Urinary arginine and ornithine in occupational exposure to 2-ethylhexanoic acid

Nine sawmill workers were divided into two groups according to their exposure to 2-ethylhexanoic acid, (EHA), a pesticide which has replaced the older pentochlorophenol. The men with lower exposure excreted 30±10 nmol EHA/mmol creatinine (mean ±SD,n=4) in urine samples taken after the workshift, whereas men with higher exposure excreted 1.8±1.6 mol EHA/mmol creatinine (mean±SD,n=5,p<0.01). The urinary ornithine and arginine concentrations were at the lower exposure 1.4±0.4 and 1.5±0.8 mol/mmol creatinine, respectively (mean±SD,n=4), and they increased significantly (p<0.01) to 4.5±2.5 and 3.2±1.5mol/mmol (mean±SD,n=5), respectively, at the higher exposure. This might have been caused by the inhibitory effect of EHA on urea synthesis which was partially compensated for by elevated arginine and ornithine concentrations to drive the urea cycle more efficiently.     

基因重组细胞生长肽和精氨酸拮抗环孢霉素A的睾丸毒性

目的 探讨基因重组细胞生长肽（bFGF)和精氨酸对环孢霉素A（CsA)在血和睾丸中药物浓度及其睾丸毒性的影响。方法 将80只大鼠随机分为4组：N组,正常对照组;A组,CsA;B组,CsA 精氨酸;C组,CsA bFGF。每天腹腔注射给药,连续3周后取血及睾丸测定CsA浓度,按抗精子发生效应积分评定法作生精功能的评价,测定曲细精管直径及作病理学检查。结果 血药浓度B组明显高于A组（P＜0．05）;A,B,C组睾丸的发生明显障碍,而B,C组比A组的精子发生障碍要轻（P＜0．05）,曲细精管的直径A,B、C组明显小于N组（P＜）．05）,但B组大于A组（P＜0．01）。结论 CsA影响睾丸的生精功能,精氨酸和bFGF能明显降低CsA对睾丸的毒性作用,精氨酸还能提高血中CsA的浓度。     

原发性高血压病人红细胞L-精氨酸/一氧化氮系统的改变

目的 :探讨原发性高血压病人红细胞精氨酸 /一氧化氮系统的改变。方法 :通过核素标记测定红细胞3H L Arg转运的特征 ;一氧化氮合酶 (NOsynthase ,NOS)改良法测定红细胞NOS活性 ;放射免疫法测定环磷酸鸟苷(cGMP)的含量。结果 :高血压组红细胞L Arg摄入的最大转运速率 (Vmax)较正常组明显降低 ,但两组L Arg转运的亲合力 (Km)无差异。其中高血压组经过Y+通道的Vmax与正常对照组比较明显下降 ,Km与正常组无差别。经过Y+L通道的Vmax与正常对照组比较无变化 ,Km升高。高血压组红细胞NOS生成量及NOS活性均降低。高血压时红细胞中的cGMP的含量也较正常人明显减少。结论 :高血压时红细胞利用精氨酸生成一氧化氮的能力下降     

精氨酸对肠粘膜屏障功能的影响

目的：了解精氨酸对肠粘膜屏障功能的影响。方法：雄性ＳＤ大鼠３０只,随机分为三组。精氨酸组予精氨酸０．２５ｇ腹腔注射,假手术组和肠梗阻组予生理盐水作对照,１次／ｄ,共５ｄ。再手术将肠梗阻组、精氨酸组大鼠结扎回肠,造成单纯性机械性肠梗阻模型,假手术组仅作剖腹探查。术后２４ｈ处死大鼠采集标本。结果：①细菌移位率和移位数水平肠梗阻组和假手术组相比明显升高,精氨酸组和肠梗阻组相比明显减少。②血浆内毒素水平肠     

