Biomedical subjects

E van Beek

Publications and source records attributed to E van Beek.

18 recordsLinked to original sources

PubMed2005

The Hazard Analysis Critical Control Point's (HACCP) concept as applied to some chemical, physical and microbiological contaminants of milk on dairy farms. A prototype.

Quality management on dairy farms becomes more and more important regarding the different areas of animal health, animal welfare and food safety. Monitoring animals, farm conditions and farm records can be extended with risk identification and risk management. The hazard analysis critical control point's system is useful as an on farm strategy to control the product as well as the production process on the areas of animal health, animal welfare and food safety. This article deals in detail with the question how to develop a qualitative method where risk can be defined as an interaction between probability and impact. Two parts of the production process (milk harvest and treatment of cows) where used as an example how to apply the hazard analysis critical control point's system on chemical, physical and microbiological contaminants of milk. Not just only by summarizing the different critical checkpoints for each area but also by giving them a precise judgement of probability and impact.

Animals↗

PubMed2004

Recurrence rate of pre-eclampsia in women with thrombophilia influenced by low-molecular-weight heparin treatment?

OBJECTIVES: (1) To assess the recurrence rate of pre-eclampsia in women with this history before 34 weeks of pregnancy and thrombophilia. (2) To evaluate the effects of low-molecular-weight heparin (LMWH) on pregnancy outcome. METHODS: In a multicentre retrospective study subsequent pregnancies of women with a history of pre-eclampsia necessitating birth before 34 weeks and thrombophilia were analysed. Of 58 women, 26 received LMWH and aspirin (ASA) and 32 ASA (22) or no (10) medication in their subsequent pregnancies. RESULTS: In eight women treated with LMWH and ASA and in 16 women receiving ASA or no medication pre-eclampsia recurred in the subsequent pregnancy. (OR 0.55, 95% CI 0.15-1.31) There were no significant differences in birth weight or gestational age between both groups. CONCLUSIONS: The recurrence rate of pre-eclampsia in women with thrombophilic disorders is high in this small retrospective study. No positive effect was found for LMWH treatment. A multicentred randomised study has been started to reach an adequate number of patients to evaluate the influence of LMWH treatment.

Anticoagulants↗

PubMed1999

Farnesyl pyrophosphate synthase is the molecular target of nitrogen-containing bisphosphonates.

Bisphosphonates (Bps), inhibitors of osteoclastic bone resorption, are used in the treatment of skeletal disorders. Recent evidence indicated that farnesyl pyrophosphate (FPP) synthase and/or isopentenyl pyrophosphate (IPP) isomerase is the intracellular target(s) of bisphosphonate action. To examine which enzyme is specifically affected, we determined the effect of different Bps on incorporation of [(14)C]mevalonate (MVA), [(14)C]IPP, and [(14)C]dimethylallyl pyrophosphate (DMAPP) into polyisoprenyl pyrophosphates in a homogenate of bovine brain. HPLC analysis revealed that the three intermediates were incorporated into FPP and geranylgeranyl pyrophosphate (GGPP). In contrast to clodronate, the nitrogen-containing Bps (NBps), alendronate, risedronate, olpadronate, and ibandronate, completely blocked FPP and GGPP formation and induced in incubations with [(14)C]MVA a 3- to 5-fold increase in incorporation of label into IPP and/or DMAPP. Using a method that could distinguish DMAPP from IPP on basis of their difference in stability in acid, we found that none of the NBps affected the conversion of [(14)C]IPP into DMAPP, catalyzed by IPP isomerase, excluding this enzyme as target of NBp action. On the basis of these and our previous findings, we conclude that none of the enzymes up- or downstream of FPP synthase are affected by NBps, and FPP synthase is, therefore, the exclusive molecular target of NBp action.

Animals↗

PubMed1999

Nitrogen-containing bisphosphonates inhibit isopentenyl pyrophosphate isomerase/farnesyl pyrophosphate synthase activity with relative potencies corresponding to their antiresorptive potencies in vitro and in vivo.

