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Z H Endre

Publications and source records attributed to Z H Endre.

At least 19 recordsLinked to original sources
PubMed1997

Regional proton nuclear magnetic resonance spectroscopy differentiates cortex and medulla in the isolated perfused rat kidney.

Volume-localized proton nuclear magnetic resonance spectroscopy was used as an assay of regional biochemistry in the isolated perfused rat kidney. This model eliminated artifacts caused by respiratory and cardiac motion experienced in vivo. Immersion of the kidney under its venous effluent reduced the susceptibility artifacts evoked by tissue-air interfaces. The rapid acquisition with relaxation enhancement imaging sequence was used for scout imaging. This gave excellent spatial resolution of the cortex, outer medulla, and inner medulla. Spectra were then acquired in 10 minutes using the volume-selective multipulse spectroscopy sequence from voxels with a volume of approximately 24 microL located within the cortical or medullary regions. Spectral peaks were assigned by the addition of known compounds to the perfusion medium and by comparison with spectra of protein-free extracts of cortex and medulla. The medullary region spectra were characterized by signals from the osmolytes betaine, glycerophosphorylcholine, and inositol. The spectra from the cortex were more complex and contained lesser contributions from osmolytes.

Animals↗
PubMed1997

Continuous measurement of gut luminal PCO2 in the rat: responses to transient episodes of graded aortic hypotension.

OBJECTIVES: To test the rapidity of a continuous PCO2 measurement system response to brief reductions in gut perfusion from transient episodes of graded aortic hypotension, and to investigate the relationship between the increase in ileal luminal PCO2 and mean aortic pressure during the episodes. DESIGN: Prospective, experimental animal study. SETTING: University research laboratory. SUBJECTS: Adult male Sprague-Dawley rats, weighing 430 to 510 g. INTERVENTIONS: Five Sprague-Dawley rats were anesthetized with intraperitoneal sodium phenobarbital and ventilated with 100% oxygen via tracheostomy to a PaCO2 of 30 to 50 torr (4.0 to 6.7 kPa). Distal aortic pressure was monitored invasively, and a sensor was inserted into the ileal lumen. Luminal PCO2 measurements were recorded every 2 secs. Normal saline was infused at 3 mL/hr, and isoflurane was titrated to a mean aortic pressure of 80 to 100 mm Hg. In each rat, paired 2-min inductions of distal aortic hypotension were induced by digital elevation of an aortic silk sling above the celiac artery to as many as possible of the following pressures (mm Hg): 60, 50, 40, 30, 20, and 10. The experiment was stopped if instability of luminal PCO2 or hypotension persisted through the intervening 8-min recovery periods. MEASUREMENTS AND MAIN RESULTS: One rat completed paired inductions of all six goal aortic pressures. Two rats completed five inductions. One rat completed four inductions, and one rat completed three inductions. The times to onset of luminal hypercapnia and to peak luminal hypercapnia were highly consistent and independent of the degree of hypotension. Onset of hypercapnia was usually detected < 1 min after aortic elevation, but peak luminal hypercapnia occurred approximately 1 min after release of the aortic sling. Regression analysis showed an inverse linear relationship between the maximum increase in luminal PCO2 above baseline and mean aortic pressure during induced hypotension (r2 = .6; p < .001). CONCLUSIONS: Continuous ileal luminal PCO2 measurement by the sensor is rapidly responsive to brief reductions in aortic pressure in a rat model. Maximum luminal PCO2 increase during such perturbations is inversely related to mean aortic pressure.

Animals↗
PubMed1996

Modulation of glycine-serine interconversion by TCA and glycolytic intermediates in normoxic and hypoxic proximal tubules.

