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1.
—Male rats of the Sprague-Dawley strain (80–250 g body wt) were fed either an adequate protein diet (18% lactalbumin) or a protein-deficient diet (0.5% lactalbumin). After 5–8 weeks of receiving the low protein diet, some of the malnourished rats were rehabilitated with an adequate protein diet. The malnourished rats exhibited significant elevations in brain levels of histidine (+415%) and homocarnosine (+100%) in comparison to findings in the control animals of similar age. Associated with the elevated brain levels of histidine in malnutrition was a prominent increase in brain content of histamine (+ 150-+ 238%). The mean brain histamine levels (ng/g) in the control rats varied from 45.96 to 56.15 in several experiments. In the protein-deficient rats, values ranged from 115 to 190. Refeeding the malnourished rats with adequate protein diet elicited reversal of histidine and histamine levels to near normal values within 1 week. The increased brain content of histamine in malnutrition was attributed to enhanced rate of production resulting from increased availability of the precursor amino acid, a conclusion consistent with elevation also of the brain content of homocarnosine (γ-aminobutyryl-l -histidine) which is another major route of disposal of histidine in the brain. The relevance of these neurochemical alterations to the behavioural changes often associated with protein malnutrition, deserves some intensive examination.  相似文献   

2.
Abstract: Male infant nonhuman primates (M. nemes-trina) born in captivity were used in the study. They were divided into three groups. The first group of three animals was fed a 20% casein diet and the second group of six monkeys received a 2.0% casein diet. The third group of four monkeys received a 20% casein diet totally devoid of ascorbic acid for 3.5 weeks before the diet was supplemented with ascorbic acid (20 mg/kg diet). All the diets were given to the animals in two daily rations of 100 g/animal. The monkeys fed a 2% casein diet failed to grow, and after about 3.5 months showed variable degrees of edema, hypoalbuminemia, evidence of psychomotor disturbance, depressed plasma levels of many essential amino acids, and other features consistent with the diagnosis of protein-energy malnutrition. Examination of the brains revealed significant alterations in the levels of histidine (+ 172%) and homocarnosine (+ 146%) in comparison with the control well-fed monkeys. Associated with the increase in brain histidine was a marked elevation of brain histamine level. Protein deficiency also led to poor brain retention of ascorbic acid but not to the same degree observed in the ascorbic acid-deficient animals. The latter group of animals, after receiving their diet for about 8 months, demonstrated a modest elevation in the plasma levels of most amino acids in comparison with controls. Ascorbic acid deficiency elicited a significant reduction (p < 0.01) in brain level of histidine, with hardly any change in homocarnosine level. In addition, vitamin C deficiency produced elevation of brain histamine level comparable to findings in the protein-energy-deficient monkeys. The results suggested that protein deficiency raised brain histamine level mainly through increased availability of the precursor amino acid histidine, while defective degradation might account for the increased brain level of this amine in ascorbic acid-deficient monkeys. Histamine has been proposed to have a predominantly depressant action on relevant neurons, and has also been shown to participate with other neuro-transmitters in influencing the function of the pituitary gland by regulating release of the hypothalamic hormones into the portal vessels. The relevance of the findings of marked increases in brain histamine in experimental protein and ascorbic acid deficiencies to the behavioral and extensive endocrinological alterations seen in human malnutrition deserves some intensive investigation.  相似文献   

3.
—Eight male monkeys (Macaca nemestrina) aged 6–9 months were divided into two groups and fed either an adequate protein diet (20% casein) or a protein deficient diet (2% casein). After 3- 5 months of receiving the low protein diet, the malnourished monkeys showed extensive fatty metamorphosis of the liver cells, distorted patterns of plasma and hepatic free amino acid pools, and other features consistent with the diagnosis of protein-calorie malnutrition. Examination of the cerebrum, cerebellum and brain stem in the malnourished animals revealed profound accumulation of 3-methylhistidine, histidine and homocarnosine in all three regions. For histidine, the cerebral, cerebellar and brain stem levels in the protein deficient animals increased by 145, 104 and 101 per cent over levels observed in corresponding regions of the brain in well-fed monkeys. Similarly, there were significant elevations in homocarnosine contents of the cerebrum (+ 99 per cent), cerebellum (+ 140 per cent) and brain stem (+ 146 per cent) in comparison to levels in control animals. In contrast, the levels of valine, serine and aspartic acid were markedly reduced in all three brain areas in the malnourished animals. Protein-calorie deficiency also produced reductions in the brain levels of taurine, glutamic acid, isoleucine, leucine and threonine which varied in magnitude in the three major regions of the brain examined. These biochemical alterations which may in part underlie some of the psychomotor changes often observed in protein-calorie malnutrition, were discussed not only in relation to the role of amino acids as precursors for the synthesis of neuroregulatory substances but also with due regard to the possibility that some of these ninhydrin-positive substances such as GABA, homocarnosine, glycine and the dicarboxylic amino acids may possess neuroexcitatory or inhibitory properties in various parts of the central nervous system.  相似文献   

