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1.
《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1999,732(1):213-220
The formation of the hydroxyl free radical (HFR) can be quantified indirectly, by measuring two products of the hydroxylation of salicylic acid, 2,3-dihydroxybenzoate (2,3-DHB) and 2,5-dihydroxybenzoate (2,5-DHB). In this study, we used reversed-phase high-performance liquid chromatography with electrochemical (coulometric) detection to measure 2,3- and 2,5-DHB levels in human platelets. The limits of detection of the method were 10 and 5 fmol on column for 2,3-DHB and 2,5-DHB, respectively. We tested the technique by measuring increases in dihydroxybenzoate levels after exposure of platelets to experimentally induced oxidative stress. Then, we measured platelet levels of 2,3- and 2,5-DHB in patients with Parkinson’s disease, under therapy with l-DOPA, and in normal subjects. We also measured platelet concentrations of l-DOPA and its major metabolite, 3-O-methyldopa (3-OMD). Parkinsonian patients showed increased levels of both 2,3- and 2,5-DHB. Platelet levels of 2,3-DHB were positively correlated with platelet levels of l-DOPA and 3-OMD. The technique we describe proved simple and extremely sensitive and may represent a useful tool for the study of oxidative stress in humans. 相似文献
2.
Salicylate hydroxylation as an early marker of in vivo oxidative stress in diabetic patients. 总被引:2,自引:0,他引:2
A Ghiselli O Laurenti G De Mattia G Maiani A Ferro-Luzzi 《Free radical biology & medicine》1992,13(6):621-626
In vivo metabolism of salicylic acid produces two main hydroxylated derivatives (2,5- and 2,3-dihydroxybenzoic acid). The former can be produced by enzymatic pathways through the cytochrome P-450 system, while the latter is reported to be solely formed by direct hydroxyl radical attack. Therefore, measurement of 2,3-dihydroxybenzoate, following oral administration of salicylate in its acetylated form (aspirin), has been proposed for assessment of oxidative stress. In this article we report plasma levels of 2,3- and 2,5-dihydroxybenzoates following the administration of 1 g aspirin and plasma levels of thiobarbituric acid-reactive material (TBARM) in well-controlled diabetic patients and in healthy subjects. 2,3-Dihydroxybenzoate levels were significantly higher (23%) in diabetic patients than in controls (63.4 +/- 20.1 versus 49.0 +/- 6.8 nM; p < .05). On the other hand, TBARM values were not significantly different between groups. These results suggest that the method is useful to reveal in vivo oxidative stress independently from the peroxidation of lipids, and they support the hypothesis that oxygen radicals are involved in the pathogenesis of chronic complications of diabetes. 相似文献
3.
Maroof Husain Rakesh Shukla Madhu Dikshit Pradeep K. Maheshwari Devika Nag Rikhab C. Srimal Prahlad K. Seth Vinay K. Khanna 《Neurochemical research》2009,34(8):1427-1432
A case-control study was undertaken to investigate the status of platelet monoamine oxidase-B (MAO-B) activity in Indian cases
of idiopathic Parkinson’s disease. A significant increase in the activity of platelet MAO-B was observed in Parkinson’s cases
(n = 26) as compared to controls (n = 26). No significant change in the activity of the enzyme was observed while the data was analysed with respect to age,
sex and duration of disease. A trend of decrease in platelet MAO-B activity was observed in Parkinson’s cases with respect
to stage although the change was not significant. No correlation in platelet MAO-B activity was observed with respect to age
and sex in the control subjects. Parkinson’s cases treated with L-DOPA and MAO-B inhibitor exhibited decreased platelet MAO-B
activity as compared to drug naive cases and those treated with L-DOPA alone. Interestingly, Parkinson’s cases treated with
L-DOPA and amantadine also had lower platelet MAO-B activity as compared to drug naive cases and those treated with L-DOPA
alone. Activity of platelet MAO-B in Parkinson’s patients was increased in naive cases and those treated with L-DOPA alone
or in combination with other drugs compared to controls. The results of the present study indicate that phenotypic activity
of platelet MAO-B is high in Indian Parkinson’s cases. Further, action mechanism of drugs used in the treatment of Parkinson’s
disease could be understood by assay of platelet MAO-B activity. It is an interesting observation and may be looked further
in large number of cases. 相似文献
4.
