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Biomedical subjects

F H Derkx

Publications and source records attributed to F H Derkx.

At least 55 records · Page 3Linked to original sources
PubMed1995

Plasma semicarbazide-sensitive amine oxidase activity is elevated in diabetes mellitus and correlates with glycosylated haemoglobin.

1. Semicarbazide-sensitive amine oxidase is a common name for a group of heterogeneous amine oxidases which are present in various mammalian tissues, especially in vascular smooth muscle cells, cartilage and adipose tissue, but also in plasma. 2. Plasma semicarbazide-sensitive amine oxidase activity was elevated in a group of 104 patients with insulin-dependent diabetes mellitus compared with normal control subjects (555 +/- 172 versus 352 +/- 102 m-units/l, P < 0.0005). 3. Plasma semicarbazide-sensitive amine oxidase activity was higher in subgroups with either retinopathy or nephropathy or both [583 +/- 116 (n = 34), 581 +/- 229 (n = 10) and 646 +/- 249 m-units/l (n = 19), respectively] than in the subgroup without overt complications [486 +/- 129 m-units/l (n = 41), P < 0.005]. 4. Plasma semicarbazide-sensitive amine oxidase activity was positively correlated with plasma glycosylated haemoglobin (r = 0.40; P < 0.0001) and with log urinary albumin excretion (r = 0.26; P < 0.025). 5. The possibility that semicarbazide-sensitive amine oxidase, by its conversion of endogenous amines like methylamine and aminoacetone into cytotoxic aldehydes, plays a role in the development of microvascular complications in diabetes mellitus, needs further investigation.

Adult↗
PubMed1995

Prorenin and renal function in NIDDM patients with normo- and microalbuminuria.

OBJECTIVES: To assess whether prorenin is elevated and perhaps a predictor of deteriorations in albuminuria and/or renal function in NIDDM patients with normo- and microalbuminuria. DESIGN: A cross-sectional and a longitudinal study. SETTING: Outpatient diabetic clinic. SUBJECTS: Twenty-eight NIDDM patients (16 with normoalbuminuria, 12 with microalbuminuric) and 16 healthy subjects, matched for sex, age and BMI. Fifteen patients were reinvestigated after (mean [range]) 3.1 (2.1-4.3) years. MAIN OUTCOME MEASURES: Serum prorenin and renin, urinary albumin excretion rate, and glomerular filtration rate. RESULTS: Serum prorenin was similar in both normoalbuminuric (116x/divided by) 1.9 microU ml-1 (geometric meanx/divided by antilog SD) and microalbuminuric (124x/divided by) 1.7 microU ml-1) as well as in healthy control subjects (90x/divided by) 1.7 microU ml-1). Prorenin did not correlate to either urinary albumin excretion rate or glomerular filtration rate. No difference between baseline and follow-up levels of albuminuria, glomerular filtration rate or prorenin were observed. The annual changes in albuminuria, glomerular filtration rate and prorenin were not correlated, and no correlation was found between baseline prorenin levels and annual changes in albuminuria or glomerular filtration rate. CONCLUSIONS: Serum prorenin levels are not elevated in either normoalbuminuric or microalbuminuric NIDDM patients, and serum prorenin is not a valid predictor of long-term changes in albuminuria in this patient group.

Aged↗
PubMed1995

Effect of atrial natriuretic peptide on renal and vascular permeability in diabetes mellitus.

Synthetic human atrial natriuretic peptide (ANP) (102-126) 0.01 microgram/kg per minute or vehicle was intravenously infused for 2 h in 10 patients with insulin-dependent diabetes mellitus and microalbuminuria (albumin excretion, 20 to 200 micrograms/min) and in 10 healthy subjects. In the diabetic group, the immunoglobulin G clearance was higher, but both size index and charge index as calculated from albumin and immunoglobulin clearances were equal compared with normal values. The fractional clearances of small dextrans (< 3.6 nm) were lower in diabetics, which was compatible with a depressed hydraulic permeability (Kf). During ANP infusion, the excretion of albumin and immunoglobulin G increased in the diabetic subjects (189 +/- 12 to 521 +/- 84 and 7.1 +/- 3.5 to 21 +/- 8.1 micrograms/min, respectively; both P < 0.05) only. In the diabetics, the clearance of dextrans > 54 A increased and our calculations indicated an increase in "shut-flow" (omega o). The transcapillary escape rate of albumin, which was elevated in the diabetics at baseline, increased in the diabetic group only. Thus, ANP uncovers altered size selectivity of the filtration barrier in a phase that is otherwise characterized by charge-selective changes only. Moreover, the increased susceptibility of the glomerular capillaries in diabetics to ANP seems to be part of a more generalized capillary abnormality, because ANP also increases the transcapillary escape of albumin.

