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PubMed1975

Preservation of early discharge of muscle afferents in acrylamide neuropathy.

1. Responses to stretch and the 'early discharge' have been studied in acrylamide neuropathy in the expectation that functional block of the nerve terminals would allow these two processes to be dissociated. 2. Of 538 single group I and group II muscle afferents which were nonresponsive to stretch, ninety-nine displayed 'early discharge' which appeared to be identical with that described in normally functioning muscle stretch afferents. 3. Preservation of 'early discharge' in non-responsive fibres indicates these impulses do not arise from excitation of the muscle spindle itself. The evidence indicates that 'early discharge' is usually ephaptically excited by the muscle action potential.

Acrylamides↗
PubMed2003

Characterization of N-(1-Acetyl-2,3-dihydro-1H-indol-6-yl)-3-(3-cyano-phenyl)-N-[1-(2-cyclopentyl-ethyl)-piperidin-4yl]acrylamide (JNJ-5207787), a small molecule antagonist of the neuropeptide Y Y2 receptor.

The in vitro pharmacological properties of N-(1-Acetyl-2,3-dihydro-1H-indol-6-yl)-3-(3-cyano-phenyl)-N-[1-(2-cyclopentyl-ethyl)-piperidin-4yl]-acrylamide (JNJ-5207787), a novel neuropeptide Y Y(2) receptor (Y(2)) antagonist, were evaluated. JNJ-5207787 inhibited the binding of peptide YY (PYY) to human Y(2) receptor in KAN-Ts cells (pIC(50) = 7.00 +/- 0.10) and to rat Y(2) receptors in rat hippocampus (pIC(50) = 7.10 +/- 0.20). The compound was >100-fold selective versus human Y(1),Y(4), and Y(5) receptors as evaluated by radioligand binding. In vitro receptor autoradiography data in rat brain tissue sections confirmed the selectivity of JNJ-5207787. [(125)I]PYY binding sites sensitive to JNJ-5207787 were found in rat brain regions known to express Y(2) receptor (septum, hypothalamus, hippocampus, substantia nigra, and cerebellum), whereas insensitive binding sites were observed in regions known to express Y(1) receptor (cortex and thalamus). JNJ-5207787 was demonstrated to be an antagonist via inhibition of PYY-stimulated guanosine 5'-O-(3-[(35)S]thio)triphosphate binding ([(35)S]GTPgammaS) in KAN-Ts cells (pIC(50) corrected = 7.20 +/- 0.12). This was confirmed auto-radiographically in rat brain sections where PYY-stimulated guanosine 5'-O-(3-[(35)S]thio)triphosphate binding was inhibited by JNJ-5207787 (10 microM) in hypothalamus, hippocampus, and substantia nigra. After intraperitoneal administration in rats (30 mg/kg), JNJ-5207787 penetrated into the brain (C(max) = 1351 +/- 153 ng/ml at 30 min) and occupied Y(2) receptor binding sites as revealed by ex vivo receptor autoradiography. Hence, JNJ-5207787 is a potent and selective pharmacological tool available to establish the potential role of central and peripheral Y(2) receptors in vivo.

Acrylamides↗
PubMed2004

AMG 9810 [(E)-3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4] dioxin-6-yl)acrylamide], a novel vanilloid receptor 1 (TRPV1) antagonist with antihyperalgesic properties.

The vanilloid receptor 1 (VR1 or TRPV1) is a membrane-bound, nonselective cation channel expressed by peripheral sensory neurons. TRPV1 antagonists produce antihyperalgesic effects in animal models of inflammatory and neuropathic pain. Here, we describe the in vitro and in vivo pharmacology of a novel TRPV1 antagonist, AMG 9810, (E)-3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamide. AMG 9810 is a competitive antagonist of capsaicin activation (IC50 value for human TRPV1, 24.5 +/- 15.7 nM; rat TRPV1, 85.6 +/- 39.4 nM) and blocks all known modes of TRPV1 activation, including protons (IC50 value for rat TRPV1, 294 +/- 192 nM; human TRPV1, 92.7 +/- 72.8 nM), heat (IC50 value for rat TRPV1, 21 +/- 17 nM; human TRPV1, 15.8 +/- 10.8 nM), and endogenous ligands, such as anandamide, N-arachidonyl dopamine, and oleoyldopamine. AMG 9810 blocks capsaicin-evoked depolarization and calcitonin gene-related peptide release in cultures of rat dorsal root ganglion primary neurons. Screening of AMG 9810 against a panel of G protein-coupled receptors and ion channels indicated selectivity toward TRPV1. In vivo, AMG 9810 is effective at preventing capsaicin-induced eye wiping in a dose-dependent manner, and it reverses thermal and mechanical hyperalgesia in a model of inflammatory pain induced by intraplantar injection of complete Freund's adjuvant. At effective doses, AMG 9810 did not show any significant effects on motor function, as measured by open field locomotor activity and motor coordination tests. AMG 9810 is the first cinnamide TRPV1 antagonist reported to block capsaicin-induced eye wiping behavior and reverse hyperalgesia in an animal model of inflammatory pain.