U Bonuccelli A Nuti P Del Dotto P Piccini C Martini G Giannaccini A Lucacchini A Muratorio 《Life sciences》1991,48(12):1185-1190
Peripheral benzodiazepine (BDZ) receptors are located in a variety of tissues, including platelets, in the nuclear and/or mitochondrial membranes. We studied the density of peripheral BDZ receptors in platelets of 10 de novo Parkinson's disease (PD) patients, 18 PD patients treated with a levodopa/carbidopa combination, and in 15 healthy subjects matched for sex and age. The binding assay was conducted using [3H]PK 11195, a specific ligand for peripheral BDZ receptors. A significant decrease in the density of [3H]PK 11195 binding sites has been observed in PD patients with respect to controls (p less than 0.01), but not between de novo and treated PD patients. No correlation has been found between the decrease in density of [3H]PK 11195 binding sites in platelets and either the duration or severity of PD. Peripheral BDZ receptors are implicated in the regulation of mitochondrial respiratory function. Thus, their decrease in PD might parallel the abnormalities in mitochondrial function recently found in this neurologic disease. 相似文献
5.
Kim L.L. Habets Leendert A. Trouw E.W. Nivine Levarht Suzanne J.A. Korporaal Petra A.M. Habets Philip de Groot Tom W.J. Huizinga René E.M. Toes 《Arthritis research & therapy》2015,17(1)
IntroductionAlthough the role of platelets in rheumatoid arthritis (RA) is relatively unexplored, recent studies point towards a contribution of platelets in arthritis. We set out to determine platelet phenotype in RA and studied whether this could be influenced by the presence of anti-citrullinated protein antibodies (ACPA).MethodsPlatelets from healthy controls were incubated in the presence of plasma of patients with RA or age- and sex-matched healthy controls and plasma from ACPAneg or ACPApos patients or in the presence of plate-bound ACPA. Characteristics of platelets isolated from patients with RA were correlated to disease activity.ResultsPlatelets isolated from healthy controls displayed markers of platelet activation in the presence of plasma derived from RA patients, as determined by P-selectin expression, formation of aggregates and secretion of soluble CD40 ligand (sCD40L). Furthermore, levels of P-selectin expression and sCD40L release correlated with high ACPA titres. In accordance with these findings, enhanced platelet activation was observed after incubation with ACPApos plasma versus ACPAneg plasma. Pre-incubation of platelets with blocking antibodies directed against low-affinity immunoglobulin G receptor (FcγRIIa) completely inhibited the ACPA-mediated activation. In addition, expression of P-selectin measured as number of platelets correlated with Disease Activity Score in 44 joints, C-reactive protein level, ACPA status and ACPA level.ConclusionsWe show for the first time that ACPA can mediate an FcγRIIa-dependent activation of platelets. As ACPA can be detected several years before RA disease onset and activated platelets contribute to vascular permeability, these data implicate a possible role for ACPA-mediated activation of platelets in arthritis onset.
Electronic supplementary material
The online version of this article (doi:10.1186/s13075-015-0665-7) contains supplementary material, which is available to authorized users. 相似文献6.
