Amino Acid Metabolism in Acute Renal Failure: Influence of Intravenous Essential L-Amino Acid Hyperalimentation Therapy

A solution of 8 essential I-amino acids and hypertonic dextrose was administered to 5 patients in acute postoperative renal failure in a program of hyperalimentation designed to decrease the patient's catabolic state and to accrue certain metabolic benefits. A sixth patient receiving intravenous glucose alone served as a control. The pretreatment plasma concentrations of amino acids in all 6 patients did not differ significantly from normal; following intravenous essential amino acids at a dose of approximately 12.6 gm/24 hours, no significant elevations out of the normal range of these substances occurred. Since urinary excretion rates did not dramatically increase, urinary loss was excluded as a possible cause for the failure of increase of plasma concentrations. The results suggest that the administration of an intravenous solution of 1-amino acids and hypertonic dextrose is associated with rapid clearance from the blood of these substances and, with a failure of increased urinary excretion, indirect evidence of amino acid utilization for protein synthesis has been obtained. Histidine supplementation in patients with acute renal failure is probably unnecessary based on the lack of significant decreases in histidine concentrations in these patients.     

Amino Acid Loss During Hemofiltration

Loss of free amino acids during hemodiafiltration therapy-was investigated in 5 dogs. Hemodiafiltration was performed with a cellulose-acetate membrane with a limit of molecular separation at MW 19, 000. The concentration of amino acids was investigated in ultrafiltrate and in blood at the beginning and at the end df diafiltration.

Loss of amino acids in the ultrafiltrate was seven times as much as free amino acid content of plasma, whereas amino acid concentration in plasma decreased only slightly (20 %).

Applying these results to hemodiafiltration in man, it is concluded that loss of amino acids in hemodiafiltration is not greater than in conventional hemodialysis therapy.     

Substrate Interaction in Intravenous Feeding. Comparative Effects of Carbohydrate and Fat on Amino Acid Utilization in Fasting Man

Data are presented on the metabolic and endocrine effects of intravenous infusions in normal fasting man observed under highly controlled conditions over a period of six to eight days duration. There are comparative data on a variety of intravenous feeding programs. The data on total starvation are based on studies from the literature, some of which were carried out in this laboratory. The data on low dose glucose, high dose glucose, glycerol, fat emulsion, and amino acids, each given separately, demonstrate changes seen with simple infusion of a single substrate in fasting. These data are now compared with the utilization of amino acid infusions when accompanied by low dose glucose, high dose glucose, glycerol, and fat emulsion. In all, nine experimental intravenous feeding programs are presented, based on data from 35 subjects observed over a total of 370 subject-days. The findings show a strong interaction between glucose or lipid and protein metabolism. In fasting, glucose had protein sparing effect, most evident when given at high dose. Glycerol, in an amount equal to that contained in 2000 ml of ten per cent fat emulsion, had a mild protein sparing effect. Fat emulsion was no more effective. When amino acids were given alone, normal fasting human subjects were always in negative nitrogen balance with the daily nitrogen loss half that seen in starvation alone. Although amino acids given alone have a protein sparing effect, this is accomplished only at the expense of a high nitrogen excretion including an amount equivalent to the entire infusion plus an additional loss from the body's native proteins.The provision of energy yielding non-protein substrates with the amino acids markedly improved nitrogen economy in the following order: glycerol, low dose glucose, fat emulsion and high dose glucose. When caloric provision with glucose approached the isocaloric level for normal diet, the utilization of amino acids was maximized. When given with amino acids, fat emulsion was more effective than the available glycerol alone.THE ACCOMPANYING ENDOCRINE AND BIOCHEMICAL CHANGES SUGGEST THAT THE MILIEU FOR IDEAL UTILIZATION OF INFUSED AMINO ACIDS IS VARIABLE: ketones at low range (carbohydrate) or moderately elevated (fat emulsion); insulin elevated (carbohydrate) or unchanged (fat emulsion). The utilization of the infused amino acids was markedly improved in both endocrine settings, suggesting that it is the provision of energy as substrate as well as the endocrine setting that determines amino acid utilization. There were other changes in plasma intermediates, particularly fatty acids, glucose and urea, all consistent with the concept that when amino acids are given without other substrates, the amino acids must be maximally utilized for gluconeogenesis. When other substrates are provided (particularly glucose at high dose) then this mandate no longer exists and protein synthesis from the amino acids is favored.Several of the plasma amino acid concentrations responded to glucose when added to amino acid infusion. Amino acids alone produced increases in concentration of all the amino acids found in the infusion with the exception of alanine, arginine, and threonine. Many of these increases were abated by the addition of glucose to the amino acid infusion, suggesting an increased utilization rate. Glycerol and fat emulsion, while modulating increases in the plasma amino acid concentration, did so to a lesser extent than did glucose. This lowering of amino acid concentration was unaccompanied by an increase in urinary excretion. The assumption is therefore made that the provision of the added glucose favors the incorporation of amino acid into protein. There is no evidence from these data to suggest that a rising concentration of ketones in the blood favors amino acid utilization or protein synthesis.     

