Showing papers by "University of Antwerp published in 1991"

Release of nitric oxide upon stimulation of nonadrenergic noncholinergic nerves in the rat gastric fundus.

Abstract: The possible role of nitric oxide (NO) as inhibitory nonadrenergic noncholinergic (NANC) neurotransmitter was studied in the rat gastric fundus. NO induced tetrodotoxin-resistant NANC relaxations in longitudinal muscle strips similar to those induced by electrical stimulation. Incubation with the stereospecific inhibitors of the NO biosynthesis NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine (L-NNA) resulted in an increase of the basal tension which was reversed partly by L-arginine, but not by D-arginine. L-NMMA and L-NNA inhibited the relaxations to electrical stimulation, but not those induced by ATP, vasoactive intestinal polypeptide (VIP), norepinephrine or NO. This inhibitory effect was prevented by L-arginine, but not by D-arginine. In a second series of experiments, the gastric fundus served as donor tissue in a superfusion bioassay with de-endothelialized rings of rabbit aorta as detector tissue. The fundus released a labile factor with vasodilator activity upon electrical stimulation. This release was inhibited by tetrodotoxin and L-NNA, whereas it was increased by L-arginine. The biological activity was enhanced by superoxide dismutase and eliminated by hemoglobin. Our results indicate that NO is formed and released upon brief stimulation of the NANC nerves in the rat gastric fundus which is essential for the transient relaxations in this preparation. Therefore, we suggest NO or a NO releasing substance as inhibitory NANC transmitter in the rat gastric fundus.

Male song as a cue for mate choice in the European starling

Abstract: This study had two aims. First, we looked at individual differences in song characteristics between males of the European starling, and we related song behaviour to factors such as male age, pairing date, polygyny and male breeding success. Second, we experimentally tested whether song has an effect on female mating decisions. 1. During the breeding season, male starlings sing a very long and complex song consisting of a rapid succession of large number of different song types. We observed marked differences between males in average song bout length (a song bout was defined as a period of at least five seconds of song containing no pauses larger than 1.5 seconds) and in song repertoire size. Average song bout lengths ranged from 16 to 35 seconds. The individual repertoire size ranged from 23 to 67 song types. Repertoire size and average song bout length were positively correlated. 2. Both in the field and in captivity, yearling males sang shorter average song bout lengths and had smaller repertoire sizes than older males. 3. Males singing longer average song bouts and having larger repertoire sizes attracted females for pairing before their rivals with shorter average song bouts and smaller repertoire sizes.

Morphine differentially affects the sensory and affective pain ratings in neurogenic and idiopathic forms of pain.

Abstract: In a double-blind, placebo controlled crossover study, the effect of morphine on the affective and sensory pain ratings in different forms of chronic pain was investigated. Six patients suffering from central neurogenic pain, 8 from peripheral neurogenic pain and 6 from idiopathic pain participated in the study. Morphine (0.3 mg/kg bodyweight) and placebo (saline) were administered intravenously. Both the affective and sensory dimensions of pain sensation were assessed by means of the 101-point rating scale. From our results it appeared that morphine reduced the affective but not the sensory dimension of pain sensation in both groups of neurogenic pain patients. In the idiopathic pain group, neither the affective nor the sensory dimension of pain sensation were affected. The observed differences in opioid responsiveness were neither the result of differences in opioid consumption nor of differences in baseline pain levels.

Fucosidosis revisited: a review of 77 patients.