《Redox report : communications in free radical research》2013,18(6):259-266
AbstractOver-expression of nitric oxide synthase (NOS) and nitric oxide (NO) formation are associated with the pathogenesis of liver cirrhosis. NO-related stress alters the functions of biomolecules, especially proteins, probably as a result of nitration. The aim of this study was to assess the level of protein nitration and its correlation with the severity of the disease. Liver cirrhosis patients with different grades of severity (grades A, B, and C according to the Child–Pugh classification) were enrolled in this study. Nitroprotein content, arginine, citrulline, NO in terms of total nitrite, nitrosothiol (RSNO) and protein carbonyls were measured in blood. Immunohistochemical detection of nitroprotein was carried out in liver sections of cirrhosis patients. A significant elevation in the levels of serum and platelet arginine, arginase, citrulline, plasma, and platelet nitroproteins, RSNO, total nitrite, protein carbonyls and also a significant amount of nitrated proteins by immunohistochemical detection in tissue were observed in cirrhosis patients. The alterations were highly significant in grade C patients with bleeding complications when compared to those of grade B and A patients. In platelets, both cytosolic and cytoskeletal proteins were found to be nitrated significantly. The level of nitrite seems to have positive correlation with the level of nitroproteins in different grades of cirrhosis. The level of nitroproteins in plasma, platelets and liver tissue can be correlated with the severity of liver cirrhosis. 相似文献
7.
D Raaz H Wallaschofski C Stumpf A Yilmaz I Cicha L Klinghammer W G Daniel T Lohmann C D Garlichs 《Hormones et métabolisme》2006,38(11):767-772
Prolactin and leptin are newly recognized platelet co-stimulators due to enhancement of ADP-induced platelet aggregation. The aim of our study was to assess whether both hormones prolactin and leptin play a role as co-activators of platelet activation in patients with acute coronary syndromes. Twenty-one patients with acute coronary syndromes, 10 with stable angina pectoris and 10 controls were studied. Patients with acute coronary syndromes showed significantly higher prolactin and leptin values and a significant increased P-selectin expression on platelets compared to patients with stable angina pectoris or controls. However, patients with acute myocardial infarction as a subgroup of acute coronary syndromes showed the highest prolactin levels as well as ADP stimulated P-selectin expression. In the myocardial infarction subgroup prolactin values showed a significant correlation to ADP stimulated P-selectin expression on platelets (r (2)=0.41; p=0.025), whereas leptin was not correlated. Our data indicate an association between increased prolactin values and enhanced P-selectin expression on platelets in patients with acute coronary syndromes. Therefore, the stress hormone prolactin could be a co-stimulator of platelet activation in these patients. In contrast, the putative platelet activator leptin does not seem to play a major role in acute coronary syndromes. 相似文献
8.
Zellner M Baureder M Rappold E Bugert P Kotzailias N Babeluk R Baumgartner R Attems J Gerner C Jellinger K Roth E Oehler R Umlauf E 《Journal of Proteomics》2012,75(7):2080-2092
Monoamine oxidase-B (Mao-B) catalysing the breakdown of the neurotransmitter dopamine, is known to be involved in the pathophysiology of Parkinson's (PD) and Alzheimer's disease (AD). Increased brain Mao-B activity is associated with AD. This alteration can also be seen in platelets, albeit the cause has hitherto remained elusive. To gain a deeper understanding of the etiology of AD, the platelet proteome was characterised, (2D DIGE pH6-9, including Mao-B) from 150 individuals: 34 AD, 13 vascular dementia, 15 non-demented PD patients, 49 matched controls, 18 oldest old and 21 young individuals. One significant change was noted after applying false discovery rate with the upregulation of the Mao-B expression (30% adjusted P value<0.001; effect size 1.31) in AD compared to age- and sex-matched controls. In contrast, Mao-B levels were unchanged in PD to matched controls. Western blot and mRNA analyses verified these findings. Moreover, Mao-B concentration correlated with age in the cognitive healthy individuals (r=0.53; P<0.001) and PD patients but not in those suffering from AD (r=-0.03; P=0.874). Mao-B activity correlated with the increased Mao-B protein expression in AD (r=0.81; P=0.016). We suggest that Mao-B platelet protein level may serve as a biomarker for age-related dementia, especially AD. 相似文献
9.
