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Biomedical subjects

J de Boer

Publications and source records attributed to J de Boer.

At least 19 recordsLinked to original sources
PubMed1992

Human bronchial cyclic nucleotide phosphodiesterase isoenzymes: biochemical and pharmacological analysis using selective inhibitors.

1 The aims of the present study were to characterize the cyclic nucleotide phosphodiesterase (PDE) isoenzyme activities present in human bronchi and to examine the ability of selective isoenzyme inhibitors to relax histamine and methacholine precontracted preparations of human bronchi. 2 Three separations of pooled human bronchial tissue samples were performed. Ion-exchange chromatography showed that the soluble fraction of human bronchial preparations contains PDE I, II, III, IV and V isoenzyme activities. Multiple forms of PDE I and PDE IV were observed and PDE IV was the main cyclic AMP hydrolytic activity. 3 3-Isobutyl-l-methylxanthine (IBMX) non-selectively inhibited all separated isoenzyme activities. Zaprinast selectively inhibited PDE V, but also effectively inhibited one of the two PDE I isoforms identified. The PDE IV selective inhibitors rolipram and RO-201724, inhibited the PDE IV activities as did the dual PDE III/IV inhibitor, Org 30029. Org 9935, a PDE III selective inhibitor, potently attenuated part of the PDE IV activity peak in one of three separations performed, indicating that some PDE III activity may co-elute with PDE IV under the experimental conditions employed. 4 PDE IV-selective (rolipram), PDE III-selective (Org 9935) and dual PDE III/IV (Org 30029) inhibitors were effective relaxants of human bronchial smooth muscle. The PDE V/PDE I inhibitor, zaprinast was relatively ineffective. 5 The present study demonstrates in human bronchi, as in animal airways smooth muscle, that inhibitors of PDE III, PDEIV and dual PDE III/IV have potentially useful bronchodilator activity and are worthy of further consideration as anti-asthma drugs.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1991

Continuous monitoring of extracellular lactate concentration by microdialysis lactography for the study of rat muscle metabolism in vivo.

A method is described for the measurement and on-line monitoring of muscular extracellular lactate concentration in both anaesthetized and freely moving rats. This method is based on microdialysis sampling and lactic dehydrogenase-catalysed nicotinamide adenine dinucleotide, reduced (NADH)-fluorescence detection techniques. In vivo calibration revealed a resting extracellular lactate concentration of 1.92 +/- 0.13 mmol/l (+/- SEM) in the gastrocnemius muscle of adult male Wistar rats (n = 6), while the average whole-blood lactate level was 0.76 +/- 0.12 mmol/l (+/- SEM). This measured extracellular lactate concentration was 1.73-times higher than that deduced from the arterial lactate concentration. Blocking glycolysis with iodoacetate reduced the extracellular lactate concentration to 52 +/- 6% (+/- SEM, n = 4) of the resting level. The extracellular lactate concentration in rat gastrocnemius muscle had increased to significantly (P less than or equal to 0.05) different levels, 2.4 +/- 0.03 (+/- SEM) or 4.0 +/- 0.55 (+/- SEM) times the control value, 1 h after aortic clamping (n = 3) or cardiac arrest (n = 3), respectively. Stimulation of the sciatic nerve induced elevations of the extracellular lactate concentration in the tibialis anterior muscle which were linearly related to the recorded isometric force-time integral. We also monitored on-line the changes in extracellular lactate concentration in the tibialis anterior muscle of a swimming rat. Our results indicate that microdialysis lactate reflects also intracellular metabolism. Lactography may be a useful alternative to biopsies and nuclear magnetic resonance spectroscopy in clinical medicine and physiology for the monitoring of metabolism in vivo.

Animals↗
PubMed1991

The presence of five cyclic nucleotide phosphodiesterase isoenzyme activities in bovine tracheal smooth muscle and the functional effects of selective inhibitors.