Acrylamides↗
PubMed1965

SERUM PROTEIN ELECTROPHORESIS IN ACRYLAMIDE GEL: PATTERNS FROM NORMAL HUMAN SUBJECTS.

Technical improvements in the method for vertical acrylamide gel electrophoresis (Raymond) have resulted in improved resolution and reproducibility. In a survey of approximately 200 normal human serums, ten lines were found to be common in all specimens. Interposed with these constant lines and in addition to known variations in the pattern reflecting haptoglobin and transferrin types, at least one line followed that of albumin and three followed that of transferrin; the presence or absence of these varied from individual to individual. Based on these variations, the electrophoretic patterns of normal humans may be divided into at least 12 discrete groups.

Acrylamide↗
PubMed1972

Acrylamide polymerization: new method for determining the oxygen content in blood.

A new principle for determining the oxygen content of 0.1-milliliter blood samples has been developed, based on measurement of the delay in gelation during copolymerization of acrylamide and bisacrylamide initiated by free radicals. The logarithm of this time interval is linearly proportional to the oxygen content of the blood sample over the range 0 to 22 milliliters of oxygen per 100 milliliters of whole blood. Physiological variations of pH and pCO(2) do not affect the sensitivity of the assay.

Acrylamides↗
PubMed1971

Motor and sensory nerve conduction velocity in the baboon: normal values and changes during acrylamide neuropathy.

Nerve conduction velocity and the amplitude of nerve and muscle action potentials have been measured in the median and anterior tibial nerves of normal adult and infant baboons. The effect of altered temperature on velocity has also been investigated. Seven adult baboons were intoxicated with acrylamide. In animals given 10-15 mg/kg/day, the gradual development of a peripheral neuropathy was accompanied by a decline in the amplitude of both muscle and nerve action potentials. There was also a gradual fall in conduction velocity. In some cases maximal motor velocity in the median nerve fell by as much as 34%, and in the anterior tibial nerve by as much as 49%, the largest falls being seen in animals showing the greatest reductions in response amplitude. Histological studies, reported elsewhere, have shown that the main pathological change in our animals was a degeneration of the peripheral nerves, with little demyelination. Fibre diameter histograms indicated that large fibres were particularly severely affected, and it seems likely that the reduced maximal conduction velocities were due to this selective loss of large-diameter fibres.

Acrylamides↗
PubMed1982

Abnormalities in the vagus nerve in canine acrylamide neuropathy.

Dogs exposed to acrylamide develop a sensorimotor peripheral neuropathy and megaoesophagus. The presence of neuropathy was confirmed electrophysiologically and histologically. Hindlimb motor conduction velocity was reduced and there was a loss of large diameter myelinated fibres in the dorsal common digital nerve and the tibial nerve. The conduction velocity of vagal motor fibres innervating the thoracic oesophagus was not decreased; there was a reduction in the conduction velocity of the mixed nerve action potential of the vagus. Degenerating nerve fibres were observed in the vagus in the midthoracic region. The damage to vagal nerve fibres may be an important factor in the causation of megaoesophagus.

Acrylamides↗
PubMed2004

Heritable translocations induced by dermal exposure of male mice to acrylamide.

Acrylamide (AA) is an important industrial chemical used mainly in the production of polymers. It can be absorbed through the skin. AA was shown to be a germ cell clastogen that entails a genetic risk for exposed workers. The genetic risk calculation was based on mouse heritable translocation test data obtained after acute intraperitoneal (ip) exposure (Adler et al., 1994). To obtain a correction factor between ip and dermal exposure, dominant lethal and heritable translocation tests were carried out with dermal exposure of male mice to AA. In the dominant lethal test, male (102/El x C3H/El)F1 mice were exposed by dermal application to the shaved backs of 50 mg/kg AA per day on five consecutive days or to five daily ip injections of 50 mg/kg AA. One day after the end of exposure, the males were mated to untreated females of the same hybrid stock for four days and females were changed every four days for a total of five matings. Dominant lethal effects were found during matings 1-3. For ip exposure, these values were 81.7, 85.7 and 45.4%, respectively; for dermal exposure the corresponding values were 22.1, 30.6 and 16.5%, respectively. In the heritable translocation assay, male C3H/El mice were treated with five dermal exposures of 50 mg/kg AA and mated 1.5-8.5 days after the end of exposure to untreated female 102/El mice. Pregnant females were allowed to come to term and all offspring were raised to maturity. Translocation carriers among the F1 progeny were selected by a sequential fertility testing and cytogenetic analysis including G-band karyotyping and M-FISH. A total of 475 offspring were screened and 41 translocation carriers were identified. The observed translocation frequency after dermal exposure was 8.6% as compared to 21.9% after similar ip exposure (Adler, 1990). The calculated ratio of ip vs. dermal exposure of 0.39 can be applied to obtain a more realistic calculation of genetic risk for dermally exposed workers.