Adult↗
PubMed1995

Optimising glomerular filtration rate and effective renal plasma flow measurements using a simple pharmacokinetic model.

We applied an open one compartment pharmacokinetic model for the determination of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) based on a rapid intravenous loading dose followed by a constant infusion of 125I-iothalamate and 131I-orthoiodohippurate in order to ensure constant plasma levels of the two clearance markers. The loading dose was based on the assumption that the volume of distribution of the two markers equals the extracellular volume (25% of the body weight). The infusion rate as calculated after the clearance of thalamate was estimated from body weight, age, sex and serum creatinine using Cockcrofts formula. The clearance of hippurate was assumed to be four times that of thalamate. We studied the reliability of this model in 212 patients with insulin dependent diabetes mellitus (IDDM; n = 74), nephrotic syndrome (NS; n = 18) and heart (HTX; n = 69) or kidney (KTX; n = 51) transplants. A steady state concentration was obtained in all patient groups, even when GFR was markedly depressed. In patients with diabetes, we observed more variance between plasma and urinary clearances of thalamate, which could be due to inaccuracies in urine sampling. In these patients, GFR should be measured using a method that is not dependent on urine collection. Also, the estimation of GFR by means of Cockcrofts equation seems to underestimate GFR in diabetic subjects.

Glomerular Filtration Rate↗
PubMed1994

A mutant renin gene in familial elevation of prorenin.

A case of familial elevation of plasma prorenin levels was discovered during an epidemiological survey of a Dutch population. Trypsin-activated prorenin was elevated in the 58-year-old father, his son, and one of his sisters. All family members were normotensive and had normal plasma renin activities. Exon sequencing of the renin gene of the proband and of his son after polymerase chain reaction amplification identified a point mutation in the last exon of the gene (exon 10). A cytosine to thymine transition creates a premature stop codon at position 387 resulting in a truncated form of renin with 20 amino acids deleted from the carboxyl terminus. All family members presenting high levels of plasma prorenin were heterozygous for the mutation. Expression vectors carrying normal or mutated renin cDNA were transiently transfected into AtT-20 cells to test in vitro the functional consequences of this mutation. Measurements of renin activity and pulse-chase experiments indicated that the truncated renin is inactive and not secreted from transfected cells. We hypothesize that the abnormal gene product of the mutated allele alters renin sorting and propose that plasma prorenin elevation may result from a compensatory mechanism.

Animals↗
PubMed1994

Glomerular barrier function following conversion from cyclosporine to azathioprine in renal transplant recipients.

The renal side effects are the major limitation of the use of cyclosporine in clinical transplantation. We studied the reversibility of changes in renal hemodynamics and glomerular barrier function in 17 patients with moderately impaired renal function at least 1 year after kidney transplantation. All patients were studied both during cyclosporine treatment and 3 months after conversion to azathioprine. During azathioprine treatment both glomerular filtration rate and effective renal plasma flow increased significantly (from 44.3 +/- 4.2 mL/min to 63.5 +/- 5.4 mL/min and from 192 +/- 12.8 mL/min to 260 +/- 14.6 mL/min, respectively). Despite the marked changes in renal hemodynamics, no significant changes were observed in the fractional clearances of uncharged dextrans. When calculating the characteristics of the filtration barrier, we observed a trend toward an increase in the ultrafiltration coefficient (Kt). This trend was abolished when an increase in net filtration pressure (delta P) was assumed to result from reduced prerenal vasoconstriction. We conclude that despite marked improvement of renal perfusion and glomerular filtration, conversion from cyclosporine to azathioprine did not significantly alter the permeability characteristics of the glomerular filtration barrier in renal transplant recipients with moderately reduced renal function. Improvement in renal function following conversion could result from an increase in either Kf or delta P. Since renal plasma flow was increased significantly, the observed improvement in glomerular filtration rate is likely to be, at least in part, due to an increase in glomerular capillary plasma flow.

Adult↗
PubMed1994

Reduction of blood pressure with oral magnesium supplementation in women with mild to moderate hypertension.