1. The profile of cyclic nucleotide phosphodiesterase (PDE) isoenzymes and the relaxant effects of isoenzyme selective inhibitors were examined in bovine tracheal smooth muscle. The compounds examined were the non-selective inhibitor 3-isobutyl-1-methylxanthine (IBMX), zaprinast (PDE V selective), milrinone and Org 9935 (4,5-dihydro-6-(5,6-dimethoxy-benzo[b]thien-2-yl)-5-methyl-1 (2H)-pyridazinone; both PDE III selective), rolipram (PDE IV selective) and Org 30029 (N-hydroxy-5,6-dimethoxy-benzo[b]-thiophene-2-carboximidamide HCl a dual PDE III/IV inhibitor). 2. Ion exchange chromatography showed three main peaks of PDE activity. The first peak was stimulated by Ca2+/calmodulin (PDE I), the adenosine 3':5'-cyclic monophosphate (cyclic AMP) hydrolytic activity of the second peak was stimulated by guanosine 3':5'-cyclic monophosphate (cyclic GMP) (PDE II) whilst that of the third peak was not significantly modified by any regulator (PDE IV). Calmodulin affinity chromatography revealed the additional presence of cyclic GMP-specific PDE (PDE V) in the first peak. A clearly distinct peak of cyclic GMP-inhibited PDE (PDE III) was not observed. However, Org 9935 inhibited the third activity peak more effectively in the presence, than in the absence, of rolipram (3 mumol l-1), indicating the presence of PDE III activity. 3. Rolipram was the most potent inhibitor of PDE IV. The mean -log50 IC50 values for rolipram, IBMX, milrinone, Org 30029, Org 9935 and zaprinast were 5.9 +/- 0.1, 4.9 +/- 0.1, 4.7 +/- 0.1, 4.6 +/- 0.1 and 4.6 +/- 0.1, respectively. 4. Rolipram was a potent relaxant of both histamine (1 pumol -') and methacholine (0.03 pmol -') precontracted preparations; (pD2 values; histamine 7.1 +/- 0.1, methacholine 6.8 /-+ 0.2 and 4.5 +/- 0.1, biphasic relaxation). IBMX also relaxed all preparations (pD2 values; histamine 5.6 +/- 0.1, methacholine 5.6 +/- 0.1) whilst zaprinast (pD2 values; histamine 5.2 +/- 0.1, methacholine 4.4 +/- 0.3), milrinone (pD2 values; histamine 5.2 + 0.1, methacholine 4.3 + 0.3) and Org 9935 (pD2 values; histamine 4.1 + 0.1, methacholine 4.1 +/- 0.2) did not completely relax preparations at concentrations up to 100 pImol I-. Org 30029 (pD2 values; histamine 6.2 +/- 0.1, methacholine 5.4 +/- 0.1) was a more effective relaxant than can be explained on the basis of PDE IV inhibition alone.5. We conclude that bovine tracheal smooth muscle contains five distinct PDE isoenzymes. PDE IV appears to be more important in the modulation of tissue function than PDE III and PDE V.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1990

Lactography as an approach to monitor glucose metabolism on-line in brain and muscle.

1. Thus far metabolic processes in the intact animal (or man) have been studied either by the analysis of body fluids, of biopsies, of tissue obtained post mortem or by techniques, requiring dedicated and expensive equipment (such as positron emission tomography or magnetic resonance spectroscopy). 2. Here we describe a relatively simple and inexpensive technique, that can be applied in vivo to study metabolism in brain regions and muscle in the freely moving rat and in human peripheral tissue. 3. The method is based on microdialysis allowing continuous sampling from the extracellular space, the enzymatic conversion of lactate and the on-line detection of fluorescent NADH. 4. Examples of the application of our technique include the monitoring of lactate efflux from various brain regions of behaving animals under a variety of stress exposures, during ischemia or hypoxia and drug treatments. 5. The results indicate that in brain lactate is not exclusively formed under hypoxia and that neuronal activation leads also to lactate formation, possibly due to the compartmentation of both the involved enzymes and the energy metabolism. 6. The increase of lactate formation in contracting or ischemic muscle or during exercise could also be followed on-line in the rat, suggesting that our approach allows the continuous monitoring of anaerobic metabolism in man e.g. during traumatic or arteriosclerotic limb ischemia or lactic acidosis in shock states. 7. The principle of our approach can easily be adapted to other metabolites, thus enabling to monitor other metabolic pathways in vivo as well.

