13C-Enrichment of Urinary Uric Acid after l-[Ring-2-13C]Histidine Dose in Adult Humans

We determined whether ring-2 carbon of histidine is folate-dependently transferred to carbons 8 (C₈) and/or 2 (C₂) in urinary uric acid in humans. Two adults collected each urine void for four days. Aliquots of urine for the first day were used for baseline values; then the subjects ingested 0.7 g (3.3 mmol) of l-[ring-2-¹³C]histidine and collected urine for three experimental days. Aliquots were analyzed for percentage ¹³C-content at C₂ and C₈ by a liquid-chromatography-mass spectrometry method. Percentage enrichment was determined by subtracting time-of-day paired baseline percentage ¹³C-content from experimental percentage ¹³C-content for each void. C₂ was predominantly ¹³C-enriched in the majority of voids. The percentage enrichments at C₂ for two subjects were 0.14 (±0.028 [SEM], n = 26) and 0.18 (±0.049, n = 21), whereas at C₈, they were 0.008 (±0.006) and −0.005 (±0.008), respectively. The mean C₂-enrichments were significantly greater than zero (p < 0.01), whereas those of C₈ were not (p > 0.2). The enrichment had a diurnal rhythm peaking in the morning. Our results may be useful in the estimation of the timing for the administration of drugs that interfere with purine nucleotide biosynthesis in the treatment of cancer and autoimmune disease.     

亚硒酸钠对胃粘膜细胞非程序DNA合成、LPO和ras P21表达的影响

目的研究亚硒酸钠对甲基硝基亚硝基胍（ＭＮＮＧ）所致胃粘膜细胞损伤的防护作用．方法观察了亚硒酸钠对ＭＮＮＧ所致胃粘膜细胞非程序ＤＮＡ合成（ＵＤＳ）、脂质过氧化物（ＬＰＯ）和ｒａｓＰ２１表达的影响．结果胃粘膜细胞先用１０μｍｏｌ／Ｌ或１μｍｏｌ／Ｌ亚硒酸钠预处理４ｈ，再给ＭＮＮＧ组细胞的非程序ＤＮＡ合成水平（ｃｐｍ／×１０－６ｍｉｎ－１，１１６６±１５６或１５６６±１８７ｖｓ１８３８±２０５，Ｐ＜００１～００５），脂质过氧化物（２０ｄ，μｍｏｌ／Ｌ，４５±０６或４７±０６ｖｓ７４±０７，Ｐ＜００１）和ｒａｓＰ２１蛋白含量（２０ｄ，Ａ，０６８±００８或０８６±００７ｖｓ１０８±０１１，Ｐ＜００１～００５）均显著低于ＭＮＮＧ组．结论一定剂量亚硒酸钠对ＭＮＮＧ诱导的胃粘膜细胞损伤有防护作用．     

The effect of maternal caffeine ingestion on pancreatic function in the neonatal rat

Summary Pancreatic function was investigated in neonatal suckling offspring of caffeine-ingesting dams, with or without maternal sucrose supplementation, throughout pregnancy and lactation. In offspring of rats ingesting caffeine without sucrose supplementation, there was initial hyperinsulinaemia, followed by a progressive fall of plasma insulin to subnormal levels. This fall in plasma insulin coincided with depletion of pancreatic insulin stores. Both the fall in plasma insulin and depletion of pancreatic insulin stores were prevented by sucrose supplementation of caffeine-ingesting dams. Offspring of dams fed sucrose alone and control offspring also maintained pancreatic insulin stores and circulating insulin levels over the first 14 days of postnatal life. Pancreases from offspring of caffeine-exposed animals tested in vitro showed enhanced sensitivity of the insulin release process to glucose. This was reflected in the glucose concentration required to elicit half-maximal insulin release (2.4 ± 0.2 mmol/l for caffeine offspring, 2.3 ± 0.2 mmol/l for caffeine with sucrose, 3.8 ± 0.3 mmol/l for sucrose and 4.1 ± 0.3 mmol/l for control offspring, mean ± SEM). In contrast, offspring of sucrose-supplemented (with or without caffeine) dams showed increased sensitivity of the proinsulin biosynthetic process to glucose, whereas offspring of dams ingesting caffeine alone showed no significant enhancement of the biosynthetic process compared with control offspring. Thus enhanced sensitivity of the insulin secretory process to glucose without a change in the sensitivity of the biosynthetic process in the offspring of the caffeine ingesting (nonsucrose supplemented) dams could explain the progressive depletion of pancreatic insulin stores and eventual hypoinsulinaemia seen in this group.     

Differential inhibitory action of cationic amino acids on protein synthesis in pancreatic rat islets

Summary The effect of cationic amino acids, i.e. L-arginine and L-lysine, on protein synthesis in isolated rat islets of Langerhans has been investigated. Except for prosomatostatin, the formation of islet proteins is strongly depressed by these amino acids. This effect can be demonstrated within a few minutes and is rapidly reversible. For proglucagon, efficient concentrations of arginine are in the range of 1 to 10 mmol/l. The sensitivity of proinsulin formation to arginine is glucose-dependent: at 2.5 mmol/l, inhibitory concentrations of arginine are 10-fold lower than in the case of proglucagon. High glucose (20 mmol/l) almost completely protects proinsulin synthesis from this inhibition. The proteolytic conversion steps in hormonal precursor processing are not influenced by cationic amino acids as studied in intact islets and in a cell-free translational system. It is concluded that arginine and lysine inhibit protein synthesis in islet cells at the translational level. The release of these amino acids by prohormone conversion may exert a feed-back control on proinsulin formation that is modulated by glucose.     