Glycine-serine interconversion is important to numerous metabolic processes and serine release by the kidney. Incubation of freshly isolated rat renal proximal tubules with 5 mM glycine 75% 13C-labelled in the 2-position resulted in 13C-labelled incorporation into serine of 69 micromol.g protein(-1) (+/- 14, n = 16) at 20 min. Addition of 5 mM glucose, 4 mM lactate, 1 mM alanine, 1 mM butyrate and 1 mM glutamate increased 13C-label incorporation into serine to 173 micromol.g protein(-1) (+/- 32, n = 4) at 60 min, 50% greater than tubules incubated with 5 mM glycine alone (P < 0.05). The increase was prevented by hypoxia. Reoxygenation for 20 min restored the rate of incorporation of 13C-label into serine. The fraction of unlabelled serine remained approximately 47% at 20, 40 and 60 min in each group. The results indicate that in the presence of oxygen, TCA and glycolytic intermediates stimulate serine synthesis via the glycine cleavage complex and serine hydroxymethyltransferase pathways and not the phosphorylated pathway. In addition, significant serine production occurs from an unidentified source, which is also tightly coupled to glycine metabolism. Both in the presence and absence of added TCA and glycolytic intermediates, glycine was the principle source of the methylene group in methylene tetrahydrofolate.

Animals↗
PubMed1996

Serine isotopmer analysis by 13C-NMR defines glycine-serine interconversion in situ in the renal proximal tubule.

[2-(13)C]glycine metabolism was studied in freshly isolated rat renal proximal tubules. Mitochondrial coupling of the glycine cleavage complex (GC) and serine hydroxymethyltransferase (SHMT) was confirmed by the formation of three serine isotopomers, [2-(13)C]-, [3-(13)C]- and [2,3-(13)C]serine, detected by 13C-NMR. Incubation with different fractions of 13C-labelled glycine altered the labelling pattern of the serine isotopomers predictably and allowed calculation of the 13C-labelled fractions of total glycine and methylene in N5,N10-methylenetetrahydrofolate (m-THF) available for serine metabolism. Within 20 min there was a fall in labelled glycine (to 42 +/- 3, 68 +/- 3 and 93 +/- 2%, (n = 4, mean +/- S.D.) from 50%, 75% and 100% 13C-labelled added glycine respectively), followed by a slow rate of endogenous glycine formation for up to 80 min incubation. The C2 of glycine was the source of more than 90% of the methylene group of m-THF formed. Gas chromatography-mass spectroscopy (GC-MS) showed that greater than 50% of serine formed was unlabelled. GC and SHMT proceeded in the direction of serine formation. Serine isotopomer analysis by NMR and GC-MS allowed the actions of GC and SHMT and de novo contributions to glycine, serine and m-THF to be monitored in situ in fresh renal proximal tubules.

Animals↗
PubMed1996

Detection of hydroxyl and carbon-centred radicals by EPR spectroscopy after ischaemia and reperfusion of the rat kidney.

Recent studies suggest that oxygen-derived free radicals are involved in mediating renal reperfusion injury. EPR spectroscopy and spin trapping with the spin traps DMPO and PBN, were used to detect and quantitate the formation of hydroxyl radicals in rat kidney after ischaemia-reperfusion in vivo and in vitro in the isolated rat kidney perfused in the absence of leucocytes. EPR analysis of homogenised kidneys and of venous samples did not detect radical adducts with either spin trap. With PBN, radical adducts were not detected in vitro. When DMPO was used as the spin trap in kidneys perfused without albumin in the perfusate, EPR signals characteristic of hydroxyl and carbon-centred radical adducts were detected during early reperfusion following ischaemia. These studies confirm the generation of hydroxyl radicals during ischaemia-reperfusion in kidney. During reperfusion the total DMPO adduct concentration reached 4.35 +/- 1.05 nmol/g kidney/3 min, p < 0.05. In control kidneys total adduct were present at lower concentration (2.55 +/- 1.1 nmol/g kidney/3 min). Addition of 15 mM dimethylthiourea abolished formation of these adducts following ischaemia-reperfusion but did not prevent a reduction in glomerular filtration rate. These results indicate that significant levels of hydroxyl and carbon-centred radicals are formed in the absence of circulating neutrophils during early renal reperfusion following ischaemia.

Animals↗
PubMed1995

Hydroxyl radical generation following ischaemia-reperfusion in cell-free perfused rat kidney.