4.
Abstract— Seventeen monkeys (M. nemestrina and M. fascicularis) aged 10 months to about 5 yr were divided into two groups and fed either an adequate protein diet (20% casein) or a low-protein diet (2% casein). The diets were supplied to the animals in restricted amount (200 g/animal in two daily rations). In one experiment, the malnourished animals were initially fed a diet containiing 8 per cent protein and the protein content of the diet was gradually reduced over a period of 9 months, to 2 per cent. After about 3 months on the 2 per cent protein diet, the malnourished monkeys showed growth failure, severe anorexia, peri-ocular oedema, tremors of the head and limbs, atrophy of several visceral organs, fatty liver, hypoalbuminaemia, and depressed serum levels of many essential amino acids with an elevation of the ratio of non-essential to essential amino acids. These features are consistent with protein-calorie malnutrition. Examination of the brains revealed significant alterations in the levels of glycerophosphoethanolamine (—40 per cent), glutamic acid (—25 per cent), histidine (+230 per cent), homocamosine (+185 per cent), 3-methyl-histidine (+147 per cent), lysine (+55 per cent), phenylalanine (+33 per cent) and tyrosine (+26 per cent) in comparison to findings on the well-fed monkeys. The possible implications of elevated cerebral contents of homocarnosine in malnourished monkeys are discussed in the light of several reported human cases in whom neurological disorders are associated with increased histidine-containing dipeptides in the brain, CSF, blood and urine.  相似文献   

5.
Abstract: Levels of histamine and its major metabolites in brain, tele -methylhistamine (t-MH) and tele -methylimidazoleacetic acid (t-MIAA), were measured in rat brains up to 12 h after intraperitoneal administration of l -histidine (His), the precursor of histamine. Compared with saline-treated controls, mean levels of histamine were elevated at 1 h (+ 102%) after a 500 mg/kg dose; levels of t-MH did not increase. Following a 1,000 mg/kg dose; levels mean histamine levels were increased for up to 7 h, peaked at 3 h, and returned to control levels within 12 h. In contrast, levels of t-MH showed a small increase only after 3 h; levels of t-MIAA remained unchanged after either dose. Failure of most newly formed histamine to undergo methylation, its major route of metabolism in brain, suggested that histamine was metabolized by another mechanism possibly following nonspecific decarboxylation. To test this hypothesis, other rats were injected with α-fluoromethylhistidine (α-FMHis; 75 mg/kg, i.p.), an irreversible inhibitor of specific histidine decarboxylase. Six hours after rats received α-FMHis, the mean brain histamine level was reduced 30% compared with saline-treated controls. Rats given His (1,000 mg/kg) 3 h after α-FMHis (75 mg/kg) and examined 3 h later had a higher (+112%) mean level of histamine than rats given α-FMHis, followed by saline. Levels of t-MH and t-MIAA did not increase. These results imply that high doses of His distort the simple precursor-product relationship between histamine and its methylated metabolites in brain. The possibility that some His may undergo nonspecific decarboxylation in brain after His loading is discussed. These findings, and other actions of His independent of histamine, raise questions about the validity of using His loading as a specific probe of brain histaminergic function.  相似文献   

