Contraluminal transport of small aliphatic carboxylates in the proximal tubule of the rat kidney in situ

In order to study the characteristic of contraluminal transport of hydrophylic small fatty acids the in situ stopped flow microperfusion technique [12] has been applied. By measuring with 4 s contact time the decrease in the contraluminal concentration of the respective radiolabelled substances the concentration dependence of the influx into the cortical cells was tested. The 4 s decrease in contraluminal concentration of chloroacetate,l-lactate,d-lactate, 3-hydroxybutyrate and acetoacetate was between 26% and 31%. For each substance the percent decrease was the same, no matter whether it was offered in a concentration of 0.1 or 10 mmol/l. Contraluminal disappearance of 0.1 mmol/ll-lactate was not influenced by 5 mmol/l H₂DIDS, probenecid, phloretin, mersalyl or cyanocinnamate, but it was significantly (37%) inhibited by 5-nitro-2-(phenyl-propyl-amino) benzoate, a blocker of the nonspecific anion channel. The percent decrease in propionate uptake was somewhat larger — between 36% and 39% — but again not different at 0.01, 0.1, 1.0 and 10 mmol/l. With pyruvate the contraluminal decrease was 20% at 0.1 mmol/l and 31% at 10 mmol/l. The percent disappearance of the aromatic pyrazinoate was 38% and 34% at 0.1 and 10 mmol/l and for nicotinate 42% and 22%, respectively. The disappearance of nicotinate (0.1 mmol/l) was significantly inhibited by 10 mmol/l pyrazinoate and paraaminohippurate (PAH). The data are in agreement with the hypothesis that the hydrophilic small fatty acids traverse the contraluminal cell side by simple diffusion, possibly via the unspecific anion channel [14], pyruvate via the dicarboxylic acid pathway in a cooperative manner and pyrazinoate, as well as nicotinate, via the PAH pathway.     

Hormonal and metabolic response to three types of exercise of equal duration and external work output

Summary Five normal men, aged 20–30 years, participated in three types of exercise (I, II, III) of equal duration (20 min) and total external work output (120–180 kJ) separated by ten days of rest. Exercises consisted of seven sets of squats with barbells on the shoulders (I; Maximal Power Output _max=600−900 W), continuous cycling at 50 rev · min⁻¹ (II; _max=100−150 W) and seven bouts of intermittent cycling at 70 rev · min⁻¹ (III; _max=300−450 W). Plasma cortisol, glucagon and lactate increased significantly (P<0.05) during the exercise and recovery periods of the anaerobic, intermittent exercise (I and III) but not in the continuous, aerobic exercise (II). No consistent significant changes were found in plasma glucose. Plasma insulin levels decreased only during exercise II. The highest increase in cortisol and glucagon was not associated with the highest , , _max or HR; however it was associated with the anaerobic component of exercise (lactic acid). It is suggested that in exercises of equal duration and total external work output, the continuous, aerobic exercise (II) led to lowest levels of glucogenic hormones.     

Active and inactive renin after exercise

Summary The effects of graded exercise on plasma concentrations of active and inactive renin were studied in seven healthy men. Exercise was performed on a cycle ergometer at four different exercise intensities (corresponding to 30%, 50%, 80% and 87% of ) for 10 min each. Concentrations of active renin and total renin after activation by trypsin were measured by direct immunoradiometric assay. Non-trypsin-activated renin concentration (inactive) was obtained by subtraction. Active renin concentrations at 30%, 50%, 80% and 87% of were 1.2, 1.9, 3.1 and 4.6 times higher than the control concentration, respectively. Similar increases in plasma renin concentration, determined by conventional enzymatic assay, were observed at every stage. In contrast, changes in inactive renin concentration were not significant at any stage. Significant increases in noradrenaline concentration were found at every exercise stage, but adrenaline, aldosterone and lactate concentrations were significantly elevated only after exercise at 50%, 80% and 87% of . The similarity between the changes in concentration of active renin and noradrenaline would suggest that sympathetic nerve activity may have been responsible either for the release of active renin or for the conversion of inactive renin to its active form in the kidney.     

