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Amino acid phosphoramidates of adenosine were synthesized and determined by positive and negative ion electrospray ionization mass spectrometry (ESI-MS) in conjunction with tandem mass spectrometry (MS/MS). The fragmentation pathways were investigated. In the positive ion mass spectra abundant characteristic fragment ions appeared, and many complementary ions were found. In the negative ion mass spectra only a few fragment ions were observed, and most of them contained phosphoryl groups. The results show that ESI-MS is a useful tool for structural determination of amino acid phosphoramidates of nucleosides.

To investigate melamine-induced pathological changes in the kidney.Wistar rats were fed with a diet containing 0, 1% and 2% melamine for 15 weeks. After melamine feeding was stopped, various outcome measures were observed for 4 weeks.Rats fed with melamine showed reduced caloric intake, slower weight gain and impaired renal function. The blood urea nitrogen of group A and B [(13.23 ± 5.10) mmol/L and (18.30 ± 5.90) mmol/L, respectively] and serum creatinine levels of group B [(19.90 ± 2.90) mmol/L] were higher than that of group C [(8.23 ± 2.30) mmol/L and (10.04 ± 1.73) mmol/L](P0.01, respectively). Additionally, the kidney coefficients of group A and B were higher than that of group C (P0.01, respectively). Crystals, tubular ectasia and interstitial inflammation and fibrosis were found in the kidneys of melamine fed rats. Four weeks after discontinuation of feeding with melamine-contained diet, the caloric intake and weight of the rats increased, the coefficients of the kidney decreased, and the blood urea nitrogen of group A and B [(17.96 ± 2.04) mmol/L and (19.20 ± 3.36) mmol/L, respectively] and serum creatinine levels of group B [(24.20 ± 5.28) mmol/L], which became worse than 4 weeks before (P0.01;P0.05, respectively), and were still higher than that of group C [(8.30 ± 1.79) mmol/L and (9.87 ± 2.71) mmol/L, P0.01, respectively]. Crystals remained inside the kidney, changes in the renal interstitium did not improve.(1) Melamine-induced urinary calculus rat model can be established by feeding 3-week old male Wistar rats with a diet containing 2% melamine for 15 weeks. The main constituent of the urinary calculus was melamine (90%), with a little uric acid and traces of cyanuric acid. (2) Melamine damaged the renal function, formed renal crystals, and led to the pathological changes of kidneys. All the influences seemed to be dose-depended and was related with the obstruction of the crystals or calculus in the kidney. (3) The renal function and the pathological changes did not improve 4 weeks after discontinuation of feeding with melamine-contained diet.

A total of 25 Chinese patients aged 6 to 36 months hospitalised at Beijing Children’s Hospital due to melamine-induced kidney stones complicated by acute obstructive renal failure in 2008 were included in a study in order to diagnose and treat these special cases more effectively. Feeding history, clinical presentation, ultrasound findings, treatments and effects were summarised. Twelve to seventeen months follow-up was reported also. Ultrasound examination showed that calculi were located at the kidney and ureters. Stones were composed of both uric acid and melamine in a molar ratio of 1.2:1 to 2.1:1. Treatments providing liquid plus alkalisation of urine proved to be effective in helping the patients pass the stones. Surgical intervention was needed in severe cases. Renal function returned to normal in all 25 patients after various durations of therapy. Sixty-eight percent of the patients expelled all of the calculi within 3 months, 90% in 6 months and 95% in 9 months, without sequelae till now. Melamine-contaminated milk formula can cause kidney stones in infants, which should be diagnosed by feeding history, clinical symptoms and ultrasound examination. Composition of the stones was not only of melamine but also uric acid. Providing liquid orally or intravenously plus alkalisation of urine proved to promote the removal of the stones. Follow-up of 12 to 17 months after discharge showed no sequelae.

