Connective tissue metabolism in children with chronic renal failure

To assess the characteristics of connective tissue metabolism in chronic renal failure (CRF), urinary excretion of glycosaminoglycan (GAG) fractions and hydroxyproline (HYP) was determined in ten patients with CRF and in ten age-matched healthy children. CRF was found to be associated with elevated free HYP (19.9±6.1 vs 9.8±3.6 mol/day,P<0.05) and depressed peptide HYP excretion (33.1±13.5 vs 225.2±17.7 mol/day,P<0.01), a low rate of total GAG excretion (7.0±2.4 vs 16.1±1.9 mol uronic acid/day,P<0.05) with low chondroitin 4 — sulphate + chondroitin 6 — sulphate (Ch-Ss) (14.0±9.9 vs 65.0±22.1%) and a high proportion of non-sulphated or under-sulphated fractions, i.e. hyaluronic acid + chondroitin + heparan sulphate (HA+Ch+HS) (75.3±11.4 vs 31.5±5.7%). Urinary 3-methyl-histidine (3-met-HIS) excretion and plasma essential free amino acids did not differ in the two groups. In response to haemodialysis no consistent change occurred in urinary excretion of 3-met-HIS, peptide-bound HYP, total GAG or percentage distribution of individual GAG fractions. After haemodialysis all plasma amino acids decreased significantly, and there was a significant increase in urinary excretion of free HYP (P<0.05). We conclude that the alterations in urinary excretion of total and individual GAGs observed in CRF may reflect disturbed connective tissue metabolism which does not appear to be accounted for by protein malnutrition or enhanced protein breakdown and remains uninfluenced by haemodialysis therapy.     

Cardiovascular reflexes and low long-term exposure to mercury vapour

Summary Subjective symptoms related to autonomic dysfunction and quantitative non invasive tests measuring both sympathetic and parasympathetic functions of the autonomic nervous system were studied among a group of 41 chlorine-alkali workers with low long-term exposure to mercury (Hg') vapour and their matched referents. The test battery included measurements of pulse rate variation in normal and deep breathing, in the Valsalva manoeuvre and in vertical tilt as well as blood pressure responses during standing and isometric work. The exposure time had been 16 years on average, and the mean exposure to Hg vapour was estimated to have been about 30 g/m³ of air. Only a tendency for a subtle reduction of cardiovascular reflex responses and a slight increase of subjective symptoms were seen in the exposed group, but no significant autonomic dysfunction was associated with the low level of exposure.     

Biochemical characterisation of para-aminophenol-induced nephrotoxic lesions in the F344 rat

The acute biochemical effects of the nephrotoxin p-aminophenol (PAP) were studied in detail using a combination of conventional bioanalytical and ¹H-NMR spectroscopic methods. Dosing PAP (25–100 mg/kg) to male F344 rats resulted in a dose-related proximal nephropathy with consequent elevations in urinary enzymes, glucose, and urine total protein as shown by conventional methodology. ¹H-NMR spectroscopy at 400 MHz of urine from PAP-treated rats also revealed a characteristic glycosuria, with concomitant amino aciduria. The increased excretion of these compounds indicates functional defects in the proximal tubule and reduced solute reabsorption efficiency. In addition, ¹H-NMR urinalysis and conventional enzymatic analysis showed a dose-related lactic aciduria. Other changes detected by ¹H-NMR included a dose-related reduction in the excretion of citrate (confirmed by a conventional biochemical method) and an increase in the excretion of acetate. The degree of abnormalities shown by ¹H-NMR urinalysis agreed well with histopathological observations and conventional biochemical indices of nephrotoxicity. ¹H-NMR urinalysis therefore serves to highlight changes in the excretion of low MW urine components not routinely studied by conventional biochemical analysis.Abbreviations ALP alkaline phosphatase - APAP paracetamol - BUN blood urea nitrogen - GFR glomerular filtration rate - GOT glutamate oxaloacetate transaminase - LAP leucine aminopeptidase - LDH lactate dehydrogenase - MW molecular weight - NAG N-acetyl--D-glucosaminidase - PAP p-aminophenol - ppm parts per million - TMAO trimethylamine N-oxide - UFR urine flow rate     

The early phase of experimental acute renal failure

Summary Experiments were designed to determine whether leakage of substances across the tubular epithelium, which are impermeant in the normal kidney, falsifies the measurement of glomerular filtration rate in acute renal failure. Permeability to those substances most commonly used for filtration rate determination, polyfructosan, inulin and ferrocyanide, was estimated by measuring their recoveries following perfusion through various nephron segments in haeme pigment, ischaemic and nephrotoxic models of actue renal failure. Late proximal recovery of¹⁴C ferrocyanide was only marginally decreased compared to controls, by a maximum of 6%. Distal recovery of polyfructosan,¹⁴C and³H inulin were depressed somewhat more, by a maximum of 11%. Urinary recovery of¹⁴C inulin was reduced by only 15% in kidneys showing severely restricted renal function. It is concluded that tubular leakage is not a feature of significance in the early phase of moderate acute renal failure, that ferrocyanide and inulin are reliable markers for the determination of nephron filtration rate and water reabsorption, and that the reduction in whole kidney inulin or polyfructosan clearance reflects primarily a reduction in glomerular filtration rate.     