Aromatic hydroxylation as a potential measure of hydroxyl-radical formation in vivo. Identification of hydroxylated derivatives of salicylate in human body fluids. 总被引:8,自引:1,他引:8
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Attack by .OH radicals, generated by a Fenton system, upon salicylate produces 2,3-dihydroxybenzoate and 2,5-dihydroxybenzoate as major products and catechol as a minor product. H.p.l.c. separation combined with electrochemical detection was used to identify and quantify 2,3-dihydroxybenzoate and 2,5-dihydroxybenzoate in human plasma and synovial fluid. We propose that conversion of salicylate into 2,3-dihydroxybenzoate, or of other aromatic compounds into specific hydroxylated products, may be a useful assay for .OH formation in the human body. 相似文献
10.
Kathrin R. Sidell † Sandra J. Olson Joyce J. Ou § Yueli Zhang Ventkataraman Amarnath Thomas J. Montine†‡§ 《Journal of neurochemistry》2001,79(3):510-521
Recent results have suggested that some products of mercapturic acid pathway (MAP) metabolism of oxidized dopamine (DA) may contribute to mesostriatal dopaminergic neurodegeneration, and that at least one product, 5-S-cysteinyldopamine (Cys-DA), is elevated in patients with advanced Parkinson's disease (PD) who have been treated with L-DOPA. Here we investigated MAP enzymes and products in the midbrain and striatum of control individuals and patients with dementia with Lewy bodies (DLB) who had less severe dopaminergic degeneration than PD patients and who were not treated with L-DOPA. We also determined the biological activity of MAP metabolites of oxidized DA using primary rat mesencephalic cultures, rat cerebral synaptosomes, and rat striatum in vivo microdialysis. Our results showed that the human mesostriatal dopaminergic pathway generates Cys-DA but has limited enzymatic capacity for mercapturate formation, that striatal levels of MAP products of oxidized DA are not elevated in DLB patients compared with controls, and that Cys-DA interferes with trafficking of DA in vitro and in vivo. These results indicate that while Cys-DA is not increased in striatum of patients with mild dopaminergic neurodegeneration, it may interfere with uptake of DA in patients with advanced PD. 相似文献
11.
This study delineates the role of peroxiredoxin 3 (Prx3) in hair cell death induced by several etiologies of acquired hearing loss (noise trauma, aminoglycoside treatment, age). In vivo, Prx3 transiently increased in mouse cochlear hair cells after traumatic noise exposure, kanamycin treatment, or with progressing age before any cell loss occurred; when Prx3 declined, hair cell loss began. Maintenance of high Prx3 levels via treatment with the radical scavenger 2,3-dihydroxybenzoate prevented kanamycin-induced hair cell death. Conversely, reducing Prx3 levels with Prx3 siRNA increased the severity of noise-induced trauma. In mouse organ of Corti explants, reactive oxygen species and levels of Prx3 mRNA and protein increased concomitantly at early times of drug challenge. When Prx3 levels declined after prolonged treatment, hair cells began to die. The radical scavenger p-phenylenediamine maintained Prx3 levels and attenuated gentamicin-induced hair cell death. Our results suggest that Prx3 is up-regulated in response to oxidative stress and that maintenance of Prx3 levels in hair cells is a critical factor in their susceptibility to acquired hearing loss. 相似文献
12.
Acne vulgaris is one of the common dermatological diseases and its pathogenesis is multifactorial. In this study, we aim to determine the effects of oxidative stress in acne vulgaris. Forty-three consecutive acne patients and 46 controls were enrolled. The parameters of oxidative stress such as catalase (CAT), glucose-6-phosphate dehydrogenase (G6PD), superoxide dismutase (SOD), and malondialdehyde (MDA) in the venous blood of cases were measured spectrophotometrically. The values compared with control group, the relation between the severity and distribution of acne, and the correlation of each enzyme level were researched. CAT and G6PD levels in patients were found to be statistically decreased, and SOD and MDA levels were found to be statistically increased (P < .001). However, any statistical difference and correlation could not be found between the severity and distribution of lesions and the mean levels of enzymes. In addition, we found that each enzyme is correlated with one another. Our findings show that oxidative stress exists in the acne patients. It will be useful to apply at least one antioxidant featured drug along with the combined acne treatment. 相似文献
13.
