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Biomedical subjects

Stan H M van Uum

Publications and source records attributed to Stan H M van Uum.

6 recordsLinked to original sources
PubMed2006

Bromide as a marker to measure adherence to drug therapy.

OBJECTIVE: Several methods have been described to measure adherence to prescribed drug therapy. However, most of these have been shown to be inaccurate. Bromide is an anion that is readily absorbed in the gut and has an elimination half-life of about 12 days. In the present study, we investigated the pharmacokinetic properties of bromide with the objective to use it as a measure of drug adherence. METHODS: Three groups of each 8 healthy volunteers took 15, 24 or 30 mg potassium bromide, respectively, daily for 20 weeks. Serum concentrations of bromide were measured every two weeks. RESULTS: There was a linear relationship between the daily dosage taken and the mean increase of bromide concentration. In every group considerable inter-individual variability was seen. Correction for body weight resulted in an improved correlation between daily bromide dose and increase in concentration (r=0.78, p<0.01). CONCLUSIONS: Unfortunately, the inter-individual variability in clearance of bromide was considerable. This limits the use of bromide to primarily measuring adherence in individual patients during long term follow-up. Bromide appears to be a potentially useful marker to be added to drugs for assessment of individual adherence to long term drug therapy. This needs to be investigated in various patients, particularly for patients with relatively asymptomatic diseases (e.g. hypertension).

Bromides↗
PubMed2004

Cortisol, 11beta-hydroxysteroid dehydrogenases, and hypertension.

Hypersecretion of cortisol is associated with hypertension. In addition, an abnormal cortisol metabolism may play a role in the pathogenesis of hypertension. The 11beta-hydroxysteroid dehydrogenase (11beta-HSD) isozymes catalyze interconversion of cortisol and cortisone and play an important role in the regulation of the effects of cortisol. Activity of 11beta-HSD type 2, converting active cortisol in inactive cortisone, is crucial in preventing access of cortisol to the renal mineralocorticoid receptors (MRs). Decreased activity of this isozyme in the kidney, either congenitally in Apparent Mineralocorticoid Excess syndrome or acquired following licorice consumption, allows cortisol access to the MRs, resulting in hypokalemic hypertension. In normotensive subjects, an association has been demonstrated between blood pressure increase on a high-salt diet and a mild decrease of renal 11beta-HSD2 activity. In ectopic adrenocorticotropic hormone (ACTH), plasma cortisol levels are very high, resulting in mineralocorticoid hypertension caused by saturation of the available renal 11beta-HSD2 capacity. Activity of the 11beta-HSDs has also been demonstrated in many extrarenal sites. Several studies have demonstrated extrarenal effects of cortisol on blood pressure, as well as a possible role for altered extrarenal 11beta-HSD activities in the pathogenesis of hypertension. More studies are needed to clarify the role of 11beta-HSDs in the pathogenesis of hypertension.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2002

Effect of glycyrrhetinic acid on 11 beta-hydroxysteroid dehydrogenase activity in normotensive and hypertensive subjects.

The 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) isoenzymes catalyse the interconversion of cortisol and cortisone. Type 1 11 beta-HSD mainly converts cortisone into active cortisol. Type 2 11 beta-HSD inactivates cortisol in mineralocorticoid target tissues, and its activity can be inhibited by glycyrrhetinic acid (GA). Inactivation of cortisol to cortisone is impaired in a subgroup of patients with primary hypertension. To study where this defect is located, we measured cortisol and cortisone concentrations in arterial plasma, in saliva and across the forearm at baseline and after administration of GA in normotensive and hypertensive subjects. GA (500 mg) or placebo was administered orally to 20 normotensive subjects in a placebo-controlled double-blind fashion. Further, we compared the effect of GA in 20 patients with primary hypertension with that in 20 normotensive subjects. Cortisol and cortisone were measured in plasma from the brachial artery and vein and in saliva. Samples were obtained at 0, 90 and 150 min. Forearm blood flow (FBF) was measured simultaneously. Forearm production of corticosteroid hormones was assessed by multiplying the arteriovenous difference in corticosteroid concentration by FBF. The cortisol/cortisone ratio in arterial plasma remained at baseline levels after placebo (4.9 +/- 1.2; mean +/- S.D.), while after GA the ratio increased similarly in normotensive subjects (12.3 +/- 3.4) and in hypertensive patients (12.2 +/- 3.7). A similar effect of GA on the salivary cortisol/cortisone ratio was found. In both normotensive subjects and hypertensive patients no forearm production of cortisol or cortisone could be demonstrated, either at baseline or after administration of GA. Thus, both before and after GA administration, we did not find any difference in systemic and salivary 11 beta-HSD type 2 activity between subjects with primary hypertension and normotensive controls. Further, both at baseline and after GA administration we were not able to demonstrate net inactivation or re-activation of cortisol and cortisone by the 11 beta-HSD isoenzymes in the forearm in either normotensive or primary hypertensive subjects.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2002

Inflammatory response in the acute phase of deep vein thrombosis.

