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B Odlind

Publications and source records attributed to B Odlind.

At least 37 records · Page 2Linked to original sources
PubMed1988

Tissue distribution of 125I-labelled bovine superoxide dismutase (SOD) in the rat.

Bovine copper/zinc superoxide dismutase (SOD) was labelled with 125I using the chloramine-T method. The tissue distribution of 125I-SOD (dose of SOD 5 mg/kg) was studied with whole-body and microautoradiography at various times after an intravenous injection. The distribution of 125I-SOD showed a remarkable organ specificity in that the localization of the enzyme to the kidneys and the urinary tract completely dominated the autoradiograms. The time pattern of localization of 125I-SOD also gives a clear picture of the renal handling of the enzyme in that, as a consequence of the renal elimination, the enzyme rapidly disappears from the circulation with an elimination half time of about 6 min. Up to 20 min. after the injection, there were high concentrations of 125I-SOD in the renal pelvis, ureter and urinary bladder showing that in addition to renal uptake there was an initial substantial urinary excretion of the enzyme. From the microautoradiography it is clear that the grains were exclusively localized over proximal tubular cells and tended to be concentrated at the luminal rather than the peritubular side of tubule. This would be compatible with renal uptake secondary to glomerular filtration of 125I-SOD, which is what one would expect from the renal handling of a protein with a molecular weight around 31,000 and an isoelectric point around pH 5.4. Pretreatment with a large dose of SOD (88 mg/kg) tended to competitively decrease the renal uptake of labelled SOD after 5 min. and apparently further increase its renal excretion. However, a noticeable renal uptake of 125I-SOD was still apparent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Plasma elimination kinetics and renal handling of copper/zinc superoxide dismutase in the rat.

The renal handling of bovine and human superoxide dismutase (SOD) was investigated in Sprague-Dawley and Munich-Wistar rats. Under normal physiological conditions the half-time of the major rapid component of the plasma elimination curve was estimated at 6.0 +/- 0.5 min, the volume of distribution at 35.7 +/- 3.3 ml kg-1, i.e. the plasma volume and the corresponding plasma clearance at 4 ml min-1 kg-1. After a single intravenous dose, most of the enzyme was distributed to and eliminated by the two kidneys, whereas the non-renal clearance was low, 0.5 ml min-1 kg-1. The single nephron filtration of SOD, as assessed from micropuncture of Bowman's space, was 10.4 +/- 1.0 nl min-1, which was 26 +/- 2% of that for inulin. The total elimination of SOD by glomerular filtration would thereby be 2.5 ml min-1 kg-1, i.e. the glomerular ultrafiltration process would account for the largest part of the elimination of SOD from circulating plasma. After the dosage of 20 mg kg-1, about two-thirds of the injected SOD was excreted as the intact molecule into the urine, whereas one-third was found to be reabsorbed and metabolized by the proximal tubular epithelial cells. In animals suffering from unilateral post-ischaemic acute renal failure, the elimination half-time was 13 +/- 1.9 min, a value which increased by 55 +/- 5 min after bilateral functional nephrectomy. By contrast, the distribution volume remained essentially unchanged.

Acute Kidney Injury↗
PubMed1987

Preferential localization of 3H-pentosanpolysulphate to the urinary tract in rats.

Endogenous glycosaminoglycans probably have a protective effect in the urinary tract, e.g. against stone formation. The synthetic sulphated polysaccharide pentosanpolysulphate (PPS) has been suggested to exert a similar protective effect e.g. by inhibition of crystallization and bacterial anti-adhesion. We have studied the distribution in rats of tritium-labelled PPS. Chromatography showed this material to contain two distinct peaks with approximate molecular weight around 2.700 (60-70%) and 1.000 (30-40%) daltons. PPS was administered orally and intravenously (5 mg/kg b.wt.) to Sprague-Dawley rats, which were killed 1 and 4 hours later, respectively, and subjected to whole-body autoradiography. Autoradiograms of sections from intravenously injected rats showed an extensive distribution of radioactivity in the whole animal, with a notable labelling of connective tissues, while bone and cartilage had low activity. There was upper intestine activity, suggesting some hepatic excretion. The most conspicuous finding, however, was the high concentration in urine and a preferential localization of activity corresponding to the lining of the urinary tract (pelvis, ureter, and bladder). The distribution was similar, but the activity lower after oral administration. In one experiment, PPS was applied intravesically under anaesthesia, with and without epithelial destruction caused by instillation of 0.4 M HCl. After vigorous rinsing, with saline, the radioactivity was still retained in the bladder wall. In other intravenous experiments, the bladder was extirpated, everted and rinsed in saline or urea of increased osmolality. High amount of radioactivity could be rinsed off by 0.5 M saline. Chromatography of the rinsing solution showed presence of both fractions of PPS previously found in the injection solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1987

Prevention of ischaemic acute renal failure with superoxide dismutase and sucrose.