The difficulty in direct detection of oxygen-derived free radicals (OFR) in the intact kidney has left uncertain the role of OFR in renal hypoperfusion injury. Salicylate hydroxylation was used as a sensitive method of estimating the extent of production of highly reactive hydroxyl radicals in renal ischaemia-reperfusion injury in the intact rat kidney perfused with recirculating cell-free medium. The reaction products were detected and quantified by HPLC with electrochemical detection. Hydroxyl radicals were detected as 2,5-dihydroxybenzoic acid (2,5-DHBA). Ischaemia for 15 min followed by reperfusion for 15 min caused more than a twofold increase in 2,5-DHBA concentration (to 2279 +/- 225 pg/g tissue weight) compared to controls (933 +/- 103, P < 0.001). Addition of 15 mM dimethylthiourea (DMTU) before induction of ischaemia prevented this increase. Induction of hypoxia for 15 min with continued perfusion (as a model of low-flow ischaemia) had no significant effect on hydroxyl radical formation. We conclude that significant quantities of hydroxyl radicals form in the absence of circulating leucocytes during reperfusion following ischaemia, but not during hypoxia in the perfused rat kidney.

Animals↗
PubMed1995

Renal glomerular lesions in unselected patients with cirrhosis undergoing orthotopic liver transplantation.

Renal biopsies were obtained from 23 patients at the time of orthotopic liver transplantation. Twelve biopsies showed minor glomerular abnormalities, 2 exhibited IgA nephropathy and one showed mesangiocapillary glomerulonephritis type I. The remaining 8 patients had glomerular lesions diagnosed as hepatic glomerulosclerosis (HGS). Immunofluorescence, available in 6 of the 8 biopsies with HGS, revealed granular deposits of immunoglobulins and complement in glomerular capillary walls and/or the mesangium. IgA was seen in 5 biopsies with HGS, but the staining for this protein was no more intense than that for the other immunoglobulins in 4 of these. Electron microscopy in HGS revealed partial mesangial interposition, hypertophy of mesangial and endothelial cells, granular material in a widened subendothelial space, slender projections of endothelial cytoplasm extending into the subendothelial space, and clusters of vesicles in the mesangium and glomerular capillary walls. These ultrastructural abnormalities have not hitherto been reported as a group of associated pathological changes. The renal biopsies were obtained from patients with advanced hepatic disease not selected because of urinary abnormalities or renal dysfunction. The frequency of lesions in this group of patients therefore probably reflects the true incidence of glomerular lesions in cirrhosis and related conditions. Progressive decline in renal function was not observed in any patient during follow up which ranged from 11 days to 55 mths.

Adolescent↗
PubMed1995

Siggaard-Andersen algorithm-derived p50 parameters: perturbation by abnormal hemoglobin-oxygen affinity and acid-base disturbances.

The p50 and derived indexes, calculated by using the Siggaard-Andersen algorithm from a single measurement of arterial blood gas tensions and hemoglobin-oxygen saturation, are used to assess tissue oxygen availability in critical illness. We tested the accuracy of the Siggaard-Andersen p50 algorithm over a wide range of pathophysiologic conditions. Blood gases, cooximetry, and calculation of standard and in vivo p50 were performed at multiple saturations, CO2 tensions, and H+ concentrations on blood with normal (standard p50 of 26.1 and 26.7 mm Hg), increased (19.0 and 25.4), and reduced (33.9 and 38.2) hemoglobin-oxygen affinity, as well as on high-affinity blood from two patients with diabetic ketoacidosis (16.7 and 20.8). Log p50 in vivo/pH plots were constructed to determine the Bohr effect. Except in the normal affinity specimens (coefficient of variation < 1.7%), standard p50 values showed high variability (coefficient of variation > 5.9%), with saturation-linked bias and distortion of the Bohr effect. Standard p50 was overestimated by up to 11 mm Hg as saturation approached 97%. Although base deficit correction of the stored specimens (6.9 < pH < 7.1) restored the Bohr effect and improved the accuracy of standard p50 calculations (coefficient of variation = 4.4% and 2.9%), saturation-linked bias persisted. We conclude that Siggaard-Andersen p50 calculations may be misleading when there are disturbances of hemoglobin-oxygen affinity and acid-base balance, owing to changes in shape of the hemoglobin-dissociation curve. When metabolic acidosis occurs with high hemoglobin-oxygen affinity, as can occur in critical illness, indexes derived by the Siggaard-Andersen algorithm on arterial blood may greatly overestimate oxygen availability.

