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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inbred Wistar-Kyoto rats which are behaviorally more reactive to stress have a shorter life span than Brown-Norway rats. This is paralleled by higher basal activity and more pronounced changes in the septohippocampal cholinergic system of Wistar-Kyotos after stress. Age- and strain-dependent differences were therefore characterized in the septohippocampal system of 3- and 24-month-old (aged) Wistar-Kyotos and Brown-Norways, and in 30-month-old Brown-Norways. High affinity [3H]choline uptake and newly synthesized [3H]acetylcholine release served as markers for cholinergic terminals in the hippocampus. [3H]Quinuclidinylbenzilate binding served as a marker of muscarinic receptors in the hippocampus. Choline acetyltransferase activity served as a marker for cholinergic neurons and their terminals in the septum and hippocampus respectively. Acetylcholinesterase histochemical staining served to localize cholinergic neurons and their terminals in the septum and hippocampus respectively. In the hippocampus of aged Wistar-Kyotos choline uptake and acetylcholine release were reduced by approximately 50% compared to their young counterparts, but remained unchanged in aged Brown-Norways. Hippocampal choline acetyltransferase activity, acetylcholinesterase staining and muscarinic binding were unchanged in aged rats of both strains. Pyramidal cell loss (observed in Cresyl violet stained sections) was detected in hippocampus of 24-month-old Wistar-Kyotos and 30-month-old, but not younger Brown-Norways. Numbers of acetylcholinesterase-stained cells in the septum were reduced by 45 and 25% in 24-month-old Wistar-Kyotos and Brown-Norways respectively, and by 50% in 30-month-old Brown-Norways. Mean diameter of these cells was increased only in aged Wistar-Kyotos (approximately 46%) and in 30-month-old Brown-Norways (40%). The results indicate: (1) there is an ongoing age-dependent degeneration of septohippocampal cholinergic neurons which is associated with two principal compensatory changes in remaining cholinergic neurons: (a) hypertrophy of perikarya and (b) relative increase in activity of presynaptic markers in terminals with unchanged regional distribution, suggesting possible collateral sprouting; (2) age-dependent loss of septal cholinergic neurons precedes loss of hippocampal pyramidal neurons and (3) loss of pyramidal neurons in the hippocampus is associated with a compensatory increased muscarinic binding by remaining target hippocampal neurons. The results imply that higher basal and stress-induced activity of septohippocampal cholinergic neurons may be correlated with an accelerated and more pronounced age-dependent degeneration of this cholinergic system.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Age-dependent loss and compensatory changes of septohippocampal cholinergic neurons in two rat strains differing in longevity and response to stress. 343 31

The distribution of choline acetyltransferase activity in the cochlear nucleus of Sprague-Dawley albino rats was quantitatively compared to those in two strains of pigmented rats, Long Evans hooded and Brown Norway, using microdissection and radiometric assay techniques. Although activities tended to be, on the whole, higher in the albino rats, the differences were fairly minor. The relative distributions of choline acetyltransferase activity were generally similar among the 3 rat strains, not only among regions, but also within regions. Stain for acetylcholinesterase activity in the cochlear nucleus also had a similar appearance among the 3 rat strains. These chemical results are consistent with previous anatomical and physiological studies suggesting that auditory differences between albino and pigmented animals may not be as great in the cochlear nucleus as in the superior olivary complex.
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PMID:Quantitative inter-strain comparison of the distribution of choline acetyltransferase activity in the rat cochlear nucleus. 343 48

The activity of choline acetyltransferase is over twice as high in the hippocampus of Wistar Kyoto (WKY) than in Brown Norway (BN) rats, and this is paralleled by a comparable difference in acetylcholinesterase staining intensity within the hippocampal formation. However, the size of the whole hippocampus is smaller in WKY than in BN rats. There are no strain differences in the activities of the neurotransmitter-synthesizing enzymes: tyrosine hydroxylase in the septum and glutamic acid decarboxylase in the hippocampus. The findings indicate the existence of strain-dependent inverse relationship between the septo-hippocampal cholinergic system and the size of the hippocampus.
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PMID:Stain-dependent differences between the septo-hippocampal cholinergic system and hippocampal size. 611 23

