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101.
Latency changes in brain stem auditory evoked potentials associated with impaired brain myelination.
Interference with myelin deposition and brain growth was produced in rats by administering p-chlorophenylalanine (PCPA), alone or with phenylalanine (PHE), from the fifth postnatal day. Treatment with PCPA + PHE until 20 days of age resulted in significantly greater developmental impairment than that produced by PCPA alone. The extent of the maturational arrest was reflected in a corresponding failure to achieve the progressive latency decrements observed in the brain stem evoked potentials of normally maturing animals. In rats treated until 30 days of age the metabolic and electrophysiologic abnormalities were attenuated. Synaptosomal content at either age and under both experimental conditions did not appear to differ from that of the control brains. Rats which received PCPA or PCPA + PHE for a brief period later in development (from 17 to 20 days of age) maintained relatively normal myelin deposition and brain growth. The latencies of their brain stem evoked potentials also remained normal despite the presence of low cerebral serotonin concentrations. These data suggst that this latency provides a general measure of brain development which seems particularly sensitive to changes in the rate of myelination. 相似文献
102.
BACKGROUND: Stable isotope 13C-labelled phenylalanine breath test has been applied to enable the quantitative evaluation of hepatic functional reserve, but the mechanism underlying the changes in function has not been resolved. This study evaluated the correlation between expression of the mRNA of key enzymes mediating phenylalanine metabolism and the metabolism of L-[1-13C] phenylalanine (13C-phe) assessed by the excretion of 13C-CO2 in the breath of rats with, and without, chronic hepatic injury induced by administration of carbon tetrachloride (CCl4). MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats (n = 29) were given subcutaneous injections of CCl4 to induce chronic hepatic injury. L-[1-13C] phenylalanine breath tests (PheBT) were then applied to the rats to assess hepatic function. Expression of phenylalanine hydroxylase (PHH) and tyrosine transaminase (TYT) mRNA in liver was detected by real-time fluorescence quantification RT-PCR, using TaqMan as the probe. It was then determined whether the PheBT results correlated with PHH and/or TYT mRNA expression. In addition, immunohistochemical labelling was used to visualize PHH protein expression in the control and injured liver tissue. RESULTS: There were significant decreases in PheBT and PHH mRNA expression in the cirrhotic rats relative to the uninjured controls and these two measures of liver function were correlated. However, TYT mRNA expression was not changed by CCl4-induced liver injury. The immunohistochemical analysis revealed that PHH protein was expressed predominantly in the cytoplasm of liver cells. CONCLUSIONS: The results of the PheBT were consistent with the changes in PHH gene expression following liver injury. The present findings indicate that decreased expression of the rate-limiting enzyme PHH, but not of TYT, might underlie the functional deficits detected as decreased PheBT. The 13C excretion rate constant per mass liver (PheBT-k/LW) was the most sensitive index that could be used to evaluate the PHH mRNA expression in the liver. 相似文献
103.
104.