Abstract: Fucosidosis is a rare, autosomal recessive, lysosomal storage disorder caused by a severe deficiency of alpha-L-fucosidase in all tissues. We have conducted a review of fucosidosis, compiling data from published reports and an international questionnaire survey. Seventy-seven patients affected with fucosidosis of which 19 had not been reported before have been identified. A major aim of the present study was to define the natural history of fucosidosis. The clinical picture of fucosidosis consists of progressive mental (95%) and motor (87%) deterioration, coarse facies (79%), growth retardation (78%), recurrent infections (78%), dysostosis multiplex (58%), angiokeratoma corporis diffusum (52%), visceromegaly (44%), and seizures (38%). Whereas the original fucosidosis patients described by Durand et al. (Pediatr 75:665–674, 1969) were decerebrate and died before age 5 years, most fucosidosis patients have a slower course of degeneration. Mortality before age 5 years was observed in only 7 patients (9%), whereas 36 patients (64%) reached the second decade. We did not find evidence for the existence of clinical heterogeneity with a rapidly progressive type I and a slowly progressive type II fucosidosis as suggested in the literature. Instead, there seems to exist a wide continuous clinical spectrum. At the biochemical level no heterogeneity in residual fucosidase enzyme activity or crossreacting immunoreactive fucosidase protein was observed. At the DNA level at least 4 different mutations must be responsible for fucosidosis. These genotypic differences however do not explain the observed phenotypic differences.

4'-Hydroxy-3-methoxyflavones with potent antipicornavirus activity.

Abstract: 4'-Hydroxy-3-methoxyflavones are natural compounds with known antiviral activities against picornaviruses such as poliomyelitis and rhinoviruses. In order to establish a structure-activity relationship a series of analogues were synthesized, and their antiviral activities and cytotoxicities were compared with those of flavones from natural origin. The 4'-hydroxyl and 3-methoxyl groups, a substitution in the 5 position and a polysubstituted A ring appeared to be essential requirements for a high activity. The most interesting compound was 4',7-dihydroxy-3-methoxy-5,6-dimethylflavone possessing in vitro TI99 values of greater than 1000 and greater than 200 against poliovirus type 1 and rhinovirus type 15, respectively. This compound was also active against other rhinovirus serotypes (2, 9, 14, 29, 39, 41, 59, 63, 70, 85, and 89) tested, having MIC50 values ranging from 0.016 to 0.5 micrograms/mL. Finally in contrast to quercetin it showed to be not mutagenic in concentrations up to 2.5 mg in the Ames test.

Evidence for nitric oxide as mediator of non-adrenergic non-cholinergic relaxations induced by ATP and GABA in the canine gut

Abstract: 1 The effects of haemoglobin, and the nitric oxide (NO) biosynthesis-inhibitors NG-monomethyl-L-arginine (L-NMMA), its enantiomer D-NMMA, and NG-nitro-L-arginine (L-NNA) were investigated on nonadrenergic non-cholinergic (NANC)-mediated relaxation of circular muscle strips of the canine terminal ileum and ileocolonic junction induced by electrical stimulation, adenosine 5'-triphosphate (ATP), gamma-aminobutyric acid (GABA) and NO. 2 Tetrodotoxin, L-NMMA and L-NNA, but not D-NMMA, inhibited the relaxations induced by electrical stimulation, ATP and GABA, but not those in response to NO. 3 The inhibitory effect of L-NMMA and L-NNA was prevented by L-arginine, but not by D-arginine. L-Arginine did not potentiate any of the NANC relaxations. 4 Haemoglobin reduced the relaxation induced by electrical stimulation, ATP and GABA, and abolished those in response to NO. 5 Our results demonstrate that the ATP- and GABA-induced relaxations resulting from stimulation of intramural NANC neurones, in addition to those induced by electrical impulses, are mediated by NO or a NO releasing substance and thus provide further evidence in support of the proposal that NO is the final inhibitory NANC neurotransmitter in the canine terminal ileum and ileocolonic junction.

High-pressure properties of wurtzite- and rocksalt-type aluminum nitride

Abstract: Electronic and ground-state properties of both wurtzite- and rocksalt-structure AlN are evaluated in the local-density-functional formalism using nonlocal norm-conserving pseudopotentials. For the wurtzite structure we obtain a=3.129 \AA{} and c=4.988 \AA{} and an internal parameter of 0.3825, which deviates considerably from the ideal value. In the case of the rocksalt structure we get a=4.032 \AA{}. Both modifications are large-band-gap semiconductors with a direct gap in the wurtzite structure and an indirect gap in the rocksalt structure. The transition pressure from hexagonal to cubic was calculated to be 12.9 GPa, in reasonable agreement with the experimental value.

