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Biomedical subjects

E B Pedersen

Publications and source records attributed to E B Pedersen.

At least 127 records · Page 7Linked to original sources

Effects of rapamycin on renal hemodynamics, water and sodium excretion, and plasma levels of angiotensin II, aldosterone, atrial natriuretic peptide, and vasopressin in pigs.

We have investigated the acute effects of rapamycin on renal hemodynamics, water, sodium and lithium excretion rates, and plasma levels of angiotensin II, aldosterone, atrial natriuretic peptide and vasopressin in 34 Lancaster/Yorkshire female pigs, a breed that has a renal structure/function resembling that of the human kidney. Three different dosages were given over a 1-hr period: dose A, 0.1 mg/kg (n = 8); dose B, 0.2 mg/kg (n = 8); dose C, 0.4 mg/kg (n = 8); and P, placebo vehicle (n = 10). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by constant infusion clearance technique using 125I-iothalamate and 131I-hippuran, and hormonal parameters were measured by RIA. Renal hemodynamics, water and sodium excretion rates, and tubular function, evaluated by the lithium clearance technique, were unchanged both during and up to 2 hr after rapamycin infusion, although GFR and RPF increased when rapamycin was given in supratherapeutic dosages of 0.4 mg/kg (GFR: P, 4.4%; A, 7.9%; B, 2.5%; C, 13.3% [P < 0.05]; RPF: P, 7.1%; A, 4.9%; B, 3.9%; C, 15.3% [P < 0.01], median values). It is concluded that infusion of rapamycin has no acute deleterious effects on renal function in pigs in therapeutic to supratherapeutic dosages.

Aldosterone↗

[Angiotensin-converting enzyme inhibitor renography. Physiopathological, diagnostic and therapeutic aspects in renal artery stenosis].

Angiotensin converting enzyme inhibitor renography (ACE-I-renography) can be used partly to screen for renovascular hypertension and partly to evaluate the possibility for successful revascularization. In patients with an important renal artery stenosis with a high intrarenal activity of the renin-angiotensin-system ACE-inhibition results in a change in renal haemodynamics which can be detected by renography. ACE-I-renography has a high positive and negative predictive value in diagnosing renal artery stenosis. Significant alterations in the renogram induced by ACE-inhibition in renal artery stenosis seem to have a good predictive value with regard to the effect of correction of the stenosis. ACE-I-renography is recommended in patients with arterial hypertension and a moderate or high probability for renovascular hypertension based on clinical criteria.

Angiotensin-Converting Enzyme Inhibitors↗

S-glucosylated hydantoins as new antiviral agents.

S-Glycosylation took place on reaction of 5-alkylidene- and 5-arylidene-3-aryl-2-thiohydantoins with glycosyl halides under alkaline conditions. Bisglucosylation also took place when N-3 unsubstituted hydantoins were reacted. The bisglucosylated hydantoins produced N-3 glucosylated hydantoins on treatment with ammonia in methanol. In antiviral studies the most active compounds against both HSV-1 and HSV-2 were 5-(2-thienylmethylene)-3-phenyl-2-(2,3,4,6- tetra-O-acetyl-beta-D-glucopyranosyl)-2-thiohydantoin and 5-(2-thienylmethylene)-3-(4-chlorophenyl)-2-(2,3,4,6-tetra-O-acety l-beta-D- glucopyranosyl)-2-thiohydantoin.

Animals↗

Synthesis and antiviral evaluation of hydantoin analogues of AZT.

3'-Azidonucleosides 4 have been synthesized by condensation of silylated (Z)-5-ethylidenehydantoin and (Z)-5-benzylidenehydantoin with methyl 3-azido-5-O-tert-butyldiphenylsilyl-2,3-dideoxy-D-erythro-pento furanoside (3). The nucleosides 4 were deblocked on treatment with tetrabutylammonium fluoride. The ethylidene group isomerized from Z to E configuration during the nucleoside synthesis. The new nucleosides did not show any appreciable activities against HIV-1 or HSV-1.