Shane P. Comer Sarah Cullivan Paulina B. Szklanna Luisa Weiss Steven Cullen Sarah Kelliher Albert Smolenski Claire Murphy Haidar Altaie John Curran Katherine OReilly Aoife G. Cotter Brian Marsh Sean Gaine Patrick Mallon Brian McCullagh Niamh Moran Fionnuala Ní inle Barry Kevane Patricia B. Maguire On behalf of the COCOON Study investigators 《PLoS biology》2021,19(2)
Coronavirus Disease 2019 (COVID-19), caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has affected over 30 million globally to date. Although high rates of venous thromboembolism and evidence of COVID-19-induced endothelial dysfunction have been reported, the precise aetiology of the increased thrombotic risk associated with COVID-19 infection remains to be fully elucidated. Therefore, we assessed clinical platelet parameters and circulating platelet activity in patients with severe and nonsevere COVID-19. An assessment of clinical blood parameters in patients with severe COVID-19 disease (requiring intensive care), patients with nonsevere disease (not requiring intensive care), general medical in-patients without COVID-19, and healthy donors was undertaken. Platelet function and activity were also assessed by secretion and specific marker analysis. We demonstrated that routine clinical blood parameters including increased mean platelet volume (MPV) and decreased platelet:neutrophil ratio are associated with disease severity in COVID-19 upon hospitalisation and intensive care unit (ICU) admission. Strikingly, agonist-induced ADP release was 30- to 90-fold higher in COVID-19 patients compared with hospitalised controls and circulating levels of platelet factor 4 (PF4), soluble P-selectin (sP-selectin), and thrombopoietin (TPO) were also significantly elevated in COVID-19. This study shows that distinct differences exist in routine full blood count and other clinical laboratory parameters between patients with severe and nonsevere COVID-19. Moreover, we have determined all COVID-19 patients possess hyperactive circulating platelets. These data suggest abnormal platelet reactivity may contribute to hypercoagulability in COVID-19 and confirms the role that platelets/clotting has in determining the severity of the disease and the complexity of the recovery path.The reason for the increased thrombotic risk associated with SARS-CoV-2 infection remains unclear. This study reveals that disease severity is associated with increased mean platelet volume and decreased platelet:neutrophil ratio; moreover, all COVID-19 patients possess hyperactive circulating platelets, with agonist-induced ADP release 30-to-90 fold higher than controls. 相似文献
14.
Calcium, copper, iron, magnesium, silicon and zinc content of hair in Parkinson's disease. 总被引:1,自引:0,他引:1
Giovanni Forte Alessandro Alimonti Nicola Violante Marco Di Gregorio Oreste Senofonte Francesco Petrucci Giuseppe Sancesario Beatrice Bocca 《Journal of trace elements in medicine and biology》2005,19(2-3):195-201
The aetiology of Parkinson's disease (PD) is still unknown, but some hypotheses have focused on the imbalances in body levels of metals as co-factors of risk. To assess whether hair could be a reliable marker of possible changes, calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), silicon (Si) and zinc (Zn) were determined in hair from 81 patients affected by PD and 17 age-matched controls. Care was taken to eliminate external contamination of the hair by thorough washing. Digestion of the matrix was achieved by an acid-assisted microwave procedure. Quantification of the elements was performed by inductively coupled plasma atomic emission spectrometry. Results indicated significantly lower levels of Fe in the hair of patients (p=0.018) compared with controls. Ca and Mg levels were slightly lower while Zn levels were higher in patients, although these differences were not significant; neither were variations in Cu and Si. Ca and Mg were at least 1.5 times higher in females than in males in both controls and patients. In addition, Ca correlated positively with Mg in both groups and in both sexes (p-value always less than 0.03), and negatively with age in patients (p<0.01). Finally, element levels did not correlate with either the duration or the severity of the disease or with anti-Parkinson treatment. 相似文献
15.