Infants in some areas of China developed urinary lithiasis after being fed with powdered milk that was tainted with melamine in 2008 and very small proportion of the infants developed acute renal failure caused by urinary tract calculus obstruction. The aim of this article was to summarize clinical characteristics, diagnosis and treatment of infants with urinary calculus and acute renal failure developed after being fed with melamine tainted formula milk.Data of infant patients with urinary calculus and acute renal failure due to melamine tainted formula milk admitted to the Beijing Children's Hospital Affiliated to the Capital Medical University and the Xuzhou Children's Hospital in 2008 were used to analyze the epidemiological characteristics, clinical manifestations, imaging features as well as effects of 4 types of therapies.All the 34 infants with urinary calculus were complicated with acute renal failure, their blood urea nitrogen (BUN) was (24.1+/-8.2) mmol/L and creatinine (Cr) was (384.2+/-201.2) micromol/L. The chemical analysis on the urinary calculus sampled from 15 of the infants showed that the calculus contained melamine and acidum uricum. The time needed for the four types of therapies for returning Cr to normal was (3.5+/-1.9) days for cystoscopy group, (2.7+/-1.1) days for lithotomy group, (3.8+/-2.3) days for dialysis group, and (2.7+/-1.6) days for medical treatment group, which had no statistically significant difference (P=0.508). Renal failure of all the 34 infants was relieved within 1 to 7 days, averaging (3.00+/-1.78) days.Melamine tainted formula milk may cause urinary calculus and obstructive acute renal failure. It is suggested that firstly the patients with urinary calculus complicated with acute renal failure should be treated with dialysis or medication to correct electrolyte disturbance, in particular hyperkalemia, and then relieve the obstruction with available medical and surgical methods as soon as possible. It was observed that the short-term prognosis was satisfactory.

Aminoacyl adenylate pentacoordinated phosphorus compounds were analyzed by field desorption (FD) and fast atom bombardment (FAB) mass spectrometries, together with the B/E linked scan technique, and their mass spectral fragmentation pathways were investigated. For the five bonds (one P-N bond, three P-O bonds and one mixed anhydride bond P-O-CO), the cleavage usually occurred more on the P-N bond, the mixed anhydride bond and the O-C bond adjacent to the P-O bond, and less on the P-O bond. Ion YH(+), corresponding to water loss from protonated 2',3'-O-isopropylidene-adenosine, was the base peak. The results reflect the structural characteristics of aminoacyl adenylate pentacoordinated phosphorus compounds. Copyright 1999 John Wiley & Sons, Ltd.

To summarize clinical characteristics, diagnosis and treatment of infants with urinary calculus and acute renal failure developed after being fed with melamine tainted formula milk.Data of infant patients with urinary calculus and acute renal failure due to melamine tainted formula milk admitted to the Beijing Children's Hospital affiliated to the Capital Medical University and the Xuzhou Children's Hospital in 2008 were used to analyze the epidemiological characteristics, clinical manifestations, image features as well as effects of 4 types of therapies.All the 34 infants with urinary calculus were complicated with acute renal failure, their blood urea nitrogen (BUN) was (24.1 +/- 8.2) mmol/L and creatinine (Cr) was (384.2 +/- 201.2) micromol/L. The chemical analysis on the urinary calculus sampled from 14 of the infants showed that the calculus contained melamine and acidum uricum. The time needed for the four types of therapies for returning Cr to normal was (3.5 +/- 1.9) d for cystoscopy group, (2.7 +/- 1.1) d for lithotomy group, (3.8 +/- 2.3) d for dialysis group, and (2.7 +/- 1.6) d for medical treatment group, which had no statistically significant difference (P = 0.508). Renal failure of all the 34 infants was relieved within 1 to 7 days, averaging (3.0 +/- 1.8) d.Melamine tainted formula milk may cause urinary calculus and obstructive acute renal failure. It is suggested that firstly the patients with urinary calculus complicated with acute renal failure should be treated with dialysis or medication to correct electrolyte disturbances, in particular hyperkalemia, and then relieve the obstruction with available medical and surgical methods as soon as possible. It is observed that the short term prognosis is satisfactory.

Amino acid-nucleotide conjugates have important biological functions and therapeutic applications. For example, aminoacyl adenylates are key intermediates in aminoacyl tRNA synthetase reactions. They may also be involved in the prebiotic synthesis of polypeptides. Finally, various amino acid carbomethoxy aryl phosphoramidates of nucleotide prodrugs may be activated through a mechanism involving a pentacoordinated phosphorane intermediates. In order to understand better the chemistry of these compounds, a phenylalanyl adenylate pentacoodinated phosphorane has been synthesized in 72% yield and its decomposition in aqueous solution studied. Hydrolysis gave 2′,3′-O-isopropylidene adenosine 5′-monophosphate, 2′,3′-O-isopropylidene adenosine, and phenylalanine. The results provide model chemistry for the enzymatic degradation mechanism of antiviral aryl amino acid phosphodiester amidates in cells, which leads to their activation.