Bisphosphonates, synthetic compounds which suppress bone resorption, are used in the treatment of skeletal disorders. Their mode of action and intracellular targets have not yet been identified. Recent evidence suggested that enzymes of the mevalonate pathway are the potential targets. In this study, we examined the effect of four potent nitrogen (N)-containing bisphosphonates, clodronate and NH2-olpadronate, an inactive analogue of olpadronate, on isopentenyl pyrophosphate isomerase/farnesyl pyrophosphate synthase, geranylgeranyl pyrophosphate synthase, and protein geranylgeranyl transferase I activity. We found that all N-containing bisphosphonates inhibited isopentenyl pyrophosphate isomerase/farnesyl pyrophosphate synthase activity dose dependently with relative potencies corresponding to their antiresorptive potencies in vitro and in vivo, whereas clodronate and NH2-olpadronate had no effect. Furthermore, none of the bisphosphonates tested affected geranylgeranyl pyrophosphate synthase or geranylgeranyl transferase I activity. Our study reveals for the first time the intracellular target of N-containing bisphosphonates and supports the view that all bisphosphonates do not share the same molecular mechanism of action.

Animals↗

PubMed1998

A new method for plasma volume measurements with unlabeled dextran-70 instead of 125I-labeled albumin as an indicator.

A method has been developed to determine plasma volume with dextran-70 without the use of a fluorescent label. The results obtained are compared to those found using the 125I-labeled albumin method, which is taken as the gold standard. The CV of the method is about 5%, compared to 3% with the gold standard. It is shown to be of use for the determination of an increase in plasma volume during pregnancy.

Dextrans↗

PubMed1998

Persistent abnormalities in plasma volume and renal hemodynamics in patients with a history of preeclampsia.

OBJECTIVE: The objective was to test the hypothesis that women with a recent history of preeclampsia have abnormalities in renal hemodynamics and volume status. STUDY DESIGN: We studied a group of 26 primiparous women with history of preeclampsia and a group of 12 parous women with a history of uneventful pregnancies (control group). At least 4 months post partum we compared the following variables between these groups: effective renal plasma flow, glomerular filtration rate, plasma volume, plasma concentration of active renin, plasma concentration of angiotensin II, plasma concentration of aldosterone, and plasma concentration of atrial natriuretic peptide. RESULTS: Both plasma volume and plasma concentration of atrial natriuretic peptide were lower in the formerly preeclamptic group. Compared with the control subjects, the formerly preeclamptic group also had a lower effective renal plasma flow, a higher filtration fraction, and a higher renal vascular resistance. Intergroup differences in plasma concentration of active renin, plasma concentration of angiotensin II and plasma concentration of aldosterone were small and inconsistent. CONCLUSIONS: Women with history of preeclampsia are relatively hypovolemic and tend to have lower effective renal plasma flow and higher renal vascular resistance and filtration fraction than do control subjects. These findings support the hypothesis that otherwise healthy women with a history of preeclampsia show abnormalities in their volume status and renal hemodynamics, irrespective of their blood pressure.

Adult↗

PubMed1998

Differential effects of aminosubstituted analogs of hydroxy bisphosphonates on the growth of Dictyostelium discoideum.

Replacing the hydroxyl group in the bone-binding site of three clinically useful bisphosphonates (etidronate, pamidronate, and olpadronate) by an amino group resulted in great differences in their antiresorptive potencies in vitro. In the present study, this is also shown in vivo in mice treated with the six bisphosphonates at doses of up to 16 microM/kg/day for 12 days. Because binding to bone mineral is nearly the same for all tested bisphosphonates, these findings suggest that the aminosubstitution affects the cellular action of the bisphosphonates. This was tested in the cellular slime mould Dictyostelium discoideum in which cellular effects of bisphosphonates can be examined independently of binding to bone mineral. Etidronate and its aminosubstituted analog were equipotent in inhibiting amebal growth, while pamidronate was somewhat more potent than its analog. Whereas olpadronate was a potent inhibitor of axenic growth of Dictyostelium amebae, the aminosubstitution reduced its potency drastically (IC50 12 microM and 700 microM, respectively). The similarities between the inhibitory effects of the bisphosphonates tested on bone resorption in vitro and in vivo and on the growth of Dictyostelium amebae confirm that the differences in antiresorptive potencies found reflect differences in cellular effects and suggest that bisphosphonates may bind to more than one intracellular target.

