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Sixth mycelial fraction acetone (6-MFA), an interferon inducer modulates acrylamide neurotoxicity.

A single i.p. administration of an immunomodulatory agent 6-MFA (a biological response modifier and antiviral agent of fungal origin, 10 mg/100g b.wt.), on 5th day of repeated acrylamide (ACR, 50 mg/kg b.wt.) treatment significantly protected rats against its specific neurotoxic effects. Corpus striatal 3H-spiperone binding elevated (24%) while glutathione-S-transferase (GST) activity decreased (33%) in ACR group but values were markedly restored in 6-MFA alone and co-exposed group. Development of hind limb paralysis was also protected by 6-MFA. Results warrant the possible involvement of immune mechanisms and certain other factors such as lymphokines, hormones and microglia at the target site, which in turn facilitate the repair mechanism suggesting a therapeutic role of 6-MFA in clinical cases of toxic neuropathies in future.

Acrylamides↗

[Polymer materials for biomedical use obtained by radiation methods. III. Radiation cross-linking of acrylamide and N-vinylpyrrolidone].

The course of the radiation formation of hydrogels in aqueous solutions of acrylamide and N-vinylpyrrolidone was investigated on the base of gel-sol analysis. Using relations from Inokuti's equation as a test of crosslinking mechanism it was pointed out that creation of gels takes place according to classical mechanism e.g. through four-functional joining points. In the systems containing oxygen gel formation results from simultaneous crosslinking and degradation. On the base of swelling measurements of gels (ROCH method) the yields of radiation processes were calculated. Using a method of pulse radiolysis the absorption spectra of macroradicals were recorded, their structures discussed and the rate constants of crosslinking estimated.

Acrylamides↗

Influence of ganglioside treatment on acrylamide neuropathy in mice. A morphometric study.

Female CBA/J mice were given oral doses of 40 mg/kg acrylamide 3 times weekly for 7 or 11 weeks in order to induce peripheral neuropathy. Half the animals were concurrently treated with 20 mg/kg, subcutaneously, of a ganglioside mixture (Cronassial). The other half received physiological saline and served as control. At the end of 7 or 11 weeks, the tibial nerves were removed and examined histomorphometrically. Every animal had developed a neuropathy. However, the mice treated with the ganglioside mixture showed on both the examination dates a substantially larger proportion of small sprouting nerve fibres than the control. It was concluded from this that treatment with gangliosides stimulated the regenerative potential of the damaged nerves.

Acrylamides↗

A correlative neurobehavioral-morphological model of acrylamide neuropathy.

Sprague-Dawley rats were intoxicated with 50 mg/kg/day of acrylamide monomer given by daily intraperitoneal injections. The progression of disease was studied in intoxicated animals and unintoxicated controls using a functionally-oriented behavioral battery focusing on sensory-motor behaviors. Correlative morphological examination focused on neuronal cell bodies and nerve fibers at early time points. The results were compared with previous results from animals intoxicated with another prototype neurotoxin, 2,5-hexanedione (2,5-HD), and studied with the identical behavioral battery. With both toxins behavioral changes slightly preceded observed structural damage at the sites examined. Broadly similar behavioral patterns occurred with both toxins, i.e., more-complex functions showed the earliest deficits; hindlimb functions deteriorated before forelimb functions; grasp reflex deteriorated before place reflex. This pattern correlates with the established pattern of selective vulnerability of long and large axons. Although the patterns of behavioral toxicities were broadly similar, the functionally-oriented battery succeeded in detecting differences which corresponded with established neuropathological subtleties in the two dying-back processes. We discuss potential difficulties in correlating behavioral/clinical results with morphological data but stress the importance of such correlations.

Acrylamides↗

Charge effects on the dynamic quenching of fluorescence of 1,N6-ethenoadenosine oligophosphates by iodide, thallium (I) and acrylamide.

Systematic studies were carried out to determine how the dynamic quenching of fluorescence was affected by electrostatic interaction between charges carried by the fluorophore and the quencher. 1,N6-Ethenoadenosine oligophosphates (epsilon-ATP, epsilon-ADP, epsilon-AMP, and epsilon-Ad) were used as fluorophores; these compounds have the same luminous group (epsilon-adenine ring) with variously charged phosphate groups. Acrylamide and the iodide (I-), well known to be effective quenchers carrying zero and one negative charge, respectively, were used as quenchers. The thallium (I) (Tl+) was also found to be an effective quencher as a result of studies of the quenching activity of various positively charged ions. Results which agreed qualitatively with those expected were obtained for the charge effects on the dynamic quenching and the effects of ionic strength on it. That is, the repulsive force exerted between I- and phosphate groups decreased the quenching rate, and increasing ionic strength of solutions mitigated these charge effects. The results obtained, however, were not quantitatively consistent with theoretical expectations for ionic reaction rates in solutions. One reason for the quantitative disagreement is that the negatively charged phosphate groups are located at a distance from the luminous group. By theoretical analysis of the quenching data, the distance was calculated to be 9.6 A + delta r, where delta r changes according to the number of phosphate groups. Furthermore, through a theoretical analysis of the disagreement, we found a new factor, the "size effect" of a luminous group, which modifies the charge effects on dynamic quenching. The size effect provides information on the gradient of the electric potential generated by the phosphate groups. These studies provide a basis for the study of electric potential at local regions of proteins.