Hexamethylene diisocyanate, HDI, a starting material in the production of many polyurethane products, was found to inhibit stoichiometrically mammalian and electric eel cholinesterases in an in vivo system (W. E. Brown, A. H. Green, M. H. Karol, and Y. Alarie , 1982, Toxicol . Appl. Pharmacol. 62, 45-52). The current study examined in vivo effects on guinea pig cholinesterases resulting from inhalation of HDI. Guinea pigs were exposed to atmospheres of 0.5, 1.8, or 4.0 ppm HDI (ceiling value = 0.02 ppm) for up to 6 hr. Blood samples were drawn prior to exposure and at specified times during exposure. No inhibition of serum cholinesterase was detected following exposure to 0.5 ppm HDI for 6 hr, to 1.8 ppm HDI for 2 hr, or to 4.0 ppm HDI for 3 hr. Similarly, no inhibition was detected when erythrocytes from each blood sample were assayed for acetylcholinesterase activity. Last, animals were sacrificed and cholinesterase activity determined in bronchial lavage fluid. Enzyme levels of HDI-exposed animals were not significantly different (P greater than 0.05) from those of control animals exposed to water vapor. In conclusion, although in vitro experiments had demonstrated potent anticholinesterase activity by HDI, in vivo inhalation exposure of guinea pigs to HDI at concentrations 25-200 times above the recommended (ACGIH) ceiling value did not produce measurable inhibition of cholinesterase activity.
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PMID:Effects of inhaled hexamethylene diisocyanate (HDI) on guinea pig cholinesterases. 672

Necator americanus (Nematoda: Strongyloidea), a human hookworm parasite, is known to release considerable amounts of acetylcholinesterase (AChE) [Pritchard, D. I., Leggett K. V., Rogan, M. T., McKean, P. G. & Brown, A. (1991) Necator americanus secretory acetylcholinesterase and its purification from excretory/secretory products by affinity chromatography, Parasite Immunol. 13, 187-199]. The present study deals with AChE activity recovered in sequential somatic extracts, and excretory/secretory products, of the adult stage of the parasite. 97% of AChE was extractable in low-salt and high-salt detergent-free buffers, and only 3% was solubilised by a further extraction in the presence of Triton X-100. AChE in all three extracts was affected by the AChE inhibitors eserine, bis(4-allyldimethylammoniumphenyl)pentan-3-one dibromide and edrophonium chloride, but was resistant to the effects of tetramonoisopropylpyrophosphortetramide, a butyrylcholinesterase inhibitor. Sucrose density centrifugation revealed that AChE in all somatic extracts (low-salt, high-salt and detergent) resolved almost exclusively as a single peak between 6.9-7.5 S, while excretory/secretory products resolved at 8.2 S. These values are all compatible with dimers of catalytic subunits and no evidence was found for the presence of higher oligomers such as asymmetric forms. The only sample to show a shift in sedimentation following the inclusion of detergent (Triton X-100, Brij 96) in the gradient was a component of the detergent-soluble extract, indicating the existence of a minor amphiphilic form. In low-salt-soluble and high-salt-soluble extracts, AChE was solubilised as a hydrophilic globular form, probably a dimeric G2. The analysis of diisopropylfluorophosphate-labelled extracts by SDS/PAGE, and unlabelled extracts by immunoblotting using a polyvalent antiserum to N. americanus AChE, indicated that the AChE isolated in each extract was biochemically and immunologically similar. The banding patterns obtained were comparable to that seen when purified AChE was analysed by SDS/PAGE and immunoblotted. This suggests that the basic catalytic subunit has a mass of 66-70 kDa with the active site being located in a 30-kDa domain. All experimental data indicate the existence of only one AChE class in Necator homologous to AChE of class B from Caenorhabditis elegans. The solubility characteristics and globular nature of this hookworm AChE suggest that its major function is as an excretory or secretory product. This again raises the question of the true biological function of this 'non-cholinergenic' nematode secretion.
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PMID:The molecular forms of acetylcholinesterase from Necator americanus (Nematoda), a hookworm parasite of the human intestine. 830 98