Acrylamide↗
PubMed2003

Surface modification of poly-L-lactic acid (PLLA) membrane by grafting acrylamide: an effective way to improve cytocompatibility for chondrocytes.

Poly-L-lactic acid (PLLA) membranes were photo-oxidized in hydrogen peroxide solution under ultraviolet light (UV) to introduce hydroperoxide groups onto the PLLA membrane surfaces. The photo-oxidized membranes were then immersed in acrylamide (AAm) solution containing Fe2+ to graft polyacrylamide (PAAm) onto the PLLA membrane surfaces. The density of the hydroperoxide groups introduced on the PLLA membrane surfaces varied with the temperature and the photo-oxidization time. The occurrence of grafting was verified by X-ray photoelectron spectroscopy (XPS). The degree of grafting increased with the monomer concentration and the polymerization time. Water contact angle measurements showed that the wettability of the modified PLLA membranes had improved. Chondrocytes proliferated more rapidly and were more spread out on the modified membrane than on the control PLLA membrane, indicating that the PAAm-grafted PLLA membrane has better cytocompatibility for chondrocytes.

Acrylamide↗
PubMed2004

Polymer composition and acidification effects on the swelling and mechanical properties of poly(acrylamide-co-acrylic acid) superporous hydrogels.

Poly(acrylamide-co-acrylic acid) (poly(AM-co-AA)) superporous hydrogels (SPHs) were synthesized and the acidification effects on the swelling and mechanical properties were studied. Gelation exotherms were measured to determine the optimum introduction time for adding a blowing agent. The gelation kinetics decreased with increasing the AA concentration. The maximum equilibrium swelling was observed around an AA weight fraction of 0.4, but the compressive strength decreased monotonically with increasing the AA concentration. Poly(AM-co-AA) SPHs were much less swollen in acidic solution than in distilled water of pH 6.7. The swelling ratio decreased with increasing acidity (decreasing pH). Reduction of water absorption content by acidification led to considerable increase in the mechanical strength.

Acrylamide↗
PubMed1987

Ultrastructural and clinicopathological studies on the toxicity of cationic acrylamide-based flocculant to rainbow trout.

Rainbow trout (Salmo gairdneri) of two age groups were exposed to a cationic acrylamide-based flocculant at various concentrations in static bioassay chambers. At lethal concentrations the flocculant produced severe gill alterations in all fish. The principal alterations were necrosis and separation of the respiratory epithelial cells covering secondary lamellae. Many necrotic chloride cells were also seen, their apical plasma membrane was destroyed, and mitochondria were swollen with separated cristae. An influx of a large amount of fluid into the interstitial spaces caused partial or complete separation of subepithelial spaces from the covering epithelial cells and basement membranes of underlying blood vessels. Clinicopathological alterations included marked decreases in blood pH, partial pressure of oxygen, bicarbonate and plasma sodium, and chloride concentrations. Hematocrit, total protein, and blood glucose were increased. Fish exposed to sublethal concentrations had gill alterations characterized by hypercellularity and thickening of the secondary lamellae. These were due to undifferentiated cell proliferation and macrophage and lymphocyte infiltration between the covering epithelial cells and the underlying blood vessels. Macrophages and undifferentiated cells had large phagolysosomes containing cytoplasmic organelles, an indication of cell injury and increased turnover.

Acrylamides↗
PubMed2004

Human exposures to acrylamide are below the threshold for carcinogenesis.

Dose-response calculations for a threshold of carcinogenesis in animal studies do not support the notion that acrylamide (ACR) with the present status of consumption in food is carcinogenic for humans. This is in agreement with the recent reassuring epidemiological studies which have shown a lack of correlation between exposure to ACR in food and the incidence of cancer.