Amines↗

PubMed1997

[The pathogenesis of preeclampsia].

The central factor in the pathogenesis of preeclampsia appears to be placental ischaemia which is supposed to be caused by an initial defective placentation. The impaired placental function leads to generalized endothelial cell dysfunction, which in its turn gives rise to hypertension, proteinuria, oedema, thrombocytopenia and hypoperfusion, especially of liver and kidneys. The link between placental ischaemia and endothelial dysfunction could consist of a toxic circulating 'factor X' and the multifactorial origin of the defective placentation. Impaired development of immunological tolerance may lead to an activated immune system during trophoblast invasion which then causes defective placentation. Genetic predisposition and maternal vascular pathology could be modulating factors in this process. The recent finding of latent abnormalities in haemostasis, in metabolism (giving rise to thrombophilia), and in volume homeostasis in patients with a history of preeclampsia in suggestive of an important role of these vascular mediators in the pathogenesis of preeclampsia.

Endothelium↗

PubMed1997

Net-shaped hydroxyapatite implants for release of agents modulating periodontal-like tissues.

Periodontal-like tissues and, in particular, alveolar bone- and root cementum-like material can theoretically be modulated by release of biochemical agents such as bisphosphonate (PCP), growth hormone (GH) and alkaline phosphatase (ALP) from the implant surface. The present research focused on porous ceramic hydroxyapatite (PCHA) implants. In the past the PCHA implants were machined on a lathe out of simple blocks of PCHA ceramic. This was a tedious and cumbersome method, often resulting in implants with undesirable characteristics: different porosities, cracks and fractures. Therefore a moulding technique was developed to sinter near-net-shaped PCHA implants at 2 different sintering temperatures: 1170 degrees C and 1280 degrees C, resulting in PCHA implants with porosities of 62.06% (PCHA type 1) and 40.74% (PCHA type 2), respectively. After 1 h incubation in a 10(-2) M solution of PCP, the total amounts adsorbed onto PCHA type 1 and type 2 were 114.9 +/- 2.1 micrograms and 46.1 +/- 1.5 micrograms, respectively. This was approximately 5 times higher than after incubation for 1 wk in a 10(-4) M solution of PCP. The total amounts of PCP released after the observation period of 75 d from PCHA type 1 and type 2 after incubation in the 10(-2) M solution were 103.1 +/- 1.8 micrograms and 42.8 +/- 1.5 micrograms, respectively. The total amounts released from type 1 and 2 after incubation in the 10(-4) M solution were 7.4 +/- 0.4 micrograms and 4.1 +/- 0.1 micrograms, respectively. After 2 wk of incubation in a liver/bone/kidney ALP solution the total amount of ALP adsorbed onto PCHA type 1 implants was 5039 +/- 412 mU/ml. The total amounts of ALP released were 4674 +/- 438 mU/ml and 53 +/- 20 mU/ml after 1 and 2 wk, respectively. The release of ALP was high at the beginning but slowed down thereafter. It was evident that despite the well-known high bonding affinity of PCP to HA the release of PCP occurred steadily, over a long period of time in vitro.

Adsorption↗

PubMed1997

Degradable bisphosphonate-alkaline phosphatase-complexed hydroxyapatite implants in vitro.