Animals↗
PubMed1989

Rat striatal cation shifts reflecting hypoxic-ischemic damage can be predicted by on-line impedance measurements.

We investigated the earliest time at which irreversible damage takes place after hypoxia-ischemia in the Levine preparation of rats. In 60 rats anesthetized with chloral hydrate and maintained at one of three body temperatures, we unilaterally ligated the left common carotid artery and placed electrodes in the striatum to measure impedance (reflecting the extracellular space) during hypoxia, recovery, and/or cardiac arrest. We measured blood gases and pH at regular intervals during hypoxia in 47 rats and assessed blood-brain barrier function with Evans blue and tissue damage using Na+:K+ ratios. Shortly after hypoxia, impedance normalized in 24 rats without brain damage (normal Na+:K+ ratios, 4 hours of recovery). Sustained elevation of striatal impedance during recovery in six rats was related to an elevated Na+:K+ ratio and a disrupted blood-brain barrier. Damage was not obviously related to blood gases, pH, or the net reduction of the extracellular space during hypoxia. Hypothermia in 17 rats prevented impedance changes, and no striatal damage was found. Thus, irreversible brain damage very likely occurs during or very shortly after hypoxia. Persistent reduction of the extracellular space indicates tissue damage and can be used to monitor potential in vivo therapeutic measures.

Animals↗
PubMed1987

Sensitization to methylenedianiline and para-structures.

A toxic-allergic skin reaction of the face, neck and arms due to accidental contact with methylenedianiline (syn: 4-4'-diaminodiphenylmethane) is reported in a cleaner at a chemical plant. Patch tests revealed sensitization to chemicals of the para-group. Earlier exposure to it was unlikely. Previous sensitization to related chemicals and possible cross-sensitization was considered to be the primary cause of the allergy and the clinical manifestations.

Adult↗
PubMed1985

An alarm procedure.

Each disaster procedure is initiated by an alarm scheme, alerting all involved personnel, directly or indirectly in this procedure. Certain mathematical principles can be applied to calculate the number of people who can be reached within a fixed period of time, or to calculate the time needed to alert a fixed number of people. With this methodology a formidable amount of people can be reached within a few minutes. The advantages and disadvantages are further described.

Disaster Planning↗
PubMed1977

Urinary hydroxyproline as a measure in fracture healing.

The determination of any pattern in urinary total OH-proline following bone fractures has been the purpose of this investigation. This was carried out in a group of 11 patients with major fractures, a group of 8 patients with minor fractures and a control group of 10 healthy laboratory technicians. Indeed, some patterns could be detected. In patients with major fractures a considerable elevation of urinary total OH-proline was found which was correlated to the size and number of fractures and the healing tendency of the fracture. Normal to only slightly elevated urinary total OH-proline values during the course of the healing process of major fractures could perhaps indicate delayed union, or even malunion. Since fracture healing is usually assessed by X-ray examination and clinical experience, this study could provide a more accurate measure of the healing process of fractures.

Fractures, Bone↗
PubMed1976

Chemocommunication among domestic cats, mediated by the olfactory and vomeronasal senses. I. Chemocommunication.

Chemocommunication functions are known in many social mammals, such as gerbils, hamsters, and deer. But also mammals known as at least partly solitary do communicate by chemical signals. The existence and use of pheromones in domestic cats was the subject of this study. It turned out that male and female cats spent much time in exploring their own and foreigners' urine and skin gland secretion rubbed off on several objects. Male receivers performed sniffing and flehmen more frequently than females on the same urine, whereas female cats paid more attention to skin gland secretion. Both urine and cheek gland secretion of the female donor appeared to contain pheromones which inform the tomcat about her hormonal phase.

Animals↗