Antiviral Agents↗

Identical effects of indomethacin on renal function in healthy uninephrectomized subjects and in healthy control subjects.

1. Animal studies have shown that prostaglandins are important for renal function after unilateral nephrectomy. In order to investigate the importance of prostaglandins for renal function in the fully adapted remnant kidney in healthy uninephrectomized subjects, the acute effects of indomethacin on renal haemodynamics, lithium clearance, urinary excretion rates of prostaglandin E2, sodium and water, and plasma levels of angiotensin II, aldosterone, atrial natriuretic peptide and arginine vasopressin were measured in 14 healthy uninephrectomized subjects (median time after nephrectomy 1.7 years) and in 14 matched healthy control subjects. In addition, nine healthy control subjects were studied without indomethacin and served as a time-control group. 2. Before indomethacin ingestion there was a significantly higher single-kidney urinary excretion rate of prostaglandin E2 in the uninephrectomized group (uninephrectomized group, 349.2 fmol/min; control group, 76.6 fmol/min; time-control group, 96.3 fmol/min). 3. Indomethacin ingestion resulted in equal changes in all parameters in both groups. These were significant decreases in glomerular filtration rate (-11.3% versus -14.6%), renal plasma flow (-6.5% versus -13.0%), urinary flow rate (-49.8% versus -49.4%), fractional sodium excretion (-44.5% versus -47.4%), lithium clearance (33.2% versus -23.8%) and urinary excretion rate of prostaglandin E2 (-93.8% versus -86.7%) (uninephrectomized versus control subjects, values are medians). In the time-control group no changes were observed in these parameters. 4. It is concluded that healthy uninephrectomized subjects with a fully adapted remnant kidney have a normal renal response to acute indomethacin-induced inhibition of prostaglandin synthesis.

Adult↗

Renal haemodynamic changes, renal tubular function, sodium and water homeostatic hormones in patients with chronic glomerulonephritis and in healthy humans after intravenous infusion of amino acids.

To determine whether renal reserve capacity was preserved in patients with chronic glomerulonephritis with well-preserved kidney function, and how sodium was handled in proximal and distal tubules, 13 healthy control subjects and 13 patients with biopsy-verified chronic glomerulonephritis were studied before and during a continuous 120-min amino-acid infusion. Glomerular filtration rate (GFR), renal plasma flow (RPF), and tubular function evaluated by the lithium clearance method, were determined during six clearance periods of 30 min each. Plasma concentrations of angiotensin II, atrial natriuretic peptide (ANP), aldosterone, arginine vasopressin (AVP), glucagon, amino acid and serum osmolality were determined before, 60, and 120 min after infusion. GFR and RPF increased about 10% in both groups; filtration fraction (FF) was unchanged. Proximal tubular reabsorption of sodium and water decreased, and distal tubular reabsorption of sodium and water increased, and thus the net excretion of sodium and water was unchanged. Angiotensin II and aldosterone were reduced in control subjects, but not in the patients. ANP and glucagon increased equally in both groups. Most amino acids increased two- or threefold. It is concluded that renal reserve capacity and glomerulotubular balance are intact in patients with chronic glomerulonephritis with well-preserved renal function, but there is an abnormal lack of suppression of the renin-angiotensin-aldosterone system in response to an amino acid infusion in these patients.

Adult↗

Pressure-dependent, enhanced natriuretic response to low-dose, atrial natriuretic peptide infusion in essential hypertension.