膀胱抗菌机制—粘膜抗菌蛋白初步研究

本文报道以１％乙酸冲洗雌性Ｗｉｓｔａｒ大鼠膀胱和雌性新西兰白兔膀胱，分别获得其膀胱酸溶性提取物。ＡＵ－ＰＡＧＥ分析表明，两种膀胱粘膜酸溶性提取物都有十余条主蛋白带，而不含常见的杀菌物质溶菌酶和防御素样分子。琼脂糖弥散法杀菌试验显示，两种膀胱粘膜酸溶性提取物对致病性大肠杆菌ＭＬ－３５ｐ耐药株都有杀菌活性。进一步采用电泳凝胶琼脂糖弥散法杀菌试验分析，结果表明大鼠膀胱粘膜酸溶性提取物中有两条蛋白带具明显的杀菌活性，我们称这两条蛋白带为ＲａｔＢＰ－１和ＲａｔＢＰ－２。而兔膀胱粘膜酸溶性提取物的杀菌活性亦与两条被称为ＲａｂＢＰ－１和ＲａｂＢＰ－２的蛋白带相关。本文首次提示，在膀胱粘膜内存在抗菌蛋白，可能是膀胱粘膜杀菌作用的分子基础。     

The early phase of experimental acute renal failure

Experiments were conducted to establish whether diminished solute reabsorption in the loop of Henle during acute renal failure could explain the loss of urinary concentration and participate in generating a tubuloglomerular feedback-mediated reduction in filtration rate. The electrolyte content of the fluid in the ascending limb of the loop of Henle was determined in situ by monitoring its electrical conductivity after propulsion into the distal tubule with a sudden burst perfusion. The value of the minimum electrolyte concentration decreased exponentially with increasing equilibration time, reaching a steady-state value equivalent to 27±9 mM NaCl in normal kidneys, 34±15 mM in mercuric chloride kidneys and 53±22 mM following ischaemia. A mathematical model was derived to describe the process of sodium chloride dilution from which it was possible to calculate both the permeability and transport velocity of the cortical thick ascending limb. In the normal kidney, the transport velocity was calculated to be 4.65±0.92 ·10^–5 cm/s, a value not significantly different from that of the mercuric chloride or ischaemic kidneys, and the estimated permeability was 1.13±0.52·10^–5 cm/s, not different from that of the mercuric chloride kidneys but significantly lower than that calculated for the ischaemic kidneys. It is concluded that for the more severely damaged ischaemic model, the loss of urinary concentrating ability was accompanied by a reduction in diluting ability of the ascending limb of the short loop of Henle, which appears to be due, at least in part, to an elevation of the passive permeability to sodium chloride in this segment.     

Cystometric changes in the early phase of streptozotocin-induced diabetes in rats: evidence for sensory changes not correlated to diabetic neuropathy

Summary 1. The effect of streptozotocin (STZ) induced diabetes on rat urinary bladder function was investigated by means of in vivo cystometry and in vitro recording of bladder strips contractility. A group of sucrose-fed animals was included to determine to what extent the STZ-induced changes were ascribable to the increased diuresis. 2. After 7–9 weeks from STZ injection there was a marked increase in weight of bladder and ureters. Cystometry revealed a marked increase in bladder capacity (volume threshold) although pressure threshold and amplitude of micturition contraction were unaffected. Sucrose-fed animals, having normal blood glucose levels but a similar increase in urine production exhibited cystometric changes identical to those of STZ animals. 3. In vitro experiments indicated that the response to field stimulation (0.1–20 Hz) is reduced in STZ-pretreated but increased in sucrose-fed animals, as compared to controls. 4. The content of urinary bladder and ureters in sensory neuropeptides (substance-P, neurokinin-A and calcitonin-gene related peptide-like immunoreactivity) was increased by STZ diabetes when values were corrected for the increased weight of these organs. 5. The capsaicin-induced contraction of the rat isolated bladder strips, presumably caused by neuropeptides released from intramural sensory nerves, is unaffected by STZ diabetes. 6. These findings indicate that STZ diabetes produces, at an early stage, changes similar to those reported to occur in the human disease, e. g. a greater bladder capacity with unimpaired voiding function. The increased bladder capacity of STZ-rats seems largely, if not solely, ascribable to changes in physical properties of the detrusor muscle, thereby allowing accomodation of greater than normal volumes with similar increase of intraluminal pressure. No sign of diabetic neuropathy of the capsaicin-sensitive sensory nerves can be observed at this stage (7–9 weeks) of STZ diabetes. Send offprint requests to P. Santicioli at the above address