Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Azirines”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 325 records · Page 18Linked to original sources
PubMed1987

The binding of ciamexone to globin: its demonstration and some accompanying effects in rats.

The 2-cyanaziridines Ciamexone and Azimexone in doses of 100 and 500 mg/kg lead to a reversible dose-dependent formation of thermolabile hemoglobin and Heinz bodies, a lowered erythrocyte count, and splenomegaly. According to our investigations these effects may have been caused by a covalent binding of the 2-cyanaziridines or their metabolites to globin in the erythrocytes. This binding was shown by gel electrophoresis using 14C-labeled Ciamexone. The change of the globin had no influence on the oxygen affinity of the hemoglobin.

2,3-Diphosphoglycerate↗
PubMed1986

Prevention of lupus diseases in MRL/1, NZBxNZW, and BXSB mice treated with a cyclophosphazene derived drug.

A polyclonal activation of lymphocytes (PA) has been suggested to play a pathogenic role in autoimmune and immune complex diseases, particularly in mouse lupus. "DIAM 4," a cyclophosphazene derived drug, selected on the basis of its ability to modulate a PA has been used to treat female MRL/1, female NZBxNZW, and male BXSB mice. In these three strains of mice, the treatment was found to induce an inhibition of the PA, to prevent the increase of anti-DNA antibody levels and the simultaneous decrease of C3 levels, to prevent the appearance of proteinuria, the deposition of immune complexes in glomeruli, and the development of kidney lesions. Moreover in MRL/1 mice, lymphoproliferation was prevented. These results suggest that drugs able to modulate a PA might be efficient in the treatment of mouse lupus nephritis. Such a principle of immunomodulation might open the way to new possibilities of treatment of lupus and other immune complex diseases.

Albuminuria↗
PubMed1984

Behavioral and neurochemical effects of intraventricular AF64A administration in rats.

Ethylcholine aziridinium ion solution (AF64A), a putative specific cholinergic neurotoxin, was injected bilaterally into the lateral ventricles of rats. Following administration of 3 or 6 nmoles of AF64A, drinking and eating were depressed but returned to normal levels after several days; increased activity in the 6 nmole group persisted throughout the 21 days of observations. Performance on complex place and cue tasks indicated that injected animals were impaired in reference memory only on the place task, but working memory was impaired on both tasks. Neurochemical measurements in a separate group of animals one week after AF64A injections found large depletions of acetylcholine in hippocampus and corpus striatum, but not depletions of norepinephrine (hippocampus) or dopamine (striatum). Histological examination of the injection site revealed extensive damage to the fimbria-fornix similar to that seen after electrolytic lesions. Since the behavorial and neurochemical changes are similar to those previously found following fimbria-fornix lesions, it is concluded that the present results are possibly due to non-specific lesion effects of the neurotoxin rather than a specific effect on cholinergic systems.

Acetylcholine↗
PubMed1985

Passive avoidance deficits in mice following ethylcholine aziridinium chloride treatment.

High-affinity choline uptake (HACU) appears to be the rate-limiting step in the synthesis of the neurotransmitter acetylcholine. The present experiment was designed to examine the effects of irreversible inhibition of HACU by ethylcholine aziridinium chloride (ECA) on passive avoidance retention in mice. Animals were injected intracerebroventricularly, and one-trial passive avoidance retention evaluated 21 days later. A significant retention deficit was observed in ECA-treated animals upon retest 24 hours after training. ECA-induced changes in retention were accompanied by significant reductions in choline acetyltransferase (CAT) activity in only two of seven brain regions tested, hippocampus (48% of control) and cerebellum (76% of control). The results support the involvement of hippocampal cholinergic activity in mediation of passive avoidance learning.

Animals↗
PubMed1987

Hippocampal electrical activity in relation to behavior following ethylcholine aziridinium ion (AF64A) treatment.