Cationic amino acid fluxes beyond the proximal convoluted tubule of rat kidney

To investigate the fluxes of cationic amino acids beyond the proximal convolution, we micropunctured and microperfused superficial tubules of male Wistar rats in vivo et situ. In free-flow micropuncture experiments, the concentrations of endogenous L-arginine⁺, [Arg], and of intravenously infused L-homoarginine⁺, [HoArg], were determined by HPLC. Fluorescein isothiocyanatelabeled inulin was detected on-line in the same tubular fluid samples. To determine undirectional fluxes, radiolabeled Arg and inulin were (1) microperfused through short loops of Henle and (2) microinfused into different tubule segments to measure urinary recovery of the radiolabel. At a mean [Arg]_plasma of 116 mol/l, [Arg] was 9.3 mol/l in the late proximal tubule (LPT), and 35.6 mol/l in the early distal tubule (EDT) corresponding to fractional deliveries (FD) of 0.055 in LPT and 0.078 in EDT. Fractional urinary excretion (FE) of Arg was 0.00033 (P<0.05 vs FD_EDT). Infusion of HoArg (2.5 or 7.5 mol/min) led to respective mean [HoArg]_plasma values of 1.44 and 3.73 mmol/l, and resulted in respective FD_LPT values for HoArg of 0.23 and 0.53, respective FD_EDT values of 0.29 and 0.41, and finally, respective FE values for HoArg of 0.25 and 0.58. When short loops of Henle were microperfused with 1 or 50 mmol/l [¹⁴C]Arg (+[³H]inulin), fractional recovery (FR) of ¹⁴C (relative to inulin) in the EDT was 0.13 and 0.36, respectively. During microinfusion of radiolabeled Arg (1 or 50 mmol/l) and inulin into LPT, the urinary FR of the radiolabel was 0.14, or 0.59, respectively. If 0.007, 1 or 50 mmol/l radiolabeled Arg were microinfused into EDT, the respective urinary FR of the radioactivity was 1.02, 1.10, or 1.01. Microperfusion of microinfusion of 1 mmol/l [¹⁴C]Arg plus 50 mmol/l HoArg resulted in a FR_EDT of ¹⁴C of 0.43 (loop, perfusion) and an FE for ¹⁴C of 0.69. Five conclusions can be drawn. First, cationic amino acids can enter and leave the lumen of short loops of Henle through specific carrier(s) at high rates, although, secondly, net transport is small or absent. Thus, medullary tubule cells can be supplied with Arg from the lumen of short loops of Henle for urea and nitric oxide production. Thirdly, the distal convolution of superficial nephrons and the collecting duct are not permeable to Arg. Thus, fourthly, the difference between FD_EDT and urinary FE of Arg must be explained by an inter-nephron heterogeneity between deep and superficial nephrons. Finally, the process responsible for the different Arg handling in deep nephrons is not accessible to HoArg or, if so, it is saturated at millimolar concentrations.     

Nitric oxide synthase activity is inducible in rat,but not rabbit alveolar macrophages,with a concomitant reduction in arginase activity

Alveolar macrophages were obtained by broncho-alveolar lavage of isolated rat and rabbit lungs and cultured (2.5 × 10⁶ cells/dish) for 18 h in the absence or presence of bacterial lipopolysaccharides (LPS) alone or in combination with cytokines. Thereafter, accumulation of ³H-citrulline (NO synthase activity) and ³H-ornithine (arginase activity) were determined.During incubation of rat alveolar macrophages with ³H-arginine clear amounts of ³H-citrulline and ³H-ornithine (3.8 and 4.6% of the added ³H-arginine, respectively) were formed and most of these metabolites appeared in the incubation medium (ratios extra-/intracellular of 17 and 70 for ³H-citrulline and ³H-ornithine, respectively). When rat alveolar macrophages had been cultured with LPS the formation of ³H-citrulline was increased about 30-fold and this was accompanied by a reduction in ³H-ornithine formation of about 60%. The effects of LPS were largely attenuated by dexamethasone (10 mol/1). Inhibition of NO synthase by N^G-monomethyl-l,-arginine (l-NMMA, 100 mol/1) in LPS treated alveolar macrophages reduced the formation ³H-citrulline by more than 90% and restored the ³H-ornithine formation. After culturing in the presence of LPS the ratios extra/intracellular of ³H-citrulline and ³H-ornithine were markedly enhanced and this effect was not dexamethasone sensitive. During incubation of rabbit alveolar macrophages a marked formation of ³H-ornithine (about 5.3% of the added ³H-arginine), but no significant formation of ³H-citrulline could be detected. Pretreatment with LPS tended to enhance the formation of ³H-ornithine (by 50%) without effects on ³H-citrulline. Rabbit-interferon and/or tumor necrosis factor- present together with LPS during the culture period did not result in a significant ³H-citrulline formation. Under all conditions tested, culture media of rabbit alveolar macrophages did not contain significant amounts of nitrite (less than 0.5 nmol) whereas in culture media of untreated rat alveolar macrophages 22 nmol nitrite (per 18 h) were detected, and LPS induced a 3-fold nitrite accumulation, an effect prevented by dexamethasone.In conclusion, in rabbit alveolar macrophages NO synthase activity was not detectable and could also not be induced by LPS and different cytokines, whereas in rat alveolar macrophages NO synthase was readily inducible. Alveolar macrophages of both species showed marked arginase activity. After induction of marked NO synthase activity, ornithine formation was largely reduced possibly by concomitant inhibition of arginase and/or withdrawn of arginine from arginase.     