Amino Acid Derangements in Patients With Sepsis: Treatment With Branched Chain Amino Acid Rich Infusions

Sepsis is a major catabolic insult resulting in modifications in carbohydrate and fat energy metabolism, and leading to increased muscle breakdown and nitrogen loss. Insulin resistance, which develops in sepsis, decreases glucose utilization, but plasma insulin levels are sufficiently elevated to prevent lipolysis, resulting in a further energy deficit. The availability of fuels in sepsis is therefore limited, and the body resorts to muscle breakdown, gluconeogenesis, and amino acid oxidation for energy supply. Previous work has not defined, however, the exact alterations in amino acid metabolism. Therefore, the following studies were undertaken. Blood samples were drawn from fifteen patients in whom the diagnosis of sepsis was clinically established; the samples were analyzed for amino acid, beta-hydroxyphenylethanolamines, glucose, insulin and glucagon concentrations. The plasma amino acid pattern observed was characterized by an increase in total amino acid content, due mainly to high levels of the aromatic amino acids (phenylalanine and tyrosine) and the sulfur-containing amino acids (taurine, cystine and methionine). Alanine, aspartic acid, glutamic acid and proline were also elevated, but to a lesser degree. The branched chain amino acids (valine, leucine and isoleucine) were within normal limits, as were glycine, serine, threonine, lysine, histidine and tryptophan. Those patients who did not survive sepsis had higher levels of aromatic and sulfur-containing amino acids as compared to those patients surviving sepsis. On the other hand, those patients surviving sepsis had higher levels of alanine and the branched chain amino acids. In a second group of five patients with overwhelming sepsis accompanied by a state of metabolic encephalopathy, a parenteral nutrition solution consisting of 23% dextrose, and an amino acid formulation enriched with branched chain amino acids was administered. In these five patients, normalization of the plasma amino acid pattern and reversal of encephalopathy was observed. The following sequence of events may be postulated: The septic patient develops insulin resistance in the peripheral tissues, primarily muscle, while the adipose tissue is much less affected. The insulin resistance and the inability to utilize fat leads to increased muscle proteolysis. Muscle breakdown results in release into the blood of enormous amounts of various amino acids; the muscle itself is able to oxidize the branched chain amino acids, supplying the muscles' own energy requirements and alanine for gluconeogenesis. The extensive muscle proteolysis coupled with relative hepatic insufficiency occurring early in sepsis results in the appearance in the plasma of high levels of most of the amino acids present in muscle, particularly the aromatic and the sulfur-containing amino acids. The outcome of patients with sepsis might be positively affected by combined therapy with glucose, insulin and branched chain amino acids.     

Osmotic Nephropathy Resulting from Maltose-Based Intravenous Immunoglobulin Therapy

Intravenous immunoglobulin preparations are being used for an increasing number of indications. To minimize adverse reactions, sugar additives such as sucrose, maltose, and glycine are added to some preparations to serve as stabilizing agents. Intravenous immunoglobulin infusion induces acute renal failure (ARF) via a mechanism of osmotic nephrosis. Most reported cases are related to the use of sucrose-based intravenous immunoglobulin. Herein, we describe a patient with lupus nephritis treated with an immunoglobulin preparation containing maltose who developed ARF with histologic changes characterized by vacuolization and swelling of renal proximal tubular cells. Our case draws nephrologists' attention to the potential of maltose-based immunoglobulin in producing renal failure. Awareness and exercising caution in high-risk groups is elementary to the prevention of this condition.     

四种脱蛋白骨氨基酸分析

通过对Oswestry骨、Kiel骨、乙醇、乙醚四种方法制备的牛脱蛋白骨(bDPB)的氨基酸成份分析间接推断其机械性能及抗原性差异。结果表明,四种方法制备的抗原性都低,而其中用20％H_2O_2脱蛋白,乙醚脱脂24h方法制备的bDPB芳香族氨基酸含量最低,而胶原类氨基酸含量最高,因而具有抗原性低,机械强度好的特点,加之来源广泛,制作简单,作为骨移植的材料或BMP的载体有较强的临床应用价值。     

