Terminal Deoxynucleotidyl Transferase Amplification Based DNA-Copper Nanoclusters Sensor for Detection of L-Histidine / 分析化学

A terminal deoxynucleotidyl transferase ( TdT ) amplification based DNA-copper nanoclusters (CuNCs) sensor was developed for detection of L-histidine ( L-His). Single strand DNA containing poly-thymine ( T) sequences were synthesized by TdT in the presence of dTTP. In blank control, poly-T sequences worked as templates of CuNCs due to the affinity between thymine and copper ions( II) . Fluorescence intensity was enhanced when CuNCs formed with reducing agents. In the presence of L-His, the imidazolyl group of L-His worked as a chelating agent that formed L-His-Cu2+ chelated complex. Thus less copper ions were induced in poly-T sequences, and less CuNCs were obtained to produce week fluorescence signals. A good linear correlation was obtained between fluorescence change and the logarithm of the L-His concentration over the range of 5. 0 ×10-9-5. 0 ×10-4 mol/L. The detection limit was estimated as 3. 4 ×10-9 mol/L. And the recoveries were 97. 4%-104. 6% for the actual urine samples. Compared with other methods of synthetic CuNCs, this method allowed to specifically determining L-histidine without template or labeling, which showed good potential in biomedical and clinical analysis.

Terminal Deoxynucleotidyl Transferase Amplification Based DNA-Copper Nanoclusters Sensor for Detection of L-Histidine / 分析化学

A terminal deoxynucleotidyl transferase ( TdT ) amplification based DNA-copper nanoclusters (CuNCs) sensor was developed for detection of L-histidine ( L-His). Single strand DNA containing poly-thymine ( T) sequences were synthesized by TdT in the presence of dTTP. In blank control, poly-T sequences worked as templates of CuNCs due to the affinity between thymine and copper ions( II) . Fluorescence intensity was enhanced when CuNCs formed with reducing agents. In the presence of L-His, the imidazolyl group of L-His worked as a chelating agent that formed L-His-Cu2+ chelated complex. Thus less copper ions were induced in poly-T sequences, and less CuNCs were obtained to produce week fluorescence signals. A good linear correlation was obtained between fluorescence change and the logarithm of the L-His concentration over the range of 5. 0 ×10-9-5. 0 ×10-4 mol/L. The detection limit was estimated as 3. 4 ×10-9 mol/L. And the recoveries were 97. 4%-104. 6% for the actual urine samples. Compared with other methods of synthetic CuNCs, this method allowed to specifically determining L-histidine without template or labeling, which showed good potential in biomedical and clinical analysis.

Origin of the Recommended Intake of L-Histidine by Infants.