Acrylamides↗

Antiallergic activity and mode of action of N-[4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3-(6-methyl-3- pyridyl)acrylamide in experimental animals.

Antiallergic effects of AL-3264 (N-[4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3-(6-methyl-3- pyridyl)acrylamide, CAS 118420-47-6) were compared with those of ketotifen, oxatomide, azelastine and tranilast in experimental animals. AL-3264 inhibited passive cutaneous anaphylaxis (PCA) in rats with an ED50 value of 6.1 mg/kg p.o. In inhibiting PCA, AL-3264 was the most potent among the antiallergic drugs examined. The anti-PCA effect of AL-3264 was long-lasting. Tolerance was not produced by repeated administration of AL-3264. AL-3264 inhibited antigen-induced bronchoconstriction in actively sensitized rats and in passively sensitized guinea pigs, with ED50 values of 14.5 and 0.44 mg/kg p.o., respectively. In the in vitro experiments, AL-3264 inhibited 5-lipoxygenase activity of guinea pig leukocytes with an IC50 value of 4.9 mumol/l, being the most potent among antiallergic drugs examined, and suppressed the antigen-induced histamine release from rat peritoneal mast cells with an IC50 value of 12.2 mumol/l. AL-3264 antagonized histamine-induced contractions in isolated guinea pig trachea with an IC50 value of 0.16 mumol/l. These results suggest that AL-3264 is an orally active, potent and long-lasting antiallergic compound which inhibits 5-lipoxygenase activity, histamine release and histamine H1 receptors at the similar concentrations.

Acrylamides↗

Dissociation between central and peripheral antihistamine activities of the new antiallergic agent N-[4-[4-(diphenylmethyl)-1-piperazinyl]-butyl]-3-(6-methyl-3-pyridyl) acrylamide in rats and monkeys.

In order to examine the penetration of N-[4-[4-(diphenylmethyl)-1-piperazinyl]-butyl]-3-(6-methyl-3-pyrid yl) acrylamide (AL-3264, CAS 118420-47-6), a new antiallergic agent, into the brain, the antihistamine activities in the central and peripheral tissues from the rats and monkeys orally treated with AL-3264 were measured in comparison with those of ketotifen, oxatomide, mequitazine and terfenadine. These 5 drugs dose-relatedly suppressed the histamine-induced dye leakage in the rat skin and, except terfenadine, inhibited the binding of 3H-mepyramine to brain homogenates obtained from the rats treated orally with the drugs. The ratio (0.07) of AL-3264 for the central (3H-mepyramine binding) to peripheral (dye leakage) antihistamine activities was lower than that of ketotifen, oxatomide and mequitazine, and higher than that of terfenadine. The serum and cerebrospinal fluid (CSF) samples, which were collected from the monkeys treated with 80 mg/kg p.o. of AL-3264, terfenadine or oxatomide, inhibited the histamine-induced contractions in isolated guinea pig trachea. The ratio (0.003) of AL-3264 for the central (CSF) to peripheral (serum) antihistamine activities was lower than that of terfenadine and oxatomide. These results suggest that AL-3264 is poorly accessible to the brain, and may be regarded as a non-sedative antiallergic agent.

Acrylamides↗

A catechol derivative (4-methylcatechol) accelerates the recovery from experimental acrylamide-induced neuropathy.

Acrylamide (ACR) monomer produces neuropathy of the dying-back type and 4-methylcatechol (4-MC) is a potent stimulator of endogenous nerve growth factor synthesis. In the present study, we investigated the efficacy of 4-MC in promoting recovery from experimental ACR neuropathy in rats. Twenty-two Sprague-Dawley rats were made neuropathic by ACR injections. They showed hindlimb paralysis, increment of landing foot spread distance and a statistically significant reduction in motor nerve conduction velocity. After the ACR neuropathy had been established, 12 of the rats were administered 4-MC for 2 weeks, and the other 10 were injected with phosphate-buffered saline alone. 4-MC-administered ACR neuropathy rats showed improvement, i.e., a decrease in landing foot spread distance, increase in motor nerve conduction velocity and increase in nerve growth factor content in the sciatic nerves in comparison with the corresponding values for ACR neuropathy rats given phosphate-buffered saline alone. A decreased number of large myelinated fiber with a reciprocal increase in small myelinated fiber number also was seen in the ACR neuropathy rats; however, this change was ameliorated in part by the administration of 4-MC. Therefore, these findings suggest that 4-MC can accelerate the recovery process clinically, electrophysiologically, biochemically and neuropathologically.