OBJECTIVE: To examine whether the effect of atrial natriuretic peptide (ANP) on renal glomerular and tubular segmental handling of sodium in patients with essential hypertension is pressure dependent. DESIGN: Part 1. The renal effects of a low-dose continuous infusion (10 ng kg-1 min-1) with ANP for 1 h were compared in 10 untreated essential hypertensives (EH) and 13 normotensive control subjects (CS). Part 2. The hypertensives were studied on another day with ANP infusion during preceding acute BP reduction with sodium nitroprusside infusion (NP). The results were compared with those obtained during infusion with ANP+placebo (Part 1). METHODS: Lithium clearance was used to estimate the proximal tubular reabsorption of sodium. RESULTS: Part 1. Atrial natriuretic peptide caused an exaggerated increase in urinary sodium excretion (+102 vs. +38%: P < 0.05), fractional excretion of sodium (+80 vs. +37%: P < 0.05), and urinary output (+56 vs. +8.3%; P < 0.05) in EH compared with CS. Glomerular filtration rate and filtration fraction increased to the same degree in both groups. Absolute lithium clearance (CLi) increased and FELi tended to increase (P = 0.061) in EH, but these were unchanged in CS. The increase in plasma cyclic guanosine 5'-phosphate (cGMP) and urinary excretion of cGMP and the decrease in plasma aldosterone during ANP infusion were the same in the two groups. Part 2. During NP infusion the natriuresis caused by ANP in EH was reduced (+51 vs. +99%; P < 0.05). The relative changes in GFR, CLi, and FELi during ANP infusion were not affected by the preceding BP reduction with NP. Mean arterial pressure was reduced from 122 to 101 mmHg during NP infusion. The relative increase in sodium excretion in EH was significantly correlated to mean arterial pressure. CONCLUSIONS: Low-dose ANP infusion causes an exaggerated natriuresis in untreated essential hypertensives due to a more pronounced reduction in tubular reabsorption. After BP reduction, the natriuresis induced by ANP in essential hypertensives is decreased, probably due to a less pronounced reduction in tubular reabsorption beyond the proximal tubules. We suggest that the enhanced natriuretic response to ANP in EH in secondary in some degree to the elevated systemic pressure.

Adult↗

Effects of captopril on renal function in healthy uninephrectomized subjects and in healthy control subjects.

OBJECTIVES: To study the importance of the renin-angiotensin-II system for renal haemodynamics and sodium and water handling in the adapted remnant kidney in healthy uninephrectomized subjects. DESIGN: Case-control study. SETTING: All subjects were investigated at laboratory C, Department of Medicine and Nephrology, Skejby Hospital. SUBJECTS: Fourteen healthy uninephrectomized (Unx) and 14 matched healthy control subjects (Cs). INTERVENTION: Captopril, 25 mg orally. MAIN OUTCOME MEASURES: The glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by the constant infusion clearance technique using 125I-iothalamate and 131I-hippuran as reference substances, tubular function was evaluated by the lithium clearance technique (CLi), urinary flow rate (V), sodium excretion (UNaV), fractional sodium excretion (FENa), mean blood pressure (MBP) and heart rate (HR) were measured by conventional methods and plasma levels of angiotensin II (Ang-II), aldosterone (Aldo), arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) were measured by radioimmunoassay. RESULTS: In both groups captopril ingestion resulted in a significant decrease in the MBP (Unx: 87.1 to 83.5 and Cs: 86.8 to 83.8 mmHg, median values), filtration fraction (Unx: 24.6 to 22.1 and Cs: 24.1 to 22.5%, median values) and Ang-II (Unx: 10.5 to 7.7 and Cs: 12 to 7.6 pmol-1, median values). Single kidney GFR, V, and CLi were unchanged in both groups. FENa and single kidney RPF were significantly increased in only the Cs group; FENa (Unx: 1.81 to 1.91 and Cs: 1.56 and 1.90%, median values). The plasma level of ANP was significantly decreased in only the Unx group. CONCLUSION: The data suggest that sodium handling in the remnant kidney in uninephrectomized subjects could be less sensitive to Ang-II than in healthy control subjects, and that this might be as a result of adaptive changes in the distal parts of the nephron.

Adult↗

Systemic and renal effect of intravenous infusion of endothelin-1 in healthy human volunteers.