The preventive effects of intravenously administered superoxide dismutase (SOD) and of SOD combined with sucrose on acute renal failure were investigated in rat kidneys exposed to 45 min of warm ischaemia. Superoxide dismutase (20 mg) given just before primary ischaemia and in the early recirculation phase was found to ameliorate the red cell aggregation in the renal medulla, in particular, in the inner stripe of the outer zone the volume of trapped red cells decreased from 11.2 +/- 1.6% in untreated animals to 0.02 +/- 0.001%, thus allowing improved restoration of medullary blood flow. This was also accompanied by an expected restoration of the urine osmolality reaching almost 400 mOsm kg-1 after administration of SOD + sucrose. Superoxide dismutase also restored the capillary macromolecular permeability as evidenced by normalization of plasma to lymph transport of proteins. Micropuncture studies showed that in ischaemically damaged but untreated kidneys the tubules were obstructed and that the proximal tubular pressure rose to such a level that the net driving force for filtration approached zero. This explains the marked decrease in glomerular filtration rate (GFR) from a normal value of about 1 ml min-1 to 0.01 +/- 0.02 ml min-1. After treatment with SOD the tubules were still largely obstructed, resulting in a depression of the net driving force and a decrease in single nephron glomerular filtration rate (SNGFR) to about 11 nl min-1, that is, to only 25% of the normal SNGFR. The total filtration was 0.09 +/- 0.04 ml min-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1987

Pharmacokinetic-pharmacodynamic relationship of piretanide in healthy and uremic subjects. Determinants of the diuretic effect of a loop diuretic.

The pharmacokinetics of the loop diuretic piretanide and its diuretic effects were studied in 6 healthy volunteers, 12 pre-dialysis (GFR 7-28 ml/min) and 10 dialysis patients (c-creat. 1-7 ml/min). Single doses up to 96 mg i.v. and orally were well tolerated and audiometry showed no hearing changes. Pharmacokinetic data showed rapid and almost complete absorption (bioavailability 92%) and a rapid elimination with renal clearance of 50% of the total 200 ml/min in the normals and renal clearance of about 50% of actual GFR in the patients. Extrarenal clearance was the same in normals and patients. The rapid extrarenal elimination reduces the risk of accumulation in renal patients but also reduces the active fraction of the dosage being cleared by the kidneys. Therefore, a high dosage and high plasma levels of piretanide were necessary for diuretic effect in uremic patients. The relation between the urinary piretanide excretion rate and the chloruretic effect was similar in normals and uremic patients; Cl- excretion increased 40 mMol per mg piretanide excreted.

Adult↗
PubMed1987

Some effects of metolazone on electrolyte transport.

Metolazone action was studied 1) in vitro on isolated operculum of Fundulus heteroclitus (active chloride transport) using an Ussing chamber (metolazone conc 500 microM) and in vivo 2) using the modified Sperber technique in the hen (metolazone infusion rate 0.75-1.2 micrograms/kg/min) and 3) in healthy volunteers using clearance techniques (metolazone infusion rate 10 mg/h). Metolazone reduced (p less than 0.05) short circuit current potential differences with 20% from average control values (p less than 0.05), while direct current resistance was unchanged. This is comparable to thiazide but much lower than loop diuretic effects. True tubular excretion fraction of metolazone before and after novobiocin (2.7 mumol/kg/min coinfusion averaged 14.1 and 4.5%, resp. (p less than 0.01; n = 8). Thus metolazone is partly eliminated by renal tubular secretion. However, the diuretic effect (sodium, chloride and potassium excretion)--and clearances of Cr51-EDTA and I125-Na-o-iodohippurate--were symmetrical, i.e. independent of metolazone urinary excretion rate, as previously shown for thiazides. Renal clearance of metolazone in healthy volunteers. (HPLC-method) averaged 173 +/- 20 ml/min (n = 8). Probenecid (1 g iv.) significantly reduced the renal clearance of metolazone to 33 +/- 7 ml/min and potassium excretion with maximum 30%, while diuretic and saluretic effects were significantly increased with maximum 30%. Thus, also in humans the diuretic effect of metolazone is not coupled to the urinary excretion rate of the drug, but suggests that its diuretic effect is elicited primarily from the peritubular side of the nephron. Probenecid apparently dissociates sodium from potassium excretion effects of metolazone. This implies a luminal, sodium-independent kaliuretic effect of the drug.

Adult↗
PubMed1986

Serum azathioprine and 6-mercaptopurine levels and immunosuppressive activity after azathioprine in uremic patients.