The Brown Treesnake (Boiga irregularis), a rear-fanged member of the polyphyletic family Colubridae, is an introduced predator on Guam which has been responsible for numerous human envenomations. Because little is known about this species' venom, we characterized venom proteins from B. irregularis using enzyme assays, one and 2D electrophoresis, Western blot analysis, mass spectrometry, HPLC and toxicity assays. Venom yields and protein content varied significantly with snake size, and large adult specimens averaged over 500 microl venom (19.2 mg, protein content approximately 90%). Only two enzymes, azocaseinolytic metalloprotease and acetylcholinesterase, were detected in venoms, and both activities increased with snake size/age. Western blot analysis demonstrated a 25 kDa CRiSP homolog in venoms from both neonate and adult snakes. 2D electrophoresis showed variation between venoms from neonate and adult snakes, especially with respect to metalloprotease and acetylcholinesterase. Analysis by MALDI-TOF mass spectrometry revealed the presence of numerous proteins with molecular masses of approximately 8.5-11 kDa. Adult B. irregularis venom was quite toxic to domestic chickens (Gallus domesticus; 1.75 microg/g) and lizards (Hemidactylus geckos: 2.5 microg/g and Carlia skinks: 4.5 microg/g), and intoxication was characterized by rapid paralysis of all species and neck droop in chickens. Toxicity of venom from neonates toward geckos was 1.1 microg/g, consistent with the presence of a greater diversity of 8-11 kDa proteins (suspected neurotoxins) in these venoms. All of these values were notably lower than murine LD50 values (neonate: 18 microg/g; adult: 31 microg/g). Like venoms of several front-fanged species, B. irregularis venom showed an ontogenetic shift in enzyme activities and toxicity, and neonate snakes produced more toxic venoms with lower protease and acetylcholinesterase activities. High toxicity toward non-mammalian prey demonstrated the presence of taxa-specific effects (and thus toxins) in B. irregularis venom, likely a characteristic of many colubrid snake venoms. We hypothesize that the lack of significant envenomation effects in humans following most colubrid bites results from this taxa-specific action of colubrid venom components, not from a lack of toxins.
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PMID:Venom of the Brown Treesnake, Boiga irregularis: ontogenetic shifts and taxa-specific toxicity. 1654 13

The Puerto Rican Racer Alsophis portoricensis is known to use venom to subdue lizard prey, and extensive damage to specific lizard body tissues has been well documented. The toxicity and biochemistry of the venom, however, has not been explored extensively. We employed biological assays and proteomic techniques to characterize venom from A. portoricensis anegadae collected from Guana Island, British Virgin Islands. High metalloproteinase and gelatinase, as well as low acetylcholinesterase and phosphodiesterase activities were detected, and the venom hydrolyzed the alpha-subunit of human fibrinogen very rapidly. SDS-PAGE analysis of venoms revealed up to 22 protein bands, with masses of approximately 5-160 kDa; very little variation among individual snakes or within one snake between venom extractions was observed. Most bands were approximately 25-62 kD, but MALDI-TOF analysis of crude venom indicated considerable complexity in the 1.5-13 kD mass range, including low intensity peaks in the 6.2-8.8 kD mass range (potential three-finger toxins). MALDI-TOF/TOF MS analysis of tryptic peptides confirmed that a 25 kDa band was a venom cysteine-rich secretory protein (CRiSP) with sequence homology with tigrin, a CRiSP from the natricine colubrid Rhabdophis tigrinus. The venom was quite toxic to NSA mice (Mus musculus: LD(50)=2.1 microg/g), as well as to Anolis lizards (A. carolinensis: 3.8 microg/g). Histology of the venom gland showed distinctive differences from the supralabial salivary glands (serous vs. mucosecretory), and like the Brown Treesnake (Boiga irregularis), another rear-fanged snake, serous secretory cells are arranged in densely packed secretory tubules, with little venom present in tubule lumina. These results clearly demonstrate that venom from A. portoricensis shares components with venoms of front-fanged snakes as well as with other rear-fanged species. Venom from A. portoricensis, in particular the prominent metalloproteinase activity, likely serves an important trophic function by facilitating prey handling and predigestion of prey.
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PMID:Biological and proteomic analysis of venom from the Puerto Rican Racer (Alsophis portoricensis: Dipsadidae). 1983 6

