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71.
Hydroxyl Radical-Mediated Oxidation of Serotonin: Potential Insights into the Neurotoxicity of Methamphetamine 总被引:1,自引:1,他引:0
Monika Z. Wrona Zhaoliang Yang Michelle McAdams Susan O'Connor-Coates Glenn Dryhurst 《Journal of neurochemistry》1995,64(3):1390-1400
Abstract: When incubated with a hydroxyl radical (HO?)-generating system (ascorbic acid/Fe2+-EDTA/O2/H2O2), 5-hydroxytryptamine (5-HT; serotonin) is rapidly oxidized initially to a mixture of 2,5-, 4,5-, and 5,6-dihydroxytryptamine (DHT). The major reaction product is 2,5-DHT, which at physiological pH exists as its keto tautomer, 5-hydroxy-3-ethylamino-2-oxindole (5-HEO). Rapid autoxidation of 4,5-DHT gives tryptamine-4,5-dione (T-4,5-D), which reacts with the C(3)-centered carbanion of 5-HEO to give 3,3′-bis(2-aminoethyl)-5-hydroxy-[3,7′-bi-1H-indole]-2,4′,5′-3H-trione (7). The latter slowly cyclizes to 3′-(2-aminoethyl)-1′,6′,7′,8′-tetrahydro-5-hydroxyspiro[3H-indole-3,9′-[9H]pyrrolo[2,3-f]quinoline]-2,4′,5′(1H)- trione (9). A minor amount of T-4,5-D dimerizes to give 7,7′-bi-(5-hydroxytryptamine-4-one) (7,7′-D). In the presence of GSH, the reaction of T-4,5-D with 5-HEO is diverted and, in the presence of sufficient concentrations of this tripeptide, completely blocked. This is because GSH preferentially reacts with T-4,5-D to give 7-S-glutathionyltryptamine-4,5-dione (11). The results of this investigation suggest that 5,6-DHT, 5-HEO, 7, and 9 are products unique to the HO?-mediated oxidation of 5-HT. Thus, the observation of other investigators that 5,6-DHT is formed in the brains of rats following a large dose of methamphetamine (MA) suggests that this drug might evoke HO? formation. However, the present in vitro study indicates that 5,6-DHT is a rather minor, unstable product of the HO?-mediated oxidation of 5-HT and suggests that detection of 5-HEO, 7/9, and 11 in rat brain following MA administration could provide additional support for HO? formation. Furthermore, one or more of the intermediates and major products of oxidation of 5-HT by HO? might, in addition to 5,6-DHT, contribute to the MA-induced degeneration of serotonergic neurons. 相似文献
72.
J. D. Penschow Michelle E. Giles John P. Coghlan R. T. Fernley 《Histochemistry and cell biology》1997,107(5):417-422
Carbonic anhydrase VI (CA VI) is a secreted enzyme produced predominantly by serous acinar cells of submandibular and parotid
glands. We have investigated the developmental pattern of CA VI production by these glands in the sheep, from fetal life to
adulthood, using immunohistochemistry. Also, a specific radioimmunoassay for CA VI was used to measure changes in enzyme expression
in the parotid gland postnatally. CA VI is detectable by immunohistochemistry in parotid excretory ducts from 106 days gestation
(term is 145 days), in striated ducts from 138 days and in acinar cells from 1 day postnatal. The duct cell content of CA
VI declined as the acinar cell population increased, a feature also of CA VI immunoreactivity in the submandibular gland.
Production of CA VI by submandibular duct cells was detectable initially at 125 days gestation, and acinar production was
not seen before 29 days post-natal. Apart from the differing ontogeny of CA VI production in ducts and acini of parotid and
submandibular glands, there was a parallel pattern of CA VI expression during the development of these major salivary glands.With
the development of the acinar tissues in the postnatal lamb, there was a dramatic increase (about 600-fold) in the level of
expression of CA VI in the parotid gland between days 7 and 59 as measured by radioimmunoassay.
Accepted: 19 December 1996 相似文献
73.