Background: In mid-2012, Food Standards Australia New Zealand (FSANZ) received an application to change the Australia New Zealand Food Standards Code so that the minimum L-histidine content of infant formula sold in Australia and New Zealand could be reduced from 12 to 10 mg/100kJ. Infant formula refers to breast milk substitutes that satisfy nutritional requirements of infants up to 12 months of age. L-histidine is an essential amino acid. Although there is a population nutrient recommendation regarding total protein intake for infants in Australia and New Zealand, there are no recommendations regarding intake of the essential amino acids. The 12 mg/100kJ level that was in existence in 2012 had originally been set in 2002 based on the 1985 Joint FAO/WHO/UNU Expert Consultation report (updated in 1991). This report had estimated amino acid requirements calculated from breast milk composition data from four papers. In 2007, Codex Alimentarius adopted a minimum of 10 mg/100kJ for L-histidine based on the 2005 ESPGHAN Co-ordinated International Expert Group report. The Policy Guideline on the Regulation of Infant Formula Products issued in 2011 by the Australia and New Zealand Food Regulation Ministerial Council recommends that the primary reference for the compositional requirements of infant formula and follow-on formula should be breast milk. Therefore, the FSANZ risk assessment examined which studies of breast milk composition had been included in earlier reports and whether there was more recent data that should be included. Aim: To determine if infant formula containing a minimum content of L-histidine of 10 mg/100kJ is consistent with reported levels in breast milk and will support normal growth in formula-fed infants. It is assumed that the amount of L-histidine in breast milk is adequate to meet the requirements of infants for normal growth. The review focused on infants <6 months of age because older infants would be receiving complementary foods. Methods: The studies which contributed to the average L-histidine amount in breast milk calculated in the FAO/WHO and ESPGHAN reports and similar reports from prominent bodies in Europe and the US were examined. A literature review of the cited studies and related research reporting L-histidine content of breast milk going back to 1954 was done. Because there was great variability in the units used to describe the L-histidine content of breast milk (e.g. nmol L-histidine/ml of milk, mg L-histidine/g milk, mg L-histidine/g nitrogen, g L-histidine/kg/day etc.) all values for L-histidine were converted to mg/g crude protein to allow comparison. After examining previous reports, the estimated L-histidine content in breast milk was updated by selecting studies based on criteria around sample collection, analytical methods for amino acid analysis and measurement of protein content, and reporting items (such as full and available publication in the peer-reviewed literature). To confirm whether a lower L-histidine level would support an infant’s physiological requirements, additional literature was reviewed to examine effects of formulas with different histidine concentrations on growth and plasma histidine concentration. Results: The six reports that were examined calculated the average L-histidine intake from studies of breast milk as the basis of their recommendations. The 1985 and 1991 FAO/WHO reports recommended an intake of 26 mg/g crude protein based on four studies of breast milk. None of the studies cited in these two reports were cited by the later reports, probably because they were conducted prior to the development of modern analytical techniques. The later reports used primary data from a total of 11 studies between them, but their recommendations, which ranged from 21-23 mg L-histidine/g crude protein, were obtained by averaging data from three to seven studies (see table below). Other studies were often cited in these reports but were not included when calculating the average. No reasons were given for inclusion or exclusion of studies. Ten studies met the inclusion criteria specified by FSANZ. Of these, only five had been included in calculations by one or more of the earlier reports. FSANZ calculated an unweighted mean of 24 mg L-histidine/g crude protein. Using appropriate composition data for protein, fat and carbohydrate in breast milk, this is equivalent to 10 mg Lhistidine/ 100 kJ milk. Human milk has a variable composition and depends on a range of factors including the duration of the feed and length of lactation. In the FSANZ calculation, all of the studies used convenience samples of women and reported L-histidine concentrations ranging from 18-40 mg/g crude protein. Only one study (Raiha et al. 2002) examined physiological and biochemical outcomes in infants. In combination with six additional studies examining growth patterns and plasma concentrations of amino acids in breast and formula-fed infants, FSANZ determined that formula-fed infants consuming a formula containing 10 mg L-histidine/100 kJ are comparable to breastfed infants on the basis of the physiological and biochemical outcomes examined. Conclusion: The conversion of results from different studies to a common base, combined with rounding, inevitably introduces error when deriving a mean value. There was a 2-fold range of L-histidine concentrations across the individual studies examined. FSANZ concluded that 24 mg L-histidine/g crude protein (10 mg L-histidine/100kJ) is consistent with the average composition of breast milk and would support growth. This analysis also highlights the variability of the evidence base used by bodies making recommendations for amino acid intakes by infants. Systematic literature searching with justification for inclusion or exclusion of studies does not seem to have been widely used when deriving intake recommendations for L-histidine in infants. References are given in the full report. The complete report “Supporting document 1 – Comparative Nutrition Safety Assessment” can be downloaded for free from the FSANZ website: http://www.foodstandards.gov.au/code/applications/documents/A1074_SD11.pdf

L-histidine provokes a state-dependent memory retrieval deficit in mice re-exposed to the elevated plus-maze