Acrylamides↗

Effects of 4-methylcatechol, a stimulator of endogenous nerve growth factor synthesis, on experimental acrylamide-induced neuropathy in rats.

Acrylamide monomer (ACR) causes central-peripheral distal axonopathy. We induced neuropathy in rats by means of ACR injection as an experimental model of the dying-back type of peripheral neuropathy to assess the potential efficacy of 4-methylcatechol (4-MC), a potent stimulator of endogenous nerve growth factor (NGF) synthesis, as a therapeutic agent for the axonal nerve lesion. ACR-induced neuropathy in rats resulted in a dying- back type of axonal degeneration, and a statistically significant reduction in motor nerve conduction velocity (MNCV), and density of large myelinated fibers. We administered 4-MC and ACR together to rats intraperitoneally and found improved clinical signs, and significantly more NGF content in sciatic nerves, faster MNCV, and greater myelinated fiber density than in rats given ACR alone. These findings suggest that 4-MC can prevent the progression of ACR-induced neuropathy and decreased NGF levels may be involved in the pathogenesis of ACR neuropathy.

Acrylamides↗

[A study on neurotoxicity of acrylamide and glycidamide].

Glycidamide (GA) is an epoxide metabolite of acrylamide (AA). Neurotoxicity of both GA and AA was compared by their performance in behavioral, neuro-biochemical and neuropathological studies. Male rats were injected peritoneally with AA (25 or 50 mg/kg) or GA (50 or 100 mg/kg) once daily for eight days. Results showed that toxic effects of AA were greater than those of GA in wheel rotation test, hind limb splay test, and activities of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in peripheral nerves in rats. Results of neuropathological examinations in experimental rats also provided evidence that AA could cause damage to peripheral nerves, but GA did not. It indicated that nerve tissue was more vulnerable to AA than to GA. Also, it suggested that neurotoxic effects of AA was caused by itself, and influenced less by its metabolite GA.

Acrylamides↗

Design of reactive porous polymer supports for high throughput bioreactors: poly(2-vinyl-4,4-dimethylazlactone-co-acrylamide- co-ethylene dimethacrylate) monoliths.

Enzymatic bioreactors with both high flow characteristics and mechanical stability based on macroporous poly(2-vinyl-4, 4-dimethylazlactone-co-acrylamide-co-ethylene dimethacrylate) monoliths have been prepared. Covalent immobilization of trypsin on these support is achieved in a single reaction step using the azlactone functional groups. Optimization of hydrophilic/hydrophobic properties of the monolith affords a support that does not shrink in water and leads to immobilized enzyme that shows high activity in the hydrolysis of both low and high molecular weight substrates such as L-benzoyl arginine ethyl ester and casein. The catalytic activity of the monolithic reactor is maintained even at a flow velocity of 180 cm/min, which substantially exceeds those reported in the literature for packed bed reactors.

Bioreactors↗

Electrophoretic separation of ubiquitin and single amino acid residue ubiquitin extensions using a commercial modified acrylamide gel electrophoresis system: an assay to determine catalytic capacities of deubiquitinating enzymes.

We have chemically synthesised a number of ubiquitin extension proteins, with carboxyl-terminal single amino acid residue extensions, to use as substrates to assess the catalytic capacities of deubiquitinating enzymes (DUBs). Here we describe a modified acrylamide gel electrophoresis system which allows separation of peptide- or isopeptide-linked ubiquitin-lysine from ubiquitin (77 and 76 residue proteins respectively) in only 2 h. Western blotting, using antibodies against ubiquitin, allows both substrate (i.e. ubiquitin-lysine) and product (i.e. ubiquitin) of DUB-catalyzed cleavage reactions to be detected. Catalytic capacities of DUBs may be indicative of in vivo functions of these proteases.

Catalysis↗

Production and characterization of liquid-core capsules made from cross-linked acrylamide copolymers for biotechnological applications.

