G. van den Berg

Influence of single- and multiple-dose omeprazole treatment on nifedipine pharmacokinetics and effects in healthy subjects

SummaryThe effects of single dose (20 mg) and short-term (20 mg/day for 8 days) oral treatment with omeprazole on the pharmacokinetics and effects of oral nifedipine (10 mg capsule) and on gastric pH have been investigated in a randomized, double-blind, placebo-controlled cross-over study in 10 non-smoking healthy male subjects.The single dose of omeprazole had no significant effect on any pharmacokinetic parameter of nifedipine, nor on gastric pH, or blood pressure or heart rate.Short-term omeprazole treatment increased the AUC of nifedipine by 26% (95% confidence interval 9–46%), but all other pharmacokinetic parameters of nifedipine, including elimination half-life, Cmax, tmax, and recovery of the main urinary metabolite, were not significantly changed. The median gastric pH during the absorption phase of nifedipine was increased by short-term omeprazole (pH 4.2) compared to placebo treatment (pH 1.4). Blood pressure and heart rate did not differ between treatments.The interaction between nifedipine and omeprazole is not likely to be of major clinical relevance.

Global branches of multi-bump periodic solutions of the Swift-Hohenberg equation

Abstract: In this paper we study the existence of single- and multi-bump periodic solutions of a class of fourth order ordinary differential equations arising in problems of pattern formation. Measuring the tendency to form patterns by a parameter q∈ℝ, we view the problem as a nonlinear eigenvalue problem. With the use of analytical as well as numerical methods, branches of periodic solutions are investigated, both locally and globally.

Quality of life is impaired in association with the need for prolonged postoperative therapy by somatostatin analogs in patients with acromegaly.

OBJECTIVE To assess the influence of long-acting somatostatin analogs (SSTA) after initial pituitary surgery on long-term health-related quality of life (HR-QoL) in relation to disease control in patients with acromegaly. DESIGN This is a cross-sectional study in two tertiary referral centers in The Netherlands. PATIENTS AND METHODS One hundred and eight patients with acromegaly, in whom transsphenoidal (n=101, 94%) or transcranial (n=7, 6%) surgery was performed. Subsequently, 46 (43%) received additional radiotherapy and 41 (38%) were on postoperative treatment with SSTA because of persistent or recurrent disease at the time of study. All subjects filled in standardized questionnaires measuring HR-QoL. Disease control at the time of study was assessed by local IGF1 SDS. RESULTS IGF1 SDS were slightly higher in patients treated with SSTA in comparison with patients without use of SSTA (0.85±1.52 vs 0.25±1.21, P=0.026), but the percentage of patients with insufficient control (IGF1 SDS >2) was not different (17 vs 9%, P=0.208). Patients using SSTA reported poorer scores on most subscales of the RAND-36 and the acromegaly QoL and on all subscales of the multidimensional fatigue inventory-20. A subgroup analysis in patients with similar IGF1 levels (SSTA+, n=26, IGF1 SDS 0.44±0.72 vs SSTA-, n=44, IGF1 SDS 0.41±0.65) revealed worse scores on physical functioning, physical fatigue, reduced activity, vitality, and general health perception across all HR-QoL questionnaires in patients treated with SSTA. CONCLUSION QoL is impaired in association with the need for prolonged postoperative therapy by SSTA in patients with acromegaly despite similar IGF1 levels.

Aberrant expression of multiple hormone receptors in ACTH-independent macronodular adrenal hyperplasia causing Cushing's syndrome

OBJECTIVE Aberrant adrenal expression of various hormone receptors has been identified in ACTH-independent macronodular adrenal hyperplasia (AIMAH) causing cortisol hypersecretion regulated by hormones other than ACTH. We aimed to determine aberrant expression of multiple hormone receptors in vivo and in vitro in adrenal tissue of a patient with AIMAH. DESIGN The design of the study includes clinical case description, and biochemical and immunohistochemical analysis to demonstrate aberrant expression of multiple hormone receptors in AIMAH. METHODS The subject of the study is a male diagnosed with Cushings syndrome because of AIMAH. Directly after laparoscopic removal of the adrenals, adrenal tissue was incubated with and without test substances (ACTH, forskolin, arginine vasopressin (AVP), desmopressin, epinephrine, norepinephrine, purified human chorionic gonadotropin (hCG), metoclopramide and the combinations of AVP with ACTH, epinephrine and metoclopramide). LH/hCG-receptor (hCG-R) immunohistochemistry and RT-PCR analyses were performed to demonstrate aberrant expression of LH/hCG-R and V(1-3)-AVPR. RESULTS AIMAH was characterized by in vivo cortisol responsiveness to AVP and in vitro cortisol responses to AVP, hCG, epinephrine, and norepinephrine suggesting aberrant adrenal expression of the receptors for AVP (the V(1-3)-AVPRs), catecholamines (the beta-AR), and LH (the LH/hCG-R). Incubation with combinations of AVP and ACTH and of AVP with epinephrine induced a stronger cortisol response compared with incubation with the individual agents. Moreover, we demonstrated adrenal V(1-3)-AVPR and LH/hCG-R expression. CONCLUSIONS AIMAH tissue may simultaneously express multiple aberrant hormone receptors, and individual ligands may potentiate each other regarding cell proliferation and cortisol production.

The triplet wave function of C60 from W-band electron nuclear double resonance spectroscopy

Electron-nuclear double resonance spectra at 95 GHz and electron-spin-echo envelope-modulation spectra at 9.5 GHz are reported for a frozen solution of fully 13C enriched C60 molecules in their photoexcited triplet state. Analysis of these data reveals that the triplet wave function is largely localized on a part of the molecule. Upon excitation, the C60 molecule adopts a structure of D5d symmetry with four symmetry inequivalent carbon atoms. The equator atoms each carry 3.8% of the spin density and the atoms next to the equator 1.1%, together accounting for 98% of the total spin density. These π-spin densities make the hyperfine interaction mainly anisotropic. A slight s-spin density on the equator atoms adds a sizable isotropic hyperfine coupling. The triplet wave function is calculated quantum-chemically and compared with the observed spin-density distribution.

Influence of food on the bioavailability of metoprolol from an OROS system; a study in healthy volunteers

SummaryThe influence of food intake on the bioavailability of metoprolol from an OROS system has been investigated. No significant difference was found between OROS administration to fasting subjects or after breakfast in any of the kinetic parameters (AUC, Cmax, tmax, C24 and lag time).Therefore, metoprolol OROS can be administered with breakfast.

Deficiencies in fat-soluble vitamins in long-term users of somatostatin analogue: Fat-soluble vitamins and somatostatin analogues

Aliment Pharmacol Ther 2010; 32: 1398–1404