Pharmacokinetics of arginine butyrate in patients with hemoglobinopathy

Recent reports have demonstrated improvement in the clinical status and hemoglobin levels with use of intravenous arginine butyrate in patients with homozygous β-thalassemia and sickle cell disease.

To allow optimalization of therapy, we conducted pharmacokinetic studies in nine patients, five with sickle cell disease and four with β-thalassemia, treated with continuous intravenous infusion of arginine butyrate.

The disappearance of the drug after discontinuation was characterized by a biphasic elimination with an initial rapid phase followed by a slower phase. Redistribution was noted in five of the patients after 11.2 ± 4.0 min. The short half life was the result of both rapid clearance rate of 93.6 ± 31.9 ml/kg/min and small Vc (0.21 ± 0.26 l/kg) and Vss (0.31 ± 0.37 l/kg).

While preliminary results of the effectiveness of arginine butyrate are encouraging with a rise of γ-globin mRNA and F reticulocytes in some patients, the rapid elimination of this agent will probably limit its current use to administration by continuous infusion.     

Spike conduction properties of T-shaped C neurons in the rabbit nodose ganglion

Noradrenaline (NA) and angiotensin II (A II) were infused intravenously in conscious dogs without (series I) and with (series II) additional infusions of sodium nitroprusside at doses re-establishing normal levels of mean arterial pressure (MAP). In series I, NA infusion (1.6 g/min per kg for 30 min) initially elevated MAP by some 25 mm Hg and lowered heart rate by some 30 beats/min. Plasma concentrations of arginine vasopressin (AVP) remained constant, while those of A II and atrial natriuretic factor were slightly, but significantly, increased. Infusion of A II (10 or 20 ng/min per kg for 30 min) induced similar rises in MAP and slight reductions of heart rate and increased plasma AVP by 70% and atrial natriuretic factor by 60%. In series II, sodium nitroprusside (1–4 g/min per kg) was added for 30 min to infusions of NE (1.6 g/min per kg) and A II (20 ng/min per kg) in order to maintain MAP at its control level. This resulted in an 11-fold increase in plasma AVP during NA infusion and a 19-fold increase during A II infusion. Infusing sodium nitroprusside (4 g/min per kg) alone lowered MAP to clearly hypotensive levels, but the resulting rises in plasma AVP were less than, rather than equal to, those seen at normotensive MAP levels during the combined infusions of sodium nitroprusside with A II or NA, respectively. It is concluded that both NA and A II exert strong stimulatory actions on AVP release which are, however, counteracted by inhibitory influences arising from the hypertensive effects of NA and A II.     

AccQ-Tag法测定复方精氨酸胶囊中精氨酸的含量

目的：建立测定复方精氨酸胶囊中精氨酸含量的AccQ—Tag法^[1,2,3]。方法：以6-氨基喹啉-N-羟基琥珀酰亚胺基甲酸酯(AQC)为衍生剂，与复方精氨酸胶囊中精氨酸柱前定量衍生，用Waters HPLC仪，AccQ—Tag^TM氨基酸分析柱，以pH4．95醋酸钠缓冲液为流动相A，乙腈—水(3：2)为流动相B，进行梯度洗脱，检测波长为248nm。结果：线性范围：0．1006～0．9054μg，r=0．9995(n=5)。回收率：99．7％，RSD0．38％(n=5)。结论：本法快速、简便，辅料无干扰，结果满意。