The pharmacokinetics of azathioprine (AZA) and 6-mercaptopurine (6-MP) was studied in uremic patients after 100 mg AZA intravenously (fifteen patients) and orally (eight patients). 6-MP was analysed with gas chromatography mass spectrometry following extractive alkylation. AZA was determined indirectly assuming quantitative conversion to 6-MP in whole blood. The plasma concentration of AZA fell rapidly after i.v. administration. The mean half-time of elimination for the first rapid phase (t1/2 alpha) was 6.1 min (S.D. +/- 4.1) and for the terminal phase (t1/2 beta) 50 min (+/- 31). The total plasma clearance (Cl) was 6.9 1./min (+/- 3.0). AZA was rapidly converted to 6-MP in vivo, and maximal plasma concentrations of 6-MP were found as early as 5 min after i.v. injection of AZA. The mean t1/2 alpha was 4.6 min (+/- 2.2), t1/2 beta 74 min (+/- 58) and Cl 8.0 1./min (+/- 5.8). The plasma levels of both AZA and 6-MP were either low or undetectable 4-6 h after dose. In erythrocytes AZA levels were low or undetectable indicating rapid conversion to 6-MP in these cells. 6-MP concentration - time curve in erythrocytes was similar to that in plasma, except for a somewhat slower terminal phase of elimination. Oral administration of AZA generated flat plasma curves for AZA and 6-MP. The area under the concentration - time curve (AUC) was considerably smaller than after i.v. administration, 18 and 41% for AZA and 6-MP, respectively. There seems to be little danger of accumulation of AZA/6-MP in uremia. We also studied inhibition of Leucoagglutin (LA) stimulated lymphocyte proliferation by patient plasma at different times in six of the patients following AZA i.v. Sera drawn at 5, 10 and 30 min significantly inhibited the LA-induced proliferation, with an estimated minimum effective concentration of 6-MP in the cultures of about 0.02-0.04 microM. This suggests the possibility of a therapeutic effect even of the low plasma levels of 6-MP obtained after AZA orally. The combined use of sensitive pharmacokinetic and immunological assays as described should be useful in studying the relationship between plasma levels of AZA/6-MP and their immunosuppressive effect and toxicity.

Administration, Oral↗
PubMed1986

Renal handling and effects of [3H]digoxin and interactions with quinidine in the avian kidney.

Renal handling and effects of tritium digoxin and interactions with quinidine in the avian kidney were studied using a modified Sperber technique. Results showed that tritium digoxin was extracted at the peritubular side of the nephron in a process competitively inhibited by increasing amounts of unlabelled digoxin. Light microscope autoradiography showed distinct concentrations of silver grains only over distal tubules in the injected kidney. Inhibition of the proximal tubular transport systems for organic anions and cations, respectively, did not change extraction. Addition of quinidine to the injection solution up to an estimated concentration of 1.4 X 10(-5) M in systemic blood significantly lowered 1 min peritubular extraction of tritium digoxin. However, when the amount of quinidine was further increased, extraction of tritium digoxin augmented significantly. Tritium recovery in urine after renal portal bolus injection of tritiated and unlabelled digoxin already showed a distinct ipsilateral peak 2 min after injection with an equally distinct peak of ipsilateral sodium excretion appearing 1 min later. When quinidine was added to the bolus ipsilateral tritium recovery in urine (0-7 min) was halved, with the true tubular excretion fraction (TTEF) lowered by two-thirds, but without changes in the magnitude of ipsilateral natriuresis. Contralateral natriuresis increased more than four-fold with quinidine in the bolus in spite of unchanged tritium recovery in the urine. Thus, our results show tritium digoxin to be extracted from peritubular blood through a specific process probably localized to the distal nephron of the avian kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Is 125I iothalamate an ideal marker for glomerular filtration?

The triiodinated angiographic contrast medium, iothalamate, has (usually labelled 125I) been used extensively as a marker for glomerular filtration. We have studied the renal handling of 125I iothalamate (IOT) in vivo and in vitro in several species. In renal cortical slices from chicken, rabbit, rat, and monkey, the tissue-to-medium ratio of IOT was twice that of 51Cr-EDTA (EDTA) at 37 degrees C; a difference that was abolished at 0 degree C and markedly reduced by added o-iodohippurate or iodipamide. In five chickens the steady-state renal clearance of IOT (CIOT) was twice (P less than 0.05) that of EDTA (CEDTA) or 3H inulin (C1); a difference that was abolished by administration of 100 mg/kg/hr of novobiocin, an organic anion transport inhibitor. CEDTA was similar to C1 before as well as after transport inhibition. Utilizing the Sperber technique the mean apparent tubular excretion fraction (ATEF) of IOT was 8%, while that of EDTA was 1% (P less than 0.01; N = 10). After novobiocin coinfusion (new steady-state) ATEFIOT was significantly reduced (P less than 0.01) and not different from that of EDTA (-1%). In the same animals the total urinary recovery of IOT was 84 and 57% (P less than 0.01) before and after novobiocin, respectively, while corresponding values for EDTA was unchanged by the inhibitor. In seven rats the renal extraction of IOT was reduced from 29 to 17% (P less than 0.05) by coinfusion of probenecid (5 mg/kg/hr). Corresponding extractions were 82 to 34% (P less than 0.005) and 22% (unchanged) for PAH and EDTA, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Renal tubular accumulation of organic substances: a new in vivo method which differentiates between luminal and peritubular uptake.