6.
The intracerebroventricular administration of compound 48/80 or polymixin B to rats 0 to 60 days old, produced a decrease both in the histamine which sediments in the crude nuclear fraction, as well as in the number of mast cells in the brain. In contrast, the histamine-releasers did not affect histamine levels in subcellular fractions where neuronal histamine is found. Once released, histamine disappeared rapidly (t 1/2 = 3.8 min). In untreated animals and in those treated with histamine releasers, the number of mast cells/g in the whole brains of developing rats and in the cerebral regions of adult rats showed a close correlation with the histamine levels in the crude nuclear fraction. The content of histamine per mast cell in adult rat brain was estimated to be about 13 pg/cell. Histologic examination of the subcellular fractions revealed the presence of intact mast cells in the crude nuclear fraction obtained from untreated animals, and of degranulated mast cells in the same fraction obtained from animals treated with histamine releasers. The mast cell contribution to adult rat brain histamine levels was about 22%. Our results strongly support that most of the histamine which sediments in the crude nuclear fraction of the rat brain is located in mast cells. Determination of histamine in the crude nuclear fraction and in the supernatant of this fraction is proposed as an easy way for identifying the cellular pool altered by any treatment affecting brain histamine levels.  相似文献   

7.
Histamine content and diamine oxidase activity in rat brain under hyperbaric oxygenation have been studied. Under 0,3 MPa histamine level decreases in brain of more sensitive rats, but it does not change in brain of more resistant animals in comparison with the control ones. High oxygen pressure (0,7 MPa) causes a significant increase of histamine concentration. Diamine oxidase activity decreases under hyperoxia. Under the consequent action of high and low pressure (0,3 MPa during 1 h and 0,7 MPa) convulsions in rats begin later and alterations of histamine content in brain are less than under 0,7 MPa oxygen action only. The role of histamine at compensate reaction and cause of increasing resistance of animals to hyperoxia are discussed.  相似文献   

8.
Newly-weaned male guinea pigs were fed an ascorbic acid-deficient diet ad libitum and compared with control animals pair-fed an adequate diet for a similar duration. The ascorbic acid-deficient animals demonstrated prominent elevations in serum concentrations of tyrosine (+427%), phenylalanine (+36%) and arginine (+21 %) with concomitant depressions in levels of glycine (–57 %), histidine (–39 %), ethanolamine (–38%) and glutamic acid (–22 %). With few exceptions, the alterations in the liver amino acid profiles were in the same directions as those observed in the serum. The scorbutic brains showed 28–36 per cent of the retention of total ascorbic acid found in control animals and were characterized by marked elevation (+83%) in tyrosine content, hardly any alteration in phenylalanine (–9%), and depressed levels of histidine (–33 %), arginine (–25%), phosphoserine (–50%) and GABA (–12%). The implications of such abnormal changes in free amino acid patterns were evaluated in the light of the role of some of these amino acids as precursors for the synthesis of neuroregulatory substances. No difference was observed in the brain polysomal profiles as isolated from the two groups of animals. Incubation of polysomes from ascorbic acid-deficient brains with autologous pH 5 enzyme derived from cell sap not passed through Sephadex G-25 revealed low uptake of [14C]phenylalanine in comparison to that for a similar system from control animals. Use of pH 5 enzymes prepared from Sephadex-treated and dialysed cell saps eliminated the difference in specific activities of the two groups of ribosomes, an observation suggesting that ascorbic acid deficiency either intensified the activity of the inhibitory components or reduced the low molecular weight stimulatory substances present under normal conditions in the brain postmicrosomal fraction.  相似文献   

9.
In the brains of W/Wv mutant mice that have no mast cells, the histidine decarboxylase (HDC) level is as high as in the brain of congenic normal mice (+/+), but the histamine content is 53% of that of +/+ mice. The effects of alpha-fluoromethylhistidine (alpha-FMH) on the HDC activity and histamine content of the brain of W/Wv and +/+ mice were examined. In both strains, 30 min after i.p. injection of alpha-FMH the HDC activity of the brain had decreased to 10% of that in untreated mice. The histamine content decreased more gradually, and after 6 h about half of the control level remained in +/+ mice, whereas histamine had disappeared almost completely in W/Wv mice. It is concluded that the portion of the histamine content that was depleted by HDC inhibitor in a short time is derived from non-mast cells, probably neural cells. The half-life of histamine in the brain of W/Wv mice was estimated from the time-dependent decrease in the histamine content of the brain after administration of alpha-FMH: 48 min in the forebrain, 103 min in the midbrain, and 66 min in the hindbrain.  相似文献   