The effect of biguanides on secretion and biosynthesis of insulin in isolated pancreatic islets of rats

Summary Based on the clinical observation that biguanide treatment of obese patients may alter insulin levels, the influence of metformin and phenformin on basal and glucose stimulated insulin secretion, as well as on insulin biosynthesis, was studied in isolated islets of rats. — Biguanide concentrations of 100 g/ml, or higher, significantly reduced glucose stimulated insulin secretion. Both dose dependence and a difference in the intrinsic activities of metformin and phenformin were demonstrated. Incubating the same islets for a second period without biguanides, glucose stimulated insulin secretion was still decreased. Addition of glibenclamide during this second period increased insulin secretion, but did not overcome complete inhibition achieved after incubation at very high biguanide concentrations. Glucose stimulated biosynthesis of proinsulin and insulin was decreased in the presence of biguanides and completely suppressed at very high concentrations. Inhibition of cell respiration in the islet cells effected by high biguanide doses may be the reason for the inhibition of secretion and biosynthesis of insulin. — On the other hand, an insulin release was found at the highest phenformin concentration of 10 mg/ ml and during perfusion of the isolated rat pancreas with higher biguanide doses. — Biguanide concentrations found to be effective in this study are very high compared with therapeutic levels. Moreover, biguanide actions are known to be highly dependent on species, concentration and metabolic situation. — Definite conclusions from these findings regarding clinical significance, therefore, seem unwarranted.Supported by Deutsche Forschungsgemeinschaft, Bonn-Bad Godesberg.     

sparse inflorescence1 encodes a monocot-specific YUCCA-like gene required for vegetative and reproductive development in maize

The plant growth hormone auxin plays a critical role in the initiation of lateral organs and meristems. Here, we identify and characterize a mutant, sparse inflorescence1 (spi1), which has defects in the initiation of axillary meristems and lateral organs during vegetative and inflorescence development in maize. Positional cloning shows that spi1 encodes a flavin monooxygenase similar to the YUCCA (YUC) genes of Arabidopsis, which are involved in local auxin biosynthesis in various plant tissues. In Arabidopsis, loss of function of single members of the YUC family has no obvious effect, but in maize the mutation of a single yuc locus causes severe developmental defects. Phylogenetic analysis of the different members of the YUC family in moss, monocot, and eudicot species shows that there have been independent expansions of the family in monocots and eudicots. spi1 belongs to a monocot-specific clade, within which the role of individual YUC genes has diversified. These observations, together with expression and functional data, suggest that spi1 has evolved a dominant role in auxin biosynthesis that is essential for normal maize inflorescence development. Analysis of the interaction between spi1 and genes regulating auxin transport indicate that auxin transport and biosynthesis function synergistically to regulate the formation of axillary meristems and lateral organs in maize.     

Liver transplantation and artificial liver support in fulminant hepatic failure

INTRODUCTIONFulminant hepatic failure(FHF)is a severe disease with devastating consequences;the incidence is high in China.Before the availability of liver transplantation,the mortality rate was more than 80%[1,2].The advent of liver transplantation revolutionized the outcome of FHF[3,4].However,many patients were unwilling to accept liver transplantation until very late,hence most of them died because of donor shortage and urgency of the disease[5-7],To overcome he problems,we performed orthotopic liver transplantation(OLT)in combination with artificial liver support(ALS) in the treatment of FHF in the past 2 years with satisfactory results.Our experience was reported below.     

Three thioredoxin targets in the inner envelope membrane of chloroplasts function in protein import and chlorophyll metabolism

Thioredoxins (Trxs) are ubiquitous small proteins with a redox-active disulfide bridge. In their reduced form, they constitute very efficient protein disulfide oxidoreductases. In chloroplasts, two types of Trxs (f and m) coexist and play central roles in the regulation of the Calvin cycle and other processes. Here, we identified a class of Trx targets in the inner plastid envelope membrane of chloroplasts that share a CxxC motif approximately 73 aa from their carboxyl-terminal end. Members of this group belong to a superfamily of Rieske iron-sulfur proteins involved in protein translocation and chlorophyll metabolism. These proteins include the protein translocon protein TIC55, the precursor NADPH:protochlorophyllide oxidoreductase translocon protein PTC52, which operates as protochlorophyllide a-oxygenase, and the lethal leaf spot protein LLS1, which is identical with pheophorbide a oxygenase. The role of these proteins in dark/light regulation and oxidative control by the Trx system is discussed.     

Living with inborn errors of cholesterol biosynthesis: lessons from adult patients

In the last decades, nine inherited errors of the distal part of cholesterol biosynthesis have been recognized. Affected patients present complex malformation syndromes involving different organs and systems with variable degrees of severity. We report on the phenotype evolution of three patients with enzymatic defects at three distinct steps of such pathway: Smith–Lemli–Opitz syndrome, X‐linked dominant chondrodysplasia punctata type 2 and congenital hemidysplasia with ichthyosiform erythroderma and limb defects syndrome. The patients' natural history, from childhood to adulthood, is thoroughly described in order to contribute for a better knowledge of these diseases. Our ultimate goals are to contribute for a better characterization of the long‐term course of these metabolic disorders and for the recognition of such diseases in older patients.