Pereira Lde P da Silva RO Bringel PH da Silva KE Assreuy AM Pereira MG 《Journal of ethnopharmacology》2012,139(2):642-648
Ethnopharmacological relevance
Caesalpinia ferrea (Caesalpinioideae), known as pau-ferro or juca, has been used in the traditional medicine in North and Northeast of Brazil in inflammatory disorder, among others. Thus, experimental evaluation of the anti-inflammatory activity of extracts and fraction polysaccharides of Caesalpinia ferrea pods, and correlation with its anti-inflammatory activity and popular use is important.Materials and methods
Total polysaccharides (TPL) were applied to ion exchange chromatography and eluted stepwise. Paw edema was induced s.c. by λ-carrageenan, dextran, histamine, serotonin, compound 48/80, bradykinin, prostaglandin E2 (PGE2) or l-arginine and analyzed by plethysmometry and protein leakage by spectrophotometry. Peritonitis was induced i.p. by carrageenan or N-formyl-methionyl-leucyl-phenylalanine (fMLP) and analyzed 4 h later for leukocyte migration and protein leakage. Animals were treated i.v. with TPL or polysaccharide fractions (0.01, 0.1, 1 mg/kg) 30 min before stimuli in both models. Toxicity (variation of body/organ mass and hematological/biochemical parameters) was evaluated after the seven-day treatment with the most active polysaccharide fraction (1 mg/kg; i.v.).Results
Chromatography of TPL (2.8% yield) provided three major polysaccharide fractions (FI, FII, FIII). At 1 mg/kg, TPL inhibited the paw edema induced by carrageenan (60%) and FIII (fraction presenting high carbohydrate and low protein content) inhibited the inflammatory parameters in the paw edema induced by the following stimuli: carrageenan (70%), dextran (53%), histamine (65%), serotonin (62%), bradykinin (60%), PGE2 (63%), nitric oxide (61%) and compound 48/80 (36%). Additionally, FIII at 1 mg/kg inhibited the carrageenan-induced edema in animals with intact mast cells, but only the late phase of those with degranulated mast cells elicited by compound 48/80. Moreover, FIII inhibited cell migration and protein leakage in the model of peritonitis elicited by carrageenan (88%) and fMLP (64%), being well tolerated by animals.Conclusions
Extracts and polysaccharide fractions of Caesalpinia ferrea pods exhibit potent anti-inflammatory activity via negative modulation of histamine, serotonin, bradykinin, PGE2 and NO released in the carrageenan-induced edema, showing involvement of mast cells. FIII could be interfering not only in the vascular, but also in cellular inflammatory events, revealing to be an important active component of traditionally prepared remedies used to treat inflammatory states. 相似文献105.
Objectives
This study investigated the effect of hypertonic saline on the role of polymorphonuclear neutrophils (PMNs) in the inflammatory response and the effect of hypertonic saline infused at different phases in relation to an inflammatory stimulus.Materials and methods
PMNs were isolated from peripheral blood of healthy volunteers (Boyum''s method) and cultured in three different media ([Na+] = 140 mmol/l, 180 mmol/l, and 200 mmol/l). PMNs were then stimulated with fMLP (N‐formyl‐methionyl‐leucyl‐phenylalanine) and H2O2 synthesis was quantified by flow cytometry at 5, 30, 60, 120, and 180 minutes. PMNs were treated with hypertonic saline before, simultaneously with, and after fMLP stimulation, and H2O2 synthesis quantified again.Results
H2O2 synthesis was two or three times higher in fMLP stimulated than in non‐stimulated PMNs, and it reached maximum level at 120 minutes. In the absence of fMLP stimulation, there was no significant difference between control and hypertonic saline with regard to activity of H2O2 synthesis. In the presence of fMLP stimulation, H2O2 synthesis significantly decreased in PMNs treated with hypertonic saline. There was no significant difference between the two hypertonic saline solutions ([Na+] = 180 mmol/l and 200 mmol/l) with regard to H2O2 synthesis. However, H2O2 synthesis decreased in PMNs treated with hypertonic saline before and simultaneously with fMLP stimulation, but was not significantly decreased in the cells treated with hypertonic saline after fMLP stimulation.Conclusions
Hypertonic saline appears to decrease H2O2 in stimulated neutrophils. This may be a further beneficial role of hypertonic saline when used clinically as an early resuscitation fluid. 相似文献106.
B. Fitzgerald J. Morgan N. Keene R. Rollinson A. Hodgson & J. Dalrymple-Smith 《Journal of intellectual disability research : JIDR》2000,44(1):53-59
There is evidence in the literature which suggests that adults with previously untreated phenylketonuria (PKU) benefit from a low phenylalanine diet. A prospective study providing a phenylalanine-restricted diet to five subjects with severe intellectual disability arising from untreated PKU is reported. Physical, social and behavioural measures were used to monitor the effects of the diet. Four out of the five subjects derived considerable benefit. It is concluded that the restricted diet is worth trying in most individuals with previously untreated PKU, and that possible benefits are in the areas of concentration, alertness, mood, irritability and adaptive behaviour. 相似文献
107.