Degradable hydroxyapatite (HA) implants complexed with the resorption inhibiting agent bisphosphonate (PCP) and the mineralizing agent alkaline phosphatase (ALP) can theoretically maintain alveolar bone mass directly after extraction of teeth. The present in vitro study investigated the surface properties of PCP-ALP-complexed HA implants in relation to the requirements of implant behavior and action. Adsorbed PCP (pH 3.49) resulted in a flattening and broadening of the phosphate peaks and the formation of carbonate peaks in the HA pattern of the implant indicating a chemical alteration of the HA surface. Adsorption of ALP onto PCP-altered HA surfaces was 26% lower than onto HA implant blank surfaces. PCP-ALP-complexed HA implants released the PCP and ALP steadily and continuously over observation periods of, respectively, 75 and 14 days. During these observation periods, the ceramic grains of the HA implant became smaller and intergrain boundaries became broader. These morphologic characteristics suggested preconditioning of the HA implant surface for future bonding and degradation in vivo. Individual grains were no longer bonded to other grains and detached from the implant which had become rounded in shape. From in vitro mice experiments we found that PCP concentrations between 10(-4) and 10(-3) M resulted in 45Ca-release from the bone HA. Our calculations showed, however, that only a total concentration of 1.4 x 10(-4) M PCP was gradually released over the whole observation period. In another experiment, it appeared that a PCP concentration in solution < 10(-3) M did not reduce ALP activity. It is concluded that release of PCP by the PCP-ALP-complexed implants is maintained at levels in the range to impair osteoclast bone resorption but not high enough to block osteoblast activity. The amount of ALP released can lead to induction of bone formation onto implant surfaces. pH-induced alterations in the microstructure and chemistry of the HA surface allow for controlled degradation of the HA implants in vitro. A PCP-ALP-complexed HA implant acting as temporary scaffolding for alveolar bone growth enhancement, mineralization, and maintenance seems to be a reasonable concept for preservation of the edentulous alveolus.

Absorption↗

PubMed1996

Bisphosphonates inhibit the adhesion of breast cancer cells to bone matrices in vitro.

Bisphosphonates are used with increasing frequency in the management of skeletal complications in patients with breast cancer. In this paper, we have investigated whether bisphosphonates, besides their known beneficial effects on tumor-associated osteoclastic resorption, are capable of inhibiting breast cancer cell adhesion to bone matrix. For that we used two in vitro models for bone matrix (cortical bone slices and cryostat sections of trabecular bone from neonatal mouse tails). Four bone matrix-bound nitrogen-containing bisphosphonates (pamidronate, olpadronate, alendronate, and ibandronate) inhibited adhesion and spreading of breast cancer cells to bone dose-dependently, whereas etidronate and clodronate had little or no effect. Strikingly, the relative order of potency of the bisphosphonates in inhibiting the adhesion of cancer cells to cortical and trabecular bone corresponded to their relative antiresorptive potencies in vivo as well as their ranking in in vitro bone resorption assays with predictive value for their clinical efficacy. It appears that nitrogen-containing bisphosphonates alter selectively the adhesive properties of the extracellular bone matrix preventing the attachment of breast cancer cells to it. Besides the beneficial effects of bisphosphonates on tumor-induced osteoclastic resorption, the previously unrecognized effect presented in this paper makes these agents suitable for earlier pharmacologic intervention in patients with breast cancer at risk of developing bone metastases.

Animals↗

PubMed1996

Peripheral haemodynamics and renal function in relation to the menstrual cycle.

1. The objective of this study was to investigate whether the luteal phase of the menstrual cycle differs from the follicular phase by the development of a state of general vascular relaxation. 2. Once in the follicular and once in the luteal phase of the menstrual cycle, we measured by non-invasive techniques: arterial blood pressure (by finger blood pressure measurements), vascular tone (by pulse-wave velocity and plethysmography), blood flow to skin (by laser-Doppler), blood flow to forearm (by plethysmography) and blood flow to kidneys (by para-aminohippurate clearance), and the glomerular filtration rate (by inulin clearance). The data points obtained in the luteal phase were compared with those in the follicular phase by non-parametric tests. 3. Arterial blood pressure, vascular tone and the blood flows to the forearm and kidneys were comparable in the two phases of the menstrual cycle. In contrast, the blood flow to the skin was consistently lower, and the glomerular filtration rate higher in the luteal phase of the menstrual cycle. 4. The results of the present study do not support our hypothesis of a general vascular relaxation in the luteal phase of the menstrual cycle. The lower skin flow in the luteal phase may be an adaptation needed to ensure the higher core temperature of 0.3-0.5 degree C in the luteal phase. The higher glomerular filtration rate was in most case paralleled by a higher renal blood flow in the luteal phase. This suggests that the higher glomerular filtration rate is secondary to a selective vasorelaxation of the afferent renal arterioles.