OBJECTIVE: Deep vein thrombosis (DVT) is a multifactorial disease. Recently, inflammation has been suggested as a risk factor for DVT. The question is whether inflammation is a cause of venous thrombosis or rather a result of the thrombotic process. METHODS: We studied the inflammatory response in the acute phase of DVT with interleukin-6, interleukin-8, and C-reactive protein (CRP) as inflammatory markers. Plasma concentrations were measured on the day of admission (day 0) in 40 patients with acute DVT confirmed with phlebography and in 33 patients with clinical suspicion of DVT but negative phlebography results (controls). In patients with DVT, inflammatory markers were also examined on five subsequent days. RESULTS: On day 0, the median concentrations in plasma of interleukin-6, interleukin-8, and CRP were 15.0 pg/mL (range, <3 to 70 pg/mL), 7.0 pg/mL (range, <3 to 76 pg/mL), 37.5 mg/L (range, <7 to 164 mg/L), respectively, in the patient group and less than 3 pg/mL (range, <3 to 11 pg/mL; P <.001), 6.0 pg/mL (range, <3 to 52 pg/mL; P =.08), and 5.0 pg/L (range, <7 to 66 pg/L; P <.001), respectively, in the controls. During the next days, interleukin-6 concentration showed a gradual decline in patients with DVT from 15.0 to 5.5 pg/mL (P <.001), interleukin-8 concentration was relatively constant in time, and CRP concentration declined from 37.5 to 21.5 mg/L (P =.01). CONCLUSION: Our data show an apparent inflammatory response with highest measured concentrations of inflammatory markers on the day of admission and a subsequent decrease during the next days. This response supports the hypothesis that elevated inflammatory markers are a result rather than a cause of venous thrombosis.

Acute-Phase Reaction↗
PubMed2002

Acute intrarenal administration of cortisol has no effect on renal blood flow in hypertensive individuals.

BACKGROUND: Cortisol is known to increase blood pressure. One possible mechanism is the reported increase in renal vascular resistance (RVR). It is unknown whether this is due to a direct effect of cortisol on the kidneys. OBJECTIVE: To study the effect of infusion of cortisol directly into the renal artery on renal blood flow (RBF) and on renal 11beta-hydroxysteroid dehydrogenase (11beta-HSD)-mediated conversion of cortisol to cortisone in patients with primary hypertension. DESIGN AND METHODS: Twenty-seven patients with primary hypertension participated in this study. Fifteen received placebo and 12 received glycyrrhetinic acid (GRA; 500 mg) orally 2.5 h before the study. After a 10 min infusion of 5% glucose, cortisol was infused in stepwise increasing doses (0.625, 1.25 and 2.5 microg/kg per min), for 10 min each dose. At the end of each infusion step, RBF was measured using the xenon-133 washout technique. Plasma samples from the femoral artery and renal vein were taken for measurement of cortisol and cortisone. Urine was collected for measurement of steroid concentrations for 6 h on the day before the infusion and for 6 h after the infusion. RESULTS: After placebo or GRA, cortisol infusion did not change RVR, RBF or blood pressure. RVR values were 0.72 (0.45-0.89) mmHg/ml per min per 100 ml tissue [median (first and third quartiles)] and 0.71 (0.64-0.91) mmHg/ml per min per 100 ml tissue during infusion of 5% glucose and infusion of the highest dose of cortisol, respectively ( P= NS). Cortisol infusion increased the venous-arterial difference in plasma cortisone concentration across the kidney from 76 (40-115) nmol/l to 138 (100-186) nmol/l (P< 0.05) and increased the cortisol : cortisone ratios in the renal vein and in urine (both P< 0.05). As compared with placebo, administration of GRA increased the cortisol : cortisone ratios in peripheral and renal veins and in the urine. CONCLUSION: Acute infusion of cortisol in high doses directly into the renal artery in patients with primary hypertension did not affect RBF or RVR. Infusion of cortisol resulted in increased cortisol-cortisone conversion by renal 11beta-HSD2, but the concurrent increase in renal and urinary cortisol : cortisone ratio suggests a relative insufficiency of renal 11beta-HSD2 activity as a result of enzyme saturation. This may enhance mineralocorticoid receptor stimulation by cortisol.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