L-DOPA does not enhance hydroxyl radical formation in the nigrostriatal dopamine system of rats with a unilateral 6-hydroxydopamine lesion 总被引:4,自引:0,他引:4
The debate about the toxicity of L-DOPA to dopaminergic neurons has not been resolved. Even though enzymatic and nonenzymatic metabolism of L-DOPA can produce hydrogen peroxide and oxygen free radicals, there has been controversy as to whether L-DOPA generates an oxidant stress in vivo. This study determined whether acute or repeated administration of L-DOPA caused in vivo production of hydroxyl radicals in striatum and other brain regions in rats with a unilateral 6-hydroxydopamine lesion of the dopaminergic nigrostriatal projections. Salicylate trapping combined with in vivo microdialysis provided measurements of extracellular 2,3-dihydroxybenzoic acid (2,3-DHBA) in striatum following L-DOPA administration systemically (100 mg/kg, i.p.) or by intrastriatal perfusion (1 mM, via the microdialysis probe). Tissue concentrations of 2,3-DHBA and salicylate were also measured in striatum, ventral midbrain, and cerebellum following repeated administration of L-DOPA (50 mg/kg, i.p., once daily for 16 days). In each instance, treatment with L-DOPA did not increase 2,3-DHBA concentrations, regardless of the nigrostriatal dopamine system's integrity. When added to the microdialysis perfusion medium, L-DOPA resulted in a significant decrease in the striatal extracellular concentration of 2,3-DHBA. These results suggest that administration of L-DOPA, even at high doses, does not induce hydroxyl radical formation in vivo and under some conditions may actually diminish hydroxyl radical activity. Furthermore, prior damage to the nigrostriatal dopamine system does not appear to predispose surviving dopaminergic neurons to increased hydroxyl radical formation following L-DOPA administration. Unlike L-DOPA, systemic administration of methamphetamine (10 mg/kg, s.c.) produced a significant increase in the concentration of 2,3-DHBA in striatal dialysate, suggesting that increased formation of hydroxyl radicals may contribute to methamphetamine neurotoxicity. 相似文献
16.
D P Mikhailidis V Fonseca M A Barradas R A Hutton J Y Jeremy O Epstein N McIntyre P Dandona 《Prostaglandins, leukotrienes, and essential fatty acids》1988,31(3):131-138
Platelet function was assessed in 28 patients with primary biliary cirrhosis (PBC), of whom 10 were receiving D-penicillamine. Patients not on D-penicillamine treatment had platelet aggregation similar to that in the healthy control group; the group treated with D-penicillamine showed significantly enhanced platelet aggregation in response to threshold doses of adrenaline and collagen but not ADP. Median thromboxane B2 production was also higher in D-penicillamine treated patients than in controls or untreated patients; this difference did not reach statistical significance. The addition of D-penicillamine in vitro to platelet rich plasma from normal subjects was shown to enhance adrenaline- and collagen-induced platelet aggregation. Abnormalities of platelet function in PBC patients did not correlate with serum cholesterol concentration or with liver function tests but were related to the stage of disease. The present study emphasises the need to consider the aetiology, disease stage and type of treatment when assessing platelet function and prostanoid release in liver disease. 相似文献
17.
《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1995,664(1):247-252
Based on a detailed study of retention parameters, reversed-phase ion-pair chromatographic methods were developed for the simultaneous determination of dihydrocybenzoates, indicators of in-vivo hydroxyl free radical formation, transmitter amines and some metabolites to facilitate neurochemical investigations in rodent brain. Coupling of the separation methods with electrochemical detection and the use of short-chain perfluorinated carboxylic acids for ion-pairing, allowed for a fast and sensitive determination of salicylate-derived 2,3- and 2,5-dihydroxybenzoic acids and the major electroactive, hydroxylated aromatic compounds present in brain samples. Detection limits for the dihydroxybenzoates (signal-to-noise ratio = 2) were 18–22 fmol injected on the column. Basal levels of 2,3-dihydroxybenzoate and 2,5-dihydroxybenzoate in the striatum of mice treated with salicylate were 72±13 and 94±11 ng/g wet tissue, respectively. 相似文献
18.
