ABSTRACT
Objective To summarize the acylcarnitine profile in children with malnutrition,with an attempt to distinguish it from those of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency,multiple acylCoA dehydrogenase (MAD) deficiency,or glutaric aciduria type Ⅱ (GA Ⅱ).Methods Thirteen pediatric patients with malnutrition and 214 children of the same age but without malnutrition,which was set as the control group,were included in this study.The blood samples were collected at admission,and the concentration of carnitine and acylcarnitines were measured in bloodspots by tandem mass spectrometry using samples nnderivatized.Results The concentrations of acylcarnitines which were involved in fatty acid oxidation,including octadecanoyl (C18) to acetyl (C2) acylcarnitines and ketonic acylcarnitines,were higher in malnutrition group than in the control group.Particularly,the concentration of decanoyl acylcarnitine (C10) in the malnutrition group was (0.203 ±0.105) μmol/L,which was out of the normal rang (0-0.200 μmol/L),was significantly higher than that [(0.054 ±0.030) μmol/L] in the control group (P ＜0.001).There was no significant difference in the concentrations of acylcarnitines [e.g.propionyl (C3),isovaleryl (C5),3-hydroxy-isovaleryl (C5OH),and glutaryl (C5DC) acylcamitines] involved in amino acid decomposition between the malnutrition and control groups.Conclusions The concentrations of acylcarnitines related to fatty acid oxidation elevate in children with malnutrition.In particular,the medium-chain acylcarnitines C10 is out of the normal range,which can be used to differentiate malnutrition from MCAD and MAD.
ABSTRACT
Objective To provide methodological references for laboratories to carry out newborn screening for disorders of amino acid metabolism,we compared the difference and distribution of ten amino acids including alanine (Ala),arginine (Arg),citrulline (Cit),glycine (Gly),leucine (Leu),methionine (Met),ornithine (Orn),phenylalanine (Phe),tyrosine (Tyr),and valine (Val) from newborn dried blood spots specimen using derivatization or non-derivatization as sample preparation methods.Method It is a comparative research study.A total of 4135 newborn screening dried blood spot samples for inborn errors of metabolism were collected from January to June,2012.All specimens came from neonatal screening center of shanghai children's hospital.Samples were prepared by two different techniques,the corresponding kits and the procedures were used as follows:(1) Simultaneous detection of 100 dried blood spot specimens using two methods respectively to compare the paired difference of each amino acid.(2) 2000 cases of normal newborn specimens were detected respectively to obtain the normal distribution of ten neonatal amino acids.(3) 35 specimens from patients previously diagnosed positively as inborn errors of metabolism were simultaneously detected with 7 amino acids to verify the consistency of two techniques in clinical judgment.Results The amino acid levels of normal newborns analyzed by one-sample.kolmogorovSmirnov test (Z value ranged from 1.997 to 6.229) showed a skewed distribution (P ＜ 0.01).Except for Leu and Tyr,non-derivatization techniqueshowed a lower concentration than derivatization technique,and the CVs of nine amino acids were ＜ 10％ except for Met (the CV of Met was 47.8％),and the average CV is 7.8％.Except for Met,Phe and Tyr,the levels of other 7 amino acids measured by two techniques showed no significant difference (P ＞ 0.05).According to 0.5th to 99.5th percentiles,the normal reference range for derivatization method were greater than on-derivatization method,and the average value was 25.3％.After clinic judgment,the results of the abnormal indicators of children with true metabolism disorders showed no statistically significant between two methods (P ＞ 0.05),the detection rate was 100％.Conclusions There was a slight difference between derivatization and the non-derivatization techniques in detecting multiple amino acids.The results of the abnormal indicators of amino acid metabolism disordersshow no statically significant difference between the two methods,and no difference in clinical judgment.Both methods can be used in detecting amino acid metabolism disorders in newborn screening.
ABSTRACT
Objective To investigate the blood levels of amino acids in children aged 0-15 year, with an attempt to provide evidence for evaluating amino acid status and diagnosing metabolic diseases of amino acid.Methods The blood levels of eleven amino acids in 1900 children aged 0-15 years were determined by tandem mass spectrometry (MS/MS). Results The blood levels of leucine & isoleucine, valine, phenylalanine tyrosine,glycine, proline, ornithine, and alanine gradually decreased after birth, reaching the lowest levels at the ages of 4-6 months, and then gradually increased, reaching the normal range at the ages of 7 months-1 year. The blood levels of alanine and glycine reach the second peaks on the ages of 9 years in girls and on 11 years in boys. The blood levels of methionine and arginine were lowest in the first week of age, became highest in 1-3 months, decreased to the normal ranges after 4-6 months, and kept the level afterwards. The ratios between prosomatic amino acid and productive amino acid, between ornithine and arginine, between citrulline and arginine, and between ornithin and citrulline were highest in the first week of age and decreased to normal values after 3 to 12 months. The concentrations of amino acids in group of 7 months-15 years were significantly different from the group of 1 day-1 month and group of 2-6 months (P ＜0. 05 or P ＜0. 01 ). The concentrations of amino acids were significantly higher in females than in males in the group of 1 day-1 month and in all age groups (P ＜0. 05 or P ＜0. 01 ) . Conclusions The concentrations and profiles of amino acids change remarkably during the first year of age. Age should be carefully considered when evaluating the nutritional status of amino acid and diagnosing metabolic diseases of amino acids.
ABSTRACT
Aim: To explore the in situ intestinal absorption in rats of ZLR-8, an insoluble NO-donor drug, and to compare the intestinal absorption enhancement by spray-dried emulsion. Methods: Intestine of rats was cannulat-ed for in situ perfusion. UV and HPLC methods were used to monitor phenolsulfonphthalein and ZLR-8, respec-tively. The effects on ZLR-8 absorption of the intestinal segments, the concentration of ZLR-8 and the pH of the circulating perfusate were studied. The absorption of ZLR-8 suspension was compared to that of the spray-dried emulsion. Results: 1-h in situ intestinal perfusion of the spray-dried emulsion allowed the estimation of the absor-tion percentage to be (23. 54 ± 1. 40) %, (15. 95 ± 0. 09) %, (12. 30 ± 0. 74) %, (3. 98 ± 0. 12) %, respec-tively; the absorption rate constants in duodenum, colon, jejunum and ileum to be (0.248 6 ±0.046 0) h~(-1), (0. 143 7 ±0. 036 0) h~(-1), (0. 069 2 ±0. 001 3) h~(-1), (0. 020 8 ±0. 000 4) h~(-1), respectively. Significant differ-ences in absorption characteristics were found among intestinal segments. In the range of 3. 4-9. 4, pH of the per-fuate had significant influence on the absorption of ZLR-8, and better absorption appeared at pH of 5. 4 to 7. 4. It was found that the absorption rate constant was unaffected by ZLR-8 concentration. However, the absorption amount was proportional to ZLR-8 concentration. Compared to the ZLR-8 suspension, the in situ intestinal absorption of ZLR-8 in rats given the spray-dried emulsion increased significantly. Conclusion: It was only found that ZLR-8 administered in suspension has minor absorption in rat duodenum while no apparent absorption occurred in other segemnts. ZLR-8 in spray-dried emulsion was fairly absorbed in the rat intestinal segments. Passive diffusion was invloved in the absorption of ZLR-8. Spray-dried emulsion significantly enhanced the intestinal absorption of ZLR-8 in rats.