Expression of Bcl-2 protein in the epiphyseal plate cartilage and trabecular bone of growing rats 总被引:2,自引:0,他引:2
Ying Wang Renée Toury Michelle Hauchecorne N. Balmain 《Histochemistry and cell biology》1997,108(1):45-55
The protooncogene protein, Bcl-2, protects cells from apoptosis and ensures their survival in vitro by inhibiting the action
of the apoptosis-inducer, Bax. Its expression in proliferative and long-lived cells in vivo also indicates that it protects
against cell death. The chondrocytes of the epiphyseal plate cartilage undergo a series of maturation steps and deposit mineral
in the cartilage matrix before dying. The possibility that Bcl-2 helps protect chondrocytes until mineral deposition is completed
was investigated by determining the distribution of Bcl-2 immunoreactivity in the epiphyseal plate cartilage of growing rats
and its subcellular localization, using a specific antibody. The involvement of Bax in the triggering of chondrocyte death
was checked by immunocytochemistry. Bcl-2 expression in the osteoblasts and the final result of their evolution, the osteocytes,
was also examined in trabecular bone. Bcl-2 immunoreactivity was non-uniformly distributed throughout the epiphyseal cartilage.
It was maximal in proliferative chondrocytes, decreased in mature chondrocytes, and low in hypertrophic chondrocytes, whereas
there was Bax immunoreactivity in all chondrocytes examined. Immunolabeling was intense in osteoblasts but considerably lower
in fully differentiated osteocytes. Bcl-2 immunoreactivity was mainly in the cytoplasm of chondrocytes, osteoblasts, and early
osteocytes; the nuclei appeared clear. The subcellular distribution of Bcl-2 immunolabeling in chondrocytes, revealed by gold
particles in the electron microscope, showed that gold particles were frequently concentrated in the mitochondria in all the
cartilage zones and lay mainly within the organelles, not at their periphery. The endoplasmic reticulum contained moderate
immunoreactivity and there were few gold particles in the cytoplasm and nuclei. The number of gold particles decreased in
all the subcellular compartments from proliferative to hypertrophic chondrocytes. In contrast, Bax immunoreactivity changed
little during chondrocyte terminal evolution, and its subcellular distribution mirrored that of Bcl-2. These immunocytochemical
data indicate that Bcl-2 helps maintain chondrocytes and osteoblasts until their terminal maturation.
Accepted: 19 February 1997 相似文献
74.
Ecological correlates of hind-limb length in the Carnivora 总被引:1,自引:0,他引:1
What determines the lengths and proportions of mammalian limbs? While the answer to this question is still largely unknown, a number of workers have recently begun analysing the selection of morphology in a rigorous framework, searching for quantitative links between structure, performance, and their ecological and behavioural context. The present study investigates a variety of ecological and behavioural variables to determine whether or not they are correlated with hind-limb length in the Carnivora. Data were analysed by using phylogenetically independent contrasts and phylogenetic analysis of covariance. We found that traditional perceptions of limb length are often inaccurate; some species widely regarded as relatively long-legged actually have limb lengths near those expected for their body size. Interestingly, relative hind-limb length is not a significant predictor of distance moved daily, home-range area, or prey size. Phylogenetic ANCOVA results, however, indicate a relationship between prey-capture behaviour and relative hind-limb length. These findings suggest that the evolution of carnivoran limb length has been most influenced by selection for prey-capture behaviour. These results, coupled with those of other studies, can be used to suggest which performance variables could most fruitfully be studied in the laboratory to understand the selection of the structure of the mammalian limb. We suggest that relevant performance variables might be: maximum jump height and/or length, the ability to generate outforces, and levels of stress tolerance in limb bones during prey pursuit/capture. 相似文献
75.