In a double-blind controlled trial, 91 middle-aged and elderly women with mild to moderate hypertension who were not on antihypertensive medication were randomly assigned to treatment with magnesium aspartate-HCl (20 mmol Mg/d) or placebo for 6 mo. Magnesium aspartate-HCl in the given dose was well-tolerated and was not associated with an increased frequency of diarrhea compared with placebo. At the end of the study, systolic blood pressure had fallen by 2.7 mm Hg (95% CI -1.2, 6.7; P = 0.18) and diastolic blood pressure by 3.4 mm Hg (1.3, 5.6; P = 0.003) more in the magnesium group than in the placebo group. Blood pressure response was not associated with baseline magnesium status, as measured by dietary magnesium intake and urinary magnesium excretion. Urinary magnesium excretion in the magnesium group increased by 50% during the intervention period. No changes were seen in other biochemical indexes, including serum concentrations of total and high-density-lipoprotein cholesterol. The findings suggest that oral supplementation with magnesium aspartate-HCl may lower blood pressure in subjects with mild to moderate hypertension.

Administration, Oral↗
PubMed1994

Diurnal variation in prorenin in relation to other humoral factors and hemodynamics.

Diurnal variation has been demonstrated for blood pressure and heart function. Several hormones influence these hemodynamic parameters. This study investigates the diurnal variation in plasma prorenin in relation to renin, atrial natriuretic peptide (ANP), norepinephrine, and hemodynamic changes. Circulating plasma prorenin may be able to serve as a marker for the activity of the local renin-angiotensin system. In 12 healthy male volunteers who were allowed to carry out quiet activity, hemodynamic factors and the plasma levels of hormones were monitored at 2-h intervals for 26 h. Blood pressure was measured every hour. In accordance with the literature, during the night blood pressure (4%), cardiac index (19%), stroke index (10%), and heart rate (10%) decreased in a classic day-night pattern. Systemic vascular resistance increased during the night (23%). No classic day-night pattern was found for ANP, although it increased (15%) at night and showed a peak early in the night. This peak seemed to be influenced by posture. A classic day-night pattern was demonstrated for norepinephrine and prorenin. Norepinephrine was lower (18%) at night and increased as soon as the subjects awoke, while they were still in bed. Therefore, plasma norepinephrine levels seemed to be related to awakening. Plasma prorenin decreased at night (6%). Renin fluctuated throughout the day, but showed no clear day-night pattern. In conclusion, renin fluctuated throughout the day and did not show a classic day-night pattern. In contrast, prorenin fluctuated less and showed 6% higher levels during the day compared to the night. The origin and clinical significance of this small diurnal variation in prorenin is not clear yet.

Adult↗
PubMed1994

Cardiac renin and angiotensins. Uptake from plasma versus in situ synthesis.

The existence of a cardiac renin-angiotensin system, independent of the circulating renin-angiotensin system, is still controversial. We compared the tissue levels of renin-angiotensin system components in the heart with the levels in blood plasma in healthy pigs and 30 hours after nephrectomy. Angiotensin I (Ang I)-generating activity of cardiac tissue was identified as renin by its inhibition with a specific active site-directed renin inhibitor. We took precautions to prevent the ex vivo generation and breakdown of cardiac angiotensins and made appropriate corrections for any losses of intact Ang I and II during extraction and assay. Tissue levels of renin (n = 11) and Ang I (n = 7) and II (n = 7) in the left and right atria were higher than in the corresponding ventricles (P < .05). Cardiac renin and Ang I levels (expressed per gram wet weight) were similar to the plasma levels, and Ang II in cardiac tissue was higher than in plasma (P < .05). The presence of these renin-angiotensin system components in cardiac tissue therefore cannot be accounted for by trapped plasma or simple diffusion from plasma into the interstitial fluid. Angiotensinogen levels (n = 11) in cardiac tissue were 10% to 25% of the levels in plasma, which is compatible with its diffusion from plasma into the interstitium. Like angiotensin-converting enzyme, renin was enriched in a purified cardiac membrane fraction prepared from left ventricular tissue, as compared with crude homogenate, and 12 +/- 3% (mean +/- SD, n = 6) of renin in crude homogenate was found in the cardiac membrane fraction and could be solubilized with 1% Triton X-100. Tissue levels of renin and Ang I and II in the atria and ventricles were directly correlated with plasma levels (P < .05), and in both tissue and plasma the levels were undetectably low after nephrectomy. We conclude that most if not all renin in cardiac tissue originates from the kidney. Results support the contentions that in the healthy heart, angiotensin production depends on plasma-derived renin and that plasma-derived angiotensinogen in the interstitial fluid is a potential source of cardiac angiotensins. Binding of renin to cardiac membranes may be part of a mechanism by which renin is taken up from plasma.