The effects of buffer ingestion on metabolic factors related to distance running performance

We examined the effects of sodium bicarbonate (BIC) and sodium citrate (CIT) ingestion on distance running performance. Seven male runners [mean = 61.7 (SEM 1.7) ml · kg^–1 · min^–1] performed three 30-min treadmill runs at the lactate threshold (LT) each followed by a run to exhaustion at 110% of LT. The runs were double-blind and randomly assigned from BIC (0.3 g · kg body mass^–1), CIT (0.5 g · kg body mass^–1) and placebo (PLC, wheat flour, 0.5 g · kg body mass^–1). Venous blood samples were collected at 5, 15 and 25 min during the run and immediately post-exhaustion (POST-EX) and analysed for pH, and the concentrations of lactate ([1a^–]_b) and bicarbonate ([HCO₃ ^– ]). Performance was measured as running time to exhaustion at 110% of LT (TIME-EX). The pH was significantly higher (P 0.05) for the BIC and CIT trials during exercise, but not POST-EX compared to PLC. The [1a^–]_b was significantly higher (P 0.05) for the CIT trial compared to PLC during exercise, and for both CIT and BIC compared to PLC at POST-EX. Blood [HCO₃ ^–] was significantly higher (P 0.05) during exercise for BIC compared to PLC. TIME-EX was not significantly different among treatments: BIC 287 (SEM 47.4) s; CIT 172.8 (SEM 29.7) s; and PLC 222.3 (SEM 39.7) s. Despite the fact that buffer ingestion produced favourable metabolic conditions during 30 min of high intensity steady-state exercise, a significant improvement in the subsequent maximal exercise run to exhaustion did not occur.     

Effects of glucose in protected ischemic kidneys

Summary Energy reserves (TAN) and anaerobic substrates (glucose, glycogen) are lower in renal than in myocardial tissue. Euro-Collins-solution contains nearly 200 mmol/l glucose, while the HTK-solution of Bretschneider contains none. Therefore the influence of glucose on kidney lactate production, on energy reserves (TAN), intrarenal pH and on morphology during the protection of ischemic kidneys was analysed using either Euro-Collins-solution, or modified Euro-Collins-solution, containing mannitol instead of glucose, or HTK-solution with and without the addition of 5, 10 and 20 mmol/l glucose. Glucose content changed during kidney perfusion with Euro-Collins-solution from about 60 to 800 mol/g_dw. While intrarenal pH decreased from 7.1 to 5.1 in Euro-Collins-kidneys during 420 min of ischemia at 25°C, pH decreased to 6.7 with the modified, mannitol containing Euro-Collins-solution. In HTK-protected kidneys intrarenal pH decreased with increasing glucose addition to the solution. Although Total Adenine Nucleotides are highest at the end of ischemia with Euro-Collins-solution, structural protection after the same ischemic stress was best in HTK-protected kidneys without glucose addition. We conclude that glucose stimulated lactate production, reduced interstitial pH in the kidney even in combination with a highly buffered solution and that it might cause greater membrane permeability leading to a structural detoriation. Mannitol seemed more appropriate than glucose in this respect, although other substances, which provide energy substrate and prevent structural damage, may exist.Supported by the Deutsche Forschungsgemeinschaft, SFB 89 —Kardiologie Göttingen     

改良琼脂糖凝胶电泳法测定血清LDH同工酶的应用

目的 寻求更加准确、简便、快速、实用的乳酸脱氢酶同工酶（LDH）测定方法。方法 据LDH同工酶等电点不同,选择琼脂糖胶作支持物,对以往LDH同工酶测定方法进行改进,将五型LDH同工酶进行分离并定量测定。结果 改进后的LDH同工酶测定方法稳定,区带清晰,重复性好,结果可靠,试剂可长期保存。结论 改良琼脂糖凝胶电泳法测定血清LDH同工酶应用前景良好。     