10.
Fatty acids play a critical role in brain function but their specific role in the pathophysiology of Parkinson disease (PD) and levodopa-induced motor complications is still unknown. From a therapeutic standpoint, it is important to determine the relation between brain fatty acids and PD because the brain fatty acid content depends on nutritional intake, a readily manipulable environmental factor. Here, we report a postmortem analysis of fatty acid profile by gas chromatography in the brain cortex of human patients (12 PD patients and nine Controls) as well as in the brain cortex of monkeys (four controls, five drug-naive MPTP monkeys and seven levodopa-treated MPTP monkeys). Brain fatty acid profile of cerebral cortex tissue was similar between PD patients and Controls and was not correlated with age of death, delay to autopsy or brain pH. Levodopa administration in MPTP monkeys increased arachidonic acid content (+7%; P < 0 .05) but decreased docosahexaenoic acid concentration (-15%; P < 0.05) and total n-3:n-6 polyunsaturated fatty acids ratio (-27%; P < 0.01) compared to drug-naive MPTP animals. Interestingly, PD patients who experienced motor complications to levodopa had higher arachidonic acid concentrations in the cortex compared to Controls (+13.6%; P < 0.05) and to levodopa-treated PD patients devoid of motor complications (+14.4%; P < 0.05). Furthermore, PD patients who took an above-median cumulative dose of levodopa had a higher relative amount of saturated fatty acids but lower monounsaturated fatty acids in their brain cortex (P < 0.01). These results suggest that changes in brain fatty acid relative concentrations are associated with levodopa treatment in PD patients and in a non-human primate model of parkinsonism.  相似文献   

11.
Abstract: The mast cell-deficient [ Ws/Ws ( W hite spotting in the skin)] rat was investigated with regard to the origin of histamine in the brain. No mast cells were detected in the pia mater and the perivascular region of the thalamus of Ws/Ws rats by Alcian Blue staining. The histamine contents and histidine decarboxylase (HDC) activities of various brain regions of Ws/Ws rats were similar to those of +/+ rats except the histamine contents of the cerebral cortex and cerebellum. As the cerebral cortex and cerebellum have meninges that are difficult to remove completely, the histamine contents of these two regions may be different between Ws/Ws and +/+ rats. We assume that the histamine content of whole brain with meninges in Ws/Ws rats is <60% of that in +/+ rats. So we conclude that approximately half of the histamine content of rat brain is derived from mast cells. Next, the effects of ( S )α-fluoromethylhistidine (FMH), a specific inhibitor of HDC, on the histamine contents and HDC activities of various regions of the brain were examined in Ws/Ws rats. In the whole brain of Ws/Ws rats, 51 and 37% of the histamine content of the control group remained 2 and 6 h, respectively, after FMH administration (100 mg/kg of body weight). Therefore, we suggest that there might be other histamine pools including histaminergic neurons in rat brain.  相似文献   

12.
Hypocholesteremic and antioxidant effects of Withania somnifera (WS) Dunal (Solanaceae) were investigated in hypercholesteremic male albino rats. When the root powder of WS was added to the diet at 0.75 and 1.5 gm/rat/day, hypercholesteremic animals registered significant decreases in total lipids (-40.54%; -50.69%), cholesterol (-41.58%; -53.01%) and triglycerides (-31.25%; - 44.85%) in plasma. On the other hand, significant increases in plasma HDL-cholesterol levels (+15.10%; +17.71%), HMG-CoA reductase activity (+19.51%; +26.02%) and bile acid content (+24.64%; +30.52%) of liver were noted in these animals. A similar trend was also noted in bile acid (+22.43%;+28.52%), cholesterol (+14.21%; +17.68%) and neutral sterol (+12.40%; +18.85%) excretion in the hypercholesteremic animals with WS administration. Further, a significant decrease in lipid-peroxidation (-35.29%; -36.52%) occurred in WS administered hypercholesteremic animals when compared to their normal counterparts. However, it appeared that WS root powder is also effective in normal subjects for decreasing lipid profiles.  相似文献   