Adult↗

PubMed1995

Effects of experimental conditions on the release of 45calcium from prelabeled fetal mouse long bones.

Embryonic/neonatal bones in culture are commonly used for the study of osteoclastic resorption in vitro. For this purpose, the release of 45calcium (45Ca) from prelabeled bones is measured as an index of resorption. We studied 45Ca release from two types of long bone explants after different preparation methods: 17-day-old fetal mouse radii/ulnae with and without cartilage ends (intact radii/ulnae and shafts, respectively), and intact 18-day old metacarpals/metatarsals. In addition, we examined the effect of different culture conditions, such as cultures performed under the surface of the medium or at the interphase of medium and air, on 45Ca release and histology. When intact radii/ulnae were cultured under the surface of the medium, there was always a significant amount (10%) of net basal 45Ca release (corrected for physicochemical exchange) that was not due to osteoclastic resorption, as it could not be suppressed by inhibitors of resorption even at high concentrations. Moreover, histologically TRAcP-positive cells were almost absent after culture and the bone marrow/stromal cells in the center of the bone appeared necrotic, possibly due to a lack of oxygen. Under these culture conditions, osteoclasts could survive in shafts as well as in PTH-stimulated intact radii/ulnae, but a constant amount of 10% 45Ca, not due to resorption, was still released in the medium. When these explants were cultured at the interphase of medium and air, basal and stimulated 45Ca release originated from osteoclastic resorption. In contrast, in 18-day-old fetal mouse metacarpals/metatarsals, the experimental conditions applied did not affect 45Ca release, which was always due to resorption of the explants by osteoclasts.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗

PubMed1994

Structural requirements for bisphosphonate actions in vitro.

We investigated the structural requirements for the binding of bisphosphonates to bone mineral and the relation between their affinity for bone and their effects on bone resorption in vitro. For this we used fetal mouse long bones in culture and bisphosphonates with variable R1 and R2 structures. In addition, we studied the effect of structural differences in the incorporation of calcium into bone. We found that bisphosphonates containing a hydroxyl group in the R1 position have the highest affinity for bone mineral. This was related to their capacity to inhibit the incorporation of calcium into long bones but not to their antiresorptive potency. The latter was primarily determined by R2. Furthermore, the effect of bisphosphonates on calcification, but not on resorption of bone explants, was mainly determined by the mode of addition. The continuous presence of bisphosphonate during culture inhibited calcification even at very low concentrations, but short incubation of the bones with relatively high concentrations had no effect. This is probably a result of differences in the availability of the compound to the process of calcification. Because, in vivo, the more potent bisphosphonates inhibit resorption without adversely affecting mineralization of the skeleton and they disappear rapidly from the circulation after administration, we suggest that cultures of bone explants incubated with bisphosphonates for short times rather than cultures in which the drugs are continuously present provide more accurate information about the in vivo effect of these compounds on both resorption and calcification.

Animals↗

PubMed1994

Ceramic hydroxyapatite implants for the release of bisphosphonate.

Maintaining bone mass after extraction of teeth is a major problem in the prevention of oral disease. Maintenance theoretically could be enhanced by immediate implantation of submerged ceramic hydroxyapatite (HA) implants releasing the bone resorption-inhibiting agent bisphosphonate (P-C-P). Four different types of ceramic HA implants were designed as release systems for an in vitro study and assayed in saline at a temperature of 37 degrees C during 3 months. The implants were either rod- or tube-shaped, with densities of 3.104 g/cm3 and 1.408 g/cm3 (microporous) or 2.369 g/cm3 (macro/microporous). Loading of the implants with the P-C-P was done by adsorption into the ceramic (rod-shaped implants) or by filling the reservoir of the implant (tube-shaped implants). Despite the fact that P-C-P has a high bonding affinity to HA it appeared that the release of adsorbed P-C-P from the ceramic HA occurred steady, controlled and over a long period of time. The rod-shaped implants had much better release properties than the tube-shaped implants. Microporous ceramic HA rods sintered at 800 degrees C and macro/microporous rods sintered at 1300 degrees C are considered to be promising release systems for P-C-Ps.