Almitrine and doxapram decrease fatigue and increase subsequent recovery in isolated rat diaphragm 总被引:1,自引:0,他引:1
McGuire Michelle; Carey Michael F.; O'Connor John J. 《Journal of applied physiology》1997,83(1):52-58
McGuire, Michelle, Michael F. Carey, and John J. O'Connor.Almitrine and doxapram decrease fatigue and increase subsequent recovery in isolated rat diaphragm. J. Appl.Physiol. 83(1): 52-58, 1997.The effects ofalmitrine bimesylate and doxapram HCl on isometric force produced by invitro rat diaphragm were studied during direct muscle activation at37°C. Doxapram and almitrine ameliorate respiratory failureclinically by indirectly increasing phrenic nerve activity. This studywas carried out to investigate possible direct actions of these agentson the diaphragm before and after fatigue of the fibers. Two age groupsof animals were chosen [6-14 wk (group1) and 50-55 wk (group2)] because it is known that increasing agedecreases a muscle fiber's resistance to fatigue. Muscle strips wereisolated from both group 1 and group 2 and directly stimulated (2-mspulse duration, 5-15 V) to produce twitch tensions of 1.3 and 2.1 N/cm2, respectively. At lowconcentrations, doxapram (20 µg/ml) and almitrine (12 µg/ml)had no effect on twitch contraction or 100-Hz tetanic tension. However,40 µg/ml doxapram and 30 µg/ml almitrine increased twitch tensionby 9.0 ± 1.4 and 11.6 ± 1.9%, respectively, in animals ofgroup 2 (n = 5). A fatigue protocol consistingof low-frequency stimulation (30-Hz trains, 250-ms duration every 2 sfor 5 min) caused a reduction of twitch tension in animals ofgroup 1 (48 ± 4% ofcontrol) and group 2 (28 ± 4% ofcontrol). At 90 min postfatigue, the twitch tension recovered to 72 ± 3 and 42 ± 2% of control values ingroup 1 and group2, respectively. In the presence of doxapram (20 µg/ml), there was a significant increase in the recovery of twitchtension at 90 min in group 1 andgroup 2 (84.5 ± 3.2 and 80.1 ± 2.8%, respectively) compared with controls at 90 min postfatigue. Inthe presence of almitrine (12 µg/ml), there was a full recovery fromfatigue in group 1 animals (100% ofcontrol) and a recovery to 95.6 ± 2.1% of control ingroup 2 animals at 90 min. Theseresults demonstrate a significant improvement in the rapidity andmagnitude of recovery from fatigue in the rat diaphragm muscle in thepresence of both doxapram and, especially, almitrine. These effects maybe due to changes in intracellular calcium, ADP/ATP ratios, or oxygenfree radical scavenging. 相似文献
76.
Dr J. O. Lopes D. V. Pereira L. A. Streher A. A. Fenalte S. H. Alves J. P. Benevenga 《Mycopathologia》1995,130(2):89-92
A case of cutaneous zygomycosis caused byAbsidia coryabifera in a leukemic patient submitted to chemotherapy is reported. The lesion was located on the little finger of the right hand and probably resulted from a latent osteomyelitis. It progressed to form extensive necrotic area. No systemic infection was detected and the lesion did not appear to be associated with any trauma. 相似文献
77.
Ann-Charlotte E. Granholm Michelle L. Price Michael D. Owen 《Cell and tissue research》1995,280(1):49-57
We have investigated the distribution of tyrosine-hydroxylase-like immunoreactivity in the cerebral ganglia of the American cockroach, Periplaneta americana. Groups of tyrosine-hydroxylase-immunoreactive cell bodies occur in various parts of the three regions of the cerebral ganglia. In the protocerebrum, single large neurons or small groups of neurons are located in the lateral neuropil, adjacent to the calyces, and in the dorsal portion of the pars intercerebralis. Small scattered cell bodies are found in the outer layers of the optic lobe, and clusters of larger cell bodies can be found in the deutocerebrum, medial and lateral to the antennal glomeruli. Thick bundles of tyrosine-hydroxylase-positive nerve fibers traverse the neuropil in the proto- and deutocerebrum and innervate the glomerular and the nonglomerular neuropil with fine varicose terminals. Dense terminal patterns are present in the medulla and lobula of the optic lobe, the pars intercerebralis, the medial tritocerebrum, and the area surrounding the antennal glomeruli, the central body and the mushroom bodies. The pattern of tyrosine-hydroxylase-like immunoreactivity is similar to that previously described for catecholaminergic neurons, but it is distinctly different from the distribution of histaminergic and serotonergic neurons. 相似文献
78.