24-hour phenylalanine loading tests were done in 5 children with persistent hyperphenyl-alaninemia off diet. The urinary excretion of phenylalanine were compared to the excretion after loading of phenylketonuric children on diet. Serum phenylalanine of children with persistent hyperphenylalaninemia returned to preloading levels (285 μmol/l) within 24 hours. These children, however, excreted phenylalanine during phenylalanine loading in lesser quantities than patients with phenylketonuria on diet. Serum phenylalanine of phenylketonuric children on diet attained preloading levels (300 μmol/l) approximately 14 days after loading. Thus, the present data do not support the hypothesis that hyperphenylalaninemic patients are phenylketonurics protected by increased urinary excretion of phenylalanine. 相似文献
108.
早期筛查诊断治疗的57例苯丙酮尿症患儿智力发育分析 总被引:4,自引:0,他引:4
[目的]通过对北京地区10年间经新生儿疾病筛查并确诊的苯丙酮尿症(phenylketonuria,PKU)患儿智力发育做出现状调查,并就起始治疗时间,治疗浓度等与智力发育水平的关系进行分析,了解PKU新生儿疾病筛查和早期治疗对患儿疾病预后的影响,以便完善治疗方案.[方法]北京市1996年1月~2005年1月经新生儿疾病筛查确诊的苯丙酮尿症患儿57名,选用Gesell智力测查法评估患儿智力发育情况.[结果]90%以上经新生儿疾病筛查并确诊的早期开始治疗的PKU患儿智力达到正常水平.生后3个月内即开始治疗对智力发育水平无影响.确诊时Phe血浓度高低与预后无直接关系.治疗过程中Phe控制水平与预后呈负相关关系.[结论]苯丙酮尿症的治疗宜在患儿生后3个月内开始,严格控制Phe血浓度是改变疾病结局的关键因素. 相似文献
109.
目的:建立手性固定相正相高效液相色谱法拆分首次报道合成的 D、L-苯丙氨酸衍生物的光学异构体。方法:采用 O,L′-二(3,5-二甲基苯甲酰)-N,N′-二烯丙基-L-酒石酸肼(KR100-CHI-I DMB)手性色谱柱(4.6 mm×250mm,5μm),流动相为正己烷-无水乙醇-三氟醋酸(100:10:0.4),流速:0.5 mL·min~(-1),检测波长:220 nm。结果:除2,5-二氯-苯丙氨酸外的3对 D、L-卤代苯丙氨酸光学异构体得到了分离,并用建立的分离方法对酶拆分得到的卤代苯丙氨酸进行了纯度检查。结论:方法简单、灵敏,可用于检查卤代苯丙氨酸的纯度。 相似文献
110.
L C. S. Silva R. F. Pires J. C. Coelho L B. Jardim R. Giugliani 《Clinical genetics》1997,51(4):231-235
Classical phenylketonuria (PKU) is an inborn error of metabolism of autosomal recessive inheritance characterized by the accumulation of phenylalanine (Phe) in tissues due to Phe-4-hydroxylase deficiency. Several methods have been developed for the detection of PKU heterozygotes based on the determination of plasma Phe and tyrosine (Tyr) levels, on the analysis of the Phe/Tyr and Phe2 /Tyr ratios and on the use of discriminant functions. The objective of the present study was to test the value of loading with aspartame (a sweetener consisting of Phe, aspartate and methanol) for the identification of PKU carriers. The study was conducted on 22 obligate heterozygotes and 27 controls. Two blood samples were collected (under fasting conditions and 30 min after the loading) for fluorometric determination of Phe and Tyr. Phe, Phe/Tyr and Phe2 /Tyr values were higher in heterozygotes, whereas Tyr was higher in controls in both situations investigated. Linear discriminant function was considered to be the best parameter for differentiation of the individuals in the two groups. Under the conditions employed in the present study, aspartame loading did not show any advantages in discriminating between PKU carriers and normal individuals when compared to the same analysis performed under fasting conditions. 相似文献