The effect of intravenous infusion of endothelin-1 (ET-1) at a rate of 1 pmol.min-1.kg-1 for 60 min (n = 9) or placebo (n = 9) was investigated in 18 healthy human volunteers with a mean age of 30 yr. In response to ET-1 infusion, concentration of ET-1 increased from 0.88 +/- 0.27 to 10.73 +/- 4.79 (SD) pmol/l. Diastolic blood pressure increased by 7.8% (P < 0.01) and heart rate decreased by 14.0% (P < 0.01), whereas systolic blood pressure did not change. Renal plasma flow decreased by 34.7%, glomerular filtration rate decreased by 16.1%, and renal vascular resistance increased by 66.0% (P < 0.01 all). Urinary sodium excretion decreased by 57.9% and urinary flow rate by 40.2% (P < 0.01 for both). As judged from the clearance of lithium, we found that ET-1 did not change absolute reabsorption of sodium and water in the proximal tubules, but in the distal tubules absolute reabsorption of both sodium and water decreased significantly. Plasma concentrations of angiotensin II, aldosterone, arginine vasopressin, and atrial natriuretic peptide did not change in response to ET-1 infusion. It is suggested that ET-1 at plasma concentrations found in certain pathophysiological conditions in humans may influence renal perfusion and renal sodium and water excretion.

Adult↗

Serum propeptides of type I and III procollagens in renal transplant recipients. A comparison of cyclosporine and azathioprine treatment.

Chronic cyclosporine nephrotoxicity is characterized morphologically by cortical interstitial fibrosis. The most important collagens involved in renal fibrosis are collagen types I and III. In order to estimate the synthesis of type III and type I collagens, we analyzed serum levels of the amino-terminal propeptide of type III procollagen (PIIINP) and the carboxy-terminal propeptide of type I procollagen (PICP) in 11 renal transplant recipients receiving cyclosporine (group CY) and a comparable group of 16 renal transplant recipients treated with azathioprine (group AZ). In addition, 27 healthy subjects and 15 patients with chronic renal disease and reduced renal function (group CRD) were examined. The cyclosporine-treated patients had serum PIIINP and PICP similar to the azathioprine-treated patients. Both groups of renal transplant recipients had significantly increased serum PIIINP compared to healthy controls (2p < 0.01) and serum PIIINP levels similar to group CRD in which serum PIIINP was also elevated compared to healthy controls (2p < 0.01). Mean serum PIIINP levels were: group CY 0.81 U/l (n = 11); group AZ 0.98 U/l (n = 16); controls 0.62 U/l (n = 27); and group CRD 1.06 U/l (n = 15). The renal graft recipients--both cyclosporine- and azathioprine-treated patients--had significantly increased PICP serum levels compared to healthy controls, but the patients with chronic renal disease had serum PICP levels which did not differ from that of healthy controls. Mean serum PICP levels were: group CY174 micrograms/l; group AZ151 micrograms/l; controls 106 micrograms/l; and group CRD119 micrograms/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Increased serum erythropoietin level during azathioprine treatment in renal transplant recipients.

One hundred and six renal transplant patients were studied. During the first 12 months after renal transplantation all patients were treated with cyclosporine (Cy) and prednisone. At 12 months after transplantation the patients were randomly allocated to either conventional treatment with azathioprine (Az) and prednisone (group Az) or to continued treatment with Cy and prednisone (group Cy). Serum erythropoietin (s-EPO), glomerular filtration rate (GFR) and hematocrit (Hct) were measured at 12, 18 and 24 months after transplantation. s-EPO rose in the group Az from 19 U/l (mean) at 12 months to 28 U/l (p < 0.01) at 18 months and remained elevated at 24 months at 29 U/l compared with baseline level and with healthy subjects without anemia 18 U/l (p < 0.01). There was no significant change in s-EPO in group Cy during the study. The Hct in the two groups was not significantly different. GFR was the same in the two groups at 12 months and after 24 months. In conclusion, a switch from Cy to Az 1 year after renal transplantation results in a sustained rise in s-EPO which may in part represent a compensatory phenomenon to bone marrow suppression.

Adolescent↗

Reduced production, absorption, and elimination of erythropoietin in uremia compared with healthy volunteers.