The effects of intracerebroventricular (ICV) injections of ethylcholine aziridinium ion (AF64A; 3 nmol/3 microliters/side) on the pattern of hippocampal electrical activity were studied in freely moving and urethane anesthetized rats. AF64A treated rats showed a significantly smaller increase in 6-12 Hz hippocampal rhythmical slow activity (RSA) with struggling in the no drug condition in comparison to the vehicle injected rats. However, neither AF64A treatment nor a control injection abolished the presumed cholinergic form of RSA that is present during urethane anesthesia. Systemic injection of atropine in waking rats did not significantly alter RSA in either the AF64A or vehicle injected rats. Analysis of histological brain sections revealed extensive damage to the fimbria-fornix, CA3 of the hippocampus, corpus callosum, neocortex and striatum. Acetylcholinesterase staining of the remaining hippocampus appeared normal in the AF64a treated rats. The data indicate that the depletion of cholinergic markers in the hippocampus following ICV administration of AF64A is not sufficient to disrupt the cholinergic form of RSA. Further, the question is discussed as to whether AF64A produces its cholinoselective effects via a specific pharmacological action or through a nonspecific destruction of the fimbria-fornix.

Animals↗
PubMed1987

Neurochemical and behavioral effects of N-ethyl-acetylcholine aziridinium chloride in mice.

N-ethyl-choline aziridinium (ECA) and N-ethyl-acetylcholine aziridinium (EAA) were shown to be inhibitors of high affinity choline uptake in vitro (IC50 = 0.4 microM and 1.5 microM, respectively), and intraventricular administration showed that EAA was more selective in its inhibition of hippocampal choline uptake in vivo. EAA significantly reduced the activity of choline acetyltransferase in the hippocampus 3 to 28 days following intraventricular infusion, but not in the striatum or parahippocampal cortex. Neither muscarinic receptor binding nor glutamic acid decarboxylase activity were affected in any of the three brain regions. EAA (12 or 16 nanomoles, intraventricular) significantly impaired memory performance of mice in a radial arm maze when tested two weeks after treatment. A subgroup analysis implicated long-term reference memory as the mechanism disrupted.

Animals↗
PubMed1987

Biochemical and behavioral effects of intrahippocampal AF64A in rats.

AF64A (ethylcholine aziridinium, 1 nmole) injected into the dorsal hippocampus of the rat decreased choline acetyltransferase activity there by 20% without greatly affecting adjacent areas. The decrease was maximal by 3 days, and persisted for at least 3 weeks. The acetylcholine concentration at the injection site was decreased by 25-30% from 3 days to 4 weeks. Rats were trained on a continuous reinforcement (CRF) food-reinforced lever press schedule and then injected bilaterally in the dorsal and ventral hippocampus. Subsequent switching to a daily CRF-extinction schedule resulted in increased responding during extinction compared to controls which persisted for at least 13 session. However, injection after switching schedules increased it for only 2 sessions. This indicates that the persistently increased extinction responding is due mainly to impaired learned habituation to a new schedule. Most of the extinction effect of the intrahippocampal AF64A was due to its injection at the dorsal site. Separate rats which were trained on the 8-arm radial maze task (a test of short-term spatial working memory) and injected as above only showed marginally impaired task performance even at higher doses. We conclude that even relatively minor, localized, cholinergic deficits confined to the hippocampus can produce significant learning and memory impairments in situations where intermediate or long term memory formation is required.

Acetylcholine↗
PubMed1985

Method for the quantitation and characterization of the cholinergic neurotoxin, monoethylcholine mustard aziridinium ion (AF64A).

Monoethylcholine aziridinium ion (AF64A), which is generated from the precursor, acetylcholine mustard hydrochloride, exerts selective neurotoxic effects against brain cholinergic neurons when injected intracerebrally. Conditions associated with optimal generation of AF64A were examined. The results indicate that hydrolysis and cyclization of the precursor are optimal at 25 degrees C with the former occurring at pH 9.0 and the latter at pH 7.3. The aziridinium ion is best stabilized at pH 7.3 at 4 degrees C.