13.
Earlier we showed that chronic administration of engineered nanoparticles (NPs) from metals, e.g., Cu, Ag, or Al (50–60 nm, 50 mg/kg, i.p. daily for 1 week) alter blood–brain barrier (BBB) disruption and induce brain pathology in adult rats (age 18 to 22 weeks). However, effects of size-dependent neurotoxicity of NPs in vivo are still largely unknown. In present investigation, we examined the effects of different size ranges of the above-engineered NPs on brain pathology in rats. Furthermore, the fact that age is also an important factor in brain pathology was also investigated in our rat model. Our results showed that small-sized NPs induced the most pronounced BBB breakdown (EBA +480 to 680 %; radioiodine +850 to 1025 %), brain edema formation (+4 to 6 %) and neuronal injuries (+30 to 40 %), glial fibrillary acidic protein upregulation (+40 to 56 % increase), and myelin vesiculation (+30 to 35 % damage) in young animals as compared to controls. Interestingly, the oldest animals (30 to 35 weeks of age) also showed massive brain pathology as compared to young adults (18 to 20 weeks old). The Ag and Cu exhibited greater brain damage compared with Al NPs in all age groups regardless of their size. This suggests that apart from the size, the composition of NPs is also important in neurotoxicity. The very young and elderly age groups exhibited greater neurotoxicity to NPs suggests that children and elderly are more vulnerable to NPs-induced brain damage. The NPs-induced brain damage correlated well with the upregulation of neuronal nitric oxide synthase activity in the brain indicating that NPs-induced neurotoxicity may be mediated via increased production of nitric oxide, not reported earlier.  相似文献   

14.
Mothers' nutrition during lactation programs growth in their offspring. We studied the contribution of the growth hormone (GH) for this programming, evaluating GH mRNA expression. Lactating dams were grouped as follows: C, control diet with 23% protein; PR, 8% protein-restricted diet; and ER, energy-restricted diet, receiving the control diet in restricted quantities of the PR group's ingestion. Some pups were killed at weaning; the others received the control diet until they were sacrificed as adults. Pituitary GH mRNA was analyzed by Northern blot analysis. At weaning, the ER and PR animals had lower GH mRNA levels (-29% and -18%, respectively) and lower length as well as body weight. Ninety-day-old PR offspring showed a lower body length (-5%), whereas ER offspring showed a higher one (+5%); however, at 180 days, the lengths were not different. Both 90- and 180-day-old animals showed body weight differences against control animals, with PR offspring showing a lower (-10%) and ER offspring showing a higher (+12%) body weight. GH mRNA was higher in ER offspring at 90 and 180 days (+19% and +22%, respectively); it was lower in PR offspring at 90 and 180 days (-19% and -17%, respectively). Thus, we showed a direct relation between GH mRNA expression and length as well as body weight. We suggest that malnutrition during lactation may program GH mRNA expression patterns in adulthood and that these changes could be responsible for differences in growth patterns.  相似文献   

15.
alpha-Fluoromethylhistidine, a histidine decarboxylase inhibitor, induced a significant depletion in the hypothalamic, midbrain, and cortical brain histamine amounts in 12- and 3-month-old rats. In all three brain regions the most evident depletion occurred 2 h after treatment. In both groups of rats midbrain histamine levels returned to control values 6 h after treatment; however, hypothalamic histamine depletion was still significant and more evident in the old than in the young animals. Cortical brain histamine also remained significantly depleted in old rats, but returned to control values in young animals 6 h after alpha-fluoromethylhistidine treatment. These results suggest that old rats show a slower rate of new histamine synthesis in the cortex and hypothalamus. Regional brain histamine depletion was associated with a very significant decrease in plasma corticosterone levels, which indicates that brain histamine-corticosterone interactions do occur.  相似文献   

16.
The influence of nephrectomy on brain and peripheral tissue histamine and on brain norepinephrine, dopamine, serotonin, and 5-hydroxyindoleacetic acid was studied in germ-free and conventionally housed rats. The conventional controls had higher levels of histamine in the hypothalamus than the germ-free control animals, but no differences existed for histamine in whole brain minus the hypothalamus or in peripheral tissues. Nephrectomy increased brain histamine and 5-hydroxyindoleacetic acid levels in both germ-free and conventional rats, but had no effect on norepinephrine, dopamine or serotonin. In contrast, the histamine level in the heart of the nephrectomized germ-free animals was lower than that for germ-free controls. There were no changes in the heart or liver histamine levels of the conventional nephrectomized rats.  相似文献   