The purpose of this study was to investigate the metabolism of erythropoietin (EPO) in uremia compared with healthy subjects. Twenty-one patients (nine men and 12 women) with end-stage renal failure and anemia and 12 healthy volunteers (3 women and nine men) were studied. The pharmacokinetic parameters were calculated after an i.v. and a femoral sc injection of 100 U/kg of recombinant human EPO. The serum EPO (s-EPO) was measured by radio-immunoassay at regular intervals until 48 h (i.v.) and 120 h (sc). In uremia, the median terminal elimination half-life was significantly longer (8.31 versus 4.92 h; P < 0.001) and the clearance was reduced (5.00 versus 7.88 mL/min per 1.73 m2; P < 0.01). The volume of distribution was (3.70 versus 3.31 L/1.73 m2) not significant. The estimated endogenous EPO production was significantly lower in uremia (146 versus 290 U/day per 1.73 m2; P < 0.001). After sc administration, the bioavailability was significantly lower in the patients (23.7 versus 38.5%; P < 0.01), and the maximal s-EPO was lower (113 versus 153 U/L; P < 0.05) and delayed (15.4 versus 11.0 h; P < 0.02), but the mean input time (sc) was not significantly different (23.3 versus 27.8 h). The basal s-EPO was lower in the uremic patients (20.0 versus 26.3 U/L; P < 0.05). There was no difference between patients treated with hemodialysis and peritoneal dialysis or between uremic men and women. There was no correlation between the pharmacokinetic parameters and age.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

Effects of indomethacin on renal function in normotensive patients with chronic glomerulonephritis with preserved renal function.

Thirteen normotensive patients with biopsy verified chronic glomerulonephritis (GN) with preserved renal function and 12 healthy control subjects (CS) were studied before and during prostaglandin synthesis inhibition by indomethacin. Glomerular filtration rate (GFR), renal plasma flow (RPF), urinary output (V), sodium excretion (UNa V), fractional lithium excretion (FELi), plasma levels of angiotensin II (Ang II), aldosterone (Aldo), atrial natiuretic peptide (ANP), arginine vasopressin (AVP) and endothelin (ir-ET) and urinary excretion rates of PGE2, mean blood pressure (MBP) and heart rate (HB) were determined on two separate occasions at least 7 days apart. During basal conditions without indomethacin administration no significant differences were found between the two groups. Indomethacin administration (100 mg 12 h and 1 h before clearance investigations) resulted in significant and almost identical decreases in GFR, RPF, V, UNa V, FELi and HR and increases in MBP in both the GN group and the CS group. It is concluded that normotensive patients with a biopsy verified chronic glomerulonephritis but with preserved renal function and without nephrotic syndrome have no increased risk of acute deterioration of renal function during administration of a non-steroidal anti-inflammatory drug compared with healthy control subjects.

Adult↗

Endothelin in renovascular and essential hypertension.

Immunoreactive endothelin (ir-ET) was measured in peripheral venous plasma in 12 patients with renovascular hypertension (RVH) due to unilateral renal arterial stenosis, in 12 patients with essential hypertension (EH), and in 12 control subjects (C). In the patients with RVH, ir-ET was also measured in the aorta and in both renal veins before and 1 h after 25 mg of captopril was given orally. In peripheral venous plasma, ir-ET was the same in RVH (median 1.02 pmol/l (range 0.53-1.65)) as in EH (0.96 pmol/l (0.76-1.32)) and in C (1.00 pmol/l (0.77-1.16)). In RVH, the concentrations of ir-ET decrease from the aorta to the renal vein of both the affected (0.88 pmol/l (0.54-1.28) vs 0.68 (0.51-1.24), p < 0.01) and in the unaffected kidney (0.85 pmol/l (0.62-1.38) vs 0.78 pmol/l (0.36-1.25), p < 0.01). Renal extraction of ir-ET was the same on the affected side (15.1% (-3.7-33.2)) and on the unaffected side (11.2% (0.5-46.4)). In the aorta, ir-ET was significantly lower than in peripheral venous plasma (p < 0.05). The renal handling of ir-ET did not change in response to captopril in either the affected or unaffected kidney. It is concluded that circulating levels of ir-ET are normal in renovascular hypertension associated with unilateral renal artery stenosis and in essential hypertension. There is significant renal extraction of ir-ET which is unaffected by renal artery stenosis and captopril.

Adult↗