Using a modification of the Sperber technique we studied cellular uptake of organic substances in the kidney. A test substance was mixed with an extracellular marker (ethylenediaminetetraacetate or inulin), both radiolabelled with an activity ratio close to I, and injected into the renal portal system on one side via a leg vein. The animals were killed 1-10 min after injection and the radioactivity in different organs determined. Results showed significantly higher ipsilateral (injection) to contralateral (control) kidney ratios (substance to marker) at 1 min after injection for 125I-Na-o-iodohippurate (125I-Hipp; P less than 0.001), 14C-tetraethylammonium bromide (14C-TEA; P less than 0.001), 3H-dihydromorphine (3H-DHM; P less than 0.01), and 125I-iothalamate (P less than 0.01), with a progressive decrease in injection kidney ratios for 125I-Hipp and 14C-TEA when death occurred after a longer period. Inhibition of renal tubular transport with novobiocin or mepiperphenidol markedly reduced 1- and 4-min injection kidney ratios for 125I-Hipp and 14C-TEA, respectively. When death occurred after a longer period, ratios in both kidneys increased significantly for 125I-iothalamate. A good correlation was found between peak cellular accumulation in the kidney and excretion efficiency of test substances. Thus, the results indicate that 125I-Hipp, 125I-iothalamate, 14C-TEA, and 3H-DHM were accumulated from the peritubular side of the nephron through the transport systems for organic acids and bases, respectively, and that 125I-iothalamate also showed luminal uptake. In conclusion, this new in vivo technique is simple and well suited for studying renal tubular accumulation of organic substances and offers the advantage of being able to distinguish luminal from peritubular uptake.

Animals↗
PubMed1985

Renal handling of 125I-labelled insulin in the hen.

Renal handling of 125I-insulin was studied using a modification of the Sperber technique. Results showed 125I-insulin to be extracted at the peritubular side of the nephron in a process that was competitively inhibited by increasing amounts of unlabelled insulin, but not ACTH, in the injection mixture. When unlabelled insulin instead was injected 30 sec after the labelled insulin it showed significantly less interference with peritubular extraction of 125I-insulin, indicating strong attachment to the cell membrane or possible internalization of 125I-insulin into proximal tubular cells. Light microscope autoradiography 1 min after injection of 125I-insulin showed grains over proximal tubules only. On the ligated side localization was preferably peritubular while on the control side it was luminal. Electron microscope autoradiography showed sparsely distributed grains, however, frequently located over basal parts of proximal tubular cells. Pretreatment with lysine hydrochloride lowered renal extraction of 125I-insulin and increased urinary recovery of iodine label bilaterally. 125I-glucagon and 125I-C-peptide were not extracted from the peritubular circulation. In conclusion, the model has provided evidence of a rapid and significant peritubular extraction of 125I-insulin by proximal tubular cells in a process probably involving specific insulin receptors. Following receptor binding probably only minor amounts of 125I-insulin enters the proximal tubular cells, while the greater part is degraded at the cell surface or released into the circulation.

Adrenocorticotropic Hormone↗
PubMed1985

Acute tolerance to furosemide diuresis in humans. Pharmacokinetic-pharmacodynamic modeling.

Furosemide, 40 mg, was given to eight healthy volunteers as an i.v. dose and as oral doses (tablet and solution) with and without food intake. The urine and plasma were sampled frequently and analyzed on their content of furosemide (high-performance liquid chromatography). The urine flow and chloride excretion rate were used as measures of the effect. In spite of a 3-fold difference (28 vs. 9 mg/8 hr, P less than .001) in the cumulative urinary excretion of furosemide between i.v. and postprandial oral administration, no significant difference in the diuretic effect was found (2-2.2 liters/8 hr). The drug excretion-response curves showed parallel shifts depending on mode of administration of furosemide. Clockwise hysteresis, indicating acute tolerance development to the diuretic effect, was seen after the oral doses after food intake. This within-dose development of tolerance was modeled with an extended Hill equation. The tolerance development seems to have a near relationship to acute volume depletion (inadequate substitution of urine losses), probably activating some intrarenal mechanism for extracellular fluid volume preservation. Thus, the time course of furosemide excretion, as well as the degree of renal compensation, determine the renal sensitivity to furosemide. This has important implications for the proper design and interpretation of studies of the excretion-response relationship of diuretics.

Adult↗