalate, hydroxypropylmethylcellulose phthalate or polymethacrylic acid ester did not change disintegration time after 2 years storage at 20 degrees C. After storage at 40 degrees C the number decreased to 40%. After 5 years at 20 degrees C number of products which were not stable increased.

Chemistry, Pharmaceutical