A novel chemistry has been developed for the production of capsules composed of a hydrophobic liquid core surrounded by a cross-linked polyacrylamide/alginate membrane. These liquid-core capsules may be used in capsular perstraction for the removal of inhibitory products from bioprocesses and bioconversions. They have the advantage of having a high surface area to promote rapid mass transfer, while separation of the organic core phase from the aqueous environment by the capsule membrane prevents the formation of stable emulsions and potential problems associated with toxicity of the organic phase for microbial cells or enzymes. Monodisperse spherical liquid-core capsules of between 800 microm and 1.6 mm diameter, with high mechanical resistance, have been prepared by co-extrusion, using the jet break-up technique. Capsules produced from a solution of MBA/total monomer (5%) were found to be more elastic and have a higher burst force when exposed to chelating agents such as phosphate or citrate. The mechanical resistance was unaffected by buffer solutions in the pH range 4-9 and after sterilization at 121 degrees C for 20 min. Capsules having membranes composed of a copolymer of acrylamide and N-hydroxymethylacrylamide exhibited even higher mechanical stability toward chelating agents.

Acrylic Resins↗

Favourable biospecific reactivity of blood group B antigenic trisaccharide chemically attached to poly-N-(2-hydroxyethyl)acrylamide-coated porous glass.

Blood group B antigenic trisaccharide-beta-aminopropyl glycoside (B-TSAP) covalently attached to poly-N-(2-hydroxyethyl)acrylamide-coated porous glass interacts with anti-B monoclonal antibodies faster than the ligand coupled to CNBr-activated Sepharose 4B and Affi-Gel 10. Rates of hydrophobic adsorption of antibodies on the butyl derivatives of the same supports were measured to evaluate the diffusion input to overall kinetics. The lowest average affinity adsorption time [t1(aff) = 250 s] observed for polymer-coated glass probably arises because of the flexibility of the extended segments of chemisorbed N-substituted polyacrylamide acting as effective spacer arms.

ABO Blood-Group System↗

Separation of oligonucleotides and DNA fragments by capillary electrophoresis in dynamically and permanently coated capillaries, using a copolymer of acrylamide and beta-D-glucopyranoside as a new low viscosity matrix with high sieving capacity.

New copolymers of acrylamide and beta-D-glucopyranoside were synthesized and characterized. The different reactivity of the two monomers towards radical polymerization meant we could control the growth of the polymer chains whose length was inversely related to the number of glucose residues incorporated in the copolymers. The properties of these polymers were investigated in the separation of oligonucleotides and double-stranded DNA by capillary electrophoresis (CE) in coated and uncoated capillaries. The new copolymers were a suitable matrix for CE due to their high-resolving capacity and low viscosity. We also looked into the advantages of a new method of dynamic suppression of electroosmotic flow based on the addition of small amounts (0.03-0.05%) of dimethylacrylamide to the sieving and to the running buffer. A complete test was run on the reproducibility and efficiency of separations carried out in a permanently and dynamically coated capillary, and the advantages and disadvantages of the two methods were compared.

Acrylic Resins↗

Acrylamide-agarose copolymers: improved resolution of high molecular mass proteins in two-dimensional gel electrophoresis.

A method was developed in order to analyse high molecular mass proteins by two-dimensional (2-D) electrophoresis using a copolymer of acrylamide and allyl agarose instead of Bis cross-linked polyacrylamide (PA) gels in sodium dodecyl sulphate-electrophoresis. In this work, the matrix composition was optimised to improve the resolution of proteins larger than 200 kDa. The new gel type does not entrap large proteins and protein complexes at the application site. Mechanical properties were investigated through rheological measurements, which suggested the formation of a highly entangled elastomeric soft gel. A high 2-D resolution of proteins, extracted from membranes of red blood cells, was obtained in these gels. An example of tryptic digestion, peptide extraction and matrix-assisted laser desorption/ionisation-time of flight mass spectrometry was reported. The results demonstrate that the new gel is fully compatible with mass spectrometry protein analysis.

Acrylic Resins↗

Luminescent visualization of low amounts of cytochrome P450 and hemoproteins by luminol in acrylamide gels.

In this paper we apply luminol (5-amino-2,3-dihydro-1,4-phthalazinedione), a light-emitting substrate, in conjunction with H2O2 to the luminescence labeling of hemoproteins. We describe in detail a photodetection device which permits an efficient recording of the light emitted by heme-containing proteins resolved in acrylamide gels. The sensitivity of this procedure, when compared to the classical 3,3'-5,5'-tetramethylbenzidine staining method, results in a 5- to 20-fold enhancement with standard hemoproteins (lactoperoxidase, catalase, cytochrome P450 2B4, horseradish peroxidase, hemoglobin, myoglobin, and cytochrome b5). The potential applications of this technique are illustrated by the detection of cytochrome P450 in microsomes from plant as well as from animal extrahepatic tissues which possess low amounts of this cytochrome.

Animals↗