Angiotensinogen↗
PubMed1994

Effects of DDAVP on renal hemodynamics and renin secretion in subjects with essential hypertension.

Intravenous (i.v.) infusion of the selective vasopressin (V2) agonist 1-desamino-8-D-arginine vasopressin (DDAVP, Desmopressin) in humans causes a fall in blood pressure, an increase in heart rate, and a rise in plasma renin and noradrenaline. The present study was designed to demonstrate the vasodilatory properties of DDAVP in the renal circulation and to describe the effect of DDAVP on renin secretion. Seven male subjects (31-63 years) with hypertension, who showed no signs of renal parenchymal disease, received an i.v. infusion of DDAVP (400 ng/kg in 10 minutes). They were studied at the time they were undergoing renal vein renin sampling and renal angiography as part of the diagnostic work-up of their hypertension. 131I-Hippurate clearance was used to measure effective renal plasma flow (ERPF). True renal plasma flow was calculated as ERPF divided by the renal extraction ratio of 131I-hippurate. 125I-Thalamate clearance was used to measure glomerular filtration rate (GFR). Measurements were made before and 15-20 minutes after administration of DDAVP. Angiography was performed in the same session after the last blood samples had been collected. In all patients the renal arteries were normal and the extraction ratios of 131I-hippurate and 125I-thalamate (Ehip, Ethal) were not different for the left and right kidney, and in all seven patients a diagnosis of essential hypertension was made. After DDAVP systolic blood pressure decreased by 14.4 mmHg (2.0-26.8) (mean, 95% confidence interval, p < 0.05). Diastolic blood pressure decreased by 12.1 mmHg (2.9-21.7, p < 0.01). Heart rate increased by 17.5 bpm (11.7-23.2, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Angiotensin levels in the eye.

PURPOSE: Ocular tissues contain renin and ocular fluids contain prorenin in amounts that are too high to be explained by admixture with blood or diffusion from blood. It was the purpose of the present study to obtain further evidence for the presence of a local renin-angiotensin system (RAS) in the eye. METHODS: The authors measured the concentrations of angiotensins I and II (ANG I and II) in vitreous fluid and ocular tissues of anesthetized pigs and in human aqueous, vitreous, and subretinal fluid obtained during eye surgery. RESULTS: In tissues obtained from normal porcine eyes (anterior uveal tract, neural retina, retinal pigment epithelium + choroid), ANG I and II were 5- to 100-fold higher than could be accounted for by contamination with blood. ANG I and II in ocular tissues are therefore unlikely to be derived from the circulation. In porcine vitreous fluid, ANG I and II were close to the limit of detection. In addition, during a 2-hour infusion of 125I-ANG I in the rabbit, 125I-ANG I in vitreous fluid reached a level only 1% of the level in arterial plasma. Thus, in the presence of an intact blood-retinal barrier, little or no ANG I or II enters the vitreous compartment. In human ocular fluids obtained from diseased eyes, ANG I and II levels were readily measurable and correlated linearly with the level of serum albumin, indicating that after partial breakdown of the BRB, diffusion of ANG I and II from the circulation into the eye may occur. CONCLUSION: Results indicate that both ANG I and II are generated locally in ocular tissues with little leakage into ocular fluids. These findings, together with previously published data on renin and prorenin, show a high degree of compartmentalization of the RAS in the eye and are in agreement with similar findings in other tissues, where there is evidence for the existence of a local RAS.

Adolescent↗
PubMed1993

Comparison of blood pressure and angiotensin responses to the renin inhibitor Ro 42-5892 and the angiotensin converting enzyme inhibitor enalapril in essential hypertension.