Three Lycopodiaceae species from French Polynesia, Lycopodium venustulum C. Gaudichaud, Lycopodiella cernua (C. Linnaeus) R. E. Pichi Sermolli and Lycopodium henryanum E. D. Brown were investigated for their alkaloidal composition by UHPLC/ESI-TOF-MS. Ten alkaloids were identified, with lycopodine and lycodoline being the main constituents in the three species. The acetylcholinesterase-inhibitory activities of the three species are probably due to the occurrence of huperzine A, huperzine B, huperzine E, huperzinine and lycopodine.
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PMID:Detection by UPLC/ESI-TOF-MS of alkaloids in three Lycopodiaceae species from French Polynesia and their anticholinesterase activity. 1991 69

Factors impacting life stage-specific sensitivity to chemicals include toxicokinetic and toxicodynamic changes. To evaluate age-related differences in the biochemical and behavioral impacts of two typical N-methyl carbamate pesticides, we systematically compared their dose-response and time-course in preweanling (postnatal day, PND, 18) and adult male Brown Norway rats (n=9-10/dose or time) ranging from adolescence to senescence (1, 4, 12, 24 mo). Carbaryl was administered orally at 3, 7.5, 15, or 22.5mg/kg and data were collected at 40 min after dosing, or else given at 3 or 15 mg/kg and data collected at 30, 60, 120, and 240 min. Methomyl was studied only in adult and senescent rat (4, 12, 24 mo) in terms of dose-response (0.25. 0.6, 1.25, 2.5mg/kg) and time-course (1.25mg/kg at 30, 60, 120, 240 min). Motor activity as well as brain and erythrocyte (RBC) cholinesterase (ChE) activity were measured in the same animals. In the carbaryl dose-response, PND18 rats were the most sensitive to the brain ChE-inhibiting effects of carbaryl, but 12- and 24-mo rats showed more motor activity depression even at similar levels of brain ChE inhibition. We have previously reported that brain ChE inhibition, but not motor activity effects, closely tracked carbaryl tissue levels. There were no age-related differences in methomyl-induced ChE inhibition across doses, but greater motor activity depression was again observed in the 12- and 24-mo rats. Carbaryl time-course data showed that motor activity depression reached a maximum later, and recovered slower, in the 12- and 24-mo rats compared to the younger ages; slowest recovery and maximal effects were seen in the 24-mo rats. Acetylcholinesterase sensitivity (concentration-inhibition curves) was measured in vitro using control tissues from each age. Inhibitory concentrations of carbaryl were somewhat lower in PND18, 12-, and 24-mo tissues compared to 1- and 4-mo, but there were no differences with methomyl-treated tissues. Thus, in the dose-response and time-course, there were dissociations between brain ChE inhibition and the magnitude as well as recovery of motor activity changes. The explanation for this dissociation is unclear, and is likely due to early development followed by aging-related decline in both kinetic parameters and neurological responsiveness.
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PMID:Assessment of biochemical and behavioral effects of carbaryl and methomyl in Brown-Norway rats from preweaning to senescence. 2570 86