小鼠内毒素休克某些血液变化和细胞超微结构损伤的发生

小鼠内毒素休克有血液的乳酸、ＮＰＮ、ＡＫＰ、ＬＤＨ水平升高和ｐＨ值降低并可用６５４－２或ＡＬ所预防，只是预防ＮＰＮ升高的效应须在早期的肾血管挛缩消失后才能显示出来；心、肝、肠和肺的ＭＤＡ含量升高并可被６５４－２预防，除肺外还可被ＡＬ预防；将高肺ＭＤＡ只能用６５４－２预防结合注射内毒素后１０ｍｉｎ有ＷＢＣ入肺扣押来看，损伤肺的自由萁坷能主要来自被激活的中性粒细胞；血中ＡＫＰ和ＬＤＨ升高分别反映溶酶体     

Antemortem diagnosis of Leigh’s disease: Role of magnetic resonance studies

A two-and-a-half-year-old male child presented with recurrent attacks of intractable vomiting, psychomotor retardation since 14 months of age. He had also lower cranial nerve palsy and corticospinal involvement. Magnetic resonance imaging had shown multiple well circumscribed areas of hypointusity in T, weighted image which were brightly hyperintense in heavily T₂-weighted image. The lesions were seen in basal ganglia, thalamii and brainstenvand spared mamillary bodies. Magnetic resonance spectroscopy demonstrated lactate peak in the affected areas confirming the diagnosis of Leigh’s disease. The child responded well to large dose of vitamin ‘B’, therapy.     

Continuous monitoring of extracellular lactate concentration by microdialysis lactography for the study of rat muscle metabolism in vivo

A method is described for the measurement and on-line monitoring of muscular extracellular lactate concentration in both anaesthetized and freely moving rats. This method is based on microdialysis sampling and lactic dehydrogenase-catalysed nicotinamide adenine dinucleotide, reduced (NADH)-fluorescence detection techniques. In vivo calibration revealed a resting extracellular lactate concentration of 1.92±0.13 mmol/l (± SEM) in the gastrocnemius muscle of adult male Wistar rats (n=6), while the average whole-blood lactate level was 0.76±0.12 mmol/l (± SEM). This measured extracellular lactate concentration was 1.73-times higher than that deduced from the arterial lactate concentration. Blocking glycolysis with iodoacetate reduced the extracellular lactate concentration to 52±6% (± SEM, n= 4) of the resting level. The extracellular lactate concentration in rat gastrocnemius muscle had increased to significantly (P0.05) different levels, 2.4±0.03 (± SEM) or 4.0±0.55 (± SEM) times the control value, 1 h after aortic clamping (n=3) or cardiac arrest (n=3), respectively. Stimulation of the sciatic nerve induced elevations of the extracellular lactate concentration in the tibialis anterior muscle which were linearly related to the recorded isometric force-time integral. We also monitored on-line the changes in extracellular lactate concentration in the tibialis anterior muscle of a swimming rat. Our results indicate that microdialysis lactate reflects also intracellular metabolism. Lactography may be a useful alternative to biopsies and nuclear magnetic resonance spectroscopy in clinical medicine and physiology for the monitoring of metabolism in vivo.     

Effects of lead,copper, and zinc on the rat's lactate dehydrogenase in vivo and in vitro

Following subacute intoxication of rats with Pb-, Cu-, and Zn-salts (separately or in mixture) for 5 weeks, the chelating agent D-penicillamine was administered for 3 weeks. In the course of the 3-month experiment, lactate dehydrogenase (LDH) was estimated in serum and in cytoplasmic fraction of the kidney. Pb²⁺ treatment resulted in an increase of LDH activity, Cu²⁺ in a slight decrease, whereas Zn²⁺ had no effect, respectively. Mixture of these metals caused a significant rise in the enzymatic activity. Seven weeks after the stoppage of the administration of toxic substances, altered LDH activity, both in serum and in kidney returned to normal. D-penicillamine treatment was found to accelerate a restoration of the enzyme activity.In the experiments in vitro, Cu²⁺ inhibited significantly the kidney LDH activity, Pb²⁺ and Zn²⁺ being 100- and 400-times less efficient, respectively. Cu²⁺ inhibition was reversed by D-penicillamine, whereas inhibition of LDH by Zn²⁺ or Pb²⁺ was irreversible.