The effects of L-histidine (LH) on anxiety and memory retrieval were investigated in adult male Swiss Albino mice (weight 30-35 g) using the elevated plus-maze. The test was performed on two consecutive days: trial 1 (T1) and trial 2 (T2). In T1, mice received an intraperitoneal injection of saline (SAL) or LH before the test and were then injected again and retested 24 h later. LH had no effect on anxiety at the dose of 200 mg/kg since there was no difference between the SAL-SAL and LH-LH groups at T1 regarding open-arm entries (OAE) and open-arm time (OAT) (mean ± SEM; OAE: 4.0 ± 0.71, 4.80 ± 1.05; OAT: 40.55 ± 9.90, 51.55 ± 12.10, respectively; P > 0.05, Kruskal-Wallis test), or at the dose of 500 mg/kg (OAE: 5.27 ± 0.73, 4.87 ± 0.66; OAT: 63.93 ± 11.72, 63.58 ± 10.22; P > 0.05, Fisher LSD test). At T2, LH-LH animals did not reduce open-arm activity (OAE and OAT) at the dose of 200 mg/kg (T1: 4.87 ± 0.66, T2: 5.47 ± 1.05; T1: 63.58 ± 10.22; T2: 49.01 ± 8.43 for OAE and OAT, respectively; P > 0.05, Wilcoxon test) or at the dose of 500 mg/kg (T1: 4.80 ± 1.60, T2: 4.70 ± 1.04; T1: 51.55 ± 12.10, T2: 43.88 ± 10.64 for OAE and OAT, respectively; P > 0.05, Fisher LSD test), showing an inability to evoke memory 24 h later. These data suggest that LH does not act on anxiety but does induce a state-dependent memory retrieval deficit in mice.

L-histidine reduces inhibitory avoidance in Carassius auratus submitted to cerebellar ablation

The effect of post-training treatment with L-histidine (LH) on the memory consolidation of inhibitory avoidance was investigated in Carassius auratus submitted to cerebellar ablation. The inhibitory avoidance procedure included 3 days: one habituation day, one training day (5 trials, T1-T5) and one test day. On the training day, each fish was placed individually in a white compartment separated from a black compartment by a sliding door. When the fish crossed into the black compartment, a weight was dropped in front of it (aversive stimulus) and the time to cross was recorded. Saline or LH (100 mg/kg) was injected intraperitoneally 10 min after the trials. Data were log10 transformed and analyzed by ANOVA and the Student-Newman-Keuls test (P < 0.05). In T5, all groups [ablation/LH (N = 15; 189.60 ± 32.52), ablation/saline (N = 14; 204.29 ± 28.95), sham/LH (N = 14; 232.36 ± 28.15), and sham/saline (N = 15; 249.07 ± 25.82)] had similar latencies that were significantly higher than T1 latencies [ablation/LH (89.33 ± 20.41), ablation/saline (97.00 ± 25.16), sham/LH (73.86 ± 18.42), and sham/saline (56.71 ± 17.59)], suggesting acquisition of inhibitory avoidance. For the test, there was a significant reduction in latencies of ablation/LH (61.53 ± 17.70) and sham/saline (52.79 ± 25.37) groups compared to the ablation/saline (213.64 ± 29.57) and sham/LH (199.43 ± 24.48) groups, showing that cerebellum ablation facilitated retention of inhibitory avoidance and LH reversed the effect of ablation. The results support other evidence that LH impairs memory consolidation and/or reduces the interpretation of aversion value.

Anticonvulsant action of L-histidine in mice / 中国临床药理学与治疗学

AIM: To observe the anticonvulsant action of L-histidine in mice. METHODS: The anticonvulsant effect of L-histidine, and the antagonism of dl-chlorpheniramine to L-histidine were observed in convulsion mice induced by pentylenetetrazole (PTZ) and electric stimulation. RESULTS: L-histidine exerted remarkable anticonvulsant action with dose-response relationship in convulsion mice induced by pentylenetetrazole and electric stimulation, and the action was partly antagonized by dl-chlorpheniramine. CONCLUSION: L-histidine has anticonvulsant effect, and the action was partly antagonized by dl-chlorpheniramine, suggesting that L-histidine can pass the BBS and enter the central nervous system.

Study on the Breeding of Histidine Producing Mutant and Its Properties / 微生物学通报

A L-histidine producing mutant was derived from Corynebacterium glutamicum HZ4221(TRA R DCP R AMT R histidase - )by means of mutagenesis with N-methy-N′-nitro- N-nitrosoguanidine(NTG).Contrast to original strain,the amount of histidine accumulation reached to a level of 5.31g/L in a medium containing 80g/Lglucose and 30g/L ammonium sulfate after cultured for 72 hours; the transketolase activity reduced to a degree of 15.7%.The utilization of the carbon sources,genetic stability,effect of metal ions were also been investigated in this paper.