Itraconazole penetrates the nail via the nail matrix and the nail bed--an investigation in onychomycosis.

Abstract: Nail-matrix kinetics were studied in 21 patients (19 with onychomycosis, two with tinea corporis) as soon as taking itraconazole (Sporanox) 100 mg daily for up to 7 months. Itraconazole was detected in the distal nail as soon as 1 month after the start of therapy (42 ng/g in fingernails and 16 ng/g in toenails). During the course of treatment, this concentration rose and reached a mean of 160 ng/g in fingernail clippings and 197 ng/g in toenail clippings. Moreover, in fingernails of 12 out of 21 patients and in toenails of six out of 20 patients, itraconazole was detected in the distal nail clippings before full outgrowth of the fastest-growing nail. In most patients, itraconazole was detected in the distal nail clippings earlier than would be expected if the drug were incorporated only via the nail matrix, indicating that in addition to the nail matrix, a second route of penetration into the nail exists, i.e. the nail bed.

The evolutionary position of the rhodophyte Porphyra umbilicalis and the basidiomycete Leucosporidium scottii among other eukaryotes as deduced from complete sequences of small ribosomal subunit RNA

Abstract: The complete small ribosomal subunit RNA (srRNA) sequence was determined for the red algaPorphyra umbilicalis and the basidiomyceteLeucosporidium scottii, representing two taxa for which no srRNA sequences were hitherto known. These sequences were aligned with other published complete srRNA sequences of 58 eukaryotes. Evolutionary trees were reconstructed by a matrix optimization method from a dissimilarity matrix based on sections of the alignment that correspond to structurally conservative areas of the molecule that can be aligned unambiguously. The overall topology of the eukaryotic tree thus constructed is as follows: first there is a succession of early diverging branches, leading to a diplomonad, a microsporidian, a euglenoid plus kinetoplastids, an amoeba, and slime molds. Later, a nearly simultaneous radiation seems to occur into a number of taxa comprising the metazoa, the red alga, the sporozoa, the higher fungi, the ciliates, the green plants, plus some other less numerous groups. Because the red alga diverges late in the evolutionary tree, it does not seem to represent a very primitive organism as proposed on the basis of morphological and 5S rRNA sequence data.

The role of nitric oxide in inhibitory non-adrenergic non-cholinergic neurotransmission in the canine lower oesophageal sphincter

Abstract: 1. The role of nitric oxide (NO) in non-adrenergic non-cholinergic (NANC) neurotransmission was studied on circular muscle strips of the canine lower oesophageal sphincter (LOS). Electrical field stimulation evoked frequency-dependent relaxations, which were resistant to adrenergic and cholinergic blockade and abolished by tetrodotoxin. 2. Exogenous administration of NO induced concentration-dependent and tetrodotoxin-resistant relaxations which mimicked those in response to electrical stimulation. 3. NG-nitro-L-arginine (L-NNA), a stereospecific inhibitor of NO-biosynthesis, inhibited the relaxations induced by electrical stimulation but not those by exogenous NO or vasoactive intestinal polypeptide (VIP). 4. The effect of L-NNA was prevented by L-arginine, the precursor of the NO biosynthesis but not by its enantiomer D-arginine. 5. Haemoglobin abolished the NO-induced responses and reduced those evoked by electrical stimulation. 6. Cumulative administration of VIP induced concentration-dependent relaxations, which were slow in onset and sustained. A complete relaxation to VIP was not achieved and the relaxations were not affected by L-NNA. 7. In conclusion, our results provide evidence that NANC relaxations are mediated by NO, suggesting NO or a NO releasing substance as the final inhibitory NANC neurotransmitter in the canine LOS.

Tutorial to robust statistics

Abstract: In this tutorial we first illustrate the effect of outliers on classical statistics such as the sample average. This motivates the use of robust techniques. For univariate data the sample median is a robust estimator of location, and the dispersion can also be estimated robustly. The resulting ‘z-scores’ are well suited to detect outliers. The sample median can be generalized to very large data sets, which is useful for robust ‘averaging’ of curves or images. For multivariate data a robust regression procedure is described. Its standardized residuals allow us to identify the outliers. Finally, a survey of related approaches is given. (This review overlaps with earlier work by the same author, which appeared elsewhere.)