17.
The extracellular amino acid content was measured in the parietal cortex in portacaval and sham operated rats, using the brain dialysis technique. The amino acid content of the perfusate was determined for 10 min before and during stimulation with potassium chloride. Basal levels of aspartate, glutamine, glycine, methionie, valine, phenylalanine and leucine were 2-to 6-fold higher in the PC-shunted as compared to the sham operated rats. For glutamate, taurine, and GABA no differences were observed between the two groups. After KCl stimulation the release of glutamate and GABA increased significantly in both groups. For GABA this rise was approximately twice as high in the PC-shunted rats (+300%,P<0.01) as in the sham operated rats (+150%,P<0.01 as compared to basal). In the sham operated, but not in the PC-shunted rats, methionine and valine levels rose significantly (+200%,P<0.05) and glutamine release decreased (–50%,P<0.05). These findings suggest that the brain metabolism of amino acids is altered after a portacaval shunt. This could in turn alter the neurotransmission and partly explain the low spontaneous motor activity seen in these animals.  相似文献   

18.
Dynamics of the regulation of histamine levels in mouse brain   总被引:16,自引:9,他引:7  
Abstract— The intraperitoneal administration of L-histidine in a dose of 1000 mg/kg increased threefold the whole brain levels of histamine in the mouse. This increase was evident in all brain regions except the medulla oblongata-pons. The subcellular localization of histamine and histidine was the same in mice administered bhistidine as in salinetreated animals. Cold exposure and restraint further augmented the elevation of histamine elicited by histidine treatment. a-Hydrazino-histidine and 4-bromo-3-hydroxybenzyloxyamine (NSD-1055) but not a-methyl-DOPA inhibited histidine decarboxylase [EC 4.1.1.221 activity in mouse brain homogenates and prevented the increase in brain histamine after histidine administration. NSD-1055 and a-hydrazino-histidine also lowered brain levels of histamine by 50 per cent. NSD-1055 lowered whole brain levels of histamine rapidly, with a half-life for the depletable histamine pool of about 5 min. Assuming that inhibition of histidine decarboxylase accounted for the reduction in histamine, then the rate of histamine decline reflects the rate of histamine turnover, and our results suggest that a portion of mouse brain histamine turns over quite rapidly. Reserpine lowered brain levels of histamine by about 50 per cent, whereas the antihistaminic agent, dexbrompheniramine, and sodium pentobarbital elevated histamine levels.  相似文献   

19.
A study was made of the content of some neurotransmitters in the rat brain during neurogenic gastric lesions induced by excessive irritation of the body. The 3-hour electric stimulation combined with immobilization of the animals and mechanical stimulation of the pyloroduodenal reflexogenic zone led to a noticeable reduction in the content of histamine, serotonin and GABA in the brain. It is suggested that histamine-, serotonin- and GABA-ergic systems are involved in the central mechanisms of the development of neurogenic gastric lesions.  相似文献   

20.
We compared the changes in monocarboxylate transporter 1 (MCT1) and 4 (MCT4) proteins in heart and skeletal muscles in sedentary control and streptozotocin (STZ)-induced diabetic rats (3 wk) and in trained (3 wk) control and STZ-induced diabetic animals. In nondiabetic animals, training increased MCT1 in the plantaris (+51%; P < 0.01) but not in the soleus (+9%) or the heart (+14%). MCT4 was increased in the plantaris (+48%; P < 0.01) but not in the soleus muscles of trained nondiabetic animals. In sedentary diabetic animals, MCT1 was reduced in the heart (-30%), and in the plantaris (-31%; P < 0.01) and soleus (-26%) muscles. MCT4 content was also reduced in sedentary diabetic animals in the plantaris (-52%; P < 0.01) and soleus (-25%) muscles. In contrast, in trained diabetic animals, MCT1 and MCT4 in heart and/or muscle were similar to those of sedentary, nondiabetic animals (P > 0.05) but were markedly greater than in the sedentary diabetic animals [MCT1: plantaris +63%, soleus +51%, heart +51% (P > 0.05); MCT4: plantaris +107%, soleus +17% (P > 0.05)]. These studies have shown that 1) with STZ-induced diabetes, MCT1 and MCT4 are reduced in skeletal muscle and/or the heart and 2) exercise training alleviated these diabetes-induced reductions.  相似文献   

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