Acrylamide↗
PubMed1989

Acrylamide derivatives as antiallergic agents. III. Synthesis and structure-activity relationships of N-[4-(4-diphenylmethyl-1-piperazinyl)butyl]- and N-[4-(4-diphenylmethylene-1-piperidyl)butyl]-3-heteroarylacry lamides.

A new series of 3-heteroarylacrylamides 2 and 4 was prepared and the inhibitory activities against the rat passive cutaneous anaphylaxis (PCA) reaction and the enzyme 5-lipoxygenase (5-LO) were tested. Most of the compounds exhibited an anti-PCA activity superior to or equivalent to ketotifen and had a 5-LO inhibitory activity. The 3-heteroarylacrylamide derivatives including 3-(3-pyridyl)acrylamides represent a new structural class of compound that exhibits not only an in vivo anti-PCA activity but also an in vitro 5-LO inhibitory activity.

Acrylamides↗
PubMed2006

Acrylamide analog as a novel nitric oxide-independent soluble guanylyl cyclase activator.

Soluble guanylyl cyclase (sGC) is a target enzyme for endogenous nitric oxide (NO), and it converts GTP to cyclic GMP (guanosine 3',5'-cyclic monophosphate) as part of a cascade that results in physiological processes such as smooth muscle relaxation, neurotransmission, and inhibition of platelet aggregation. Here we examine a representative of the novel class sCG activators, A-778935 ((+/-)-cis-3-[2-(2,2-dimethyl-propylsulfanyl)-pyridin-3-yl]-N-(3-hydroxy-cyclohexyl)-acrylamide). A-778935 activated sGC synergistically with sodium nitroprusside (SNP) over a wide range of concentration, inducing up to 420-fold activation. A specific inhibitor of sGC, ODQ (1H-[1,2,4]-oxadiazolo[4,3-alpha]quinoxalin-1-one), did not block basal sGC activity, but competitively inhibited the activation by A-778935. A-778935, with or without SNP, did not activate heme-deficient sGC, indicating that the activation of sGC by A-778935 is fully heme-dependent. A-778935 increased intracellular cGMP level dose-dependently in smooth muscle cells. In the presence of 1 microM SNP, a lower concentration of A-778935 increased cGMP than A-778935 alone, and the cGMP concentration reached the same level at 100 microM of A-778935. A-778935 relaxed cavernosum tissue strips in a dose-dependent manner; and in the presence of 1 microM SNP, A-778935 relaxed the strips more potently, shifting the dose-response curve to the left. This novel activator of sGC may have potential efficacy for the treatment of a variety of disorders associated with reduced NO signaling.

Acrylamides↗
PubMed2006

Examination of conditions inhibiting the formation of acrylamide in the model system of fried potato.

Acrylamide (AAm) is produced in food through the reaction of asparagine and reducing sugar. We examined several methods of reducing the level of AAm using potato tubers. The fried model system that we employed consisted of thin slices that were first treated in water under different conditions before frying. A sufficient amount of water present in the fry material acts as an inhibitor against the formation of AAm and allows only a negligible amount of AAm to form. It was found that given the low content of water, the fry material temperature was sufficiently high to allow a relatively large level of AAm to form. Examination of water treatment prior to frying revealed that higher-temperature treatment water and longer treatment time resulted in the formation of lower levels of AAm. Moreover, removing some of the residual heat had an inhibiting effect on the formation of AAm.

Acrylamide↗
PubMed2005

Suppressive effect of trehalose on acrylamide formation from asparagine and reducing saccharides.

The influence of saccharides on the formation of acrylamide (AcA) was investigated. The reducing saccharides reacted with asaparagine to form AcA, but the non-reducing saccharides, except sucrose, gave no AcA. AcA formation from a mixture containing glucose and asaparagaine was suppressed by the non-reducing saccharides, especially trehalose (76% suppression) and neotrehalose (75% suppression). Glucose is heat-degraded into pyruvaldehyde and 5-hydroxymethyl-2-furfural in the water system. The degradation products react with asparagines to generate AcA. Trehalose appears to inhibit not only the formation of these intermediates and asparagines for AcA, but also the AcA formation from these intermediates.

Acrylamide↗
PubMed1980

[The toxicity of acrylamide (author's transl)].

Acute and chronic toxicities of acrylamide (AAM) are reviewed with special reference to its dose-response relationship from literature concerning the general toxicology and industrial hygiene. Although the total doses of AAM for producing chronic neuropathy in animals showed considerable variation among literature sources, estimated mean concentrations of the compound in the nervous tissues do not seem to differ very much at any stage of the poisoning. Reports of human poisoning, most of them being due to occupational exposure, are referred and symptoms of the poisoning are summarized from these cases.

Acrylamides↗