Bioassay of nitric oxide released upon stimulation of non-adrenergic non-cholinergic nerves in the canine ileocolonic junction.

Abstract: 1. The release and the nature of the inhibitory non-adrenergic non-cholinergic (NANC) neurotransmitter was studied in the canine ileocolonic junction. A circular muscle strip of the canine ileocolonic junction served as donor tissue in a superfusion bioassay in which rings of rabbit aorta with the endothelium removed served as detector tissue. 2. The ileocolonic junction released a labile factor with vasodilator activity upon stimulation of non-adrenergic non-cholinergic (NANC) nerves in response to electrical impulses and the nicotinic receptor agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP). This release was respectively frequency- and concentration-dependent. 3. The release was reduced by the blocker of neuronal conductance, tetrodotoxin, and by the inhibitor of the nitric oxide (NO) biosynthesis NG-nitro-L-arginine. The biological activity was enhanced by superoxide dismutase and eliminated by haemoglobin. Hexamethonium abolished only the release in response to DMPP. 4. Injection of adenosine 5'-triphosphate (ATP) or vasoactive intestinal polypeptide (VIP) onto the cascade induced relaxations of the rabbit aorta but they were different from those induced by NO or the transferable factor. 5. Based on organ bath experiments in which the reactivity of different parts of the circular smooth muscle layer of the ileocolonic junction was investigated, a muscle strip of superficial circular muscle with submucosa was chosen as the detector strip in the bioassay cascade. 6. The ileocolonic junction dose-dependently relaxed in response to nitroglycerin and NO. NO was much more potent in the rabbit aorta than in the canine ileocolonic junction. 7. In conclusion, our results demonstrate the release of a transferable vasorelaxant factor in response to NANC nerve stimulation which behaves pharmacologically like NO but not like ATP or VIP. Therefore, we suggest that NO or a NO releasing substance is the inhibitory NANC neurotransmitter in the canine ileocolonic junction.

Influence of dosage schedule on renal cortical accumulation of amikacin and tobramycin in man.

Abstract: The pathogenesis of aminoglycoside nephrotoxicity is directly related to the accumulation of drug within the renal cortex. To identify measures that might prevent aminoglycoside nephrotoxicity, we investigated the influence of various dosage regimens on the renal cortical accumulation of amikacin and tobramycin in man. Patients undergoing nephrectomy for a renal tumour with normal renal function and no proteinuria received (i) a single dose of either amikacin (15 mg/kg) or tobramycin (4.5 mg/kg) given iv over 30 min, or (ii) a 24-h continuous infusion of either drug or (iii) amikacin as two injections of 7.5 mg/kg or tobramycin as three injections of 1.5 mg/kg over the 24 h preceding nephrectomy. Serum aminoglycoside pharmacokinetics were examined and renal cortical tissue was sampled for drug determination at operation. A single injection yielded cortical concentrations of 115.4 +/- 21.8 and 68.9 +/- 30.3 mg/kg for amikacin and tobramycin, respectively. Tissue levels after continuous infusion were 171.7 +/- 42.9 and 100.0 +/- 30.0 mg/kg for amikacin and tobramycin, respectively. Two injections of 7.5 mg/kg amikacin resulted in renal cortical concentrations of 196.9 +/- 54.9 and three injections of 1.5 mg/kg tobramycin resulted in renal cortical concentration of 76.5 +/- 18 mg/kg. The AUC for the three dosage regimens was not significantly different for the two aminoglycosides indicating linear serum pharmacokinetics for these drugs. In the case of amikacin, a single injection resulted in significantly lower drug levels than did a continuous infusion or administration of the same dose over three injections.(ABSTRACT TRUNCATED AT 250 WORDS)