OBJECTIVE: To compare the responses of angiotensin II (Ang II) and blood pressure to the renin inhibitor Ro 42-5892 and the angiotensin converting enzyme (ACE) inhibitor enalapril. SUBJECTS: Eight non-sodium-restricted patients with mild-to-moderate essential hypertension. DESIGN: A single-blind crossover study. Ro 42-5892 (600 mg orally, once a day) and enalapril (20 mg orally, once a day) were given for 8 days before detailed investigations were carried out. METHODS: Ambulatory blood pressure was measured directly for 24 h by the Oxford technique on three occasions. Off-treatment and on day 8 of treatment with Ro 42-5892 and with enalapril. Ang II was measured by radioimmunoassay after separation by high-performance liquid chromatography. RESULTS: Plasma renin activity and Ang II were lowered by 83% [95% confidence interval (CI) 61-105] and 68% (95% CI 49-87), respectively, 0.5-1 h after Ro 42-5892, but after only 3 h values had returned to baseline. Unlike this rapid and short-term suppression of Ang II, the maximal antihypertensive response to Ro 42-5892 (fall in blood pressure 12.9/9.0 mmHg) occurred only after 6 h. Blood pressure returned to baseline after 8 h. In response to enalapril, Ang II was maximally suppressed by 63% (95% CI 32-94) after 2 h and by 83% (95% CI 76-90) after 8 h. Despite early maximal Ang II suppression, the maximal antihypertensive response to enalapril occurred only after 12 h (fall in blood pressure 25.3/16.3 mmHg). With this compound a significant antihypertensive effect was still present 24 h after dosing. CONCLUSIONS: Compared with enalapril at 20 mg once a day, repeated oral administration of a single dose of Ro 42-5892 at 600 mg caused only short-term suppression of Ang II and blood pressure. Suppression of Ang II and reduction in blood pressure were temporally dissociated, both with the ACE inhibitor and the renin inhibitor. This implies that the blood pressure lowering effect of these inhibitors is caused partly by Ang II suppression outside the circulation.

Adult↗
PubMed1993

Regional angiotensin II production in essential hypertension and renal artery stenosis.

To study regional metabolism and production of angiotensin II, we measured steady-state plasma levels of 125I-angiotensin I and II and endogenous angiotensin I and II in the aorta and the antecubital, femoral, renal, and hepatic veins during systemic infusion of 125I-angiotensin I or II. Extraction of arterially delivered angiotensin II ranged from 30-50% in the limbs to 80-100% in the renal and hepatomesenteric vascular beds both in essential hypertension (n = 13) and in unilateral renal artery stenosis (n = 7). Across the limbs, 20-30% of arterially delivered angiotensin I was converted to angiotensin II in both groups, and there was no arteriovenous gradient in endogenous angiotensin II. No conversion of arterially delivered angiotensin I was detected across the renal and hepatomesenteric beds, and there was net extraction of angiotensin II from the systemic circulation by these beds. Although regional production of angiotensin I at tissue sites made a significant contribution to its level in the veins, little of this locally produced angiotensin I reached the regional veins in the form of angiotensin II, even in the kidney with artery stenosis, where the venous levels of locally produced angiotensin I were particularly high. These results provide no evidence for a source of circulating angiotensin II other than blood-borne angiotensin I and illustrate the high degree of compartmentalization of angiotensin I and II production.

Adult↗
PubMed1993

Glomerular hyperfiltration in insulin-dependent diabetes mellitus is correlated with enhanced growth hormone secretion.

Enhanced GH secretion and hyperglycemia are suggested to play a role in the pathogenesis of glomerular hyperfiltration in insulin dependent diabetes mellitus. In this study we measured the GH response to GHRH (1 microgram/kg body weight), metabolic control, and renal function in 44 patients in order to explore a possible association between these parameters. Hyperfiltration [glomerular filtration rate (GFR) > 130 ml/min/1.73 m2] was present in 21 patients and normofiltration in 23. The duration of diabetes, plasma concentrations of renin, catecholamines, insulin-like growth factor-1 and blood glucose during renal function measurements were not different. GH response was significantly higher in patients with hyperfiltration. There was a positive relation between GH response and GFR (r = 0.51, P < 0.001) and effective renal plasma flow (r = 0.39, P < 0.01). GFR was correlated with insulin dose (r = 0.48, P < 0.001). There was no difference in glycosylated hemoglobin between the two groups. Patients with hyperfiltration used more insulin, had more frequent blood glucose values below the threshold level for activation of GH secretion, and had greater glycemic excursions than patients with normofiltration. The results suggest that GH hypersecretion and glomerular hyperfiltration are related and they support the possibility of a linkage between GH hypersecretion and glucose variability.

Adolescent↗