Acid-Base Imbalance↗
PubMed1994

23Na NMR detects protection by glycine and alanine against hypoxic injury in the isolated perfused rat kidney.

Protection against hypoxic injury by supraphysiological glycine and alanine concentrations was investigated in the isolated perfused rat kidney (IPRK). 23Na NMR detects consistent increases in total renal Na in IPRK during hypoxic perfusion. Increasing the concentration of glycine and alanine to 5 mM each produced a 34% (p < 0.001) reduction in the increase in total renal Na following 30 minutes of hypoxia compared to a matched control group supplemented with 5 mM each of serine and glutamine. There was also a trend (p = 0.067) to improvement in the fractional excretion of sodium (FENa) in the glycine plus alanine treated group. Hypoxic alterations of other physiological parameters were not prevented by supraphysiological glycine plus alanine. This suggests that monitoring total renal Na is a more sensitive method of defining renal injury and protection than monitoring changes in FENa, fractional excretion of potassium (FEK) and inulin clearance.

Alanine↗
PubMed1993

23Na-NMR detects hypoxic injury in intact kidney: increases in sodium inhibited by DMSO and DMTU.

Hypoxic injury in the isolated perfused rat kidney (IPRK) was monitored using 23Na-NMR in the presence or absence of 1.5 and 15 mM dimethylthiourea (DMTU) or 15 mM dimethylsulphoxide (DMSO) before and after inducing hypoxia. Hypoxia induced a prompt exponential increase in total renal 23Na+, renal vascular resistance, and sodium excretion and decreased inulin clearance and adenine nucleotides and reduced glutathione concentrations. Lipid peroxide metabolites were unaltered. The increase in 23Na+ was significantly reduced (P < 0.001) by both DMTU and DMSO although hypoxic perturbations of function and biochemical parameters were not. Posthypoxic increases in renal 23Na+ include approximately 10% from the intratubular compartment, but principally reflect the intracellular and interstitial compartments. The results demonstrate that 23Na-NMR is a sensitive indicator of hypoxic renal injury in intact kidney and suggest that DMTU and DMSO protect against hypoxic injury by a mechanism independent of free radical-binding.

Animals↗
PubMed1992

Glomerular abnormalities in children undergoing orthotopic liver transplantation.

A prospective study of renal function was undertaken on an unselected group of 8 children with chronic progressive liver disease on whom a renal biopsy was performed subsequently at the time of orthotopic liver transplantation. Two patients had abnormal urinalyses and 2 elevated urinary albumin/creatinine ratios. The remainder had no clinical evidence of renal dysfunction. All had normal serum creatinine concentrations. Glomerular abnormalities were present in all renal biopsies and were of two types: hepatic glomerulosclerosis (n = 5) and minor glomerular abnormalities (n = 3). IgM immunofluorescence was present in all biopsies and IgA in 6. Elevated serum immunoglobulin levels were observed in all patients, with IgM elevation in 6, IgA in 4 and IgG in 6. C3 and/or C4 were reduced in 5 patients and increased circulating immune complexes containing IgM were noted in 4. The clinical significance of these cirrhosis-associated glomerular abnormalities can only be established by long-term follow-up studies after orthotopic liver transplantation.

Albuminuria↗
PubMed1992

Universal occurrence of glomerular abnormalities in patients receiving liver transplants.