A "splitting" look at chronic nonspecific lung disease (CNSLD): common features but diverse pathogenesis

Abstract: The term chronic nonspecific lung disease (CNSLD) was proposed by the Ciba Symposium in 1959 as an umbrella term grouping chronic bronchitis, asthma, emphysema and irreversible or persistent obstructive lung disease. However, it has only been widely used by proponents of the Dutch Hypothesis, which states that these diseases all result from a common genetic root and should be considered as one disease. A major reason for proposing this hypothesis in 1961 was that these different entities share some common features, especially airway hyperresponsiveness. Although not formally disproven, evidence is accumulating--and reviewed here--against this "one disease concept"; hence, common features should not necessarily imply a common pathogenesis. Overlap features are sufficiently frequent in clinical practice to cause problems for labelling patients within the scope of CNSLD. The term could still be used as a starting point for a "splitting approach", identifying a small number of important basic features in order to allow a more systematic use of established labels for diseases within CNSLD. Our proposal for labelling emphasizes a consistent use of asthma, emphysema and chronic obstructive pulmonary disease (COPD), but restricts the use of chronic bronchitis to those patients with chronic bronchial hypersecretion without chronic airways obstruction.

Tumour necrosis factor stimulates human skin mast cells to release histamine and tryptase

Abstract: Besides its effects on tumour cells, tumour necrosis factor (TNF) also acts on a variety of other cells, thus enhancing inflammatory and immune processes. In view of the prominent role of the mast cell in such processes, the aim of the present study was to assess the effects of recombinant TNF-alpha on human mast cells. Mast cells from the infant foreskin obtained during circumcision were dispersed by an enzymatic technique using collagenase and hyaluronidase. Cells thus obtained were pooled, washed and separated by Percoll gradient centrifugation. Mast cells, with a purity of 70-90% were incubated for 60 min with 10(-11) to 10(-7) M rTNF-alpha. Histamine and tryptase levels were assessed in the cell supernatant by spectrofluorometry and radioimmunoassay (RIA) respectively. A concentration dependent release of histamine was observed, which reached a maximum of 11.5 +/- 2.2 nmol/10(6) cells at 10(-8) M rTNF. Release of tryptase was also concentration dependent and reached a maximum of 293 +/- 105 mU/10(6) cells (10(-8) rTNF). rTNF-alpha thus appears to be a direct stimulus for mast cells to degranulate and to release both histamine and tryptase.

Donor transition energy in GaAs superlattices in a magnetic field along the growth axis

Abstract: The transition energies between the ground state (1s-like) and two excited states (2${\mathit{p}}^{\ifmmode\pm\else\textpm\fi{}}$-like) are calculated for shallow donor impurities in GaAs superlattices in the presence of a magnetic field along the growth axis. Results are obtained as a function of the magnetic field and the well width for various widths and heights of the barriers of the superlattices. The dependence of the transition energies on the position of the donors and the effect of band nonparabolicity are also investigated. The calculation is based on a variational approach in which Gaussian-type trial wave functions with two variational parameters are used. Polaron correction to these energies is studied within second-order perturbation theory in which only the three-dimensional-bulk phonon modes of GaAs are included. We found that the polaron effect and band nonparabolicity have to be included in order to correctly describe the experimental transition energies.

"Tweed" structure of Fe-doped YBa2Cu3O7-δ

Abstract: Fe-doped YBa 2 Cu 3 O 7−δ single crystals have been prepared by a flux method from an Y-Ba-Cu-O precursor with copper partially substituted by iron. Electron diffraction and microscopy were applied to study the domain structure of the material. Superposed on a broad twin band texture, as also observed in undoped material, all samples reveal a finer “tweed” structure of overlapping lenticular domains oriented along [120] and [1 1 0]. This suggests a two-step formation process of the domain structure. The displacement field, corresponding with the tweed structure, resembles that of microtwinning in undoped, quenched YBa 2 Cu7 3 O 7−δ samples. The randomly dispersed Fe-ions act as pinning centers or fragment the structure by the induction of twin interfaces. Monte Carlo simulations support this idea.