Adsorption↗

PubMed1992

Osteoclast formation together with interleukin-6 production in mouse long bones is increased by insulin-like growth factor-I.

Insulin-like growth factor-I (IGF-I) is a potent stimulator of bone formation. Whether this growth factor also induces bone resorption has not been studied in detail. We used two organ culture systems to examine the direct effect of IGF-I on bone resorption. Fetal mouse radii/ulnae, containing mature osteoclasts, showed no response to IGF-I, indicating that osteoclastic activity is not influenced by IGF-I. Fetal mouse metacarpals/metatarsals, containing just osteoclast precursors and progenitors, showed an increase in resorption in response to IGF-I, indicating that IGF-I stimulates the formulation of osteoclast precursors/progenitors and thereby increases the number of osteoclasts. Interleukin-6 (IL-6) has been hypothesized to be a mediator of bone resorptive agents such as parathyroid hormone (PTH). Both radii/ulnae and metacarpals/metatarsals reacted to IGF-I with an increase in IL-6 production. IL-6 production by UMR-106 osteogenic osteosarcoma cells was positively modulated by IGF-I, indicating that osteoblasts are likely to be the cells responsible for increased IL-6 production by the bones, and that IL-6 might be a mediatory of IGF-I-stimulated bone resorption.

Animals↗

PubMed1991

Umbilical artery velocimetry and non-stress test in monitoring high-risk pregnancies. A comparative longitudinal study.

In a longitudinal comparative study, umbilical artery velocimetry and the non-stress test were used in parallel for surveillance of 153 hospitalized high-risk pregnancies. The occurrence of abnormal flow velocity waveforms of the umbilical artery, with increased pulsatility index but maintained diastolic flow velocity, was an inconsistent finding and often related to pregnancy complications other than intrauterine growth retardation. Among patients with small-for-gestational age fetuses or pre-eclampsia with a small-for-gestational age fetus, there was a significantly higher frequency of abnormal umbilical flow velocity waveforms. This was a consistent finding and was often associated with an absence of diastolic flow velocity and operative delivery for fetal distress. An abnormal non-stress test had a significant relationship with intrauterine growth retardation, but a lower predictive capacity for this condition than the abnormal umbilical artery flow velocity waveform. In patients with small-for-gestational age fetuses and no other complication of pregnancy, umbilical artery velocimetry can be used as a reliable tool for identifying those fetuses that need intensified surveillance. In cases with additional complications, a combined use of blood velocimetry and the non-stress test is advocated.

Journal Article↗

PubMed1989

The validity of screening for small-for-gestational-age and low-weight-for-length infants by Doppler ultrasound.

A prospective blind study assessed the efficacy of Doppler examination of the umbilical arteries (pulsatility index) as a screening procedure for predicting small-for-gestational-age and low-weight-for-length (low ponderal index) infants. Birthweight below the 2.3rd and 10th centile and ponderal index below the 3rd and 10th centile were chosen as 'cut-off' levels. Of pregnant women from our university hospital population, 400 were examined at 28 and 34 weeks gestation. The sensitivity of the test was low, ranging from 16.9 to 41.7% for the different indices. The predictive value of a negative screening test also was unsatisfactory, ranging from 79.6% to 97.9%. It is concluded that a single umbilical artery Doppler examination at 28 or 34 weeks does not satisfy the need in obstetrics for a simple and accurate technique to screen for small-for-gestational-age and low-weight-for-length infants in an unselected obstetric population.

Embryonic and Fetal Development↗