纳滤技术用于氨基酸溶液的提纯

为进一步分离提纯已用超滤处理的γ-氨基酸（GABA）发酵液，用两款纳滤膜先后处理超滤的滤波。MWCO为800的SR2膜对氨基酸和盐均无明显的截留作用，可以截留较大的分子。MWCO为200的SR3膜能将氨基酸很好地截留，对盐也有一定的截留作用。两款纳滤膜分离与离心分离和超滤一起，可以脱除GABA发酵液中的大部分杂质，使GABA的纯度达到31．63％，取得了较好的分离效果。     

用氨基酸组分预测含顺式肽键蛋白质

以含有820个蛋白质结构数据的SLCTBASE数据库作为样本库,根据蛋白质序列氨基酸百分含量与顺式肽键的关联信息,构建了基于序列整体氨基酸含量的顺式构象势函数.利用此函数拟合得出的20种氨基酸的顺式构象因子值,进行两类蛋白质序列的分类和预测.训练集和测试集相同时和不相同时的预测准确率分别可达66%和64%.     

复方氨基酸胶囊联合克罗米芬治疗男性重度少精子症的疗效

目的:探究复方氨基酸胶囊联合克罗米芬治疗重度少精子症的疗效。方法:2018年1～9月就诊的104例重度少精子症患者纳入研究,随机分为试验组与对照组,试验组60例,对照组为44例。试验组口服复方氨基酸胶囊(0.70 g/次,2次/d)联合克罗米芬(50 mg/次,1次/d)12周,对照组口服克罗米芬(50 mg/次,1次/d)12周,对比及观察两组治疗前及用药后第4、8、12周精子浓度,前向运动(PR)精子百分率,精子总活率[PR+非前向运动(NP)精子百分率],以及用药期间的妊娠率。结果:试验组治疗前及治疗后第4、8、12周的精子浓度分别为(3.13±1.29)、(12.06±2.24)、(22.10±2.65)、(28.13±3.59)×10~6/ml;PR分别为(14.03±2.49)%、(21.05±3.14)%、(29.08±4.70)%、(35.08±3.70)%;PR+NP分别为(20.10±4.05)%、(27.10±4.87)%、(36.09±5.64)%、(45.04±6.69)%;对照组治疗前及治疗后第4,8,12周的精子浓度分别为(3.27±1.46)、(10.21±2.35)、(19.89±2.74)、(25.23±3.69)×10~6/ml,PR分别为(13.32±3.12)%、(17.02±3.26)%、(22.13±3.70)%、(27.18±2.54)%、PR+NP分别为(21.30±4.87)%、(24.22±5.07)%、(30.03±5.33)%、(35.05±5.69)%。与治疗前相比两组治疗后第4、8、12周精液参数有明显改善(P0.01),试验组同时段的精液参数均显著高于对照组(P0.01)。试验组和对照组用药后第4、8、12周配偶临床妊娠分别为1.72%vs 0.53%、4.21%vs 2.87%、8.32%vs 6.32%,均有显著差异(P0.01)。两组患者治疗期间均未见明显的不良反应。结论:复方氨基酸胶囊联合克罗米芬可明显改善重度少精子症患者精液参数,并有较好的安全性。     

Glutamine and Other Amino Acid Losses During Continuous Venovenous Hemodiafiltration

Abstract: Serum amino grams and daily losses of glutamine (Gin) and other amino acids (AAs) into diafiltrate were measured during the first 5 days of continuous venovenous hemodiafiltration (CVVHDF) in 6 ICU patients with acute renal failure (ARF). Four patients had ARF as a part of multiple organ failure (MOF) of septic origin, and 2 patients had isolated ARF because of primary renal disease. During the study, all the patients received defined total parenteral nutrition (TPN). The mean daily AA losses into dialysate were relatively low (0.61 ± 0.1 g N ) and reached 4.5% of the daily AA substitution. Gln represented 32.7 ± 5.9% of the total AA losses (0.19 ± 0.04 g N ). Serum levels of Gin (p = 0.002) and of most other AAs were significantly lower in the patients than in the control subjects (AA analysis in 16 healthy volunteers). Phenylalanine (Phe) was the only AA that was increased significantly (p < 0.01) in the patients. The mean patient serum concentrations of Phe and tyrosine were significantly higher (p < 0.03) than the correspondent concentrations in dialysate, but the lysine concentration was higher in dialysate (p < 0.03). The serum and dialysate concentrations of other AAs did not differ. Gin in serum decreased significantly (p < 0.03) on the second day of CVVHDF but returned to the baseline levels subsequently. Serum concentrations of Phe increased on the second day of CVVHDF (p < 0.05). Serum concentrations of other AAs remained stable during the whole study. We conclude that Gin losses into dialysate during CVVHDF are relatively low, but CVVHDF itself may induce changes in Gin metabolism and distribution that are reflected by a decrease of serum Gin levels at the institution of this treatment. Therefore, the need for Gin supplementation in ICU patients is even greater in the first days of CVVHDF.