Parkinson's disease (PD) is a degenerative neurological disorder. Recent studies have demonstrated reduced activity of complex I of the electron transport chain in brain and platelets from patients with PD. Platelet mitochondria from parkinsonian patients were found to have lower levels of coenzyme Q10 (CoQ10) than mitochondria from age/sex-matched controls. There was a strong correlation between the levels of CoQ10 and the activities of complexes I and II/III. Oral CoQ10 was found to protect the nigrostriatal dopaminergic system in one-year-old mice treated with MPTP, a toxin injurious to the nigrostriatal dopaminergic system. We further found that oral CoQ10 was well absorbed in parkinsonian patients and caused a trend toward increased complex I activity. These data suggest that CoQ10 may play a role in cellular dysfunction found in PD and may be a potential protective agent for parkinsonian patients. 相似文献
19.
Analysis of Erythrocyte and Platelet Membrane Proteins in Various Forms of β-Thalassemia 总被引:1,自引:0,他引:1
Major membrane proteins have been quantitatively analyzed in erythrocytes and platelets from patients with homozygous (splenectomized and non-splenectomized) and heterozygous forms of beta-thalassemia depending on severity of clinical manifestation of this disease. Quantitative analysis of erythrocyte membrane proteins revealed increase in alpha- and beta-spectrin. (In non-splenectomized patients with homozygous beta-thalassemia the amount of this protein was lower than in corresponding controls.) Besides spectrin, the increase of 2.1-2.3 fractions of ankyrin, and the decrease of band 3 protein (anion-transport protein), 4.1, palladin, and glyceraldehyde-3-phosphate dehydrogenase were also found. Analysis of major platelet membrane proteins revealed significant increase in gelsolin. This increase was found in all forms of beta-thalassemia irrespective of gender. Significant changes in platelet membrane protein fractions were found in patients (especially non-splenectomized) with homozygous beta-thalassemia. These included significant decrease in myosin, profilin, and gamma-actin and increase in actin-binding protein in both male and female patients. The content of other protein fractions (alpha-actinin, tubulin, tropomyosin) remained unchanged. Changes in protein fractions of erythrocytes and platelets correlated with severity of clinical manifestation of the disease. 相似文献
20.
Dopaminergic denervation enhances susceptibility to hydroxyl radicals in rat neostriatum 总被引:2,自引:0,他引:2
To determine if greater amounts of hydroxyl radical (*OH) are formed by dopamine (DA) denervation and treatment with L-dihydroxyphenylalanine (L-DOPA), the neostriatum was DA denervated (99% reduction in DA content) by 6-hydroxydopamine treatment (134microg icv, desipramine pretreatment) of neonatal rats. At 10 weeks the peripherally restricted dopa decarboxylase inhibitor carbidopa (12.5mg/kg i.p.) was administered 30min before vehicle, L-DOPA (60mg/kg i.p.), or the known generator of reactive oxygen species, 6-hydroxydopa (6-OHDOPA) (60mg/kg i.p.); and this was followed 30min later (and 15 min before termination) by the spin trap, salicylic acid (8micromoles icv). By means of a high performance liquid chromatographic method with electrochemical detection, we found a 4-fold increase in the non-enzymatically formed spin trap product, 2,3-dihydroxybenzoic acid (2,3-DHBA), with neither L-DOPA nor 6-OHDOPA having an effect on 2,3-DHBA content of the neostriatum. Basal content of 2,5-DHBA, the enzymatically formed spin trap product, was 4-fold higher vs. 2,3-DHBA in the neostriatum of untreated rats, while L-DOPA and 6-OHDOPA each reduced formation of 2,5-DHBA. We conclude that DA innervation normally suppresses *OH formation, and that the antiparkinsonian drug L-DOPA has no effect (2,3-DHBA) or slightly reduces (2,5-DHBA) *OH formation in the neostriatum, probably by virtue of its bathing the system of newly formed *OH. 相似文献