Aziridines↗
PubMed1988

Formation and degradation of 1-(ethyl)-1-(2-hydroxyethyl) aziridinium chloride in aqueous media--a comparative NMR study.

The formation and decomposition of 1-(ethyl)-1-(2-hydroxyethyl) aziridinium chloride in aqueous media (10 mM solutions) was studied by NMR spectroscopy. Compared to 1-diethyl aziridinium chloride which lacks the hydroxyl group, the degradation of the title compound at 37 degrees C and pH = 7.4 is about 10 times faster. However, liquid nitrogen frozen solutions of both aziridinium salts are stable for long periods of time (1-6 months).

Aziridines↗
PubMed1988

Role of the aziridinium moiety in the in vivo cholinotoxicity of ethylcholine aziridinium ion (AF64A).

To assess the role of the aziridinium moiety for the cholinotoxicity of ethylcholine aziridinium ion (AF64A) we compared in vitro and in vivo effects of AF64A with those of various precursors as well as decomposition products of AF64A. In vitro, AF64A was the most effective irreversible inhibitor of high-affinity choline transport (HAChT) in hippocampal synaptosomes. The uncyclized precursor acetylethylcholine mustard and the acetylated form of AF64A were about 3 times less potent. Their potency, however, was reduced considerably when hydrolysis of the choline esters was prevented by physostigmine. Destruction of the aziridinium ring either by high pH (alcohol formation) or by thiosulfate (formation of Bunte salt) resulted in a loss of biological activity. This was also the case for the in vivo cholinotoxicity, as assessed by the decline in hippocampal concentration of acetylcholine (ACh) 7 days after intracerebroventricular (i.c.v.) infusion. The most pronounced reduction in ACh content was achieved after i.c.v. infusion of AF64A, whereas the precursor and the acetylated analog of AF64A induced a significant, but smaller reduction in the ACh content. These data indicate that the aziridinium ring of AF64A is essential for both the inhibition of HAChT in vitro and the cholinotoxicity in vivo. However, cyclization of the precursor compound as well as hydrolysis of acetylated AF64A also occur in tissue, leading to a partial activity of these compounds.

Animals↗
PubMed1989

Noradrenaline depletion protects cholinergic neurons in rat hippocampus against AF64A-induced damage.

The role of the noradrenergic system in the cholinotoxicity of ethylcholine aziridinium ion (AF64A) was studied in rats. Male Sprague-Dawley rats were treated with the noradrenergic neurotoxin DSP-4 (N-(2-chloroethyl)-n-ethyl-2-bromobenzylamine; 50 mg/kg i.p.) in the presence of the serotonin uptake inhibitor fluoxetine, 14 days prior to bilateral intracerebroventricular injection of AF64A (2 nmol/lateral ventricle). In rats in which noradrenaline (NA) was depleted by 94%, the loss of acetylcholine (ACh) in hippocampus induced by AF64A was significantly attenuated (p less than 0.02). However, when there was only a partial depletion of NA (50% reduction), the AF64A-induced loss of ACh was a pronounced as in rats with intact noradrenergic function. These findings indicate that the noradrenergic lesion has to be complete before a protective effect is apparent. Moreover, they imply that noradrenergic input is involved in AF64A-induced cholinergic damage in the hippocampus.

Adrenergic Fibers↗
PubMed1990

Electrophoretic map of acidic and neutral human spermatozoal proteins.