Carlos F. de Mello Diego D. De La Vega Leandro T. Pizutti Fabiane P. Lopes Maribel A. Rubin Jaime G. Homerich Dr. Carlos R. Melo Joana E. Somer Diogo O. Souza Moacir Wajner 《Neurochemical research》1995,20(12):1437-1441
The effect ofl-pyroglutamic acid, a metabolite that accumulates in pyroglutamic aciduria, on different neurochemical parameters was investigated in adult male Wistar rats. Glutamate binding, adenylate cyclase activity and G protein coupling to adenylate cyclase were assayed in the presence of the acid.l-pyroglutamic acid decreased Na+-dependent and Na+-independent glutamate binding Basal and GMP-PNP stimulated adenylate cyclase activity were not affected by the acid. Furthermore, rats received unilateral intrastriatal injections of 10–300 nmol of bufferedl-pyroglutamic acid. Vehicle (0.25 M Tris-Cl, pH 7.35–7.4) was injected into the contralateral striatum. Neurotoxic damage was assessed seven days after the injection by histological examination and by weighing both cerebral hemispheres. No difference in histology or weight could be identified between hemispheres. These results suggest that, although capable of interfering with glutamate binding, pyroglutamate did not cause a major lesion in the present model of neurotoxicity. 相似文献
79.
Marcela F. Lopes Vânia Lúcia C. Merquior JoséMauro Peralta Lúcia M. Teixeira 《FEMS immunology and medical microbiology》1995,12(3-4):205-211
Abstract Exosubstances (cohemolysins) produced by Streptococcus agalactiae (CAMP-factor) and Streptococcus uberis (Uberis-factor) showing hemolytic synergism with β-lysin produced by Staphylococcus aureus were compared. Cohemolytic activity was evaluated in the supernatants of bacterial cultures, before and after ammonium sulfate precipitation. Sheep erythrocytes sensitized with β-lysin were used as substrate. The assays were performed in microtiter plates and results were expressed as cohemolytic units/ml. Maximum cohemolytic activity was detected, respectively, after 8 h and 14 h of growth in Columbia broth in S. uberis and S. agalactiae cultures. Cohemolytic activities of both microorganisms showed similarities when submitted to various physical and chemical treatments. They were significantly decreased by heating at 60°C and 100°C, or in presence of trypsin, and were abolished in the presence of Tween 20. Activities were found to be stable in crude supernatants and concentrated preparations maintained at −20°C for 3 months. Differences were related to levels of activity and kinetics of detection during the growth cycle. The results indicate the proteic nature, at least in part, of the Uberis factor. Analysis by PAGE in the presence or absence of SDS allowed us to correlate Uberis activity with a protein band with apparent molecular mass of 42 kDa, while CAMP activity was associated with a protein band of 27 kDa. 相似文献
80.
A. van Rotterdam F. H. Lopes da Silva J. van den Ende M. A. Viergever A. J. Hermans 《Bulletin of mathematical biology》1982,44(2):283-305
A linear spatially distributed model of a chain of neurons and interneurons was investigated in relation to the generation
of propagated alpha rhythmic activity. It was assumed that the elements of the chain were interconnected by means of recurrent
collaterals and inhibitory fibres in such a way that the connectivity functions were assumed to be homogeneous and their strength
was an exponentially decreasing function of distance. It was found that such a neuronal chain shows propagation properties
for frequencies in the alpha band. The results obtained with the model are in agreement with the phase velocities encountered
experimentally. In this way, it was possible to estimate the length of the neural fibres responsible for the phenomenon of
propagated activity. The estimates obtained are in good agreement with recent quantitative neuroanatomical data on the circuitry
of the neocortex. 相似文献