We conducted a prospective study of renal histology and function in 18 consecutive nonalcoholic patients who underwent orthotopic liver transplantation (OLT). Despite well-preserved renal function, all patients had abnormal renal biopsies. Four patterns of glomerular injury were identified: minor glomerular abnormalities (eight patients), hepatic glomerulosclerosis (seven), membranoproliferative glomerulonephritis (one), and IgA nephropathy (one). In one patient there was insufficient tissue to allow classification. There was a trend toward lower plasma bilirubin and higher plasma albumin in patients with minor glomerular abnormalities than in the group of patients with more severe forms of glomerular injury (29 v 82 mumol/L, 35.5 v 30 g/L; P = 0.1, 0.1 greater than P greater than 0.05, respectively). Glomerular changes persisted in the three patients who died within 7 weeks post-OLT. IgM immunofluorescence was present in all biopsies and IgA in 11. IgM-containing circulating immune complexes occurred in five patients, suggesting a pathogenic role for IgM immune complex deposition. The significance of cirrhosis-associated glomerular abnormalities is not yet known. They may contribute to the hepatorenal syndrome and the renal dysfunction that occurs in up to 94% of patients post-OLT.

Adolescent↗
PubMed1990

Hypophosphataemia after renal transplantation: relationship to immunosuppressive drug therapy and effects on muscle detected by 31P nuclear magnetic resonance spectroscopy.

Plasma phosphate values were examined in 72 renal transplant patients in a randomised trial of immunosuppression with azathioprine and prednisolone versus cyclosporin alone. From 21 to 77 days after transplantation, in patients with plasma creatinine concentrations of 75-150 mumol/l, mean plasma phosphate was 0.98 (SEM 0.04) mmol/l in cyclosporin-treated patients, compared with 0.65 (SEM 0.12) mmol/l in cyclosporin-treated patients receiving pulse methylprednisolone for rejection (P less than 0.003), and 0.68 (SEM 0.02) mmol/l in patients treated with azathioprine and prednisolone (P less than 0.001). There was no difference between the mean plasma creatinine of these groups of patients. A preliminary study by nuclear magnetic resonance spectroscopy of four patients with asymptomatic chronic hypophosphataemia showed reduced concentrations of intracellular phosphate in resting muscle, and further abnormalities developed on exercise. Thus, exogenous steroid administration is a major contributing factor of hypophosphataemia in the early post-transplant period. In addition chronic hypophosphataemia may be associated with reduced intracellular inorganic phosphate concentrations detectable by nuclear magnetic resonance spectroscopy, although these changes are not apparently associated with any clinical symptoms.

Azathioprine↗
PubMed1989

Skin cancer in renal transplant recipients.

Skin cancer was found in 31 of 598 patients transplanted in Oxford. No cases occurred during the first 3 years after transplantation but the prevalence rose after 12 years to 18.2 per cent. The main risk factors predisposing to skin cancer were the time after transplantation and male sex. Comparison with data from other centres suggests that exposure to ultraviolet light is a major aetiological factor in the speed of development of skin cancer. As the incidence of new cases rose progressively with time in our patients, it would seem that skin cancer is likely to become a major clinical problem as more patients enjoy prolonged survival after renal transplantation. Preventative and screening measures should be taken by transplant units both in the UK and in other countries with similar temperate climates.

Adolescent↗
PubMed1989

Toxicity of dysprosium shift reagents in the isolated perfused rat kidney.

Sodium and water spectra were acquired from the isolated perfused rat kidney by using a double-tuned probe designed to have high X nucleus sensitivity and low 1H sensitivity. Both DyTTHA and DyPPP were used to distinguish intra and extracellular 23Na resonances before and after the onset of hypoxia. Only DyPPP was useful in separating the two compartments, with a maximal chemical shift difference produced at a concentration of 4.5 mM. Both shift reagents were nephrotoxic at concentrations under 5 mM and produced an immediate decrease in renal-concentrating capacity and increases in fractional sodium and potassium excretion and increased renal vascular resistance. These disturbances of renal physiological parameters were accompanied by progressive broadening of the renal H2O resonance. 1H NMR may be a subtle means of monitoring nephrotoxicity.

Animals↗