A high resolution two dimensional electrophoretic technique (2-D), isoelectric focusing followed by polyacrylamide gel electrophoresis, for separation of neutral and acidic human spermatozoal proteins was established. Silver stained 2-D gels revealed over 260 proteins with Mr 20-200 kDa and pI between 4.5 and 7.8. Membrane proteins were radio-iodinated in their hydrophobic cores with the hydrophobic photoactivatable reagent 3 (trifluoromethyl)-3-(m-[125I]iodophenyl) diazirine (TID). Externally exposed carbohydrate side chains were radiolabelled by NaB(3H)4 reduction. 2-D lectin blotting was performed with horseradish peroxidase conjugated Concanavalin A (Con A), biotinylated Vicia faba agglutinin (VFA) and Solanum tuberosum agglutinin (STA). A map of 258 human spermatozoal proteins is presented and 48 TID-labelled proteins have been biochemically characterized.

Affinity Labels↗
PubMed1978

Cytogenetic and other effects of the chemosterilants tepa, metepa, apholate an hempa in insects (a review).

A review of the literature revealed that the chemosterilants tepa (tris(1-aziridinyl)phosphine oxide), metepa (tris(2-methyl-1-aziridinyl) phosphineoxide), apholate (2,2,4,4,6,6-hexakis(1-aziridinyl)-2,2,4,4,6,6-hexahydro-1,3,5,2,4,6-triazatriphosphorine), and hempa (hexamethylmelamine) affected both reproductive and somatic tissues in over 65 species of insects. The effects were cytological, physiological, and genetic and varied from slight to severe. In some cases the deleterious effects may have been species-specific, but in general, they appeared to be dose-dependent. More than 150 publications are cited.

Animals↗
PubMed1975

Mutagenic studies of aziridine derivatives derived from various diamines.

Various aziridine derivatives derived from diamines were studied in several biological systems to evaluate their effects on reproduction and as potential mutagens. Considerable variations in the biological activities of these compounds were seen among animal species and among the varied chemical structures. In general, mutagenic responses paralleled the antifertility effects in mice and houseflies and the anticancer effects in mice. The lack of an antifertility effect by N,N'-bis(aziridinylacetyl)-1,8-octamethylenediamine in the rat was quite unexpected in view of its chemosterilant activity in houseflies and mice.

Animals↗
PubMedDate not supplied

Sister-chromatid exchanges and chromosomal aberrations in lymphocytes of male albino rats treated with an alkylating agent, apholate (NSC 26, 812; ENT 26, 316).

A lymphocyte culture system was used to study the frequency of chromosomal aberrations and SCEs at various time intervals after an intraperitoneal injection of apholate (0.5 mg/kg b.w.) in male albino rats. Treatment with apholate increased the frequency of chromosomal aberrations significantly (P less than 0.001). The majority of chromosomal aberrations were single chromatid breaks, although other aberrations were also present. The distribution of chromatid breaks was non-random and the large chromosomes were affected to a greater extent. SCEs frequency in lymphocytes of apholate-treated rats was more than 5-fold higher in comparison to controls. The highest number of chromosomal aberrations and SCEs/rat was recorded at 48 h post-treatment, after which there was a gradual decline in both SCE and chromosomal aberration frequency. The results indicate that apholate is a mutagenic compound and it may also be carcinogenic.

Animals↗
PubMed1988

Behavioral differences in the developing rat following postnatal anoxia or postnatally injected AF-64A, a cholinergic neurotoxin.

Rat pups were submitted postnatally to one of two procedures: a 25-min exposure to 100% nitrogen or an i.c.v. bilateral injection of AF-64A, 2 nmol contained in 1-microliter saline. Throughout further development of either group, their performance in passive and active avoidance tests and in amphetamine-induced stereotype behavior was followed and compared. Both groups exhibited hyperactivity which persisted until 42 days of age in the anoxia group and beyond 120 days in the AF-64A group. Both groups were equally inferior to controls in the passive avoidance test, but only the anoxia group was inferior to controls in the active avoidance test. Amphetamine-induced stereotype behavior was much less pronounced in the anoxia group relative to AF-64A-treated rats or to controls. The results suggest that the lesion induced by the neurotoxin is more specific and less widespread than the one caused by anoxia.

Animals↗